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M Kuskowski

Publications and source records attributed to M Kuskowski.

At least 19 recordsLinked to original sources
PubMed2006

Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats.

Selectively-bred obesity-resistant [diet resistant (DR)] rats weigh less than obesity-prone [diet-induced obese (DIO)] rats, despite comparable daily caloric intake, suggesting phenotypic energy expenditure differences. Human data suggest that obesity is maintained by reduced ambulatory or spontaneous physical activity (SPA). The neuropeptide orexin A robustly stimulates SPA. We hypothesized that DR rats have greater: 1) basal SPA, 2) orexin A-induced SPA, and 3) preproorexin, orexin 1 and 2 receptor (OX1R and OX2R) mRNA, compared with DIO rats. A group of age-matched out-bred Sprague-Dawley rats were used as additional controls for the behavioral studies. DIO, DR, and Sprague-Dawley rats with dorsal-rostral lateral hypothalamic (rLHa) cannulas were injected with orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol/0.5 microl). SPA and food intake were measured for 2 h after injection. Preproorexin, OX1R and OX2R mRNA in the rLHa, and whole hypothalamus were measured by real-time RT-PCR. Orexin A significantly stimulated feeding in all rats. Orexin A-induced SPA was significantly greater in DR and Sprague-Dawley rats than in DIO rats. Two-mo-old DR rats had significantly greater rLHa OX1R and OX2R mRNA than DIO rats but comparable preproorexin levels. Eight-mo-old DR rats had elevated OX1R and OX2R mRNA compared with DIO rats, although this increase was significant for OX2R only at this age. Thus DR rats show elevated basal and orexin A-induced SPA associated with increased OX1R and OX2R gene expression, suggesting that differences in orexin A signaling through OX1R and OX2R may mediate DIO and DR phenotypes.

Age Factors↗
PubMed2005

Tau suppression in a neurodegenerative mouse model improves memory function.

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.

Aging↗
PubMed2001

Clonal relationships and extended virulence genotypes among Escherichia coli isolates from women with a first or recurrent episode of cystitis.

To identify bacterial predictors of recurrence and/or persistence in acute cystitis, extended virulence genotypes were compared with clonal background and epidemiologic status among 74 Escherichia coli urine isolates from women with first or recurrent episodes of urinary tract infection (UTI). Sequential isolates from patients with recurrent UTI were classified, using macrorestriction analysis, as having caused an isolated recurrence versus a single or multiple same-strain recurrences. papA, papG allele II, iha, and iutA predicted multiple same-strain recurrences, whereas nfaE and the absence of sfaS or fyuA predicted isolated recurrences. Phylogenetic group B2 accounted for 70% of isolates and for most of the putative virulence factors (VFs) studied. The meningitis-associated O18:K1:H7 clonal group comprised 18% of isolates, exhibited multiple VFs, and caused "once-only" recurrences less commonly than did other strains. These findings identify specific VFs and clonal groups against which preventive interventions might be beneficial and illustrate the importance of delineating pathogenetically relevant subgroups within the "recurrent cystitis" population.

Acute Disease↗
PubMed2001

Phylogenetic and pathotypic similarities between Escherichia coli isolates from urinary tract infections in dogs and extraintestinal infections in humans.

Seventeen Escherichia coli isolates from dogs with urinary tract infection (UTI) were characterized with respect to phylogenetic background and virulence genotype and were compared with the E. coli reference (ECOR) collection and with human clinical isolates with similar serotypes from patients with diverse extraintestinal infections. Most of the canine urine isolates were from (virulence-associated) E. coli phylogenetic groups B2 or D, expressed papG allele III, and exhibited numerous other putative virulence genes that are characteristic of human extraintestinal pathogenic E. coli (ExPEC). Close phylogenetic and pathotypic correspondence was documented within 5 clonal groups among individual canine and human isolates, including archetypal human ExPEC strains CFT073 (O6:K2:H1), 536 (O6:K15:H31), and J96 (O4:K-:H5). These findings suggest that canine UTI isolates, rather than being dog-specific pathogens, as previously suspected, may pose an infectious threat to humans. Commonality between canine and human ExPEC has potentially important implications for disease prevention, antibiotic resistance avoidance, and studies of pathogenesis.

Animals↗
PubMed2001

Ongoing horizontal and vertical transmission of virulence genes and papA alleles among Escherichia coli blood isolates from patients with diverse-source bacteremia.

The phylogenetic distributions of multiple putative virulence factors (VFs) and papA (P fimbrial structural subunit) alleles among 182 Escherichia coli blood isolates from patients with diverse-source bacteremia were defined. Phylogenetic correspondence among these strains, the E. coli Reference (ECOR) collection, and other collections of extraintestinal pathogenic E. coli (ExPEC) was assessed. Although among the 182 bacteremia isolates phylogenetic group B2 predominated, exhibited the greatest concentration of individual VFs, and contained the largest number of familiar virulent clones, other phylogenetic groups exhibited greater concentrations of certain VFs than did group B2 and included several additional virulent clones. Certain of the newly detected VF genes, e.g., fyuA (yersiniabactin; 76%) and focG (F1C fimbriae; 25%), were as prevalent or more prevalent than their more familiar traditional counterparts, e.g., iut (aerobactin; 57%) and sfaS (S fimbriae; 14%), thus possibly offering additional useful targets for preventive interventions. Considerable diversity of VF profiles was observed at every level within the phylogenetic tree, including even within individual lineages. This suggested that many different pathways can lead to extraintestinal virulence in E. coli and that the evolution of ExPEC, which involves extensive horizontal transmission of VFs and continuous remodeling of pathogenicity-associated islands, is a highly active, ongoing process.

Adult↗
PubMed2000

Phylogenetic distribution of extraintestinal virulence-associated traits in Escherichia coli.

The 72 member strains of the Escherichia coli Reference collection were assessed as to genotype for 31 putative extraintestinal virulence factor (VF) genes and DNA sequence for papA, the P fimbrial structural subunit gene. Although most VFs were concentrated in phylogenetic group B2 or jointly in groups B2 and D, others were concentrated primarily in group D, were broadly distributed (without group-specific associations), and/or occurred only outside of group B2. Statistical correlations among VFs suggested linkage on pathogenicity-associated islands or plasmids. Isolates from humans and nonhuman primates had more VFs than did isolates from other animals. Sequence diversity was minimal within each F type-specific papA allele group but was substantial among different papA allele groups. The distribution patterns of papA variants and other VFs suggested multiple horizontal transfer events. These findings provide new insights into the phylogenetic origins of extraintestinal VFs in E. coli.

Animals↗
PubMed2000

Utility of positron emission tomography in predicting improved left ventricular ejection fraction after coronary artery bypass grafting among patients with ischemic cardiomyopathy.

The objective of this study was to determine whether preoperative estimates of regional myocardial uptake of (18)-F-fluorodeoxyglucose (FDG) could predict postoperative improvement in ejection fraction in patients undergoing coronary artery bypass grafting (CABG) for ischemic cardiomyopathy. 20 consecutive patients [left ventricular ejection fraction (LVEF) </=27%] were referred for preoperative positron emission tomography (PET) to measure regional myocardial FDG uptake and were deemed candidates for CABG. All individuals had technically adequate vessels and significant viability. The left anterior descending (LAD) coronary artery was severely diseased in all patients. Because of the importance of the anterior wall to overall ventricular performance, FDG uptake was semiquantitated in those regions and related to postoperative LVEF. 17 patients underwent CABG with an uneventful recovery. LVEF increased from 22 +/- 4 to 26 +/- 7% 2 weeks postsurgery (p < 0.05), with >/=5% change noted in 7 patients (group 1) and <5% noted in 10 patients (group 2). No preoperative or perioperative clinical variable could predict those with improved ventricular function. The relative amount of FDG uptake in the anterior wall was higher in group 1 compared with group 2 (93 +/- 9 vs. 81 +/- 13%; p < 0.05) and correlated with the change in LVEF post-CABG (r = 0.50; p < 0.05). >88% of FDG uptake in the LAD region had a positive predictive accuracy of 67% and negative predictive accuracy of 88% for improved LVEF postbypass. Late follow-up estimates of LVEF (median of 10 months) showed that early changes in function were sustained. In summary, among patients with severe coronary artery disease and depressed LVEF, ventricular function may improve early postrevascularization. PET estimates of relative FDG uptake in the anterior wall help predict those individuals who are likely to have the greatest increment in LVEF.

Aged↗
PubMed2000

Withdrawal of chronic systemic corticosteroids in patients with COPD: a randomized trial.

The benefits of chronic systemic corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are not well established. To determine whether chronic corticosteroid treatment can be safely withdrawn in "steroid-dependent""COPD patients, we performed a double-blind, placebo-controlled study of 38 patients with steroid-dependent COPD. Patients were randomly assigned to receive their usual maintenance prednisone dose for 6 mo (continuous group) or to be withdrawn from prednisone at a rate of 5 mg per week (demand group). The number of COPD exacerbations per patient (primary outcome) was 2.5 +/- 2.7 (mean +/- SD) in the continuous group and 2.7 +/- 2.5 in the demand group (p = 0.60, 95% confidence interval for the difference: -1.1 to 1.7). Spirometric results, dyspnea, and health-related quality of life did not differ significantly in the two groups. The average daily corticosteroid dose was 10.7 +/- 5.2 mg in the continuous group and 6.3 +/- 6.4 mg in the demand group (p = 0.003). Weight decreased in the demand group by 4.8 +/- 2.0 kg, compared with an increase in the continuous group of 0.5 +/- 3.5 kg (p = 0.007). Discontinuation of chronic systemic corticosteroid treatment in steroid-dependent COPD patients did not cause a significant increase in COPD exacerbations, but did reduce total systemic corticosteroid use and body weight. Larger studies may be warranted to establish the relative risks and benefits of chronic corticosteroid treatment of patients with COPD.

Aged↗
PubMed1998

Polysomnographic sleep is not clinically impaired in Vietnam combat veterans with chronic posttraumatic stress disorder.

BACKGROUND: Because sleep is typically disturbed in posttraumatic stress disorder (PTSD), this study was undertaken to evaluate a group of Vietnam combat veterans with the disorder using clinical polysomnographic techniques. METHODS: Eighteen Vietnam combat veterans with PTSD and 10 healthy non-combat-exposed Vietnam era veterans participated in 2 nights of polysomnographic study and a multiple sleep latency test. RESULTS: No significant differences between subjects and controls were noted except for greater sleep onset latency to stage 2 (p < .03), and lower arousals/hour from stages 3 & 4 (p < .04) on night 2, and lower subjectively estimated total sleep time on night 1 (p < .005) in the case of PTSD subjects. Otherwise, results from the second night served to replicate those from the first, and no significant differences appeared on 2 successive nights for any polysomnographic variable. No daytime hypersomnolence was detected. CONCLUSIONS: Polysomnographically recorded sleep was notably better than expected in the presence of clinically significant PTSD with typical histories of disrupted sleep. In these subjects, there is no clinically significant sleep disorder or typical pattern of sleep disturbance detectable by standard polysomnography.

Adult↗
PubMed1998

Measuring delirium severity in older general hospital inpatients without dementia. The Delirium Severity Scale.

The authors evaluated the validity, reliability, and sensitivity to change of the Delirium Severity Scale (DSS), a 10-minute assessment consisting of Forward Digit Span and Similarities. Twenty-two older inpatients with delirium but not dementia and 15 control patients were administered the DSS during hospitalization. Scores were significantly inversely correlated with experts' quantitative ratings of severity at all three time-points examined. The DSS showed significant improvement over time (P < 0.001) and significant correlation with improvement in expert ratings (P = 0.026). The DSS shows promise as a valid and reliable measure sensitive to changing symptom severity.

Age Factors↗
PubMed1997

Smoking in nursing homes: conflicts and challenges.

Nursing home social workers were surveyed to determine nursing home smoking policies and the effect these policies may have on resident and staff interaction. Data analyses suggest that in the past five years there has been a trend toward facilities becoming smoke-free. Facilities that permit smoking face greater conflicts between residents and staff. Social workers are expected to be resident advocates as well as mediators in such areas of conflict. This difficult position is further complicated by the social workers' personal views regarding smoking and "guest" standing in medical settings.

Adult↗
PubMed1996

Trends in photoprotection in American fashion magazines, 1983-1993. will fashion make you look old and ugly?

BACKGROUND: During the past 50 years recreational sun exposure has greatly increased in the United States. OBJECTIVE: The purpose of this study was to examine the photoprotecion message of American fashion magazines and to identify recent trends. METHODS: We evaluated models for tan, skin exposure, and other sun-related criteria in six leading fashion magazines between 1983 and 1993. We also recorded the number of sunscreen advertisements and sun awareness articles. RESULTS: We evaluated 3031 models. Adult models had darker tans and greater skin exposure than adolescents and children. Men had darker tans than women. We noted trends toward lighter tans, more women wearing hats, more sunscreen advertisements, and sun awareness articles. Many sunscreen advertisements glorified tanning. Their models had darker tans and more skin exposure, and fewer wore a hat than did nonadvertisement models. CONCLUSION: The fashion industry and especially sunsreen manufacturers promote excessive sun exposure. Although we found encouraging trends, gains were modest, especially in men's magazines.

Adolescent↗
PubMed1996

Delirium and right-hemisphere dysfunction in cognitively impaired older persons.

Cognitive impairment has been repeatedly shown to be a delirium risk factor. Much indirect evidence suggests that right-hemisphere dysfunction plays a particularly important role. This retrospective, case-controlled study, from a 148-patient memory loss clinic database, compared neuropsychological measures of hemispheric function in cognitively impaired elderly veterans with and without a history of delirium. Eleven study subjects had a history compatible with DSM-III-R criteria for delirium. Controls selected from the same database had no known history of delirium and were matched for Mini-Mental State Examination scores and Geriatric Depression Scale scores. Compared to the controls, subjects with a history of delirium had significantly lower scores on Object Assembly and Visual Reproduction (p < .05), tests that are predominantly right-hemisphere dependent. There were no significant differences in left-hemisphere measures. It is concluded that right-hemisphere dysfunction may prove to be an important risk factor for delirium.

Aged↗
PubMed1995

Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study.

OBJECTIVE: To evaluate the relationship between total serum anticholinergic activity (SAA) and the presence or absence of delirium in older hospitalized persons on general medical wards. DESIGN: Case-control study and within-subjects repeated-measures in recovered delirious patients. SETTING: Minneapolis Veterans Affairs Medical Center medical wards. PARTICIPANTS: Eleven male delirious patients (DSM-III-R criteria) aged 60 or older and 11 comparably aged male nondelirious controls. MEASUREMENTS: Radioreceptor bioassay of total SAA using tritiated quinuclidinyl benzilate (QNB) binding to muscarinic receptors. Results are expressed in terms of atropine equivalents (nM). MAIN RESULTS: Mean SAA was significantly elevated in the delirious group (mean +/- SD = 6.05 +/- 2.97 nM atropine equivalents) compared with the controls (3.38 +/- 2.49; t(20) = 2.28, P < .05). At study entry, mean SAA was significantly higher in delirious subjects whose symptoms eventually resolved completely (mean +/- SD = 7.77 +/- 2.37) compared with subjects whose delirious symptoms persisted (3.99 +/- 2.30; t(9) = 2.68, P < .05). All six patients in whom delirium resolved completely had a decrease in serum anticholinergic activity when measured during delirium (7.77 +/- 2.37) and after symptom resolution (3.92 +/- 2.61; t(5) = 3.29, P < .05). CONCLUSIONS: Our findings suggest that serum anticholinergic activity may play a role in delirium in medical inpatients. The relationships between SAA and delirium in medical patients and between total SAA and medication use warrant further study.

Aged↗
PubMed1992

The Symptom Checklist-90: Obsessive-Compulsive Subscale: A reliability and validity study.

Twenty-three nondepressed patients with DSM-III obsessive-compulsive disorder completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Symptom Checklist-90 (SCL-90), and the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-GOCS) once a week for a total of three times during a 2-week medication-free period and 10 times during a 10-week double-blind drug treatment period. The pretreatment test-retest reliabilities were determined for the Y-BOCS, NIMH-GOCS, and the SCL-90-Obsessive-Compulsive Subscale (SCL-90-OCS). Comparisons of the three instruments revealed that the Y-BOCS and the NIMH-GOCS were significantly more reliable than the SCL-90-OCS. Posttreatment correlations were obtained between change scores on the Y-BOCS and NIMH-GOCS and the SCL-90-OCS. Correlations were high and statistically significant for both the Y-BOCS and the NIMH-GOCS, but the correlations of the SCL-90-OCS with the Y-BOCS, NIMH-GOCS, Physician's Global Rating, and the Patient's Global Rating were poor. The findings suggest that the SCL-90-OCS may not be a sensitive instrument in assessing change in obsessive-compulsive symptoms.

Adult↗
PubMed1992

Haloperidol and reduced haloperidol in saliva and blood.

A total of 18 outpatients (17 male, 1 female) ranging in age from 36-66 years old were on a constant dosage of haloperidol in equally divided doses at 9:00 a.m. and 9:00 p.m. for at least 1 month. DSM-III-R diagnoses included schizophrenia (N = 9), schizoaffective disorder (N = 3), bipolar disorder (N = 4), organic mental disorder (N = 1), and delusional disorder (N = 1). Blood samples for steady-state concentrations of plasma and red blood cell haloperidol (H) and reduced haloperidol (RH) were drawn at 9:00 a.m. (12 hr trough). The haloperidol dosage was held at 9:00 a.m. until samples of whole saliva and parotid saliva could be collected for flow rates and concentrations of H and RH. Haloperidol dosages ranged from 1 mg/day to 60 mg/day (mean 11 +/- 15). Correlation coefficients were calculated for saliva concentrations versus blood levels and for saliva secretion rates versus blood levels. The correlations between whole saliva measures and blood concentrations were all higher than the correlations between parotid saliva measures and blood concentrations. In one case the higher correlation reached statistical significance. There was only one case in which substitution of saliva secretion rate improved the correlation between measures with saliva concentration. Our findings suggest that saliva measures of H and RH are useful alternatives to plasma concentrations in monitoring maintenance haloperidol treatment.

Adult↗
PubMed1991

Seasonal distribution of births in Alzheimer's disease.

We obtained season-of-birth data in 727 autopsy-confirmed cases of Alzheimer's Disease (AD) and compared these data with expected general population birth rates. There were no significant differences between quarterly birth rates in the AD group and expected quarterly birth rates. Edward's test for cyclical trends did not establish a peak period of birth in the AD sample. No significant differences between observed and expected quarterly birth rates were found when data were analyzed with regard to either family history of dementia or to gender. Edward's test for peak quarter was significant for AD females, however, with the peak period occurring early in the first quarter. These negative findings between observed and expected quarterly birth rates, based on the large number of autopsy-confirmed AD cases in this study, suggest that a season-of-birth effect in AD is highly unlikely.

Aged↗