Molecular evolution of immunoglobulin and fibronectin domains in titin and related muscle proteins.

The family of regulatory and structural muscle proteins, which includes the giant kinases titin, twitchin and projectin, has sequences composed predominantly of serially linked immunoglobulin I set (Ig) and fibronectin type III (FN3) domains. This paper explores the evolutionary relationships between 16 members of this family. In titin, groups of Ig and FN3 domains are arranged in a regularly repeating pattern of seven and 11 domains. The 11-domain super-repeat has its origins in the seven-domain super-repeat and a model for the duplications which gave rise to this super-repeat is proposed. A super-repeat composed solely of immunoglobulin domains is found in the skeletal muscle isoform of titin. Twitchin and projectin, which are presumed to be orthologs, have undergone significant insertion/deletion of domains since their divergence. The common ancestry of myomesin, skelemin and M-protein is shown. The relationship between myosin binding proteins (MyBPs) C and H is confirmed, and MyBP-H is proposed to have given rise to MyBP-C by the acquisition of some titin domains.

Effects of electroconvulsive therapy in adolescents with severe endogenous depression resistant to pharmacotherapy.

BACKGROUND: This open, prospective study examined the effects of electroconvulsive therapy (ECT) in 10 adolescents with primary, endogenous, psychotic depression who were resistant to antidepressant pharmacotherapy. METHODS: Change in symptom severity from baseline was assessed weekly with Hamilton Depression Rating Scale (HDRS) ratings, and outcome was measured additionally at 1 month, and again at 1 year, post-ECT. RESULTS: All but 1 patient demonstrated dramatic improvement, with statistically significant decreases in mean HDRS score detected after the first week of treatment. All responders maintained the benefits of their treatment. CONCLUSIONS: The results provide evidence of the clinical effectiveness of ECT in adolescents with phenomenological characteristics shown to be predictive of ECT response in adults.

Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study.

Early morning sleep deprivation (patient awake from 0200 to 2200 hours) produces a same-day antidepressant effect in approximately one-half of patients with major depression. Unfortunately, these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours. Recent work suggests, however, that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinically useful. In a 30-day study, we compared the abilities of four different treatments (lithium plus early morning sleep deprivation, lithium plus a control sleep deprivation procedure, and desipramine with either of the two sleep manipulations) to induce a rapid (next-day) and sustained antidepressant response in 16 depressed patients. Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation, and the response was sustained for at least 30 days. In this design, however, lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission. These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted.

Proposals for the mechanism of action of convulsive therapy: a synthesis.

The convulsive therapies have been powerful additions to somatic treatment in psychiatry and have enjoyed widespread application for the benefit of many. A number of theories have been advanced in efforts to account for therapeutic efficacy but none has been comprehensive. These theories can be distinguished by whether they posit a central therapeutic role for stimulation, inhibition, psychological effects, or mixed processes induced by treatment. After critically reviewing extant theories, we propose a model for the effects of the convulsive therapies: Convulsive therapy is essentially nonspecific; "nonphysiological" depolarizations are distinctly important for the restoration of aberrant intravesicular transmitter ratios with resultant therapeusis. We present this model as a working hypothesis that may contribute to the guidance of research in the mechanism of action of convulsive treatment and offer several testable hypotheses in this regard.

Poor interrater reliability of MECTA EEG recordings of ECT seizure duration.

The electroencephalogram (EEG) tracings of seizure durations recorded by the MECTA SR-1 for 24 patients undergoing right unilateral electroconvulsive therapy (ECT) were estimated independently by four psychiatrists and a neurologist. Differences among raters were often large and, overall, were statistically significant. The literature on interrater reliability for the MECTA EEG remains contradictory, and caution in MECTA EEG use appears warranted.

Attorneys' perceptions of electroconvulsive therapy: impact of instruction with an ECT videotape demonstration.

The knowledge of attorneys from the Los Angeles Superior Court was studied before and after education about electroconvulsive therapy. They viewed a videotape explaining ECT and questions were answered. There were significant improvements in overall knowledge and in positive opinions regarding ECT.

Urinary phenylacetate and response to methylphenidate.

Phenylacetate (PAA) is the metabolic end-product of phenylalanine, a catecholamine precursor, and of phenylethylamine, a centrally active neurochemical substance which has been implicated in the actions of stimulant medications. PAA has been reported to be low in unipolar depression. We measured 24-h urinary PAA in normal controls (N = 21) and in-patients with unipolar depression (N = 33; 12 drug-free) and did subsequent dexamethasome suppression tests (DST). We also gave patients methylphenidate challenges, examining mood response. There were no significant differences between depressed patients and controls in 24-h urinary PAA excretion (P greater than 0.9). However, the variance in PAA excretion was higher in patients than normals and 5 patients had values at or above the 99% confidence limits for the normal control group. There was no association of DST results with PAA excretion (P greater than 0.4). Patients with a worsened mood after taking methylphenidate excreted less PAA than those with an improved mood, however (P less than 0.025). The clinical and theoretical significance of these results is discussed.

Relatives' descriptions of changes in symptoms of dementia of the Alzheimer type: a comparison of retrospective and concurrent ratings.

Although relatives' retrospective reports are often used in characterizing the onset and progression of symptoms in dementia of the Alzheimer type (DAT), little is known about the accuracy of these accounts. The primary purpose of this paper is to summarize preliminary data obtained from relatives in an ongoing family study of DAT. Preliminary findings suggest there is rough reliability to relatives' recall of the progression of symptoms over time. This observation is discussed in relation to literature from other areas (e.g. child development, psychopathology) where the reliability of relatives' retrospection has been more thoroughly examined.

Prolongation of the antidepressant response to partial sleep deprivation by lithium.

Depressed patients given a loading dose of lithium on the first of 2 successive days of partial sleep deprivation (PSD), and kept at maintenance levels thereafter, showed significantly greater prolongation of the antidepressant effects of PSD than patients treated with PSD and placebo, even though the acute elevation in mood derived from PSD was as great on placebo as on lithium. Depression was assessed 3 days after PSD with an augmented version of the Hamilton Rating Scale for Depression. Patients on lithium alone, without PSD, did not have the acute elevation in mood seen in the two PSD groups and had significantly less improvement in depression than those who received PSD with lithium.

Medical, judicial, and statutory regulation of ECT in the United States.

The standards for ECT recommended by an APA task force report and those embodied in federal court orders and state statutes and regulations are compared. The authors conclude that there is serious boundary and role confusion owing to progressive intrusion of state authority into areas traditionally held to lie in the domain of medical judgment and clinical care. In spite of comprehensive safeguards promulgated by the psychiatric community, overregulation by legislatures and courts is commonplace, interposing law between physicians and patients and resulting in delays or denials of service while failing to resolve critical legal issues involving competence and consent.

A comparison of national and in-house examinations of psychiatric knowledge.

The search continues for the optimum method of assessing psychiatric residents' knowledge. In 1982, 72% of the U.S. residency programs gave the Psychiatry Resident In-Training Examination ( PRITE ). The authors compared the PRITE with an examination developed by their program. The two tests yielded highly correlated percentages of correct responses and resident rank orders for advanced residents, detected similar areas of weakness, had comparable dollar costs, and elicited similar, moderately high resident satisfaction. Important differences were the amount of information and feedback provided to residents and to the residency program and the time between the test and the feedback.

Clinical differentiation of primary degenerative and multi-infarct dementia: a critical review of the evidence. Part I: Clinical studies.

For patient care and for research purposes there is an obvious need for a valid and reliable set of clinical criteria to distinguish antemortem between primary degenerative dementia (PDD) and multi-infarct dementia (MID). To this end, specific diagnostic criteria for each have been promulgated in the official nomenclature, and a rating scale devised to differentiate these disorders is in wide use. These efforts suggest a diagnostic capability that is not, however, well supported by the literature. This critical analysis of representative clinical studies and articles published over the past two decades reveals important drawbacks in methodologic approaches and interpretation of data which seriously undermine confidence in making the clinical distinction between PDD and MID.

Clinical differentiation of primary degenerative and multi-infarct dementia: a critical review of the evidence. Part II: Pathological studies.

A critical examination of representative pathological studies published over the past four decades reveals that this literature fails to provide sufficient support for the antemortem differentiation of primary degenerative dementia (PDD) from multi-infarct dementia (MID) on the basis of clinical criteria. Similar conclusions with respect to clinical studies and articles are presented in Part I of this overview. Among the difficulties commonly encountered in the literature are sampling bias, retrospective design, nonblind assessments, inadequate sample size, failure to consider overlap (i.e., mixed cases), absence of pathological verification in the clinical studies and post hoc reasoning. The necessity to assure that one is dealing with a case of PDD as opposed to some other dementing process is self-evident. However, these reviews show that this capability has not been adequately established with respect to the differential diagnosis of PDD and MID; the evidence to date indicates that the clinical diagnosis of MID, in particular, should be made with caution until more conclusive methods become available.

Behavioral responses to amphetamines in identical twins.

Male, monozygotic twins (six pairs) were repeatedly tested before and after d-amphetamine, l-amphetamine, or placebo administration. Drug effects on cognitive, psychomotor, personality, mood, and pain variables were assessed. Members of a twin pair tended to respond similarly on several tests under placebo conditions, indicating genetic determination of the behavioral variables. In addition, cotwins tended to show similar responses to amphetamine as measured by one test of cognitive function, by several mood and personality variables (hostility, autonomic arousal, friendliness, feelings of tension and loss of control), and tended to have similar plasma levels of both amphetamine isomers. Although shared environmental effects cannot be ruled out, the results are consistent with genetic mediation of a variety of behavioral effects of amphetamines.

Diagnosis and treatment of dementia in the aged.

Dementia affects an estimated 5 percent of the population 65 years of age and older, with 20 percent being affected at 75 years or older. Although the most common forms, primary degenerative and multi-infarct dementia, currently lack specific treatments, it is estimated that a thorough diagnostic evaluation will uncover a treatable cause in 10 percent to 20 percent. The differential diagnosis includes benign senescent forgetfulness, depression, adjustment disorder, paranoid states, amnestic syndrome, delirium, drug effects, systemic illnesses and intracranial conditions. The approach to each patient involves a history, physical examination, mental status evaluation and laboratory tests that focus on identifying treatable conditions. When no specific treatments are available, however, symptomatic treatments, including pharmacotherapy, environmental management, family supports and psychotherapy, can offer relief for both patients and their families and improve the daily functioning of the elderly patient with dementia.