Binding characteristics of the new thromboxane A2/prostaglandin H2 receptor antagonist [3H]BAY U 3405 to washed human platelets and platelet membranes.

The new thromboxane A2 antagonist [3H]BAY U 3405 was characterized for its binding to washed human platelets and platelet membranes. In washed platelets the specific binding was reversible, selective and stereospecific, but not saturable. The dissociation constant (Kd) was 6 +/- 2.5 nM, the number of specific binding sites 1177 +/- 306 per platelet. Three structurally different thromboxane A2 (TXA2)/prostaglandin H2 (prostaglandin endoperoxide) (PGH2) receptor ligands completely inhibited the specific binding of [3H]BAY U 3405 in a concentration-dependent manner, indicating that the observed high affinity binding site is the TXA2/PGH2 receptor. In platelet membranes, however, specific [3H]BAY U 3405 binding showed saturability in addition to reversibility, selectivity, and stereospecifity. The Kd of the binding was 9.6 +/- 2.3 nM in kinetic studies and 8.7 +/- 3.7 nM in saturation studies, the inhibition constant (Ki) was 10 +/- 1.1 nM in displacement studies. The TXA2/PGH2 receptor agonists U 46619 and CTA2, and the antagonists Daltroban (BM 13505), I-PTA-OH and SQ 29548 all completely inhibited the specific binding of [3H]BAY U 3405 thus defining the observed binding site as the TXA2/PGH2 receptor. In conclusion, the data suggest that the previously reported TXA2 antagonism of BAY U 3405 is mediated by binding to a specific high affinity binding site of human platelets and platelet membranes that represents the TXA2/PGH2 receptor.     

Air accidents, pilot experience, and disease-related inflight sudden incapacitation

The epidemiology of sudden death, the etiology of inflight sudden incapacitation, and the influence of pilot age and experience on air accident rates are reviewed in order to determine the aeromedical emphasis needed to minimize accidents. Sudden deaths in men over age 35 are nearly all due to coronary artery disease, whereas in those under 35 years they are mostly due to hypertrophic cardiomyopathy. The incidence of fatal accidents from human error is, however, far greater than that from physical illness. Since inexperienced pilots have a 2-3 times increased incidence of mishaps due to pilot error, the estimated risk of disease related in-flight sudden incapacitation should be balanced by consideration of pilot experience. Therefore, it may be preferable to grant waivers to experienced pilots with an increased incidence of disease-related inflight sudden incapacitation than to replace them with novices. We conclude that overly strict medical criteria may paradoxically increase accident rates.     

Wilson's disease tremor is associated with magnetic resonance imaging lesions in basal ganglia structures.

Wilson's disease (WD) is an inherited disorder of copper metabolism yielding marked motor deficits, including a severely disabling tremor. As a structural correlate of the disease, a variety of cerebral abnormalities has been revealed. However, the relationship between motor deficits and cerebral lesions has remained largely unknown. Here, we investigated correlation between WD tremor and cerebral magnetic resonance imaging (MRI) findings. Cerebral MRI abnormalities in 6 symptomatic WD patients were compared to findings in 6 asymptomatic WD patients and 10 healthy controls. All patients were treated with long-term copper chelating therapy. Motor symptoms including tremor were determined by Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). MRI findings in symptomatic WD patients revealed significant symmetric T2*-weighted hypointense signal alterations of globus pallidus, head of the caudate nucleus, and substantia nigra. In contrast, MRI of asymptomatic WD patients did not differ from healthy controls. Correlation analysis revealed a significant positive correlation between MRI basal ganglia lesions and UPDRS action tremor score. Our results demonstrate for the first time that Wilson's disease tremor is associated with lesions of the globus pallidus, the head of the caudate nucleus, and the substantia nigra.     

Passive Pneumatic Stabilization Device for Assisting in Reduction of Femoral Shaft Fractures

Abstract During treatment of femoral shaft fractures, not only the actual fracture reduction but also the retention of the achieved reduction is essential. Substantial forces may apply to the bone fragments, due to multidirectional muscular contraction. Furthermore, forces from manipulation of one bone fragment may be transferred over the soft tissues onto the other fragments, thus hindering accurate fracture reduction. Once a sufficient reduction has been achieved, this position must be retained whilst definitive internal fixation is performed. Conventional methods comprise mounting patients on a traction table and applying manual distraction or employing special distraction devices, such as the AO distractor device. These approaches, however, only insufficiently stabilize both main fragments. For example, on the traction table the proximal femoral fragment can pivot around the hip joint thus complicating precise reduction. A novel pneumatic stabilization device to assist surgeons during operative procedures is described. This passive holding device “Passhold” connects to one main fragment through a minimally invasive bone interface and statically locks the fragment’s position. Thereafter, only the other main fragment is manipulated to achieve reduction. Mutual interference of the reciprocal fragment positions, due to soft-tissue force transfer during manipulation, is avoided. The authors examined the stability of the novel retention device on a test rig and proved its functionality under sterile settings using cadaver tests. It is concluded that this device largely facilitates the operative procedure in femoral shaft fractures, is sufficiently stable and ergonomically suitable for intraoperative deployment.     

Predicting work status following interdisciplinary treatment for chronic pain.

The effectiveness of interdisciplinary treatments for chronic pain is well established. In general, these treatments decrease psychosocial distress and increase physical abilities. Further, return to work rates following interdisciplinary treatment tend to be quite high. Previous studies have highlighted a number of factors that individually influence return to work rates; however, there is a need for more comprehensive and unified models that allow an evaluation of the inter-relations among these factors. The present investigation examined how demographic and treatment outcome variables interacted to influence post-treatment return to work rates in a sample of individuals with chronic pain following interdisciplinary treatment. Results indicated that patient age, lifting ability, pain duration, depression level, and reported disability were individually related to return to work; however, when these variables were evaluated relative to one another, level of depression and patient age had the best ability to predict post-treatment work status. These results add to the literature by specifically highlighting post-treatment factors that best discriminate patients who had returned to work from those that had not. Furthermore, they provide evidence that general emotional distress is perhaps the most important predictor of work status following treatment.     

Über die Brauchbarkeit Einiger Neueren Trübungs- und Flockungs-Reaktionen für die Serodiagnose der Syphilis

Zusammenfassung Auf Grund unserer vergleichenden Versuche empfehlen wir, neben der WaR. stets mehrere Trübungs- und Flockungsreaktionen auszuführen. Als recht brauchbar haben sich uns die Kahn-, Citochol- und Meinicke-Trübungs-Reaktion erwiesen, da sie schnell und leicht anzustellen und abzulesen und hinsichtlich Empfindlichkeit und Spezifität der WaR. gleichgestellt, in manchen Fällen sogar überlegen sind.     

Electrophysiology and metallosis: support for an oxidative (free radical) mechanism in the human eye

Nine cases of metal intraocular foreign body are presented. This study investigates the use of electrodiagnostic techniques in the diagnosis of metallosis and as a prognostic indicator. The electro-oculogram (EOG) and the electoretinogram (ERG) indicate that there are two mechanisms of metallosis, one of which involves cytotoxic damage by siderosomes, and the other lipid peroxidation of photoreceptor outer segments and retinal pigment epithelium. The evidence suggests that the location of the foreign body in the eye determines whether either or both of these mechanisms occur. We propose that these tests can help the ophthalmologist decide when a foreign body has to be removed and give information as to the mechanism of the pathological process.     

Rehospitalization for respiratory illness in infants of less than 32 weeks' gestation

All 133 surviving infants of gestational age less than or equal to 32 weeks born July 1, 1985, to June 30, 1986, as well as a socioeconomically matched full-term control group were observed prospectively for 2 years to determine the incidence of rehospitalization for respiratory illness. Perinatal and seasonal factors associated with increased risk for such hospitalizations were also examined. Forty-seven (36%) preterm infants were rehospitalized compared with 3 (2.5%) of 121 term infants (P less than .001). Preterm infants with and without rehospitalization were similar for mean birth weight (1104 +/- 329 g and 1188 +/- 360 g, respectively) and gestational age (28 +/- 2 weeks for both groups); however, infants who were subsequently rehospitalized had required more days of mechanical ventilation, supplemental oxygen therapy, and neonatal intensive care. While a history of bronchopulmonary dysplasia was a risk factor for rehospitalization (45% compared with 25% of those without bronchopulmonary dysplasia, P less than .05), preterm infants with no history of bronchopulmonary dysplasia still showed a 10-fold increase compared with control infants. Among the 43 infants who required no mechanical ventilation beyond the day of birth, 10 (23%) required rehospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization and phenotypic analysis of differentiating CD34+human bone marrow cells in liquid culture

Abstract: Our current understanding of human haematopoietic stem cell biology is based in part on the characterization of human CD34⁺ bone marrow cell differentiation in vitro. CD34 is highly expressed on early stem cells and haematopoietic progenitor cells with clonogenic potential and is gradually lost during differentiation and commitment. However, CD71 (transferrin receptor) is expressed at low levels on early stem cells and generally increases during haematopoietic progenitor cell proliferation. We reasoned that the combination of these surface markers would provide a useful framework for the simultaneous analysis of multiple lineage differentiation of CD34⁺ haematopoietic progenitor cells in liquid culture. In this report, we identify the phenotype of distinct subpopulations of myeloid, erythroid and lymphoid cells in liquid suspension culture using differential expression of CD34 vs. CD71 in combination with specific lineage markers. Freshly isolated human CD34⁺ bone marrow cells were introduced into suspension culture and monitored over a 6-d period using 3-colour flow cytometry. This is the first demonstration that differential expression of CD34 vs. CD71 can be used to simultaneously monitor differentiation of multiple haematopoietic cell lineages in liquid suspension culture, facilitating the study of cytokine-, drug- or chemical-induced alterations in haematopoietic progenitor cell differentiation in vitro.