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31.
Daniel G. Lang Aileen K. Ritchie 《Pflügers Archiv : European journal of physiology》1987,410(6):614-622
Single Ca2+-activated K+ channels were studied in membrane patches from the GH3 anterior pituitary cell line. In excised inside-out patches exposed to symmetrical 150 mM KCl, two channel types with conductances in the ranges of 250–300 pS and 9–14 pS were routinely observed. The activity of the large conductance channel is enhanced by internal Ca2+ and by depolarization of the patch membrane. This channel contributes to the repolarization of Ca2+ action potentials but has a Ca2+ sensitivity at –50 mV that is too low for it to contribute to the resting membrane conductance. The small conductance channel is activated by much lower concentrations of Ca2+ at –50 mV, ad its open probability is not strongly voltage sensitive. In cell-attached patches from voltage-clamped cells, the small conductance channels were found to be active during slowly decaying Ca2+-activated K+ tails currents and during Ca2+-activated K+ currents stimulated by thyrotropin-releasing hormone induced elevations of cytosolic calcium. In cell-attached patches on unclamped cells, the small conductance channels were also active at negative membrane potentials when the frequency of spontaneously firing action potentials was high or during the slow afterhyperpolarization following single spontaneous action potentials of slightly prolonged duration. The small conductance channel may thus contribute to the regulation of membrane excitability. 相似文献
32.
Although common in Japan, early gastric cancer (EGC = gastric adenocarcinoma confined to the mucosa and submucosa of the stomach, with or without regional lymph node metastases) is thought to be an infrequent occurrence in the United States. However, a review of all "curative" resections for carcinoma of the gastric body and antrum at the University of Virginia between 1974 and 1982 revealed EGC in five of 31 patients (16%). The purpose of the present study was to compare EGC to more advanced gastric cancer (ADV; n = 26) to determine whether any presenting historical, laboratory, x-ray, or endoscopic features distinguished the two groups before surgery and to ascertain whether postoperative survival in the United States mimicked the Japanese experience. All surviving patients were contacted, all charts were abstracted, all pathologic specimens were reexamined, and all radiographs were reviewed blindly by an experienced radiologist. Statistical evaluation was accomplished using Kaplan-Meier plots, chi square analysis, and unpaired "t" tests, as appropriate. At presentation, patients with EGC were younger (44 +/- 6 vs. 67 +/- 2 years, p less than 0.01) with higher admission albumin levels (4.1 +/- 0.2 vs. 3.7 +/- 0.1 mgm/dl, p less than 0.01). Although not significantly different, admission hemoglobin tended to be higher (41 +/- 2 vs. 35 +/- 2%), the incidence of weight loss tended to be less (40 vs. 65%), duration of symptoms tended to be longer (21 +/- 11 vs. 8 +/- 3 months), and tumor diameter tended to be smaller (1.7 +/- 0.6 vs. 5.8 +/- 0.7 cm) in EGC. No differences were apparent with respect to endoscopic or radiographic appearance, tumor location (greater than 70% antrum), presence of regional lymph node metastases (EGC = 2/5; ADV = 20/26), or type of resection (subtotal gastrectomy in 4/5 EGC, in 19/26 ADV). On median 5-year follow-up, however, survival with EGC has been 100%. In contrast, the Kaplan-Meier estimate of 5-year survival in ADV is 15% (42% with muscularis invasion, 0% with serosal invasion, 12% with extra-gastric spread; p less than 0.01 vs. EGC). One suture line recurrence in EGC was successfully treated by re-resection. No ADV patient with recurrence survives (p less than 0.01). Thus, EGC behaves similarly in the United States and Japan; for example, prognosis is excellent even in the presence of lymph node metastases. Inability to distinguish EGC from ADV before surgery justifies an aggressive surgical approach to all patients with resectable gastric neoplasms. 相似文献
33.
34.
Ioannis P Fouyas Paul A T Kelly Isobel M Ritchie Ian R Whittle 《British journal of pharmacology》1997,121(1):49-56
- Evidence that nitric oxide (NO) bioactivity is altered in chronic hypertension is conflicting, possibly as a result of heterogeneity in both the nature of the dysfunction and in the disease process itself. The brain is particularly vulnerable to the vascular complications of chronic hypertension, and the aim of this study was to assess whether differences in the cerebrovascular responsiveness to the NO synthase (NOS) inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), and to the NO donor 3-morpholinosydnonimine (SIN-1) might indicate one possible source of these complications.
- Conscious spontaneously hypertensive (SHR) and WKY rats, were treated with L-NAME (30 mg kg−1, i.v.), 7-NI (25 mg kg−1, i.p.), SIN-1 (0.54 or 1.8 mg kg−1 h−1, continuous i.v. infusion) or saline (i.v.), 20 min before the measurement of local cerebral blood flow (LCBF) by the fully quantitative [14C]-iodoantipyrine autoradiographic technique.
- With the exception of mean arterial blood pressure (MABP), there were no significant differences in physiological parameters between SHR and WKY rats within any of the treatment groups, or between treatment groups. L-NAME treatment increased MABP by 27% in WKY and 18% in SHR groups, whilst 7-NI had no significant effect in either group. Following the lower dose of SIN-1 infusion, MABP was decreased to a similar extent in both groups (around −20%). There was no significant difference in MABP between groups following the higher dose of SIN-1, but this represented a decrease of −41% in SHR and −21% in WKY rats.
- With the exception of one brain region (nucleus accumbens), there were no significant differences in basal LCBF between WKY and SHR. L-NAME produced similar decreases in LCBF in both groups, ranging between −10 and −40%. The effect of 7-NI upon LCBF was more pronounced in the SHR (ranging from −34 to −57%) compared with the WKY (ranging from −14 to −43%), and in seven out of the thirteen brain areas examined there were significant differences in LCBF.
- Following the lower dose of SIN-1, in the WKY 8 out of the 13 brain areas examined showed significant increases in blood flow compared to the saline treated animals. In contrast, only 2 brain areas showed significant increases in flow in the SHR. In the rest of the brain areas examined the effects of SIN-1 upon LCBF were less marked than in the WKY.
- Infusion of the higher dose of SIN-1 resulted in further significant increases in LCBF in the WKY group (ranging between +30% and +74% compared to saline-treated animals), but no significant effects upon LCBF were found in the SHR. As a result, there were significant differences in LCBF between SIN-1-treated WKY and SHR in six brain areas. In most brain areas examined, cerebral blood flow in SHR following the higher dose of SIN-1 was less than that measured with the lower dose of SIN-1.
- Despite comparable reductions in MABP (∼20%) in both groups, calculated cerebrovascular resistance (CVR) confirmed that the vasodilator effects of the lower dose of SIN-1 were significantly more pronounced throughout the brain in the WKY (ranging between −3% and −50%; median=−38%) when compared to the SHR (ranging between −10% and −36%; median=−26%). In the animals treated with the higher dose of SIN-1, CVR changes were broadly similar in both groups (median=−45% in WKY and −42% in SHR), but with the reduction in MABP in SHR being twice that found in WKY, this is in keeping with an attenuated blood flow response to SIN-1 in the SHR.
- The results of this study indicate that NO-dependent vasodilator capacity is reduced in the cerebrovasculature of SHR. In addition, the equal responsiveness to a non-specific NOS inhibitor but an enhanced effectiveness of a specific neuronal NO inhibitor upon LCBF in the SHR could be consistent with an upregulation of the neuronal NO system.
35.
Both flexible and rigid cysto-urethroscopy are routinely used in the surveillance of transitional cell bladder tumours. This study addressed the issue of patient selection for either rigid or flexible cystoscopy. What proportion of positive findings at flexible cystoscopy and negative findings at rigid cystoscopy are acceptable? Standards were set of 10% for the former and 50% for the latter and our practice was then audited. A retrospective analysis of 800 patients undergoing check cystoscopy revealed a positive finding rate of 8.3% using the flexible instrument and 48.1% using the rigid instrument. 相似文献
36.
Regulatory peptides in the heart and major vessels of man and mammals 总被引:10,自引:0,他引:10
Studies on the distribution of peptides in human tissues have been made either by measuring responses to localized stimuli or by subjecting extracts of different regions to radioimmunoassay (RIA). Attempts at isolating regulatory peptides from the mammalian tissues have resulted in the isolation of many bioactive fragments. Later, modification of initial isolation methods led to the identification of the native molecules in various tissues and body fluids. The present study examined atrial natriuretic peptide (ANP) and several other peptides in cardiac tissues of several species of laboratory mammal and human beings; using a sensitive and highly specific radioimmunoassays.In all the species studied, ANP-like immunoreactivity appeared to be highest in the heart tissue of rat. The peptide was highest in the right atrium (RA) of rat and lowest in the RA of guinea pig (P< 0.002). Neuropeptide Y (NPY) another abundant cardiac peptide was present in the cardiac tissues of all species but was more in the left atrium (LA) than the RA of all species (P<0.05). Calcitonin gene-related peptide (CGRP) was present throughout the cardiovascular system of the rat and guinea pig. Small but detectable amount of Neurotensin (NT) immunoreactivity was found in the rat but was consistently negative in the guinea pig cardiac tissues (P< 0.05). Substance P (SP) immunoreactivity was detected in the rat and higher quantities being in the Aorta but no trace of the peptide was detected in the left ventricle, aorta nor the pulmonary vein of post mortem human.Though the structure of most of the species studied has been elucidated, the primary structure of guinea pig ANP has not been fully generated. Thus the data obtained may suggest that in keeping with these mammalian peptides, the primary structures may be variant. With most of the peptides studied (e.g. ANP, Neuropepdide Y), immunoreactivity occurs predominantly in the atrial tissues, but is also present in vessels outside the heart, a finding which may be of functional significance. 相似文献
37.
Paw withdrawal threshold in the von Frey hair test is influenced by the surface on which the rat stands 总被引:5,自引:0,他引:5
The effect of testing surface on the rat hind paw withdrawal threshold in the von Frey hair test is investigated in this study. The data indicate that wire mesh, which is typically used to apply von Frey hairs, may have an effect on the paw withdrawal threshold. For example, in control rats tested on the wire mesh, variability in the withdrawal threshold was observed between the left and the right hind paws (51.04+/-12.29 and 64.31+/-9.37 g, respectively) and on different days of testing (35.24+/-9.54 and 45.83+/-12.97 g for the left and right hind paws, respectively, 7 days later). In an attempt to reduce this variability, a customized platform was used to measure the von Frey hair-induced paw withdrawal in the rat. It consists of an opaque, flat-surfaced plastic platform with holes through which von Frey hairs are inserted and applied to the plantar surface of the paw. In control rats tested with von Frey hairs using this customized platform, variability in the paw withdrawal thresholds between the left and right hind paws in single rats over time as well as between different rats was reduced (49.86+/-6.97 and 49.29+/-6.56 g for the left and right hind paws, respectively, on day 0; 48.29+/-5.82 and 53.00+/-4.59 g for the left and right hind paws, respectively, 7 days later). Furthermore, in rats in which a 2 mm polyethylene cuff was used to constrict the left common sciatic nerve, the ipsilateral as well as the contralateral hind paw withdrawal thresholds were decreased (2.45+/-0.65 and 26.09+/-5.86 g, respectively, 7 days later). In similar rats tested on the wire mesh, the ipsilateral but not the contralateral paw withdrawal threshold decreased (12.80+/-2.21 and 65.00+/-10.28 g, respectively, at 7 days). The data suggest that the flat surface and opaque properties of the customized platform enable accurate, reliable and repeatable measurements of ipsilateral and contralateral paw withdrawal threshold using von Frey hairs in normal and nerve-injured rats. 相似文献
38.
Ritchie DF 《Pharmacy practice management quarterly》1996,16(2):4-8
Numerous factors are considered in the design of an antibiotic formulary, consisting primarily of indicators of clinical efficacy and safety, as well as economic viability. Similarly, there are many potential strategies for subsequent antibiotic formulary management ranging from global educational efforts to comprehensive required antibiotic justification programs. Antibiotic formulary management programs should be tailored to individual institutions and utilize a multidisciplinary approach where possible. The primary outcome goals of such programs are generally controlled antibiotic costs, optimized clinical efficacy, minimization of adverse events, and reduced microbial resistance development, although quantification of program impact on these parameters continues to be a challenge. 相似文献
39.
Pretreatment with the mild irritant 1 mmol acidified taurocholate protects the gastric mucosa from the injury induced by the subsequent application of 5 mmol acidified taurocholate, a phenomenon referred to as "adaptive cytoprotection." How this occurs remains an enigma. The purpose of this study was to investigate the role of sensory neurons and mucus secretion in this phenomenon. Prior to injury with 5 mmol acidified taurocholate (pH 1.2), the stomachs of six groups of rats were subjected to the following protocol. Two groups were topically pretreated with either saline or the mild irritant 1 mmol acidified taurocholate. Two other groups received the topical anesthetic 1% lidocaine prior to pretreatment with either saline or 1 mmol acidified taurocholate. The last two groups got the mucolytic agent 10% N-acetylcysteine (NAC) after pretreatment with either saline or 1 mmol acidified taurocholate. Injury was assessed by measuring net transmucosal ion fluxes, luminal appearance of deoxyribonucleic acid (DNA), and gross and histologic injury. Pretreatment with the mild irritant 1 mmol acidified taurocholate significantly decreased bile acid-induced luminal ion fluxes and DNA accumulation, suggesting mucosal protection (corroborated by gross and histologic injury analysis). This effect was negated by lidocaine but not by NAC. Thus, it appears that sensory neurons, and not increased mucus secretion, play a critical role in adaptive cytoprotection. 相似文献
40.
BACKGROUND--Hospital reimbursement by Medicare's prospective payment system depends on accurate identification and coding of inpatients' diagnoses and procedures using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). A previous study showed that 20.8% +/- 0.5% (mean +/- SE) of hospital bills for 1985 contained errors that changed their diagnosis related group (DRG) and that a significant 61.6% +/- 1.3% of errors overreimbursed the hospitals. This DRG "creep" improperly increased net reimbursement by 1.9%, +308 million when projected nationally. The present study updated our previous study with 1988 data. METHODS--The Office of Inspector General, US Department of Health and Human Services, obtained a simple random sample of 2451 hospital charts for Medicare discharges from 1988. The American Medical Record Association reabstracted the ICD-9-CM codes on a blinded basis, grouped them to DRGs, and determined the reasons for discrepancies. RESULTS--Coding errors declined to 14.7% +/- 0.7% in 1988, and a nonsignificant 50.7% +/- 2.6% of DRG errors overreimbursed the hospitals. Projected nationally, hospitals did not receive a significant overreimbursement. Physician misspecification of the narrative diagnoses underreimbursed the hospitals, while billing department resequencing overreimbursed them. CONCLUSIONS--The attestation requirement may have deterred DRG creep due to attending physician upcoding, but the peer review organizations' sentinel effect and educational activities have not eliminated hospital resequencing. 相似文献