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Biomedical subjects

P Koch

Publications and source records attributed to P Koch.

At least 19 recordsLinked to original sources
PubMed1995

Allergic contact dermatitis from purified eosin.

We report on a patient, seen in 1993, who developed sensitization to eosin from topical preparations. The patient had a positive patch test reaction to pure tetrabromofluorescein but not to its impurities separated by thin-layer chromatography. Our findings suggest that the allergen was eosin itself.

Aged↗
PubMed1992

[Cardiac interactions between ketanserin and the calcium antagonist nifedipine].

Ketanserin and calcium antagonists are frequently used for the treatment of arterial hypertension in the elderly. The possibility that combined treatment with ketanserin and the calcium antagonist nifedipine have a pro-arrhythmic effect was investigated in 20 normal volunteers aged > 60 years with normal or slightly elevated blood pressure. Each subject received monotherapy with ketanserin or nifedipine for 1 week and the combined treatment during the following week. Clinical and biochemical parameters, ECG and 24-hour ECG recording were monitored before and at the end of the first and second treatment weeks. Ketanserin and nifedipine given in monotherapy or in combination did not modify, on average, blood pressure, heart rate, the biochemical variables and the QT interval. In the 24-hour ECG recordings, 2 normal subjects developed a marked increase in the frequency of ventricular ectopics, couplets and ventricular tachycardia after combined treatment. Therefore, the present investigation does not exclude the possibility that combined treatment with ketanserin and nifedipine could increase the prevalence of arrhythmia in some elderly patients.

Aged↗
PubMed1992

A new case of Zimmermann-Laband syndrome with atypical retinitis pigmentosa.

This paper reports a case study of a 10-year-old girl exhibiting symptoms of a Zimmermann-Laband syndrome (ZLS), including an ocular involvement not previously observed. In addition to the case reported, we have also discovered 21 patients described in the literature. Major clinical findings, defined as being present in more than 75% of the cases under discussion, are presented.

Child↗
PubMed1991

alpha Interferon maintenance therapy in patients with low-grade non-Hodgkin's lymphomas after cytoreductive chemotherapy with prednimustine and mitoxantrone.

A combination of prednimustine 100 mg/m2/day orally, days 1-5, and mitoxantrone 8 mg/m2/day intravenously, days 1 and 2, was administered to 19 patients with advanced low-grade non-Hodgkin's lymphoma after failure on or relapse after standard chemotherapy. The prednimustine and mitoxantrone (PmM) regimen was repeated every 4-6 weeks to a maximum of six cycles. Thirteen patients, achieving a complete (4) or partial (9) remission (CR or PR), received two additional courses for consolidation followed by interferon alfa-2b 5 million units (MU) subcutaneously (s.c.) three times weekly until progression or relapse. At the present time, remission duration ranges from 4.5+ to 17.5+ months, with a median of 14.5 months. In a historical comparison to unmaintained first remission preceding the PmM/interferon trial, a tendency towards a longer period of freedom from progression was apparent in the 13 patients receiving interferon maintenance treatment during their second PR or CR. These data provided the basis for a currently ongoing multicentre study randomly comparing initial chemotherapy with PmM versus cyclophosphamide/vincristine (Oncovin)/prednisone (COP) in patients with advanced centroblastic-centrocytic and centrocytic non-Hodgkin's lymphomas, followed by a second randomization in CR and PR patients for maintenance with alpha interferon versus observation only.

Adult↗
PubMed1991

High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study.

We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.

Adolescent↗
PubMed1991

Value of sonography in monitoring the therapeutic response of mediastinal lymphoma: comparison with chest radiography and CT.

The aim of this retrospective study was to assess the diagnostic value of mediastinal sonography, compared with that of chest radiographs and CT, in the follow-up of patients with mediastinal lymphomas and in the prediction of clinical outcome. The sonograms, chest radiographs, and CT scans of 40 consecutive patients with Hodgkin (n = 29) and non-Hodgkin (n = 11) lymphoma obtained before and after completion of therapy were analyzed blindly and independently by three radiologists and compared with clinical outcome. Nine patients were treated with radiotherapy, 12 with chemotherapy, and 19 with combined therapy. Therapeutic response was assessed from all available clinical and biochemical findings as well as from the combined results of all imaging studies performed on further follow-up. The sonograms showed obvious changes in the size and echogenicity of the mediastinal lymphomas that corresponded closely with the response to therapy. Sonography showed complete regression of the lymphomas in 30 patients who had complete remission. In five patients with incomplete remission, sonographic diagnoses were correct. All lymph nodes, irrespective of size, detected with sonography after a phase of complete remission indicated recurrence (five patients). Sonographic findings corresponded with those of CT in 25 (81%) of 31 cases. Clinical outcome suggested that the sonographic findings were more reliable in the five cases in which CT and sonographic findings conflicted. Chest radiographs were inadequate for monitoring the response of mediastinal lymphomas to therapy; in 17 (43%) of 40 cases, a false impression was obtained of the extent and therapeutic response of mediastinal lymphomas. The results of this study indicate that sonography is clearly superior to chest radiographs and comparable to CT for monitoring patients with mediastinal lymphomas.

Adolescent↗
PubMed1990

Treatment of refractory Hodgkin's disease with high-dose cytosine arabinoside and mitoxantrone in combination. Results of a clinical phase II study of the German Hodgkin Study Group.

In the present study, the activity and side effects of high-dose cytosine arabinoside (HD-Ara-C) in combination with mitoxantrone (mitox) (HAM) was evaluated in 32 heavily pretreated patients with refractory Hodgkin's disease. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours days 1 and 2 and mitox 10 mg/m2/d days 3 to 5. In subsequent steps, HD-Ara-C was escalated to six and eight doses for 3 and 4 days, respectively, and mitox to four doses on days 2 to 5. Thirty-two patients 17 to 55 years of age entered the study. Twenty-five cases presented with extranodal disease and disseminated organ involvement and 21 revealed systemic (B) symptoms. Eighteen patients (56%) responded with five complete and 13 partial remissions, ten patients (31%) had refractory disease, and four patients died from infections during treatment-induced cytopenia. The predominant toxicity was severe myelosuppression in all patients with major infections occurring during 55% of treatment courses. Ten of the responding 18 patients underwent subsequent autologous (n = 9) or allogeneic bone marrow transplant (BMT). Seven of these cases are currently alive at 5+ to 22+ months, six of them without evidence of disease. Among the remaining eight patients not receiving BMT, three are alive at 6+ to 19+ months from the initiation of HAM, two of them in ongoing remissions of 2+ and 5+ months' duration. Two patients died from transplant-related complications and six patients succumbed to progressive disease following relapse. The median survival for all treated patients is 6.2 months. These data indicate that HAM has a significant activity in refractory Hodgkin's disease. However, the substantial side effects and the lack of an obvious superiority to alternative, less intensive regimens limits the further application of the two-drug combination in its present form. Modifications in timing and dosage and the addition of hematopoietic growth factors will be evaluated in subsequent trials.

Adolescent↗
PubMed1990

Treatment of relapsed acute lymphocytic leukemia in adults.

Thirty-three patients with ALL/AUL in first relapse were treated with an induction of prednisone, vindesine, daunorubicin, Erwinia asparaginase, i.t. MTX (phase I), high-dose cytarabine, and etoposide (phase II). Twenty-one (64%) achieved a complete remission, one a partial remission. Side effects of induction-phase I were predominantly hematological with subsequent infections and gastrointestinal toxicity. In phase II some patients had additional cutaneous, ocular, and hepatic toxicity. The treatment efficiently induced remissions with tolerable toxicity in relapsed ALL. The disease-free survival, however, needs to be improved.

Adolescent↗
PubMed1990

An approach to differentiate between noradrenaline-elicited contractile processes in the rat isolated aorta.

The aim of the present study was to assess the different processes contributing to the contraction induced by noradrenaline (NA, 1 mumol/l) in the rat isolated aorta. Pretreatment with maximally effective concentrations of nifedipine or cromakalim reduced the NA-induced contraction to 80 +/- 3.5% or 63 +/- 2.0%, respectively, without alteration of the shape of the response. After pretreatment with Mn2+, NA caused a transient phasic contraction followed by a sustained tonic component, comparable to the response obtained in "Ca2(+)-free" medium. Ryanodine--in the presence of extracellular Ca2(+)-caused a slight increase in resting tension, but did not modify the NA-induced contraction. In "Ca2(+)-free" medium the contraction elicited by NA consisted of a transient phasic and a sustained tonic component. The amplitude of the phasic contraction decreased exponentially with the time of exposure to "Ca2(+)-free" medium. The phasic component was identified as elicited by Ca2+ released from the sarcoplasmic reticulum (SR) by means of ryanodine. If Ca2+ depleted tissues (80 min in "Ca2(+)-free" solution) were exposed to Ca2+ in the presence of Mn2+ or cromakalim, the NA-induced phasic response was inhibited, suggesting that Mn2+ and cromakalim blocked the refilling of the store. It can be concluded that activation of alpha 1-adrenoceptors in the rat aorta by NA elicits Ca2(+)-entry processes which have a different sensitivity to nifedipine, cromakalim and Mn2+. The Ca2+ released from SR contributes about 20% to the overall contractile response. Our data suggest that the depleted SR can be refilled from the extracellular space via a direct cromakalim- and Mn2(+)-sensitive pathway.

Animals↗
PubMed1990

Uncertainties in pharmacokinetic modeling for perchloroethylene. I. Comparison of model structure, parameters, and predictions for low-dose metabolism rates for models derived by different authors.

In recent years physiologically based pharmacokinetic models have come to play an increasingly important role in risk assessment for carcinogens. The hope is that they can help open the black box between external exposure and carcinogenic effects to experimental observations, and improve both high-dose to low-dose and interspecies projections of risk. However, to date, there have been only relatively preliminary efforts to assess the uncertainties in current modeling results. In this paper we compare the physiologically based pharmacokinetic models (and model predictions of risk-related overall metabolism) that have been produced by seven different sets of authors for perchloroethylene (tetrachloroethylene). The most striking conclusion from the data is that most of the differences in risk-related model predictions are attributable to the choice of the data sets used for calibrating the metabolic parameters. Second, it is clear that the bottom-line differences among the model predictions are appreciable. Overall, the ratios of low-dose human to bioassay rodent metabolism spanned a 30-fold range for the six available human/rat comparisons, and the seven predicted ratios of low-dose human to bioassay mouse metabolism spanned a 13-fold range. (The greater range for the rat/human comparison is attributable to a structural assumption by one author group of competing linear and saturable pathways, and their conclusion that the dangerous saturable pathway constitutes a minor fraction of metabolism in rats.) It is clear that there are a number of opportunities for modelers to make different choices of model structure, interpretive assumptions, and calibrating data in the process of constructing pharmacokinetic models for use in estimating "delivered" or "biologically effective" dose for carcinogenesis risk assessments. We believe that in presenting the results of such modeling studies, it is important for researchers to explore the results of alternative, reasonably likely approaches for interpreting the available data--and either show that any conclusions they make are relatively insensitive to particular interpretive choices, or to acknowledge the differences in conclusions that would result from plausible alternative views of the world.

Animals↗
PubMed1990

A continuum model of activity waves in layered neuronal networks: a neuropsychology of brainstem seizures.

We model and brainstem as two layers of respectively purely excitatory and purely inhibitory cells, with instantaneous synaptic interactions within a layer, but with a variable time delay between the layers. For appropriate values of the connection parameters, this configuration provides an attentional mechanism. As the inhibitory delay increases, input signals are, at first, increasingly amplified and confined spatially. At larger delays, the amplified activity propagates into other regions allowing for spatial summation. The temporal frequency of the amplified activity decreases with increasing delay, but its spatial frequency remains relatively constant. As the delay increases through a critical region, a new regime is reached in which highly amplified activity occurs simultaneously over large areas. This regime exhibits many properties of seizure activity.

Brain Stem↗
PubMed1990

[Femoral fractures following total hip prosthesis].

Fractures of the ipsilateral femur after hip arthroplasty are a serious problem. In most cases, minimal trauma is responsible for the fracture. Predisposing factors, such as severe osteoporosis, loosening of the stem of the prosthesis, or cortex perforations, are often found. Such fractures occurred between 1979 and 1989 in 30 patients, i.e. 2.3% of our patients who had received primary prosthesis and 2.9% of those who had undergone revision. The patients' ages at the time of fracture ranged from 41 to 88 years (mean 63 years), 33% of the patients in these group being female. The time lapse from implantation of the prosthesis to the fracture varied between 1 month and 11 years (mean 4.4 years). The fracture was at the level of the proximal trochanteric region in 3% of these patients, between the trochanteric line and the tip of the prosthesis in 20%, and below the tip of the prosthesis in 70%. Operative treatment was performed in 29 patients. Fractures were fixed with a compression plate in 19 (63%), and in 3 the plate fixation was reinforced with intramedullary cement. In 2 osteoporotic patients with supracondylar fractures the osteosynthesis ruptured and a successful revision operation with cement was performed. In 3 others internal fixation was combined with replacement of the prosthesis; 3 patients received a Wagner revision prosthesis and 1 a long-stem Protek tumor prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗