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Biomedical subjects

J Young

Publications and source records attributed to J Young.

At least 253 records · Page 14Linked to original sources
PubMed1997

A prospective analysis of 949 long-term central venous access catheters for ambulatory chemotherapy in patients with gastrointestinal malignancy.

We present a prospective analysis of the insertion complications and longevity of 949 cuffed, tunnelled central venous catheters used for ambulatory chemotherapy. Mean catheter life span was 121.8 days, 13.4% had complications at insertion, 17.7% had complications not necessitating removal and 18.6% had complications requiring removal. The more experienced operators had fewer complications inserting catheters (P < 0.0001). Late-onset shoulder pain occurred in 4.8% and was associated with an increased incidence of venous thrombosis (P < 0.0001) and infection (P = 0.06). Complications necessitating removal were not predicted by patient' age, site of insertion or malignancy, chemotherapy regimen, insertion platelet and fibrinogen counts, insertion complications, leucocyte count or cuff distance from the exist site. Catheters inserted with their tip in the superior vena cava were more at risk of removal (2.57 times) than those in the right atrium (P = 0.003).

Adolescent↗
PubMed1997

Mapping ESTs to the TSC1 candidate interval by use of the 'Science 96' transcript map.

The transcription map of the human genome published by Schuler et al. (1996) is a valuable resource in which approximately one quarter of all human genes have been mapped with respect to genetic framework markers using radiation hybrids. We have taken information from this map to provide potential genes within the TSC1 candidate region on chromosome 9q34. In so doing we have been able to provide an independent assay of the quality of the radiation hybrid mapping by using somatic cell hybrids and a 2 Mb cosmid contig covering the TSC1 region as mapping tools. In addition, we have built sequence contigs of ESTs for 25 clusters. This has shown that about 20% of the relevant EST clusters in the Unigene resource (Boguski & Schuler 1995) contain chimaeric clones.

Animals↗
PubMed1997

Regulation of Pdha-2 expression is mediated by proximal promoter sequences and CpG methylation.

Spermatogenesis is a complex process requiring the coordinate expression of a number of testis-specific genes. One of these, Pdha-2, codes for the murine spermatogenesis-specific isoform of the E1a subunit of the pyruvate dehydrogenase complex. To begin to delineate the mechanisms regulating its expression in vivo, we have generated transgenic mice lines carrying Pdha-2 promoter deletion constructs. Here we report that transgenic mice harboring a construct containing only 187 bp of promoter and upstream sequences (core promoter) is sufficient for directing the testis-specific expression of a chloramphenicol acetyltransferase (CAT) reporter gene. Like the endogenous Pdha-2, the CAT gene is expressed in testis in a stage-specific manner. Our studies also show a correlation between CpG methylation within the core promoter and its capacity to regulate transcription. In NIH 3T3 cell lines stably transfected with the Pdha-2 core promoter-CAT construct, high levels of CAT reporter expression are observed, whereas the endogenous Pdha-2 gene is repressed. In these cells, the CpG dinucleotides residing within the transfected promoter are hypomethylated whereas those residing in the endogenous promoter are methylated. Furthermore, promoter activity can be abated by the in vitro methylation of its CpG dinucleotides. DNase I footprint analysis indicates that at least one site for the methylation-mediated repression may occur through the ATF/cyclic AMP response element binding element located within the core promoter. Mutations within this element reduces activity to approximately 50% of the wild-type promoter activity. These results suggest that tissue-specific gene expression may be modulated by other mechanisms in addition to specific transcription factor availability and cooperativity. We propose that methylation may be a mechanism by which repression of the testis-specific Pdha-2 gene is established in somatic tissue.

3T3 Cells↗
PubMed1997

A qualitative study of specialist nurse support for stroke patients and care-givers at home.

BACKGROUND: The involvement of five specialist nurses in providing a stroke support service was evaluated quantitatively in a recent randomized controlled trial. This complementary study used qualitative methods to evaluate trial outcomes more comprehensively. AIMS: To identify whether the nurses' intervention may have influenced the process of stroke recovery. METHOD: A purposefully selected subsample of 30 patients and 15 care-givers were interviewed within 1-3 months of their final quantitative assessment (12 months after recruitment to the randomized trial). Fifteen of the patients and eight of the care-givers had received visits from a specialist nurse. A semistructured interview was designed to include questions on perceptions of the recovery process and evaluation of services received. RESULTS: Some differences were evident between the accounts of control and intervention group subjects. The less tangible aspects of nurses' interventions--concern, attention, empathy and interest, when combined with sound professional knowledge, had identifiable value to the patients and care-givers. It appeared that the nurses had employed considerable sensitivity and skill in identifying and responding to particular needs at appropriate times. CONCLUSION: The qualitative evaluation offers a different picture to the quantitative results of the randomized controlled trial. In general, the findings of the qualitative study are more positive and encouraging than the quantitative results. The majority of patients and care-givers in the intervention group believed that they had benefited from the specialist nurse's visits.

Caregivers↗
PubMed1997

Free luteinizing-hormone beta-subunit in normal subjects and patients with pituitary adenomas.

Most clinically nonfunctioning pituitary adenomas (NFPA) are found to be gonadotropinomas when assessed by immunocytochemistry. However, they are rarely associated with increased basal plasma levels of FSH, LH and/or alpha-subunit. It has been claimed that the paradoxical free LHbeta response to TRH may be a useful clinical tool for determining the gonadotropic nature of NFPA. We used a very specific and sensitive immunoradiometric assay (IRMA) for free LHbeta measurement and another specific IRMA to check the absence of free CGbeta, to study normal subjects and 26 patients with NFPA. Basal plasma levels of LHbeta were undetectable in normal men and premenopausal women in the early follicular phase. In contrast, normal postmenopausal women had increased basal plasma LHbeta, parallel to dimeric LH and alpha-subunit levels. In healthy subjects, stimulation with GnRH elicited an increase in LHbeta while TRH was ineffective. In patients with NFPA, LHbeta hypersecretion was found basally and/or after stimulation with TRH in 3 of 16 men, 3 of 5 premenopausal women, and 1 of 5 postmenopausal women, i.e. 7 of 26 patients (26%). In 3 of these 7 cases, alpha-subunit and/or FSH levels were also increased. The LHbeta measurement was thus truly informative on the gonadotropic nature of NFPA in only 4 out of 26 cases (15%). In addition, increased LHbeta levels and/or a positive response of free LHbeta to TRH was observed in 3 patients with pure prolactinomas but in no patients with GH-secreting adenomas. Thus, using this very sensitive and specific IRMA, free LHbeta measurement is rarely helpful for determining the gonadotropic nature of NFPA.

Acromegaly↗
PubMed1997

Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone (DHEA) in humans.

The physiological importance and therapeutical interest of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are still controversial. Panhypopituitarism is characterized by the absence of secretion of adrenal and gonadal steroids and thus the production of their metabolites. The conversion of DHEA given orally into delta 5 derivatives, androgens, androgen metabolites, and estrogens was studied in ten patients with complete panhypopituitarism. Sex steroid therapy was withdrawn for at least 2 months. Each patient received, at 1-month intervals and in a random order, two single oral doses of DHEA (50 mg and 200 mg) and placebo. During each treatment, urine samples were collected for 24 h, and blood samples were drawn at hourly intervals for 8 h. In patients with pituitary deficiency, plasma DHEA and DHEAS were not detectable and increased, with the 50 mg dose, up to levels observed in young adults. The administration of 200 mg of DHEA induced an increase of both steroids to supraphysiological plasma levels. A small increase of delta 5-androstenediol was observed. In contrast, the increase of plasma delta 4-androstenedione was important and dose dependent. DHEA was also converted into the potent sex steroid testosterone (T). The administration of a 50 mg dose of DHEA restored plasma T to levels similar to those observed in young women. The 200 mg dose induced an important increase of plasma T, slightly below the levels observed in normal men. The increase of plasma dihydrotestosterone levels was small at both doses of DHEA, in contrast with the large conversion of DHEA into androsterone glucuronide and androstanediol glucuronide. Finally, DHEA administration induced a significant and dose dependent increase of plasma estrogens and particularly of estradiol. In conclusion, this short term study demonstrates that: 1) panhypopituitarism is a model of interest to study the metabolism of DHEA; 2) in the absence of pituitary hormones and of adrenal and gonadal steroids, DHEA given orally is mainly converted into delta 4 derivatives, which in turn are strongly metabolized into 5 alpha-3keto-reduced steroids; 3) a significant increase of sex active hormones was observed in plasma after 200 and even 50 mg of DHEA. Thus, biotransformation of DHEA into potent androgens and estrogens may explain several of the reported beneficial actions of this steroid in aging people.

Adult↗
PubMed1997

Design of a Web interface for anatomical images.

Interactive documents for use with the World Wide Web have been developed for viewing multi-dimensional radiographic and visual images of human anatomy, derived from the Visible Human Project. Emphasis has been placed on user-controlled features and selections. The purpose was to develop an interface which was independent of host operating system and browser software which would allow viewing of information by multiple users. The interfaces were implemented using HyperText Markup Language (HTML) forms, C programming language and Perl scripting language. Images were pre-processed using ANALYZE and stored on a Web server in CompuServe GIF format. Viewing options were included in the document design, such as interactive thresholding and two-dimensional slice direction. The interface is an example of what may be achieved using the World Wide Web. Key applications envisaged for such software include education, research and accessing of information through internal databases and simultaneous sharing of images by remote computers by health personnel for diagnostic purposes.

Anatomy, Cross-Sectional↗
PubMed1996

Rehabilitation and older people.

Rehabilitation is concerned with lessening the impact of disabling conditions. These are particularly common in older people and considerable health gain can be achieved by successful rehabilitation. Hospital doctors and general practitioners should be aware of the core principles of rehabilitation, be able to recognise rehabilitation need in their patients, and have sufficient knowledge of their local rehabilitation services to trigger the referral process.

Activities of Daily Living↗
PubMed1996

Specialist nurse support for patients with stroke in the community: a randomised controlled trial.

OBJECTIVE: To evaluate whether specialist nurse visits enhance the social integration and perceived health of patients with stroke or alleviate stress in carers in longer term stroke care. DESIGN: Stratified randomised controlled trial; both groups assessed at time of recruitment and at 3, 6, and 12 months. SETTING: Patients with disability related to new stroke who lived in their own homes in the Bradford Metropolitan District. SUBJECTS: 240 patients aged 60 years or over, randomly allocated to control group (n = 120) or intervention group (n = 120). Intervention--Visits by specialist outreach nurses over 12 months to provide information, advice, and support; minimum of six visits during the first six months. The control group received no visits. MAIN OUTCOME MEASURES: The Barthel index (functional ability), the Frenchay activities index (social activity), the Nottingham health profile (perceived health status). Stress among carers was indicated by the general health questionnaire-28 (28 items). The nurses recorded their interventions in trial diaries. RESULTS: There were no significant differences in perceived health, social activities, or stress among carers between the treatment and control groups at any of the assessments points. A subgroup of mildly disabled patients with stroke (Barthel index 15-19) had an improved social outcome at six months (Frenchay activities index, Median difference 3 (95% confidence interval 0 to 6; P = 0.03) and for the full 12 months of follow up (analysis of covariance P = 0.01) compared with the control group. CONCLUSIONS: The specialist nurse intervention resulted in a small improvement in social activities only for the mildly disabled patients. No proved strategy yet exists that can be recommended to address the psychosocial difficulties of patients with stroke and their families.

Aged↗
PubMed1996

Off-label drug use in human immunodeficiency virus disease.

We wished to determine the extent to which drugs used to treat HIV disease and its clinical manifestations are prescribed for conditions other than those listed on the U.S. Food and Drug Administration's approved drug label, how such "off-label" use varies by patient characteristics and type of HIV-related medical condition, and the extent to which physicians alter the way they treat HIV-related conditions because of reimbursement problems associated with off-label drug use. We surveyed 1,530 primary care providers for people with HIV disease between February and May 1993. A three-part survey instrument was used to obtain data on the drugs prescribed for the last three patients with HIV disease treated by the provider, the preferred choice of therapy for 32 specific HIV-related conditions, and the extent to which providers faced reimbursement problems regarding the use of drugs for off-label indications. Three drug compendia were used as cited sources of off-label drug uses. In all, 387 (32%) evaluable surveys were returned, yielding data on 1,148 patients. The majority (81%) of patients received at least one drug off-label, and almost half (40%) of all reported drug therapy was off-label. Most off-label drug use was for treatment and prevention of HIV-related opportunistic infections, which frequently represented the community standard of practice (e.g., trimethoprim/sulfamethoxazole for prevention of Pneumocystis carinii pneumonia), or the de facto standard of practice when no licensed therapies were available (e.g., drugs for treatment of Mycobacterium avium complex, MAC). More than 75% of off-label usage was cited in at least one of the three authoritative medical compendia. The use of drugs for off-label indications in HIV care is common and frequently represents community standards of care. Reliance on drug compendia for support of off-label drug use accounts for the majority of such uses, although many legitimate off-label uses may not be included because of compendia publication lag. The prevalence of off-label drug use in routine clinical practice and the development of newer and more costly drugs for treatment of HIV and its medical complications argues for the articulation of an explicit national reimbursement policy for off-label uses of prescription drugs so that medically appropriate therapies will be available to those with insurance in a rational, consistent way.

AIDS-Related Opportunistic Infections↗
PubMed1996

Chiral kinetics and dynamics of ketorolac.

It has been shown that the analgesic and cyclooxygenase inhibitor activity of ketorolac tromethamine (KT), which is marketed as the racemic mixture of (-)S and (+)R enantiomers, resides primarily with (-)S ketorolac and that the ulcerogenic activity of this agent also resides in (-)S ketorolac. Resolution of individual enantiomers for analysis in plasma samples has been accomplished by two methods: derivatization to form diastereomers that are separated by HPLC, or direct HPLC using a chiral phase column. When mice and rats were given oral solutions of (-)S and (+) KT, it was found that the kinetics and interconversion of the enantiomers were species and dose dependent. Interconversion was higher in mice than in rats; when (-)S KT was administered, 71% of the area under the concentration-time curve (AUC) was due to (+)R ketorolac in mice, compared with 12% in rats. More interconversion was observed at higher doses; the percent of AUC due to (-)S ketorolac when (+)R KT was administered increased from 12% to 25% in mice and from 2% to 8% in rats. In general, more interconversion occurred from (-)S to (+)R ketorolac in the animal studies. Human subjects were given single oral solution doses of racemic KT (30 mg), (-)S KT (15 mg), and (+)R KT (15 mg). The plasma concentrations of (-)S ketorolac were lower than (+)R ketorolac at all sample times after racemic KT (22% of the AUC was due to (-)S ketorolac). When (+)R KT was administered, (-)S ketorolac was not detectable and interconversion was essentially 0%. When (-)S KT was administered, significant levels of (+)R ketorolac were detectable and interconversion was 6.5%. After all doses, plasma half-life was shorter and clearance greater for (-)S ketorolac than for (+)R ketorolac. Thus, in humans very little or no interconversion of (+)R to (-)S was observed, and interconversion of (-)S to (+)R was minimal (6.5%). These data demonstrate that the kinetics and interconversion of the enantiomers of ketorolac is different in animals and humans as well as from most other NSAIDs. This may be due to more rapid excretion or metabolism of (-)S ketorolac and a different mechanism of interconversion.

Animals↗
PubMed1996

A mouse mutant strain highly resistant to methyl beta-carboline-3-carboxylate-induced seizures.

The convulsant properties of methyl beta-carboline-3-carboxylate (beta-CCM) were evaluated in the TaT-fm/GncTa+/+Tfm strain carrying the tabby coat color (Ta) and/or the testicular feminization (Tfm) gene. When injected intraperitoneally within a 5-60 mg/kg dose range, beta-CCM-induced convulsions in less than 25% of the mice, thus providing evidence for a high resistance of this strain, as compared to classical strains of mice. However, this strain responds normally to the convulsant pentylenetetrazol (PTZ), suggesting a specific resistance to beta-CCM. Both the Ta gene and the TaTfm/Gnc genetic background were involved in the high resistance to beta-CCM. In addition, concentrations of neurosteroids and benzodiazepine binding, both modulating GABAA receptor efficacy, have been measured in order to elucidate the biological mechanisms of drug resistance.

Animals↗
PubMed1996

Neurosteroids in the mouse brain: behavioral and pharmacological effects of a 3 beta-hydroxysteroid dehydrogenase inhibitor.

Inhibition of the aggressive behavior of castrated male mice toward lactating female intruders by dehydroepiandrosterone (DHEA) is correlated with a decrease of pregnenolone sulfate (PREG S) concentrations in brain. We attempted to establish a cause to effect relationship by preventing the decrease of PREG S with trilostane (TRIL), a competitive inhibitor of delta 5-3 beta-hydroxysteroid dehydrogenase delta 5 --> 4 isomerase enzyme. Indeed, TRIL elicited a large increase of PREG levels in brain. Those of PREG S were, however, unchanged, and TRIL unexpectedly decreased the aggressive behavior of control castrated males and did not counteract the inhibition elicited by DHEA. The neurosedative progesterone (PROG) metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one (TH PROG), undetectable in the brain of control mice, reached nanomolar concentration range in TRIL-treated ones. However, injection of appropriate amounts of PROG, producing an even larger increase of brain TH PROG, had no antiaggressive effect. Finally, the latter was attributed to the large (up to 80 nM) TRIL-induced increase of brain 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one, which like TH PROG potentiates inhibitory gamma-aminobutyric acid (GABA)ergic neurotransmission.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Acute hypoglycemia masquerading as head trauma: a report of four cases.

Hypoglycemia, a commonly encountered metabolic emergency, is most often easily diagnosed and rapidly treated with satisfactory patient outcome. If not recognized and treated promptly, hypoglycemia may cause irreversible central nervous system injury; it rarely results in death. The classic presentation of hypoglycemia, a patient with diabetes mellitus on medical therapy (Insulin or oral hypoglycemic agents) who presents with an altered sensorium, is frequently seen in the emergency department (ED). Less often, patients with this metabolic emergency present to the ED in a manner suggestive of a situation other than hypoglycemia. Patients may present with seizure activity or focal neurological deficits, leading the physician to treat a primary neurological syndrome and not immediately recognize the primary cause of the problem. Alternatively, patients with hypoglycemia will present to the ED with an altered mental status after a traumatic event. The physician may again assume that the alteration in consciousness has resulted from a head injury and not a metabolic disorder. Four cases are presented in which the medical history of the event (i.e., trauma) suggested head injury as an explanation of the presentation when, in fact, hypoglycemia was responsible for the altered sensorium. The diagnosis of hypoglycemia is easily made with the performance of a bedside screening test which can be subsequently confirmed by laboratory blood analysis. It is imperative that emergency physicians consider hypoglycemia in all patients with any mental status abnormality, focal neurological deficit, or seizure activity, even when the findings seem to be explained initially by other etiologies.

Acute Disease↗