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Biomedical subjects

M Roy

Publications and source records attributed to M Roy.

At least 253 records · Page 14Linked to original sources
PubMed1988

Particle size study of nine metered dose inhalers, and their deposition probabilities in the airways.

This study deals with the particle size measurement of nine aerosol metered dose inhalers. Calibration was made possible by the use of a laser particle velocimeter (aerodynamic Particle Sizer from TSI). The count median aerodynamic diameters (CMAD) show little variation, from 0.63 to 0.73 micron, with standard deviations (sigma g) between 1.2 and 1.8. Aerodynamic diameter aerosol diagram analysis showed multimodal mass distribution for all the tested dose inhalers. Calculations for the airway deposition probabilities (extrathoracic, tracheobronchial and alveolar) refer to the studies made by W. Stahlhofen and co-workers. As most aerosol metered dose inhalers have a predominantly bronchial therapeutic destination, the deposition at the bronchial level could be enhanced with the following parameters: inspired volume of 1500 ml, inspiratory time of 2 sec, aerosol mass median aerodynamic diameter (MMAD) of 7.5 microns, with a monodispersed distribution. The respective influences of the excipients and propellents used for the aerosolization of these dose metered inhalers are also discussed.

Aerosol Propellants↗
PubMed1988

Dominantly inherited ataxias in Portugal.

We analysed the clinical features of 82 patients with dominantly inherited ataxia in a cohort survey. All patients fulfilled the diagnostic criteria for Machado-Joseph disease. The mean age of onset of symptoms was 39.8 (+/- 12.5) years and the duration of the disease was 9.2 (+/- 6.7) years. Ataxia, peripheral neuropathy, and fasciculation scores correlated with age of onset and duration of disease. Upper motor neuron scores failed to correlate with age of onset. In a follow-up study we analysed the clinical data of 46 patients two years after the first examination. A paired t-test was used to compare differences between observations. The results are in agreement with those of the cross-section in time, suggesting a deterioration of the symptoms with the evolution of the disease. We conclude that dynamic definition of the disease according to age of onset and duration of symptoms is preferable to subdivision into classical types.

Adult↗
PubMed1988

Toxicity of abdominopelvic radiation in advanced ovarian carcinoma patients after cisplatin/cyclophosphamide therapy and second-look laparotomy.

Twenty-seven advanced ovarian carcinoma patients who had received six courses of cyclophosphamide/cisplatin and had either microscopic disease (15 patients) or no pathologically detectable disease (12 patients) after second-look laparotomy were treated with abdominopelvic radiation (2250 cGy to the abdomen and pelvis and a 2250-cGy pelvic boost). Acute myelosuppression or gastrointestinal toxicity prevented completion of treatment in only three patients. However, bowel obstruction occurred in 13 (48%), ten of whom required surgery. Five of these ten had recurrent tumor, but the other five did not. Subsequently two of the latter five did develop a recurrence, one in the lung and one in the liver. A third patient died as an indirect result of radiation damage to the bowel. Median follow-up duration is 17 months from completion of radiation. So far, 13 (48%) have developed progressive disease: four (33%) of the 12 who had a negative second-look laparotomy and nine (60%) of the 15 who had microscopic disease before radiation. While acute toxicity is tolerable, the incidence of serious chronic bowel toxicity is high. Efforts should be made to alter this therapy in order to decrease the frequency of long-term morbidity.

Abdomen↗
PubMed1987

The binding components for 2,3,7,8-tetrachlorodibenzo-p-dioxin and polycyclic aromatic hydrocarbons. Separation from the rat and mouse hepatic cytosol and characterization of a light density component.

Using sucrose density gradient centrifugation in a vertical rotor, we have separated three major binding components contained in hepatic cytosols from C57BL/6 mice and Sprague-Dawley rats. Using this preparative method we have obtained, after a 3-h run of 2.4 ml of crude cytosol from 1,4-bis[2-(3,5-dichlorodipyridyloxy)]benzene-treated C57BL/6 mice (approximately 50 mg of protein: 10,000 fmol of Ah receptor) 50 and 75% yields of isolated Ah receptor and carcinogen-binding protein (4 S binding protein), respectively. Both binding components may be kept at -70 degrees C for several months without loss of activity. A third binding component, which did not sediment in a sucrose density gradient (5-20%), even after a 4-h run at 63,000 rpm, was recovered from the top fractions of gradients. When applied to Sephacryl S-300 columns this component was eluted in the void fraction. Resistant to the direct degradative action of nucleases and proteases, this large complex was sequentially converted to its subcomponents by lipoprotein-lipase, proteinase K, and phospholipases. Only the phospholipases are able to abolish the binding capacity of this light density component (LDC) for [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin: hence, we conclude that phospholipids are the true binders of this radioligand. In vitro, this lipoprotein irreversibly binds many hydrophobic radioligands (2,3,7,8-tetrachlorodibenzo-p-dioxin,3-methylcholanthrene, benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, and dexamethasone). Using single vertical spin density gradient ultracentrifugation, the major part (80%) of LDC was characterized as a very low-density lipoprotein, and a minor part (20%) as a low-density lipoprotein. This conclusion was supported by the size of LDC particles (about 25-75 nm) observed in electron microscopy.

Animals↗
PubMed1987

Estrogenic contributions to sexual differentiation in the female guinea pig: influences of diethylstilbestrol and tamoxifen on neural, behavioral, and ovarian development.

We administered the synthetic estrogen, diethylstilbestrol (DES), or the antiestrogen, tamoxifen, to pregnant guinea pigs and observed the consequences for sexual differentiation of their female offspring. Hormones were administered during the period when treatment of fetuses with testosterone influences the development of sex-related traits (approximately Days 30 to 65 of gestation). Ovarian function, masculine and feminine sexual behavior, and the structure of a sexually dimorphic neural region in the preoptic area were assessed in adulthood in hormone-exposed animals and in oil-treated and untreated controls. Prenatal exposure to DES dipropionate (DESDP) caused masculinization and defeminization. DESDP-treated females mounted more than control females, both without hormonal stimulation and when given testosterone propionate (TP) as adults. The sexually dimorphic neural region was also masculinized in these females. In regard to defeminization, they showed delayed vaginal opening, impaired progesterone (P) production, an absence of corpora lutea, and impaired lordosis and mounting responses to estradiol benzoate (EB) and P. Prenatal treatment with tamoxifen produced a complicated pattern of results. Tamoxifen-exposed females evidenced less masculine-typical behavior, showing diminished mounting without hormonal stimulation and in response to TP. However, they also showed delayed vaginal opening, enhanced P production, and impaired mounting in response to EB and P. Their lordosis behavior and the volume of the sexually dimorphic neural region were unaffected. These results suggest that estrogens play a substantial role in sexual differentiation in the guinea pig. High levels of estrogen promote masculine-typical development, and unusually low levels may impair some aspects of both masculine-typical and feminine-typical development.

Animals↗
PubMed1987

Inhaled particle deposition and clearance from the normal respiratory tract.

Tracheo-bronchial and pulmonary deposited fractions of inhaled insoluble particles and their clearances rates were studied in 16 healthy non-smokers. After oral inhalation of radioactive particles (Mean Mass Aerodynamic Diameter (MMAD) = 3 microns, sigma g = 1.4 labelled with 111In) incorporated radioactivity was measured for each subject both by a gamma camera from to until the 3rd day, then from the 3rd until the 5th day first by a gamma camera and then by a low background profile scanner and from the 5th until the 35th day by a low background profile scanner alone. Clearance rates were calculated from the biological half lives of the deposited tracers. All subjects performed respiratory function tests. Experimental data were fitted to a two-compartment exponential system with two biological half lives: T1 = 76 min for 30%, T2 = 3.15 days for 40% of the deposited material. The delayed clearance phase for the remaining 30% of the deposited material approaches a constant rate. Our clearance values were compared with those of the Task Group of Lung Dynamics (T.G.L.D.) and other authors' results, especially for T1 and T2. These values are analyzed in terms of mucus velocity and mucociliary transport in distal conductive airways. Impaired transport reduces natural defenses and increases toxicological hazards. Therefore reliable techniques for detecting such impairment may be important in evaluating pulmonary involvement in environmental respiratory disease.

Adult↗
PubMed1987

A predictive index of cure versus no cure in advanced ovarian carcinoma patients--replacement of second-look laparotomy as a diagnostic test.

Three hundred forty-two Stage III and IV epithelial ovarian carcinoma patients received cytoreductive surgery followed by Adriamycin and cisplatin, 50 mg/m2 each, q 4 weeks for 9 courses. One hundred ninety-seven were clinically NED at completion of treatment and 173 of these 197 had a second-look laparotomy. One hundred twenty had persistent disease. Fifty-three were second-look negative and had no further treatment. Thirty of these latter patients relapsed--all (with one exception) within 2 years. Those not relapsing after negative second-look are considered "cured" (median follow-up 42 months, range 24-68 months) and all others "failures." Stage was a significant predictor of treatment failure--there were no Stage IV "cures." In Stage III patients, age and largest residual tumor diameter post initial surgery were significant predictors of failure. Performance status was marginally significant. In our series, any patient with Stage IV disease or Stage III disease with at least two of the following three poor prognostic factors had a chance of cure of 2.2% (2 "cures" out of 90 patients): age greater than 60 years, macroscopic residual initially, or initial performance status of 2 or 3. Under normal circumstances a second-look procedure to identify persistent disease in this group of patients does not appear justified.

Adult↗
PubMed1987

Ecogenetics of Parkinson's disease: prevalence and environmental aspects in rural areas.

We make use of the unique combination of a homogeneous genetic and racial origin in the rural population of Quebec and the facilities of free and universal access to medical care, to study the distribution of the prevalence of Parkinson's disease in the 9 rural hydrographic regions of the Province. Through 3 different methods of ascertainment, confirmed by two control probes, we demonstrate that the prevalence of Parkinson's disease is of uneven distribution within rural areas. We further investigated the characteristics of the regions of high prevalence. These regions which are predominantly agricultural and areas of intensive market gardening were also the areas with the highest use of pesticides.

Geography↗
PubMed1987

Altered contractile proteins in skeletal muscle of diabetic rats.

The ATPase activity of myofibrils and myosin from hindlimb muscle was investigated in animals 4 wk after the induction of diabetes by an intravenous injection of streptozotocin (65 mg/kg). Ca2+-stimulated ATPase in myofibrils was increased in diabetic muscle at various times of incubation (1-7 min) as well as at different concentrations of free Ca2+ (10(-7)-10(-5) M Ca2+). Such an increase in Ca2+-stimulated ATPase was evident as early as 1 wk after streptozotocin injection, but Mg2+-ATPase activity remained unaltered. Treatment of diabetic animals with insulin Ca2+-ATPase and actin-activated ATPase activities of pure myosin were similarly increased in diabetic muscle. Myosin ATPase was also activated by K+- or NH4+-EDTA; these responses were more in diabetic muscle. However, sodium dodecyl sulfate gel electrophoresis failed to reveal differences in the patterns of contractile proteins, and pyrophosphate gels did not show significant changes in myosin isozyme patterns between diabetics and controls. The results of this study demonstrate an activation of contractile protein ATPase of skeletal muscle in diabetes and seem to indicate that such an alteration may be responsible for enhanced contractile function of skeletal muscle in this disease.

Actins↗
PubMed1987

Purification of a syngeneic cross-reactive autotumorolytic factor.

An autotumorolytic fraction (ATF) derived from sera of mice bearing spontaneous mammary adenocarcinoma has been purified by sequential chromatography on Sephacryl 200 SF, DEAE Sephacel, hydroxylapatite, and Sephacryl 200 SF. At each stage of the purification, tumorolytic activity was assessed by the ability of the active material to induce lysis of a 2-week-old mammary tumor, and verified by histopathological analysis. Active fractions obtained during the stages of purification were capable of inducing lysis of tumors in both the original donor mice and the syngeneic tumor-bearing mice. Lytic activity was specific only for tumor tissue. This syngeneic crossreactivity of partially purified materials permitted pooling of serum samples for purification purposes. The resultant final preparation of ATF is an homogenous protein fraction, as verified by gradient SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance liquid chromatography. The molecular weight of active ATF is approximately 50,000 Da, as determined by gradient SDS-PAGE.

Activating Transcription Factors↗
PubMed1987

Second-line chemotherapy of stage III-IV ovarian carcinoma: a randomized comparison of melphalan to melphalan and hexamethylmelamine in patients with persistent disease after doxorubicin and cisplatin.

A total of 205 women with stage III or IV ovarian cancer who had persistent disease after initial treatment with doxorubicin and cisplatin were randomized to receive melphalan (8 mg/m2 orally for 4 days) or the combination of melphalan (6 mg/m2 for 4 days) and hexamethylmelamine (120 mg/m2 for 14 days) every 4 weeks. Only one of 64 patients with measurable disease had an objective response. The major determinants of survival after randomization were the amount of residual disease after initial chemotherapy and the type of response to initial chemotherapy. There was no overall difference in survival between the two chemotherapy regimens, but the small group of patients whose disease progressed on initial chemotherapy survived significantly longer when treated with the two-drug combination. Neither of these regimens provided effective therapy for women whose disease was not eliminated by first-line treatment. However, the superior results obtained in one subgroup with the addition of hexamethylmelamine suggest that the place of this agent in treating ovarian cancer should be carefully evaluated.

Adult↗
PubMed1987

Triazene metabolism. VI. 3-Azidomethyl-3-alkyl-1-aryltriazenes, a new class of anti-tumour triazene with potential pro-drug applications.

The synthesis of a new series of 3-azidomethyl-3-methyl-1-aryltriazenes is described. 3-Acetoxymethyl-3-methyl-1-aryltriazenes react with a large molar excess of sodium azide in aqueous acetone to afford the 3-azidomethyltriazenes in high yield. The rate of formation of the azidomethyltriazene increasing azide concentration, suggesting either an SN2 mechanism or a significant ionic strength effect on an SN1 reaction. In the absence of azide ion, the acetoxymethyltriazene undergoes a slow hydrolysis to give a bis-anilinomethane, which presumably arises via hydrolysis of the triazene to the aniline followed by condensation with formaldehyde released during the hydrolysis. The azidomethyltriazenes undergo facile hydrolysis in aqueous buffer solution with identical kinetic parameters to those of the hydrolysis of hydroxymethyltriazenes, suggesting that the azides may be good pro-drugs for the cytotoxic monomethyltriazene, the hydrolysis product derived from the hydroxymethyltriazene. Indeed, the azidomethyltriazenes have comparable anti-tumour activity against the P388 and PC6 tumours to other triazenes in this series. Furthermore, the azidomethyltriazenes display selective toxicity towards a human tumour cell line (the BE cell line) which is deficient in the repair of O6-methylguanine lesions, suggesting that these triazenes are capable of generating the monomethyltriazene without the need for metabolic activation.

Antineoplastic Agents↗
PubMed1987

Linkage studies of Friedreich ataxia by means of blood-group and protein markers.

Friedreich ataxia (FA) is an autosomal recessive, neuro-degenerative disorder in which the pathogenetic mechanism remains unidentified despite extensive biochemical studies. Genetic-linkage studies provide an alternative approach to determining the basic defect. Linkage analysis between FA and 36 polymorphic-blood-group and protein markers has been carried out on three separate patient populations--16 families from the inbred Acadian population of Louisiana, 21 French-Canadian families from Quebec, and nine apparently unrelated British families--in an attempt to determine the chromosomal location of the disease mutation. Neither evidence of linkage to any of the markers investigated nor heterogeneity among the populations was found for any of the comparisons. The negative lod scores exclude the locus for FA from greater than 20% of the genome.

Blood Group Antigens↗
PubMed1987

Population genetic study in ten endogamous groups of West Bengal, India.

Ten endogamous population groups of West Bengal (India)--Rabhas, Garos, Mechs, Rajbanshis, Jalia Kaibartas, Bagdis, Lodhas, Mundas, Brahmins, Vaidyas--have been typed for twelve polymorphic systems: ABO, Gm, Km, Hp, Cp, Tf, Alb, Hb, aP, EsD, AK and PGM1. The results are compared with those obtained on other Indian populations. Serological and anthropometric data, which have been included into population comparisons, reveal a considerable genetic variability of the groups under study. This variability is obviously connected with the population history of West Bengal.

Blood Group Antigens↗