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Biomedical subjects

R H Glew

Publications and source records attributed to R H Glew.

At least 73 records · Page 4Linked to original sources

Decreased polyunsaturated fatty acids in sickle cell anaemia.

The purpose of this study was to determine if the growth retardation often associated with sickle cell anaemia could be related in part to a deficiency of essential fatty acids. We reported recently that children with sickle cell disease in Jos, Nigeria have lower levels of serum amino acids and higher levels of urinary amino acids than their healthy counterparts. In the current study, we determined that the serum phospholipids of children with sickle cell anaemia did not deviate in the proportions of the essential fatty acids, linoleic and alpha-linolenic they contain compared to controls. However, their serum phospholipid profiles were significantly different in the proportions of four other fatty acids. Specifically, the phospholipids of children with sickle cell anaemia contained 19 per cent more palmitic acid (P = 0.006), 22 per cent more oleic acid (P = 0.014), 18 per cent less arachidonic acid (P = 0.008), 51 per cent less eicosapentaenoic acid (P = 0.0008), and 43 per cent less decosahexaenoic acid (P = 0.001). These data show that children with sickle cell anaemia are not deficient in essential fatty acids, but that the fatty acid elongation and desaturation pathway is somehow disturbed in this disease.

Anemia, Sickle Cell↗

Lysosomal enzymuria in protein energy malnutrition.

Protein energy malnutrition (PEM) is common in underprivileged populations in many parts of the world and results from diets deficient in protein (kwashiorkor) or protein and calories (marasmus). The literature documents renal tubular abnormalities in children with PEM. In PEM the reabsorption of amino acids and phosphate is defective. In many kidney disorders in which renal tubular function is impaired (e.g., diabetes, preeclampsia, nephrotic syndrome, sickle cell anemia), lysosomal enzymuria ensues. We compared the urinary excretion of the following five lysosomal enzymes in 31 Nigerian children with marasmus, kwashiorkor, or marasmic-kwashiorkor: beta-hexosaminidase, alpha-galactosidase, beta-galactosidase, beta-glucuronidase, and alpha-mannosidase. All of the protein energy malnourished children and the 18 age- and gender-matched controls were from the city of Jos, located in central Nigeria. In the severely malnourished children, the urine levels of all five lysosomal enzymes (expressed as units of enzyme activity per mg creatinine) were markedly increased. The greatest increases were seen with beta-hexosaminidase (16-fold) and beta-glucuronidase (14-fold). Routine clinical analyses also revealed that, relative to the control population, the sera of the 14 most severely malnourished patients contained 2- to 5-fold more vitamin B12 and markedly reduced levels (15%, p < 0.00001) of calcium. These data are significant in that they document lysosomal enzymuria in Nigerian children with severe PEM and point to the potential diagnostic utility of the urinary beta-galactosidase determination for assessing renal function in children with this disorder.

Child, Preschool↗

Rickets and protein malnutrition in northern Nigeria.

The aim of the study was to explore the relationship between protein nutritional status and the development of rickets in children living in northern Nigeria. The diagnosis of rickets in 16 children between the ages of 10 months and 7 years was confirmed using established, and recently developed clinical and biochemical parameters. Twenty-seven children devoid of skeletal stigmata were age- and sex-matched to the rachitic patients. A battery of clinical laboratory and anthropometric measurements designed to assess calcium homeostasis, skeletal growth, the extent of bone remodeling or resorption, and protein nutritional status were performed on all subjects. Our central finding was that although the rachitic children were moderately malnourished, their protein nutritional status was significantly better as measured by the serum prealbumin concentration (15.4 v. 12.5 mg/dl, P = 0.0012) when compared with the severely malnourished children who were devoid of any indication of rickets. This may be due, in part, to the fact that actively growing children are more likely to develop rickets than are children whose linear growth is impeded. Unexpectedly, we found that the mean concentrations of serum 1,25-dihydroxyvitamin D in both the rachitic and control group were higher than any values for the active vitamin D metabolite previously reported in the literature.

Albumins↗

Serum and urinary amino acid levels in sickle cell disease.

Neonates with sickle cell disease (SCD) are of normal size at birth in terms of height and weight. However, by the sixth month of life their growth begins to lag significantly behind that of non-sicklers. We hypothesize that such growth retardation could be explained, at least in part, by the increased excretion of free amino acids in the urine of children with SCD. It is well established that in SCD there are abnormalities in the proximal tubules where amino acids are reabsorbed. We collected serum and urine samples from 13 patients with SCD (age range, 10 months to 14 years), and 17 age-and gender-matched controls, and analysed these specimens for free amino acids and creatinine. The SCD population was less well nourished than the controls, as evidenced by the lower serum prealbumin levels in the former group (91.3 v. 127 mg/l, P = 0.01). The serum concentrations of all of the essential amino acids were significantly reduced (21-47 per cent, P < 0.01) in the SCD subjects, as were those of most of the non-essential amino acids (exceptions: alanine, glutamic acid, proline). The urine concentrations of seven of the essential amino acids (indexed to creatinine) were increased in the SCD children. The greatest difference in urinary amino acid excretion was seen with methionine; the SCD subjects excreted 3.6-fold more methionine than the controls. These data indicate that reduced levels of serum amino acids resulting from increased urinary loss of these amino acids in children with SCD could contribute to the decreased growth rates one sees in children with this genetically inherited hematologic disorder.

Amino Acids↗

Relationship between students' performances on the NBME Comprehensive Basic Science Examination and the USMLE Step 1: a longitudinal investigation at one school.

PURPOSE: To examine students' growth in basic science knowledge during medical school and to evaluate the accuracy of students' scores on the National Board of Medical Examiners Comprehensive Basic Science Subject Examination (CBSE) as predictors of their performances on Step 1 of the United States Medical Licensing Examination (USMLE). METHOD: A public medical school in the southwestern United States evaluated 58 students from the entering class of 1993 by administering the CBSE in April 1994, December 1994, and February 1996. These students then sat for the USMLE Step 1 in June 1996. For each CBSE administration, descriptive statistics were calculated and least-squares regression analyses were performed to predict the students' Step 1 scores from their CBSE scores. RESULTS: The students' CBSE scores improved as they progressed through their basic science course work and clinical clerkships. The strongest correlation (r = .85) between the students' CBSE scores and their Step 1 scores was for the second CBSE administration; the weakest correlation (r = .73) was for the first CBSE administration. CONCLUSION: These results indicate that basic science knowledge continues to grow throughout the first three years of medical school and that the CBSE is a useful tool for the identification of students at risk for failing the USMLE Step 1.

Curriculum↗

Effect of zinc concentration in Mueller-Hinton agar on susceptibility of Pseudomonas aeruginosa to imipenem.

The susceptibility of Pseudomonas aeruginosa to imipenem has been shown to vary according to zinc concentration in the media. MICs of imipenem for 68 unique clinical isolates of P. aeruginosa were determined in media supplemented with zinc at concentrations between 0.5 and 6.0 micrograms/ml. In agar containing up to 3 micrograms of zinc/ml, 75 to 82% of the strains were susceptible to imipenem at an MIC of < or = 4 micrograms/ml. In agar supplemented to contain 6 micrograms of zinc/ml, however, only 40% of the strains were susceptible to imipenem. Manufacturers should ensure that the concentration of zinc in commercial media is below 3 micrograms/ml to avoid false classification of isolates as resistant to imipenem.

Agar↗

Kidney and breast cysts: a comparative study of fluids.

The contributions of amino acids to the overall osmotic activity of cyst fluids were sought in this comparative study of fluids from the cysts of autosomal dominant polycystic disease (ADPKD) and gross cystic disease of the breast (GCDB). Fluids (n = 18) from 18 women with GCDB and from 8 patients with ADPKD (n = 25), grouped on the basis of sodium concentrations, were analyzed for potassium, chloride, protein, and osmolality by routine methods and for amino acids by reversed-phase high-pressure liquid chromatography. Similarities between kidney and breast cyst fluids included relative isosmolality, a wide range of sodium concentrations, an inverse relationship between sodium and potassium concentrations, higher concentrations of amino acids in low-sodium fluids, and significant correlations between sequential concentrations of amino acids in cyst fluids versus blood and some of its components. Therefore, cyst fluids in ADPKD and GCDB share compositional characteristics, and amino acids, possibly of blood protein origin, accumulate in small but osmotically significant amounts in some, particularly low-sodium, cysts of kidney and breast.

Amino Acids↗

Calcium and vitamin D status of pregnant teenagers in Maiduguri, Nigeria.

This study investigates parameters related to calcium and bone metabolism by determining the concentrations of total calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, and phosphorous in young pregnant women. The patient population was 30 pregnant Nigerian teenage women grouped by trimester (10 per group), 10 women immediately following delivery, and 21 healthy age-matched controls. On the basis of serum prealbumin levels, the general nutrition of the pregnant women was found to be significantly below that of the more privileged and better-educated nonpregnant controls. The mean total calcium concentration in sera of the third-trimester women was 8.83 mg/dL, which was significantly below that of the controls (9.77 mg/dL) and the first-trimester group (9.30 mg/dL). Despite the 10% to 15% decline in the serum level of total calcium during pregnancy, the parathyroid hormone level decreased markedly from 0.60 to 0.61 ng/mL in the first and second trimesters to 0.41 ng/mL in the third trimester. Serum vitamin D and 1,25-dihydroxyvitamin D levels in the second and third trimesters were within the normal range. These data indicate that toward the end of gestation, pregnant teenagers in northern Nigeria appear to become calcium deficient and do not exhibit the expected increase in serum parathyroid hormone levels normally seen in pregnant women.

Adolescent↗

Primary structure of the cytosolic beta-glucosidase of guinea pig liver.

The cytosolic beta-glucosidase (EC 3.2.1.21) present in the livers of mammalian species is distinguished by its broad specificity for sugars and its preference for hydrophobic aglycones. We purified the cytosolic beta-glucosidase from guinea pig liver and sequenced 142 amino acid residues contained within 12 trypsin digest fragments. Using degenerate oligonucleotide primers deduced from the peptide sequences, a 622 bp cytosolic beta-glucosidase cDNA was amplified by reverse-transcriptase PCR, using total guinea pig liver RNA as template. The 'rapid amplification of cDNA ends (RACE)' method [Frohman (1993) Methods Enzymol. 218, 340-356] was used to synthesize the remaining segments of the full-length cDNA. The complete cDNA contained 1671 nucleotides with an open reading frame coding for 469 amino acid residues. The amino acid sequence deduced from the cDNA sequence included the amino acid sequences of all 12 trypsin digest fragments derived from the purified enzyme. Amino acid sequence analysis indicates that the guinea pig liver cytosolic beta-glucosidase is a Family 1 beta-glycosidase and that it is most closely related to mammalian lactase-phlorizin hydrolase. These results suggest that the cytosolic beta-glucosidase and lactase-phlorizin hydrolase diverged from a common evolutionary precursor.

Amino Acid Sequence↗

Glycohydrolases as markers of hepatic ischemia-reperfusion injury and recovery.

Advances in liver surgery and transplantation have lead to a steady increase in the number of these interventions. Prompt quantitative assessment of hepatic of hepatic function and a patient's subsequent morbidity and mortality following surgery remain difficult despite the currently utilized historic markers of hepatic parenchymal injury (e.g., aspartate transaminase [AST], lactate dehydrogenase [LDH] gamma-glutamyl transpeptidase [GGT]). Increases in serum glycohydrolase activities appear to provide sensitive and quantitative markers of hepatic ischemia/reperfusion injury. In 10 male swine (25 to 35 kg body weight) following 30, 45, and 90 minutes of acute hepatic ischemia, the systemic release of eight different glycohydrolases and lipid peroxides into serum were determined and compared with pre- and postischemic serum levels of LDH, GGT, and AST. The rapid release of glycohydrolases into serum was directly proportional to the length of the ischemic period from 30 to 90 minutes; e.g., beta-glucosidase, mean 1.9-fold increase at 30 minutes; 8.3-fold at 45 minutes; and 22.8-fold at 90 minutes; P < .002) and the activities peaked within the first 3 hours postischemia. In constrast, AST, LDH, and GGT were released slowly and peaked 20 to 30 hours after hepatic blood flow was restored. In swine with fatal outcomes (90 minutes of ischemia), all enzyme levels increased continuously during the final hours of life. However, in swine that survived hepatic ischemia/reperfusion injury (45 minutes of ischemia) the glycohydrolases, but not AST, LDH, and GGT, declined after 2 to 3 hours' postischemia and the serum lipid peroxide levels followed the same pattern. Serum beta-galactosidase and beta-glucosidase levels are sensitive markers that rise as quickly as traditional enzyme markers (AST, LDH, GGT) following hepatic ischemic injury; moreover, the glycohydrolases have the added value of serving as predictors of survival.

Acid Phosphatase↗

Lysosomal enzymuria in preeclampsia.

We hypothesize that the preeclamptic patient has proximal tubule epithelial injury, which leads to the release of lysosomal enzymes, and that the excretion of these enzymes might serve as a diagnostic or predictive marker in preeclamptic women. The study group consisted of 14 women with preeclampsia (10 severe and 4 mild, as defined by The American College of Obstetricians and Gynecologists criteria) and 28 normotensive controls with singleton pregnancies at 27 to 41 weeks. There were no significant differences between the two groups for gestational age, maternal age, or race. Maternal serum and urine specimens were prospectively obtained and analyzed for beta-glucuronidase, beta-hexosaminidase, alpha-galactosidase, beta-galactosidase, and alpha-mannosidase using fluorometric assays. Median serum and urine activities and fractional excretions of each of the five hydrolases were compared between the two study groups using the Mann-Whitney two-sample rank test. The serum enzyme activities of beta-hexosaminidase (P = 0.002), alpha-galactosidase (P = 0.0001), and alpha-mannosidase (P = 0.02) were significantly lower in preeclamptic patients than in controls. The urine enzyme activities of beta-glucuronidase (P = 0.001), alpha-galactosidase (P = 0.002), beta-galactosidase (P 0.0003), and alpha-mannosidase (P = 0.003) were significantly higher in the preeclamptic patients. The fractional enzyme excretions of all five lysosomal hydrolases were higher in preeclamptic patients than in controls with P < or = 0.0003 for each enzyme. Preeclampsia is associated with a significant decrease in serum activities of three of the five hydrolases studied, a significant increase in urine enzyme activities in four of the five hydrolases studied, and a significant increase in the fractional excretion of all five lysosomal hydrolases.

Adolescent↗

Serum vitamin A, vitamin E, and beta-carotene levels in preeclamptic women in northern nigeria.

We compared the serum levels of beta-carotene, vitamin A (retinol), and vitamin E (alpha-tocopherol) in healthy pregnant women and their counterparts who exhibited the signs and symptoms of preeclampsia or eclampsia, including: systolic blood pressure greater than 160 mm Hg, edema, and proteinuria. The study was conducted in the cities of Maiduguri and Bauchi, which are located in the semi-arid northeastern region of Nigeria. Most of the pregnant subjects: (1) were teenagers, though they ranged in age from 14 to 25 years; (2) had 2 or fewer prior pregnancies; and (3) were predominantly of the Muslim faith and members of the Hausa, Fulani, or Kanuri ethnic groups. Few of the women had received prenatal care. Serum levels of vitamins A and E and betacarotene were quantified using high pressure liquid chromatography. The serum vitamin A levels of the 9 preeclamptic women (15.3 mg/dL) and the 7 eclamptic women (8.3 mg/dL) were significantly reduced (p < 0.01) relative to the serum vitamin A levels of healthy women in the third trimester (24.2 mg/dL). For the healthy pregnant controls, the levels of vitamins A and E and beta-carotene were relatively constant throughout pregnancy. The mean serum beta-carotene levels for both the preeclamptic and eclamptic groups of subjects were half as high as those of healthy control women in the third trimester (p = 0.004). The serum vitamin E levels of the preeclamptic and eclamptic women were 15% and 30% lower, respectively, than those of the corresponding controls (p < 0.01). The serum levels of these three lipids in the healthy pregnant and non-pregnant women we studied are similar to values reported by others for North American and European women of childbearing age. These results support the hypothesis that preeclampsia-eclampsia deplete natural lipid antioxidants and suggest that the reduced levels of vitamin A in such women experiencing hypertension of pregnancy, if they happen to be infected with the HIV-1 virus, may place them at increased risk for mother-child transmission of the virus.

Adolescent↗

Serum beta-carotene deficiency in HIV-infected children.

Representative levels of serum micronutrients specifically, beta-carotene and vitamins A and E, were studied in symptomatic human immunodeficiency virus (HIV)-infected children. The nutritional status of 23 symptomatic African-American and Hispanic HIV-infected children were compared with an appropriate control group comprised of 36 uninfected children matched for age and sex, using body mass index. Serum beta-carotene and vitamin A and E levels were randomly determined on 15 of the infected children. Beta-carotene concentration was 4.9-fold reduced in symptomatic HIV-infected children when compared with the control group. There was a 6.5-fold decrease in the serum level for children without acquired immunodeficiency syndrome (AIDS) and a 13-fold reduction in children with AIDS. No differences in the mean values for serum vitamins A and E were observed in the groups studied. Although the nutritional status of the symptomatic HIV-infected children was not different from that of the control population, their serum beta-carotene levels were profoundly deficient. This finding may have immunologic and clinical implications for children with rapidly progressing HIV disease.

Acquired Immunodeficiency Syndrome↗

Effects of oligosaccharide binding on glycogen debranching enzyme activity and conformation.

Glycogen debranching enzyme contains two catalytic activities (4-alpha-glucanotransferase and amylo-1,6-glucosidase) on its single polypeptide chain, and they are affected differently by the binding of oligosaccharides. Glucose, maltose, and maltotriose are competitive inhibitors of the amylo-1,6-glucosidase activity measured by the hydrolysis of alpha-glucosyl fluoride, whereas saccharides with four or more glucose units are activators of the same activity, showing apparent "uncompetitive" kinetics. This suggests that they do not bind until the alpha-glucosyl fluoride is bound. In either case the potency of the effect increases with the length of the oligosaccharide chain. On the other hand, all oligosaccharides tested (maltose to maltohexaose, alpha-cyclodextrin, and beta-cyclodextrin) are competitive inhibitors of the transferase activity and also cause a decrease in the intrinsic fluorescence, both functions again increased by chain length, thus indicating that these saccharides do bind to the free enzyme. These interesting results can be reconciled if the extended main chain resulting from the transferase reaction has to be reoriented into a different binding mode in order to position the alpha-1,6-linked side-chain glucose into the correct position for the glucosidase reaction. Therefore, activating oligosaccharides behave kinetically as if they had not been previously bound. It is concluded that the main chain of the natural limit dextrin substrate has a different mode of binding for the two catalytic reactions in order to position properly first the maltotetraosyl side chain in the transferase catalytic site and then the glucosyl side chain in the glucosidase catalytic site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serum levels of the pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin in rachitic children in Nigeria.

OBJECTIVES: We measured the levels of the pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) in the serum of 12 rachitic and 27 healthy Nigerian children, and compared the performance of these relatively new markers of bone metabolism with established laboratory parameters of skeletal disease. DESIGN AND METHODS: Active rickets was diagnosed on the basis of clinical and biochemical criteria. Serum calcium and phosphorus concentration and alkaline phosphatase activity were determined using clinically accepted methods. Radioimmunoassay was performed to quantify parathyroid hormone, 1-,25-dihydroxyvitamin D, OC, and ICTP. RESULTS: The rachitic children had statistically significant serum elevations of ICTP and osteocalcin as compared with age- and sex-matched controls. Serum levels of ICTP correlated with alkaline phosphate activity. CONCLUSIONS: As a marker of abnormal bone metabolism, ICTP performs at least as well as alkaline phosphate. ICTP and OC are valuable additions to the growing repertoire of bone markers.

Age Factors↗

Decreased urinary excretion of beta-glucuronidase in sickle cell anemia in Nigeria.

The activities of five lysosomal hydrolases--namely beta-glucuronidase, beta-hexosaminidase, beta-galactosidase, alpha-galactosidase, and alpha-mannosidase--were measured in the plasma and urine of children (ages, 7 to 15 years) with sickle cell anemia (n = 11) and controls (n = 11) from Jos, Nigeria. The presence of SS hemoglobin was confirmed by electrophoresis of red cell hemolysates. Albuminuria was absent in all of the patients with sickle cell anemia. The creatinine-indexed urinary activity level (units of enzyme activity/milligrams creatinine) and the fractional enzyme excretion (FEE) value, which is defined as the ratio of enzyme clearance to creatinine clearance, were determined for each of the five lysosomal enzymes and compared between the two groups. The mean FEE values for beta-glucuronidase and alpha-galactosidase in the sickle cell patients were 10- and 3.5-fold lower, respectively, than the corresponding control values, and these differences were statistically significant (p < .03) for both enzymes; however, beta-hexosaminidase, beta-galactosidase, and alpha-mannosidase levels in urine were not different between the two groups. When indexed to creatinine, a comparison of the urinary enzyme levels of control and sickle cell patients showed significant differences for beta-glucuronidase (p < .01) and alpha-galactosidase (p < .05) but not for the other three enzymes. Differences in level of plasma enzyme activity between control and sickle cell patients were not significant, except for alpha-galactosidase (p < .05), which was increased slightly (25%) in the sickle cell group. These data indicate that there may be abnormalities in the metabolism of lysosomal enzymes in the kidneys of patients with sickle cell anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗