Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene

Background Familial partial lipodystrophy (FPLD) is a monogenic form of diabetes characterised by a dominantly inherited disorder of adipose tissue associated with the loss of subcutaneous fat from the limbs and trunk, with excess fat deposited around the face and neck. The lipodystrophy causes severe insulin resistance, resulting in acanthosis nigricans, diabetes, dyslipidaemia, and increased risk of cardiovascular disease. Preliminary results from animals and man suggest that increasing subcutaneous fat by treatment with thiazolidinediones should improve insulin resistance and the associated features of this syndrome. Case report We report a 24-year-old patient with FPLD caused by a mutation in the LMNA gene (R482W) treated with 12 months of rosiglitazone. Subcutaneous fat increased following rosiglitazone treatment as demonstrated by a 29% generalised increase in skin-fold thickness. Leptin levels increased from 5.8 to 11.2 ng/ml. Compared with treatment on Metformin, there was an increase in insulin sensitivity (HOMA S% 17.2–31.6) but no change in glycaemic control. The lipid profile worsened during the follow-up period. Conclusion This initial case suggests that, for modification of cardiovascular risk factors, there are no clear advantages in treating patients with FPLD with rosiglitazone despite increases in subcutaneous adipose tissue. Larger series will be needed to identify moderate beneficial effects and treatment may be more effective in patients with generalised forms of lipodystrophy.     

Localized osteolysis in stable, non-septic total hip replacement

We are reporting four cases of extensive, localized bone resorption adjacent to a rigidly anchored, cemented total hip replacement. None of these hips showed evidence of infection on clinical, bacteriological, or pathological evaluation. The tissue from the regions of osteolysis showed sheets of macrophages and foreign-body giant cells invading the femoral cortices. Abundant methylmethacrylate particulate debris was present in the tissues, but polyethylene wear debris was absent. The histological appearance of this tissue resembled that reported about loosened total hip implants with the exception of the synovial-like layer at the cement surface. The cases reported here show that aggressive bone lysis may occur around stable cemented total hip arthroplasties without the presence of sepsis or malignant disease.     

Interaction between insulin and glucose-delivery route in regulation of net hepatic glucose uptake in conscious dogs

In the presence of fixed basal levels of insulin, the route of intravenous glucose delivery (protal vs. peripheral) determines whether net hepatic glucose uptake (NHGU) occurs. Our aims were to determine if the route of intravenous glucose delivery also plays a role in regulating NHGU in the presence of hyperinsulinemia and to determine if length of fast (18 vs. 36 h) influences regulation of NHGU. Five conscious dogs fasted 18 h were given somatostatin and replacement insulin (245 +/- 34 microU.kg-1.min-1) and glucagon (0.65 ng.kg-1.min-1) infusions intraportally. After a 40-min control period, the insulin infusion rate was increased fourfold, and glucose was infused for 3 h. Glucose was given either through a peripheral vein or the portal vein for 90 min to double the glucose load reaching the liver. The order of infusions was randomized. NHGU was measured with the arterial - venous difference technique. Insulin and glucagon levels were 12 +/- 2, 35 +/- 6, and 36 +/- 5 microU/ml and 55 +/- 12, 61 +/- 13, and 59 +/- 7 pg/ml during the control, peripheral, and portal infusions, respectively. The glucose infusion rate, the load of glucose reaching the liver, and the arterial-portal plasma glucose gradient were 0, 9.58 +/- 2.28, and 10.44 +/- 2.94 mg.kg-1.min-1; 29.4 +/- 3.6, 56.8 +/- 3.4, and 56.8 +/- 2.8 mg.kg-1.min-1; and 2 +/- 1, 5 +/- 1, and -51 +/- 15 mg/dl during the same periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sleep spindles in normal elderly: comparison with young adult patterns and relation to nocturnal awakening, cognitive function and brain atrophy

Visual measurements of sleep spindles were carried out in 48 elderly and 20 young normal adults. Computed tomography brain scans and psychometric testing were also performed. Earlier findings of reduced spindle abundance, amplitude and duration in the elderly were confirmed. In addition, we demonstrated a linear increase in spindle density and duration across NREMPs in young adults that was absent in the elderly, indicating that age affects the temporal pattern as well as the quantity of spindles. Contrary to what seemed a highly plausible hypothesis, the amount of waking in the elderly was not inversely correlated with spindle abundance, confirming earlier observations (Feinberg et al. 1967) but in a much larger group. This finding suggests that spindle abundance does not reflect the integrity of the systems that maintain the brain in NREM sleep. We also were unable to show any clear evidence that relative preservation of spindles in the elderly is associated with relative preservation of cognitive skills: psychometric performance and spindle measures were, in most instances, not significantly correlated. However, the test of this hypothesis was limited by the high level of function and the narrow range of impairment of these Ss. One intriguing positive finding was the significant inverse relation between ratings of sulcal atrophy and spindle amplitude. This observation suggests an etiology for the reduced amplitude of the sleep EEG in old age. This change is one of the most striking effects of age on brain electrophysiology.     

A prophylactic bolus of thiopentone does not protect against prolonged focal cerebral ischaemia

Barbiturate coma is still recommended for brain protection during periods of temporary focal ischaemia such as during carotid endarterectomy. We tested the hypothesis that a single dose of barbiturate given before a period of protracted severe focal ischaemia would protect against focal cerebral infarction. Sixteen cats had the proximal left middle cerebral artery (MCA) occluded. Eight cats received halothane alone titrated to keep their pulse and blood pressure within the normal range. Eight cats received, in addition to halothane, a bolus of thiopentone sufficient to produce an isoelectric EEG immediately prior to MCA occlusion. Six hours after the occlusions the animals were sacrificed and the brains scored histologically to assess both size and severity of ischaemia. There was no statistically significant difference in the size or severity of the infarcts between the groups. We conclude from this study that the extent of the histological injury was not reduced by a single prophylactic bolus of thiopentone given before prolonged focal cerebral ischaemia.     

Neonatal intensive care admissions: changing profile in Georgia, 1974 to 1982

Birthweight-specific admission rates were reviewed from 1974 to 1982 for Georgia's five regional perinatal centers. Analysis of birthweight-specific neonatal intensive care unit (NICU) admissions as a proportion of total live births revealed an upward trend for infants weighing 1,000 to 1,499 gm and a downward trend for those weighing 2,000 gm or more. This method revealed no significant trends for infants of weight groups less than 500 gm or 500 to 999 gm. Analysis of birthweight-specific admissions as a proportion of total NICU admissions revealed significant increases for all birthweight groups of less than 2,000 gm, with decreases in admissions for infants weighing more than 2,000 gm. Analysis of mortality data revealed improved survival for infants weighing less than 1,500 gm, but some centers showed increases in neonatal mortality, postneonatal mortality, or infant mortality among infants weighing 2,500 gm or more. During this study, low birthweight infants comprised an increasingly larger proportion of neonatal intensive care admissions. This trend evolved gradually through the process of regionalization and can be directly linked to the cost requirements of regional neonatal intensive care units.     

Reaction of chromium (VI) with hydrogen peroxide in the presence of glutathione: reactive intermediates and resulting DNA damage

The reaction of chromium(VI) with hydrogen peroxide was studied in the presence of glutathione. In vitro, reaction of chromium(VI) with hydrogen peroxide alone led to production of hydroxyl radical as the significant reactive intermediate, while reaction of chromium(VI) with glutathione led to formation of two chromium(V)-glutathione complexes and the glutathione thiyl radical. Incubation of chromium(VI) with glutathione prior to addition of hydrogen peroxide led to formation of peroxochromium(V) species and a dramatic increase in hydroxyl radical production over that detected in the reaction of chromium(VI) with hydrogen peroxide alone. In contrast, addition of chromium(VI) to a preincubated mixture of glutathione and hydrogen peroxide led to a decrease in hydroxyl radical production over that obtained in the reaction of chromium(VI) with hydrogen peroxide. When pBR322 DNA was added to the above reactions, the extent of chromium(VI)-induced DNA strand breakage correlated with the relative amount of hydroxyl radical formed. Reaction of chromium(VI) with calf thymus DNA in the presence of a preincubated mixture of glutathione and hydrogen peroxide led to detection of the 8-hydroxydeoxyguanosine adduct, whose formation correlated with that of hydroxyl radical production. No significant chromium-DNA adduct formation was detected. The results suggest that, in the cellular metabolism of chromium(VI), preformed chromium(V)-glutathione complexes may react with hydrogen peroxide in a Fenton-type manner to produce hydroxyl radical as the DNA-damaging agent. However, if glutathione reacts with hydrogen peroxide prior to exposure to chromium(VI), the amount of hydroxyl radical generated may not be sufficient to cause significant DNA damage.(ABSTRACT TRUNCATED AT 250 WORDS)