Studies on the optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for preparation of a safe and potent pertussis vaccine

The optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for the production of a safe and potent whole cell pertussis vaccine were investigated. Two bacterial harvests from B. pertussis strain 10536 were treated with glutaraldehyde, each with 0.025, 0.05 and 0.1% concentrations of glutaraldehyde for 10, 60 and 120 min. The nine types of glutaraldehyde-inactivated pertussis vaccine (GIPV) and conventional heat-inactivated pertussis vaccine (HIPV) preparations made from two bacterial harvests were comparatively evaluated for the mouse weight gain test (MWGT), potency, and the histamine-sensitization (HS) and leucocytosis-promoting-factor (LPF) tests. The minimum period for killing the B. pertussis organisms with glutaraldehyde was>10 min for 0.025%, 10 min for 0.05% and 5 min for 0.1% concentration. The average loss in opacity varied from 5 to 10% for GIPV preparations and was 14% for HIPV preparations. The GIPV preparations except those inactivated with 0.025% glutaraldehyde for 10 min (GIPV-A) were much less toxic than the HIPV preparations in the MWGT. The GIPV-A preparations did not pass the MWGT. The GIPV preparations were also much less toxic in HS and LPF tests than the HIPV preparation. The potency of GIPV preparations inactivated with 0.05% glutaraldehyde for 10 min (GIPV-D) was similar to that of HIPV preparations. The prolonged treatments with glutaraldehyde reduced the potency. The GIPV-D preparation with good potency and less toxicity was found to be inactivated with glutaraldehyde under optimal conditions. All the preparations were innocuous in the abnormal toxicity test.     

Smoking--a major cause of polycythaemia.

The importance of smoking in the aetiology of polycythaemia has been assessed in a group of patients referred to a general haematology clinic. All patients with true and relative polycythaemia (excluding those with polycythaemia rubra vera) were studied. Of the 21 such patients evaluated, 14 were smokers and had raised carboxyhaemoglobin levels and had no other demonstrable cause for their polycythaemia. The commonest physiological abnormality in these patients was a raised red cell mass combined with a low plasma volume. Six of the 14 patients were able to reduce their smoking with subsequent improvement in their haematocrits. These results suggest that smoking is a major cause of polycythaemia in an unselected series of referrals to a general haematology clinic. The early identification of these patients may be useful in planning therapy.     

Analysis of the factors involved in cosmetic failure following excision of the eye.

We graded the overall cosmetic outcome of 56 patients who required excision of the eye. Each patient was then subjected to a more detailed analysis of the specific abnormalities associated with excision of the eye in order to discover which are associated most consistently with a poor cosmetic result. The only factor showing a statistically significant variation with the overall cosmetic outcome was the degree of upper lid sulcus. Taken individually the other features showed no statistically significant correlation. When each finding was scored, the averaged sum of the scores was related to cosmetic outcome with statistical significance. A method of quantifying orbital volume loss is described.     

Increasing evidence of the rise of cancer in workers exposed to vinylchloride.

The results of a cancer mortality study among workers employed in the production of vinylchloride and polyvinylchloride between 1939 and 1977 suggest a significant increase in deaths from malignancies of the lymphatic and haemopoietic tissues. Mortality for tumours of the digestive organs, respiratory system, bone and connective tissues, brain, and skin are also greater than in the general population. There were no registered cases of liver angiosarcoma in the study cohort during the follow up period. The risk of cancer was highest among the workers exposed to concentrations of VC of 300 mg/m3 and more who had worked at the plant for 15 to 19 years. The relatively high number of leukaemias and lymphomas in the study group and the absence of liver angiosarcomas probably reflects specific carcinogenic action of different doses of vinylchloride.     

Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.