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Biomedical subjects

F Meyer

Publications and source records attributed to F Meyer.

At least 73 records · Page 4Linked to original sources
PubMed2001

Combination chemotherapy with docetaxel and cisplatin for locally advanced and metastatic gastric cancer.

BACKGROUND: Poor treatment results obtained with palliative chemotherapy for advanced gastric cancer indicate the need for new effective and well-tolerated regimens. PATIENTS AND METHODS: Forty-three patients with locally advanced or metastatic gastric cancer were enrolled in a phase II study to evaluate the efficacy and safety of combination chemotherapy with doxetacel 75 mg/m2 and cisplatin 75 mg/m2 given every three weeks. RESULTS: Thirty-nine patients were evaluable for response. Four achieved a complete response and twelve a partial response, for an overall response rate of 37.2% (16 of 43 patients; 95% confidence interval (CI): 22.98-53.72). Median time to progression was 6.1 months and median overall survival 10.4 months. Forty-two percent of all patients were still alive at one year and twelve percent at two years. The major toxicity was leukopenia which reached grade 3-4 in 18.6% (n = 8) of the patients. However, no febrile neutropenia occurred. Non-haematological toxicities were usually mild to moderate. Grade 3 toxicities included diarrhea (9% of the patients), nausea and vomiting (7%), and alopecia (7%). Severe ototoxicity with or without peripheral neuropathy developed after completion of chemotherapy in two patients. CONCLUSIONS: These results suggest that the combination of docetaxel and cisplatin has moderate toxicity and is an effective regimen for the treatment of advanced gastric cancer, both with regard to response rate and survival.

Adult↗
PubMed2001

Current options for palliative treatment in patients with pancreatic cancer.

Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression.

Antimetabolites, Antineoplastic↗
PubMed2001

Prognostic parameters determining survival in pancreatic carcinoma and, in particular, after palliative treatment.

Prognosis and outcome of patients with pancreatic carcinoma is poor. The aim of the study was to investigate (1) which factors of medical history and clinical status as well as which laboratory parameters determine survival in pancreatic carcinoma and (2) whether specific data can be used as prognostic parameters or for early diagnosis of pancreatic carcinoma. In total, 287 patients with pancreatic carcinoma were enrolled in the study. In 193 subjects, only palliative treatment was possible. Survival was assessed using univariate survival probability curves by Kaplan-Meier. Comparison of patient groups with regard to survival was achieved using the log-rank test. Multivariate analysis was carried out using the Cox regression model. Overall, 22 factors, showing a significant impact on survival in pancreatic carcinoma were found, e.g., tumor-associated factors such as (1) tumor stage according to the UICC classification including TNM-based staging, grading, tumor site, and vascular infiltration; (2) preoperative habits and signs and symptoms (physical condition, pain, loss of appetite, ethanol consumption); (3) change of laboratory parameters (CA 19-9, bilirubin, prothrombin time, urea, C-reactive protein), and (4) type of intervention (surgical approach, R0/1/2 resection). Using multivariate analysis, seven factors (UICC tumor stage and site, surgical intervention including number of resected lymph nodes, chemotherapy, occurence of a carcinoma in relatives, preoperative physical condition, night sweat) were determined. In the 193 patients with palliative treatment, only ten factors (among them UICC tumor stage including the presence of metastases; data from the medical history such as physical condition, loss of appetite, and carcinoma in relatives, and laboratory parameters including prothrombin time, protein content, and aspartate aminotransferase levels) were found to be important. Chemotherapy had the strongest impact on survival which was confirmed by multivariate analysis, followed by tumor stage (UICC) and preoperative appetite. Besides tumor-associated determinants, data from the medical history, and pathological laboratory parameters, the prognosis in pancreatic carcinoma is considerably determined by the treatment such as interventional and/or using antineoplastic agents.

Adult↗
PubMed2001

Ergotamine-induced acute vascular insufficiency of the lower limb--a case report.

Ergotamine-containing drugs are widely used in the treatment of acute migraine attacks. Spastic vasoconstriction is one of the possible side effects usually affecting the lower extremities and sometimes leading to gangrene. A 28-year-old woman was hospitalized for severe acute arterial insufficiency of the limbs. The initial surgical approach was not successful since the diagnosis was missed. Overuse of ergotamine derivative was acknowledged by the patient, who had a long history of migraine headaches. Therefore, the patient was treated conservatively with intravenous heparin and prostaglandin infusion and sympatheticolysis via epidural catheter. The vascular complications, angiographic findings, and different modalities of treatment of ergotamine-induced peripheral vascular insufficiency of the lower limb are reviewed.

Acute Disease↗
PubMed2001

Sequential coil embolization of bilateral internal iliac artery aneurysms prior to endovascular abdominal aortic aneurysm repair.

PURPOSE: To report the endovascular repair of concomitant aneurysms of the abdominal aorta and both internal iliac arteries. CASE REPORT: A 72-year-old man with a 5.5-cm abdominal aortic aneurysm (AAA) extending to the right common iliac artery also presented with separate aneurysms of both internal iliac arteries. The patient refused conventional surgery, so an endovascular strategy was devised. Initially, the iliac aneurysms were sequentially coil embolized, allowing several weeks to elapse between the embolization sessions to encourage collateral development. A bifurcated Talent endograft was inserted successfully 8 months after the initial intervention; no evidence of endoleaks or mesenteric ischemia has been seen over a 1-year follow-up. CONCLUSIONS: This case illustrates the feasibility of inducing collateralization prior to endovascular AAA repair that would jeopardize internal iliac artery circulation bilaterally. Sequential embolization of the internal iliac arteries over several months initiates this response, paving the way for eventual endovascular repair of the primary aortic aneurysm.

Aged↗
PubMed2001

Gene therapy: progress and challenges.

Gene therapy is the delivery of new genetic material into a patient's somatic cells for the treatment of disease and is made possible through the development of viral and non-viral gene transfer vectors. In the first five years of gene therapy, clinical studies failed to yield efficacy data with the vectors available at that time. The lack of consistent clinical benefit prompted the United States National Institute of Health Recombinant DNA Advisory Committee to evaluate gene therapy research and conclude that substantial improvements in gene transfer vectors were needed in the areas of vector safety and control of the level and duration of gene expression, and to increase the understanding of the biological interaction of gene transfer vectors with the host. We will describe the progress in development of gene delivery technology, focusing on improvements in vector safety, analysis of vector biodistribution and GMP manufacturing of viral and non-viral gene transfer systems over the last six years since the report. Whereas 5 years ago, investigators tested every vector for every potential disease indication, the accumulated database now enables investigators to select a single vector based upon it's known performance in a wide number of animal models and human clinical studies. We will also highlight several directions investigators have taken to improve the safety and efficacy of gene therapy vectors.

Adenoviridae↗
PubMed2001

[Value of a new non-contact biometer for intraocular crystalline lens power calculation].

PURPOSE: One of cataract surgery's current imperatives involves refraction: the power of the lens implant must be calculated as accurately as possible. Here we present a new method of biometric ocular measurement using the partial optical consistency interferometer. MATERIAL AND METHODS: This investigation studied the axial length measurement of 100 eyes. Five measurements were taken with a classic echobiometric contact technique using the ultrasonic mode; 5 others were taken with the infrared noncontact technique (IOL Master, Zeiss Humphrey). The latter technique is based on interferometric biometry with optical consistency and measurements were taken with an infrared luminous ray. With extreme rapidity and no contact, the device provides a complete biometry, including axial length, keratometry, and anterior chamber depth. It includes a built-in computer. RESULTS: Comparing the ultrasonic and infrared measurements emphasizes the precision and particularly the high reproducibility of the infrared method. The standard deviations of the samples were significantly lower for the 100 measurements. Its limitations depends on the type of cataract since success was not obtained for certain posterior subcapsular opacities. DISCUSSION: This new method of performing a biometry with a partial consistency interferometer contributes a number of advantages: speed, its noninvasive nature with no contact, the high reproducibility of the exam, as well as precise measurements as shown by the difference in the standard deviations of the two methods. CONCLUSION: Biometry using the optical consistency interferometer seems to be a reliable, reproducible, and precise technique that brings great precision for the calculation of the power of the intraocular implant in cataract surgery.

Diagnostic Techniques, Ophthalmological↗
PubMed2000

Chromosome 9 deletions and recurrence of superficial bladder cancer: identification of four regions of prognostic interest.

In a previous study, loss of heterozygosity (LOH) of 28 chromosome 9 microsatellite markers was assessed on 139 Ta/T1 bladder tumors. LOH at one or more loci was detected in 67 tumors, 62 presenting subchromosomal deletions. One hundred and thirty-three of these patients have now been followed for up to 8 years. The purpose of the present study was to evaluate the potential biological significance of chromosome 9 deletions in superficial bladder tumors at initial diagnosis. High grade was associated with LOH (P=0.004). Large tumors carried more frequently 9p deletions (P=0.022). Female patients had more chromosome 9q LOH than male patients did (P=0.010). Chromosome 9 LOH at all loci was associated with an elevated risk of recurrence but four regions were associated with a particularly high risk of recurrence. Multivariate analysis taking into account grade, stage, size and number of tumors showed that tumors deleted in the regions 9ptr-p22, 9q22.3, 9q33, and 9q34 recurred significantly more rapidly than those without deletions (Recurrence rate ratio=2.32, 2.53, 2.52 and 2.43 respectively). Log-rank statistics comparing Kaplan-Meier survival curves for the same chromosomal regions confirmed the correlation (P=0.0002, 0.010, 0.002 and 0.009 respectively). Only four patients progressed to muscle-invasive disease. They all had extensive deletions on 9q but none had deletions at 9ptr-p22. This study suggests a link between chromosome 9 anomalies and recurrence of superficial bladder cancer.

Aged↗
PubMed2000

Induction of 8-oxo-dGTPase activity in human lymphoid cells and normal fibroblasts by oxidative stress.

The pre-mutagen 8-Oxo-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP) is formed during normal cellular metabolism and its incorporation into DNA leads to transversion mutations. Human cells possess the hMTH-1 gene encoding the enzyme 8-oxo-dGTPase, which catalyzes the hydrolysis of 8-oxo-dGTP to the corresponding 8-oxo-dGMP, preventing mutations. To elucidate the involvement of 8-oxo-dGTPase in carcinogenesis, we studied hMTH-1 gene expression and enzyme activity in response to oxidative stress to human skin fibroblasts and Jurkat cells. In fibroblasts, ranges from 0 to 100 microM H(2)O(2) caused a 2-fold induction of hMTH-1-mRNA expression and a 3-fold induction of enzyme activity. A 1.7-fold induction of mRNA expression and a 3.5-fold induction of enzyme activity was obtained in Jurkat cells after treatment ranging from 0 to 300 microM H(2)O(2). Cytotoxic concentrations of hydrogen peroxide lead to an almost complete loss of enzyme activity and an inhibition of hMTH-1 mRNA expression. Induction of hMTH-1 gene expression was prevented by addition of actinomycin D and cycloheximide. These data indicate the inducibility of the hMTH-1 gene expression and enzyme activity by prooxidative molecules, such as hydrogen peroxide. These parameters can thus be used as a marker of oxidative stress.

Cell Survival↗
PubMed2000

Tumorigenic pathways in low-stage bladder cancer based on p53, MDM2 and p21 phenotypes.

Our aim was to determine whether the pattern of expression of the interrelated proteins p53, MDM2 and p21 could shed light on the etiopathogenic mechanisms of superficial bladder tumors. Protein expression was detected by immunohistochemistry (IHC) using monoclonal antibodies (MAbs) Pab 1801 for p53, IF2 for MDM2 and EA10 for p21 on 269 newly diagnosed bladder tumors (214 pTa and 55 pT1; 93 grade I, 145 grade 2 and 31 grade 3). While no p21 immunoreactivity was found in normal urothelium, 85% of tumors were strongly p21-positive. MDM2 was overexpressed in 44% of tumors, almost all being also positive for p21. p53 was overexpressed in 20% of cases: 66% of p53-positive tumors were also MDM2 positive, compared with only 38% of p53-negative tumors. p53 mutations were studied by direct DNA sequencing in a subset of 24 high-grade tumors. Both MDM2 and p21 were less frequently expressed in p53 mutated tumors compared with tumors with a wild-type gene. Distinct phenotypes were correlated with the frequency of poorly differentiated (grade 3) tumors. The most common phenotypes were p21+/MDM2-/p53- and p21+/MDM2+/p53- observed in 38% and 29% of tumors, respectively. Grade 3 tumors were found in 4% and 8% of these 2 groups, in contrast with 30% frequency in p21+/p53+ tumors (p = 0.002) regardless of their MDM2 phenotype. Four of the 5 (80%) tumors that were p53-positive but negative for p21 were grade 3. Our data suggest that several tumorigenic pathways for superficial bladder tumors can be reflected by the expression pattern of these 3 proteins.

Aged↗
PubMed2000

Lifetime occupational physical activity and incidental prostate cancer (Canada).

OBJECTIVES: The objective of this study was to assess the risk of incidental prostate cancer associated with occupational physical activity in a population of patients treated for benign prostatic hyperplasia (BPH) by transurethral resection of the prostate (TURP). METHODS: This case-control study was conducted in men aged 45 and over referred for TURP to relieve the symptoms of BPH in one of the eight hospitals of the Quebec City area between October 1990 and December 1992. Cases (n = 64) were all men incidentally diagnosed with prostate cancer and controls were the 546 patients with solely a histological diagnosis of BPH. At the time of their interview, the patients completed a diet history questionnaire and a general questionnaire including a lifetime occupational history. Physical activity was estimated for each job according to data from the US Department of Labor. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) of incidental prostate cancer associated with occupational physical activity while adjusting for confounders. RESULTS: A positive association was observed between "ever having a job with sedentary/light work" and incidental prostate cancer (OR = 1.9; 95% CI = 1.1-3.3). ORs for prostate cancer associated with 0%, 1-49%, and > or =50% of life spent in jobs with sedentary/light work were 1.0, 1.6 (95% CI = 0.8-3.1), and 2.5 (95% CI = 1.2-5.2), respectively (p-value for trend = 0.01). Occupational physical activity in the job held during the longest period was inversely associated with prostate cancer: ORs were 1.0, 0.5 (95% CI = 0.2-1.2), 0.4 (95% CI = 0.2-0.9) and 0.2 (95% CI = 0.1-0.7) for sedentary, light, moderate, and high/very high levels, respectively (p-value for trend = 0.008). CONCLUSIONS: The results of this study suggest that physical activity at work could have a beneficial effect on the occurrence of prostate cancer.

Aged↗
PubMed2000

Selective embolization of a renal artery aneurysm.

The treatment modalities for renal artery aneurysm have changed. The aim in the presented case was to evaluate the endovascular therapy in a 52-year-old woman (with hematuria as the only symptom) with a saccular aneurysm at the first bifurcation of the right main renal artery, which was diagnosed with contrast-enhanced computerized tomography and angiography. We approached the aneurysm with minimally invasive supraselective embolization. There were no postoperative complications, as confirmed with control angiography, during the intervention and after an interval of 4 weeks. In conclusion, selective coil embolization as first-line therapy to treat saccular renal artery aneurysm is feasible. In this case, minimally invasive procedure provided maximum functioning kidney tissue.

Aneurysm↗
PubMed2000

P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers.

Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G-->A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for >/=30 years and if former smokers, had stopped for </=5 years. However, no correlation was found between the presence of p53 point mutations and the number of cigarettes smoked. The deletion mutation was the only one present in a tumor from a non-smoker. The data suggest that duration of exposure to carcinogens is the most critical factor in p53 mutagenesis in bladder cancer.

Genes, p53↗
PubMed2000

Modulation of innate cytokine responses by products of Helicobacter pylori.

The gastric inflammatory and immune response in Helicobacter pylori infection may be due to the effect of different H. pylori products on innate immune mechanisms. The aim of this study was to determine whether bacterial components could modulate cytokine production in vitro and thus contribute to Th1 polarization of the gastric immune response observed in vivo. The effect of H. pylori recombinant urease, bacterial lysate, intact bacteria, and bacterial DNA on proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) from H. pylori-negative donors was examined as a model for innate cytokine responses. Each of the different H. pylori preparations induced gamma interferon (IFN-gamma) and interleukin-12p40 (IL-12p40), but not IL-2 or IL-5, production, and all but H. pylori DNA stimulated release of IL-10. Addition of anti-IL-12 antibody to cultures partially inhibited IFN-gamma production. In addition, each bacterial product inhibited mitogen-stimulated IL-2 production by PBMCs and Jurkat T cells. The inhibitory effect of bacterial products on IL-2 production correlated with inhibition of mitogen-stimulated lymphocyte proliferation, although urease inhibited IL-2 production without inhibiting proliferation, suggesting that inhibition of IL-2 production alone is not sufficient to inhibit lymphocyte proliferation. The results of these studies demonstrate that Th1 polarization of the gastric immune response may be due in part to the direct effects of multiple different H. pylori components that enhance IFN-gamma and IL-12 production while inhibiting both IL-2 production and cell proliferation that may be necessary for Th2 responses.

Animals↗
PubMed2000

Emergency stent-graft repair of a ruptured hepatic artery secondary to local postoperative peritonitis.

PURPOSE: To describe the use of a stent-graft for emergent repair of life-threatening hepatic artery hemorrhage. METHODS AND RESULTS: A 57-year-old man with a 17-year history of myxoid liposarcoma underwent surgery for a recurrent abdominal mass. Multivisceral resection including a Kausch-Whipple procedure with an extended right hemicolectomy was performed. Three weeks later, an episode of gastrointestinal bleeding prompted surgical repair of the hepatic artery, which had been eroded by infection due to a leaking bilioenteric anastomosis. After 3 weeks of programmed abdominal lavage, bleeding recurred. Angiography documented another rupture of the proximal hepatic artery. After an unsuccessful attempt at coil embolization, a Hemobahn stent-graft was implanted percutaneously during simultaneous cardiopulmonary resuscitation. Hemostasis was secured, and the patient recovered. Over the 10-month follow-up, no bleeding or infection has been observed at the site of the repair, and flow through the hepatic artery endograft remains satisfactory. CONCLUSIONS: Percutaneous stent-graft placement can be employed for emergent treatment of visceral artery rupture in patients at high risk for conventional surgical repair.

Abdominal Neoplasms↗