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Biomedical subjects

C H Barton

Publications and source records attributed to C H Barton.

At least 73 records · Page 4Linked to original sources

Hypomagnesemia and renal magnesium wasting in renal transplant recipients receiving cyclosporine.

Following the adoption and use of cyclosporine as the drug of choice in the management of renal allograft recipients, several cases of symptomatic hypomagnesemia were noted. These observations prompted the current prospective study of serum concentration and urinary excretion of magnesium in 27 renal transplant recipients treated with cyclosporine and prednisone. Relevant laboratory measurements were obtained shortly before and regularly after transplantation. The results were compared with those obtained in a group of 17 allograft recipients treated with azathioprine and prednisone. The cyclosporine-treated patients showed a significant reduction in the serum magnesium concentration and an inappropriately increased urinary excretion and fractional excretion of magnesium, suggesting renal magnesium wasting. The observed hypomagnesemia required magnesium supplementation in nearly all cyclosporine-treated patients. In contrast, azathioprine-treated patients showed normal serum magnesium concentrations and required no magnesium supplementation. In conclusion, administration of cyclosporine in renal allograft recipients appears to be commonly associated with renal magnesium wasting and hypomagnesemia. Therefore, it is recommended that serum levels of magnesium be monitored regularly in renal allograft recipients receiving cyclosporine and that magnesium supplementation be employed as needed to avoid magnesium depletion.

Adult↗

A comparative study of the anti-proliferative effects of calmodulin antagonists in cultured cells--W7 derivatives of improved cytostatic potential.

We have compared the effects of the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalene-sulphonamide (W7) and relatives of the parent compound, modified by substituting the 5-chloro- for an iodo-residue and increasing stepwise the length of the carbon chain from 6 to 12, for their ability to inhibit cell proliferation in tissue culture. These species showed improved specificity and potency, as determined against a calcium calmodulin-dependent beef heart phosphodiesterase in vitro, exhibited time courses of inhibition similar to the parent compound W7, but were more potent at inhibiting DNA synthesis in K562 human leukaemic cells cultured in serum-free medium. The elevation observed in the percentage of cells in G1 of the cell cycle following drug exposure indicated that these drugs, like W7, arrested growth by inhibiting entry of cells into and through S phase. Higher doses of all drugs were irreversibly cytotoxic as determined by the inability of the cells to recover DNA synthetic capacity and to form colonies in soft agar or to recover their normal cell cycle distribution. We also discuss the possible implications of extracellular calmodulin and antagonism thereof on cell proliferation.

Animals↗

Changes in immunoreactive malic enzyme in liver and brown adipose tissue during development of the rat.

There is a good correlation between changes in malic enzyme activity and immunoreactive protein in both hepatic and brown adipose tissue during postnatal development of the rat. Furthermore, the previously observed premature appearance of hepatic malic enzyme during the suckling period, in response to triiodothyronine, can also be achieved through dichloroacetate administration. A combination of triiodothyronine and dichloroacetate induces malic enzyme activity and immunoreactive protein in a synergistic manner, indicating different sites of action in the control of synthesis of hepatic malic enzyme although neither agent was found to affect the level of malic enzyme in brown adipose tissue. There is evidence to suggest that changes in the ability of the liver to express malic enzyme in response to triiodothyronine administration occur early in postnatal life.

Adipose Tissue, Brown↗

Sex-linked changes in immunoreactive glucose-6-phosphate dehydrogenase in rat liver.

The level of hepatic immunoreactive glucose-6-phosphate dehydrogenase protein was found to correlate well with the enzyme activity in adult rats fed the stock laboratory diet in a variety of hormonal conditions. The amount of immunoreactive protein and enzyme activity was 2-fold greater in sexually mature female rats compared with aged matched male animals. However, this difference was absent in diabetic animals, and furthermore although triiodothyronine administration to the diabetic male rat could restore the level of enzyme activity to that of the normoglycaemic animal, it was much less effective in the female animal. In contrast, administration of insulin to the normoglycaemic animal increased the level of glucose-6-phosphate dehydrogenase in the female, but was without effect in the male. These results are discussed in relation to the possible role of thyroid status and steroid sex hormones in the regulation of hepatic glucose-6-phosphate dehydrogenase.

Animals↗

The effect of modified transurethral sphincterotomy on autonomic dysreflexia.

Autonomic dysreflexia continues to be a major problem in spinal cord injury patients. In our report 16 patients with spinal cord lesions above the T6 level and a history of autonomic dysreflexia also had detrusor-sphincter dyssynergia. Of these patients 12 (75 per cent) had evidence of dysreflexia during cystometry. In addition, the dysreflexic response in blood pressure was shown to correlate with the high intravesical and urethral pressures measured during cystometry. Modified transurethral sphincterotomies subsequently were performed on all patients as recommended therapy for detrusor-sphincter dyssynergia. Repeat cystometry revealed significant decreases in intravesical and urethral pressures compared to before sphincterotomy (p less than 0.001) along with an associated significant decrease in blood pressure (p less than 0.01). Other dysreflexic responses also were markedly attenuated. These results suggest an association among detrusor-sphincter dyssynergia, high intravesical and urethral pressures, and autonomic dysreflexia. Our data indicate further that the frequency and magnitude of autonomic dysreflexia can be diminished significantly by modified external sphincterotomy.

Adult↗

Prevention of metabolic alkalosis induced by gastric fluid loss using H2 receptor antagonist.

Gastric fluid loss is a common cause of metabolic alkalosis. We studied various acid-base parameters in 20 patients undergoing continuous nasogastric (NG) suctioning for periods ranging from 3 to 17 days. Ten patients received cimetidine 300 mg intravenously every 6 hr (cimetidine-treated group). The remaining 10 patients received an antacid compound through the NG tube (control group). The rise in plasma bicarbonate concentration was significantly greater in the control group as compared to the cimetidine-treated group. As expected, gastric acid output was considerably lower in the cimetidine-treated group than in the control group. We conclude that cimetidine administration may be used in preventing metabolic alkalosis associated with gastric fluid loss by inhibiting gastric secretion of HCl.

Adolescent↗

Association of ureteropelvic pseudo-obstruction with cryptorchidism.

A variety of upper urinary tract anomalies have been described in cryptorchidism. This report is of an asymptomatic patient with cryptorchidism, who appeared to have bilateral ureteropelvic-junction obstruction on excretory urography. Further investigations, including urodynamic studies and glomerular- and tubular-function tests, revealed no abnormalities. Ureteropelvic pseudo-obstruction can, therefore, be added to the list of numerous renal and urinary tract anomalies known to be associated with cryptorchidism.

Adolescent↗

Urinary excretion and deficiency of prothrombin in nephrotic syndrome.

Plasma and urinary prothrombin concentration and plasma prothrombin activity were measured in a group of 17 patients with the nephrotic syndrome. An immunologic assay using a monospecific antibody against human prothrombin was employed in the measurement of prothrombin concentration in the plasma and urine. Prothrombin-deficient plasma was used as the substrate in the measurement of plasma prothrombin activity. A control group consisting of five normal volunteers was included for comparison. Both the activity and concentration of prothrombin were significantly lower in the nephrotic group as compared with the control group. Significant quantities of immunoreactive prothrombin were detected in the urine of the majority of nephrotic patients. This study has provided unequivocal evidence of urinary excretion and acquired deficiency of prothrombin in the nephrotic syndrome.

Adolescent↗

Renal magnesium wasting associated with amphotericin B therapy.

The effect of amphotericin B on magnesium metabolism was studied in 10 patients (aged 30 to 68 years) with systemic fungal infections. Renal magnesium wasting resulting in mild to moderate hypomagnesemia was demonstrated by the second week of therapy following relatively small cumulative dosages of amphotericin B (208 +/- 40 mg). The lowest serum levels and largest fractional excretions of magnesium were observed by the fourth week of therapy after cumulative dosages of 510 +/- 118 mg. A plateauing of the renal magnesium wasting is suggested, as there were no further increases or reductions in fractional magnesium excretion and serum magnesium level, respectively, despite continued amphotericin B administration. Reversibility of the magnesium wasting is indicated by data in three of the patients approximately one year following discontinuation of amphotericin B therapy, in whom the serum magnesium level and fractional magnesium excretion had returned to pretreatment baseline values. Although the available data do not allow precise localization of this defect, increased urinary excretion of magnesium despite its reduced filtered load suggests a tubular defect in magnesium reabsorption. Therefore, routine monitoring of the serum magnesium level during treatment with amphotericin B is recommended.

Adult↗

Endocrine pathology in spinal cord injured patients on maintenance dialysis.

We studied the histopathological changes of the thyroid, adrenal and parathyroid glands, testes and pancreata in 15 patients with end-stage renal disease associated with long-standing spinal cord injury. All patients were males aged 42.7 +/- 9.4 years and were treated with maintenance haemodialysis for 20.4 +/- 17.7 months. Thyroid amyloidosis was present in eight of 12 glands and was extensive in four and moderate in four. Thyromegaly was noted in five of the glands with amyloid involvement. Of the 30 available adrenal glands, 26 showed amyloid involvement which was extensive in ten and moderate in 16. Of 18 testes examined all exhibited marked atrophy, decreased or absent spermatogenesis and marked peritubular and interstitial fibrosis. Amyloid involvement was also noted in two subjects. Pancreata were examined in 15 subjects with amyloidosis and pancreatitis noted in eight and four glands, respectively. Of the 22 parathyroid glands examined in nine subjects, hyperplasia was noted in 13 glands (four patients) and moderate amyloidosis was noted in six glands (two patients). Our results demonstrate a high prevalence of endocrine organ pathology in dialysis patients with longstanding spinal cord injury. Functional significance of these pathological findings is unclear and requires further investigation.

Adrenal Glands↗

Renal pathology in end-stage renal disease associated with paraplegia.

In the present study we report the renal pathological findings from autopsy material along with relevant clinical data on 21 spinal cord injury patients with end-stage renal disease (SCI-ESRD) treated with maintenance haemodialysis. These data are compared with the relevant clinical and post-mortem findings on 43 ambulatory dialysis patients who expired during the same time period. The SCI-ESRD patients exhibited markedly different clinical and renal histopathological data when compared to the ambulatory--ESRD group. Chronic pyelonephritis and amyloidosis dominated the findings and were the major causes of renal insufficiency. Acute pyelonephritis, papillary necrosis, calculous disease, pyonephrosis and perinephric abscess formation were also more frequently present in the SCI-ESRD patients. Hypertension and nephrosclerosis, which were common findings in the ambulatory--ESRD patients were comparatively rare in the SCI-ESRD patients. In addition, the incidence of acquired cystic disease (ACD) was considerably less in the SCI-ESRD group. Although the reasons for these findings are not entirely clear several possible explanations are given. Infection with gram negative sepsis was the predominant cause of death in the SCI-ESRD patients, while death secondary to cardiovascular disease predominated in the ambulatory-ESRD group. Furthermore, the urinary tract and infected decubitus ulcers were determined to be the major source for sepsis in the SCI patients. From these findings it would follow that more effective prevention and control of these infections would result in not only a lower incidence of renal failure but also a substantially reduced morbidity and mortality in chronic SCI.

Adult↗

Clinicopathological characteristics of dialysis patients with spinal cord injury.

Forty-three spinal cord injured patients with endstage renal disease (ESRD) maintained on hemodialysis were studied. The most prevalent renal lesions consisted of chronic pyelonephritis and amyloidosis while the main renal functional features included nephrotic range proteinuria, high urine output and relatively low serum creatinine for the degree of renal insufficiency. Normocytic, normochromic anemia with low reticulocyte response, low serum iron and iron binding capacity and high transfusion requirement and serum ferritin were noted. Various cardiovascular, pulmonary and gastrointestinal abnormalities were found with considerable frequencies. The incidence of amyloidosis was much higher than that reported previously. This is thought to be due to continued progression of amyloidosis occasioned by longer survival in the present series.

Adult↗

Nutritional evaluation of hemodialysis patients with and without spinal cord injury.

Both end stage renal disease (ESRD) and spinal cord injury (SCI) represent major disabling conditions that may be associated with protein-calorie malnutrition (PCM). The prevalence of PCM in ESRD, however, remains unknown, and virtually no data exist regarding the status of PCM in patients with both SCI and ESRD. In this study we evaluated 23 ambulatory-ESRD patients and 11 SCI-ESRD patients utilizing a range of parameters recommended for assessing nutritional status in ESRD. Based on these parameters, our results show evidence for PCM in a substantial proportion of both groups. When the two groups were compared, however, the frequency and severity of PCM were significantly greater in the SCI-ESRD patients. Important factors felt to adversely influence nutritional status in the SCI-ESRD patients were intercurrent infection and amyloidosis that were found to frequently complicate this setting. It is also probable that the combined effects of PCM and ESRD significantly predispose these patients to further infection, establishing a vicious cycle.

Adult↗

Effects of long-term testosterone administration on pituitary-testicular axis in end-stage renal failure.

The endocrine effects of long-term testosterone administration were studied in 6 end-stage renal failure patients. During a 3-month control period where no androgens were administered the mean plasma testosterone level (7.3 nmol/l) was depressed while mean plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were elevated at 41.2 mU/ml, 105.5 mU/ml, and 63 ng/ml, respectively. These values were repeated during a 6-month study period where each subject was administered testosterone enanthate (400 mg) intramuscularly once a week. Plasma testosterone levels markedly increased in all subjects with a mean elevation of 72.4 nmol/l, while reductions were observed in FSH and LH levels with values of 2.7 and 16.3 mU/ml, respectively. When compared with control period values, these changes were statistically significant (p less than 0.05). Although the mean plasma PRL level of 49.0 ng/ml was reduced when compared with the control period values, this reduction was not statistically significant. Our control period findings of low plasma testosterone levels coupled with high plasma LH and FSH are consistent with Leydig cell dysfunction. The significant reductions in plasma FSH and LH noted during the study period indicate a negative feedback effect produced by the pharmacologic doses of testosterone. Long-term testosterone administration, however, did not significantly affect the elevated mean PRL levels observed in these subjects.

Adult↗