Efficacy and tolerability of milnacipran: an overview.

The relative benefits and risks of milnacipran, a novel antidepressant which selectively inhibits the reuptake of serotonin and noradrenaline, have been evaluated in comparative trials against tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs). A total of 2462 patients with major depressive disorders have been investigated. At the optimal dose (50 mg twice a day), the efficacy of milnacipran was equivalent to that of the TCAs, with response rates of approximately 65% in both cases.

An early antigen-presenting cell defect in HIV-1-infected patients correlates with CD4 dependency in human T-cell clones.

We have used a defined panel of nine HIV peptide-specific T-cell clones (TLC) generated from a healthy volunteer to evaluate the antigen-presenting cell (APC) function of human immunodeficiency virus-1 (HIV- 1)-infected patients. Peripheral blood mononuclear cells (PBMC) from HLA-matched seropositive and uninfected volunteers were compared for their capacity to present peptide to TLC specific for the V3 loop of HIV- 1 envelope glycoprotein gp120, influenza haemagglutinin or the mycobacterial 19,000 MW antigen APC from uninfected volunteers (HIV- APC) invariably presented peptides to all TLC with comparable efficiency. In contrast using APC from HIV- 1-infected subjects (HIV+ APC) three patterns of responsiveness were observed.

Impaired glucose tolerance and mild hyperglycemia in sucrose-fed rats does not impair insulin secretion.

We fed normal rats a high sucrose diet in order to test the hypothesis that mild hyperglycemia can induce defects in pancreatic beta-cell function and impair glucose-stimulated insulin release. Rats provided with free access to a sucrose solution (35%) voluntarily consumed 50% more carbohydrate than control per day. After 7 days of sucrose feeding, glucose tolerance was significantly impaired; the area under the glucose tolerance test curve (GTT) was 683 +/- 61 mmol/120 min compared with 472 +/- 56 mmol/120 min in controls (P < 0.

Immunosuppressive properties of monoclonal antibodies and human polyclonal alloantibodies to the R80K protein of trophoblast.

Problem: The R80K protein on human trophoblast is antigenically polymorphic, and in all placentae of successful pregnancies, the protein is covered by maternal alloantibody. Alloantibody eluted from human placenta has been shown to inhibit killing by human NK cells. Do those antibodies to R80K that inhibit NK killing also affect the murine abortion models?

Methods: We made three murine monoclonal antibodies to conserved epitopes, on human R80K, all of which also reacted with the homologous murine molecule.

Angiotensin-converting enzyme and enkephalinase in human breast cyst fluid.

Palpable breast cysts with an apocrine epithelial lining (type 1) are reported to be associated with a higher risk of developing breast cancer. The composition of breast cyst fluid (BCF) might include those factors involved in this increased risk. In this study peptidase activities that were active against the substrate [125I]metenkephalin-Arg-Phe were detected in BCF.

Pharmacokinetics of oestrone-3-O-sulphamate.

The sulphatase pathway is thought to be the major route of oestrogen synthesis in breast tumours in postmenopausal women. There is currently considerable interest in developing a potent steroid sulphatase inhibitor to block oestrogen synthesis by this route. One of the most potent inhibitors discovered so far is oestrone-3-O-sulphamate (EMATE) which is active in vivo.

Overnight metabolic fuel deficiency in patients treated conventionally for hypopituitarism.

Background: Hormone replacement in hypopituitary adults attempts to reproduce normal physiology. Conventional regimens fail to mimic normal hormone profiles over 24 hours.

Objective: To investigate the metabolic consequences of conventional hormone replacement in hypopituitary adults by measuring circulating levels of the major fuels, glucose, non-esterified fatty acids (NEFA), glycerol and 3-hydroxybutyrate (3-OHB) over 24 hours in hypopituitary subjects and controls.

Role of macrophages in acetaminophen (paracetamol)-induced hepatotoxicity.

Research into the pathogenesis of acetaminophen (paracetamol)-induced hepatotoxicity has concentrated on the generation of toxic metabolites by the hepatocytes. It has, however, recently been shown that human macrophages cultured with acetaminophen secrete increased quantities of tumour necrosis factor (TNF). This study examines whether macrophages have a direct role in acetaminophen toxicity, using a mouse model in which it is possible to eliminate more that 99 per cent of hepatic macrophages by previously injecting liposomes containing dichloromethylene disphosphonate (DMDP).

Community service needs of people with HIV infection in London.

The objectives of this study were to describe the expressed needs for community services of HIV-infected individuals by disease stage, gender and transmission category and the barriers which prevent the receipt of such services. Structured interviewer-administered questionnaires concerning a 6-month retrospective period were used to obtain information on need for community services and problems which prevented the receipt of services. The study sample included 70 homosexual men with asymptomatic HIV disease, 42 homosexual men with symptomatic non-AIDS, 53 homosexual men with AIDS, 23 heterosexual men, 29 heterosexual women, 9 male and 9 female injecting drug users.

Depletion of resistance vessel polyamines attenuates angiotensin II induced blood pressure rise in rats.

Vascular structural changes in hypertension are proposed to contribute to raised peripheral resistance. Endogenous polyamines (putrescine, spermidine and spermine) have an essential role in cellular growth and may be required in vascular restructuring. We have previously shown raised polyamines in resistance vessels in response to angiotensin II (angII) infusion in the rat and here we examined whether polyamine depletion influences the hypertensive process.

Reversal of the inhibitory effects of HIV-gp120 on CD4+ T cells by stimulation through the CD28 pathway.

The effects of exposure to HIV-gp120 on proliferation and cytokine production by T cell lines were investigated. T cell lines were generated by stimulation of peripheral blood mononuclear cells from several healthy donors with cross-linked anti-CD3 antibodies and IL-2. These T cell lines exhibited the characteristics of Th1 cells, producing IL-2 and interferon-gamma (IFN-gamma), but not IL-4, on stimulation with anti-CD3 antibodies.

Bacterial vaginosis in pregnancy: distribution of bacterial species in different gram-stain categories of the vaginal flora.

Vaginal swabs for microbiological culture were taken from 174 pregnant women whose vaginal flora had been evaluated by Gram's stain; 50 had grade III flora (bacterial vaginosis, BV), 50 grade II (intermediate), 41 had vaginal flora graded as abnormal which then reverted to grade I (revertants) and 33 had normal flora (controls). The aim was to determine whether bacterial species isolated from women with grade II flora differed from those with grade III flora. Isolation of Lactobacillus spp.

Regulation of epidermal growth factor receptor synthesis by ovarian steroids in human endometrial cells in culture.

The aim of this study was to investigate the effect of oestradiol and progesterone on epidermal growth factor (EGF) binding in human endometrial glands and stromal cells in culture. Monolayers of isolated glands or stromal cells were cultured for 6 days in the presence or absence of steroids which were replenished daily. Binding of 125I-labelled EGF was measured in the presence and absence of unlabelled EGF.

A double blind, placebo-controlled study to assess the effect of famciclovir on virus replication in patients with chronic hepatitis B virus infection.

This is the first double-blind controlled study of famciclovir, an oral antiviral agent, as potential therapy for chronic hepatitis B virus (HBV) carries. A fall of more than 90% in HBV DNA levels was noted in six of 11 evaluable patients treated with a 10 day course of oral famciclovir. Further studies with more prolonged therapy are ongoing.

Pathogenesis of chronic hepatitis C and associated clinical manifestations.

In 20% of patients exposed to hepatitis C virus, infection is transient but, after a few months, the patient remains susceptible to infection with the same strain. Protective immunity is short-lived. This suggests that recovery is related to the cellular immune response, which presumably lyses infected cells, and that the need during recovery for a virus-neutralizing anti-envelope response, is transient.

Does moderate aerobic activity have a stimulatory effect on 24 h resting energy expenditure: a direct calorimeter study.

This study was designed to establish whether moderate aerobic exercise (2 h at 30-35% VO2 max) in lean non-athletic male adults had a prolonged stimulatory effect on energy expenditure while at rest. Four weight maintaining male adults had their 24 h energy expenditure measured by direct calorimetry on four separate occasions. During the 24 h in the calorimeter each subject received a diet which in total supplied 35 kcal (146 kJ) per kg body weight.

The cost of treatment of psychiatric emergencies: a comparison of hospital and community services.

This study aimed to compare the costs of treatment by community-based and hospital-based psychiatric services. The design entailed random allocation of patients presenting with psychiatric emergencies over a subsequent 3-month period to one of two services, followed by retrospective quantification of service use and its cost for each group. One hundred patients with emergency presentations to the psychiatric service via the Accident and Emergency Department, liaison psychiatrist and approved social worker were included in the study.

Survey of difficult to contain and treat children and adolescents.

Child psychiatrists and paediatricians are faced by a number of disturbed children and adolescents who become a major treatment challenge due to a combination of their dangerous and/or disruptive behaviour and the unavailability of resources. Paediatricians and psychiatrists in one regional health area were questioned about the number of such children and adolescents under 18 years of age seen over a 20 month period. The response rate was 44% (86/194 specialists approached).

Sevoflurane degradation by soda lime in a circle breathing system.

Sevoflurane is degraded by soda lime to a vinyl ether commonly referred to as compound A. We measured the concentration of compound A in the circle breathing system of 31 patients receiving sevoflurane anaesthesia. Inspiratory and expiratory gas samples were analysed using gas chromatography and flame ionisation detection.

Heterogeneity of human intestinal spirochaetes demonstrated by one-dimensional polyacrylamide gel electrophoresis of proteins visualised by (35)S-methionine labelling and Coomassie blue staining.

The relatedness of strains of a human intestinal spirochaete was investigated by comparison of electrophoretic protein profiles produced by Coomassie Blue staining of proteins separated by polyacrylamide gel electrophoresis (PAGE) of lysed organisms and by examination of autoradiographs following PAGE of lysed (35)S-methionine-labelled organisms. A wide diversity of strains was revealed by both techniques but clustering of strains was different by the two methods. These findings support the view that the human intestinal spirochaetes comprise a group of bacteria of considerable heterogeneity.

Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomised controlled trial.

Objective: To determine whether prepregnancy pituitary suppression of luteinising hormone secretion with a luteinising hormone releasing hormone analogue improves the outcome of pregnancy in ovulatory women with a history of recurrent miscarriage, polycystic ovaries, and hypersecretion of luteinising hormone.

Design: Randomised controlled trial.

Setting: Specialist recurrent miscarriage clinic.