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Biomedical subjects

M Cole

Publications and source records attributed to M Cole.

At least 145 records · Page 8Linked to original sources

Improvement of the bioavailability of the anti-herpes virus agent BVDU by use of 5'-O-alkoxycarbonyl derivatives with increased metabolic stability.

(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was found by HPLC analysis to be rapidly metabolized in mice and in liver homogenates from mouse and man to the antivirally inactive (E)-5-(2-bromovinyl) uracil (BVU) but was comparatively stable in blood from both species. Of a series of 5'-O-alkoxycarbonyl derivatives of BVDU, the 5'-O-tert.-butoxycarbonyl derivative (BRL 37000) was the most stable in mouse and human blood and liver homogenates, neither its ester bond nor its N-glycosidic linkage being readily cleaved enzymically. Oral administration of BRL 37000 and the 5'-O-ethoxycarbonyl derivative (BRL 36101) to mice gave prolonged serum concentrations of BVDU and delayed the appearance of BVU compared with the BVDU control. BRL 36101 was more active than BVDU when administered orally to mice infected cutaneously with herpes simplex virus type 1.

Animals↗

The significance of cardiotocographic monitoring in pregnancy complicated by intrauterine growth retardation and prematurity.

Intrauterine growth retardation is a condition of chronic fetal compromise. The most accurate method of fetal assessment in this condition is by serial cardiotocography. In pregnancy associated with intrauterine growth retardation, abnormal cardiotocography with spontaneous decelerations may be an indicator of imminent fetal death in utero. Delivery should be effected immediately if the fetus is at a gestation where viability is probable.

Adult↗

Structure-activity relationships amongst beta-lactamase inhibitors.

Using a variety of beta-lactamases including those from Escherichia coli (TEM-1), Enterobacter cloacae P99 and Staphylococcus aureus the inhibition profiles (I50 values) were determined for various groups of compounds including penicillins, penicillanic acid derivatives (sulphone and beta-halo substitutions), olivanic acids and clavulanic acid derivatives including substituted ethers and amines. Some of the latter compounds had higher activity than clavulanic acid with and without preincubation of enzyme with inhibitor but they still had poor activity against the P99 enzyme. Improvements in activity against Class I cephalosporinases were obtained with some derivatives of clavulanic acid but this was usually achieved at the expense of activity against clavulanate susceptible beta-lactamases. The olivanic acids had the highest activity against the widest range of beta-lactamases.

Bacteria↗

The quality of life after major thermal injury in children: an analysis of 12 survivors with greater than or equal to 80% total body, 70% third-degree burns.

Twenty-one children admitted between December 1981 and May 1985, with greater than 80% total body surface area burn (TBSAB), underwent total excision and grafting of all of their wounds within 72 hours of injury. Twelve survivors (with an average TBSAB of 89%, 82% third degree) were studied in detail describing the length of hospital stay (77 +/- 10 days), number of operative procedures (7.8 +/- 0.8), total blood loss (12 +/- 2 blood volumes), the number of patients who experienced septic episodes (three), the number of patients who required amputation (four), range of motion, degree of scarring, ability to perform daily activities, and psychological adjustment. Physical impairment, according to standard scales, was approximately 60%; however, 50% of the children old enough to be tested were completely independent in activities of daily living. One third of the children had excessive fear, regression, and neurotic and somatic complaints, but all of them showed remarkable energy in adapting to their disabilities. We conclude that the final outcome, for these patients, can only be assessed as they achieve late adolescence and young adulthood.

Activities of Daily Living↗

The effect of malnutrition on caries development and saliva composition in the rat.

The purpose of this study was to investigate the effect in rats of malnutrition on caries development and on some antibacterial substances in saliva. By gastric intubation, two groups of ten rats each were fed a liquid basic diet (100% diet), and two similar groups were fed the basic diet diluted with an equal volume of water to contain 50% of the nutrients of the basic diet (50% diet). One group on undiluted and one group on the diluted basic diet were offered sucrose as a supplement by mouth 17 times daily, using a programmed feeding machine, and the other two groups were offered starch in a similar manner. The extent and depth of the caries lesions were five times greater in the low-nourished (50% diet) sucrose group in comparison with the group given the undiluted diet supplemented with sucrose. The 50% diet group ate more frequently from the offered supplement. The 50% diet induced lower salivary lactoperoxidase activities, and there was an additive effect of starch as supplement. Higher concentrations of sIgA were found in the saliva of animals fed the 50% diet supplemented with sucrose than in those fed sucrose and the 100% diet. Significantly greater levels of sIgA and IgG were found in the saliva from the 50% diet-sucrose group than in the 50% diet-starch group. Plaque scores differed slightly but not significantly between the groups. The starch group receiving 100% diet showed a slightly lower level of S. mutans infection as compared with the 50% diet-starch group; the caries scores in the starch groups did not differ.

Animals↗

Hereditary dysphasic dementia and the Pick-Alzheimer spectrum.

Hereditary dysphasic dementia is described in terms of its clinicopathological, ultrastructural, and transmissibility characteristics. Its mode of inheritance is autosomal dominant, and its clinical manifestations of progressive dementia and severe dysphasic disturbances are expressed in late adulthood. Complete neuropathological examination of four patients reveals findings typical for Pick's disease (asymmetrical focal cerebral atrophy), Alzheimer's disease (profuse neuritic plaques), and paralysis agitans (neuronal depigmentation, depletion, and Lewy body formation in substantia nigra) in addition to a striking but nonspecific spongiform degeneration of superficial cortical layers. This unique combination of gross morphological and histopathological features qualifies hereditary dysphasic dementia as a distinct entity, but its precise relationship to the well-recognized adult cortical dementias has been difficult to establish by conventional classification methods. This disorder and other unusual dementing illnesses may be best considered as part of a Pick-Alzheimer spectrum of cortical neuronal degenerations.

Aged↗

Affinity of temocillin for Escherichia coli K-12 penicillin-binding proteins.

Temocillin is a 6 alpha-methoxy penicillin which shows poor affinity for the penicillin-binding proteins (PBPs) of Escherichia coli K-12 when tested by competition with [14C]penicillin G or [125I]penicillin X. When the reaction conditions for the radiolabeled penicillin used in this procedure were modified by lowering the temperature (2 degrees C) and reducing the incubation time (3 min), temocillin showed a much higher affinity for PBP-3 and improved affinity for the other PBPs, with the exception of PBP-2. Direct labeling procedures with [14C]temocillin also showed that the compound had affinity for PBPs 1a and 3. These results are more consistent with the effects of temocillin on the morphology of E. coli than the poor affinity values obtained by the classical competitive procedure. Reasons for the disparity between these assay systems are discussed.

Anti-Bacterial Agents↗

Boxers--computed tomography, EEG, and neurological evaluation.

During the last three years, 40 ex-boxers were examined to determine the effects of boxing in regard to their neurological status and the computed tomographic (CT) appearance of the brain. Thirty-eight of these patients had a CT scan of the brain, and 24 had a complete neurological examination including an EEG. The results demonstrate a significant relationship between the number of bouts fought and CT changes indicating cerebral atrophy. Positive neurological findings were not significantly correlated with the number of bouts. Electroencephalographic abnormalities were significantly correlated with the number of bouts fought. Computed tomography and EEG of the brain should be considered as part of a regular neurological examination for active boxers and, if possible, before and after each match, to detect not only the effects of acute life-threatening brain trauma such as subdural hematomas and brain hemorrhages, but the more subtle and debilitating long-term changes of cerebral atrophy.

Adolescent↗

The beta-lactamase stability of amoxycillin with the beta-lactamase inhibitor, clavulanic acid.

The stability of low concentrations of amoxycillin in the presence of clavulanic acid (potassium salt) was determined for a wide range of clinically important beta-lactamases including the staphylococcal and TEM plasmid mediated enzymes. Even with enzyme preparations which completely hydrolysed the amoxycillin within a minute, clavulanic acid provided significant protection. The time course of the protection of amoxycillin reflected the time dependent action of clavulanic acid.

Amoxicillin↗

Plasma angiotensin II and aldosterone in unselected diabetic patients.

The concentrations of angiotensin II and aldosterone in plasma were measured in 101 consecutive unselected out-patient diabetic patients and in fifty-three normal controls. The concentration of angiotensin II was similar in diabetics without complications and controls, but was significantly lower in patients with hypertension or peripheral neuropathy. In contrast, plasma aldosterone was not reduced in any sub-group. The concentrations of angiotensin II and aldosterone were positively correlated in controls, in diabetes without complications and in hypertensive diabetics, but this relationship was not found in patients with peripheral neuropathy, retinopathy or nephropathy. There was no evidence of overt hypoaldosteronism in any of the diabetic patients. No individual aldosterone concentration was below the range found in controls and no plasma angiotensin II concentration is reduced in patients with specific diabetic complications such as neuropathy, plasma aldosterone may be maintained by factors other than the renin-angiotensin system. This would explain why hypoaldosteronism is rare among unselected diabetics.

Adolescent↗