A miniaturized self-contained single-use disposable quantitatitve test for hemoglobin A1c in blood at the point of care.

DRx HbA1c is a finger-stick (< or =10 microL) test for hemoglobin A1c (HbA1c) developed by Metrika, Inc., for rapid quantitative testing at the point of care. It incorporates microelectronics, optics, and dry reagent chemistry inside a self-contained, integrated, single-use device. Test results (%HbA1c) are displayed in numeric form on the device's liquid crystal display within 8 min after sample application. Having no switches or buttons, DRx HbA1c self-activates upon addition of sample. It contains two dry reagent lateral flow strips, each having an HbA1c immunoassay test zone and a total hemoglobin (Hb) test zone. An on-board microprocessor calculates %HbA1c from the reflectances of the test zones. The microprocessor also corrects for lot-specific reagent characteristics and optical variation, in addition to checking electrical functioning and proper sample volume. For testing accuracy, subjects both with and without diabetes were recruited in order to obtain samples with a wide range of HbA1c values. Whole blood samples were analyzed using both DRx HbA1c units and a laboratory method (Bio-Rad DiaSTATT). DRx HbA1c testing was performed by laboratory personnel and by subjects who received brief training. Repeatability, linearity, sample volume tolerance, diluted sample stability and hematocrit tolerance of the DRx HbA1c test were assessed by trained laboratory personnel as described in the text. The linear %HbA1c range of the assay extended from approximately 3% to 15%. Hb was measurable from 6.8 to 20.0 g/dL, encompassing over 99.8% of the normal population. DRx HbA1c clinical sample test results (n = 50) correlated linearly to the Bio-Rad DiaSTAT method (r = 0.935) with slope and intercept values of 0.994 and 0.003, respectively. The repeatability for %HbA1c was within 5-9% CV. We conclude that DRx HbA1c performance is closely equivalent to that of existing tests.

A mechanism for valine-resistant growth of Escherichia coli K-12 supported by the valine-sensitive acetohydroxy acid synthase IV activity from ilvJ662.

Acetohydroxy acid synthase (EC 4.1.3.18; AHAS) isozymes I and III are expressed in Escherichia coli strain K-12 and, when inhibited by L-valine, cannot support cell growth. AHAS IV, expressed from mutation at ilvJ662, exhibits valine-sensitivity similar to that of AHAS III, yet AHAS IV does support cell growth in valine minimal medium. Rate equations were derived for AHAS III and AHAS IV reaction in crude extracts and for partially purified AHAS IV. Values of kinetic constants in these equations were determined in order to model a probable reaction mechanism. Computer modeling of initial velocity reactions at physiological substrate concentrations simulated consequences of valine-inhibition and revealed that AHAS IV synthesized AHB at a maximal rate over four times faster than AHAS III under these conditions. The simulations predicted that cells depending upon AHAS III for growth in valine minimal medium would accumulate higher levels of 2-ketobutyrate than cells using AHAS IV. Experiments on growth inhibition by valine revealed more than a five-fold difference in 2-ketobutyrate accumulation, thus confirming these predictions. These data support the hypothesis that valine inhibition of growth is a consequence of 2-ketobutyrate accumulation to toxic levels. We propose that the valine-inhibited AHAS IV activity prevents growth inhibition by keeping 2-ketobutyrate accumulation to a lower level than resulting from AHAS III activity.

Surgical management of severe thoracic lordosis. A new technique to restore normal kyphosis.

A technique of combined anterior and posterior surgery for correction of severe thoracic lordosis with the restoration of normal kyphosis is described. The results in three patients are presented. Preliminary results suggest that this is a valid procedure for obtaining a normal thoracic kyphosis, and that correction of thoracic lordosis may result in improved pulmonary function.

Comparative study of Björk-Shiley and Starr-Edwards prostheses for aortic valve replacement.

Thirty-nine patients received aortic valve replacement prostheses. The 19 patients who received Starr-Edwards (SE) caged-ball valve prostheses and the 20 patients who received Björk-Shiley (BS) tilting-disc valve prostheses were followed up for a mean period of 20 and 19 mo, respectively. The cumulative mortality rate was 5.3% in the SE group and 15% in the BS group. The clinical improvement was more remarkable in the BS than in the SE series. Major thromboembolic complications developed in three patients in each group, and two patients in each group developed infectious endocarditis. Tests for intravascular hemolysis indicated a higher rate in the SE than in the BS group. The serum haptoglobin levels were 39 +/- 22 and 102 +/- 63 g/dl (mean +/- SD), respectively (P less than 0.001). The hemoglobin level was 12.4 +/- 1.8 g/dl in the SE group and 13.4 +/- 0.6 g/dl in the BS group (P less than 0.03). The BS tilting-disc valve caused less hemolysis and the smaller size led to greater clinical improvement.

Leiomyosarcoma of the rectum: diagnostic criteria and surgical approach.

A case of leiomyosarcoma of the rectum is reported. There was difficulty in establishing the correct histologic diagnosis. Diagnostic criteria, including electron microscopy examination, are reviewed. Abdominoperineal resection of the rectosigmoid is the common therapeutic procedure recommended.

Enhanced allosteric regulation of threonine deaminase and acetohydroxy acid synthase from Escherichia coli in a permeabilized-cell assay system.

A permeabilized-cell technique for rapid assay of enzyme activity has revealed enhanced allosteric regulation of both threonine deaminase (L-threonine hydrolyase (deaminating), EC 4.2.1.16) and acethohydroxy acid synthease (acetolactate pyruvate-lyase (carboxylating), EC 4.1.3.18) in Escherichia col K-12. In the permeabilized cell assay threonine deaminase exhibited a higher Hill coefficient for inhibition by L-isoleucine, and acetohydroxy acid synthase exhibited a hypersensensitivity to allosteric inhibition by L-valine when compared to studies on crude extracts. We propose that these effects reflect the in situ microenvironments of both enzymes. Preliminary evidence further indicates that acetohydroxy acid synthase may loosely associate with the cell membrane.