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Biomedical subjects

J K Rockstroh

Publications and source records attributed to J K Rockstroh.

At least 91 records · Page 5Linked to original sources

A comparative study of different enzyme immunosorbent assays for human tumor necrosis factor-alpha.

Enzyme immunosorbent assays (ELISA) for human tumor necrosis factor-alpha (TNF-alpha) are available from many companies. Although this cytokine is meanwhile well established in scientific work its detection in human blood still leads often to conflicting results. We studied the analytical performance of three different commercial ELISA (Amersham, Immunotech and Medgenix Diagnostics) in plasma samples of 30 human immunodeficiency virus (HIV) infected individuals. All kits showed significantly different mean concentrations of TNF-alpha in the study population (p < 0.05). Kit A: 30.9 pg/ml +/- 46.6 vs. kit B: 46.9 pg/ml +/- 24.8 vs kit C: 11.8 pg/ml +/- 11.6. Results of assays A and B (r = 0.34) as well as A and C (r = 0.31) were not significantly correlated. A good statistical relation between values was only found for assay B and assay C (r = 0.80. p < 0.001). Three plasma samples were spiked with TNF-alpha standard of the corresponding kit to a final concentration of 200 pg/ml. The detection results of these samples were compared with the variation conceded by the manufacturer. Assay A detected two samples above the corresponding coefficient of intra-assay variation (recovery: 81.8% and 89.2%). All three values obtained with assay B were markedly out of its variation range (recovery: 88.7%, 84.6% and 89.0%) while assay C showed again two results above the intra-assay variation (recovery: 92.1% and 89.6%). In our observations we found relevant differences between commercial ELISA kits of different manufacturers, which made interpretation of TNF-alpha in human plasma samples difficult. Additionally, it should be taken into consideration that plasma specimen may contain cytokine-binding proteins or autoantibodies which are capable of blocking epitopes of TNF-alpha. This may lead to the loss of the necessary immunoreactivity which prevents detection antibodies from recognizing these molecules.

Enzyme-Linked Immunosorbent Assay↗

[HIV-associated Pneumocystis carinii pneumonia, primary pentamidine inhalation prophylaxis notwithstanding. Are there differences with Pneumocystis carinii pneumonia without prophylaxis?].

OBJECTIVE: To study the effect of pentamidine aerosol inhalation, known to be effective and well tolerated in the primary prevention of HIV-associated Pneumocystis carinii pneumonia (PCP), on the severity, on clinical and radiological findings and prognosis of break-through PCP. PATIENTS AND METHODS: Data were obtained from the case notes of 17 men (mean age 36 [23-55] years) with HIV-associated PCP, treated between 1989 and 1994, who had received primary prophylaxis with pentamidine aerosol. During the same period 42 patients with HIV-associated PCP but no pentamidine prophylaxis (39 men, three women; mean age 36 [21-67] years) were also treated. Bronchoalveolar lavage of the most affected segment was performed. Diagnostic measures and treatment remained constant during the period of observation. RESULTS: The clinical presentation was the same in the two groups. There was also no difference between them regarding sensitivity to the lavage (94 and 98%). However, infiltration of the upper segments was significantly more common in the prophylaxis group (90 and 43%; P < 0.02). There was no statistically significant difference between the two groups in death rate (13 and 7%) and the long-term prognosis after PCP (survival time 18 and 24 months, respectively). CONCLUSION: Primary prophylaxis of PCP had no significant effect other than altering the distribution pattern of the pneumonic infiltrates towards the apical segments.

Acquired Immunodeficiency Syndrome↗

Effect of long-term primary aerosolized pentamidine prophylaxis on breakthrough Pneumocystis carinii pneumonia.

Aerosolized pentamide is a well-tolerated primary prophylaxis regimen for Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. It is now commonly administered for prolonged periods. We therefore studied the effect of long-term inhalation on breakthrough PCP. We recorded clinical, immunological, radiological and microbiological data, as well as therapy and clinical course of all episodes with confirmed PCP diagnosed at our institution between January 1, 1990 and June 30, 1995. Furthermore, data of all patients on primary aerosolized pentamidine since May 1, 1989 were retrieved. Prophylaxis failures were subdivided into "early" (< or = 12 months of inhalation time) and "late" (> 12 months of inhalation time) failures and were compared with episodes without any prophylaxis. Thirty patients without any prophylaxis, six with early and 14 with late failures represented the study population. Mean +/- SD inhalation times were 4.9 +/- 4.8 and 26.3 +/- 14.1 months, respectively. No significant differences could be detected with regard to clinical presentation, severity of PCP, and in-hospital as well as long term outcome. Early as well as late prophylaxis failures had a higher incidence of upper lobe infiltrates on chest radiography (50% without prophylaxis versus 100% with early and 83% with late failure, respectively; p < 0.05). No extrapulmonary or disseminated pneumocystosis was observed in either group. The sensitivity of site-directed bronchoalveolar lavage was conserved after long-term inhalation (86% versus 100% without prophylaxis and 97% in early failure; p = NS). The severity and outcome of Pneumocystis carinii pneumonia is not altered by long-term primary aerosolized pentamidine prophylaxis. Presentation with upper lobe infiltrates is a radiographic pattern also of late failures. Bronchoalveolar lavage should, therefore, be performed using the site-directed technique in this setting.

AIDS-Related Opportunistic Infections↗

Splenic abscesses and abdominal tuberculosis in patients with AIDS.

Tuberculous splenic abscesses do virtually not occur in immunocompetent patients. Tuberculous abscesses have been reported only from areas, where the prevalence of both HIV infection and tuberculosis is very high such as Central Africa. In our institution two of seven patients with AIDS and disseminated tuberculosis who were treated during the year 1994 developed tuberculous splenic abscesses. Both patients were resident in Central Europe and had fever and weight loss prior to admission. Multiple hypoechoic lesions up to 1.5 cm in diameter developed in the spleen of both patients on day 11 and 16 after admission, respectively. Initially no symptoms related to the splenic involvement and no leucocytosis were seen in both patients. One patient developed leucocytosis and left sided flank pain caused by a subtotal splenic abscess because the diagnosis and therapy of tuberculosis was delayed. Both patients responded promptly to triple drug antituberculous therapy without surgical intervention. We conclude that also in European patients multiple hypoechoic/hypodense lesions in the spleen of HIV positive patients are highly suggestive of disseminated tuberculosis. Follow-up by ultrasound may help to establish the correct diagnosis and may further prevent unnecessary complications in these patients.

AIDS-Related Opportunistic Infections↗

[Improved prognosis of first episode HIV associated Pneumocystis carinii pneumonia without preventive treatment: etiology and sequelae].

OBJECTIVE: The prognosis of first episodes of HIV-associated PCP has markedly improved. The knowledge about the reasons for this progress could bear important implications for the management of HIV-infected patients. PATIENTS AND METHODS: Clinical and laboratory parameters, as well as therapy and clinical course were documented. Prognostic analysis was performed using a logistic regression model. Early (1985-1988) and late (1989-1994) episodes were compared with regard to the results of the prognostic analysis. RESULTS: 67 patients (61 male, six female, mean age 35 +/- 12 years) without any prophylaxis presenting with a first episode of PCP were treated from 1985 until 1994. 95% of patients had a known HIV-serostatus prior to the diagnosis of PCP. Hemoglobin, percentage of neutrophils in BALF as well as AaDO2 were variables significantly associated with lethal outcome. The prognosis of late episodes was significantly improved (7 versus 32% lethal outcomes, log rank p < 0.01). AaDO2 as the only parameter found to be significantly associated with outcome was significantly lower in the late episodes, accordingly. The mean time until diagnosis of PCP was five days shorter in this group. Moreover, CD8 cell-count and serum albumin were found to be significantly higher, and mean loss of weight prior to diagnosis of PCP significantly lower. CONCLUSIONS: The prognosis of first episodes of PCP without any prophylaxis is most closely associated to the severity of pneumonia as reflected by AaDO2. Causes for a minor severity of PCP include an earlier diagnosis as well as better immunity and a better clinical performance at the time of PCP. The improved prognosis therefore results from the experience of the treatment center. A known HIV-serostatus and regular medical care by an experienced treatment center contributes significantly to improved outcome of PCP also in the group non-compliant to distinctive recommendations with regard to prophylaxis for PCP.

AIDS-Related Opportunistic Infections↗

Immunosuppression may lead to progression of hepatitis C virus-associated liver disease in hemophiliacs coinfected with HIV.

OBJECTIVE: The aim of this study was to examine the interaction between HIV and hepatitis C virus (HCV) in hemophiliacs coinfected with the viruses and to investigate the possible relationship between immunosuppression and liver failure. METHODS: To identify risk factors for impending liver failure in hemophiliacs coinfected with HIV and HCV, we analyzed clinical and laboratory parameters, including CD4 count, aminotransferases (ALT, AST), cholinesterase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase, during 3 yr of follow-up (1990-1993) in four groups of patients: hemophiliacs with progressive immunodeficiency who were coinfected with HCV and HIV (group A, n = 49); hemophiliacs with stable immune function who were seropositive for HIV and HCV (group B, n = 95); hemophiliacs who were infected with HCV but not HIV (group C, n = 72); and homosexuals with progressive immunodeficiency who were infected with HIV but not HCV (group D, n = 24). RESULTS: Univariate analysis of data for group A showed a significant rise in gamma-glutamyltransferase and alkaline phosphatase (p < 0.01) that was not seen in groups B, C, and D. In a multivariate Cox regression analysis, age (odds ratio, 1.054 per yr; 95% confidence interval, 1.014-1.096 per yr), decline in CD4 count (odds ratio, 1.063 per cell/microl; 95% confidence interval, 1.037-1.091 per cell/microl), and alkaline phosphatase level (odds ratio, 1.012 per U/L; 95% confidence interval, 1.002-1.021 per U/L) emerged as independent determinants of death. CONCLUSIONS: Our data suggest that progressive immune dysfunction in hemophiliacs coinfected with HIV and HCV may influence progression of liver failure. In these patients cholestasis is an additional prognostic marker for survival that may reflect both exhausted immunity and impaired liver function.

Acquired Immunodeficiency Syndrome↗

Gender-specific cardiovascular adaptation due to circadian blood pressure variations in essential hypertension.

To determine the effects of circadian variation in arterial pressure on early hypertensive target organ disease, we examined systemic hemodynamics (cardiac output by indocyanine green dye dilution), renal hemodynamics (renal plasma flow by iodine-131 para-aminohippuric acid clearance), left ventricular structure and function (2D-guided M-mode echocardiogram), and 24-h ambulatory blood pressure in 20 women and 46 men with untreated essential hypertension. Both gender groups were subdivided into "dippers" and "nondippers" according to the physiologic nocturnal decrease in mean arterial pressure by 10% of daytime values. Systemic and renal hemodynamics, neurohumoral findings (norepinephrine, epinephrine, dopamine, plasma renin activity), causal blood pressure values, duration of hypertension, and body weight did not differ between the two groups. In contrast, left ventricular mass and mass index was higher in female nondippers than dippers (255 +/- 68 v 184 +/- 81 g, and 137 +/- 30 v 102 +/- 39 g/m2, P < .05, respectively), while in men no significant differences were found (234 +/- 48 v 240 +/- 54 g, and 119 +/- 27 v 121 +/- 13 g/m2, P = NS, respectively). Relative wall thickness (0.45 +/- 0.06 v 0.39 +/- 0.06, P < .05) and posterior wall thickness (1.1 +/- 0.1 v 0.89 +/- 0.2 mm, P < .05) were also found to be greater in female nondippers than in dippers, whereas no significant differences were obtained in men. Thus, the degree of left ventricular hypertrophy correlated with the circadian blood pressure variations in women only, which indicates that left ventricular structure may be more load-dependent in women than in men with essential hypertension.

Adaptation, Physiological↗

[Cardiac manifestations in advanced HIV infection].

Incidence, type and clinical significance of cardiac involvement in advanced HIV infection was determined in 32 patients (30 men, two women; mean age 34.2 [21-52] years; mean CD4-cell number 52.2 [0-192]/microliters) over a period of 31 months. Any cardiac involvement was assessed diagnostically by one- and two-dimensional and Doppler echocardiography, complemented by other examinations and results of treatment. 14 patients (43.8%) had abnormal cardiac findings, presumably AIDS-associated. This included left ventricular pump dysfunction of various degrees of severity (n = 11), left ventricular dilatation (n = 2), pericardial effusion (n = 11), as well as cor pulmonale in primary pulmonary arterial hypertension (n = 2). In one patient the first manifestation of AIDS was tubercular pericarditis; in two patients there was a likely connection to disseminated pneumocystis infection and toxoplasmosis, respectively. In 11 patients no specific cause was found for the cardiac involvement. Nine of the 14 patients (64%) had symptoms due to the cardiac involvement. These findings indicate that the incidence and clinical significance of cardiac involvement must be taken into account in any treatment concept for AIDS.

AIDS-Related Complex↗

Obesity and hypertension.

An increasing number of clinical trials have demonstrated that obese patients are more likely than lean individuals to be hypertensive. Moreover, both obesity and arterial hypertension have been identified as independent risk factors for cardiovascular disease. Pathophysiologically, obesity appears to have a major influence on the hemodynamic changes associated with hypertension. The available evidence suggests that at any given level of arterial pressure, obese hypertensive patients have a higher cardiac output and lower total peripheral resistance than do lean patients. Recent reports have indicated that obesity exerts a disparate effect on target organs in hypertension. Whereas at rest obesity seems to mitigate cardiovascular changes in the systemic vascular bed caused by hypertension, no such mitigation was observed in the renovasculature; left ventricular hypertrophy as a major cardiovascular risk factor was even exacerbated by the presence of obesity. The different hemodynamic patterns in obese hypertensive patients have recently been shown clinically relevant for treating hypertensive patients.

Antihypertensive Agents↗

Efficacy and tolerance of low-dose loop diuretics in hypertension.

Prospective studies have emphasized the key role for diuretics in the treatment of high blood pressure. Short-acting loop diuretics have not achieved the same acceptance as the thiazides in treatment of hypertension. Newer long-acting compounds, however, such as torasemide, have now been found to be as efficacious as the thiazides, particularly as they can be given once daily and have a low side-effect profile. Adverse laboratory side-effects are rare in hypertensive patients treated with torasemide; carbohydrate intolerance, dyslipidaemia, or hypokalaemia have seldom been observed during its long-term administration. For these reasons, torasemide is therapeutically attractive due to its antihypertensive efficacy with once-daily administration, low incidence of adverse side-effects, and sustained improvement of the cardiovascular risk profile.

Blood Pressure↗

Pneumocystis carinii infections in HIV-infected hemophiliacs during aerosolized pentamidine prophylaxis.

The frequency, presentation, diagnosis and clinical course of Pneumocystis carinii infections (PCI) were studied during aerosolized pentamidine prophylaxis (AP) and its impact on the spectrum of AIDS-related and other pulmonary infections in HIV-infected hemophiliacs. We conducted an open study on primary (PP) and secondary (SP) AP. Breakthrough P. carinii infections (BPCI) and other infectious complications were analyzed retrospectively. Hemophiliacs without prior P. carinii pneumonia (PCP) who had been reluctant to any prophylaxis and who developed PCP served as control group. Statistical analysis of the efficacy of prophylaxis was performed by calculating confidence intervals of binomial p. Of 73 hemophiliacs (56 on PP and 17 on SP) 10 developed BPCI (7 in PP and 3 in SP) during a mean observation time of 14.9 months (range 0.5-30); total 13.6% (6.7%; 23.7%), PP 12.5% (5.1%; 24%), SP 17.6% (3.7%; 43.4%), confidence intervals at a level of 95%. Three BPCI presented atypically with cavitation (1), pneumothorax (2), Pneumocystis pleuritis (1), dissemination (2) as compared to none in the control group. Sensitivity of bronchoalveolar lavage (BAL) was 88.9%, specificity 100% (both 100% in the control group). PCP was the leading AIDS manifestation (21.3%), CNS manifestations taken together were more frequent (36.2%). Bacterial pneumonia was the most frequent respiratory infection. One patient of the study group with recurrent pneumothorax possibly died of BPCI as compared to no BPCI-related deaths in the control group. Efficacy of prophylaxis in hemophiliacs was comparable to other risk groups. AP alone may be insufficient for the control of PCI in patients with long-term profound immunodeficiency, especially in SP. 30% of BPCI presented atypically.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

Pneumocystis carinii pneumonia presenting as an upper lobe cavity after aerosolized pentamidine prophylaxis in an HIV-infected patient.

We describe an atypical diagnostic feature of a breakthrough Pneumocystis carinii pneumonia (PCP) during primary prophylaxis with aerosolized pentamidine. Our case disclosed infiltrates restricted to the left upper lobe. After 2 weeks a solitary cavity developed. Diagnosis was easily established by bronchoalveolar lavage when performed in the affected segment bronchus. Cavitation clearly demonstrated localized infection, with tissue destruction as one main pathogenetic pattern of a breakthrough PCP during aerosolized pentamidine prophylaxis.

Adult↗

[Immunoglobulin therapy for systemic lupus erythematosus].

A 25-year-old patient with lupus erythematosus was admitted with myositis and erythema of the skin under chloroquine therapy. After improvement of clinical symptoms with cyclophosphamide and prednisolone he was again progredient with myositis. The changing of therapy to methotrexate showed a hepatotoxic side effect with elevated liver enzymes. Under subsequent therapy with azathioprine and prednisolone he developed leukopenia and sepsis. Because of persistent erythema of the skin under therapy with different immunosuppressives we performed a therapy with high-dose intravenous immunoglobulins. After application of immunoglobulins we observed an improvement of the erythema after 10 days, which was persistent after dose reduction for about 4 months.

Adult↗

Stress response pattern in obesity and systemic hypertension.

Under resting conditions obese hypertensive patients have been described as having a greater cardiac output and lower total peripheral resistance than lean hypertensive patients. To evaluate the hemodynamic patterns under stress conditions, we determined the hemodynamic response to mental stress (first study) and during isometric exercise (second study) in hypertensive patients with a body mass index > 27 kg/m2 (obese) and < 27 kg/m2 (lean). The cohort exposed to mental stress comprised 54 white male patients (30 were lean, 24 were obese) with untreated stage I or II essential hypertension according to the World Health Organization. Obese subjects responded with a higher increase in total peripheral resistance (p < 0.02) and lower increases in heart rate (p < 0.01), cardiac output (p < 0.01) and stroke volume (p < 0.02) when compared with their lean counterparts. This was independent of any differences in chemical or baseline hemodynamic characteristics at rest. The cohort exposed to isometric stress consisted of 57 patients (30 were lean, 27 were obese) with World Health Organization stage I or II essential hypertension. Obese subjects responded with exaggerated increases in systolic (p < 0.04) and diastolic (p < 0.01) pressures, and heart rate (p < 0.04) when compared with lean patients. Body mass index emerged as an independent determinant of the increase in systolic (r = 0.03) and diastolic (r = 0.01) pressure as well as of heart rate (r = 0.03). These results indicate that obese hypertensive patients respond to (1) mental stress with vasoconstriction instead of the expected vasodilation, and to (2) isometric stress with an exaggerated increase in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗