DNA polymerase beta mutations in human colorectal cancer.

Increasing numbers of alterations have been found in protooncogenes (e.g., ras, myc), as well as tumor suppressor genes (e.g., p53, Rb) in various types of tumors. The multiple mutations cannot be explained by the spontaneous mutation rate. It has been suggested that mutator phenotypes leading to the accumulation of these mutations may be required in the early stages of tumorigenesis. To test this hypothesis, the entire coding region of DNA polymerase beta, a repair enzyme, mRNA from colorectal tumors, and corresponding normal mucosa were amplified by polymerase chain reaction, cloned, and sequenced. Mutations in the catalytic domain of DNA polymerase beta were detected in colorectal tumor specimens compared to the normal colorectal mucosa, placenta, and blood samples. Since these mutations changed the structure of polymerase beta, it is expected that the efficiency of the DNA repair system would be impaired and thus may account for the high mutation rate observed in colorectal carcinomas.     

Bancroftian filariasis in Pondicherry, south India--epidemiological impact of recovery of the vector population.

An Integrated Vector Management (IVM) strategy was implemented from 1981 to 1985 in one part of Pondicherry, South India, for the control of the bancroftian filariasis vector Culex quinquefasciatus (the IVM area). The rest of the town (the comparison area) received the conventional larvicidal input. After 1985 both the areas were managed conventionally. The switch to conventional strategy resulted in an increase of vector density in both areas. The microfilaraemia prevalence in humans showed a general decline (P less than 0.05) from 1986 to 1989 only in the IVM area whereas its intensity did not change significantly in either area. While the age-specific rate of gain of infection was generally unchanged in the IVM area, an increase in all age classes was observed after 1985 in the comparison area, where the Annual Transmission Index was high during the previous years. In both areas the rate of loss of infection increased during 1986-9 compared to 1981-6. The results suggest that 3 years is too short a period to relate the changes in entomological parameters to those in the microfilaraemia status of the population.     

Adverse perinatal factors in the causation of sensorineural hearing impairment in young children

The study involves aetiological evaluation of various adverse perinatal causes leading to bilateral sensorineural hearing impairment in children born during the 5-year period of 1981-1985 (inclusive) in the Greater Manchester area of England, United Kingdom. This group comprised over 12% of the total number of hearing-impaired children in the area. Individual possible adverse factors are discussed in the light of present understanding of the pathogenesis and previous reports.     

The effects of prior exposure to silicone on capsule formation, histology, and pressure

Investigations into the effects of prior silicone exposure on subsequent capsule formation around silicone implants assume particular relevance in light of the exponential increase in the medical application of polymers such as silicone. The inert nature of silicone has been in question with regard to its effects on the immune system, specifically whether or not it may act as a hapten or antigen. The present study analyzes the effects of prior silicone exposure on subsequent capsule formation, histological consistency, and pressures when an animal is reexposed to a silicone implant. Twelve female Lewis rats (body weight 250 g) were randomly divided into two groups. Group 1 (n = 6) rats were subcutaneously injected with 2.5 ml of Freund's Complete Adjuvant, Group 2 (n = 6) rats were injected with an equal volume of adjuvant sonicated with silicone gel. At 4 weeks a gel-filled silicone implant was placed subcutaneously in each animal. Capsule pressures were obtained at 4 months and the capsules from 3 rats from Group 2 were excised and examined microscopically. Pressures were measured again at 8 months and all remaining capsules were excised and examined. No statistically significant differences were noted when comparing two profiles over time between silicone-exposed and nonexposed animals in regard to capsule thickness or capsule pressure. However, capsule pressures were significantly lower at 8 months than at 4 months in both groups (p less than 0.034). In this model, significant reductions in capsule pressure were noted in both groups over time, but prior exposure to silicone did not appear to alter capsule histology, thickness, or pressure.     

Pharmacokinetics and Inflammatory Fluid Penetration of Clinafloxacin

A single 200-mg dose of clinafloxacin was given orally to each of nine healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h in the case of urine). The mean maximum concentration in plasma was 1.34 μg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the inflammatory fluid was 1.3 μg/ml at 3.8 h postdose. The mean elimination half-life of clinafloxacin in plasma was 5.65 h. The overall penetration into the inflammatory fluid was 93.1%, as assessed by determining the ratio of area under the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24 h and 71.8% by 48 h postdose.     

Cardiac injuries--a clinical and autopsy profile

One hundred two patients sustaining cardiac injuries over a 4-year period were analysed to highlight the natural history of the cardiac injuries. There were 45 blunt, 36 stab, and 21 gunshot injuries. The injury involved the ventricle in 85, atrium in seven, pulmonary artery in five cases, and resulted in crush injury to the heart in the remaining five cases. Thirty-three patients (32.3%) died on the scene and 58 (56.9%) died during the transportation. Only 11 patients (10.8%) reached the hospital alive, and ten of these patients survived following thoracotomy and repair of the cardiac injury. The factors influencing the natural course of cardiac injury were analysed: 2.2% of patients with blunt cardiac trauma reached the hospital alive compared to 19.4% with stab and 14.3% with gunshot injuries; ventricular injuries had a greater prehospital mortality compared to atrial or pulmonary artery injuries; 11.3% of patients sustaining injury to right ventricle reached the hospital alive compared to 3% of those with left ventricular injuries. These data emphasize the need for rapid transport, immediate recognition, and aggressive surgical management, to make a favourable impact on the natural history of cardiac injuries.     

Extraperitoneal closure of colostomy in children.

In 12 children colostomy wound closure was undertaken with liberal extraperitoneal mobilisation of the bowel. In all the cases adequate length of the colonic loops could be achieved for resection of the colostomy and end to end anastomosis. There was only minor wound infection in 3 cases. There was no faecal fistula nor any postoperative intestinal obstruction.     

Reconstruction of the external carotid artery

The external carotid artery (ECA) is an underestimated but important collateral to the cerebral hemisphere and eye in patients with severe disease of the internal carotid artery. Fifteen symptomatic patients with total occlusion of the internal carotid artery underwent ECA reconstruction. Ipsilateral ECA reconstruction was performed upon all patients with no mortality or neurologic deficits. Contralateral disease of the carotid artery was noted in 11 and required correction in seven patients. Follow-up study of the patients ranged from one to 68 months (a mean of 26.8 months) after operation. Vertebrobasilar symptoms persisted in two patients, both with contralateral disease. One of these patients successfully underwent extracranial-intracranial bypass. One ipsilateral and one contralateral stroke occurred during follow-up study, both in patients with contralateral disease. Eleven patients were alive and asymptomatic at last follow-up examination. Symptomatic selected patients with occlusion of the internal carotid artery and ECA stenosis or cul-de-sac formation should be considered for operation. ECA reconstruction is associated with little morbidity and three-fourths of the patients remain asymptomatic. A high incidence of contralateral disease of the carotid artery is present. Extracranial-intracranial bypass should only be considered when symptoms persist after correction of contralateral disease of the carotid artery and any ECA lesions.