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PubMed2005

Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix.

Maspin is a serine protease inhibitor with tumor suppression activity. It is expressed in normal breast and prostate tissue but is downregulated or absent in breast and prostate tumors. Recent reports have shown that decreased expression is associated with a greater propensity for metastasis in oral squamous cell carcinomas. We know that some high-grade cervical intraepithelial neoplasia progress to invasive carcinomas while others either persist at the same degree of atypia or regress. The pattern of maspin expression in cervical intraepithelial neoplasia-grade 3, microinvasive squamous carcinomas and overtly invasive squamous cell carcinomas of the uterine cervix was studied to determine the relationship between the extent of maspin expression and the progression of cervical intraepithelial neoplasia to squamous cell carcinoma. In total, 36 cases were evaluated: 18 cases of cervical intraepithelial neoplasia-grade 3, seven cases of microinvasive squamous cell carcinoma and 11 cases of invasive squamous cell carcinoma. A monoclonal antibody was used on paraffin-embedded tissues. Immunoreactivity was scored semiquantitatively using a scale of 0-3. The sums of the scores of the different groups were compared using the Mann-Whitney U-test. A significant decrease in maspin scores was noted between cervical intraepithelial neoplasia-grade 3 vs invasive squamous cell carcinoma (P<0.005), microinvasive squamous cell carcinoma vs invasive squamous cell carcinoma (P<0.05), and cervical intraepithelial neoplasia-grade 3 vs tumor emboli (P<0.005). Although not statistically significant, scores of cervical intraepithelial neoplasia-grade 3 associated with invasive squamous cell carcinoma were lower compared to that cervical intraepithelial neoplasia-grade 3 without invasive squamous cell carcinoma. These findings suggest that maspin likely plays a role in disease progression from in situ to invasive carcinoma. Virtual absence of maspin immunopositivity in tumor emboli indicates that maspin may also play a role in metastasis.

Carcinoma, Squamous Cell↗

PubMed2003

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients.

Originally identified as a B-cell marker, expression of the cell surface molecule CD24 has meanwhile been observed in a variety of human malignancies. It appears to function as a ligand of P-Selectin, an adhesion molecule that is present in activated platelets and endothelial cells. We aimed to determine the rate of CD24 expression in our nonsmall cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters including patients' survival. A total of 89 NSCLC were analysed immunohistochemically using a monoclonal CD24 antibody (clone 24C02) and a standard detection system (LSAB, DAKO) on NSCLC tissue microarrays (TMA). The staining was semiquantitatively scored (0, 1+, 2+, 3+) and grouped into high (2+, 3+)- and low (0, 1+)-level expression for statistical analysis. A high level of CD24 expression was observed in 45% of the cases, preferentially adenocarcinomas. Patients whose tumours had a high CD24 expression showed a significantly shorter median survival time of 23 months vs 38 months (P=0.033, log-rank test). Similarly tumour, grading, nodal status and clinical stage were significant prognostic markers in univariate survival analysis. Importantly, in the Cox regression-based multivariate analysis, CD24 expression (P=0.025) together with tumour stage (P=0.006) and grade (P=0.011) proved to be independent prognostic parameters. We hypothesise that the decreased survival of NSCLC patients with strongly CD24-positive tumours is related to an enhanced propensity of haematogenous metastasis formation, which might be P-Selectin mediated.

Adult↗

PubMed2000

Comparative pathogenicity of different Actinobacillus suis O/K serotypes.

The pathogenicity of Actinobacillus suis serotypes O1/K1 (strain SO4), O1/K2 (strain C84), and O2/K2 (strain H91-0380) was evaluated in specific-pathogen-free (SPF) piglets challenged by intraperitoneal inoculation with approximately 1 x 10(7) colony-forming units per mL. All 3 strains produced peritonitis, but differences were observed in the composite histopathologic scores (P = 0.001) and in their ability to spread (P = 0.008) at 7 h post challenge. The O2/K2 strain caused the most severe peritonitis and disseminated most widely to other tissues. Moderate lesions were seen with the O1/K2 strain while the O1/K1 strain caused mild lesions and remained largely localized to the peritoneum. In an attempt to explain the basis of observed differences, the serum sensitivity of 9 A. suis strains with different O and K types was assessed. Regardless of the O/K type, all of the isolates tested were serum resistant. Moreover, most A. suis isolates grew as well or better in complement-replete sera as they did in complement-depleted sera. These observations indicate that although 02 and K2 strains had a greater propensity to cause a disseminating septic inflammatory response in pigs, they were no more resistant to complement-mediated killing than O1 strains.

Actinobacillus↗

PubMed1995

Airborne irritant contact dermatitis from metal dust adhering to semisynthetic working suits.

2 workers at an aircraft factory were employed in a plasma sparying unit. Soon after they were equipped with new semisynthetic working suits, they started to complain of pruritic eruptions after heavy exposure to metal dust. They noted that the dust was not as easily blown off the clothes by pressurized air as previously. Clinical findings consisted of discrete macular and papular lesions, partly follicular, on the ventral and medial thighs. Atopy score, IgE level and a standard series of prick tests ruled out atopic disposition. Patch tests revealed no reactions. A diagnosis of occupational airborne irritant contact dermatitis from metal dust was therefore made. To elucidate the role of the working suit, extensive physical investigations of the physical properties of the textile were performed. Microscopic pictures at low magnification showed more dust particles on the semisynthetic working suit, compared to the former pure cotton suit. This impression could not be confirmed by particle count because of too uneven particle distribution at higher magnification. Hairiness of the 2 textiles was low and ruled out irritation by the semisynthetic textile itself. No difference in electrostatic properties between the 2 working suits could be established either. Both textiles showed high static electrical propensity. When use of the semisynthetic overall was discontinued, the patients reported no recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational↗

PubMed1994

Induction of silent myocardial ischemia with mental stress testing: relation to the triggers of ischemia during daily life activities and to ischemic functional severity.

OBJECTIVES: This study examined the relations among the triggers of ischemia during the activities of daily life, mental stress-induced ischemia in the laboratory and functional severity of ischemia on exercise testing. BACKGROUND: Myocardial ischemia is readily induced with exercise testing, but most episodes of ischemia in daily life occur during relatively sedentary activities. Although mental and emotional arousal are known to trigger myocardial ischemia, mental stress testing induces ischemia in only approximately 50% of patients with active coronary disease. It is not known whether such patients are particularly susceptible to nonexertional ischemia during daily activity. METHODS: We studied 45 men (mean age +/- SD 58 +/- 9 years) with coronary artery disease by means of 48-h Holter ambulatory electrocardiography for ST segment analysis and quantification of physical and mental activity with a structured diary system. These data were cross-tabulated with new left ventricular dyssynchrony (detected on two-dimensional echocardiography) induced by two mental stressors and by bicycle exercise. RESULTS: During mental stress testing, 24 patients (53%) (Group I) had a new wall motion abnormality; the other 21 patients (Group II) did not. The average wall motion dyssynchrony score increased from 1.20 +/- 0.29 to 1.34 +/- 0.36 (p = 0.001), but the increase was less than that with exercise stress (1.52 +/- 0.41, p = 0.001). The total duration of ischemia during sedentary activities was greater in Group I (22.9 +/- 24.5 min) than in Group II (3.6 +/- 3.9 min, p = 0.025). Group I had more ischemic events while sedentary (23 of 290 diary entries) than did Group II (8 of 256 diary entries, p = 0.015). The magnitude of dyssynchrony with mental stress and the number of mental stressors capable of triggering ischemia were related to severity of ischemia with exercise. CONCLUSIONS: Patients with ischemia during mental stress testing also have increased ischemia during sedentary activities in daily life. This finding may reflect greater functional severity of coronary artery disease or a propensity toward coronary vasoconstriction while sedentary.

Activities of Daily Living↗

PubMed2026

EscaPRRS-ORF5: a structure-aware evolutionary framework for prioritizing immune escape-prone variants in porcine reproductive and respiratory syndrome virus.

MOTIVATION: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a rapidly evolving RNA virus causing significant economic losses, posing a formidable challenge to vaccine efficacy due to its high mutational variability and immune escape. As the viral mutants evolve, their ability to sustain in population is driven by a range of host biology factors such as receptor binding, fusion, and uncoating. Existing tools that predict viral fitness and escape propensities rely heavily on extensive, up-to-date sequence data and lack integration of biochemical host interactions, limiting mechanistic understanding of the mutational landscape. We introduce Esca, a sequence-only toolchain framework that identifies immune escape-prone residues by exhaustively scanning each residue position for all amino acid substitutions using a Bayesian Variational Autoencoder (VAE) trained on protein language model embeddings. We demonstrate Esca on the GP5(ORF5) glycoprotein of PRRSV (EscaPRRS-ORF5) by training on ESM-2 embeddings of 32 146 GP5 sequences (2015-2022) spanning 140 sub-lineages. RESULTS: Despite being trained only on GP5 sequence data, EscaPRRS-ORF5 recovered 85.7% of the surface-exposed receptor binding interfaces as escape-prone regions. We use a mutation-sensitive fitness scoring scheme that goes beyond Hamming distances, to predict antibody escape tendencies, supporting surveillance of (re) emerging PRRSV variants. We do not claim that ORF5 alone captures PRRSV evolution or serves as a surveillance endpoint; rather, Esca offers a scalable path toward whole-genome, structure-aware surveillance. AVAILABILITY AND IMPLEMENTATION: EscaPRRS-ORF5 is freely available at https://doi.org/10.6084/m9.figshare.32661033 with an interactive Colab notebook at https://colab.research.google.com/drive/1TEgzAhPwvNAZ01VXeJbIFibfri2jnDA5? usp=sharing.

Porcine respiratory and reproductive syndrome viru↗

PubMed2006

Racial differences in attitudes toward innovative medical technology.

BACKGROUND: New medical technologies are used at different rates among whites and blacks. This variation may be partially explained by racial differences in patient innovativeness-the propensity of patients to adopt unfamiliar therapies. OBJECTIVE: To measure how innovativeness varies among patients and how it may influence patients' attitudes toward new medical technologies. DESIGN: Cross-sectional survey. PARTICIPANTS: Primary care patients (n=171-108 blacks, 63 whites) at an urban Veterans Affairs medical center. MEASUREMENTS: Respondents answered questions about their general innovativeness and innovativeness regarding medical technology, and they responded to a vignette describing either a hypothetical new prescription drug or implantable device. RESULTS: There were no significant racial differences in general innovativeness, but whites had higher medical technology innovativeness (P=.001). Whites were also more likely to accept the new prescription drug (P=.003), but did not differ from blacks in acceptance of the new implantable device. In multivariate analyses, lower medical technology innovativeness scores among blacks were significantly associated with less favorable reactions to both the prescription drug (P<.001) and the medical device (P<.001). In contrast, although whites with lower medical technology innovativeness were similarly less inclined to accept the new implantable device (P=.02), there was no significant association between medical technology innovativeness and positive attitudes to the new prescription drug among whites. CONCLUSIONS: Blacks and whites have differing attitudes toward medical innovation. These differences are associated with significant racial differences in response to particular health care technologies. These findings suggest potentially remediable causes for racial differences in the utilization of innovative medical technologies.

Attitude to Health↗

PubMed2001

Adolescents at risk for mistreating their children. Part I: Prenatal identification.

OBJECTIVE: To determine if the Family Stress Checklist helps prenatal care providers identify adolescents who are at risk for mistreating their children. METHODS: We studied 262 participants in a comprehensive, adolescent-oriented maternity program. During the prenatal period, the Family Stress Checklist was used to quantify abuse potential, with scores >25 defining high risk. Information about the social context of the pregnancy and the pattern of health care utilization was obtained with a self-administered questionnaire, and by reviewing the medical records. Major disruption of primary care giving by the adolescent mother was classified hierarchically as abuse, neglect, and abandonment. RESULTS: Family Stress Checklist scores ranged from 0 to 65 (mean + SD = 20.1 + 1.4); 113 (43%) of the 262 teenagers were classified as high risk. High and low risk adolescent mothers made an equivalent number of health maintenance and Emergency Department visits, but the high risk group initiated significantly more acute care visits (6.0 + 4.1 compared to 3.9 + 3.3; p < .0001). After controlling for pre-existing sociodemographic differences, high risk 1-year-olds were 8.41 (95% CI: 1.77-40.01) times and high risk 2-year-olds 5.19 (95% CI: 1.99-13.60) times more likely to have been mistreated than their low risk counterparts. CONCLUSIONS: Prenatal care providers can use the Family Stress Checklist to systematically identify a subgroup of adolescent mother whose excessive use of the acute medical care services and propensity for mistreating their children suggests the need for additional support services.

Adolescent↗

PubMed2001

Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma and its relationship to pathologic and clinical parameters.

Despite the exceedingly poor prognosis of pancreatic cancer, it is often histologically well to moderately differentiated. The apparent resistance to conventional therapeutic modalities is poorly understood and may be related to the molecules involved in its progression or its propensity for perineurial invasion. Cyclooxygenase-2 (COX-2) is an inducible enzyme homologous to COX-1 that is responsible for production of prostaglandins at sites of inflammation. It is activated by a variety of growth factors and tumor promoters, and it has been implicated in cancer progression. It may also have a role in the resistance to therapy. Anti-COX-2 agents have been documented to have antitumor activity, and some are now being tested in the therapy for various cancers, including those of the pancreas. Experience regarding the rate of COX-2 expression in pancreatic cancer and its relationship to the clinical and biologic parameters is very limited. In this study, immunohistochemical stains for COX-2 have been performed on 120 cases of pancreatic ductal adenocarcinoma. The stains were scored according to the percentage (0: no staining, 1: < 10%, 2: 10-50%, and 3: >50% of the cells staining) and intensity (0 for no staining, 1 for mild staining, and 2 for dark staining) of staining. Based on the combined score for each case, they were divided into low expressors (percentage and intensity < or =1) and high expressors (percentage or intensity >1). In addition to global scoring for each case, the glandular and solid (poorly differentiated) components, when present, were scored separately. The global scores were correlated with clinical and biologic parameters. Seventy-four percent of the cases exhibited expression of COX-2 and 53% were high expressors. No significant association was observed when comparing the global COX-2 expression to survival, tumor size, stage, and vascular invasion. Increased perineural invasion was found to be significantly associated with COX-2 expression (p < 0.05). Increased expression was also more common in the glandular component as compared with the solid component of the tumors (68% versus 35%, p < 0.05). Of the 34 patients who received radiotherapy, 9 were low expressor (median survival 19.5 months) and 25 were high expressors (median survival 14 months). The difference in survival was not statistically significant.

Adult↗

PubMed1993

Effects of prolonged wakefulness on cyclic alternating pattern (CAP) during sleep recovery at different circadian phases.

Two separate groups of healthy subjects aged between 20 and 30 years underwent a random sequence of two non-consecutive polysomnographic recordings under standard conditions (night basal sleep) and after continuous sleep deprivation (recovery sleep). In the first group of 6 subjects (3 males and 3 females) recovery sleep occurred in the morning (after 24 h of prior waking); in the second group of 6 subjects (3 males and 3 females) recovery sleep occurred in the night (after 36 h of prior waking). In all cases the recording time was restricted to 500 minutes. Scoring was accomplished on conventional sleep variables and on Cyclic Alternating Pattern (CAP) parameters, while statistical analysis was based on a 2 x 2 ANOVA test. Compared to the night basal conditions, total sleep time and total NREM sleep were significantly longer in night recovery sleep and shorter in morning recovery sleep, respectively. No significant differences were found for sleep latency, intra-sleep awakenings, stage 2, REM sleep, NREM stages and slow-wave sleep. Total CAP time, CAP time in slow-wave sleep and all CAP rates were significantly higher in morning recovery sleep and lower in night recovery sleep. The enhanced amounts of CAP time and CAP rates during morning recovery sleep may be the outcome of two opposite forces, i.e. high sleep pressure versus maximum wake propensity. In contrast, the lower values of CAP during night recovery sleep suggest an in-phase associations between strong sleep pressure and the circadian clock.

Journal Article↗

PubMed2002

A new method to estimate ligand-receptor energetics.

In the discovery of new drugs, lead identification and optimization have assumed critical importance given the number of drug targets generated from genetic, genomics, and proteomic technologies. High-throughput experimental screening assays have been complemented recently by "virtual screening" approaches to identify and filter potential ligands when the characteristics of a target receptor structure of interest are known. Virtual screening mandates a reliable procedure for automatic ranking of structurally distinct ligands in compound library databases. Computing a rank score requires the accurate prediction of binding affinities between these ligands and the target. Many current scoring strategies require information about the target three-dimensional structure. In this study, a new method to estimate the free binding energy between a ligand and receptor is proposed. We extend a central idea previously reported (Bock, J. R., and Gough, D. A. (2001) Predicting protein-protein interactions from primary structure. Bioinformatics 17, 455-460; Bock, J. R., and Gough, D. A. (2002) Whole-proteome interaction mining. Bioinformatics, in press) that uses simple descriptors to represent biomolecules as input examples to train a support vector machine (Smola, A. J., and Schölkopf, B. (1998) A Tutorial on Support Vector Regression, Neuro-COLT Technical Report NC-TR-98-030, Royal Holloway College, University of London, UK) and the application of the trained system to previously unseen pairs, estimating their propensity for interaction. Here we seek to learn the function that maps features of a receptor-ligand pair onto their equilibrium free binding energy. These features do not comprise any direct information about the three-dimensional structures of ligand or target. In cross-validation experiments, it is demonstrated that objective measurements of prediction error rate and rank-ordering statistics are competitive with those of several other investigations, most of which depend on three-dimensional structural data. The size of the sample (n = 2,671) indicates that this approach is robust and may have widespread applicability beyond restricted families of receptor types. It is concluded that newly sequenced proteins, or those for which three-dimensional crystal structures are not easily obtained, can be rapidly analyzed for their binding potential against a library of ligands using this methodology.

Drug Design↗

PubMedDate not supplied

Radiation-induced apoptosis: predictive and therapeutic significance in radiotherapy of prostate cancer (review).

Current therapy for advanced prostate cancer is hampered by the propensity of the disease to progress from an androgen-dependent state to an androgen-independent state. Current treatment for advanced disease is palliative. Therefore, the therapeutic goal for prostate cancer treatment today is to arrest the disease at an early state when it is still localized to the gland. The standard treatment for clinically localized disease is radical prostatectomy or radiation therapy by way of external beam irradiation or local radioactive seed implants (brachytherapy). In advanced disease, the use of radiation therapy is limited to palliation of pain secondary to bone metastases and for spinal cord compression. Tracking residual disease and predicting outcome is limited to following the level of prostate specific antigen (PSA) production, evaluating for bone or solid organ metastasis, and analyzing their preoperative clinical stage, PSA and Gleason's score. Apoptosis as a molecular process of genetically regulated cell death has a critical endpoint that coincides with the goal of successful treatment of human malignancies. Since in cancer treatment the therapeutic goal is to trigger tumor-selective cell death, activation of the apoptotic pathway in prostatic tumor cells offers attractive and potentially effective therapeutic targets. As our understanding of the vital role of apoptosis in the development and growth of the prostate gland has expanded, numerous genes that encode apoptotic regulators have been identified that are severely impaired in prostate tumors. Human prostate cancer cells undergo apoptosis in response to androgen ablation, chemotherapeutic agents and ionizing irradiation. The expression of apoptotic modulators within individual prostate tumors appears to correlate with the cancer cell's sensitivity to traditional therapeutic modalities, including radiotherapy. No strict correlation between radiation-induced apoptosis and longevity of prostate cancer patients has emerged, possibly because the ability to achieve an initial remission alone does not adequately predict long-term outcome and patient survival. In this review we summarize the current understanding of the effects of radiation therapy on prostatic tumor cells within the context of the therapeutic significance of radiation-induced apoptosis in the effective elimination of androgen independent prostate cancer cells. As we enter a new millenium, identification of distinct molecular markers predictive of therapeutic response of prostatic tumors to radiation therapy may afford alternative prognostic indicators in optimizing our treatment protocols for advanced disease.

Apoptosis↗

PubMed1994

Reemergence of apoptotic cells between fractionated doses in irradiated murine tumors.

PURPOSE: The purpose of this investigation was to follow up our previous studies on the development of apoptosis in irradiated murine tumors by testing whether an apoptotic subpopulation of cells reemerges between fractionated exposures. METHODS AND MATERIALS: Mice bearing a murine ovarian carcinoma, OCa-I, were treated in vivo with two fractionation protocols: two doses of 12.5 Gy separated by various times out to 5 days and multiple daily fractions of 2.5 Gy. Animals were killed 4 h after the last dose in each protocol, and the percent apoptosis was scored from stained histological sections made from the irradiated tumors according to the specific features characteristic of this mode of cell death. RESULTS: The 12.5 + 12.5 Gy protocol yielded a net total percent apoptosis of about 45% when the two doses were separated by 5 days (total dose = 25 Gy), whereas the 2.5 Gy per day protocol yielded about 50% net apoptotic cells when given for 5 days (total dose = 12.5 Gy). These values are to be compared to the value of 36% apoptotic cells that is yielded by large single doses (> 25 Gy). Thus, these results indicate that an apoptotic subpopulation of cells reemerged between the fractions in both protocols, but the kinetics appeared to be delayed in the 12.5 + 12.5 Gy vs. the multiple 2.5 Gy protocol. CONCLUSION: This reemergence of cells with the propensity for radiation-induced apoptosis between fractionated exposures is consistent with a role for this mode of cell death in the response of tumors to radiotherapy and may represent the priming of a new subpopulation of tumor cells for apoptosis as part of normal tumor homeostasis to counterbalance cell division.

Animals↗

PubMed2001

Abdominal fat and birth size in healthy prepubertal children.

BACKGROUND: Studies examining the foetal origins hypothesis suggest that small birth size may be a marker of foetal adaptations that programme future propensity to adult disease. We explore the hypothesis that birth size may relate to fat distribution in childhood and that fat distribution may be a link between birth size and adult disease. OBJECTIVE: To investigate the relationship between birth size and abdominal fat, blood pressure, lipids, insulin and insulin:glucose ratio in prepubertal children. DESIGN: Cross-sectional study, based on a birth cohort of consecutive full-term births. SUBJECTS: Two hundred and fifty-five (137 females) healthy, 7- and 8-y-old children. MEASUREMENTS: Body composition and abdominal fat was measured by dual energy X-ray absorptiometry. Lipid, glucose and insulin profiles were measured after an overnight fast and an automated BP monitor was used for blood pressure measurements. RESULTS: There was a negative association between abdominal fat and birth weight s.d. score across a range of normal birth weights (beta=-0.18; 95% CI=-0.31 to -0.04, P=0.009) and a positive association with weight s.d. score at 7/8 y (beta=0.35; 95% CI=0.24 to 0.46, P<0.001). Children who were born with the lowest weight s.d. score and had the greatest weight s.d. score at 7/8 y had significantly more (P<0.001) abdominal fat, as a percentage of total fat (6.53+/-1.3%) than those who had the highest birth weight s.d. score and the lowest weight s.d. score at 7/8 y (4.14+/-0.5%). Similar results were seen if head circumference, but not ponderal index, was used as an indicator of birth size. Increased abdominal fat was associated with higher total cholesterol:HDL cholesterol, higher triglyceride concentration and increased diastolic blood pressure. CONCLUSIONS: Birth weight independently predicted abdominal fat. Children with the highest amount of abdominal fat were those who tended to be born lighter and gained weight centiles. Increased abdominal fat was associated with precursor risk factors for ischaemic heart disease.

Abdomen↗

PubMed1991

Effects on vigilance performance and sleepiness of alcohol given in the early afternoon ('post lunch') vs. early evening.

There is a propensity for sleepiness in the early afternoon ('post-lunch dip'), that contrasts with the circadian peak of alertness in the evening. Alcohol has a soporific effect, and one might expect it to be more potent in the early afternoon than in the evening. This is a little explored area. Four, two or nil (English) units of alcohol (producing maximum blood alcohol concentrations [BACs] of approx. 70, 35 and less than 5 mg alcohol 100/ml blood respectively) were given with food to eight women, at 1300h or 1830h, in a double-blind randomized repeated-measures design. After this consumption, subjects underwent 1 h of vigilance testing. They rated themselves for sleepiness on a half-hourly basis. There were significant main effects for dose and for time of day with: reaction time, hits and sleepiness scores. There was also a significant dose x time of day interaction with: reaction time and hits. That is, two and four units of alcohol produced greater impairment in the afternoon compared with the corresponding evening values. Implications of these findings for driving behaviour are discussed (the maximum legal BAC for car drivers in the UK is 80 mg/100 ml blood).

Alcohol Drinking↗

PubMed2006

Model for predicting and phenotyping at normal weight the long-term propensity for obesity in Sprague-Dawley rats.

Tests were conducted to determine whether weight gain or nutrient intake measures during the first week of exposure to a macronutrient diet can accurately predict an animal's long-term propensity towards obesity. In multiple groups of normal-weight Sprague-Dawley rats (n=35-70/group), daily weight gain during the first 5 days on a high-fat diet (45-60% fat) was found to be strongly, positively correlated (r=+0.71 to r=+0.82) with accumulated body fat in 4 dissected depots after 4-6 weeks on the diet. This measure consistently identified obesity-prone (OP) rats which, relative to the obesity-resistant (OR) rats, were only slightly heavier (+15 g, 4%) and hyperphagic (+9 kcal, 8%) after 5 days but markedly heavier (+70g) with up to 2-fold greater fat mass after several weeks on the diet. Other dietary conditions and measures revealed weaker relationships to ultimate body fat accrual. The OP rats identified by their 5-day weight-gain score exhibited at this early stage clear disturbances characteristic of markedly obese rats. These included elevated leptin, insulin, triglycerides and glucose, along with increased lipoprotein lipase activity (LPL) in adipose tissue and galanin expression in the paraventricular nucleus. Most notable were significant reductions in muscle of LPL activity and ratio of beta-hydroxyacyl-CoA dehydrogenase to citrate synthase activity, indicating a decline in lipid transport and capacity of muscle to metabolize lipids. By occurring early with initial weight gain, these hypothalamic and metabolic disturbances in OP rats, favoring fat storage in adipose tissue over fat oxidation in muscle, may have causal relationships to long-term accumulation of body fat.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2005

Lumbar disc herniation: evaluation of information on the internet.

STUDY DESIGN: An original study was performed evaluating the information presented on existing web sites for the topic of lumbar disc herniation. OBJECTIVES: The purpose of this study was to evaluate the type and quality of internet information available to patients on the topic of lumbar disc herniation. Our secondary objectives were to rank the identified World Wide Web sites with respect to the caliber of relevant information and to determine the propensity for secondary commercial gain by the web site sponsors. SUMMARY OF BACKGROUND DATA: Two-thirds of the United States population "surfs" the internet. A substantial percentage of internet users search for medical information on the World Wide Web. Because no standards exist regarding the publication of medical literature on the internet, the relevant web sites vary dramatically in terms of content and quality. Misleading or inaccurate information poses a theoretical risk to patients seeking treatment for medical conditions. METHODS.: Five search terms (lumbar disc herniation, herniated nucleus pulposus, herniated disc, slipped disc, and sciatica) were entered into 5 commonly used search engines. The first 25 links displayed by each engine were evaluated for a theoretical total of 625 web sites. Each site was evaluated in terms of content, authorship, and secondary commercial gain. An information quality score of 0 to 25 points was generated for each site; a score of 20 or greater was indicative of "high-quality" content. RESULTS: Our search identified 169 unique web sites of which only 16 (9.5%) scored >or=20 on the information quality score; 103 (60.9%) scored <or=10. The overall mean information quality score was 9. Highest mean scores were noted for commercial corporate (13.1) and hospital-based sites (11.2). Overall, 34.3% of sites sought secondary commercial gain. Higher scoring sites were more likely to appear within the first 10 links identified by each search engine. CONCLUSIONS: The quality of internet information on lumbar disc herniation is variable. Less than 10% of relevant web sites were determined to be of high-quality. The vast majority of sites were of poor informational value and more than one-third sought secondary commercialgain. The rank list of high quality sites generated from ourinformational quality score should prove useful to patients seeking information on the internet pertaining to lumbar disc herniation.

Humans↗

PubMed1998

[Cisatracurium in patients with compromised kidney function. Pharmacodynamic and intubation conditions under isoflurane-nitrous oxide anesthesia].

OBJECTIVES: The choice of cisatracurium, especially for patients with organ dysfunction, seems to be beneficial, because of organ-independent Hofmann-elimination and less histamine release propensity. This study was designed to investigate pharmacodynamics and intubating conditions after bolus administration of 0.15 mg/kg cisatracurium (3 x ED95) in patients with renal failure and maintained with isoflurane/N2O in oxygen. METHODS: 20 patients with renal failure and 19 patients with normal renal function were studied. Anaesthesia was induced with fentanyl (2-3 micrograms/kg) and thiophentone (4-7 mg/kg). After rapid bolus administration of 0.15 mg/kg cisatracurium (3 x ED95), onset time and intubating conditions were assessed. Clinical duration (DUR 25%), recovery index and duration 90% were investigated by acceleromyography. Changes of mean arterial blood pressure and/or heart rate > or = 20% were defined as clinically significant. RESULTS: The onset time (3.1 +/- 0.8 min) was shorter in patients without renal failure (Cis-1) than in patients with normal renal function (3.6 +/- 0.8 min), but without statistical significance. Intubating conditions, scored according to a 3-step scale, were slightly better in patients with normal renal function. Other pharmacodynamic parameters did not differ significantly. However, a small tendency to a prolonged recovery with a wide inter-individual variety was characteristic for patients with renal failure. Regarding the hemodynamic actions, only minor individual cardiovascular changes occured. No clinical evidence of histamine release was observed in any patient. CONCLUSIONS: The result of this clinical study suggest, that cisatracurium is a suitable choice for patients with renal failure. The necessity for an intraoperative neuromuscular monitoring is given by the marked heterogeneity in the recovery parameters in patients with renal failure.

Adolescent↗