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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 991 records · Page 55Linked to original sources

Insulin-mediated and non-insulin-mediated metabolic effects of gastroenteropancreatic peptides in type I and type II diabetes.

In this brief review of regulatory function of gastroenteropancreatic peptides in control of intermediary metabolism in normal and diabetic states, with and without mediation by insulin and/or glucagon, a variety of possible mechanisms have been described. It is apparent that the pharmacologic actions of the peptides identified in various locations provide models for multiple routes of delivery and modes of action of effectors in this control system. Examples already exist of each of the hypothetical mechanisms illustrated in the scheme in Figure 4. It is clear that a great deal of study will be necessary in identification of the active agents and assessment of their importance in the physiology of intermediary metabolism. With respect to the possible pathophysiologic roles of regulatory peptides of the gastroenteropancreatic system other than insulin and glucagon, a number of considerations of Type I and Type II diabetes have been raised. The balance of the evidence suggests that Type I diabetes may be viewed as an insulin deficiency syndrome, so that physiological replacement with insulin may be expected to result in correction of the metabolic abnormalities. Nevertheless, the difficulty of physiologic replacement treatment, which may call for portal delivery of insulin, is well recognized, and abnormalities secondary to insulin deficiency even in "well-treated" Type I diabetes may be compounded by the effects of gastroenteropancreatic peptides other than insulin, exerted through the various mechanisms discussed. In Type II diabetes mellitus, current understanding of the pathophysiology is much less complete and no convincing description of the etiology exists. The various metabolic actions of the gastroenteropancreatic peptides, and their interactions with other endocrine, paracrine and nervous regulatory mechanisms, represent a dauntingly complex control system. The elucidation of this system can provide fertile ground for the development and testing of hypotheses for the pathophysiology of disordered metabolism in Type II diabetes mellitus.

Blood Glucose↗

Prophylactic lymphadenectomy for B16 melanoma in C57/BL6 mice: survival based on size and heterogeneous variant of the primary.

Survival following prophylactic lymphadenectomy by hip disarticulation in mice with three B16 melanoma variants was studied. C57/BL6 mice inoculated with viable tumor cells (F1, F10, and BL6) into the left hind foot pad were randomized to wide excision (WE) of the primary tumor alone or wide excision plus prophylactic lymphadenectomy (WE plus PL) at 1-, 2-, 3-, 4-, and 5-mm primary tumor sizes (each group, N = 6). Overall survival time was improved by WE plus PL. A significant survival advantage and cure was apparent for the F1 and F10 variants with primary tumor sizes of 2 and 3 mm (F1, 2 and 3 mm, P less than 0.001; F10, 2 mm, P less than 0.006; 3 mm, P less than 0.001), but not for the BL6 variant. Prophylactic lymphadenectomy provides a therapeutic advantage in mouse melanomas of intermediate size in two of the three variants of B16.

Animals↗

Comparison of leuprolide and diethylstilbestrol for stage D2 adenocarcinoma of prostate.

In a controlled, prospective, randomized clinical trial, we evaluated the safety and efficacy of leuprolide, a superactive analog of luteinizing hormone releasing hormone, given in a single subcutaneous injection dose of 1 mg per day, versus diethylstilbestrol (DES) 3 mg per day by mouth in patients with previously untreated Stage D2 prostatic adenocarcinoma. Eleven leuprolide patients and 10 DES patients were evaluated for therapeutic response. Eighty per cent of patients in each group experienced subjective improvement in bone pain and urinary obstructive signs and symptoms. Although the pooled percentages of complete, partial, and stable objective responses were greater for the leuprolide group than the DES group, the sums of the percentages of complete and partial objective responses were comparable for both treatment groups during the first forty-eight and sixty weeks of the study, respectively. In addition, patients not responding to leuprolide generally experienced no benefit with crossover to DES, and vice versa. Serious adverse reactions were more common in the DES group and included fatal myocardial infarction, arrhythmia, deep venous thrombosis, and gynecomastia. Vasomotor flushing, disease flare, and injection site irritation occurred most often in leuprolide patients, but did not require modification or discontinuation of treatment.

Acid Phosphatase↗

The importance of surgical evaluation of patients with "Turner-like" sex chromosomal abnormalities.

Children with "pure" gonadal dysgenesis do not require abdominal explorations to remove their gonads, because the risk of development of malignancy is minimal. Children with "mixed" gonadal dysgenesis, who usually present with sexual ambiguity, need to have gonadectomy because of the high incidence of malignancy in these gonads. We present four children (three adolescents and one two year old) who presented with minimal somatic anomalies, who did not have sexual ambiguity. The prominent features were primary amenorrhea and short stature in the adolescents, and minor dysmorphic features in the small child. On the basis of these physical features, complete genetic evaluation was carried out, and a Y chromosome or an unidentifiable fragment was identified in all four cases. At exploration, bilateral genital streaks were found, and were removed. In addition to the usual microscopic features of the streaks, Leydig cells and tubular structures resembling rete testis were seen in all the gonads. In one gonad, a gonadoblastoma was found. Since this type of gonad is "at risk" for the development of gonadoblastoma, the need for complete genetic evaluation of all females with "Turner-like" chromosomal abnormalities, although phenotypically female, is emphasized. If a Y chromosome or any unusual fragment is identified, exploration should be carried out, and any gonad that is not a normal ovary should be removed.

Adolescent↗

Overflow urinary incontinence due to carbamazepine.

We describe the first well documented case of overflow urinary incontinence owing to prolonged carbamazepine treatment for temporal lobe seizures. Carbamazepine increased the bladder capacity to 1,700 ml. and was accompanied by symptoms of urgency and frequency. After carbamazepine was discontinued and the patient was given primidone the voiding symptoms disappeared. Post-voiding catheterization of the bladder showed minimal residual urine volume. In a review of urological adverse reactions of anticonvulsant drugs that are effective in the management of temporal lobe seizures we found that only primidone and phenobarbital have not been convincingly associated with such side effects. However, phenytoin and clonazepam have been linked with urinary incontinence, and valproic acid with enuresis.

Adolescent↗

Delineation of peripheral and coronary detail by intraoperative angioscopy.

In this study, the development of intraoperative angioscopy, the value of the information obtained, and the problems encountered with the procedure are reported. Eight angioscopes, 1.5 to 2.8 mm in diameter, with a line resolution of greater than 0.4 mm at 5 mm, were used. One-hundred ten angioscopic investigations were performed in 46 patients; 24 at peripheral bypass surgery and 22 at coronary artery bypass surgery. These included 68 arteries, 28 new anastomoses, six old grafts, five laser angioplasties, and three in situ vein grafts. The most important finding was that angioscopic data provide information not available from probes or angiography. Angioscopic findings were responsible for a change in surgical procedures in 12 patients (26%) including three anastomotic revisions, three alterations in graft site placement, and two repeat thrombectomies. The most significant technical problems were lack of steerability and insufficient irrigation, which resulted in poor angiographic images. Further technical development is necessary before routine intraoperative angioscopy is practical. Nevertheless, if these problems are resolved, angioscopy will provide unique, high-resolution information which can directly alter surgical therapy.

Angioplasty, Balloon↗

Physical capacities of sightless adolescents.

Nineteen sightless children and adolescents aged between 11 and 18 years were tested for physical condition and performance. Their residential school provided four adapted physical education lessons a week, lasting for 45 minutes. Their physical condition and performance was found to be comparable with that of normal sighted children. A supplementary training programme consisting of three extra 60-minute sessions a week for four months to test whether their fitness could be developed further produced only minor changes. It is concluded that a well-designed, adapted physical education programme, in four sessions per week, is sufficient to ensure a normal level of physical condition for sightless children.

Adolescent↗

A scanning and transmission electron microscopic examination of Rickettsia tsutsugamushi-infected human endothelial, MRC-5, and L-929 cells.

Monolayers of primary human endothelial cells were infected with the Karp strain of Rickettsia tsutsugamushi and examined by scanning and transmission electron microscopy. The results were compared with those obtained with similarly infected L-929 and MRC-5 cells and with uninfected cells of all three types. The rickettsiae grew to slightly higher titers in the human endothelial cells. Transmission electron microscopy revealed significant changes in the host cell organelles; a reduction in ribosome-coated endoplasmic reticulum and in Golgi activity, swelling of mitochondria, and an increase in vacuolation within the cytoplasm. Since human endothelial cells are known to retain their in vivo structural and functional qualities when cultured in vitro, it is likely that these effects are similar to those which occur during the infectious process in human scrub typhus.

Animals↗

A light and electron microscopic examination of Ehrlichia sennetsu in cultured human endothelial cells.

Umbilical cord-derived human endothelial cells were used for the propagation of Ehrlichia sennetsu. Scanning electron microscopic studies revealed numerous pleomorphic ehrlichiae extending from the surface of infected human endothelial cells. Transmission electron microscopic examination of the cells revealed E. sennetsu-induced cytopathic changes at the ultrastructural level. Ehrlichiae of variable size, shape and density were located individually and in clusters enclosed within membrane lined vacuoles. The cultured human endothelial cell provides an optimal environment for the growth of E. sennetsu and is a suitable in vitro model for the study of the cytopathic effects of this human pathogen.

Animals↗

Pharmacokinetics of piperacillin in hospitalized patients.

Piperacillin is an extended-spectrum penicillin active against Pseudomonas. It has been documented to be effective in the treatment of complicated urinary tract infections and urosepsis. Much of the pharmacokinetic information available is obtained from normal subjects. The purpose of this study is to evaluate piperacillin pharmacokinetics in hospitalized patients. Ten clinically stable hospitalized urology patients were given 4 grams of piperacillin intravenously in a single dose. Serial blood samples were then obtained and serum piperacillin concentrations were determined by high performance liquid chromatography. The following pharmacokinetic parameters (mean +/- SD) were determined: half-life = 1.09 +/- 0.31 h, elimination rate constant = 0.69 +/- 0.22 h-1, volume of distribution = 0.36 +/- 0.13 l/kg, total body clearance = 0.230 +/- 0.054 l/h/kg. These parameters are comparable to those obtained in normal subjects except for the volume of distribution which is slightly higher than that reported in healthy volunteers. Pharmacokinetic information obtained in healthy subjects may, therefore, be applied to the clinically stable hospitalized urology patient. However, changes in pharmacokinetic characteristics may be found in the critically ill patient with compromise in hemodynamics and significant third spacing of fluid.

Adult↗

Does dehydration contribute to retarded fetal growth in rats exposed to alcohol during gestation?

An earlier study showed that pregnant rats given ethanol in drinking water exhibited a significant degree of dehydration. The objective of the present study was to determine whether dehydration alone contributes to fetal growth retardation in alcohol treated rats. Female Sprague-Dawley rats were divided into 4 dietary groups. Group 1 (alcohol) received 20% ethanol in drinking water for four weeks prior to mating and 30% alcohol in drinking water throughout pregnancy and a stock diet ad libitum. Group 2 (pair-fed) was given an amount of food equal to that consumed by the alcohol group with the alcohol isocalorically substituted by corn starch. Water was available ad libitum. Group 3 (pair-water) was given an amount of food and water equal to that consumed by the alcohol animals. Group 4 (ad libitum) was given food and water ad libitum. On day 21 of gestation body weights of the alcohol exposed fetuses were significantly lower than those of the other three treatment groups. The difference in fetal body weights between the pair-fed and pair-water groups was not significant. Placentas were significantly heavier in the alcohol group than in the pair-fed and pair-water groups. Maternal plasma osmolality was significantly higher in the alcohol treated rats when compared to the pair-fed and ad libitum controls but not the pair-water group. No significant differences were seen in fetal plasma osmolality among the four treatment groups. It is concluded that dehydration does not contribute significantly to retarded fetal growth in rats given alcohol in drinking water as the sole source of fluid prior to and during gestation.

Animals↗

Effects of serotonin on cerebellar Purkinje cells are dependent on the baseline firing rate.

Serotonin applied iontophoretically to cerebellar Purkinje cells elicited one of three effects: inhibition (62% of the cells), biphasic response (27%), and excitation (11%). This study describes a correlation between the spontaneous discharge rate of Purkinje cells and the action of serotonin. Purkinje neurons that responded to serotonin with an increase in firing rate had a significantly slower pre-drug firing frequency (40 Hz) than those cells that were suppressed by serotonin (51 Hz). Furthermore, it was shown that with increasing firing rates the proportion of excitations decreased, and the proportion of depressions increased. A quantitative comparison revealed a statistically significant correlation between the spontaneous discharge rate of cells displaying excitation and the magnitude of the excitatory response. On several occasions, the direction of the Purkinje cell response to serotonin reversed following a decrease or increase in the baseline spontaneous rate. Glutamate- or asparate-induced excitations elicited an augmentation of serotonin-mediated inhibition and in some cases a reversal of excitation to inhibition. Likewise, the lowering of neuronal activity by the continuous application of glycine augmented excitation and reduced and reversed serotonin inhibitions. Preliminary results from experiments in which various receptor antagonists were tested against serotonin actions suggest that the effects of serotonin occur, at least in part, at postsynaptic sites on Purkinje cells. These results strongly suggest that the overall qualitative effects of serotonin is to set Purkinje cells at a preferred firing rate. In this sense, the term biaser or modulator may best describe the role of serotonin in the cerebellum.

Action Potentials↗