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Biomedical subjects

L Havelec

Publications and source records attributed to L Havelec.

At least 19 recordsLinked to original sources

Thyroid autoimmunity and hypothyroidism during long-term treatment with recombinant interferon-alpha.

Forty-five patients with myeloproliferative or myelodysplastic syndromes, treated with recombinant interferon-alpha (rIFN-alpha) for a minimum of 1 up to 4 years, were examined for the occurrence of thyroid autoimmunity. During treatment, the rate of thyroid autoimmunity rose to more than 20%. The decrease in severity and frequency of thyroid autoimmunity after withdrawal of IFN shows that this is a potentially reversible side effect. The key determinant for the manifestation of this IFN-related autoimmune phenomenon seems to be a predisposition for autoimmunity, since patients with initially detectable thyroid antibodies are prone to exacerbations of thyroid autoimmunity. Concurrent with thyroid autoimmunity, hypothyroidism occurred but did not correlate with the levels of thyroid antibodies, although severe hypothyroidism in two patients was accompanied by increased levels of thyroid antibodies. This investigation shows that thyroid autoimmunity and consecutively hypothyroidism must be expected in certain patients treated with rIFN-alpha during long periods. Furthermore, it may be assumed that IFN-alpha does not induce the development of autoimmunity, but rather enhances the levels of pre-existent thyroid antibodies.

Adult

[Comparison of results of daily blood pressure self-monitoring and general practice monitoring within the scope of a study assessing treatment of hypertension with quinapril].

24 hour blood pressure monitoring is a well established method in the field of antihypertensive research. Patients self recorded blood pressure values are an additional option to overcome the disadvantages of casual office readings--however they are not frequently used within intervention trials. To prove the usefulness of selfrecordings in clinical trials we investigated both selfrecordings taken twice a day and casual readings within intervals of 1 to 3 weeks, in this study on the efficacy and tolerability of the ACE-inhibitor Accupro. 108 hypertensive patients (grade WHO I to II) were included in this trial for ten weeks. Although blood pressures were measured by the patients using sphygmomanometers of the same type and the physicians, decisions to treat or to increase dosage were based on the patients' recordings only. Accupro was dispensed according to the package leaflet at a daily dosage of 5 mg up to 40 mg. In case of failing response to monotherapy, Accupro was combined with Diltiazem or with a diuretic. 7 patients discontinued the treatment due to mild adverse events, one did not cooperate. 82 of the remaining patients were treated effectively with Accupro monotherapy--60 (73%) got one dose daily, 22 (27%) 2 doses per day,--and in 18 patients a drug combination was required. Therapeutic response (RRd < or = 90 mm Hg) was gained within 86 of the 100 evaluable patients according to the doctors' and 83 according to the patients' records. In this respect the two methods used gave comparable overall results. This somewhat surprising fact is due to the design of the study, because treatment decisions were based on the selfrecordings only. Clinical trials based on selfrecordings are in some points preferable to casual office readings: As patients being normotensive at home should not be included into an interventional study, a change of dosage within this group is avoided. Additionally the compliance of a cooperative patient taking his blood pressure twice daily is at a high level. Measurements of each single patient may be evaluated statistically by time series-analysis regarding longterm distribution of blood pressure-values. Taking the means of selfrecordings over adequate time-intervals eliminates the influence of "outliers" (occasionally extremely high or low values) and also reduces the standard deviation compared to that of the casual readings. Research work based on self recordings provides more information and therefore more security for treatment decisions.

Angiotensin-Converting Enzyme Inhibitors

[Transrectal sonographic (TRUS) prostatic volumetry in assessing tumor response to radiation].

The aim of this study was to document the grading-related response of carcinoma of the prostate to radiotherapy, especially in views of the fact that the PSA values of hormonal therapy are not evaluable if hormonal therapy is done prior to radiotherapy or in patients with high likelihood of metastatic spread. Controls were done on 55 patients before, during and after primary external radiotherapy of carcinoma of the prostate with volumetric analysis of transrectal ultrasound (TRUS) of the prostate. There were significant differences between G1 and G2 tumors on the one hand and G3 tumors on the other hand. The latter had a much larger volume to start with and their volume reduced more rapidly after therapy.

Aged

MDR1 gene expression and treatment outcome in acute myeloid leukemia.

To prospectively assess the role of MDR1 gene expression in patients with de novo acute myeloid leukemia (AML), levels of MDR1 RNA in blast cells were determined at diagnosis and correlated with treatment outcome in 63 patients. MDR1 RNA levels were negative in 29% and positive in 71% of the patients. The complete remission rate in response to induction chemotherapy was 89% for MDR1 RNA-negative patients and 53% for MDR1 RNA-positive patients (P = .008). Expression of the MDR1 gene was observed in most patients who died early or had resistant disease. Kaplan-Meier curves revealed a decrease in both disease-free survival and overall survival of patients with detectable MDR1 gene expression compared with the disease-free survival and overall survival of MDR1 RNA-negative patients (P = .029 and P = .009, respectively). These data indicate that MDR1 gene expression is an unfavorable prognostic factor and suggest that multidrug resistance is important in AML.

Adolescent

Duplex Doppler sonography in renal parenchymal disease. Histopathologic correlation.

To evaluate the histopathologic changes influencing Doppler measurements of the resistive index (RI) in renal arteries in renal parenchymal diseases, 68 kidneys in 34 consecutive patients with various forms of renal parenchymal diseases were studied by duplex Doppler ultrasound (duplex US) immediately before percutaneous renal biopsy. The RI, renal length, and renal cortical echogenicity were correlated with the amount of glomerular, interstitial, and vascular changes graded on a scale from 0 to 100. The renal vascular resistance and therefore the RI are significantly correlated with the prevalence of arteriolosclerosis, glomerular sclerosis, arteriosclerosis, edema, and focal interstitial fibrosis. There was no significant difference of the RI in five groups of different renal parenchymal diseases. Of 34 patients, 24 presented with an RI less than 0.7, which was thought to be within the normal range so far. Additionally, the RI increases as the patient's age increases, due to higher incidence of arteriosclerosis. Of our patients, 44% presented with normal cortical echogenicity. Quantitative duplex US using the RI does not reliably distinguish different types of renal medical disorders.

Adult

[5-Fluorouracil (5-FU)/leucovorin in comparison to other current chemotherapy protocols in metastasizing colorectal carcinoma].

17 patients with metastasizing colorectal cancer were treated in a phase II-study with systemic intravenous chemotherapy (Petrelli N, Proc ASCO 286, 1987) consisting of leucovorin 500 mg/m2 in a 2 hr infusion and 5-fluorouracil (5-FU) 600 mg/m2 bolus one hour after the commencement of the leucovorin infusion. Limiting toxicities were gastrointestinal, in form of nausea/vomiting of WHO grade 3 (n = 1) and of diarrhoea of maximal grade 4 (n = 5), as well as haematological with a maximal nadir of leucocytes of WHO grade 4 (n = 1) and of thrombocytes of WHO grade 1 (n = 1). Of the 14 evaluable patients an objective response was achieved in 21% of cases (CR: n = 1, PR: n = 2). 64% of the patients showed no change and 14% showed progression of their disease, 7 out of the 17 patients have died; the median survival was 24 months. With respect to objective remission, our result of 21% response rate is lower than the median of 32% of 24 different studies comprising 695 patients; nevertheless, the present response rate is within the range observed in the published studies of between 0% and 67%. In order to estimate the antitumoral efficacy of the new regimen 5-FU/leucovorin more objectively, a retrospective comparison of the therapy regimens used most frequently in disseminated colorectal cancer (5-FU monotherapy, 5-FU/methotrexate (MTX), 5-FU/MTX/low dose leucovorin, 5-FU/cisplatin, 5-FU/leucovorin) has been performed. The continuous administration of 5-FU monotherapy, with an objective response rate of 26%, was superior to standard 5-FU monotherapy as a bolus injection or short-term infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Factors affecting survival in primary superficial bladder cancer.

In a retrospective study of 345 patients with primary superficial transitional cell carcinoma of the bladder, factors present at the time of initial evaluation and which affect survival were identified. All patients were treated initially by transurethral resection with separate resection of the tumor base and margin. 89 patients received no further treatment after resection of the tumor, 256 patients received adjuvant topical instillation therapy over a period of 6 weeks. The distribution of risk factors in both groups was comparable; the survival rate after 5 years showed no significant difference. The tumor-related mortality rate was 12.5%. The Cox regression model showed carcinoma in situ in the tumor margin and the absence of a tumor-associated tissue inflammatory reaction to be the most important risk factors. Beside these associated risk factors, poor differentiation of the tumor parameter was the most important prognostic factor.

Aged

[Comparative studies of the effectiveness of specific immunotherapy in house dust mite allergy].

In a prospective study, 60 patients with allergic rhinoconjunctivitis and/or asthma due to house dust mites were chosen for hyposensitization treatment with Migen (M) or Pharmalgen (P). Immunotherapy stretched over a whole year and every 3 months clinical results were evaluated by the patient's symptom score, by results of skin prick and conjunctival provocation tests, as well as by RIA and ELISA regarding the total and specific IgE and also specific IgG and IgG4 levels. Out of 30 patients of the M group, 15 were followed up over the whole therapeutic regimen, 4 of whom showed a very good, 7 a good to moderate clinical outcome and 4 showed no improvement at all. In the P group, 17 out of 30 patients were followed up whereby 9 showed a very good and 8 a good to moderate response. In both groups of patients a statistically significant decrease in skin and conjunctival sensitivity to mite allergens was observed after 12 months of therapy. However, there was no correlation between this observation and the failure or success of immunotherapy. Furthermore, in both groups there was significant increase in total and specific IgE (with a slight decrease after 6 to 12 months) and also in specific IgG and IgG4 (especially in the P group), but again these changes in antibody levels gave no indication of a good or bad clinical outcome. Hence, we believe other reasons than the usually presented thesis of inducing "blocking antibodies" by immunotherapy to be responsible for the well-known effects of hyposensitization.

Adult

Possible adverse effect of failed adjuvant chemotherapy on the prognosis of women receiving consecutive chemotherapy for recurrent breast cancer.

This study tried to evaluate the impact of adjuvant chemotherapy on the induction of chemoresistance in radically operated upon breast cancer patients. Remission rate, remission duration and survival of a group of women (n = 22) treated with combination chemotherapy (adriamycin and cyclophosphamide, AC) for recurrent breast cancer after failed adjuvant therapy (cyclophosphamide, methotrexate, fluorouracil, vinblastine) were retrospectively compared with the clinical data of non-pre-treated patients (n = 28) receiving the same regimen (AC). The two groups of patients were comparable with regard to their risk factors. In the group of women with prior adjuvant chemotherapy only 3 out of 22 had a partial response, lasting 3, 8, and 16 months; the median survival was 50 months. In the group without prior adjuvant therapy 3 complete and 7 partial remissions with a median remission duration of 15.5 months (range 2-54 months) were found; the median survival was 104 months. The percentage of objective responses among the non-pre-treated patients at 36% was almost significantly higher than that of the pretreated women with 14% (p less than 0.1). Responders to chemotherapy after relapse profited in terms of survival within the first 3 years after radical mastectomy, although no statistically significant difference was observed. The survival data shown assume a "shifting" of women from a group with better prognosis to a group with unfavourable prognosis following failed adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

[Prevention of thromboembolism in accident surgery--angiospastic complications with DHE-heparin. A multicenter study].

In immobilized patients different drugs are used for thromboembolism prophylaxis. Arterial vasospastic complications have recently been reported after Heparin-DHE. In our clinical observation five of these cases were treated. A multicenter study was performed in 82 Austrian trauma units investigating the incidence and outcome of complications of Heparin DHE prophylaxis. 147,290 patients had different drugs for thromboembolism prophylaxis. 61,092 got Heparin-DHE. Complications could be observed at 142 patients but only in the group receiving Heparin DHE. 135 cases were treated conservatively (amputation of limbs became necessary in seven patients). In seven other cases immediate operative exposure of the vessels and balloon catheter dilatation was successfully performed. Vasospasm occurred only in patients with Heparin DHE prophylaxis. It is important to realize this possibility, so that early therapeutic measurements can be taken to avoid unnecessary permanent ischaemic damages and limb amputation.

Clinical Trials as Topic

Assessment of the human tumor cloning assay for urologic malignancies with special emphasis on bladder cancer.

Specimens of different urologic malignancies such as cancer of the bladder, renal pelvis, prostate, testis and renal cell carcinomas were sent to our laboratory for cultivation with the clonogenic assay. Of the 62 samples--biopsies, bladder barbotages and effusions--48% were considered to be evaluable; the others had to be excluded from evaluation because of negative histologic/cytologic findings, insufficient cell viability, inadequate tumor material, or contamination. All test procedures were done using a slightly modified human tumor cloning assay originally described by Hamburger and Salmon [Science 197: 461-463, 1977]. Overall growth was seen in about one third of all tumors cultivated; the mean colony count being 13 +/- 8, the mean cloning efficiency 0.0026%. About one third of bladder cancer specimens and half of the renal cell carcinomas showed colony growth. No correlation between tumor stage or grade and the overall colony growth rate in vitro was seen. Furthermore, it was impossible to correlate the growth rate in vitro and the overall survival of the patients included in the study.

Biopsy

The human tumour cloning assay in the management of breast cancer patients.

A tumour cloning system was used to cultivate breast cancer specimens. Fifty-six percent of 87 samples were adequate for evaluation, showing clonal growth in about one third (35%). Effusions yielded significantly better growth than solid specimens, the median colony numbers being 64 and 18 respectively. An attempt was made to examine whether there was any association between parameters accepted as prognostic factors for breast cancer and clonal growth in vitro. No correlation was found between preoperative tumour burden, histopathologic grading, menopausal status or overall survival and clonal growth in vitro, whereas we observed an inverse trend between progesterone receptor content of the tumours and their growth potential (P less than 0.01). In those few cases where in vitro and in vivo data could be compared, a high accuracy of the predicted sensitivities was found with respect to chemotherapy, but not in relation to hormonal treatment. A statistically significant higher overall chemosensitivity was associated with the absence of oestrogen receptors (P less than 0.01).

Breast Neoplasms

Measurement of adenine uptake as an in vitro screen for antitrichomonal agents.

A semi-automated microdilution test was adapted for the in vitro testing of potential antitrichomonal agents. Washed cell suspensions of the pathogenic protozoan Trichomonas vaginalis were incubated in microtitration plates for 4 h at 37 degrees C in the presence radiolabelled adenine and serial dilutions of the test compounds. After automatic harvesting of the cells onto filter paper discs, the extent of adenine uptake was estimated by scintillation counting. From the dose-response data it was possible to quantify accurately and rapidly the antitrichomonal activity of a range of compounds based on the inhibition of adenine uptake.

Adenine

Carcinoembryonic antigen (CEA) plasma level determination in the management of gastric cancer patients.

Carcinoembryonic antigen (CEA) levels of 161 patients with gastric cancer and of 12 patients with noncarcinomatous diseases of the stomach were retrospectively analyzed. In this study, we examined the correlation between CEA level and histologic type, T and N stage, and the value of the preoperative CEA determination for diagnosis, operability and prognosis for patients with gastric cancer. Summarizing our results: There exist significant higher CEA levels in patients with gastric cancer in comparison with patients with noncarcinomatous disease of the stomach (p less than 0.01), but the absolute CEA titer is not a reliable parameter for the prediction of the existence or absence of gastric cancer for the individual patient. A positive correlation between the CEA level and the histologic type in the subgroup of radically operable patients was found, the intestinal type having lower titers (p less than 0.05). The operability of two different histologic entities (diffuse or intestinal type) was equally high. No conclusion can be drawn from CEA plasma levels concerning the operability of the individual gastric cancer patient; on one hand, 30% of the patients with normal preoperative CEA titers could not be radically operated, whereas 34% of the patients with elevated preoperative CEA titers (greater than 5.0 ng/ml) had radical surgery. Furthermore, the absolute value of the preoperative CEA level does not predict the course of the disease, whereas continuously rising postoperative CEA levels are indicative of tumor progression.

Aged

[Transfer factor as adjuvant immunotherapy in invasive cervix cancer. Report of a double-blind study].

From 1977 to 1982 a prospective randomized double-blind study comparing transfer-factor (TF) versus placebo was conducted in invasive cervical cancer patients after radical surgery and irradiation. The husbands of the cancer patients were selected as leukocyte donors for TF preparations. 60 patients entered the study; 28 patients received placebo and 32 patients received TF. The comparability of both collectives was excellent concerning age and tumor stage. One patient treated with TF died intercurrently. The rate of recurrence of cancer was 5 in the 31 TF-treated patients and 11 in the 28 patients receiving placebo, which was significantly different (p less than 0,05). This difference was even greater when only patients treated for at least 3 months were compared (3 recurrences in the TF-group and 11 recurrences in the placebo-group). Further aspects of this clear clinical results are discussed.

Adult