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Biomedical subjects

K Donovan

Publications and source records attributed to K Donovan.

At least 19 recordsLinked to original sources

Randomized controlled trial of a cannabis-focused intervention for young people with first-episode psychosis.

OBJECTIVE: To evaluate a cannabis-focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first-episode psychosis (FEP). METHOD: Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single-blind randomized controlled trial compared CAP (n = 23) with a clinical control condition (psychoeducation, PE; n = 24). There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post-intervention. RESULTS: There were no significant group differences on psychopathology and functional ratings at follow-up. A significant reduction in cannabis use was observed for both groups over time. CONCLUSION: PE and specific cannabis-focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population.

Adolescent↗

Population requirements for vascular access surgery.

The native arterio-venous fistula provides the best access for haemodialysis. The dialysis population is growing in number, becoming more elderly, and has increasingly complex medical co-morbidity. The ability to establish and maintain optimal haemodialysis access in this population requires the planning and commissioning of operating and diagnostic facilities and the training of sufficient suitable surgical specialists. This article outlines the major factors that influence the demand for and requirements of a vascular access service for the renal failure population.

Arteriovenous Shunt, Surgical↗

Longitudinal course of behavioral problems during Alzheimer's disease: linear versus curvilinear patterns of decline.

BACKGROUND: Patients with Alzheimer's Disease (AD) are commonly assumed to experience a linear decline in behavioral functioning that parallels progressive cognitive decline. However, some researchers have suggested that specific behavioral problems either decline at different rates or improve in late dementia. METHODS: The present analyses examined 150 AD patients at an initial assessment, 61 of whom were also evaluated annually on two additional occasions. Measures of cognitive impairment and behavioral problems were obtained. RESULTS: Cross-sectional results indicated curvilinear associations between dementia severity and certain behavioral problems (forgetful behaviors, and emotional and impulsive behaviors). Longitudinal analyses further indicated trends for curvilinear rates of behavioral disturbance across time, with some problem areas showing improvement as AD progresses through the most severe stages. CONCLUSIONS: Even though Alzheimer's disease is a progressive dementia characterized by increasing cognitive deterioration, it appears to be inaccurate to expect behavioral functioning to show the same linear decline across time.

Aged↗

Antibody therapy for treatment of multiple myeloma.

Monoclonal antibody therapy has emerged as a viable treatment option for patients with lymphoma and some leukemias. It is now beginning to be investigated for treatment of multiple myeloma. There are relatively few surface antigens on the plasma cells that are suitable for antibody-directed treatment. Possible molecules include HM1.24, CD38, ICAM-1 (CD54), CD40, CD45, CD20, and syndecan 1. There is now some clinical experience with anti-CD38 antibody in lymphoma and myeloma. However, to date, there has been minimal clinical activity observed. Additional antibodies are entering clinical trials. A new approach involves the generation of an anti-CD38 single-chain variable fragment (scFv) construct that acts as the carrier of a toxin gene instead of being conjugated directly to the toxin itself. It is hoped that expression of the toxin by CD38+ plasma cells will promote suicide of the malignant cells without affecting normal cells or generating an immunologic response to the toxin. Ongoing clinical trials are also attempting to target B-cell antigens such as CD20. Although CD20 is present only on 20% of myeloma cells, it may be present on myeloma precursor cells. This treatment has met with success in follicular lymphoma and is now being evaluated in clinical trials in both Europe and the United States for myeloma. Although these clinical trials are in very early stages, researchers are beginning to understand that antibody therapy can be used not only as a carrier molecule of radioisotopes and toxins, but also as molecules that can trigger tumor cells and promote growth arrest or apoptosis.

Antibodies, Monoclonal↗

Immune responses during an Antarctic summer.

The immune status of 29 members of the Australian National Antarctic Research Expeditions (ANARE) was investigated before, during, and after a 56 day summer voyage to Antarctica and correlated with psychological and physiological parameters. All subjects were healthy. Expedition personnel demonstrated decreased cell mediated immune responses (CMI) assessed by the CMI Multi-test; 21% were hypoergic. The major associated observation was a significant negative correlation with anxiety in Antarctica. However, perceived anxiety was greater before and after the voyage. No significant changes were found in T and B lymphocyte subsets, immunoglobulin and complement components and cutaneous blood flow, nor was there any clinical evidence of illness. Of the hormones examined only cortisol was low predeparture which may reflect increased perceived anxiety at that time. Changes in immune control mechanism were apparent as shown by reduced CMI responses and lowered tetanus antibody levels. Stress factors are postulated to induce depression of the immune response in Antarctica. The association with anxiety suggests that brain peptides or associated cytokines may have a role in mediating these immune events. Such alterations in immune status have implications for health management in isolated and extreme conditions.

Adult↗

Identification of target genes regulated by homeotic proteins in Drosophila melanogaster through genetic selection of Ultrabithorax protein-binding sites in yeast.

A method based on the transcriptional activation of a selectable reporter in yeast cells was used to identify genes regulated by the Ultrabithorax homeoproteins in Drosophila melanogaster. Fifty-three DNA fragments that can mediate activation by UBX isoform Ia in this test were recovered after screening 15% of the Drosophila genome. Half of these fragments represent single-copy sequences in the genome. Six single-copy fragments were investigated in detail, and each was found to reside near a transcription unit whose expression in the embryo is segmentally modulated as expected for targets of homoeotic genes. Four of these putative target genes are expressed in patterns that suggest roles in the development of regional specializations within mesoderm derivatives; in three cases these expression patterns depend on Ultrabithorax function. Extrapolation from this pilot study indicates that 85-170 candidate target genes can be identified by screening the entire Drosophila genome with UBX isoform Ia. With appropriate modifications, this approach should be applicable to other transcriptional regulators in diverse organisms.

Animals↗

Cardiac rehabilitation in the time of health-care reform.

Cardiac rehabilitation has evolved into a medically efficacious, cost-effective intervention for patients with ischemic heart disease. Most aspects of this therapy are well developed, and guidelines for programs exist. As the health-care delivery system undergoes scrutiny and evolution, it would be prudent for the practitioners of cardiac rehabilitation to evaluate the methods they use to deliver their services. Program administrators should reconsider traditional approaches that are largely based on reimbursement criteria. Goal-directed, patient-centered service delivery will allow individualization of care. A model for such an approach to cardiac rehabilitation is presented.

Cost-Benefit Analysis↗

Fluorescent in situ hybridization assessment of chromosome 7 copy number in uncultured lung and kidney cells.

Trisomy 7 is common in cells cultured from nonneoplastic lung and kidney tissues, but the frequency of trisomy 7 in uncultured lung and kidney has not been determined. In this study, we used fluorescent in situ hybridization (FISH) to assess chromosome 7 copy number in uncultured interphase nuclei from lung and kidney specimens. All specimens had low level mosaicism for trisomy 7(1.5-5.25%), but control experiments indicated a potential wide margin of error in quantifying these events.

Aged↗

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics.

The pharmacokinetics and selected pharmacodynamic responses to methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC50) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC50 values for effects of methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response.

Adult↗

Fixed time versus fixed distance protocols for the blood lactate profile in athletes.

Laboratory studies of blood lactate accumulation often use a fixed time protocol to define the onset (4 mM) of blood lactate accumulation (OBLA) or other indices of blood lactate concentration. For practical reasons, field studies with athletes often use a fixed distance protocol to accomplish the same goal. Whether these variations of protocol are comparable has not been established. We studied 10 subjects in the laboratory during fixed time (4 minute) and fixed distance (2 km) exercise protocols on a racing bicycle attached to a wind load simulator. The fixed distance studies required 3-6 minutes to complete. We also studied the subjects during fixed distance (2 km) rides in the field. In the laboratory there were no systematic differences in the velocity (34.3 4.6 vs 34.2 +/- 4.6 km.hr-1), VO2 (2.78 +/- 0.60 vs 2.84 +/- 0.62 liters.min-1), or heart rate (159 +/- 16 vs 155 +/- 14 beats.min-1) at OBLA in the fixed time vs fixed distance protocols. The correlation coefficients for velocity (r = 0.97), VO2 (r = 0.97) and heart rate (r = 0.94) further indicate the similarity of results. In the field study there was a significant difference in velocity (29.9 +/- 4.8 vs 34.2 +/- 4.6 km.hr-1) but not heart rate (155 +/- 18 vs 155 +/- 15 beats.min-1) at OBLA versus the fixed distance laboratory study. The correlations for velocity (r = 0.47) and heart rate (r = 0.93) support these data. The results suggest that the practical modification of the lactate profile technique of using fixed distance versus fixed time exercise stages does not systematically influence the outcome, at least for exercise stage durations approximating 4 minutes.

Female↗

Clonal rearrangement of chromosome band 6p21 in the mesenchymal component of pulmonary chondroid hamartoma.

Pulmonary chondroid hamartomas (PCH) are biphasic benign tumors that contain both mesenchymal and epithelial populations. In this report we describe two PCH in which clonal translocations at chromosome band 6p21 were demonstrated in mesenchymal cells. One of these had a unique translocation, t(6;14)(p21;q24), that was also found in one of two PCH karyotyped previously. The t(6;14) has not been described in other varieties of benign or malignant neoplasia. The 6p21 aberrations are of particular interest because break points in this chromosomal region appear to be characteristic of endometrial polyps. Endometrial polyps, like PCH, are biphasic benign tumors in which mesenchymal clonality has been demonstrated.

Adult↗

Ovarian granulosa-stromal cell tumors are characterized by trisomy 12.

Eleven ovarian granulosa-stromal cell tumors including 1 thecoma, 2 fibromas, 6 fibrothecomas, and 2 granulosa cell tumors, were karyotyped after direct harvest and/or short-term tissue culture. Bilateral fibrothecomas from one patient appeared to lack cytogenetic aberrations: the remaining nine tumors were characterized by trisomy for chromosome 12. Cytogenetic aberrations in the two granulosa cell tumors were much less complex than those described previously in undifferentiated carcinomas; accordingly cytogenetic analyses might be useful in distinguishing these categories. The consistent occurrence of trisomy 12 in different varieties of granulosa-stromal cell tumors suggests a common mechanism of oncogenesis within this diverse group of neoplasms. That mechanism probably involves promotion of low-grade, orderly cell proliferation.

Chromosomes, Human, Pair 12↗

Measuring blood pressure in the elderly: does atrial fibrillation increase observer variability?

OBJECTIVE: To compare the interobserver and intraobserver variability of blood pressure measurements in geriatric patients in atrial fibrillation and in sinus rhythm. DESIGN: Prospective assessment of blood pressure measurements carried out in random order in two groups of elderly patients by five doctors unaware of the aims of the study. SETTING: Acute assessment wards for geriatric medicine, Cardiff Royal Infirmary. PATIENTS: 50 Elderly patients in sinus rhythm and 50 in atrial fibrillation. MAIN OUTCOME MEASURES: Interobserver and intraobserver variability of blood pressure measurements in the two groups expressed as the coefficient of variability and compared by the Mann-Whitney U test. RESULTS: Interobserver variability was significantly greater in the patients with atrial fibrillation for both systolic and diastolic pressures. Intraobserver variability was significantly greater in the atrial fibrillation group for diastolic pressures but the difference was not significant for systolic pressures. These differences were not related to pulse rate, age, or level of blood pressure. CONCLUSIONS: The findings suggest that in the presence of atrial fibrillation physicians' interpretations of Korotkoff sounds are less uniform, which may have important clinical implications. Possibly a standardised methodology may overcome this problem.

Aged↗