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PubMed2001

Focus group data pertinent to the prevention of obesity in African Americans.

The increased prevalence of obesity among African-American women makes it likely that they bear a disproportionate burden of comorbidities attributable to obesity, such as diabetes, hypertension, and hyperlipemia. These observations suggest that intensive efforts to prevent obesity should be directed at this group. This presentation provides a summary of the findings of focus groups that convened prior to the Sisters Together, Move More, Eat Better campaign in Boston. This pilot campaign was designed to increase awareness of the importance of healthy eating and physical activity among young adult African-American women. In addition, data collected by the Division of Nutrition and Physical Activity of the US Centers for Disease Control and Prevention (CDC) provide additional information about attitudes toward diet and physical activity among African American youth. Such data are essential to understand the attitudinal changes necessary to prevent obesity in these vulnerable populations.

Attitude to Health↗
PubMed2005

Sacred disease secrets revealed: the genetics of human epilepsy.

Neurons throughout the brain suddenly discharging synchronously and recurrently cause primarily generalized seizures. Discharges localized awhile in one part of the brain cause focal-onset seizures. A genetically determined generalized hyperexcitability had been predicted in primarily generalized seizures, but surprisingly the first epilepsy gene discovered, CHRNA4, was in a focal (frontal lobe)-onset syndrome. Another surprise with CHRNA4 was its encoding of an ion channel present throughout the brain. The reason why CHRNA4 causes focal-onset seizures is unknown. Recently, the second focal (temporal lobe)-onset epilepsy gene, LGI1 (unknown function), was discovered. CHRNA4 led the way to mutation identifications in 15 ion channel genes, most causing primarily generalized epilepsies. Potassium channel mutations cause benign familial neonatal convulsions. Sodium channel mutations cause generalized epilepsy with febrile seizures plus or, if more severe, severe myoclonic epilepsy of infancy. Chloride and calcium channel mutations are found in rare families with the common syndromes childhood absence epilepsy and juvenile myoclonic epilepsy (JME). Mutations in the EFHC1 gene (unknown function) occur in other rare JME families, and yet in other families, associations are present between JME (or other generalized epilepsies) and single nucleotide polymorphisms in the BRD2 gene (unknown function) and the malic enzyme 2 (ME2) gene. Hippocrates predicted the genetic nature of the 'sacred' disease. Genes underlying the 'malevolent' forces seizing 1% of humans have now been revealed. These, however, still account for a mere fraction of the genetic contribution to epilepsy. Exciting years are ahead, in which the genetics of this extremely common, and debilitating, neurological disorder will be solved.

Calcium Channels↗
PubMed1994

Cardiovascular birth defects and prenatal exposure to female sex hormones: a reevaluation of data reanalysis from a large prospective study.

In data of the U.S. Collaborative Perinatal Study (CPS), the Drug Epidemiology Unit (DEU) reported a relative risk of about 2.3 between maternal female sex hormone exposure during months 1 to 4 of pregnancy and cardiovascular malformation in infants (Heinonen et al., '77a N. Engl. J. Med., 296:67-70). Wiseman and Dodds-Smith ('84, Teratology, 30:359-370) reexamined the original CPS data and found the DEU had made some errors in classification of exposure and disease. Also they challenged the classification of cases as "exposed" in those born to mothers who received the compounds outside the day 19 to 50 window of cardiovascular embryogenesis. Wiseman and Dodds-Smith stated that their reanalysis "clearly showed that there was [in the data used by the DEU] no statistically significant association between exposure in the critical organogenic period of pregnancy and cardiac malformation in offspring." They did not undertake any statistical analysis, but their reanalysis resulted in a wide-spread nonacceptance of the association reported by the DEU. The study reported here reclassified the cases of the original DEU study in accord with the implications of the Wiseman and Dodds-Smith reanalysis of exposure and disease. After this reclassification, an effect magnitude measure of association, the relative risk rose from 2.33 to 2.48 and remained nominally significant statistically at the .05 level. Thus, if anything, the quantitative consequences of the Wiseman and Dodds-Smith review of the data, when applied in an unbiased manner, result in an increase in the measure of effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed2002

Standards and guidelines for performing central dual X-ray densitometry from the Canadian Panel of International Society for Clinical Densitometry.

The International Society for Clinical Densitometry (ISCD) is a multidisciplinary nonprofit global organization formed to ensure excellence in densitometry imaging, interpretation, and application. The Canadian panel of the ISCD represents ISCD in Canada and oversees Canadian bone densitometry certification programs. The standards of care from the Canadian panel of the ISCD have been developed in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. A variety of techniques are available for skeletal assessment of bone mineral density, which vary in accuracy, precision, and clinical utility as well as availability. This article focuses on central dual X-ray absorptiometry in adults and does not address densitometry in the pediatric population. Other technologies will be addressed in a subsequent article.

Absorptiometry, Photon↗
PubMed2000

Diabetes and periodontal diseases. Committee on Research, Science and Therapy. American Academy of Periodontology.

This position paper on diabetes mellitus was prepared by the Research, Science and Therapy Committee of The American Academy of Periodontology. It is intended to: 1) update members of the dental profession on the diagnosis and medical management of patients with diabetes mellitus; 2) summarize current knowledge on the relation between diabetes mellitus and periodontal diseases; 3) provide an overview of factors in diabetic patients relevant to understanding the pathogenesis of periodontal diseases in these subjects; 4) outline special considerations associated with treatment of periodontal diseases in diabetic patients; and 5) discuss possible approaches to the management of diabetic emergencies in the dental office.

Collagen↗
PubMed1994

Fetal biometry of skeletal dysplasias: a multicentric study.

Twenty-three diagnostic centers worldwide contributed 127 cases of 17 skeletal dysplasias. Discriminant analysis showed that the femur length was the best biometric parameter to distinguish among the five most common disorders in this series (thanatophoric dysplasia, osteogenesis imperfecta type II, achondrogenesis, achondroplasia and hypochondroplasia). Fifty-four percent of fetuses with femur length below 30% of the mean for gestational age had achondrogenesis. Seventy-eight percent of measurements between 40 and 60% of the mean for gestational age represented either thanatophoric dysplasia or osteogenesis imperfecta type II. Fetuses who had over 80% of the mean for gestational age had predominantly hypochondroplasia, achondroplasia, and osteogenesis imperfecta type III.

Bone Diseases, Developmental↗
PubMed1996

Processed bovine pericardium as patch angioplasty for carotid endarterectomy: a preliminary report.

Although the routine use of a patch for closure of the arteriotomy after carotid endarterectomy is still debated, patch angioplasty is frequently used to avoid residual stenosis and to lower the incidence of later restenosis. Several materials are widely used for carotid patching, notably, autologous vein, Dacron and polytetrafluorethylene (PTFE). During recent years a heterologous stabilized graft made from bovine pericardium has been introduced. This paper reports the authors' experience of 52 carotid endarterectomies in which a patch of bovine pericardium was used to close the arteriotomy. The patients were followed with colour-duplex scanning over 12-30 months. This biograft did not require preclotting and proved to be easy to suture. Follow-up did not uncover any complications related to graft use. Although this is a preliminary report, it is concluded that bovine pericardium is a promising material for carotid patch angioplasty.

Animals↗
PubMed2005

Validation of male-specific, 12-locus fluorescent short tandem repeat (STR) multiplex.

Y chromosome-specific short tandem repeat (Y-STR) analysis has become another widely accepted tool for human identification. The PowerPlex Y System is a fluorescent multiplex that includes the 12 loci: DYS19, DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439. This panel of markers incorporates the 9-locus European minimal haplotype (EMH) loci recommended by the International Y-STR User Group and the 11-locus set recommended by the Scientific Working Group on DNA Analysis Methods (SWGDAM). Described here are inter-laboratory results from 17 developmental validation studies of the PowerPlex Y System and include the following results: (a) samples distributed between laboratories and commercial standards produced expected and reproducible haplotypes; (b) use of common amplification and detection instruments were successfully demonstrated; (c) full profiles were obtained with standard 30 and 32 cycle amplification protocols and cycle number (24-28 cycles) could be modified to match different substrates (such as direct amplification of FTA paper); (d) complete profiles were observed with reaction volumes from 6.25 to 50 microL; (e) minimal impact was observed with variation of enzyme concentration; (f) full haplotypes were observed with 0.5-2x primer concentrations; however, relative yield between loci varied with concentration; (g) reduction of magnesium to 1mM (1.5 mM standard) resulted in minimal amplification, while only partial loss of yield was observed with 1.25 mM magnesium; (h) decreasing the annealing temperature by 2-4 degrees C did not generate artifacts or locus dropout and most laboratories observed full amplification with the annealing temperature increased by 2 degrees C and significant locus dropout with a 4 degrees C increase in annealing temperature; (i) amplification of individual loci with primers used in the multiplex produced the same alleles as observed with the multiplex amplification; (j) all laboratories observed full amplification with >or = 125 pg of male template with partial and/or complete profiles observed using 30-62.5 pg of DNA; (k) analysis of < or = 500 ng of female DNA did not yield amplification products; (l) the minor male component of a male/female mixture was observed with < or =1200-fold excess female DNA with the majority of alleles still observed with 10,000-fold excess female; (m) male/male mixtures produced full profiles from the minor contributor with 10-20-fold excess of the major contributor; (n) average stutter for each locus; (o) precision of sizing were determined; (p) human-specificity studies displayed amplification products only with some primate samples; and (q) reanalysis of 102 non-probative casework samples from 65 cases produced results consistent with original findings and in some instances additional identification of a minor male contributor to a male/female mixture was obtained. In general, the PowerPlex Y System was shown to have the sensitivity, specificity and reliability required for forensic DNA analysis.

Animals↗
PubMed2005

Treated and treatment-naive alcoholics come from different populations.

In most research on alcoholism, convenience samples of individuals who have been in some type of treatment are used. Berkson's fallacy results when the associations found in studies of select samples are incorrectly presumed to apply to all alcoholics (i.e., including untreated alcoholics in the general population). In the current study, we examined whether treated and untreated alcoholics have similar early alcohol use histories by comparing abstinent alcoholics (treated and sober at least 6 months) with treatment-naive alcoholics (active drinkers). We studied 14 pairs of women and 25 pairs of men matched on the age at which they first met criteria for heavy alcohol use (women, 80 drinks per month; men, 100 drinks per month). The timeline follow-back interview method was used to gather retrospective alcohol use information. Alcohol dose and duration of use were subsequently computed for two intervals: (1) time between the person's first drink and date at which the person met criteria for heavy drinking and (2) period between when criteria for heavy drinking were met and current age of the treatment-naive person from each pair. During the period before the matching "heavy drinking" criteria were met, alcohol dose did not differ between groups. In the period after criteria for heavy alcohol use were met, in comparison with treatment-naive alcoholics, the treated alcoholics had higher average and peak alcohol doses. We rejected the hypothesis that the treatment-naive alcoholics and the treated alcoholics have similar alcohol use trajectories over time, with the treatment-naive sample simply being observed earlier in its alcohol use histories. Instead, we concluded that the two groups come from different populations with regard to alcohol use. In fact, the treated alcoholics had alcohol doses more than 50% higher than those of treatment-naive alcoholics in the years just after they began drinking heavily. This finding supports the suggestion that results from studies of alcoholics in treatment or after treatment (i.e., most studies of alcoholics) cannot be generalized to untreated individuals (who make up the majority of alcoholics).

Adult↗
PubMed2005

Purified mouse dopamine neurons thrive and function after transplantation into brain but require novel glial factors for survival in culture.

Cell replacement therapy in Parkinson's disease depends on a reliable source of purified dopamine (DA) neurons (PDN) and the identification of factors relevant to their survival. Our goal was to genetically tag and purify by flow cytometry embryonic midbrain DA neurons from a transgenic mouse line carrying 11 kb of human tyrosine hydroxylase promoter driving expression of the enhanced green fluorescent protein(GFP) for studies in vivo and in vitro. A 99% purification of GFP+ cells was achieved. When transplanted into 6-hydroxydopamine-treated rat striatum, PDN survived, became well-integrated and produced recovery from amphetamine-induced motor behaviors. However, when grown in culture, PDN died within days of plating. No known growth factors prevented PDN death as did incubation with novel factors in glia/glial-conditioned media. We conclude that GFP-tagged DA neurons can be purified to homogeneity and can survive and function when grown with glial factors in vitro or after transplantation in vivo.

Animals↗
PubMed2006

Apparent clearance of sirolimus in heart transplant recipients: impact of primary diagnosis and serum lipids.

The study was aimed to identify factors affecting sirolimus apparent clearance (CL/F) in de novo heart transplant recipients using a population pharmacokinetic approach. A total of 31 patients (7 female and 24 male) originally included in a formal clinical trial, contributed 524 sirolimus blood concentrations with the time after dose ranging from 11.08 to 31.83 hours. Sirolimus concentrations were measured using liquid chromatography-tandem mass spectrometry and data analysis was carried out using NONMEM (Globomax LLC, Hanover, MD) software. Factors screened included age, weight, gender, primary diagnosis, biochemical and hematological indices, cyclosporine dose, days post-transplant and potential interacting medications. The predictive performance of the final model was evaluated using a data-splitting method. Sirolimus apparent clearance (CL/F) was decreased by 20.8% for every 100 mg increase in cyclosporine daily dose and was 62.1% lower in patients with primary diagnosis of ischemic heart disease (IHD). Sirolimus apparent clearance was 37.8% lower when triglyceride was greater than 2 mmol/L. Based on the final model, the average values for sirolimus CL/F and apparent volume of distribution were 7.09 and 1350 L/h, respectively. Inter-subject variability in CL/F was 27.5% and residual random error was 24.1%. This study identified cyclosporine dose, hypertriglyceridemia and primary diagnosis of IHD as the most important factors affecting sirolimus CL/F. This information may assist in dose individualization of sirolimus in heart transplant recipients.

Adolescent↗
PubMed1991

Identification of transposition proteins encoded by the bacterial transposon Tn7.

The bacterial transposon, Tn7, encodes an elaborate array of transposition genes, tnsABCDE. We report here the direct identification of the TnsA, TnsB, TnsC and TnsD polypeptides by immunoblotting. Our results demonstrate that the complexity of the protein information devoted to Tn7 transposition is considerable: the aggregate molecular size of the five Tns polypeptides is about 300 kDa. We also report the sequence of the tnsA gene and of the 5' ends of tnsB and tnsD. This analysis reveals that all five tns genes are oriented in the same direction within Tn7.

Amino Acid Sequence↗
PubMed1997

Public release of cardiac surgery outcomes data in New York: what do New York state cardiologists think of it?

BACKGROUND AND OBJECTIVE: Since 1990, risk-adjusted outcomes for patients undergoing coronary artery bypass graft surgery in New York state have been released to the public. The purpose of this study was to assess the extent to which referring cardiologists share these data with patients and use these data to make referrals. METHODS: A survey questionnaire was sent to all cardiologists in New York in the New York State Chapter of the American College of Cardiology. RESULTS: Four hundred fifty cardiologists responded to the survey. Most (94%) found the report "easy to read." A majority (67%) found the report to be "very accurate" or "somewhat accurate" in capturing differences in the performance of cardiac surgeons, whereas 33% found it to be "not at all accurate." Twenty-two percent reported that they "routinely discuss the reports with their patients," and 38% responded that the information has affected their referrals to surgeons "very much" or "somewhat." CONCLUSIONS: A majority of cardiologists has not generally changed their well-established referral patterns as a result of the New York coronary artery bypass graft surgery reports. However, there has been a modest impact on referrals resulting from the distribution of these reports. The findings also suggest that increased dialogue between clinicians and policy makers regarding the format and structure of public releases would be a valuable undertaking.

Attitude of Health Personnel↗
PubMed2001

Inhibition of ALDH3A1-catalyzed oxidation by chlorpropamide analogues.

In our efforts to identify agents that would specifically inhibit ALDH3A1, we had previously studied extensively the effect of an N(1)-alkyl, an N(1)-methoxy, and several N(1)-hydroxy-substituted ester derivatives of chlorpropamide on the catalytic activities of ALDH3A1s derived from human normal stomach mucosa (nALDH3A1) and human tumor cells (tALDH3A1), and of two recombinant aldehyde dehydrogenases, viz. human rALDH1A1 and rALDH2. The N(1)-methoxy analogue of chlorpropamide, viz. 4-chloro-N-methoxy-N-[(propylamino)carbonyl]benzenesulfonamide (API-2), was found to be a relatively selective and potent inhibitor of tALDH3A1-catalyzed oxidation as compared to its ability to inhibit nALDH3A-catalyzed oxidation, but even more potently inhibited ALDH2-catalyzed oxidation, whereas an ester analogue, viz. (acetyloxy)[(4-chlorophenyl)sulfonyl]carbamic acid 1,1-dimethylethyl ester (NPI-2), selectively inhibited tALDH3A1-catalyzed oxidation as compared to its ability to inhibit nALDH3A1-, ALDH1A1- and ALDH2-catalyzed oxidations, and this inhibition was apparently irreversible. Three additional chlorpropamide analogues, viz. 4-chloro-N,O-bis(ethoxycarbonyl)-N-hydroxybenzenesulfonamide (NPI-4), N,O-bis(carbomethoxy)methanesulfohydroxamic acid (NPI-5), and 2-[(ethoxycarbonyl)oxy]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (NPI-6), were evaluated in the present investigation. Quantified were NAD-linked oxidation of benzaldehyde catalyzed by nALDH3A1 and tALDH3A1, and NAD-linked oxidation of acetaldehyde catalyzed by rALDH1A1 and rALDH2, all at 37 degrees C and pH 8.1, and in the presence and absence of inhibitor. NPI-4, NPI-5 and NPI-6 were not substrates for the oxidative reactions catalyzed by any of the ALDHs studied. Oxidative reactions catalyzed by the ALDH3A1s, rALDH1A1 and rALDH2 were each inhibited by NPI-4 and NPI-5. NPI-6 was a poor inhibitor of nALDH3A1- and tALDH3A1-catalyzed oxidations, but was a relatively potent inhibitor of rALDH1A1- and rALDH2-catalyzed oxidations. In all cases, inhibition of ALDH-catalyzed oxidation was directly related to the product of inhibitor concentration and preincubation (enzyme+inhibitor) time. As judged by the product values (microM x min) required to effect 50% inhibition (IC(50)): (1) nALDH3A1 and tALDH3A1 were essentially equisensitive to inhibition by NPI-4 and NPI-5, and both enzymes were poorly inhibited by NPI-6; (2) rALDH1A1 was, relative to the ALDH3A1s, slightly more sensitive to inhibition by NPI-4 and NPI-5, and far more sensitive to inhibition by NPI-6; and (3) rALDH1A1 was, relative to rALDH2, essentially equisensitive to inhibition by NPI-5, whereas, it was slightly more sensitive to inhibition by NPI-4 and NPI-6.

Aldehyde Dehydrogenase↗
PubMed2002

Early drop-outs, late drop-outs and completers: differences in the continuation phase of a clinical trial.

OBJECTIVE: The purpose of this study was to assess the differences between early (EDs), late drop-outs (LDs) and completers in the continuation phase of a clinical trial. METHODS: The authors studied 119 outpatients who were treatment responders in an 8-week open trial with fluoxetine 20 mg/day, and who were then enrolled in a 26-week clinical trial comparing the efficacy of fluoxetine versus fluoxetine and cognitive behavior therapy (CBT). Patients were assessed using the Structured Clinical Interview for DSM-III-R-Axis I (SCID-Patient Edition), Hamilton Depression Rating Scale (HAMD-17) and the following self-rated scales: Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Anxiety Sensitivity Index (ASI) and the Symptom Questionnaire (SQ) prior to starting the 26-week continuation phase. We defined 'EDs' as patients who dropped out either at or prior to Visit 2 (which was at 2 months into the 6-month continuation phase); those dropping out at Visit 3 or later were defined as 'LDs' (ED < or = 2 months and LD > 2 months). The Kruskal-Wallis and the Mann-Whitney U tests were used for data analysis. RESULTS: Of the 119 outpatients, 83 were completers (mean age: 42.1 +/- 9.0 years, 46 [55%] women, age of onset of major depressive disorder [MDD] = 24.3 +/- 12.5 years), 11 were EDs (mean age: 38.1 +/- 13.0 years, 4 [36%] women, age of onset of MDD = 22.0 +/- 11.1 years) and 25 were LDs (mean age: 35.2 +/- 10.4 years, 12 [48%] women, age of onset of MDD = 24.6 +/- 11.6 years). LDs were significantly younger than completers (P<.01). There was no significant difference in age between EDs and LDs, nor between EDs and completers. EDs and completers were depressed for a longer period of time compared to LDs (P<.05). EDs also had significantly greater overall impairment in social adjustment compared to completers (P<.05). CONCLUSIONS: Our data suggest that LDs are significantly younger than completers, although age is not a predictor between EDs and LDs. Further, EDs and completers are depressed for a longer duration than LDs, and EDs have significantly greater social impairment compared to completers. Our study identified some patient characteristics significantly associated with dropping out of a long-term clinical trial.

Adult↗
PubMed1997

Roles of phospholipases A2 in brain cell and tissue injury associated with ischemia and excitotoxicity.

Phospholipase A2 (PLA2) activity is an important contributor to destructive cellular processes in the central nervous system. Two cytosolic forms of calcium dependent PLA2 have been characterized in the gerbil brain and the neuronal cultures from rat brain. PLA2 enzymatic activity in cell free extracts from cortical neuronal cultures is upregulated after cells are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhanced PLA2 activity. Stable activation of the two cytosolic forms of PLA2 occur prior to evidence of cell death and this activation is reversible. The larger molecular mass form was characterized as cPLA2. The smaller form (approximately 14 kDa) was distinct from Group I and II PLA2. Exposure to glutamate shifted the calcium activation curve of the smaller form to the left suggesting a novel mechanism of regulation of PLA2. Glutamate-induced stable enhancement of PLA2 activity, by processes involving calcium and protein kinase C activation, is a potential molecular switch likely mediating changes in synaptic function and contributing to excitotoxicity.

Animals↗