Mutagenic and chemotherapeutic activity in L1210 leukemia of several monofunctional alkylating agents.
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Alkylating Agents↗
Biomedical subjects
J Webster
Publications and source records attributed to J Webster.
Creatinine excretion over 24 hours as a measure of body composition or of completeness of urine collection.
Continuous collections of urine for up to 3 weeks from obese patients on a meat-free low-energy diet showed fluctuations in creatinine excretion so that the coefficient of variation was 8.7-34.4 per cent. Urine creatinine excretion was poorly correlated with measures of lean body mass such as density, body water or body potassium. Under the conditions of our study creatinine excretion is not a reliable indicator of either lean body mass nor the completeness of urine collection. We also conclude that the increased lean body mass in obese women contains a relatively small proportion of muscle.
Body Composition↗
Comparative rating of consultation performance: a preliminary study and proposal for collaborative research.
Factors governing the appropriateness, reliability and validity of rating scales in the measurement of professional performance are reviewed. The origin and preliminary testing among undergraduated and general practitioners of a brief consultation rating schedule is described.Statistical criteria are proposed for the analysis of ratings, by groups, in the comparison of consultation performance. Using these criteria the capacity of the 10 rating schedule items to discriminate between two contrasting consultations was examined. Each of the items was used at some time by students or doctors to express significant preference for the same consultation; and on this basis all the items are considered to merit inclusion. One item showed highly significant intra- and inter-observer reliability.The schedule is reproduced in full, together with a data-collection document and significance chart, with the aim of encouraging groups of doctors to test the validity of the items in the comparison of other pairs of consultations. It is proposed that future versions of the schedule should reflect the experience of such groups in testing existing items and in defining additional items which satisfy the proposed criteria.
Clinical Competence↗
Quetelet's index (W/H2) as a measure of fatness.
A weight-height index of adiposity should indicate the relative fatness of subjects of differing height unless obesity is itself correlated with height. The average body fat among adult women attending a hospital outpatient clinic for obesity was 40.5 percent of body weight. The height of an unselected series of 286 of these outpatients was found to be similar to that of the general population of women of similar age, which indicates that obesity in adult women is not significantly related to height. Body composition was measured by body density, body water and body potassium in a series of 104 female and 24 male subjects aged 14-60 years. In both sexes density, water and potassium gave progressively higher estimates of body fat (kg), and there was a significant difference between the values by different methods. The average of the estimates by these three methods was taken to be the 'true' value for each individual (F kg). Regression of F/H2 on W/H2 (Quetelet's index) gave a correlation coefficient of 0.955 for women and 0.943 for men. The deviation of the body fat estimated from Quetelet's formula from the 'true' value was not much greater than that when density, water or potassium were used as a basis for estimating body fat. It is concluded that Quetelet's formula is both a convenient and reliable indicator of obesity.
Adipose Tissue↗
Male infertility successfully treated by in-vitro fertilisation.
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Female↗
Influence of arm position on measurement of blood pressure.
A series of measurements of blood pressure in normotensive and hypertensive subjects showed that measurements made with a sphygmomanometer with the arm dependent by the side were consistently higher than those made with the arm horizontal at heart level. The mean difference in a group of 90 hypertensive outpatients was 11/12 mm Hg. Failure to appreciate the importance of arm position may lead to erroneous measurements of blood pressure. This has important implications for clinical practice and research.
Arm↗
Simultaneous determination of chloroprocaine hydrochloride and its degradation product 4-amino-2-chlorobenzoic acid in bulk drug and injection solutions by high-performance liquid chromatography.
A high-performance liquid chromatographic method has been developed for the simultaneous determination of chloroprocaine hydrochloride and its hydrolytic degradation product, 4-amino-2-chlorobenzoic acid. Separation is achieved using a mu-Bondapak C18 column and the eluant, water-acetonitrile-methanol-glacial acetic acid (74:20:5:1) containing 0.05-0.08% (w/v) sodium 1-heptanesulfonate, at a flow rate of 2 mL/min. Benzoic acid and p-nitroacetophenone were used as internal standards. A variable-wavelength UV detector (278 nm) was used for detection of the compounds. The method is simple, accurate, and precise.
Chromatography, High Pressure Liquid↗
Evaluation of an electrothermal atomisation procedure for the determination of lead in potable water.
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Electrochemistry↗
Flurbiprofen interaction with single doses of atenolol and propranolol.
In patients with mild hypertension, flurbiprofen in a dose of 100 mg daily for 7 days attenuated the hypotensive effect of a single dose of propranolol 80 mg but not of atenolol 100 mg. The attenuation was not due to an effect on the pharmacokinetic profile of either propranolol or atenolol. An alternative explanation is required.
Adult↗
Vetting forages for dairy cows.
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Animal Feed↗
Effect of single dose of omeprazole on the gastrointestinal peptide response to food.
The gastrointestinal peptide response to food was assessed in 6 healthy subjects following oral administration of 40 mg omeprazole. There was a small but statistically significant increase in basal plasma gastrin six hours after the dose of omeprazole, but the post-prandial plasma gastrin was not significantly increased. There was no significant effect on basal or post-prandial levels of somatostatin, insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, neurotensin, cholecystokinin, secretin, vasoactive intestinal peptide and gastrin-releasing peptide or blood glucose concentration.
Adult↗
The assessment of cognitive abilities in clinical medicine.
A study to test the hypotheses that discrete cognitive abilities necessary to clinical practice can be identified and their achievement reliably assessed by methods applicable to a large number of students is described. Eight supposedly discrete cognitive abilities related to clinical consultation were defined and the performance of medical students in them tested by short-answer question papers. In addition, knowledge of specific definitions and of therapeutics was examined. The study, conducted over one academic year, involved 222 medical students--102 in the penultimate, and 120 in the final year of their undergraduate course. Marking strictly to a previously agreed schedule was undertaken independently by three examiners; and students' performance in relation to each ability (and area of knowledge) determined. The findings showed intra- and inter-marker reliability to be highly satisfactory; and student performance in any one ability to be independent of that in any other. This suggests that the cognitive abilities chosen are indeed discrete. The importance of cognitive abilities is discussed in relation to education and training in clinical medicine.
Cognition↗
Joint contractures and diabetic retinopathy.
It has been suggested that joint contractures may be an early marker of microangiopathy, especially retinopathy, in diabetic patients. To investigate this possibility, the prevalence of contractures of the finger joints, as assessed by the painted hand technique, was compared in 106 diabetic patients without, and 105 with retinopathy (proliferative in 66%). There was an increased prevalence of contractures in those with diabetes (25.2%) as compared with an age-matched control of 106 subjects (7.5%, P less than 0.01). The prevalence of contractures was similar in those diabetics with and without retinopathy (29.5% v. 20.8%, P less than 0.1), and did not vary with the type of retinopathy. The contracture prevalence rate was also similar in those with a diabetes duration of 5 or more years (retinopathy 29.3%, no retinopathy, 30%) or of similar diabetic duration (retinopathy 20.8%, no retinopathy, 25%). Diabetic control, as assessed by HbA1, was similar in retinopathic patients with or without contractures. We conclude that although finger joint contractures are more prevalent in adult diabetic patients, they are not necessarily a reliable early indicator of the development of retinopathy of any specific type.
Adult↗
Vaccination of piglets against post-weaning "E. coli" enterotoxicosis.
E. coli enterotoxicosis is one of the main causes of neonatal diarrhea in piglets. For their protection against this disease a vaccine has been prepared based on K88 and LT. Pregnant sows were vaccinated, thereby transferring passive immunity to their offspring through colostrum and milk. Protection was obtained in terms of decrease in mortality, occurrence of diarrhea and excretion of enteropathogenic bacteria. Piglets from non-immune sows could be immunized shortly after birth. However, piglets from immune sows vaccinated once after birth failed to show an active antibody response; only by two vaccinations, 4 weeks apart, was an antibody formation induced. From the results presented it is concluded that a proper vaccination schedule makes it possible to immunize piglets from both immune and non-immune sows and induce protection against post-weaning diarrhea.
Animals↗
Biological and biochemical effects of N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea on two transplantable murine colon tumors.
Other investigators have reported that transplantable murine colon Tumor 26 is more sensitive than transplantable colon Tumor 38 to treatment with N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea. The present report presents the results of several kinds of in vivo and in vitro experiments that were performed to compare the effects of this agent upon these two tumors or upon cultured cells derived from them. In the in vivo experiments, data were also obtained for the spleens, colons, and marrow of the host animals. In the in vivo experiments, it was observed that: (a) approximately equal quantities of 14C from the 2-chloroethyl-14C-labeled agent were fixed to the DNA of the two tumors and the three host tissues following a single i.p. injection of the radioactive agent; (b) in all of the tissues examined at 24 hr after treatment, the drug caused greater inhibition of the synthesis of DNA than of the synthesis of RNA or protein, and the extents of inhibition of DNA synthesis were greater at 24 hr after treatment than at 6 hr after treatment; (c) the inhibition of DNA synthesis was slightly greater for Tumor 26 than for Tumor 38; (d) although the extents of inhibition of synthesis of DNA by Tumor 26 and by the colonic mucosa were similar at 24 hr after treatment of the animal, colonic mucosa much more quickly recovered the ability to synthesize DNA; and (e) the agent had no significant effect upon the sizes of the pools of purine and pyrimidine ribonucleoside phosphates. Cultured cells derived from the two tumors retained their tumorigenicity upon reimplantation into mice and their differential sensitivities to the agent, although approximately equal quantities of the 14C of the radioactive agent were fixed to the nuclei of the cells. In the in vitro experiments, the main effect of the agent upon the synthesis of macromolecules was the delayed inhibition of synthesis of DNA by Tumor 26 cells. Several experimental methods yielded evidence that the agent caused strand scission of the DNA of both kinds of cells, and there was more evidence of cross-linking of the DNA of Tumor 26 cells than of Tumor 38 cells. These results are consistent with the possibility that the differences in sensitivity of the two tumors to the agent are due to differences in the extents of cross-linking of the DNA. This explanation would be in agreement with the proposal suggested by other investigators who worked with other experimental systems.
Animals↗
Biological effects and structure-activity relationships of 1,2-dihydropyrido[3,4-b]pyrazines.
The effects of a number of 1,2-dihydropyrido[3,4-b]pyrazines (1-deaza-7,8-dihydropteridines) upon the proliferation and the mitotic index of cultured L1210 cells and upon the survival of mice bearing P388 leukemia were determined. The 1,2-dihydrostructure and amino groups or masked amino groups at positions 5 and 7 were necessary for activity, and various substituents at positions 2 and 3 had considerable influence upon the activity. A number of these pyrazines had significant activity against i.p. P388 leukemia in mice, and several pyrazines were more active than the corresponding oxazines or thiazines in both the in vitro and the in vivo systems. The effects of the pyrazines upon the cultured cells were reversible, and the rate and degree of reversibility were influenced by the substituents at positions 2 and 3. Tests performed with two of the pyrazines yielded results that indicate that these compounds, like the known agent nocodazole, might compete with colchicine for binding to tubulin. Synergistic killing of cultured L1210 cells was obtained with combinations of one of the pyrazines and vincristine.
Animals↗