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T H Goodship

Publications and source records attributed to T H Goodship.

At least 19 recordsLinked to original sources
PubMed1999

Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency.

BACKGROUND: In a recent study of three families we have found that inherited haemolytic uraemic syndrome (HUS) maps to a region of chromosome 1q containing the gene for complement factor H. In one of these families and also in a case of sporadic D-HUS, we have identified mutations in the factor H gene. A further family with inherited HUS has therefore been investigated. METHODS: DNA extracted from the family members and DNA extracted from archival post-mortem material from a deceased family member, was studied. Review of renal biopsies and study of complement components was also undertaken. RESULTS: This family demonstrates an inherited deficiency of complement factor H. Non-diarrhoeal HUS has affected at least two family members with half normal levels of factor H. CONCLUSION: These findings represent further evidence of the association between factor H dysfunction and HUS.

Adolescent↗
PubMed1998

Factor H--US?

Explore the source record for details and available documents.

Complement Factor H↗
PubMed1998

Genetic studies into inherited and sporadic hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) in adults carries a high morbidity and mortality, and its cause remains unknown despite many theories. Although familial HUS is rare, it affords a unique opportunity to elucidate underlying mechanisms that may have relevance to acquired HUS. We have undertaken a genetic linkage study based on a candidate gene approach. A common area bounded by the markers D1S212 and D1S306, a distance of 26 cM located at 1q32 segregated with the disease (Z max 3.94). We demonstrate that the gene for factor H lies within the region. Subsequent mutation analysis of the factor H gene has revealed two mutations in patients with HUS. In an individual with the sporadic/relapsing form of the disease we have found a mutation comprising a deletion, subsequent frame shift and premature stop codon leading to half normal levels of serum factor H. In one of the three families there is a point mutation in exon 20 causing an arginine to glycine change, which is likely to alter structure and hence function of the factor H protein. Factor H is a major plasma protein that plays a critical regulatory role in the alternative pathway of complement activation. In light of these findings and previous reports of HUS in patients with factor H deficiency, we postulate that abnormalities of factor H may be involved in the etiology of HUS.

Adult↗
PubMed1996

The correction of acidosis does not increase dietary protein intake in chronic renal failure patients.

In normal humans and in patients with chronic renal failure (CRF), acidosis increases whole-body protein degradation. Correction of acidosis reduces protein degradation. The mechanisms underlying these changes in protein metabolism are unclear. However, one possibility is that dietary protein intake is reduced in acidosis and that this causes increased protein degradation. This possibility has not been tested. In this study the effects of acidosis on protein intake in patients with CRF have been assessed using 7-day weighed dietary inventories in the acidotic state (venous bicarbonate 15.6 +/- 1.0 mmol/L) and following treatment with oral sodium bicarbonate (venous bicarbonate 21.0 +/- 1.4 mmol/L). Protein intake was also derived from urinary nitrogen excretion. There was no significant difference in protein intake calculated from dietary records (1.0 +/- 0.09 g/kg/d v 1.06 +/- 0.1 g/ kg/d) or calculated from urinary nitrogen (1.13 +/- 0.07 g/kg/d v 1.06 +/- 0.06 g/kg/d) between the untreated and bicarbonate-treated states in eight patients with CRF. We conclude that acidosis in CRF patients does not affect dietary protein intake and that dietary changes therefore do not contribute significantly to the changes in protein metabolism seen in acidosis.

Acidosis↗
PubMed1996

Correction of acidosis in CAPD decreases whole body protein degradation.

Correction of acidosis in CAPD decreases protein degradation and synthesis but has no effect on leucine oxidation. The effect of the correction of metabolic acidosis in CRF patients treated with CAPD was determined from the kinetics of infused L-[1-13C]leucine. Seven CAPD patients were studied before (acid) and after correction of acidosis (bicarbonate) (pH:acid 7.39 +/- 0.01, bicarbonate 7.41 +/- 0.01, P = 0.005). Leucine appearance from body protein (PD) [corrected] and leucine disappearance into body protein (PS) [corrected] decreased significantly with correction of acidosis. (PS: acid 211.7 +/- 9.8, bicarbonate 142.3 +/- 4.2 micromol x kg-1 x hr-1, P < 0.001; PD: acid 200.6 +/- 8.5, bicarbonate 132.4 +/- 3.7 micromol x kg-1 x hr-1, P < 0.001). There was no significant change in leucine oxidation or plasma amino acid concentrations. These results demonstrate that optimal correction of acidosis in CAPD is beneficial in terms of protein turnover.

Acidosis↗
PubMed1996

Withdrawal of renal replacement therapy in Newcastle upon Tyne: 1964-1993.

BACKGROUND: Termination of renal replacement therapy (RRT) is common in North America and Australia but is considered to be rare in Europe. METHODS: In order to review the phenomenon of RRT termination in all patients treated in Newcastle upon Tyne between 1964 and 1993 a retrospective study of clinical case notes was undertaken. In all RRT patients sex, age at start of RRT, renal diagnosis and history of RRT were recorded. In addition, mortality data and marital and residential status were recorded in all patients who died, and Karnofsky index, bodyweight, complications, history of bereavement, place of death, overall survival, survival after withdrawal of treatment, other medical problems, higher mental function and surgical history in all patients stopping treatment. RESULTS: 1639 patients started RRT between 1964 and September 1993 inclusive. Eighty-eight patients were identified in whom death was a result of treatment being stopped (17% of all deaths). The first was in 1985. In these patients, age was greater (62 vs 47 years, P < 0.001) and diabetes was more prevalent (15 vs 7%, P < 0.03) than in the total RRT population. The Karnofsky index was 70 at the start and 33 at withdrawal of treatment (P < 0.001). The Karnofsky index at the start of RRT was weakly related to that at withdrawal and overall survival (r = 0.36 and 0.28 respectively, P < 0.01). The Karnofsky index at treatment withdrawal correlated with the following survival (r = 0.40, P < 0.001). The median survival of patients stopping treatment was significantly lower than in all RRT patients (16 vs 74 months, P < 0.001) and the majority survived less than 2 years. After dialysis withdrawal the median survival was 8 days, 15 patients survived 3 days or less and 19 more than 10 days. The majority (80%) received terminal care in hospital. At treatment withdrawal 11 patients were demented and 34 showed signs of early dementia. Seventy-eight patients (89%) stopped treatment as a consequence of multiple medical problems. The possibility of dialysis withdrawal was raised by physicians in 50.5%, the patient in 23.8% and the patients' relatives in 21.9% of cases. Four patients (3.8%) committed suicide. CONCLUSIONS: Death from dialysis termination is a relatively common cause of death in RRT patients in Newcastle upon Tyne. These patients are older with a higher prevalence of diabetes. In 89% of cases the decision to stop treatment was related to multiple medical problems with a recent deterioration. Physicians raised the issue of withdrawal in the majority of cases and most patients subsequently received terminal care in hospital.

Decision Making↗
PubMed1995

Insulin-mediated changes in PD and glucose uptake after correction of acidosis in humans with CRF.

To test the hypothesis that acidosis contributes to the insulin resistance of chronic renal failure (CRF) and impairs the action of insulin to decrease protein degradation, eight CRF patients were studied using the combined L-[1-13C]leucine-euglycemic clamp technique before (acid) and after (NaHCO3) 4 wk treatment with NaHCO3 (pH: acid 7.29 +/- 0.01 vs. NaHCO3 7.36 +/- 0.01, P < 0.001). Protein degradation (PD) was estimated sequentially from the kinetics of a primed continuous infusion of L-[1-13C]leucine in the basal state and during a hyperinsulinemic euglycemic clamp. Insulin sensitivity was measured during the clamp. The correction of acidosis significantly increased the glucose infusion rate necessary to maintain euglycemia (acid 6.44 +/- 0.89 vs. bicarbonate 7.38 +/- 0.90 mg.kg-1.min-1, P < 0.01) and significantly decreased PD in the basal state (acid 126.4 +/- 8.1 vs. bicarbonate 100.1 +/- 6.9 mumol.kg-1.h-1, P < 0.001). Hyperinsulinemia decreased PD in both studies (acid basal 126.4 +/- 8.1 vs. clamp 96.5 +/- 7.7, P < 0.001; bicarbonate basal 100.1 +/- 6.9 vs. clamp 88.2 +/- 5.5 mumol.kg-1.h-1, P = 0.06), its effect being unaltered by acidosis, with a reduction of 24% before and 12% after the correction of acidosis. In conclusion, acidosis contributes to the insulin resistance of CRF but does not affect the action of insulin on PD.

Acidosis↗
PubMed1994

1% amino acid peritoneal dialysate: single-cycle study in diabetic patients with end-stage renal disease.

Uremia is associated with multiple abnormalities of carbohydrate and protein metabolism, which are partially corrected by continuous ambulatory peritoneal dialysis with dextrose-based solutions. The hormonal and metabolic effects of amino acid (AA)-based peritoneal dialysis have been studied in nondiabetic uremic patients. Such solutions may be particularly suitable for diabetic patients with end-stage renal disease provided the safety and efficacy of such solutions can be established. We have studied and compared the metabolic and hormonal responses to a single-cycle exchange of dextrose versus a 1% AA-based continuous ambulatory peritoneal dialysis solution in six diabetic patients with end-stage renal disease. In the fasting state and under similar free insulin concentrations, use of the AA solution led to a higher mean glucose concentration (109 +/- 16 mg/dL with dextrose solution v 128 +/- 25 mg/dL with AA solution, P < 0.05). Levels of alanine, lactate, pyruvate, glycerol, non-esterified fatty acids, and triglycerides were similar with the use of either solution. Use of the AA-based solution led to increases in the mean values of the branched chain AAs for the period of the study (valine 131 +/- 10 mumol/L with dextrose solution v 331 +/- 40 mumol/L with AA solution, P < 0.01; leucine 72 +/- 7 mumol/L with dextrose solution v 129 +/- 11 mumol/L with AA solution, P < 0.01; isoleucine 48 +/- 5 mumol/L with dextrose solution v 103 +/- 11 mumol/L with AA solution, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Recovery of 13C in breath from infused NaH13CO3 increases during euglycaemic hyperinsulinaemia.

1. The effect of euglycaemic hyperinsulinaemia on the recovery of 13C in expired CO2 has been assessed in six normal subjects. Each was studied on three occasions: once with a 6 h primed constant infusion of NaH13CO3 combined with a euglycaemic hyperinsulinaemic clamp for the last 3 h (study 1), once with a 6 h primed constant infusion of NaH13CO3 alone (study 2) and once with a 6 h infusion of normal saline combined with a hyperinsulinaemic clamp for the last 3 h (study 3). Measurements of 13C enrichment of expired CO2 were made in the third and sixth hour of each infusion. 2. There was no significant increase in enrichment during study 3 (3 h 0.00047 +/- 0.00016 versus 6 h 0.00069 +/- 0.00028 atom per cent excess) with potato-starch-derived D-glucose used to maintain euglycaemia. 13C recovery increased in the sixth hour of both study 1 and 2 (study 1: 3 h 74.4 +/- 2.0 versus 6 h 85.5 +/- 2.6%, P < 0.01; study 2: 3 h 72.1 +/- 2.4 versus 6 h 81.7 +/- 1.4%, P < 0.01). There was no significant difference in recovery between studies 1 and 2. 3. These results suggest that increased recovery during a sequential euglycaemic clamp is predominantly time-dependent. Studies which use this technique to examine the effect of insulin on substrate oxidation should take this into account.

Adult↗
PubMed1994

Acid-base regulation in peritoneal dialysis.

To prevent increased protein degradation and renal bone disease, optimal correction of acidosis should therefore be a priority in the management of CAPD patients. Initial results suggest that bicarbonate solutions may be more biocompatible than lactate, and one would expect increasing use over the next decade. Manufacturers could help to improve acid-base regulation in CAPD by providing a range of solutions with varying lactate and bicarbonate concentration, so that correction of acidosis could be optimized individually.

Acid-Base Equilibrium↗
PubMed1994

Production of interleukin 1 receptor antagonist and interleukin 1 during haemodialysis with cellulose membranes.

An in vivo cross-over study has investigated plasma and cellular levels of IL-1 (IL-1 alpha IL-1 beta and IL-1Ra) when using Cuprophan (C) and cellulose triacetate (CTA) membranes to assess the roles of complement activation and dialysate endotoxin content in the induction of cytokines during the dialysis procedure. The mean C5a level during Cuprophan dialysis was 29.9 +/- 0.63 ng/ml (Mean +/- SEM), while for the cellulose triacetate dialysis was 3.09 +/- 0.7 ng/ml. The endotoxin content of the dialysate was 0.31 +/- 0.34 EU/ml and 0.68 +/- 1.39 EU/ml. These two factors failed to produce measurable changes in plasma or cellular IL-1 alpha and IL-1 beta levels during treatment. The plasma IL-1Ra levels predialysis were similar to those for normal controls (CTA 769 +/- 156 ng/ml, C739 +/- 93, normal controls 635 +/- 33) with a considerable day to day variation. A membrane independent fall in plasma IL-1Ra at 15 minutes was noted (CTA 420 +/- 92 ng/ml, C 503 +/- 139) with a return to pre-dialysis levels by the end of treatment. Cellular IL-1Ra levels pre-dialysis were similar to the normal group--(CTA 1904 +/- 291 ng/ml, C 1564 +/- 292 and normal control 1971 +/- 368). However, on average, the values when using cellulose triacetate were 655 +/- 623 pg/ml higher than for Cuprophan (p = 0.03). These findings indicate that the measurement of plasma cytokine levels is of limited use in the study of cytokine induction by the haemodialysis procedure and that IL-1Ra may be a better indicator of the host response to cytokine stimuli during treatment. However, a considerable inter-patient and intra-treatment variation is present and further studies are required to elucidate the factors involved.

Aged↗