Antianginal efficacy of the combination of felodipine-metoprolol 10/100 mg compared with each drug alone in patients with stable effort-induced angina pectoris: a multicenter parallel group study. The TRAFFIC Study Group.

OBJECTIVE: The primary objective of this randomized, double-blind, parallel group trial was to compare the antianginal and antiischemic efficacy of a combination tablet of felodipine-metoprolol 10/100 mg once daily with both drugs given separately once daily in patients with stable effort-induced angina pectoris. The secondary objective was to compare the tolerability of the 3 treatments. METHODS: The main criteria for inclusion were stable effort-induced angina pectoris for at least 2 months before the enrollment and a positive bicycle exercise test result. Patients were allocated to once-daily treatment with either felodipine-metoprolol 10/100 mg, felodipine 10 mg, or metoprolol 100 mg. The duration of active double-blind treatment was 4 weeks. There were 3 primary efficacy variables in the study; time until end of exercise, time until onset of chest discomfort, and time until 1-mm ST depression during a standardized exercise test. RESULTS: The number of patients randomized was 397. There was a statistically significant improvement in time until end of exercise with felodipine-metoprolol 10/100 mg compared with metoprolol 100 mg (P =.04) and felodipine 10 mg compared with metoprolol 100 mg ( P =.03). However, for time until onset of pain or time until 1-mm ST-depression there were no significant differences among the treatment groups. At highest comparable workload, ST depression was less pronounced with felodipine-metoprolol than with metoprolol alone (P =.04), and the rate-pressure product was significantly lower in the groups receiving felodipine-metoprolol and metoprolol than in the group receiving felodipine alone. The combination and metoprolol were better tolerated than felodipine alone. CONCLUSIONS: In stable angina pectoris, the combination felodipine-metoprolol 10/100 mg and felodipine 10 mg alone increased exercise time compared with metoprolol 100 mg. The combination tablet and metoprolol 100 mg alone showed a more favorable tolerability profile than felodipine 10 mg alone.

Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin.

A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.

Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism.

Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 age- and sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia.

Change in renal tubular sodium and water handling during progression of polycystic kidney disease: relationship to atrial natriuretic peptide.

Renal tubular sodium and water handling determined by the lithium clearance technique, plasma concentrations of atrial natriuretic peptide (ANP), angiotensin II, aldosterone, arginine vasopressin (AVP), and urinary excretion of prostaglandin E2 (PGE2) were determined both during basal conditions and before and after intravenous sodium loading with a 2.5% sodium chloride solution in patients with polycystic kidney disease (PKD), ten with normal or slightly reduced kidney function (PKDN) and seven with moderately reduced kidney function (PKDR), and in 15 healthy controls. In PKDN tubular function was normal, whereas in PKDR both proximal and distal reabsorption of sodium and water were reduced. Angiotensin II and aldosterone were normal in both groups of patients. During basal conditions ANP was higher in PKDR than in PKDN. PGE2 was significantly higher in PKDR than in PKDN. For all patients significant correlations were found between GFR and both ANP (rho = -0.51, n = 17, P less than 0.05) and PGE2 (rho = -0.53, n = 17, P less than 0.05). It is concluded that renal sodium handling is normal in the early stages of PKD. With deterioration of kidney function both proximal and distal tubular reabsorption of sodium is reduced and the accompanying changes in ANP and PGE2 may be compensatory phenomena counteracting declining glomerular filtration rate.

Simplified immunoglobulin treatment of idiopathic thrombocytopenic purpura.

The recommended dose of intravenous IgG for idiopathic thrombocytopenic purpura has been 0.4 g/kg on 5 consecutive days. A simplified approach, giving a single infusion of 0.8-1.0 g/kg over 8 hours, has been tried in a series of 11 children with newly diagnosed disease. In 8 cases the infusion produced a prompt platelet response culminating at 128-502 X 10(9)/l after 3-13 days, and 4 of these cases required no further treatment while 2 needed a booster infusion due to an early relapse and 2 followed a chronic course. In 3 cases platelet responses were poor in spite of supplementary doses to a total of 1.4-2.0 g/kg: 2 infants failed to achieve normal platelet counts and 1 case with fulminant bleeding manifestations proved completely resistant. Significant side effects were not observed. These results indicate that IgG-therapy practically may be initiated with a single infusion, the resulting platelet response indicating the need for further infusions.

Ibuprofen-induced meningitis in a male with systemic lupus erythematosus.

A 36-year-old male with systemic lupus erythematosus developed aseptic meningitis after ingestion of ibuprofen. He was unconscious, had a universal rash, high fever and a pathological CSF. Being severely ill he was treated with high doses of corticosteroids and plasmapheresis and recovered within a week.

Platelet number and volume during myocardial infarction in relation to infarct size.

Platelet number and mean platelet volume (MPV) were measured in 100 patients with acute chest pain, 41 with acute myocardial infarction (AMI), 33 with angina pectoris (AP) and 26 with non-coronary event (NCE), and compared with 21 controls. We found no significant difference in platelet count on admission in the patient groups, but it was lower compared with controls. There were no significant differences in MPV between the patient groups nor between patients and controls. Thirty patients with AMI were followed for 10 days and showed an initial 12% fall in platelet count followed by a 36% increase. Initially there was an increase in MPV (2%) followed by a fall (8%). The fall in platelet count and increase in MPV correlated with infarct size (maximum activity of lactate dehydrogenase (LDH)) and might reflect consumption of platelets. The precise role of platelets in the process of infarction is still unknown.

Yersinia enterocolitica infection complicated by severe thrombocytopenia resistant to high-dose intravenous immunoglobulin.

A young female patient developed severe thrombocytopenia 10 days after an infection with Yersinia enterocolitica, serotype 3. She was treated with high-dose intravenous immunoglobulin without effect, and later corticosteroids also failed to induce remission. After 10 days of profuse bleeding the platelet count rose slowly to normal. Her tissue type was HLA-B27. To our knowledge, thrombocytopenia complicating Yersinia infection has not been reported before.

Platelet number and platelet volume in healthy young men during exercise and changes in posture.

In ten healthy young men, alterations in platelet number (B-Thro) and mean platelet volume (MPV) during 15 min of moderate exercise on a bicycle ergometer and 30 min of rest in supine position were determined. During exercise B-Thro increased 10.9% and MPV increased 1.5%. During rest in supine position B-Thro decreased 8.7% whereas MPV was unchanged. From concomitant alterations in leucocyte number, erythrocyte number and concentration of albumin it is concluded that part of the alterations in B-Thro is caused by transfer of water between the vascular system and the interstitial compartment and part is the result of a release of platelets from reservoirs during exercise and a sequestration of platelets in reservoirs during rest in supine position. The alteration in MPV during exercise is explained by a larger average volume of platelets being released from reservoirs when compared with the average volume of platelets already circulating.

Assessment of left ventricular filling pressure in myocardial infarction using the first derivative of the apexcardiogram.

We recorded the apexcardiogram (ACG) and its first derivative (dA/dt) in 24 patients with acute or recent myocardial infarction. From dA/dt, an index I = X 10 dRFW/dS was defined (dRFW and dS = peaks of dA/dt corresponding to the rapid filling wave and to the systolic upstroke of the ACG). A significant correlation was found between I and pulmonary capillary wedge pressure (PCW, mmHg). PCW = 2.3 X I + 6.5 (r = 0.80, p less than 0.001). Normal PCW was found in 15 patients who all had an I less than 2.8. Elevated PCW was found in 9 patients who all had an I greater than 2.8. Thus the ability of I to predict elevated PCW was 100% (95% confidence limit greater than 66.4%). The ability to predict normal PCW was 100% (95% confidence limit greater than 76.2%). No significant correlation was found between I and cardiac index (r = 0.29, p greater than 0.1).

High-dose intravenous immunoglobulin for post-transfusion purpura.

Successful treatment of a case of post-transfusion purpura with high-dose i.v. human immunoglobulin is reported. A 62-year-old multiparous woman developed severe thrombocytopenia in the wake of transfusions given during and after vascular surgery. A platelet alloantibody with anti-Zwa-specificity was demonstrable by an indirect immunofluorescence technique. A single infusion of Sandoglobulin 1 g/kg body weight caused an immediate platelet response with cessation of haemorrhagic manifestations within 12 h, and the platelet count became normal within 3 d. Thrombocytopenia recurred 8 d after the infusion, but one further dose of Sandoglobulin 0.5 g/kg body weight caused definitive reversal of the thrombocytopenia.