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Biomedical subjects

M J Sullivan

Publications and source records attributed to M J Sullivan.

At least 55 records · Page 3Linked to original sources
PubMed1996

Unravelling the genetics of vesicoureteric reflux: a common familial disorder.

Primary vesicoureteric reflux (VUR) is one of the more common genetic disorders. Little is yet known about the genetics of this potentially manageable childhood condition, which is characterised by regurgitation of urine from the bladder to the kidney. The VUR phenotype is associated with shortness of the submucosal segment of the ureter due to congenital lateral ectopia of the ureteric orifice. VUR is found in 30-50% of infants and young children with a urinary tract infection. A serious concern in families with an affected patient is that approximately one half of siblings or offspring will be affected, but up to a half of these affected siblings and offspring may be asymptomatic in childhood. If left untreated, these patients may present later in life with proteinuria, hypertension or renal failure. VUR is the commonest cause of end-stage renal failure in children, and an important cause in adults. As the kidney damage resulting from severe VUR is preventable, early detection is desirable. The techniques for clinical diagnosis are invasive and costly, reinforcing the importance of identification of a gene for VUR to facilitate genetic screening. Although family studies suggest a major dominant gene, the inheritance pattern is still a matter of debate. In rare instances, VUR occurs in association with other diseases, such as the coloboma-ureteric-renal syndrome, which is caused by a PAX2 gene mutation. In this review, we present evidence that this common disorder may be caused by mutations in the developmental pathway of which the PAX2 gene forms a part.

DNA-Binding Proteins↗
PubMed1996

Nonpharmacologic interventions in the treatment of heart failure.

Chronic heart failure represents a significant challenge to caregivers because these patients are fragile, care is complex, and the numbers of patients are increasing dramatically. The anticipated illness trajectory is also rapidly changing due to the advent of pharmacologic interventions that offer greatly improved outcomes and quality of life for these patients. Despite such advances, mortality and morbidity remain high. Therefore, an important goal is to develop and evaluate nonpharmacologic interventions as adjuvant therapy to the traditional pharmacologic approach. Although relatively few studies have examined nonpharmacologic treatment strategies, it appears that many patients with heart failure may benefit significantly from participation in long-term aerobic exercise conditioning programs. Psychological and biobehavioral interventions also have the potential to substantially enhance treatment outcomes and quality of life for patients with chronic heart failure. This article reviews the available literature about nonpharmacologic strategies in the treatment of heart failure along with specific recommendations for practice.

Exercise Therapy↗
PubMed1996

Medicine taking in Southampton: a second look.

1. A 1 in 200 sample of the Southampton electorate were sent a postal questionnaire in January 1993. Of the 756 adults surveyed, 400 (52.9%) returned completed questionnaires. One hundred and eighty-eight (47.0%) of the respondents had been prescribed a medicine within the previous month. 2. Compared with a survey 9 years earlier, medicine taking had increased amongst men (44.1% vs 33.7% NS) and drugs acting on the respiratory system were in more widespread use (19 vs 7 patients P < 0.05). 3. Patterns of storage of medicines were almost identical to those found in 1984. However, methods of disposal were significantly different with 34% of the respondents stating that they would return left-over medicines to the Doctor or Pharmacist compared with 17% in the previous study (P < 0.01). 4. Of those taking medicines 120 (63.8%) had received a manufacturers' information leaflet. Medicines used to treat disorders of the respiratory and cardiovascular systems were most likely to be accompanied by such a leaflet (74% and 70% respectively). 5. Those who received a leaflet were almost all satisfied by it. However, patient awareness of potential side effects remained poor with only 30% being aware of any which their medicine might cause. 6. Despite improvements in attitudes towards medicine taking over time patients awareness of potential adverse effects remains limited. Further research is necessary in order to determine how best to educate patients on this topic.

Adolescent↗
PubMed1995

Altered specificity of IGF2 promoter imprinting during fetal development and onset of Wilms tumour.

The specificity of IGF2 promoter imprinting was examined in embryonal tissues and Wilms tumour. In several fetal tissues of approximately 12 weeks gestation, IGF2 was found to be monoallelically expressed from all IGF2 promoters i.e. P1, P2, P3 and P4. However, in tissues of slightly older gestation age (15-17 weeks) relaxation of imprinting at the P1 promoter was evident, although the P2-P4 promoters remained imprinted. These data indicate that early in embryogenesis a population of cells exists in which all IGF2 promoters are imprinted, but that as development proceeds the imprinting of the P1 promoter is relaxed. The pattern of IGF2 promoter imprinting was also analysed in Wilms tumour. In some tumours, the pattern of promoter imprinting was identical to that found in early fetal kidney, indicating that this tumour originates within early embryonic kidney tissue. In contrast, in tumours in which relaxation of imprinting had occurred, imprinting relaxation affected all IGF2 promoters. This aberrant pattern of promoter imprinting, which was not detected in fetal kidney, provides further evidence that pathological relaxation of IGF2 imprinting is involved in the genesis of Wilms tumour.

Adult↗
PubMed1995

Epigenetic changes encompassing the IGF2/H19 locus associated with relaxation of IGF2 imprinting and silencing of H19 in Wilms tumor.

In most tissues IGF2 is expressed from the paternal allele while H19 is expressed from the maternal allele. We have previously shown that in some Wilms tumors the maternal IGF2 imprint is relaxed such that the gene is expressed biallelically. We have now investigated this subset of tumors further and found that biallelic expression of IGF2 was associated with undetectable or very low levels of H19 expression. The relaxation of IGF2 imprinting in Wilms tumors also involved a concomitant reversal in the patterns of DNA methylation of the maternally inherited IGF2 and H19 alleles. Furthermore, the only specific methylation changes that occurred in tumors with relaxation of IGF2 imprinting were solely restricted to the maternal IGF2 and H19 alleles. These data suggest that there has been an acquisition of a paternal epigenotype in these tumors as the result of a pathologic disruption in the normal imprinting of the IGF2 and H19 genes.

Alleles↗
PubMed1995

Screening for major depression in the early stages of multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is associated with a high risk of developing major depression, but depression in MS patients frequently goes undetected and untreated. The current study examined the clinical utility of the Beck Depression Inventory (BDI) as a screening measure for major depression in newly diagnosed MS patients. METHODS: Forty-six new referrals to an MS clinic completed the BDI and participated in a structured interview for major depression, within 2 months of the diagnosis of MS. RESULTS: According to DSM-III-R criteria, 40% of patients were diagnosed with major depression, 22% had adjustment disorder with depressed mood, and 37% showed no evidence of mood disorder. Sensitivity and specificity values, and positive and negative predictive values are reported for every BDI cut-off score between 9 and 21. CONCLUSIONS: A BDI cut-off score of 13 (sensitivity = .71, specificity = .79) is recommended as optimal for use in screening for major depression in newly diagnosed MS patients. The use of the BDI as a screening measure for major depression must proceed with caution given that a cut-off score of 13 still yielded a false-negative rate of 30%.

Adult↗
PubMed1995

Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux.

Paired box (PAX) genes play a critical role in human development and disease. The PAX2 gene is expressed in primitive cells of the kidney, ureter, eye, ear and central nervous system. We have conducted a mutational analysis of PAX2 in a family with optic nerve colobomas, renal hypoplasia, mild proteinuria and vesicoureteral reflux. We report a single nucleotide deletion in exon five, causing a frame-shift of the PAX2 coding region in the octapeptide domain. The phenotype resulting from the PAX2 mutation in this family was very similar to abnormalities that have been reported in Krd mutant mice. These data suggest that PAX2 is required for normal kidney and eye development.

Abnormalities, Multiple↗
PubMed1995

Structural versus functional modulation of the arterial baroreflex.

Structural changes in large arteries are often considered the predominant mechanism responsible for decreased baroreflex sensitivity and baroreceptor resetting in hypertension, atherosclerosis, and aging. Recent work has demonstrated that "functional" mechanisms, both at the level of the peripheral sensory endings and within the central nervous system, contribute significantly to altered baroreflex responses. We have conducted both reductive studies of mechanoelectrical transduction in cultured baroreceptor neurons and integrative studies with in vivo recordings of the activity of baroreceptor afferent fibers and efferent sympathetic nerves. Results suggest that the primary mechanism of mechanical activation of baroreceptor neurons involves opening of stretch-activated ion channels susceptible to blockade by gadolinium. Baroreceptor nerve activity is modulated by the activity of potassium channels and the sodium-potassium pump and by paracrine factors, including prostacyclin, oxygen free radicals, and factors released from aggregating platelets. Endothelial dysfunction and altered release of these paracrine factors contribute significantly to the decreased baroreceptor sensitivity in hypertension and atherosclerosis. The central mediation of the baroreflex depends on the pulse phasic pattern of afferent baroreceptor discharge. Baroreflex-mediated inhibition of sympathetic nerve activity is well maintained during pulse phasic afferent activity. Continuous, nonphasic baroreceptor discharge or a rapid (> 1.5 Hz) pulse phasic discharge results in disinhibition of sympathetic activity. This disinhibition during continuous baroreceptor input is exaggerated with aging. Thus, a defect in central mediation of the baroreflex may be a major cause of the impaired baroreflex and sympathoexcitation in the elderly. In summary, functional neural mechanisms, in addition to structural vascular changes, contribute importantly to altered baroreflex responses in normal and pathophysiological states.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Depression before and after diagnosis of multiple sclerosis.

Depression was examined in 45 patients evaluated within 2 months of diagnosis of MS. At the time of testing, 40% of the MS sample met the diagnostic criteria for major depression, 22% had adjustment disorder with depressed mood and 37% showed no evidence of mood disorder. Personal and family history of depression in patients with MS was also examined and compared with a sample of patients with chronic low back pain (CLBP) who were matched for age, gender, marital and employment status and current level of depression. Fifty-two per cent of patients with MS reported experiencing a depressive episode before the onset of MS compared with 17% of patients with CLBP (P < 0.001). Sixteen patients with MS (35%) reported family history (parent or sibling) of treatment for depression compared with seven (15%) of patients with CLBP (P < 0.05). MS patients with a history of depression reported more initial symptoms than MS patients without a history of depression. Clinical and theoretical implications of the findings are discussed.

Adult↗
PubMed1995

Rapid analysis of mandibular margins.

Evaluating surgical margins during composite resection of carcinoma is limited by analysis of the bone margins. The standard pathologic evaluation of bone is by decalcification. A method of analysis was devised based on histologically proven methods of cortical invasion and subsequent spread. Frozen section analysis (FSA) of the cancellous bone was investigated as a rapid method of evaluating adequacy of the mandibular resection. Subjects consisted of 29 patients undergoing full-thickness mandibular resection, with 16 cases of histologically proven mandibular invasion qualifying for evaluation. Results of FSA were then compared to the permanent section analysis of the cancellous bone and to the decalcified specimen. Complete correlation was found between frozen and permanent section results. Frozen section analysis was able to correctly predict adequacy of resection in 32 (97%) of 33 margins.

Carcinoma, Squamous Cell↗
PubMed1994

Health care reform in the states.

Challenged by relentless increases in health care spending, state governments have been forced to experiment with health care system reform. Medicaid has been expanded by Congress, forcing states to provide a broader array of health benefits to more recipients. As states consider reform, federal limitations mandated by Medicaid and by the Employee Retirement Income Security Act (ERISA) of 1974 on state activity pose significant obstacles. ERISA sharply limits a state's ability to raise revenue to fund these health programs. Several states have responded to these limitations by seeking waivers. Despite these obstacles, 8 states already have enacted comprehensive health reform measures, and virtually every state is considering legislative reform.

Health Care Reform↗
PubMed1994

Skeletal muscle pH assessed by biochemical and 31P-MRS methods during exercise and recovery in men.

The present study was designed to compare evaluation of skeletal muscle metabolism (vastus lateralis) evaluated by 31P-magnetic resonance spectroscopy (MRS) and biochemical analysis. During identical isometric knee extensor exercise protocols to fatigue in eight men, biopsy samples were taken at rest, peak exercise, and 32 s postexercise and 31P-MRS data were collected continuously for phosphocreatine (PCr), pH, ATP, and P(i) at 8- or 32-s intervals. There was no difference in ATP or pH measurements between the two techniques at rest, during peak exercise, or in recovery. Corresponding measurements of pH by the two techniques were closely related (r = 0.88, P < 0.01), and pH measured by 31P-MRS was closely related to muscle lactate accumulation (r = -0.84, P < 0.001). The level of PCr at peak exercise, expressed as a percentage of the baseline value, was not different between the two techniques (42 +/- 15 vs. 46 +/- 15%). The results indicate that, in skeletal muscle in normal subjects, 1) measurements of pH and PCr at rest and during exercise do not differ between the 31P-MRS and biopsy techniques and 2) muscle pH measured by 31P-MRS is closely related to lactate accumulation in men. Our data suggest that direct comparison of results of studies of exercise metabolism using these two techniques is warranted.

Adenine Nucleotides↗
PubMed1994

Patients' perspectives: subjective responses in a primary care setting.

To determine patients' responses to the evaluation and treatment of primary care outpatient medical complaints, 103 consecutive patient encounters are analyzed. Diagnostic certainty is classified as either high or low and the patients' subjective responses categorized as improved, unchanged, or worse. The overall patient response rates are: 69% improved; 27% unchanged; and 4% worse. Subgroup analysis identify patients with low diagnostic certainty and chronic medical conditions as having reduced subjective improvement rates.

Adult↗