Role of nitric oxide in relaxation of the longitudinal layer of rectal smooth muscle

PURPOSE: This study was designed to investigate the role of nitric oxide in neurogenic relaxation of the longitudinal layer of human rectal smooth muscle. METHODS: Tissue was obtained from the mid rectum of patients undergoing anterior resection for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isometric tension recording. In preliminary experiments to determine the response of strips to cholinergic, adrenergic, and potential excitatory agonists, strips were superfused with standard Krebs solution (37±0.5°C; pH, 7.4±0.05). Investigation of inhibitory, nonadrenergic noncholinergic responses required the addition of 3×10⁻⁶ M histamine to induce reproducible and stable tension for five-minute “test” periods, during which electrical field stimulation (EFS) and additional drugs were applied. In these experiments, strips were superfused with Krebs solution that contained atropine sulfate (3×10⁻⁶ M) and guanethidine (3×10⁻⁶ M). RESULTS: The response to cholinergic and adrenergic agonists was typical of nonsphincter specialized gastrointestinal smooth muscle. EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips, which were reduced in dose-dependent fashion by addition ofNω-nitro-l-arginine and restored by addition of 3×10 ⁻⁴ M l-arginine but not by d-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFS. CONCLUSION: Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inhibitory innervation mediated by nitric oxide. Supported and financed by the Medical Research Council, United Kingdom. John Stebbing is in receipt of a Medical Research Council Clinical Training Fellowship. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

The MRC OX-22- CD4+ T cells that help B cells in secondary immune responses derive from naive precursors with the MRC OX-22+ CD4+ phenotype

CD4+ T cells in the rat can be divided into two nonoverlapping subsets by their reactivity with the mAb MRC OX-22, which binds some of the high molecular weight forms of the CD45 antigen. The lineage relationship between subsets of CD4+ T cells expression different forms of CD45 has been a controversial issue for some time. Experiments described in this paper address this question using in vivo assays of T cell reactivity. Analysis of primary antibody responses in vivo show that it is MRC OX-22+ CD4+ T cells that are active in these assays, whereas antigen-primed T cells that provide helper activity for secondary antibody responses in vivo have the MRC OX-22- CD4+ phenotype. It is demonstrated that these memory T cells derive from MRC OX-22+ CD4+ T cell precursors and not from a putative separate lineage. It is concluded that with respect to the provision of help for B cells, MRC OX-22+ CD4+ T cells are precursors of memory cells with the phenotype MRC OX-22- CD4+.     

Diagnosis of traumatic cardiac contusion

Cardiac contusion following blunt chest trauma remains a diagnostic problem because of a lack of sensitive diagnostic tests. This study evaluated thallous chloride Tl 201 single-photon-emission computed tomography in a series of 48 patients following blunt chest trauma. Of the 48 patients, 23 had normal scans. None of these patients proved to have serious arrhythmias during three days of continuous monitoring. Of 25 patients with abnormal or ambiguous studies, five (20%) developed serious arrhythmias requiring therapy. Single-photon-emission computed tomography scanning thus was sensitive in indicating that group of patients at risk of serious arrhythmias, and may therefore prove to be a useful screening test to determine the need for hospitalization and arrhythmia monitoring following blunt chest trauma.     

The logical structure and validity of experimental designs in pharmacokinetics and clinical pharmacology

Much of the literature on research design in clinical pharmacology and pharmacokinetics emphasizes statistical concerns, thus suggesting that a primary ingredient of a valid research design is an appropriate plan for statistical analysis of data. However, statistical validity is only one of several ways to evaluate an experimental study. The present paper reviews the underlying logic and sources of invalidity of experimental drug research suggesting influences and factors which may deceive or lure an experimenter into erroneous conclusions.     

Alteration in myelin-associated proteins following spinal cord irradiation in guinea pigs.

The aim of this study was to investigate the pathological and cellular basis for radiation-induced myelopathy in guinea pigs by monitoring biochemical alterations in levels of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Guinea pigs were irradiated to the lumbar region with various doses of neutrons or cobalt gamma irradiation. The ED50s for paralysis were 17.2 Gy and 67.5 Gy for neutron and cobalt irradiation, respectively, and was histologically associated with demyelination. In spinal cords taken from animals at the onset of paralysis myelin basic protein levels were decreased in direct relationship to the radiation dose. The lowest doses to cause paralysis led to a 25% decrease in MBP levels. In a separate experiment, alterations in MBP were measured in the spinal cords over the time period leading up to paralysis. Surprisingly, decreases in MBP were found immediately after the end of the 4 week irradiation period. These early changes in MBP were not markedly dose dependent and occurred with nonparalyzing doses. Dose-dependent decreases were found only just before the onset of paralysis. CNPase activity measured in the same specimens showed changes that were essentially similar to those for MBP. In the CSF, MBP levels were essentially constant until onset of paralysis. This study showed that demyelination, as assessed by the levels of the myelin-associated proteins MBP and CNPase, can occur soon after spinal cord irradiation but that profound dose-dependent changes are seen only immediately preceding the onset of paralysis. Although increases in MBP in the CSF were associated with the onset of radiation-induced myelopathy, its assay is unlikely to predict this complication of irradiation.