Dynamic response of the occipito-atlanto-axial (C0-C1-C2) complex in right axial rotation.

The torque-angular deformation in right axial rotation until failure of the ligamentous occipito-atlanto-axial complex subjected to variable loading rate (dynamic) axial torque was characterized using a biaxial MTS system. A special fixture and gear box that permitted right axial rotation of the specimen until failure without imposing any additional constraints were used to obtain the data. The specimens were divided into three groups and tested until failure at three different dynamic loading rates: 50, 100, and 400 degrees/s. A previous study by the authors provided data for quasi-static (4 degrees/s) loading conditions. The torque versus rotation curves can be divided into two straight regions and two transition zones. The plots clearly indicated that at loading rates higher than 4 degrees/s, the specimens became stiffer in the region of steadily increasing resistance prior to failure. The increase in stiffness was maximum at 100 degrees/s. The stiffness decreased somewhat at 400 degrees/s in comparison with 100 degrees/s, but this decrease was not significant. The resulting torque-right axial rotation curves were also examined to estimate the magnitude of maximum resistance (torque) and the corresponding angular rotation value. The average maximum resistance torque increased from 13.6 Nm at 4 degrees/s to 27.8 Nm at 100 degrees/s. The corresponding right angular rotation data (65-78 degrees), however, did not show any significant variation with loading rate. Posttest dissection of the specimens indicated that the type of injury observed was related to the rate of axial loading imposed on a specimen during testing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Checklist for the qualitative evaluation of clinical studies with particular focus on external validity and model validity

Background  

It is often stated that external validity is not sufficiently considered in the assessment of clinical studies. Although tools for its evaluation have been established, there is a lack of awareness of their significance and application. In this article, a comprehensive checklist is presented addressing these relevant criteria.     

Radiation therapy in the management of low-grade supratentorial astrocytomas

The records of 167 patients with grade 1 or 2 supratentorial pilocytic astrocytomas (41 patients), ordinary astrocytomas (91 patients), or mixed oligoastrocytomas (35 patients) diagnosed between 1960 and 1982 are retrospectively reviewed. The extent of surgical tumor removal was gross total or radical subtotal in 33 patients (20%) and subtotal or biopsy only in the remaining 134 patients (80%). Postoperative radiation therapy was given to 139 (83%) of the 167 patients, with a median dose of 5000 cGy (range 600 to 6500 cGy). Multivariate analysis revealed that a pilocytic histology was the most significant prognostic variable associated with a good survival. The 5- and 10-year survival rates were, respectively, 85% and 79% for the 41 patients with pilocytic astrocytomas compared to 51% and 23% for the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas. Postoperative irradiation did not appear to be associated with improved survival times in the patients with pilocytic astrocytomas; however, in the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas, those who received "high-dose" radiation (greater than or equal to 5300 cGy) had significantly better survival times than those who received "low-dose" radiation (less than 5300 cGy) or surgery alone. The 5- and 10-year survival rates were, respectively, 68% and 39% for the 35 patients receiving high-dose radiation, 47% and 21% for the 67 receiving low-dose radiation, and 32% and 11% for the 19 treated with surgery alone. The survival rate was poor for the 23 patients with ordinary astrocytomas and oligoastrocytomas who underwent gross total or radical subtotal tumor removal (14 of whom were also irradiated): 52% at 5 years and 21% at 10 years, with 19 of 23 patients developing tumor progression and dying 1 to 12 years postoperatively. In contrast, all 10 patients with pilocytic astrocytomas who had gross total or radical subtotal tumor removal alone were long-term survivors, with follow-up periods of about 4 to 25 years.     

Primary myocardial disease in the cat. A model for human cardiomyopathy.

Thirty-four cats with primary myocardial disease were studied. The cats were divided into two groups, depending on the clinical, hemodynamic, angiocardiographic, and pathologic findings. Group A consisted of those cats with hypertrophic cardiomyopathy and Group B consisted of those cats with congestive cardiomyopathy. Similarity in the characteristics of cardiomyopathy in the human cat was found. Both Group A and Group B consisted predominantly of mature adult male cats. The most common presenting signs were dyspnea and/or thromboembolism, systolic murmurs with gallop rhythms on auscultation, cardiomegaly with (Group A) or without (Group B) pulmonary edema, abnormal electrocardiograms, elevated left ventricular end diastolic pressures, and angiocardiographic evidence of mitral regurgitation with left ventricular concentric hypertrophy (Group A) or left ventricular dilatation (Group B). Some cats in Group A also had evidence of left ventricular outflow obstruction. The principal pathologic findings in these cats were left atrial dilatation, symmetric hypertrophy or asymmetric septal hypertrophy of the left ventricle (Group A), and dilatation of the four cardiac chambers (Group B). Aortic thromboembolism was commonly observed in both groups. These clinical and pathologic findings indicate that cardiomyopathy in the cat is similar to the two most common forms of cardiomyopathy in the human (hypertrophic cardiomyopathy, with and without obstruction, and congestive cardiomyopathy).     

Improvement of Accuracy in a High-Capacity, Six Degree-of-freedom Load Cell: Application to Robotic Testing of Musculoskeletal Joints

This study investigated a previously unaccounted for source of error in a high-capacity, six degree-of-freedom load cell used in multi-degree-of-freedom robotic testing of musculoskeletal joints, an application requiring a load cell with high accuracy in addition to high load capacity. A method of calibration is presented for reducing the error caused by changes in universal force-moment sensor (UFS) orientation within a gravitational field. Uncorrected, this error can exceed a magnitude of 1% of the full-scale load capacity—the manufacturer-stated accuracy of the UFS. Implementation of the calibration protocol reduced this error by approximately 75% for a variety of loading conditions. This improvement in load cell accuracy (while maintaining full load capacity) should improve both the measurement and control of specimen kinetics by robotic/UFS and other biomechanical testing systems. © 1999 Biomedical Engineering Society. PAC99: 8719Rr, 8780Vt, 0620Fn, 0620Dk, 8719Ff     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Taste receptor cells express pH-sensitive leak K+ channels

Two-pore domain K+ channels encoded by genes KCNK1-17 (K2p1-17) play important roles in regulating cell excitability. We report here that rat taste receptor cells (TRCs) highly express TASK-2 (KCNK5; K2p5.1), and to a much lesser extent TALK-1 (KCNK16; K2p16.1) and TASK-1 (KCNK3; K2p3.1), and suggest potentially important roles for these channels in setting resting membrane potentials and in sour taste transduction. Whole cell recordings of isolated TRCs show that a leak K+ (Kleak) current in a subset of TRCs exhibited high sensitivity to acidic extracellular pH similar to reported properties of TASK-2 and TALK-1 channels. A drop in bath pH from 7.4 to 6 suppressed 90% of the current, resulting in membrane depolarization. K+ channel blockers, BaCl2, but not tetraethylammonium (TEA), inhibited the current. Interestingly, resting potentials of these TRCs averaged -70 mV, which closely correlated with the amplitude of the pH-sensitive Kleak, suggesting a dominant role of this conductance in setting resting potentials. RT-PCR assays followed by sequencing of PCR products showed that TASK-1, TASK-2, and a functionally similar channel, TALK-1, were expressed in all three types of lingual taste buds. To verify expression of TASK channels, we labeled taste tissue with antibodies against TASK-1, TASK-2, and TASK-3. Strong labeling was seen in some TRCs with antibody against TASK-2 but not TASK-1 and TASK-3. Consistent with the immunocytochemical staining, quantitative real-time PCR assays showed that the message for TASK-2 was expressed at significantly higher levels (10-100 times greater) than was TASK-1, TALK-1, or TASK-3. Thus several K2P channels, and in particular TASK-2, are expressed in rat TRCs, where they may contribute to the establishment of resting potentials and sour reception.     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.