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Biomedical subjects

D O'Shea

Publications and source records attributed to D O'Shea.

At least 19 recordsLinked to original sources
PubMed2000

Diagnostic yield and development of a neurocardiovascular investigation unit for older adults in a district hospital.

BACKGROUND: Dizziness, syncope, and falls are common occurrences in elderly people. Neurocardiovascular investigation units aim to detect those patients who fall due to disturbances of blood pressure control or cardiac conduction. Specialist units have a high diagnostic yield in the investigation of these problems. Does this translate to less specialized centers? We report on the diagnostic findings of a district general hospital neurocardiovascular investigation unit. METHOD: A total of 120 consecutive patients over the age of 65 presenting to a single geriatrician were assessed. After a full history and physical examination, patients underwent neurocardiovascular investigation: blood pressure and heart rate response to active stand, carotid sinus massage, and 30-minute head-up tilt. RESULTS: The 120 patients assessed had a mean age of 78 years (range 66-94 years); in this group, 85 were women. Of these patients, 23% presented with falls, 14% with blackouts, and 30% with dizziness. The remaining 33% had overlap of symptoms. Neurocardiovascular investigations produced a diagnosis in 57% of the patients: 22% had cardioinhibitory carotid sinus syndrome (CSS): 15% had vasodepressor CSS; 29% had orthostatic hypotension; and 3% had vasovagal syncope. Thirteen percent had more than one neurocardiovascular abnormality, and 18% had benign positional vertigo. Five patients had postural instability causing falls. Hyperventilation syndrome, aortic stenosis, dysrhythmia, cervical spondylosis, and epilepsy each accounted for one case. Seventeen percent of the subjects remained undiagnosed after integrated neurocardiovascular assessment. CONCLUSION: Management of falls requires access to neurocardiovascular assessment. It is feasible to provide such a service in the district general hospital setting, with a comparable diagnostic yield to tertiary referral centers.

Accidental Falls↗
PubMed2000

Diagnosis of carotid sinus hypersensitivity in older adults: carotid sinus massage in the upright position is essential.

OBJECTIVE: To assess the diagnostic value of supine and upright carotid sinus massage in elderly patients. DESIGN: Prospective controlled cohort study. SETTING: Three inner city accident and emergency departments and a dedicated syncope facility. PATIENTS: 1375 consecutive patients aged > 55 years presenting with unexplained syncope and drop attacks; 25 healthy controls. INTERVENTIONS: Bilateral supine carotid sinus massage, repeated in the 70 degrees head up tilt position if the initial supine test was not diagnostic of cardioinhibitory and mixed carotid sinus hypersensitivity. MAIN OUTCOME MEASURES: Diagnosis of cardioinhibitory or mixed carotid sinus hypersensitivity; clinical characteristics of supine v upright positive groups. RESULTS: 226 patients were excluded for contraindications to carotid sinus massage. Of 1149 patients undergoing massage, 223 (19%) had cardioinhibitory or mixed carotid sinus hypersensitivity; 70 (31%) of these had a positive response to massage with head up tilt following negative supine massage (95% confidence interval, 25.3% to 37.5%). None of the healthy controls showed carotid sinus hypersensitivity on erect or supine massage. The initially positive supine test had 74% specificity and 100% sensitivity; these were both 100% for the upright positive test. The clinical characteristics of the supine v upright positive subgroups were similar. CONCLUSIONS: The diagnosis of carotid sinus hypersensitivity amenable to treatment by pacing may be missed in one third of cases if only supine massage is performed. Massage should be done routinely in the head up tilt position if the initial supine test is negative.

Aged↗
PubMed2000

Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline.

We describe the case of a patient who developed depression following bilateral orchidectomy for cryptorchidism. He was treated with a conventional selective serotonin reuptake inhibitor antidepressant, but continued to take St John's wort (hypericum) against medical advice. He subsequently developed a manic episode. We discuss postulated modes of action of St John's wort and the possible aetiological importance of testosterone replacement and abnormal gonadotrophin levels in this case.

Administration, Oral↗
PubMed2000

Determining needs and setting priorities for HIV-affected and HIV-infected persons: northeast Ohio and San Diego.

The Ryan White Comprehensive AIDS Resources Emergency (CARE) Act of 1991 requires that communities receiving Title I funding engage in a needs assessment and priority process to guide the allocation of those funds to various services within the local community. This paper reports on the process and results of the needs assessments in northeast Ohio and San Diego County for 1996-1997 and 1998. Data from northeast Ohio's 1998 needs assessment indicated significant differences between whites and nonwhites in the utilization of HIV specialist care, HIV-related prescription medications such as antiretrovirals, and health insurance. A need for additional dental care, complementary therapies, housing, and assistance with utility payments was found in both geographic areas. Consumer participation in San Diego's health department-based needs assessment process was more extensive than in northeast Ohio's academic-based approach but was also related to increased community-borne expense.

Adult↗
PubMed2000

The management of traumatic ankylosis during orthodontics: a case report.

Dental ankylosis may be a significant complication in orthodontic clinical practice. This case report describes the management of a malocclusion, complicated by an ankylosed maxillary central incisor, which arose during orthodontic treatment, following an acute traumatic injury. The use of the ankylosed incisor in successfully managing the significant Class II division 1 malocclusion is described.

Child↗
PubMed1999

Frequent loss of imprinting of PEG1/MEST in invasive breast cancer.

The human PEG1 gene is a newly identified imprinted gene on 7q32. Genetic aberrations of this chromosomal region are often detected in invasive breast carcinomas. In this study, we show monoallelic PEG1 expression in normal breast tissue, indicating the presence of a functional imprint, and more importantly, we demonstrate loss of imprinting (LOI) in all of seven informative invasive breast carcinomas. In contrast to this, in one case of atypical ductal hyperplasia (ADH) found in residual breast, imprinting was maintained. This raises the possibility that aberrant imprinting of PEG1 may be involved in the progression from hyperplasia to invasive breast cancer.

Alleles↗
PubMed1999

Failure of erythromycin breath test to correlate with midazolam clearance as a probe of cytochrome P4503A.

BACKGROUND: Cytochrome P4503A (CYP3A) activity exhibits considerable interindividual variability, and an in vivo probe to measure such differences would serve several purposes. The erythromycin breath test (ERBT) is an established approach that has proven useful in this regard, but it has several limitations. More recently, the hydroxylation of midazolam has been suggested as an alternative in vivo probe approach, because it is possible to estimate CYP3A activity in the intestinal epithelium as well as in the liver. The purpose of this study was to investigate the relationship, if any, between the ERBT and midazolam's CYP3A-mediated metabolism. METHODS: Twenty healthy, medication-free young (24 to 46 years) European Americans (10 women) each received on separate days, in random order, either 3 microCi [14C-N-methyl]-erythromycin intravenously, 1 mg midazolam intravenously, or 2 mg midazolam orally. An ERBT value was determined 60 minutes after administration, and clearances were estimated after midazolam administration. In addition, an endogenous 0- to 4-hour urinary 6beta-hydroxycortisol/cortisol ratio was measured. RESULTS: All three measured drug trait values varied approximately threefold to fivefold, whereas the endogenous phenotype measure exhibited far greater variability (>100-fold). No statistically significant (P < .05) correlations existed between any of the trait values, including the ERBT value, obtained after intravenous administration of the radiolabeled probe and the systemic clearance of midazolam, expressed in terms of either total or unbound drug, or on an absolute or a body weight-corrected basis (r = 0.03 to r = 0.24; P = .08 to P = .90). Substratification according to sex generally did not improve such relationships. CONCLUSION: Although both erythromycin N-demethylation and the metabolism of midazolam by hydroxylation are mediated by CYP3A, the phenotypic trait measures associated with these two in vivo probe drugs do not provide the same information about the catalytic activity of the enzyme. An indirect measure such as the ERBT may reflect CYP3A activity and be useful for some purposes, but the estimation of the oral and intravenous clearance of midazolam has additional advantages, and they may be more applicable and have broader usefulness as quantitative estimates of CYP3A activity.

Adult↗
PubMed1999

Loss of heterozygosity of the Wilms' tumor suppressor gene (WT1) in in situ and invasive breast carcinoma.

The Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis. WT1 allelic integrity was examined by loss of heterozygosity (LOH) studies in formalin-fixed, paraffin-embedded (FFPE) ductal carcinoma in situ (DCIS, n = 20) and fresh frozen primary invasive breast carcinomas (n = 24). Loss of heterozygosity (LOH) at the WT1 locus (11p13) was examined by PCR evaluation of an Hinf1 restriction fragment length polymorphism (RFLP) and correlated to tumor stage (in situ and invasive). After identification of the heterozygous/informative breast lesions, 1 of 12 (8.3%) DCIS (high-grade micropapillary) and 3 of 14 (21.4%) of infiltrating carcinomas (high grade) showed loss of one allele, suggesting that LOH of the WT1 locus is a rare genetic event in early breast cancer, becoming more common in invasive and in high-grade lesions.

Breast Neoplasms↗
PubMed1999

Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat.

Central nervous system glucagon-like peptide-1-(7-36) amide (GLP-1) administration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (i.c.v.) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9-39), affects food intake and body weight. Daily i.c.v. injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 +/- 5 g (P < 0.02 compared with saline-injected controls). Daily i.c.v. administration of 30 nmol exendin-(9-39) to schedule-fed rats for 3 days caused an increase in food intake and increased body weight by 7 +/- 2 g (P < 0.02 compared with saline-injected controls). Twice daily i.c.v. injections of 30 nmol exendin-(9-39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 days increased food intake and increased body weight by 28 +/- 4 g compared with 14 +/- 3 g in neuropeptide Y-injected controls (P < 0.02). There was no evidence of tachyphylaxis in response to i.c.v. GLP-1 or exendin-(9-39). GLP-1 may thus be involved in the regulation of body weight in the rat.

Animals↗
PubMed1999

The midnight to morning urinary cortisol increment is an accurate, noninvasive method for assessment of the hypothalamic-pituitary-adrenal axis.

The optimal method for assessing the hypothalamic-pituitary-adrenal axis (HPA) remains controversial. The insulin tolerance test (ITT) is considered the gold standard, but is invasive and potentially dangerous. The short Synacthen test (SST) is the most commonly used alternative, but its concordance with the ITT is poor. Using sleep as a reliable stimulus to ACTH release, we proposed that the increment in urinary cortisol levels between midnight and waking could provide a noninvasive, physiological means for the assessment of the HPA axis. Double voided urine samples were collected at home at midnight and waking in 40 patients with pituitary disease and 40 controls. Cortisol and creatinine levels were measured, and the cortisol/creatinine (Cort/Cr) ratio was calculated. The Cort/Cr increment was defined as the morning Cort/Cr ratio minus the midnight Cort/Cr ratio. The Cort/Cr increment of the patients was compared to the results of their ITT or SST. Using the results from the 40 controls, a normal Cort/Cr increment was defined as greater then 9. The positive predictive value of a Cort/Cr increment for the diagnosis of HPA insufficiency was 95%. These findings suggest that the midnight to morning Cort/Cr increment is a reliable, noninvasive alternative to the ITT/SST for assessment of the HPA.

Adrenal Glands↗