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Biomedical subjects

C Mark Taylor

Publications and source records attributed to C Mark Taylor.

9 recordsLinked to original sources
PubMed2006

Renal transplantation in HUS patients with disorders of complement regulation.

Haemolytic uraemic syndrome (HUS) is the primary diagnosis of 4.5% of children on chronic renal replacement therapy. Approximately 5% of all HUS cases have an "atypical" or recurrent course. Atypical HUS is an inadequate term that applies to a heterogeneous group of conditions. We describe this group as non-diarrhoeal (D-) ), non-EHEC (EHEC - ) HUS. Patients in the non-diarrhoeal, non-EHEC, relapsing group are much more likely to exhibit severe hypertension, histological findings of arterial as well as arteriolar disease, chronic and end-stage renal failure. In general, these patients have an alarmingly high risk of graft loss from disease recurrence or thrombosis ranging from 60-100%. Family history is crucial, and where family members have relapsing disease, transplantation is a very high risk procedure (recurrence 100%). Patients with (D-)HUS need very careful consideration before transplantation, including molecular investigation of complement regulators (and von Willebrandt protease (ADAMTS13) activity, although this goes beyond the scope of this review). Guidelines are accessible under http://www.espn.ucwm.ac.uk . On no account should live related donation take place unless the risks of graft loss are understood. International collaboration to identify safer ways of transplanting these challenging patients is urgently needed.

ADAM Proteins↗
PubMed2005

Effect of verocytotoxins (Shiga-like toxins) on human neutrophils in vitro.

Neutrophil activation occurs in diarrhoea-associated HUS and correlates with disease severity, implying a role in pathogenesis. Verocytotoxin (Shiga-like toxin) has been shown to stimulate endothelium to release chemokines and express leukocyte adhesion molecules that would lead to indirect neutrophil-endothelial interaction. A direct action of verocytotoxin (VT) on neutrophils has been proposed, although in vitro studies of this are controversial. In this report we examine the effect of verocytotoxin-1 (Shiga-like toxin-1) (VT1) and verocytotoxin-2 (VT2) on human neutrophils in vitro with regard to priming, the release of superoxide and elastase, and chemotaxis. Neutrophils were incubated with VT1 or VT2 and superoxide and elastase release was measured over 120 and 45 minutes respectively. Priming was investigated by pre-treating the neutrophils with VT1 or VT2, exposing them to formyl-met-leu-phe (fMLP) or phorbol myristic acid (PMA) and measuring superoxide release. Neutrophil chemotaxis towards fMLP was assessed with and without pre-incubation with VT1 and VT2. We found that neither of the toxins induced superoxide or elastase release. Priming with VT1 significantly reduced superoxide release when neutrophils were stimulated with fMLP or PMA. VT2 priming gave a reduced superoxide release with PMA but not fMLP. Heat-inactivation of the toxins gave similar results. Pre-treatment of neutrophils with VT1 or VT2 did not affect chemotaxis towards fMLP after a 2-hour incubation period. In conclusion, VT1 and VT2 do not activate primed neutrophils in vitro. Nor do they affect chemotaxis towards fMLP. They may impair neutrophil priming.

Animals↗
PubMed2005

Childhood hemolytic uremic syndrome, United Kingdom and Ireland.

We conducted prospective surveillance of childhood hemolytic uremic syndrome (HUS) from 1997 to 2001 to describe disease incidence and clinical, epidemiologic and microbiologic characteristics. We compared our findings, where possible, with those of a previous study conducted from 1985 to 1988. The average annual incidence of HUS for the United Kingdom and Ireland (0.71/100,000) was unchanged from 1985 to 1988. The overall early mortality had halved, but the reduction in mortality was almost entirely accounted for by improved outcome in patients with diarrhea-associated HUS. The principal infective cause of diarrhea-associated HUS was Shiga toxin-producing Escherichia coli O157 (STEC O157), although in the 1997-2001 survey STEC O157 phage type (PT) 21/28 had replaced STEC O157 PT2 as the predominant PT. The risk of developing diarrhea-associated HUS was significantly higher in children infected with STEC O157 PT 2 and PT 21/28 compared with other PTs. Hypertension as a complication of HUS was greatly reduced in patients with diarrhea-associated HUS.

Adolescent↗
PubMed2004

Prognosis, treatment and outcome of childhood mesangiocapillary (membranoproliferative) glomerulonephritis.

BACKGROUND: Prognostic factors and outcome are incompletely known in childhood mesangiocapillary glomerulonephritis (MCGN). This study aimed to correlate renal outcome with clinical and histopathological variables. METHODS: We conducted a two-centre retrospective analysis of children with MCGN. RESULTS: Fifty-three children presented at a mean age of 8.8 years (range: 13 months-15 years). They were followed for a median of 3.5 years (range: 0-17 years). Histological classification identified 31 type 1, 14 type 2, two type 3 and six undetermined type. Mean renal survival [time to end-stage renal failure (ESRF)] was projected to be 12.2 years [confidence interval (CI): 9.7-14.6 years]. Five and 10 year renal survival was 92% (CI: 88-100%) and 83% (CI: 74-92%), respectively. Those with nephrotic syndrome at presentation had mean renal survival of 8.9 years (CI: 7.1-10.7 years) vs 13.6 years for those without (CI: 10.8-16.5 years) (P = 0.047). The mean estimated glomerular filtration rate (eGFR) at 1 year in those who progressed to ESRF was 52 vs 98 ml/min/1.73 m2 in those who did not (P < 0.001). Chronic damage scored on the first biopsy in 31 children (one centre) was positively associated with adverse renal outcome at 5 years: <20% was associated with 100% and > or =20% with 71% 5-year renal survival (P = 0.006). In 29 children treated with steroid there was a higher proportion (76%) with reduced eGFR at presentation and a significantly higher incidence of nephrotic syndrome (P = 0.002) and hypertension (P = 0.037). There were no significant differences in outcome eGFR, hypertension or proteinuria. CONCLUSIONS: Nephrotic syndrome at presentation and subnormal eGFR at 1 year were adverse features. The finding that structural disease at onset predicted poor renal outcome at 5 years has implications for the design of therapeutic trials. Treatment of MCGN was variable and not evidence-based.

Adolescent↗
PubMed2004

Urinary L-lactate excretion is increased in renal Fanconi syndrome.

BACKGROUND: Measurement of l-lactate in body fluids is an established clinical tool to identify disorders of cellular respiration. However, there is very little known about the clinical value of urinary lactate measurements. We investigated urinary lactate excretion in children with renal Fanconi syndrome. METHODS: Freshly voided urine samples were obtained from children with Fanconi syndrome and controls both with and without renal disease. Urine lactate was estimated by conversion to pyruvate in the presence of lactate dehydrogenase and NAD. The NADH produced was measured photometrically. Urine lactate was factored for urine creatinine. RESULTS: Children with Fanconi syndrome had a significantly higher urine lactate/creatinine ratio [mean: 84 x 10(-2) mmol/mmol; 95% confidence interval (CI): 40.8-127.1 x 10(-2) mmol/mmol] than healthy controls (mean: 1.3 x 10(-2) mmol/mmol; CI: 1.1-1.5 x 10(-2) mmol/ mmol) and those with a variety of renal diseases (mean: 3.1 x 10(-2) mmol/mmol; CI: 1.8-4.5 x 10(-2) mmol/mmol). CONCLUSIONS: Urinary lactate is increased in Fanconi syndrome. The increase is likely to be due to reduced lactate co-transport in the proximal tubule. Urinary lactate/creatinine has clinical utility as a sensitive test of disordered proximal renal tubular function.

Adolescent↗
PubMed2003

Renal length and inulin clearance in the radiologically normal single kidney.

Compensatory hypertrophy of a single functioning kidney is well described and has been shown to occur in utero. The long-term effects of hypertrophy and hyperfiltration in this situation are unknown. This study defined the growth parameters for single kidneys during childhood and correlated them with inulin clearance. Patients were those who had a radiologically "normal" single kidney, where the contralateral kidney was known to be non-functioning from infancy. Data were obtained from 74 children (40 boys and 34 girls) drawn from a registry of cases with a single kidney, and in whom simultaneous measurements of inulin clearance and renal length had been made at around 5, 10, and 16 years of age. Renal length was taken as the maximal bipolar measurement using real-time ultrasound scan. Inulin clearance was by continuous infusion technique. Nomograms for single kidney growth were determined against age, height, weight, and body surface area. Renal growth was correlated with inulin clearance. Renal length was found to correlate best with body surface area ( r=0.85, P<0.001), but this was not significantly superior to correlations with age, height, or weight separately. Inulin clearance per body surface area correlated positively with standardized renal length, i.e., Z score for renal length normalized for body surface area ( r=0.53, P<0.001). The larger kidneys have a higher glomerular filtration rate. Provided that the nephron number in the single kidney is similar to that in a paired kidney, single kidneys are hypertrophied and the single nephron glomerular filtration rate is likely to be abnormally high in these children.

Adolescent↗
PubMed2003

Sudden blindness caused by anterior ischemic optic neuropathy in 5 children on continuous peritoneal dialysis.

The authors report the occurrence of sudden blindness in 5 children (mean age, 32 months; range, 11 to 60) during continuous peritoneal dialysis regimen. All children presented with loss of light perception, visual fixation and ocular pursuit, and bilateral mydriasis unreactive to bright light. Fundoscopic examination found signs of anterior ischemic optic neuropathy with disc swelling, edema, and hemorrhages. Whereas 1 patient was dehydrated, the 4 other patients appeared well and not dehydrated. Nevertheless, blood pressure was below the normal range in all of them. Therefore, hypovolemia is highly suspected to have been the cause of ischemic optic neuropathy in all cases. Treatment consisted of steroids (4 patients), anticoagulation or antiagregation drugs (3 patients), plasma or macromolecules infusions (2 patients), vasodilatators (2 patients), and transient dialysis interruption (1 patient). One child with hepatic cirrhosis died 4 days later of acute liver insufficiency owing to ischemic hepatic necrosis. The other children had only partial improvement of vision during the following months. Because the prognosis of ischemic optic neuropathy is very poor, diagnosis and treatment of chronic hypovolemia in children on continuous peritoneal dialysis is essential to prevent such a devastating complication.

Blindness↗
PubMed2002

Appraisal of doctors: problems with terminology and a philosophical tension.

The term appraisal lacks useful definition. It is used to describe both the summative assessment which forms part of performance management, as well as an educational process sometimes referred to as formative assessment. In this analysis we trace the purpose of each of these components as applied to career grade doctors. In the first, authority for the process, and the motive for applying it, lies with management. Within a publicly funded health service the purpose of this is directed towards equality of health care, and to obtain the greatest performance available with the resources available. By contrast, appraisal which supports a doctor's self-directed learning is likely to address issues of quality. The two processes exist in tension with each other, and are mutually informative. We argue that in the appraisal of doctors the two processes and purposes should be made explicit.

Education, Medical, Continuing↗