Psychotherapy of refractory depressions

Psychotherapy is a potentially valuable intervention for treatment-resistant depression. This review provides a brief, general overview of the use of psychotherapy to treat depression and more focused consideration of time-limited interpersonal, behavioral, and cognitive behavioral strategies for patients who are not responsive to antidepressant medication. Effective strategies emphasize individualized assessment, psychoeducation, a high level of structure and therapist activity, operationalized short-term goals, self-help and homework activities, and an empirical-collaborative approach to treatment. Although some treatment-resistant patients respond to therapy alone, more promising evidence is emerging from studies of combined strategies.     

Skin problems in the traveler

Skin lesions are common in travelers and include a mix of mundane dermatologic problems and rare diseases acquired only in remote or tropical regions. The morphology, distribution, and progression of the lesions are useful in assessing possible causes. Early in the evaluation it is important to determine whether the patient might have a process that is rapidly progressive, treatable, or transmissible. In addition to routine laboratory studies, biopsy and serologic tests are often necessary to confirm a specific diagnosis.     

An analytical methodology to quantify the incorporation of enzymes in polyalkylcyanoacrylate nanoparticles based on size exclusion chromatography

The recently determined structure of octameric mitochondrial creatine kinase has provided new insights into the functioning of this enzyme and its role in channelling energy from the mitochondria to the cytoplasm. Creatine kinase, a member of the family of guanidino kinases, is structurally similar to glutamine synthetase, suggesting a possible evolutionary link between both protein families.     

A cDNA-dependent scintillation proximity assay for quantifying apolipoprotein A-I

We have developed a cDNA-dependent scintillation proximity assay (SPA) for rabbit apolipoprotein A-I that follows a classic radioimmunoassay scheme, in that antiserum and radiolabeled ligand are used in a process to quantify a source containing unlabeled ligand. To synthesize radiolabeled ligand we isolated a full-length rabbit apolipoprotein A-I (apoA-I) cDNA, transcribed the corresponding RNA in vitro, and synthesized radiolabeled apoA-I by including tritiated leucine in an in vitro translation reaction. Assay conditions were established which allowed quantification of unlabeled apoA-I over a range of 0.2 to 4 nanograms with intra- and interassay coefficients of variation of 5% and 10%, respectively. Purified rabbit apoA-I, apoA-I in rabbit liver parenchymal cell conditioned media, and apoA-I contained in rabbit plasma all generated parallel titration curves. Quantification of rabbit plasma apoA-I was not affected when sheep anti-rabbit apoA-I serum was mixed with sheep anti-rabbit apoB or apoE serum; thus, the antibody need not be specific to quantify the ligand of interest. To show utility of the assay, apoA-I mass was quantified in in vitro and in vivo models displaying altered apoA-I levels. In each model apoA-I values from the cDNA-dependent SPA and the established methodologies of Western blotting and electroimmunodiffusion were highly correlated. The approach outlined in this report should permit rapid development of scintillation proximity assays for other proteins given the widespread availability of full-length cDNAs.     

Role of cytopathology in the diagnosis of ocular malignancies

OBJECTIVE: To determine the positive predictive value of ocular cytologic specimens and to describe the cytopathologic findings encountered in ocular samples from patients with intraocular neoplasms. STUDY DESIGN: Intraocular fluids and ocular fine needle aspirates (FNAs) cytologically diagnosed as either suspicious or positive for malignancy during a 15-year period were reviewed, and follow-up was obtained. RESULTS: Seventeen patients with intraocular samples diagnosed as suspicious or positive for malignancy (9 vitreous, 6 anterior chamber, 3 FNAs) were identified. The mean patient age was 58 years (range, 3-91). Cytologic diagnoses included: lymphoma (5), suspicious for lymphoma (2), melanoma (6), suspicious for melanoma (2), carcinoma (2) and retinoblastoma (1). Clinical and/or surgical follow-up was available in 12 cases and was consistent with the presence of malignancy in all but one case, which proved to be fungal endophthalmitis. One of two patients with a cytologic diagnosis of carcinoma had melanoma on follow-up. Cytologic samples suspicious or positive for lymphoma showed single, large cells with scant cytoplasm and prominent nucleoli. Cytologic samples suspicious or positive for the epithelioid type of melanoma showed loosely cohesive groups or single cells, marked cellular pleomorphism, large nucleoli, scant to moderately abundant cytoplasm and variable amounts of melanin. Cytologic samples from spindle cell melanomas showed spindle cells without nuclear or cellular pleomorphism, without hyperchromasia, and with inconspicuous nucleoli and occasional nuclear grooves. Loose aggregates of small cells with hyperchromatic nuclei and scant cytoplasm characterized the retinoblastoma samples. CONCLUSION: The positive predictive value of intraocular fluid cytology was 92%. Reactive lymphoid processes may be difficult to differentiate from lymphoma and epithelioid melanoma from carcinoma in intraocular cytologic specimens.     

Iron supplementation during pregnancy. Standards and alternatives]

CONTEXT: Contraceptive use has been legal in France for the past 30 years, and patterns of use changed substantially from the 1960s to the 1980s. Given the rapidity with which use patterns change and the possible impact of rising concern about infection with HIV and other sexually transmitted diseases, it is important to determine trends of contraceptive practice into the 1990s. METHODS: A total of 5,900 French households were selected in 1994 for inclusion in the Fertility and Family Survey. Respondents were questioned about their contraceptive use patterns and family formation status. The results were compared with those of comparable surveys conducted in 1978 and 1988. RESULTS: Two-thirds of French women used some form of reversible contraceptive method in 1994. Oral contraceptive use has grown steadily in France: About 40% of women aged 20-44 reported using the pill alone or combined with another method in 1994, compared with 34% in 1988 and 28% in 1978. Condom use has also been on the rise: Nearly 8% of women were using condoms alone or combined with another method in 1994, up from 5% in 1988 and 6% in 1978. IUD use has declined from 19% in 1988 to 16% in 1994, and both male and female sterilizations remain rare. CONCLUSIONS: Contraceptive behavior in France appears unique among developed countries, with fairly high levels of oral contraceptive use--even among older women--relatively high levels of IUD use and little reliance on either male or female sterilization. As with other countries, however, condom use has climbed in recent years, and is especially common at first intercourse.     

Hypothalamic-pituitary-gonadal axis in the mutant weaver mouse

The weaver (wv) mutant mouse manifests severe locomotor defects, a deficiency in granule cells of the cerebellum, and cellular deficits in the midbrain dopaminergic system. The wv phenotype is associated with a missense mutation in the pore region of the G-protein-gated inwardly rectifying potassium channel, GIRK2. The homozygous male wv mouse is essentially infertile due to an inadequate level of sperm production. Females are fertile although they also manifest the neurological phenotype. Homozygotes of both sexes have reduced body weight. We have evaluated the hypothalamic-pituitary-gonadal axis in heterozygote and homozygote male and female wv mutants in comparison with wild-type controls. Testicular weight was significantly reduced in the homozygous males, due to degenerative changes of seminiferous epithelium. Serum and pituitary content of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were normal in all groups, and the normal sex differences were noted (FSH and LH higher in males, prolactin higher in females). Pituitary growth hormone (GH) concentration was normal, with control and mutant males showing higher GH than females. Serum testosterone levels were normal in the mutants, as was testicular testosterone. Testicular alpha-inhibin content was mildly reduced, but high in proportion to testicular weight. The defect in spermatogenesis appeared predominantly in the postmeiotic stages. In situ hybridization was consistent with expression of some GIRK2 mRNA isoforms in seminiferous epithelium. There were no significant differences between genotypes in the levels of dopamine, dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the mediobasal and preoptic hypothalamic regions. Homovanillic acid levels in these two areas were, however, reduced in wv homozygotes compared to wild-type animals. In the light of normal pituitary hormone levels, normal hypothalamic monoamine concentrations and normal sex differences in gonadotropins, we conclude that the infertility in the male homozygote wv mouse lies within the tubule and is probably a primary defect in the germ cells. The hormonal data suggest that Leydig cell function, and at least some aspects of Sertoli cell function, are normal in the mutant mice.     

Protective vaccination against primary and recurrent disease caused by herpes simplex virus (HSV) type 2 using a genetically disabled HSV-1

The vaccine potential of a mutant herpes simplex virus (HSV) type 1, with a deletion in the glycoprotein H (gH) gene, was evaluated. The virus requires a gH-expressing cell line for multi-cycle growth but can complete a single cycle of infection in noncomplementing cells. Such viruses, termed DISC (disabled infectious single cycle) viruses, should be safe, yet still able to stimulate humoral and cell-mediated responses against a broad range of virus antigens in vaccinated hosts. Prophylactic vaccination of guinea pigs with DISC HSV-1, by ear scarification or direct infection of the vaginal mucosa, afforded a high degree of protection against HSV-2-induced primary genital disease and reduced significantly the frequency of subsequent disease recurrence. There was also a trend toward reduced recurrence following therapeutic vaccination of animals already infected with HSV-2. DISC HSV vaccination, therefore, offers an effective route for control of HSV disease.