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Biomedical subjects

W Scheithauer

Publications and source records attributed to W Scheithauer.

At least 145 records · Page 8Linked to original sources
PubMed1990

Effect of recombinant interferon-alpha2C on reticuloendothelial function in patients with thrombocytosis.

The aim of the study was to investigate the influence of recombinant interferon-alpha 2C (rIFN-alpha 2C) on the in vivo Fc-dependent phagocytic activity of the reticuloendothelial (RE) system. Fourteen patients with excessive thrombocytosis due to myeloproliferative disorders were studied before and 3 months after initiation of therapy. RE function was determined by measuring the clearance of autologous red blood cells (RBC) labeled with 51Cr and sensitized with anti-D antibody. Eleven of the 14 patients responded to rIFN-alpha 2 treatment (platelets, less than 440 X 10(9)/liter). Rather in contrast to a shortening of platelet half-life and an increase (trendwise) in platelet-bound IgG, rIFN-alpha 2 caused a significant impairment of RE function. Although this finding could in part be accounted for by the treatment-related decrease in splenic volume, statistical analysis revealed a direct influence of rIFN-alpha 2 on RBC clearance (p less than 0.01). Our study results might be explained by an interferon (IFN)-induced, intensified expression of Fc receptors on platelet (and leukocyte) surfaces, possibly enhancing unspecific binding of IgG to their cellular membranes. The subsequent increased platelet uptake may lead to an overloading of the RE system causing impaired reactions to additional stimuli such as IgG-coated RBC.

Aged↗
PubMed1989

[Gestagen receptor-positive, solid-cystic acinar-cell tumor of the pancreas].

In a 16-year-old girl with left upper abdominal pain of two months' duration fine-needle biopsy (guided by computed tomography) revealed a solid-cystic acinar-cell tumour of the pancreas. The tail of the pancreas was resected and the spleen removed. On inspection, the tumour--about 9 cm in diameter--was encapsulated and consisted of soft, brownish, partly haemorrhagic tissue. Histologically and immunohistochemically the diagnosis of an acinar-cell tumour was confirmed. Analysis of steroid hormone receptors revealed a high progestogen content. Since the operation the patient has remained symptom-free without any sign of tumour recurrence.

Adolescent↗
PubMed1989

Serological screening for a mucine-like carcinoma-associated antigen (MCA) in patients with gastrointestinal tract malignancies.

Mouse monoclonal antibody b-12 identifies a high-molecular-mass glycoprotein antigen strongly expressed by breast carcinoma cells. Since immunohistochemical studies have also demonstrated some reactivity with other epithelial neoplasms, and since "mucine-like carcinoma-associated antigen" (MCA) has gained considerable interest as a tumor marker in breast cancer, we have investigated 34 patients with histologically proven advanced gastrointestinal malignancies for the presence of elevated MCA serum levels. Our data suggest that screening for and/or monitoring of MCA in these tumors is unlikely to have any practical clinical relevance. The possible role of MCA as a marker in tissue specimens for abortive adenomatous differentiation in gastrointestinal (and other) neoplasms, however, remains to be determined.

Antigens, Neoplasm↗
PubMed1989

Alpha-fetoprotein-positive adenocarcinoma of the pancreas.

A case of a poorly differentiated ductal adenocarcinoma arising in the body and tail of the pancreas with diffuse intraabdominal metastases in an adult is reported. Serum alpha-fetoprotein (AFP) level was markedly elevated in this patient, but fell transiently when a partial tumor response to combination chemotherapy was achieved. Both the occurrence of biochemical and anatomical responses, and the immunohistochemical finding of AFP in the tumor tissue clearly indicate that oncofetal protein is produced by the tumor cells. The patient survived 10.5 mo after the onset of symptoms.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Performance evaluation of medical expert systems using ROC curves.

This paper presents a performance evaluation of the diagnostic accuracy of the medical expert system CADIAG-2/PANCREAS. The study included 47 clinical cases from a university hospital with 51 diagnosis of pancreatic diseases (four patients had two pancreatic diseases). As gold standard, the histologically or clinically confirmed diagnoses were assumed. Performance was studied along three lines: (a) each case was evaluated twice, first, by restricting patient data to history, physical examination, and basic laboratory tests and, second, by utilizing the complete set of data including also special laboratory tests. US. X ray, CT-scan, ECG, and biopsy, if available: (b) considering CADIAG-2's hypotheses generation, each evaluation series was also carried out twice, first, by testing whether the gold standard was the first diagnosis in the ranked list of hypothesis and, second, whether the gold standard was among the hypotheses: (c) receiver operating characteristic (ROC) curves were determined by varying an internal threshold which determined the extent of CADIAG-2's diagnostic hypotheses generation. The evaluation showed that CADIAG-2's initial list of diagnostic hypotheses, based on patient history, physical examination, and basic laboratory tests usually has already included the gold standard diagnosis and thus an application of CADIAG-2 at a very early stage of the diagnostic process seems achievable. Moreover, it turned out that given the complete set of patient's medical data the gold standard is usually ranked at the first place in the list of hypotheses. except for patients with chronic diseases where only unspecific findings are available. The last test series showed that ROC curves do not only allow optimal adjustment of the expert system's internal ad hoc decision criteria such as thresholds, weights, and scores but also provide a basis for better comparing the performance of different medical expert systems.

Diagnosis, Computer-Assisted↗
PubMed1989

VMCP chemotherapy with or without interferon-alpha-2 in newly diagnosed patients with multiple myeloma.

Fifty-two previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon (rIFN) alpha-2 and chemotherapy or chemotherapy alone. Patients were treated with vincristine, melphalan, cyclophosphamide and prednisolone every 4-6 weeks. In the combined treatment arm rIFN was administered concurrently with chemotherapy as well as during chemotherapy free intervals. The combined regimen effected 17/21 (80.9%) responses as compared to 19/27 (70.4%) responses in VMCP treated patients. Addition of rIFN to chemotherapy did not enhance hematologic toxicity. These findings suggest a somewhat higher rate of objective response in the VPMC + rIFN group, although a significant improvement in median survival by adding rIFN to conventional first line polychemotherapy in myeloma patients has not yet been achieved.

Adult↗
PubMed1989

Application of a new radiometric system for identification of potentially useful drug combinations for treatment of human gastrointestinal adenocarcinoma.

As an alternative to empirical clinical evaluation of combined drug effects in human tumors, and in an attempt to establish whether the combination of mitoxantrone (DHAD) with other standard drugs would be of any benefit to the patient with advanced gastrointestinal cancer, we have examined the results of simultaneous single-agent testing in vitro in a panel of 8 human colorectal (HCC) and 5 gastric cancer (HGC) cell lines. Cytotoxic drug effects were measured by the use of a new semiautomated radiometric technique (Bactec system), and were quantitated with attention to potentially clinically relevant plasma concentrations. Among several different drug combinations tested, maximal synergistic cell kill was found for DHAD + 5-fluorouracil; continuous incubation of the cells at 1/100 of the peak plasma concentration achievable in humans yielded in vitro responses in 8/8 HCC and 5/5 HGC cell lines. With regard to our results of single-agent testing, our finding of a significant level of in vitro arabinoside-C activity, using prolonged exposure at an in vitro dose corresponding to a clinical high-dose regimen, may provide a rational basis for (re)evaluation of the compound in gastrointestinal cancer patients.

Adenocarcinoma↗
PubMed1989

Phase II evaluation of 5-fluorouracil, folinic acid and cisplatin in advanced-stage colorectal adenocarcinoma.

Twenty-seven patients with advanced measurable colorectal carcinoma were treated with a combination protocol consisting of folinic acid (FA) 200 mg/m2 i.v. bolus followed by 5-fluorouracil (5-FU) 550 mg/m2, and cisplatin (CIS) 20 mg/m2 each administered as a 2-hour i.v. infusion. Treatment was given on 4 consecutive days at 3- to 4-weekly intervals. Of 25 evaluable patients, 1 achieved complete remission and 5 partial remission for an overall response rate of 24%, while 9 patients (36%) had stable disease. Two out of 6 responders had previously progressed on 5-FU-containing regimens. The 95% confidence interval for response is 7-41%. Median survival time for all 27 patients enrolled in the study is 27+ weeks. Tolerance was remarkable and consisted primarily of mild and reversible gastrointestinal symptoms and myelosuppression. This 3-drug-regimen had significant palliative activity in our patient population. Its definitive role in the treatment of metastatic colorectal cancer as well as the potential improvement of the therapeutic index of 5-FU/FA by addition of CIS, require further evaluation in a randomized phase III trial.

Adenocarcinoma↗
PubMed1989

Combined alpha-2C-interferon/VMCP polychemotherapy versus VMCP polychemotherapy as induction therapy in multiple myeloma: a prospective randomized trial.

Thirty-three previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon-alpha-2C (rIFN-alpha-2C) plus vincristine/melphalan/cyclophosphamide and prednisone (VMCP) or VMCP chemotherapy alone. The combined regimen effected 67% responses and 26% minor responses, while 35 and 47% of VMCP-treated patients had a pathologically documented remission, respectively. Despite the somewhat earlier achievement and duration (12.0 vs. 8.0 months) of objective response, and the marginal survival benefit observed in the rIFN-alpha-2C + VMCP treatment arm, a significant improvement in therapeutic gain by adding a biologic response modifier to conventional first-line polychemotherapeutic drug treatment in myeloma patients has not yet been achieved. The combined regimen was well tolerated without unusual or unexpected toxic effects.

Adult↗
PubMed1988

Application of a new preclinical drug screening system for cancer of the large bowel.

We report a prospective evaluation of three human, continuous colorectal cancer cell lines and a new semiautomated radiometric technique (Bactec system) as a primary screening procedure for cytotoxic compounds with activity against cancer of the large bowel. COLO 320DM, Ht-29, and the metastatic OM-1 colon cancer cell line that have previously been shown to yield clinically relevant information in terms of drug sensitivity patterns in humans were all tested against 11 new compounds currently being investigated in phase I or early phase II clinical trials. Our results suggest that trimetrexate, DUP-785, didemnin B, and flavone-8-acetic acid may be clinically effective for the treatment of colorectal cancer.

Colonic Neoplasms↗
PubMed1988

Acute oliguria associated with chlorprothixene overdosage.

The occurrence of acute reversible oliguria is described in a 23-year-old male after ingestion of 1,500 mg of chlorprothixene in a suicidal attempt. In contrast to earlier reports hypothesizing that the pathophysiology of the renal insufficiency associated with chlorprothixene intoxication may be attributed to direct nephrotoxic effects of the compound or to ischaemia owing to transitory unrecognized shock, a careful diagnostic work-up including renal biopsy, disclosed the presence of acute interstitial nephritis.

Acute Disease↗
PubMed1988

[Interferon therapy in multiple myeloma].

Natural leukocyte interferon and recombinant interferon alpha-2 have effected remission rates between 10 and 20% in the treatment of multiple myeloma. Response rates have been higher in untreated patients than in relapsing or primarily refractory cases. Patients with slowly proliferating tumors, early tumor stage or IgA-monoclonal protein seem to show increased sensibility to interferon as compared to patients without those characteristics. First trials using combined interferon chemotherapy regimens suggest that the toxicity associated with this treatment modality remains acceptable. At present, however, one cannot definitely decide whether and to which degree the combination therapy will improve the response rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[Chemotherapy of advanced pancreatic cancer with 5-fluorouracil, doxorubicin and high-dose methotrexate].

The aim of the present phase II clinical trial was to investigate the therapeutic efficacy and tolerance of a combination chemotherapeutic protocol consisting of 4-weekly intervals of 5-fluorouracil, doxorubicin and high-dose methotrexate (FAMeth-regimen) in patients with advanced measurable pancreatic cancer. After a median treatment duration of 4 (2-12) months, one complete and one partial response were achieved in the 13 evaluable patients. Two additional patients had evidence of objective tumour regression, although response was less than 50% of pretreatment tumor measurements. Stable disease was noted in 3 patients, and the tumour progressed in 6. The median survival of all evaluable patients from start of therapy is 7 (2-17) months. Side-effects associated with FAMeth-chemotherapy were generally mild and reversible and primarily included gastrointestinal symptoms (38%) and leukopenia (62%). There was 1 treatment related death due to pancytopenia and sepsis. Our preliminary data suggest some antitumour activity of the regimen against pancreatic cancer, although final assessment of therapeutic results must await accrural of additional patients.

Adult↗
PubMed1987

Search for improved culture conditions for clonogenic growth of human colorectal cancer cells in vitro.

In order to analyze and define potentially better growth conditions for colonic stem cell proliferation, we chose four established human colorectal cancer cell lines that differed in biologic cell properties. We studied variables of standard cloning conditions including culture medium, serum supplement, solidifying agent, addition of specific growth factors and use of capillaries as an alternative culture vessel. While modulation of serum concentration as well as use of various standard formulations of culture base media did not result in a reproducible increase of plating efficiencies (PEs), a significant increase in colony formation (when compared to the conventional assay procedure) was achieved; by use of 0.3% agarose or boiled agar as semisolid matrix and by culturing of cells in enriched 'GMF medium'. Specific growth factors, such as EGF or glucagon resulted in "occasionally better" in vitro growth. This suggests a retention of the ability of cells in culture to respond to physiologic regulators of growth. To verify and extend these initial results obtained with continuous cell lines, growth enhancing modifications of the original cloning technique were subsequently applied to in vitro growth of 15 human colorectal cancer specimens obtained directly from patients. Specimens that grew 30 or more colonies under standard plating conditions displayed a more than two-fold increase in PEs which was reproducible for the two specific variables mentioned above, but the overall success rate of the assay could not be improved. In addition to the possibility that several deficient basic requirements for achieving optimal environmental conditions for colonic stem cell growth have not been defined, we believe a major reason for failing to improve the number of drug-assayable specimens is related to an inherent interneoplastic diversity in terms of growth requirements of human colorectal malignancies.

Cell Line↗
PubMed1987

VAD protocol for treatment of advanced refractory multiple myeloma.

Twenty-three patients with advanced refractory multiple myeloma were treated with a combination chemotherapeutic regimen consisting of four-day continuous infusion of vincristine and doxorubicin plus intermittent high-dose dexamethasone (VAD). All patients included in the study were heavily pretreated with cytostatics and radiotherapeutic measures, and generally presented in poor general condition. In 3 of the 16 evaluable patients (18%) a response, and in 7 patients (44%) an improvement as defined by a reduction in tumor mass by more than 50% was achieved. Six patients had progressive disease. Evaluation of survival for responders (15 mos) versus non-responders (2 mos) by the landmark method seems to confirm the relative therapeutic efficacy of the VAD protocol in refractory multiple myeloma. The somewhat inferior response rate as well as the occurrence of considerable toxicity in several cases (when compared to the recent M. D. Anderson trial) may be related to differences in clinical features and pretreatment status of the two studies' population.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Medical expert and consultation systems: review and examples for their use].

After a general introduction into the area of medical expert and consultation systems, a survey about different types of medical expert systems is given. The different objectives and modes of application of medical expert systems are presented and explained in detail. In the second part of this paper, the applicability of computer systems for fully automated interpretation of hepatitis serology findings in the clinical laboratory and for aiding differential diagnosis in internal medicine is described. With the examples given, it is demonstrated that expert systems for clinical decision aid can be of great benefit for the physician in the hospital or the doctor's office.

Antibodies, Viral↗