Search PubMed⌕ Search

Biomedical subjects

J Kemp

Publications and source records attributed to J Kemp.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of zolmitriptan (Zomig) on central serotonergic neurotransmission as assessed by active oddball auditory event-related potentials in volunteers without migraine.

In this randomized, double-blind, three-period crossover trial, 24 healthy volunteers without migraine received zolmitriptan 5 mg, dexfenfluramine 15 mg or placebo orally. At 2, 6, and 24 h postdose, auditory stimuli of 1000 Hz (nontarget tone) and 2000 Hz (target tone) were randomly and binaurally presented in an active oddball paradigm (4:1 ratio). Cortical auditory evoked responses were recorded for 500 msec poststimulus. Plasma concentrations of zolmitriptan and a 17-lead quantitative EEG were assessed at the same timepoints. Relative to placebo, zolmitriptan reduced the maximum absolute amplitude, amplitude difference (from nontarget tone noise) and area under the curve of the cortical auditory target tone event-related potential (P300 ERP). The most dramatic effect of zolmitriptan was to diminish the point estimate of noise during the 200-400 msec poststimulus epoch. The effect of zolmitriptan appeared concentration dependent. The latency of the P300 ERP was unaffected by zolmitriptan and there was no clinically significant effect on the EEG. Modification by zolmitriptan of the cortical electrical activity evoked by auditory stimuli confirms a central action of this drug in humans, which appears to affect cortical information processing without global alteration of the quantitative EEG.

Acoustic Stimulation↗
PubMed1999

A comparison of the pharmacokinetics and tolerability of the novel antimigraine compound zolmitriptan in adolescents and adults.

This open-label, parallel-group study assessed pharmacokinetics and tolerability of zolmitriptan, a 5-HT1B/1D agonist for the acute treatment of migraine, and its active metabolite, 183C91, in adolescents compared with adults. Twenty-one healthy adolescent and 18 healthy adult volunteers (with and without history of migraine) received a single 5-mg dose of zolmitriptan. Mean ages were 14.5 years (range 12-17) for adolescents (13 girls, 8 boys) and 39.1 years (range 18-65) for adults (12 women, 6 men). The area under the curve (AUC) and highest observed plasma concentration (Cmax) of zolmitriptan were similar in both age groups; the half-life was 3.01 hours in adolescents versus 3.75 hours in adults. The AUC and Cmax of 183C91, however, were 36% and 39% higher in adolescents, respectively; the half-life was similar in both age groups. Adverse events were similar in both groups in terms of nature, intensity, and frequency. Exposure to zolmitriptan was not significantly different in adolescents compared with adults, but a shorter half-life in adolescents suggests faster elimination in this age group. Exposure to 183C91 was higher in adolescents, suggesting that formation of the metabolite is at least one of the elimination routes of zolmitriptan that occurs at a faster rate in adolescents.

Adolescent↗
PubMed1998

Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction.

BACKGROUND: Patients with mild asthma frequently have only exercise-induced bronchoconstriction, a symptom of inadequate control of asthma. We evaluated the ability of montelukast, a leukotriene-receptor antagonist, to protect such patients against exercise-induced bronchoconstriction. METHODS: We randomly assigned 110 patients (age, 15 to 45 years) with mild asthma and a decrease in the forced expiratory volume in one second (FEV1) of at least 20 percent after exercise on two occasions during a placebo run-in period to receive 10 mg of montelukast (54 patients) or placebo (56 patients) once daily at bedtime for 12 weeks in a double-blind study. Treatment was followed by a two-week, single-blind washout period during which all patients received placebo. Exercise challenges were performed at base line; 20 to 24 hours after dosing at weeks 4, 8, and 12; and at the end of the washout period. The primary end point was the area under the curve for FEV1 (expressed as the percent change from base-line values) in the first 60 minutes after exercise. This measure summarized the extent and duration of bronchoconstriction after exercise. RESULTS: At 12 weeks, montelukast therapy offered significantly greater protection against exercise-induced bronchoconstriction than placebo therapy (expressed as the percentage of inhibition of the end points), as evidenced by the improvement in the area under the FEV1 curve (degree of inhibition, 47.4 percent; P=0.002). Montelukast therapy was also associated with a significant improvement in the maximal decrease in FEV1 after exercise (P=0.003) and the time from the maximal decrease in FEV1 to the return of lung function to within 5 percent of pre-exercise values (P=0.04). The differences between groups in the various measures of lung function were similar at 4, 8, and 12 weeks; there was no evidence of rebound worsening of lung function in the montelukast group after the washout period. After 12 weeks of treatment, patients in the montelukast group were more likely to rate their asthma control as better and less likely to require rescue therapy with a beta-agonist during or after exercise challenge. The rates of adverse events were similar in the two groups. CONCLUSIONS: As compared with placebo, once-daily treatment with montelukast provided significant protection against exercise-induced asthma over a 12-week period. Tolerance to the medication and rebound worsening of lung function after discontinuation of treatment were not seen.

Acetates↗
PubMed1998

Defective expression of p56lck in an infant with severe combined immunodeficiency.

Severe combined immune deficiency (SCID) is a heterogeneous disorder characterized by profound defects in cellular and humoral immunity. We report here an infant with clinical and laboratory features of SCID and selective CD4 lymphopenia and lack of CD28 expression on CD8(+) T cells. T cells from this patient showed poor blastogenic responses to various mitogens and IL-2. Other T cell antigen receptor- induced responses, including upregulation of CD69, were similarly inhibited. However, more proximal T cell antigen receptor signaling events, such as anti-CD3 induced protein tyrosine phosphorylation, phosphorylation of mitogen-associated protein kinase, and calcium mobilization were intact. Although p59fyn and ZAP-70 protein tyrosine kinases were expressed at normal levels, a marked decrease in the level of p56lck was noted. Furthermore, this decrease was associated with the presence of an alternatively spliced lck transcript lacking the exon 7 kinase encoding domain. These data suggest that a deficiency in p56lck expression can produce a SCID phenotype in humans.

Antigens, CD↗
PubMed1998

Effect of hepatic impairment on the pharmacokinetics of zolmitriptan.

Zolmitriptan, an oral 5HT1D agonist for the acute treatment of migraine, is cleared from the systemic circulation mainly by hepatic metabolism. Consequently, changes in hepatic function may result in changes in the pharmacokinetics of zolmitriptan. This open, parallel-group study was conducted to compare the pharmacokinetics and tolerability of a single 10-mg dose of zolmitriptan in healthy subjects and patients with hepatic impairment. A total of 37 participants entered and completed the study, including 10 healthy volunteers, 11 patients with moderate hepatic impairment, 10 patients with severe hepatic impairment without ascites, and 6 patients with severe hepatic impairment with ascites. The metabolism of zolmitriptan was reduced in patients with severe hepatic impairment compared with healthy subjects, resulting in higher peak plasma concentrations (47%), increased exposure (226%), and prolonged half-life (157%). The changes were similar in the presence and absence of ascites. Smaller changes were observed in patients with moderate hepatic impairment. Plasma concentrations of the three major metabolites of zolmitriptan were reduced in the patients with hepatic impairment. Patients with moderate hepatic impairment require no dosage adjustment, but the recommended daily intake of zolmitriptan may need to be reduced in patients with severe hepatic impairment.

Adult↗
PubMed1998

Antenatally diagnosed surgical anomalies: the psychological effect of parental antenatal counseling.

BACKGROUND: Increasing numbers of infants have the diagnosis of a surgical malformation made before birth. This allows (1) fetal intervention, (2) in utero transfer and planned delivery in a surgical center, and (3) antenatal counseling of likely prognosis and outcome. The aim of this study was to assess the effectiveness of antenatal counseling in terms of the parental psychological response. METHODS: Antenatal counseling by a pediatric surgeon and neonatal nurse was given after ultrasound diagnosis of a fetal surgical malformation (eg, gastroschisis, diaphragmatic hernia). Anxiety levels were measured using the Spielberger State-Trait Anxiety Inventory, a tool used by psychologists to assess the inherent level of anxiety, or Trait anxiety (STAI-T), and the current level of anxiety, or State anxiety (STAI-S). RESULTS: Fifty six prospective mothers filled out Spielberger questionnaires (subjects, n = 26; controls, n = 30). Nineteen subjects' partners also completed questionnaires. There was no significant difference in Trait anxiety scores between subjects and controls (41 [interquartile range, 30 to 511 v 38.5 [range, 32 to 47]; P = .58). There was no significant correlation between maternal and paternal Trait anxiety (P = .11). There was a significant reduction in State anxiety scores in both subject mothers (49.5 [interquartile range, 27 to 73) v38 [range, 31 to 49]; P = .01) and fathers (47 [interquartile range, 36 to 55] v 37 [interquartile range, 32 to 49]; P = .006) after pediatric surgical consultation. CONCLUSION: Counseling by specialist staff reduced levels of parental anxiety associated with the diagnosis of fetal surgical malformation.

Adult↗
PubMed1998

Effect of creatine supplementation on sprint exercise performance and muscle metabolism.

The aim of the present study was to examine the effect of creatine supplementation (CrS) on sprint exercise performance and skeletal muscle anaerobic metabolism during and after sprint exercise. Eight active, untrained men performed a 20-s maximal sprint on an air-braked cycle ergometer after 5 days of CrS [30 g creatine (Cr) + 30 g dextrose per day] or placebo (30 g dextrose per day). The trials were separated by 4 wk, and a double-blind crossover design was used. Muscle and blood samples were obtained at rest, immediately after exercise, and after 2 min of passive recovery. CrS increased the muscle total Cr content (9.5 +/- 2.0%, P < 0.05, mean +/- SE); however, 20-s sprint performance was not improved by CrS. Similarly, the magnitude of the degradation or accumulation of muscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate, lactate, and glycogen) and plasma metabolites (e.g. , lactate, hypoxanthine, and ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These data demonstrated that CrS increased muscle total Cr content, but the increase did not induce an improved sprint exercise performance or alterations in anaerobic muscle metabolism.

Adenine Nucleotides↗
PubMed1997

Exon/intron structure of the human transferrin receptor gene.

A PCR-based intron jumping strategy has been utilized to investigate the exon/intron structure of the human transferrin receptor gene and determine the sequences of exon/intron junctions. There are 18 exons and introns 5' to a large exon encoding the last translated segment and a sizable 3' untranslated segment. All of the translated segments are encoded by exons 2-19. The tight turn motif, which is critical to the process of endocytosis, is encoded by exon 3. Based on recent studies of human/chicken receptor chimeras, it appears that the residues most likely to be involved in transferrin binding are encoded by exons 17-19. Exon 12 exhibits the greatest degree of homology with the gene for the prostate specific membrane antigen. A polymorphism has been tentatively identified at nucleotide position 519 in exon 4; the presence of either adenine or guanine should result in either serine or glycine, respectively, at position 142 of the amino acid sequence. This analysis of genomic structure will permit further detailed studies of the regulation, expression and evolution of the human transferrin receptor gene.

Amino Acid Sequence↗
PubMed1997

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

Alleles↗
PubMed1997

How do they grow? A study of south-eastern Nigerian adolescent girls.

This study assessed the nutritional status of Nigerian adolescent girls living in two areas of south-eastern Nigeria. A cross sectional survey was undertaken in a rural village in Ogoniland, and five secondary schools in Port Harcourt, south-eastern Nigeria. All (386) menarcheal girls aged 14-19 y living in the rural village, and a stratified cluster sample (845) of menarcheal girls aged 14-19 in the five urban schools were investigated. Mean heights and weights of rural girls were around -1 Z-score below the British reference median. 10.4% of rural and 4.7% of urban girls were stunted (< OR =2nd centile, British 1990 reference values). After calculating mean body mass index-for-age, various cut-off points for low body mass index were tested. At a cut-off of < OR =9th centile, 15.6% of rural and 8.0% of urban girls would be classified as thin. Girls with a haemoglobin <10.Og/dl were significantly more likely to have a low body mass index than those with haemoglobin values > OR =10.0 g/dl. More studies are needed to refine the definition and interpretation of low body mass index in adolescents.

Adolescent↗
PubMed1997

Karyotype 69,XXX/47,XX,+15 in a 2 1/2 year old child.

We present the clinical findings in a 2 1/2 year old girl with an unusual mosaic karyotype. Amniocentesis was performed at 35 weeks because of intrauterine growth retardation. The in situ cultures showed 47,XX,+15 in seven colonies, 69,XXX in four colonies, and in two colonies 46,XX was detected. Subcultures showed 69,XXX/47,XX,+15 with no normal cells. A small dysmorphic baby was born at term. Cytogenetic studies were performed on cord blood, amnion, and placental tissue immediately after birth and further studies on peripheral blood, bone marrow, muscle biopsy, and skin cultures at 1 1/2 years of age. FISH with two autosomal centromeric probes was performed on the peripheral blood sample. A normal cell line could not be seen in any postnatal tissue by either technique. The predominant cell line postnatally was 69,XXX. There were no cytogenetic polymorphisms and the parental origin of the different cell lines was not determined. Marked red cell macrocytosis of peripheral blood was noted on routine blood count. Bone marrow aspiration showed megaloblastic haemopoiesis without evidence of vitamin B12 or folate deficiency. At 2 1/2 years, the patient has significant developmental problems.

Abnormalities, Multiple↗
PubMed1995

Reproductive tract infections and abortion among adolescent girls in rural Nigeria.

Few studies from developing countries have investigated reproductive tract infections or other indicators of sexual health among unmarried adolescent girls in rural areas. We have obtained baseline demographic, clinical, and microbiological data on reproductive tract infections and induced abortion in girls in a rural area of southeast Nigeria, in order to assess the need for health care for adolescents. 868 females attended for interview and examination: 458 aged 20 and above and 410 aged 12-19, the latter representing 93.4%of the adolescent population. 43.6% of those < 17 and 80.1% aged 17-19 years were sexually active and at least 24.1% had undergone an induced abortion; only 5.3% had ever used a modern contraceptive. Vaginal discharge was reported by 82.4%, though few sought treatment. 94.1% of sexually active adolescents and 97.6% of sexually active women 20 years old or over were gynaecologically examined and screened for reproductive tract infections. Of those aged less than 17, 19.8% had symptomatic candida and 11.1% trichomonas infections. Among those aged 17-19 years, chlamydia was detected in 10.5%, and symptomatic candidosis in 25.6%; this was the group most likely to have any infection (43.8%). 42.1% of sexually active adolescents had experienced either an abortion or a sexually transmitted disease. Syphilis was the only infection for which the incidence clearly increased with age. Health-care services for adolescents in this community are needed and should include sex education, contraceptive provision (especially barrier methods), and access to treatment for reproductive tract infections. Investments in health for this age group will have an effect on subsequent reproductive health.

Abortion, Induced↗
PubMed1994

Prenatal diagnosis and post-mortem study of a fetus with mosaic trisomy 14 due to a dic(14)(p11).

Amniocentesis at 17 weeks' gestation revealed a mosaic karyotype--46,XX/46,XX,-14,+dic(14)(p11). No abnormalities were detected on ultrasound. Growth and placentation were normal. The fetus was examined after termination of pregnancy and micrognathia and pulmonary hyperlobation were the only abnormalities detected. Several tissues were set up for cytogenetics, including fetal skin, kidney, ovary, and placenta. The diagnosis was confirmed by these studies. The level of mosaicism varied between tissues, with the trisomy 14 cell line highest in amniotic fluid.

Adult↗
PubMed1994

Career paths revisited: the experiences of graduates in nursing who no longer work full-time.

Reports on the progress of British graduates in nursing focus on their early careers, when they are employed full-time. Part-time and non-employment is not discussed. This paper draws upon a longitudinal study, which began in 1981, to describe the cause and effect of graduates leaving full-time employment. The experiences of 45 female graduates in nursing from the University of Hull show that departure from full-time employment is associated especially with the establishment of a stable relationship, with child-rearing and, to a lesser extent, time for personal development.

Employment↗
PubMed1992

A familial lymphoproliferative disorder presenting with primary pulmonary manifestations.

A familial lymphoproliferative disorder presented in three male siblings with primary pulmonary involvement manifested as either lymphoid interstitial pneumonia or an angiodestructive polymorphous infiltrate morphologically resembling lymphomatoid granulomatosis. The polymorphous infiltrate consisted chiefly of mature T-cells with a few B-cells and plasma cells, and gene rearrangement studies failed to show clonality. Epstein-Barr virus, frequently associated with proliferative lesions in males in the X-linked lymphoproliferative syndrome, was not demonstrated in any of the pulmonary lesions. An HLA haplotype shared among the affected siblings was A1, B8, DR4. The unusual clinical presentation plus the lack of involvement by EBV in the pulmonary lesions suggests that this is a previously undescribed familial lymphoproliferative disorder.

Adolescent↗