An anti-CD44 antibody does not enhance engraftment of DLA-identical marrow after low-dose total body irradiation

920 cGy total body irradiation (TBI) is adequate for consistently successful engraftment of marrow from dog leukocyte antigen (DLA)-identical littermates; however, the dose is inadequate to ensure a marrow graft from DLA-nonidentical unrelated donors. Such mismatched grafts are successful only after 1800 cGy, given in three fractions. While anti-T-cell reagents enhance engraftment of DLA-identical littermate marrow after 920 cGy, they fail to be effective in the DLA-nonidentical setting. However, a monoclonal antibody (mAb) to CD44, S5, was found to be very effective in enhancing engraftment of DLA-nonidentical marrow. The current study asked whether mAb S5 was also effective in the setting of DLA-identical littermate transplants. To this purpose, the TBI dose was lowered to 450 cGy, a dose after which 70% of such grafts failed. Four dogs were treated with antibody S5, 0.2 mg/kg on days −7 though −2 (per previously published protocol), given 450 cGy TBI followed by marrow grafts from their DLA-identical littermates. All four dogs rejected their grafts; two of these died from marrow aplasia, and two survived with endogenous marrow recovery. This result was not statistically significantly different from that in 17, historical (n = 5) and concurrent (n = 12), control dogs where 11 of 17 animals rejected. Even if ten experimental animals were transplanted and all six remaining dogs engrafted, the results still would not have been significantly different from control. This result is in contrast to the successful engraftment promoted by pretreatment with antibody S5 of DLA-nonidentical unrelated dogs, consistent with the notion that different host cells are involved in graft rejection in the two disparate histocompatibility settings.     

THE PITUITARY-LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early Intervention for Trauma: Current Status and Future Directions

Although psychological debriefing (PD) represents the most common form of early intervention for recently traumatized people, there is little evidence supporting its continued use with individuals who experience severe trauma. This review identifies the core issues in early intervention that need to be addressed in resolving the debate over PD. It critiques the available evidence for PD and the early provision of cognitive-behavioral therapy (CBT). Based on available evidence, we propose that psychological first aid is an appropriate initial intervention, but that it does not serve a therapeutic or preventive function. When feasible, initial screening is required so that preventive interventions can be used for those individuals who may have difficulty recovering on their own. Evidence-based CBT approaches are indicated for people who are at risk of developing posttraumatic psychopathology. Guidelines for managing acutely traumatized people are suggested and standards are proposed to direct future research that may advance our understanding of the role of early intervention in facilitating adaptation to trauma.     

Effect of calcium antagonist drugs on calcium currents in mammalian skeletal muscle fibers

The calcium channel-inhibiting drugs diltiazem, verapamil and nitrendipine represent three general classes of organic calcium antagonists. In the present study, the effect of these drugs on calcium currents (ICa++) in rabbit sternomastoid muscle fibers was examined. ICa++ were recorded at room temperature using a vaseline gap voltage clamp. ICa++ measured had similar kinetics to those reported in rat skeletal muscle, were partially blocked by 0.5 mM CdCI2 and could be reduced by substitution of Mg++ for Ca++. Diltiazem reversibly blocked ICa++ in a concentration-dependent manner with the 50% inhibitory concentration (IC50) being 63 microM. Verapamil was slightly more potent with approximately 50% block of ICa++ occurring at 10 microM. In contrast, nitrendipine at concentrations from 1 to 10 microM had no blocking action on ICa++, even after 20 min of exposure. Thus, although Ca++ channels in mammalian skeletal muscle fibers are readily blocked by cadmium, diltiazem and verapamil, these channels appear to be insensitive to the dihydropyridine compound nitrendipine.     

Membrane flow within the myelin sheath in IDPN neuropathy

This report describes some aspects of beta,beta'-iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X-ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross-sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X-ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane-membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer.     

Update on adolescent pregnancy in the Black community.

Adolescent pregnancy is a social issue that severely jeopardizes the quality of life for young parents and their children. It is estimated that if fertility rates remain unchanged, the United States will see a 26% increase in the number of adolescent pregnancies and births due to an increase in the adolescent population (Henshaw, 1996). With a disproportional rate of Black adolescents becoming pregnant, there is a need to examine factors related to the high adolescent pregnancy rate among the Black community. Black adolescent mothers and their children face additional adverse psychosocial effects due to healthcare disparities, a higher incidence of health problems, and an increase risk of financial hardship (Hogan, Astone, & Kitagawa, 1985; J. V. Horn, 1998; Morgan, Chapar, & Fisher, 1995). Although the teenage pregnancy rate has declined, it is important for practitioners to continue to implement interventions that promote abstinence and increase contraceptive use among sexually active adolescents.     

A path analysis of medical school and residency performance. Implications for housestaff selection.

The selection and subsequent performance of 212 internal medicine residents was examined by factor analysis and path analysis. A three-factor solution accounted for most of the variance among the nine selection variables. These three factors, labeled Board Scores, Faculty Evaluations, and Academic Distinction, were then combined with in-training residency performance evaluations and composite scores on the ABIM certifying examination to produce a comprehensive path model of house staff selection and performance. The Academic Distinction factor emerged as the strongest predictor of residency performance,; the Faculty Evaluations factor was also a significant component of the model. Standardized test scores correlated poorly with clinical performance. The data suggest that increased attention to the content of letters of reference could substantially improve their predictive validity. Other means of reporting subjective evaluations may also be needed to increase the stature of non-cognitive attributes in house staff selection decisions.     

Attentional Bias in Posttraumatic Stress Disorder

This study investigated preferential encoding of threat material in subjects with posttraumatic stress disorder (PTSD) with a modified dot-probe paradigm. This paradigm indexes attentional bias by measuring response latency to name neutral target words that are presented adjacent to or distant from threat words. Motor vehicle accident survivors with PTSD (n = 15), subclinical PTSD (n = 15), and low anxiety (n = 15) were required to name target words that were presented either adjacent to or distant from strong threat, mild threat, positive, and neutral words. PTSD subjects named targets faster when they were in close proximity to mild threat words. Results suggested that PTSD subjects' attention was drawn to the mild threat stimuli and are discussed in the context of network models of PTSD.