RESPONDENT'S BRIEF

ON

RECONSIDERATION

RICHARD K. TURNER, ESQ.
Attorney for Respondent
Robert J. Sinaiko, M.D.

ACKNOWLEDGMENTS

Authors of books acknowledge those who helped in preparation of the book. Authors of briefs do not.

I change that here.

First, I want to honor Shula Edelkind, medical research assistant extraordinaire, without whose tireless work and expertise this brief would not have happened.

Others whose help and support were essential and for which Dr. Sinaiko and I are most grateful are:

• California Medical Association (CMA)
• Union of American Physicians and Dentists
• Robert Fellmeth and Julie D'Angelo Fellmeth, The Center For Public Interest In Law at the University of San Diego Law School
• Officials at the Food & Drug Administration Center for Drug Evaluation & Research
• Bristol-Myers Squibb Company
• Kenneth Freeman, Esq.
• Prem Hunji Turner, Esq.
• Nancy Cahill, Esq.
• Marc Poster, Esq.
• Shirley Johnson and crew
• Colleen Smethers
• California Academy of Attorneys Representing Health Care Professionals
• Feingold Association
• National Health Federation
• Citizens for Health
• . . . and those individuals and organizations who have contributed to the incredible financial needs to support Dr. Sinaiko and protect medical advance, who must necessarily remain anonymous. You know who you are.

  Thank you one and all.

  Richard K. Turner
  Robert J. Sinaiko, M.D.

  
  
  
  
  

Table of Appendices

APPENDIX A -- EVIDENCE BY OFFICIAL NOTICE
APPENDIX B -- EXHIBITS IN EVIDENCE
APPENDIX C -- LTS CHARTS AND RELATED DOCUMENTS
APPENDIX D -- SEYMOUR v. BOARD OF MEDICAL QUALITY ASSURANCE
APPENDIX E -- COURT FILE
APPENDIX F -- TRANSCRIPT ERRORS - VOLUME 25
APPENDIX G -- CMA AMICUS BRIEF IN CTA v. STATE OF CALIFORNIA
APPENDIX H -- DECLARATION OF NANCY CAHILL, ESQ.

One night in early 1847, Jacob Kolletschka, a professor of medicine, cut his finger during an autopsy at the Vienna General Hospital, and died from septicaemia. His death profoundly affected an assistant physician in the maternity clinic by the name of Ignaz Semmelweis.

In Ward One, handled by medical students, so-called "Childbed Fever" raged. Twenty-nine percent of the women died. On Ward Two, where midwifery students attended, the mortality rate was 3 percent.

Semmelweis switched the medical and midwifery students between the wards; the high mortality rate followed the medical students. Professor Kolletschka's death confirmed his suspicion that the mothers were infected during delivery. The medical students came directly from autopsies with soiled hands and instruments to attend the delivery.

Semmelweis ordered hand-washing with chlorinated lime water before deliveries -- mortality plummeted in both wards. Hospital and medical authorities resisted his findings and disbelieved this supposed cause and effect of Childbed Fever.

Semmelweis resigned and left Vienna for Budapest. In spite of his appeals to physicians and natural scientists in several countries, they rejected his teachings. Some say he was driven mad by the rejection and derision of his colleagues. In 1865 Semmelweis was admitted to a Viennese mental hospital where, it is said, he died of streptococcal infection!

•

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•

"Where are these little beasts? Show them to us, and we shall believe in them. Has anyone seen them yet?"

--John Hughes Bennett (1812-1875)
Surgeon and Professor, Edinburgh

BACK

No physician is safe from a career-ending, financially devastating prosecution for practicing as doctors practice every day if the Prosecution's theories and charges are adopted by the California Medical Board ("Board"). Unable to find a single patient who was harmed by Dr. Sinaiko, not presenting a single patient at the hearing to testify against him, the Prosecution nonetheless asks that his license be taken because he dares to be just a bit different. He is slandered by accusations of "voodoo medicine" and labeled a "quack" because he diagnoses known human conditions such as chronic fatigue and multiple chemical sensitivity as sometimes organically, based; because he suggests treatments that in his clinical experience he believes have scientific validity though others may disagree. Indeed, his practices are those of a substantial minority and in many instances supported by a majority of practitioners.

This case is about the freedom of all doctors to advise treatments for their patients which have not (yet) been blessed by a double-blind study acceptable to the Medical Board's chosen experts.⁽¹⁾ It is about patients' freedom to choose as well.

This case is about trial and error, and trial and success. It is truly about how doctors practice medicine every day. Therapeutic trial and error is the soil in which all medical scientific discovery is planted, and such discovery is both root and flower of any advance in medicine. We must water this soil, not render it fallow. For discovery is not the exclusive domain of universities and governments. It happens every day, in clinical treatment which doctors are trained to do.

This case is not about magic "black box" treatments or about a doctor out of the mainstream. Dr. Sinaiko is not some "fringe" practitioner as the Prosecution would have you believe. Some physicians disagree with his views; others agree. Such a debate, essential to progress in medicine, doesn't mean any doctor is either wrong or should be prosecuted. Rather the debate should be encouraged, not used to dampen or deny innovation -- lest there be none.

This prosecution puts all physicians on notice: March to a different drummer, even though the march may be played to a rational scientific beat, and we'll destroy you. Here is where patient harm will indeed happen for the patients will continue to wait, while the doctors -- armed with the treatments that can cure or at least help -- will stand by, waiting for word from the lawyers for the Board, waiting to be told that the academics (or the industry) have produced "enough" studies, and the treatment will be no longer considered harmful - to the doctor.⁽²⁾

The Prosecution asks this Board to arbitrate such debates, and the winner take all. This case, and its enormous expense,⁽³⁾ didn't need to happen. There really is serious harm to patients, by incompetent and careless physicians, which needs to be discovered and stopped. This case isn't one of them.

This Panel is asked by the Attorney General to become an all-knowing all-seeing Scientific Court, to choose sides in legitimate scientific debates, to suddenly become the official government agency which is now going to tell all doctors the only way they may diagnose and treat their patients.

The Board's role, function, and purpose is perverted by this prosecution! By pitting groups of physicians against each other, one camp enjoying the favor (and protection) of the Board, this prosecution denigrates the medical profession. An atmosphere which should welcome innovation, debate and discussion about medical issues -- the only way new cures, new treatments happen -- is stifled by this prosecution. Dr. Sinaiko, an extraordinary physician, has been destroyed by it.

BACK

To decide questions of law, California, as well as all other states and the federal government, has a system of appellate courts which rule on legal issues and set down what the law is. Even though there may be rational legal arguments on both sides, the appellate courts rule for one side or the other, state what the law is as they deem it to be, and the lawyers, their clients, and the general public must accept it. We don't have such a system in medicine. There is no "high court of medicine" that rules on medical issues and orders what diagnoses and treatments are appropriate. This is fortunate, as there is no body of men and women who have such all-knowing abilities to decide at any one time what diagnoses and treatment are appropriate. Rather than a system by which medical innovation and advance are ordered from on-high, innovation and treatment evolve over time as a result of the research and actions of thousands of individuals and hundreds of institutions, tests and studies by universities and medical schools, private profit and non-profit institutions, and, significantly, by clinical trial in every day medical practice.

It has never been the mission of the Medical Board to decide for all California physicians and their patients what conditions may be diagnosed or how, or what treatments are allowed. The Medical Board's role in quality of care issues is rather to determine whether doctors are incompetent, that is, they don't know what they are doing, or if doctors are negligent in performing their medical tasks. This is a very different function from that of a Supreme Court of law which tells us what the law is. The Medical Board of California does not do that. It does not tell us what "medicine is."

In this case, however, the Medical Board is asked to be the Scientific Supreme Court of California and to tell doctors what they can and cannot diagnose and how they can and cannot treat certain conditions, a task which, with all due respect, is beyond the capability of this Medical Board or any medical board for that matter.

The quality of care issues in this case have been disguised by the prosecution as questions of negligence and incompetence when the issues are really typical debates over the efficacy of new ideas and new treatments.

The history of medicine is replete with such debates and unfortunate efforts, as in this case, to obscure or deny attempts to advance medicine. In the 1800s, taking vital signs was called "quackery." In 1847, Dr. Semmelweis was roundly criticized for promoting hand washing with chlorinated water before delivering babies. Lister, in 1865, developed an antiseptic ritual during operations. His mortality rate plummeted. His work was ridiculed by his peers even though his procedure and results were published in Lancet in March 1867. Dr. Robert Tait, denying the reality of bacteria, growled in 1898: "Let us hear no more of the nonsense about the bad results in surgery of pre-Listerian times as having been cured by Lister. It is not the truth." Cancer hospitals set up by physicians in the late 1800s were dismissed as "quack emporia" and these physicians universally condemned.^{(4) (5)}

The point is that almost every advance in medicine has come about through controversy and debate, in many cases accompanied by ridicule and denunciation. Had there been a Medical Supreme Court in any previous time, ruling on what treatments passed muster, the medical advances we enjoy today might not have come about. That is the situation before this Panel.

Panel B is being asked to anoint the opinions of some medical doctors and denounce the medical opinions of others. It is as if the prosecution in this case asks that a poll be taken and that winner take all, that those in the minority, however scientifically fit, be drummed out of the profession and their patients denied treatments which may turn out in the future to enjoy majority support but for the prosecution in this case.

The Medical Board should not engage in this dangerous game. Every new idea, every new concept or theory of causation, every new treatment, even a tiny change from what has been accepted, is a departure from "standard care." There is a big difference in a departure from "standard care" instead of the "standard of care."

The prosecution in this case confuses these concepts: To the Deputy Attorney General a change, something new, something not yet approved by the majority (however that's determined) is a departure from the "standard of care" and therefore, negligent and therefore, "unprofessional conduct" and so any doctor who dares to be different, even though right, should be punished, should lose his or her license!

Equating change with negligence doesn't work in any life endeavor. Departing from "the standard" in "high tech" is applauded and expected if success is to be achieved. The "state-of-the-art" is to be vigorously sought, in medicine as well as "high tech." To prosecute doctors who seek new and legitimate ways to heal, based on those who insist on the status quo and perhaps don't understand or who are threatened by change for whatever reason, is lunacy.

Exploring the "cutting edge," as they say, is not a departure from the "standard of care" or there would never be progress. Who will risk what has befallen Dr. Sinaiko, a mainstream doctor, who tries a few new concepts to heal? This is bad? Of course it's not, so long as there's some rational basis to try a safe treatment or to search for what is wrong with the patient. We thus cannot use the "standard of care" as the yard stick by which new diagnostic modalities and treatments are judged.

We ask this Panel to refuse to take either side on the disputed medical and scientific issues presented in this case. The Medical Board must steer clear of taking sides on medical debates in disciplinary cases which over time will work themselves out through clinical trial-and-error and institutional research.

Indeed, the District Court of Appeal has instructed the Medical Board not to use the punitive power of the State to decide disputes within medical science over diagnoses and treatments. The Court, in Seymour v. Board of Medical Quality Assurance (1987, 3 Civil C000268)⁽⁶⁾, ruled:

"It appears the experts were in substantial disagreement over the questions of hemodynamic monitoring and whether plaintiff's care, treatment and diagnosis of his patient was acceptable. . . . the record demonstrates that on the question of hemodynamic monitoring there is no ascertainable practice within the industry. What the evidence does show is that hemodynamic monitoring was and is a disputed question of medical science. The same can be said for the questions of whether plaintiff adequately treated his back patient and whether hospitalization is required for treatment of dyskinesis. . . . '[T]he court found that Board's expert witnesses were "more credible" than plaintiff's witnesses on the necessity or hemodynamic monitoring, and on that basis concluded the plaintiff was incompetent for failing to use hemodynamic monitoring. Likewise, the court characterized plaintiff's course of treatment of his back patient as "disorganized" and implicitly rejected plaintiff's treatment methods as unacceptable. Finally, the court concluded hospitalization for drug withdrawal was unwarranted in the circumstances presented here.

"The court thus assumed the posture of a court of science, and improperly set the standard for the medical profession, rather than deciding whether there had been a departure from a set standard. The court went one step further in setting standards for the profession in concluding that even though there are several alternatives of converting heart arrhythmia, and plaintiff used one of these, he was incompetent for not also choosing the hemodynamic monitoring alternative. This approach to professional discipline was questioned in James v. Board of Dental Examiners (1985) 172 Cal. App. 3d 1096. There the issue was whether the dentist's conduct in fitting dentures and fabricating them from acrylic rather than chrome cobalt constituted negligence. The court questioned whether the dentist "should be held responsible for both failing to use the appropriate material whose impropriety flowed from the fact it could not be adjusted . . . [T]he acrylic plate possible could be adjusted by insertion of a wire or metal bar to reinforce the acrylic denture after allowance for the patient's mouth structure. Such [evidence] indicates the fabrication in acrylic, while perhaps not preferable, was at least an acceptable choice." (Id., at p. 1116; emphasis added).

"Since Board has not prescribed a standard by which to measure incompetence, and the evidence merely shows that the treatment methodologies employed by plaintiff were disputed, we conclude the trial court erred in upholding the Board's finding of incompetence as it related to plaintiff's care, diagnosis and treatment of patients." (Id. at p. 22-25)

This court ruling (and the James decision on which it relies) should be followed by the Board here.⁽⁷⁾

The Board is bound by the Seymour ruling by the Third District Court of Appeal, Sacramento.

To choose the route disapproved by the Court of Appeal would turn over control of scientific inquiry and disputes to lawyers and lay staff persons, none of whom are competent to replace physicians and medical researchers in that process.

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III.

PROCEDURAL AND FAIRNESS ISSUES

A.	THE PROSECUTION'S MISCONDUCT WAS SO EGREGIOUS AS TO DENY DR. SINAIKO A FAIR TRIAL
	1.	In an Attempt to Prejudice the Trier of Fact, the Prosecution Used Name-calling and Slurs to Brand Dr. Sinaiko as a Physician to Be Reviled

Counsel presenting the Board's case at hearing, Deputy Attorney General Alfredo Terrazas, began his case at hearing by stating:

"Before beginning, I believe that it is important that a working knowledge of the lexicon or the jargon of the, quote, "alternative health," unquote, approach to medicine is in order.

"It is going to be vital to the proper presentation of the case to have a very good working knowledge of the nomenclature found in this entire genre of medicine.

"Methods that are not based on established scientific knowledge have been called many things. Their critics most often choose among unproven, conventional, unorthodox, scientific, non-scientific, questionable, dubious, cult, faddism, fraudulent, quack and quackery.

"Many promoters of quackery (i.e., Dr. Sinaiko) are true believers, zealots, and devotees whose real problem is the failure to apply skepticism to the favored therapy, very much like the religious fanatic who blindly accepts the faith. Their apparent sincerity and self-confidence help persuade people to try their methods and discourage those who become disillusioned from trying to seek justice."

Throughout his presentation, before the Administrative Law Judge and in his prior brief before this Board, Mr. Terrazas used terrible and untrue slurs, just like someone would make racial or ethnic slurs, to label and thus prejudice Dr. Sinaiko.

The following are just some of Mr. Terrazas' name-calling:

• "Quack" (RT Vol. 1, pp. 40,41)
• "Quackery" (RT Vol. 1, pp. 40, 41)
• "Quack Theory" (RT Vol. 1, p. 47)
• "Uses patients as 'experimental subjects'" (Argument on Reconsideration ("AOR"), p. 13)
• "Perpetrating a 'cruel and profitable hoax'" (AOR, p. 13)
• "Selling a bogus treatment" (AOR, p. 14)
• "'Preys' on desperate people" (AOR, p. 14)
• "Voodoo medicine" (AOR, p. 14)
• "Pseudoscience" (AOR, p. 14)
• "Mumbo-jumbo" theories (AOR, p. 14)
• "Akin to a religion" (AOR, p. 14)
• "cult-like beliefs" (AOR, p. 14)
• "Bogus" (AOR, p. 15)
• "Incorrigible" (AOR, p. 15)
• "Grandiose" (AOR, p. 16)
• "Aggressive Loose Cannon" (AOR, p. 16)
• "Suffers from delusions, paranoia, grandiosity" (AOR, p.16)
• "Has persecutory delusions" (AOR, p. 17)
• "He will 'mutate his practice into some other form of quackery'" (AOR, p. 17)
• "Guilty of health care fraud" (AOR, p.17)
• "Promotes bogus illnesses (chronic fatigue syndrome and multiple chemical sensitivity)" (AOR, p. 17)
• "Phony treatments" (AOR, p. 17)
• "Looks for 'holistic' approaches" (AOR, p. 17)
• "History of defying rules" (AOR, p. 18)
• "Endangers the public" (AOR, p. 18)
• "Controlling" (AOR, p. 18)
• "Manipulative" (AOR, p. 18)
• "A 'victim'" (AOR, p. 18)
• "Petulant" (AOR, p. 19)
• "Sophist" (AOR, p. 19)
• "Insidious" (AOR, p. 22)
• "Uses 'junk science'" (AOR, p. 23)

His closing brief at the administrative hearing was even worse in its vituperation and defamatory attack. We await with concern what further epithets will be added to these by the prosecution, what further smears will be made to destroy a decent and generous man. This is shameful and unprofessional conduct by an officer of the court, and it should not be countenanced by this adjudicatory body.

2.

In an Attempt to Prejudice The Trier of Fact, The Prosecution Submitted to Panel B, at The Hearing on Reconsideration on November 6, 1998, a Document it Knew Was Excluded From Evidence by The Judge in a Written Pretrial Order, a Document The Prosecution Knew Contained False Allegations And Was Not Relevant to Any Charges in The Accusation

Prior to the hearing a letter written by Suzanne Northington under the pseudonym "Samantha Simon" was specifically excluded from evidence by Administrative Law Judge Michael C. Cohn at the prehearing conference.

Judge Cohn ruled that the "Samantha Simon" letter, numbered by the prosecution as its Exhibit 21, could only be introduced if Dr. Sinaiko raised the defense of selective prosecution.⁽⁸⁾ Otherwise, the "Simon" letter was excluded. The selective prosecution defense was never raised and the "Simon" letter was never re-offered in evidence during the hearing before Judge Astle, the hearing judge. It was a letter full of lies and fabrications by a former patient of Dr. Sinaiko's who was dismissed from Dr. Sinaiko's practice and referred to a psychiatrist.

Northington's allegations were not a part of this case; they were never alleged in the accusation.

Notwithstanding, at the hearing on reconsideration on November 6, 1998, before Panel B, Mr. Terrazas put before the Panel this very exhibit, included with other exhibits in a black binder. This was offered (supposedly) to counter Dr. Sinaiko's alleged claim that there were no patient complaints in this case. A copy of the black binder was given to each Panel member and the video tape of the November 6^th hearing shows panel members reviewing the binder.⁽⁹⁾

Mr. Terrazas put this highly inflammatory and totally irrelevant exhibit in front of Panel B knowing that:

(a) "Samantha Simon" is a pseudonym for Suzanne Northington.

(b) The "Simon" letter is entirely a fabrication!

(c) The "Simon" letter had been specifically excluded from evidence by Order of Judge Cohn.

(d) Northington's "complaints" were never charged in the Accusation and were not a part of the case against Dr. Sinaiko and were therefore entirely irrelevant. (If the Attorney General thought Northington's [posing as "Simon"] complaints were valid, surely they would have been charged as part of the Accusation!)

(e) The excluded "Simon" letter was never offered again in evidence. (Mr. Terrazas, as an experienced lawyer, well knows in order to re-submit evidence in court which has already been excluded, counsel must specifically re-offer the specific evidence and argue its admission to the court. This was never done.)

The "Simon" letter contains page after page of false accusations against Dr. Sinaiko, but Panel B wouldn't know that by virtue of Mr. Terrazas misrepresenting that this letter was a legitimate exhibit, supposedly in evidence, when he provided it to the Panel on November 6, 1998. The prejudice to Dr. Sinaiko of such inflammatory and false representations is overwhelming and egregious, and the conduct of the deputy attorney general in placing before the adjudicating body a document so prejudicial which he knew had been excluded from evidence is inexcusable.

The only appropriate remedy for such misconduct and unfair dealing on the part of the prosecution is dismissal of the Accusation in its entirety. Moreover, this misconduct puts the Panel on notice that fair dealing throughout the presentation of the prosecution's case is not to be expected.

The Legislature enacted Business and Professions Code section 2230.5 on August 17, 1998. The statute provides:

"(a) Except as provided in subdivision (b), any accusation filed against a licensee pursuant to Section 11503 of the Government Code shall be filed within three years after the board, or a division thereof, discovers the act or omission alleged as the ground for disciplinary action, or within seven years after the act or omission alleged as the ground for disciplinary action occurs, whichever occurs first.

"(b) An accusation filed against a licensee pursuant to Section 11503 of the Government Code alleging the procurement of a license by fraud or misrepresentation is not subject to the limitation provided for by subdivision (a)."

At the same time, the Legislature declared section 2230.5 to be an urgency statute:

"This act is an urgency statute necessary for the immediate preservation of the public peace, health, or safety within the meaning of Article IV of the Constitution and shall go into immediate effect. The facts constituting the necessity are: In order for the Medical Board of California to enforce actions involving physician and surgeon licensure in the most appropriate and timely manner, it is necessary that this act take effect immediately."

(a) Regarding JH:

Paragraphs 50-53, First Amended and Supplemental Accusation. These charges allege incidents that occurred 7 years before the First Amended Accusation was filed. (February 26, 1997)

(b) Regarding SL:

Paragraphs 61-70⁽¹⁰⁾, First Amended and Supplemental Accusation. These charges allege incidents that occurred 7 years before the First Amended Accusation was filed.

(c) Regarding LTS:

The entire case against LTS is barred by the Medical Board's Statute of Limitations. The "complaint" filed by LTS's father, Ray S., was received by the Board on June 11, 1993.⁽¹¹⁾ The Accusation was filed November 1, 1996, more than 3 years after the Board was aware of the incidents.

To the extent the charges are not barred by the Board's Statute of Limitations, they are barred by laches.

(a)	The Problem: the Board's Failure to Protect the Public Health and Safety and Physicians' Rights by Prompt Investigation and Enforcement

In 1990, the Legislature overhauled California's medical disciplinary system by adopting the Medical Judicial Procedure Improvement Act (Stats. 1990, ch. 1597). In the Act, the Legislature declared the existing disciplinary system inadequate to protect the health, safety, and welfare of Californians and created a new system intended to afford an expeditious and efficient adjudicatory system that affords fair review and hearing "without excessive delay." (Stats. 1990, ch. 1597, §1.) The Legislature added Business and Professions Code section 2319, which required the Board to "set as a goal the improvement of its disciplinary system by January 1, 1992 so that an average of no more than six months will elapse from the receipt of the complaint to the completion of an investigation" and for more complex cases, a goal of "no more than one year to investigate."

Eight years later, in 1998, the Board had made little progress towards its goals. Stale, ten-year-old matters were still being investigated and prosecuted while current matters, involving present potential threats to public health and safety were becoming the next millennium's stale claims.

(b)	The Legislature's Solution: Section 2230.5 Requires That the Board Stop Pursuing Stale Matters and Concentrate on Current Ones

In the interest of fairness to the physicians, and to protect the public from far greater and immediate public health concerns, the Legislature finally put down its collective foot and unanimously enacted Business and Professions Code section 2230.5 as an urgency measure. The Legislature was clearly insisting that the Board re-allocate its resources to current matters and not continue to investigate and prosecute exceptionally old ones. The Legislature drew no distinction between exceptionally old cases in which an accusation had been filed and exceptionally old cases in which an accusation had not been filed. The Board was commanded to drop the stale matters and devote all its energies and resources to the most immediate and pressing matters.

(c)	The Board's Unavailing Attempt to Evade its Legislative Mandate

Inexplicably, the Board has forged ahead on the barred accusations. In the Board's view, an accusation filed on August 16, 1998, involving a 12-year-old incident, may be prosecuted, while a proceeding filed on August 17, 1998, involving a 3-year-old incident, may not. The law is not so arbitrary and whimsical.

The Board has relied on a "presumption" that legislation applies prospectively rather than retrospectively. There is no such presumption for a statute of limitations. Although substantive statutes are ordinarily construed to operate prospectively absent an express declaration of retroactivity, "procedural statutes are outside the ambit of this rule because they operate on existing causes; hence, it is a misnomer to call them 'retroactive.'" (In re Marriage of Dunmore (1996) 45 Cal.App. 4^th 1372, 1380, emphasis added.) "Statutes of limitations in civil actions are procedural, not substantive, and are not subject to the general rule against retroactivity." (Lent v. Doe (1995) 40 Cal.App. 4^th 1177, 1184, citations omitted.)⁽¹²⁾

Moreover, even if there were a presumption of prospectivity, it would apply only if there were no other evidence of the Legislature's actual intent regarding the application of the statute to pending cases. Here we have such evidence: the fact that the Legislature declared the statute an urgency statute, to take effect immediately, "In order for the Medical Board of California to enforce actions involving physician and surgeon licensure in the most appropriate and timely manner . . . ." (Stats. 1998, ch. 301, §2.)

For the statute to have the intended remedial impact, it must apply not just to future cases, but to pending cases as well. It must apply now, not a few months or a few years from now. That is why the Legislature made this particular statute an urgency statute. That is why the Legislature has provided in general that all medical disciplinary proceedings "shall be brought to a final determination under the procedures set forth in the Medical Practice Act, as amended and effective on December 12, 1975, and as thereafter amended." (Bus. & Prof. Code §2223, emphasis added.) And that is why any "lawsuit is governed by a change in procedural rules made during its pendency, and the suit is pending until its final determination on appeal." (Republic Corp. v. Superior Court (1984) 160 Cal.App. 3d 1253, 1257.)

In any event, the Legislature might be "presumed" to intend that a new statute applies prospectively only where to apply a new statute to acts that have already occurred might impair vested rights or defeat reasonable expectations of private parties. That is not the case here. The Board has no vested rights and no expectations. (Alta Loma School Dist. v. San Bernardino County Com. on School Dist. Reorganization (1981) 124 Cal.App.3d 542, 554 ["Since a school district has no vested right in its continued existence, the application of the new statute to the instant proceedings will not impair any vested right or violate any constitutional guarantee."].) The Board owes its entire existence to the Legislature. (Bus. & Prof. Code §2001) And what the Legislature gives, the Legislature can take away. The Legislature has taken away the Board's authority to continue to prosecute untimely accusations like those in this case.

In California Emp. etc. Com. v. Payne (1947) 31 Cal.2d 210, 215, the Supreme Court held:

"This principle [that an existing right cannot be cut off summarily without giving a reasonable time after the act becomes effective to exercise such right], however, does not apply where the state gives up a right previously possessed by it or by one of its agencies. Except where such an agency is given powers by the Constitution, it derives its authority from the Legislature, which may add to or take away from those powers, and therefore, a statute which adversely affects only the right of the state is not valid merely because it operates to cut off an existing remedy of an agency of the state."

A case directly in point is Weissbuch v. Board of Medical Examiners (1974) 41 Cal.App.3d 924. The Board had filed an accusation, held a hearing, and revoked Dr. Weissbuch's medical license based on his conviction for possession of marijuana, a substance classified as a narcotic. Before the Board's decision became final, however, the Legislature amended the law and declassified marijuana as a narcotic. The appellate court ruled that the amendment applied to Dr. Weissbuch's pending case and that he was "entitled to the benefit thereof," and directed the Board to vacate its decision. (Id. at p. 929)

The result was the same in Governing Board v. Mann (1977) 18 Cal.3d 819, where a school district undertook to dismiss a teacher after he pleaded guilty to possession of marijuana. During the teacher's appeal, the Legislature rewrote the marijuana laws and specifically prohibited public entities from revoking anyone's rights based on a possession of marijuana conviction. The Supreme Court rejected the district's argument that the new law did not apply to pending cases:

"Although the school district maintains that the new legislation, having taken effect after the trial court judgment, should not be applied in this proceeding, a long and unbroken line of California decisions established beyond question that the repeal of the district's statutory authority does affect the present action. As we shall explain, the cases uniformly hold that where, as here, the government's authority rests solely upon a statutory basis, 'a repeal of such a statute without a saving clause will terminate all pending actions based thereon. . . . "If final relief has not been granted before the repeal goes into effect it cannot be granted afterwards, even if a judgment has been entered and the cause is pending on appeal. The reviewing court must dispose of the case under the law in force when its decision is rendered.'" [Citation.] Accordingly, since the Legislature has now withdrawn the school district's authority to dismiss defendant on the basis of his possession of marijuana conviction, the trial court judgment in favor of plaintiff must be reversed." (Id. at pp. 822-823.)

And in the analogous case of Department of Social Welfare v. Wingo (1946) 77 Cal.App.2d 316, an existing statute authorized a State agency to recover overpayments made under the Old Age Security Law. The Legislature later amended the statute by limiting the amount of recovery in cases where the overpayments were claimed in good faith. The overpayments in Wingo were made prior to the statutory amendment but before trial of the recovery action. The appellate court held that the limiting amendment applied to the pending action. The court explained:

"It is the general rule here that where a cause of action unknown at the common law has been created by statute and no vested or contractual rights have arisen under it the repeal of the statute without a saving clause before a judgment becomes final destroys the right of action. The same rule is applied to an amendment of a statute." (Id. at p. 320.)

"An express declaration that the Legislature intended the law to be applied retroactively is not necessarily required. The context of the legislation, its objective, the evils to be remedied, the history of the times and of legislation upon the same subject, public policy, and contemporaneous construction may all indicate the legislative purpose." (Fox v. Alexis (1985) 38 Cal.3d 621, 629.) In all the circumstances, the Legislature had a sound rationale for limiting the Board's prosecution of older matters, just as it has done in many other professional disciplinary areas. (See e.g., Bus. & Prof. Code, §§5561 [architects], 5561 [landscape architects], 7091 [contractors], 7686.5 [funeral directors and embalmers], 8621 [structural pest control operators], 9726 [cemeteries], 9889.8 [auto repairers].) The state has only limited resources to devote to the protection of the public through disciplinary proceedings. It cannot follow up every allegation, however stale, against every physician. Its resources therefore must be invested wisely, and directed at current problems, at physicians who are allegedly endangering the health and safety of the public now, not five or ten years ago.⁽¹³⁾

The Board, of course, must follow the law. In continuing to prosecute accusations that are barred by the statute of limitations, the Board violates the law, exceeds its jurisdiction, and abuses its discretion. (Gallo v. Superior Court (1988) 200 Cal.App.3d 1375, 1377 [writ issued to enforce statute of limitations].)

Any person who has a license to practice an occupation or a profession in California is entitled to a fair trial when the state licensing agency threatens to discipline or remove that license. Code of Civil Procedure section 1094.5. Such a person has a vested right to the license and, as a matter of statutory and constitutional law, both state and federal, is entitled to due process of law before that right may be adversely affected. (Ettinger v. Board of Medical Quality Assurance (1982) 135 Cal.App.3d 853, 857.)

It is well settled in California that a court has inherent power to dismiss administrative actions that are not diligently prosecuted. (Gates v. DMV (1979) 94 Cal.App.3d 921.) In Gates there was a 19-month delay between the investigation and the commencement of the revocation hearing. The trial court made express findings that the delay prevented respondent from getting a fair hearing. (See also Steen v. City of Los Angeles (1948) 31 Cal.2d 542.) The agency's ignorance of the facts giving rise to the charges are an insufficient excuse for the delay. (California Administrative Hearing Practice, Cont. Ed. Bar 1984, Proceedings Before Hearing, §2.21).

In holding that due process requires the application of the doctrine of laches to medical license revocation proceedings, the court in Appeal of Plaintier (1985) 125 NH 500, 494 A2d 270, 51 ALR 4th 1129, dismissed a 9-year complaint finding that:

(a) The private interest, the doctor's license to practice his profession, affected by governmental action was substantial, noting that what was at stake in the disciplinary proceeding was the doctor's license to practice his livelihood and profession, and

(b) the risk of an erroneous deprivation of that interest was great and that the risk would be significantly decreased by the application of a laches-type doctrine.

The ALR analysis notes that the court acknowledged the government's interest in protecting the public but comments that fundamental fairness was a primary consideration under due process and it was fundamentally unfair to make a doctor defend a 9-year-old complaint when the complaint was not delayed by fraud or the lack of complainant's ability to discover the misconduct.

The test for administrative laches announced in Gates was reaffirmed in Brown v. State Personnel Board (1985) 166 Cal.App.3d 1151. In that case, the Third District Court of Appeal held that there was an unreasonable delay in initiating disciplinary action resulting in prejudice to the affected individual. The court shifted the burden of proof to the state university to show that the delay was excusable and did not prejudice the appellant.

In Brown, four years after discovery of allegations that associate professor Brown made amorous overtures to two adult female students, officials of California State University at Sacramento (CSUS) filed charges of misconduct. They charged these acts (and three others), as "a series and pattern of sexual harassment of female students," were cause for dismissal and Brown was fired. The two remote acts and one other occurring in 1979 were upheld as justifying dismissal by the State Personnel Board. Brown appealed from a judgment denying him relief by way of a writ of mandate. The court concluded that the extreme delay in filing the charges precluded their use as grounds of discipline and that the remaining ground of discipline was insufficient to sustain the charge made. The court reversed the judgment and directed Brown's reinstatement.

Reaching this conclusion, the Brown court noted that laches is an equitable remedy and the administrative agency must diligently pursue the disciplinary action as if it were seeking equitable relief. In measuring diligence, the courts apply notions of laches borrowed from the civil law.

"It is said that '[t]here is no fixed rule as to the circumstances that must exist or as to the period of time which must elapse before the doctrine of laches can be appropriately applied.' (Brown v. State Personnel Board (1941) 43 Cal.App.2d 70, 78 [110 P.2d 497].) That is so because what generally makes delay unreasonable is that it results in prejudice. 'These two factors are interrelated . . . .' (In re marriage of Modnick (1983) 33 Cal.3d 897, 908 [191 Cal.Rptr. 629, 663 P.2d 187].) If the delay has caused no material change in statu quo, ante, i.e., no detriment suffered by the party pleading the laches, his plea is in vain.' (Cite omitted)" (Brown v. State Personnel Board, supra, at p. 1159)

The Brown court goes on to state that there is one circumstance in which unreasonable delay could be found as a matter of law.

"At the common law, in cases in which equity was not strictly bound by the statute of limitations applicable to actions at law, the courts sometimes adopted for purposes of laches 'a period within which its aid must be sought, similar to that prescribed in analogous cases at law.' (1 Wood on Limitations (4^th ed. 1916) p. 276; cf. Holmberg v. Armbrecht (1945) 327 U.S. 392, 396 [90 L.Ed. 743, 747 [66 S.Ct. 582, 162 A.L.R. 719].) In such cases the burden was placed on the plaintiff to show a reasonable excuse for the delay. (Wood, supra, at p. 277, fn. 64) A similar rule has been adopted in California. In cases in which no statutes of limitations directly applies but there is a statute of limitations governing an analogous action at law, the period may be borrowed as a measure of the outer limit of reasonable delay in determining laches. (cites omitted)" (Emphasis added) (Brown v. State Personnel Board, supra, at p. 1159, 1160).

Noting that whether a borrowing should occur depends on the strength or the analogy, the court borrowed an analogous 3-year statute of limitations in civil law covering other public employees, holding that unless excused, a delay in the initiation of disciplinary proceedings for more than 3 years is unreasonable as a matter of law.

The effect of the violation of the analogous statute is to shift the burden to the administrative agency to prove that the delay was excusable and that the respondent is not prejudiced. "No effect can be given to the policy of the borrowed statute unless it establishes a presumption which shifts the burden of proof." (Brown, supra, at p. 1161).

We need not look far for an analogous statute. It is the very statute of limitations which is a part of the Medical Practice Act, Government Code section 2230.5.

The legislature passed this statute because it deemed prosecuting old cases to be unfair among other reasons. If the prosecution of old claims in a Medical Board case is unfair by virtue of a specific statute, the limitations section now in the Medical Practice Act, under Brown that same prosecution is certainly unfair by reference to the equitable principle of laches.

An administrative disciplinary proceeding, especially one which seeks to take away a vital property right, is subject to the same constitutional principles as other cases, civil or criminal. This Accusation -- many, many years too late -- is barred by the due process principle of laches. The burden of proof is shifted to the Board to show that the delay was excusable and Dr. Sinaiko is not prejudiced. Given the Attorney General's position that Dr. Sinaiko's license should be revoked, it is inherently impossible for the Board to show lack of prejudice in demanding this professional death penalty.

Having found an analogous statute, following the Brown court, we then turn to the issues of excuse and prejudice. The Attorney General sat on the LTS case for over 3 years before filing the Accusation. ALL of the SL claims and some of the JH claims are over 10 years old! There is no good excuse for this delay.

"When the election is made to forego prosecution the unreasonable delay that attends that election is not excused merely because the authorities have deferred to the wishes of the victim. It is just as unfair to let an employee 'twist slowly in the wind' regardless of who the employer permits to hold the rope." (Brown, supra, at p. 1162.)

The courts in criminal proceedings have likewise applied the doctrine of presumptive prejudice. In June 1992, the U.S. Supreme Court found that an 8-1/2 year lag between indictment and arrest violated the speedy trial act despite the lack of showing how the delay had prejudiced the defendant. (Doggett v. United States, 120 L.Ed. 2d 520). Of great interest is the court's comment regarding the harm that can result from unreasonable delay.

"We have observed in prior cases that unreasonable delay between formal accusation and trial threatens to produce more than one sort of harm, including 'oppressive pre-trial incarceration,' 'anxiety and concern of the accused,' and the possibility that the accused defense will be impaired by dimming memories and loss of exculpatory evidence.' Citing Barker v. Wingo (1972) 407 U.S. 514 (emphasis added)." Doggett v. United States, supra, at 8659.

The Government's principle contention in Doggett was that the defendant had failed to show how he was prejudiced by the delay between his indictment and trial. The court rejected the argument that the defendant had to show specific prejudice and instead found presumptive prejudice, shifting the burden of proof to the state:

"Barker explicitly recognized that impairment of one's defense is the most difficult form of speedy trial prejudice to prove because time's erosion of exculpatory evidence and testimony 'can rarely be shown.' 407 U.S., at 532. And though time can tilt the case against either side, see i.d., at 521: Loud Hawk, supra, at 315, one cannot generally be sure which of them is had prejudiced more severely. Thus, we generally have to recognize that excessive delay presumptively compromises the reliability of a trial in ways that neither party can prove or, for that matter, identify. While such presumptive prejudice cannot alone carry a Sixth Amendment claim without regard to the other Barker criteria, see Loud Hawk, supra, at 315, it is part of the mix of relevant facts, and its importance increase with the length of delay." Doggett v. U.S., supra, at 8659.

The constitutional right of due process accorded to a physician's license revocation is no less than the right of a criminal to a speedy trial. The principle of presumptive prejudice as set forth in Brown and Doggett is equally applicable to this case. Given the unreasonable delay, Dr. Sinaiko has been presumptively prejudiced, which the Board cannot deny given its counsel's position that Dr. Sinaiko is such a "quack" he should be revoked. The entire Accusation must be dismissed on the ground of laches.

We have exhaustively reviewed the entire 26 volume/2,752 page transcript in this matter. While much of the transcript seems to reflect what was actually testified to at hearing, significant parts of the transcript are garbled, erroneous, and do not reflect at all the testimony at hearing.

A defendant or respondent is entitled to have a record of the hearing prepared accurately. An inaccurate transcript, one that does not fairly reflect what occurred at trial, violates a respondent's right to a fair trial.

There are literally hundreds of unintelligible transcriptions and errors. For example, in Volume 25 alone, there are at least 249 errors! Here are a few examples:

(errors are in red; corrections are in blue):

1. Samples of the 249 Errors

Page 43, Line 6 -- "I said I like most Amphotericin in the intravenous form. Let's reassure you that this is a very safe medication when given orally."

The testimony should read:

"I said unlike Amphotericin in the intravenous form, let me reassure you that this is a very safe medication when given orally."

[error]
Page 49, Line 7 -- "He was offered Ritalin now for the previous three weeks."

The testimony should read:

He was off of Ritalin now for the previous three weeks."

2. Example of Unintelligible Transcription

Page 65, Line 27 -- "Because while studies have shown the majority of persons who are what we called double-blind placebo challenges, that's the standard in her field for cold food allergy or research that some studies have known that the majority of children who have a positive behavior double-blind placebo cold food challenged."

The above are just a few of the hundreds of such errors and garbled testimony found in just one of the 26 volumes. As a result, neither Respondent nor this Panel can determine what the testimony really was at hearing and therefore cannot really determine what the facts in this case are. The testimony was particularly mistranscribed during Dr. Sinaiko's turn as a witness. The transcript is so garbled and erroneous that it denies Dr. Sinaiko the right to a fair trial.

IV.

PHARMACOLOGICAL ISSUES

Here we set forth in plain terms the facts about medications prescribed by Dr. Sinaiko, how they were used and for what purpose. (In a subsequent section of this brief, we address the FDA regulatory issues.) The prosecution's witnesses were typically unfamiliar with the medications and the purpose for which they were used to such an extent that their testimony about them is scientifically-pharmacologically challenged, shall we say. Their testimony reminds one of a New York Yankee fan trying to explain cricket.

• ALL of the medications used by Dr. Sinaiko were legally prescribed.

• ALL were safe and effective for the purposes dispensed or administered.

• ALL were used for a valid medical purpose and upon a rational scientific basis.

By misunderstanding the medications and their appropriate use and misconstruing the laws regulating them, the deputy attorney general has caused a lot of people to trudge down a dead-end legal path -- a long and very expensive walk!

A.	WHAT IS EPD? (Enzyme Potentiated Desensitization)

Dr. Sinaiko is one of 2 allergists in the Bay Area who has adopted the use of enzyme potentiated desensitization (EPD).^{(15) (16)} EPD represents an incremental but significant improvement in the way allergy shots are given.

While traditional high-dose allergy shots are helpful for many allergic patients, this benefit comes with the risk of anaphylaxis, which kills a substantial number of patients every year.⁽¹⁷⁾ Antigen doses for EPD are far lower than with the more traditional forms of allergy desensitization, so that anaphylactic reactions do not occur with EPD. This, coupled with the fact that generally, only nine EPD injections are needed over a 2-year period of desensitization treatment, leads to markedly improved safety, and a level of convenience and patient acceptance superior to that typically obtained with traditional allergy injections.⁽¹⁸⁾

The efficacy and safety of EPD for a variety of indications have been demonstrated in a number of published double-blind placebo-controlled trials. ⁽¹⁹⁾

The reason why such a low antigen dose can be used for EPD is that incorporated into the injection is a small quantity of highly purified beta glucuronidase, a readily available natural chemical which is present in every cell of the human body, commercially available as a mollusc extract. Beta glucuronidase, concentrated at the site of injection, functions in EPD as a biological response modifier. ⁽²⁰⁾

EPD treatment relies on a very small and also very precisely determined amount of antigen ⁽²¹⁾being present at the injection site, such that extraneous allergen exposure at the time of the injection can render the treatment less effective. Also, any stimulus to the immune system during the several days following an EPD injection (such as an alimentary exposure to an antigen which stimulates IgE or IgG production in the particular patient being treated) may reduce the effectiveness of the treatment. For these reasons, in a patient with mold allergy, EPD treatment generally works best when each injection is preceded by a ten-day course of antifungal medication.⁽²²⁾

EPD is an advance over the type of allergy treatment used up to now in the United States for several reasons, the first of which is safety, as mentioned above.⁽²³⁾ Safety, however, is not the only reason it is preferable for the informed consumer. Another reason is financial. As stated above, the usual number of injections required is 9 over a period of two years. At the price of about $250 each injection, that comes to $2,250 over the two years. A person taking conventional allergy shots during that same time, at $25 twice a week, will be subjected to the price of $5,000 besides the inconvenience of missed school and/or work time⁽²⁴⁾. The third reason is health. There are many allergic conditions that simply do not respond to conventional allergy therapy but do respond to EPD.

In an effort to improve the understanding and acceptance of EPD in the United States, the EPD Society has instituted a data collection study, which is being conducted under an IRB through the Great Lakes Association of Clinical Medicine.⁽²⁵⁾ Dr. Sinaiko is currently a participating investigator under this IRB, but it should be kept in mind that this study was not in existence⁽²⁶⁾ during the time of his care of the patients in question before this Panel. All patients whose care is being reviewed by the Board were patients receiving patient care; none were participants in any study whatsoever.

B. WHAT IS ORAL AMPHOTERICIN B?

Oral Amphotericin B is a safe and effective drug for intestinal candidiasis. It has been approved by the FDA since 1971.⁽²⁷⁾ There is no legitimate issue in this case about the safety of this drug.

While the complications of the intravenous use of Amphotericin B were examined in great detail during the hearings - in spite of the fact that no-one used it intravenously - the more important problem in this case is the unfamiliarity of the drug. People - even physicians - are afraid of what is not familiar.

Amphotericin B and Nystatin are both "polyene antibiotics" -- antifungal medications active against Candida species and a broad spectrum of other fungal organisms. Both of them act on the wall of the fungal cells by changing membrane permeability. This allows the inside material to leak out, killing the cell. While all physicians agree that yeast problems in the mouth and vagina should generally be treated, not all agree that treatment or reduction of yeast or fungal growth in the GI tract, which they cannot see, should be treated. This, itself, is an ongoing debate in medicine, with vociferous claims on both sides by eminent researchers, medical texts, and vocal physicians.⁽²⁸⁾

Physicians are generally familiar with Nystatin, considered a safe, benign medication whose worst side effects are some possible nausea and diarrhea associated with large doses.⁽²⁹⁾ Nystatin can be purchased in tablet form or in a powder "for extemporaneous preparation of oral suspension."⁽³⁰⁾ While specifically approved for oral and intestinal Candida albicans,⁽³¹⁾ Nystatin is also active against a wide variety of yeasts and yeast-like fungi,⁽³²⁾ and is used "off-label" in the U.S. for this effect. Nystatin is too dangerous ever to be given intravenously.⁽³³⁾

Contrary to Mr. Terrazas' assertion of its "activity against lipid-enveloped viruses, including herpes viruses [and] several oncogenic retro viruses,"⁽³⁴⁾ -- which, if true, might have made this a new wonder drug -- Amphotericin B is an antifungal medication active against most fungi and yeasts⁽³⁵⁾ but with no activity against bacteria, rickettsias, or viruses.⁽³⁶⁾

While Amphotericin B is used in oral form in Europe,⁽³⁷⁾ and by some immunologists like Dr. Sinaiko in the U.S., the use of this drug by oral administration is not familiar to most American physicians. This unfamiliarity, coupled with what they have learned about the toxic intravenous form, creates an aura of danger, so that most physicians mistakenly believe that Nystatin has a safer "profile" than Amphotericin B. This is untrue.

Do not compare oral administration of Nystatin to intravenous administration of Amphotericin (apples to oranges) -- rather, compare oral to oral, and IV to IV (apples to apples) in the following chart:

METHOD	CAN AMPHOTERICIN B BE USED?	CAN NYSTATIN BE USED?
INTRAVENOUS	Yes. With care.	No. Deadly!
ORALLY	Yes. Not absorbed from gut.	Yes. Not absorbed from gut.
SIDE EFFECTS, ORALLY	Occasionally causes diarrhea or nausea in large doses.	Occasionally causes diarrhea or nausea in large doses.

1. IS IT SAFE -- ORALLY?

As seen in the above chart, Amphotericin B and Nystatin are equally safe when taken orally. Dr. Sinaiko's clinical experience with orally administered Amphotericin B has also shown it to have fewer side effects than Nystatin, which is one of the reasons he prefers it in a case like LTS, who in fact tolerated oral Amphotericin B without incident but developed nausea on oral Nystatin.⁽³⁸⁾

In the oral form, whether used in liquid form for thrush (oral yeast infection), or in liquid or tablet form for intestinal candidiasis, Amphotericin B is swallowed. It's action is on the cell wall of the fungi at the lining of the mouth - or the intestine -- and is not a systemic action at all when given orally. It is not significantly absorbed from the gut. Every witness knew this, including Dr. Vreeland, who wrote the "child endangerment letter."⁽³⁹⁾ Every relevant expert witness, when confronted with the fact of oral administration, knew Amphotericin B to be harmless. Below are some samples of testimony.⁽⁴⁰⁾ But every State witness insisted -- either naively or disingenuously -- that this was a "dangerous medication" with all the complications of the intravenous form. This is a problem when "experts" lack expertise.

What do the resources say about the risk of systemic toxicity of Amphotericin B when it is swallowed? ⁽⁴¹⁾

RESOURCE	RISK
British National Formulary	"Amphotericin is not absorbed from the gut."
Martindale: The Extra Pharmacopoeia	"There is little or no absorption of Amphotericin from the gastro-intestinal tract."
Goodman and Gilman's The Pharmacological Basis of Therapeutics	"Amphotericin B is poorly absorbed from the gastrointestinal tract."
Physicians' Desk Reference 1998, p.742	Amphotericin B administered as Fungizone Oral Suspension is poorly absorbed from the gastrointestinal tract.
FDA Center for Drugs(42)	"The drug is safe and effective for use as recommended in the printed labeling submitted May 12, 1971. Accordingly, the application is approved."
Pharmacology Review of NDA at FDA CDER (43)	"There appears to be little absorption even under the most abnormal conditions"
Physicians' Desk Reference, 1984, p. 1924	Given orally, Amphotericin B is extremely well tolerated and is virtually nontoxic in prophylactic doses.

It was also alleged by the Prosecution and the "expert" witness Dr. Tepper,⁽⁴⁴⁾ that a child with ADHD - being nervous and anxious - would be likely to have irritable bowel syndrome, ulcers, or lesions in the intestines which would cause this drug to become systemic. There is no support anywhere for this notion. Besides the nonsense of assuming the boy would have such disorders without anyone noticing, the fact remains that the FDA addressed this in their early research before approving the medication orally. All results of the FDA studies indicate that there is "little absorption even under the most abnormal conditions." Amphotericin B appears to be safer even than aspirin.⁽⁴⁵⁾

And if the above is not enough, it should also be mentioned that the somewhat toxic solvent, sodium desoxycholate, which is used to solubilize the injectable form⁽⁴⁶⁾ is not present in the oral formulation. This is another reason why it is not absorbed through the gut wall; it is not sufficiently soluble.

2. WAS IT LEGAL IN 1993?

Oral Amphotericin B has been approved for sale by the FDA continuously since 1971.⁽⁴⁷⁾ This approval has never been withdrawn. Before 1996, it was not sold commercially in this country, but Bristol-Myers Squibb sold it overseas. The Prosecution claims the drug is unsafe because the solid oral formulation once available in the US - a combination of Amphotericin B and Tetracycline - was withdrawn from the market. This drug combination, called Mysteclin, was withdrawn from the market because Bristol-Myers Squibb was unable to show a reason why the combination was medically necessary⁽⁴⁸⁾ but there was never any question about its safety. Looking at the PDR listing for Mysteclin, one can see that in the section on "Adverse Reactions," the entire entry for the Amphotericin B component reads: "Oral administration of Amphotericin B is usually well tolerated."⁽⁴⁹⁾ This is followed by a 6-inch column listing possible adverse effects of tetracycline. In this same PDR section, are the following notes about the Amphotericin B component of Mysteclin: "This antibiotic, first isolated and described by the Squibb Institute for Medical Research, is substantially more active in vitro against Candida strains than nystatin....Given orally, Amphotericin B is extremely well tolerated and is virtually nontoxic in prophylactic doses." [emphasis added]

Orally administered Amphotericin B was available in Europe in 1993 in solid and liquid form. The recommendations found in the resources in evidence will be mentioned below, so the Panel can compare what Dr. Sinaiko did with what others in his field worldwide were doing at that time:⁽⁵⁰⁾

RESOURCE	RISK
British National Formulary	"Dose: by mouth, intestinal candidiasis, 100-200 mg every 6 hours"
Martindale: The Extra Pharmacopoeia	"It is taken by mouth for intestinal candidiasis, sometimes as part of regimens for selective decontamination of the digestive tract..."
Goodman and Gilman's	"Oral tablets are commercially available in Europe for decreasing colonization of the intestine by Candida"
USPDI: United States Pharmacopeia Dispensing Information: Approved Drug Products and Legal Requirements (1993)	[Re: residue on ignition] "Note - Amphotericin B intended for use in preparing dermatological creams, ... and oral suspensions and capsules, yields not more than 3.0%"

3.	WAS THERE ANYTHING WRONG WITH HOW DR. SINAIKO PRESCRIBED ORAL AMPHOTERICIN B IN 1993?

(a) In the 1993 Physicians' Desk Reference (PDR)⁽⁵¹⁾ is a page called the Foreword to the Forty-seventh Edition. Beginning with the fifth paragraph, "Under the Federal Food, Drug & Cosmetic (FD&C) Act, a drug approved for marketing may be labeled, promoted, and advertised by the manufacturer only for those uses for which the drug's safety and effectiveness have been established. The FDA has also announced that the FD&C Act "does not, however, limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in approved labeling."⁽⁵²⁾ In other words, physicians may prescribe drugs for so-called "off-label" use.

(b) The California Attorney General concluded in 1978:⁽⁵³⁾

(1) "A pharmacist may compound and dispense, pursuant to an individual prescription order of a physician, dentist, podiatrist, or veterinarian, materials for an individual patient's needs so long as the component elements of such materials in any combination or singly have not been banned by state or federal law or regulation..."

(2) "The Sherman Food, Drugs, and Cosmetic Law does not prevent a physician from prescribing or administering a drug for a condition not specified in the drug's advertising approved in a federal or state new drug application."

Accordingly, Dr. Sinaiko ordered Amphotericin B for his patient, the drug was compounded by a pharmacy, all such action in concert with the Attorney General's opinion in 1978! There is nothing mysterious about any of this in spite of the Attorney General, in 1999, trying to paint this process as somehow suspect.

Physicians every day, especially allergists (including the state's witness, Dr. Terr ⁽⁵⁴⁾), order allergens from both in-state and out-of-state sources, and some doctors compound their own materials.

(C) According to the American Medical Association⁽⁵⁵⁾ in discussing prescription practices and "off-label" use of drugs:

"Unlabeled (Off-Label) Use: The prescription of a drug for an unlabeled (off-label) indication is entirely proper if the proposed use is based on rational scientific theory, expert medical opinion, or controlled clinical studies. The FDA has made eminently clear that it neither has nor wants the authority to compel prescribers to adhere to officially labeled uses, because experience demonstrates that the official label lags behind scientific knowledge and publications. New uses for drugs already on the market are often first discovered through the serendipitous observations and therapeutic innovations of physicians (Hayes, 1981; FDA Drug Bull, 1982)"

It goes on to say:

"The FDA does not have jurisdiction over drug formulations that the physician may devise for use in the normal course of his practice, provided the physician does not introduce these products into interstate commerce. Such formulations include those compounded from separate ingredients, certain readily available chemicals, or other nonpharmaceutical products that have therapeutic uses. "

(d) And, finally, in the USPDI,⁽⁵⁶⁾ the USP requirements of Amphotericin B USP includes the following note about its preparation:

"Residue on ignition (not more than 0.5% [Note: Amphotericin B intended for use in preparing dermatological creams, lotions, and ointments, and oral suspensions and capsules, yields not more than 3.0%]), and ... Amphotericin B intended for use in preparing dermatological creams, lotions, and ointments, and oral suspensions and capsules, contains not more than 15% of Amphotericin A, calculated on the dried basis])." [emphasis added]

It should be clear to all that if it were illegal to manufacture and use such tablets, the USPDI would not be publishing the directions for doing so.

This discussion should remove the confusion created at hearing by the Attorney General attempting to clothe oral Amphotericin B with the complications and risks of injectable Amphotericin B. There is no question that it was legal under both state and federal laws for Dr. Sinaiko to prescribe oral Amphotericin B. The only issue is whether there was any rational clinical or scientific basis for doing so. See section IV-D, "Why Do (Some) Allergists Use Antifungal Medications?"

C. WHAT IS IgG?

1. Comparing Allergy to Allergy

Two scientists⁽⁵⁷⁾ named Gell and Coombs, back in the 1950's, first formulated the classifications that are today generally recognized as the four types of immunopathology, or allergy:

Type 1 immunopathology (immune reaction) is also called "traditional allergy." It is generally mediated by the IgE antibody system. IgE stands for "immunoglobulin E". Some of the Panel may recall that during the 1960's, asthma and allergies were often considered psychosomatic illnesses by mainstream physicians, resulting in journal articles with names like "Psychotherapy of the Mother as the Treatment of Bronchial Asthma in Her Child" and "Patterns of Respiratory Disturbance in Asthmatic Children Evoked by the Stimulus of the Mother's Voice."⁽⁵⁸⁾

Since the Panel is surely familiar with ordinary hay-fever and rash allergies, we will not belabor the point. They are Type 1 allergy, and are mediated by IgE. They can be diagnosed by serum IgE tests (blood tests like the RAST)or by skin prick tests which are favored by physicians trained in allergy without a backround in immunology.⁽⁵⁹⁾ These are the clinical allergists, trained specifically to deal with Type 1 allergy - that would be asthma, hay fever, etc. Sometimes these allergists are called "traditional" allergists or "classical" allergists, as opposed to ear nose & throat specialists or others who may also treat allergies.

Type 2 immunopathology is a form of disease where foreign material enters the body, and attaches to an organ - such as red blood cells - such that this organ now looks "foreign" to the body's immune system. This can happen from certain drugs - the drug would enter the blood and attach to the red blood cells, or the platelets. The immune system would see this red blood cell now as "foreign"and would attack and destroy it. This could certainly be life threatening, and it was described as a side effect from a sleeping pill that was used until it was discovered to be the cause of the subsequent illness. Mostly it is the general physicians and hematologists who see this sort of reaction.

Type 3 immunopathology involves immune complexes. This involves the very prevalent and unusually small antibody called igG. It is generally protective - preventing infection at the site of any scratch or such injury to the skin, for example. IgG tends to form immune complexes: the IgG antibody has two reactive portions, and will react to two different allergens, and the allergen can also react with another antibody, until it builds up into a larger lattice-work structure or immune complex. Normally, these immune complexes are destroyed or "neutralized" by the body's scavenger system, but this scavenger system can be overwhelmed. When it is overwhelmed, for any reason, these complexes stay in the bloodstream, sort of "waiting in line to be picked up." While they are waiting, they cause inflammation, which is the Type 3 allergic reaction. There is more than one type of this inflammation depending on whether it is on a particular surface, where it may be called an "arthus"⁽⁶⁰⁾ or whether it is in the blood, in which case it's called a "serum sickness."⁽⁶¹⁾ This would have been what Dr. Abba Terr was referring to when he said the precipitin⁽⁶²⁾ test can be used to measure IgG antibodies in diagnosing serum sickness and certain forms of hypersensitivity lung disease.⁽⁶³⁾ This statement is misleading in that it would seem to limit "serum sickness" to the injection of a foreign protein, such as horse serum, into an individual. The immune complexes formed cause illness. These same immune complexes, however, can appear from other sources of foreign protein intrusion, such as eating or infection.

Type 4 immunopathology is cell-mediated and is involved in rejection of transplanted organs. People who would take care of such patients are mostly surgeons doing organ transplantation, although they may call on immunologists for help.

2. What Do IgG Antibodies Show?

From the time Professor Ishizaka wrote his paper on the antibody he had isolated in 1966, IgG has been part of the various controversies in the field of allergy and immunology.

Some in the allergy profession have found that using this discovery has been helpful to improve the accuracy of their approach. Others opt for skin testing, possibly because it is more lucrative.

Dr. Terr testified that IgG antibodies show only that the immune system is doing what it is supposed to do - and does not indicate any disease state. In other words, he says, the test itself is bogus and indicates nothing except that the person's immune system is functioning.⁽⁶⁴⁾

The first part of Dr. Terr's statement is correct - the presence of IgG antibodies do show that the immune system is functioning. Dr. Marinkovich also says that "everyone has IgG antibodies to foods.⁽⁶⁵⁾ There are normal levels of IgG, and then there are elevated levels. The levels of IgG were "normed" on blood sera from 250 people who were donating blood at the blood bank, and who did not have any symptoms or diseases related to migraine, bowel syndromes, arthritis, or any other non-IgE-mediated immune disorder.⁽⁶⁶⁾

To say that IgG does not indicate illness, as Dr. Terr maintains, is like saying that blood sugar is a normal component of the blood and indicates that your metabolism is working correctly - and denying that elevated blood sugar could indicate a problem.

What immunologists often find is that a person appearing to suffer allergies goes to an allergist, but the IgE antibodies are negative - and they are told that they do not have allergies. Immunologists have found, however, that in studying such patients, and looking at the relationship of IgE and IgG, there appear to be some patients, or some situations, in which the production of IgE converts to production of IgG in such a way that IgG may be 1000,000 times the amount of  IgE produced. These patients are experiencing allergic symptoms, but the IgE cannot be detected in abnormal amounts. Their "Type 1" allergy is now a "Type 3" allergy. In fact, it is the person with IgE allergy who is not making IgG at all who is most at risk for anaphylactic type sensitivity,⁽⁶⁷⁾ which is a life-threatening reaction - possibly because they cannot convert to IgG production to help them deal with their allergy.

For immunologists interested in Type 3 allergy - which can be serious as in serum sickness, or more chronic and moderate, as in a child like LTS who showed elevated levels to only a few items - for immunologists interested, this is an exciting field offering them the opportunity to help many people who could not be helped previously. For allergists who are not trained to deal with Type 3 allergy, or who are unfamiliar with IgG allergies, or who define all allergy as IgE-related, this field is a closed book. This is a choice each allergist must make based on his training, reading, and inclination toward acceptance of developments in his field. It is not something to be decided by legislation or administrative rules or order.

3. Who Does IgG Testing?

One of the companies who test for IgG antibodies is MAST Immunosystems. The laboratory manager is Richard Driver, a licensed medical technologist, who testified during the hearing in this case.⁽⁶⁸⁾ This laboratory is owned by Hitachi Chemical, and Dr. Vincent Marinkovich, who also testified for Dr. Sinaiko as a voluntary witness expert in this field, and is the laboratory's Medical Director.

When a physician wishes to order an IgG test, he writes an order and then sends the patient to a facility that is regulated for drawing blood samples, whether in their office or a laboratory. A blood sample is collected based on the ordered test, and then sent to a laboratory.⁽⁶⁹⁾

4. What Do the Test Results Mean?

For reference, see the test results of LTS.⁽⁷⁰⁾ The column labeled "THREAD NUMBER" is simply a list or positioning number of the 36 individual tests that were done on this panel. To the left of the Thread column are some asterisks which corresponds to the test response.

The column labeled "MAST CLASS" indicates the value of the test response. At the lower left corner of the page is a small chart with two columns labeled "Voltage Range and MAST Class." The classes are assigned to the different ranges, correlated with responses on another in vitro allergy test called the RAST (Radioallergosorbent test). Generally, the higher the number in the MAST Class column, the higher the level of antibody in the serum, and the more reactive the patients blood was to that particular item.⁽⁷¹⁾ As can be seen on this report, LTS's results for the two molds Cladosporium and Penicillium are "high positive" which is Class 3 - next to the highest class. A third mold, Aspergillus, is in Class 2, as is milk, and a few other food items, namely eggs, cheese, and onion, are in the lower positive range - Class 1.

5. Is IgG Testing Legal? What about the "FOR INVESTIGATIONAL USE" notation?

The Attorney General claimed that the IgG test was "investigational" because the test form had a notation on it "for investigational use," and therefore, he said, it was illegal for Dr. Sinaiko to use the test. This is preposterous. It is another example of the Attorney General concocting a false issue.

As Richard Driver testified,⁽⁷²⁾ laboratories that develop their own in-house test did not need to include this notation in 1993 because it did not apply to them. It was apparently a misunderstanding of the FDA regulation requiring that note on materials sold to research centers. Mr. Driver himself, when he first came to work at MAST Immunosystems, saw the memo sent to the programmer of the software to delete that notation from the laboratory report used for physicians. The laboratories are regulated by HIFCA and use the regulations established under the CLIA 1967 and 1988. The form used for the tests ordered by Dr. Sinaiko were labeled with this statement by mistake. The MAST Allergy Testing Service used individual components provided by MAST Immunosystems, Inc. to provide the IgG tests for his patients. They were thus excluded from the FDA regulations to use the "For Investigational Use Only" statement. This notation has not appeared on the forms since 1993, when the error was discovered.

Again, the statement was erroneously included on the patient reports. It was removed from the patient reports during 1993. The person who decided to include the statement on these reports is no longer working at MAST Allergy Testing Service.

Clinical laboratories operate under CLIA, the Clinical Laboratory Improvement Act, and under "home brew" statues CLIA regulations don't require an investigational new device application (IND) with FDA. Mr. Driver also explained that "home brew" means that the laboratory buys the reagents and does in-house validation on the test. They are not buying a specific commercial product. He explained that "home brew" testing has been in use since the time of Aristotle, but has become a concern of the FDA only in the last few years. Regulations of what used to be called "home brew policy" and later termed Analyte Specific Reagents (ASR's) relate to this. However, as Mr. Driver repeatedly explained, his laboratory was operating under regulation of all the CLIA rules and was not required to put any such label, or have any such restrictions on these reports.

It is ludicrous that the Attorney General continues to insist that this test was used illegally or improperly when the head of the lab himself came and admitted before the court that it was an error of printing, and that the statement "For Investigational Use Only" was neither true nor binding in any way. The Manager of the laboratory came at his own expense to apologize for this misunderstanding and to explain how it happened.

D. WHY DO (SOME) ALLERGISTS USE ANTIFUNGAL MEDICATIONS?

Sudhir Gupta, MD, PhD, Chief of the Allergy and Immunology Department at the School of Medicine at the University of California, Irvine, has observed, and teaches, that allergic disease is made worse by the colonization of the GI tract by Candida.⁽⁷³⁾ The immunologic mechanisms to explain this phenomenon are complex, and many of its details are being worked out as new investigative tools become available to the experimental immunology community.

Practicing allergists fall into two groups, those who agree with Prof. Gupta's teachings about the effect of fungi on the immune system in general and on allergy in particular, and those who disagree with Gupta. The debate among allergists as to when, in clinical allergy practice, antifungal medications are helpful, is an ongoing and legitimate scientific controversy, one that cannot be resolved satisfactorily by the fiat of any public agency, and one that is likely to remain undecided for some time. It is certainly inappropriate to attempt to discipline a doctor because of his or her adherence to one side or the other in such a debate.

The fact that Candida (a fungus that most frequently produces yeast infections) does exert a number of profound immunological effects has been well-demonstrated in many peer-reviewed reports published in major journals, and is no longer a proper subject for debate. In fact, only those unfamiliar with this extensive literature continue to do so. This body of scientific information is partially summarized in the chapter of Kurstak's 1989 textbook Immunology of Fungal Diseases.⁽⁷⁴⁾ Research immunologists know today that Candida colonization produces an imbalance between the dominance of Th1 and Th2 subsets of CD4 lymphocytes, and that such imbalance is a critical factor in the immunopathogenesis of many diseases. ^{(75) (76)}

Antifungal medications are useful for eradicating or limiting fungal or yeast colonizations of the GI tract. This helps normalize immune function and treat allergic and other immunologically mediated diseases. But antifungal medications also have other uses, making them an important tool for those allergists who have learned to use them. An explanation of some of these uses follows:

1. Antifungals for Alimentary Allergy to Yeast and Fungi

It has long been known that Candida and other fungi are potent allergens. ⁽⁷⁷⁾ Dermatologists have been aware,⁽⁷⁸⁾ since early research on this subject by Maibach, that in women with recurring yeast vaginitis, painting the vulvar region with a suspension of dead yeast cells produces a local allergic inflammatory condition indistinguishable from infection by viable yeast organisms.

Like any foodstuff, food yeasts can produce allergic reactions in susceptible individuals who ingest them. While this form of allergy is not especially common, one of the cases currently before this Panel, JH, provides an example of it⁽⁷⁹⁾. This man noted allergic symptoms (severe itching and rash) each time he would ingest a particular nutritional supplement made from yeast. When he discontinued this supplement, the symptoms improved but did not clear. Further improvement occurred when he excluded yeast-containing foods like breads from his diet, but he continued to experience symptoms. On a diagnostic trial of Nystatin, significant further clearing occurred.

In cases of yeast allergy, the body has no good way of knowing whether the yeast got into the GI tract by being swallowed or by replicating there.⁽⁸⁰⁾ In either case, in susceptible individuals, allergic reactions can be expected to result from alimentary contact with the antigen, and proper treatment depends on avoidance, whether by dietary exclusion or by treating to prevent fungal GI colonization, or both. Colonization can be prevented very safely, since the polyene antifungals, Nystatin and Amphotericin B, are not significantly absorbed across the intestinal mucosa. For this reason, as we have discussed in the section, "What is Amphotericin B?" they can be used safely both for a brief diagnostic trial and, if needed, for prolonged treatment of yeast allergy, without significant risk.

2. Antifungals for Allergic Sinus Disease

Invasive fungal infections of the sinuses are rare, except in immunocompromised patients.⁽⁸¹⁾ Allergic fungal sinusitis (AFS), on the other hand, is common and, according to the many experts who have published articles on the subject in recent years, is greatly underdiagnosed⁽⁸²⁾. For example, Dr. Sinaiko treated RS for fungal sinusitis.

Because elevated levels of IgG against specific fungi indicate fungal exposure, the lack of IgG against fungi, measured by commercial in vitro specific IgG tests such as MAST, ^{(83) (84)} will tend to rule against a diagnosis of AFS or other conditions related to mold allergy. Oral, nonabsorbed antifungal medicines (Nystatin and Amphotericin B) can reduce fungal-specific IgG production by reducing alimentary (GI tract) exposure to fungi, reducing the ongoing stimulus to fungal specific IgG production. Therefore, the allergic sinus inflammation of AFS may be reduced by reducing levels of antifungal IgG. Thus, some experts advocate the routine use of antifungals for AFS. ⁽⁸⁵⁾

3. Antifungals in ADHD

Many years of studies published in the peer-reviewed medical literature, including double-blind placebo-controlled food challenges, have demonstrated that a diverse array of natural and synthetic components of foods, differing widely from one another in their chemical structures, can trigger behavioral symptoms and learning disabilities in a susceptible subset of children with ADHD.⁽⁸⁶⁾ Owing to this diversity, experts who have tried to generalize about which food components can trigger these changes, and which ones cannot, have been frustrated in their efforts to develop any rules that apply to every case.⁽⁸⁷⁾

In fact, so far as we know, any substance introduced into the GI tract has the potential to produce these behavioral changes, with individual susceptibility the only reliable determinant. As noted above, the body is unable to distinguish the origin of the substances found in the intestinal contents. A particular chemical or antigenic material might have arrived there either by virtue of having been ingested or as a natural product of a microbial component of the intestinal flora.

In view of this, it is hardly surprising that there is a subset of children with ADHD who react to microbial products in the intestine, especially those produced by fungi which colonize the intestine, either in place of or in addition to ingested food materials. In order to diagnose these sensitivities, it is necessary to exclude the suspected offending substances, and then observe for the symptomatic improvement which is necessary if the child's ADHD is to be traced back to allergy or intolerance. The use of safe, nonabsorbed antifungal medicines in this context can be an essential part of the diagnostic process, and insofar as there are children for whom natural products of intestinal fungi are among the allergic or chemical triggers of their ADHD symptoms, such a medication trial can extend the diagnostic efficiency observed with exclusion diets alone. For this, an allergist should work closely with a psychologist or other practitioner skilled in observing changes in the child's behavior.

For children who don't respond well to stimulant medication, or for parents who do not wish to use that sort of medication, this can be a useful option.

4. Antifungal Medications as Pretreatment for EPD

Please see the section, "What is Enzyme Potential Desensitization?" for more information. EPD treatment relies on a very small and also very precisely determined amount of antigen being present at the injection site, such that even a moderate amount of extraneous allergen exposure at the time of the injection can render the treatment less effective. Also, any stimulus to the immune system during the several days following an EPD injection (such as an intestinal exposure to an antigen which stimulates IgE or IgG production) may reduce the effectiveness of the treatment. For these reasons, in a patient with mold allergy, EPD treatment generally works best when each injection is preceded by a ten-day course of antifungal medication.⁽⁸⁸⁾

5. Antifungal Medications for Multiple Chemical Sensitivities

A chapter in the Fall 1987 issue of Occupational Medicine, Workers With Multiple Chemical Sensitivities,⁽⁸⁹⁾ a chapter by Robert K. McLellan outlines treatments for this condition. On page 770, antifungal medications are advocated in the treatment of patients with MCS who have abnormally elevated antibody levels against Candida.

According to McLellan, several theories have evolved that explain how Candidiasis may contribute to chemical intolerance:

(a) Decreased mucosal integrity

(b) Induction of immunological changes by Candida

(c) The effect of toxins produced by Candida

(d) Activation of phagocytosis leading to oxidant stress

McLellan goes on to write:

. . .[F]or those patients with MCS and evidence of chronic Candidiasis, treatment of the Candida problem may bring some relief of the MCS syndrome ... the regimen usually involves dietary modification (a decrease in simple sugars and yeast and mold foods), prolonged oral Nystatin along with topical Nystatin when appropriate, and sometimes immunotherapy with the Candida antigen.

This approach is a useful tool to add to the arsenal of the physician in the field in his/her fight against disease - the physician faced with the patient who asks for help beyond what medical science has yet "proven," and for whom the physician must probe the borders of known science to help.