Experiences of supporting older persons in completion of an exercise and nutrition intervention: an interview study with nursing home staff.

BACKGROUND: The interactions between nursing home (NH) staff and their residents are crucial not only for the atmosphere at the NH but also for achieving care goals. In order to test the potential effects of daily physical activities (sit-to-stand (STS) exercises) combined with oral nutritional supplementation (ONS), a randomized intervention trial (the Older Person's Exercise and Nutrition (OPEN) Study) was performed in NH residents. One aspect of the study was to interview and report the NH staff's experiences of supporting the residents in fulfilling the intervention. METHODS: In this qualitative study, individual and focus group interviews were performed in eight NH facilities with NH staff who had assisted residents in performing the 12-week ONS/STS intervention. An interview guide developed for this study was used to assess staff experiences of the intervention and its feasibility. The transcribed interviews were analyzed inductively following a constant comparative method and with input from experts in the area, described in Grounded Theory as a reliable technique for researchers to form theory and hypothesis in unexplored areas. RESULTS: Three main themes relating to the health-promoting intervention emerged. These included: 1) insights into attitudes towards health in general and NH care specifically; 2) intervention-related challenges, frustrations and needs, and 3) aspects of collaboration and opportunities. The overarching hypothesis derived from the analysis reads: A health-promoting intervention such as the OPEN-concept has great potential for integration into NH life if a combined empathic and encouraging attitude, and a structure to keep it sustainable, are in place. CONCLUSIONS: NH staff experienced the health-promoting intervention as a potentially positive concept, although it was suggested that it works best if introduced as a general routine in the unit and is integrated into the daily planning of care. TRIAL REGISTRATION: ClinicalTrials.govIdentifier: NCT02702037 . Date of trial registration February 26, 2016. The trial was registered prospectively.

Participation in activities and secondary health complications among persons aging with traumatic spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe participation in activities and explore the relationship with secondary complications among persons aging with a traumatic spinal cord injury (SCI). SETTING: A regional SCI outpatient center in Sweden. METHODS: Data were collected through a phone survey, which included 10 activities from the instrument PARTS/M-v3 (PARTicipation Survey/Mobility version-3) together with data from the participants' medical records. Cross-tabulation and χ2 were used for data analysis. RESULTS: In this study, 121 persons matched the inclusion criteria and the final study sample comprised 73 participants (60% response rate): 55 men and 18 women. Mean age was 63.7±9.4 years, and mean time since injury was 36.3±9.2 years. Regardless of duration of SCI, all 73 participated in dressing, bathing and leisure activities. Women reported better health than men. Particularly for those who lived 36-55 years after injury; increasing pain, fatigue, spasticity and decreased muscle strength were negatively affecting participation in activities, especially exercise and active recreation. Additionally, a need to save strength/energy was also a reason for not participating in the activities. Perceived future support and concerns in relation to personal assistance, assistive devices and rehabilitation was also reported. CONCLUSION: Increasing secondary health complications and a need to save strength/energy influenced participation in activities. Laws and/or governmental policies regarding personal assistance and assistive devices did not always support participation in activities. Interventions should aim to create a balance among activities in everyday life.

RANTES promotes growth and survival of human first-trimester forebrain astrocytes.

We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferentially in human fetal astrocytes in an age-dependent manner. Astrocytes from 5-week-old brains showed high proliferation and reduced survival, whereas 10-week-old astrocytes exhibited opposite effects. These effects were suppressed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by recombinant RANTES. RANTES induced tyrosine phosphorylation of several cellular proteins and nuclear translocation of STAT-1 in astrocytes. Interferon-gamma (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gamma and only 10-week-old astrocytes expressed the IFN-gamma receptor. Blocking of IFN-gamma with antibody reversed the effects of RANTES, indicating that cytokine/chemokine networks are critically involved in brain development.

Do Malnutrition, Sarcopenia and Frailty Overlap in Nursing-Home Residents?

OBJECTIVES: To study the prevalence and overlap between malnutrition, sarcopenia and frailty in a selected group of nursing home (NH) residents. DESIGN: Cross-sectional descriptive study. SETTING: Nursing homes (NH). PARTICIPANTS: 92 residents taking part in an exercise and oral nutritional supplementation study; >75 years old, able to rise from a seated position, body mass index ≤30 kg/m2 and not receiving protein-rich oral nutritional supplements. MEASUREMENTS: The MNA-SF and Global Leadership Initiative on Malnutrition (GLIM) criteria were used for screening and diagnosis of malnutrition (moderate or severe), respectively. Sarcopenia risk was assessed by the SARC-F Questionnaire (0-10p; ≥4=increased risk), and for diagnosis the European Working Group of Sarcopenia in Older People (EWGSOP2) criteria was used. To screen for frailty the FRAIL Questionnaire (0-5p; 1-2p indicating pre-frailty, and >3p indicating frailty), was employed. RESULTS: Average age was 86 years; 62% were women. MNA-SF showed that 30 (33%) people were at risk or malnourished. The GLIM criteria verified malnutrition in 16 (17%) subjects. One third (n=33) was at risk for sarcopenia by SARC-F. Twenty-seven (29%) subjects displayed confirmed sarcopenic according to EWGSOP2. Around 50% (n=47) was assessed as pre-frail or frail. Six people (7%) suffered from all three conditions. Another five (5%) of the residents were simultaneously malnourished and sarcopenic, but not frail, while frailty coexisted with sarcopenia in 10% (n=9) of non-malnourished residents. Twenty-nine (32%) residents were neither malnourished, sarcopenic nor frail. CONCLUSIONS: In a group of selected NH residents a majority was either (pre)frail (51%), sarcopenic (29%) or malnourished (17%). There were considerable overlaps between the three conditions.

Acute management of traumatic spinal cord injury in a Greek and a Swedish region: a prospective, population-based study.

STUDY DESIGN: Prospective, population-based study. This paper is part of the Stockholm Thessaloniki Acute Traumatic Spinal Cord Injury Study (STATSCIS). OBJECTIVES: To characterize patient populations and to compare acute management after traumatic spinal cord injury (TSCI). SETTINGS: The Greater Thessaloniki region in Greece and the Greater Stockholm region in Sweden. METHODS: Inception cohorts with acute TSCI that were hospitalized during the study period, that is September 2006 to October 2007, were identified. Overall, 81 out of 87 cases consented to inclusion in Thessaloniki and 47 out of 49 in Stockholm. Data from Thessaloniki were collected through physical examinations, medical record reviews and communication with TSCI cases and medical teams. Data from Stockholm were retrieved from the Nordic Spinal Cord Injury Registry. RESULTS: There were no significant differences between study groups with regard to core clinical characteristics. In contrast, there were significant differences in (1) transfer logistics from the scene of trauma to a tertiary-level hospital (number of intermediate admissions, modes of transportation and duration of transfer) and (2) acute key therapeutic interventions, that is, the use of mechanical ventilation (49% in Thessaloniki versus 20% in Stockholm), and performance of tracheostomy (36% in Thessaloniki versus 15% in Stockholm); spinal surgery was performed significantly more often and earlier in Stockholm than in Thessaloniki. CONCLUSIONS: Despite largely similar core clinical characteristics, Stockholm and Thessaloniki cases underwent significantly different acute management, most probably to be attributed to adaptations to the differing regional approaches of care one following a systematic approach of SCI care and the other not.

Expression of the beta-nerve growth factor gene in hippocampal neurons.

In situ hybridization with complementary DNA probes for nerve growth factor (NGF) was used to identify cells containing NGF messenger RNA in rat and mouse brain. The most intense labeling occurred in hippocampus, where hybridizing neurons were found in the dentate gyrus and the pyramidal cell layer. The neuronal identity of NGF mRNA-containing cells was further assessed by a loss of NGF-hybridizing mRNA in hippocampal areas where neurons had been destroyed by kainic acid or colchicine. RNA blot analysis also revealed a considerable decrease in the level of NGF mRNA in rat dentate gyrus after a lesion was produced by colchicine. This lesion also caused a decrease in the level of Thy-1 mRNA and an increase in the level of glial fibrillary acidic protein mRNA. Neuronal death was thus associated with the disappearance of NGF mRNA. These results suggest a synthesis of NGF by neurons in the brain and imply that, in hippocampus, NGF influences NGF-sensitive neurons through neuron-to-neuron interactions.

Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system.

In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.

Clinician perceived good practice in end-of-life care for patients with COPD.

Patients with chronic obstructive pulmonary disease (COPD) have significant end-of-life needs, but are much less likely than patients with cancer to access or receive appropriate palliative care. Little is known about the existing availability or quality of available services within the United Kingdom. We surveyed 100 NHS acute hospitals enquiring into the provision of care for patients with COPD and requesting examples of current good practice that might be used to set standards. Forty-two percent of hospitals had formal palliative care arrangements for patients with COPD, whereas 59% had plans to develop or further develop services. Analysis of qualitative data suggested four strands that highlighted good practice; teams, care pathways, service components and linkages. These data may help to inform the debate leading to the development of standards in end-of-life care for patients with COPD.

Smoking during early pregnancy affects the expression pattern of both nicotinic and muscarinic acetylcholine receptors in human first trimester brainstem and cerebellum.

Prenatal nicotine exposure is associated with an increased risk of complications during pregnancy and childhood. In this study the expression of nicotinic and muscarinic acetylcholine receptors in first trimester pons, medulla oblongata and cerebellum from abortus (5-12 weeks of gestation) of smoking and nonsmoking women was compared. A significant age-related increase in binding of nicotinic receptor subtype alpha4 was found in both pons and cerebellum only in fetal tissue from non-smoking women, while a similar increase was observed in medulla oblongata from fetuses exposed to smoking. A significant age-related increase in binding of muscarinic receptor subtype m2 was observed in pons from abortus of smoking compared with non-smoking women. The gene expression pattern of both alpha4 and alpha7 nicotinic receptor subunits was changed after smoking in all three regions investigated. Smoking also changed the expression of m1 and 2 muscarinic receptor mRNA in pons, m1 mRNA in cerebellum and the m3 mRNA in medulla oblongata. The findings indicate that early prenatal nicotine exposure affects the normal developmental pattern of the cholinergic system in human fetal brain.

Spontaneous axonal regeneration in rodent spinal cord after ischemic injury.

Here we present evidence for spontaneous and long-lasting regeneration of CNS axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament (NF)-immunolabeled axons was estimated after photochemically induced ischemic spinal cord lesions using a stereological tool. The total length of all NF-immunolabeled axons within the lesion cavities was increased 6- to 10-fold at 5, 10, and 15 wk post-lesion compared with 1 wk post-surgery. In ultrastructural studies we found the putatively regenerating axons within the lesion to be associated either with oligodendrocytes or Schwann cells, while other fibers were unmyelinated. Immunohistochemistry demonstrated that some of the regenerated fibers were tyrosine hydroxylase- or serotonin-immunoreactive, indicating a central origin. These findings suggest that there is a considerable amount of spontaneous regeneration after spinal cord lesions in rodents and that the fibers remain several months after injury. The findings of tyrosine hydroxylase- and serotonin-immunoreactivity in the axons suggest that descending central fibers contribute to this endogenous repair of ischemic spinal cord injury.

Initial studies of embryonic transplants of human hippocampus and cerebral cortex derived from schizophrenic women.

Human fetal brain tissue was obtained from first-trimester elective abortions of two women who also had schizophrenia. Portions of the embryonic hippocampus or cerebral cortex were transplanted into the anterior eye chamber of immunologically compromised athymic nude rats. In this environment, embryonic brain tissue derived from normal women generally continues organotypic growth and development for many months. Although initial survival after transplantation was normal, the tissue derived from schizophrenic women manifested less robust growth. However, cells in the transplants showed typical neuronal differentiation, with development of different neuronal types, such as pyramidal cells, granule cells, and gamma-aminobutyric acid (GABA)-containing interneurons. Rhythmic electrical activity was also observed, indicative of some local synaptic organization. The presence of messenger RNA (mRNA) for brain-derived neuronotrophic factor (BDNF) was observed using in situ hybridization. The reason for the decreased rate of growth of these transplants remains unknown and the significance of the finding cannot be assessed from only two fetuses. However, these preliminary findings suggest that fetal transplants may be a useful model system for the detection of developmental pathogenic processes in the expression and transmission of schizophrenia.

Multiple changes in noradrenergic mechanisms in the coeruleo-hippocampal pathway during aging. Structural and functional correlates in intraocular double grafts.

Age-related changes of the coeruleo-hippocampal noradrenergic system were investigated using intraocular double transplants. Pieces of fetal hippocampus were grafted into the anterior chamber of the eye and placed into contact with previously inserted locus coeruleus grafts. Ages of both transplants and hosts were varied to enable studies of intrinsic versus extrinsic determinants of aging in an isolated neuronal circuit. Four different experimental groups, with the approximate age in months of grafts/hosts at the time of recording given in parentheses, were studied; young grafts in the eyes of young hosts (3/7), young grafts in the eyes of old hosts (3/23), mature transplants in adult host rats (8/12) and aged transplants in the eyes of aged rats (21/25). Extracellular recordings from the hippocampal part of the double grafts were performed. Superfusion with alpha-adrenergic antagonists and the alpha 2-agonist clonidine elicited significant increases in the discharge rate of the grafted hippocampal neurons in all groups except the aged transplants in the aged hosts (21/25), where a small excitation was elicited with clonidine and no effect at all was seen with alpha-adrenergic antagonists. The host age did not seem to be important since young transplants in the old hosts (3/23) showed a similar increase in discharge rate as transplants in the young and adult hosts. Tyrosine hydroxylase immunohistochemistry and high-performance liquid chromatography revealed that hippocampal transplants remaining in oculo for a minimum of 6-10 months became permanently hyperinnervated by noradrenergic fibers from the locus coeruleus grafts. The density of noradrenergic fibers was significantly lower in young transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of axonal ingrowth into area dentata as studied by sequential, double intraocular brain tissue transplantation.

The anterior eye chamber was used as a model environment to study, in isolation, the interaction of embryonic area dentata transplants with transplants of one of three important sources of in situ innervation: entorhinal cortex, locus coeruleus or septal nuclei. None of these brain regions significantly affected the morphogenesis or in oculo growth of area dentata transplants. All three brain regions innervated the area dentata transplant. Entorhinal cortical transplants sent nerve fibers into a limited, and apparently specific, region of area dentata that was adjacent to the entorhinal transplant. This light innervation contrasts to the predominant innervation of area dentata by entorhinal cortex in situ. The fluorescent, noradrenergic neurons of locus coeruleus provided the area dentata transplant with an abundance of fine varicose nerve fibers. Given about 100 noradrenergic neurons in the locus coeruleus transplant and 4 to 6 months joint survival, the area dentata transplant was noradrenergically hyperinnervated. The cholinergic neurons of the septal nuclei transplant had a prolific ingrowth of acetylcholinesterase (AChE)-positive nerve fibers to the area dentata transplant. There appeared to be a mutual exclusion between the extrinsic AChE-positive fibers and the intrinsic Timm's-positive granule cell mossy fibers in the area dentata transplant. We conclude that isolated replicas of the coeruleo-, septo-, and entorhinal cortico-dentate pathways can be made through sequential intraocular double grafting. The nature of the in oculo connectivity between these replicates offers clues as to the mechanisms that might account for the regulation of nerve growth.

Lingual BDNF and NT-3 mRNA expression patterns and their relation to innervation in the human tongue: similarities and differences compared with rodents.

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNAs are expressed in developing and adult rodent tongue and are important for the proper development of lingual gustatory and somatosensory innervation in rodents. Here, we wished to determine whether the findings in rodents apply to humans. By using in situ hybridization histochemistry, distinct, specific, and in some instances overlapping patterns of BDNF and NT-3 mRNA expression were found in the developing and adult human tongue, gustatory papillae, and taste buds. BDNF mRNA was expressed in the superior surface epithelium of the developing fungiform papillae (i.e., developing taste buds), in the epithelium covering the circumvallate papillae, and in the subepithelial mesenchyme. Interestingly, BDNF mRNA was expressed in the lingual epithelium before nerve fibers reached the epithelium, indicating a prespecialization of the gustatory epithelium before the arrival of nerves. In the adult fungiform papillae, BDNF mRNA labeling was found in taste buds and in restricted areas in the non-gustatory lingual epithelium. NT-3 mRNA was found in the developing lingual epithelium and gustatory papillae. NT-3 mRNA labeling was observed in the adult fungiform taste buds, overlapping with BDNF mRNA labeling, in contrast to what was seen in rodents. NT-3 mRNA was additionally found in restricted areas in filiform papillae. Protein gene product 9.5 (PGP) antibodies were used to investigate a possible correlation between lingual innervation and sites of neurotrophin gene activity. Adult human tongue innervation differed from that of rodents, possibly in part due to a different neurotrophin expression pattern in the human tongue. Based on these findings, we suggest that BDNF and NT-3 are important for the initiation and maintenance of the gustatory and somatosensory innervation also in humans. The broader and somewhat overlapping expression patterns of BDNF and NT-3 mRNAs, compared with rodents, suggest additional and possibly somewhat overlapping roles for BDNF and NT-3 in the human tongue and also indicate differences between species. It is important that interspecies differences be taken into consideration.

Appearance and distribution of neurofilament immunoreactivity in iris nerves.

We have used antiserum raised against neurofilament (NF) protein and indirect immunofluorescence techniques to visualize neuronal structures in rodent, cat, and cow irides. In the adult rat iris a large population of nerve fibers with a nonautonomic distribution show NF-like immunoreactivity. In whole mounts, smooth fluorescent fibers were seen in a fine-meshed plexus from the sphincter margin to the ciliary processes. Superimposed, a sparse pattern of thick meandering axon bundles were seen. Electroblotting and peroxidase immunochemical staining techniques unequivocally showed the presence of all three NF polypeptides in the adult rat iris. Adult mouse irides showed a somewhat sparser pattern of NF-positive nerves than that of the rat. Adult guinea pig irides contained irregular NF-positives fibers and few axon bundles. In cryostat-sectioned cat iris numerous irregularly distributed individual fibers were found, whereas in similarly sectioned cow iris thick NF-positive axon bundles were more numerous. By embryonic day 18 numerous sparse NF-positive axons were seen, and the subsequent gradual increase in both axons in bundles and fine-meshed plexuses of individual fibers produced an appearance similar to that in the adult by 6 days of postnatal age. One week after grafting of irides to the anterior eye chamber, most NF-positive nerves had disappeared from the iris grafts. Sympathetic and parasympathetic denervation of the irides did not influence the distribution of the NF-positive iris nerves. Five days after electrothermal lesion of the trigeminal nerve just distal to its ganglion a large proportion of the NF-positive nerves had disappeared from the iris. All perikarya in the parasympathetic ciliary and most perikarya in the superior cervical sympathetic and in the trigeminal sensory ganglion showed NF immunoreactivity. The present report shows a way to visualize nonautonomic nerve populations in stretch-prepared as well as sectioned irides by immunofluorescence techniques using an antiserum to neurofilament protein.

Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up.

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.

Chronic pain-related syndrome in rats after ischemic spinal cord lesion: a possible animal model for pain in patients with spinal cord injury.

We examined a pain-related syndrome, which includes mechanical allodynia and autotomy, in rats after ischemic spinal cord injury photochemically induced by laser irradiation for 5-20 min. This procedure results in an acute allodynia-like phenomenon which lasts for several days and is possibly related to dysfunction of the GABAB system in the spinal cord. In some animals this is followed by a chronic allodynia-like symptom with an onset varying between 1 week and 1.5 months after injury, expressed as a clearly painful reaction to light pressure applied to a skin area at or near the dermatome of the injured spinal segments. In the majority of rats the allodynia persists over several months, in some cases accompanied by autotomy of the hind paws. Pharmacological studies indicated that the allodynia in the majority of rats could be relieved by systemic tocainide (75 mg/kg). Morphine was only effective at a sedative dose (5 mg/kg). The allodynia was not relieved by baclofen, muscimol, clonidine or carbamazepine. Low-dose systemic pentobarbital (5 mg/kg) had a slight beneficial effect. Guanethidine (20 mg/kg, s.c.) did not abolish the allodynia in most of the rats. Histological examination revealed massive damage in the spinal cord. The dorsal roots of the irradiated segments were also injured. No morphological abnormalities were seen in the dorsal root ganglia. The mechanism that may account for this chronic pain-related syndrome in spinally injured rats probably involves abnormalities in the central nervous system. The allodynia seen in chronic spinally injured rats was similar to some painful symptoms in patients after spinal cord injury or stroke. It is suggested that the chronic allodynia-like phenomenon may represent an animal model for studying the mechanisms of chronic central pain.

Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation.

We report behaviours suggesting the presence of allodynia elicited by non-noxious brushing and mechanical pressure following photochemically induced ischaemic spinal cord injury in the rat. Female rats were intravenously injected with Erythrosin B and the T10 vertebra was irradiated with a laser beam for 1, 5 or 10 min. These procedures initiated an intravascular photochemical reaction, resulting in ischaemic spinal cord injury. After irradiation a clear allodynia was observed in most rats. The animals vocalized intensely to light touch during gentle handling and were clearly agitated to light brushing of the flanks. The vocalization threshold in response to the mechanical pressure measured with von Frey hairs was markedly decreased during this period. In some animals the existence of spontaneous pain was suggested by spontaneous vocalization. The duration of the allodynia varied among animals from several hours to several days. The severity and duration of allodynia seemed not to be related to the duration of irradiation. In sham-operated rats a slight, transient allodynia was also noted around the wound within a few hours after surgery, which was effectively relieved by systemic morphine (2 mg/kg, i.p.). Morphine (2 mg/kg, i.p.) also partially relieved the allodynia in spinally injured rats 4 h after irradiation. However, morphine, even at a higher dose (5 mg/kg, i.p.), failed to alleviate the allodynia in spinally injured rats 24-48 h after the injury. Systemic injection of the GABAB agonist baclofen (0.01-0.1 mg/kg, i.p.), but not the GABAA agonist muscimol (1 mg/kg, i.p.), effectively relieved allodynia during this period. Pretreatment with guanethidine 24 h and just prior to the irradiation (20 mg/kg, s.c.) did not prevent the occurrence of allodynia in spinal cord injured rats. The present observation is the first to show that ischaemic spinal cord injury could result in cutaneous mechanical allodynia. This phenomenon is resistant to morphine and may not involve the sympathetic system. Histological examination of allodynic animals 3 days after spinal cord injury revealed considerable morphological damage in the dorsal spinal cord of a rat irradiated for 5 min. The related dorsal roots were also slightly affected in this animal, while the dorsal root ganglia were normal. However, in rats irradiated for 1 min, despite the existence of strong allodynia, no damage could be found at this time in the spinal cord, dorsal roots or dorsal root ganglia. It is suggested that functional deficits in the GABAB system in the spinal cord may be related to this allodynia-like phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)

Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies.

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy. In one fetus with alpha-thalassemia, one with sickle cell anemia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11. The fetus with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4 x 10(8) cells/kg) and in the 31st weeks of gestation (1.2 x 10(8) cells/kg), and is now two years of age. One fetus with sickle cell anemia received its transplant in the 13th week of gestation (16.7 x 10(8) cells/kg), and is now one year old. The fetus with beta-thalassemia was transplanted in 18th week (8.6 x 10(8) cells/kg), and is now three months old. Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PCR (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alpha- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 months of age, respectively. In neither of these cases were we able to detect convincing evidence of stem cell engraftment. Thus, the administration of fetal stem cells to fetal recipients after the 12th week of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earlier transplantations and/or higher cell doses.

Neurofilament and glial fibrillary acid protein-related immunoreactivity in rodent enteric nervous system.

Using antisera raised against neurofilaments and the glial fibrillary acidic protein (GFAP) we have examined the appearance and distribution of neurofilament- and GFAP-like immunoreactivity in the enteric nervous system of rat, mouse and guinea-pig. In whole mounts of the external circular and longitudinal muscle layers, including the myenteric plexus, a high number of neurofilament-positive perikarya were visualized both in the ganglia and in the circularly running interconnecting strands in all three species. These cells were large, usually with eccentrically placed nuclei and single, relatively thick neurofilament-positive processes. In addition, in guinea-pig myenteric plexus a small number of cells with multiple processes could be seen. Both in the longitudinal and circular interconnecting strands a large number of thin, smooth, neurofilament-positive fibres were observed. This regular network of ganglia and strands was superimposed on a sparse system of thin, usually individual neurofilament-positive fibres in the underlying circular muscle layer. Cryostat sections revealed neurofilament-positive cell bodies in the submucous plexus, whereas fibres showing neurofilament-like immunoreactivity were observed in all layers of the gut wall, with the exception of the epithelium. In whole mounts including rat and mouse myenteric plexus, a large number of cells and fibres showing GFAP-like immunoreactivity were visualized. The GFAP-positive cells were smaller and more numerous than the neurofilament-positive ones. They were present both within the ganglia and in the interconnecting strands. Several short fluorescent processes could frequently be seen emanating from the cell body. Both the strands and the ganglia contained a high number of thin, GFAP-positive fibres. Fluorescent fibres and cells were also observed in the circular muscle layer. In sections of rat and mouse small intestine, cells were observed throughout the gut wall, with the exception of the epithelium. Double labelling experiments clearly showed that neurofilament- and GFAP-positive cells represented separate cell populations. Furthermore, GFAP-positive cells and fibres outlined the neurofilament-positive perikarya. It is thus likely that the GFAP-positive cells represent enteric glial cells. The pre- and postnatal development of neurofilament- and GFAP-like immunoreactivity was studied in whole mounts from rat embryos and pups. Furthermore, the presence of neurofilament and GFAP-positive fibres was observed in whole mount preparations of rat and mouse mesenterium.(ABSTRACT TRUNCATED AT 400 WORDS)