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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 379 records · Page 21Linked to original sources
PubMed1999

Elevated mid-trimester maternal corticotrophin-releasing hormone levels in pregnancies that delivered before 34 weeks.

OBJECTIVE: To test whether maternal corticotrophin-releasing hormone levels are elevated in the mid- trimester for those women who subsequently had spontaneous preterm delivery and to assess the clinical utility of the measurement in the prediction of preterm delivery. DESIGN: A prospective observational study. SETTING: Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong. POPULATION: 1047 low risk pregnant women recruited at 15-20 weeks of gestation. METHODS: Venous samples were assayed for levels of corticotrophin-releasing hormone. The investigators responsible for the laboratory assay were blinded to the obstetric outcome. MAIN OUTCOME MEASURES: Incidence of preterm, term and post-term pregnancies. RESULTS: Those who were delivered spontaneously at a preterm gestational age (before 34 weeks) had significantly higher corticotrophin-releasing hormone levels in the mid-trimester, compared with those who were delivered at term or post-term. There was a trend towards lower corticotrophin-releasing hormone levels with more advanced gestational age at delivery. When the measurement of corticotrophin- releasing hormone was used to predict delivery before 34 weeks, the best cut off was 1.9 MoM, which produced a sensitivity of 72.7% and specificity of 78.4%. This translated to a positive predictive value of 3.6%, negative predictive value of 99.6% and relative risk of 9.4 when the background prevalence of spontaneous preterm delivery before 34 weeks was 1.1%. The likelihood ratio was 3.4. CONCLUSIONS: Mid-trimester maternal corticotrophin-releasing hormone levels are elevated in pregnancies destined to deliver preterm before 34 weeks. When used alone in a low risk population, the measurement has a low predictive power for preterm delivery. However, the likelihood ratio of 3 4 implies that in high risk populations the test may be considerably more valuable.

Adult↗
PubMed1999

Sources of uncertainty in dose-response modeling of epidemiological data for cancer risk assessment.

Epidemiologic data is increasingly being used for dose-response analysis in risk assessment. The Environmental Protection Agency (EPA) and other U.S. agencies have expressed a preference for using epidemiologic data rather than toxicologic data when possible. However, there are a number of important sources of uncertainty in using epidemiologic data for this purpose that need to be clearly recognized and, when possible, quantified. This paper presents a critical review of the major sources of uncertainty in the use of epidemiologic data for cancer risk assessment. These may include: (1) study design issues such as potential confounding and other biases, inadequate sample size, and followup, (2) the choice of the data set, (3) specification of the dose-response model, (4) estimation of exposure and dose, and (5) unrecognized variability in susceptibility. Examples from risk assessments for cadmium, asbestos, and diesel exhaust are used to illustrate the potential magnitude of some of these sources of uncertainty. It is shown that the overall uncertainty from these various sources combined may often result in highly uncertain risk estimates from dose-response modeling of epidemiologic data. For this reason, we believe it is best to present a range of possible risk estimates, which, to the extent possible, reflects the variability and uncertainty inherent in the dose-response evaluation of epidemiologic data.

Asbestos↗
PubMed1999

Detection of Cryptosporidium parvum in horses: thresholds of acid-fast stain, immunofluorescence assay, and flow cytometry.

Feces collected from three asymptomatic horses and seeded with Cryptosporidium parvum oocysts (10(1) to 10(6)/g of feces) were evaluated by acid-fast staining (AF), an immunofluorescent antibody (IFA) technique, and flow cytometry. The thresholds of detection were 5 x 10(5) oocysts/g of feces for the IFA and AF techniques and 5 x 10(4) oocysts/g for flow cytometry.

Animals↗
PubMed1999

Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations.

OBJECTIVES: To investigate whether there is an excess of leukaemias in 0-15 year old children among those living in close proximity (within 100 m) of a main road or petrol station. METHODS: Data for 0-15 year old children diagnosed between 1990 and 1994 in the United Kingdom West Midlands were used. Postcode addresses were used to locate the point of residence which was compared with proximity to main roads and petrol stations separately, and to both together. Odds ratios (ORs) were calculated with solid tumours as a control, and incidence ratios (IRs) with population density as a control. RESULTS: The method based on solid tumours as a control showed ORs of 1.61 (95% confidence interval (95% CI) 0.90 to 2.87) and 1.99 (95% CI 0.73 to 5.43), for those living within 100 m of a main road or petrol station respectively. When population was used as a control, the estimated IRs for leukaemia were 1.16 (95% CI 0.74 to 1.72) and 1.48 (95% CI 0.65 to 2.93) for residence within 100 m of a main road or petrol station respectively, but neither reached significance at the 95% level. Results for residence in close proximity to both a main road and petrol station were inconsistent, but there were few. The influence of socioeconomic factors as represented by the Townsend deprivation index on leukaemia incidence was not significant and the results were not explicable on the basis of impact of social class. CONCLUSIONS: The results are suggestive of a small increase in risk of childhood leukaemia, but not solid tumours, for those living in close proximity to a main road or petrol station. This increase in risk is not, however, significant and a larger study is warranted to establish the true risk and causes of any increase in risk.

Adolescent↗
PubMed1999

British HIV Association guidelines for prescribing antiretroviral therapy in pregnancy (1998).

The aim of antiretroviral therapy in pregnancy is to deliver a healthy uninfected child to a healthy mother, without prejudicing the future treatment opportunities of the mother. The use of zidovudine monotherapy rapidly became standard practice once it had been shown to reduce by 67% mother to child transmission in women with CD4+ lymphocyte counts above 200 x 10(6)/l. High rates of transmission are seen when maternal disease is advanced (high viral load, low CD4+ lymphocyte counts) despite zidovudine. In these women highly active antiretroviral therapy gives the best prospect for prolonged health and it is anticipated that reducing plasma viral load below the limits of detection will further reduce transmission rates. However, safety data for antiretroviral therapy in pregnancy are limited and each additional treatment exposes a significant proportion of uninfected infants to potential long term hazards. Where maternal therapy is not indicated and the sole objective of treatment is to reduce mother to child transmission, recent data suggest that short course zidovudine (especially in conjunction with prelabour caesarean section) is a reasonable option. This may minimise the emergence of viruses with reduced sensitivity to zidovudine and preserve maternal options for later therapy.

Anti-HIV Agents↗
PubMed1999

The acute-phase protein response to human immunodeficiency virus infection in human subjects.

Although several studies have shown that asymptomatic human immunodeficiency virus infection elicits an increase in whole body protein turnover, it is not known whether this increased protein turnover includes changes in the kinetics of acute-phase proteins (APPs). To answer this question, we measured 1) the plasma concentrations of four positive (C-reactive protein, alpha1-antitrypsin, haptoglobin, and fibrinogen) and four negative APPs [albumin, high-density lipoprotein (HDL)-apolipoprotein (apo) A1, transthyretin, and retinol-binding protein] and 2) the fractional (FSR) and absolute (ASRs) synthesis rates of three positive and three negative APPs using a constant intravenous infusion of [2H5]phenylalanine in five subjects with symptom-free acquired immunodeficiency syndrome (AIDS) and five noninfected control subjects. Compared with the values of the controls, the plasma concentrations, FSRs, and ASRs of most positive APPs were higher in the AIDS group. The negative APPs had faster FSRs in the AIDS group, there was no difference between the ASRs of the two groups, and only HDL-apoA1 had a lower plasma concentration. These results suggest that symptom-free AIDS elicits an APP response that is different from bacterial infections, as the higher concentrations and faster rates of synthesis of the positive APPs are not accompanied by lower concentrations and slower rates of synthesis of most of the negative APPs.

Acute-Phase Proteins↗
PubMed1999

Are cotinine assays of value in predicting adverse pregnancy outcome?

We investigated the utility of maternal cotinine concentration as a predictor of preterm and small-for-gestational-age (SGA) deliveries. Subjects were randomly selected from antenatal clinics, and their serum cotinine concentrations at approximately 16 weeks' gestation were compared with self-reports of smoking. The value of these measures in predicting preterm and SGA deliveries was examined, using likelihood ratios and logistic regression, for 845 women with singleton, live births. Smoking status alone (defined by self-report or cotinine) only weakly predicted preterm or SGA delivery. Self-reported moderate/high smoking (top 15% of smokers) had a likelihood ratio (LR) of 2 and a positive predictive value (PPV) of 17%. In contrast, moderate/high cotinine concentration (top 15% of smokers) had an LR of 5 and a PPV of 33%. The predictive value of cotinine was independent of associated maternal characteristics. Cotinine concentration may therefore be a useful predictor of poor pregnancy outcome, and should be considered as a screening tool.

Cotinine↗
PubMed1999

Lack of effect of erythromycin and ketoconazole on the pharmacokinetics and pharmacodynamics of steady-state intranasal levocabastine.

The single-dose effects of the cytochrome P-450 inhibitors erythromycin and ketoconazole on the steady-state pharmacokinetics and electrocardiographic repolarization pharmacodynamics of intranasal levocabastine, a potent and selective H1-receptor antagonist, were evaluated in healthy young male subjects. Two randomized, open-label, placebo-controlled, two-way crossover studies were performed. Levocabastine nasal spray was administered as two sprays per nostril (0.05 mg/spray) twice daily (for a total daily dose of 0.4 mg) for 6 days. On Day 7, a single dose of 0.2 mg was administered followed immediately by a single dose of either oral placebo, erythromycin 333 mg, or ketoconazole 200 mg. In all treatment groups, levocabastine was rapidly absorbed, with peak plasma concentrations reached at approximately 3 hours in the erythromycin study and 2.8 hours in the ketoconazole study. The mean terminal half-life was approximately 45 and 44 hours, respectively. In both studies, mean steady-state plasma concentrations and pharmacokinetics of levocabastine following the single doses of erythromycin or ketoconazole were not significantly different from corresponding values seen with the concomitant administration of the placebo. No clinically significant mean changes from baseline in QT or QTc (QT corrected for heart rate) intervals occurred in any of the treatment groups, and none of the subjects in either study experienced abnormally prolonged QTc intervals. Intranasal levocabastine was well tolerated, with no difference in the incidence of adverse events between treatment groups in either study; adverse events were generally mild in severity. Since levocabastine undergoes only minimal hepatic metabolism and is not a substrate for or an inhibitor of cytochrome P-450, the likelihood of systemic drug interactions with drugs affecting the cytochrome P-450 system is minimal.

Administration, Intranasal↗
PubMed1999

Fosinopril: pharmacokinetics and pharmacodynamics in Chinese subjects.

This study examined thepharmacokinetics and pharmacodynamics of fosinopril (IVand oral) in Chinese subjects to determine whether they were different from a group of somewhat heavier and older Western control subjects previously published using the same methods. It was an open-label, randomized, balanced, two-way crossover study comparing oral and IV pharmacokinetics in 12 healthy Chinese subjects in a clinic in Taiwan. Each subject received 10 mg of oral fosinopril or 7.5 mg of IV fosinoprilatin a randomized sequence with sampling for fosinoprilat concentrations over 48 hours. Standard pharmacokinetics, including AUC, Cmax Tmax, T 1/2, Vss, bioavailability, total clearance, and renal and nonrenal clearance, were determined as well as pharmacodynamic effects on angiotensin-converting enzyme (ACE) activity. Following oral administration of 10 mg fosinopril, AUC0-T and AUCinf were 1,556 +/- 586 ng x hr/mL and 1,636 +/- 620 ng x hr/mL, respectively; T 1/2 was 17.4 +/- 11.4 hr; Cmax was 183.4 +/- 59.4 ng/mL; and median Tmax was 4.0 hr, with > 99% protein binding. Following IV administration of 7.5 mg fosinoprilat, AUC0-T and AUCinf were 7,727 +/- 2,638 ng x hr/mL and 7,816 +/- 2,693 ng x hr/mL, respectively; T 1/2 was 13.0 +/- 5.2 hr; and median Tmax was 4.0 hr, with 99.5% +/- 0.22% protein binding and a Vss of 5,850 +/- 2,780 mL. Bioavailability was 22.3% +/- 7.9%. Percent urinary excretion was 7.6% +/- 2.6% after oral dosing and 42.6% +/- 6.1% after IV dosing. After IV, dosing total clearance was 1,088 +/- 439 mL/hr, renal clearance was 472 +/- 213 mL/hr, and nonrenal clearance was 617 +/- 246 mL/hr. ACE inhibition was essentially complete through 12 hours and markedly reduced through 24 hours. Compared to a somewhat heavier and older previously reported control group, pharmacokinetic values were similar except for a slightly lower AUC and total clearance in Chinese and a statistically significantly lower nonrenal clearance. Pharmacodynamic effects on ACE activity were essentially identical. There is no reason to expect significant differences in fosinopril dosing or effect in a Chinese population compared to a Western population.

Administration, Oral↗
PubMed1999

Medial longitudinal arch of the foot: stationary versus walking measures.

We describe the characteristics of the medial longitudinal arch (MLA) of the right foot in 19 healthy men while sitting/partial bodyweight, standing/full bodyweight, and during the stance phase of walking. Three measurements were selected as representative of the MLA, including: height of the arch, length of the arch, and supranavicular angle. Mean values were calculated in three dimensions for each measure in the sitting and standing conditions and for the minimum value of each measure in the walking condition. Patterns measured during walking had high association (r = 0.999) and could be related to phases of stance. In the stationary conditions, the MLA varied significantly (P<0.001). No significant relationship of arch height, arch length, or supranavicular angle was found between sitting and standing or between stationary and walking conditions. It was concluded that none of the static variables could be used to predict others and that static measures of the MLA do not predict the dynamic motion of the MLA. The MLA may not be a reasonable indicator of behavior or motion of the foot.

Adult↗
PubMed1999

Comparison of custom and prefabricated orthoses in the initial treatment of proximal plantar fasciitis.

Fifteen centers for orthopaedic treatment of the foot and ankle participated in a prospective randomized trial to compare several nonoperative treatments for proximal plantar fasciitis (heel pain syndrome). Included were 236 patients (160 women and 76 men) who were 16 years of age or older. Most reported duration of symptoms of 6 months or less. Patients with systemic disease, significant musculoskeletal complaints, sciatica, or local nerve entrapment were excluded. We randomized patients prospectively into five different treatment groups. All groups performed Achilles tendon- and plantar fascia-stretching in a similar manner. One group was treated with stretching only. The other four groups stretched and used one of four different shoe inserts, including a silicone heel pad, a felt pad, a rubber heel cup, or a custom-made polypropylene orthotic device. Patients were reevaluated after 8 weeks of treatment. The percentages improved in each group were: (1) silicone insert, 95%; (2) rubber insert, 88%; (3) felt insert, 81%; (4)stretching only, 72%; and (5) custom orthosis, 68%. Combining all the patients who used a prefabricated insert, we found that their improvement rates were higher than those assigned to stretching only (P = 0.022) and those who stretched and used a custom orthosis (P = 0.0074). We conclude that, when used in conjunction with a stretching program, a prefabricated shoe insert is more likely to produce improvement in symptoms as part of the initial treatment of proximal plantar fasciitis than a custom polypropylene orthotic device.

Adult↗
PubMed1999

Parallel phase I studies of daunorubicin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myeloid leukemia: results of cancer and leukemia group B study 9420.

PURPOSE: The Cancer and Leukemia Group B conducted parallel phase I trials of cytarabine, daunorubicin, and etoposide (ADE) with or without PSC-833 (P), a modulator of p-glycoprotein-mediated multidrug resistance. PATIENTS AND METHODS: One hundred ten newly diagnosed patients > or = 60 years of age with de novo acute myeloid leukemia (AML) were treated. All patients received cytarabine by continuous infusion for 7 days at 100 mg/m(2)/d. The starting dose of daunorubicin was 30 mg/m(2)/d for 3 days. Etoposide was administered at a dose of 100 mg/m(2)/d for 3 days, except in the last cohort administered ADEP, who received 60 mg/m(2). PSC-833 was given intravenously with a loading dose of 1.5 mg/kg over 2 hours and a simultaneous continuous infusion of 10 mg/kg/d continued until 24 hours after the last dose of daunorubicin or etoposide. RESULTS: There was no toxicity attributed to the PSC-833. Dose-limiting toxicity was primarily gastrointestinal (diarrhea, mucositis in the ADEP group). The estimated maximum-tolerated doses, calculated using a logistic regression model, were daunorubicin 40 mg/m(2)/d for 3 days with etoposide 60 mg/m(2) for 3 days in the ADEP group and daunorubicin 60 mg/m(2)/d for 3 days and etoposide 100 mg/m(2)/d for 3 days in the ADE group. Twenty-one (48%) of 44 patients achieved complete remission with ADE, compared with 29 (44%) of 66 patients treated with ADEP. CONCLUSION: It is necessary to decrease the doses of daunorubicin and etoposide when they are administered with PSC-833, presumably because of the effect of the modulator on the pharmacokinetics of these agents. A phase III trial comparing the regimens derived from this phase I trial has recently begun.

Acute Disease↗
PubMed1999

Corticotropin-releasing hormone in chimpanzee and gorilla pregnancies.

In humans, the length of gestation and the onset of parturition have been linked to the exponential production of placental CRH and a late gestational decline in maternal plasma CRH-binding protein (CRH-BP). CRH has been shown to have direct effects on the myometrium and on the fetal adrenal, where it stimulates production of the estrogen precursor dihydroepiandrosterone sulfate. In vitro placental CRH production is stimulated by cortisol and inhibited by progesterone. To determine whether this mechanism might operate in other apes, we sampled eight chimpanzees and two gorillas through their pregnancies for CRH, CRH-BP, cortisol, estradiol, progesterone, and alpha-fetoprotein. We show that both chimpanzee and gorilla maternal plasma CRH concentrations rise exponentially as observed in the human. The gorillas exhibited a human-like antepartum fall in CRH-BP, whereas CRH-BP in the chimpanzee remained stable. Pregnancy-associated changes in cortisol, estradiol, progesterone, and alpha-fetoprotein were qualitatively similar to those observed in humans. Maternal plasma cortisol correlated with plasma CRH in both gorillas (r = 0.60; P < 0.05) and chimpanzees (r = 0.36; P < 0.02). Further, there was a strong correlation between plasma estradiol and the log of plasma CRH in the gorilla (r = 0.93; P < 0.0001) and in the chimpanzee (r = 0.72; P < 0.001), which is consistent with the hypothesis that placental CRH determines the placental production of estradiol by stimulating the production of fetal adrenal dehydroepiandrosterone sulfate. Plasma CRH and progesterone were positively correlated providing no in vivo support for progesterone inhibition of CRH release.

Animals↗
PubMed1999

UFT plus calcium folinate vs 5-FU plus calcium folinate in colon cancer.

Adjuvant chemotherapy has been shown to alter the natural history of resected colon cancer. Two regimens (5-fluorouracil [5-FU] plus calcium folinate and 5-FU plus levamisole [Ergamisol]) have been found to prolong disease-free survival and overall survival in affected patients. Previous comparisons of these two regimens indicate that 5-FU plus calcium folinate may offer a small disease-free survival and overall survival advantage. The demonstration that UFT (uracil and tegafur) plus oral calcium folinate (Orzel) offers significant antitumor activity and an acceptable toxicity profile makes this a logical formulation for the adjuvant treatment of colon cancer. The National Surgical Adjuvant Breast and Bowel Project Protocol C-06 is a randomized comparison of the relative efficacies of 5-FU/calcium folinate vs UFT plus oral calcium folinate. Preliminary analysis of toxicity findings among 473 evaluable patients indicates that both regimens are well tolerated and have similar toxicity profiles. If, in the final survival analysis, UFT plus oral calcium folinate treatment yields the same or better disease-free survival and/or overall survival as the 5-FU/calcium folinate treatment and the toxicity profiles remain similar, it is likely that UFT plus oral calcium folinate will be accepted as a new standard for adjuvant treatment of colon cancer.

Antimetabolites, Antineoplastic↗
PubMed1999

[Autonomic nervous system and obstructive sleep apneas].

Understanding of the pathophysiology of obstructive sleep apnoea, a common yet relatively newly recognised condition, has advanced rapidly in recent years. This condition produces major acute haemodynamic changes and causal relationships with arterial hypertension and cardiovascular morbidity have been proposed. The role that the autonomic nervous system plays in mediating these cardiovascular changes has been the focus of intensive research activity and the development of new techniques in physiological monitoring, such as spectral analysis of heart rate variability, Finapres blood pressure monitoring, measurement of muscle sympathetic nerve activity, radionuclide tests and animal models of obstructive sleep apnoea have substantially increased the knowledge base. The acute haemodynamic changes are associated with high levels of sympathetic discharge and with fluctuating parasympathetic activity. There are also chronic changes in baroreceptor and chemoreceptor reflexes associated with an increase in baseline daytime sympathetic activity and abnormal vagal reflex responses to voluntary respiratory manoeuvres. These acute autonomic changes appear to be provoked by a combination of stimuli triggered by hypoxaemia, upper airway responses, ventilatory changes and arousal. The mechanisms of the chronic autonomic changes are less clear; it is likely that recurrent hypoxaemia is important, but the roles of recurrent ventilatory stress and arousal are not clear. Normalising respiration with CPAP therapy prevents the acute cardiovascular changes and reduces the acute sympathetic over-activity, and in compliant patients, restores abnormal vagal responses to normal and reduces excess chronic sympathetic activity. Whether or not this produces a reduction in long term cardiovascular morbidity is not established.

Autonomic Nervous System↗
PubMed1999

Managing hypertension in the southeastern United States: applying the guidelines from the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI).

The southeastern United States has the highest occurrence of heart disease and stroke and among the highest rates of congestive heart failure and renal failure in the country. The Consortium for Southeastern Hypertension Control (COSEHC) is cooperating with other organizations in implementing initiatives to reduce morbidity and mortality from hypertension-related conditions in the southeastern United States. This article outlines for clinicians special consideration for implementation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) in the southeastern United States. Clinicians are encouraged to adapt the recommendations of JNC VI to their own patient groups, paying attention to these specific areas: (1) Ensure screening for hypertension in your practice and community. (2) Evaluate all patients for accompanying risk factors and target organ damage. (3) Promote lifestyle management for individual patients and populations for prevention and treatment of hypertension. (4) Set a goal blood pressure for each patient, and monitor progress toward that goal. (5) Recognize that many patients will be candidates for blood pressure goals of <130/85 mm Hg. (6) Pay attention to compelling and special indications such as diabetes, congestive heart failure, and renal dysfunction. (7) Consider combination therapy. (8) Maximize staff contributions to enhance patient adherence. (9) Encourage patient, family, and community activities to promote healthy lifestyles and blood pressure control.

Black or African American↗