Biomedical subjects
C Ludwig
Publications and source records attributed to C Ludwig.
Combination chemotherapy with mitomycin, vindesine, and cisplatin for non-small cell lung cancer. Association of antitumor activity with initial tumor burden and treatment center.
From 1984 through 1986, 205 patients with non-small cell lung cancer were entered into a group-wide trial of the Swiss Group for Clinical Cancer Research (SAKK). This trial evaluated the combination of mitomycin (8 mg/m2 intravenously [IV] on day 1), vindesine (3 mg/m2 IV on days 1 and 8), and cisplatin (60 mg/m2 IV on day 1) with forced diuresis, repeated every 4 weeks (MiViP regimen). One hundred eighty-three patients were evaluable. Six complete and 69 partial responses were documented for an overall response rate of 41% (95% confidence interval, 34% to 50%). In the multivariate analysis the strongest predictors for response were the participating institution and the number of initially involved organ sites. The estimated median time to progression for patients with a complete response, partial response, or stable disease was 155 days (estimated inter-quartile range, 99 to 258 days). In the multivariate analysis the time to progression was significantly associated with the number of involved organ sites (P = 0.041). The estimated median survival time for the 183 evaluable patients was 239 days (estimated inter-quartile range, 137 to 436 days). In univariate and multivariate analyses performance status, number of involved organ sites, pretreatment status with radiation therapy, and participating institution were all significantly associated with survival. The principal toxicities were myelosuppression and nausea and vomiting with 16% of the patients refusing further treatment after a median of four cycles of chemotherapy. In conclusion, the MiViP regimen was an active combination chemotherapy in patients with non-small cell lung cancer in a large trial performed by the SAKK. The prognostic value of the participating institution and the number of organ sites involved by metastatic deposits in non-small cell lung cancer needs further investigation.
Laser Doppler measurements of cochlear blood flow during loud sound presentation.
The laser Doppler flowmeter may give responses to loud sound that reflect the vibration of cochlear structures rather than changes in cochlear blood flow. The present study demonstrates that the positive artifactual response (i.e., increased flow reading) to sound at frequencies above approximately 5 kHz can be eliminated by using flowmeters which have electronic filters at 4 and 12 kHz, limiting the bandwidth of the optical Doppler shifted frequency range to lower frequencies. However, when using the 4 kHz filter a "residual" immediate negative response to loud high-frequency sound (10 kHz tone at 125 dB SPL) is evident at the beginning of the exposure. These findings are discussed with regard to the suitability of the method for investigating the effect of sound/noise on cochlear blood flow.
Recombinant interferon gamma up-regulates in vivo and down-regulates in vitro monocyte CD14 antigen expression in cancer patients.
The expression of the monocyte membrane glycoprotein CD14 was measured and related to the serum interferon gamma (IFN gamma) concentration in thirteen patients with disseminated cancer during treatment with human recombinant interferon gamma (rIFN gamma). The drug was administered by continuous subcutaneous infusion using an escalating dose schedule, starting at 50 micrograms/day or 100 micrograms/day and increasing weekly up to 600 micrograms/day, if tolerated. Treatment was continued at a mean maximal tolerated dose of 200 micrograms/day for a median duration of 43 days. Serum IFN gamma concentration and monocyte CD14 antigen expression (immunofluorescence with the monoclonal antibody LeuM3 and fluorescence-activated cell sorting analysis) were determined weekly. The serum IFN gamma concentration was positively correlated with the rIFN gamma dose (P less than 0.05). Therapy induced a dose-dependent enhancement of CD14 antigen expression. The increase in mean CD14 fluorescence intensity was on average 60% after 3 weeks of treatment at a mean dose of 220 micrograms rIFN gamma/day and was reversed after withdrawal of therapy. Patients with a rapidly rising serum IFN gamma concentration (starting dose 100 micrograms/day) showed a smaller increment in CD14 fluorescence intensity than those with slowly rising serum IFN gamma levels (starting dose 50 micrograms/day). Since rIFN gamma is known to down-regulate CD14 antigen expression in vitro, monocytes from patients off therapy and from healthy volunteers were cultured with this cytokine. A similar decrease of CD14 fluorescence was observed in both groups. In patients several factors, such as IFN gamma concentration, duration of drug effect and type of serum, were evaluated and could not explain the discrepant in vivo and in vitro findings. In conclusion, the monocyte marker CD14 was found to be differentially regulated by rIFN gamma in vivo and in vitro. In vivo, secondary mediators, induced by rIFN gamma and acting on a constantly renewed cell population, may contribute to the enhanced CD14 expression.
Effectiveness and low toxicity of hepatic artery infusion with fluorouracil and mitomycin for metastatic colorectal cancer confined to the liver. The Swiss Group for Clinical and Epidemiological Cancer Research (SAKK).
The usefulness of hepatic artery infusion (HAI) with floxuridine is limited by the severe biliary and hepatic toxicity of floxuridine. This prompted the SAKK to evaluate the effectiveness, toxicity and feasibility of HAI with fluorouracil (FU) and mitomycin (MMC) administered by an external portable pump. Of 28 patients treated, partial responses were obtained in 14 (50%, 95% confidence interval: 30% to 70%) and stabilization in 11 (39%, 21% to 60%), for a median duration of 12.6+ months. Median survival was 19.5+ months. Grade I-II toxicity (WHO) consisted of nausea (46%), leucopenia (32%) thrombocytopenia (21%) and abdominal discomfort (25%). Two patients developed gastro-duodenal ulcers and two others grade III leucopenia. No life-threatening side effects, especially no sclerosing cholangitis or chemical hepatitis, were observed. In conclusion, HAI with FU and MMC is a valid alternative to floxuridine HAI in metastatic colorectal cancer confined to the liver.
Tubular confronting cisternae in hairy cells following interferon therapy.
Explore the source record for details and available documents.
[Chemosensitivity testing and the drug resistance of human tumors].
Explore the source record for details and available documents.
[Physiological parameters of guinea pigs under long-term anesthesia with controlled respiration].
56 guinea pigs were anesthetized with a mixture of alpha-chloralose and a small dose of ethyl urethane injected i.p. in order to compare the chloralose-urethane anesthesia with neuroleptanesthesia, a mixture of droperidol-fentanyl and a small induction dose of Na-pentobarbital was injected i.p. to 14 animals. All animals were maintained at constant body temperature of 38 degrees C and artificially respirated via a tracheal cannula monitoring the end expiratory CO2 concentration. Mean arterial blood pressure (carotid artery) and heart rate were continuously recorded. Arterial acid-base status and pO2 were tested. Mean arterial blood pressure and heart rate were found to be somewhat higher in the neuroleptanesthetized animals. Under chloralose-urethane anesthesia and neuroleptanesthesia the mean arterial blood pressure amounted to 56 and 62 mm Hg, respectively. These findings correspond to data given in the literature concerning the mean pressure in unanesthetized guinea pigs. The mean heart rates of 295 and 316 min-1, respectively are somewhat higher compared to the normal range. Under both anesthesias, the arterial acid-base status was within the normal limits of unanesthetized animals. The mean arterial pO2 of 80.9 and 76.5 mm Hg was relatively low. The present studies have shown that chloralose-urethane as well as droperidol-fentanyl with pentobarbital are useful, under controlled artificial respiration, to achieve long-term anesthesia maintaining nearly normal systemic circulatory and respiratory conditions.
Phase II trial of menogaril in advanced colorectal cancer.
Menogaril, a new semisynthetic anthracycline antibiotic, was administered to 35 patients with advanced colorectal cancer. The drug was infused over 2 hr at a dose of 160 mg/sqm or 200 mg/sqm repeated every 4 weeks. Twenty-seven patients were evaluable for response and no objective responses were achieved. Myelosuppression, only leukopenia, was usually of mild-moderate degree and occurred in 63% of the patients. Twenty-seven percent of the patients experienced severe leukopenia. Local erythema and phlebitis were frequently observed and were severe in 13% of the patients. Nausea/vomiting (66%) and alopecia (50%) were. of mild-moderate degree. This study suggests that menogaril at these doses and schedule had no activity in advanced colorectal cancer.
The influence of mixed venous pO2 on the natriuretic activity of cat plasma.
Plasma was taken from anaesthetised cats with high or low mixed venous pO2. Different plasma fractions were then administered to anaesthetised rats to examine the effect on sodium excretion. It was found that only the low molecular weight fraction of the plasma from cast with high mixed venous pO2 showed any natriuretic activity. A lipid soluble extract from the same plasma also increased sodium excretion. It is concluded that an increase in mixed venous pO2 in anaesthetised cats leads to the release or activation of a natriuretic factor, which has a molecular weight below 700 and is lipid soluble.
[Experiences with the Riems vaccine combination PI-3 and Riems IBR/IPV vaccines in cattle-raising stock].
Explore the source record for details and available documents.
[Diagnosis of HEV infection in the suckling pig].
Explore the source record for details and available documents.
Phase II trial of nimustine (ACNU; 3-[4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride) in patients with small cell carcinoma of the lung after failure on combination chemotherapy.
Thirty-nine previously treated patients received Nimustine in a phase II trial to test the therapeutic activity in refractory small cell lung cancer. Nimustine was given as a direct i.v. injection of 100 mg/m2 with treatments repeated every six weeks. Three partial remissions of 56, 123 and 355 days duration were noted among 34 evaluable patients. Thrombocytopenia was prominent with a median platelet nadir of 47,000/microliter. We conclude that Nimustine has minor antitumor-activity in heavily pretreated patients with small cell lung cancer. The definitive value of Nimustine in the treatment of small cell lung cancer, as well as its superiority over its parent compounds remains to be established.
A study of multimodality evoked responses in idiopathic spasmodic torticollis.
A wide variety of anatomical sites have been implicated in the pathogenesis of torticollis, based primarily on animal studies. These include lesions in the mesencephalic tegmentum, third ventricle, diencephalon, pre-tectal area, prestitial nucleus of the mid-brain, cervical cord, atlanto-axial junction and motor cortex, amongst others. This study describes the use of multimodality evoked potentials including visual, auditory, bilateral median and peroneal somatosensory evoked responses, undertaken in patients with idiopathic spasmodic torticollis. An attempt was made to non-invasively identify any physiological disruption along these major pathways which could help locate a causative lesion. Normal evoked responses were obtained both ipsilateral and contralateral to the affected side in all patients. It is concluded that the lesion in idiopathic spasmodic torticollis does not discernibly involve the visual, auditory or motor somatosensory pathways.
SP1--really a tumor marker for lymphoid malignancy?
Explore the source record for details and available documents.
[Autoimmune thrombocytopenic purpura in malignant lymphoma. Report of 2 cases and review of the literature].
Two cases are reported of thrombocytopenia mediated by platelet-directed autoantibodies occurring in a patient with Hodgkin's disease in remission and a patient with non-Hodgkin lymphoma at the time of relapse. 0.5-1.5% of patients with malignant lymphoma have autoimmune thrombopenia, but few cases have been published. The detection of anti-platelet autoantibodies involves methodologic problems, and a specialized laboratory is needed for accurate diagnosis. Treatment is aimed at the malignant lymphoma, as steroids have little effect while the malignant disease is active. However, splenectomy may help even in these cases.
Drug resistance of hypoxic tumour cells in vitro.
Explore the source record for details and available documents.
[Impairing effect of ouabain on heart muscle slices of guinea pigs].
In heart slices of guinea pig, ouabain (10(-5) M) causes not only an inhibition of the Na+,-K+-ATPase but also damage of the cell membrane. This leads to an efflux and a degradation of the cellular NADH and NAD. By addition of these constituents to the incubation medium an increasing inhibition of the tissue respiration, caused by ouabain, is prevented.