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Biomedical subjects

L Young

Publications and source records attributed to L Young.

At least 55 records · Page 3Linked to original sources

A framework for monitoring maternal and infant health status.

The Mother and Infant Network (MINET) Program was established in South Western Sydney Area Health Service (SWSAHS) in 1997. MINET developed and implemented an integrated clinical data network as a key strategy to support and inform a Continuum of Care comprising hospital and community based services. There are good data sources within the MINET program. Its scope spans care for mothers and children, which begins with the first antenatal attendance and ends at school entry. This paper has three interrelated aims: to describe the development of the MINET program; to demonstrate the benefits of a sustainable Information Culture which can assist an Area Health Services in adopting a health outcomes based approach to service delivery; and to describe how MINET has the capacity to support Health Services Research.

Female↗

Nursing student residency program: a model for a seamless transition from nursing student to RN.

It takes a relatively long time for new nursing graduates to become oriented and comfortable with work routines on the nursing unit. To address the problem, the authors formed a partnership among three educational programs and three hospitals. This article describes a 900-hour residency program for senior baccalaureate nursing students to ease their transition into the role of beginning-level staff nurse in an acute-care setting. The benefits to the hospitals were decreased orientation time, less turnover in staff (50% at 2 years), and lower recruitment costs.

Attitude of Health Personnel↗

A comparison of palatal adaptation in acrylic resin denture bases using conventional and anchored polymerization techniques.

PURPOSE: The study investigated the effects of palatal depth and a resin anchoring system on the adaptation of denture base resin to the master cast after compression molding and heat polymerization. MATERIALS AND METHODS: Forty-eight virtually identical polymethyl methacrylate dentures were fabricated on master casts with either a deep or shallow palatal vault. One half of the master casts of each palate type were altered by the addition of anchoring holes along the posterior land area, as well as perpendicularly in the midsaggital area. Anchoring holes were made with a #8 round bur to a depth of 5 mm. Twenty-four hours after polymerization, the bases on their casts were sectioned at the posterior border and evaluated for degree of adaptation using a traveling microscope. Maladaptation at the interface of the denture base and master cast was measured at predetermined mediolateral locations. A split-plot analysis of variance (alpha = 0.05) was performed followed by a post-hoc Dunn Multiple Comparison Test. RESULTS: In general, depth of the palatal vault did not significantly influence denture palatal discrepancy (p =.0780), but the use of the anchoring system significantly reduced mean gap distances (p =.000). At lateral and midpalate locations, gap distances between the denture bases and their casts were reduced from approximately 0.3 mm to approximately 0.1 mm when the anchoring system was used. CONCLUSIONS: Mean gap distances for steep palate dentures were significantly less than shallow palate dentures at vestibule and lateral palate locations, and anchoring holes placed in an edentulous master cast along the posterior land area and at the midline significantly improved the adaptation of denture bases.

Acrylic Resins↗

Impact of chronic gastrointestinal symptoms in diabetes mellitus on health-related quality of life.

OBJECTIVES: Morbidity from GI symptoms in diabetes is considered to be high, but no studies have quantified the impact of GI symptoms in diabetes on health-related quality of life. We hypothesized that diabetics reporting increased GI symptoms would experience more impaired quality of life. METHODS: Subjects from the community with diabetes (n = 892) and outpatients with diabetes (n = 209) were recruited for this study. Subjects were divided into type 1 (diabetes diagnosed at age <30 yr and requiring insulin) and type 2. A validated questionnaire measuring GI symptoms and diabetes status and the Short Form-36 were completed. The results were compared with Australian normal data. GI symptom groups measured were frequent abdominal pain, bowel-related abdominal pain, reflux, dyspepsia, constipation, diarrhea, and fecal incontinence. RESULTS: There was a clinically significant decrease in quality-of-life scores in diabetics compared with population norms across all subscales. The impact on quality of life in diabetes was predominantly observed in type 2 diabetics. The quality-of-life scores in all subscales decreased markedly with increasing numbers of distinct GI symptom groups, and this was similar in community and outpatient diabetics. For all the Short Form-36 subscales, GI symptom groups were significantly (all p < 0.0001) associated with poorer quality of life in diabetes, independent of age, gender, smoking, alcohol use, and type of diabetes. CONCLUSIONS: GI symptoms impact negatively on health-related quality of life in diabetes mellitus.

Adult↗

Psychological distress is linked to gastrointestinal symptoms in diabetes mellitus.

OBJECTIVE: Gastrointestinal (GI) symptoms are common in patients with long-standing diabetes mellitus, but the pathogenesis is controversial. We aimed to determine if GI symptoms are linked to psychological distress in diabetes. METHODS: A consecutive sample of outpatients with diabetes mellitus (n = 209) and a random sample of community diabetics (n = 892) completed a validated questionnaire measuring GI symptoms, the Hospital Anxiety and Depression (HAD) Scale for anxiety and depression, and the Eysenck short neuroticism scale. RESULTS: Overall, 42% reported one or more GI symptoms: bloating, abdominal pain, loose stools, and urgency were most common. The mean HAD and neuroticism scores were significantly higher for most GI symptoms (11 of 14, all p < 0.05), and a dose-response relationship was observed. GI symptoms were, in general, approximately twice as frequent in cases with anxiety or depression (HAD > or = 11). Anxiety, depression, and neuroticism were each independently associated with the number of GI symptoms, adjusting for age, gender, duration and type of diabetes, and self-reported glycemic control. CONCLUSIONS: Increased levels of state anxiety and depression and neuroticism are associated with upper and lower GI symptoms in diabetes mellitus. It is uncertain whether psychological distress is causally linked to symptoms, or whether GI symptoms per se increase levels of anxiety and depression.

Anxiety↗

Trisomy 17 in a bonobo (Pan paniscus) and deletion of 3q in a lowland gorilla (Gorilla gorilla gorilla): comparison with human trisomy 18 and human deletion 4q syndrome.

A female bonobo (Pan paniscus) born at the San Diego Zoo exhibited inability to nurse and progressive weakness plus multiple congenital abnormalities including aural canal atresia and stenosis, malformed auricles, clenched hands, lordosis, agenesis of the caudal vertebra and cardiac abnormalities. Chromosome analysis identified the bonobo as being trisomic for chromosome 17, the homolog of human chromosome 18. Genotyping with human microsatellites suggested the extra chromosome was maternal in origin. In addition, a male lowland gorilla (Gorilla gorilla gorilla), also born at the zoo, exhibited postnatal growth retardation, facial dysmorphisms and small hands with short fingers. Karyotype analysis revealed the gorilla carried a deletion of the distal q arm of chromosome 3, the homolog of human chromosome 4. The phenotypic and karyotypic abnormalities found in the bonobo and gorilla were consistent with the characteristics of human trisomy 18 and human deletion 4q syndrome, respectively.

Animals↗

Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy.

These neuroendocrine studies were part of a series of studies testing the hypotheses that 1) there may be reduced activity of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome and 2) low-dose augmentation with hydrocortisone therapy would improve the core symptoms. We measured ACTH and cortisol responses to human CRH, the insulin stress test, and D-fenfluramine in 37 medication-free patients with CDC-defined chronic fatigue syndrome but no comorbid psychiatric disorders and 28 healthy controls. We also measured 24-h urinary free cortisol in both groups. All patients (n = 37) had a pituitary challenge test (human CRH) and a hypothalamic challenge test [either the insulin stress test (n = 16) or D-fenfluramine (n = 21)]. Baseline cortisol concentrations were significantly raised in the chronic fatigue syndrome group for the human CRH test only. Baseline ACTH concentrations did not differ between groups for any test. ACTH responses to human CRH, the insulin stress test, and D- fenfluramine were similar for patient and control groups. Cortisol responses to the insulin stress test did not differ between groups, but there was a trend for cortisol responses both to human CRH and D-fenfluramine to be lower in the chronic fatigue syndrome group. These differences were significant when ACTH responses were controlled. Urinary free cortisol levels were lower in the chronic fatigue syndrome group compared with the healthy group. These results indicate that ACTH responses to pituitary and hypothalamic challenges are intact in chronic fatigue syndrome and do not support previous findings of reduced central responses in hypothalamic-pituitary-adrenal axis function or the hypothesis of abnormal CRH secretion in chronic fatigue syndrome. These data further suggest that the hypocortisolism found in chronic fatigue syndrome may be secondary to reduced adrenal gland output. Thirty-two patients were treated with a low-dose hydrocortisone regime in a double-blind, placebo-controlled cross-over design, with 28 days on each treatment. They underwent repeated 24-h urinary free cortisol collections, a human CRH test, and an insulin stress test after both active and placebo arms of treatment. Looking at all subjects, 24-h urinary free cortisol was higher after active compared with placebo treatments, but 0900-h cortisol levels and the ACTH and cortisol responses to human CRH and the insulin stress test did not differ. However, a differential effect was seen in those patients who responded to active treatment (defined as a reduction in fatigue score to the median population level or less). In this group, there was a significant increase in the cortisol response to human CRH, which reversed the previously observed blunted responses seen in these patients. We conclude that the improvement in fatigue seen in some patients with chronic fatigue syndrome during hydrocortisone treatment is accompanied by a reversal of the blunted cortisol responses to human CRH.

Adrenocorticotropic Hormone↗

Self-reports of physical, sexual and emotional abuse in an alcoholism treatment sample.

OBJECTIVE: There is a growing appreciation that emotional, physical and sexual abuse events are frequently part of the life histories of individuals in treatment for alcohol disorders. The present study examines reports of lifetime abuse in a clinical trial for treatment of alcohol dependency. METHOD: Data were obtained from baseline assessments conducted with participants (N = 1,726; 1,307 men) entering Project MATCH, a multisite clinical trial conducted at nine geographically dispersed research sites. Differences on a broad range of participant characteristics were examined by gender and by reported abuse type. RESULTS: More than half (59%) of the participants reported lifetime abuse. Women were more likely (77%) to report abuse than were men (54%). A lower proportion of men than women (6% vs 31%) reported experiencing both physical and sexual abuse. Gender differences were found on the majority of psychosocial measures. Comparisons of the psychosocial measures by abuse type generally indicated that participants without abuse histories had better functioning than did participants reporting abuse. CONCLUSIONS: The high frequency of lifetime abuse in this geographically dispersed sample underscores the necessity for including assessment of emotional, physical and sexual abuse with alcoholism treatment seeking populations. Participants reporting such events may require other treatment in addition to that for alcohol dependency.

Adult↗

Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase profiles of cell lines of the National Cancer Institute's Anticancer Drug Screen.

PURPOSE: To determine the expression of three targets of 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) in human tumor cell lines and to compare these with the 50% growth inhibition concentrations (GI(50)) from the National Cancer Institute database. EXPERIMENTAL DESIGN: Thymidine kinase (TK) activity was assessed by conversion of [(3)H]thymidine to [(3)H]TMP. Thymidylate synthase (TS) protein expression was determined by Western analysis. TS and dihydropyrimidine dehydrogenase (DPD) mRNA expression were measured by quantitative reverse transcription-PCR. RESULTS: The median (range) for the targets were as follows: 5-FU GI(50), 20.8 microM (0.8-536); FdUrd GI(50), 0.75 microM (0.25-237); TK, 0.93 nmol/min/mg (0.16-5.7); in arbitrary units: TS protein, 0.41 (0.05-2.95); TS mRNA, 1.05 (0.12-6.41); and DPD mRNA, 1.09 (0.00-24.4). A moderately strong correlation was noted between 5-FU and FdUrd GI(50)s (r = 0.60), whereas a weak-moderate correlation was seen between TS mRNA and protein expression (r = 0.45). Neither TS expression nor TK activity correlated with 5-FU or FdUrd GI(50)s, whereas lines with lower DPD expression tended to be more sensitive to 5-FU. Cell lines with faster doubling times and wild-type p53 were significantly more sensitive to 5-FU and FDURD: CONCLUSIONS: The lack of correlation may in part be attributable to the influence of downstream factors such as p53, the observation that the more sensitive cell lines with faster doubling times also had higher TS levels, and the standard procedure of the screen that uses a relatively short (48-h) drug exposure.

Animals↗

Patient reported complications after prostate brachytherapy.

PURPOSE: Prostate brachytherapy has gained popularity due partly to the low rates of short-term complications shown in studies from highly select clinical practices. These series rely on medical records generated by the treating physician and are prone to underreport complications. We summarize the complication reports obtained directly from patients to establish a more realistic incidence of treatment related problems. MATERIALS AND METHODS: In 1997, 160 consecutive patients treated with prostate brachytherapy at the University of Washington were studied. A questionnaire was designed to determine the rate of complications occurring within 1 year of the procedure. The questions were formulated for ease of use and conciseness, while accounting for easily recalled events associated with complications. A total of 147 (92%) patients completed the questionnaire. RESULTS: There were 8 (5%) patients who required hospital admission for an average of 2 days (range 1 to 7) as a result of the procedure. A total of 56 (38%) patients required nonroutine visits with a physician in an office setting or at an emergency room. Radiation proctitis diagnosed by endoscopy developed in 8 (5%) patients but no one needed surgical intervention. A total of 47 (32%) patients required urinary catheterization at some point after implantation. CONCLUSIONS: We demonstrated a higher rate of short-term complications than those previously reported. Fortunately, the majority of side effects were self-limited and no treatment related mortality or cardiovascular morbidity was seen. Our findings may provide a more realistic account of the complications likely to occur after implantation than might be surmised from previous reports.

Adult↗

Cloning of TC-1 (C8orf4), a novel gene found to be overexpressed in thyroid cancer.

A novel gene highly expressed in thyroid cancer, designated TC-1 (thyroid cancer-1), was cloned from suppression subtractive hybridization between papillary thyroid carcinoma and its surrounding normal thyroid tissue. Overexpression of TC-1 in thyroid cancer was confirmed in 15/16 paired samples by RT-PCR and Northern analysis. Ubiquitously expressed in human tissues, the TC-1 sequence showed no homology to any known gene, but matched a cluster of ESTs. After alignment of our sequence with the ESTs, the missing transcription start site was obtained by 5'-RACE and verified by primer extension analysis. The full-length mRNA sequence of 1327 bp has an open reading frame of 321 bp, which encodes a highly conserved protein. Three regulatory motifs were identified at the expected positions within 1 kb of the 5' flanking sequence obtained by genome walking. Using fluorescence in situ hybridization, TC-1 was localized to chromosome 8p11.2. The overexpression of TC-1 in papillary carcinoma suggests that it may have an important role in thyroid carcinogenesis.

Amino Acid Sequence↗

A novel pharmacological approach to treating cardiac ischemia. Binary conjugates of A1 and A3 adenosine receptor agonists.

Adenosine released during cardiac ischemia exerts a potent, protective effect in the heart via activation of A(1) or A(3) receptors. However, the interaction between the two cardioprotective adenosine receptors and the question of which receptor is the more important anti-ischemic receptor remain largely unexplored. The objective of this study was to test the hypothesis that activation of both receptors exerted a cardioprotective effect that was significantly greater than activation of either receptor individually. This was accomplished by using a novel design in which new binary conjugates of adenosine A(1) and A(3) receptor agonists were synthesized and tested in a novel cardiac myocyte model of adenosine-elicited cardioprotection. Binary drugs having mixed selectivity for both A(1) and A(3) receptors were created through the covalent linking of functionalized congeners of adenosine agonists, each being selective for either the A(1) or A(3) receptor subtype. MRS 1740 and MRS 1741, thiourea-linked, regioisomers of a binary conjugate, were highly potent and selective in radioligand binding assays for A(1) and A(3) receptors (K(i) values of 0.7-3.5 nm) versus A(2A) receptors. The myocyte models utilized cultured chick embryo cells, either ventricular cells expressing native adenosine A(1) and A(3) receptors, or engineered atrial cells, in which either human A(3) receptors alone or both human A(1) and A(3) receptors were expressed. The binary agonist MRS 1741 coactivated A(1) and A(3) receptors simultaneously, with full cardioprotection (EC(50) approximately 0.1 nm) dependent on expression of both receptors. Thus, co-activation of both adenosine A(1) and A(3) receptors by the binary A(1)/A(3) agonists represents a novel general cardioprotective approach for the treatment of myocardial ischemia.

Adenosine↗

Liver disease in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an autosomal dominant disorder characterized by angiodysplastic lesions (telangiectases and arteriovenous malformations) that affect many organs. Liver involvement in patients with this disease has not been fully characterized. METHODS: We studied the clinical findings and results of hemodynamic, angiographic, and imaging studies in 19 patients with hereditary hemorrhagic telangiectasia and symptomatic liver involvement. RESULTS: We evaluated 14 women and 5 men who ranged in age from 34 to 74 years. All but one of the patients had a hyperdynamic circulation (cardiac index, 4.2 to 7.3 liters per minute per square meter of body-surface area). In eight patients, the clinical findings were consistent with the presence of high-output heart failure. The cardiac index and pulmonary-capillary wedge pressure were elevated in the six patients in whom these measurements were performed. After a median period of 24 months, the condition of three of the eight patients had improved, four were in stable condition with medical therapy, and one had died. Six patients had manifestations of portal hypertension such as ascites or variceal bleeding. The hepatic sinusoidal pressure was elevated in the four patients in whom it was measured. After a median period of 19 months, the condition of two of the six patients had improved, and the other four had died. Five patients had manifestations of biliary disease, such as an elevated alkaline phosphatase level and abnormalities on bile duct imaging. After a median period of 30 months, the condition of two of the five had improved, the condition of one was unchanged, heart failure had developed in one, and one had died after an unsuccessful attempt at liver transplantation. CONCLUSIONS: In patients with hereditary hemorrhagic telangiectasia and symptomatic liver-involvement, the typical clinical presentations include high-output heart failure, portal hypertension, and biliary disease.

Adult↗

CEP-1347 increases ChAT activity in culture and promotes cholinergic neurone survival following fimbria-fornix lesion.

Recent evidence suggests that the activation of the Jun N-terminal kinase (JNK) signal transduction pathway may be important in neuronal responses to stresses such as trophic factor deprivation. Preventing the activation of JNK and expression of c-Jun may, therefore, be neuroprotective. Here, we report that the small molecule CEP-1347, which has been shown to inhibit the JNK signalling pathway, promotes cholinergic activity in cultured embryonic septal neurones. In vivo, we have shown that CEP-1347, administered either by sub-cutaneous (s.c.) injection or by continuous infusion, is partially neuroprotective, for cholinergic neurones in the medial septum, following fimbria-fornix transection. These data suggest that small molecules such as CEP-1347 may have beneficial effects in treating neurodegenerative diseases.

Animals↗

New opportunities in animal breeding and production - an introductory remark.

New opportunities in animal breeding and production will be offered by methods for embryo production and the introduction of precise genetic changes in livestock species. A review of current procedures shows that they have been improved during the last 4 years, but still have significant limitations. In the light of experience over the past 50 years it seems likely that these methods will contribute to animal health and productivity, but at some unknown time in the future and in ways that cannot be predicted precisely. When looking to the future, delegates to this meeting should take pride in what science continues to contribute.

Animal Husbandry↗