Haplotype analysis of human AMPD1 gene: origin of common mutant allele.
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Biomedical subjects
Publications and source records attributed to M Speer.
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The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based recommendations for neonatal resuscitation. These guidelines comprehensively update the last recommendations, published in 1992 after the Fifth National Conference on CPR and ECC. As a result of the evidence evaluation process, significant changes occurred in the recommended management routines for: * Meconium-stained amniotic fluid: If the newly born infant has absent or depressed respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct tracheal suctioning should be performed to remove meconium from the airway. * Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and ventilation: 100% oxygen is recommended for assisted ventilation; however, if supplemental oxygen is unavailable, positive-pressure ventilation should be initiated with room air. The laryngeal mask airway may serve as an effective alternative for establishing an airway if bag-mask ventilation is ineffective or attempts at intubation have failed. Exhaled CO(2) detection can be useful in the secondary confirmation of endotracheal intubation. * Chest compressions: Compressions should be administered if the heart rate is absent or remains <60 bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling-hands method of chest compression is preferred, with a depth of compression one third the anterior-posterior diameter of the chest and sufficient to generate a palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be administered if the heart rate remains <60 bpm after a minimum of 30 seconds of adequate ventilation and chest compressions. Emergency volume expansion may be accomplished with an isotonic crystalloid solution or O-negative red blood cells; albumin-containing solutions are no longer the fluid of choice for initial volume expansion. Intraosseous access can serve as an alternative route for medications/volume expansion if umbilical or other direct venous access is not readily available. * Noninitiation and discontinuation of resuscitation: There are circumstances (relating to gestational age, birth weight, known underlying condition, lack of response to interventions) in which noninitiation or discontinuation of resuscitation in the delivery room may be appropriate.
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the underlying pathologic entity in 5% of adults and 20% of children with end-stage renal disease (ESRD). FSGS is generally considered to be sporadic in origin. METHODS: Recently, we identified 60 families involving 190 individuals with familial FSGS, providing evidence for a subset of families in which a genetic form is segregating. Each family had at least one member with renal biopsy-confirmed FSGS and at least one other member with either renal biopsy-confirmed FSGS or ESRD. RESULTS: Twenty-six families had individuals affected in more than one generation [multigeneration (MG)], and the remaining 34 families had only a single generation (SG) affected. There was equal representation of males and females among affected individuals. Ten percent of MG families were African American, and 52% of SG families were African American. The mean age of presentation was significantly higher in the MG families (32.5 +/- 14.6 years) compared with the SG families (20.1 +/- 12.1 years, P = 0.0001). SG cases had higher levels of proteinuria at presentation (7.0 +/- 5.6 g/24 hr, compared with 3.8 +/- 3.4 g/24 hr, for the MG families, P = 0.002). On renal biopsy, tubulointerstitial damage was more severe in patients in the SG families than in the MG families; however, the level of glomerular damage did not differ between these groups. Fifty percent of the patients had progressed to ESRD by the age of 30 years. Variables measured at presentation that were independently associated with poor renal survival were decreased age, increased serum creatinine, and increased urinary protein excretion. Forty-one patients underwent successful renal transplantation, with a 10-year graft survival rate of 62%. One patient developed clinical and biopsy evidence of recurrence of FSGS in the allograft. CONCLUSION: These data confirm the existence of a non-Alport's form of hereditary glomerulonephritis, which has a morphological pattern of FSGS.
Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia. So far, two loci have been demonstrated for ORW. Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently identified as the ORW1 gene. A second locus, designated ORW2, was mapped to chromosome 12. Here we report a new 4 cM interval for ORW2 that does not overlap with any previously defined. A 1.38-Mb YAC contig spans the entire interval. It includes the activin receptor like kinase 1 gene (ACVRLK1 or ALK1), a member of the serine-threonine kinase receptor family expressed in endothelium. We report three mutations in the coding sequence of the ALK1 gene in those families which show linkage of the ORW phenotype to chromosome 12. Our data suggest a critical role for ALK1 in the control of blood vessel development or repair.
What have you done with compensation? It's the question asked of every healthcare organization in the midst of restructuring and work redesign. The prescription at the outset of these dramatic change programs was often for a heavy dose of compensation overhaul. But the reality has often been far less dramatic. A group of PFCA Executive Members, led by executives Mike Speer and Roger Gerard from United Health Group of Appleton, Wisconsin, were not content that the best thinking had been applied to culling out successful compensation improvements and with finding breakthrough redesign options. The group has completed the first of its brainstorming sessions in search of new approaches and offers these initial thoughts to the PFCA REVIEW readership.
The participants in the HR Consortium walked away satisfied that they had left "no stones unturned" in their efforts to create new compensation approaches. The major takeaway was that there is no ready panacea. The creation of an effective compensation system will be the development of an approach that does not serve as an obstacle to staff and managers in their efforts to build a hospital system that services customers in a restructured setting; rather it shadows and supports these operational changes.
Computer-based simulation has been an important method in human linkage analysis for a long time. Typically, such analyses have been performed by simulating a set of linked markers according to the intermarker recombination fractions, under the assumption of no genetic interference. A novel approach is proposed in which such simulations can be performed using chromosome-based methods, rather than traditional recombination fraction-based methods. We propose simulating pedigree data using a crossover formation (CF) process to generate the number of crossovers and their locations in Morgans along the entire length of a chromosome. By this method, one can generate simulated multilocus data for any number of loci on a chromosome much more efficiently than with the currently available methods like those used in the SLINK or SIMLINK programs. Further, interference can be incorporated directly in this method, which is not possible with existing packages.
A series of carboxyfluorescein (CF)-containing multilamellar vesicle (MLV) dispersions was prepared and extruded through polycarbonate membranes ranging in size from 0.2 to 5 microns. Vesicle dispersions were nebulized for 80 min using a Collison nebulizer, and the release of CF was monitored during nebulization. Solute retention was dependent upon the size of the vesicles and leakage ranged from 7.9 +/- 0.4% (N = 3) for vesicles extruded through 0.2-microns filters to 76.8 +/- 5.9% (N = 3) for liposomes that were not filtered. Solute release profiles obtained over greater than or equal to 420-min nebulization periods conformed to a two-compartment kinetic model and exhibited a "fast" initial phase (k1 = 0.052 +/- 0.0043) followed by a "slow" terminal phase (k2 = 0.0034 +/- 0.00018). The results show that CF retention can be increased by nebulizing small vesicles and modeling suggests that the rate of CF leakage from the bilayers is faster than from the core of the liposomes.
Two hundred twelve patients with acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) were followed prospectively. Univariate and multivariate analyses were performed to determine significant predictors of survival and development of opportunistic infection (OI) from the time of diagnosis of KS. Clinical variables analyzed were age at onset, presence of systemic symptoms, prior or coexistent OI, development of OI greater than 3 months following KS diagnosis, and extent of disease. Laboratory variables analyzed were absolute number of peripheral T-helper lymphocytes (T4), helper/suppressor ratio (T4/T8), serum beta-2-microglobulin, and serum acid labile alfa interferon. Three independent variables were predictive of shorter survival: (1) prior or coexistent OI (P = .02), (2) presence of systemic symptoms (P = .001), and (3) absolute T4 count less than 300 cells/microL (P = .002). Based on survival, patients with AIDS-related KS can be divided into four groups: (1) those with no prior or coexistent OI, no systemic symptoms, T4 greater than or equal to 300 cells/microL (median survival, 31 months): (2) those with no prior or coexistent OI, no systemic symptoms, and T4 less than 300 cells/microL (median survival, 20 months); (3) those with no prior or coexistent OI and presence of systemic symptoms (median survival, 15 months); and (4) those with prior or coexistent OI (median survival, 7 months).
Familial amyotrophic lateral sclerosis (FALS) constitutes 5 to 10% of cases of ALS and, in most families, its inheritance is consistent with an autosomal dominant trait with age-dependent penetrance. The biochemical abnormality underlying the disorder is unknown. We analyzed DNA from 131 members of 6 multigenerational ALS families, which included 13 affected members, for genetic linkage to 39 expressed and DNA markers, using the techniques of 2-point linkage analysis, multilocus linkage analysis, and exclusion mapping. We identified FALS families with structures suitable for linkage, by computer simulation techniques. A DNA bank established to provide optimum use of available FALS families provided DNA from immortalized lymphoblast cell lines and frozen postmortem tissue. We could not link FALS to any of the markers studied, but excluded chromosome regions unlikely to be a locus of the FALS gene. With the help of this exclusion data, we will concentrate on regions of the human genome that remain unexcluded.
Quinoline catabolism was investigated with different bacterial strains, able to use quinoline as sole source of carbon, nitrogen and energy. Some degradation products of quinoline were isolated from the culture fluids and identified. With Pseudomonas fluorescens and Pseudomonas putida we found 2-oxo-1,2-dihydroquinoline, 8-hydroxy-2-oxo-1,2-dihydroquinoline, 8-hydroxycoumarin and 2,3-dihydroxyphenylpropionic acid as intermediates. With a Rhodococcus strain 2-oxo-1,2-dihydroquinoline, 6-hydroxy-2-oxo-1,2-dihydroquinoline, a red meta-cleavage product and a blue fluorescent compound were isolated. The red compound was identified as 5-hydroxy-6-(3-carboxy-3-oxopropenyl)-1H-2-pyridone. From this the blue fluorescent azacoumarin 2H-pyrano-2-one-[3,2b]-5H-6-pyridone is formed by chemical decomposition. Therefore it can be considered a by-product of quinoline-degradation in Rhodococcus spec. With the present results two different degradation pathways for quinoline in different microorganisms are proposed.
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The detoxification of penicillic acid by reaction with ammonia was examined by means of a polymerase assay using two strains of Escherichia coli (pol A+ and pol A-1) and a recombination assay using two strains of Bacillus subtilis (rec+ and rec-). A 100-fold surplus of ammonia added to penicillic acid abolished the cytotoxic and genotoxic effects of penicillic acid towards the bacteria under the test conditions. The study presents the possibility of detoxifying mycotoxins in feeds by ammonia treatment and demonstrates the suitability of bacterial assays as indicators for mycotoxins.
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Three newborn infants with congestive heart failure had hemodynamic, angiographic, and echocardiographic features of hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy). Treatment with digitalis and diuretic drugs was ineffective, but improvement occurred when these agents were withheld in one patient, and when treatment with propranolol was begun in two patients. Echocardiography was helpful in establishing the diagnosis in two patients and showed resolution of the condition during the first six months of life. Serial cardiac catheterizations confirmed resolution of the outflow obstruction in the third patient. Family studies revealed no evidence of familial cardiomyopathy, but the mothers of two infants had insulin-dependent diabetes mellitus and the mother of the third was presumed to be prediabetic.
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