Neuromuscular activation patterns during treadmill walking after space flight

Astronauts adopt a variety of neuromuscular control strategies during space flight that are appropriate for locomoting in that unique environment, but are less than optimal upon return to Earth. We report here the first systematic investigation of potential adaptations in neuromuscular activity patterns associated with postflight locomotion. Astronaut-subjects were tasked with walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from their eyes after space flights of 8-15 days. Surface electromyography was collected from selected lower limb muscles and normalized with regard to mean amplitude and temporal relation to heel strike. In general, high correlations (more than 0.80) were found between preflight and postflight activation waveforms for each muscle and each subject: however relative activation amplitude around heel strike and toe off was changed as a result of flight. The level of muscle cocontraction and activation variability, and the relationship between the phasic characteristics of the ankle musculature in preparation for toe off also were altered by space flight. Subjects also reported oscillopsia during treadmill walking after flight. These findings indicate that, after space flight, the sensory-motor system can generate neuromuscular-activation strategies that permit treadmill walking, but subtle changes in lower-limb neuromuscular activation are present that may contribute to increased lower limb kinematic variability and oscillopsia also present during postflight walking.     

The role of glucose 6-phosphate in the control of glycogen synthase

Elevated blood glucose concentrations result in increased intracellular levels of glucose 6-phosphate in liver, skeletal muscle, and adipose tissue. In liver, blood glucose concentrations are the main factor in control of the synthesis of glycogen; insulin has only a potentiating effect. In skeletal muscle and adipocytes, glucose alone has little effect on the activity of glycogen synthase, the limiting enzyme in glycogen synthesis. However, insulin released as a result of elevated blood glucose stimulates the translocation of specific glucose transporters to the cell membrane, increases the uptake of glucose, and causes the covalent, dephosphorylation-mediated activation of glycogen synthase. We present evidence that elevated intracellular contents of glucose 6-phosphate provoke the activation of glycogen synthase in liver, muscle, and adipose tissue. In addition, glucose 6-phosphate may inhibit the phosphorylation of glycogen synthase by cyclic AMP-stimulated protein kinase. We show that the stimulated glucose uptake and phosphorylation appear to play a major role in the control by insulin of the enzymes involved in glycogen synthesis.     

The implantable cardioverter-defibrillator. A potential hazard for autopsy pathologists

The implantable cardioverter-defibrillator (ICD) is an implantable electronic device that has been proven to be safe and effective in treating various malignant tachyarrhythmias in susceptible individuals. As the use of ICDs becomes more widespread, more individuals with the implanted devices will be encountered at autopsy. Manipulation of an activated ICD can result in electrical shock. To avoid injury, pathologists must be properly prepared to deal with bodies containing activated ICDs. These devices can also provide valuable information that may be helpful in determining the cause and mechanism of death. Herein, we present information regarding the appropriate guidelines and safeguards for pathologists confronted with an activated ICD.     

Permissive hypercapnia with and without expiratory washout in patients with severe acute respiratory distress syndrome

BACKGROUND: Permissive hypercapnia is a ventilatory strategy aimed at avoiding lung volutrauma in patients with severe acute respiratory distress syndrome (ARDS). Expiratory washout (EWO) is a modality of tracheal gas insufflation that enhances carbon dioxide removal during mechanical ventilation by reducing dead space. The goal of this prospective study was to determine the efficacy of EWO in reducing the partial pressure of carbon dioxide (PaCO2) in patients with severe ARDS treated using permissive hypercapnia. METHODS: Seven critically ill patients with severe ARDS (lung injury severity score, 3.1 +/- 0.3) and no contraindications for permissive hypercapnia were studied. On the first day, hemodynamic and respiratory parameters were measured and the extent of lung hyperdensities was assessed using computed tomography. A positive end-expiratory pressure equal to the opening pressure identified on the pressure-volume curve was applied. Tidal volume was reduced until a plateau airway pressure of 25 cm H2O was reached. On the second day, after implementation of permissive hypercapnia, EWO was instituted at a flow of 15 l/min administered during the entire expiratory phase into the trachea through the proximal channel of an endotracheal tube using a ventilator equipped with a special flow generator. Cardiorespiratory parameters were studied under three conditions: permissive hypercapnia, permissive hypercapnia with EWO, and permissive hypercapnia. RESULTS: During permissive hypercapnia, EWO decreased PaCO2 from 76 +/- 4 mmHg to 53 +/- 3 mmHg (-30%; P < 0.0001), increased pH from 7.20 +/- 0.03 to 7.34 +/- 0.04 (P < 0.0001), and increased PaO2 from 205 +/- 28 to 296 +/- 38 mmHg (P < 0.05). The reduction in PaCO2 was accompanied by an increase in end-inspiratory plateau pressure from 26 +/- 1 to 32 +/- 2 cm H2O (P = 0.001). Expiratory washout also decreased cardiac index from 4.6 +/- 0.4 to 3.7 +/- 0.3 l.min-1.m-2 (P < 0.01), mean pulmonary arterial pressure from 28 +/- 2 to 25 +/- 2 mmHg (P < 0.01), and true pulmonary shunt from 47 +/- 2 to 36 +/- 3% (P < 0.01). CONCLUSIONS: Expiratory washout is an effective and easy-to-use ventilatory modality to reduce PaCO2 and increase pH during permissive hypercapnia. However, it significantly increases airway pressures and lung volume through expiratory flow limitation, reexposing some patients to a risk of lung volutrauma if the extrinsic positive end-expiratory pressure is not substantially reduced.     

Cisapride reduces neonatal postoperative ileus: randomised placebo controlled trial

AIM: To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery. METHODS: A prospective, randomised, double blind trial comparing rectal cisapride (1.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates. RESULTS: Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup. CONCLUSION: Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.     

Social phobia, avoidant personality disorder and atypical depression: co-occurrence and clinical implications

BACKGROUND: Increasing attention has been directed in recent years to the detection and treatment of psychiatric co-morbidity among depressed individuals. The overlap of social phobia (SP) and avoidant personality disorder (APD) has been well recognized and a relationship between these disorders and depression has been suggested. METHODS: The pattern and clinical implications of co-morbidity of SP and APD with major depressive disorder (MDD), diagnosed by DSM-III-R criteria, were studied among 243 out-patients presenting with depression. RESULTS: Overall, 26.7% of adults in our sample with MDD met criteria for SP and 28.4% for APD. Almost two-thirds of depressed adults meeting criteria for social phobia or avoidant personality disorder met criteria for both (SP+APD). Depressed adults who met criteria for both SP+APD exhibited a significantly higher proportion of atypical depression (54.8%) compared with those with neither SP nor APD (31.1%). Among depressed patients, the co-occurrence of SP with APD was also associated with an earlier age of onset of MDD, a greater number of comorbid Axis I diagnoses, and greater impairment of social adjustment and assertiveness. CONCLUSIONS: Results confirm the overlap of SP and APD in a depressed population and the high prevalence of these disorders in MDD. They suggest that depressed individuals with both SP and APD but not SP alone are at particularly high risk for atypical depression and for social dysfunction in excess of that caused by a current major depression.     

Reflex sympathetic function in cortisol-induced hypertension in humans

Nine healthy male subjects underwent measurement of reflex sympathetic function, pressor responsiveness and baroreflex sensitivity to phenylephrine (PE) and glyceryltrinitrate (GTN) before (C1) and following six days of treatment (E6) with cortisol (F), 200 mg/day. Seven subjects had washout studies (W) performed at least two weeks following the end of treatment. The BP responses to head tilt, isometric exercise and mental arithmetic were unaltered by F, however, there was a significant diminution of the diastolic BP response to cold pressor stimulus (delta DBP: 19 +/- 3 vs 25 +/- 5 vs 27 +/- 5 mmHg; E6 vs C1 vs W, p < 0.05 C1 vs E6 and W). Baroreflex sensitivity to PE was increased (28 +/- 3 vs 19 +/- 2 ms/mmHg, E6 vs C1, p = 0.03). These data demonstrate that increased BP during F treatment is not attributable to increased SNS activity, and suggest that SNS activity may be decreased by F.     

Autologous lymphokine-activated killer cell therapy of Epstein-Barr virus-positive and -negative lymphoproliferative disorders arising in organ transplant recipients

Lymphoreticular malignancies, collectively called posttransplant lymphoproliferative disorders (PTLD), eventually develop in 2-5% of organ transplant recipients. They frequently undergo regression when immunosuppression is reduced or stopped. This feature has been associated with a previous or de novo Epstein-Barr virus (EBV) infection. We herein describe immunotherapy with autologous lymphokine-activated killer (LAK) cells in seven patients with PTLD (four EBV-positive patients and three EBV-negative patients). Autologous peripheral blood mononuclear cells were obtained by leukapheresis, depleted of monocytes, and cultured in the presence of interleukin 2 for 10 to 11 days. A single dose of 5.2 x 10(9) to 5.6 x 10(10) LAK cells was given intravenously. Systemic interleukin 2 was not administered. The four patients with EBV+ PTLD had complete tumor regression; two of them developed controllable rejection. Three patients are well 13-16 months after treatment; the fourth patient died of pneumonia 41 days after infusion. Three patients with EBV- lymphomas had no response despite prior evidence that their tumors also were subject to immune surveillance. Two of these three patients died after being given other treatment, and the third patient has persistent tumor. In conclusion, autologous LAK cell infusion was effective for treatment of four EBV+ organ transplant recipients. LAK cell efficacy for three patients with EBV- PTLD was not evaluable under the management circumstances in which this treatment was utilized.     

Induction of cutaneous lymphocyte-associated antigen expression by group A streptococcal antigens in psoriasis

The cutaneous lymphocyte-associated antigen (CLA) has been proposed as a homing receptor for the selective migration of memory T cells into the skin. To investigate the effect of group A streptococci (GAS) on the migration of T cells in psoriasis, CLA expression was assessed by double-staining for CD3 and the HECA-452 epitope on peripheral blood T cells from 13 patients with psoriasis, 10 patients with other inflammatory skin diseases and 12 normal controls before and after 7 days culture with a GAS sonicate, Candida albicans (control antigen) or medium. In addition, CLA+, and CLA-, CD3+ CD45RO+ subsets were isolated from individuals in each group and V beta 2 expression and proliferation to GAS studied. Mean CLA expression by freshly isolated T cells was almost identical in the three groups. After culture with GAS, T cells from the psoriatic patients and control showed a significant increase in mean percentage CLA+ expression compared to medium (P < 0.002, P < 0.05, respectively). This induction was inhibited by the addition of anti-IL-12 antibody. However, in psoriatic patients, but not in controls, the GAS-induced increase was significantly greater than that of C. albicans (P < 0.002) and was accompanied by a decrease in T cells positive for the peripheral lymph node homing receptor, L-selectin (P < 0.05). The percentage of V beta 2+ T cells was markedly higher in the CLA+ than in the CLA- T-cell subset in psoriatic patients (P < 0.01) and controls; both subsets proliferated to GAS, in each group. These findings suggest a differential modulation of specific tissue homing receptors on T cells by GAS in psoriasis.