The practical assessment and management of bladder outflow obstruction

The initial management of bladder outflow obstruction typically related to benign prostatic hyperplasia (BPH) falls to a large extent within the remit of general practice. Referral onwards to secondary care typically arises following the failure to respond to conservative measures or when complications have supervened; the most significant of which is urinary retention. In the hospital setting, anaesthesia, constipation and immobility are the common precipitants. What follows is a practical guide to the management of these situations and provides an overview of the conservative, medical, minimally invasive and surgical treatments available.     

Potent gp120-like neurotoxic activity in the cerebrospinal fluid of HIV-infected individuals is blocked by peptide T.

The envelope protein of the human immunodeficiency virus (gp120) causes neuronal death in developing murine hippocampal cultures or rat retinal ganglion cells. In HIV-infected individuals, gp120 released from HIV-infected macrophages or other cells in the brain has been proposed as the etiology for the pathophysiology of AIDS central nervous system (CNS) disease by diffusing to act at a distance to cause damage and/or death to neighboring neurons. In this study, 28 cerebrospinal fluid (CSF) samples from HIV-infected individuals (79% were WR stage 1 and 2) and neurological disease controls were tested, blind to the investigator, for the presence of in vitro neuronal killing activity. Neurotoxic activity was detected with peak effects at a 1:10(5) dilution in CSF from 9/18 HIV-infected individuals and 1/10 neurological disease controls. Thus half of CSF from early stages of HIV disease are characterized by the presence of neurotoxic activity which is not present in control CSF (Fischers exact test, P < 0.05). The neuronal toxicity by patient CSF could be prevented by peptide T (1 nM). A monoclonal antibody to mouse CD4, RL.172, also attenuated or prevented CSF-induced neuronal killing in all four CSF samples tested. In addition, an antiserum to peptide T previously shown to bind gp120 and neutralize both infectively and direct gp120 neurotoxicity, neutralized the CSF factor. gp120, or a modified small fragment, is suggested to be the responsible toxic molecular entity. These results may be relevant to the pathophysiology of HIV-related CNS disease and the mechanism by which peptide T causes improvements.     

A VIP antagonist distinguishes VIP receptors on spinal cord cells and lymphocytes

Vasoactive intestinal peptide (VIP) is a neuropeptide which also interacts with cells of the immune system. The paucity of specific VIP receptor antagonists has hampered studies of possible receptor heterogeneity and of VIP function. To aid in achieving these goals, a new VIP antagonist, a hybrid between neurotensin and VIP, has been synthesized. This peptide interacted with VIP receptors on spinal cord cells with an affinity 10-fold greater than VIP itself. In contrast, 1000-fold higher concentrations of the antagonist were required to displace labeled VIP from its receptor on lymphoid cells as compared to VIP itself, suggesting VIP receptor heterogeneity between immune and spinal cord cells.     

Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks,chromosomal instability,and reduced life span in mice

The Brca2 tumor-suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51-interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51-interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2(lex1)) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2(lex1) mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2(lex1) mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy-terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51.     

Measuring maternal mortality: An overview of opportunities and options for developing countries

Background  

There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015.     

Telephone versus postal surveys of general practitioners: methodological considerations.

BACKGROUND. High response rates to surveys help to maintain the representativeness of the sample. AIM. In the course of a wider investigation into counselling services within general practice it was decided to assess the feasibility of increasing the response rate by telephone follow up of non-respondents to a postal survey. METHOD. A postal survey was undertaken of a random sample of 1732 general practitioners followed by telephone administration of the questionnaire to non-respondents. The identical questionnaire was administered by telephone to a separate random sample of 206 general practitioners. RESULTS. Of 1732 general practitioners first approached by mail, 1683 were still in post of whom 881 (52%) completed the postal questionnaire and a further 494 (29%) the telephone interview. Of 206 general practitioners first contacted by telephone, 197 were still in post of whom 167 (85%) completed interviews. Compared with doctors first approached by mail, those first approached by telephone were significantly more likely to report having a partner with a special interest in psychiatry (P < 0.01); and a general practitioner, practice nurse or health visitor who worked as a counsellor (P < 0.01 in each case). A comparison of doctors first approached by telephone with those who completed telephone interviews after failing to respond to the postal questionnaire showed that postal non-respondents were significantly less likely to report having a general practitioner, practice nurse, health visitor or community psychiatric nurse who worked as a counsellor (P < 0.01 in each case). CONCLUSION. These findings suggest that non-response to the postal survey was associated with lack of activity in the study area. Telephone administration of questionnaires to postal non-respondents increased response rates to above 80% but, as telephone administration enhanced the reporting of counsellors, a social desirability bias may have been introduced.     

Leucocyte Migration Test and Hypersensitivity to Glafenin

The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin.     

In utero exposure to antiandrogens alters the responsiveness of the prostate to p,p'-DDE in adult rats and may induce prostatic inflammation

DDE is an environmental pollutant with antiandrogenic properties. Following administration to pregnant rats, DDE was shown to cause feminization in the male offspring at the neonatal stages but did not affect the pubertal growth of accessory sex organs. In this study, we examined the potential of in utero exposure to antiandrogens to alter the responsiveness of the male rats to subsequent DDE challenge. Pregnant Long-Evans rats were dosed by gavage from Gestation Day 14 to 18 at 0, 10 (low dose), or 100 (high dose) mg DDE, or 40 mg flutamide/kg body wt (bw)/day (in utero treatment). At approximately 80 days of age, the male offspring from each of the four in utero treatment groups were divided into two groups. One group received the adult treatment of four daily gavage administrations of DDE at 70 mg/kg bw (adult treatment), while the second group served as the adult treatment control (adult control). The in utero treatment resulted in 18, 31, and 53% reductions of ventral prostate weights at approximately 85 days of age compared to the control for the low- and high-dose DDE and flutamide groups, respectively. These results suggest that the in utero antiandrogen treatments produced a latent effect on prostate growth that became pronounced only in the postpubertal stage. The in utero treatment also altered the responsiveness of the prostate to the adult treatment, indicated by a significant reduction in ventral prostate weight that was seen only in the control group of the in utero treatment but not in the other groups. The in utero treatment was also associated with expression of testosterone-repressed prostatic message-2 in the adult ventral prostate. In addition, a few prostates in the high-dose DDE- and flutamide-treated groups of the in utero treatment were found to have chronic suppurative prostatitis. While other types of hormonal manipulations have been shown to incite similar responses in rat prostate, the possible linkage between in utero antiandrogen treatment and prostatic inflammation needs to be further evaluated.