[Motility disorders of the esophagus]. / Motilitätsstörungen des Ösophagus.

Motility disorders of the esophagus comprise a heterogeneous spectrum of diseases. Primary malformations of the esophagus are now amenable to improved surgical and gastroenterological therapies; however, they often lead to persistent long-term esophageal dysmotility. Achalasia originates from impaired relaxation of the gastroesophageal sphincter apparatus. Systemic diseases may give rise to secondary disorders of esophageal motility. A number of visceral neuromuscular disorders show an esophageal manifestation but aganglionosis rarely extends into the esophagus. The growing group of myopathies includes metabolic and mitochondrial disorders with increasing levels of genetic characterization and incipient emergence of therapeutic strategies. Esophagitis with an infectious etiology causes severe dysmotility particularly in immunocompromised patients. Immunologically mediated inflammatory processes involving the esophagus are increasingly better understood. Finally, rare tumors and tumor-like lesions may impair esophageal motor function.

Efforts of the United States' National Marrow Donor Program and Registry to improve utilization and representation of minority donors.

SUMMARY: Haematopoietic stem cell transplantation is often used as a therapy for patients with certain blood, metabolic or immune system disorders. The United States' National Marrow Donor Program (NMDP) works to facilitate such life-saving transplants by coordinating the donor search and match process. However, concern exists that the NMDP Registry is underutilized and under-representative of racial and ethnic minorities. African-Americans and Hispanics are somewhat under-represented within the total number of donors, and it is estimated that the Registry is used by only approximately one-third of patients needing transplants. The NMDP has instituted programmes that address such concerns, resulting in an increase in both the total number of donors and the minority representation on the Registry. It has also increased efforts to recruit donors of umbilical cord blood, often a viable alternative source of haematopoietic stem cells. Over the past 8 years, the Registry has grown by more than 30% to contain over seven million donors, and the proportional distribution of racial and ethnic groups on the Registry has steadily approached their proportional distribution in the US population. Continued efforts on the part of the NMDP to maintain a Registry that is large in number and ethnically diverse should help ensure access to haematopoietic stem cell transplants for all patients who need them. The procedures and experience of the NMDP and its Registry may have implications for registries elsewhere in the world as they confront similar issues of number and diversity.

Infratentorial pediatric brain tumors: the value of new imaging modalities.

The correct assessment of the four most frequent infratentorial brain tumors in children (medulloblastoma, ependymoma, pilocytic astrocytoma and infiltrating glioma) has always been problematic. They are known to often resemble one another on conventional magnetic resonance (MR) imaging. We tested the hypothesis whether the combined strength of diffusion-weighted imaging (DWI) and proton MR spectroscopy (MRS) could help differentiate these tumors. Seventeen children with untreated posterior fossa tumors were investigated between January 2005 and January 2006 with conventional MR imaging and combined DWI and MR spectroscopy using a single-voxel technique at short and long echo time (TE) of 30 ms and 135 ms respectively. Apparent diffusion coefficient (ADC) values were retrieved after regions of interest were manually positioned within non necrotic tumor core. Water signal was quantified and metabolite signals were compared and analyzed using linear discriminant analysis. When a combination of ADC values and normalized metabolites was used, all tumors could be discriminated against one other. This could only be achieved when metabolites were normalized using water as an internal standard. They could not be discriminated when using metabolite ratios or ADC values alone, nor could they be differentiated using creatine (Cr) as an internal reference even in combination with ADC values. In conclusion, linear discriminant analysis and multiparametric combination of DWI and MRS, although not replacing histology, fully discriminates the four most frequent posterior fossa tumors in children, but metabolites have to be normalized using water and not Cr signal as an internal reference.

Cellular transformation by a unique isolate of human papillomavirus type 11.

Infection with human papillomavirus type 11 (HPV 11) is associated with benign epithelial proliferations and rarely with malignant and metastasizing tumors. Because of the biological diversity displayed in tissues infected with HPV 11, we have examined the capacity of various isolates of HPV 11 to transform cultured cells and compared their molecular differences by DNA sequence analysis. Five isolates of HPV 11 were examined for their ability to transform primary neonatal rat kidney epithelial cells and NIH 3T3 mouse fibroblasts in DNA transfection experiments using calcium phosphate precipitation. Included in these studies are the prototype isolate from a laryngeal papilloma (HPV 11P); HPV 11VC from a verrucous carcinoma of the penis; HPV 11Epi from the viral episomes of a primary squamous cell carcinoma; and two integrated genomes (HPV 11Int 1 and HPV 11Int 2) of the metastases. Only HPV 11VC cotransfected with the oncogene Ha-ras transformed neonatal rat kidney epithelial cells with an efficiency comparable to that of HPV 16 DNA. HPV 11VC DNA alone transformed NIH 3T3 cells. Analysis of the DNA sequence of HPV 11P and 11VC revealed 16 single nucleotide changes in the upstream regulatory region and open reading frames E1, E2, E4, and E5, five resulting in amino acid substitutions. This is the first demonstration of cellular transformation by a natural isolate HPV 11 DNA in vitro and illustrates that minimal changes in the DNA sequence of certain viruses confer oncogenicity to what are normally nontransforming viruses.

Genomewide association analysis for average birth interval and stillbirth in swine.

Reproductive efficiency has a great impact on the economic success of pork production. Stillborn pigs and average birth interval contribute to the number of pigs born alive in a litter. To better understand the underlying genetics of these traits, a genomewide association study was undertaken. Samples of DNA were collected and tested using the Illumina Porcine SNP60 BeadChip from 798 females farrowing over a 4-yr period (all first parity). Birth intervals and piglet birth status (stillborn or alive) were determined by videotaping each farrowing event. A total of 41,148 SNP were tested using the Bayes C option of GenSel (version 4.61) and 1-Mb windows. These 1-Mb windows explained proportions of 0.017, 0.002, 0.032, 0.029, and 0.030 of the total variation, respectively, for litter average birth interval after deletion of the last piglet born, last birth interval in the litter, number of stillborn piglets ignoring the last piglet born, number of stillborns in the last birth position, and percent stillborn ignoring the last piglet. Significant 1-Mb nonoverlapping SNP windows were identified by using a conservative approach requiring 1-Mb windows to have a genetic variance ≥1.0% of genomic variance and these were considered to be QTL. Quantitative trait loci were located for number of stillborn piglets ignoring the last piglet born (1 QTL), number of stillborns in the last birth position (1 QTL), and percent stillborn ignoring the last piglet (3 QTL). In addition, 2, 13, 3, and 6 suggestive 1-Mb nonoverlapping SNP windows were identified for litter average birth interval after deletion of the last piglet born, number of stillborn piglets ignoring the last piglet born, number of stillborns in the last birth position, and percent stillborn ignoring the last piglet, respectively. Possible candidate genes affecting both birth interval and stillbirth included () and (). Possible genes affecting only birth interval included (), and (), and those affecting only stillbirth included (), LOC100518697 (a nostrin-like gene), and (). The QTL and the suggestive 1-Mb nonoverlapping SNP windows may lead to genetic markers for marker assisted selection, marker assisted management, or genomic selection applications in commercial pig populations.

Leukocyte-platelet aggregation, platelet surface P-selectin, and platelet surface glycoprotein IIIa after percutaneous coronary intervention: Effects of dalteparin or unfractionated heparin in combination with abciximab.

BACKGROUND: Plaque disruption with resultant platelet activation and leukocyte-platelet aggregation is a pathophysiologic process common to both acute coronary syndromes and percutaneous coronary interventions. Unfractionated heparin is a standard antithrombotic therapy in patients with both acute coronary syndromes and in those undergoing percutaneous coronary interventions. Low-molecular-weight heparins have been reported to cause less platelet activation than unfractionated heparin. METHODS: Monocyte-platelet aggregates, neutrophil-platelet aggregates, platelet surface P-selectin, and platelet surface glycoprotein (GP) IIIa were measured serially by whole blood flow cytometry in 40 patients with unstable angina (randomly assigned to either unfractionated heparin 70 U/kg or the low-molecular-weight heparin dalteparin 60 IU/kg) undergoing coronary intervention with planned abciximab administration (in 2, one-half-dose boluses). Assays were performed at baseline, 5 minutes after administration of either type of heparin, 10 minutes after the first bolus of abciximab, 10 minutes after second bolus of abciximab, and 8 to 10 and 16 to 24 hours after administration of either heparin. RESULTS: No significant differences in clinical outcomes were observed between patients receiving either unfractionated heparin or dalteparin. The number of circulating P-selectin-positive platelets was increased by unfractionated heparin but not dalteparin, and abciximab reversed this increase. The number of circulating P-selectin-positive platelets was reduced below baseline levels in both treatment groups 8 to 10 and 16 to 24 hours after study drug administration. At 8 to 10 and 16 to 24 hours after administration of study drug, platelet degranulation in response to iso-thrombin receptor agonist peptide 1.5 mmol/L was significantly reduced by almost 50% (compared with immediately after study drug administration). Both unfractionated heparin and dalteparin significantly increased the numbers of circulating monocyte-platelet and neutrophil-platelet aggregates, which were subsequently reduced to baseline levels after administration of the second abciximab bolus and to below baseline at both 8 to 10 and 16 to 24 hours in all patients. After both unfractionated heparin and dalteparin administration, platelet surface GP IIIa expression was significantly increased compared with baseline at both 8 to 10 and 16 to 24 hours. CONCLUSIONS: Dalteparin in combination with abciximab in patients with unstable angina undergoing coronary intervention appears to be safe. Unfractionated heparin, but not dalteparin, degranulates platelets in patients with unstable angina. Both heparins increase the number of circulating monocyte-platelet and neutrophil-platelet aggregates. Abciximab therapy during coronary interventions rapidly reduces the number of degranulated platelets and leukocyte-platelet aggregates.

Abciximab provides cost-effective survival advantage in high-volume interventional practice.

BACKGROUND: Placebo-controlled randomized trials of platelet glycoprotein (GP) IIb/IIIa blockade during percutaneous coronary intervention have demonstrated efficacy of these agents for reducing the risk of periprocedural ischemic events. However, cost-effectiveness of this adjunctive pharmacotherapy has been scrutinized. Extrapolation of cost-efficacy observations from clinical trials to "real world" interventional practice is problematic. METHODS: Consecutive percutaneous coronary interventions (n = 1472) performed by Ohio Heart Health Center operators at The Christ Hospital, Cincinnati, Ohio, in 1997 were analyzed for procedural and long-term (6-month) outcomes and charges. Observations on cost and efficacy (survival) were adjusted for nonrandomized abciximab allocation by means of "propensity scoring" methods. RESULTS: Abciximab therapy was associated with a survival advantage to 6 months after percutaneous coronary intervention. The average reduction in mortality rate at 6 months was 3.4% (unadjusted) and 4.9% when adjusted for nonrandomization. The average charge increment to 6 months was $1512 (unadjusted) and $950 when adjusted for nonrandomization. Patients deriving the greatest reduction in mortality rates also had a reduction in total cardiovascular charges to 6 months. Distinguishing demographics of this population included multivessel coronary intervention, coronary stent deployment, intervention within 1 week of myocardial infarction, and lower left ventricular ejection fraction. The average cost per life-year gained in this study was $2875 for all patients (unadjusted) and $1243 when adjusted for nonrandomization. CONCLUSIONS: Abciximab provides a cost-effective survival advantage in high-volume interventional practice that compares favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness included multivessel coronary intervention, stent deployment, recent (<1 week) myocardial infarction, and impaired left ventricular function.

Clinical-electrocardiographic correlates of newly acquired left bundle branch block: the Framingham Study.

To determine whether any associated electrocardiographic findings in persons with newly acquired complete left bundle branch block (LBBB) correlate with the prevalence of associated clinically apparent cardiovascular abnormalities, electrocardiograms (ECGs) from all 55 members of the Framingham Study cohort in whom LBBB developed during 18 years of routine prospective biennial examinations were reviewed. A QRS axis left of or equal to 0 degrees, left atrial conduction delay and an inverted T wave in lead V6 on the first ECG with LBBB, and an abnormal ECG in the Framingham examination preceding the appearance of LBBB each correlated with the prevalence of systemic hypertension, cardiomegaly, coronary heart disease and congestive heart failure. However, neither the PR interval nor the duration of the QRS complex on the first ECG with LBBB correlated with the prevalence of any of the associated cardiovascular abnormalities. The 8 patients with neither left atrial conduction delay nor a QRS axis left of or equal to 0 degrees on the first Framingham ECG with LBBB nor an abnormal ECG on the examination preceding the appearance of LBBB were 6 times more likely to remain free of all of the clinical cardiovascular abnormalities than the 47 patients with 1 or more of these 3 electrocardiographic findings (p less than 0.001).

Comparative features of newly acquired left and right bundle branch block in the general population: the Framingham study.

Cardiovascular abnormalities were prospectively identified in all 55 persons who acquired left bundle branch block and all 70 persons who acquired right bundle branch block during 18 years of follow-up of the Framingham Study cohort. Those with left and right bundle branch block did not differ from each other in the overall prevalence of either hypertension, clinical coronary disease or diabetes. In men, but not in women, left bundle branch block was associated with a significantly greater prevalence of cardiac enlargement and congestive failure than was right bundle branch block. A trend suggesting a higher mortality rate from cardiovascular disease in those with left than in those with right bundle branch block was more apparent in men than in women. It is concluded that in the general adult population, men who acquire left bundle branch block are more likely to have or subsequently acquire advanced cardiovascular abnormalities than are men who acquire right bundle branch block. In women, however, the clinical correlates of the two conduction abnormalities are similar.

The detection of mercury, lead, and methylmercury binding sites on lysozyme by carbon-13 NMR chemical shifts of the carboxylate groups.

The chemical shift changes observed in the carbon-13 NMR spectra of the carboxylate region in conjunction with previous fluorescence data indicate that mercury and lead bind to both disulfide bridge 64-80 and to Asp-52 in hen egg-white lysozyme. Methylmercury appears to bind primarily to the disulfide linkage. The carbon-13 NMR results support previous investigations by halide ion NMR and x-ray crystallography. The combined information from all of these techniques is useful for providing a clearer description of heavy metal binding to proteins.

Age-related changes in porcine corticosteroid-binding globulin (pCBG) as determined by an enzyme-linked immunosorbent assay.

The objectives of this study were to develop an assay for the direct measure of porcine corticosteroid-binding globulin (pCBG) and to confirm age-related changes in plasma pCBG concentration. Isolation and purification of pCBG from plasma was performed by affinity chromatography and HPLC-DEAE anion exchange techniques. Analysis by SDS-PAGE revealed two polypeptides (54 and 59 kDa) having similar amino acid homology (>50%) to previously reported sequences of seven mammalian species for the first 33 amino acids. Porcine CBG (20 ng/well) was immobilized to microtiter plates and standards or samples added along with rabbit antiserum developed against the purified pCBG. Goat anti-rabbit IgG-alkaline phosphatase conjugate was added followed by p-NPP substrate. The resultant color development was read at 405 nm. Intra- and interassay coefficients of variation (n=26) of a pooled sample were 10 and 15%, respectively. Age-related changes (P<0.001) in plasma pCBG concentration (n=203) from day 3 through 168 of age confirmed that, in the pig, changes seen in the percent distribution of cortisol among protein bound and free forms around day 28 of age are associated with an increase in CBG concentration.

Protein-bound and unbound forms of plasma cortisol in piglets after castration at seven or 14 days of age.

Male piglets from seven litters were used to evaluate the long-term effects of castration and age at castration on the concentrations of cortisol and its distribution in peripheral plasma. The piglets were allotted to one of three groups of 12 animals according to whether they had been castrated at seven or 14 days old or left intact. The animals were weighed and blood samples were collected from the anterior vena cava at three, seven, 10, 14, 17, 21, 28, 35 and 42 days of age. The plasma concentrations of albumin, total protein, cortisol, and the percentage distribution of cortisol among corticosteroid binding globulin-bound (CBG-bound), albumin-bound and unbound forms, were determined. Castration at seven or 14 days of age had no effect on any of the parameters measured. In all the piglets, the percentage of unbound cortisol decreased (P < 0.001) from 24.5 to 11.6 per cent over the period of sampling. The percentage of CBG-bound cortisol increased (P < 0.001) from 19 per cent on day 17 to 47 per cent on day 21, and albumin-bound cortisol declined from 61 to 37 per cent over the same period. These results agree with previous findings of age-related changes in the percentage distribution of cortisol in the piglet and demonstrate that these patterns are unaffected by castration.

The effects of n-3 fatty acid supplementation on bleeding time, plasma fatty acid composition, and in vitro platelet aggregation in cats.

Dietary supplementation with fish and fish oils rich in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to alter eicosanoid metabolism and impair platelet function in several species. As an initial step in evaluating the antithrombotic effect of these n-3 fatty acids in cats, purified EPA and DHA were administered daily to 8 clinically normal cats for 2 months. Platelet function was evaluated biweekly by determining mucosal bleeding time and in vitro platelet aggregation parameters. Plasma fatty acid profiles were obtained before fish oil supplementation and at the termination of the study. In spite of significant increases (P < .0001) in the plasma concentrations of EPA and DHA after n-3 fatty acid supplementation, there were no significant changes in platelet aggregation or bleeding times. Although it is tempting, based on extrapolation of data from other species, to recommend dietary supplementation with fish oil for cats prone to arterial thromboembolism, these results indicate that administration of large doses of purified EPA and DHA once daily does not inhibit platelet function in normal cats and is unlikely to prevent thrombosis in cats with cardiovascular disease. Additional studies are recommended to ascertain whether more frequent administration of these purified n-3 fatty acids or continual feeding of diets high in n-3 fatty acid content will impair platelet function.

The effects of split marketing on the physiology, behavior, and performance of finishing swine.

One hundred twenty 8-wk-old barrows (20.3 +/- 2.0 kg BW) were used to examine the effect of split marketing on selected behavioral, physiological and performance parameters. Pigs were assigned by weight in a randomized complete block design to one of three treatments: SM (split-marketed), six pigs/pen (1.83 m2/pig); C (control), six pigs/pen (1.83 m2/pig); or MC (modified control), three pigs/pen (3.66 m2/pig). The heaviest half of SM animals were removed 1 wk prior to marketing penmates. Control and MC animals remained in their respective groups until marketing. Animals were videotaped during the first 72 h of the study (INITIAL), 72 h prior to (PRE), and following the removal (POST) of pigs in the SM treatment to quantify maintenance behaviors and to identify socially dominant, intermediate, and submissive pigs. A blood sample was collected from each animal upon completion of INITIAL, PRE, and POST time periods to determine neutrophil:lymphocyte ratio and plasma haptoglobin, cortisol, and corticosteroid-binding globulin (CBG) levels. Animals were weighed and feed disappearance was calculated biweekly. Tenth-rib backfat and area of the longissimus muscle at marketing were ultrasonically evaluated on all animals. Regardless of treatment, animals were more (P < 0.01) active (eating, standing/walking, fighting) at INITIAL than at PRE or POST times. Frequency and duration of fights per pen were less (P < 0.01) in MC than in C or SM pigs for all periods observed. Neutrophil:lymphocyte ratio, plasma haptoglobin, and CBG levels were greater (P < 0.01) during the INITIAL period than during the PRE or POST periods but did not differ between treatments. No treatment or time differences were detected in plasma cortisol levels. The MC pigs exhibited greater (P < 0.01) ADFI with poorer feed efficiency compared to C or SM pigs up to split marketing. During the POST period, both MC and SM pigs had greater (P < 0.01) ADFI with poorer (P < 0.01) feed efficiency than C pigs. The ADG was not different among animals as a result of treatment. There were no treatment differences for any of the carcass measurements. Significant differences in performance between the treatment groups could not be attributed to any physiological or behavioral measures reported here.

Aggregate risk study of exposure to endophyte-infected (Acremonium coenophialum) tall fescue as a risk factor for laminitis in horses.

Loline and ergot alkaloids found in endophyte-infected (Acremonium coenophialum) tall fescue (EITF) cause vasoconstriction of equine vessels in vitro. An aggregate risk study was used to evaluate the association between horses exposed to EITF and development of laminitis. Veterinary teaching hospitals participating in the Veterinary Medical Data Base were grouped by whether equine accessions were likely to have been at high, moderate, or low risk for exposure to EITF. From 1980-1990, there were 185,781 accessions, of which 5,536 had diagnosis of laminitis. Proportion of equine accessions with laminitis reported by veterinary teaching hospitals for high, moderate, and low risks, were 3.41, 3.04, and 2.00 cases/100 accessions, respectively (P < 0.0001). Comparison of the proportion of accessions with laminitis in the high- and moderate-risk groups with that in the low-risk group revealed significant differences between risk groups over all months (P = 0.063) and differences from month to month within risk groups (P = 0.0001). If the difference among risk groups is attributed entirely to exposure to EITF, the population-attributable risk is 7 cases/1,000 admissions, or 15% of all admissions for laminitis at veterinary teaching hospitals in our data base. Preliminary data support an association between horses exposed to EITF and increased risk of laminitis; however, studies at the individual animal level are indicated to confirm this hypothesis.

Screening for sarin in air and water by solid-phase microextraction-gas chromatography-mass spectrometry.

A method of screening air and water samples for the chemical-warfare agent Sarin is developed using solid-phase microextraction (SPME)-gas chromatography (GC)-mass spectrometry (MS). The SPME field kit sampler is ideal for collecting air and water samples in the field and transporting samples safely to the laboratory. The sampler also allows the sample to be introduced into the GC-MS system without further sample preparation. Results of the tests with Sarin using the SPME technique indicate that a sample collection time of 5 min is sufficient to detect 100 ng/L of Sarin in air. For water samples, Sarin is detected at a concentration of 12 microg/mL or higher. This method is ideal for screening samples for quick response situations.

Leuprolide acetate treatment of adrenocortical disease in ferrets.

OBJECTIVE: To determine the effects of leuprolide acetate, a long-acting gonadotropin-releasing hormone analog, in ferrets with adrenocortical diseases. DESIGN: Case series. ANIMALS: 20 ferrets with adrenocortical disease diagnosed on the basis of clinical signs and plasma sex hormone concentrations. PROCEDURE: Ferrets were treated with leuprolide (100 microg, IM, once), and plasma hormone concentrations were measured before and 3 to 6 weeks after treatment. RESULTS: Leuprolide treatment resulted in significant reductions in plasma estradiol, 17 alpha-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone concentrations and eliminated or reduced clinical signs associated with adrenocortical disease. Decreases in vulvar swelling, pruritus, and undesirable sexual behaviors and aggression were evident 14 days after treatment; hair regrowth was evident by 4 weeks after treatment. The response to treatment was transitory, and clinical signs recurred in all ferrets. Mean +/- SEM time to recurrence was 3.7 +/- 0.4 months (range, 1.5 to 8 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that leuprolide can be safely used to temporarily eliminate clinical signs and reduce sex hormone concentrations in ferrets with adrenocortical diseases. However, the safety of long-term leuprolide use in ferrets has not been investigated, and the long-term effects of leuprolide in ferrets with nodular adrenal gland hyperplasia or adrenal gland tumors are unknown.

Authoritarian attitudes and aesthetic preferences: a Bulgarian replication.

This report describes a Bulgarian replication with 173 students of a German study concerning the effect of stimulus properties of complexity and order and authoritarian attitudes on the perceived pleasantness of polygons. Analyses of variance yielded neither significant main effects nor significant interactions for the different measures of authoritarianisms, but there were significant main effects for order and complexity.

[Care of patients with psychiatric disorders]. / A enfermagem na assistência ao indivíduo em sofrimento psíquico.

Nursing care to the human being in psychical suffering is the theme of this investigation, developed in a psychiatric hospital, in the west region of the Paraná State. This is a qualitative research with the aim of finding out nurses' understanding about their work in psychiatric nursing. Authors used open interview to all the nurses of the institution. Then, data were grouped in thematic unities and analysed through the analysis of the content.

[Analysis of teaching practices of university professors in the health field]. / Uma análise das práticas docentes de professores universitários da área de saúde.

The study aims to describe teaching practices--in planning, execution and evaluation of the teaching-learning process--used by faculty of some courses in the health field in Brazil: Odontology, Medicine, Nursing, Pharmacy, Psychology, Nutrition, Social Work and Veterinary Medicine. The sample was made up by 29 faculties enrolled in a didactic subject course at graduate programs. They answered a questionnaire with semi-open questions. The answers obtained point to a "banking" education practice, according to Paulo Freire. This kind of education is characterized by: 1) emphasis on the transmission of information; 2) many hours of education; 3) little integration between courses and 4) lecture classes.