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Biomedical subjects

R B Williams

Publications and source records attributed to R B Williams.

At least 181 records · Page 10Linked to original sources
PubMed1983

Pyrazolo[3,4-d]pyrimidine ribonucleosides as anticoccidials. 3. Synthesis and activity of some nucleosides of 4-[(arylalkenyl)thio]pyrazolo[3,4-d]pyrimidines.

Ribonucleosides of 4-(alkylthio)-1H-pyrazolo[3,4-d]pyrimidines have been shown to be useful anticoccidial agents [Krenitsky, T. A.; Rideout, J. L.; Koszalka, G. W.; Inmon, R. B.; Chao, E. Y.; Elion, G. B.; Latter, V. S.; Williams, R. B. J. Med. Chem. 1982, 25, 32. Rideout, J. L.; Krenitsky, T. A.; Elion, G. B. U.S. Patent 4299 283, 1981]. In that study, the unsaturated 4-allylthio and 4-crotylthio derivatives (19 and 20) were shown to be more active in vivo against Eimeria tenella than their saturated congeners; therefore, some unsaturated (arylalkyl)thio derivatives were synthesized and investigated as anticoccidial agents. The novel compounds in this study (2 to 18) were prepared by the alkylation of 4-mercapto-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidine (1), which was prepared by an enzymatic method. The (E)-4-cinnamylthio derivative (2) and the 5'-monophosphate (18) were the most active compounds against E. tenella in vivo. None of the analogues with substituents in the aryl moiety (3 to 13) was more active than 2 in vivo. The geometry about the double bond was important, since the (Z)-4-cinnamylthio derivative (14) was inactive both in vitro and in vivo. The 4-(3-phenylpropynyl)thio and 4-(5-phenyl-2,4-pentadienyl)thio derivatives (15 and 16) were at least as active as 2 in vitro; however, they were less active than 2 in vivo. Compound 2 was effective in vivo against E. tenella, E. necatrix, E. maxima, and E. brunetti; these species of Eimeria were controlled when 2 was given in the diet at levels upt to 100 ppm. Infections in vivo due to E. acervulina were controlled by 2 only at about 800 ppm. The broad spectrum of anticoccidial activity shown by 2 represents a significant improvement over the activities reported for related compounds [Krenitsky, T. A.; Rideout, J. L.; Koszalka, G. W.; Inmon, R. B.; Chao, E. Y.; Elion, G. B.; Latter, V. S.; Williams, R. B. J. Med. Chem. 1982, 25, 32].

Animals↗
PubMed1983

Prospective evaluation of the risk of bacteremia and the role of antibiotics in ERCP.

To determine the frequency of bacteremia associated with endoscopic retrograde cholangiopancreatography (ERCP), we obtained blood cultures before, during, and after ERCP in 51 consecutive patients. Patients with radiographically demonstrated abnormalities in pancreatic and/or biliary ducts were routinely given antibiotic therapy after ERCP. Bacteremia after successful cannulation of the papilla of Vater was observed in only one patient with multiple strictures of the main pancreatic duct. No episodes of acute febrile illness was observed in any patient during the 48-hour follow-up period after ERCP. Our observations suggest that the risk of bacteremia from ERCP is minimal, and that any possibility of sepsis after ERCP in patients with abnormal pancreatic or biliary ducts may be prevented by administering appropriate antibiotics after the procedure.

Adolescent↗
PubMed1983

Hostility, CHD incidence, and total mortality: a 25-year follow-up study of 255 physicians.

High levels of hostility as assessed by a MMPI scale (Ho) have been found associated with increased levels of arteriographically documented coronary atherosclerosis. In this study we examined the relationship between hostility and subsequent health status in a 25-year follow-up of 255 medical students who completed the MMPI while in medical school. High Ho scores were found to be predictive of both clinical coronary disease incidence and total mortality.

Adult↗
PubMed1983

Clinical pharmacy services in a rehabilitation facility.

Clinical pharmacy services provided by pharmacists to patients in a rehabilitation facility through a contracted arrangement with a local hospital are described. Two staff pharmacists from a community hospital oversee the drug-distribution process and provide clinical services at a 40-bed private rehabilitation facility. During alternate four-week periods, each pharmacist works at the rehabilitation facility; the other four-week period is spent in traditional drug-distribution activities at the hospital. The hospital is reimbursed for clinical services separately from drug-distribution services; by keeping records of the time spent in clinical activities at the facility, the pharmacists have obtained increased reimbursement for these services since initiation of this program. Clinical services provided by pharmacists at the institute include patient education, drug-therapy monitoring and consultation, drug information activities, and management of drug therapy in selected patients. In 1982, pharmacists provided 230 drug-therapy consultations to physicians and received referrals for drug-therapy management of 47 patients on warfarin sodium, 46 on antihypertensive drugs, and 27 on phenytoin sodium. The provision of a variety of clinical pharmacy services to patients in a rehabilitation facility offers a unique and professionally rewarding practice.

Contract Services↗
PubMed1983

Preparing the operating budget.

The process of preparing a hospital pharmacy budget is presented. The desired characteristics of a budget and the process by which it is developed and approved are described. Fixed, flexible, and zero-based budget types are explained, as are the major components of a well-developed budget: expense, workload, productivity, revenue, and capital equipment and other expenditures. Specific methods for projecting expenses and revenues, based on historical data, are presented along with a discussion of variables that must be considered in order to achieve an accurate and useful budget. The current shift in emphasis away from revenue capture toward critical analysis of pharmacy costs underscores the importance of budgetary analysis for hospital pharmacy managers.

Budgets↗
PubMed1982

Type A behavior and elevated physiological and neuroendocrine responses to cognitive tasks.

Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in male college students during mental work and during sensory intake task performance. During mental work, Type A (coronary-prone) subjects showed greater muscle vasodilatation and more enhanced secretion of norepinephrine, epinephrine, and cortisol than Type B subjects. During sensory intake, Type A hyperresponsivity was found for testosterone and, among those subjects with a positive family history of hypertension, for cortisol. As a demonstration of combined cardiovascular, sympathetic nervous system, and neuroendocrine hyperresponsivity to specific cognitive tasks in Type A subjects, this study breaks ground in the search for mechanisms mediating the increased coronary disease risk among Type A persons.

Behavior↗
PubMed1982

Pyrazolo[3,4-d]pyrimidine ribonucleosides as anticoccidials. 1. Synthesis and activity of some nucleosides of purines and 4-(alkylthio)pyrazolo[3,4-d]pyrimidines.

The finding that 6-(methylthio)-9-beta-D-ribofuranosyl-9H-purine (6) was more toxic to the avian coccidium, Eimeria tenella, than to embryonic chick liver host cells in vitro prompted the synthesis and testing of analogues of this compound. It was revealed that the beta-D-ribofuranosyl moiety was an important structural feature and that several types of 2-substituents in the purine ring decreased efficacy, as did 3-deaza and 8-aza ring modifications of 6. In contrast, the pyrazolo[3,4-d]pyrimidine analogue of 6 (24) was an order of magnitude more active. Moreover, this analogue was 24-fold less toxic to the host cells than was 6. A series of 4-(alkylthio)-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidines was prepared from 4-mercapto-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidine (23) and various alkyl halides. The most effective compound in this series in vivo, 4-(ethylthio)-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidine (25), cleared chicks of the parasite at 50 ppm in the diet and was much less toxic than was 24.

Animals↗
PubMed1982

Pyrazolo[3,4-d]pyrimidine ribonucleosides as anticoccidials. 2. Synthesis and activity of some nucleosides of 4-(alkylamino)-1H-pyrazolo[3, 4-d]pyrimidines.

A series of 4-(alkylamino)-1-beta-D-ribofuranosyl-1H-pyrazolo[3, 4-d]pyrimidines was synthesized by enzymatic and chemical methods. On the basis of the previous finding that 4-(alkylthio)-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidines were effective anticoccidial agents, this series was examined for efficacy against Eimera tenella in chicks. The most active anticoccidial agent in the present study was the 4-cyclopentylamino derivative (8), which cleared chicks of the parasite at 200 ppm in the diet. Some members of this series were toxic to embryonic chick liver cells, mouse cells, and human cells in vitro. The 4-diethylamino derivative (16), which was not toxic in vitro, appeared to be toxic in chicks.

Animals↗
PubMed1982

Changes in the collagen of rat heart in copper-deficiency-induced cardiac hypertrophy.

Groups of rats were maintained from weaning on copper-supplemented or copper-deficient diets. After 2, 4, 6, 8 or 12 weeks animals were killed, their hearts were removed and the solubility and phenotype composition of the collagen of the hearts was studied. In the hearts from the copper-supplemented animals 35 to 45% of the collagen could be extracted after two treatments with pepsin but up to 74% could be extracted from the hypertrophied copper-deficient hearts. Almost all of the increase in the soluble material was found in the first pepsin extract. Electrophoretic analysis of the extracts showed that in the copper-supplemented hearts the ratio of Type III/Type I collagen increased about threefold between 2 and 6 weeks after weaning but by 8 weeks it had returned to about the level found at 2 weeks and was maintained at this level to the end of the experimental period. In the copper-deficient hearts the ratio of Type III/Type I collagen had increased about fivefold by 6 weeks after weaning and from 8 weeks to the end of the experimental period it remained at two to three times the value found in the copper-supplemented hearts. There was an indication that the relative proportion of Type V collagen was reduced in the copper-deficient hearts. The possible significance of these results in relation to the known pathological effects of copper deficiency on the cardiovascular system is discussed.

Animals↗
PubMed1982

Extra-adrenal myelolipomas compared with extramedullary hematopoietic tumors: a case of presacral myelolipoma.

A large presacral myelolipoma associated with increasing constipation is reported in a 70-year-old obese diabetic female. The resected tumor was encapsulated and dark red to yellow. Light and electron microscopy revealed mature and immature hematopoietic tissue, lymphoid aggregates and mature adipocytes. Myelolipomas arising in extra-adrenal sites are rare. Considered in the differential diagnosis are reactive extramedullary hematopoietic tumors that usually occur in patients with severe chronic anemias. Patients with extramedullary hematopoietic tumors are characterized by anemia, frequent hepatosplenomegaly and abnormal peripheral blood smears, and may be any age. The tumors are usually multiple and usually located in the mediastinum or epidural space. In contrast, patients with extra-adrenal myelolipomas are usually older than 40 years, have normal blood studies, absent hepatosplenomegaly, and usually have chronic debilitating diseases or endocrinopathies. Extra-adrenal myelolipomas are single and usually occur within the abdomen. Extramedullary hematopoietic tumors have a predominance of the hematopoietic component, with erythroid hyperplasia of that component. Extra-adrenal myelolipomas may have a predominance of either the hematopoietic or fatty component, chiefly the latter, and generally have a more conspicuous lymphocyte population. Although the components of these tumors are the same, we consider them separable clinically, pathogenetically and, in many cases, pathologically.

Aged↗
PubMed1982

Physiological and psychological variables predict compliance to prescribed exercise therapy in patients recovering from myocardial infarction.

Previous research has documented high rates of noncompliance to prescribed medical therapy in patients recovering from myocardial infarction (MI). This study was undertaken to determine if patients who subsequently drop out of a structured cardiac rehabilitation program could be prospectively distinguished from those who remain in the program based upon their initial baseline characteristics. Thirty-five consecutive patients with recent MIs underwent comprehensive physical and psychological assessments at entry into the program, and were followed for a period of 1 year. The 14 patients who dropped out of the program could be distinguished from the compliers on the basis of their reduced left ejection fraction assessed by first pass radionuclide angiography at rest and during peak exercise. In addition, their psychological profiles assessed by the MMPI indicated the dropouts were more depressed, hypochondriacal, anxious, and introverted and had lower ego strength than those who remained in the program. Statistical analysis further indicated that psychological variables were associated with noncompliance independently of physical status. These findings suggest that MI patients who are unlikely to adhere to this form of medical therapy may be prospectively identified based upon their initial physical and psychological characteristics.

Adaptation, Psychological↗
PubMed1982

Cardiovascular correlates of the psychotherapeutic process.

12 medical student volunteers were studied during 10 weekly sessions of brief dynamic psychotherapy using on-line physiological monitoring and concurrent psychotherapy process ratings. Forearm vascular resistance change from baseline for each visit was found to be related to psychotherapeutic outcome, and to some of the process variables, but to be most strongly correlated with clusters of process variables. This suggests that there may yet be a role for physiological monitoring in psychotherapy research.

Arousal↗
PubMed1981

The effects of age, sex, and zinc status on the accumulation of (copper, zinc)- metallothionein in rat kidneys.

A study has been made of the distribution of copper in the kidneys of growing rats. Renal copper concentrations increased steadily with age and were greater in female than in male animals. Most of the copper was present as (copper, zinc)-metallothionein and two forms of this protein were isolated and characterized from the kidneys of mature female rats. That copper metabolism in kidneys is subject to hormonal influence was indicated by a reduction in the concentrations of copper and (copper, zinc)-metallothionein in ovariectomized rats and by an increase in their concentrations after the administration of progesterone. Concentrations of renal (copper, zinc)-metallothionein were less in zinc-deficient than zinc-adequate rats during pregnancy and after progesterone administration.

Age Factors↗
PubMed1981

Redistribution of canine left ventricular myocardial blood flow in unloaded systole.

The left coronary arteries of dogs were cannulated and perfused with blood from support dogs. The experimental hearts were unloaded by severing the aortas to maximize strains and minimize fiber stress. In each heart we compared the transmural distribution of blood flow in two states: (1) provision of perfusion pressure (40 mm Hg) only during systole and then (2) provision of perfusion pressure throughout the cardiac cycle. The distribution of flow in each of these perfusion states was labeled with a diffusible radioisotope (42K or 86Rb, one labeling the first state; the other labeling the second). Quantitative, paired autoradiography was used to visualize the two flow distributions. The differences between the two distributions after standardization was plotted as differences between activity vs. depth in the myocardium (r = 0.91). This was fitted with a line by least squares, the slope of which was significantly different from zero at the 0.005 level. The magnitude of the gradient of the systolic flow was represented by the ratio of deep to shallow flow. The mean of these ratios was 0.54 +/- 0.12 (95% confidence interval). A graphical analysis shows that the data are consistent with a gradient of extravascular compression across the left ventricular wall.

Animals↗
PubMed1981

Assessment of conceptual tempo in the type A (coronary prone) behavior pattern.

Previous research has documented an association between a particular behavioral complex termed Type A, and increased incidence of coronary heart disease. In an effort to define further some of the behavioral characteristics that distinguish Type A subjects from their noncoronary-prone (Type B) counterparts, subjects were administered a test of conceptual impulsivity-reflection. While there were clear sex differences in performance, the results of the present study offered only qualified support for the notion that Type A individuals are more impulsive than Type B individuals. One component of Type A, Speed and Impatience, was shown to be related to increased impulsivity in women, but not in men. The findings suggest the importance of considering the interaction of gender with behavioral subcomponents of the Type A behavior pattern.

Adult↗