[Headaches]. / Kopfschmerzen.

Headaches can be so severe that patients and doctors often fear life-threatening underlying cerebral pathologies. The spectrum of causes of headache is very heterogeneous and ranges from harmless situations to severe diseases, so that it is very difficult to consider all differential diagnoses simultaneously; however, a few targeted questions and physical examinations are sufficient to be able to make a better classification of the leading symptom headache. The following article serves as a quick guide for identification of patients at risk. It describes basic findings, red flags and specials warning signs that must immediately lead to emergency admission for further diagnostics.

Improvement of HAART-associated insulin resistance and dyslipidemia after replacement of protease inhibitors with abacavir.

OBJECTIVE: To assess the effect of replacing protease inhibitors (PIs) with abacavir on insulin sensitivity and plasma lipids. - DESIGN: Pilot study including 31 patients with sustained virological control on their first PI-containing HAART regimen. 16 patients were switched from PIs to abacavir (ABC group), 15 patients continued on PIs (PI group). In all patients, nucleoside-analogue reverse transcriptase inhibitors were continued. METHODS: Insulin sensitivity (using an intravenous insulin tolerance test) and fasting total cholesterol and triglycerides were determined at baseline, month 3, 6, 9 and 12. RESULTS: In the ABC group, there was a significant increase in median insulin sensitivity from baseline within 6 months (+ 49 micromol/l/min), and a significant decrease in both triglycerides (-41mg/dl) and cholesterol (-40mg/dl) at month 3. These changes were sustained through month 12. In addition, a reversal of baseline insulin resistance, hypercholesterolemia and hypertriglyceridemia was observed in the majority of patients. In the PI group, no significant changes in insulin sensitivity, triglycerides and cholesterol were observed. There was a significant correlation between the changes in insulin sensitivity, triglycerides and cholesterol. INTERPRETATION: Switching from PIs to abacavir is associated with an improvement of insulin sensitivity and a decrease of cholesterol and triglycerides in the majority of patients with HAART-associated metabolic alterations and therefore might be an alternative for patients to PI-containing HAART regimens.

Alterations of apolipoprotein B metabolism in HIV-infected patients with antiretroviral combination therapy.

BACKGROUND: Dyslipidemia (predominantly hypertriglyceridemia) is frequently seen in patients receiving antiretroviral combination therapy (ART). However, the underlying mechanisms and long-term risks (e.g., cardiovascular events) are still unclear. OBJECTIVES/METHODS: In 5 patients with ART-associated dyslipidemia, stable isotope labeled amino acid tracer (d3-Leu) kinetic analysis over 12 days was used to investigate the metabolism of apolipoprotein B-containing lipoproteins (very low density lipoproteins [VLDL]1, VLDL2, intermediate density lipoproteins [IDL] and low density lipoproteins [LDL]). Data were compared with those in 6 healthy normolipidemic controls. RESULTS: The patients under ART showed significantly increased fasting triglycerides (359 vs. 77 mg/dl) and VLDL (54 vs. 15 mg/dl), compared with controls. They had significantly higher total cholesterol (213 vs. 157 mg/dl) and there was a nonsignificant trend toward higher LDL (136 vs. 93 mg/dl), and toward lower HDL (26 vs. 46 mg/dl). The ratio of large, buoyant LDL1 over small, dense LDL2 was markedly reduced in patients under ART (0.80 vs. 2.00). Total apo B synthesis was significantly increased (25.5 vs. 14.5 mg/kg/d) and shifted toward triglyceride rich VLDL1 (18.5 vs. 8.7 mg/kg/d) in patients receiving ART. There was also a significantly reduced rate of apo B lipoprotein transfer from VLDL1 to VLDL2 (3.7 vs. 20.7 pools/d). In addition, all patients revealed insulin resistance. CONCLUSIONS: These data indicate that increased triglycerides in HIV-infected patients with ART are primary due to reduced rates of VLDL transfer into denser lipoproteins implying a lower rate of lipoprotein lipase-mediated delipidation. In addition, total apo B synthesis was increased and shifted toward triglyceride-rich VLDL1. Overall, this lipoprotein profile in patients with ART-associated dyslipidemia implies an increased risk for cardiovascular events.

Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus.

Antiretroviral therapy (ART) is frequently associated with metabolic alterations, including insulin resistance and diabetes mellitus. In this pilot study, we evaluated the effect of the PPARgamma activator troglitazone on ART-associated insulin resistance in HIV-infected patients with ART-associated diabetes mellitus. Six patients with protease inhibitor (PI)-associated diabetes mellitus, lipodystrophy and dyslipidemia were treated with troglitazone 400 mg q.d. for 3 months. Previous oral antidiabetics were discontinued prior to the study. At baseline and after 3 months, insulin sensitivity (intravenous insulin tolerance test), body composition (multifrequence bioelectrical impedance analysis) and fat distribution (CT scan quantification) were assessed. Glycaemic control (fasting and postprandial blood glucose, fructosamine, glycosylated haemoglobin) and serum lipid status were determined monthly. In four of the six patients, there was a clear improvement in insulin sensitivity, resulting in a reversal of insulin resistance in two of these patients. Overall, there was an increase in lean body mass and a decrease in total body fat. The volume of visceral adipose tissue decreased whilst the volume of subcutaneous adipose tissue increased. Total cholesterol, LDL and HDL cholesterol increased, and total triglycerides and VLDL-cholesterol decreased. No adverse effects such as hepatotoxicity were observed. Treatment with troglitazone 400 mg q.d. can ameliorate and in some cases even reverse ART-associated insulin resistance. Therefore, further studies including non-diabetic patients with ART-associated insulin resistance may be helpful in evaluating the long-term effects of thiazolidinediones on ART-associated insulin resistance and other metabolic complications, such as adipose maldistribution and dyslipidaemia.

Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infected patients.

BACKGROUND: The use of protease inhibitors in the treatment of HIV-1 infection is associated with the new onset of diabetes mellitus, hyperlipidaemia and lipodystrophy. It is unclear whether these findings are coincidental or whether they reflect a causative effect of protease inhibitors. OBJECTIVE: To evaluate the effect of treatment with protease inhibitors on insulin sensitivity, oral glucose tolerance and serum lipids in HIV-infected patients in order to determine whether treatment with protease inhibitors can cause peripheral insulin resistance. DESIGN: Cross-sectional controlled study in HIV-infected patients treated with protease inhibitors to assess insulin sensitivity, oral glucose tolerance and changes in serum lipids. METHODS: Sixty-seven patients treated with protease inhibitors, 13 therapy-naive patients and 18 HIV-negative control subjects were tested for insulin sensitivity (intravenous insulin tolerance test). In a subgroup of 24 treated patients, oral glucose tolerance was determined. Serum lipids prior to and under treatment with protease inhibitors were compared. RESULTS: Patients on protease inhibitors had a significantly decreased insulin sensitivity when compared with therapy-naive patients (median, 75 and 156 micromol/l/min, respectively; P < 0.001). All treated patients with impaired (n=4) or diabetic (n=9) oral glucose tolerance, and four out of 11 patients with normal glucose tolerance showed peripheral insulin resistance; all therapy-naive patients had normal insulin sensitivity. Treatment with protease inhibitors led to a significant increase in total triglycerides and cholesterol in the 67 treated patients (median increase, 113 and 37 mg/ml, respectively). CONCLUSION: Treatment with protease inhibitors is associated with peripheral insulin resistance, leading to impaired or diabetic oral glucose tolerance in some of the patients, and with hyperlipidaemia. Overall, there is a large variation in the severity and clinical presentation of protease inhibitor-associated metabolic side-effects.