Investigation of the serum complement system in 25 patients with various forms of lipodystrophy showed no abnormality in three patients with total lipodystrophy; a single patient with limb lipodystrophy had evidence of activation of the classical complement pathway. However, of the 21 patients with partial lipodystrophy, 17 had low serum C3, with normal C4 and C2, concentrations, accompanied in 14 by a serum C3 splitting factor indistinguishable from nephritic factor, suggesting activation of the alternative pathway. These abnormalities occurred in 10 patients without clinically overt renal disease. Seven patients had overt nephritis; renal biopsies obtained in six showed mesangiocapillary (membranoproliferative) nephritis in all. Thus, the majority of patients with partial lipodystrophy have hypocomplementemia. Although nephritis may not invariably develop, the high rate of mesangiocapillary nephritis in these patients suggests that complement activation via the alternative pathway predisposes to the development of this form of glomerular disease.

After adjusting for APACHE II scores, personal or family history of DVT, body mass index, vasopressor use, type of thromboprophylaxis, and presence of leg DVT, NLDVTs were associated with an increased risk of PE (hazard ratio, 11.83; 95% CI,). Nonleg NLDVTs were not associated with ICU mortality (hazard ratio, 1.09; 95% CI, 0.62-1.92) in a model that adjusted for age, APACHE II scores, vasopressor use, mechanical ventilation, renal replacement therapy, and platelet count below 50 Â 109/L.Comment: The data indicate that patients who have a malignant condition seem to have a higher risk of developing NLDVT. However patients with NLDVT do not appear to be of higher risk of death. It is important to remember that this study was conducted in the context of a clinical trial comparing 2 anticoagulants so all patients were undergoing thromboprophylaxis. Of the NLDVTs in this study, 34 (1.1%) were catheter related proximal DVTs. The clinical course of the NLDVTs in these patients was actually unclear as the original study was not designed to assess outcomes of NLDVTs. What is clear is that NLDVT occurs despite the use of thromboprophylaxis and additional studies will be needed to determine the clinical relevance of NLDVT both in and outside studies of thromboprophylaxis.

. Familial insulin-resistant diabetes, multiple somatic anomalies, and pineal hyperplasia. A syndrome comprising unusual facies, dry skin, acanthosis nigricans, thickened nails, hirsutism, dental precocity and dysplasia, abdominal protuberance, and phallic enlargement is described in 2 sibs. Both have developed diabetic ketoacidosis with insulin resistance. The elder child, a girl, had recurrent septic episodes and died at the age of 7 8 years. At necropsy the pineal gland was hyperplastic, weighing 900 mg. Investigation of the younger sib over a 4-year period has shown decreasing glucose tolerance, and he was frankly diabetic with ketoacidosis by the age of 6 * 8 years. Serum insulin concentrations have always been grossly raised. Though the mechanism for insulin resistance has not been definitely established, a functional abnormality of the hypothalamus or pituitary is postulated to explain the many endocrine features of the syndrome.

SUMMARY Mendenhall's syndrome comprises insulin-resistant diabetes, pineal hyperplasia, and various somatic anomalies. A boy with this condition now aged 12 years is reported; a similarly affected sibling died aged 7.8 years. Hypophysectomy has been of short-term benefit, but the problems of insulin resistance persist. On the basis of monocyte-binding studies it seems likely that in this condition there is an inherited deficiency of insulin receptors.Mendenhall' described 3 siblings with unusual facies, dental precocity and dysplasia, thickened nails, hirsutism, acanthosis nigricans, abdominal protruberance, and phallic enlargement. All 3 died in midchildhood from insulin-resistant diabetes mellitus and at necropsy there was pineal hyperplasia.2 We previously described a further 2 siblings with this syndrome and showed that the insulin resistance could not be explained by excess production of corticosteroids, glucagon, or growth hormone, nor was it explained by circulating insulin antibodies. The elder sibling died at age 7-8 years; necropsy confirmed pineal hyperplasia.3 We now report further studies, and the progress of the second child, who has had a hypophysectomy for life-threatening diabetic ketoacidosis. Case reportThis boy was the second child of unrelated parents. He was born at term weighing 2-3 kg, and unusual facies and abdominal distension were noted at birth. An abnormal dentition started at 4 months.4 Developmental progress was normal.From his appearance it was apparent that he had the same syndrome as his elder sister, so he was first studied, before he had any symptoms, at age 3-1 years. At that time he was well nourished, and both weight and height were between the 3rd and 10th centiles. There was acanthosis nigricans of neck, axillae, and cubital fossae. The nails were thickened, there was moderate hypertrichosis, the teeth were dysplastic, and the tongue fissured. There was penile enlargement, but no pubic hair or testicular enlargement.Oral glucose tolerance tests were performed, first at age 3-1 years, and at intervals thereafter (Fig. 1).Serum insulin levels were grossly raised on each occasion, confirming that insulin resistance had been present from an early age.He remained well until 6-8 years, when he gradually developed increasing thirst and polyuria. Fasting blood glucose varied between 11-0 and 15-0 mmol/l (200-275 mg/100 ml), and urine volume was 3-4 litres daily. He was ketonuric and hypokalaemic, and oral potassium supplements were started. This development of hyperglycaemia was accompanied by a fall in concentration of serum insulin, suggesting islet cell failure. It was known from experience with his sister that only extremely large doses of insulin would be likely to have an effect on blood sugar, and as these would have been impracticable for

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