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Biomedical subjects

S Welch

Publications and source records attributed to S Welch.

At least 55 records · Page 3Linked to original sources

Influence of menstrual cycle on serum cholinesterase.

This study examined whether the variability in cholinesterase (ChE) values among and within women may be attributed to phase of menstrual cycle and/or circulating progesterone concentration. Blood was drawn from 21 female subjects once a week for 8 weeks and analyzed for ChE activity and for progesterone concentration. Women ranged in age from 25 to 55 years and five used exogenous hormones (oral contraceptives, estrogen supplements, or progesterone therapy); one woman became pregnant during the study. There was a significant positive correlation between serum ChE and progesterone values only for the two women on oral contraceptives although there were large weekly variations within individuals (CV: 4-32%). Age significantly affected ChE values with 36-40 year olds having the lowest values and 30-35 year olds the highest. This variation in serum ChE probably is due to the influence of some sex steroid but, in women, there is not a direct one-to-one relationship between the enzyme and progesterone. However, when interpreting ChE tests used to monitor exposure of women to pesticides age and hormone intake must be considered in order to avoid false positive results.

Adult↗

Ciprostene in patients with peripheral vascular disease (PVD). An open-label, tolerance trial.

Epoprostenol (Prostacyclin) has been studied with various success in patients with peripheral vascular disease (PVD). We investigated the tolerance of a new, stable prostacyclin derivative ciprostene (9-beta-methyl carbacyclin) in 9 PVD patients. The drug was infused intravenously for 8 hours a day, once a week for 4 consecutive weeks, at a dose of 120 ng/kg/min. There were 6 men and 3 women with a mean age of 63 years (42-78). The PVD was verified by arteriography (9 patients) and by clinical findings. Patient #9 was lost to follow up after the first infusion and, consequently, was excluded from further evaluation. In patient #5 with a history of arrhythmias, the last ciprostene infusion had to be discontinued at 4.5 hours due to arrhythmias but his data were included into the evaluation. The cardiac disturbances were not judged to be ciprostene-related. Patients were followed monthly for 3 months after last infusion. Ciprostene was well tolerated although it produced adverse medical events (AMEs); most of them were rated as mild. The most frequent were those typical of prostacyclin: headache, facial flushing and warmth, body warmth, jaw pain and sleepiness. No consistent changes in blood pressure and heart rate were observed. One patient who initially had 9 ischemic ulcers underwent transmetatarsal amputation at month 4. The absolute and relative claudication time was measured by treadmill. As compared to baseline, the absolute claudication time increased significantly at week 2 and 4 of the infusion period and also at the end of month 3, but not at the end of month 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Chromosome 14 markers in rheumatoid arthritis.

Phenotype frequencies for variants of the chromosome 14 markers, alpha 1 antitrypsin (protease inhibitor--Pi), and immunoglobulin heavy chain gene allotypes (Gm and Am) were examined in affected and unaffected members of multicase rheumatoid arthritis (RA) families and compared with published population data. Significantly higher frequencies of phenotypes containing Pi*Z and Pi*S were observed in unrelated index RA cases compared with UK population data. There was also a higher frequency of Pi*Z in family members without RA than in population controls but no such difference for the frequency of Pi*S. No difference in the frequency of PiM1M2 heterozygotes was seen between patients with RA and population controls. An examination of clinical data failed to show any relation between any particular feature of RA and positivity for Pi*Z or Pi*S. No significant differences in frequency of Gm phenotypes were observed between patients with RA and controls. Significant association was found, however, between Pi*Z and Gm phenotypes containing Gm(zax;g). These associations are interpreted as indicating linkage disequilibria between these alleles. No interactions between DR4 and either G1m(z), (a), or (x) allotypes were apparent in patients with RA. A significant association was seen in the index RA cases between DR4 and Pi phenotypes carrying Z or S alleles. Observations from this study provide evidence for the existence of a genetic component for RA susceptibility encoded on chromosome 14. An interactive effect of these genes with DR4 towards susceptibility appears likely.

Arthritis, Rheumatoid↗

Use of carcinoembryonic antigen in small cell lung cancer. Prognostic value and relation to the clinical course 1.

Carcinoembryonic antigen (CEA) was measured in 147 patients at diagnosis of small cell lung cancer; 17% of patients with limited disease and 51% with extensive disease had an abnormal CEA level (greater than 10 ng/ml). The median level was higher in extensive than in limited disease (11 ng/ml and 5.8 ng/ml, respectively; P less than 0.001). Multivariate analysis showed CEA level greater than or equal to 50 ng/ml to be an adverse prognostic factor (P = 0.02); median survival at this level was shorter than at less than 50 ng/ml (7 and 46 weeks, respectively; P = 0.002). No consistent directional changes of follow-up CEA values were observed in patients with initially normal CEA levels, but normalization of levels occurred in complete responders. We recommend that CEA be measured in this disease at diagnosis as an additional prognostic factor and that patients with abnormal initial CEA levels have follow-up measurements to aid in evaluating response.

Carcinoembryonic Antigen↗

Timing of elective brain irradiation: a critical factor for brain metastasis-free survival in small cell lung cancer.

Risk factors for brain metastasis in small cell lung cancer were studied in 260 patients without brain metastasis at presentation who were treated on 5 protocols. The first three protocols offered elective brain irradiation (EBI) to all available patients after 2 or 3 courses of chemotherapy (early EBI), whereas the other two offered it after 5 or 6 courses of chemotherapy (late EBI). The overall incidence of brain metastasis was higher in the late EBI group than in the early EBI group (23.6% vs. 14.3%, p = 0.08), primarily due to higher incidence of brain metastasis developing before EBI in the former. There was a higher incidence of brain metastasis in patients without than in patients with bone marrow metastasis (21.4% vs. 6.8%, p = 0.04), in patients less than 60 years old than in patients 60 years or older (23.4% vs. 13.4%, p = 0.06), and in patients with than in patients without bone metastasis (30.2% vs. 16.8%, p = 0.07). Major risk factors for short brain metastasis-free survival were bone metastasis (p = 0.008), late EBI (p = 0.03), and failure to achieve complete remission after induction chemotherapy (p = 0.001) or as a best response (p = 0.0001). The early EBI group had a longer brain metastasis-free survival than the late EBI group, even among patients with bone metastasis (p = 0.02) or bone marrow metastasis (p = 0.05) and those who achieved complete remission after induction chemotherapy (p = 0.06) or as a best response (p = 0.05). These results indicate that timing of EBI is a critical factor in brain metastasis in patients with small cell lung cancer. There was no difference in overall survival between the two groups, however, even among patients who achieved complete remission as a best response.

Adult↗

Neurotoxicity in long-term survivors of small cell lung cancer.

Chronic central nervous system neurotoxicity was studied in 38 long-term survivors (greater than or equal to 3 years) of small cell lung cancer who were treated at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1971 and 1980. All but one patient received combination chemotherapy with or without chest irradiation. Twenty-four patients received whole brain irradiation (Group I), 22 for "elective" and two for therapeutic purposes, while 14 did not (Group II). Abnormalities in computed tomographic (CT) scans of the brain were more frequently observed in Group I than in Group II (70% vs. 0%, p less than 0.01). Clinical central nervous system neurotoxicity developed in three patients in Group I, while none developed in patients in Group II (p less than 0.05). Patients who received methotrexate and procarbazine after whole brain irradiation were at a higher risk for clinical central nervous system neurotoxicity (p less than 0.05), and for development of periventricular white matter changes in CT brain scans (p less than 0.05) than were patients in Group II. Impaired methylation of the myelin sheath is proposed as a possible underlying pathogenic mechanism.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of the ability of opioid analgesics to increase endogenous opioid-like activity in the cerebrospinal fluid of rabbits.

We have previously demonstrated that the acute administration of morphine increases the level of endogenous substances, which have antinociceptive activity, in cerebrospinal fluid (CSF). The present study was conducted to determine whether other opioid analgesics exert a similar effect. CSF was withdrawn from the cisterna magna of anesthetized rabbits before and after s.c. injections of meperidine, pentazocine, levorphanol and methadone, and was bioassayed for opioid-like activity in the mouse tail-flick and phenylquinone writhing tests. The opioid-like activity of CSF taken 60 min after meperidine (50 mg/kg) was significantly increased in both bioassays, and the CSF level of meperidine was insufficient to account for this effect. Pentazocine (25-75 mg/kg) also significantly increased opioid-like activity in rabbit CSF, but the effects of methadone (5-10 mg/kg) and levorphanol (20 mg/kg) were less marked. Dextrorphan (20 mg/kg), diazepam (10 mg/kg) and pentobarbital (20 mg/kg) administration did not significantly increase opioid-like activity in CSF. It is concluded that the antinociceptive action of some opioid analgesics in rabbits may be mediated in part by the release of endogenous antinociceptive substances.

Animals↗

Studies of powder flow using a recording powder flowmeter and measurement of the dynamic angle of repose.

This paper describes the utility of the dynamic measurement of the angle of repose for pharmaceutical systems, using a variable rotating cylinder to quantify powder flow. The dynamic angle of repose of sodium chloride powder sieve fractions was evaluated using a variable rotating cylinder. The relationship between the static and the dynamic angle of repose is discussed. The dynamic angle of repose of six lots of a multivitamin preparation were compared for inter- and intralot variation. In both cases, no significant differences (p greater than 0.05) were observed. In the multivitamin formulation, lubricants at lower concentration levels did not show a significant effect (p greater than 0.05) on the dynamic angle of repose when compared with flow rates. The effect of different hopper sizes and geometry has been evaluated using the recording powder flowmeter. The results indicate that although different hoppers affect the quantitative nature of the results, the same general trends are apparent. Thus, it appears possible to use a recording powder flowmeter with small quantities of material to predict the effect of formulation and processing variables on the flow of production scale quantities. This paper does not describe a comprehensive evaluation of the pharmaceutical utility of measuring the dynamic angle of repose. However, the results discussed are not encouraging and suggest that the recording powder flowmeter is more sensitive to the effects of formulation and production variables on powder flow.

Chemistry, Pharmaceutical↗

HLA polymorphisms in Saudi Arabs.

The HLA-A, -B, -C, -DR, Bf and GLO phenotypes of 109 unrelated Saudi Arab males have been determined. HLA-A and -B antigen frequencies were compared with data reported for European Caucasoids and various Arab populations. Most similarities in antigen frequencies were seen between Saudi Arab and Iraqi populations. A high frequency of Bw50 was observed in Saudi Arabs. The frequencies of HLA-DR antigens in Saudi Arabs were compared to European Caucasoids. HLA-DR7 was at high frequency in Saudi Arabs. Linkage disequilibria between alleles of HLA loci was examined. Many instances of previously reported antigen associations were seen in Saudi Arabs, together with a number of associations which have not been described elsewhere. HLA-Cw6-Bw50-DR7-BfS0.7 is suggested as being a common haplotype in Saudi Arabs.

Complement Factor B↗

Labeling suspended aerosol particles with short-lived radionuclides for determination of particle deposition.

Radiotracer techniques were developed to examine parameters that characterize pressurized aerosols designed to deliver insoluble particles suspended in the aerosol formulation. Microaggregated bovine serum albumin microspheres that were to be suspended were labeled with iodine-131 (t1/2 = 8 d). This iodination procedure (greater than 80% effective) is also applicable to iodine-123, which possesses superior characteristics for external imaging and further in vivo studies. This report shows that for pressurized aerosols containing suspended particles, each metered dose is approximately equal (not including the priming doses and the emptying doses). Increase in the delivery of the albumin particles out of the canister was best achieved by pretreating the valve assembly with a solution of 2% (w/v) bovine serum albumin in phosphate buffer. Use of a cascade impactor delineated the particle size distribution of the micropheres, with the majority of particles ranging in size from 2 to 8 microns. The data disclosed here indicate that the techniques developed with short-lived radionuclides can be used to quantitate each metered dose, characterize the particle size distribution profile of the aerosol contents, and determine the extent of deposition of the particles in the aerosol canister and all of its components.

Aerosols↗

An age-related coagulation disorder associated with experimental infection with infectious bursal disease virus.

Specific-pathogen-free White Leghorn chickens were inoculated with a field strain of infectious bursal disease virus. One group (A) was inoculated at 17 days after the chicks were hatched, and the other groups (C and E) were inoculated at posthatch day 42. Blood samples were obtained for determination of clotting times (whole blood recalcification, prothrombin, and activated partial thromboplastin times), virus-neutralizing antibody, and total hemolytic complement. There were significant increases in clotting times for groups C and E at 3 and 5 days after they were inoculated. There were no significant increases in clotting times at 3 days after inoculation in the group A chickens (inoculated at 17 days after hatching). There were no significant decreases in total complement activity in any of these chickens (groups A, C, and E). This study indicates that the mortality and clinical symptoms observed in chickens experimentally infected with infectious bursal disease virus may be associated with a clotting abnormality because it was noted only in chickens that developed severe clinical disease (inoculated at 42 days after hatching) and was not noted in chickens that remained clinically normal (inoculated at 17 days).

Age Factors↗

Comparative studies on the human glutamate-pyruvate transaminase phenotypes--GPT 1, GPT 2-1, GPT 2.

The quantitative differences between the activity of the 3 common phenotypes of human red cell GPT has been confirmed. In addition, the activity of red cell GPT 1 was found to be greater in young children than in adults. No such difference was found for the GPT 2 phenotype. The activity of the red cell GPT 1 was found to decrease with age, reaching the adult level at the age of 10 to 12 years. Red cell GPT of all the 3 common phenotypes in both adults and children was found to show a similar response to the addition of excess pyridoxal phosphate. A method has been devised for the partial purification of human GPT (cytoplasmic) from liver. GPT 1 and GPT 2 have been purified, and very few significant differences were found amongst the physical and kinetic parameters tested.

Adult↗

Population and family studies on carbonic anhydrase II polymorphism in Gambia, West Africa.

614 individuals from the village of Keneba in Gambia (West Africa) have been typed for red cell Carbonic Anhydrase II using cellulose acetate electrophoresis followed by detection of the enzyme with the fluorogenic substrate fluorescein diacetate. Three phenotypes were found; 479 CAII 1 (80.94%), 107 CAII 2-1 (17.43%), and 10 CAII 2 (1.63%). The gene frequencies of the 2 autosomal alleles responsible for the electrophoretically distinguishable polymorphism were CAII 1 0.897 and CAII 2 0.103. A study of 72 families confirmed the simple Menedelian co-dominant inheritance.

Blood Protein Electrophoresis↗