Biomedical subjects

J Meehan

Publications and source records attributed to J Meehan.

At least 19 recordsLinked to original sources

PubMed1999

Validation of a cataplexy questionnaire in 983 sleep-disorders patients.

Our goal was to validate a self-administered narcolepsy questionnaire focusing on cataplexy. Nine hundred and eight three consecutive subjects entering the Stanford Sleep Disorder Clinic completed the questionnaire. Clinic physicians reported on the presence or absence of "clear-cut" cataplexy. Responses to 51 cataplexy-related questionnaire items were compared between subjects with clear-cut cataplexy (n = 63) and all other patients (n = 920). As previously reported, a large portion of the non-narcoleptic population was found to experience muscle weakness with various intense emotions (1.8% to 18.0%) or athletic activities (26.2% to 28.8%). Factor analysis and Receiver Operating Characteristic Curve (ROC) analysis were used to determine the most predictive items for clear-cut cataplexy. Most strikingly, cataplexy was best differentiated from other types of muscle weakness when triggered by only three typical situations: "when hearing and telling a joke," "while laughing," or "when angry." Face or neck, rather than limbs, were also more specifically involved in clear-cut cataplexy. Other items, such as length of attacks, bilaterality, and alteration in consciousness, were poorly predictive. A simple decision tree was constructed to isolate high-(91.7%) and low-(0.6%) risk groups for cataplexy. This questionnaire will be used to increase diagnostic consistency across clinical centers, thus providing more homogenous subject pools for clinical and basic research studies.

Adolescent↗

PubMed1999

Heavy long-term ethanol consumption induces an alpha- to beta-myosin heavy chain isoform transition in rat.

Alcoholic heart muscle disease is characterized by structural changes which include chamber dilation, ventricular hypertrophy, and myocyte damage. These effects often lead to contractile dysfunction and ultimately to heart failure if alcohol consumption is not terminated. In rat models for heart failure in which heart failure is induced by pressure or volume overload, there is a shift in the myosin heavy chain (MHC) isoforms, from alpha to beta. As a result of this MHC transition, there is typically a decrease in myosin ATPase activity. We utilized a rat model of chronic alcohol consumption in order to determine if alcohol causes a similar shift in MHC isoforms and changes in myosin ATPase activity. A liquid diet containing 9% ethanol (46% of daily calories; 11.8 g/kg/day) was administered to adult rats for a period of 60 or 90 days. This heavy consumption of ethanol resulted in an average blood ethanol content of 150 mg %. The relative abundance of beta-MHC isoform protein increased from a control level of 9.7% to 35.1% in hearts of ethanol-fed rats, following 90 days of ethanol consumption. In a separate set of experiments, the levels of alpha-MHC and beta-MHC mRNA were demonstrated to increase by 150% and 230%, respectively. Following a 60 day treatment, there was a significant reduction in the actomyosin Mg2+ -ATPase activity in the myofibrillar preparations from hearts of ethanol-fed rats compared to hearts from control-fed rats. In addition, the myosin Ca2+ -ATPase activity was decreased 17% and 30% after 60 and 90 days of ethanol consumption, respectively. The present study demonstrates that chronic ethanol consumption induces an increase in the proportion of the total MHC content composed of the beta-isoform. This isoform transition is accompanied by an accumulation of beta-MHC mRNA, suggesting that the switch is organized pretranslationally. A functional consequence of this transition in MHC phenotype is demonstrated by significant decreases in the myofibrillar and myosin ATPase activities.

Alcoholism↗

PubMed1997

Influence of thyroid hormone on the tissue-specific expression of cytochrome c oxidase isoforms during cardiac development.

In mammals, cytochrome c oxidase (COX) is composed of 13 different protein subunits. In the rat, two nuclear-encoded subunits, COX VIa and VIII, exist as tissue-specific isoforms: heart and liver. Using Northern-blot analysis, the levels of transcripts for the heart and liver isoforms of VIa and VIII were examined in developing rat hearts. The liver isoform was found to be the predominant form of subunit VIa and the exclusive form of VIII in the 18-day fetal hearts. The mRNA levels of the heart isoform of both subunits increased dramatically to reach adult levels by 14 days. Although the levels of the VIa- and VIII-liver isoform mRNAs remained stable throughout early development, their levels decreased by 40 and 36% respectively between the 18-day fetal stage and 18-day neonatal stage. Therefore the up-regulation of the heart isoforms and down-regulation of the liver isoforms appear to be regulated in a co-ordinated manner during development. To determine if thyroid hormone influences the expression of these developmentally regulated isoforms, the RNA was also extracted from the hearts of 2-week-old hypothyroid rats. The results showed that the levels of VIII-heart and VIa-liver COX mRNAs were approx. 40% lower in the hypothyroid hearts, while VIII-liver and VIa-heart COX isoform expression remained unchanged. These data demonstrate that the isoforms of COX subunits VIa and VIII are not co-ordinately regulated by changes in thyroid hormone levels. Therefore we conclude that, although thyroid hormone influences the expression of isoforms, it appears to do so via a different mechanism from that which regulates the developmental transition.

Animals↗

PubMed1997

A PET study of voluntary movement in schizophrenic patients experiencing passivity phenomena (delusions of alien control).

Schizophrenic patients experiencing passivity phenomena believe their thoughts and actions to be those of external, or alien, entities. We wished to test the hypothesis that voluntary motor action in such patients would be associated with aberrant patterns of activation within the cerebral motor system. We used H2(15)O PET to study patients while they performed paced joystick movements on two occasions 4-6 weeks apart. During the first scan passivity symptoms were maximal, while by the second scan these symptoms had significantly improved in five of the seven patients. Two control groups were also scanned on two occasions: deluded schizophrenic patients without passivity phenomena and normal subjects. In normal subjects, performance of freely selected joystick movements with the right hand, compared with rest, revealed relative activation of prefrontal, premotor, motor and parietal cortical regions. Schizophrenic patients with passivity showed hyperactivation of parietal and cingulate cortices. This hyperactivation remitted in those subjects in whom passivity decreased over time. This reversible hyperactivity was not a feature of schizophrenics without passivity. Given that these hyperactive cerebral regions subserve attention to internal and external bodily space, and the attribution of significance to sensory information, they provide a plausible anatomical substrate for the misattribution of internally generated acts to external entities: the cardinal feature of delusions of passivity (alien control).

Brain Mapping↗

PubMed1997

HLA DR15 (DR2) and DQB1*0602 typing studies in 188 narcoleptic patients with cataplexy.

Narcolepsy is considered a homogeneous clinical entity when excessive daytime sleepiness and cataplexy are present. Cataplexy is a polymorphic symptom that can be very mild and is thus subjectively defined. The Multiple Sleep Latency Test (MSLT) is widely used as a diagnostic test for narcolepsy. A short mean sleep latency and multiple sleep onset REM periods (SOREMPs) are typically observed in narcoleptic patients. The discovery of a tight association of narcolepsy with HLA class II antigens offers a unique opportunity to explore the respective value of the MSLT or of the presence of clear-cut cataplexy in defining an etiologically homogeneous group of narcoleptic patients. In this study, we carried out HLA typing for DR15(DR2) and DQB1*0602 in 188 narcoleptic patients with cataplexy in three ethnic groups (24 Asians, 61 Blacks, and 103 Caucasians). These results confirm the importance of DQB1*0602 typing rather than DR15 (DR2) typing in Black narcoleptic patients and demonstrate that the presence of clear-cut cataplexy is a better predictor for DQB1*0602 positivity than the presence of abnormal MSLT results.

Asian People↗

PubMed1997

Do the right thing. When it comes to your community, do you know what that is? Roundtable discussion.

What is the health care organization's responsibility to maintaining a healthy community, and how does the board fit into that role? Has the field's understandable fixation on costs and the penetration of managed care into most markets affected that role? Leaders of both for-profit and not-for-profit organizations often believe that they are fulfilling their community obligations as long as they provide uncompensated care to the indigent and the uninsured. But is that really being accountable to the community? And if it's not, then what is community accountability? The American Hospital Association's Division of Trustee Leadership and Trustee magazine posed these questions to 13 health care and community leaders last December. Their different perspectives provide for some surprising answers.

American Hospital Association↗

PubMed1996

Effect of 1,25-dihydroxyvitamin D3 on mouse thymus: role of extracellular calcium.

We recently reported that mice treated with 1,25-dihydroxyvitamin D3 ( 1,25-(OH)2D3) or 19-nor-1,25-(OH)2D2 experienced a severe loss of their thymocytes and decreased proliferation in response to concanavalin A mitogen. The present study investigated the effect of short-term treatment with 1,25-(OH)2D3 on the thymic architecture and thymocyte subsets. Daily treatment with 1,25-dihydroxyvitamin D3 at 20 ng per mouse for 4 days induced significant involution of thymic tissue. The atrophy was predominantly observed in the cortical component. Flow cytometric analysis of thymocyte subsets showed that the CD4 + CD8 + population was the primary target. Since the treated mice experienced profound hypercalcemia, we studied the effect of 1,25-(OH)2D3 on animals fed a vitamin D-deficient, low calcium diet or the same diet containing vitamin D for 25 days prior to treatment. The low calcium fed mice showed severe hypocalcemia and slight thinning of thymic cortex. Treatment with 1,25-(OH)2D3 moderately improved the hypocalcemia but had no further effect on the thymus of these animals. On the other hand, hypercalcemia and thymic atrophy were found in the animals fed the diet containing vitamin D. Overall, the atrophy effect on the thymus caused by 1,25-(OH)2D3 treatment was prevented by eliminating the hypercalcemia observed in + D + Ca treated animals. Thus, thymic atrophy probably resulted from hypercalcemia and not from 1,25-(OH)2D3 itself.

Animals↗

PubMed1995

Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells.

Human melanoma cells can process the MAGE-1 gene product and present the processed nonapeptide EADPTGHSY on their major histocompatibility complex class I molecules, HLA-A1, as a determinant for cytolytic T lymphocytes (CTLs). Considering that autologous antigen presenting cells (APCs) pulsed with the synthetic nonapeptide might, therefore, be immunogenic, melanoma patients whose tumor cells express the MAGE-1 gene and who are HLA-A1+ were immunized with a vaccine made of cultured autologous APCs pulsed with the synthetic nonapeptide. Analyses of the nature of the in vivo host immune response to the vaccine revealed that the peptide-pulsed APCs are capable of inducing autologous melanoma-reactive and the nonapeptide-specific CTLs in situ at the immunization site and at distant metastatic disease sites.

Amino Acid Sequence↗

PubMed1995

Pyomyositis in an adolescent female athlete.

A case of pyomyositis in a healthy 13-year-old female volleyball player is presented and discussed. This case is unusual because, historically, pyomyositis has been more common in males, especially those who participate in strenuous physical activity. However, competitive sports and vigorous exercise programs are becoming more widely available to young females. Therefore, a relative increase in the number of adolescent women with pyomyositis can be expected.

Abscess↗

PubMed1995

Pharmacokinetic interaction studies between felbamate and vigabatrin.

To assess the possible occurrence of pharmacokinetic interactions between the antiepileptic agents felbamate and vigabatrin, two randomized, double-blind, placebo-controlled, crossover studies were conducted in healthy male volunteers. In Study I, 18 subjects received oral vigabatrin 1000 mg every 12 h for two 8 days periods with felbamate 1200 mg every 12 h or placebo. In Study II, 18 other volunteers were administered oral felbamate 1200 mg every 12 h for two 8 days periods with vigabatrin 1000 mg every 12 h or placebo. On the eighth day of each treatment period, blood and urine samples were collected over 12 h for determination of the active S(+)- and inactive R(-)-vigabatrin enantiomer concentrations (Study I) or felbamate concentrations (Study II). In Study I, the pharmacokinetic parameters of R(-)-vigabatrin were similar during co-administration with felbamate or placebo. Felbamate produced a 13% increase in AUC(0.12 h) and an 8% increase in urinary excretion of S(+)-vigabatrin. Although these changes were statistically significant, their magnitude was small. In Study II, the pharmacokinetic parameters of felbamate were similar during concurrent administration with vigabatrin or placebo. These data indicate that there are no clinically relevant pharmacokinetic interactions between felbamate and vigabatrin in man.

Administration, Oral↗

PubMed1993