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Biomedical subjects

S L Morgan

Publications and source records attributed to S L Morgan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Homocysteine, B vitamins, and vascular-access thrombosis in patients treated with hemodialysis.

To evaluate whether increased plasma homocysteine concentrations (hyperhomocysteinemia) are associated with thrombosis of arteriovenous (AV) grafts, we determined plasma homocysteine, plasma and erythrocyte folate, plasma vitamin B12, and vitamin B6 (pyridoxal-5'-phosphate [PLP]) in 48 patients (45 black patients and three white patients) with end-stage renal disease who received hemodialysis. 5,10-Methylenetetrahydrofolate reductase (MTHFR) genotypes were also analyzed. The patients were divided into two groups, including a thrombosis-prone group with frequent graft loss (n = 24) and a control group with prolonged graft survival who were matched by age and duration of dialysis (n = 24). Hyperhomocysteinemia (>15 micromol/L) was found in 42 patients. There were no significant differences in all values, including the concentrations of homocysteine and vitamins between the two groups. Based on plasma folate and PLP concentrations, over 70% of patients appeared to have inadequate folate and/or vitamin B6 nutriture. Plasma homocysteine concentrations showed significant negative correlations with plasma and erythrocyte folate, and plasma vitamin B12 in all patients combined, whereas no significant correlation was found between plasma PLP and homocysteine concentrations. Among 48 patients, the heterozygous mutation (Val/Ala) of MTHFR was found only in three patients, two of whom belonged to the thrombosis-prone group and one to the control group, and there were no individuals with homozygous thermolabile mutation (Val/Val). All three white patients had Ala/Ala genotype, and 3 in 45 black patients (6.7%) were heterozygotes (Val/Ala).

Adult↗
PubMed1998

Clinical differences between subjects with familial and non-familial Tourette's syndrome: a case series.

OBJECTIVE: As many as 35 percent of Tourette's Syndrome patients do not acquire this disorder genetically. Since there has been little research conducted in this area, the purpose of this study was to compare the clinical differences between two groups of patients with Tourette's Syndrome (TS), one with family history of TS and one without. METHOD: Using data of eight previously diagnosed TS patients, the authors made comparisons of clinical and sociodemographic variables between a group of three patients with family history of TS and five with no family history. RESULTS: There were no differences in clinical presentation, current age, age at diagnosis, gender, and socioeconomic status. There were differences in birth history, developmental milestones, I.Q., and neurological findings between patients with family history and no family history of TS. CONCLUSIONS: Our findings support the need for testing the hypothesis of a multidetermined origin of TS, a disorder in which hereditary, neuropsychological, and environmental factors play a role.

Adolescent↗
PubMed1998

Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention.

OBJECTIVE: To determine the effect of longterm methotrexate (MTX) therapy and folic acid supplementation on folate nutriture and homocysteine levels in patients with rheumatoid arthritis. METHODS: A double blind, placebo controlled trial lasting one year was conducted at one academic medical center. A total of 79 patients taking low dose MTX were followed up to one year. The patients were randomized to receive placebo or 5 or 27.5 mg folic acid supplementation per week. RESULTS: Plasma and erythrocyte folate levels and plasma homocysteine levels were determined. The folate nutriture of patients taking low dose MTX declined without folic acid supplementation. Plasma homocysteine levels increased significantly over a one year period in the placebo group. Low folate nutriture and hyperhomocysteinemia occurred with greater frequency in the placebo group than in the folic acid supplemented groups. CONCLUSION: For longterm, low dose MTX therapy, there are now at least 3 reasons to consider supplementation with folic acid (a low cost prescription): (1) to prevent MTX toxicity, (2) to prevent or treat folate deficiency, and (3) to prevent hyperhomocysteinemia, considered by many investigators to be a risk factor for cardiovascular disease.

Adult↗
PubMed1997

Nutrient intake patterns, body mass index, and vitamin levels in patients with rheumatoid arthritis.

OBJECTIVE: To assess nutrient intakes and vitamin levels in 79 patients with rheumatoid arthritis participating in a trial and to determine whether changes in body mass index were associated with changes in disease activity. METHODS: This study evaluated baseline vitamin levels, 1-day dietary intakes, and weight every 3 months for 1 year. Linear regression analysis was used to evaluate the relationship of time to body mass index. Analysis of covariance was used to determine if body mass index, time, or treatment had an effect on disease activity. RESULTS: Deficient vitamin levels and poor nutrient intake patterns were prevalent in the study population. Changes in body mass index over time did not correlate with changes in disease activity. CONCLUSIONS: Rheumatoid arthritis patients are at high risk of obesity, abnormal vitamin levels, and poor nutrient intakes. Changes in body mass index failed to correlate with changes in disease activity.

Arthritis, Rheumatoid↗
PubMed1997

The use of an enteral expert system in the prescription of enteral formulas in a university hospital.

A personal computer-based expert system has been developed for the prescription of enteral formulas based on patient-need characteristics. Two hundred twelve inpatients in a university hospital setting were prospectively evaluated to compare the identity and cost of the enteral formula prescribed by the expert system with the identity and cost of the enteral formula prescribed by the ward team. Two hundred seven patients had complete data to allow analysis. There was a mean cost savings (+/-SD) of $1.18 +/- 7.69/d for each patient using the expert system compared with the MD-prescribed formula (P = 0.023). We project that the use of this program would save $27,564/y in our hospital (an average of 23,360 patient/days of enteral feeding per year). We conclude that the use of an expert system can be cost-effective in the prescription of enteral formulas for hospitalized patients.

Adult↗
PubMed1997

Nutrition coverage on medical licensing examinations in the United States.

The 1985 National Academy of Sciences report Nutrition Education in US Medical Schools recommended that the National Board of Medical Examiners (NBME), who develops the US Medical Licensing Examination (USMLE), cover basic nutrition knowledge. According to the NBME, the USMLE includes nutrition on their Step 1 and 2 exams; however, this coverage has been questioned. To document whether the NBME adequately addresses nutrition, the 1986 Part I and Part II and the 1993 Step 1 and step 2 exams, which replaced the Part I and II exams, were reviewed by five nutrition professionals. This review identified the nutrition-related areas of the two-part exams and how the extent of nutrition coverage changed from 1986 to 1993. Nutrition items were coded on four dimensions: 1) specific nutrition-related topic area, 2) normal or abnormal scenario, 3) related organ system, and 4) importance in clinical medicine. The percentage of nutrition-related items, as identified by the nutrition professionals, increased from 9% on the 1986 Part I exam to 11% on the 1993 Step 1 exam and from 6% on the 1986 Part II exam to 12% on the 1993 Step 2 exam. The percentage of nutrition items related to vitamin deficiencies increased from 1986 to 1993 on both halves of the exam. Nutrition coverage on the USMLE Step 1 and Step 2 seems adequate in amount, however, the content and appropriateness of the items were not evaluated. The observed increased focus on vitamin deficiencies should be further considered.

Education, Medical, Undergraduate↗
PubMed1995

Cofactor role for 10-formyldihydrofolic acid.

10-Formyl-7,8-dihydrofolic acid (10-HCO-H2folate) was prepared by controlled air oxidation of 10-formyl-5,6,7,8-tetrahydrofolic acid (10-HCO-H4folate). The UV spectra of the 10-HCO-H2folate preparation has lambda max. 234, 333 nm and lambda min. 301 nm at pH 7.4, and lambda max. 257, 328 nm and lambda min. 229, 307 nm at pH 1. 1H-NMR spectroscopy of 10-HCO-H2folate (in 2H2O; 300 MHz) suggested a pure compound and gave resonances for one formyl group proton, two protons on C-7 and C-9, and no evidence for a C-6 proton, which is consistent with the structure proposed. The spectral properties indicated that the 10-HCO-H2folate preparation is not appreciably contaminated with 10-HCO-H4folate, 5,10-methenyltetrahydrofolic acid (5,10-CH = H4folate) or 10-formylfolic acid (10-HCO-folate). The above data establish that the 10-HCO-H2folate prepared here is authentic. In contrast, a folate with a UV spectrum having lambda max. 272 nm and lambda min. 256 nm at pH 7, which was prepared by 2,6-dichloro-indophenol oxidation of 10-HCO-H4folate and reported to be 97% pure [Baram, Chabner, Drake, Fitzhugh, Sholar and Allegra (1988) J. Biol. Chem. 263, 7105-7111], is apparently not 10-HCO-H2folate. 10-HCO-H2folate is utilized by Jurkat-cell (human T-cell leukaemia) and chicken liver aminoimidazolecarboxamide ribonucleotide transformylase (AICAR T'ase; EC 2.1.2.3) in the presence of excess 5-amino-imidazole-4-carboxamide ribotide (AICAR) resulting in the appearance of approximately 1 mol of H2folate product for each mol of AICAR formylated. The present 10-HCO-H2folate preparation had a kinetic advantage over 10-HCO-H4folate resulting from a difference of approx. 5-fold in K(m) values when both folates were used as cofactors for Jurkat-cell and rat bone marrow AICAR T'ase. No substantial kinetic advantage was observed using chicken liver AICAR T'ase. 10-HCO-H2folate had little or no activity with Jurkat-cell or chicken liver glycinamide ribonucleotide transformylase (GAR T'ase, EC 2.1.2.2). The existence in vivo of 10-HCO-H2folate is suggested in mammals by several reports of detectable amounts of radiolabelled 10-HCO-folate in bile and urine after administration of radiolabelled folic acid.

Acyltransferases↗
PubMed1995

Adverse events in methotrexate-treated rheumatoid arthritis patients.

Methotrexate (MTX) is an antifolate that has been in use for the treatment of rheumatoid arthritis (RA) since the early 1980s. Its efficacy has been clearly documented [1-4] and its administration early in the course of the disease is now generally accepted [5]. Side-effects from low weekly pulse MTX have been reported [1-6] and it was our initial experience that toxicity, rather than lack of efficacy, was the major factor limiting its clinical use [7]. However, when compared with other disease-modifying antirheumatic drugs, its toxicity appears to be comparable to that of antimalarials [8, 9]. The purpose of this paper is to discuss the possible mechanisms responsible for toxicity due to MTX used at low weekly pulse doses for the treatment of RA, as well as the different toxic manifestations reported in the literature.

Antirheumatic Agents↗
PubMed1994

Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial.

OBJECTIVE: To determine the effect of two different weekly doses of folic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo-controlled study. PATIENTS: 79 persons between 19 and 78 years of age who fulfilled the American Rheumatism Association's criteria for rheumatoid arthritis. INTERVENTION: Participants were randomly assigned to visually identical placebo or to 5 mg or 27.5 mg of folic acid each week. MEASUREMENTS: Duration, intensity, and clinical severity of toxic events; efficacy (indices of joint tenderness and swelling and grip strength); plasma and erythrocyte folate levels; and other laboratory variables. RESULTS: Folic acid supplementation at either dose did not affect the efficacy of methotrexate therapy as judged by joint indices and patient and physician assessments of disease. Patients given folic acid supplements had lower toxicity scores than did participants given placebo (P < or = 0.001). Low blood folate levels and increased mean corpuscular volumes were associated with substantial methotrexate toxicity, whereas daily dietary intakes of more than 900 nmol (400 micrograms) of folic acid were associated with little methotrexate toxicity. CONCLUSIONS: Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis who are taking methotrexate from toxicity while preserving the efficacy of methotrexate.

Adult↗
PubMed1994

Differences in methotrexate and 7-hydroxymethotrexate inhibition of folate-dependent enzymes of purine nucleotide biosynthesis.

7-Hydroxymethotrexate (7-OH-MTX) is the major and, frequently the only, pteridine metabolite found in bone-marrow aspirates of patients chronically treated with low-dose oral methotrexate (MTX) [Sonneveld, Schultz, Nooter and Hahlen (1986) Cancer Chemother. Pharmacol. 18, 111-116]. The Ki values for MTX and 7-OH-MTX for avian liver 5-amino-imidazole-4-carboxamide ribonucleotide transformylase differ by 4.5-fold in favour of 7-OH-MTX as the better inhibitor, while Ki values for avian liver glycinamide ribonucleotide transformylase differ by 1.9-fold favouring MTX as the better inhibitor. Thus 7-OH-MTX possesses a different enzyme-inhibiting repertoire from its parent drug and this information may be useful in explaining the mechanism of action of low-dose MTX therapies used to treat autoimmune disease.

Acyltransferases↗
PubMed1993

Modification of a high-performance liquid chromatographic method for assay of homocysteine in human plasma.

A modification of a previously published method for analysis of total homocysteine in human serum is presented. The modification was implemented to allow use of a different derivatizing agent (i.e., 7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonamide) which reacts much faster than the original derivatizing reagent and at a lower temperature. Shorter reaction time and lower temperature lead to less destruction of some biological thiols. In order to retain an isocratic mobile phase with the new derivatizing agent, a different concentration of acetonitrile was found that affords a 7-8 min retention time.

Chromatography, High Pressure Liquid↗