PubMed Health⌕ Search

Biomedical subjects

M Clemens

Publications and source records attributed to M Clemens.

At least 19 recordsLinked to original sources
PubMed2003

Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial.

To assess the response rate and the tolerance of irinotecan as first-line therapy, 40 patients with metastatic gastric cancer received irinotecan 350 mg m(-2) every 3 weeks administered as a 30 min infusion. Among the 35 patients evaluable for response, two complete and five partial responses were recorded (response rate: 20.0% (95% CI:8.4-36.9%)). In total, 16 patients achieved stable disease and 12 progressive disease. In all, 66 percent of the patients benefited from tumour growth control. The median time to progression was 3.0 months (95% CI: 2.3-4.4%). The median overall survival was 7.1 months (95% CI: 5.2-9.0%). The probability of being alive at 6 months and 9 months was 61.0 and 32.4%, respectively. The median number of cycles per patient was 3 (range 1-14), and the relative dose intensity was 0.98. The most common grade 3-4 toxicities by patients were diarrhoea 20%, asthenia 10%, nausea 7.5%, vomiting 5.0%, abdominal pain 5%, neutropenia 38.5%, leucopenia 28.2%, anaemia 12.8% and thrombocytopenia 5.1%. Febrile neutropenia occurred in 12.5% of patients. These findings indicate that irinotecan is active and well tolerated in patients with metastatic gastric adenocarcinoma and warrants further evaluation in this clinical setting.

Adenocarcinoma↗
PubMed2002

Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.

BACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status. RESULTS: After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment. CONCLUSIONS: No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.

Adult↗
PubMed2001

Improvement of perineal wound healing by local administration of gentamicin-impregnated collagen fleeces after abdominoperineal excision of rectal cancer.

BACKGROUND: Despite significant advancements in rectal surgery, poor perineal wound healing after abdominoperineal resection (APR) of the anorectum continues to be a potential complication of the procedure. The aim of this prospective randomized multicenter study was to investigate the efficacy of a new mode of local antibiotic administration. PATIENTS AND METHODS: Ninety-seven patients who had to undergo APR for low rectal carcinoma either received sacral drainage plus primary wound closure (control group, n = 48) or the same treatment and supplementary application of three resorbable gentamicin-impregnated collagen fleeces (Septocoll; Merck Biomaterial GmbH, Darmstadt, Germany; Genta group, 49). The following target criteria were investigated: bacteriologic efficacy with respect to the eradication of Enterobacteriaceae, Staphylococcus, and Pseudomonas organisms, and clinical efficacy with respect to perineal wound healing. RESULTS: The Genta group showed a marked reduction in the investigated pathogens from the secretion obtained by sacral drainage on days 1 and 3, as well as high gentamicin concentrations (day 1, median 126.2 microg/mL; day 3, median 97.6 microg/mL). In total, bacteriologic efficacy amounted to 83.7% in the Genta group (41 of 49 patients) versus 60.4% (29 of 48 patients) in controls (P = 0.013). In concurrence with these bacteriologic results, the postoperative infection rate was significantly higher in controls: 10 patients (20.83%) in the control group versus 3 (6.1%) in the Genta group developed perineal or sacral infection (P <0.05). Postoperative complications in the recruited patients revealed no indication of gentamicin-induced adverse reactions. CONCLUSIONS: The results of the study show that the specified dose of 3 Septocoll fleeces in patients with APR is liable to significantly eliminate enterobacteria, staphylococci, and pseudomonads. The clinical course is improved as a result of the bactericidal effect exerted by the gentamicin fleece. The use of Septocoll reduced the incidence of postoperative perineal and sacral infections. Local antibiotic carriers seem to be of great advantage in poorly perfused areas such as the sacral cavity or anatomically problematic regions as the rima ani. In locally contaminated or infected areas, local antibiotic carriers achieve greater concentrations of the active substance than those achieved with systemic antibiotics, even if the latter are administered by the parenteral route.

Absorbable Implants↗
PubMed2000

Gemcitabine and cisplatin in the treatment of advanced or metastatic pancreatic cancer.

BACKGROUND: This phase II study was initiated to determine the efficacy and safety of gemcitabine plus cisplatin in patients with pancreatic cancer. PATIENTS AND METHODS: Gemcitabine 1000 mg/m2 was given on days 1, 8, and 15 of a 28-day schedule, and cisplatin 50 mg/m2 on days 1 and 15 to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Of the 41 patients enrolled (median age 57, and 61% male), median Karnofsky performance status was 80%. Patients received a median of 4.2 cycles (range 1-11). In 35 evaluable patients, one complete response (CR) and three partial responses (PR) were observed, for an overall response rate of 11% (95% confidence interval (95% CI): 3.2% -26.7%). Stable disease (SD) > 3 months occurred in 20 (57%) patients; 6 survived > or = 1 year. Median time to progressive disease was 4.3 months (95% CI: 3.0-5.7 months). For all patients, median survival was 8.2 months (95% CI: 6.1-10.6 months) with a one-year survival rate of 27%. Therapy was well tolerated. Grade 3-4 neutropenia (no grade 3-4 infection), thrombocytopenia (no bleeding), nausea/vomiting, and alopecia were reported in 29%, 13%, and 2.6% of patients, respectively. CONCLUSIONS: The combination of gemcitabine and cisplatin is a moderately active treatment for patients with locally advanced and metastatic pancreatic cancer without compromising tolerability.

Adult↗
PubMed2000

A phase II study of paclitaxel, weekly, 24-hour continous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer.

To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2 h infusion. Paclitaxel 175 mg/m2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1-4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% CI: 35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1-36+) and 14 months (range 2-36+), respectively. Neutropenia WHO III(o)/IV(o) occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III(o)/IV(o) toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive option to be tested for neoadjuvant or adjuvant treatment.

Adenocarcinoma↗
PubMed1998

Wolf-Hirschhorn and Pitt-Rogers-Danks syndromes caused by overlapping 4p deletions.

Wolf-Hirschhorn syndrome (WHS), a multiple congenital malformation syndrome, and Pitt-Rogers-Danks syndrome (PRDS), a rare condition with similar anomalies, were previously thought to be clinically distinct conditions. While WHS has long been associated with deletions near the terminus of 4p, several recent studies have shown PRDS is associated with deletions in 4p16.3. In this paper we evaluate three patients, two described as PRDS and one diagnosed as WHS. We demonstrate that the molecular defects associated with the two syndromes show a considerable amount of overlap. We conclude that both of these conditions result from the absence of similar, if not identical, genetic segments and propose that the clinical differences observed between these two syndromes are likely the result of allelic variation in the remaining homologue.

Adolescent↗
PubMed1998

Clinical presentation and therapeutic outcome in 26 patients with primary CNS lymphoma.

This retrospective study analyzes clinical features and therapeutic outcome in 26 immunocompetent patients with primary central nervous system lymphoma (PCNSL). Most patients presented with personality changes. PCNSL lesions were mainly iso- or hyperdense, enhancing lesions on CT scan, hypointensive on T1-, and hyperintensive on T2-weighted MRI. Multiple lesions were found in about 60% of patients. Nine of 11 patients receiving radiotherapy alone showed complete remission (CR). Median survival time after diagnosis (MST) was 13 months. Seven patients received intravenous and intrathecal methotrexate, radiotherapy, and postirradiation intravenous cytarabine. Six of these patients had CR and 5 patients are alive in CR after a median follow-up of 12 months. Five patients received various other radiochemotherapy regimens (MST 6 months), and 3 patients died before receiving any radio- or chemotherapy. Our preliminary treatment results show a tendency to improved survival with radiochemotherapy. This is consistent with pertinent data from the literature which favors radiochemotherapy for patients with PCNSL.

Adrenal Cortex Hormones↗
PubMed1997

Bruck syndrome (osteogenesis imperfecta with congenital joint contractures): review and report on the first North American case.

We describe a patient who was born with flexion contractures and pterygia at the elbows, clubfeet, torticollis, and several rib fractures. During infancy and childhood, multiple fractures of the lower limbs occurred with minimal trauma and led to disabling deformities. When evaluated at age 19 years, he was normally intelligent, but extremely short, with severe kyphoscoliosis compromising his pulmonary function. Pterygia limited elbow extension to 90 degrees, and severe lower limb deformities prevented ambulation. He did not have blue sclerae, dentinogenesis imperfecta, or hearing loss. X-ray studies showed demineralized bones, severe deformity and cystic change at old fracture sites, and vertebral wedging. Collagen studies on skin fibroblasts were normal.

Abnormalities, Multiple↗
PubMed1997

Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis.

Genetically obese fatty/fatty rats and obese/obese mice exhibit increased sensitivity to endotoxin hepatotoxicity, quickly developing steatohepatitis after exposure to low doses of lipopolysaccharide (LPS). Among obese animals, females are more sensitive to endotoxin liver injury than males. LPS induction of tumor necrosis factor alpha (TNF alpha), the proven affecter of endotoxin liver injury, is no greater in the livers, white adipose tissues, or sera of obese animals than in those of lean controls. Indeed, the lowest serum concentrations of TNF occur in female obese rodents, which exhibit the most endotoxin-induced liver injury. Several cytokines that modulate the biological activity of TNF are regulated abnormally in the livers of obese animals. After exposure to LPS, mRNA of interferon gamma, which sensitizes hepatocytes to TNF toxicity, is overexpressed, and mRNA levels of interleukin 10, a TNF inhibitor, are decreased. The phagocytic activity of liver macrophages and the hepatic expression of a gene encoding a macrophage-specific receptor are also decreased in obesity. This new animal model of obesity-associated liver disease demonstrates that hepatic macrophage dysfunction occurs in obesity and suggests that this might promote steatohepatitis by sensitizing hepatocytes to endotoxin.

Animals↗
PubMed1996

Pitt-Rogers-Danks syndrome: the result of a 4p microdeletion.

Pitt-Rogers-Danks syndrome (PRDS) is a rare, presumed autosomal recessive, syndrome with pre- and postnatal growth retardation, microcephaly, characteristic facial appearance, seizures, unusual palmar creases and developmental delay. Since the first description in 1984, only 7 cases have been reported. We report the identification of a 4p microdeletion in 2 new patients, who were previously diagnosed with PRDS, as well as the sibs in Pitt et al. [1984]. PRDS can no longer be considered autosomal recessive. Although our cases are attributable to a microdeletion in 4p16, it is uncertain if the critical region involves a single locus or multiple loci or to what extent this region overlaps with the critical region for Wolf-Hirschhorn syndrome.

Abnormalities, Multiple↗
PubMed1996

Cleft lip and palate, characteristic facial appearance, malrotation of the intestine, and lethal congenital heart disease in two sibs: a new autosomal recessive condition?

A chromosomally normal brother and sister shared a lethal pattern of anomalies including bilateral cleft lip and palate, hypertelorism, flat facial profile, flat occiput, complex congenital heart defect, and malrotation of the intestine. The male was large for gestational age, while his sister was normally grown. The girl had bifid thumbs, but the boy had only minor hand anomalies. These findings are not consistent with any previously recognized syndrome and represent a new condition with probable autosomal recessive inheritance.

Abnormalities, Multiple↗
PubMed1995

Analysis of olanzapine in human plasma utilizing reversed-phase high-performance liquid chromatography with electrochemical detection.

A sensitive reversed-phase HPLC method for the analysis of olanzapine in human plasma is described. Isolation of olanzapine from plasma was accomplished by solid-phase extraction utilizing an ion-exchange/reversed-phase cartridge designed for basic drug extraction. The drug was subsequently separated by reversed-phase HPLC and monitored by electrochemical detection (ED). Electrochemical analysis was used to detect olanzapine due to its uniquely low oxidative potential. Ascorbic acid was added to prevent oxidation during extraction. The limit of quantitation for the assay was established at 0.25 ng/ml utilizing a 1-ml human plasma sample. The average inter-day accuracy was 96.6% with a average precision (% C.V.) of 3.22% over the concentration range of 0.25 to 100 ng/ml. This method was applied to human plasma samples from human clinical trials with olanzapine. The HPLC-ED method compared favorably with a negative chemical ionization GC-MS method previously utilized for analysis of olanzapine in human plasma.

Antipsychotic Agents↗
PubMed1995

The PETT series, a new class of potent nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase.

To identify the minimal structural elements necessary for biological activity, the rigid tricyclic nucleus of the known human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor tetrahydroimidazobenzodiazepinthione was subjected to systematic bond disconnection to obtain simpler structures. A rational selection and testing of modeled analogs containing these potential pharmacophoric moieties led to the discovery of a new series of nonnucleoside inhibitors of RT. The lead compound of this new PETT series of nonnucleoside RT inhibitors, N-(2-phenylethyl)-N'-(2-thiazolyl)thiourea (LY73497), was found to inhibit HIV-1 but not HIV-2 or simian immunodeficiency virus in cell culture at micromolar concentrations. This derivative was also found to inhibit HIV-1 RT. Through an integrated effort involving synthesis and molecular modeling, compounds with nanomolar potency against HIV-1 in cell culture were developed. In these studies, LY300046-HCl was identified as a potent nonnucleoside inhibitor of HIV-1 RT possessing favorable pharmacokinetic properties.

Animals↗
PubMed1994

Weekly high-dose 5-fluorouracil and folinic acid as salvage treatment in advanced gastric cancer.

BACKGROUND: A weekly schedule of a 24-h high-dose 5-FU infusion in combination with folinic acid was investigated as salvage therapy in patients with advanced gastric cancer. PATIENTS AND METHODS: Seventeen patients with progressive disease after chemotherapy were treated with a weekly schedule of 500 mg folinic acid/sqm by i.v. 2-h infusion followed by an i.v. 24-h infusion of 2.6 g 5-FU/sqm times six. Fourteen of the 17 patients (82%) had been pretreated in regimens which included 5-FU/folinic acid i.v. bolus. RESULTS: Toxicity was mild, with diarrhea, mucositis and nausea; WHO grade III/IV diarrhea was observed in only two patients. Three patients achieved partial remissions (18%; 95% confidence interval: 0%-38%) and 7 patients stable disease (41%; 95% confidence interval: 17%-64%). Their median survival time was five months (range 1.5-10 months) after the onset of salvage therapy. CONCLUSIONS: This schedule of weekly 24-h infusions of high-dose 5-FU and folinic acid is effective, even in patients pretreated with or resistant to regimens including 5-FU/folinic acid i.v. bolus. Based on these data, it appears that this schedule of high-dose 5-FU/folinic acid in first-line combination chemotherapy merits investigation.

Adult↗
PubMed1994

[The value of studies of pulmonary gas exchange during exercise for evaluation of reduced arterial oxygenation at rest in asymptomatic long-term smokers].

The aim of this study was to elucidate extent and nature of an impairment of gas exchange after long time cigarette-smoking. Pulmonary gas exchange at rest as well as during steady state exercise and conventional lung function tests (LFTs) were studied in 32 clinically healthy, asymptomatic severe cigarette-smokers (S; 48.1 +/- 15.7 pack-years) and 32 healthy lifetime nonsmokers (N) between 40 and 60 years of age, respectively, individually matched for age, body height, body weight and gender. Pulmonary function tests of all subjects were within the limits of normal values. Except for a slight reduction of MEF25 in S (p < 0.05) and a slight increase of FRC (p < 0.05), the groups did not differ with respect to LFTs. At rest, however, S had markedly lower values for PaO2, TLO2, DCO and KCO, and higher values for AaDO2 and QVA/Qt. Resting measurements for VD/VE and PaCO2 did not differ between N and S. During ergometry PaO2 and TLO2 increased respectively; AaDO2 and QVA/Qt fell concomitantly with VD/VE and PaCO2. On termination of exercise no significant difference between N and S for the above variables could be discerned any longer. Our findings confirm that even in clinically healthy asymptomatic cigarette-smokers a distinct impairment of gas exchange is present. Their improvement during physical exercise primarily indicates the presence of reversible ventilation-perfusion mismatching and excludes relevant morphologic changes in the lung in these cases.

Adult↗