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Biomedical subjects

C A James

Publications and source records attributed to C A James.

At least 55 records · Page 3Linked to original sources

Clinical tutor evaluation: a 5-year study by students on an in-patient service and residents in an ambulatory care clinic.

Medical students on an in-patient service and residents working in an ambulatory care clinic have regularly evaluated their clinical tutors over the 5 years 1985-1989. Both groups of raters reliably and predictably evaluated their tutors and both emphasize between-tutor comparisons more than actual rating values for individual tutors. Tutors active in both contexts regularly receive higher ratings from the medical students than from the residents. Mid-course feedback to tutors in the medical course had no impact on end-of-course ratings. In neither context did tutor ratings improve from one evaluation to the next. Both groups reliably discriminate between the teaching skills and the personality traits of individual tutors.

Ambulatory Care↗

Cerebrovascular disease in symptomatic and asymptomatic patients with sickle cell anemia: screening with duplex transcranial Doppler US--correlation with MR imaging and MR angiography.

PURPOSE: The authors evaluated the role of transcranial Doppler ultrasonography (US) in patients with sickle cell disease (SCD) and cerebrovascular disease. MATERIALS AND METHODS: Twenty-one patients with SCD and stroke (aged 3-22 years; mean age at stroke, 9 years) were evaluated with magnetic resonance (MR) imaging and duplex transcranial Doppler US with a 2-MHz transducer. Nineteen patients also underwent MR angiography. Forty-six asymptomatic patients with SCD were also evaluated with Doppler US, MR imaging, and MR angiography. RESULTS: The following transcranial Doppler US findings were correlated with cerebrovascular disease in patients with SCD: (a) maximum velocity in the ophthalmic artery (OA) of more than 35 cm/sec; (b) mean velocity in the middle cerebral artery (MCA) of more than 170 cm/sec; (c) resistive index in the OA of less than 50; (d) velocity in the OA greater than that of the ipsilateral MCA; and (e) maximum velocity in the posterior cerebral, vertebral, or basilar arteries greater than the maximum velocity in the MCA. CONCLUSION: Transcranial Doppler US scanning has great potential as an inexpensive, easily performed screening procedure for cerebrovascular disease in patients with SCD.

Adolescent↗

The nursing role in assisted reproductive technologies.

The role of the nurse in assisted reproductive technologies (ART) has evolved as the needs of couples and infertility programs have changed. This multidimensional nursing role encompasses skill as a manager, educator, counselor, researcher, and professional. Such skills are combined with a specialized knowledge base of reproductive endocrinology and infertility. This chapter describes the various facets of the role, including the interdependence of other team members.

Adult↗

Effects of sera from patients given various anesthetics on preimplantation mouse embryo development in vitro.

This study compared the effects of sera from patients given various anesthetics on in vitro mouse preimplantation embryo development. Patients electing bilateral laparoscopic tubal sterilization were subjected to general anesthesia with nitrous oxide (N2O) that included either isofluorane (ISO/N2O) as an inhalant or fentanyl or morphine (FEN/MOR/N2O). The addition of sera collected 1 hr after anesthetic induction significantly reduced the numbers of two-cell mouse embryos that developed to blastocyst in the ISO/N2O group as compared to that of preanesthesia sera. In contrast, no detrimental effects were revealed from sera of patients given FEN/MOR/N2O. Comparison of sera from patients given ISO/N2O and FEN/MOR/N2O for laparoscopic oocyte retrieval and from patients given spinal anesthesia and/or i.v. sedation for ultrasonic retrieval also revealed a decrease in mouse embryo development in the ISO/N2O group, but no differences were seen in the other anesthetic regimens. ISO/N2O anesthesia was also associated with a significantly decreased fertilization rate of mature oocytes retrieved. However, no significant effect of ISO/N2O anesthesia on IVF pregnancy rates could be demonstrated. These studies indicate that embryo toxic effects can be detected in sera from patients given ISO/N2O and that this anesthetic may be detrimental to the success of in vitro fertilization and embryo transfer.

Adult↗

The influence of cimetidine on debrisoquine 4-hydroxylation in extensive metabolizers.

We have studied the effect of cimetidine (800 mg.day-1) administration for three days on debrisoquine 4-hydroxylation in nine healthy extensive metabolizers. The debrisoquine metabolic ratio was significantly increased (p less than 0.01), but the new ratios remained in the extensive metabolizer range (less than 12.6). These data suggest that pre-treatment with cimetidine in usual therapeutic doses will impair debrisoquine 4-hydroxylation, but not enough to alter the apparent oxidation phenotype.

Adult↗

Interaction of chemicals with cytochrome P-450: implications for the porphyrinogenicity of drugs.

Our studies lead us to suggest that in order for an organic chemical to cause porphyrin accumulation in chick embryo hepatocyte culture, it must be: 1. lipophilic; 2. resistant to biotransformation by phase I or phase II reactions to compounds which are devoid of biological activity; and 3. capable of interacting with cytochrome P-450 with concomitant destruction of the heme moiety or the generation of reactive oxygen species. The interaction of porphyrin-inducing chemicals with cytochrome P-450 results in lowering of a regulatory "free heme" pool. The "free heme" pool may be lowered by inhibiting one or more of the enzymes of heme biosynthesis or by destruction of the heme moiety of cytochrome P-450. Specific chemical features enable organic chemicals to inhibit ferrochelatase activity or to destroy the heme moiety of cytochrome P-450. Chemicals with a wide variety of structures are able to inhibit uroporphyrinogen decarboxylase activity.

5-Aminolevulinate Synthetase↗

A review of 132 consecutive patients referred for assessment of vibration white finger.

One hundred and thirty-two subjects were referred to the Institute of Occupational Health in Birmingham over a 2 year period for assessment as to whether they met the criteria for Prescribed Disease A11 (vibration white finger). A standardized questionnaire and checklist was used, and each patient with vibration white finger was staged according to the Taylor and Pelmear (1975) classification. One hundred and sixteen subjects (88 per cent) had a clinical picture consistent with a diagnosis of vibration white finger, of which 10 did not meet the DHSS criteria for prescription. For these 116 subjects, the mean age at initial occupational exposure to vibration was 27 years. The mean age when symptoms began was 40 years. Numbness was the most common symptom accompanying the periodic blanching. More claimants reported symptoms affecting their hobbies and social life than affecting their work. The main job activities that exposed these claimants to vibration were pedestal grinding, pneumatic chipping/grinding, and hand grinding. Different systems available for staging vibration white finger have inherent limitations, but a scheme that uses standardized objective tests will make the diagnosis and assessment less reliant on subjective symptoms alone.

Humans↗

Inhibition of chick embryo hepatic uroporphyrinogen decarboxylase by components of xenobiotic-treated chick embryo hepatocytes in culture.

Uroporphyrinogen decarboxylase (UROG-D) activity in the 10,000g supernatant of 17-day-old chick embryo liver homogenates was determined by measuring the conversion of pentacarboxylporphyrinogen I to coproporphyrinogen I. The optimum pH of the enzyme was found to be approximately 6.0 and enzyme activity was found to be linear with protein concentrations ranging from 0.3 to 2.0 mg/mL. At a protein concentration of 1.2 mg/mL and pH 6.0, the activity was found to be linear for a reaction time of 50 min and to be approximately 10 pmol/(mg protein.min). This enzyme assay was used to demonstrate that a UROG-D inhibitor, previously reported to accumulate in rodent liver, also accumulates in 3,3'4,4'-tretrachlorobiphenyl (TCBP) and sodium phenobarbital (PB) treated chick embryo hepatocytes in culture. This results accords with the previous demonstration of a TCBP- and PB-induced decrease in UROG-D activity in this system. Uroporphyrin accumulation in chick embryo hepatocyte culture is interpreted as resulting from a combination of two mechanisms, viz., inhibition of UROG-D activity and uroporphyrinogen oxidation to uroporphyrin catalyzed by a cytochrome P-450 isozyme.

Animals↗

Ifosfamide plasma clearance in relation to polymorphic debrisoquine oxidation.

Ifosfamide (IF) pharmacokinetics and the plasma (NBP)-alkylating activity were determined in 33 patients with different tumours after the administration of IF as single-agent chemotherapy. All subjects had been phenotyped for debrisoquine oxidation. There is a lack of correlation between the debrisoquine metabolic ratio (DMR) and either the total plasma clearance of IF (CLIF) or the AUC of the plasma NBP-alkylating activity.

Adult↗

Disruption of hepatic heme biosynthesis after interaction of xenobiotics with cytochrome P-450.

Heme biosynthesis in hepatocytes is controlled by a free heme pool, which regulates delta-aminolevulinic acid synthase. Porphyrinogenic chemicals deplete the regulatory free heme pool by interacting with cytochrome P-450 thereby inhibiting heme biosynthesis and/or causing heme breakdown. Recent developments allow us to predict which groups of chemicals are likely to be porphyrinogenic. One group is exemplified by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine. Heterocyclic compounds of this type cause mechanism-based inactivation of cytochrome P-450, leading to the formation of N-alkylporphyrins, with ferrochelatase-inhibitory activity resulting in lowering the free heme pool. Allylisopropylacetamide exemplifies a second group. Such compounds containing a terminal olefinic or acetylenic group, cause mechanism-based inactivation of cytochrome P-450. In the process, the heme moiety of cytochrome P-450 is destroyed and the free heme pool is lowered. A third group is exemplified by planar polyhalogenated or polycyclic aromatic hydrocarbons. These compounds induce specific cytochrome P-450 isozymes but are poor substrates. Active oxygen is formed, which interacts with a hepatic substrate to form a uroporphyrinogen decarboxylase inhibitor. Inhibition of this enzyme leads to depletion of the free heme pool.

Alkylation↗

Pharmacokinetics of intravenous and oral sodium 2-mercaptoethane sulphonate (mesna) in normal subjects.

The pharmacokinetics of mesna (sodium 2-mercaptoethane sulphonate) and its inactive disulphide, dimesna, were investigated using high performance liquid chromatography in six normal subjects following intravenous and oral administration of 800 mg mesna. The mean maximum mesna concentration after i.v. administration was 111 (s.d. +/- 28.3) nmol ml-1 and the mean maximum dimesna concentration was 183 (s.d. +/- 41.6) nmol ml-1. Following oral mesna dosing the mean peak mesna concentration was 19.6 (s.d. +/- 10.2) nmol ml-1 but mesna was only found in the plasma of five of the six subjects. The mean peak dimesna concentration was 22.5 (s.d. +/- 12.4) nmol ml-1. Following i.v. mesna administration, the mean half-life of mesna was 21.8 (s.d. +/- 3.1) min and total body clearance 1.23 (s.d. +/- 0.31) l kg-1 h-1. The mean half-life of dimesna was 1.17 (s.d. +/- 0.32) h. It was not possible to determine their half-lives after oral mesna administration. The mean mesna concentration in the 0-4 h urine collection was 9.6 (s.d. +/- 10.7; range 1.4-28.7) nmol ml-1 following i.v. mesna injection. After oral mesna the highest mesna concentration occurred in either the 0-4 or 4-8 h urine collections. The mean peak mesna concentration was 2.5 (s.d. +/- 1.7) mumol ml-1 (c.f. estimated uroprotective concentration of 1.7 mumol ml-1). The mean 4 h urinary clearance of the uroprotective species mesna was 0.413 (s.d. +/- 0.136) l kg-1 h-1. After both i.v. and oral mesna the urinary excretion of mesna is predominantly during the first 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Determination of debrisoquine metabolic ratio from hourly urine collections in healthy volunteers.

The possibility of simplifying the regimen for the collection of urine samples in the determination of the debrisoquine metabolic ratio (DMR) was explored in 15 normal subjects. In the extensive metaboliser subgroup (EM; n = 11), there was a close correlation between the DMR as determined by an 8 h urine collection and the debrisoquine/4-hydroxydebrisoquine ratio (D/4-OHD) in the hourly samples (excluding the first hour). In the poor metabolisers (PM; n = 4) the phenotype could be identified, but it was not possible to estimate the DMR reliably.

Debrisoquin↗

Biliary elimination of cyclophosphamide in man.

A 72-year-old male with a lymphoma and obstructive jaundice received 900 mg cyclophosphamide IV as a part of a chemotherapeutic regimen whilst external biliary drainage was in progress. Plasma, urinary, and biliary pharmacokinetics of cyclophosphamide and nitrobenzylpyridine (NBP)-alkylating metabolites were studied. In 32 h 891 ml bile was collected, and this contained unchanged cyclophosphamide and NBP-alkylating material. Despite fluctuations in biliary flow, estimates of the half-life of cyclophosphamide from plasma, urine, and bile were similar. Good correlation existed between plasma and biliary cyclophosphamide concentrations after the initial plasma had been completed. The ratio of bile to plasma concentrations was 0.7 and showed no time dependence, as evidenced by a lack of hysteresis in the correlation curve. Of the administered dose, 3.5% was excreted as unchanged cyclophosphamide in the bile over 32 h. NBP-alkylating activity was found in bile up to 25 h but not after this time, despite the presence of unchanged cyclophosphamide in plasma. NBP-alkylating material was not found in the bile when it could not be detected in plasma, and vice versa.

Aged↗