Neuronal adrenergic and muscular cholinergic contractile hypersensitivity in canine jejunum after extrinsic denervation

Extrinsic denervation may be responsible for motor dysfunction after small bowel transplantation. The aim of this study was to examine the role of extrinsic innervation of canine jejunum on contractile activity. An in vitro dose response of cholinergic and adrenergic agonists was evaluated in canine jejunal strips of circular muscle at 0, 2, and 8 weeks in a control group and after jejunoileal extrinsic denervation (EX DEN). Neurons in circular muscle were quantitated by means of immunohistochemical techniques. Adrenergic and cholinergic responses did not differ at any time in the control group. However, at 2 and 8 weeks, extrinsic denervation caused an increased sensitivity to the procontractile effects of the cholinergic agonist bethanechol at the level of the smooth muscle cells, and increased sensitivity to the inhibitory effects of the adrenergic agent norepinephrine mediated at the level of the enteric nervous system. Immunohistochemical analysis showed a reduction in all neurons and a complete lack of adrenergic fibers in the EX DEN group after 2 and 8 weeks. Extrinsic denervation induces enteric neuronal cholinergic and adrenergic smooth muscle hypersensitivity in canine jejunal circular muscle. Presented in part at the annual meeting of the American Gastroenterological Association, Orlando, Florida, May 18, 1999 (poster presentation), and published as an abstract in Gastroenterology 116:A1075, 1999. Supported by United States Public Health Service grant DK39337 from the National Institutes of Health (M.G.S.); the Swiss National Science Foundation; the Swiss Society of Gastroenterology and Hepatology; the Swiss Foundation for Medical and Biological Science; the Novartis Foundation; Astra Zeneca Pharmaceuticals, Switzerland; and the Department of Visceral and Transplantation Surgery, University of Bern, Switzerland.     

Prolactin,growth hormone and insulin-like growth factor-l in newborn children of smoking mothers*

OBJECTIVE Since maternal smoking causes fetal circulatory abnormalities, as well as disturbances of the maternal endocrine equilibrium, we measured the PRL, hGH and insulin-like growth factor-l (IGF-I) concentrations in the cord and venous blood of neonates of smoking mothers to determine whether or not the tobacco smoke affects the endocrine status of the neonate. DESIGN The above hormones were measured in the cord blood of the newborns of both smoking and non-smoking mothers. Also, PRL and hGH were determined at 24 and 72 hours after birth in newborns of both groups. PATIENTS Fifty-three newborns of smoking and 47 newborns of non-smoking mothers were investigated. Seventeen of the newborns of the smoking and 21 of the nonsmoking mothers were preterm. The remainder were full-term. MEASUREMENTS PRL was measured with a solid-phase immunoradiometric assay, hGH with a solid-phase two-site immunoradiometric assay and IGF-I with a solid-phase radioimmunoassay after extraction with acid-etha-nol. RESULTS The median value of PRL in the 17 preterm newborns of smoking mothers was 4941 mU/l (range 1322-7230), whereas in the 21 preterm newborns of nonsmoking mothers it was 2013 mU/l (range 243-4740) (P = 0 0002). The median hGH value in the above subjects was 1020 mU/l (range 35 2-208 4) and 59 8 mU/l (range 11 6-134-2), respectively (P = 0 0039). The median IGF-I was 580 7 U/l (range 253 2-4851 1) and 530 6 U/l (range 239 6-3591 5), respectively (P = 0 429). In the 36 full-term newborns of smoking mothers the median PRL value was 5171 mU/l (range 2074-7530), whereas in the 26 full-term newborns of non-smoking mothers it was 5081 (range 244-6540) (P = 0 048). The median hGH was 69 6 mU/l (range 42 3-280 0) and 32 2 mU/l (range 6 2-200 0), respectively (P = 0 0031). Also, the median IGF-I value was 926 3 U/l (range 348 5-5344 7) and 462 1 U/l (range 250 2-1578 7), respectively (P = 00024). On the 3rd day the PRL in the preterm neonates of both smoking and non-smoking mothers showed the same 16-5% drop, and thus the difference between the groups was maintained. A similar reduction in the hormone levels was observed in the full term neonates. CONCLUSIONS The findings indicate that the maternal tobacco-smoking causes disturbances of the endocrine status of the fetus, as shown by the increased levels of PRL, hGH and IGF-I, which are more pronounced between 30 and 37 weeks of gestation than at term.     

Cloning and expression of SLC1OA4,a putative organic anion transport protein

AIM:To determine if novel bile acid transporters may be expressed in human tissues.METHODS:SLC10A1 (NTCP) was used as a probe to search the NCBI database for homology to previously uncharacterized ESTs. The homology search identified an EST (termed SLC10A4) that shares sequence identity with SLC10A1 and SLC10A2 (ASBT). We performed Northern blot analysis and RT-PCR to determine the tissue distribution of SLC10A4. SLC10A4 was cloned in frame with an epitope tag and overexpressed in CHO cells to determine cellular localization and functional analysis of bile acid uptake.RESULTS:Northern analysis revealed that SLC 10A4 mRNA is ubiquitously expressed fn human tissues with the highest levels of mRNA expression in brain,placenta, and liver. In SLC10A4-transfected CHO cells,immunoblotting analysis and immunofluorescence staining demonstrated a 49-kDa protein that is expressed at the plasma membrane and intracellular compartments.Functional analysis of SLC10A4 showed no significant taurocholate uptake in the presence of sodium when compared to untransfected CHO cells.CONCLUSION:To date, we have shown that this protein has no capacity to transport taurocholate relative to SLC1041; however, given its ubiquitous tissue distribution, it may play a more active role in transporting other endogenous organic anions.     

Physiotherapy rehabilitation of the smile after long-term facial nerve palsy using video self-modeling and implementation intentions.

OBJECTIVE: To improve smiling after long-term facial nerve palsy (FNP). Physiotherapy rehabilitation of an adapted (more symmetrical) smile was investigated in FNP subjects 1 year post-onset, using video self-modeling (video replay of only best adapted smiles) and implementation intentions (preplanning adapted smiles for specific situations). STUDY DESIGN AND SETTING: Prospective, blinded clinical trial. Facial-Nerve-Palsy Clinic. RESULTS: After video self-modeling: 1) reaction time (RT) to initiation of adapted smiles became 224 ms faster whereas RT for everyday (asymmetrical) smiles became 153 ms slower; 2) adapted smiles were completed 544 ms faster; 3) adapted smiles had higher overall quality, movement control, and symmetry ratings; and 4) Facial Disability Index scores also improved. Implementation intentions after video self-modeling ensured transfer of adapted smile to everyday situations. CONCLUSION: Following intervention the smile improved, with significant changes in availability, execution speed, and quality. SIGNIFICANCE: This study supports these rehabilitation techniques to maximize quality of smiling following FNP. EBM rating: B-2b.     

Determinants of staff job satisfaction of caregivers in two nursing homes in Pennsylvania

Background  

Job satisfaction is important for nursing home staff and nursing home management, as it is associated with absenteeism, turnover, and quality of care. However, we know little about factors associated with job satisfaction and dissatisfaction for nursing home workers.     

Resolution of skin fibrosis and joint contractures in aggressive diffuse systemic sclerosis using autologous stem cell transplantation

The use of haematopoietic stem cell transplantation (HSCT) has now expanded beyond the domain of haematological diseases. Increasingly, the benefits of intense immunosuppression in the management of severe autoimmune diseases are being recognized. In diffuse systemic sclerosis (SSc), there has been increasing evidence of the efficacy of HSCT in improving morbidity and mortality. We present the first Australian patient to undergo autologous HSCT for SSc and review the current literature in the use of HSCT in SSc. Remarkably, the patient had complete resolution of skin disease (modified Rodnan skin score 27/51–0/51), tenosynovitis, synovitis and myositis.     

LIMITATIONS OF RADIOTHERAPY IN THE DEFINITIVE TREATMENT OF SQUAMOUS CARCINOMA OF THE TONSILLAR FOSSA

Between 1970 and 1990, 104 patients with squamous cell carcinoma (SCC) of the tonsil were treated. The median age was 58 years and 80% of patients were males. Distribution among clinical stages was: stage I, 19 patients; stage II, 12 patients; stage III, 23 patients; and stage IV, 48 patients. More than 70% of patients had initial radiotherapy as definitive treatment irrespective of stage, reflecting the treatment philosophy over much of this period. The overall survival rate was 26% at 5 years, with survival being significantly affected by T stage, clinical stage and age. Clinical node status did not significantly affect survival rates. Good local control of T₁N₀ cancers was achieved with radiotherapy alone, but patients with more advanced cancers did poorly. We have now moved away from a non-selective policy and use initial surgery combined with postoperative radiotherapy in most patients, reserving radiotherapy alone for mainly early tonsil cancers.     

IL-12 and IL-23: master regulators of innate and adaptive immunity

Summary: Initiation of an effective immune response requires close interactions between innate and adaptive immunity. Recent advances in the field of cytokine biology have led to an increased understanding of how myeloid cell‐derived factors regulate the immune system to protect the host from infections and prevent tumor development. In this review, we focus on the function of interleukin (IL)‐23, a new member of the IL‐12 family of regulatory cytokines produced by activated macrophages and dendritic cells. We propose that IL‐12 and IL‐23 promote two distinct immunological pathways that have separate but complementary functions. IL‐12 is required for antimicrobial responses to intracellular pathogens, whereas IL‐23 is likely to be important for the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation. These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression.