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Biomedical subjects

T H Goodship

Publications and source records attributed to T H Goodship.

At least 55 records · Page 3Linked to original sources
PubMed1993

Correction of acidosis in humans with CRF decreases protein degradation and amino acid oxidation.

The effect of correction of acidosis in chronic renal failure (CRF) was determined from the kinetics of infused L-[1-13C]leucine. Nine CRF patients were studied before (acid) and after two 4-wk treatment periods of sodium bicarbonate (NaHCO3) and sodium chloride (NaCl) (pH: acid 7.31 +/- 0.01, NaHCO3 7.38 +/- 0.01, NaCl 7.30 +/- 0.01). Leucine appearance from body protein (PD), leucine disappearance into body protein (PS) and leucine oxidation (O) decreased significantly with correction of acidosis (PD: acid 122.4 +/- 6.1, NaHCO3 88.3 +/- 6.9, NaCl 116.2 +/- 9.1 mumol.kg-1.h-1, acid vs. NaHCO3 P < 0.01, NaHCO3 vs. NaCl P < 0.01, acid vs. NaCl NS; PS: acid 109.4 +/- 5.6, NaHCO3 79.0 +/- 6.3, NaCl 101.3 +/- 7.7 mumol.kg-1.h-1, acid vs. NaHCO3 P < 0.01, NaHCO3 vs. NaCl P < 0.01, acid vs. NaCl NS; O: acid 13.0 +/- 1.2, NaHCO3 9.2 +/- 0.9, NaCl 15.0 +/- 1.9 mumol.kg-1.h-1, acid vs. NaHCO3 P < 0.05, NaHCO3 vs. NaCl P < 0.01, acid vs. NaCl NS). There were no significant changes in plasma amino acid concentrations. These results confirm that correction of acidosis in chronic renal failure removes a potential catabolic factor.

Acidosis↗
PubMed1993

Adequacy of dialysis and nutritional status in CAPD.

Urea kinetic modelling (UKM) was used to assess adequacy of dialysis in 50 CAPD patients. Nutritional status was assessed from the measurement of visceral protein status (total protein, albumin, transferrin, immunoglobulins, complement), somatic protein status (anthropometry), and dietary intake (1 week weighed dietary inventory and normalized protein catabolic rate (NPCR) from UKM). Morbidity was assessed from the peritonitis and admission history. Mean Kt/V (corrected to x3 weekly dialysis) was 0.66 +/- 0.02. Dietary protein intake estimated from the NPCR (1.08 +/- 0.03 g kg-1 day-1) correlated well (r = 0.72, P < 0.001) with that estimated from the dietary inventory (1.10 +/- 0.04 g kg-1 day-1). There was a strong correlation between Kt/V and NPCR corrected for actual weight (r = 0.65, P < 0.001), but when NPCR was corrected for IBW this correlation was weaker (r = 0.35, P < 0.05). Patients were divided by Kt/V into two groups (> 0.65, n = 22 and < 0.65, n = 28). There were no significant differences in the indices of visceral protein status between the two groups. Weight, height, BMI, fat free mass and arm muscle area were significantly greater in the group Kt/V < 0.65. Residual renal function (creatinine clearance) was higher in the group Kt/V > 0.65 (3.8 +/- 0.7 versus 1.9 +/- 0.5 1/24 h, P < 0.05) and plasma creatinine less (913 +/- 51 versus 1265 +/- 51 mumol/l, P < 0.001). Hb, potassium, bicarbonate, phosphate, alkaline phosphatase, PTH, and blood pressure were not different. Neither was there any difference between the two groups in any of the indices of morbidity.

Adult↗
PubMed1992

Ammonium chloride-induced acidosis increases protein breakdown and amino acid oxidation in humans.

The effect of acidosis on whole body protein turnover was determined from the kinetics of infused L-[1-13C]leucine. Seven healthy subjects were studied before (basal) and after (acid) the induction of acidosis with 5 days oral ammonium chloride (basal pH 7.42 +/- 0.01, acid pH 7.35 +/- 0.03). Bicarbonate recovery, measured from the kinetics of infused NaH13CO3, was increased in the acidotic state (basal 72.9 +/- 1.2 vs. acid 77.6 +/- 1.6%; P = 0.06). Leucine appearance from body protein (PD), leucine disappearance into body protein (PS), and leucine oxidation (O) increased significantly (PD: basal 120.5 +/- 5.6 vs. acid 153.9 +/- 6.2, P < 0.01; PS: basal 98.8 +/- 5.6 vs. acid 127.0 +/- 4.7, P < 0.01; O: basal 21.6 +/- 1.1 vs. acid 26.9 +/- 2.3 mumol.kg-1.h-1, P < 0.01). Plasma levels of the amino acids threonine, serine, asparagine, citrulline, valine, leucine, ornithine, lysine, histidine, arginine, and hydroxyproline increased significantly with the induction of acidosis. These results confirm that acidosis in humans is a catabolic factor stimulating protein degradation and amino acid oxidation.

Acidosis↗
PubMed1991

Osmoregulation of thirst and vasopressin release in severe chronic renal failure.

Subjects with severe chronic renal failure (CRF) have higher plasma concentrations of arginine vasopressin (AVP) than normal subjects, and some develop severe thirst. Eight patients with CRF and seven matched controls underwent hypertonic saline infusion to explore the relationship of thirst and plasma AVP with plasma osmolality. Differences in urea concentration between the two groups were controlled for by correcting measured osmolality to a urea of zero. Linear regression analysis of the relationships between plasma AVP and thirst with plasma osmolality (corrected for urea) was performed. Mean results were: control, pAVP = 0.26 (pOsmc - 283.7) versus CRF, pAVP = 0.72 (pOsmc - 282.0); and control, thirst = 4.0 (pOsmc - 279.4) versus CRF, thirst = 3.5 (pOsmc - 281.8). The apparent sensitivity (slope) of AVP release was greater in severe CRF than in normal controls (P = 0.04). There was no significant difference between the groups in thirst sensitivity, threshold for thirst onset and threshold for AVP release. Osmoregulated thirst was normal in severe CRF, but increasing osmolality leads to higher concentrations of AVP than would be expected.

Adult↗
PubMed1990

Renal replacement treatment for diabetic patients in Newcastle upon Tyne and the Northern region, 1964-88.

OBJECTIVES: To review the experience of renal replacement treatment in diabetic patients treated in Newcastle upon Tyne and the Northern region from 1964 to 1988, and to compare the morbidity and mortality of diabetic patients treated with dialysis or transplantation with those of matched controls of non-diabetic patients. DESIGN: Retrospective study of clinical case notes. SETTING: Renal units of the Northern region, particularly that in Newcastle upon Tyne. PATIENTS: All 65 diabetic patients treated by renal replacement treatment in Newcastle upon Tyne from 1964 to 1987; 42 diabetic patients were matched with 42 non-diabetic patients according to age, sex, year of starting treatment, and type of treatment (dialysis or transplantation). MAIN OUTCOME MEASURES: Sex, age, renal biopsy findings, blood pressure, history of diabetic treatment, and plasma creatinine concentration at the start of renal replacement treatment. History of renal replacement treatments, suitability for transplantation, history of transplantation, cumulative survival, and cause of death during follow up. Survival of technique, cumulative survival of the first peritoneal catheter and history of peritonitis in patients treated with continuous ambulatory peritoneal dialysis; source of graft, histocompatibility antigens, duration of associated stay in hospital, and graft survival in patients receiving renal or pancreatic transplant. RESULTS: 1259 Patients with chronic renal failure were accepted for renal replacement treatment in Newcastle upon Tyne, of whom 65 (5%) had diabetes. The first was accepted in 1974, and between 1974 and 1980 another 15 were treated (mean age 42 years; 4% of new patients). From 1981 to 1987, 49 diabetic patients (mean age 44; 9% of new patients) were treated. Fifty patients (77%) had insulin dependent diabetes and the remaining 15 (23%) non-insulin dependent diabetes. On average, the patients were aged 25 (range 5-57) when diabetes was first diagnosed and 44 (range 24-70) at the start of renal replacement treatment. The mean age at the start of treatment was 40 for patients with non-insulin dependent diabetes and 58 for patients with non-insulin dependent diabetes. Transplantation was performed in 33 of the diabetic patients, whose mean age was lower than that of those who did not receive a transplant (41 v 48 respectively, p less than 0.05). Comparison between the 42 diabetic patients and matched controls showed that the overall survival at five years was 46% and 77% respectively. The three year survival of the diabetic patients who did not receive a transplant was poor (41% v 79% respectively). Of patients transplanted, survival at five years was 73% in the diabetic patients and 90% in the controls. However, there was no significant difference in the five year graft survival (64% v 46% respectively). CONCLUSIONS: Diabetes adversely affects morbidity and mortality in patients having renal replacement treatment, but renal transplantation seems to be the best option for treating diabetic patients with end stage renal failure.

Adolescent↗
PubMed1990

HLA DQ region gene polymorphism associated with primary IgA nephropathy.

IgA nephropathy (IgAN) has been associated with HLA-DR4. We have recently described two non-allelic Taq I DQ beta gene-associated fragments sized 2.0 kb (T2) and 6.0 kb (T6), which strongly associate with DR4. T2 represents a polymorphism of the DQ beta gene and has been redesignated DQw8 (10th International HLA Workshop). The origin of the T6 fragment has not been determined, but probably represents a polymorphism of either the DQ beta or DX beta gene. When present together T2 and T6 define a subgroup of DR4 subjects at high risk of developing autoimmune disease. We have, therefore, studied DQ beta gene polymorphisms in IgAN. The DR antigen distribution was similar in IgAN and normal controls. The T2+/T6+ phenotype was present in 49% patients with IgAN compared to 15% of controls [P less than 0.0001, chi 2 = 32.8, Cramer's V = 0.41; relative risk = 5.5 (range, 2.8-11.0)]. Seventy-two percent of DR4+ IgAN patients and 29% of DR4+ controls were T2+/T6+ (P = 0.007, chi 2 = 17.0). These findings confirm the hypothesis that disease susceptibility genes are important in IgAN, and suggest that the putative gene(s) are located within or near to the DQ subregion. Moreover, similar DQ beta gene associations have been found in IDDM and pemphigus vulgaris, pointing to a common immunogenetic mechanism predisposing to several autoimmune diseases.

Blotting, Southern↗
PubMed1990

Total-body potassium in insulin-dependent diabetes mellitus.

1. Total-body potassium and fat-free mass have been measured in 31 insulin-dependent diabetic patients and 31 age- and sex-matched normal volunteers. 2. Body mass index was significantly higher in the insulin-dependent diabetic patients (24.7 +/- 0.5 vs 23.3 +/- 0.4 kg/m2; P = 0.05). 3. Total-body potassium, uncorrected and corrected for weight and for fat-free mass, was not significantly different in the two groups (3281 +/- 141 mmol, 47.3 +/- 1.3 mmol/kg body weight, 60.9 +/- 1.0 mmol/kg fat-free mass, and 3315 +/- 143 mmol, 48.6 +/- 1.0 mmol/kg body weight, 60.4 +/- 0.8 mmol/kg fat-free mass, respectively, in diabetic patients and non-diabetic subjects). There was no relationship between blood glucose control, as assessed by glycated haemoglobin concentrations, and total-body potassium. 4. These results suggest, by contrast with previous reports, that in insulin-dependent diabetic patients, showing varying degrees of glycaemic control (glycated haemoglobin range 6.1-15.3%, mean 9.0%) that: (a) there is no significant abnormality of body potassium homoeostasis, and (b) there is no relation between total-body potassium and glycaemic control.

Adolescent↗
PubMed1990

Diabetes mellitus and renal replacement therapy in Italy: prevalence, main characteristics and complications.

A number of reports on dialysis and transplantation for diabetic patients in the UK and USA are available. The aim of the present survey was to assess the prevalence, main characteristics and complications of diabetic patients treated by dialysis and transplantation in Italy. On 31 December 1987 in Italy, 1605 diabetic patients were being treated by dialysis or transplantation. The prevalence was 28 per million compared with the UK and the USA where the corresponding figures were 17 and 78 per million respectively. The annual incidence in 1987 was 9 per million (UK: 4 per million; USA: 33 per million). The mean age of the Italian diabetic patients was 59 years whereas that for British diabetic patients similarly evaluated was 48 years. Of the Italian diabetic patients 67% had NIDDM (UK: 22%; USA: 50%). Haemodialysis was used in 81% of the Italian patients, peritoneal dialysis in 14%, and only 5% were transplanted. This is in contrast to the UK where only 18% of the patients were treated by haemodialysis and 39% were transplanted. Amongst Italian patients who started RRT in 1987, 9% died within the year, and of the remainder 38% had severe bilateral visual impairment (UK 35%), 3% had had amputations (UK 6%), 7% had suffered from disabling strokes (UK 6%) and 7% had had a myocardial infarction (UK 17%). Before 31 December 1987 another 2.2% developed severe bilateral visual impairment, 0.6% underwent amputations, 1.0% had a disabling stroke and 0.6% suffered from a myocardial infarction. The proportion of diabetic patients treated by RRT in Italy is twice that of the UK but only half that of the USA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Adaptation to low-protein diets in renal failure: leucine turnover and nitrogen balance.

In normal subjects, short to intermediate responses to dietary protein restriction include decreased amino acid oxidation and protein degradation plus increased utilization of amino acids for protein synthesis; these responses are activated to improve amino acid utilization and nitrogen balance. To assess whether chronic renal failure (CRF) impairs the adaptive responses to a low-protein diet, we measured nitrogen balance and the kinetics of infused L-(15N,1-13C)leucine during fasting and feeding. In six adult CRF and four control (C) subjects, 0.6 (LP) and 1.0 (HP) g protein kg-1 day-1 diets were compared. LP reduced feeding stimulated oxidation of leucine by 26% in CRF and 33% in C (P = NS). During fasting, oxidation was unaffected by diet or CRF. For both groups, feeding suppressed protein degradation to the same extent; leucine incorporation into protein did not change. Nitrogen balance during the two diets was the same with C and CRF, as was protein balance estimated from results of measured leucine kinetics. Thus, patients with CRF can activate appropriate adaptive responses to LP inasmuch as reduced amino acid oxidation occurring with feeding and estimates of protein balance did not differ from control.

Adaptation, Physiological↗
PubMed1990

The nutritional/metabolic and hormonal effects of 8 weeks of continuous ambulatory peritoneal dialysis with a 1% amino acid solution.

Circulating intermediary metabolites, hormones and plasma amino acids (AA) were measured at intervals over 24 hours in seven non-diabetic patients with chronic renal failure treated by continuous ambulatory peritoneal dialysis (CAPD), before and after an 8-week period during which a 1% amino acid dialysis solution replaced two of the four dextrose exchanges. Mean 24-hour concentrations of plasma total and essential amino acid were higher following the AA dialysate (total pre: 2893 +/- 185; total post: 3357 +/- 244; p less than 0.05; essential pre: 751 +/- 47; essential post: 1064 +/- 57 mumol/l; p less than 0.001). Mean 24-hour concentrations of the branched chain amino acids leucine, isoleucine and valine were higher following the AA dialysate (valine pre: 201 +/- 18; valine post: 321 +/- 19; p less than 0.001; leucine pre: 102 +/- 6; leucine post: 127 +/- 9; p less than 0.01; isoleucine pre: 67 +/- 5; isoleucine post: 85 +/- 7 mumol/l; p less than 0.05). Serum albumin increased with use of the AA dialysate (pre: 36 +/- 1; 2 weeks, 40 +/- 1; 4 weeks, 40 +/- 1; 6 weeks, 41 +/- 1; 8 weeks, 38 +/- 2 g/l). 24-hour profiles and mean 24-hour concentrations of blood glucose, serum insulin, serum triglyceride, plasma non-esterified fatty acids (NEFA), plasma 3-hydroxybutyrate and plasma alanine were unchanged after the AA period. Plasma bicarbonate decreased with use of the amino acid solution (pre: 21 +/- 1; 2 weeks, 18 +/- 1; 4 weeks, 18 +/- 1; 6 weeks, 16 +/- 1; 8 weeks, 16 +/- 1 mmol/l). Use of a 1% amino acid solution over an 8-week period in CAPD patients improves the plasma amino acid profile but results in a metabolic acidosis. The other endocrine and metabolic abnormalities of uremia remain unchanged.

Adult↗
PubMed1989

Effect of a high protein diet in patients with the nephrotic syndrome.

1. Twelve patients with the nephrotic syndrome were prescribed for 4 week periods a normal protein diet (NPD) containing 1 g of protein/kg ideal body weight. They were then prescribed for further 4 week periods in random order diets with high (HPD) and low (LPD) protein contents, respectively 2.0 and 0.5 g/kg ideal body weight. 2. Compliance was confirmed by dietary history and measurement of urinary excretion. 3. Serum albumin was the same on all diets. Twenty-four hour urinary protein excretion increased progressively with increasing dietary protein (LPD 6.1 g. NPD 8.2 g. HPD 9.2 g). Recumbent plasma renin activity and serum phosphate were significantly increased on HPD (plasma renin activity: LPD 5.7, NPD 4.6, HPD 8.2 pmol of angiotensin I min-1 1(-1); serum phosphate: LPD 1.27, NPD 1.26, HPD 1.41 mmol/l). 4. There was no evidence of protein-induced hyperfiltration or hyperperfusion: 51Cr-ethylenediaminetetra-acetate and [125I]iodohippurate clearances were similar on all three diets. 5. Since proteinuria, increased plasma renin levels and hyperphosphataemia may contribute to progression of renal failure and because HPD did not improve hypoalbuminaemia, the use of HPD in the nephrotic syndrome should be abandoned. 6. Until it can be established that LPD, which is accompanied by the least proteinuria, does not, with long-term feeding, lead to malnutrition, NPD should be used in the treatment of the nephrotic syndrome.

Adult↗
PubMed1989

Hypophosphatemic effect of 1% amino acid dialysis solution.

Orally administered essential amino acids and their nitrogen free analogues have been shown to ameliorate hyperphosphatemia in uremic patients. The aim of the study was to assess the effect on serum phosphate and ionized calcium of a mixture of non-essential and essential amino acids, administered intra peritoneally as a 1% solution to a group of uremic patients who had been on continuous ambulatory peritoneal dialysis (CAPD) for at least three months. Serum phosphate and ionized calcium were measured at fortnightly intervals during the study period which lasted 16 weeks. All patients performed four 2 liter exchanges with dextrose dialysis solution for the first 4 weeks. Two of the four exchanges were then replaced by a 1% amino acid (AA) dialysis solution for a period of 8 weeks after which all patients reverted to their original regimen. Serum phosphate and calcium were measured fortnightly for a further 4 weeks. Serum phosphate fell significantly after introduction of the AA dialysis solution despite unchanged dietary protein and phosphate intake and no increase in the dose of oral phosphate binders taken by 2 of the 7 patients. Serum ionized calcium remained unchanged during the study period.

Adult↗
PubMed1987

Evidence for large intestinal control of potassium homoeostasis in uraemic patients undergoing long-term dialysis.

1. The role of the large intestine in the maintenance of K+ balance in uraemic patients established on long-term dialysis was studied with a rectal dialysis technique in 14 normal subjects, ten normokalaemic patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and seven patients undergoing haemodialysis. Dietary K+ intakes in the normal subjects, CAPD patients and haemodialysis patients were 80-100 mmol/24 h, 70-80 mmol/24 h and 60-70 mmol/24 h, respectively. 2. At an initial intraluminal K+ concentration of 45 mmol/l, rectal K+ secretion in the CAPD patients (2.4 +/- 0.4 mumol h-1 cm-2) was greater than in normal subjects (1.2 +/- 0.2 mumol h-1 cm-2, P less than 0.02). Under similar conditions, rectal K+ secretion was also greater in the haemodialysis patients than in normal subjects, both predialysis (3.7 +/- 0.4 mumol h-1 cm-2, P less than 0.001) and postdialysis (2.4 +/- 0.5 mumol h-1 cm-2, P less than 0.05), even though haemodialysis decreased plasma K+ concentration from 5.3 +/- 0.1 mmol/l to 3.5 +/- 0.2 mmol/l (P less than 0.001). 3. There were no significant differences in rectal Na+ absorption, rectal potential difference, plasma aldosterone concentration, or total body K+ content (measured by whole-body counting of 40K), between the normal subjects and either the CAPD or the haemodialysis patients. 4. These results indicate that K+ homoeostasis is maintained in uraemic patients undergoing long-term dialysis by a combination of K+ losses during dialysis, and enhanced large intestinal K+ excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Whole body leucine turnover and nutritional status in continuous ambulatory peritoneal dialysis.

1. Nutritional status and leucine turnover has been measured in ten patients with chronic renal failure before the onset of continuous ambulatory peritoneal dialysis (CAPD) and after 3 months treatment, and in five normal subjects. 2. Somatic muscle protein reserves, as judged by anthropometry and measurement of total body potassium, showed no significant changes after 3 months treatment and were not significantly different from normal. 3. Visceral protein reserves, as judged by serum albumin and plasma amino acids, showed a significant fall after 3 months CAPD and were also lower than in normal subjects. 4. Protein turnover was lower in uraemic than in normal subjects, but the balance between synthesis and breakdown was significantly higher and was maintained after 3 months on CAPD.

Amino Acids↗
PubMed1987

Short-term studies on the use of amino acids as an osmotic agent in continuous ambulatory peritoneal dialysis.

1. A 1% amino acid dialysis solution with a high concentration of the branched-chain amino acids has been compared with 1.36% glucose in short-term studies. 2. The 1% amino acid solution was as effective an agent as 1.36% glucose with respect to ultrafiltration and clearance of creatinine, urea and potassium. 3. Levels of branched-chain amino acids rose to the upper end of the normal range within 1 h and remained at this level over the entire period of the study. Total and non-essential amino acids had returned to baseline by the end of the cycle. 4. Blood glucose rose to significantly greater levels during the 1.36% glucose exchange than during the 1% amino acid exchange. There was an increase in serum insulin levels during both cycles; this was significantly greater with the 1% amino acid solution than the 1.36% glucose. 5. There was no evidence of short-term metabolic complications with the 1% amino acid solution.

Adult↗