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Biomedical subjects

C Ludwig

Publications and source records attributed to C Ludwig.

At least 73 records · Page 4Linked to original sources
PubMed1995

Quality versus quantity of life in the treatment of patients with advanced small-cell lung cancer? A randomized phase III comparison of weekly carboplatin and teniposide versus cisplatin, adriamycin, etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: Based on a promising pilot study with weekly carboplatin and teniposide (CBDCA/VM) the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with extensive-disease small-cell lung cancer aimed at the development of an effective palliative treatment with low subjective toxicity. PATIENTS AND METHODS: From September 1989 to September 1991 patients were randomised to a weekly regimen of CBDCA/VM or to our 'standard chemotherapy' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine (PAV-CyMOC). RESULTS: The trial was closed before the planned accrual of 140 evaluable patients due to a significant survival difference shown by an interim analysis. Of the 61 patients 59 were eligible and included in the final analysis. The results achieved with the PAV-CyMOC regimen were significantly better than those observed in patients treated with weekly CBDCA/VM (remission rate of 65% vs. 29%; p = 0.006). The median survival of patients treated with the PAV-CyMOC combination was significantly longer than that of patients receiving weekly CBDCA/VM (260 days vs. 147 days; p = 0.0035). The 1-year survival rate was 30% in the PAV-CyMOC arm compared to 4% in the CBDCA/VM-treated patients. As expected, side effects including myelosuppression, alopecia and mucositis were significantly more pronounced in patients treated with the PAV-CyMOC regimen. No significant difference was found in patient-rated tumor symptoms and general quality-of-life categories. CONCLUSION: Contrary to our initial expectation that we would achieve similar therapeutic results with less subjective toxicity, in this randomised prospective trial the results achieved by weekly carboplatin and teniposide were significantly inferior in terms of remission rate and survival to those of our 'standard regimen' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. The weekly regimen was less toxic than the standard chemotherapy. Whether patients are willing to accept a significant trade-off between quantity and quality of life remains to be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Boerhaave syndrome. Differential diagnosis in acute chest pain].

Spontaneous perforation of the esophagus (Boerhaave syndrome) is a rare diagnosis in acute thoracic or epigastric pain. We present the case of a swiftly diagnosed and successfully treated rupture. Apart from pathophysiology, symptoms and diagnosis, the differential diagnosis and therapeutic options are discussed in more detail.

Chest Pain↗
PubMed1994

Relationship between soluble tumor necrosis factor (TNF) receptors and TNF alpha during immunotherapy with interleukin-2 and/or interferon alpha.

Eleven metastatic cancer patients were studied during three different regimens of immunotherapy with interleukin-2 (IL-2) and/or interferon alpha (IFN alpha): group A received 4 days of IL-2 i.a. infusion (n = 3), group B IFN alpha s.c. during 5 days (n = 4), followed on day 3 by 5 days of a continuous IL-2 i.v. infusion, and group C had 4 days of IL-2 i.v. infusion together with s.c. IFN alpha on days 1 and 4 (n = 4). Soluble tumor necrosis factor receptors (sTNFR) p55 and p75 and TNF alpha concentrations in serum were analyzed before therapy and daily during 8 days of the first therapy cycle. sTNFR was measured by radioimmunoassay. sTNFR p55 increased in all patient groups from a baseline value of 5.2 +/- 0.9 ng/ml to a maximum of 13.6 +/- 1.2 ng/ml by days 3-4 (P = 0.003). sTNFR p75 increased from 7.6 +/- 1.1 ng/ml to peak values of 30.1 +/- 2.6 ng/ml in groups A and B (P = 0.02). In group C the sTNFR p75 response was weak (NS). In group B, the increase of both p55 and p75 occurred only after addition of IL-2 to IFN alpha. TNF alpha increased weakly during treatment with IFN alpha alone (group B); it rose strongly during IL-2 and the combined treatment (groups A-C) from 8 +/- 2 pg/ml to 115 +/- 13 pg/ml (P = 0.003). In group B, it reached the maximum 24 h after addition of IL-2 to IFN alpha and decreased thereafter. There was a significant relationship between TNF alpha and sTNFR p55 or sTNFR p75 in groups A and C, (P = 0.001), but not in group B. Group C was also investigated during the third therapy cycle. The increase of sTNFR p75 was stronger (P = 0.01) and that of TNF alpha weaker than in the first cycle; the sTNFR p55 response was similar in both cycles. In conclusion sTNFR p55 and p75 are rapidly induced during IL-2 and IL-2+ IFN alpha treatment, the increase of sTNF receptors parallels or exceeds that of TNF alpha and may influence the immunomodulatory effects of TNF alpha during cytokine therapy.

Adult↗
PubMed1994

Phase II trial of anaxirone (TGU) in advanced colorectal cancer: an EORTC Early Clinical Trials Group (ECTG) study.

Anaxirone, a rationally synthesised triepoxide derivative, was given to 46 patients with metastatic colorectal cancer. Good risk patients received 800 mg/m2 as a rapid intravenous injection every 4 weeks, whereas poor risk patients received 650 mg/m2. Of 46 patients, 45 were evaluable for toxicity and 42 for efficacy analysis. There were 37/45 patients with poor risk, showing no difference in toxicity as compared to good risk patients. The major toxic effect was myelosuppression with 34% of all patients experiencing grade 3 or 4 leucopenia; thrombocytopenia was less frequent. Locoregional phlebitis occurred in 66% of the patients. There was no objective tumour response to anaxirone in 42 evaluable patients. Only 4 patients achieved stabilisation of the disease lasting maximally up to 248 days. Anaxirone is inactive in metastatic colorectal cancer.

Adult↗
PubMed1994

Combined-modality treatment of small-cell lung cancer: randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: From 1980 to 1983 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with small-cell lung cancer with the objective of improving the results of induction chemotherapy and defining the role of consolidating chest irradiation. PATIENTS AND METHODS: Patients were initially randomised to induction arms AVP (adriamycin, etoposide and cisplatin given every four weeks for four cycles), EVA (cyclophosphamide, etoposide and adriamycin given every four weeks for four cycles) or MOC/AVP (methotrexate, vincristine, cyclophosphamide alternating with adriamycin, etoposide and cisplatin given for two cycles). All patients received prophylactic cranial irradiation with 30 Gy, and after four months of induction chemotherapy were randomized to maintenance chemotherapy with or without consolidating chest irradiation. The patients in the combined-modality maintenance arm first received radiation therapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. RESULTS: 266 patients were eligible and evaluable. An overall response rate of 70% with 21% of complete remissions, a median survival of 9.3 months and survival of 8% of the patients at two years were observed. The highest objective response rate was achieved with the AVP-induction chemotherapy with an 80% response rate and 32% complete remissions. Similar results were achieved with the alternating regimen of MOC/AVP. In contrast, patients treated with the EVA induction regimen had significantly lower overall remission (56%) and complete remission rates (7%). The role of consolidating chest irradiation could not be clarified in limited-disease patients due to the small number of them who were randomised to the maintenance part of the study. However, in patients with extensive disease in partial remission after induction treatment, combined maintenance therapy had a more significant adverse effect on survival than maintenance chemotherapy alone (median survival in the maintenance phase of 148 days versus 239 days, p = 0.011). CONCLUSION: We conclude that the combination of adriamycin, etoposide and cisplatin is an active induction treatment. Consolidating chest irradiation is contraindicated in patients with extensive disease in partial remission after induction when given in a sequential manner, as in our trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Changes in cochlear oxygenation, microcirculation and auditory function during prolonged general hypoxia.

Changes in cochlear microcirculation and oxygenation and auditory function were examined in anesthetized guinea pigs during prolonged hypoxic ventilation (8% oxygen in nitrogen) for 1 h. Cochlear blood flow and perilymphatic oxygen partial pressure were measured using laser Doppler flowmetry and oxygen-sensitive microelectrodes. Auditory function was examined by recording cochlear microphonics, compound action potentials and auditory evoked brainstem response. Blood pressure and heart rate were monitored. During systemic hypoxia, the perilymphatic PO2 dropped on average to about 70% of the initial value. Cochlear and brainstem potentials showed a mean reduction to 75-82%. Different effects of hypoxia on cochlear blood flow were observed and included decreases as well as increases. Mean arterial blood pressure declined significantly during hypoxia, while the heart rate remained constant. The changed variables returned to normal during reventilation with room air. The findings are discussed with regard to their significance as an animal model for the study of hypoxia-induced cochlear pathophysiology.

Action Potentials↗
PubMed1993

Intensity-related changes in cochlear blood flow in the guinea pig during and following acoustic exposure.

This study examined the effects of acoustic exposure at different intensities on cochlear blood flow (CBF) using laser Doppler flowmetry. CBF was measured in anesthetized guinea pigs exposed to either a 10 kHz pure tone at 125, 105, or 90 dB SPL, or wide-band noise at 85 dB SPL for 1 h. Mean arterial blood pressure and heart rate were recorded continuously. Arterial acid-base status, cochlear temperature, cochlear microphonics (CM), and compound action potentials (CAP) were measured before and after exposure. There was a small, but significant, steady decline in basal CBF after 40 min loud sound exposure (125 dB SPL), but no change in basal CBF occurred with the lower intensities (85-105 dB SPL). In contrast, there was a significant increase in apical CBF after 1 h exposure to either moderate wideband noise (85 dB SPL) or a 10 kHz tone at 105 dB SPL. These changes persisted during a 20-min post-exposure period. In most cases, the cochlear temperature and cardiorespiratory variables monitored remained unchanged during and after the exposures as compared to the controls. CM and CAP amplitudes showed extensive losses after acoustic overstimulation (125 dB SPL), but no permanent changes were found at the lower intensities used. The present findings confirm the occurrence of intensity-related effects of acoustic exposure on the cochlear microcirculation.

Animals↗
PubMed1993

Pharmacokinetics and immunomodulatory effects on monocytes during prolonged therapy with liposomal muramyltripeptide.

The macrophage activator muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) was infused in liposomal form in 14 metastatic cancer patients (4 mg i.v. during 30 min twice weekly for 12 weeks). Clinical, pharmacokinetic and immunological parameters were studied before and 0.5, 2, 4, 24 and 72h after start of drug infusion in week 1, 4, 8 and 12. No tumor regressions were seen. Tumors progressed in 11 patients, in 4 of them within 2 months; 3 patients had stable disease. The intensity and frequency of side effects (fever and nausea) diminished from week 1 to 12. The rate of disappearance of total and free MTP-PE from blood was rapid and mean serum concentration-time curves remained unchanged throughout 12 study weeks. MTP-PE caused a marked increase of serum TNFa, IL-1 receptor antagonist (IL-1ra) and IL-6 in week 1, but not thereafter. In contrast, MTP-PE caused a persistent, 2-fold increase in serum neopterin and young forms of granulocytes (bands) during week 1 to 12. Before therapy, monocyte tumor cytotoxicity and in-vitro monocyte derived TNFa, IL-1 beta and IL-6 production were low in 9 patients (group L, < 15%) and high in 5 patients (group H, > 40%). Monocyte cytotoxicity and in-vitro cytokine production was transiently enhanced in week 1 in group L, it declined under therapy in group H. In conclusion, MTP-PE induced marked initial immunomodulation; the extent of the ex vivo monocyte cytokine and tumor cytotoxic response was dependent on pre-therapy cell activity. A decrease of the cytokine and IL-1ra response during prolonged therapy contrasted with a persistent increase of neopterin and juvenile blood granulocytes. The long lasting biologic effects may be relevant to direct future clinical studies with liposomal MTP-PE in an adjuvant setting.

Acetylmuramyl-Alanyl-Isoglutamine↗
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↗