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[B-mode and color Doppler sonography of kidneys in healthy lambs and lambs with urolithiasis].

The objectives of this study were to determine some morphological characteristics of kidneys and resistive index (RI) changes in renal interlobar artery using B-Mode and color coded doppler sonography in lambs with urolithiasis. The study was performed in 14 male lambs (8 patients, 6 healthy) aged between 2-2.5 months in the same herd. The kidneys had a mean length of 55.6 +/- 1.6 mm, a width of 31.8 +/- 1.2 mm and a parenchymal width of 10.6 +/- 0.6 mm in healthy lambs. These values were 95.4 +/- 3.6., 52.4 +/- 1.3 and 8.75 +/- 0.5 mm, respectively in lambs with urolithiasis. These differences between both groups were significant. Furthermore, the mean resistive index values in lambs with urolithiasis (0.81 +/- 0.017 m/sn) were significantly higher than controls (0.62 +/- 0.013 m/sn). It was concluded that B-Mode and color coded doppler sonography might provide useful information for detection of changes in kidneys of lambs with urolithiasis like hydronephrosis and renal swelling as well as elevated resistance in the renal interlobar artery.

Animals↗

Errors in transfusion medicine. Detection, analysis, frequency, and prevention.

The Mayo Clinic (Rochester, Minn) Division of Transfusion Medicine evaluated the effect of methods of error detection, analysis, and prevention on the rate of errors occurring from 1982 through 1992. We defined an error as any deviation from the standard operating procedure. Twenty-four standard operating procedures were monitored for errors that related to donor processing, testing of donor blood, patient testing, and transfusion. The estimate of the overall error rate and 95% confidence interval fluctuated between 20 and 30 per 10(4) procedures. The transcription error rate declined from 21 to six per 10(4) procedures as a result of changes to systems using computer-generated labels and bar codes. We concluded that when errors are recognized, and appropriate system changes are made, these errors can be prevented.

Blood Transfusion↗

Chloroplast-coded atrazine resistance in Solanum nigrum: psbA loci from susceptible and resistant biotypes are isogenic except for a single codon change.

The 32-kDa photosystem II protein of the chloroplast is thought to be a target molecule for the herbicide atrazine. The psbA gene coding for this protein was cloned from Solanum nigrum atrazine-susceptible ('S') and atrazine-resistant ('R') biotypes. The 'S' and 'R' genes are identical in nucleotide sequence except for an A to G transition, predicting a Ser to Gly change at codon 264. The same predicted amino acid change in psbA was previously shown for an Amaranthus hybridus 'S' and 'R' biotypes which had, in addition, two silent nucleotide changes between the genes (Hirschberg, J. and McIntosh, L., Science 222, 1346-1349, 1983). Occurrence of the identical, non-silent change in psbA in different 'S' and 'R' weed biotype pairs suggests a functional, herbicide-related role for this codon position.

Amino Acid Sequence↗

[Influence of angiotensin-induced change in afterload on hemodynamics in mitral valve insufficiency. A 2-dimensional and color-coded Doppler echocardiography study].

This study assesses the consequences of angiotensin I-induced afterload-stress on mitral regurgitation by two-dimensional and color-coded Doppler echocardiography. During continuous intravenous infusion of angiotensin I in increasing doses of 0.5, 2, and 4 micrograms/min, blood pressure increased significantly from 119 +/- 7/73 +/- 3 mm Hg up to 145 +/- 8/91 +/- 4 mm Hg (+22% resp. +25%; p less than 0.0001 resp. p less than 0.0001). Heart rate did not change significantly (84 +/- 2 min-1 resp. 88 +/- 4 min-1). The enddiastolic volume index, determined by two-dimensional echocardiography, did not change significantly (104 +/- 10 ml/m2 resp. 112 +/- 3 ml/m2), the endsystolic volume index increased from 57 +/- 10 ml/m2 to 75 +/- 13 ml/m2 (+32%; p less than 0.01), the ejection fraction fell from 47 +/- 4% to 36 +/- 4% (p less than 0.001). In the RAO-equivalent view the maximal jet-length, determined by color-coded Doppler echocardiography, increased from 2.6 +/- 0.2 cm to 3.9 +/- 0.3 cm (+50%; p less than 0.001), the maximal jet-area rose from 3.4 +/- 0.6 cm2 to 7.0 +/- 1.0 cm2 (+106%; p less than 0.001); in the parasternal long axis view the maximal jet-length increased from 2.3 +/- 0.2 cm to 3.5 +/- 0.3 cm (+52%; p less than 0.001), the maximal jet-area from 2.6 +/- 0.5 cm2 to 4.9 +/- 0.8 cm2 (+89%; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Variation in the glycoprotein and VP35 genes of Marburg virus strains.

Marburg virus, the prototype of the family Filoviridae, differs genetically, serologically, and morphologically from Ebola viruses. To better define the genetic variation within the species, VP35 and glycoprotein (GP) genes of representative human isolates from four known episodes of Marburg virus hemorrhagic fever were analyzed. The percentage nucleotide differences in the GP gene coding regions of Marburg viruses (0.1-21%) was nearly equal to the percentage amino acid changes (0-23%), while the percentage nucleotide differences in VP35 coding regions (0.3-20.9%) were higher than the percentage amino acid changes (0.9-6.1%), indicating a greater number of nonsynonymous changes occurring in the GP gene. The higher variation in the GP gene and the corresponding protein, especially those changes in the variable middle region of the GP, suggests that the variability may be the result of responses to natural host pressures. Analysis of the GP gene open reading frame shows a nonrandom distribution of nonsynonymous mutations that may indicate positive Darwinian selection is operating within the variable region. A heptad repeat region and an adjoining predicted fusion peptide are found in the C-terminal third of Marburg virus GPs, as has been previously shown for Ebola virus, and are similar to those found in transmembrane glycoproteins of retroviruses, paramyxoviruses, coronaviruses, and influenza viruses. Comparative analyses showed that there are two lineages within the Marburg virus species of filoviruses. The most recent isolate from Kenya (1987) represents a separate genetic lineage within the Marburg virus species (21-23% amino acid difference). However, this lineage likely does not represent a separate Marburg subtype, as the extent of divergence is less than that separating Ebola virus subtypes.

Amino Acid Sequence↗

Analysis of exon and intron mutants in the cytochrome b mitochondrial gene of Saccharomyces cerevisiae.

The nucleotide changes present in a group of five cytochrome b mit- mutants were analyzed at the sequence level. Two single-base changes were found: one (M10-152) generated a nonsense codon in the first exon while the other (M8-181) created a missense substitution in the second exon. The other mutants all have multiple (three) substitutions that either resulted in a missense mutation in a coding region (M17-162) or else changed nucleotides in the last intron of the gene, so blocking its excision (M6-200 and M8-53). The synthesis of mitochondrial polypeptides and the steady state concentration of the complex-III subunits were examined. The Rieske protein and the core-4 and core-5 subunits were much reduced in all mutants. Consequently the overall stability of complex III is very sensitive even to amino-acid substitutions in the cytochrome b protein. Mutant M8-53 provides direct evidence for the proposed role of the P9.1 stem in the core structure of the group-I type last intron of this gene.

Apoproteins↗

Completeness and accuracy of registration of ovarian cancer in the cancer registry of Norway.

Completeness of reporting and accuracy of the diagnosis of ovarian cancer from one health region in Norway to the Cancer Registry were examined. Data kept by the Cancer Registry were evaluated against discharge diagnosis data from all 8 hospitals in the health region during the period of 1987-1996. The assessment of the accuracy of the diagnosis recorded in the Cancer Registry was based on review of all medical records in the hospital setting and on slide review of all histologic diagnoses. The overall completeness of reporting ovarian cancer to the Cancer Registry was 99.6%. The organ specific completeness of registration of histologic verified ovarian cancer within the Cancer Registry was 95.3%; 0.9% was erroneously coded and 3.5% had their diagnosis changed to ovarian cancer at re-evaluation. Of all ovarian cancer cases registered at the Cancer Registry, 91% had a primary histologic diagnosis. Among 591 cases identified with a histologic diagnosis in the Cancer Registry, the accuracy of the diagnosis was estimated at 92%. Coding errors were found in 2% of these cases, while in 6% of the cases it was not possible to reproduce the original diagnosis of ovarian cancer at re-evaluation. In order to provide data of high quality for cancer surveillance a cancer registry needs several data providers, such as histopathologic laboratory reports and clinical reports. In addition, assessment of reported data through stringent quality assurance procedures within the registry are necessary for reaching a nearly 100% completeness of registration as found for ovarian cancer in the Cancer Registry of Norway.

Female↗

Nurses taking on junior doctors' work: a confusion of accountability.

The number of hospital based posts in which nurses take over clinical work previously done by junior doctors is growing. Accountability for the scope of such new roles and the standards of practice which apply to them are still unclear. When analysed together and compared, the regulations arising from the professional bodies (GMC and UKCC), civil law concerning certain wrongs to patients, and employment law are sometimes contradictory and hard to interpret. The resulting uncertainties about appropriate management for clinical roles evolving between the professions, coupled with an increasingly litigious public, put the nurses and consultants involved at risk of complaints and of disciplinary and legal action. Drawing on our current research into changing clinical roles at the medical-nursing interface, we suggest strategies to reduce risk. Doctors and nurses should be equal partners in planning and managing these new posts, patients should be informed adequately about the nature of the postholder's role and training, significant changes in the work of such postholders should be formally acknowledged by the employer and relevant insurers, individuals taking up new roles should have access to legal advice and support to cover legal risk, and national regulatory bodies need to work together to harmonise their codes of practice in relation to changing clinical roles between the professions.

Humans↗

Activation of the protease from human adenovirus type 2 is accompanied by a conformational change that is dependent on cysteine-104.

Adenovirus codes for a protease the activity of which can be regulated in vitro by an 11 residue peptide (GVQSLKRRRCF) derived from another viral protein, pVI. Three cysteine residues, one in the activating peptide and two in the protease (C104 and C122), play a central role in both activation and catalysis. Expression of protease mutants in insect cells has shown that C104 is not essential for proteolytic activity. GVQSLKRRRCF also caused a concentration-dependent increase in tryptophan fluorescence of protease expressed in Escherichia coli that paralleled the increase in proteolytic activity, indicating that activation was accompanied by a conformational change. Tryptophan fluorescence of C104S was not increased by the addition of GVQSLKRRRCF, nor was the fluorescence of wild-type protease increased by the addition of the peptide analogues where cysteine is replaced by aspartic acid or serine, suggesting that C104 is involved in activation and C122 in catalysis.

Adenoviruses, Human↗

Mutation at minisatellite locus DYF155S1: allele length mutation rate is affected by age of progenitor.

A father/son material consisting of 1071 pairs was screened for de novo allele length mutation in locus DYF155S1. Six hundred of these pairs were also analyzed in locus DYF155S1 to detect de novo mutations in the minisatellite variant repeat (MVR)-code not resulting in a length change ("boundary switch" mutations). A modified MVR-polymerase chain reaction (PCR) method was used for this purpose. Twenty-seven de novo allele length mutations and eight "boundary switch" mutations were detected indicating mutation frequencies of approximately 2.5% and 1.3%, respectively. The combined mutation rate for MVR-code mutation is approximately 3.8%. There is a significant increase in mutation rate with paternal age (p = 0.049) in allele length mutations. In the present material, the mutation rate in the oldest age group is three times that of the youngest age group. A similar age relationship is not observed in "boundary switch" mutations. A comparison between progenitors and the other fathers in the material revealed no obvious association between mutation rate and allele length or modular structure (variation in repeat sequence). More than 75% of the length mutations involved the gain or loss of one repeat only. This finding as well as the observed paternal age influence on mutation rate, suggests replication slippage to be the major mutation mechanism in length mutations. However, in one particular case, an allele length mutant revealed rearrangements with direct duplication of repeats at distant sites within the repeat array, and with both loss and gain of repeats. Such complex structural changes could indicate that some of the mutants might arise from sister chromatide exchange. The mutation rate of "boundary switch" mutations is by far higher than would be expected if these mutations are two independent one-step allele length mutations. A different age distribution of "boundary switch" mutations than of allele length mutations also argue against such a hypothesis. Together this could indicate that "boundary switches" are products of another mutation mechanism than the one-step allele length mutations.

Adult↗

Medicare program; revisions to payment policies under the physician fee schedule for calendar year 2005. Final rule with comment period.

This final rule refines the resource-based practice expense relative value units (RVUs) and makes other changes to Medicare Part B payment policy. These policy changes concern: supplemental survey data for practice expense; updated geographic practice cost indices for physician work and practice expense; updated malpractice RVUs; revised requirements for supervision of therapy assistants; revised payment rules for low osmolar contrast media; changes to payment policies for physicians and practitioners managing dialysis patients; clarification of care plan oversight requirements; revised requirements for supervision of diagnostic psychological testing services; clarifications to the policies affecting therapy services; revised requirements for assignment of Medicare claims; addition to the list of telehealth services; and, several coding issues. We are making these changes to ensure that our payment systems are updated to reflect changes in medical practice and the relative value of services. This final rule also addresses the following provisions of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (Pub. L. 108-17) (MMA): coverage of an initial preventive physical examination; coverage of cardiovascular (CV) screening blood tests; coverage of diabetes screening tests; incentive payment improvements for physicians in shortage areas; payment for covered outpatient drugs and biologicals; payment for renal dialysis services; coverage of routine costs associated with certain clinical trials of category A devices as defined by the Food and Drug Administration; hospice consultation service; indexing the Part B deductible to inflation; extension of coverage of intravenous immune globulin (IVIG) for the treatment in the home of primary immune deficiency diseases; revisions to reassignment provisions; and, payment for diagnostic mammograms, physicians' services associated with drug administration services and coverage of religious nonmedical health care institution items and services to the beneficiary's home. In addition, this rule updates the codes subject to the physician self-referral prohibition, discusses payment for set-up of portable x-ray equipment, discusses the third five-year refinement of work RVUs, and solicits comments on potentially misvalued work RVUs. We are also finalizing the calendar year (CY) 2004 interim RVUs and are issuing interim RVUs for new and revised procedure codes for CY 2005. As required by the statute, we are announcing that the physician fee schedule update for CY 2005 is 1.5 percent, the initial estimate for the sustainable growth rate for CY 2005 is 4.3, and the conversion factor for CY 2005 is $37.8975.

Centers for Medicare and Medicaid Services, U.S.↗

Expression of silicatein in spicules from the Baikalian sponge Lubomirskia baicalensis.

Lake Baikal harbors the largest diversity of sponge species [phylum Porifera] among all freshwater biotopes. The abundantly occurring species Lubomirskia baicalensis was used to study the seasonal silicatein metabolism; the spicules of this species have an unusually thick axial filament, consisting of silicatein, which remains constant in diameter during their growth. In the course of maturation, the size of the silicic acid shell grows, until the final diameter of the spicules of about 8 microm is reached. The seasonal content of silicatein was assessed by use of antibodies raised against silicatein; they stained specifically the axial filaments. In addition we determined, by application of the enzyme-linked immunosorbent assay system, that the proteinaceous content of the spicules, the silicatein, increases from spring to late summer by 8-fold. As molecular markers to quantify the seasonal changes in expression levels of genes coding for proteins/enzymes, the genes for the calumenin-like protein and the kinesin-related protein, were selected. The expression of calumenin-like gene, involved in the intracellular signaling, is highest during September, whereas the expression of the kinesin-related protein does not change during the annual course. These results suggest that the highest metabolic activity of L. baicalensis occurs in late summer (September), in parallel with the highest accumulation of silicatein, a structural protein/enzyme of the spicules.

Amino Acid Sequence↗

Fatal poisoning in childhood, England & Wales 1968-2000.

We analysed deaths certified as due to poisoning in England & Wales, 1968-2000, in children aged <10 years by age, sex, circumstances of death, intent, and agents involved. The number of deaths fell from 165 (20.6 per million children) in 1968 to 30 (4.6 per million) in 2000, a decrease of approximately 80%. The age-specific death rates were similar in boys and girls. The rate was initially much higher, and fell more, in those aged <5 years. Most deaths (n=1923) occurred in fires, and had been attributed to inhaling combustion products. A small number (n=104) occurred in fires resulting from motor vehicle and other transport accidents. From 1979 (use of ICD-9) the coding of some of these deaths changed from poisoning with carbon monoxide to poisoning with 'other gases, fumes or vapours'. These 'fire deaths' do not appear as poisonings in mortality statistics based on a single underlying cause of death, and cannot be tabulated as poisoning in many countries. Fire deaths and deaths coded to accidental, deliberate, or undetermined poisoning (n=702) decreased substantially with time, and by 2000 numbered 14 and 10, respectively. Accidental deaths declined from 151 in 1968 to 23 in 2000, but homicides and open verdicts varied from 5 to 20 per year, with no clear trend. Deaths attributed to carbon monoxide and to 'other gases, fumes or vapours' (mostly fire-related) totalled 2431 (84% of all poisoning deaths). Overall, 10% of these deaths were either certified as homicides or open verdicts. However, homicide or open verdict was recorded in half of the 47 fatal opiate poisonings. Opioids have now superseded antidepressants as the commonest agents encountered in fatal poisoning with drugs in children.

Accidents↗

Single amino acid substitutions in conserved extracellular domains of E-cadherin differ in their functional consequences.

The calcium-dependent homophilic cell adhesion molecule E-cadherin typically connects epithelial cells. The extracellular portion of the mature transmembrane protein consists of five homologous domains. The four sequences linking these domains contain the structural amino acid motif DXXD that is thought to be involved in direct calcium binding. In gastric cancer patients mutations affecting this motif between the second and third domain are frequently seen. In order to determine the functional significance of similar sequence alterations with regard to their location, we analyzed single amino acid substitutions changing the DXXD motif to DXXA in each linker region according to a mutation found in gastric cancer (D370A). The cDNA sequences coding for DQND, DVLD and DVND were changed (D257A, D479A, D590A, respectively) and stably expressed in E-cadherin negative MDA-MB-435S mammary carcinoma cells. We found that the D257A and D370A mutations result in abnormal protein localization, changes in the actin cytoskeleton, markedly reduced homophilic cell adhesion, and altered cell morphology. Unexpectedly, the tumor-associated D370A mutation but not the D257A mutation induced increased cell motility. The D479A mutation only had slight functional consequences whereas cells expressing the D590A mutant did not differ from cells expressing the wild-type molecule. Although the putative calcium binding motif DXXD is located at repetitive positions in the extracellular portion of E-cadherin, our results indicate that it has different functions depending on the location. Remarkably, tumor cells select for mutations in the most critical domains resulting both in loss of function (decreased cell adhesion) and in gain of function (increased cell motility). Since multiple DXXD motifs are typically seen in other cadherins, our structure-function study is relevant for this gene family in general.

Actins↗

Marital interaction coding system: revision and empirical evaluation.

Given the vast amount of codeable information in marital interactions, observational coding systems must emphasize particular classes of behavior. The most widely used marital coding scheme, the Marital Interaction Coding System (MICS), like many older behavioral coding systems, emphasizes verbal content over affect. Changes made to the MICS between versions III and IV are described; they were intended to increase the system's use of coded affect and to decrease autodependence in sequential analysis. We used an archival data set of 994 couples' videotaped conflict negotiations coded with the MICS. As intended, the MICS-IV, relative to the MICS-III, was found to have the advantage of capturing more non-verbal affect expressed during marital interactions, which resulted in stronger interactional contingencies (e.g. Wife Blame-->Husband Blame, Husband Facilitation-->Wife Facilitation). The MICS-IV also yielded significantly lower levels of spurious autodependence.

Adult↗

Evolutionary conservation of possible functional domains of the human and murine XIST genes.

The human XIST gene, a candidate for a role in X chromosome inactivation, has recently been cloned and sequenced, yielding a 17 kb cDNA with no apparent significant, conserved open reading frame. In addition, the XIST transcript has been localized within the nucleus to the Barr body by RNA in situ hybridization. This subnuclear localization and lack of any significant protein-coding potential suggest that XIST may act as a functional RNA within the nucleus. In the absence of a conserved open reading frame, we have turned to evolutionary studies as a first step toward elucidating a function for XIST in the process of X inactivation. While probes for XIST detect homologues in numerous eutherians, sequence comparisons require significant gapping and reveal identity levels intermediate between those seen for coding and non-coding regions in other genes. Further, sequence comparison of the most likely candidate open reading frame among several primate species reveals sequence changes not normally associated with protein-coding regions. Other features of XIST are conserved in different species, however, including the position of a major transcription start site and active X chromosome-specific DNA methylation patterns at the gene's 5' end. Finally, a possible molecular basis for differing propensity toward X inactivation between Xce alleles in mouse is investigated by comparing the sequence of the Xist conserved 5' repeats in mouse strains carrying different Xce alleles.

Alleles↗

Cerebral haemodynamics in acute bacterial meningitis in adults.

BACKGROUND: Vascular complications are an important cause of neurological sequelae among adult survivors of acute bacterial meningitis (ABM). AIM: To examine the haemodynamic changes associated with ABM. METHODS: Serial transcranial colour-coded sonography (TCCS) and magnetic resonance angiography (MRA) were used to examine cerebrovascular changes in adult ABM patients. Outcome at 3 months was categorized using a modified Barthel index. RESULTS: We recruited 24 patients, 12 men and 12 women, aged 21-68 years. Mean cerebral blood flow velocity (V(mean)) increased from day 1 to day 4 in the middle cerebral artery (MCA), anterior cerebral artery (ACA) and posterior cerebral artery (PCA). On day 4, V(mean) values in the MCA, ACA and PCA were all significantly higher than reference values in healthy volunteers. At 3 months follow-up, 16 cases had good outcomes, while the other eight had poor outcomes. Under multiple logistic regression analysis, only Glasgow coma score (GCS) at admission was independently associated with the three-month outcome. DISCUSSION: In these patient, stenosis as demonstrated by TCCS did not wholly coincide with stenosis as demonstrated by MRA, and the presence of intracranial stenosis was not predictive of a poor outcome at 3 months. Further studies are needed to delineate the characteristics and significance of cerebrovascular changes in adult ABM.

Acute Disease↗

A novel hepatitis B virus variant in the sera of immunized children.

A novel hepatitis B virus (HBV) variant was detected in the sera of two children in The Gambia, West Africa. The children had been immunized with plasma-derived vaccine and had developed antibody titres of 1448 international units x 10(-3) (mIU)/ml and 133 mIU/ml respectively against the hepatitis B surface antigen (HBsAg). Despite the protective levels of antibodies, HBV DNA was subsequently detected in both children. The complete surface (S) protein gene sequence demonstrated that this HBV isolate was closely related to the ayw4 subtype. However, five nucleotide changes were identified and two of these were unique to the Gambian isolate. One of these changes was within the region of the S gene coding for the immunodominant a determinant of the S protein. A unique nucleotide change from adenosine to guanosine at nucleotide 421 was found, resulting in an amino acid substitution at residue 141 from lysine to glutamic acid. Previous studies have shown that amino acids 141 to 146 are critical for binding to the protective anti-HBsAg antibodies. The presence of a variant HBV in these children suggests the emergence of a novel strain of HBV which can evade immune recognition. This has potential implications for HBV diagnosis and prophylaxis.

Amino Acid Sequence↗