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Biomedical subjects

S Wellek

Publications and source records attributed to S Wellek.

18 recordsLinked to original sources
PubMed1992

DNA image cytometry in stomach carcinoma. Its relation to histomorphologic parameters and its influence on prognosis.

BACKGROUND: The influence of DNA content on the prognosis in stomach cancer is controversial. METHOD: After curative resection of stomach carcinomas (adenocarcinomas [n = 58]; signet ring cell carcinomas [n = 24]; undifferentiated carcinomas [n = 21]), the influence of the DNA content and histomorphologic parameters on the prognosis was examined. RESULTS: In the multivariate regression analysis, the prognosis depended on the lymph node status (P = 0.0009), pT stage (P = 0.02), tumor localization (P = 0.03), and histologic type (P = 0.05). The prognosis was independent of the DNA content. Furthermore, the degree of differentiation, operative procedure, safety distance, size of the tumor, and sex and age of the patient also did not influence the prognosis. CONCLUSIONS: The DNA content of the tumor cells in stomach carcinoma does not influence prognosis.

Adenocarcinoma↗
PubMed1992

[Image cytometric DNA analysis in the evaluation of the risk of recurrence after resection of rectal carcinoma].

Prognostically relevant factors derived from re-operative endoluminal US examination or the histopathological work-up of the surgical specimen in carcinoma of the rectum are well known. We investigated the question as to whether the DNA content of tumor cells is an independent influencing factor of prognosis after resection of rectal carcinoma. In 68 patients who underwent resection for rectal carcinoma, in addition to the TNM classification and the usual morphological evaluation, the paraffin-embedded tumor material was de-paraffinized, rehydrated and treated mechanically and enzymatically prior to application to microscope slides. These smears were analysed with the aid of automatic single cell cytometry, and DNA measurements were performed. In contrast to flow cytometry, this technique permits, on the basis of electronic selection criteria, selective analysis of the tumor cells, while artefacts, stroma and inflammatory cells can be excluded. Using DNA cytometry, we were able to differentiate between diploid, polyploid and aneuploid tumors. The best prognosis was associated with a diploid tumor, the poorest with aneuploid tumor. Regression analysis, however, showed that the DNA content of tumor cells is of only secondary significance.

Cytological Techniques↗
PubMed1992

[Comparison of DNA analysis with histomorphologic parameters in stomach cancer].

After curative resection of stomach carcinomas (adenocarcinomas: n = 58, signet ring cell carcinomas: n = 24, undifferentiated carcinomas: n = 21) the DNA content of the tumor cells was compared with the histomorphological parameters. There was a correlation between the DNA content and the histomorphological parameters. The DNA analysis had no additionally prognostic influence. In the multivariate regression analysis the prognosis depended on lymph node status (p = 0.0009), pT-stage (p = 0.02), tumor localization (p = 0.03) and the histological type (p = 0.05). The prognosis was independent of the DNA content. Furthermore, neither did the degree of differentiation, the operative procedure, the safety distance, the size of the tumor, the sex nor the age of the patient have any influence on the prognosis.

Adenocarcinoma↗
PubMed1992

DNA image cytometry: a prognostic tool in rectal cancer?

In 68 patients the DNA content of tumor cells was measured by image cytometry after resection of the rectum because of cancer. In the DNA histogram a differentiation between diploid (n = 19), polyploid (n = 24), hypotriploid (n = 17), and hypertriploid (n = 8) tumors was possible. The best relapse-free survival time was found in patients with diploid tumors. The prognosis worsened from polyploid to hypotriploid and was worse in hypertriploid tumors. Testing for a prognostic advantage of diploid over aneuploid tumors without adjustment for additional factors simply by means of the log-rank statistic gave a (one-sided) P of 0.1013. In a multivariate analysis the degree of differentiation turned out most important. Again, an appropriate test for prognostic relevance of DNA content failed to be significant (P = 0.3264).

Adult↗
PubMed1992

Advanced bladder cancer (stages pT3b, pT4a, pN1 and pN2): improved survival after radical cystectomy and 3 adjuvant cycles of chemotherapy. Results of a controlled prospective study.

A total of 49 bladder cancer patients with tumor stages pT3b, pT4a and/or pelvic lymph node involvement without microscopic or macroscopic evidence of residual tumor was randomized into 2 comparative groups: the chemotherapy group was to receive 3 adjuvant cycles of methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC) after radical cystectomy. The control group received no additional treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of 26 patients randomized to the chemotherapy group compared to 23 in the control group (p = 0.0015, log rank test for relapse-free survival curves). Of the 26 patients randomized for adjuvant chemotherapy 18 were treated with M-VAC or M-VEC (3 cycles in 16 patients and 2 cycles in 2). Of the remaining 8 patients 7 refused chemotherapy before or during cycle 1 and 1 received chemotherapy without cisplatin because of impaired renal function. An update of the patients in August 1991 revealed a further increase in the prognostic difference between the 2 trial arms (p = 0.0012). Of 18 patients who received treatment with M-VAC or M-VEC only 3 have had tumor progression to date compared to 18 of 23 patients in the control group. Further statistical analysis of the data was performed on the basis of Cox's regression model, incorporating various criteria as explanatory variables, including patient sex and age, pT stage and number of involved lymph nodes. This multivariate analysis revealed a significant decrease in the risk of tumor recurrence (p = 0.0007, 2-sided) after adjuvant chemotherapy. The number of lymph nodes involved was also of prognostic significance (p = 0.0028, 1-sided). The results indicate that the survival time after radical cystectomy can be prolonged considerably by adjuvant polychemotherapy in cases of locally advanced bladder carcinoma. Fortunately, all of these conclusions are not affected by switching from an intent-to-treat analysis to an analysis of the therapy actually performed. The p values obtained from the latter are 0.0005 (log rank test) and 0.0001 (Cox model with the same set of additional regressors).

Adult↗
PubMed1991

[Computer-assisted analysis of wall motion of the right ventricle in a normal patient sample and diagnosis of right heart infarction using transesophageal echocardiography].

Using 2D and M-Mode transesophageal short axis cross sections, right ventricular systolic wall motion was quantified in 15 normal patients. A further group of 39 patients with right ventricular infarction was investigated. In the normal group fractional shortening of the septum was -19.6% (-45 to 8%), that of the lateral wall 51.6% (37 to 73%), of the posterior wall 33.9% (5 to 50%) and of the anterior wall 42.7% (18 to 57%). Right ventricular infarction (RVI) was associated in 33 patients with posterior left ventricular infarction (85%) and in three patients with anterior infarction. In two cases only an isolated RVI was found. Right ventricular dilation occurred in 24 patients (61%). Hemodynamic criteria were fulfilled in eleven out of 21 patients (53%). RVI was confirmed in one patient by surgery and in ten patients by autopsy. Recognition of regional wall motion abnormalities by transesophageal echocardiography permits an accurate bedside identification of RVI. 2D and M-Mode registration of the short axis improves RVI assessment. Wall motion analyses offer the possibility to determine the extent of right ventricular infarction.

Adult↗
PubMed1991

Hydrochlorothiazide and verapamil in the treatment of hypertension. The Verapamil Versus Diuretic (VERDI) Trial Research Group.

The efficacy and tolerability of hydrochlorothiazide, sustained-release verapamil, and their combination was compared in patients with mild to moderate hypertension. The design was a multicenter, randomized, double-blind clinical trial with a single-blind placebo baseline period of 2 weeks. Three hundred sixty-nine patients with a diastolic blood pressure of 95-120 mm Hg were included. Treatment consisted of 12.5 mg of hydrochlorothiazide once daily, then 25 mg once daily, and finally 25 mg twice daily; the other group received verapamil at a dose of 120 mg once daily, then 240 mg once daily, and finally 240 mg twice daily. Patients not achieving target blood pressure (less than 90 mm Hg diastolic) were given the combination of hydrochlorothiazide and verapamil, that is, 25 and 240 mg once daily and twice daily. During all time points during the study patients receiving verapamil achieved target blood pressure more often than patients receiving hydrochlorothiazide (after 8 weeks, 57.7 and 42.7%; after 24 weeks, 46.8 and 26.4%; and after 48 weeks, 44.8 and 24.7%, respectively). Adding verapamil to hydrochlorothiazide was more effective in lowering blood pressure than adding hydrochlorothiazide to verapamil. The number of treatment withdrawals was essentially the same with the two drugs. Therefore, in the doses currently used in antihypertensive treatment, verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension.

Adult↗
PubMed1991

Elements of significance testing with equivalence problems.

The paper outlines an approach to the general methodological problem of equivalence assessment which is based on the classical theory of testing statistical hypotheses. Within this frame of reference it is natural to search for decision rules satisfying the same criteria of optimality which are customarily applied in deriving solutions to one- and two-sided testing problems. For three standard situations very frequently encountered in medical applications of statistics, a concise account of such an optimal test for equivalence is presented. It is pointed out that tests based on the well-known principle of confidence interval inclusion are valid in the sense of guaranteeing the prespecified level of significance, but tend to have an unnecessarily low efficiency.

Confidence Intervals↗
PubMed1990

Hemodynamics during PEEP ventilation in patients with severe left ventricular failure studied by transesophageal echocardiography.

The effects of mechanical ventilation with PEEP were investigated in five patients with normal cardiopulmonary function (group A) and in 11 patients with severe left ventricular failure (group B). Cross-sectional area of the right and left atrium (RA/LA), left ventricle (LV), and right ventricle (RV) was determined at EDA/ESA using transesophageal echocardiography. Hemodynamic parameters and transesophageal pressure were measured simultaneously at PEEP levels 0, 4, 8, 12, and 16 cm H2O. End-diastolic area of the right atrium decreased significantly in both groups. The RA pressure increased, while transmural pressure remained unaltered. The CI decreased in both groups. The decrease in cardiac output by PEEP ventilation was related to the decrease in RV filling volume by external compression. In patients with congestive heart failure, PEEP ventilation with 8 to 10 cm H2O did not worsen LV function.

Adult↗
PubMed1990

Reference standards for software evaluation.

The field of automated ECG analysis was one of the earliest topics in Medical Informatics and may be regarded as a model both for computer-assisted medical diagnosis and for evaluating medical diagnostic programs. The CSE project has set reference standards of two kinds: In a broad sense, a standard how to perform a comprehensive evaluation study, in a narrow sense, standards as specific references for evaluating computer ECG programs. The evaluation methodology used within the CSE project is described as a basis for presentation of results which are published elsewhere in this issue.

Diagnosis, Computer-Assisted↗
PubMed1989

Verapamil versus hydrochlorothiazide in the treatment of hypertension: results of long term double blind comparative trial. Verapamil versus Diuretic (VERDI) Trial Research Group.

OBJECTIVE: To compare the efficacy and tolerability of hydrochlorothiazide, sustained release verapamil, and their combination in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial of 48 weeks' duration with a double blind comparison of hydrochlorothiazide and verapamil followed by an open trial of combined treatment for patients not achieving the target diastolic blood pressure (less than 90 mm Hg) during treatment with a single drug. SETTING: Outpatient departments in 10 clinics and 10 private practices of general practitioners or internists. PATIENTS: 369 Hypertensive patients with a diastolic blood pressure of 95-120 mm Hg during a placebo run in period of two weeks. INTERVENTIONS: Initial treatment consisted of 12.5 mg hydrochlorothiazide (n = 187) or 120 mg sustained release verapamil (n = 182) once daily (regimen I). If the target diastolic blood pressure of less than 90 mm Hg was not achieved within four weeks doses were increased to 25 mg hydrochlorothiazide or 240 mg verapamil once (regimen II) and twice daily (regimen III). Patients not achieving target blood pressure were given the combination of hydrochlorothiazide and verapamil--that is, 25 and 240 mg once (regimen IV) and twice daily (regimen V). MAIN OUTCOME MEASURE: Blood pressure determined with a device permitting automatic repeated measurements with printouts. RESULTS: After eight weeks of treatment with a single drug 76 out of 178 (43%) and 101 out of 175 (58%) patients achieved the target blood pressure with hydrochlorothiazide and verapamil, respectively. During follow up until 48 weeks patients treated with verapamil reached the target blood pressure more often and at lower doses and were less likely to switch to combination treatment than patients randomised to hydrochlorothiazide treatment. Adding verapamil to hydrochlorothiazide was more effective than the addition of hydrochlorothiazide to verapamil. At the end of the study 42 out of 169 (25%) and 73 out of 163 (45%) patients initially randomised to hydrochlorothiazide and verapamil, respectively, were at target blood pressure without combination treatment. After adding verapamil to hydrochlorothiazide or hydrochlorothiazide to verapamil an additional 58 (34%) and 29 (18%) patients reached the target blood pressure, respectively. Altogether 92 out of 332 (28%) patients failed to achieve target blood pressure with regimen V. There were four, 10, seven, and seven withdrawals due to possible adverse effects to treatment with hydrochlorothiazide, verapamil, combining verapamil with hydrochlorothiazide, and combining hydrochlorothiazide with verapamil, respectively. CONCLUSIONS: In doses currently used in antihypertensive treatment verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension, whereas withdrawal rates caused by side effects possibly related to treatment were similar.

Adult↗
PubMed1979

[Acute leukemia in multiple myeloma: case histories, a review of the literature and assessment of the incidence].

The results of a follow-up study of 112 patients with multiple myeloma are presented. Three of these patients developed acute leukaemia during the respective period of clinical observation (maximum: 11 years)--one case of acute myeloblastic leukaemia, myelomonocytic leukaemia and erythroleukaemia, respectively. For estimating the incidence of acute leukaemia in the presence of multiple myeloma an extended life table method was applied. On the basis of our data this method gave a probability of 5.9% for a patient to develop acute leukaemia at any time after the diagnosis of multiple myeloma. In a statistical discussion this result is considered to confirm the assumption of a highly increased AL-risk in patients with multiple myeloma. In a survey of the literature some important data of 100 cases with the association acute leukaemia--multiple myeloma are reported.

Acute Disease↗
PubMedDate not supplied

[Medulloblastoma therapy studies MBL 80 and MED 84 of the Society of Pediatric Oncology and the Société Internationale d'Oncologie Pédiatrique (SIOP)].

In both trials the principle of "sandwich" chemotherapy (administered between surgery and postoperative irradiation) is studied in medulloblastoma. GPO-MBL 80 was essentially a one-arm trial; results after a mean observation period of 3 years show an expected event-free survival rate of 46% at 6 years. "Maintenance" chemotherapy with CCNU and vincristine did not further improve the results. Preliminary results of the joint, prospective, randomised forearm SIOP-GPO trial MED 84 are presented. It is apparently too early to answer any of the two main questions asked by this trial: a) is "sandwich" chemotherapy (as administered) of any value? b) can radiotherapy doses to the supratentorial area and to the spine be moderately reduced in so-called "low risk" patients without compromising long-term results? Thus far, we cannot observe any prognostic influence of the "classical" risk factors as established by other studies.

Adolescent↗
PubMedDate not supplied

[Significance of pathological alpha-1-fetoprotein levels in the framework of prenatal diagnosis].

Merkatz (1984) showed that in 68% of live birth with Down Syndrome maternal age was 34 years or less. It would be desirable to define a high risk collective of women younger then 35 years with the help of a screening test, which could further on lead to a prenatal diagnostics. Several studies showed that low maternal serum alpha-fetoprotein levels (SAFP) in pregnancy is associated with fetal chromosomal abnormalities. The results of a retrospective study at the Department of Obstetrics and Gynecology at University of Mainz showed that maternal SAFP-level does not accomplish the demand of a prenatal screening test, because only 17% of the Down Syndrome could be diagnosed by this parameter. In case of trisomy 13 and 18 SAFP-concentrations were normal or even increased, maybe on account of the combination with other malformations like neural-tube or abdominal-wall defects.

Adult↗