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Biomedical subjects

R Holle

Publications and source records attributed to R Holle.

At least 73 records · Page 4Linked to original sources
PubMed1988

Calcitonin-related peptides in patients with acute leukemia: association of human calcitonin with poor prognosis.

Elevated serum levels of peptides hormones in patients with acute leukemia and production of these agents by the leukemic blasts have been described. In 77 patients with acute leukemia the influence of common risk factors and elevations of serum levels of calcitonin-related peptides on clinical outcome was evaluated. By multivariate analysis, only age and elevated serum level of h-CT were found to be significantly correlated to survival. CGRP and s-CT showed no influence on outcome. Closer inspection of the clinical course of these patients showed that patients with elevated h-CT are not likely to survive the first 4 weeks after diagnosis. The possibility that this hormone may influence the biological behavior of the leukemic cells is discussed.

Acute Disease↗
PubMed1987

Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial.

A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

The prognostic value of response to the first cycle of chemotherapy in small cell lung cancer. Results of a multicenter German trial.

The prognostic significance of evaluation of response according to chest X-ray after only one cycle of treatment was investigated in patients with small cell lung cancer (SCLC). Three hundred and six patients entered a multicenter randomized German trial testing alternating vs. sequential chemotherapy. Decrease of tumor size after the first cycle was seen to be 78% in the alternating group and 70% in the sequential group. Stable disease occurred in 25% of the sequentially treated and 19% of the alternatingly treated patients. No substantial differences in pretreatment characteristics were noticed between patients with stable disease in sequential and alternating treatment. In sequential therapy, median survival was 323 days for patients with decrease of tumor size after the first cycle and 219 days for patients with no change. Only five out of 21 patients with no change after one cycle responded to continuous administration of this regimen including one complete remission. In alternating therapy, median survival was 347 days for patients with decrease in tumor size after the first cycle and 378 days for patients with no change indicating no difference in prognosis. Twelve out of 18 patients with no change responded to continuous administration of alternating treatment including six complete remissions. We concluded that response to the first cycle according to chest X-ray is a reliable and prognostically valid response criterion if sequential therapy is used. In this treatment modality no change in tumor size after the first cycle indicates poor prognosis, and improvement of the patients' outcome may be achieved by a switch to a second non-cross resistant drug combination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Incidence of recurrence and long-term survival in small cell bronchial carcinoma].

Analyses of relapse in small cell lung cancer (SCLC) were performed in 443 evaluable patients included in two multicenter trials. The time to first progression mainly depended on best response to therapy. Nearly all patients with no change (NC) suffered from progression within 6 months. In patients with partial remission (PR), progression occurred within 12 months in nearly all cases. If complete remission (CR) was achieved, no relapse was seen within the first 6 months after the onset of treatment. Between the 6th and 8th month a slowly increase and after the 8th month a rapid increase of relapse was noticed. In the majority of patients with limited disease relapse was localized in the area of the primary tumor, whereas in patients with extensive disease relapse mostly was due to the development of distant metastases. Of the 443 patients, 35 achieved 2-year survival (8%). Main prognostic factors for the achievement of 2-year survival were extent of disease and sex. Patients with distant metastases and CR had a poor chance of achieving a 2-year survival, while patients without distant metastases and CR had a 30% chance. Females with limited disease and a Karnofsky score of 70% or more had a 40% chance of achieving 2-year survival, the corresponding probability for males was less than 10%. Because of the high frequency of relapse in SCLC, the stabilization of best response has to be considered as a main objective in therapy. In our opinion, two different strategies may be useful in order to achieve higher 2-year survival rates: a) periodic controls and renewal of therapy as soon as possible after relapse has occurred or b) reinduction therapy in intervals of about 8 weeks or more in order to delay or prevent the development of relapse. To find out if one of these strategies is superior to the other, is one of the objectives of our new randomized trial in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Cisplatin/etoposide versus ifosfamide/etoposide combination chemotherapy in small-cell lung cancer: a multicenter German randomized trial.

A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.

Adult↗
PubMed1986

Two randomized trials for alternating polychemotherapy of small cell lung cancer.

Patients with small cell carcinoma of the lung (SCCL) were treated in two multicenter trials with different cytostatic drug regimens including ifosfamide. In the first randomized study, including 306 patients, alternating chemotherapy with VP 16, ifosfamide, vindesine (VPIV), adriamycin, cisplatinum, vincristine (APO), and cyclophosphamide, methotrexate, CCNU (CMCC) was compared against standard treatment with ACO (adriamycin, cyclophosphamide, vincristine). It was shown that the alternating therapy resulted in a higher response rate (88% vs 78%) and a longer median survival time (11 months vs 10 months). Regarding toxicity, VPIV was similar to ACO, whereas APO and CMCC had more side-effects, leading to an increase in the number of drop-outs. In the second randomized study 144 patients were treated either with ifosfamide/VP 16 (IVP) or with cisplatinum/VP 16 (PVP). In the case of no further response, no change, or progression the induction therapy was changed to ACO. Interim analyses show that both regimens have similar therapeutic effects; but higher toxicity was observed in patients treated with cis-platinum/VP 16 than in patients treated with ifosfamide/VP 16. According to the response rate in patients treated with ACO after first-line therapy there was less cross-resistance of IVP than of PVP to ACO.

Age Factors↗
PubMed1986

Use of bronchoalveolar lavage to diagnose acute diffuse pneumonia in the immunocompromised host.

We compared the diagnostic information obtained by bronchoscopy and needle aspiration of the lung with information obtained concurrently by open-lung biopsy in 15 marrow transplant recipients. Bronchoscopy included a wash, brush, and bronchoalveolar lavage. Laboratory evaluation included standard histological and cytological methods, specific immunofluorescence with monoclonal antibodies, and DNA hybridization to detect cytomegalovirus (CMV). Bronchoscopy permitted diagnosis of five of six patients with CMV pneumonia, whereas needle aspiration alone permitted diagnosis of only one of six. Bronchoalveolar lavage alone provided the diagnosis in four of six patients. Bronchoscopy also identified the bacterial component of a combined infection and identified one case of primary lung hemorrhage. Immunofluorescent staining and hybridization studies each diagnosed one case of CMV pneumonia not identified by standard techniques. The diagnostic sensitivity of the bronchoscopy was 89%, as compared with 17% for needle aspiration, and there were no complications.

Antibodies, Monoclonal↗
PubMed1986

[Analysis of the effect of selection in a therapy study].

282 patients with SCLC were treated for the first time at the Chest-Hospital Heidelberg-Rohrbach from July 1981 until November 1983. Only 85 were integrated into a German randomized multicenter study of combined chemo- and radiotherapy, the other 197 were treated with individual therapeutic regimens. Generally, randomized and non-randomized patients were similar with respect to the prognostic factors and survival, but the group of excluded patients was more heterogeneous. Further analysis revealed prognostic relevance to surgical treatment, emergency treatment, various contra-indications and a poor general condition, but patients older than 70 years should not be generally excluded. General implications for clinical trials are that the clinical and methodological relevance of each criterion of exclusion should be critically examined and the baseline data on all excluded patients collected prospectively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

Racial analysis of the volume-renin relationship in human hypertension.

We studied 29 normotensive men (14 black, 15 white) and 36 hypertensive men (27 white, nine black) to examine the association of race with blood pressure, blood volume, and peripheral renin activity (pra). Blood volume was lower in white hypertensive men than in white normotensive men, but was similar in all blacks. When subjects were tested in the supine position, PRA was lower in black normotensive subjects than white normotensive subjects. The PRA did not differ among groups tested in an upright posture, while furosemide-stimulated PRA was lower in hypertensive than normotensive subjects of both races despite lower blood volumes in white hypertensive subjects. Differences of volume and renin measurements appear to reflect basic differences between whites and blacks with essential hypertension. We emphasize the need to consider race in the investigation of human hypertension.

Adult↗
PubMed1978

Urinary kallikrein activity in the hypertension of renal parenchymal disease.

To learn more about the regulation of blood pressure in renal parenchymal disease, 57 subjects (18 normal controls, 25 patients with essential hypertension and 14 with renal parenchymal disease and hypertension) were evaluated for peripheral renin activity, 24-hour urinary kallikrein activity and whole-blood volume. Blood volumes were significantly lower in patients with essential hypertension (P less than 0.001) and those with renal disease and hypertension (P less than 0.001) than in normotensive subjects. Renin activities (measured after the subjects were standing) were also lower in patients with essential hypertension and hypertension due to renal disease (P less than 0.01 and P less than 0.02, respectively). Kallikrein activity was similar in subjects with renal disease and those with hypertension (P less than 0.05) but markedly diminished in both groups as compared with normotensive subjects (P less than 0.001 and P less than 0.01, respectively) when glomerular filtration rates were taken into account. The kallikrein-kinin system may be involved in the hypertension associated with renal parenchymal disease.

Adult↗
PubMed1978

Renal vasculature in essential hypertension: racial differences.

In an attempt to explain the greater morbidity from essential hypertension in the black as compared with the white race, we evaluated the intrarenal vasculature of 27 patients with hypertension (19 white and 8 black). All patients had mild-to-moderate hypertension (mean arterial pressure, 110 to 125 mm Hg), normal renal function, and minimal target-organ damage. All patients had selective renal angiograms, which were evaluated for arterial nephrosclerosis. Additionally, renal blood flow was estimated by the clearance of para-aminohippurate. Patient age, blood pressure, and plasma renin activity did not differ between the two races. Black hypertensives had significantly (P less 0.01) more severe nephrosclerosis than the white patients. Renal blood flow was lower (P less than 0.05) in black patients (390 +/- 35 ml/min - m2 body surface area) than white patients (473 +/- 19 ml/min - m2 body surface area). These findings may help to explain racial differences in morbidity and mortality from essential hypertension.

Adult↗
PubMed1978

A composite analysis of renin classification methods.

We investigated the possibility that variability in classification of patients with essential hypertension into low, normal, or high renin activity subgroups depends on the subject preparation that precedes the measurement of plasma renin activity (PRA). In 47 essential hypertensives, PRA was measured with patients supine and ambulatory who were receiving both an unrestricted dietray sodium intake and a low sodium diet. Additionally, PRA was determined following salt restriction, oral furosemide therapy, and ambulation. These results were compared, using several analytical techniques, to those of a group of age-, race-, and sex-matched normotensive controls. Extreme variability in classification was the rule, with only 28% of patients consistently classified as having normal PRA. No single approach provided maximal detection of both the low and high renin states. We conclude that renin classification of hypertensive patients requires a matched control population and that subtyping appears to be variable depending on diet, posture, and analytical approach.

Adult↗
PubMed1977

Physiologic and pharmacologic influences on adrenergic regulation of renin release.

Changes in hemodynamic variables and plasma renin activity (PRA) induced by short-term alteration of blood pressure and sympathetic nervous system activity were studied in normotensive and hypertensive men on high-sodium and low-sodium intake. Blood pressure and heart rate alterations caused by standard cold pressor tests, amyl nitrite inhalation, phentolamine infusion, and phenylephrine infusion were recorded. PRA was measured at time 0, 5, 15, and 30 min. No change in PRA occurred in either group following cold pressore test and amyl nitrite inhalation. Phenylephrine suppressed PRA in normal but not hypertensive subjects, and phentolamine elevated PRA in normotensive and hypertensive subjects regardless of diet. Short-term stimulation of the sympathetic nervous system does not appear to elevate PRA in man. Suppression of PRA by an alpha agonist was not observed in hypertensives and may reflect barorecptor insensitivity in this group of subjects.

Adult↗
PubMedDate not supplied

Gender differences in emotional disability and negative health perception in cardiac patients 6 months after stent implantation.

OBJECTIVES: In this study we evaluate gender differences in affective adaptation and health perception in patients 6 months after stent implantation. BACKGROUND: Assessment of gender-specific behavioral strategies to cope with serious cardiac disease conditions has not been given much attention until now. Preliminary data suggest greater impairments in female patients, which might be of clinical relevance. METHODS: Three hundred seventeen patients were eligible for the 6-month follow-up investigation, 78 (24.6%) of whom were women. The women were significantly older but did not differ from men in their cardiac risk features and treatment procedures. There were no gender differences in prevalence of hypertension, hypercholesterolemia, and family history. Men had a significantly higher prevalence of smoking than women, whereas women had a significantly higher prevalence of diabetes than men. A structured interview and a standardized psychodiagnostic assessment was carried out, which covered domains of affective dysfunction (depression, anxiety, intrusion, and avoidance), vegetative symptoms (sleeping disorders), and parameters of negative health perception. RESULTS: There were no significant gender differences in the prevalence of depressive symptoms. Women exhibited higher mean values of anxiety than men, which did not reach significance. Sleeping disorders were significantly more prevalent in women. The absolute level of being distressed by intrusive thoughts and avoidance behavior related to the severe underlying disease process was low in the total group of patients examined. Measurable gender differences did not emerge. Fifty-one (16.5%) patients exhibited pessimistic anticipation of dire consequences and severe signs of negative health perception (NHP group). There was a trend, although not statistically significant, toward more women being in the NHP group. The distribution of cardiac risk factors, however, was completely balanced in the NHP(+) and NHP(-) patient groups. Objective somatic cardiac disease parameters did not account for the negative health perception. NHP was, however, associated with significantly more prestent angina pectoris (p < 0.040) and poststent angina pectoris (p < 0.0001). High levels of anxiety, depression, and of disturbed sleep also led to a sharp separation between patients with high degrees of an anticipated incapacitation due to the disease process. Univariate regression analysis suggested an effect of female gender on the occurrence of NHP (odds ratio 1. 70; 95% CI 0.88 to 3.25), which was of borderline significance. Control for confounders in a multiple regression model, however, eliminated the gender effect (odds ratio 1.04, 95% CI 0.48 to 2.23). Poststent chest pain (odds ratio 7.75, 95% CI 3.28 to 18.32) and sleeping disorders (odds ratio 1.32, 95% CI 1.16 to 1.51) were identified as the most powerful confounders of the gender-NHP association. CONCLUSION: Contrary to expectation, women were not per se more distressed than men in all areas of adaptation of the midterm course after stent implantation, although the higher levels of anxiety and sleeping disorders in women deserve attention. A considerable proportion of patients exhibited a pessimistic disease perspective independent of their somatic status, which was associated with affective morbidity. The tendency toward more negative health perception in women may be due to their more frequent occurrence of chest pain and sleeping disorders.

Adaptation, Psychological↗
PubMedDate not supplied

[The problem of response in epidemiologic studies in Germany (Part II)].

The first part of this paper introduced various definitions of response and discussed their significance in the context of different study types. This second part addresses incentives as a method to increase response and evaluates the impact of non response or delayed response on the validity of the study results. Recruitment aims at minimising the proportion of refusal. To achieve this, incentives can be used and potential participants can be contacted in a sequence of increasing intensity. The effectiveness of different incentives was investigated within the pretest of the German survey on children and adolescents by the Robert Koch Institute. A low response is often interpreted in terms of non-response bias. This assumption, however, is as incorrect as would be opposite conclusion, that a high response guarantees valid results. Any study of the influence of nonresponse requires information on non-responders. The comparison between early and late responders as an indirect method to evaluate systematic differences between participants and non-participants by wave analysis is demonstrated within the Northern Germany Leukaemia and Lymphoma study (NLL). The German guidelines for Good Epidemiologic Practice recommend to solicit a minimum of information on the principal hypotheses of a study from non-participants. The example of a population-based health survey (Cooperative Health Research in the Region of Augsburg, KORA) illustrates how information on non-responders within a quantitative non-responder analysis can be achieved and used for the estimation of prevalences. Recommendations how to deal with the response in epidemiological studies in Germany are suggested.

Adolescent↗