Evaluation of Fourier transform infrared spectroscopy for the rapid identification of glycopeptide-intermediate Staphylococcus aureus

Objectives To evaluate Fourier transform infrared (FTIR) spectroscopy as a rapid method for distinguishing glycopeptide-intermediate Staphylococcus aureus (GISA) from glycopeptide-susceptible methicillin-resistant S. aureus (MRSA) and to compare three data analysis methods. Methods First-derivative normalized spectra of dried films of bacterial growth on Que-Bact® Universal Medium No. 2 were examined by singular value decomposition to identify key spectral regions. Region selection was analysed by principal component analysis (PCA), self-organizing maps (SOMs) and the K-nearest neighbour (KNN) algorithm. The initial data set included 35 GISA (including GISA Mu50 and heterogeneous GISA Mu3) and 25 epidemic MRSA. The regions were then tested using enlarged data sets that included 22 sporadic and 85 additional epidemic MRSA. Results Epidemic MRSA and GISA/hGISA were separated into two distinct clusters on the basis of spectral data from regions 1352-1315 and 1480-1460 cm−1, the former providing 100% correct classification by all three analyses and the latter providing 96.67% correct by PCA, 98.34% by SOM and 100% by KNN. The 1480-1460 cm−1 region was more effective for distinguishing GISA/hGISA from a set combining sporadic and epidemic MRSA, with two GISA/hGISA and four sporadic MRSA misclassified by PCA and SOM (92.69% correct), while the KNN method misclassified three of the four sporadic MRSA (93.90% correct). The addition of 85 other epidemic MRSA this set increased the fraction of correctly classified isolates to 96.41% and 97.01% by PCA, SOM and KNN, respectively. Conclusions As only 6 of 167 isolates were misclassified, FTIR spectroscopy may provide means of rapid and accurate identification of GISA and hGISA among isolates of MRS

Diagnosis of autosomal dominant polycystic kidney disease in utero and in the young infant.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135563/1/jum198765249.pd

Bioavailability Studies of Acetaminophen and Nitrofurantoin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97190/1/j.1552-4604.1974.tb02312.x.pd

Hepatic Abnormalities Associated with Aluminum Loading in Piglets

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141476/1/jpen0293.pd

Aluminum toxicity in childhood

Aluminum intoxication is an iatrogenic disease caused by the use of aluminum compounds for phosphate binding and by the contamination of parenteral fluids. Although organ aluminum deposition was noted as early as 1880 and toxicity was documented in the 1960s, the inability to accurately measure serum and tissue aluminum prevented delineation of its toxic effects until the 1970s. Aluminum toxicity has now been conclusively shown to cause encephalopathy, metabolic bone disease, and microcytic anemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47831/1/467_2004_Article_BF00869743.pd

C-Terminal Extension of the Yeast Mitochondrial DNA Polymerase Determines the Balance between Synthesis and Degradation

Saccharomyces cerevisiae mitochondrial DNA polymerase (Mip1) contains a C-terminal extension (CTE) of 279 amino acid residues. The CTE is required for mitochondrial DNA maintenance in yeast but is absent in higher eukaryotes. Here we use recombinant Mip1 C-terminal deletion mutants to investigate functional importance of the CTE. We show that partial removal of the CTE in Mip1Δ216 results in strong preference for exonucleolytic degradation rather than DNA polymerization. This disbalance in exonuclease and polymerase activities is prominent at suboptimal dNTP concentrations and in the absence of correctly pairing nucleotide. Mip1Δ216 also displays reduced ability to synthesize DNA through double-stranded regions. Full removal of the CTE in Mip1Δ279 results in complete loss of Mip1 polymerase activity, however the mutant retains its exonuclease activity. These results allow us to propose that CTE functions as a part of Mip1 polymerase domain that stabilizes the substrate primer end at the polymerase active site, and is therefore required for efficient mitochondrial DNA replication in vivo

Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of polyexponential equations which have been fitted to the data

It is shown that if the numerical values of the coefficients and exponents of the polyexponential equation describing the whole blood (plasma or serum) concentration after administration of a drug by bolus intravenous injection, or during or after termination of a constantrate intravenous infusion, are known, then many needed pharmacokinetic parameters may be obtained directly. Parameters readily calculated by simple arithmetic are as follows: plasma or serum clearance, Cl p ; volume of plasma compartment, V p ; volume of distribution at steady state, V dss ; V{darea} or V β , extrapolated volume of distribution, V dexr ; half-life of elimination, t 1/2 ; amount metabolized and/or excreted to time t, (A e ); amount in the body at time t, A b ; amount in the plasma (reference) compartment at time t, A p ; and amount in other compartments at time t, A o . Simulations have shown that the equations yield the correct answers for an n-compartment mammillary model with central compartment elimination only, when rate constants, dose, and a value of V p have been assigned. Since whole blood (plasma or serum) concentrationtime data always lead to ambiguities as to which specific model is involved, the equations are most appropriate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45069/1/10928_2005_Article_BF01062831.pd

Renal obstructive dysplasia: Ultrasound diagnosis and therapeutic implications

57 cases of renal obstructive dysplasia (defined as the abnormal development of nephronic and ductal structures due to in utero obstruction of the urinary tract) were evaluated in terms of sonographic findings, renal and other associated anomalies, and current status of the child. More than one-third of the cases had bilateral disease and although not uniformly fatal bilateral involvement was associated with significant morbidity and mortality. In 12 of the 33 cases with unilateral dysplasia there was an association with contralateral renal problems including ureteropelvic junction obstruction, vesicoureteral reflux and aplasia. Almost one-half of the cases had congenital anomalies, these included VACTERL association, congenital heart disease, cranial abnormalities and gastrointestinal malformations. Fifteen stillborns and 12 of the patients with bilateral involvement and four with unilateral involvement have died. Four patients are on dialysis (two with bilateral involvement and two with unilateral renal obstructive dysplasia). Only one-quarter are otherwise normal. More serious problems are reported in this mixed age population of patients with obstructive renal dysplasia than has been identified in previous studies. Management decisions of the fetus and child must be based on this new age-expanded population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46696/1/247_2005_Article_BF02018623.pd

Obesity surgery makes patients healthier and more functional - real world results from the United Kingdom National Bariatric Surgery Registry

Background The National Bariatric Surgery Registry (NBSR) is the largest bespoke database in the field in the United Kingdom. Objectives Our aim was to analyze the NBSR to determine whether the effects of obesity surgery on associated co-morbidities observed in small randomized controlled clinical trials could be replicated in a "real life" setting within U.K. healthcare. Setting United Kingdom. Methods All NBSR entries for operations between 2000 and 2015 with associated demographic and co-morbidity data were analyzed retrospectively. Results A total of 50,782 entries were analyzed. The patients were predominantly female (78%) and white European with a mean age of 45 ± 11 years and a mean body mass index of 48 ± 8 kg/m2. Over 5 years of follow-up, statistically significant reductions in the prevalence of type 2 diabetes, hypertension, dyslipidemia, sleep apnea, asthma, functional impairment, arthritis, and gastroesophageal reflux disease were observed. The "remission" of these co-morbidities was evident 1 year postoperatively and reached a plateau 2 to 5 years after surgery. Obesity surgery was particularly effective on functional impairment and diabetes, almost doubling the proportion of patients able to climb 3 flights of stairs and halving the proportion of patients with diabetes related hyperglycemia compared with preoperatively. Surgery was safe with a morbidity of 3.1% and in-hospital mortality of .07% and a reduced median inpatient stay of 2 days, despite an increasingly sick patient population. Conclusions Obesity surgery in the U.K. results not only in weight loss, but also in substantial improvements in obesity-related co-morbidities. Appropriate support and funding will help improve the quality of the NBSR data set even further, thus enabling its use to inform healthcare policy

Pharmacokinetics of ethanol after oral administration in the fasting state

A nonlinear relationship between the total area under the blood ethanol concentration-time curve and the orally administered dose (mg/kg) of ethanol was observed in fasting subjects. A preliminary model, based on physiological considerations, was elaborated and shown, for the first time, to describe the entire time course of blood alcohol concentrations after four different doses of alcohol. The model could be refined by further experimentation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45071/1/10928_2005_Article_BF01065396.pd