PubMed Health⌕ Search

Biomedical subjects

C Ludwig

Publications and source records attributed to C Ludwig.

At least 19 recordsLinked to original sources
PubMed1992

[Adjuvant therapy in colorectal carcinoma].

Patients with colorectal carcinoma and histological evidence of regional lymph node involvement (N+ or Dukes' C) or tumor invasion into the adjacent pericolic or perirectal fat tissue (T3-T4 or Dukes' B2-B3) still have an unfavourable prognosis if treated by surgery only. In colonic cancer, several clinical studies carried out in the early 1980s using postoperative chemotherapy showed no therapeutic benefit. Only the combination of 5-fluorouracil and levamisole, used in two large randomized studies, resulted in a significant prolongation of the disease-free interval and overall survival in patients with Dukes' C colonic cancer. This treatment has few side effects. In patients with rectal cancer, it was the combination of chemo- and radiotherapy which led to therapeutic improvement: the incidence of local relapses--often very painful and distressing for the patient--was significantly reduced and overall survival prolonged. However, this combined treatment modality carries the risk of delayed toxicity with complications mainly involving the small bowel. It is the general practitioners' duty to decide, together with the specialists involved, whether an individual patient with colonic or rectal cancer appears suitable for such adjuvant treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Intensity-dependent changes in oxygenation of cochlear perilymph during acoustic exposure.

This study examined the effects of acoustic exposure at different intensities on local oxygenation of the cochlea. The oxygen partial pressure (pO2) of perilymph in the basal scala tympani was measured polarographically in anesthetized guinea pigs exposed to either wide-band noise at 85 dB SPL or a 10 kHz pure tone at 90, 105, or 125 dB SPL for 1 h. Cochlear temperature, heart rate, arterial blood pressure and acid-base status were monitored. The cochlear microphonics (CM) and compound action potentials (CAP) were recorded before and after exposure. There were clear intensity-dependent differences in the effect of acoustic exposure on perilymphatic oxygenation. Moderate exposure intensities (85-90 dB SPL) were found to increase the pO2 by an average of about 20% of the initial level. In contrast, high intensity acoustic exposure (125 dB SPL) resulted in a mean decrease of about 20%. These changes persisted within a subsequent 30-min post-exposure period. There was no significant change in cochlear temperature and cardiorespiratory variables during and after any of the exposures as compared to the controls. CM and CAP amplitudes showed an extensive loss after acoustic overstimulation (125 dB SPL), but no permanent change with lower exposure intensities. These findings suggest that intracochlear oxygenation plays an important role in inner ear physiology during acoustic stimulation.

Acoustic Stimulation↗
PubMed1992

Prolonged interferon-gamma application by subcutaneous infusion in cancer patients: differential response of serum CD14, neopterin, and monocyte HLA class I and II antigens.

This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Chlamydia as the cause of abortions in horses].

Between 1982 and 1989 59 equine fetuses were investigated for chlamydiae using animal experiments and embryonated eggs. Chlamydiae were isolated from 16 fetuses (27.1%) originating from 8 studs. The macroscopical lesions of the fetal organs were characterized by extensive haemorrhages. The histological picture shows severe lesions of the blood vessels of different organs. In 6 studs in which chlamydiae had been isolated, blood sera of clinically healthy and pregnant mares were investigated for antibodies during 1989 and 1990. Antibody titres between 1:10++ and 1:40 were detected by using complement fixation test in sera of mares of 4 studs.

Abortion, Veterinary↗
PubMed1991

Effect of cytokines and lipopolysaccharide on CD14 antigen expression in human monocytes and macrophages.

The 52 kD myeloid membrane glycoprotein CD14 represents the receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP); it is involved in LPS induced tumor necrosis factor-alpha production. Expression of CD14 increases in monocytes differentiating into macrophages, and it is reduced by rIFNg in monocytes in vitro. In the present study CD14 membrane antigen expression was investigated in cultures of human mononuclear leucocytes (PBL), in elutriated, purified monocytes, and in blood monocyte derived Teflon cultured macrophages. Cells were incubated for 15 or 45 h with rIL-1, rIL-2, rIL-3, rIL-5, rIL-6, rTNFa, rGM-CSF, rM-CSF, rTGFb1, rIFNa, lipopolysaccharide (LPS), and, as a control, rIFNg. The monoclonal antibodies Leu-M3 and MEM 18 were used for labelling of CD14 antigen by indirect immunofluorescence and FACS analysis of scatter gated monocytes or macrophages. IFNg concentrations were determined in PBL culture supernatants by ELISA. rIFNa and rIL-2 reduced CD14 in 15 and 45 h PBL cultures, an effect mediated by endogenous IFNg, since it was abolished by simultaneous addition of an anti-IFNg antibody. rIFNa and rIL-2 were ineffective in purified monocytes or macrophages. rIL-4 strongly reduced CD14 in PBL and purified monocytes after 45 h, whereas in macrophages the decrease was weak, although measurable after 15 h. The other cytokines investigated did not change CD14 antigen expression. Cycloheximide alone reduced CD14, but when added in combination with rIFNg the effect on CD14 downregulation was more pronounced. The effect of rIFNg on CD14 in PBL cultures was dose-dependently inhibited by rIL-4 and this inhibition is probably due to an IL-4 mediated blockade of IFNg secretion. LPS at a low dose increased CD14, at a high dose it produced a variable decrease of CD14 in PBL, which was probably due to LPS induced IFNg secretion. LPS strongly enhanced CD14 in 45 h cultures of purified monocytes. The results, showing that CD14 antigen expression is upregulated by LPS and downregulated by rIFNg and rIL-4, suggest that the LPS-LBP receptor is involved in the feedback response of IFNg and IL-4 to LPS stimulation.

Antibodies↗
PubMed1991

Measurements of perilymphatic oxygen tension in guinea pigs exposed to loud sound.

Using different types of custom-made oxygen-sensitive microelectrodes, the perilymphatic oxygen partial pressure (PO2) was determined in anesthetized guinea pigs. Cochlear temperature, heart rate, and arterial blood pressure and acid-base status were monitored. The PO2 in the basal scala tympani perilymph (200 microns below the round window membrane) was found to be 53 +/- 17 mmHg (mean +/- SD) in 33 normal animals. In 11 guinea pigs exposed to loud sound for 15 min (10 kHz pure tone, 125 dB SPL) there was on average a continuous decline in the perilymphatic PO2, which was significant only 30 min post-exposure. A considerable variation in response was found in individual animals. Mean arterial blood pressures showed a slightly increasing time course, while heart rates did not change significantly during the whole period of the experiment. Arterial acid-base status and PO2 values remained within normal limits and did not change significantly. Cochlear microphonics and compound action potentials were substantially decreased after acoustic overstimulation. The results are discussed with due consideration of sources of error.

Acoustic Stimulation↗
PubMed1991

Nootropic drugs in Alzheimer's disease: symptomatic treatment with pramiracetam.

The cognitive-enhancing effects of pramiracetam in animal models of learning and memory are characterized by an inverted U-shaped dose-response curve. We evaluated antidementia efficacy of this drug in 10 patients with probable Alzheimer's disease employing a 2-phase, placebo-controlled, enrichment-type trial design. Eight patients evidenced a best dose in the dose-finding phase, but in the subsequent replication phase only two again improved to a similar degree. PETs with fluorodeoxyglucose obtained in two individuals showed no definite change. Doses up to 4,000 mg pramiracetam are unlikely to confer symptomatic benefit to Alzheimer's disease patients.

Aged↗
PubMed1991

Estimates of genetic parameters for live animal ultrasound, actual carcass data, and growth traits in beef cattle.

Growth and carcass measurements were made on 2,411 Hereford steers slaughtered at a constant weight from a designed reference sire program involving 137 sires. A second data set consisted of ultrasound measures of backfat (USFAT) and longissimus muscle area (USREA) from 3,482 yearling Hereford cattle representing 441 sires. Restricted maximum likelihood procedures were used to estimate genetic parameters among carcass traits and live animal weight traits from these two separate data sets. Heritability estimates for the slaughter weight constant steer carcass backfat (FAT) and longissimus muscle area (REA) were .49 and .46, respectively. In addition, FAT had a negative genetic correlation with REA (-.37), weaning weight (-.28), and yearling weight (-.13) but positive with marbling (.19) and carcass weight (.36). Marbling was moderately heritable (.35) and highly correlated with total postweaning average daily gain (.54) and feedlot relative growth rate (.62). Heritability estimates for weight constant USFAT and USREA were .26 and .25, respectively. The genetic correlation between weight constant USFAT and USREA was positive (.39), indicating that in these young animals USFAT does not seem to be an indication of maturity. Mean USFAT measures and variability were small (.48 +/- .17 cm, n = 3,482). Results indicate that carcass fat on slaughter steers and ultrasound measures of backfat on young breeding animals may have different relationships with growth and muscling. These relationships need to be explored before wide scale selection based on ultrasound is implemented.

Adipose Tissue↗
PubMed1990

[Oncogenes].

Explore the source record for details and available documents.

Cell Division↗
PubMed1990

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.

Adult↗
PubMed1990

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.

Animals↗
PubMed1990

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.

Adult↗
PubMed1990

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.

Adult↗
PubMed1989

[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.

Anesthesia↗
PubMed1988

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.

Adult↗
PubMed1988

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.

Animals↗