A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.).

Silicon micromachined ultrasonic scalpel for the dissection and coagulation of tissue.

This work presents a planar, longitudinal mode ultrasonic scalpel microfabricated from monocrystalline silicon wafers. Silicon was selected as the material for the ultrasonic horn due to its high speed of sound and thermal conductivity as well as its low density compared to commonly used titanium based alloys. Combined with a relatively high Young's modulus, a lighter, more efficient design for the ultrasonic scalpel can be implemented which, due to silicon batch manufacturing, can be fabricated at a lower cost. Transverse displacement of the piezoelectric actuators is coupled into the planar silicon structure and amplified by its horn-like geometry. Using finite element modeling and experimental displacement and velocity data as well as cutting tests, key design parameters have been identified that directly influence the power efficiency and robustness of the device as well as its ease of controllability when driven in resonance. Designs in which the full- and half-wave transverse modes of the transducer are matched or not matched to the natural frequencies of the piezoelectric actuators have been evaluated. The performance of the Si micromachined scalpels has been found to be comparable to existing commercial titanium based ultrasonic scalpels used in surgical operations for efficient dissection of tissue as well as coaptation and coagulation of tissue for hemostasis. Tip displacements (peak-to-peak) of the scalpels in the range of 10-50 µm with velocities ranging from 4 to 11 m/s have been achieved. The frequency of operation is in the range of 50-100 kHz depending on the transverse operating mode and the length of the scalpel. The cutting ability of the micromachined scalpels has been successfully demonstrated on chicken tissue.

Biochemical alterations in livers of rats exposed to vinyl chloride.

Sprague-Dawley rats were exposed to vinyl chloride to determine the earliest sequential biochemical changes occurring with liver injury before anglosarcoma development. Activity of glucose-6-phosphatase, a key gluconeogenic enzyme in the liver microsomal fraction, decreased 25% with respect to controls after 70 h of exposure. Glucose-6-phosphate dehydrogenase activity increased twofold after more than 100 h of exposure. Nonprotein sulfhydryl levels (glutathione and/or cysteine) showed a slight but progressive elevation, whereas glutathione reductase activity increased 50-60% during exposure to vinyl chloride.NADPH-cytochrome c reductase and mixed function oxidase were unchanged in the same microsomal fraction. There markers of liver mitochondrial, cytosol, and microsomal function. No significant histological changes were found on light microscopic examination during this exposure period. However, with electron microscopy, dilation of rough endoplasmic reticulum was seen in the animals exposed for more than 137 h. These enzymatic changes are considered to reflect early hepatocellular adaptation to vinyl chloride exposure with very mild or limited hepatocellular injury in its earliest stage.

Selected prognostic variables for mammographic parenchymal patterns.

Conjecture exists about the influence of numerous risk-factors for breast cancer on mammographic parenchymal patterns. To allow more precise documentation of the common variables considered influential in alterations of breast parenchyma, we conducted a randomized retrospective analysis. Of 10,132 women participants in the Louisville Breast Cancer Detection Demonstration Project, every tenth participant was randomly selected for evaluation using SPSS statistical programming. Each accessioned patient had discriminant analysis for the risk factors of age, parity, age at birth of first child, family history, personal history, previous history of breast biopsy, and exogenous estrogen therapy. One-thousand-and-two women were examined for the significance of the selected prognostic variable association with Wolfe mammographic parenchymal patterns (WMPP). Each prognostic factor was tested by chi-square analysis for the low-risk pattern (N1P1) versus the high-risk pattern (P2DY). A high correlation existed between the age of patient and WMPP (P = 0.0002) in the subjects evaluated (50--85 years, mean 60). Similarly, a very significant correlation was evident between WMPP and parity (P = 0.0002), age at birth of first child (P = 0.0014), family history of breast cancer (P = 0.097), and history of previous breast biopsy (P = 0.0066). Little correlation existed between the Wolfe parenchymal pattern classification and a personal history of breast cancer (P = 0.7779) or the use of exogenous estrogens (P = 0.5776).