A diagnostic algorithm for male genital oedema

Male genital oedema can be defined as swelling or the appearance of swelling of the scrotum and/or the penile shaft and prepuce. Despite the various causes of genital oedema reported in the published work, a concise approach to the evaluation and management has not been sufficiently addressed.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Cancer incidence and mortality around the Pan Britannica Industries pesticide factory, Waltham Abbey.

OBJECTIVES: To examine the incidence and mortality of cancer near the Pan Britannica Industries factory, Waltham Abbey, after reports of a possible cluster of all cancers and brain cancer in the vicinity. METHOD: Small area study of cancer incidence 1977-89, and mortality 1981-92, within a 7.5 km radius of the factory site. Postcoded cancer registrations and deaths in the study area were extracted from national data sets held by the Small Area Health Statistics Unit and compared with expected numbers computed by applying national rates stratified for age, sex, and deprivation to the local population (1981 and 1991 censuses). Observed/ expected (O/E) ratios were examined from 0-1 km and 0-7.5 km of the plant, and tests applied for a decline in relative risk with distance up to 7.5 km. RESULTS: There were 12,859 incidence cancers (1977-89) from 0-7.5 km (O/E ratio 1.04; 95% confidence interval (95% CI) 1.02 to 1.06) and 385 from 0-1 km (O/E 1.10; 1.00 to 1.22). There was an excess of skin melanoma from 0-1 km based on 11 cases (O/E 2.13; 1.06 to 3.80), and an excess from 0-7.5 km of cancer of the lung, stomach and pancreas combined, and prostate (O/Es ranged from 1.09 to 1.13). Only the findings from lung cancer were suggestive of a decline in risk with distance, especially in the later period (1982-9). There were 9196 cancer deaths (1981-92) from 0-7.5 km (O/E 1.04; 95% CI 1.02 to 1.06) and 308 from 0-1 km (O/E 1.24; 1.11 to 1.39); and 25507 non-cancer deaths (O/E 1.02; 1.01 to 1.04) from 0-7.5 km and 745 (O/E 1.14; 1.06 to 1.22) from 0-1 km. There was evidence of a decline in mortality with distance for all cancers combined, lung cancer (P = 0.001 for each), and colorectal cancer (P < 0.05), and also for non-cancers (P = 0.001). Proportional mortality analyses suggested a decline in risk with distance for lung cancer (P = 0.003) but not for all cancers or the site specific cancers examined. There was no evidence of an excess in the incidence or mortality from brain cancer. For cancer mortality in the inner-most wards, the findings were, for the most part, well within the range of variation across the region as a whole. CONCLUSIONS: The study provides limited and inconsistent evidence for a localised excess of cancer in the vicinity of the PBI plant. At present, further investigation does not seem warranted other than continued surveillance of mortality and cancer incidence in the locality.     

A preliminary, clinical pharmacological assessment of L-659,066, a novel alpha 2-adrenoceptor antagonist.

1. The alpha 2-adrenoceptor antagonist activity of L-659,066 has been investigated in studies of healthy normotensive males to whom doses of up to 8 mg were administered by short intravenous infusion. 2. L-659,066 had no effect on basal levels of glucose or insulin and no significant effect on the plasma glucose and plasma insulin time profiles following an intravenous glucose load. 3. There was a non-significant trend for plasma noradrenaline concentrations to be higher after L-659,066. 4. L-659,066 had no significant effects on mood changes or on physical symptom scores. 5. There were no significant effects on supine blood pressure but there were consistent increases in heart rate both supine (non-significant) and erect (P < 0.01). 6. Ex vivo platelet aggregation studies confirmed alpha 2-adrenoceptor antagonist activity with L-659,066 but with an approximately 9-fold lesser potency than yohimbine. 7. While L-659,066 has alpha 2-adrenoceptor antagonist activity these results suggest that it is unlikely to present a new therapeutic approach for improving insulin release.     

Anti-peptide antibodies to cathepsins B, L and D and type IV collagenase. Specific recognition and inhibition of the enzymes.

Anti-peptide antibodies were raised against synthetic peptides selected from the sequences of human cathepsins B and L, porcine cathepsin D and human type IV collagenase. Sequences were selected from the active site clefts of the cathepsins in the expectation that these would elicit immunoinhibitory antibodies. In the case of type IV collagenase a sequence unique to this metalloproteinase subclass and suitable for immunoaffinity purification, was chosen. Antibodies against the chosen cathepsin B sequence were able to recognize the peptide but were apparently unable to recognise the whole enzyme. Antibodies against the chosen cathepsin L sequence were found to recognise and inhibit the native enzyme and were also able to discriminate between denatured cathepsins L and B on Western blots. Antibodies against the chosen cathepsin D sequence recognised native cathepsin D in a competition ELISA, but did not inhibit the enzyme. Native type IV collagenase was purified from human leukocytes by immuno-affinity purification with the corresponding anti-peptide antibodies.