Mara Shochina

The Effectiveness of Locomotor Therapy Using Robotic-Assisted Gait Training in Subacute Stroke Patients: A Randomized Controlled Trial

To evaluate the effectiveness of early and prolonged locomotor treatment with the use of a robotic‐assisted gait training (RAGT) device (Lokomat; Hocoma Inc., Zurich, Switzerland) on the functional outcomes of patients after subacute stroke.

Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease.

AIMS: To study the localisation of the endothelial nitric oxide synthase (eNOS) in the normal placenta, with special emphasis on the implantation site in the first trimester of pregnancy, and in the different subtypes of trophoblastic cells in gestational trophoblastic disease. METHODS: The immunoperoxidase technique with an antibody directed against eNOS was applied to paraffin sections from first and second trimester placentas, placenta accreta, partial and complete hydatidiform moles, and choriocarcinoma. Immunoperoxidase staining for human placental lactogen (hPL) was performed on parallel sections. RESULTS: Prominent immunoreactivity for eNOS was found to be present in the intermediate trophoblastic cells of the cell columns of the anchoring villi and in trophoblastic cells at the implantation site. Staining was also present in the syncytiotrophoblast, most conspicuous at the apical cell border. In trophoblastic disease, proliferating large mononuclear cells, which were strongly positive for hPL, were found to be immunoreactive for eNOS. CONCLUSIONS: eNOS immunoreactivity is strongly positive in the extravillous trophoblastic cells and to a lesser extent in the syncytiotrophoblast. In the former it may play a role in implantation and vascular invasion. Cells with differentiation to intermediate trophoblast in complete hydatidiform mole and choriocarcinoma also show high levels of eNOS, which may be associated with the haematogenous mode of spread of trophoblastic disease.

Heat acclimated hypohydrated rats: Age dependent vasomotor and plasma volume responses to heat stress

Abstract 1. 1. Heat tolerance, tail blood flow ( T t ), plasma volume (PV) and heart rates (HR) of heat stressed (at 40°C) young (YR) and 15 months old (OR) rats were measured before and after acclimation to heat (1 month at 34°C) with and without additional hypohydration stress. 2. 2. During heat stress, in non-acclimated rats, tail vasodilation in OR lagged behind YR, although T t vs rectal temperature ( T re ) were similar. Following hypohydration, vasomotor response of OR was retarded compared to that of hypohydrated YR and heat tolerance was significantly shorter. 3. 3. Heat acclimation improved heat tolerance of hypohydrated OR only (182 ± 31 min , compared with 166 ± 31 and 109 ± 15 for the hypohydrated non-acclimated YR and OR, respectively). Under that condition vasomotor differences between YR and OR disappeared. 4. 4. Heat induced plasma expansion of OR at the initiation of heating was smaller in OR both before and after acclimation. However, following hypohydration PV expansion was observed in OR only. 5. 5. It is suggested that the improved endurance of acclimated OR under condition of heat stress and hypohydration is associated with greater PV reserves and improved vasomotor response.

The effects of hibernation on the myenteric plexus of the golden hamster small and large intestine

Abstract We have examined the effects of hibernation on the neurochemical composition of myenteric neurones in the small and large intestine of the golden hamster using immunohistochemical and histochemical techniques. Hibernation was induced in golden hamsters by altering the photoperiod and external ambient temperature. Age-matched hamsters kept at room temperature and those kept at 5°C but which failed to hibernate were used as controls. Cell counts were carried out to examine possible changes in the numbers of cell bodies immunoreactive to all of the markers examined. The results demonstrated a significant increase during hibernation in the number of neurones immunoreactive to vasoactive intestinal polypeptide, substance P and calcitonin gene-related peptide; cell bodies positive for tyrosine hydroxylase, which were largely absent in the control animals, were prominent in the hibernating animals. There was a significant decrease in the number of neurones immunoreactive to 5-hydroxytryptamine, and no significant changes in the numbers of neurones immunoreactive to protein gene-product and nitric oxide synthase. It is suggested that selective upregulation and downregulation of myenteric neurones containing certain neurotransmitters may occur as a protective mechanism during hibernation to maintain the integrity of the muscular and mucosal layers of the intestine in the absence of luminal contents.

Cognitive and functional outcomes of terror victims who suffered from traumatic brain injury

Primary objective: To describe the outcomes of terror victims suffered from traumatic brain injury (TBI). Research design: Retrospective chart review of 17 terror and 39 non-terror TBI patients treated in a rehabilitation department during the same period. Methods and procedure: Variables include demographic data, Injury Severity Scale (ISS), length of stay (LOS) and imaging results. ADL was measured using the Functional Independence Measurement (FIM), cognitive and memory functions were measured using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) battery and the Rivermead Battery Memory Test (RBMT), respectively. Main outcome and results: Terror TBI patients were significantly younger, had higher ISS score and higher rates of intracerebral haemorrhage (ICH), brain surgery and penetrating brain injuries than the non-terror TBI group. There was no difference in mean LOS, mean FIM values, mean FIM gain and mean cognitive and memory improvement between groups. Terror victims suffered from a higher percentage of post-traumatic epilepsy (35% vs. 10%, p= 0.05), whereas the rate of PTSD and the rate of return to previous occupation were similar between groups. Conclusions: Although TBI terror victims had more severe injury, they gained most of ADL functions and their rehabilitation outcomes were similar to non-terror TBI patients. These favourable results were achieved due to a comprehensive interdisciplinary approach to terror victims and also by national support which allowed an adequate period of treatment and sufficient resources as needed.

Immunoreactivity for nitric oxide synthase and endothelin in the coronary and basilar arteries of renal hypertensive rats.

Abstract.The ultrastructural localization of immunoreactivity to nitric oxide synthase (type-III and type-II) and endothelin-1 was examined by using pre-embedding peroxidase-antiperoxidase techniques in the coronary and cerebral basilar arteries in renal hypertensive rats. Renal hypertension was produced by excision of the right kidney and clipping of the left renal artery. Controls were normotensive sham-operated rats (right surgical nephrectomy; a clip inserted near the left renal artery). Both in controls and hypertensive rats, immunoreactivities for nitric oxide synthase-III and endothelin-1 were localized within subpopulations of endothelial cells. In addition, signs of translocation of nitric oxide synthase-III were noted from the cytoplasm to the Golgi complex in endothelial cells of the basilar artery of hypertensive animals. Neither controls nor hypertensive rats showed immunoreactivity for nitric oxide synthase-II. Preparations of the right coronary artery from hypertensive rats displayed fewer endothelial cells positive to nitric oxide synthase-III than in controls, although there were no significant changes in the distribution of endothelin-1-positive endothelial cells in the coronary artery of hypertensive rats. In contrast, the basilar artery from hypertensive rats displayed no changes in the percentage of endothelial cells immuno-positive either for nitric oxide synthase-III or for endothelin-1. In consequence, the ratio of nitric oxide synthase-III:endothelin-1 was reduced in the coronary but not in the basilar artery. Therefore, the nitric oxide/endothelin-1 system appears to play different roles in the coronary and cerebral circulations during renal hypertension.

Heat acclimation and hypohydration in aged rats: The involvement of adrenergic pathways in thermal-induced vasomotor responses in the portal circulation

Abstract 1. 1. The beneficial effects of heat acclimation on thermal induced vasomotor responses of hypohydrated aged rats were assessed by measuring the isometric tension of aortic and portal rings of old and young rats under heat acclimation and hypohydration in response to α-adrenergic (α-AR) and β-adrenergic (β-AR) stimulation (phenylephrine 10 −9 –10 −2 mM and isoprenaline 10 −9 –10 −4 respectively). In parallel, portal blood flow (PBF), which drains the splanchnic vasculature, was measured in conscious rats, before and during heat stress (42°C). 2. 2. In the aorta, heat acclimation augmented phenylephrine (α-AR) induced tension, to a great extent in the older rats. Hypohydration increased α-AR sensitivity in all experimental groups. Acclimation and aging brought about decreased responsiveness in isoprenaline induced relaxation (β-AR) in both the aorta and the portal vein. Hypohydration increased β-AR responsiveness in the portal vein of OR, acclimated and acclimated-hypohydrated rats. 3. 3. Normothermic euhydrated resting PBF was similar for young and old rats. Hypohydration decreased resting PBF. Upon heat stress, thermal induced vasoconstriction in hypohydrated YR and OR occurred earlier than in the euhydrated groups and was more pronounced. The latter responses were attenuated in the old rats. 4. 4. Taken together, these results imply that chronic environmental stressors such as heat acclimation and hypohydration produce selective alterations in AR responsiveness of the vasculature in both young and old rats. Consequently, thermoregulatory vasomotor mediated mechanisms, as exhibited in this study in PBF, may differ in their responsiveness in these two age groups.

Neurochemical coding in the myenteric plexus of the upper gastrointestinal tract of hibernating hamsters.

As part of our investigation of the plasticity of autonomic nerves in physiological and pathological conditions, we have examined the effect of hibernation on the neurochemical content of myenteric nerves and nerve cell bodies of the upper gastrointestinal tract of the non‐seasonal hibernator, the golden hamster. Age matched hamsters kept at room temperature and those kept at 5°C but failed to hibernate, were used as controls. Possible changes in nerve fibers and nerve cell bodies containing the general neuronal marker, protein gene product 9.5, the peptides, vasoactive intestinal polypeptide, substance P (SP) and calcitonin gene‐related peptide (CGRP), the catecholamine synthesizing enzyme tyrosine hydroxylase and the enzyme responsible for synthesizing nitric oxide, nitric oxide synthase, were examined in the oesophagus, proventriculus and proximal and distal stomach of the golden hamsters using immunohistochemical techniques. The results of the present study revealed a significant increase in the number of nerve cell bodies and density of nerve fibers containing SP‐immunoreactivity and increased number of CGRP‐immunoreactive cell bodies but not the other markers examined in the proximal stomach and proventriculus. In contrast, there was no change in the distribution of any of the neuroactive substances examined in the myenteric plexus of the oesophagus and distal stomach. It is suggested that the change in the environment of the hibernating hamsters perturbs the normal digestive physiology in the proximal stomach and proventriculus that is reflected by the selective changes in SP‐ and CGRP‐containing enteric nerves; these changes may be part of protective reflex mechanisms to the environmental changes resulting from hibernation, where upgrading of nerve cell bodies expessing CGRP and SP has occurred.

Paper presentationCourse 215. Stroke research and clinical pearlThe Effectiveness of Locomotor Therapy Using Robotic-assisted Gait Training in Subacute Stroke Patients: A Randomized Controlled Trial

Disclosures: Z. Meiner, None. Objective: To evaluate the effectiveness of early and prolonged locomotor treatment using a robotic-assisted gait training (RAGT) device (Lokomat) on the functional outcomes of subacute stroke patients. Design: A non-blinded prospective, randomized, controlled study. Setting: Rehabilitation department in tertiary university medical center. Participants: Sixty-seven subacute stroke patients in the first 3 months following the stroke were randomized into 2 groups as follows. Thirty-seven patients were treated by RAGT and 30 were treated by regular physiotherapy. Inclusion criteria were first stroke, independent ambulation before the stroke, and neurological severity between 6 and 20 according to the National Institutes of Health Stroke Scale (NIHSS). Interventions: RAGT treatment was administered 3 times a week for 30 minutes, combined with regular physiotherapy for 6 weeks. Control patients received the equivalent additional time of regular physiotherapy. Main Outcome Measures: The primary outcome was the ability to walk independently, assessed by the Functional Ambulatory Capacity scale (FAC). The secondary outcomes included the neurological status according to the NIHSS, functional motor assessment using the Stroke Activity Scale (SAS), and gait parameters including gait velocity, endurance, and number of climbed stairs. Results: In the intention-to-treat analysis the RAGT group exhibited greater gains than control group in their ability to walk independently, as expressed by a higher FAC score (P .01) and in their neurological status according to NIHSS (P .01). Among those who achieved independent walking, non significant differences between groups were noted according to secondary outcome measures of gait parameters except from step climbing. Conclusions: This controlled study showed that 6 weeks of locomotor therapy using RAGT combined with regular physiotherapy was superior to regular physiotherapy alone in achieving functional walking ability in subacute stroke patients.

Heat Acclimatization Protects the Left Ventricle from Increased Diastolic Chamber Stiffness Immediately after Coronary Artery Bypass Surgery: A Lesson from 30 Years of Studies on Heat Acclimation Mediated Cross Tolerance

During the period of 1986–1997 the first 4 publications on the mechanical and metabolic properties of heat acclimated rats heart were published. The outcome of these studies implied that heat acclimation, sedentary as well as combined with exercise training, confers long lasting protection against ischemic/reperfusion insult. These results promoted a clinical study on patients with coronary artery disease scheduled for elective coronary artery bypass operations aiming to elucidate whether exploitation of environmental stress can be translated into human benefits by improving physiological recovery. During the 1998 study, immediate-post operative chamber stiffness was assessed in patients acclimatized to heat and low intensity training in the desert (spring in the Dead Sea, 17–33°C) vs. patients in colder weather (spring in non-desert areas, 6–19°C) via echocardiogram acquisition simultaneous with left atrial pressure measurement during fast intravascular fluid bolus administration. We showed that patients undergoing “heat acclimatization combined with exercise training” were less susceptible to ischemic injury, therefore expressing less diastolic dysfunction after cardiopulmonary bypass compared to non-acclimatized patients. This was the first clinical translational study on cardiac patients, while exploiting environmental harsh conditions for human benefits. The original experimental data are described and discussed in view of the past as well as the present knowledge of the protective mechanisms induced by Heat Acclimation Mediated Cross-tolerance.