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Biomedical subjects

B J Ransil

Publications and source records attributed to B J Ransil.

At least 91 records · Page 5Linked to original sources

In vivo aortic muscle cell growth kinetics. Differences between thoracic and abdominal segments after intimal injury in the rabbit.

Focal proliferation of smooth muscle cell (SMC) is an integral part of atherosclerotic plaque formation: characterization of regional variation in SMC growth kinetics is therefore important to the understanding of atherogenesis. SMC growth kinetics of rabbit abdominal and thoracic segments were compared. Rabbit aortas were denuded of endothelium and the animals killed after 3H-thymidine and Evans blue injections at 0 to 48 days after denudation. Incorporation of 3H-thymidine into both aortic segments peaked at 48 hours; no detectable incorporation occurred in the first 24 hours. Abdominal segment DNA specific activity (SA, dpm/micrograms DNA) and total kinetic activity (TKA, dpm/0.1 mm internal elastic lamina) at 48 hours were significantly greater than values for the thoracic aorta. Abdominal SA and TKA curves decreased exponentially after the 48-hour peak and parallel thoracic levels after day 7. SA and TKA values for each segment reflected the subsequent SMC intimal growth rates as measured morphometrically. Therefore, both segments share similar growth kinetic characteristics; however, the abdominal response to initimal injury is greater than the thoracic and leads to greater myointimal proliferation. The difference in response to injury in the two segments suggests regional variation in SMC's which are phenotypically similar.

Animals↗

Vascular smooth muscle cell kinetics: a new assay for studying patterns of cellular proliferation in vivo.

A new quantitative assay for studying the kinetics of vascular smooth muscle cells in vivo is reported. The assay was used to determine the specific activity of DNA from rabbit aortic smooth muscle cells stimulated to grow by removal of the endothelial layer. The specific activity of the DNA was correlated with the rate of tritiated thymidine incorporation as measured by autoradiography and with the rate of DNA synthesis as estimated by direct measurement of cellular proliferation. Smooth muscle cells exhibit a 24-hour latent period in vivo prior to DNA synthesis; the synthesis peaks at 48 hours and then rapidly declines. The decline in DNA synthesis is not related to endothelial regrowth, and may be of homeostatic significance in limiting luminal stenosis. The assay offers a rapid and reliable alternative to autoradiographic and morphometric techniques for evaluating growth kinetics and growth regulation in vivo.

Animals↗

Q-aTc interval as a clinical indicator of hypercalcemia.

The charts were reviewed of more than 200 patients discharged from the hospital between 1972 and 1977 with a diagnosis implying abnormal calcium metabolism. When all other variables known to affect the Q-T interval were eliminated, serum calcium concentrations on 65 occasions in 39 patients were found to correlate significantly (P less than 0.001 or better) with the following electrocardiographic intervals: Q-aTc (beginning of QRS complex to apex of T wave), Q-oTc (beginning of QRS complex to onset of T wave) and Q-Tc (beginning of QRS complex to end of T wave). Of these, the Q-aTc interval was the more easily and precisely measured at elevated calcium levels and exhibited the strongest correlation (P less than 0.0001) over the range of calcium levels measured. The relation was linear and could be used to estimate serum calcium levels from measured Q-aTc intervals. For a Q-aTc interval of 0.29 second or less (range 0.23 to 0.29) the serum calcium was estimated to +/- 1.9 mg/dl with 95 percent confidence. For a Q-aTc interval of 0.27 second or less, the correspondence with hypercalcemia in the study series was 90 percent or better. When all other factors known to affect the Q-T interval are ruled out, the shortening of the Q-aTc interval appears to be a useful clinical indicator of hypercalcemia.

Calcium↗

Sustained effect of orally administered isosorbide dinitrate on exercise performance of patients with angina pectoris.

The efficacy of oral isosorbide dinitrate was evaluated in nine hospitalized patients with chronic angina pectoris and positive maximal bicycle exercise tests. Patients were randomized double-blind to receive either 20 mg of isosorbide dinitrate or placebo on successive days after a control maximal upright bicycle exercise test. On each day hourly exercise tests were performed for 4 hours after drug administration to an end point of fatigue or angina pectoris. Mean systolic blood pressure 4 hours after the administration of isosorbide dinitrate was 25 mm Hg less than the control value (P less than 0.001). The values for resting heart rate and exercise-attained heart rate-blood pressure product were not significantly different from the values after placebo. The duration of exercise was prolonged (P less than 0.025) for at least 3 hours, and less ST depression (P less than 0.01) was observed up to 3 hours after the administration of isosorbide dinitrate compared with control values. The demonstration of sustained imporved exercise performance and previously described hemodynamic effects with the use of higher doses suggests that adequate blood levels of isosorbide dinitrate or mononitrate metabolites may be important for the efficacy of oral organic nitrates.

Administration, Oral↗

A prospective study of Doppler pressures and segmental plethysmography before and following aortofemoral bypass. Implications for predicting success and for adopting a uniform method of classifying arterial disease.

To determine the clinical and hemodynamic changes associated with aortofemoral bypass, 44 limbs of 31 patients underwent segmental plethysmography (PVR) and Doppler pressures (DSP) before operation, immediately after operation, and again at 6 months. Prior to operation patients were separated by angiographic criteria into two groups: aortoiliac segment disease alone (AI) (n = 22), and aortoiliac and femoropopliteal segment disease (AIFP) (n = 22). At 6 months the two groups were subdivided into four groups based on relief (oSx) or lack of relief (+Sx) of symptoms. Before operation the only significant difference between the four groups was a higher thigh PVR and calf DSP in the AI + Sx group. Six month PVR values in AIoSx were improved nearly twofold over preoperative measurements at the thigh and calf, but at the thigh level only for AIFPxSx. DSP was increased at all three levels in both AI and AIFPoSx groups. No hemodynamic improvement occurred in either the AI or the AIFP + Sx groups. A derivative index of PVR (thigh-ankle/15 mm) or the FPomega was significantly lower in AIFOsSx before operation. There was a significant disparity between classification by hemodynamics and by symptoms prior to operation which lessened somewhat after operation. These studies suggest that success or failure can be predicted before operation in AIFP by FPomega, and arterial disease should be classified by a combination of symptoms, angiography, and hemodynamics.

Angiography↗

The effect of sodium salicylate on acute Chagasic myocarditis in C3H mice.

In two separate experiments, six months apart, utilizing different controls and different methods, sodium salicylate in anti-inflammatory doses was administered by gavage to mice with acute Chagasic myocarditis (T. cruz) at the onset of parasitemia. Sodium citrate was used as a control. Animals given salicylate showed decreased blood trypanosome counts and myocardial pseudocyst formation, both absolutely and in the rates of formation. Decreased inflammation and necrosis were associated with salicylate therapy. Survival of the animals was not increased by treatment. The effects cannot be explained by sodium ion concentration, the technique of gavage, or any factor except the presence of salicylate ion.

Animals↗

Variability of 24-hour urinary creatinine excretion by normal subjects.

Creatinine excretion was studied in eight healthy males who collected 54 to 97 24-hour urine specimens. Significant differences among subjects in mean creatinine excretion were only partly explained by differences in body weight and surface area. Considerable daily within-subject variation in creatinine excretion during normal activity was found. Standard deviations were from 10.5 to 14.4 per cent of the mean, and ranges varied from 50 to 79 per cent of the mean. Day-to-day variation appeared to be time dependent rather than entirely random, and could not be explained by unreliability of the assay technique or by incomplete collections. Creatinine excretion values were normally distributed in seven of eight subjects. Individual variation from day to day limits the value of urinary creatinine excretion as an index of the completeness of 24-hour urine collections.

Adult↗

Inhibition by iodine of the release of thyroxine from the thyroid glands of patients with thyrotoxicosis.

A method has been devised which is free of many of the shortcomings of serial epithyroid counting techniques as an index of the rate of thyroid hormone secretion. By means of this method, the effect of treatment with Lugol's iodine on the rate of thyroidal secretion of thyroxine (T(4)) has been assessed in eight patients with thyrotoxicosis due to diffuse or multinodular goiter. The technique involves administration of a tracer dose of inorganic (125)I followed several days later by an intravenous tracer dose of (131)I-labeled T(4). Serial observations of serum protein-bound (PB) (125)I and (131)I are accompanied by frequent measurements of endogenous serum T(4) (T(4)-(127)I) concentration. Regardless of whether or not its administration was anteceded and accompanied by the administration of large doses of methimazole, iodine induced a rapid decrease in serum T(4)-(127)I concentration which could not be explained by an increase in the peripheral turnover of T(4), as judged from the metabolism of the (131)I-labeled hormone. Hence, the decreased serum T(4) concentration could only have resulted from decreased secretion of the hormone by the gland. Analyses of specific activity relationships between PB(125)I or T(4)-(127)I and PB(131)I made possible estimations of the extent to which iodine had decreased the rate of secretion of T(4). From such analysis, and in view of other considerations, it is concluded that the rapid decrease in T(4) secretion induced by iodine is not the result of an acute, sustained inhibition of T(4) synthesis, but rather results from an abrupt decrease in the fractional rate of thyroidal T(4) release.

Adult↗

Evidence for systematic temporal variation in 24-hour urinary creatinine excretion.

Five hundred fifty-seven 24-hour urinary creatinine specimens from eight healthy males collected in six-day sequences separated by two- to ten-week intervals over six to ten months were analyzed for factors contributing to the large observed standard deviation and range (14% and 50% of the total mean, respectively). Subject means correlated significantly with weight and surface area. Between-sequence differences were significantly greater than within-sequence differences in all subjects. Statistically significant linear and/or curvilinear time dependences were found in each subject. Elimination of subject variation and pooling yielded one cycle of a biphasic function, approximately 12 months in duration, oscillating about the mean with an amplitude approximately 6% of the mean; the maximum and minimum exhibited a seasonal correspondence. Upper limits to sources of eror are estimated as measurement +/- 3%, biological +/- 6%, mixed biologic-temporal +/- 6%, and random +/- 5%.

Adult↗

The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected beta-amyloid in the rat brain.

The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (beta AP1-40) was studied in rats. A synthetic peptide with the reverse sequence (beta AP40-1) or the vehicle alone were injected in the contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that beta AP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. beta AP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that beta AP1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease.

Acetylcholinesterase↗

Utilization and effectiveness of a hospital autologous preoperative blood donor program.

The utilization and effectiveness of a hospital preoperative autologous blood donation program were analyzed. Over 16 months, 180 donors, or 11.6 percent of eligible patients (those undergoing elective surgical procedures where blood was routinely crossmatched), were enrolled in the program. They donated an average of 2.2 units of red cells, or 59 percent of the mean order of 3.7 units. Donations were completed in 17.9 days, leaving 10.7 days between the last donation and hospitalization. Of all scheduled donations, 25.5 percent were cancelled due to deferrals; 47.8 percent of patients were deferred at least once. Most patients were able to donate a unit of blood weekly, with minimal drops in hematocrit (mean 3.2%). The reaction rate, 4.8 percent, was comparable to figures reported for homologous donors. Nearly two-thirds of participants used no homologous blood during their hospitalization: 28.6 percent used no blood whatsoever, and 36.9 percent used only autologous components. Including released autologous components subsequently administered to other recipients, transfused autologous red cells were 2.1 percent and fresh-frozen plasma (FFP) 7.2 percent of the hospital's blood supply. Although the high deferral rate complicated the administration of the program, this complication was offset by the demonstration of donor safety, reduction in the proportion of patients who used homologous blood, and the contribution of autologous blood components to the hospital's blood inventory.

Adolescent↗

Autologous versus homologous donors. Evaluation of markers for infectious disease.

Autologous blood donations may provide a new source of blood when components not used by the donors are deemed suitable for homologous use. However, the risk of transfusion-transmitted diseases form such donors has not been evaluated. We compared the prevalence of infectious markers and rate of abnormal responses to a confidential donor ballot in autologous donors from two blood collection programs, one blood center and one hospital-based, to corresponding homologous blood programs. The incidence of abnormal test results in autologous donors for HIV antibodies (either Western blot confirmed or repeatedly reactive, unconfirmed), HBsAg, ALT, and anti-HBc were not statistically different from homologous rates. The incidence of STS abnormalities in autologous donors was statistically significant, although all positive results were biologic false positives. The rate of abnormal responses to the confidential ballot was statistically significant only in autologous donors whose collections were already determined to be unsuitable for homologous use due to medical history problems. Although the data do not address infectious complications in transfusion recipients, this study offers no evidence that autologous blood components are less safe than their homologous equivalents.

Blood Donors↗