Search

PU-H71 is a purine-scaffold Hsp90 inhibitor that, in contrast to other Hsp90 inhibitors, displays unique selectivity for binding the fraction of Hsp90 that is preferentially associated with oncogenic client proteins and enriched in tumor cells (teHsp90). This property allows PU-H71 to potently suppress teHsp90 without inducing toxicity in normal cells. We found that lymphoma cells infected by Epstein-Barr virus or Kaposi sarcoma-associated herpes virus (KSHV) are exquisitely sensitive to this compound. Using PU-H71 affinity capture and proteomics, an unbiased approach to reveal oncogenic networks, we identified the teHsp90 interactome in KSHV(+) primary effusion lymphoma cells. Viral and cellular proteins were identified, including many involved in nuclear factor (NF)-κB signaling, apoptosis, and autophagy. KSHV vFLIP is a viral oncoprotein homologous to cFLIPs, with NF-κB-activating and antiapoptotic activities. We show that teHsp90 binds vFLIP but not cFLIPs. Treatment with PU-H71 induced degradation of vFLIP and IKKγ, NF-κB downregulation, apoptosis and autophagy in vitro, and more importantly, tumor responses in mice. Analysis of the interactome revealed apoptosis as a central pathway; therefore, we tested a BCL2 family inhibitor in primary effusion lymphoma cells. We found strong activity and synergy with PU-H71. Our findings demonstrate PU-H71 affinity capture identifies actionable networks that may help design rational combinations of effective therapies.

Purpose: To describe women's condom use patterns over time and assess predictors of dual method use 12 months after initiating hormonal contraceptives., Methods: We conducted a prospective cohort study among women aged 15-24 years initiating oral contraceptive pills, patch, ring, or depot medroxyprogesterone and attending public family planning clinics. Participants completed questionnaires at baseline and 3, 6, and 12 months after enrollment. We used multivariable logistic regression to assess baseline factors associated with dual method use at 12 months among 1,194 women who were sexually active in the past 30 days., Results: At baseline, 36% were condom users, and only 5% were dual method users. After initiation of a hormonal method, condom use decreased to 27% and remained relatively unchanged thereafter. Dual method use increased to a peak of 20% at 3 months but decreased over time. Women who were condom users at baseline had nearly twice the odds of being a dual method user at 12 months compared with nonusers (adjusted odds ratio [AOR] = 2.01, 95% CI: 1.28-3.14). Women who believed their main partner thought condoms were "very important," regardless of perceived sexually transmitted infection risk or participant's own views of condoms, had higher odds of dual method use (AOR = 2.89, 95% CI: 1.47-5.71)., Conclusions: These results highlight a potential missed opportunity for family planning providers. Providers focus on helping women initiate hormonal methods, however, they may improve outcomes by giving greater attention to method continuation and contingency planning in the event of method discontinuation and to the role of the partner in family planning., (Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Caspase 2 was initially identified as a neuronally expressed developmentally down-regulated gene (HUGO gene nomenclature CASP2) and has been shown to be required for neuronal death induced by several stimuli, including NGF (nerve growth factor) deprivation and Aβ (β-amyloid). In non-neuronal cells the PIDDosome, composed of caspase 2 and two death adaptor proteins, PIDD (p53-inducible protein with a death domain) and RAIDD {RIP (receptor-interacting protein)-associated ICH-1 [ICE (interleukin-1β-converting enzyme)/CED-3 (cell-death determining 3) homologue 1] protein with a death domain}, has been proposed as the caspase 2 activation complex, although the absolute requirement for the PIDDosome is not clear. To investigate the requirement for the PIDDosome in caspase-2-dependent neuronal death, we have examined the necessity for each component in induction of active caspase 2 and in execution of caspase-2-dependent neuronal death. We find that both NGF deprivation and Aβ treatment of neurons induce active caspase 2 and that induction of this activity depends on expression of RAIDD, but is independent of PIDD expression. We show that treatment of wild-type or PIDD-null neurons with Aβ or NGF deprivation induces formation of a complex of caspase 2 and RAIDD. We also show that caspase-2-dependent execution of neurons requires RAIDD, not PIDD. Caspase 2 activity can be induced in neurons from PIDD-null mice, and NGF deprivation or Aβ use caspase 2 and RAIDD to execute death of these neurons.

Unlabelled: Unilateral exploration based upon preoperative imaging has become increasingly applied in the management of patients with primary hyperparathyroidism. Unilateral surgical exploration purportedly has high rates of disease control, limited morbidity, and shortened operative time. Unfortunately, significant cohorts of patients with primary hyperparathyroidism are unable to have abnormal glands localized on preoperative imaging evaluation., Aim: The aim of our study was to evaluate the efficacy of Tc(99m) sestamibi preoperative imaging, intraoperative Tc(99m) sestamibi with gamma probe, and intraoperative parathyroid hormone (IOPTH) assessment in a large cohort of patients with primary hyperparathyroidism., Results: A total of 427 patients were prospectively evaluated who were deemed surgical candidates for the treatment of primary hyperparathyroidism. Of these patients, 240 (56%) presented with positive Tc(99m) sestamibi imaging. Another 105 (25%) presented with equivocal Tc(99m) sestamibi imaging. Finally, 82 (19%) presented with negative Tc(99m) sestamibi imaging. Intraoperative rapid assessment of parathyroid hormone was performed at the time of surgical exploration in all patients with negative and equivocal preoperative imaging. All 240 patients with positive preoperative imaging underwent unilateral surgical exploration utilizing intraoperative Tc(99m) sestamibi with gamma probe. The most common finding in the positive Tc(99m) sestamibi scan group was single adenoma in 235 (98%). Normocalcemia was achieved in 233 (97%) of these patients, although in 25 (10%) this was normocalcemia with a persistent elevation in parathyroid hormone (PTH). The most common surgical finding in the equivocal Tc(99m) sestamibi scan group was single adenoma in 85 (81%). Additionally 85 (81%) of these equivocal patients were able to undergo unilateral exploration limited by IOPTH assessment. Normocalcemia was achieved in 101/105 (96%) of patients; although, 10 patients were normocalcemic with persistently elevated PTH and 2 patients had normocalcemia with low PTH. All patients with negative Tc(99m) sestamibi scan underwent bilateral cervical exploration plus IOPTH; 52/82 (63%) were found to have a single adenoma which was the most common surgical finding. Normocalcemia was achieved in 77/82 (94%) of the negative Tc(99m) sestamibi cohort; although 5 patients had normocalcemia with persistently elevated PTH and 2 had normocalcemia with low PTH. Only 3 (0.7%) overall recurrent laryngeal nerve injuries were encountered, and only 1 (0.2%) was permanent. Wound complication rates are reported in detail and were low and comparable for all three Tc(99m) sestamibi imaging based cohorts., Conclusions: Tc(99m) sestamibi preoperative imaging, intraoperative Tc(99m) sestamibi with gamma probe, IOPTH, and combinations of these strategies allow for excellent opportunities for targeted excision of pathologic parathyroid tissue with the least dissection necessary while achieving excellent long-term calcium control and low rates of complication.

Legal approaches to civil commitment in the United States and the United Kingdom are compared. A concise overview of the historical evolution of civil commitment in both countries precedes a discussion of the present scheme of commitment standards in each system. These current standards in U.S. and U.K. jurisdictions are then applied to a hypothetical case of delusional disorder. A discussion of the constructive use of civil commitment in patients with delusional disorder who may be dangerous focuses on its value as a preventive measure against potential harm to self or others, as well as the pros and cons of coercive assessment and treatment. Despite the many differences in approach to commitment, the authors concur that in both countries the patient with delusional disorder was committable before the commission of a serious criminal offense.

The use of complementary and alternative medicine (CAM) in developed countries has increased significantly over the years. Among the most popular are the weight loss supplements or "fat burners." Liver failure due to these popular remedies has been widely recognized. Usnic acid has been an ingredient of dietary supplements that cause liver failure. Its hepatotoxicity has not been recognized because it is usually mixed with other ingredients that are presumably hepatotoxic. We describe a case of a 28-yr-old woman who presented with fulminant liver failure requiring orthotopic liver transplantation, after taking pure usnic acid for weight loss. This is the first report on fulminant liver failure associated with the ingestion of pure usnic acid. A discussion about hepatotoxicity of the different compounds of dietary supplements is presented. This is a reminder for the clinicians about the potential side effects of CAM.

De Clérambault's Syndrome or Erotomania was originally described as a delusional disorder in which a woman believes that an older man of higher social status is passionately in love with her. The patient's relentless pursuit of the delusional love object, often with escalating intrusiveness, may eventually involve threats or overt acts of retaliation, in response to repeated rejection, unrequited love, or alleged betrayal. Cases from the literature are reviewed in which the delusional romantic attachment involves the patient's psychiatrist or another medical specialist. The authors present a case involving a patient suffering from erotomania who develops a delusional fixation on her psychiatrist and, after her advances are repeatedly rejected, sues him for malpractice, alleging she had a sexual relationship with him in the course of treatment. The implications of the litigious paranoid, who uses the legal system to act out delusional concerns and retaliatory fantasies, are discussed. This is the first known case of an erotomanic patient claiming malpractice on the grounds that her psychiatrist had a sexual relationship with her.

Paranoid symptomatology involving suspicions, a sense of being wronged and persecuted, along with an implacable will to retaliate against one's enemies, often translates into litigious struggles. Paranoids resort to the judicial arena to act out their own internal psychopathologic needs. Examples are offered of the many ways litigious paranoids may present within the legal system, as well as how interventions by the psychiatrist may be useful. Criminal behavior by paranoids, under the sway of full-blown delusions of various types, is discussed and analyzed. Historical cases are described (Hadfield, M'Naghten), and more contemporary cases are discussed according to diagnostic subtypes. The central importance of paranoid delusions in insanity defense cases and the exculpatory effect of various delusional subtypes are examined.

The authors discuss the general outlines of the Tarasoff duty of psychotherapists to protect potential victims of their violent patients. They describe the flexible range of clinical responses that therapists have utilized, as well as their professional concerns about preserving patient confidentiality (or at least strictly circumscribing the scope of disclosure when confidentiality must be breached). A recent case is reported that illustrates a striking new extension of Tarasoff, involving a police search and seizure of a psychotherapist's confidential treatment records and tapes, in response to a third-party complaint that the records contained evidence of his patients' violent acts and propensities. The implications of this case are that the therapist's discretion in the assessment of his duty to protect, the selection of a proper course of action, and the implementation of specific responses may be taken out of his hands, for all intents and purposes, and expropriated by law and order officials. Moreover, regardless of whatever clinical approach he adopts and whether or not he issues a warning, his attempts to preserve patient confidentiality are bound to prove unsuccessful in any future legal proceedings. Patient communications are likely to lose their confidential status on the grounds that they caused or triggered the Tarasoff warning (or that they should have triggered it). If the patient directed serious threats against the therapist himself, the court may find that, as a consequence, a "genuine therapeutic relationship" ceased to exist and thereafter all patient disclosures were no longer confidential on that basis.(ABSTRACT TRUNCATED AT 250 WORDS)

The legal context of voluntary and involuntary intoxication is delineated. The author reports a case of involuntary intoxication involving scopolamine toxic psychosis or delirium, in which he testified as a psychiatric expert witness. The specific psychological and physiological symptomatology produced by scopolamine intoxication is outlined. The forensic psychiatrist should be alert to the involuntary intoxication defense in these cases and should familiarize himself with the specific toxicity of scopolamine, in view of the significant increase in the number of incidents in which it is utilized as "knockout" drops in certain jurisdictions.

The R-CRAS (Rogers' Criminal Responsibility Assessment Scales) purports to be a systematic and empirically based approach to evaluations of criminal responsibility. This 'insanity detector' has been heralded as a reliable instrument in the resolution of the psycholegal controversies surrounding the plea of insanity. It is contended that, regardless of its possible scientific merit, most courts will find that the R-CRAS fails to satisfy the Frye test for admissibility of novel scientific evidence (that is, general acceptance by the relevant scientific community). Moreover, it is argued that the R-CRAS's potential for prejudice outweighs its probative value, in that it might unfairly bolster the testimony of the expert witness who relies upon it and might overwhelm the jury because of its 'aura of special reliability and trustworthiness'. Until such time as the R-CRAS does gain widespread acceptance and is shown to be sufficiently reliable to outweigh any potential prejudice (if ever), the author is of the opinion that forensic psychiatrists and psychologists may have to continue to conduct evaluations of criminal responsibility 'the old-fashioned way'. 'Truth does less good in the world than its appearances do harm' --La Rochefoucauld.

Whether or not the psychiatrist testifies on the ultimate issue in insanity defense cases, it is critically important that he familiarize himself with the applicable legal standards and interpretations in order properly to relate his clinical findings to the relevant criteria for insanity and thereby enhance the probative value of his testimony. This is the third in a series of articles which attempts to explicate judicial and statutory standards of insanity and correlate them with the psychiatrist's findings of psychopathology. This article analyzes the Model Penal Code formulation of insanity, with special emphasis on the all important distinction between "know" and "appreciate." This formulation permits the defendant possessed of mere surface knowledge or cognition to be exculpated, requiring that he have a deeper affective appreciation of the legal and moral import of the conduct involved if he is to be held criminally responsible. The Model Penal Code approach more readily lends itself to application as a standard of responsibility in cases involving affective disorders. An important disorder within this group, postpartum depression, is discussed in the context of raising the insanity defense in a case of infanticide.

One neglected but important measure of early morbidity after coronary artery bypass graft (CABG) operations is rehospitalization. As part of a prospective study of recovery after elective CABG procedures conducted at four academic medical centers, data from all readmissions occurring within the first six postoperative months were collected for 326 patients. A total of 24% of patients had readmissions. The most common categories of readmission discharge diagnoses were cardiac (57%), noncardiac (26%), and surgical sequelae (17%). Factors from the initial hospitalization identified as risk factors for rehospitalization included: length of stay in intensive care unit after surgery, severe noncardiac complications, duration of preoperative cardiac symptoms, intra-aortic balloon insertion, and preoperative resting angina. These findings help to identify a subset of at risk patients for whom more careful surveillance might be beneficial.

To evaluate current practices regarding intensive-care units (ICU's), we collected data on 2693 consecutive admissions to a medical ICU during a two-year period and studied indications for admission, specific interventions, costs, and outcomes. The need for noninvasive monitoring rather than immediate major interventions prompted 77 per cent of the admissions. Only 10 per cent of monitored patients had subsequent indications for major interventions. The 23 per cent who required immediate interventions accounted for disproportionate shares of total charges (37 per cent) and deaths during hospitalization (58 per cent). Demographic and diagnostic data indicate that the aged and chronically ill have become the principal consumers of intensive care. Overall mortality during hospitalization was 10 per cent; cumulative mortality during follow-up study (mean duration, 15 months) was 25 per cent. We conclude that identification of sensitive predictors of complications and specific predictors of mortality can lead to more efficient and effective ICU practices.

A laminar-flow dye cell with continuously variable thickness (tunable without removal of the dye solution) provides an excellent way of optimizing passively mode-locked lasers. Varying the cell thickness adjusts low-light-level transmittance to match the total cavity and excitation energy conditions and also varies pulse duration. Acceptable cell thicknesses and dye concentrations can be calculated theoretically using well-known parameters. The cell can be conveniently retuned to compensate for dye degradation or to provide conditions for Q switching. Experimental evidence is presented for a Nd:YAG laser.

Attacks on the credibility of the psychiatric expert witness are termed impeachment. This article provides an in-depth review of the various impeachment techniques used by lawyers during cross-examination and offers specific suggestions to the psychiatric expert witness on how to prepare for and counter some of these trial ploys. Bolstering and rehabilitation of the expert's credibility are also discussed. Finally, improper use of impeachment tactics is also considered. Excerpts from trial transcripts and court opinions are supplied to illustrate these points. Although impeachment remains a formidable weapon in the lawyer's armamentarium, it is suggested that the well-prepared and experienced psychiatric expert witness will be more than equal to the task.

This case study addresses one problem brought on by a significant increase in patient volume: the inability of appointment desk clerks to answer the telephone within a reasonable amount of time. In response to mounting complaints from both patients and clinic staff, conversion to a computerized appointment system was undertaken. However, when the conversion led to no immediate relief of the problems at hand, an automatic call distributor was installed. Though this experience in instituting two new systems simultaneously was not without its problems, it did prove successful in effectively smoothing clinic operations.

This study describes the long-term functional outcomes of a medical and coronary care ICU population. Baseline and 1-yr follow-up data were collected prospectively from all 2213 patients admitted during a 2-yr period. Patients were stratified into three groups based on their preadmission functional status: active (n = 917), sedentary (n = 1017), or severely limited (n = 279). Those with severe functional limitation before admission were twice as likely to undergo major interventions (p less than .005). This group also had a significantly (p less than .001) higher mortality and incurred significantly (p less than .01) higher hospital charges than the other two groups, even though hospital lengths of stay were similar. Finally, cumulative mortality was significantly (p less than .001) greater for the severely limited patients: 33% expired in the ICU, 42% died while still in the hospital, and 63% died after discharge. Most survivors regained their preadmission functional status, with 60% of the previously employed returning to work. However, even for hospital survivors, mortality was high and was related to prior functional status: active 7%, sedentary 20%, severely impaired 37%.

To assess the clinical utility of serum digoxin tests in the elderly and to ascertain the use by physicians of test results, digoxin levels were obtained from 77 consecutive, elderly patients (means age 72 years) taking digoxin on admission to a rehabilitation hospital. Blood samples were drawn the morning following admission (prior to the administration of digoxin) and were repeated in two weeks. Signs or symptoms of digoxin toxicity were seen in all 13 patients with levels above the therapeutic range. Of 38 patients with therapeutic levels, 16 had signs or symptoms compatible with underdigitalization or digoxin toxicity. Physicians were significantly more likely to respond to both the initial and follow-up serum digoxin test result when the first test result was above the therapeutic range.

Psychiatrists are called on to evaluate the credibility (and incredibility) of complaining witnesses in criminal proceedings despite a longstanding controversy about their ability to accurately make such determinations. The author discusses the history of such psychiatric activity from Freud through the Alger Hiss prejury trial, its current status in terms of benefits to the criminal justice system, the legal and social questions it raises (e.g., the competing issue of the complainant's right to privacy), andthe court's restrictions on the psychiatrists. He presents two illustrative case histories.

In the wake of Hinckley, widespread public dissatisfaction with the role of psychiatrists in insanity defense litigation prompted Congress in 1984 to amend the Federal Rules of Evidence to prohibit psychiatric testimony on the ultimate legal issue of whether or not a defendant is insane. APA's Statement on the Insanity Defense served as the ably articulated premise for this evidentiary amendment. APA argued that in going beyond their psychiatric expertise by answering ultimate issue questions as to whether defendants are legally insane, experts are likely to confuse the jury and undermine public confidence in psychiatry. APA also asserted that there was an impermissible logical leap between scientific psychiatric inquiry and moral-legal conclusions on the ultimate issue of insanity. This article reviews the origins, history, and vicissitudes of the Ultimate Issue Rule and analyzes the Statement on the Insanity Defense from both a legal and psychiatric perspective on the issue of whether psychiatrists should answer the ultimate question in insanity cases. The analysis suggests that APA's conclusions are not supported on scientific or evidentiary grounds, but may be warranted as a policy consideration to safeguard the public image of psychiatry.

Although delusions are prima facie evidence of psychosis, their mere presence is not a sufficient condition for exculpation on the grounds of insanity. In most cases, a determination of insanity will depend on the specific content of the delusions and whether, as a result of these delusions, the defendant was unable to know or appreciate the wrongfulness of his or her act. Delusions may be subdivided into four types, according to their content: 1) delusions of being controlled, 2) delusions of grandiosity, 3) delusions of persecution, and 4) delusions of jealousy. An analysis is undertaken of these delusional subtypes in terms of their exculpatory effect within the jurisdictions which follow each of the three respective standards of wrongfulness (i.e., the illegality standard, the subjective moral standard, and the objective moral standard). The criminal law does not recognize a transcendent constancy in the legal insanity status of psychotic individuals whose offense was the result of their delusional ideation. In most such cases, exculpation is based primarily on the specific content of their delusions and how it comports with the law of the jurisdiction specific content of their delusions and how it comports with the law of the jurisdiction in which the act was committed (the lex loci delicti commissi).

Lawyers have argued that surveillance of the forensic psychiatric examination is often necessary to protect clients' rights and assure more accurate reporting of the findings. This paper reports a new phenomenon which adds a disconcerting dimension to the current controversy over surveillance of such examinations, namely, surreptitious recording by patient/examinees of their own forensic examination. Their motivations range from psychotic delusions to perceptions that they are acting to protect their legal interests. Neither legal nor ethical code prohibitions in any way serve to bar such conduct. Moral arguments for and against secret recording by patient/examinees are explored, and its relationship to other techniques used to monitor professional practices in the health fields (such as pseudopatient studies) is discussed.

To investigate admissions from nursing homes to a medical intensive care unit (ICU), the authors detailed the major interventions, costs, and outcomes for such patients (n = 67) over a 3-year period and then compared them with those for ICU patients receiving home care or visiting nurse services (240 patients) before admission and all others older than 65 years of age (949 patients). These three groups comprised 37% of total ICU admissions. In contrast to younger patients admitted primarily with acute ischemic heart disease, nursing home patients were more likely to be admitted with cardiopulmonary arrest, infection, and gastrointestinal bleeding. Major interventions of intubation and mechanical ventilation were most frequent for nursing home patients, but total hospital charges differed little among the groups. In-hospital mortality for the nursing home group (28%) was significantly higher than for the home care group (7%) and others older than 65 years of age (7%). Cumulative mortality for the nursing home group reached 66% by 8 months, versus 32% and 26% in the other groups, respectively.

All admissions (2,693) to a medical intensive and coronary care unit (ICU/CCU) during a two-year period were reviewed to compare indications for admission, major interventions, and outcomes for elderly patients with those for younger patients. Once admitted to the ICU/CCU, older patients were more likely to receive major life-support interventions such as mechanical ventilation but less likely to survive. Major interventions were used in 32% of patients aged 75 years or older, in 26% of those 65 to 74 years, and in 22% of those 55 to 64 years. Nonetheless, elderly patients had no longer mean lengths of stay and no greater mean hospital charges. Hospital mortality for the oldest patients was 16%, compared with 14% and 8% for the younger age groups. Cumulative mortality one year after discharge for those older than 75 years was 44%. Elderly hospital survivors returned to their preadmission living situation but did not regain their preadmission activity level.

Nine Experimental Medical Care Review Organizations (EMCROs) review the process and outcome of medical care, using insurance billing claims or medical record abstracts as the data source. The cost of EMCRO insurance billing claims processing in 1972, including peer review, ranged from $0.47 to $2.50 per claim. Three EMCROs reviewed the necessity for elective hospital admission prospectively for $2.50, $8.50, and $10.02 per case. The EMCROs developed innovative methods for abstracting hospital, nursing home, and ambulatory medical records at a cost of $0.40 to $4.00 per abstract. These EMCRO cost estimates were not derived from uniform accounting methods. Problems of accuracy and comparability of data for peer review are discussed. The EMCRO experience may aid local implementation of Professional Standards Review Organizations (PSROs).

Preoperative predictors of postoperative employment status were studied in 228 patients (aged 25 to 64 years) who underwent cardiac surgery. Of the 150 patients working in the year before surgery, 73% returned within six months. Of those not so employed, 18% started working. Patients who expected preoperatively to return to work did so at an 82% rate compared with 39% of the others. This was a strong predictor in the multiple regression analysis. Educational level and family income were stronger predictors than occupation or level of physical exertion required. Rates of return were higher in patients with less severe angina and less fatigue preoperatively, but did not differ significantly by sex, surgical procedure, or duration of illness. Seven variables predicted work status correctly for 86% of persons. These results suggest that determinants of return to work are largely present before surgery and that patients' attitudes and expectations play an important role.

Although the law generally does not permit an individual to profit by his own wrongdoing, that equitable principle may be inapplicable in the case of an individual who has been adjudicated insane (and therefore has not committed a wrong in the eyes of the law). This paper discusses three unusual legacies of a determination of insanity: the inheritance cases (permitting the insane killer to inherit from his own victim), the life insurance cases (permitting the beneficiary to recover when the insured commits suicide while insane), and the effect of insanity on publication rights agreements in sensational criminal cases.

De Clérambault's syndrome (erotomania) has invariably been regarded as a female disorder (with male victims); however, a number of recent reports describe male patients with the disorder, especially in violence-prone male offender populations. Seven cases are presented of violence-prone men suffering from the disorder, including Hinckley and Poddar. The syndrome is discussed from a nosological point of view and in terms of its impact on competency to stand trial. Psychiatrists should be aware that the syndrome is not a rarity among men, as previously thought, and that proper diagnosis and management are essential in view of the clinical course of the disorder and the potential for violence when the patient's "love" is persistently unrequited by the delusional love object.

In insanity defense litigation, the precise legal definition of wrongfulness is often critically important. References in the M'Naghten Rules to the appropriate standard of wrongfulness were ambiguous, resulting in a divergence of judicial opinion as to whether wrongfulness means legal wrong, subjective moral wrong, or objective moral wrong. This article reviews and analyzes these three judicial standards of wrongfulness in the context of case law from jurisdictions that follow each of the respective standards. The evolution of knowledge of right and wrong tests of criminal responsibility is traced back to its philosophical roots. Most psychiatrists claim no expertise in matters of morality or law. The American Psychiatric Association would bar psychiatric expert testimony on the ultimate issue of insanity, on the grounds that there are "impermissible leaps in logic" when psychiatrists opine on the probable relationship between medical concepts and moral-legal constructs. Whether or not they testify on the ultimate issue, psychiatrists should ascertain the applicable standard of wrongfulness in order to properly relate their findings to the relevant legal criteria for insanity and thereby enhance the probative value of their testimony.

In lawsuits involving complex scientific issues of causation, dispute resolution requires that a final decision be reached in each case, regardless of whether science is able to provide definitive answers to the questions of causation raised at trial. Proving causation before science has is a concept that scientists may find disconcerting and foreign to some of their basic assumptions. This paper explores the foregoing issues, discusses medical versus legal concepts of causation, outlines the legal tests for admissibility of novel scientific evidence (including Federal Rule of Evidence 702 and the Frye test of general acceptance by the relevant scientific community), and presents a toxic tort case in which expert psychiatric testimony addressed the issue of causation of schizophrenia. The paper articulates concerns about the "misleading aura of certainty" posed by scientific evidence and the burden of decision making that is cast upon the legal system in such scientific issue cases.