Biomedical subjects
Publications and source records attributed to A Collins.
Tissues acquired at autopsy from four patients with MS and biopsies from one patient with a probable diagnosis of MS were probed for the presence of OC43 RNA. This human coronavirus was not detected.
Forty-four patients with non-small cell carcinoma of the lung were treated every 3 weeks with vinblastine (4 mg/m2/day iv X 2) and cisplatin (20 mg/m2/day iv X 3). Of the 28 patients with metastatic disease, eight (29%; 90% confidence interval of true response, 17%-47%) achieved objective response, for a median duration of 27 weeks. Median survival in this group was 47 and 28 weeks for responders and nonresponders, respectively. Of the 16 patients with advanced regional disease, 11 (69%; 90% confidence interval of true response, 49%-86%) achieved objective response. Thirteen of these patients received consolidation radiotherapy (4500 cGy/25 fractions/5 weeks), with a boost of 1000 cGy/5 fractions/1 week in those patients who achieved response. In the three patients who did not receive radiotherapy, two died during the induction phase, one from grade 4 leukopenia and sepsis and the second from unrelated factors. The third patient had systemic progression of disease during induction chemotherapy. Six patients experienced overall improvement in their chemotherapy response from the radiotherapy. Two patients who did not respond to the chemotherapy achieved partial response with irradiation. Four patients who had partial response to the chemotherapy achieved complete response with irradiation, and seven patients had no further change in their degree of response to irradiation. The overall median survival of this group was 81 weeks. Maintenance chemotherapy was not given. After radiotherapy, the site of first failure was outside the radiation field in nine of 13 patients (69%). Hematologic toxicity was dose-limiting. Other toxic effects that were not dose-limiting included nephrotoxicity, neurotoxicity, and acute nausea and vomiting. In the patients with advanced regional disease, there was no increase in the radiation toxicity attributable to the chemotherapy. We conclude that: (a) this dose schedule of vinblastine and cisplatin has reproducible activity in non-small cell carcinoma of the lung; (b) the response and median survival of patients with advanced regional disease are superior to those of patients with metastatic disease; and (c) in patients with advanced regional disease, treatment with chemotherapy followed by radiotherapy yielded an overall response rate of 81% (90% confidence interval of true response, 60%-93%) and improved survival compared to a similar group of patients studied by others receiving radiotherapy alone. We recommend further testing of this concept.
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U.v. damage to the DNA of HeLa cells induces the polymerisation of ADP-ribose, but only if repair synthesis is inhibited so that incomplete repair sites (i.e., DNA breaks) accumulate to abnormally high levels. 3-Aminobenzamide greatly reduces the ADP-ribose polymerisation response. However, 3-aminobenzamide does not reduce the rate of rejoining of the accumulated breaks when the inhibition of repair synthesis is reversed. Therefore, rejoining of these DNA breaks (in contrast to the rejoining of other kinds of break) appears not to depend on activation of polynucleotide ligase by ADP-ribosylation.
The formation of macroaggregates weighing up to 9 g was observed in optimal additive red cells. Such aggregates, with a mean wet weight of 3 g, formed progressively during storage and were present in up to 85% of units. They were composed of leucocyte and platelet debris, together with some fibrin. Macroaggregates formation was halved by less stringent centrifugation during preparation and was reduced by use of an optimal additive system in which the additive solution contained citrate. Extra mixing during transfer of the additive solution only delayed aggregate formation. Partial leucocyte depletion or addition of 200,000 KIU of the enzyme inhibitor aprotinin did not prevent macroaggregate formation.
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The results of a population survey of blood pressure in the adult residents of two highland villages in the Asaro Valley, Papua New Guinea are reported. The survey was conducted in 1983 as part of a wider epidemiological investigation of non-communicable disease in Papua New Guinea. Response to the survey was 95%, and 308 subjects were examined. Population estimates of both systolic and diastolic blood pressures were low and there was a virtual absence of hypertension, as defined by internationally recommended criteria. There was no evidence of a rise in blood pressure with age, and the association between blood pressure and indices of obesity was weak. These findings are consistent with previous studies of blood pressure in traditional Papua New Guinean societies. The two villages differed with respect to their degree of modernisation. An unexpected finding was that in both sexes, both systolic and diastolic blood pressures were higher in the more traditional village. In each case, these differences were consistent across the three age groups examined, and they could not be explained by differences between the villages with respect to the indices of obesity. Analysis of variance showed that the higher blood pressures in the more traditional village were most unlikely to be due to chance (p less than 0.001). The explanation for this finding remains obscure.
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A diabetes survey was conducted in the highlands of Papua New Guinea in June 1983. Two villages in the Asaro Valley, Eastern Highlands Province, were selected for study. The subjects were of Melanesian ancestry, and were free of Austronesian genetic admixture. The response rate was 95% and 308 subjects were examined. As defined by current WHO criteria, there was a total absence of non-insulin-dependent diabetes (NIDDM) in these communities. The prevalence of impaired glucose tolerance (IGT) was 2%. These estimates of glucose intolerance are the lowest yet to be reported from the Pacific, using currently accepted diagnostic criteria and standardized survey methods. The 2-hr plasma glucose and insulin concentrations were positively correlated in both sexes. Of the two villages studied, one had undergone a greater degree of acculturation than the other. Both the total distribution and the mean value of 2-hr plasma glucose concentration were lower in the more traditional village, and these findings could not be explained by differences in age or obesity between the two communities. Mean 2-hr plasma insulin concentration did not differ significantly between the two villages, and was very low in both. The results of this study support the theory that Melanesians free of Austronesian genetic admixture are relatively, though not absolutely resistant to the deleterious influence of acculturation upon glucose tolerance seen in other Pacific populations. However, the notion that in this population cultural change has been insufficient, or of too recent onset for a deterioration in glucose tolerance to be manifest cannot be excluded.
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Aphidicolin, a potent and specific inhibitor of eukaryotic DNA polymerase alpha, has been reported to inhibit repair DNA synthesis in ultraviolet-irradiated, normal human fibroblasts but not in HeLa cells. By the use of assays for repair other than the measurement of repair synthesis, it is shown here that repair in HeLa cells is in fact susceptible to aphidicolin. Severe inhibition of DNA repair, with failure of individual repair events to be completed, and a smaller number of lesions removed, can occur even though repair synthesis continues.
A series of 248 consecutive patients undergoing cardiac surgery were examined in a prospective study of post-transfusion hepatitis in a single British centre. Patients received a total of 1796 units of blood or blood products (mean blood transfusion 6.28 units per patient). During five to 30 days after operation 38 of the patients showed an increase in serum transaminase activities. There was no serological evidence for fresh infection by hepatitis A or B virus, cytomegalovirus, Epstein-Barr virus, or herpes virus in any of these patients. The increase in transaminase activities was unexplained and reached over 100 IU/l (normal less than 40 IU/l) in six patients. The incidence of acute short incubation post-transfusion non-A, non-B hepatitis was therefore thought to be 2.4%. These six patients had normal liver function six months after transfusion but a further two of the surviving 228 patients had raised serum transaminase activities at six months. In one of these, liver biopsy disclosed chronic persistent hepatitis; in the other, alcoholic liver disease was suspected. The incidence of significant chronic liver disease after blood transfusion possibly attributable to a non-A, non-B hepatitis agent was therefore only 0.4%.
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To assess the role that action on sodium channels may play in the physiological effects of cocaine and to obtain information on the structure-activity relationships of this action, cocaine, norcocaine, N-allynorcocaine, (+)-pseudococaine, (-)-pseudococaine, (+/-)-allococaine, (+/-)-allopseudococaine, ecgonine, ecgonine methyl ester, O-benzoylecgonine and atropine were tested for their effects on sodium channels. The method employed was a sodium channel specific equilibrium 22Na+ uptake assay with rat brain membrane homogenates. All of the compounds listed with the exception of the ecgonines were found to be single affinity competitive inhibitors of veratridine activation of sodium channels. Ecgonine showed no inhibition at concentrations as high as 10(-3) M while ecgonine methyl ester and O-benzoylecgonine showed inhibition only at very high concentrations. The order of inhibition potencies was found to (+)-pseudococaine congruent to norcocaine congruent to N-allynorcocaine greater than cocaine greater than (-)-pseudococaine congruent to (+/-)-allopseudococaine greater than (+/-)-allococaine greater than atropine greater than O-benzoylecgonine greater than ecgonine methyl ester greater than ecgonine. This ordering of potencies is in good agreement with published reports of the local anesthetic potencies of these agents.
The long-term consequences of acute lung injury during critical growth periods of the lung were evaluated by inducing mild bronchiolitis with nitrogen dioxide (NO2) in 3-day-old (newborn) and 21-day-old (young) hamsters. Hamsters were exposed to 30 ppm NO2 for 7 days. Age-matched animals exposed to room air served as controls. Lung volumes, static deflationary pressure-volume curves, mean linear intercept, and internal surface area were measured when the animals reached 1 yr of age. Newborns exposed to NO2 showed an increased volume at 25 cm H2O pressure (V25) adjusted for body weight, a decreased transpulmonary pressure at 60% of V25, and an increased mean linear intercept when compared with control animals. The internal surface area was less than that in the control animals; the difference approached significance. In the young exposed group there were no differences for any measurements when compared with the control group. These data indicate that a mild injury imposed during the newborn period may result in physiologic and morphometric changes that simulate mild emphysema in the mature animal.
This is a case report of a male infant who was hypotonic at birth, failed to maintain his respiratory effort, and despite ventilation died at 27 days of age. Infrequent fetal movements were noted and the possibility of a neuromuscular disorder was suggested antenatally. Electromyography in the neonatal period was indicative of a neurogenic disorder, but muscle biopsy at 16 days of age showed the characteristic histologic appearance of myotubular (centronuclear) myopathy. There was no family history of muscle disease, and the mother has subsequently given birth to a normal male child. The relationship of the present case to other reports of severe congenital myotubular myopathy is discussed.