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Biomedical subjects

A Shenkin

Publications and source records attributed to A Shenkin.

At least 163 records · Page 9Linked to original sources

Renal tubular peptide catabolism in chronic vascular rejection.

Chronic vascular rejection (CR) is the commonest cause of renal transplant loss, with few clues to etiology, but proteinuria is a common feature. In diseased native kidneys, proteinuria and progression to failure are linked. We proposed a pathogenic role for this excess protein at a tubular level in kidney diseases of dissimilar origin. We demonstrated in both nephrotic patients with normal function and in those with failing kidneys increased renal tubular catabolism and turnover rates of a peptide marker, Aprotinin (Apr), linked to increased ammonia excretion and tubular injury. These potentially injurious processes were suppressed by reducing proteinuria with Lisinopril. Do similar mechanisms of renal injury and such a linkage also occur in proteinuric transplanted patients with CR, and if so, is Lisinopril then of beneficial value? We now examine these aspects in 11 patients with moderate/severe renal impairment (51CrEDTA clearance 26.2+/-3.3 mL/min/1.73 m2), proteinuria (6.1+/-1.5 g/24 h) and biopsy proven CR. Lisinopril (10-40 mg) was given daily for 2 months in 7 patients. Four others were given oral sodium bicarbonate (Na HCO3) for 2 months before adding Lisinopril. Renal tubular catabolism of intravenous 99mTc-Apr (Apr* 0.5 mg, 80MBq), was measured before and after Lisinopril by gamma-ray renal imaging and urinary radioactivity of the free radiolabel over 26 h. Fractional degradation was calculated from these data. Total 24 h urinary N-acetyl-beta-glucoaminidase (NAG) and ammonia excretion in fresh timed urine collections were also measured every two weeks from two months before treatment. After Lisinopril proteinuria fell significantly (from 7.8+/-2.2 to 3.4+/-1.9 g/24 h, p<0.05). This was associated with a reduction in metabolism of Apr* over 26 h (from 0.5+/-0.05 to 0.3+/-0.005% dose/h, p < 0.02), and in fractional degradation (from 0.04+/-0.009 to 0.02+/-0.005/h, p<0.01). Urinary ammonia fell, but surprisingly not significantly and this was explained by the increased clinical acidosis after Lisinopril, (plasma bicarbonate fell from 19.1+/-0.7 to 17.4+/-0.8 mmol/L, p < 0.01), an original observation. Total urinary NAG did fall significantly from a median of 2108 (range 1044-3816) to 1008 (76-2147) micromol/L, p < 0.05. There was no significant change in blood pressure or in measurements of glomerular hemodynamics. In the 4 patients who were given Na HCO3 before adding Lisinopril, both acidosis (and hyperkalemia) were reversed and neither recurred after adding Lisinopril. These observations in proteinuric transplanted patients after Lisinopril treatment have not been previously described.

Adult↗

Symptomatic selenium deficiency in a child on home parenteral nutrition.

A 27-month-old girl with microvillous atrophy who was maintained on long-term home parenteral nutrition presented with regression of walking skills. She was found to have a tender skeletal myopathy affecting both legs only. Plasma selenium level was less than 0.05 mumol/L (0.4 microgram/dl) (normal 0.8-1.6 mumol/L; 6.3-12.6 micrograms/dl), red blood cell glutathione peroxidase was undetectable, and plasma glutathione peroxidase was 6 U/L (normal 90-350 U/L). Electromyography was abnormal, muscle biopsy showed a nonspecific myopathy, and muscle selenium was 0.23 micrograms/g dry weight (normal 0.45-1.05 micrograms/g dry weight). Following replacement with intravenous sodium selenite, there was a rapid improvement with complete disappearance of muscle pain and tenderness within 1 week. Crawling and walking skills were regained within 6 weeks, indicating that selenium deficiency was the cause of her symptoms. It is suggested that selenium be monitored and supplemented in children on long-term total parenteral nutrition particularly if enteral absorption is deficient.

Electromyography↗

Mg deficiency in chronic inflammatory bowel disease and requirements during intravenous nutrition.

Assessment of magnesium (Mg) status by serum and 24-hr urine estimations has been used to study a group of 17 patients with severe Crohn's disease, 10 of whom have required intravenous (IV) nutrition. Mg depletion was present in 15 (88%) and severe enough to cause symptoms in two. Urine levels were low in most patients and would appear to be a more sensitive indication of Mg depletion than serum levels alone. Serum Mg levels were significantly lower in the Crohn's group than in a group of hospital controls; 5-10 mmol of IV Mg were required daily to prevent Mg depletion during IV nutrition and some patients required higher intakes. Three patients with particularly severe malabsorption required oral Mg supplements in the long-term. The rationale for using our method of assessing Mg status, and the importance of recognizing and treating chronic Mg deficiency are presented.

Adolescent↗

Hyperkalemia in patients on enteral feeding.

The amount of potassium (K) in proprietary enteral feeds varies considerably from 2.7-9.2 mmol K+/g N. It has been suggested that up to 7 mmol K+/g N is required by the anabolic patient. The aim of this study was to determine the effect of a proprietary feed (Triosorbon MCT), containing 6.9 mmol K+/g N, on serum and urinary K in 13 patients requiring nutritional support. Serum electrolytes in all patients and urinary electrolytes in 7 were measured both before feeding commenced and when they had achieved an intake of between 2.4 and 3.0 liter/day (102-127 mmol K+/day) of full strength feed for a period of 1 wk. Ther serum K rose in all patients from 4.2 +/- 0.5 mmol/liter (mean +/- SD) before feeding to 5.1 +/- 0.5 after feeding for 1 wk (p less than 0.001; pair-difference t-test). The daily urinary K excretion rose from 37.8 +/- 24.2 mmol/day to 61.8 +/- 26.6 over the same period (p less than 0.001) The serum urea rose from 4.7 +/- 2.0 mmol/liter to 6.3 +/- 3.2 (p less than 0.05). No significant change was observed in other serum electrolytes, creatinine, or urinary electrolytes. During the whole course of feeding (range 1-11 wk) it was necessary to discontinue Triosorbon in 2 patients whose serum K concentration became elevated to greater than 6 mmol/liter. We conclude that the recommended levels of K intake may be too high and that serum K should be carefully monitored during enteral feeding.

Blood Urea Nitrogen↗

Vitamin status during total parenteral nutrition.

Plasma concentrations of vitamins A and E, serum and erythrocyte folic acid, serum B12 and erythrocyte enzyme activations (to assess vitamins B1, B2 and B6 status) were measured at the start and finish of 39 courses of total parenteral nutrition (TPN). The daily regimen was standard. Plasma vitamin A, E, and folate concentrations and vitamin B6 status improved significantly during TPN. Three patients developed low levels of vitamin A and two patients developed high transketolase activations (B1 depletion) during therapy. The adequacy of vitamin replacement and the monitoring of vitamin status during TPN is discussed.

Adult↗

Intravenous nutrition and hepatic dysfunction.

Abnormalities in biochemical liver function tests in 127 general surgical patients who had a course of intravenous nutrition have been reviewed. Only 26 patients had liver function tests considered to be normal on commencing intravenous nutrition and they were included in this retrospective study. During intravenous nutrition the most sensitive biochemical test of liver dysfunction was gamma-glutamyl transpeptidase--all patients having an elevated gamma-glutamyl transpeptidase level by week 4. Most abnormalities were transient whereas the elevation of alkaline phosphatase was prolonged beyond week 9. Patients with major sepsis were found to have almost double the incidence of abnormal liver function test values compared with patients with no evidence of sepsis. Only patients who were transfused more than 8 units of blood showed a significant rise in bilirubin. Liver function tests in patients who received smaller transfusions showed no difference from patients who did not receive any blood. Patients with below normal anthropometric measurements on commencing intravenous nutrition were more likely to develop abnormalities in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase.

Alanine Transaminase↗

Maintenance of vitamin and trace element status in intravenous nutrition using a complete nutritive mixture.

Complete nutritive mixtures (CNM) of all intravenous nutrients including fat emulsions are being used increasingly because of their convenience. However, this may lead to chemical interactions and reduce the amount of active vitamins and trace elements made available to the patient. We have studied the effects on micronutrient status of provision of all nutrients in one 3-liter bag (CNM: amino acids, dextrose, Intralipid 20%, a nine-element trace metal mixture, and complete fat- and water-soluble vitamin mixtures) in 10 postoperative surgical patients [median intravenous nutrition (IVN) 14.5 days, range 7-38]. A similar group received the fat emulsion plus water- and fat-soluble vitamins as a separate infusion (SI) from a 3-liter bag (median IVN 14.0 days, range 8-28). Serum and urine magnesium, zinc, copper, manganese, chromium, and selenium, serum vitamins A, E, C, folate, and B12, RBC B1, B2 B6, and folate and leukocyte vitamin C were measured at weekly intervals. All patients in both groups maintained or improved their status for all the micronutrients analyzed. No significant differences between the CNM and SI groups were found in blood concentrations of any of the elements or vitamins. Only for urine copper did the CNM lead to increased excretion (1.51 +/- 0.59 mumol/24 hr; copper input 20 mumol/day), compared to SI (1.00 +/- 0.70 mumol/day, p less than 0.001 Mann-Whitney test) suggesting possible interaction. It is concluded that micronutrient status was maintained during short-term IVN with the CNM and that it did not lead to a significantly greater loss of vitamins or essential trace elements than the SI system.

Adult↗

The effects of an anabolic steroid and peripherally administered intravenous nutrition in the early postoperative period.

Sixty patients undergoing colorectal surgery for malignancy were randomized to receive the anabolic steroid stanozolol (n = 30) or to a control group (n = 30). Patients were further randomized to receive on the first 4 postoperative days a) a standard dextrose-saline regimen (DS), b) an amino acid regimen (AA), or c) a glucose-amino acid-fat regimen (GAF) via a peripheral vein. Fat and carbohydrate oxidation rates were calculated pre- and postoperatively using indirect calorimetry. Postoperative nitrogen balance (NB) in patients receiving amino acids was significantly improved (p less than 0.02) by the administration of stanozolol. Fat and carbohydrate oxidation rates were not significantly affected by stanozolol. Patients in the stanozolol and control AA groups showed a fall in carbohydrate oxidation (p less than 0.01) and a rise in fat oxidation (p less than 0.05) postoperatively, whereas no significant changes in fat and carbohydrate oxidation occurred in the two DS and two GAF groups. Cumulative NB for the first 4 postoperative days was significantly better (p less than 0.01) in the two AA groups than in the two DS groups, due to an improved NB in the two AA groups on the 1st and 2nd days only. Cumulative NB in the two GAF groups was significantly better (p less than 0.01) than in all the other groups. This study shows that stanozolol improves postoperative NB in patients receiving amino acids alone, whereas the provision of a more complete nutritional regimen containing glucose, amino acids, and fat results in a positive NB unaffected by stanozolol.

Evaluation Studies as Topic↗