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Biomedical subjects

J Kemp

Publications and source records attributed to J Kemp.

At least 19 recordsLinked to original sources

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗

Screening for pulmonary tuberculosis: an acceptable intervention for antenatal care clients and providers?

SETTING: Five purposively sampled health facilities in Kasungu District, Malawi. OBJECTIVES: To explore 1) the acceptability of introducing pulmonary tuberculosis (PTB) screening into antenatal care (ANC) clinics amongst ANC clients and ANC service providers; and 2) the acceptability of tuberculosis (TB) treatment during and after pregnancy among women registered for TB treatment. METHODS: Fourteen focus group discussions and 40 in-depth interviews with ANC clients (15), ANC service providers (10) and women registered for TB treatment (15). RESULTS: Most clients found the introduction of PTB screening into ANC clinics acceptable. Some expressed concern at submitting a second sputum specimen, citing transportation/distance as the main obstacle. Other concerns were stigma and fear relating to the human immunodeficiency virus and the acquired immune-deficiency syndrome (HIV/AIDS) and taking TB treatment during pregnancy and breast-feeding. All ANC service providers supported the idea, but were concerned about increased workload. CONCLUSION: PTB screening in the ANC setting would be an acceptable intervention and could serve to increase PTB case notification in Malawi. However, alternative diagnostic strategies need to be explored. The negative associations with HIV/AIDS and some of the misconceptions surrounding TB treatment need to be addressed to avoid PTB screening becoming a potential barrier to seeking ANC. The main challenge will be whether over-stretched staff will be able to cope with this additional service.

Breast Feeding↗

Distribution of intranasal C-zolmitriptan assessed by positron emission tomography.

Nine healthy volunteers aged 18-28 years were recruited into this open, single-centre, two-phase trial. In phase 1, two volunteers received a single dose of 11C-zolmitriptan 2.5 mg administered as a nasal spray and then underwent positron emission tomography (PET) scanning to determine the most appropriate times for scanning in phase 2. In phase 2, six volunteers received two doses and an additional volunteer one dose of 11C-zolmitriptan 2.5 mg intranasally. Volunteers underwent PET scanning over sectors covering one of the nasopharynx, lungs or abdomen, for up to 1.5 h postdose. The brain was also scanned and plasma zolmitriptan levels were measured. Almost 100% of the administered dose was detected in the nasopharynx immediately after dosing. This declined thereafter to about 50% at 20 min and to 35% at 80 min after dosing. Radioactivity appeared slowly in the upper abdomen, with 25% of given radioactivity detected at 20 min and persisting until 80 min after dosing. Minimal radioactivity was detected in the lungs. Radioactivity was detectable within brain tissue suggesting central penetration of zolmitriptan. Zolmitriptan in plasma had approached its maximum concentration by 15 min postdose. The data indicate initial absorption across the nasal mucosa contributing to an early systemic availability. 11C-Zolmitriptan administered intranasally was well tolerated.

Administration, Inhalation↗

'Lost' smear-positive pulmonary tuberculosis cases: where are they and why did we lose them?

SETTING: Ntcheu District, rural Malawi. OBJECTIVES: 1) To locate smear-positive pulmonary tuberculosis patients who were identified during the first 6 months of 2000 but did not start treatment ('lost cases'); 2) to describe these patients' pathways to diagnosis, health status and socio-demographic characteristics; and 3) to explore why these patients did not start treatment. METHODS: Lost cases were traced from programme registers and interviewed using the qualitative research critical incidents narrative (CIN) interviews technique. Results were triangulated with responses from health care workers through focus group discussions. RESULTS: The laboratory registered 157 new smear-positive patients. Twenty three (15%) of these were 'lost' (did not appear in the treatment register). CIN interviews were conducted with five lost patients and 14 carers of lost patients who had died. Long pathways to diagnosis were the norm. Health system structural barriers were the main factors behind these pathways, including requirement for hospital attendance, delays in symptom recognition and receipt of sputum results, and the misconception that negative smears excluded tuberculosis. CONCLUSION: Some smear-positive cases experience very long pathways to diagnosis and are lost from this free public health system. The diagnostic process needs to become more responsive to patients' needs.

Adult↗

A flowchart for managing sexually transmitted infections among Nigerian adolescent females.

OBJECTIVE: To devise a flowchart suitable for assessing risk of trichomoniasis, chlamydia and gonorrhoea in an adolescent population, not all of whom will be sexually experienced or currently in a relationship. METHODS: The data used to derive the flowchart were generated from cross-sectional microbiological surveys of girls aged 14-19 years in Port Harcourt, Nigeria. The flowchart screened on the basis of: (i) sexual experience; (ii) recent sexual activity; (iii) a positive urine leukocyte esterase (LE) test; and (iv) among LE negatives, a history of malodorous/pruritic discharge. FINDINGS: Using this flowchart, we found that 26.2% of all adolescents screened would receive treatment for cervicitis and vaginitis. Chlamydial, gonococcal, and trichomonal infections were correctly diagnosed in 37.5%, 66.7%, and 50% of the cases, respectively. CONCLUSION: Although the flowchart is more suitable for an adolescent population than the vaginal discharge algorithm used in syndromic management protocols, it still lacks precision and needs adapting to local settings.

Adolescent↗

The pharmacokinetics of the antimigraine compound zolmitriptan in Japanese and Caucasian subjects.

BACKGROUND: Zolmitriptan is a 5HT(1B/1D) receptor agonist effective in the acute treatment of migraine. Clinical trials in the USA and Europe have demonstrated the optimal oral therapeutic dose to be 2.5 mg. The 2.5-mg oral tablet has recently been licensed in Japan. OBJECTIVE: To compare the pharmacokinetics of zolmitriptan and its metabolites in Japanese and Caucasian subjects and evaluate the effect of gender on these pharmacokinetics in Japanese volunteers. METHODS: In this open, parallel-group study, 30 Japanese and 30 Caucasian volunteers (20-45 years) received a single 2.5-mg zolmitriptan tablet in the fasting state. Blood samples were taken up to 15 h post-dose to determine plasma concentrations of zolmitriptan and its active metabolite, 183C91. Urinary excretion of zolmitriptan, 183C91 and the inactive N-oxide and indole acetic acid metabolites were measured over 24 h. RESULTS: Japanese volunteers were, on average, smaller and lighter than Caucasian volunteers. Plasma-concentration profiles of zolmitriptan and 183C91 were similar in the two groups. Although geometric mean zolmitriptan and 183C91 area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) were slightly higher in Japanese subjects (up to 20%), these differences were not considered to be of clinical relevance as the 90% confidence interval for the ratio of AUCs fell within pre-specified limits (0.67 to 1.5). Mean zolmitriptan and 183C91 half-lives were around 2.5 h for both populations. Urinary excretion of the four analytes was similar in Japanese and Caucasians. Plasma concentrations of zolmitriptan were higher in Japanese females than males (AUC 40% and C(max) 29% higher), consistent with the results previously obtained in Caucasians. CONCLUSION: Pharmacokinetic parameters of zolmitriptan were similar between Caucasian and Japanese volunteers.

Administration, Oral↗

Measuring and modelling VOC biotransformation rates.

A new protocol was used to determine biotransformation rate coefficients for volatile organic compounds in activated sludge systems. The values obtained from the protocol were compared to biotransformation rates obtained from a pilot plant. It was seen that biotransformation rates were easier to obtain from the protocol. Observations also showed that acclimation of the microorganisms to the volatile organic compounds did not change the biotransformation rates. The experimental conditions were then modelled using TOXCHEM+, a mechanistic model to predict volatile organic compound behaviour. The TOXCHEM+ predictions, using system default biotransformation rates, compared favourably with the low biotransformation rates measured by the protocol for bromoform and the chlorinated compounds, while under predicting the biotransformation rates for the non-chlorinated volatile organic compounds.

Biotransformation↗

Is caspase-3 inhibition a valid therapeutic strategy in cerebral ischemia?

Neurodegenerative diseases are characterized by progressive impairment of brain function as a consequence of ongoing neuronal cell death. Apoptotic mechanisms have been implicated in this process and a major involvement of caspase-3, a typical pro-apoptotic executioner protease, has been claimed. In this review, the role of caspase-3 in neuronal cell loss in animal models of stroke is discussed and critically evaluated. In summary, it is concluded that the biochemical evidence favoring caspase-3 as a therapeutic target in cerebral ischemia is not convincing, and the development of selective caspase-3 inhibitors for the treatment of human stroke must be viewed as high risk.

Journal Article↗

Nurse education in Mbarara, Uganda.

AIM: To describe the establishment of a professional development programme for qualified nurses at Mbarara University Teaching Hospital, Uganda. BACKGROUND: Between 1997 and 1999, a group of hospital-based nurses and university lecturers in Hull, United Kingdom, planned and delivered a series of modules to set the Ugandan nurses on course for continuing professional development. APPROACH: A descriptive account of the delivery of the programme. FINDINGS: Evaluation of the programme indicates that the nurses' morale was raised by satisfactory completion of the modules and that there were visible improvements in the organization of patient care in the hospital. CONCLUSIONS: This professional development programme was a learning experience for all the parties involved. Support from Hull for the education of nurses in Mbarara will continue.

Curriculum↗

Blood transfusions and risk of non-Hodgkin's lymphoma subtypes and chronic lymphocytic leukemia.

Allogeneic blood transfusion has been suggested as a risk factor for non-Hodgkin's lymphoma (NHL), possibly specific to certain NHL subtypes, or chronic lymphocytic leukemia (CLL). Self-reported transfusion history and risk of NHL subtypes and CLL were examined in a cohort of 37,934 older Iowa women, using data from a questionnaire mailed in 1986. Through 1997, 229 cases of NHL and 57 cases of CLL in the cohort were identified through linkage to the Iowa Surveillance, Epidemiology and End Results Cancer REGISTRY: Women who reported ever receiving a blood transfusion were at increased risk for all NHLs [age adjusted relative risk (RR), 1.6; 95% confidence interval (CI), 1.2-2.1). On the basis of the Working Formulation classification, blood transfusion was positively associated with low-grade NHL (RR, 2.7; 95% CI, 1.7-4.5) but not with intermediate-grade NHL (RR, 1.1; 95% CI, 0.7-1.6); there were only 8 cases of high-grade NHL. Blood transfusion was positively associated with follicular (RR, 2.8; 95% CI, 1.6-5.1) and small lymphocytic (RR, 3.4; 95% CI, 1.5-7.9) NHL subtypes but not with diffuse NHL (RR, 1.0; 95% CI, 0.7-1.5). There was also a positive association with CLL (RR, 1.7; 95% CI, 1.0-3.0). Finally, transfusion was associated with nodal (RR, 1.8; 95% CI, 1.3-2.5) but not extranodal (RR, 1.2; 95% CI, 0.7-2.1) NHL. Further adjustment for marital status, farm residence, diabetes, alcohol use, smoking, and red meat and fruit consumption did not alter these associations. In conclusion, prior blood transfusion was associated with NHL and CLL, and the strongest associations were seen for low-grade NHL, particularly follicular and small lymphocytic NHL.

Aged↗

Spectrum of color gene deletions and phenotype in patients with blue cone monochromacy.

Blue cone monochromacy (BCM) is an X-linked ocular disease characterized by poor visual acuity, nystagmus, and photodysphoria in males with severely reduced color discrimination. Deletions, rearrangements and point mutations in the red and green pigment genes have been implicated in causing BCM. We assessed the spectrum of genetic alterations in ten families with BCM by Southern blot, polymerase chain reaction, and sequencing analysis, and the phenotype was characterized by ophthalmoscopy, fluorescein angiography, and a battery of tests to assess color vision in addition to routine ophthalmological examination. All families showed clinical features associated with BCM. Acuities were reduced in all affected males, and photopic b-wave was reduced by more than 90% in seven families. In three families, however, the photopic b-wave response showed uncharacteristic relative preservation of 30-80% (of the clinical low-normal value). The color vision was unusually preserved in two affected males, but this was not correlated with photopic electroretinography retention. Progressive macular atrophy was observed in affected members of two BCM families while the rest of the families presented with normal fundus. In nine families deletions were identified in the gene encoding the red-sensitive photopigment and/or in the region up to 17.8 kb upstream of the red gene which contains the locus control region and other regulatory sequences. In the same nine families the red pigment gene showed a range of deletions from the loss of a single exon to loss of the complete red gene. In one family no mutation was found in the exons of the red gene or the locus control region but showed loss of the complete green gene. No association was observed between the phenotypes and genotypes in these families.

Adult↗

Smoking and risk of non-Hodgkin lymphoma subtypes in a cohort of older women.

Although non-Hodgkin lymphoma (NHL) has not been considered to be a smoking-related malignancy, recent investigations suggest otherwise. We evaluated this association in a cohort of 37,336 women, aged 55-69 years, who reported in a mailed questionnaire in 1986 information regarding smoking history as well as demographic, medical history and dietary factors. Cancer and mortality experience through 1996 was determined by linkage to the Iowa Cancer Registry and other databases; there were 200 incident cases of NHL during the 380,231 total person-years of follow-up. Compared to never smokers, former (age-adjusted RR = 1.0; 95% CI 0.8-1.5) and current smokers (age-adjusted RR = 1.0; 95% CI 0.7-1.5) were not at elevated risk of NHL, and there was no trend with pack-years smoked (Ptrend = 0.3). Multivariate adjustment for other NHL risk factors did not alter these findings. Age-adjusted analysis by NHL subtype revealed a suggestive positive association of smoking with follicular NHL [(RRformer = 1.3; 95% CI 0.6-2.8), (RRcurrent = 1.8; 95% CI 0.8-3.8)], which strengthened after multivariate adjustment [(RRformer = 1.6; 95% CI 0.7-3.4), (RRcurrent = 2.3; 95% CI 1.0-5.0)]; there was no association for diffuse or small cleaved-cell NHL. Our study findings, which are consistent with other recent investigations, suggest that smoking may be associated with an increased risk of follicular NHL.

Age Factors↗

Juvenile X-linked retinoschisis from XLRS1 Arg213Trp mutation with preservation of the electroretinogram scotopic b-wave.

PURPOSE: To present an Arg213Trp missense mutation in the XLRS1 gene in a family with juvenile X-linked retinoschisis in which one affected male had a normal electroretinogram scotopic b-wave amplitude. METHODS: Two affected males and one unaffected male from this family with X-linked retinoschisis underwent standard clinical examination including an electroretinogram. Mutations in the XLRS1 gene were detected by sequence analysis and by restriction enzyme assay for loss of an MSP-I restriction site. RESULTS: A missense mutation of C to T at nucleotide position 637 was identified in exon 6 of the XLRS1 gene. This changed the positively charged arginine to a nonpolar tryptophan (Arg213Trp) within the biologically important discoidin domain. Clinical examination revealed intraretinal cysts in a spoke-wheel distribution and early macular atrophy of the retinal pigment epithelium. Whereas the older affected patient had an "electronegative" electroretinogram typical of retinoschisis, the 13-year-old grandson with the same XLRS1 mutation had a normal electroretinogram scotopic b-wave. CONCLUSION: Although the electroretinogram is a key diagnostic test for X-linked retinoschisis, this report of a normal electroretinogram scotopic b-wave in a male with molecularly confirmed X-linked retinoschisis indicates that caution is advised in relying on the electroretinogram in differential diagnosis of this condition.

Adolescent↗

The problems of treating adolescent asthma: what are the alternatives to inhaled therapy?

The prevalence of asthma in children and adolescents continues to increase world-wide, with asthma remaining the most common chronic illness of childhood. Morbidity is high in the latter age group, indicating that many adolescents with asthma symptoms are not receiving appropriate treatment for their condition. Inadequate symptomatic control should alert the physician to the possibility of non-compliance, which is not limited to those patients with a poor understanding of their condition. Psychosocial problems, such as isolation and low self-esteem, are inherent in adolescents with asthma due, in part, to the highly visible nature of symptoms and the method of delivery of current inhaled therapy. Compliance with therapy in adolescents in particularly low if the dosing regimen is more than twice daily, with poor inhaler technique contributing to ineffective control. Failure to take asthma medication can result in asthma exacerbations and increased disease severity, with the resultant need for powerful medication and hospitalization (incurring substantial patient and healthcare costs). Although better management techniques, such as tailoring medication and individualizing treatment regimens may improve compliance in this group, there is an obvious need for alternative treatment options. An effective and well tolerated oral tablet therapy, with a simple unobtrusive regimen, would provide a potential solution to the high level of non-compliance seen in this age group. The leukotriene receptor antagonists offer a practical alternative amongst existing oral therapies, and their efficacy and simple oral dosing regimen may prove valuable in increasing compliance in adolescents.

Administration, Oral↗

Rapid onset of control with budesonide Turbuhaler in patients with mild-to-moderate asthma.

BACKGROUND: Budesonide (Pulmicort) is an inhaled corticosteroid with high topical potency but low systemic activity. Turbuhaler is a novel breath-actuated, multi-dose, dry-powder inhaler. OBJECTIVES: This study was conducted to determine the efficacy and safety of two different dose regimens of budesonide Turbuhaler, compared with placebo, in adult patients with mild-to-moderate asthma not well-controlled with bronchodilator therapy. METHODS: This double-blind, randomized, placebo-controlled, parallel-group, multicenter study compared the efficacy and safety of 200 microg and 400 microg of budesonide, administered twice daily via Turbuhaler, with placebo, in 273 adult patients (aged 19 to 70 years) with mild-to-moderate asthma (FEV1 67% of predicted normal), not well-controlled with bronchodilator therapy. Efficacy was assessed by pulmonary function tests and patient assessments of asthma symptom control. Safety was assessed in terms of adverse events, laboratory evaluations, and physical examinations. RESULTS: Two hundred and 400 microg of budesonide bid were significantly more effective than placebo at improving morning PEF (mean differences from placebo of 43.63 L/min and 40.10 L/min, respectively; P < .001) and FEV1 (mean differences from placebo of 0.44 L, and 0.50 L, respectively; P < .001) over the 12-week treatment period. Onset of action as assessed by morning PEF was within two days. Basal and stimulated plasma cortisol concentrations were not significantly affected by budesonide treatment compared with placebo. CONCLUSIONS: Treatment of adults suffering from mild-to-moderate asthma with budesonide Turbuhaler is well tolerated and results in a rapid onset of asthma control which is maintained over time.

Administration, Inhalation↗