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Biomedical subjects

W Griffiths

Publications and source records attributed to W Griffiths.

At least 19 recordsLinked to original sources

Lutein associated with a transthyretin indicates carotenoid derivation and novel multiplicity of transthyretin ligands.

Transthyretins isolated from different species bind hydrophobic compounds and are often obtained in a yellow form. Such a transthyretin from chicken serum was purified by chromatography using Sepharose-coupled human retinol-binding protein. The yellow chromophore was extracted with methanol and purified by reverse phase HPLC followed by normal-phase chromatography on a nitrile column. Ultraviolet-visible absorbance and mass spectrometry identified the yellow compound as lutein, i.e. xanthophyll, (all-trans)-beta, epsilon-carotene-3,3'-diol, estimated to constitute 10-30% of associated colourless compounds. These components are different from the yellow component isolated from human transthyretin and establish that carotenoid-derived pigments can be associated with transthyretins.

Animals

Variation in coverage by ethnic group of neonatal (Guthrie) screening programme in south London.

OBJECTIVES: To determine whether coverage of the neonatal (Guthrie) screening programme in Britain is different for groups at highest risk of sickle cell disease and to identify possible reasons for incomplete coverage. DESIGN: Descriptive study of coverage of screening programme and its variation by mobility, district of residence, and ethnic group. SUBJECTS: 1727 infants born between 1 October and 31 December 1991. SETTING: Former West Lambeth and Camberwell District Health Authorities, London. MAIN OUTCOME MEASURE: Proportion of infants with an identifiable screening test result. RESULTS: Screening covered 1663/1727 (96.3%) infants overall (745/786 (94.8%) in West Lambeth; 918/941 (97.6%) in Camberwell). The relative odds ratio of an African infant not having been tested compared with a white infant was 3.05 (95% confidence interval 1.30 to 7.14) (2.08 (0.86 to 5.01) after adjustment for mobility and district of residence). For infants whose families moved into the districts after the birth compared with those born and resident in the districts the relative odds ratio of having been tested was 10.16 (4.85 to 21.29). The odds ratio of locally delivered infants in West Lambeth not having been tested compared with those in Camberwell was 2.12 (1.08 to 4.16) after adjustment for ethnic group. CONCLUSION: Coverage of the screening programme is incomplete and poorer in infants of African ethnic group than in white infants. Poorer coverage is also associated with mobility of the family around the time of birth. The findings have implications for using the neonatal programme for testing for sickle cell disease and other disorders. Arrangements for monitoring the existing screening programme are inadequate and an improved system should be established, similar to the scheme that monitors the immunisation programme.

Africa

C595--a monoclonal antibody against the protein core of human urinary epithelial mucin commonly expressed in breast carcinomas.

Urinary mucins which express determinants for the anti-breast carcinoma monoclonal antibody, NCRC-11 (IgM), closely resemble the mammary mucins found in milk fat globules and carcinomas. An IgG3 monoclonal antibody, C595, was prepared against urinary mucins isolated on a NCRC-11 antibody affinity column, and this 'second generation' antibody was shown to have a very similar pattern of reactivity to the original NCRC-11 antibody. By immunohistology, the profile of reactivity of both antibodies with tumour and normal tissue specimens was virtually identical. Both antibodies reacted with epithelial mucins isolated from breast tumours or normal urine using an NCRC-11 antibody affinity column, although the antibodies were unreactive with other antigen preparations. Heterologous immunoradiometric assays ('sandwich' tests) confirmed that NCRC-11 and C595 epitopes were co-expressed on the same molecule. C595 antibodies inhibited the binding of radiolabelled NCRC-11 antibodies to antigen, suggesting that the two epitopes were in close topographical proximity. The protein core of the mammary mucins has recently been shown to consist predominantly of a repeated 20 amino acid sequence (Gendler et al., 1988). Peptides with this complete sequence and small fragments were synthesised, and the C595 antibody was found to recognise an epitope within this repeat. The ability to identify and synthesise monoclonal antibody-defined determinants, as well as those in the adjacent or overlapping sequences within the protein core of epithelial mucins, is viewed as a strategy for facilitating the production of antibodies of new and novel specificity to complement the panels of existing anti-breast cancer reagents.

Antibodies, Monoclonal

Characterization of monoclonal antibodies to chicken gizzard talin.

Eleven monoclonal antibodies against chicken gizzard talin, a major focal adhesion protein, have been produced. In order to determine the degree of homology between talin molecules from different sources, these antibodies were used to immunolocalize talin in five different vertebrate species. Three representative talin antibodies are described in this report.

Animals

False positive urine drug screens from quinine in tonic water.

Urine surveillance of patients is a universal procedure in drug treatment programs for monitoring frequency and type of illicit drug use. The method is also being increasingly utilized by employers to screen employees for drug use. The presence of a prescribed substance in a subject's urine is considered objective evidence of illicit drug use, and is used to confront subjects. However, studies have demonstrated that urine surveillance is not infallible. The presence of inaccuracy in urine surveillance has definite negative consequences of both individuals and the testers. In this paper, we report that a positive urine test for quinine, which may be evidence of illicit drug use, results from the consumption of the amount of tonic water present in a mixed drink. The implications of this finding are discussed.

Adult

Altered methadone pharmacokinetics in pregnancy: implications for dosing.

Lower plasma methadone levels have been reported in pregnant women receiving methadone maintenance for heroin addiction. Methadone pharmacokinetics was examined in a 24-year-old woman 8 months pregnant with twins, who experienced severe withdrawal symptoms beginning 10-12 hours after her daily 30 mg methadone dose. Methadone plasma concentration-time data were fit to a one-compartment pharmacokinetic model by extended least-squares regression. Estimated half-life for methadone was 8.1 hours, which is much shorter than the usual methadone half-life (greater than 24 hours). Plasma methadone concentrations were estimated for the cases of a) increasing the 30 mg methadone dose by 50% and administering it once daily and b) continuing the 30 mg methadone dose but administering it at 12-hour intervals. Although the model is derived from a single subject, the simulations performed clearly suggest a need for altered methadone dosing in pregnancy. More sustained plasma methadone levels are achieved with twice-daily dosing of methadone than are achieved by administering an increased methadone dose once daily. Twice-daily dosing would be expected to produce fewer withdrawal symptoms and, ultimately, improved compliance with treatment.

Adult

Elevated nicotine levels in patients undergoing hemodialysis. A role in cardiovascular mortality and morbidity?

The incidence of cardiovascular disease in patients with end-stage renal disease undergoing long-term maintenance hemodialysis is excessively high. The reason for this excess morbidity and mortality has remained unclear. Cigarette smoking is one factor that has been associated with increased cardiovascular risk. To learn more about the effects of tobacco smoking in these patients, nicotine levels were assayed in the serum of 10 patients with end-stage renal disease undergoing maintenance hemodialysis. Specimens were obtained before and after smoking one cigarette and following dialysis or an equivalent period in control subjects. Serum nicotine levels (+/-SEM) in control subjects measured 19.0 +/- 7.2 ng/ml initially, 36.1 +/- 8.2 ng/ml after smoking, and 9.3 +/- 3.5 ng/ml after a period of 4.35 hours. These compare with respective values of 76.6 +/- 16.8 ng/ml (p less than 0.004), 132.9 +/- 19.7 ng/ml (p less than 0.001), and 51.9 +/- 10.5 ng/ml (p less than 0.001) in patients undergoing hemodialysis. These data demonstrate markedly higher nicotine levels in hemodialysis patients compared with control subjects, which may have serious implications regarding morbidity and mortality.

Adult

Can human behavior be modified?

Human behavior is constantly being modified, though not as rapidly or always in the direction that health professionals might wish. In cancer prevention and detection programs, human behavior is modified by several common interrelated methods: the mass media; face-to-face communications; risk-immunization measures; economic forces; and the enactment of laws and regulations. Information and education are the preferred methods and have over a period of time achieved encouraging results. Further emphasis should focus on improving communication skills of health professionals, especially physicians; the promotion of hospital health education programs; and the support of more effective school health education programs. They should keep the public informed about the latest scientific advances while guarding against oversimplifying scientific facts that can be misinterpreted. They must be aggressive in the battle against cancer quackery, and they must keep abreast of the self-care and self-help movements, supporting those that contribute to cancer prevention and detection.

Adolescent

Care and safety.

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Accident Prevention

Pulmonary sporotrichosis in Oklahoma in susceptibilities in vitro.

Six cases of pulmonary sporotichosis were observed in 2 institutions in Oklahoma City, Okla. Three of the patients were treated with iodides with or without surgery. Although one patient required a second course of iodides, the patients have remained well after at least 34 months of follow-up. Three patients treated with amphotericin B, single course as well as multiple courses, and other antifungal agents (hydroxystilbamidine and miconazole) have all relapsed. These cases and a reviewed of more than 40 cases of pulmonary sporotrichosis susceptibilities of Sporothrix schenckii that we observed in vitro suggest that amphotericin B is not an effective agent for the treatment of pulmonary sporotrichosis. It is our opinion that the treatment of choice for pulmonary sporotrichosis is a supersaturated solution of potassium iodide. If the patient is allergic to the medication or fails to respond, then a combination of amphotericin B plus flucytosine may be tried.

Adult

Clostridial myonecrosis ('gas gangrene') during cephalosporin prophylaxis.

Four cases of clostridial myonecrosis that developed in open fractures were treated with surgical debridement and with intravenous cephalosporins as antibiotic prophylaxis. All patients recovered following amputation of the involved extremity, and treatment with high-dose penicillin in three cases, and erythromycin plus high-dose cephalothin in the fourth. This complication was not seen in patients with similar injuries that were managed surgically but used other antibiotics, usually penicillin, as prophylaxis. In vitro susceptibility tests of clostridia to cephalothin were performed; the results demonstrated that nearly 50% of clostridia tested were resistant to cephalothin.

Adult