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Biomedical subjects

M A Katz

Publications and source records attributed to M A Katz.

At least 19 recordsLinked to original sources

Pharmacokinetics of an immediate-release oral formulation of Fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury.

Plasma concentration profiles of the K+ channel-blocking compound Fampridine were obtained from (1) control subjects (n = 6) following oral administration of doses of 10, 15, 20, and 25 mg and (2) patients with spinal cord injury (SCI) (n = 11) following a single oral dose of 10 mg of an immediate-release formulation. Plasma concentrations were determined using a reversed-phase ion-pair high-performance liquid chromatography (HPLC) assay with ultraviolet light detection employing liquid extraction. The drug was rapidly absorbed with a tmax approximately 1 hour for both groups; tmax was independent of dose. Cmax and AUC0-infinity were linearly related to dose, and t 1/2 was 3 to 4 hours for both groups. There were no obvious differences in the (10-mg) plasma concentration profiles between control subjects and SCI patients. The drug was well tolerated, with only mild and transient side effects of light-headedness, dysesthesias, and dizziness.

4-Aminopyridine↗

Refinements in stress echocardiographic techniques improve inter-institutional agreement in interpretation of dobutamine stress echocardiograms.

AIMS: To determine the degree of inter-institutional agreement in the assessment of dobutamine stress echocardiograms using modern stress echocardiographic technology in combination with standardized data acquisition and assessment criteria. METHOD AND RESULTS: Among six experienced institutions, 150 dobutamine stress echocardiograms (dobutamine up to 40 microg x kg(-1) min(-1) and atropine up to 1 mg) were performed on patients with suspected coronary artery disease using fundamental and harmonic imaging following a consistent digital acquisition protocol. Each dobutamine stress echocardiogram was assessed at every institution regarding endocardial visibility and left ventricular wall motion without knowledge of any other data using standardized reading criteria. No patients were excluded due to poor image quality or inadequate stress level. Coronary angiography was performed within 4 weeks. Coronary angiography demonstrated significant coronary artery disease (> or = 50% diameter stenosis) in 87 patients. Using harmonic imaging an average of 5.2+/-0.9 institutions agreed on dobutamine stress echocardiogram results as being normal or abnormal (mean kappa 0.55; 95% CI 0.50-0.60). Agreement was higher in patients with no (equal assessment of dobutamine stress echocardiogram results by 5.5+/-0.8 institutions) or three-vessel coronary artery disease (5.4+/- 0.8 institutions) and lower in one- or two- vessel disease (5.0+/-0.9 and 5.2+/-1.0 institutions, respectively; P=0.041). Disagreement on test results was greater in only minor wall motion abnormalities. Agreement on dobutamine stress echocardiogram results was lower using fundamental imaging (mean kappa 0.49; 95% CI 0.44-0.54; P<0.01 vs harmonic imaging). CONCLUSION: Modern echocardiographic technology in combination with standardized digital image processing and uniform reading criteria results in a higher inter-institutional agreement in the interpretation of dobutamine stress echocardiogram compared to historic reports.

Adrenergic beta-Agonists↗

Evaluation of the sigmoid notch with computed tomography following intra-articular distal radius fracture.

A classification system for disruption patterns of the sigmoid notch of the radius associated with distal radius fractures has not been established. Using plain x-rays and corresponding computed tomography (CT) scans we characterized and quantified the types of sigmoid notch involvement in 20 consecutive distal radius fractures with radiocarpal joint extension. Plain radiographs revealed fracture extension into the sigmoid notch in only 7 cases (35%) and the CT scans demonstrated fracture extension into the sigmoid notch in 13 cases (65%). Of the 13 fractures with sigmoid notch involvement, 9 (69%) were displaced and 4 (31%) were nondisplaced. Sigmoid notch articular step-off (n = 7) and gapping (n = 9) were detectable on the CT scans but not on the x-rays. Plain x-rays appear to underestimate sigmoid notch involvement following distal radius fractures. In addition, CT appears to be a superior diagnostic modality for quantifying sigmoid notch fracture step-off and articular gapping.

Adult↗

Computed tomography scanning of intra-articular distal radius fractures: does it influence treatment?

The purpose of this study is to determine whether the addition of computed tomography (CT) results in changes in the evaluation and treatment of intra-articular distal radius fractures. Fifteen intra-articular distal radius fractures were evaluated independently by 4 hand surgeons. Plain x-rays were reviewed initially followed by the corresponding CT scans for comparison of articular step-off and gapping, comminution, and treatment. Kappa coefficients (kappa) of intraobserver and interobserver reliability for treatment plans were generated. Computed tomography scans improved the sensitivity of measurement of articular surface gapping, improved the accuracy of detection of comminution and distal radioulnar joint involvement, and altered proposed treatment plans within observers (intraobserver agreement: kappa =.54, moderate) and improved agreement of proposed treatment plans between observers (kappa =.34 to kappa =.44, fair to moderate). Computed tomography scanning influenced observers to change treatment plans and resulted in increased interobserver reliability in the proposed management of these injuries.

Humans↗

Effects of forearm rotation on the clinical evaluation of ulnar variance.

Neutral rotation radiographs of the wrist are recommended to standardize the measurement of ulnar variance because it is known that changes in forearm rotation result in changes of this measurement. The purpose of this study was to examine whether there are clinically measurable differences in ulnar variance between radiographs in various degrees of forearm rotation in human subjects. Forty-five wrist radiographs of 15 normal adults were obtained in 3 positions: maximum forearm pronation, neutral rotation, and maximum supination. The ulnar variance on each view was measured by 3 independent observers using a standard millimeter ruler. The average absolute difference in ulnar variance was 0.4 mm between pronation, 0.6 mm between pronation and supination, and 0.2 mm between neutral and supination. Although we found a statistically significant difference in ulnar variance between the pronated and neutral positions, this difference may not be clinically significant and may not justify concerns of forearm position during the radiographic evaluation of ulnar variance.

Adult↗

Determining femoral rotational alignment in total knee arthroplasty: reliability of techniques.

Several anatomic axes routinely are used for determining femoral rotational alignment in total knee arthroplasty. The purpose of this study was to determine the reliability of these techniques. The transepicondylar axis, anteroposterior axis, and balanced flexion gap tension line were identified relative to the posterior condylar axis in 8 fresh frozen cadaver knees by 3 independent observers. The flexion-extension axis was defined in each knee for comparison. The anteroposterior and balanced tension axes defined most reliably the flexion-extension axis and best balanced the flexion gap with no significant interobserver differences. The transepicondylar axis was less predictable and significantly more externally rotated than the anteroposterior axis (P < .005) and the balanced tension line (P < .00001). Flexion gap tensioning may offer superior reliability because of its independence of obscured or distorted bone landmarks.

Arthroplasty, Replacement, Knee↗

Nodular fasciitis of the hand: a case report.

Nodular fasciitis is a benign, reactive fibroblastic soft tissue tumor. Involvement of the hand is exceedingly rare. A case of nodular fasciitis involving the dominant hand of a 38-year-old woman is reviewed, and its clinicopathologic features are presented. Because of its rapid growth and aggressive histologic appearance, nodular fasciitis can be mistaken for a soft tissue sarcoma, despite its benign clinical behavior. For this reason, aggressive surgical resection should be avoided.

Adult↗

Contribution of acetabular labrum to articulating surface area and femoral head coverage in adult hip joints: an anatomic study in cadavera.

The purpose of our study was to describe the gross anatomy of the adult acetabular labrum and to determine its contribution to the depth, surface area, and volume of the acetabulum. Fifty-five embalmed hips were studied. Each hip was disarticulated, and standardized measurements were taken. Calculations of the acetabular articulating surface area and volume, with and without the labrum, were performed based on these measurements. Average width of the acetabular labrum was 5.3 mm (SD, 2.6 mm). The labrum was wider anteriorly and superiorly than posteriorly. The surface area of the acetabulum without the labrum was 28.8 cm2; with the labrum, it was 36.8 cm2 (P < .0001). The volume of the acetabulum without the labrum was 31.5 cm3; with the labrum, it was 41.1 cm3 (P < .0001). There was no side-to-side difference in contribution of the labrum to either surface area or volume between right and left hips. Comparison of these indices for males and females showed statistically significant differences in absolute but not relative increases.

Acetabulum↗

The glomerular barrier fits a two-pore-and-fiber-matrix model: derivation and physiologic test.

Failure of the glomerular barrier causing proteinuria has been modeled chiefly by Chang, Deen, and Brenner. They have refined models from an isoporous filter to a mostly isoporous membrane, which during proteinuric disease opens up nondiscriminating shunts. This report extends these concepts by measuring a larger distribution of macromolecular tracer sizes and bringing in a fiber matrix. By clearance methods, glomerular sieving curves of relatively neutral tetramethyl rhodamine aminodextran from radii of 15 to over 80 A were obtained and fitted to theory. Two pores filled with matrix fit all data without exception, and no other model did. Five parameters described the curve in control rats and in proteinuric rats made so by albumin injections. From highest to lowest degree of confidence, these were small and large pore radii ros = 42.7 +/- 0.9 SEM A and rol = 926 +/- 156 A; small to large pore density ns/nl = 3859 +/- 942; mean fiber radius rf = 20.3 +/- 1. 1 A; and fiber void volume ratio epsilon = 0.52 +/- 0.05. In proteinuria, ros rose 13% (P = 0.002), nl increased 150% (P = 0.04), and there was a compensatory rise in rf of 26% (P = 0.002). The consideration of basement membrane and glycocalyx remain to be incorporated into the model. Moreover, the closeness of rf to ros indicates that fiber matrix theory may need modification for a complete description.

Animals↗

[Hemostatic closure of arterial puncture site using Angio-Seal after diagnostic heart catheterization or coronary intervention].

Conventional manual compression and subsequent application of pressure bandages is associated with prolonged immobility and significant patient discomfort. Routine anticoagulation as well as the use of new interventional devices and platelet inhibiting strategies lead to a higher incidence of local bleeding complications after diagnostic cardiac catheterization or coronary angioplasty. Immediate sheath removal increases patient comfort. The Angio-Seal system uses a biodegradable anchor and collagen plug for sealing of arterial puncture sites. Several studies showed the safety and efficacy of this device. Technical deployment success ranges between 88 and 100%. Significant reduction in time to hemostasis allows for earlier patient ambulation and shorter in-hospital stay compared to manual compression with peripheral complications not being increased.

Angioplasty, Balloon, Coronary↗

Albumin reduces basement membrane hydraulic conductance in part due to arginyl side groups.

Albumin reduces capillary hydraulic conductance (Lp) even at low concentrations. To determine if part of this barrier protective effect might be extracellular, we studied the effects of bovine serum albumin (BSA) on Lp of self-assembled basement membrane (Matrigel). Lp with tris(hydroxymethyl)aminomethane (Tris) buffer superfusate was stable at 1.77 +/- 0.22 x 10(-5) (SE) cm.s-1.cmH2O-1 over several hours. At 0.1 g/dl BSA, experimental/control (Tris) Lp fell to 83.1 +/- 6.0% (2P < 0.025), with decreases to 72.4 +/- 3.7% at 1 g/dl (2P < 0.005), 45.3 +/- 5.1% at 2.5 g/dl (2P < 0.001), and 45.0 +/- 4.8% at 4.0 g/dl (2P < 0.001). In separate experiments, BSA arginine groups were neutralized by 1,2-cyclohexanedione (CHD), and experimental/control Lp values were measured. At 2.5 g/dl, CHD-BSA depressed Lp to 54.4 +/- 4.8%, while unmodified BSA reduced Lp to 40.8 +/- 3.5% of Tris control (2P = 0.05). Finally, soluble arginine at three- and sixfold the arginine in BSA was added to BSA superfusate. For threefold, Lp rose to 120 +/- 8% of BSA level and for sixfold to 129 +/- 9% (2P < 0.05). We conclude that some part of the albumin protective effect is very likely due to consequences on extracellular matrix and that at least 18-22% of this effect is related to arginine groups on albumin when computed from Lp, and up to 34% when viscosity is taken into account. Membrane-saturable arginine-binding sites can be unbound with arginine, thus nullifying part of the barrier protective effect of BSA.

Animals↗

Fiber matrix descriptors from permeability data without requiring membrane thickness: theory, results, and optimization.

OBJECTIVE: Permeability of basement membrane and all other barriers contains a term for membrane thickness (delta x). This naturally leads to development of methods for measuring delta x that are imprecise, inaccurate, expensive, subject to preparation artifact, and inattentive to variability. Although height and shape of permeability (P) vs. probe radius (aE) curves are sensitive to delta x, In(P) or In (P/free diffusivity or D0) curves have shapes independent of delta x. It should, thus, be possible using such characteristics to determine fiber radius (rf) and void volume ratio (epsilon) without delta x. We developed such a method to derive membrane structure by the standard model of Ogston and present its experimental evaluation. METHODS: Basement membranes were self-assembled using 1:1 Matrigel: 0.01 M Tris/150 mM NaCl/1.0 mM CaCl2 buffer on 0.4-mu polycarbonate supports with transport measured in diffusion chambers using FITC-labeled hydroxyethyl starch probes from 25 to 102 A in radius. Sampling was at 0.5 hr and then for each hour up to 5. Other membranes were measured 7 days after formation. RESULTS: The best fit of the new technique occurred at 3 hr with R2 = 0.949 +/- 0.003 SEM, rf = 36.8 = 2.4 A, and epsilon = 0.87 +/- 0.02. Membranes studied for 7 days showed more variability but essentially the same characteristics. CONCLUSIONS: Membrane thickness is not necessary to reduce permeability of basement membrane to structure, and optimum sampling time is 3 hr.

Animals↗

The fate of hypertonic saline administered during hemodialysis.

The possibility of postdialysis hypernatremia is one reason nephrology nurses do not administer hypertonic saline (HS) to treat hypotension or muscle cramps during the last hour of hemodialysis (HD). A single group time series quasi-experimental design was used to evaluate the effect of 50 mEq of HS given during the last hour of HD on interdialytic weight and serum sodium (PNa) and dialysate sodium (DNa) levels. Ten subjects experiencing hypotension or cramps during the last hour of HD, but not during the final 15 minutes, received 50 mEq of HS. One preinjection PNa and DNa sample was obtained, followed by the collection of 8 PNa and 42 DNa samples during the 5 minutes subsequent to the HS injection. Interdialytic weight was evaluated for differences. The results indicated that a statistically significant, but minor amount of sodium was removed in the dialysate (8.77% mEq/L + .96). In addition, the amount of sodium retained over a longer time scale was clinically insignificant, as evidenced by no significant change in the interdialytic weight following administration of 50 mEq of HS. PNa rose 12.7 + 1.3 mEq/L to a peak of 152.2 + 1.6 mEq/l in 54 + 2 seconds, returning to 3 + 0.3 mEq above baseline at 5 minutes. In conclusion, administration of HS up to the final 15 minutes of HD is safe therapy for hypotension and muscle cramps because it does not cause an increased interdialytic weight gain.

Adult↗

Experimental preeclampsia produced by chronic constriction of the lower aorta: validation with longitudinal blood pressure measurements in conscious rhesus monkeys.

OBJECTIVES: Our goals were (1) to determine whether hypertension, proteinuria, and glomerular endotheliosis can be produced by chronic reduction of lower aortic pressure in pregnant rhesus monkeys and (2) to study the time course of the development of hypertension by means of longitudinal arterial blood pressure measurements in conscious, unrestrained pregnant rhesus monkeys. STUDY DESIGN: Indwelling arterial catheters were placed at 103 +/- 4 days of gestation (term 160 days) for measurement of arterial pressure before and after reduction of lower aortic pressure. At 116 +/- 7 days lower aortic pressure was reduced by 24 +/- 11 mm Hg in 11 monkeys (experimental group) by a stricture on the aorta just below the renal arteries; six monkeys (controls) underwent a sham operation. Resting on the aorta just below the renal arteries; six monkeys (controls) underwent a sham operation. Resting pressures were measured three to five times per week by a tether-and-swivel system. RESULTS: Baseline arterial pressure averaged 81 +/- 6 mm Hg. In the experimental group four monkeys had adverse outcomes (one maternal death with severe hypertension, one abruptio placentae with stillbirth, and two spontaneous preterm deliveries with hypertension). There was one preterm delivery in the control group. Of the seven monkeys with aortic stricture who continued to term, four developed sustained hypertension (mean pressure 18 +/- 6 mm Hg above baseline), proteinuria, and moderate-to-severe glomerular endotheliosis. None of the controls had hypertension or proteinuria, but two had endotheliosis. CONCLUSION: These observations confirm that a syndrome resembling preeclampsia can be produced by a reduction of lower aortic pressure, and they demonstrate that the associated hypertension is not an artifact of anesthesia. This model may prove useful in studying the pathophysiologic mechanisms of preeclampsia.

Animals↗