[The "diagnostic error" concept].
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Cause of Death↗
Biomedical subjects
W Kirch
Publications and source records attributed to W Kirch.
Erythema nodosum of dental origin.
The association of erythema nodosum and dental infectious foci has rarely been described in the literature. This report concerns four women who developed erythema nodosum either following dental treatment associated with gingival bleeding or due to infectious dental foci. In these cases, tooth extraction, removal of dental deposits, interrupted pulp treatment, apical periodontitis, or a relicted root were identified as causes of the development of erythema nodosum. Upon admission to the hospital, these patients also presented fever and and a maximally elevated erythrocyte sedimentation rate (ESR). In all instances, surgical treatment of the dental foci and/or administration of antibiotics rapidly led to the regression of the erythema nodosum, as well as to the normalization of body temperature and ESR. The cases described indicate that antecedent dental treatment and the possible presence of infectious dental foci should be considered in the differential diagnosis of erythema nodosum when taking the patient's medical history. This approach may avoid unnecessary, possibly invasive diagnostic procedures and can lead to rapid improvement in the patient's clinical status.
Adult↗
Haemodynamic effects of roxatidine, an H2-receptor antagonist.
The haemodynamic effects of roxatidine were investigated in 12 patients with congestive heart failure (New York Heart Association class II) in a placebo-controlled, double-blind, randomized, cross-over study. Impedance and mechanocardiography were determined following successive 7-day treatment periods with placebo and roxatidine 150 mg once daily. Comparison with placebo values showed roxatidine to significantly increase the preejection period (109.7 +/- 2.7 ms versus 117.3 +/- 2.7 ms, 1.5 h after administration). Heart rate and blood pressure remained the same. In contrast to other, newer H2-receptor antagonists, which decrease stroke volume and/or cardiac output, roxatidine did not reduce these parameters but increased the preejection period and the ratio of the preejection period to the left ventricular ejection time, indicating a slight negative influence on cardiac performance.
Blood Pressure↗
Divergent effects of different enzyme-inducing agents on endogenous and exogenous testosterone.
The effects of three different enzyme-inducing drugs (antipyrine 1200 mg, phenobarbital 100 mg, rifampicin 600 mg per day for 7 days) on plasma and urinary testosterone concentrations, plasma gonadotropin levels, antipyrine kinetics, and urinary 6 beta-hydroxycortisol excretion were studied in 18 healthy volunteers. Changes in plasma and urinary testosterone concentrations following exogenous testosterone undecanoate (TU) were also investigated. Although both antipyrine and rifampicin increased antipyrine clearance by about 60%, they produced contrary effects on testosterone: antipyrine lowered the total morning plasma testosterone and plasma testosterone AUC following TU, while rifampicin led to increases of about 20% and 78%, respectively. By contrast, phenobarbital did not significantly alter the endogenous and exogenous plasma testosterone concentrations, but it increased the urinary excretion of testosterone by more than 60%. The other two enzyme inducers did not alter this parameter. Gonadotropin levels remained unchanged. The results indicate that different enzyme-inducing agents exert divergent effects on endogenous and exogenous testosterone concentrations and suggest that the effect of enzyme induction on endogenous testosterone depends on the type of microsomal enzyme-inducing drug used rather than on the extent of the induction achieved.
Adult↗
Stereoselective pharmacokinetics of oral nitrendipine in elderly hypertensive patients with normal and impaired renal function.
The pharmacokinetics of the enantiomers of nitrendipine has been studied in seven elderly patients with chronic renal failure (CRF) and in six control subjects (mean creatinine clearance 30 and 97 ml.min-1 respectively). Racemic nitrendipine 20 mg was given once daily for seven days and the pharmacokinetics of the enantiomers over the last dosage interval were determined using a stereospecific assay. In both groups nitrendipine exhibited stereoselective pharmacokinetics (AUC, Cmax), but the half-lives of the enantiomers did not differ in individual subjects. As an index of stereoselectivity, the mean S/R ratio of AUCs in control subjects (2.07) was not significantly different from the ratio in patients with CRF (2.68). The mean AUCs of (S)- and (R)-nitrendipine during the last dosage interval were increased in CRF by 132% and 85%, respectively. The observed doubling of the half-lives and the increases in Cmax did not reach significance because of the large variability in each group. Thus, the pharmacokinetics of oral nitrendipine is altered in CRF, but there was no change in the stereoselectivity of its pharmacokinetics.
Administration, Oral↗
Influence of prolonged neuropsychological testing on immunoregulatory cells and hormonal parameters in patients with systemic lupus erythematosus.
The influence of a 2-h neuropsychological stress test on plasma catecholamines, cortisol, and on the distribution of lymphocyte subpopulations was studied in 14 patients with systemic lupus erythematosus (SLE), 10 patients on prednisone treatment (without collagenosis), and 14 sex-and-age-matched healthy controls. Psychological stress induced comparably significant increases in plasma adrenaline and noradrenaline levels as compared with baseline values (P less than 0.05) in all three groups, whereas plasma cortisol remained unchanged. The rise in plasma catecholamines was accompanied by a significant cell mobilization in healthy subjects and prednisone-treated patients, but not in patients with SLE. CD19+ cells increased significantly in number from baseline in healthy subjects and prednisone-treated controls (P less than 0.05), while remaining unchanged in SLE patients. In conclusion, SLE patients showed a reduced cell mobilization due to psychological stress despite hormonal alterations paralleling those of healthy subjects or prednisone-treated patients without collagenosis.
Adult↗
Hemodynamic and humoral effects of the novel calcium antagonist Ro 40-5967 in patients with hypertension.
The tolerability and hemodynamic and humoral effects of the structurally novel calcium antagonist Ro 40-5967 were investigated in 64 patients with hypertension. In a double-blind, placebo-controlled study, ascending oral doses of 50, 100, 150, or 200 mg were administered once daily for 8 days in a solution. Ro 40-5967 was well tolerated up to 150 mg, but treatment was stopped in one patient in the 200 mg group because of bradycardia. Blood pressure was dose-dependently reduced over the full 24-hour dosing period with more pronounced effects on day 8 than on day 1. The maximum blood pressure reduction was obtained after 150 mg (supine blood pressure, -34/-25 mm Hg, p less than 0.001). Despite a slight decrease in supine heart rate, cardiac output increased. PQ time was dose-dependently increased and concentration-effect analysis showed that relevant atrioventricular conduction disturbances occur only at concentrations much higher than those required to reduce blood pressure. Changes in catecholamines, plasma renin activity, and aldosterone were small and inconsistent. In conclusion, Ro 40-5967 has a long-lasting antihypertensive effect after once-daily administration.
Aldosterone↗
Hemodynamic effects of quinidine and famotidine in patients with congestive heart failure.
In a randomized, placebo-controlled, double-blind study, 12 patients with congestive heart failure (New York Heart Association class II) were successively treated for 1 week each with placebo, 40 mg famotidine, and 1000 mg quinidine. On the seventh treatment day, heart rate, blood pressure, systolic time intervals, impedance cardiography, and Doppler ultrasound were measured. Heart rate and blood pressure were not markedly altered by either drug. By contrast, quinidine and famotidine significantly decreased stroke volume and cardiac output in impedance cardiography and Doppler ultrasound (p less than 0.05). A high correlation between both noninvasive methods was found for cardiac output and stroke volume (r = 0.93 and r = 0.97 for stroke volume 1 1/2 hours after quinidine and placebo administration, respectively). In addition, the mechanocardiographic ratio of the preejection period to the left ventricular ejection time in systolic time intervals increased significantly 1 1/2 and 3 hours after administration of quinidine and famotidine (p less than 0.05). In conclusion, both quinidine and famotidine exert similar negative effects on cardiac performance, with no significant differences in hemodynamic parameters emerging between the antiarrhythmic agent and the H2-receptor antagonist.
Cardiac Output↗
Haemodynamic effects of H2-receptor antagonists.
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Animals↗
Pharmacokinetics of temafloxacin in patients with liver impairment.
A multicentre study was conducted to determine whether liver impairment would alter the pharmacokinetics of temafloxacin, a new fluoroquinolone antimicrobial agent. 16 patients with cirrhosis and 12 healthy volunteers (the control group) received a single oral 600mg dose of temafloxacin. Blood and urine were sampled at frequent intervals after drug administration and assayed by high performance liquid chromatography. The mean age of patients with liver impairment was greater than that of the control group; they also had a lower creatinine clearance and urine output. There was no difference between the groups in either the peak plasma temafloxacin concentration or the time to reach peak concentration. However, the volume of distribution and elimination rate constant of temafloxacin were significantly lower in the group with liver impairment, as were total temafloxacin clearance, renal clearance, and the ratio of renal:creatinine clearance. Nonrenal clearance was similar in patients and controls. Creatinine clearance and urine output were found to account for most of the intersubject variability in total clearance as determined by multiple linear regression analysis. Because the altered temafloxacin pharmacokinetics appear to be primarily due to impaired renal function, this should be the main determinant of temafloxacin dosage in patients with liver disease.
Adult↗
Effects of acute febrile infectious diseases on the oral pharmacokinetics and effects of nitrendipine enantiomers and of bisoprolol.
In 2 longitudinal studies with 10 patients each, the stereoselective pharmacokinetics of nitrendipine and the pharmacokinetics of racemic (rac) bisoprolol (both 20mg orally) were investigated during acute febrile infectious diseases and at least 6 weeks later in the healthy state. The area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) of rac-nitrendipine were increased in the infectious state by 89% [95% confidence interval (CI): 24 to 187%] and 95% (95% CI: 22 to 209%), respectively. Similar increases were observed for both S- and R-nitrendipine. Nitrendipine exhibited stereoselective pharmacokinetics in both the healthy state and the infectious state, but the mean ratios of S:R AUC values [healthy: 1.79 (95% CI: 1.36 to 2.11); infectious: 1.87 (95% CI: 1.62 to 2.11)] were not different. The elimination half-life, protein binding and haemodynamic effects of nitrendipine also did not differ between the infectious and the healthy state. The mechanism for the disease effects may be related to suppression of hepatic cytochrome P450 activity by mediators of inflammatory reactions. On the other hand, none of the pharmacokinetic parameters, including nonrenal clearance, of rac-bisoprolol was changed during febrile infectious disease, indicating specificity in the effects of acute febrile disease on oxidative drug metabolism.
Acute Disease↗
Cardiovascular effects of omeprazole and famotidine.
In a randomized, placebo-controlled, double-blind, crossover comparison, 12 patients with congestive heart failure (New York Heart Association class II) and dyspeptic complaints were treated orally for 1 week each with placebo, 40 mg omeprazole daily, and 40 mg famotidine daily. Non-invasive haemodynamic measurements were taken on the last day of treatment. Although omeprazole did not alter cardiac performance in impedance cardiography and mechanocardiography, the administration of famotidine led to a significant fall in stroke volume and cardiac output as compared with placebo (both p less than 0.05). Thus, omeprazole did not exert any relevant cardiovascular effects, in contrast to the H2-receptor antagonist famotidine.
Aged↗
Ranitidine increases the bioavailability of nitrendipine in patients with arterial hypertension.
1. In a randomized placebo-controlled study, 12 hypertensive patients were treated po for one week with 20 mg nitrendipine once daily plus placebo, twice daily and later with the same dose of nitrendipine plus 300 mg ranitidine (150 mg twice a day). 2. When ranitidine was coadministered, plasma nitrendipine levels (0-24 h) were significantly increased (P < 0.001), although no significant increase in peak plasma nitrendipine level (Cmax) was observed due to the wide range of variation of this parameter (Cmax) in hypertensive patients. 3. Ranitidine coadministration increased the area under the curve for 24-h (AUC0-24) plasma concentration vs time, from 49.07 +/- 6.28 micrograms.h/l to 82.35 +/- 2.57 micrograms.h/l (P < 0.01). This significant increase caused a reduction in total body clearance from 2008.33 +/- 246.33 to 1284.00 +/- 182.16 ml/min (P < 0.002). 4. Nitrendipine bioavailability was increased by 89% when ranitidine was coadministered but the kinetic effect of this drug interaction is unlikely to be of clinical relevance since no adverse effects were observed in patients evaluated after ranitidine association.
Adult↗
Neuropsychological impairment in auto-immune disease.
Estimations of the prevalence of central nervous system involvement in patients with systemic lupus erythematosus (SLE) vary from 25 to 75%. In order to assess possible deficits in memory, attention, and/or reaction time, a battery of neuropsychological tests was administered to 15 patients with SLE and to two matched groups of control subjects; eight patients on corticosteroids and 15 healthy controls. The test battery included the Multiple Choice Word Fluency Test (MWT-B), Benton Visual Memory Scale, Syndrome Short Test (SKT; attention and memory), Attention and Concentration Test (d2), Wechsler Adult Intelligence Scale (WAIS) subtests for Comprehension, Digit Span, Block Design, a Computer Controlled Reaction Time task (CCRT), and a Learning and Memory Test (LGT-3). Results revealed a statistically significant short-term memory deficit (for all six relevant subtests used) and a marked delayed simple reaction time in SLE patients as compared with scores in healthy subjects. An attention deficit as well as the expected difference between the estimated premorbid and actual level of intelligence could not be demonstrated. With three exceptions (SKT-9 figural recognition, Benton Visual Memory, and LGT-3 figural recognition), patients treated with corticosteroids did not differ from healthy controls. They also did not differ from SLE patients in any of the parameters tested. It therefore appears that the demonstrated deficit in short-term memory and reaction time in SLE patients may not only be due to the neuropsychiatric manifestation of SLE but possibly also result from medication side-effects.
Adult↗
Modulation of the immune response to stress in patients with systemic lupus erythematosus: review of recent studies.
Physical and psychological stress in healthy subjects leads to characteristic alterations of plasma hormone concentrations and the lymphocyte subset distribution. After short-term bicycle ergometry or acoustic stress, and after a 2-h-long neuropsychological examination, a rise in B- and T-suppressor/cytotoxic lymphocytes and a decrease in T-helper lymphocytes has been shown to occur. This cell mobilization was accompanied by an elevation in plasma catecholamines. Although the rise in catecholamine levels was similar in patients with systemic lupus erythematosus (SLE) and in healthy subjects, the alterations in the lymphocyte subsets were less pronounced in SLE patients after bicycle ergometry as well as after psychological testing than in healthy subjects, patients with sarcoidosis, and patients without collagenosis under treatment with corticosteroids. Differences between short-term physical exercise and the acoustic stress test on the one hand, and the 2-h-long neuropsychological test on the other, were observed only for the absolute lymphocyte count. After short-term stress, a rise in the leukocyte and lymphocyte count was noted, whereas after long-term testing, only an increase in leukocytes and a decrease in lymphocytes could be found. In conclusion, sympathomimetic stimulation by bicycle ergometry or by psychological stress led to a characteristic cell mobilization in all the groups investigated. The extent of cell mobilization was attenuated in SLE patients despite the fact that comparable increases of plasma catecholamines were observed.
Adult↗
Modulation of lymphocyte subsets due to psychological stress in patients with rheumatoid arthritis.
The influence of a 1-hour neuropsychological stress test on the distribution of lymphocyte subpopulations and on plasma catecholamine levels was investigated in 18 patients with rheumatoid arthritis (RA) and 14 sex- and age-matched controls. Despite significant increases in lymphocyte counts in both groups, lymphocyte subsets did not change accordingly. A wide scattering of catecholamine levels in plasma before and after stress was observed. Plasma levels of lymphokines such as interleukin (IL)-1 beta and IL-6 could not be detected in RA patients. Enzyme immunoassay of markers of lymphocyte activation such as HLA-DR and cell-bound IL-2 receptor showed only a significant elevation of HLA-DR marked cells in RA patients at baseline. Significantly higher amounts of the soluble IL-2 receptor were detected in patients with RA before the stress test, but stress testing did not alter this parameter. In conclusion, lymphocyte activation in RA and a defect in the expression of IL-2 receptor on the cell surface of lymphocytes were confirmed in the present study.
Arthritis, Rheumatoid↗
[Indirect azygos-vein-continuation syndrome with aneurysm of the inferior vena cava].
Nausea and emesis after exercise were leading symptoms in a 28 year old patient with indirect vena azygos continuation syndrome. This anomaly was verified by sonography, abdominal CT and by venography. The CT examination revealed initially structures of malignant appearance low to the renal position by angiography. This appeared to be distended collaterals. Therapeutic intervention aims primarily to the prevention of complications such as thrombosis of the distal venous flow or venous insufficiency of the lower extremities. Prophylactically we suggest low dose heparin and compression stockings.
Adult↗
[Effectiveness of pravastatin and bezafibrate in primary hypercholesterolemia].
The efficacy and safety of pravastatin and bezafibrate (in retard form) were compared in a randomised double-blind trial comprising 96 patients (48 men, 48 women; mean age 52.5 [20-68] years) with primary hypercholesterolaemia types IIa and IIb. After four weeks' treatment 6 out of 38 patients (400 mg/d bezafibrate) and 27 out of 58 patients (20 mg/d pravastatin) reached a LDL cholesterol level of 190 mg/dl or less. In the other 31 patients of the pravastatin group the dose was raised to 40 mg/d. During the twelve-week course of pravastatin total cholesterol concentration fell from a mean of 364 +/- 75 mg/dl (initial value) to 281 +/- 61 mg/dl (P less than 0.01), while LDL-cholesterol fell from 288 +/- 81 mg/dl to 206 +/- 64 mg/dl (P less than 0.01) and triglyceride concentration from 168 +/- 83 mg/dl to 148 +/- 80 mg/dl (P less than 0.05). During the twelve-week course of treatment with 400 mg bezafibrate total cholesterol concentration fell from a mean of 363 +/- 91 mg/dl to 325 +/- 73 mg/dl (P less than 0.01), LDL-cholesterol level fell from 284 +/- 88 mg/dl to 242 +/- 70 mg/dl (P less than 0.01) and the triglyceride concentration from 173 +/- 91 mg/dl to 121 +/- 83 mg/dl (P less than 0.01). HDL cholesterol concentration rose by 9% in the bezafibrate group and by 8.4% in the pravastatin group (P less than 0.05). Except in the case of HDL-cholesterol, the falls were significantly different in the two treatment groups: pravastatin was superior to bezafibrate in terms of the reductions in both total and LDL-cholesterol (P less than 0.01 for each). However, bezafibrate produced a greater fall in serum triglycerides (P less than 0.05). No serious side effects were associated with either drug.
Adult↗