Implosive therapy for the treatment of combat-related PTSD

Implosive therapy for the treatment of post-traumatic stress disorder is based on the principle of exposing the patient to trauma-related cues until there is a reduction in the anxiety associated with the cues. It is a relatively specialized procedure regarding which few clinicians receive extensive supervised training, despite the numerous case studies that demonstrate its effectiveness. The present paper addresses a number of procedural issues and offers guidelines for conducting implosive therapy with traumatized combat veterans. Elements of controversy regarding the application of implosive therapy are discussed.     

Identification of the phenotype in psychiatric genetics

Summary Statistical procedures and molecular genetic techniques have attained a fine degree of resolution. Their ability to find disease genes has revolutionized medicine and raised hopes for breakthroughs in psychiatry. However, such breakthroughs may require an equally discriminating nosology. A psychiatric genetic nosology seeks to classify patients into categories that correspond to distinct genetic entities by addressing the problem of diagnostic accuracy: the degree to which a diagnosis correctly classifies people with and without a putative genetic illness. We review methods that deal with misclassification in genetic studies. These are clinical and epidemiological approaches that deal directly with how to define the observable manifestation of a putative genotype. We discuss two groups of methods: those that use known phenotypes and those that design new phenotypes.     

Cysteine Conjugate beta-Lyase-Dependent Metabolism of Compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in Human Subjects Anesthetized with Sevoflurane and in Rats Given Compound A

Background: Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene), which is nephrotoxic in rats and undergoes metabolism via the cysteine conjugate beta-lyase pathway in those animals. The objective of these experiments was to test the hypothesis that compound A undergoes beta-lyase-dependent metabolism in humans.

Methods: Human volunteers were anesthetized with sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby exposed to compound A. Urine was collected at 24-h intervals for 72 h after anesthesia. Rats, which served as a positive control, were given compound A intraperitoneally, and urine was collected for 24 h afterward. Human and rat urine samples were analyzed by19 F nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry for the presence of compound A metabolites.

Results: Analysis of human and rat urine showed the presence of the compound A metabolites [S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L-cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N-acetyl-L-cyst eine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3-trifluorolactic acid, and inorganic fluoride. The presence of 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in human urine was confirmed by gas chromatography-mass spectrometry.     

Home ventilation in Northern Ireland.

Thirteen patients were identified as receiving assisted ventilation at home in Northern Ireland in 1994. Two patients have since died. An increasing number of patients are starting home ventilation, especially by nasal mask. Recognition of the needs of these patients and provision of care require further consideration.     

Low tolerability of carbamazepine in psychiatric patients may restrict its clinical usefulness

There are reports of prophylactic efficacy of carbamazepine (CBZ) in manic depres sives when compared with placebo and chlorpromazine. Following a successful open pilot study by one of the authors, an attempt was made to compare carbamazepine and lithium carbonate in a double-blind, crossover trial, each patient being assigned to take each drug for 9 months in random order. However, of the first 14 patients to take carbamazepine four were withdrawn because of drug rashes and another two because of other adverse effects. The trial was discontinued, and a casenotes survey of 50 consecutive psychiatric patients who had been prescribed carbamazepine for mood disorders was then carried out, to establish the tolerability of the drug in clinical practice. Of these, 22 per cent had suffered dizziness, nausea or unsteadiness despite slow introduction of doses. Drug rashes occurred in 16 per cent of patients within the two weeks of starting treatment. A further 14 per cent had other unwanted effects. In total, 36 per cent of the patients had the drug stopped because of adverse effects. With regard to efficacy, in those taking the drug for more than 4 weeks, clinicians reported a definite or probable advantageous effect in 62 per cent of the sample, definite or probable lack of effect in 19 per cent and no opinion in 19 per cent. This low tolerability is not in accordance with previous reports of 2-6 per cent incidence of drug rashes and 10 per cent overall intolerance in neurological patients. We conclude that tolerability is a major drawback to the use of carbamazepine in some groups of psychiatric patients, although all the side- effects were reversible. However, clinical impressions suggested that in a number of patients no other therapeutic strategy was as effective in preventing mood swings.     

Cellular interactions determining the production of collagenase by a rat mammary carcinoma cell line

The cellular interactions regulating the production of collagenase by a cell line derived from a spontaneously arising rat mammary carcinoma have been studied. The cell line, BC1, was grown permanently under defined serum-free conditions, so that the poorly characterized and variable effects of serum on collagenase expression were avoided. Two stable subpopulations of cells present in BC1 cultures were defined as epithelioid cells ("E-cells") and myoepithelioid cells ("M-cells"). These subpopulations differed in their morphology, pattern of growth and susceptibility to detachment from culture vessels by trypsin. Seven clones of M-cells and 7 clones of E-cells, obtained by the limiting dilution technique, were used to determine the cellular source of collagenase and the interactions which led to its expression. M-cells displayed an absolute dependence on a soluble factor produced by E-cells for their survival in vitro. The presence of both cellular types in culture was necessary for collagenase secretion to occur, E-cells being the major source of enzyme in mixed cultures. A soluble factor produced by M-cells was largely, if not completely, responsible for the induction of collagenase secretion by E-cells. Clones representative of both subpopulations were tumorigenic in syngeneic host animals. These results suggest that the phenotypic diversity which occurs within populations of neoplastic cells may give rise to subpopulations of cells which display a more aggressive phenotype in coexistence than in isolation.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.