[Gastroduodenoscopy for screening of patients scheduled for oral anticoagulant therapy: incidence and age dependence for potentially bleeding pathologies]. / Die Gastroduodenoskopie als Screeninguntersuchung vor oraler Antikoagulationstherapie--Häufigkeit und Altersabhängigkeit blutungsrelevanter pathologischer Befunde.

UNLABELLED: This retrospective study was designed to shed light on the incidence and age-dependence of potentially bleeding pathologies in the upper gastrointestinal tract of asymptomatic patients scheduled for oral anticoagulant therapy. Gastroduodenoscopy was routinely performed during screening studies. The incidence of abnormalities was compared with gastroscopy findings of patients with epigastric symptoms. Only pathologies likely to bleed were considered. These included gastric ulcers, duodenal ulcers, esophageal varices, esophagitis, erosions, malformations and hemorrhages. RESULTS: 18.23% of the patients (n = 746) undergoing gastroscopy prior to scheduled oral anticoagulant therapy were found to present with abnormalities versus 18.44% of those with epigastric symptoms (n = 1,627). In the group scheduled for oral anticoagulant therapy, the rate of pathologies did not significantly increase with increasing age. CONCLUSIONS: The unexpectedly high incidence of potentially bleeding pathologies in asymptomatic patients scheduled for anti-coagulant therapy should prompt screening gastroduodenoscopies irrespective of the patients' age prior to instituting treatment.

[Stroke management on general medical departments. A multicenter study in Austria]. / Insultbehandlung an Internen Abteilungen. Eine österreichische Multizenterstudie.

BACKGROUND AND OBJECTIVE: Despite the claimed superiority of Stroke Units a majority of patients with acute stroke is still treated on general medical departments in many countries. In Austria 90 % of 121 medical departments state that they take care of stroke patients routinely or at least sometimes. Therefore, our aim was to evaluate whether stroke management on medical wards meets up-to-date standards. PATIENTS AND METHODS: 55 medical departments all over Austria participated in a prospective multicenter registry documenting diagnostics, treatment and the in-hospital course of unselected patients admitted with an acute stroke according to a standardised protocol. RESULTS: 1100 patients, 56 % female, with a median age of 75 years were assessed. Median hospital stay was 14 days. In 96 % a cranial computer tomogram was performed. 81 % of cerebral lesions were ischemic, 10 % haemorrhagic. Only 10 % had no risk factor or accompanying medical disease. 31 % suffered at least one medical and 18 % one neurological complication (p = 0.00000003). In-hospital mortality was 17 %, functional outcome was poor in 27 % (Rankin scale [RS] 4 or 5) and good in 56 % (RS 0-3). 74 % of discharged patients could leave to their home, 13 % were transferred to a nursing home and 13 % to a rehabilitation center. 95 % of surviving patients left on either an antiplatelet or an anticoagulant medication and 73 % received antihypertensives. CONCLUSION: Outcome of stroke patients treated on general medical departments seems to be fairly comparable to that commonly reported by neurological Stroke Units. Further improvements may be obtained by implementation of integrated "mixed assessment" units into medical departments.

Acute jejunal ileus in intestinal lymphangiectasia.

A 26-year-old patient presented with epigastric pain of sudden onset and severe puffy swelling of both legs and forearms. An irregularly shaped nodular filling defect on selective jejunal films, severe hypoproteinemia, low IgG concentration, and lymphopenia were suggestive of primary intestinal lymphangiectasia with protein-losing enteropathy, and the patient was placed on a low-fat diet with medium-chain triglycerides. This initially improved his condition, but some weeks later he developed obstructive ileus of the small intestine. On laparotomy yellowish to whitish deposits were found to be present in some segments of the small intestine and a fist-sized mass 100 cm distal to the duodenojejunal flexure was resected without complications. Histologically, the submucosal lymphatics were dilated, and the jejunal wall showed extensive pseudocystic, intramural submucosal lymph edema with secondary bleeding and tight stenosis of the jejunal lumen. During the 14-month follow-up time after discharge the patient has been asymptomatic and working, on no treatment other than a low-fat diet with medium-chain triglycerides.

[Prospective study of determining the value of D-dimer in diagnosing pulmonary embolism]. / Prospektive Untersuchung zur Erfassung der Wertigkeit von D-Dimer in der Pulmonalembolie-(PE)-Diagnostik.

Pulmonary embolism (PE) is still misdiagnosed in a high proportion of cases. 107 patients admitted for suspected pulmonary embolism were studied prospectively to shed light on the value of ELISA-D-dimer and Latex-D-dimer. Pulmonary embolism was ruled out by negative perfusion scans in 66 patients (61.7%) and by angiography in 24 patients. 58% of the scans suggesting a high probability of PE were confirmed by angiography, but only 18% of the scans suggesting a low or intermediate probability of PE. Sensitivity and specificity were 88% and 79%, respectively for the D-dimer ELISA, versus 94% and 90% for the Latex agglutination test. The Latex test increased the positive predictive value of lung scanning suggesting low to intermediate probability of PE (group B) from 18% to 75% and that of lung scanning suggesting high probability of PE (group C) from 58% to 93%. The positive predictive value was improved by ELISA-D-dimer in both groups to 75%. In order to augment the diagnostic efficacy in clinical practice the determination of Latex-D-dimer simultaneously with lung scanning is recommended.

[Effectiveness and tolerance of amlodipine in treatment of patients with mild to moderate hypertension. Results of a long-term study with a new calcium antagonist]. / Wirksamkeit und Verträglichkeit von Amlodipin in der Behandlung von Patienten mit leichter bis mittelschwerer. Hypertonie Ergebnisse einer Langzeitstudie mit einem neuen Kalziumantagonisten.

The efficacy and safety of amlodipine in the long term treatment of outpatients with mild to moderate hypertension were examined in an open, non-comparative study. 87 patients were enrolled in the study, 62 (71%) of whom were observed for 27 months under controlled conditions. Daily doses of 5-10 mg amlodipine led to a statistically significant decrease in systolic and diastolic blood pressure (-30.5/-20.7 mmHg, p less than 0.01) while there was no substantial influence on heart rate or decrease in efficacy. Amlodipine was tolerated very well; only 17% of the patients reported side effects, most of which were either mild or moderate and were tolerated or disappeared with continued treatment. No clinically significant changes were noted in clinical laboratory or ECG examinations. Based on its special pharmacological and pharmacokinetic properties, amlodipine is a novel calcium antagonist from the dihydropyridine class which has proved to be effective in the treatment of hypertension. The antihypertensive effect, which is sustained for more than 24 hours, parallels the circadian variations in blood pressure and thus induces beneficial pharmacodynamic effects. Due to the low incidence of side effects and the once-daily dosage regimen, an improvement in patient compliance can be expected.

[Pamidronate in the treatment of tumor-associated hypercalcemia]. / Pamidronat in der Behandlung der tumorassoziierten Hypercalcämie.

After a 48-hour rehydration period 28 of 31 patients with cancer-associated hypercalcemia (serum calcium greater than or equal to 2.8 mmol/l) were treated intravenously with the bisphosphonate pamidronate. In three patients fluid repletion with 0.9% saline solution had already normalized serum calcium levels. Pamidronate was given in a single infusion on day 0, the dose of pamidronate adapted to the severity of hypercalcemia. If the serum calcium concentration was greater than or equal to 2.8 mmol/l on day 3, application of pamidronate was repeated. In all patients normocalcemia was restored; mean serum calcium decreased from 3.2 +/- 0.35 on day 0 to 2.15 +/- 0.32 on day 12. Hypercalcemia recurred in 11 patients, seven of these underwent pamidronate treatment according to the same therapeutical regimen. Normal calcium levels were attained in five cases. Side effects were of minor gravity: brief hyperthermia occurred in four patients and transient, asymptomatic hypocalcemia was noticed in nine cases.

Phase I-II study on weekly administration of pirarubicin in patients with metastatic breast cancer.

A phase I-II study of weekly low-dose pirarubicin was performed in 19 patients with advanced breast cancer. The goal was to establish the optimal dose intensity, i.e., the maximal dose applicable at tolerable toxicity within the intended schedule. Each of the four different dose groups used (20, 24, 25, and 27 mg/m2) comprised 4-5 patients. In over 47% of patients, objective remissions were obtained (confidence interval 26%; 71%) including one complete and eight partial remissions; the median duration of remission was 41 weeks (range 16-72), and the median time to reach remission was 12 weeks (range 6-36). Efficacy of treatment was more dependent on prior chemotherapy than on pirarubicin dosage. The weekly i.v. push injection of the drug was easily applicable at an outpatient clinic and well tolerated. WHO grade 3 was the highest toxicity observed for leukopenia (3/19), leukopenia associated with infection (1/19), nausea/vomiting (2/19) and alopecia (6/19). More severe myelosuppression was avoided by interrupting the weekly application until recovery of leukocytes to greater than or equal to 3.5 x 10(3)/mm3. No clinical signs of cardiotoxicity were observed. Generally, mild to moderate signs of cardiac dysfunction acquired during therapy were detected by special cardiac monitoring. Only in 3 of 19 patients was a cumulative dose of more than 550 mg/m2 surpassed. This was accepted as the upper limit for conventional anthracycline therapy. The median cumulative dose applied was 325 mg/m2/week (range 58.2-800.0). Because of maldistribution of prognostic factors, no dose-response relationship could be established. With respect to the total time for which each patient was studied, the dose group of 27 mg/m2 achieved the highest dose intensity with a median of 17.4 mg/m2/week (range 13.5-22.4). Therefore, the dosage of 27 mg/m2/week is recommended to be used in further phase II-III trials of weekly applied pirarubicin.

B-immunoblastic lymphoma arising in angioimmunoblastic lymphadenopathy.

We present a female patient with a B-immunoblastic lymphoma of the IgM-lambda type arising in angioimmunoblastic lymphadenopathy. An increased ratio of helper/inducer to suppressor/cytotoxic lymphocytes in the lymph node could have triggered the proliferation of B cells. Evolution of IgM cryoglobulinemia was paralleled by malignant transformation in the lymph node. A short-term in vitro chemosensitivity test could predict response to COP combination chemotherapy suggesting that in vitro chemosensitivity testing can be useful for the therapeutic management of angioimmunoblastic lymphadenopathy.

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.

Simultaneous and sequential determinations of steroid hormone receptors in human breast cancer. Influence of intervening therapy.

Estrogen (ER), progesterone (PgR), and androgen (AR) receptors were measured in two simultaneous or subsequent specimens taken each from 259 patients with breast cancer. We studied in 182 patients results from receptor assays, either from one tumor or from the primary tumor, and a lymph node metastasis, and in 77 sequential biopsies with or without intervening therapy. All assays were performed in a single laboratory, considering 10 fmol/mg cytosol protein bound ligand as receptor positive. The concordance rate in simultaneous ER assays was 85%; however, we found a considerable high discordance rate for PgR in primary tumor and lymph node metastasis (25%). The overall discordance rate in sequential biopsies for ER was 38% and for PgR 25%. This discordance rate was primarily dependent on the receptor quality of the first assay (ER+: 50%, ER-: 24%, PgR+: 68%, PgR-: 9%). Considering only the ER+ and PgR+ cases, we found the greatest discordance rate in the patients having endocrine treatment following the first biopsy (55% and 84%, respectively). We conclude that the receptor status of one tumor biopsy is highly representative for other tumor or lymph node biopsies. Because of the high discordance rate of primarily receptor + cases in subsequent recurrences, the receptor quality of these lesions should be analyzed whenever possible.

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.

[Is routine bone scanning justified during the after-care for breast cancer?]. / Ist die routinemässige Skelettszintigraphie in der Nachsorge des Mammakarzinoms gerechtfertigt?

In a retrospective study of 254 women with carcinoma of the breast (mean age 55.4 years) the occurrence of bone pain was compared with results of skeletal scanning, skeletal X-ray examinations and routine biochemical findings. Typical signs of skeletal metastases were found in bone scans of 119 patients, 88 (74%) of whom had bone pain. Alkaline phosphatase was elevated in 54 (45%), LDH in 32 (27%), and gamma-GT in 69 patients (58%). There was a statistical correlation between the number of affected skeletal parts and the absolute level of alkaline phosphatase (P less than 0.001) and of LDH (P less than 0.05). Skeletal scans gave no evidence of bone metastases in 36 patients who had bone pains. In this group of patients alkaline phosphatase was elevated in 4, LDH in 1 and gamma-GT in 12 patients. Routine scanning of 254 patients revealed skeletal metastases in 12% without any clinical symptoms. Bone pain and (or) increased activity of alkaline phosphatase occurred in 91% of patients with skeletal metastases. In our view, bone scan in the postoperative control of breast cancer is justified only after onset of clinical symptoms and (or) if there is an abnormally raised alkaline phosphatase activity.

[Plasmapheresis in extra-intestinal manifestations of Crohn's disease]. / Plasmapherese bei extraintestinalen Manifestationen des Morbus Crohn.

An assessment was undertaken of the value of plasmapheresis in patients with circulating immune complexes and/or extraintestinal manifestations of Crohn's disease (arthritis, iridocyclitis, erythema nodosum, pyoderma gangrenosum, stomatitis, fever). In 17 patients aged 20 to 50 years (median 34 years) 46 plasmaphereses were performed using a continuous flow-cell separator. Before and after plasmaphereses the concentrations of circulating immune complexes, of complement C4, of the immunoglobulins IgG and IgM and of the proteins alpha-1-antitrypsin, CRP, prealbumin and beta-lipoprotein were determined. 71% of patients given plasmaphereses showed clinical remission of the extraintestinal manifestations and 85% demonstrated a reduction of circulating immune complexes. Clinical follow-up of the patients was documented by the Crohn's Disease Activity Index (CDAI), which was reduced by plasmaphereses to a highly significant degree (p less than 0.005). For patients displaying an acute phase of Crohn's disease with extraintestinal manifestations and/or circulating immune complexes plasmapheresis represents an effective mode of therapy, which, moreover, lacks serious side effects.

[Cytostatic therapy in metastatic breast cancer]. / Zytostatikatherapie des metastasierenden Mammakarzinoms.

Although no breast cancer patient can be cured after metastases have been found, the fact that survival is prolonged and the symptoms and signs of advanced disease can be relieved, often impressively, by the administration of cytostatic chemotherapy justifies their implementation. Chemotherapy is only one aspect of a comprehensive treatment modality in this controversial field and has to be strictly reviewed in the light of indications and contraindications in every single patient. Step-by-step development over the past twenty years has proven the clear-cut advantages of polychemotherapy over a single-drug regimen. Adriamycin, the parent drug of the large group of anthracyclines has proved to be a highly efficacious substance in the treatment of metastatic breast cancer. Chronic administration of this compound is associated with the development of dose-dependent cardiotoxicity. This side effect is the most important limiting factor for the unrestricted use of this drug. Over the past years several anthracycline analogues have been developed which appear to be as effective against metastatic breast cancer as the parent compound. Moreover, there is some slight evidence that these drugs show less cardiotoxic activity than adriamycin. However, on objective review of the common treatment schedules in current use or under trial at present, it must be concluded that not one fully satisfies the ideal criteria of a safe and practicable procedure which does not stress the patient and is universally effective.

[Clinical experiences with high-dose methotrexate]. / Klinische Erfahrungen mit hochdosiertem Methotrexat.

40 patients with various forms of malignant disease, who had already been subjected to conventional regimens of treatment, were treated between 1976 and 1981 at the Department of Chemotherapy, Vienna University, with high-dose methotrexate (MTX) as sole therapeutic agent. 18 patients received MTX in moderately high doses of 250 mg/m2 to 750 mg/m2 at 10-day intervals. 19 patients were treated with high doses of 5 to 15 g MTX at 10-day intervals. In 2 cases of severe malignant non-Hodgkin's lymphoma one patient received 2 X 1 g MTX with an interval of 19 days between doses and the other received a single dose of 5 g MTX by infusion. One patient with alveolar soft part cell sarcoma was given ultra-high therapy, with a cumulative dose of 205 g. None of the patients in the group given moderately high-dose MTX therapy, whereas three in the high-dose group had an objective remission. Objective remission was obtained neither in the two lymphoma patients nor in the ultra-high-dose treated case. Complications such as leucopenia and/or thrombopenia were found in 9%, reversible transaminase activity increases in 45%, as well as a decrease in creatinine clearance in 10% of the cases. Irreversible severe kidney insufficiency was found in none of the cases. One patient with lymphoma died as a result of severe toxic epidermiolysis with involvement of the gastrointestinal mucosa, whilst the other suffered from pulmonary complications in the form of the respiratory distress syndrome. On the basis of our experience the use of high-dose MTX therapy as an alternative method following trials of all conventional regimens is not recommended.

[Analgesic effect of tramadol in patients with malignant diseases]. / Analgetische Wirkung von Tramadol bei Patienten mit malignen Erkrankungen.

The new synthetic opioid Tramadol [1-(m-Methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexane-1-ol] was examined in 30 patients with different malignant diseases. An excellent or sufficient pain relief could be found in 86%. Only 14% of all patients did not respond. The analgetic effect throughout the day could be observed in most cases (92%) after the application of maximally 200 mg/die. Optimal or moderate subjective tolerance was found in 95% of all cases. Fatigue (65.8%), dryness of the mouth (68.4%), dizziness (14.3%) and perspiration (12.2%) were the main side effects. For this reason Tramadol can be recommended as a highly useful analgesic drug in the treatment of tumor induced pain.

[Mitoxantrone in the primary treatment of metastasizing breast cancer]. / Mitoxantrone zur Erstbehandlung des metastasierten Mammakarzinoms.

25 females (57.7 +/- 11.1 years) and 1 male (71 years) with histologically verified metastasizing breast cancer were submitted to mitoxantrone therapy. Secondary tumours were found in following organ systems: bone: 19 cases; lung: 13 cases; liver: 6 cases; skin: 5 cases; locoregional and nodal: 5 cases; brain: 1 case. All patients showed normal bone marrow and heart function before commencement of treatment. Mitoxantrone was given in form of a 30-minute infusion at a dosage of 14 mg/m2. In 4 patients dosage was increased to 20 mg/m2. Treatment cycles were repeated every 3 weeks according to peripheral blood counts. All patients were cardiologically monitored throughout the study by means of electrocardiogram, systolic time interval measurement and radionuclide angiography. The mean observation period was 169 +/- 98 days. The response of the patients was as follows: 1 complete remission, 5 partial remissions, 4 unchanged disease and 16 progressive disease. Side effects were normally mild; only nausea, leucopenia and moderate hair loss were of clinical relevance. Cardiac decompensation was not observed. No significant electrocardiographic alterations were found throughout the study. Results of systolic time interval measurements (PEPI, PEP:LVET) and radionuclide angiography (LVEF) gave evidence of moderate depression of heart function. In view of the optimal benefit/risk ratio of mitoxantrone this drug could be used in combined modality treatment schedules in metastasizing breast cancer.

[Significance of laboratory chemical parameters for the detection of metastases in breast cancer]. / Bedeutung laborchemischer Parameter zur Erfassung von Metastasen beim Mammakarzinom.

The diagnostic value of 7 laboratory parameters for the detection of metastases was investigated in 136 patients with verified breast carcinoma after mastectomy. The post-operative interval was 6 to 80 months (means = 27.5). 61 patients had multiple metastases as determined by physical examination, X-rays, computertomography, sonographic and scan procedures, while the other 75 patients had no evidence of metastases. Carcinoembryonic antigen (CEA), alkaline phosphatase (AP) and lactate dehydrogenase (LDH) proved to be reliable parameters for the presence of metastases; the combination of these 3 parameters had a sensitivity of 73.0% and a specificity of 94.7% in the detection of metastases. The additional determination of gamma-glutamyltranspeptidase (gamma-GT), blood sedimentation rate (BSR), C-reactive protein (CRP) and serum iron (Fe) increased the sensitivity of metastases detection to 83.8%, but the specificity decreased to 46.2%.