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Biomedical subjects

J Kaye

Publications and source records attributed to J Kaye.

At least 19 recordsLinked to original sources
PubMed2006

Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease.

LY450139 dihydrate, a gamma-secretase inhibitor, was studied in a randomized, controlled trial of 70 patients with Alzheimer disease. Subjects were given 30 mg for 1 week followed by 40 mg for 5 weeks. Treatment was well tolerated. Abeta(1-40) in plasma decreased by 38.2%; in CSF, Abeta(1-40) decreased by 4.42 +/- 9.55% (p = not significant). Higher drug doses may result in additional decreases in plasma Abeta concentrations and a measurable decrease in CSF Abeta.

Alanine↗
PubMed2006

A semantically enabled formalism for the knowledge management of Parkinson's disease.

Bio-ontology is a formal representation of biological concepts that is used in the interchange of communication between computers and humans alike. They can then be used in the formulation and retrieval of knowledge. In developing a knowledge-based system for Parkinson's Disease, a procedure of knowledge map was used to capture and harness the intellectual resources of an organization, and new paradigms for knowledge mapping were also formulated. Knowledge bases for symptoms and drugs, physiotherapy, speech and language therapy, and dieting that affect patient care were developed. Finally, the knowledge bases were merged to form a single central repository of knowledge base.

Diet↗
PubMed2005

Symptomatic hypocalcaemia and renal impairment associated with bisphosphonate treatment in patients with multiple myeloma.

We report three cases of severe hypocalcaemia associated with i.v. bisphosphonate treatment in patients with multiple myeloma. All patients had symptomatic hypocalcaemia, including a tonic-clonic seizure and tachyarrhythmia in one case. Two cases were associated with the development of acute renal failure, whereas the third patient had pre-existing renal impairment. We recommend that bisphosphonates be used with caution in patients with myeloma and renal impairment, that vitamin D deficiency be corrected prior to treatment (to reduce the risk of hypocalcaemia) and that serum calcium and renal function be monitored during treatment.

Acute Kidney Injury↗
PubMed2004

Acute carbon dioxide exposure in healthy adults: evaluation of a novel means of investigating the stress response.

Acute hypercapnia was studied to assess its potential as a noninvasive and simple test for evoking neuroendocrine, cardiovascular and psychological responses to stress in man. A single breath of four concentrations of carbon dioxide (CO(2)), 5%, 25%, 35% and 50%, was administered to nine healthy volunteers in a randomized, single-blind fashion. Although no adverse effects occurred, most subjects were unable to take a full inspired vital capacity breath of 50% CO(2). In response to the remaining exposures, subjective and somatic symptoms of anxiety increased in a dose-dependent manner. Unlike 5% and 25% CO(2), 35% CO(2) stimulated significant adrenocorticotropic hormone and noradrenaline release at 2 min and cortisol and prolactin release at 15 min following inhalation. This same dose also provoked a significant bradycardia that was followed by an acute pressor response. No significant habituation of psychological, hypothalamic-pituitary-adrenal (HPA) or cardiovascular responses following 35% CO(2) was seen when this dose was repeated after 1 week. A single breath of 35% CO(2) safely and reliably produced sympathetic and HPA axis activation and should prove a useful addition to currently available laboratory tests of the human stress response.

Adaptation, Physiological↗
PubMed2003

Metastases to the breast revisited: radiological-histopathological correlation.

Metastases to the breast from extramammary tumours are infrequent. The main challenge in diagnosis is differentiating them from primary breast cancer. Radiologically this can be difficult as there are no specific imaging characteristics for metastases to the breast. Cytopathological evaluation, as well as full radiological assessment, is vital to avoid unnecessary surgery. Sources of primary tumours include a wide variety of cancers. In this pictorial review we illustrate a number of the commonest sources of primary tumours including lymphoma, lung, ovarian and cervical carcinoma, intestinal carcinoid and rare cases of Ewing's sarcoma and malignant pigmented melanocytic schwannoma (low-grade malignant melanoma).

Adult↗
PubMed2003

Multidisciplinary rehabilitation for people with Parkinson's disease: a randomised controlled study.

OBJECTIVE: To determine whether a programme of multidisciplinary rehabilitation and group support achieves sustained benefit for people with Parkinson's disease or their carers. METHODS: The study was a randomised controlled crossover trial comparing patients and carers who had received rehabilitation four months before assessment with those who had not. Patients were recruited from a neurology clinic, attended a day hospital from home weekly for six weeks using private car or hospital transport, and received group educational activities and individual rehabilitation from a multidisciplinary team. Patients were assessed at entry and at six months using a 25 item self assessment Parkinson's disease disability questionnaire, Euroqol-5d, SF-36, PDQ-39, hospital anxiety and depression scale, and timed stand-walk-sit test. Carers were assessed using the carer strain index and Euroqol-5d. RESULTS: 144 people with Parkinson's disease without severe cognitive losses and able to travel to hospital were registered (seven were duplicate registrations); 94 had assessments at baseline and six months. Repeated measures analysis of variance comparing patients at the 24 week crossover point showed that those receiving rehabilitation had a trend towards better stand-walk-sit score (p = 0.093) and worse general and mental health (p = 0.002, p = 0.019). Carers of treated patients had a trend towards more strain (p = 0.086). Analysis comparing patients before and six months after treatment showed worsening in disability, quality of life, and carer strain. CONCLUSIONS: Patients with Parkinson's disease decline significantly over six months, but a short spell of multidisciplinary rehabilitation may improve mobility. Follow up treatments may be needed to maintain any benefit.

Activities of Daily Living↗
PubMed2002

Soft tissue uptake on 99mTc methylene diphosphonate bone scan imaging: pictorial review.

99mTechnetium methylene diphosphonate (MDP) bone isotope may accumulate in many extra-osseous sites due to a variety of both benign and malignant conditions. This finding on a bone scan can be crucial to the diagnosis and may not be apparent in other imaging or the clinical evaluation of the patient. We present a pictorial review sampling some of the many causes of extra-osseous 99mTc MDP accumulation.

Bone and Bones↗
PubMed2001

Requirement for sustained MAPK signaling in both CD4 and CD8 lineage commitment: a threshold model.

Although there is general agreement that the RAS/MAPK signaling pathway is required for positive selection of CD4 T cells in the thymus, the role of this pathway in CD8 lineage commitment remains controversial. We show here that the differentiation of isolated cultured thymocytes to the CD8 as well as CD4 T cell lineage is sensitive to MEK inhibition and that both CD4 and CD8 thymocyte differentiation requires sustained MEK signaling. However, CD4 lineage commitment is promoted by a stronger stimulus for longer duration than required for CD8 lineage commitment. Interestingly, CD4 lineage commitment is not irreversibly set even after 10 h of signaling, well past early changes in gene expression. These findings are presented in the context of a model of lineage commitment in which a default pathway of CD8 lineage commitment is altered to CD4 commitment if the thymocyte achieves a threshold level of active MAPK within a certain time frame.

Animals↗
PubMed2001

Parkinson's disease, CYP2D6 polymorphism, and age.

OBJECTIVE: PD may be caused by genetic susceptibility to neurotoxins. CYP2D6 is a candidate gene for PD because it regulates drug and toxin metabolism, but association studies have been inconsistent. The aim of this study was to test if the CYP2D6*4 allele (poor metabolizer phenotype) is associated with earlier age at onset. METHODS: Five hundred seventy-six patients with PD and 247 subjects without PD were studied using standard diagnostic, genotyping, and statistical techniques. RESULTS: Surprisingly, mean onset age was significantly later in *4-positive patients. Frequency of *4 was significantly higher in late-onset PD than early-onset PD. When early- and late-onset PD were analyzed separately, *4 had no effect on onset age; hence, the association with delayed onset was likely an artifact of an elevated *4 frequency in late-onset PD. Contrary to a common assumption that CYP2D6 frequencies do not change with age, *4 frequency rose significantly with advancing age, both in patients with PD (from 0.16 at mean age of 56.5 years to 0.21 at mean age of 72) and subjects without PD (from 0.09 at mean age of 45.5 years to 0.21 at mean age of 72). *4 Frequencies in patients with early- and late-onset PD, although different from each other, were in agreement with similarly aged subjects without PD, suggesting the elevated *4 frequency in late-onset PD was likely an age effect, unrelated to PD. CONCLUSION: The CYP2D6*4 allele is not associated with earlier PD onset. *4 May be associated with survival. Inconsistent results from allelic association studies may have been due to an unrecognized age effect.

Age of Onset↗
PubMed2001

Genetic research on the UK population--do new principles need to be developed?

Governments around the world are beginning to generate population databases as resources for genetic research. In the UK, a proposal has been tabled that plans to incorporate National Health Service information--a move that will effectively create a database of around 60 million. However, this new population collection will not conform to standards established by other national genetic databases, and the UK government report has not accounted for key ethical issues.

Bioethics↗
PubMed2001

Predictors of healthy brain aging.

To determine if superior health at old age protects against cognitive impairment (CI) and Alzheimer's disease (AD), we prospectively studied 100 optimally healthy oldest-old (> or =85 years) individuals. Initially, subjects represented the top 3% of the oldest old for health. During 5.6 +/- 0.3 years of follow-up, 34 subjects developed CI, and 23 progressed to AD. By age 100, probability of CI and AD were.65 +/-.09 and.49 +/-.10. Median onset age was 97 years for CI and 100 for AD. Clearly, superior health at old age does not guarantee protection against cognitive decline. Lifetime risks were similar to the general population but onset ages were later, suggesting factors that delay onset are key to improving cognitive health in the elderly. In this population, absence of apolipoprotein E-epsilon4 and male gender were associated with delayed onset, whereas estrogen use and education had no detectable effect on cognitive outcome.

Age of Onset↗
PubMed2001

Redesigning geriatric healthcare: how cross-functional teams and process improvement provide a competitive advantage.

This study examines the consequences of adding a geriatric subacute unit to the traditional health care mix offered by a nonprofit hospital. Historically, geriatric health care offerings have been limited to either acute care units or long-term care facilities. The study's findings demonstrate that the addition of a subacute unit that is operated by an interdisciplinary team is a competitively rational move for two reasons. First, it provides a continuum of care that integrates services and departments, thereby reducing costs. Second, it provides a supportive environment for patients and their families. As a consequence patients have a higher probability of returning home than patients who are assigned to more traditional modes of care.

Activities of Daily Living↗
PubMed2001

Pheochromocytoma presenting as life-threatening pulmonary edema.

Acute cardiogenic pulmonary edema as the first presentation of pheochromocytoma is uncommon and usually rapidly fatal. A 39-yr-old man presented in acute cardiogenic shock with global ventricular dysfunction that required high-dose iv inotrope support and an intraaortic balloon pump assist device. Abdominal imaging to exclude aortic dissection revealed a 6-cm right adrenal mass. Significant myocardial infarction (electrocardiographic changes and elevated cardiac enzymes) contributed to the cardiac decompensation. After withdrawal of inotrope support, 24-h urinary catecholamine levels revealed 2,155 nmol/d (<125) of adrenaline and 7,437 nmol/d (<560) of noradrenaline, confirming a pheochromocytoma. The tumor was successfully removed at laparotomy; however, the patient's course was complicated by a thromboembolic cerebrovascular accident with paraplegia. He recovered cardiac function almost completely within 3 wk of medical therapy alone. Although uncommon, this case highlights the need to consider pheochromocytoma early in the management of unexplained cardiogenic shock.

Adrenal Gland Neoplasms↗
PubMed2001

Patency of radial arterial catheters.

BACKGROUND: Data on the influence of flush methods, blood-sampling methods, and site location on the patency of radial arterial catheters used for pressure monitoring are sparse. OBJECTIVES: To determine the effects of flush and blood-sampling methods, insertion site, and sex of patients on catheter patency. METHODS: In a randomized trial, 174 patients requiring radial arterial pressure monitoring were assigned to 4 groups: fast flush as needed and nonwaste blood sampling; fast flush as needed and waste blood sampling; fast flush every 4 hours and waste blood sampling; and fast flush every 4 hours and nonwaste blood sampling. All site locations were evaluated for patency, and all monitoring systems were maintained with isotonic sodium chloride solution. RESULTS: Nonpatent catheters were 4.23 times more likely in patients with insertion sites 3 cm or higher above the bend of the wrist than in patients with lower sites (P = .01). Duration of patency did not differ between catheters maintained with fast flush every 4 hours and those flushed as needed or between catheters according to the method of blood sampling. Women were 3.05 times more likely than men to have nonpatent catheters (P = .02). With insertion sites 3 cm or higher above the radiocarpal joint, nonpatency was 7.3 times more likely in women than in men (P < .001). CONCLUSIONS: Insertion sites closest to the bend of the wrist increase chances of maintaining patency. Catheters can be maintained with as-needed flushes, and either waste or nonwaste blood sampling can be used.

Aged↗