Citations

Abstract Carpal instability can be defined as the lack of ligamentous and skeletal support adequate to maintain a wrist stable to external forces of pinch and grasp. This instability may be static or dynamic. It has been classified as (a) carpal instability, dissociated (CID), a situation in which one or more of the ligaments are torn, and (b) carpal instability, nondissociative (CIND), a situation in which the ligaments are intact but stretched. Carpal instability can also be the result of carpal bone malalignment from various causes. Arthroscopy can be particularly useful in assessing carpal instability, however arthrography with contrast medium, fluoroscopy, and stress loading should precede this arthroscopic assessment. Arthroscopy allows visualization of the volar radiocarpal and ulnocarpal ligaments of the wrist, and the arthroscopic examination can be combined with manual manipulation of the carpal bones to detect laxity of those ligaments, to examine stability of the scapholunate and lunotriquetral interosseous ligaments, and to show instability of the distal radioulnar joint.

Abstract The compliance, capacity, and the position of minimum intraarticular pressure were measured in 13 thawed, fresh‐frozen human elbows. The capacity of the joint capsule was 23 ± 4 ml. The intraarticular pressure was the lowest at 80° of flexion. Capsular rupture occurred at relatively low intraarticular pressures—80 ± 42 mm Hg. Knowledge of the capacity of the normal elbow joint combined with the fact that this joint capsule tends to rupture or permit extravasation of fluid into the periarticular soft tissues should be considered when infusing fluids during arthroscopy. Finally, the “resting position” of 80° of flexion minimizes capsular tension and therefore might contribute to the development of joint contracture associated with prolonged immobilization in this position. This would be consistent with the observation that patients with posttraumatic elbow stiffness have an average arc of flexion of 60–90°.

The purpose of this article is to determine the abilities of severely depressed elderly to consent to electroconvulsive therapy (ECT) and to investigate the impact of educational intervention on their capacity. Forty severely depressed adults referred for ECT, with Mini-Mental State Examination scores greater than 20, were recruited. Using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), decisional capacities were assessed at baseline and reassessed after education. Between the 2 assessments, all subjects received standard education, and half of the group was subsequently randomized to receive further education. At baseline, the geriatric group scored lower on understanding, reasoning, and choice and higher on appreciation. After education, all MacCAT-T scores increased for both age groups. Depressed elderly in the sample, as a group, had adequate decisional capacities to consent to ECT. They showed greater improvement in decisional capacity with education. The findings highlight the importance of providing education to the elderly to optimize their ability to give informed consent.

The authors evaluated the relationship between blood lactate accumulation and hemodynamics in a prospective controlled animal study. Seven healthy pigs were anesthetized and mechanically ventilated with a 0.6 fraction of inspired oxygen to achieve a normal PaCO 2 . Catheters for blood sampling, lactate infusion, and hemodynamic assessment were inserted into the femoral vein and femoral artery. Bolus infusions (466 µmol • kg — 1 over 1 minute) of a neutral solution of sodium lactate were given at 0, 30, 60, and 90 minutes. Each bolus was followed by continuous infusion of the same lactate solution (31.7 µmol • kg — 1 • min —1 after the first, with the rate doubled after each subsequent bolus). Arterial blood samples were drawn at baseline and at 30, 60, 90, and 120 minutes, with simultaneous hemodynamic assessment. Significant increases were seen in blood lactate (from 1.6 ± 0.4 mmol/L at baseline to 4.4 ± 0.8 at 30 minutes, 8.0 ± 1.0 at 60 minutes, and 14.4 ± 2.1 at 90 minutes), pH (from 7.40 ± 0.03 to 7.44 ± 0.05 at 30 minutes, 7.50 ± 0.05 at 60 minutes, and 7.56 ± 0.04 at 90 minutes), and HCO 3 — (from 28 ± 1.4 mmol/L to 30 ± 0.7 at 30 minutes, 34 ± 0.9 at 60 minutes, and 37 ± 1.2 at 90 minutes). PaCO 2 decreased significantly from 44 ± 3 torr at baseline to 40 ± 4.7 torr at 90 minutes. Blood pressure decreased after each lactate bolus, recovering within 2 minutes initially but not after later injections. Cardiac output, heart rate, and glucose increased significantly, mean arterial pressure and systemic vascular resistance decreased, and stroke volume did not change. Thus, the accumulation of blood lactate due to exogenous administration of a neutral solution of sodium lactate was associated with significant systemic vasodilation, increased cardiac output, increased heart rate, and metabolic alkalosis.

Homeostasis in the intact organism is achieved implicitly by repeated incremental feedback (inhibitory) and feedforward (stimulatory) adjustments enforced via intermittent signal exchange. In separated systems, neurohormone signals act deterministically on target cells via quantifiable effector-response functions. On the other hand, in vivo interglandular signaling dynamics have not been estimable to date. Indeed, experimentally isolating components of an interactive network definitionally disrupts time-sensitive linkages. We implement and validate analytical reconstruction of endogenous effector-response properties via a composite model comprising ( i ) a deterministic basic feedback and feedforward ensemble structure; ( ii ) judicious statistical allowance for possible stochastic variability in individual biologically interpretable dose–response properties; and ( iii ) the sole data requirement of serially observed concentrations of a paired signal (input) and response (output). Application of this analytical strategy to a prototypical neuroendocrine axis in the conscious uninjected horse, sheep, and human ( i ) illustrates probabilistic estimation of endogenous effector dose–response properties; and ( ii ) unmasks statistically vivid (2- to 5-fold) random fluctuations in inferred target-gland responsivity within any given pulse train. In conclusion, balanced mathematical formalism allows one to ( i ) reconstruct deterministic properties of interglandular signaling in the intact mammal and ( ii ) quantify apparent signal-response variability over short time scales in vivo . The present proof-of-principle experiments introduce a previously undescribed means to estimate time-evolving signal-response relationships without isotope infusion or pathway disruption.

Purpose To determine the effectiveness of an infusional chemotherapy regimen in patients with HIV-associated lymphoma treated before and after the use of highly active antiretroviral therapy (HAART) in routine clinical practice. Patients and Methods Ninety-eight assessable patients with HIV-associated intermediate- or high-grade non-Hodgkin’s lymphoma received cyclophosphamide 200 mg/m2/d, doxorubicin 12.5 mg/m2/d, and etoposide 60 mg/m2/d (CDE) given by continuous intravenous infusion for 4 days (96 hours) every 4 weeks plus filgrastim. Concurrent antiretroviral treatment consisted of the nucleoside analog didanosine in the first 43 patients enrolled before December 1996 (pre-HAART group), or HAART in the remaining 55 patients enrolled after that time (HAART group). Results Complete response occurred in 44 patients (45%; 95% CI, 35% to 55%). Failure-free survival and overall survival (OS) at 2 years was 36% (95% CI, 26% to 46%) and 43% (95% CI, 33% to 53%), respectively. At the time of the analysis, 30% in the pre-HAART group were alive compared with 47% in the HAART group; when adjusted for varying length of follow-up, patients in the HAART group had improved OS (P = .039). Patients in the HAART group experienced less grade 4 nonhematologic toxicity (22% v 42%; P = .037), thrombocytopenia (31% v 52%; P = .033), and anemia (9% v 27%; P = .021), and had fewer treatment-associated deaths (0% v 10%; P = .013). Conclusion Infusional CDE is an effective and potentially curative regimen for patients with HIV-associated lymphoma. Patients treated in the HAART era have less chemotherapy-associated toxicity and improved survival.

Intracellular trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) is a focus of attention because it is defective in most patients with cystic fibrosis. ΔF508 CFTR, which does not mature conformationally, normally does not exit the endoplasmic reticulum, but if induced to do so at reduced temperature is short-lived at the surface. We used external epitope-tagged constructs to elucidate the itinerary and kinetics of wild type and ΔF508 CFTR in the endocytic pathway and visualized movement of CFTR from the surface to intracellular compartments. Modulation of different endocytic steps with low temperature (16°C) block, protease inhibitors, and overexpression of wild type and mutant Rab GTPases revealed that surface CFTR enters several different routes, including a Rab5-dependent initial step to early endosomes, then either Rab11-dependent recycling back to the surface or Rab7-regulated movement to late endosomes or alternatively Rab9-mediated transit to the trans-Golgi network. Without any of these modulations ΔF508 CFTR rapidly disappears from and does not return to the cell surface, confirming that its altered structure is detected in the distal as well as proximal secretory pathway. Importantly, however, the mutant protein can be rescued at the plasma membrane by Rab11 overexpression, proteasome inhibitors, or inhibition of Rab5-dependent endocytosis.

Epithelial cells in vivo form tight cell-cell associations that spatially separate distinct apical and basolateral domains. These domains provide discrete cellular processes essential for proper tissue and organ development. Using confocal imaging and selective plasma membrane domain activation, the type I and type II transforming growth factor-β (TGFβ) receptors were found to be localized specifically at the basolateral surfaces of polarized Madin-Darby canine kidney (MDCK) cells. Receptors concentrated predominantly at the lateral sites of cell-cell contact, adjacent to the gap junctional complex. Cytoplasmic domain truncations for each receptor resulted in the loss of specific lateral domain targeting and dispersion to both the apical and basal domains. Whereas receptors concentrate basolaterally in regions of direct cell-cell contact in nonpolarized MDCK cell monolayers, receptor staining was absent from areas of noncell contact. In contrast to the defined basolateral polarity observed for the TGFβ receptor complex, TGFβ ligand secretion was found to be from the apical surfaces. Confocal imaging of MDCK cells with an antibody to TGFβ1 confirmed a predominant apical localization, with a stark absence at the basal membrane. These findings indicate that cell adhesion regulates the localization of TGFβ receptors in polarized epithelial cultures and that the response to TGFβ is dependent upon the spatial distribution and secretion of TGFβ receptors and ligand, respectively.