Diabetes with partial lipodystrophy following sclerodermatous chronic graft vs. host disease.

BACKGROUND: The importance of adipose tissue in metabolism, as a target for insulin action and a secretor of metabolic regulatory proteins, is increasingly recognized. Lipodystrophic conditions are often associated with significant insulin resistance. The commonest acquired form occurs with highly active antiretroviral therapy (HAART) for human immunodeficiency virus infection. Other medical conditions and drugs also have the potential to cause chronic subcutaneous fat damage. CASE REPORT: We describe an unfamiliar partial lipodystrophy in a young woman, associated with markedly insulin-resistant diabetes, acquired following allogeneic bone marrow transplantation for childhood leukaemia complicated by late sclerodermatous chronic graft vs. host disease (GVHD). Clinical examination revealed scarring and lipodystrophy affecting mainly legs, thighs, buttocks and forearms but sparing her face, neck and thorax. Her serum adiponectin level was markedly reduced. CONCLUSIONS: However, although thiazolidinediones lower insulin resistance and increase subcutaneous peripheral fat in Type 2 diabetes, pioglitazone treatment had little effect on either serum adiponectin, glycaemic control or the lipoatrophy. In this case, effective glycaemic control was best achieved using a combination of metformin and highly concentrated soluble insulin injections.

Cure of hyperparathyroidism in pregnancy by sternotomy and removal of a mediastinal parathyroid adenoma.

Primary hyperparathyroidism is rarely reported during pregnancy but can cause significant maternal and neonatal morbidity. We report a case of hyperparathyroidism during pregnancy requiring a median sternotomy for resection of a mediastinal parathyroid adenoma. Surgery resulted in normalisation of serum calcium, resolution of symptoms, and prevented neonatal hypocalcaemia.

Insulin action and hepatic glucose cycling in Cushing's syndrome.

OBJECTIVE: Although it is well established that hypercortisolism causes insulin resistance, the mechanisms responsible for impaired insulin action in Cushing's syndrome are unclear. This study investigated the contribution of the glucose/glucose-6-phosphate substrate cycle (G/G6P). PATIENTS: Eight patients with Cushing's syndrome and seven control subjects were studied. All had normal fasting plasma glucose. DESIGN: Insulin action was assessed using the euglycaemic glucose clamp at insulin infusion rates of 0.4 and 2.0 mU/kg/min combined with a simultaneous infusion of [2(3)H]- and [6(3)-H]-glucose. Glucose/ glucose-6-phosphate cycle activity was calculated as the difference in glucose turnover rates determined separately for [2(3)H]- and [6(3)H]-glucose by selective enzymatic detritiation. MEASUREMENTS AND RESULTS: Exogenous glucose infusion rates required to maintain euglycaemia were significantly lower in Cushing's patients compared to controls, during the 0.4 mU/kg/min (7.8 +/- 1.2 vs 15.7 +/- 0.5 mumol/kg/min, P < 0.001) and the 2.0 mU/ kg/min insulin infusions (26.2 +/- 2.8 vs 51.5 +/- 3.5 mumol/ kg/min, P < 0.001). Endogenous glucose production was similar in both groups in the postabsorptive state (10.2 +/- 0.3 vs 10.8 +/- 0.4 mumol/kg/min, P = 0.50) and suppressed to a similar degree during hyperinsulinaemia. G/G6P cycle activity was markedly increased in the Cushing's group in the postabsorptive state (5.4 +/- 1.1 vs 2.0 +/- 0.5 mumol/kg/min, P = 0.028) and during the 0.4 mU/kg/min (3.2 +/- 0.6 vs 1.2 +/- 0.4 mumol/kg/min, P = 0.014) and 2.0 mU/kg/min insulin infusions (3.3 +/- 0.8 vs 1.1 +/- 0.5 mumol/kg/min, P = 0.049). CONCLUSIONS: Patients with Cushing's syndrome show marked peripheral insulin resistance and enhanced hepatic G/G6P cycle activity. In the fasting state increased glucose/glucose-6-phosphate cycle activity may be a protective mechanism limiting hyperglycaemia. During hyperinsulinaemia G/G6P cycle activity was increased but insulin resistance was predominantly due to reduced peripheral glucose uptake.

Pancreas transplantation restores epinephrine response and symptom recognition during hypoglycemia in patients with long-standing type I diabetes and autonomic neuropathy.

Impaired epinephrine secretion and symptom unawareness are characteristic of severe hypoglycemia in individuals with long-standing type I diabetes. Recently, the avoidance of clinical hypoglycemia has been reported to improve epinephrine and symptom responses to hypoglycemia in type I patients. However, the extent to which these defects can be restored in individuals with long-standing type I diabetes and autonomic neuropathy has not been assessed, nor has it been determined whether pancreas transplantation, which not only obviates hypoglycemia but also prevents hyperglycemia, results in the complete recovery of either epinephrine response or symptom awareness during insulin-induced hypoglycemia. We performed stepped hypoglycemic clamp studies in successful pancreas transplantation recipients to assess epinephrine and other counterregulatory hormone responses during hypoglycemia and to determine the degree to which hypoglycemic symptom recognition could be restored. Thirteen pancreas transplant recipients and matched control subjects were studied utilizing stepped hypoglycemic clamp protocol to achieve target glucose levels of 3.9, 3.3, 2.8, and 2.2 mmol/l (70, 60, 50, and 40 mg/dl, respectively). Plasma epinephrine response was significantly greater in healthy control subjects and pancreas transplant patients compared with type I subjects at the glucose plateaus of 3.9, 3.3, and 2.8 mmol/l. However, epinephrine response in pancreas transplant recipients was significantly less than that seen in either healthy control subjects or nondiabetic kidney transplant recipients at each of these glucose plateaus. The magnitude of the epinephrine response in pancreas transplant type I patients did not correlate with either the duration of diabetes, the duration of transplantation, or the measures of autonomic nerve function. Hypoglycemic symptom recognition was significantly greater in pancreas transplant subjects than type I patients and did not differ between pancreas transplant and control groups. No improvement in norepinephrine response was observed after pancreas transplantation, while glucagon responses to hypoglycemia were normalized in pancreas transplant patients. In conclusion, these studies uniquely demonstrate that successful pancreas transplantation improves epinephrine response and normalizes hypoglycemia symptom recognition in patients with long-standing diabetes and established autonomic neuropathy. No correlation was observed between the severity of autonomic neuropathy or the duration of diabetes and the recovery of either the epinephrine or symptom responses to hypoglycemia.

The defective glucagon response from transplanted intrahepatic pancreatic islets during hypoglycemia is transplantation site-determined.

The optimal site for pancreatic islet cell transplantation is presently unclear, although the liver has been the most commonly used. However, glucagon secretion from islets that have been autotransplanted in liver has been reported to be unresponsive to hypoglycemia yet responsive to arginine. To determine whether this selective glucagon secretory defect is related to the intrahepatic site of islet implantation or to the process of transplantation per se, we studied counterregulatory responses to hypoglycemia in dogs with pancreatic islet autotransplantation in the hepatic parenchyma (the intrahepatic [IH] group, n = 9) or the peritoneal cavity (the intraperitoneal [IP] group, n = 9), following total pancreatectomy, and compared them with the responses in normal controls (n = 10). Dogs were subjected to a hypoglycemic hyperinsulinemic (5 mU x kg-1 x min-1) clamp for 90 min under general anesthesia. Arterial glucose concentrations were clamped at 2.7 mmol/l for the final 45 min of the clamp. Immediately following the clamp, glucagon responses to IV arginine (5 g) were also assessed. During hypoglycemia, glucagon responses in the IH group (maximal incremental glucagon = 33 +/- 21 ng/l; glucagon area under curve [AUC] = 713 +/- 1,022 ng x l-1 x min-1) were significantly lower than either the IP (maximal incremental glucagon = 92 +/- 32 ng/l; glucagon AUC = 4,090 +/- 1,600 ng x l-1 x min-1) or control (maximal incremental glucagon = 154 +/- 71 ng/l; glucagon AUC = 6,943 +/- 2,842 ng x l-1 x min-1) group (IH vs. IP group, P < 0.05; control vs. IH group, P < 0.01). Glucagon responses in the IP group did not differ significantly from the control group. Epinephrine responses to hypoglycemia were similar in all groups, whereas neither of the transplanted groups (IH and IP) had pancreatic polypeptide responses. There was a prompt rise in plasma glucagon after intravenous arginine in all groups. These data indicate that glucagon unresponsiveness to hypoglycemia is specific to intrahepatically transplanted islets, rendering the liver a disadvantageous site for optimal alpha-cell function.

Hepatic insulin resistance after pancreas transplantation in type I diabetes.

Hyperinsulinemia and peripheral insulin resistance caused by systemic insulin delivery and prednisone therapy are recognized consequences of pancreas transplantation. However, there is little information about insulin action on the liver. To investigate hepatic insulin sensitivity in recipients of pancreas transplants, we devised a staged euglycemic hyperinsulinemic clamp to measure hepatic glucose production (HGP) in 10 type I diabetic pancreas transplant recipients, 10 pair-matched healthy control subjects, and 6 nondiabetic kidney transplant recipients. Clamps were performed in two sequential stages. In stage 1, a 2-h low-dose insulin infusion (0.4 mU.kg-1.min-1) was used to partially suppress HGP. In stage 2, insulin-mediated suppression of HGP was challenged by a 1.5-h glucagon infusion (0.8 ng.kg-1.min-1), while continuing the hyperinsulinemic euglycemic-clamp conditions. During both stages, somatostatin (250 micrograms/h) was infused to suppress endogenous insulin secretion. All subjects underwent stage 1, and all except one pancreas recipient and a respective matched healthy control subject completed stage 2. Fasting HGP was greater in pancreas recipients than in healthy control subjects (15.1 +/- 0.7 vs. 12.0 +/- 0.4 mumol.l-1.kg-1.min-1, P < 0.005) but similar in healthy control subjects and in kidney recipients. During stage 2, both total (706 +/- 28 vs. 469 +/- 31 mumol.l-1.kg-1, P < 0.005) and incremental (62 +/- 20 vs. -21 +/- 16 mumol.l-1.kg-1, P < 0.005) HGP responses to glucagon infusion were significantly greater in pancreas recipients than in healthy control subjects. Changes in HGP in kidney recipients during stage 2 were not significantly different from those in healthy control subjects. In conclusion, fasting HGP is increased in pancreas transplant recipients. Furthermore, recipients have hepatic insulin resistance as demonstrated by an enhanced stimulatory effect of glucagon on HGP during insulin-mediated HGP suppression. Because the magnitude of hepatic insulin resistance was a significant (P < 0.01) predictor of HbA1c level, we suggest that variable hepatic insulin resistance may be responsible for some of the variance observed in glycemic levels after successful pancreas transplantation.

Blood pressure responses to phenylephrine infusions in subjects with Cushing's syndrome.

The pathogenesis of the hypertension associated with Cushing's syndrome is not completely understood. Sensitivity to pressor agents may play a role. We have investigated this possibility by measuring blood pressure (BP) during incrementally increasing infusions of the alpha-adrenergic agonist phenylephrine. Ten subjects (8 women: 2 men), aged 40 +/- 5 years (mean +/- s.e.m.) with Cushing's syndrome were studied. All had raised BP but none had received any anti-hypertensive treatment for at least 16 days before study. Ten age- (40 +/- 5 years) and sex-matched control subjects were also studied. At 13.30, 30 min after a light meal, subjects had an intravenous cannula inserted, ECG leads and a sphygomanometer cuff attached, and then rested supine in a quiet room for 30 min. Phenylephrine was then infused incrementally at intervals of 5 min. The doses used were 0.3, 0.6, 0.9, 1.35 and 2 micrograms/kg/min. Basal mean blood pressure (MAP) was 108 +/- 2 mm Hg (mean +/- s.e.m.) in patients and 74 +/- 3 mm Hg in controls (P < 0.05) and pulse rate was 75 +/- 5 and 68 +/- 3 beats/min (NS), respectively). MAP increased and pulse rate decreased linearly with time. The rate of rise of MAP was 1.7 +/- 0.4 mm Hg/min in subjects and 1.1 +/- 0.2 mm Hg/min in controls (NS). The rate of decrease of pulse was significantly more rapid in Cushing's subjects than in controls (1.4 +/- 0.2; 0.6 +/- 0.1 beats/min2; P < 0.05). The lack of any increased BP response to alpha-adrenergic stimulation suggests that altered sensitivity is not a major cause of the increased BP seen in patients with Cushing's syndrome.

Failure of complete suppression of endogenous glucose production by euglycaemic hyperinsulinaemia in normal humans.

In normal subjects, endogenous glucose production (EGP) is usually assumed to be completely suppressed during euglycaemic clamp studies performed at high insulin levels (> 100 mU L-1). However, this assumption is based on non-steady-state tracer measurements of EGP which are prone to negative errors. We have used purified [6-(3)H]glucose in an optimal tracer infusion protocol to assess the suppression of EGP during 4 h euglycaemic clamps in eight normal men. An insulin infusion rate of 5 mU kg-1 min-1 was chosen to achieve supraphysiological (> 500 mU L-1) plasma insulin concentrations. Using a labelled exogenous glucose infusion, plasma glucose (mean +/- SEM 5.3 +/- 0.1 mmol L-1) and glucose specific activities (mean 100 +/- 3% of basal) were maintained constant from 80 to 240 min. During hyperinsulinaemia, isotopically determined glucose appearance rates (Ra) were greater than glucose infusion rates (GIR) throughout the euglycaemic clamp period (P < 0.001) and EGP (Ra-GIR) was always greater than zero. In seven of the eight subjects studied EGP was partly suppressed but showed a wide variation (EGP 5 to 91% of basal at 80-120 min and 12 to 87% of basal at 200-240 min) while in one subject EGP rose above basal (by 72% at 80-120 min and 49% at 200-240 min). We conclude that EGP is not completely suppressed during euglycaemic clamps at high insulin levels.

The effect of cortisol on glucose/glucose-6-phosphate cycle activity and insulin action.

Increased glucose/glucose-6-phosphate (G/G6P) substrate cycle activity may be an early marker of disordered hepatic glucose metabolism. To investigate the effects of glucocorticoids on G/G6P cycle activity and insulin resistance, we studied eight normal subjects using the euglycemic glucose clamp technique with high pressure liquid chromatography-purified [2(3)H]- and [6-3H]glucose tracers at insulin infusion rates of 0.4 and 2.0 mU/kg.min after 24-h cortisol (2 micrograms/kg.min) and saline infusions. Endogenous glucose production ([6-3H]glucose) was greater after cortisol than saline in the postabsorptive state (13.3 +/- 0.5 vs. 12.2 +/- 0.5 mumol/kg.min; P < 0.05) and during 0.4-mU insulin infusion (10.5 +/- 0.7 vs. 5.0 +/- 0.8 mumol/kg.min; P < 0.005). During 2.0-mU insulin infusion, endogenous glucose production was suppressed similarly (5.1 +/- 0.4 vs. 4.1 +/- 0.5 mumol/kg.min), but glucose disappearance was less after cortisol than saline (38.7 +/- 3.5 vs. 64.6 +/- 4.3 mumol/kg.min; P < 0.001). G/G6P cycle activity after cortisol and saline was similar in the postabsorptive state and during 0.4 mU insulin. During 2.0 mU insulin, cycle activity was greater after cortisol than saline (3.6 +/- 0.9 vs. 0.8 +/- 0.5 mumol/kg.min; P < 0.005). In conclusion, cortisol induces hepatic insulin resistance without significantly changing G/G6P cycle activity. At high glucose turnover rates, G/G6P cycle activity is increased by cortisol; however, reduced glucose disappearance is the main cause of impaired insulin action.

An association between ANCA positive renal disease and malignancy.

The detection of anti-neutrophil cytoplasmic antibodies (ANCA) is now a routine part of the evaluation of patients clinically suspected of suffering from small vessel vasculitis. The factor(s) that trigger the development of these autoantibodies and their role in the pathogenesis of vasculitis is still unclear. We describe four patients who presented to us since June 1990. All patients had positive ANCA serology and had clinical evidence of vasculitis. In all patients soon after the establishment of ANCA positivity, a carcinoma of either the respiratory or urinary tracts was diagnosed. We suggest that in some cases of ANCA-associated vasculitis, malignant disease may be a trigger for either the generation of these autoantibodies, or the development of vasculitis.

Contribution of glucose/glucose 6-phosphate cycle activity to insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus.

It has been suggested that increased glucose/glucose 6-phosphate substrate cycling impairs net hepatic glucose uptake in Type 2 (non-insulin-dependent) diabetes mellitus and contributes to hyperglycaemia. To investigate glucose/glucose 6-phosphate cycle activity and insulin action in Type 2 diabetes we studied eight patients and eight healthy control subjects, using the euglycaemic glucose clamp and isotope dilution techniques with purified [2-3H]- and [6-3H] glucose tracers, in the post-absorptive state and eight patients and five healthy control subjects during consecutive insulin infusions at rates of 0.4 and 2.0 mU.kg-1 x min-1. [2-3H]glucose and [6-3H]glucose radioactivity in plasma samples were determined using selective enzymatic detritiation, allowing calculation of glucose turnover rates for each isotope, the difference being glucose/glucose 6-phosphate cycling. Endogenous glucose production ([6-3H]glucose) was greater in diabetic than control subjects in the post-absorptive state (15.6 +/- 1.5 vs 11.3 +/- 0.4 mumol.kg-1 x min-1, p < 0.05) and during the 0.4 mU insulin infusion (10.1 +/- 1.3 vs 5.2 +/- 0.3 mumol.kg-1 x min-1, p < 0.01) indicating hepatic insulin resistance. Glucose/glucose 6-phosphate cycling was significantly greater in diabetic than in control subjects in the post-absorptive state (2.6 +/- 0.4 vs 1.6 +/- 0.2 mumol.kg-1 x min-1, p < 0.05) but not during the 0.4 mU insulin infusion (2.0 +/- 0.4 vs 2.0 +/- 0.3 mumol.kg-1 x min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of growth hormone on glucose-glucose 6-phosphate cycle and insulin action in normal humans.

Increased activity of the hepatic glucose-glucose 6-phosphate (G/G-6-P) cycle is associated with hepatic and peripheral insulin resistance in acromegaly. To determine whether a similar association occurs after short-term growth hormone (GH) elevation within the physiological range, two-step euglycemic hyperinsulinemic clamps were performed in normal human males after 12-h GH (2.2 ng.kg-1 x h-1) and control infusions. G/G-6-P cycle activity and endogenous glucose production (EGP) were determined by [2-3H]- and [6-3H]-glucose using labeled exogenous glucose infusions and selective enzymatic detritiation. GH increased levels of circulating lipid intermediates despite a twofold increase in basal insulin (P < 0.005), but plasma glucose, EGP, and G/G-6-P cycle activity were unchanged. GH impaired insulin suppression of EGP and lipid intermediates and impaired insulin stimulation of glucose disposal, but G/G-6-P cycle activity was unchanged. We conclude that increased activity of the G/G-6-P cycle does not contribute to the hepatic insulin resistance induced by GH under these conditions but that changes in fatty acid metabolism may be partly responsible for the impairment in hepatic and peripheral insulin action.

Insulin action and hepatic glucose cycling in essential hypertension.

Peripheral insulin resistance is a feature of essential hypertension, but there is little information about hepatic insulin sensitivity. To investigate peripheral and hepatic insulin sensitivity and activity of the hepatic glucose/glucose 6-phosphate (G/G6P) substrate cycle in essential hypertension, euglycemic glucose clamps were performed in eight untreated patients and eight matched controls at insulin infusion rates of 0.2 and 1.0 mU.kg-1.min-1. A simultaneous infusion of (2(3)H)- and (6(3)H)glucose, combined with a selective detritiation procedure, was used to determine glucose turnover, the difference being G/G6P cycle activity. Endogenous hepatic glucose production (EGP) determined with (6(3)H)glucose was similar in hypertensive and control groups in the postabsorptive state (11.0 +/- 0.3 v 10.9 +/- 0.3 mumol.kg-1.min-1) and with the 0.2 mU insulin infusion (4.9 +/- 0.5 v 4.0 +/- 0.8 mumol.kg-1.min-1). With the 1.0 mU insulin infusion, glucose disappearance determined with (6(3)H)glucose was lower in the hypertensive group (21.8 +/- 2.4 v 29.9 +/- 2.4 mumol.kg-1.min-1, P less than .001). G/G6P cycle activity was similar both in the postabsorptive state (2.2 +/- 0.4 v 2.7 +/- 0.4 mumol.kg-1.min-1) and during insulin infusion (0.2 mU, 2.5 +/- 0.3 v 2.9 +/- 0.4; 1.0 mU, 4.7 +/- 0.3 v 5.3 +/- 1.1 mumol.kg-1.min-1 for hypertensive and control groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of low dose insulin infusions on the renin angiotensin and sympathetic nervous systems in normal man.

To examine the effects of physiological insulin concentrations on the renin-angiotensin and sympathetic nervous systems, healthy volunteers were studied by the euglycaemic glucose clamp technique with sequential 60 min 0.5 and 1.0 mU kg-1 min-1 insulin infusions and, subsequently, by a control infusion simulating clamp conditions. Plasma renin activity increased from 0.8 +/- 0.1 ng ml-1 h-1 basally to 1.0 +/- 0.2 ng ml-1 h-1 during the 0.5 mU infusion to 1.4 +/- 0.1 ng ml-1 h-1 during the 1 mU infusion but did not change during control infusion (0.9 +/- 0.3 ng ml-1h-1 to 0.9 +/- 0.2 ng ml-1h-1 to 1.0 +/- 0.1 ng ml-1h-1) (P less than 0.001 insulin vs. control by ANOVAR). Plasma angiotensin II increased during insulin (21.2 +/- 1.8 to 25.2 +/- 2.3 to 29.3 +/- 2.4 pg ml-1) but not during control infusion (24.0 +/- 2.8 to 23.6 +/- 2.6 to 23.5 +/- 2.5 pg ml-1) (P less than 0.001 insulin vs. control). Serum aldosterone did not change significantly during either infusion (insulin: 239 +/- 89 pmol l-1 to 237 +/- 50 pmol l-1 to 231 +/- 97 pmol l-1, control: 222 +/- 79 to 237 +/- 50 to 213 +/- 97 pmol l-1). Plasma noradrenaline increased to a greater extent during insulin (1.03 +/- 0.2 to 1.14 +/- 0.8 to 1.27 +/- 0.17 nmol l-1) than control infusion (0.86 +/- 0.09 to 0.97 +/- 0.09 to 0.99 +/- 0.09 nmol 1-1 (P less than 0.01 insulin vs. control). Changes in mean systolic blood pressure during insulin infusion were significantly different from control (+ 3 vs. -4 mmHg, P less than 0.001). In conclusion acute hyperinsulinaemia within the physiological range increases circulating hormones of the renin-angiotensin and sympathetic nervous systems and also increases systolic blood pressure.

Underestimation of glucose turnover determined using [6-3H]glucose tracer in non-steady state. The role of a tritiated tracer impurity.

The use of tritiated glucose tracers may result in underestimation of glucose turnover during hyperinsulinaemic clamps giving paradoxical negative endogenous glucose production rates. While mathematical modelling errors in the analysis of tracer data are major determinants of this underestimate in the non-steady state, the relative importance of tracer contamination under these conditions remains in doubt. We have used high performance liquid chromatography to assess the possible contribution to this problem of a labelled tracer impurity found in [6-3H]glucose. In conventional 4 h hyperinsulinaemic clamps performed in six normal subjects, labelled impurity increased as a percentage of the neutral plasma radioactivity fraction from 5.3 +/- 0.9% after a 2 h equilibration period (0 min) to 13.5 +/- 2.2% at 120 min and 15.4 +/- 2.4% at 240 min, as plasma glucose specific activities fell following the infusion of insulin. Negative endogenous glucose production rates were observed both at 90-120 min (-8.8 +/- 1.6 mumol.kg-1min-1) and at 210-240 min (-8.5 +/- 1.4 mumol.kg-1min-1) implying a persistent underestimate in isotopically determined glucose appearance rate. Using chromatography data to correct for impurity increased glucose appearance rates by 7.9 +/- 2.1% at 120 min and 11.0 +/- 2.5% at 240 min. Purified tracer was then used for a further six clamps. When the conventional protocol was used with unlabelled glucose infusion an obvious negative error persisted only at 90-120 min. In contrast, labelled infusions gave exclusively positive values for endogenous glucose production.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating immune complexes in sarcoidosis, a clinical role for the Raji assay?

Many immunological abnormalities, including circulating immune complexes (CICs), have been described in patients with sarcoidosis. The relationship of these abnormalities to clinical states is uncertain. In 31 proven cases of sarcoidosis we used the Raji assay in the investigation of the relationship between disease activity and the presence of CICs. Circulating immune complexes (greater than 49 micrograms.ml-1) were found in 11 of 14 patients with evidence of recent significant disease deterioration, whereas only one of 17 patients with chronic stable sarcoidosis demonstrated CICs (p less than 0.001). At follow-up, it was found that eight of the 11 cases with active disease and detectable CICs had resolved clinically. Resolution was accompanied by normalization of CICs in seven and persistence in one. The remaining three patients did not improve clinically and continued to demonstrate CICs. Measurements of complement levels did not demonstrate any significant difference between the two groups of patients. It is concluded that elevated levels of CICs, as detected by the Raji assay, are commonly found in association with significantly deteriorating sarcoidosis, often normalize following disease improvement and, consequently, may have a useful clinical role as a marker of activity.

Sunbed-induced melanoma in a rheumatoid patient.

The development in a rheumatoid patient of a cutaneous malignant melanoma following repeated exposure to UV-A Radiation from a sunbed for its supposed therapeutic effect, is described. A causal-effect relationship is proposed and the potential risks to other arthritic patients and in particular those with pigmented skin lesions, is highlighted.