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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 559 records · Page 31Linked to original sources

Strontium-89 therapy for the pain of osseous metastases.

A Phase I and II study has been conducted of the safety and efficacy of 89Sr (injected i.v. as the chloride) to alleviate bone pain due to osseous metastatic disease. Potential attendant hematologic toxicity was also examined. Strontium-90 impurities were always less than 1.5%, employing a new quality control technique which detects the 90Y "daughter". Thirty-eight patients with pain due to osseous metastases requiring regular narcotic more than twice a day, documented by an abnormal bone scan and radiography, received 45 doses (1-4.5 mCi, 16-70 microCi/kg) of 89Sr after informed consent. The performance status (Karnofsky scale) ranged from 20-80%. One patient had complete pain relief while 22 other doses yielded at least a 25% reduction in narcotic requirement lasting at least 1 mo and/or 20% improvement in Karnofsky scale rating. Two patients had marked to complete relief in tumor sites which were not fractured, with no change in fracture pain. Twenty-two did not respond. Response was independent of narcotic requirements, tumor type, or Karnofsky status. No hematologic toxicity occurred. Strontium-89 may be useful as adjuvant therapy for diffuse bone pain, but a double-blind study comparing it to other nonnarcotic modalities is required.

Bone Neoplasms↗

Treatment of insulin reactions in diabetics.

Using a modification of the glucose clamp technique, we have studied the efficacy of commonly used foods to correct hypoglycemia in insulin-dependent diabetics. After lowering the plasma glucose level to 55 mg/dL at a steady-state plasma free insulin concentration of about 50 microU/mL, patients were fed 20 g of carbohydrate as milk, orange juice, or D-glucose or 40 g of carbohydrate as orange juice. The data indicate that 20 g of carbohydrate as D-glucose corrects hypoglycemia without rebound hyperglycemia. In an outpatient setting, this treatment also proved effective in spontaneous episodes of hypoglycemia. We conclude that (1) the D-glucose content of the ingested carbohydrate is an important determinant of the glycemic response, and (2) at times of moderately severe hypoglycemia, ingestion of 20 g of D-glucose provides an effective glycemic response for periods of at least 40 minutes. In view of these data, a table is provided listing some common sources of 20 g of D-glucose.

Adult↗

Rat brain preproenkephalin mRNA. cDNA cloning, primary structure, and distribution in the central nervous system.

A cDNA-clone library was constructed from poly-adenylated RNA of Fischer rat striatum and screened for inserts coding for the enkephalin precursor preproenkephalin. The insert of one positive clone, pRPE2, was sequenced and found to contain the coding sequence (810 bases), as well as 316 and 155 bases of the 3' and 5' untranslated regions, respectively, of rat preproenkephalin mRNA. The primary structure of rat preproenkephalin (269 amino acids, Mr 30,932) is similar to those of previously sequenced bovine and human preproenkephalins (78 and 82% matched residues, respectively), and contains four copies of Met-enkephalin, one of Leu-enkephalin, one of Met-enkephalin-Arg6-Gly7-Leu8, and one of Met-enkephalin-Arg6-Phe7. Cell-free translation of rat striatal mRNA selected by hybridization with pRPE2 DNA resulted in the synthesis of a 31,000-Da protein. Southern analysis of rat genomic DNA with 32P-labeled pRPE2 fragments is consistent with a single preproenkephalin gene. A 32P-labeled pRPE2 fragment hybridized specifically with preproenkephalin mRNA (approximately 1500 bases) on Northern blots of polyadenylated or total RNA of all brain regions but not liver. Relative abundances of preproenkephalin mRNA in total RNA of specific regions of the rat central nervous system, determined by a sensitive dot-blot hybridization assay, had the following order: striatum much greater than hypothalamus, pons-medulla, spinal cord greater than cerebellum, midbrain, frontal cortex greater than hippocampus, thalamus. The pRPE2 probe is useful for the analysis of the dynamics of preproenkephalin mRNA in rat neurons.

Amino Acid Sequence↗

Influence of penicillamine and various analogs on matrix-induced bone formation in rats.

D-penicillamine and a variety of analogs have been tested for their ability to interfere with the various stages of bone development using a model for endochondral bone formation. At the highest dose tested (40 mg/rat/day), D-penicillamine inhibited mineralization, D-2-Amino-3-methyl-3-[(2-acetamidoethyl)dithio]butanoic acid (II), at a relatively low dose (10 mg/day), decreased the amount of insoluble collagen in skin, mesenchymal cell proliferation on Day 3, and inhibited bone formation on Day 14. Several other compounds tested, sodium 4-[(D-1, 1-dimethyl-2-amino-2-carboxyethyl)-dithio]butanesulfinate (IV), 2-acetamidoethyl-2-acetamidoethanethiolsulfonate (V), and sodium 4-mercaptobutanesulfinate trihydrate (VI), also inhibited osteogenesis on Day 14.

Animals↗

An investigation of S-100 protein in embryonic dental papillae of rats.

We attempted to identify S-100 protein, a marker of neural crest tissue, within cells of the developing dental papillae of 18-day rat fetuses by means of the immunoperoxidase technique. Although there is experimental evidence that dental papillae are derived from neural crest, no marker protein was identified in this study.

Animals↗

Stimulus generalization of conditioned taste aversion in rats.

Relatively little information is available regarding the intradimensional stimulus generalization of conditioned taste aversion (CTA). Experiment 1 employed a between-groups generalization test to examine the extent to which conditioned flavor aversion to one sucrose solution generalized to other concentrations of sucrose in adult rats. Evidence of a gradient of aversion was obtained. Because generalization gradients in other tasks have been found to flatten over a retention interval, Experiment 2 investigated the effects of delayed testing (2, 7, or 21 days) upon the slope of the generalization gradient. The generalization gradient flattened at the intervals, suggesting that subjects forgot the specific attributes of the conditioning concentration and avoided generalized stimuli as if they were the original CS. Experiment 3 used a long delay between taste and toxicosis to degrade the associative contingency and found no evidence that the generalization gradients found in the first two experiments could be explained in terms of enhanced neophobia due to poisoning. These findings provide further evidence (cf. A. W. Logue, 1979, Psychological Bulletin, 86, 276-296; M. Domjan, 1980, in J. S. Rosenblatt, R. A. Hinde, C. Beer, & M. Busnel (Eds.), Advances in the study of behavior, Vol. 11, New York: Academic Press) that CTA shares a number of similarities with other learning processes. Further, they illustrate that stimulus forgetting can be detected in a paradigm considered relatively immune to retention loss.

Animals↗

The cocarcinogenic effect of intrarectal deoxycholate in rats is reduced by oral metronidazole.

Bile acids enhance colorectal carcinogenesis in animals and man, perhaps after degradation by faecal anaerobes. The promotional effect of sodium deoxycholate (SDC) and its relationship to bacteria was examined in male Sprague-Dawley rats (n = 115) which had received a 6-week course of azoxymethane (total dose 90 mg kg-1 s.c.) Two groups received 3 X weekly intrarectal (i.r.) instillations of N saline or 0.12 M SDC for 18 weeks. Another group received SDC i.r. plus metronidazole (22.5 mg kg-1) daily in the drinking water. Controls had no instillations or metronidazole alone. By 28 weeks SDC had increased mean colonic crypt depth by 9% (P less than 0.001), and had almost trebled colorectal tumour yields from 2.4 +/- 0.4 per rat (mean +/- s.e.) in controls to 6.4 +/- 0.5 (P less than 0.001). Tumour yields after SDC + metronidazole (4.2 +/- 0.5) remained 75% higher than in controls (P less than 0.01) but were 33% less than after SDC alone (P less than 0.01), and the increase in crypt depth was maintained at 7% (P less than 0.001). Neither metronidazole alone nor saline i.r. had any effect on tumour yield, but metronidazole alone reduced crypt depth by 9% (P less than 0.001). Deoxycholate is a potent cocarcinogen and also stimulates mucosal hyperplasia. Metronidazole reduces its tumour-promoting effect, suggesting that faecal anaerobes are important in bile acid cocarcinogenesis.

Animals↗

Vitamin D metabolism and anticonvulsant therapy: effect of sunshine on incidence of osteomalacia.

To study the association between anticonvulsant therapy and osteomalacia or rickets, we evaluated 450 epileptic patients receiving anticonvulsants and residing in an institution for the mentally retarded in Florida. Fifty-five of them with increased mean serum alkaline phosphatase and mildly depressed mean serum calcium levels were identified as being at risk for having osteomalacia. None of them, however, had low serum levels of vitamin D (25[OH]D) or radiologic evidence of osteomalacia or rickets. In contrast to reports from northern climates, we found minimal evidence of anticonvulsant-induced bone disease. The study suggests that exposure to sunshine in our patients probably prevented the development of anticonvulsant-induced osteomalacia or rickets.

Adult↗

Pasteurization of C1 inactivator in the presence of citrate salts.

Conditions have been determined under which the C1 inactivator (C1-INA) can be pasteurized to reduce the risk of transfusion hepatitis associated with its use for replacement therapy in patients with genetic or acquired deficiencies. Recovery of 90% of the biological and immunological activity of a C1-INA concentrate was achieved following heat treatment for 10 h at 60 degrees C in the presence of 3 M potassium citrate. Crossed immunoelectrophoresis in heparinized agarose was used to demonstrate the ability of the pasteurized C1-INA to bind heparin and to form a precipitation pattern with antibody which was almost indistinguishable from that of an unheated control. High pressure liquid chromatography and enhancement of the fluorescence of 1,8-anilinonaphthalene sulfonate were used to show that other proteins present in the concentrate were also stabilized.

Citrates↗

A single-step method for the isolation of antithrombin III.

A single-step method is described for the isolation of a highly purified antithrombin III (AT III) concentrate at a recovery of over 30% using affinity chromatography on heparin-Sepharose (HS). The polyethylene glycol precipitation step frequently employed in the preparation of AT III concentrates for clinical use has been eliminated and purification is accomplished entirely by optimizing the salt concentration in the HS washing buffer to enhance the desorption of impurities prior to elution of AT III. Pasteurization of the AT III concentrate in the presence of 0.5 M sodium citrate to minimize the risk of hepatitis decreases the recovery by about 20% and induces changes in the patterns obtained by polyacrylamide gel electrophoresis and by crossed immunoelectrophoresis in heparinized agarose gel.

Antithrombin III↗

Variable staffing: an alternative to traditional practice for pharmacy.

There are a variety of programs designed to monitor the utilization of hospital pharmacy labor and to measure fluctuations in workload. Few, however, address the problem of forecasting labor needs and adjusting staffing levels accordingly. This paper describes a system used by one hospital, whereby workload is correlated to census to provide variable staffing levels corresponding to fluctuating workload demands. This hospital's pharmacy uses a core level staff, supplemented by on call pharmacists and technicians. The following day's workload is forecast from the current day's level, and staff are scheduled accordingly.

Efficiency↗

Hepatitis B transmission in school contacts of retarded HBsAg carrier students.

A prospective study was performed to assess the rate of transmission of hepatitis B from mentally retarded carrier students to susceptible mentally retarded peer students or school staff. Eighteen hepatitis B carriers were integrated into a public school program for the developmentally disabled, and serum hepatitis B markers were monitored in staff and students over 14 months. During this time no susceptible staff acquired hepatitis B serologic markers. Of susceptible students, 1.8% demonstrated seroconversion, but the route of infection is likely to have been outside the classroom environment. The results indicate that the risk of hepatitis B transmission is low in this particular school program.

Adolescent↗

Naloxone attenuates self-abusive behavior in developmentally disabled clients.

The opiate antagonist naloxone was effective in reducing self-abusive behavior in two mentally retarded clients with an extensive history of such behavior. Three doses of naloxone (0.1, 0.2, 0.4 mg) were compared with a vehicle solution in a double-blind, crossover design. Naloxone greatly attenuated self-abusive episodes in one client and eliminated them entirely in the second client. In addition, use of self-restraining behavior by one client was reduced. The findings suggested that some clients with self-injurious behavior may have disturbances of the endogenous opiate system. Maintenance of self-abuse by tonically elevated pain threshold and/or by the putative addictive characteristics of such behavior was discussed.

Adult↗

Cardiovascular and metabolic responses of trained and untrained middle-aged men to a graded treadmill walking test.

A treadmill walking test was developed in order to provide a suitable method of assessing the fitness levels of sedentary middle-aged men (mean age, 44.3 yrs) at submaximal intensity. The incremental stages of the test enabled subjects to terminate the workload whenever undue discomfort was experienced. The test procedure was used in a preliminary experiment to compare the cardiovascular and metabolic responses of trained and untrained middle-aged men to exercise. Heart rate responses to the test were significantly higher (p less than 0.01) in the untrained, compared with the trained, men as were the post-exercise blood lactic acid concentrations (p less than 0.01), Respiratory Exchange Ratios (p less than 0.01), Ventilatory Equivalents (p less than 0.05) and Rate of Perceived Exertion (p less than 0.01). However, there were no differences in the oxygen cost of walking between the two groups.

Adult↗