Antibodies to components of neutrophil cytoplasm: a new diagnostic tool in patients with Wegener's granulomatosis and systemic vasculitis

Eleven patients with symptoms highly suggestive of Wegener's granulomatosis are described. In spite of extensive investigation, only in two patients was a firm histological diagnosis of Wegener's granulomatosis obtained, while the remaining patients were either diagnosed as having unclassifiable systemic vasculitis or had no histological diagnosis made. This sometimes resulted in diagnostic and therapeutic delay and irreversible organ damage. Antibodies to components of neutrophil cytoplasm--recently demonstrated to be specific for Wegener's granulomatosis--were detected by indirect immunofluorescence in 10 of 11 patients, and it appears likely that antibodies to components of neutrophil cytoplasm will prove to be of great value in early diagnosis.     

Determination of capillary leakage due to recombinant interleukin-2 by means of noninvasive conductivity measurements

Summary One of the most common side effects of treatment with recombinant interleukin-2 (IL-2) is capillary leakage. Its genesis is not completely understood. The aim of the study was to determine whether capillary leakage can be monitored by means of a non-invasive conductivity technique and to study its starting point. Eight patients with advanced renal cell cancer were studied in a medium care section of the Department of Medical Oncology, University Hospital over 4 days during treatment sessions of continuous, intravenously administered IL-2 (mean dose of 15.6 × 10⁶ IU · m^–2 · day ^–1). The fluid shift from the intravascular to the extra- and intracellular compartments was monitored by means of noninvasive conductivity measurements. Changes in blood volume were calculated from serial erythrocyte counts. The clinical parameters of capillary leakage (oliguria, positive fluid balance, and gain in mass) were recorded. The mean gain in mass was 9% after 4 days of IL-2 treatment. The extracellular fluid volume increased significantly [46 (SD 23.2)%; P < 0.01], whereas the intracellular fluid volume did not change. The increase in blood volume (BV) amounted to 7% (P < 0.05). The decline in albumin concentration was significantly more than the increase in BV [38 (SD 4.3) %; P < 0.01], indicating capillary albumin leakage. The main changes were observed after the 2nd day of treatment. From this study, it is suggested that conductivity measurements are a suitable method to monitor capillary leakage induced by IL-2, and could be used to detect the exact onset and severity of this leakage. The leakage started within the first 24 h of treatment and was detected as a fluid shift from the intravascular to the extracellular space, while the intracellular compartment remained stable. These measurements could be useful during intervention studies with the aim of preventing this adverse effect of IL-2.     

A comparison of labetalol and prazosin combined with atenolol in non-responders to atenolol plus hydrochlorothiazide in uncomplicated hypertension

Summary After screening two local populations in the northern part of The Netherlands for hypertension, patients with a diastolic pressure (DP) between 95 and 120 mmHg were treated daily either with 50 mg hydrochlorothiazide or 100 mg atenolol. Non-responders were given the combination and if necessary the dose of atenolol was increased to 200 mg. Non-responders to the latter combination were randomized and treated either with 50 mg hydrochlorothiazide and labetalol or with 50 mg hydrochlorothiazide, 200 mg atenolol and prazosin. If after 1 month a DP90 mmHg had been reached the patient was reassessed after a further 3 months. If a DP>90 mmHg was found the dose of labetalol or prazosin was increased and the patient was re-examined after 1 month.This protocol was followed until the maximum dose was reached or adverse reactions prevented a further increase in dosage.During 6 months of treatment there was a further drop in systolic and diastolic blood pressures under both regimens of, respectively, 8.6 and 2.4 mmHg for labetalol, and 7.7 and 5.0 mmHg for the prazosin group. At the end of the period the average daily doses of labetalol and prazosin were 1256 mg and 4.3 mg, respectively. There was no significant difference in the average number of complaints between the labetalol and the prazosin group.     

The influence of Ringer's lactate and gelatin infusion on the internal fluid balance of healthy volunteers measured by a non-invasive conductivity technique

Eight healthy male volunteers received in random order at an interval of 1 week 2 litres of Ringer's lactate or 0.8 litre of gelatin (Gelofusine) over half an hour, after overnight fasting. At the end of the infusion period, blood volume and mean arterial pressure had increased significantly in both groups but the increase in blood volume was more pronounced with the colloid. Extracellular fluid volume increased significantly after Ringer's lactate, while a significant decrease was noticed after gelatin. A small decrease in intracellular fluid volume was noted after infusion of Gelofusine, whereas it did not change after infusion of Ringer's lactate. During the 30 min after infusion, blood volume decreased significantly after both treatments but after the colloid it remained higher than the initial value. During the post-infusion period, no significant changes in either intra- or extracellular volume were seen after either treatments. At the end of the study, urine production was significantly more after the Ringer's lactate. It can be concluded that infusion of 0.8 litre of gelatin results in a larger and longer lasting increase in blood volume than 2 litres of Ringer's lactate, probably due to mobilization of extracellular fluid volume. It also leads to extracellular fluid accumulation. The decrease in blood volume after infusion is caused by increased urine production, since no changes were seen in intra- and extracellular fluid volume during this period.     

Carotid artery stiffness in patients with end-stage renal disease: no effect of long-term homocysteine-lowering therapy

BACKGROUND: The excess of cardiovascular disease in end-stage renal disease (ESRD) patients is unexplained, but could relate to altered intrinsic vascular wall properties, such as increased arterial stiffness, which could be mediated by hyperhomocysteinemia. We investigated potential determinants of carotid artery stiffness in ESRD patients and the effect of long-term homocysteine-lowering treatment. PATIENTS AND METHODS: Fifty-four patients on maintenance dialysis treatment were studied at baseline. Fourty-one patients completed the treatment protocol, which consisted of a 12-week treatment with folic acid 5 mg daily with or without betaine 4 g per day, and of 1 or 5 mg of folic acid thereafter for 40 weeks. Both phases were randomized. Compliance and distensibility coefficients (CC and DC) and the stiffness index (beta) of the common carotid artery were determined at baseline and after 52 weeks of treatment using a non-invasive vessel wall movement detector system. RESULTS: At baseline, plasma total homocysteine was elevated (44.1+/-33.7 micromol/l), but showed no relationship with CC, DC or beta. Age and mean arterial pressure (MAP) were the only independent determinants of CC and DC, whereas beta was associated with age only. Plasma homocysteine showed a sustained decrease after therapy (20.7+/-9.0 micromol/l at week 52). No significant changes occurred in CC (from 0.59+/-0.21 to 0.60+/-0.22 mm2/kPa; p = 0.47), in DC (from 14.9+/-6.1 to 15.3+/-6.2 10(-3)/kPa; p = 0.55), or in beta (from 10.9+/-4.7 to 11.2+/-4.4; p = 0.64). No independent determinants were detected for the change in CC, whereas the change in DC was inversely related to the change in MAP (stand. r = -0.58; p<0.0002). The decrease in MAP after therapy was significant (p = 0.003) and was related to the dialysis mode (p = 0.003) and smoking status (p = 0.02). CONCLUSION: Folic acid treatment of hyperhomocysteinemia has no major effect on carotid artery stiffness in chronic dialysis patients. The results do, however, emphasize the importance of tight blood pressure control in these patients.