Advantages of branched peptides in serodiagnosis. Detection of HIV-specific antibodies and the use of glycine spacers to increase sensitivity.

The reactivities of antibodies with branched and monomeric peptides were compared in ELISA assays. We found that lower amounts of antibodies could be detected with branched peptides than with monomeric peptides. This was observed with a monoclonal antibody and with antibodies in the sera of various HIV-positive individuals. To investigate the physical aspects of branched peptides important for the observed increase in sensitivity, glycine spacers of different lengths were introduced between the branched lysine core and the epitope reacting with the monoclonal antibody. The effect of the number of glycine residues, both on the sensitivity of antibody detection and on the amount of branched peptide needed to produce a given signal, was studied and the optimum was found at 4-5 residues. We discuss the basis for these findings and conclude that the routine use of branched peptides for serodiagnosis will give both greater sensitivity and appreciable cost savings.     

Post-marketing surveillance of enalapril: experience in 11 710 hypertensive patients in general practice

Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.7% of patients, though most of these were not thought to be related to the treatment. The incidence rates of death (0.09%), stroke (0.11%) and myocardial infarction (0.15%) were compatible with rates predicted from age, sex and blood pressure considerations. Other events reported were hypotension (0.3%), angioneurotic oedema (0.03%), rash (0.5%), taste disturbance (0.2%) and cough (1.0%). The degree of blood pressure reduction attained was similar to that previously reported from pre-marketing development studies, as was the overall nature and frequency of both serious and non-serious adverse events. The most frequently reported event during enalapril therapy was of an improvement in well-being (19.8%).     

Spectrum of dolichospondylic dysplasia: two new patients with distinctive findings

Dolichospondylic dysplasia (DD) is a rare skeletal dysplasia primarily characterized by tall vertebral bodies and disproportionate short stature. Radiographic manifestations include tall vertebral bodies and gracile bones of the hands. Patients usually have eye and ear findings in addition to borderline mental retardation; however, tall vertebral bodies and slender tubular bones are also seen in the 3-M syndrome. Patients with the 3-M syndrome have a characteristic face with a triangular shape, frontal bossing, a flattened malar region, full eyebrows, a short nose with a bulbous tip, upturned nares, and full lips. We present two unrelated patients who share a distinct phenotype and have tall vertebral bodies, overtubulation of long bones, and short tubular bones of the hands and feet. We discuss the overlapping and distinguishing features between DD and the 3-M syndrome. Patient 1 was a 13-year-old female, and patient 2 was an unrelated adult female. These patients had normocephaly and short stature. They shared a common phenotype consisting of mild malar hypoplasia, a narrowed nasal body with a fleshy tip, full lips, and normal intelligence. In addition, they showed mild hand and foot abnormalities. These two patients lack many of the typical clinical features of both DD and the 3-M syndrome. They share a common phenotype and likely represent a distinct disorder. The spectrum of disorders with tall vertebral bodies as a key feature may include different entities that may be further defined with the characterization of the molecular defect(s).     

Respiratory syncytial virus infection does not increase allergen-induced type 2 cytokine production, yet increases airway hyperresponsiveness in mice

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen-sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines.     

Characterization of a Helicobacter pylori neutrophil-activating protein.

Helicobacter pylori-associated gastritis is mainly an inflammatory cell response. In earlier work we showed that activation of human neutrophils by a cell-free water extract of H. pylori is characterized by increased expression of neutrophil CD11b/CD18 and increased adhesiveness to endothelial cells. The work reported here indicates that the neutrophil-activating factor is a 150,000-molecular-weight protein (150K protein). Neutrophil proadhesive activity copurified with this protein, which is a polymer of identical 15K subunits. Specific antibody, prepared against the purified 15K subunit, neutralized the proadhesive activity of the pure protein and of water extracts obtained from different strains of H. pylori. The gene (napA) for this protein (termed HP-NAP, for H. pylori neutrophil-activating protein) was detected, by PCR amplification, in all of the H. pylori isolates tested; however, there was considerable strain variation in the level of expression of HP-NAP activity in vitro. HP-NAP could play an important role in the gastric inflammatory response to H. pylori infection.     

Randomised controlled trial of pelvic floor muscle exercises and manometric biofeedback for erectile dysfunction.

BACKGROUND: The pelvic floor muscles are active in normal erectile function. Therefore, it was hypothesised that weak pelvic floor muscles could be a cause of erectile dysfunction.AIMS: To compare the efficacy of pelvic floor muscle exercises and manometric biofeedback with lifestyle changes for men with erectile dysfunction.Design of study: Randomised controlled trial.SETTING: The Somerset Nuffield Hospital, Taunton, United Kingdom.METHOD: Fifty-five men with erectile dysfunction (median age 59.2 years; range 22-78 years) were enrolled from a local urology clinic. Of these, 28 participants were randomised to an intervention group and engaged in pelvic floor exercises, as well as receiving biofeedback and suggestions for lifestyle changes. Twenty-seven controls were solely advised on lifestyle changes. Baseline, 3- and 6-month assessments were: erectile function domain of International Index of Erectile Function (IIEF), Partner's International Index of Erectile Function (PIIEF), Erectile Dysfunction-Effect on Quality of Life (ED-EQoL), anal manometry, digital anal measurements, and clinical assessment by an assessor blind to treatment allocation. After 3 months, the control group were transferred to the active arm.RESULTS: At 3 months, compared with controls, men in the intervention group showed significant mean increases in the erectile function domain of the IIEF (6.74 points, P = 0.004); anal pressure (44.16 cmH(2)O, P <0.001); and digital anal grades (1.5 grades, P <0.001). All showed further improvement in these outcomes at 6 months. Similar benefits were seen in men of the control arm after transfer to active treatment. A total of 22 (40.0%) participants attained normal function, 19 (34.5%) participants had improved erectile function, and 14 (25.5%) participants failed to improve.CONCLUSION: Pelvic floor muscle exercises and biofeedback are an effective treatment for men with erectile dysfunction.     

Social work and general practice: A report of a three-year attachment

Much has been written about social worker/general-practitioner collaboration, particularly about conflict of roles, differing functions, avenues of accountability, and problems of distributing scarce resources.

We suggest that if the two professions are to work more comfortably together, then it is imperative that both also share the despair, hopelessness, anxiety, and anger that are the occupational hazards of each. We suggest ways in which doctors and social workers can look at the pain their patients are suffering to the benefit of the patient and their own working relationship.

     

Electrodermal Lability and Visual Information Processing

Individual differences in electrodermal lability have been related to performance in vigilance and reaction time tasks. The goal of the present study was to employ an "additive factors" approach to identify the stages of information processing that might underlie these effects. Nineteen labile and 17 stabile subjects performed a choice reaction time task in which a visual imperative stimulus was presented under two conditions of intensity (presumed to affect the speed of pre-processing operations) X three conditions of degradation (which influences later encoding processes related to feature extraction). Measures of both reaction time and movement time were obtained. The major findings were: (a) labile subjects had faster reaction times than stabiles, and (b) lability interacted significantly with stimulus degradation. Labiles also tended (p less than .10) to have faster movement times. This pattern indicates that labiles and stabiles differ in the performance of later encoding operations, and possibly in the speed of motor processes as well. However, they do not appear to differ in the early pre-processing of the simple physical attributes of a stimulus.