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Biomedical subjects

N Rifai

Publications and source records attributed to N Rifai.

At least 127 records · Page 7Linked to original sources
PubMed1996

Failure of current guidelines for cholesterol screening in urban African-American adolescents.

OBJECTIVE: The National Cholesterol Education Program (NCEP) and the American Academy of Pediatrics recommend selective screening to detect children and adolescents with hypercholesterolemia. We compared the effectiveness of these guidelines with other potential screening strategies in urban African-American adolescents. SUBJECTS AND METHODS: Two hundred sixty African-American adolescents and young adults (192 females and 68 males; age range, 12 to 20 years) who were free from illnesses or medications that disrupt lipid metabolism were included in the study. Participants completed a questionnaire regarding their smoking habits, blood pressure, contraceptive pill use, and family history of early heart disease and high cholesterol and had their blood lipids, lipoproteins, and apolipoproteins measured (152 fasting and 108 nonfasting). RESULTS: Nineteen percent of participants reported family histories of hypercholesterolemia; 26% reported family histories of premature heart disease; and 8% had family histories of both hypercholesterolemia and premature heart disease. Therefore, 37% of these participants would have been targeted for cholesterol screening, compared with the 25% predicted by the NCEP. Less than 50% of the participants with low-density lipoprotein cholesterol (LDL-C) levels greater than 110 or 130 mg/dL would have been detected by selective screening. Total cholesterol was superior as a screening test to apolipoprotein B in predicting LDL-C levels greater than 110 mg/dL (sensitivity, 92% vs 59%). However, total cholesterol minus high-density lipoprotein cholesterol showed better positive predictive value (100%) at LDL-C levels greater than 110 mg/dL than total cholesterol in the fasting (80%) and total groups (90%). CONCLUSIONS: In this population, selective screening with total cholesterol, as recommended by the NCEP, has such poor sensitivity and positive predictive value that other options may be superior. As an alternative, we recommend the measurement of high-density lipoprotein cholesterol together with total cholesterol at the initial screening step in adolescents and universal screening for those older than 16 years to capture a greater proportion of young adults with increased LDL-C. Furthermore, we recommend using the less stringent treatment guidelines established by the Adult Treatment Panel II for premenopausal women and men younger than 35 years for older adolescents and young adults.

Adolescent↗
PubMed1996

Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.

High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

Adolescent↗
PubMed1995

Prolonged survival in pyruvate carboxylase deficiency: lack of correlation with enzyme activity in cultured fibroblasts.

OBJECTIVE: To report the clinical history and laboratory evaluation of a patient presenting with lactic acidosis secondary to pyruvate carboxylase deficiency. METHODS AND RESULTS: Enzyme analysis of cultured skin fibroblasts revealed 2-5% of normal pyruvate carboxylase activity. Although most patients with this condition die in early infancy, this child has survived to age 8-1/2 years, with only occasional episodes of metabolic acidosis, usually responding rapidly to intravenous hydration and bicarbonate. Despite having a seizure disorder and moderate mental retardation, he continues to thrive and make progress in his acquisition of motor and language skills. Of the 35 patients described in the literature with pyruvate carboxylase deficiency, only two other patients have lived beyond 5 years of age. CONCLUSION: There does not seem to be a correlation of prolonged survival with residual pyruvate carboxylase activity on assay of cultured fibroblasts. Possible explanations for this patient's prolonged survival include tissue heterogeneity, increased residual enzyme activity in vivo, or partial stabilization of the enzyme by supplemental biotin.

Acidosis, Lactic↗
PubMed1995

Evaluation of the APEC analyzer for whole blood glucose. Testing in a pediatric setting.

The APEC glucose analyzer (APEC, Danvers, MA) was analyzed in a pediatric clinical chemistry laboratory and its performance was compared with glucose determinations on the YSI 2300 STAT analyzer (Yellow Springs Instrument [YSI], Yellow Springs, OH). One hundred sixty-nine samples were simultaneously analyzed by the APEC and the YSI systems. The agreement between the two analyzers was excellent, with r = 0.986, slope = 1.04, and y intercept = -0.094. Analysis of the run-to-run precision yielded a CV of < or = 4.1% for both the APEC and the YSI instruments. Both analyzers displayed a sensitivity to at least 1.1 mmol/L (20 mg/dL) and both produced a linear response up to 27.8 mmol/L (500 mg/dL). Neither instrument was affected by icteric or hemolyzed samples. Variations in the patient's hematocrit did not lower the whole blood glucose values when these were compared with the equivalent plasma levels. In conclusion, the APEC glucose analyzer is suited for whole blood glucose testing in pediatric settings.

Blood Chemical Analysis↗
PubMed1995

A high-performance liquid chromatographic assay for the determination of itraconazole concentration using solid-phase extraction and small sample volume.

Itraconazole has been shown to be highly effective against a broad spectrum of fungi, particularly aspergillus. In order to achieve the desired pharmacological effect, the itraconazole plasma concentration should be > 250 ng/ml. We developed a high-performance liquid chromatography assay for the rapid determination of plasma itraconazole concentration using solid-phase extraction and small sample volume. The assay possessed linearity up to 5,000 ng/ml, sensitivity of 50 ng/ml, average recovery of 100.8%, and run-to-run precision (n = 10) for concentrations of 100, 200, and 500 ng/ml of 12, 6.6, and 5.8%, respectively. Furthermore, the assay proved to be free of interference from 48 commonly prescribed and some over-the-counter medications. We conclude that the method described here is ideally suited for the therapeutic monitoring of itraconazole.

Acetonitriles↗
PubMed1995

Assessment of the immunoreactivity of digoxin metabolites and the cross-reactivity with digoxin-like immunoreactive factors in the Roche-TDM ONLINE digoxin assay.

Immunoassays for digoxin measurement have long had the problem of low specificity. Antisera used in these assays may not only measure digoxin and the active metabolites but also cross-react with the noncardioactive metabolites and digoxin-like immunoreactive factors (DLIFs). In this study, we describe the analytical performance of the newly introduced Roche-TDM ONLINE digoxin assay on the COBAS FARA II centrifugal analyzer. The assay possessed linearity up to 5.0 ng/ml, sensitivity of 0.19 ng/ml, average recovery of 100.4%, and day-to-day variability of < 6%. The assay demonstrated no cross-reactivity with DLIFs or spironolactone and its metabolites and negligible reactivity with the digoxin noncardioactive metabolites. In addition, the immunoreactivity of the digoxin active metabolites reflected their cardioactivity. We conclude that the Roche-TDM ONLINE digoxin assay is highly specific and precise and suitable for the therapeutic monitoring of this drug.

Antibodies, Monoclonal↗
PubMed1995

Oral administration of clotrimazole and blockade of human erythrocyte Ca(++)-activated K+ channel: the imidazole ring is not required for inhibitory activity.

The Ca(++)-activated K+ (Gardos) channel of erythrocytes plays a crucial role in K+ loss and dehydration of sickle erythrocytes; a potential therapeutic strategy would be to prevent dehydration by specifically blocking this channel. The authors report here on the activity of the clotrimazole (CLT) metabolite, 2-chlorophenyl-bis-phenyl-methanol, which accounts for a portion of the blockade of the erythrocyte Gardos channel when CLT is given orally to normal volunteers. Administration of a single oral dose of 1 g of CLT to four normal healthy volunteers (approximately 15 mg/kg of body weight) resulted in 51% to 92% peak inhibition of the Gardos channel measured in whole blood 2 to 4 hr later. Inhibition remained detectable for 24 to 34 hr. Inhibition of the Gardos channel correlated best with the summed levels of CLT plus its two major metabolites (P < .002; apparent IC50 = 0.65 +/- 0.19 microM). In vitro experiments with 2-chlorophenyl-bis-phenyl-methanol revealed dose-dependent inhibition of K transport and displacement of specifically bound 125I-charybdotoxin. Thus, the imidazole ring of CLT, which is required for antimycotic activity and associated with most of the historically observed toxicity, is not necessary for inhibition of the Gardos channel.

Administration, Oral↗
PubMed1995

HPLC measurement, blood distribution, and pharmacokinetics of oral clotrimazole, potentially useful antisickling agent.

Clotrimazole (CLT) has recently been shown to be a potent and specific inhibitor of the Ca(2+)-activated K+ channel and to thereby prevent K+ loss and cellular dehydration of sickled erythrocytes. This evidence suggests that oral CLT may be a useful new therapy for sickle cell disease. Here, we describe the development of an HPLC assay to measure CLT, a method we used to study the pharmacokinetics and transport of CLT in normal volunteers. The assay's linear range extended to 10 mumol/L; the detection limit was 0.1 mumol/L, analytical recovery 97.7%, and run-to-run imprecision (CV) < 4.7%. In unaffected subjects, CLT concentration peaked within 6 h of oral administration and returned to close to baseline by 24 h. High-density lipoproteins appear to be the main carriers of this drug in both normo- and hypertriglyceridemic plasma. We conclude that the method described here is ideally suited for therapeutic monitoring of CLT concentrations.

Adenosine Triphosphatases↗
PubMed1994

Efficacy of felbamate in therapy for partial epilepsy in children.

Thirty children (2 to 17 years of age) with refractory partial seizures received open-label felbamate as an add-on medication to their background antiepileptic drugs. The dose was increased up to a maximum of 45 mg/kg. Compared with baseline seizure activity, there was a 53% decrease in seizure frequency during felbamate therapy; 50% of the patients had more than a 50% decrease in seizure frequency. Patients older than 10 years of age were more likely to have a favorable response. Age correlated positively with felbamate concentrations and negatively with apparent felbamate clearance. Transient weight loss occurred in 57% of the patients; the weight loss was maximal after 12 weeks of initiation of felbamate, and subsided after the twentieth week of treatment. Anorexia and insomnia were reported in 20% and 16% of the patients, respectively. Adverse effects were generally tolerable; felbamate therapy was discontinued because of side effects in only one patient, because of a rash. We conclude that felbamate can be a useful and well-tolerated medication in the treatment of refractory partial epilepsy in children. However, increased apparent clearance of this drug in younger children should be considered in treatment of this age group.

Adolescent↗
PubMed1994

Serum lipids, neuroendocrine, and cardiovascular responses to stress in men and women with mild hypertension.

In this study, we examined the relation between serum lipid levels, gender, and cardiovascular and neuroendocrine stress reactivity in patients with mild hypertension. Ninety-nine individuals (62 men, 37 women) with mild hypertension performed four mental stress tasks: mental arithmetic, public speaking, cold stress, and a computer videogame. Cardiovascular reactivity scores were computed by subtracting the minimum resting blood pressure (BP) and heart rate (HR) values from the maximum values obtained during each task. Neuroendocrine reactivity was calculated as the change from epinephrine and norepinephrine values from mean rest to mean task. High and low reactors were identified on the basis of median splits of reactivity scores, averaged across all four stressors. High systolic blood pressure reactors had higher levels of total (TC), low-density lipoprotein cholesterol (LDL-C), and apo-B than did low reactors. High diastolic blood pressure reactors had lower levels of high-density lipoprotein cholesterol (HDL-C) and higher levels of LDL-C and apo-B than did low reactors. High HR reactors had higher apo-AI:apo-AII ratios than low reactors. Lipid levels were not different for high and low epinephrine and norepinephrine reactors. Although women were noted to have more favorable lipid profiles than men, both male and female hypertensive patients who were high reactors had less favorable lipid profiles than low reactors.

Adult↗
PubMed1994

Urinary N-acetyl-beta-glucosaminidase and beta-2-microglobulin in the diagnosis of urinary tract infection in febrile infants.

Urinary N-acetyl-beta-glucosaminidase (NAG) and beta-2-microglobulin (B2M) concentrations were measured in 24 pediatric patients with febrile urinary tract infection (UTI) and compared with the technetium-99m-labeled dimercaptosuccinic acid (DMSA) renal scan results, in order to evaluate a noninvasive means to localize the site of UTI. Increased urinary B2M and NAG were not associated with renal inflammation (pyelonephritis), as defined by positive dimercaptosuccinic acid scan. Median NAG concentrations were 114.2 mumol/hour/mg creatinine (CR) (range, 5.7 to 305.4) in 17 febrile UTI patients vs. 13.8 (range, 3.4 to 104.3) in 17 age and sex-matched febrile controls with negative urine cultures, P = 0.0001. The sensitivity and specificity of NAG > or = 40 mumol/hour/mg of CR in predicting UTI in febrile patients, regardless of the site of infection, were 88 and 88%, respectively. Increased urinary NAG is associated with UTI in febrile patients regardless of the level of infection (scan status), and may be an informative indicator of UTI.

Acetylglucosaminidase↗
PubMed1994

Measurement of felbamate by wide-bore capillary gas chromatography and flame ionization detection.

Felbamate, a newly developed antiepileptic agent, has been demonstrated to control partial and generalized seizures effectively. We have developed a gas-chromatographic method for the determination of felbamate, using a wide-bore capillary column, a flame ionization detector, and a simple extraction procedure. The assay day-to-day precision (n = 20) was 5.2% and 3.6% for drug concentrations of 50 and 150 mg/L, respectively; average recovery over a wide range of felbamate concentrations was 95%; the detection limit was 5 mg/L; and assay linearity extended to 300 mg/L. Although 9 of the 27 drugs tested were coextracted with felbamate, they exhibited significantly different retention times and showed no interference. A short-term stability study showed that plasma felbamate is stable at 4, -20, or -78 degrees C for at least 1 month. Plasma felbamate concentrations in 66 pediatric patients ranged from 7 to 154 mg/L (mean +/- SD 44 +/- 24.7). We consider the method ideally suited for therapeutic monitoring of plasma felbamate concentration.

Anticoagulants↗
PubMed1993

Effective control of hypercholesterolemia in children with dietary interventions based in pediatric practice.

BACKGROUND: Based on recent recommendations, the number of hypercholesterolemic children who would require dietary therapy could overwhelm current preventive pediatric cardiology resources. No previous studies have established the efficacy of such therapy in the pediatrician's office. The purpose of this study was to evaluate two programs of office-based therapy. METHODS: We randomly assigned 295 children with hypercholesterolemia (> 185 mg/dl) two interventions: one single or four multiple 90-min sessions of family-oriented nutritional education, based in pediatric practices. We examined total cholesterol, 3-day food records, height and weight, and in the multisession group high-density lipoprotein cholesterol and triglycerides at the beginning and at intervals of 8.5-9 and 21 to 33 weeks (single-session and multisession groups, respectively). RESULTS: Total cholesterol was lowered equally in both treatment groups over the course of the study. This was accompanied by dietary changes: a decrease in calories derived from total and saturated fats, and increased intake of fiber, protein, and carbohydrate. However, more single-session patients withdrew from the program during the study. CONCLUSIONS: The two interventions were equally effective in lowering total and low-density lipoprotein cholesterol and in reducing intake of total and saturated fat. However, the higher completion rate of the multisession group suggests that this approach may be the more effective.

Adolescent↗
PubMed1993

Incidence of lead poisoning in young children from inner-city, suburban, and rural communities.

The Centers for Disease Control (CDC) have recently lowered the acceptable blood lead concentration in young children from < or = 25 to < or = 10 micrograms/dl (< or = 1.21 to < or = 0.48 mumol/L). The incidence of lead toxicity with respect to geographical areas and socioeconomic status has not yet been defined. We evaluated the incidence of increased lead concentration in inner-city, suburban, and rural children aged 9 months to 3 years. Seven hundred eighty of the 4,196 studied inner-city samples (18.6%) had lead concentrations > or = 10 micrograms/dl (0.48 mumol/L), of which only 71 (1.6%) had lead values > or = 25 micrograms/dl (1.21 mumol/L). Only 5 of the 212 studied children (2.4%) from suburbia and 7 of the 120 children (5.8%) from rural communities had blood lead concentrations > or = 10 micrograms/dl (0.48 mumol/L). None of these children, however, had a lead concentration > or = 15 micrograms/dl (0.73 mumol/L). In contrast, 276 inner-city subjects (6.6%) had lead values > or = 15 micrograms/dl (0.73 mumol/L). Our data indicate that a correlation exists between geographical location and blood lead concentration in young children. Government health agencies at all levels should prioritize their limited resources for those areas that are most at risk for lead poisoning.

Centers for Disease Control and Prevention, U.S.↗
PubMed1993

Role of free radicals in cancer and atherosclerosis.

As aerobic creatures, normal living requires that not only are human beings exposed to oxygen but are dependent on oxygen. Humans have evolved mechanisms to cope with living in an aerobic environment; however, modern humans may be more exposed to oxidant stresses. Much indirect evidence implicates reactive oxygen species in diseases such as cancer and atherosclerosis. There are also other diseases that are influenced by oxidative balance, including the normal process of aging. Common environmental factors that could cause oxidative stress include a low intake of dietary antioxidants, a high intake of polyunsaturated fatty acids, and exposure to ozone, ionizing radiation, and cigarette smoke. The recent development of overall measures of oxidant status, such as breath pentane; highly sophisticated measures, such as electron spin resonance and specific measures of base damage to DNA by mass spectrometry; and other methods will allow much more specific data to be collected on the importance of reactive oxygen species in many disease states. Such measures can serve as end points for a variety of studies in experimental animals and humans that will allow for the testing of many potential prooxidant and antioxidant compounds. Other important evidence will be available soon from, for example, large scale chemoprevention trials that are currently under way. As an indicator of the increased interest in oxidant balance, several reference laboratories now have nutritional biochemistry sections that offer measurement of specific free-radical scavenging enzymes. These enzyme measures complement the more routinely available measurements of trace element and antioxidant nutrients.

Animals↗