[Drug-induced ulcer in rats. V. Serotonin].
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Animals↗
Biomedical subjects
M Martin
Publications and source records attributed to M Martin.
Induction chemotherapy in head and neck cancer: results of a phase III trial.
Between December 1982 and October 1986, 131 patients with stage II-III-IV squamous cell carcinoma of the oropharynx or oral cavity were randomized to induction chemotherapy, consisting of bleomycin (10 mg/m2/day in continuous infusion from day 1 to day 5), methotrexate (120 mg/m2 on day 2) followed by folinic acid, 5-fluorouracil (5 FU) (600 mg/m2 on day 2), and cisplatin (120 mg/m2 on day 4) every 4 weeks for a total of three cycles followed by definitive locoregional treatment versus locoregional treatment alone. The modalities of definitive treatment (radiotherapy +/- surgery) were chosen prior to randomization. A total of 116 patients were evaluable. Of 55 patients in the chemotherapy arm, four (7%) had a complete response (CR) and 23 (42%) a partial response (PR) following the induction regimen. At the completion of locoregional treatment, 76% (42 of 55) of patients in the experimental group were in CR compared to 89% (54 of 61) in the control group. There was no difference in survival, cause-specific survival, and pattern of relapse between both groups. The median survival was 22 months in the chemotherapy group and 29 months in the control group. Responders to chemotherapy did not fare better than nonresponders. Chemotherapy-related toxicities were few and most of them related to cisplatin which was reduced to 100 mg/m2 for 35 patients. There were no treatment-related deaths and, in the experimental arm of the trial, no increased morbidity from locoregional treatment. This induction regimen does not offer any advantages over standard treatment.
Antineoplastic Combined Chemotherapy Protocols↗
Safe laparoscopic cholecystectomy in a community setting, N = 762.
Laparoscopic cholecystectomy (LC) can be introduced into a community with morbidity and mortality rates equal to that of open cholecystectomy. The entire general surgical community of Greensboro, NC, learned the technique of LC on animal models prior to offering this innovation to the community. Over the ensuing 12 months, they served as surgeons or assistant surgeons to each other on 762 LCs with morbidity and mortality rates comparable to open cholecystectomy. This retrospective study examined the first 1 year of experience beginning 8/13/90. This work represents all of the LCs performed in Greensboro, and all of the surgeons participated in this review. All of the surgeries were done with an electrocautery and utilized a 0 degree forward-viewing scope. Cases were performed at two hospitals with a surgeon as both operator and assistant, and no effort was made to exclude high-risk or elderly patients from this procedure. Patients averaged 50 years of age and ranged from 14 to 96 years. Static cholangiograms were performed in 27% of patients. Conversion to open cholecystectomy was seen in 4.8%. There were two cardiac deaths (0.26%) and significant complications were seen in 3.4%. Seven patients required reoperations. There were no major common bile duct injuries. This retrospective review indicates that this new procedure can be introduced into a community setting by novice laparoscopic surgeons acting both as operators and assistant with a morbidity and mortality rate comparable to that reported for open cholecystectomy.
Cholangiography↗
Cytoskeleton modifications induced by phenobarbital, 2-acetylaminofluorene and 4-acetylaminofluorene in normal and initiated/selected hepatocytes: relation with the "resistant" phenotype.
Initiated/selected (ISH) and normal (NH) rat hepatocytes were used to study cytoskeleton modifications induced by three liver acting chemicals: 2-AAF, a liver complete carcinogen; PB, a liver tumor promoter; and 4-AAF, a non-carcinogen analogue of 2-AAF. Cytoskeleton alterations were visualized by disappearance of F-actin fibers and tubulin depolymerization. The three drugs induced actin fragmentation in normal hepatocytes; a net loss of actin protein was observed with PB. They also induced varied tubulin depolymerization. The principal difference between chemicals is that 2-AAF led to non-reversible effects, in comparison with PB and 4-AAF which induced reversible damages on cytoskeleton. By contrast to normal hepatocytes, the cytoskeleton of ISH obtained from rats subjected to the "resistant" hepatocyte protocol was much less susceptible to the effect of the three chemicals. Moreover, we observed a lack of LDH release in the culture medium and a very rapid inducibility of GST activity after exposure of ISH to drugs. The moderate effect of the three chemicals on actin and tubulin in ISH could thus be explained by the "resistant" metabolic profile of these cells.
2-Acetylaminofluorene↗
In vivo and in vitro pharmacokinetics and metabolism of vincaalkaloids in rat. I. Vindesine (4-deacetyl-vinblastine 3-carboxyamide).
Vindesine (VDS) pharmacokinetics, including tissue distribution, metabolism and elimination, were investigated in rats using both in vivo and in vitro models. VDS was found to be intensively distributed in tissues after i.v. injection in rat. The most important drug accumulation site was the spleen (615.0 ng/g at 24 h). Liver and kidneys also retained VDS in significant amounts (respectively 170.1 +/- 11.0 ng/g and 145.0 +/- 17.0 ng/g at 24 h). Urine excretion of drug over 7 days was low (10.1 +/- 1.8% of total dose) and consisted mainly of unchanged drug (more than 85%). The major excretion route for VDS was the feces (69.6 +/- 2.5% of total dose) via the bile (50% of total dose excreted in 72 h). High performance liquid chromatography analysis (HPLC) of collected bile samples revealed the excretion of three VDS biotransformation products. These results were confirmed in vitro using freshly isolated rat hepatocytes in suspension. Rapid and high VDS uptake by liver cells, probably through a passive diffusion mechanism followed by a tight cellular binding, was demonstrated. Moreover, VDS was intensively converted, in vitro, into four metabolites which were rapidly excreted into the extracellular medium. In contrast, the intracellular medium contained almost exclusively unchanged drug, presumably fixed to tubulin proteins. Two anti-VDS monoclonal antibodies with different specificities were used to test metabolite immunoreactivities. The results suggested that some structural modifications occurred in the catharantine moiety of the molecule but that the VDS dimeric structure seemed well conserved after biotransformation.
Animals↗
In vivo and in vitro pharmacokinetics and metabolism of vincaalkaloids in rat. II. Vinblastine and vincristine.
Vinblastine and Vincristine pharmacokinetics, including tissue distribution, metabolism and biliary excretion, were investigated, using both "in vitro" and "in vivo" models, after i.v. injections in rats. Plasma kinetic curves were best fitted to a two-compartment open model. The average terminal half-lives of VLB and VCR were 14.3 h and 7.5 h, respectively. The systemic clearance and apparent distribution volume for VLB, respectively 1.49 l/h/kg and 11.46 l/kg, were significantly greater than those of VCR, 0.12 l/h/kg and 0.41 l/kg. VCR was found to be widely distributed in tissues after i.v. injections in rats. The highest drug accumulation site was the intestine (122.0 ng/g wet tissue at 24 h). Liver and kidneys also retained high proportions of drug (respectively, 47.0 ng/g and 44.4 ng/g at 24 h). Biliary excretion was more rapid for VCR (42.7% of total radioactivity excreted over 24 h) than VLB (28.2% of total dose over 24 h). For both molecules, the percentage of radioactivity excreted in bile over 30-48 h ranged between 40-50% of total dose. At high doses, either biliary excretion rate or cumulated excretion was reduced. High performance liquid chromatography analysis of bile samples revealed four biotransformation products for VLB and three for VCR. When incubated in freshly isolated rat hepatocytes, VLB penetrated more rapidly and intensely into the cells (more than 90% of total dose taken up over 20 min) than VCR (only about 40% accumulated), probably through a passive diffusion mechanism followed by tight cellular binding. "In vitro" metabolism patterns were similar to those found "in vivo", except for the most polar metabolites observed "in vitro". Two anti-Vinca monoclonal antibodies with different specificities were used to test VCR metabolite immunoreactivities. The results suggested that some structural modifications occurred in the catharantine moiety of the molecule but that the dimeric structure seemed to be well conserved after biotransformation.
Animals↗
Thrombolytic therapy is arterial thromboembolism.
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Acenocoumarol↗
Mutagenic activation of 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole(Trp-P-1) and 3-amino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2) by primary cultures of adult rat hepatocytes: effect of Aroclor induction in vitro.
The mutagenic activation of tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, was studied in a Salmonella TA98/hepatocyte mutagenesis assay. Adult rat hepatocytes in primary culture were either untreated or induced by the addition of Aroclor 1254 (2 micrograms/ml) 18-20 h before the mutagenesis test which was performed at day 1 and at day 2 after the isolation of hepatocytes. The mutagenic activation of Trp-P-1 and Trp-P-2 was studied as a function of the time of incubation and of the concentration of chemical. Trp-P-1 and Trp-P-2 incubated for 20 min in the presence of untreated hepatocytes and bacteria gave rise to a weak number of revertants which doubled the level of spontaneous mutants. Aroclor-induced hepatocytes became highly competent in mutagenic activation of tryptophan pyrolysis products and the induction ratio reached 4.9 and 7.1 for Trp-P-1 and Trp-P-2, respectively, after 60 min of incubation, on day 2 of the experiment. It should be noted that the induction ratio was higher on day 2 than on day 1. When conditions were standardized, i.e. Aroclor-induced hepatocytes on day 2, final concentration of cellular protein about 1 mg/ml, 20 min of incubation, the Salmonella/hepatocyte assay produced a linear concentration-dependent mutagenic response for Trp-P-1 and Trp-P-2. By comparing the results obtained with Aroclor-induced hepatocytes and Aroclor-induced liver S9 fraction in the Salmonella test, it could be estimated that hepatocytes were 3 times less active than the S9 fraction with regard to mutagenic activation of both Trp-P-1 and Trp-P-2.
Animals↗
Binding of IgG to amyloid beta A4 peptide via the heavy-chain hinge region with preservation of antigen binding.
Amyloid beta A4 peptide is found in the extracellular region of the senile plaque and in the angiopathy of Alzheimer's disease. Several other proteins, including IgG, also reside in these abnormal structures. In an attempt to understand how these structures are assembled and to determine how proteins are recruited, interactions of various proteins with synthetic beta A4 peptide have been examined in vitro. Purified IgG binds directly to synthetic beta A4 peptide with high avidity. The domain between amino acids 12-28 of beta A4 binds IgG. beta A4 peptide binds the hinge region of the immunoglobulin heavy chain, and preserves the ability of the immunoglobulin to bind antigen. A protein which does not bind directly to beta A4 peptide can be targetted to the senile plaque and angiopathy by binding to IgG, which avidly binds beta A4 peptide.
Amyloid beta-Peptides↗
Cystometric characteristics in continent adults of various ages.
Cystometry was carried out in 40 women and 31 men without incontinence symptoms. The average patient age was 73.3 +/- 8.34 and 68.7 +/- 11.4 years, respectively. Three parameters were analysed: (1) bladder volume at first urgency (VolFU), (2) bladder volume at the point of involuntary micturition (VolM) and (3) difference between the volumes at involuntary micturition and at first urgency (continence reserve, CR). The results demonstrated an age-related progressive drop in all three parameters in women as well as in men, VolM and CR being the most affected values. The average age of individuals with a < 50 ml was 78.7 +/- 5.59 years with a CR between 50 and 99 ml it was 73.3 +/- 7.26 years; and with a CR of 100 ml or more it was 68.5 +/- 10.1 years. These data underline the fact that age impairs micturition patterns even in subjects without overt incontinence problems.
Journal Article↗
Iridium 192 implantation of squamous cell carcinomas of the oropharynx.
From 1970 to 1984, 127 patients with T1 or T2 carcinomas of the oropharynx were treated with external irradiation to the primary tumor and neck nodes to a dose of 45 Gy, followed by a further 30 Gy delivered by an iridium 192 implant to the primary tumor. Patients with clinically positive nodes had either further neck irradiation using electrons or a neck dissection. Crude 5-year disease-free survival was 66% for tonsillar carcinomas, 43% for soft palate, and 51% for base of tongue. Local control was 98%, 85%, and 76%, respectively. Regional control was 97% for N0 patients and 88% for N1-3. Soft tissue ulceration occurred in 17 patients; all healed spontaneously. The high rate of local control achieved in these patients while preserving function and minimizing xerostomia supports the use of this approach.
Adult↗
Exocrine pancreatic response to CCK in rats after long-term hydrocortisone administration.
The effects of prolonged administration of hydrocortisone (10 mg/kg/day) on exocrine pancreatic secretion were examined, analyzing the quantitative and qualitative variations in secretion at 7, 18 and 30 days of treatment. The weight of the pancreata was found to increase during the period of hydrocortisone treatment. After the 7th day of treatment the hormone significantly decreases basal exocrine pancreatic secretion, maintaining similar values up to the 30th day of treatment. Hydrocortisone enhances the pancreatic response to CCK since the percent increase in acinar secretion under stimulation compared to basal secretion surpassed control levels in all cases. However, the inhibitory effect on secretion shown by hydrocortisone opposes and surpasses the stimulatory effect of the secretagogue, secretion being reduced in the treated animals. Hydrocortisone especially affected the amylase fraction of the juice, to a larger extent inhibiting the isoenzyme A1, with an IEP of 8.5 when the animals were treated over 30 days; thus, a considerable reduction was observed in the amylase secreted both in resting conditions and under stimulation with CCK. There is a possibility that chronic treatment with glucocorticoids may sensitize the acinar cells, alter the composition of the pancreatic juice and inhibit secretion, effects that may involve pancreatic dysfunction.
Analysis of Variance↗
Emergency department echocardiography in the diagnosis and therapy of cardiac tamponade.
A 44-year-old male presented to the emergency department in shock with jugular venous distension and upper chest cyanosis. Superior vena cava syndrome was ruled out by computed tomography (CT scan). However, a large pericardial effusion was found on CT scan and confirmed by sonography. Pericardial tamponade was diagnosed by emergency physicians and sonography-guided pericardiocentesis was performed with marked improvement in symptomatology.
Adult↗
[Cesarean section for failed vacuum extraction: risk factors and maternal and neonatal outcomes].
OBJECTIVE: To evaluate risk factors associated with failed attempts of vacuum extraction and their outcomes. PATIENTS AND METHODS: All trial vacuum extractions (metal Minicup) from 1992 to 2000 in Besançon University Hospital Center were retrospectively analysed, namely 2447 cases. Univariate and multivariate analyses of failed vacuum extraction risk factors and descriptive analyse of outcomes were performed. RESULTS: The rate of failed vacuum extractions was 3.47% (85/2447). A multivariate analysis showed the following independent risks factors in failed extraction: extraction above pelvic level + 2 (OR = 1.8; CI 95%: 1.1-3), newborn weight (OR = 2.9; CI 95%: 1.8-4.9), parity >2 (OR = 0.08; CI 95%: 0.01-0.6). In case of failed vacuum extraction, newborns had a significantly higher rate of Apgar score <7 at 1 min (P = 0.0002), but not at 5 min. These newborns were most regularly admitted in pediatric care units (P = 0.01). CONCLUSION: The failed trial attempt vacuum extraction rate stays low. These failed instrumental extractions are more common in an extraction above pelvic + 2, a high fetal weight and an arrest during the second stage of labor. There is an increased adverse neonatal outcome. Clinical fetal weight estimation and diagnosis of presentation level in mother pelvis must be performed before vacuum extraction.
Adolescent↗
[Otitis medias with effusion: association with the Eustachian tube dysfunction and adenoiditis. The case of the Central Hospital of Maputo].
INTRODUCTION: Although the aetiology of otitis media is known to be multifactorial, adenoids infections and Eustachian tube dysfunction, have been frequently associated with the incidence of middle-ear effusion. Middle-ear effusion cases are frequent in Maputo, Mozambique, and very often insertion of tympanostomy tubes and adenoidectomy alone or with amigdalectomy have been used to treat these cases and to prevent further episodes. The objective of this study is to describe the association of these factors with otitis medias with effusion in patients that visit the Otorrinolaringology department (ENT) at the Central Hospital of Maputo (HCM), as well as to describe the clinical and epidemiological profile of these patients. PATIENTS AND METHODS: A cross sectional study was conducted. 4157 clinical files of all patients who made their first visit to the ENT department at the HCM, with otitis media during a period of 4 years (1995 to 1998). RESULTS: 23.3% of patients who visited the ORL service of Maputo with otitis media, are children under 3 years; the major proportion of otitis media with effusion was observed in children aged from 3 to 7 years old (49.2%). In boys under, otitis media with effusion is strongly associated with the history of adenoiditis and/or Eustachian tube dysfunction (OR=9.53) and in older patients (OR=12.26). CONCLUSION: The proportion of otitis media with effusion increases more evidently in patients with disfuntion tube syndrome. Other factor that can be important in patients under seven, is the presence of adenoiditis.
Adenoids↗
Early cellular effects of Trp-P-1 on adult rat hepatocytes in primary culture.
Trp-P-1, a DL-tryptophan pyrolysis product, was previously known for its mutagenic and hepato-carcinogenic properties and for inducing nucleolar damage in adult rat hepatocytes in primary culture. In this paper, the effect of Trp-P-1 was investigated on DNA, RNA and protein synthesis in hepatocytes treated with 1, 5 and 10 micrograms/ml for 1, 2 and 4 h in order to determine the cascade of events which could occur in cells exposed to this agent. The inhibition of the 3 biosynthetic pathways was linearly dependent on the concentration of Trp-P-1 in the culture medium for each duration of treatment. For a given concentration, the degree of inhibition depended on the duration of incubation and varied according to the type of synthesis. DNA synthesis appeared as the most rapidly and strongly impaired: 16% of control values in hepatocytes treated with 10 micrograms/ml Trp-P-1 for 1 hour against 50.7% for RNA and 66.7% for protein synthesis. These data indicated that DNA should be the primary target of Trp-P-1 action in good agreement with the genotoxic activity of this agent. The complete recovery of RNA synthetic capability within 2 h after the removal of Trp-P-1 from the medium could however indicate that transcription was not definitely altered. By contrast the lack of protein synthesis recovery in a Trp-P-1 free medium for 24 h might signify the extended impairment of a step of translational process at the cytoplasmic level.
Animals↗
Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication.
The prevalence of obesity in inpatients of a German psychiatric rehabilitation center for adolescents and young adults (mean age 19.5 years) is assessed and set into relationship to diagnosis and medication regimen. In a cross-sectional naturalistic study body weights and heights of 151 inpatients, 109 of whom presented with ICD-10 schizophrenia spectrum disorders, were measured for the calculation of body mass indices (BMI, kg/m2); current medication regimen including the duration of treatment was assessed from medical records. BMIs were plotted into gender- and age-specific BMI-percentiles representative for the German population. Among the whole study population, obesity (BMI > or =90th percentile) was apparent in 44/98 (45%) of the male and in 31/53 (59%) of the female inpatients (overall: 50%). With respect to schizophrenia spectrum disorders, 36/70 (51%) males and 25/39 (64%) females (overall: 56%) were obese in contrast to 14/42 (33%) among the individuals without schizophrenia. Set into relationship to the treatment groups, the prevalence rates of obesity were 64% in patients treated with clozapine (n=69), 56% for other atypical antipsychotics (olanzapine, sulpiride, risperidone; n=27), 30% for classic antipsychotics (haloperidol, flupentixol, perazine; n=20) and 28% for the currently drug-free group (n=25). Together with other published findings in adults, these results suggest an increased prevalence of obesity among young patients with schizophrenia and especially among patients chronically treated with atypical antipsychotics.
Adolescent↗
Program evaluation of a sex education curriculum for women with mental retardation.
The effectiveness of a sexual education and health promotion program for 252 women with mental retardation was analyzed using an evaluation model. We used confirmatory factor analysis (LISREL) to explain the pathways of learning and related the number of instructional contacts with the outcomes. Three factors (hygiene, social interaction, and sexual experience) affected sexual knowledge directly. An increase in sexual knowledge was directly associated with a greater number of instructional contacts. The analysis indicates that our program is effective and adds to our understanding of factors contributing to sexual knowledge for adults with mental retardation.
Adult↗