ACE is not likely to play a role as a determinant of ADPKD phenotype severity.

Hypoglycaemia and lactic acidosis are potentially life-threatening, poorly understood sequelae of Plasmodium falciparum infections. We investigated relationships between clinical status, treatment, and glucose and lactate kinetics during management of falciparum malaria in 14 Vietnamese adults. Nine had severe malaria, of whom 4 were administered quinine (Group 1a) and 5 artesunate (Group 1b). Five uncomplicated cases received artesunate (Group 2). Glucose and lactate turnover were studied on 3 occasions: (i) immediately after initial antimalarial treatment, (ii) at parasite clearance a median of 3 days later, and (iii) at discharge from hospital a median of 9 days post-admission. Steady-state glucose and lactate kinetics were derived from plasma isotopic enrichment during a primed-continuous infusion of D-[6,6-D2]glucose and a parallel infusion of L-[1-13C]lactate. Group 1a patients had the lowest plasma glucose concentrations in the admission study (median [range] 3.9 [3.6-5.1] vs 6.3 [4.9-7.1] and 4.5 [4.3-5.5] mmol/L in Groups 1b and 2 respectively; P < 0.05 vs Group 1b), but glucose production rates and serum insulin concentrations that were similar to those in the other groups (P > 0.17). This was also the case at parasite clearance and suggested an inappropriate beta cell response. Group 1a patients had the highest admission lactate production (60 [36-77] vs 26 [21-47] and 22 [4-31] mumol/kg.min in Group 1b and 2 respectively; P < 0.05 vs Group 2). Amongst the 9 severe cases, there was an inverse association between plasma glucose and lactate production at admission and parasite clearance (P < 0.05), but no correlation between admission lactate production and serum bicarbonate (P = 0.73). The present data confirm previous studies showing that quinine depresses plasma glucose through stimulation of insulin secretion. It is hypothesized that the low plasma glucose activates Na+,K(+)-ATPase through increased plasma catecholamine concentrations, leading to accelerated glycolysis and increased lactate production in well-oxygenated tissues. In some severely ill patients with falciparum malaria, a raised plasma lactate on its own may, therefore, be an unreliable index of a developing acidosis.

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We have demonstrated that heterozygous FHBL subjects with apoB truncations shorter than apoB-48, and therefore only a single fully-functional apoB-48 allele, have decreased TRL production but normal postprandial TRL particle clearance.

SUMMARY Thresholds for cutaneous warming and cooling stimuli were measured in 20 diabetics with neuropathic foot ulcers. All patients had a profound disturbance of sensory perception in the ulcerated foot with complete loss ofperception ofwarming; thresholds for vibration and cooling were highly abnormal in all but two patients. Measurements of thermal threshold were made on both feet in 10 patients: warming was lost bilaterally in all, and cooling was bilaterally absent in six. There was no clear pattern of sensory loss in those diabetics with unilateral foot ulceration to suggest that sensory impairment was the determining factor for the development ofa plantar ulcer. Measurements of thermal thresholds were made at additional sites in 13 patients and although the most marked abnormalities of sensation were always found in the feet, in some severe neuropaths, abnormal thresholds on the hand and even the face were demonstrated. Thresholds for warming were invariably more abnormal than thresholds for cooling. The diabetics with neuropathic ulceration in this study all had severe generalised peripheral nerve disease involving large myelinated as well as both small myelinated and unmyelinated sensory fibres. The quantitative evidence on the distribution of sensory loss for thermal sensations supports the hypothesis that the neuropathic process affecting the small myelinated and unmyelinated fibres is length dependent.Although loss of sensation is not the sole aetiological factor in the pathogenesis of diabetic plantar ulceration,' profound neuropathy does appear to be an essential feature for the development of this complication. The view that ulceration occurs as a consequence of repeated mechanical trauma on an insensitive sole23 is probably an over simplification and the loss of other neural functions, such as those subserved by the autonomic innervation may alse be important.It has long been recognised that painless plantar foot ulcers occur in diabetics with severe generalised neuropathy. More recently, emphasis has been placed on the severity of the small myelinated and unmyelinated fibre dysfunction that occurs in these patients. The occurrence of a generalised autonomic neuropathy was demonstrated by studies ofcardiovascular reflexes which showed particularly severe defects in diabetics with foot ulcers.' Means of specifically