Morphological and functional characterization of vascular muscle cells enzymatically dispersed from dog mesenteric arteries.

The objective of this study was to compare the properties of single smooth muscle cells enzymatically dispersed from the dog mesenteric arteries to the properties of similar cells functioning in tissue strips. The isolated cells remained relaxed in nominally Ca(2+)-free medium for about 1-2 h after exposure to 1 mM Ca2+ and like intact mesenteric artery rings did not contract spontaneously. Enzymatically dispersed cells maintained all the characteristic morphological features observed in strips of muscle prior to isolation except that the amorphous materials covering the smooth muscle cell surfaces (basal lamina) were absent after enzymatic dispersion. Addition of 100 mM KCl to these vascular muscle cells elicited maximal shortening in the presence but not in the absence of extracellular Ca2+ and KCl-induced cell shortening was prevented by 10(-7) M nifedipine indicating the presence of functional voltage-operated Ca2+ channels. However, in contrast to the vascular muscle strips, in which graded contractile responses were observed with increasing KCl concentrations, isolated vascular muscle cells underwent nearly maximal contraction at concentrations as low as 15 mM KCl. Both intact tissue and isolated cell preparations responded similarly to phenylephrine in a concentration-dependent manner and the responses were blocked by prazosin. In contrast to muscle strips, the isolated cells did not shorten in response to phenylephrine in Ca(2+)-free medium. Isolated muscle shortened in the presence of sarcoplasmic reticulum selective Ca2+ transport ATPase inhibitors, cyclopiazonic acid or thapsigargin. Ryanodine also caused contraction. We conclude that enzymatically dispersed smooth muscle cells from dog mesenteric arteries are potentially useful for studies of the regulation of smooth muscle contractility, but have significantly increased sensitivity to external K+, implying an altered membrane potential or voltage dependence of ion channels. Their impaired ability to contract to phenylephrine in Ca(2+)-free medium implies some alteration in intracellular Ca2+ stores of their coupling to cellular activation. These differences will affect how the data obtained from freshly isolated enzymatically dispersed vascular muscle cells may be extrapolated to cell studies in intact tissues.     

Clinical significance of CT-defined minimal ascites in patients with gastric cancer

AIM: To study the clinical significance of minimal ascites, which was only defined by the CT and whose nature was not determined preoperatively, in the relationship with the peritoneal carcinomatosis. METHODS: The medical records and the dynamic CT films of 118 patients with gastric cancer were reviewed. Factors associated with peritoneal carcinomatosis were analyzed in 40 patients who had CT-defined ascites of which the nature was surgically confirmed. RESULTS: Only 12.5-25% of the CT-defined minimal ascites, whose volume was estimated to be less than 50 mL, were associated with peritoneal carcinomatosis. When the estimated CT-defined ascitic volume was 50 mL or more, peritoneal carcinomatosis was identified in 75-100%. When CT-defined lymph node enlargements were not found beyond the regional gastric area, perigastric invasions were not suspected, and the size of tumor was less than 3 cm, peritoneal carcinomatosis seemed significantly less accompanied at the univariate analysis. However, except for the minimal volume of CT-defined ascites in comparison with the mild or more, other factors were not confirmed multivariately. CONCLUSION: In the patients with gastric cancer, CT-defined minimal ascites alone is rarely associated with peritoneal carcinomatosis, if it does not accompany other signs suggestive of malignant seeding. Therefore, consideration of active curative resection should not be hesitated, if CT-defined minimal ascites is the only delusive sign.     

Anomalous origin of the left main coronary artery from the right sinus of Valsalva: disabling angina and syncope with noninterarterial courses case report of two patients

Anomalous origin of the left main coronary artery from the right sinus of Valsalva or the right coronary artery is a rare coronary anomaly. This anomaly has been associated with sudden cardiac death in younger patients, depending on its course relative to the pulmonary artery. The authors report this rare anomaly in two patients. It presented as unstable angina in the first patient with a septal course. In the second patient, it presented as syncope with an anterior free wall course and absent left circumflex artery. A septal course causing unstable angina has not been reported previously.     

Growth hormone treatment of short Chinese children with β-thalassaemia major without GH deficiency

OBJECTIVE Despite regular transfusion and desferoxamine treatment, growth failure Is commonly seen In adolescent children with β-thalassaemla major. The growth failure has been thought to be due to GH resistance rather than GH deficiency. We Investigated the effect of GH on short non-GH deficient children with β-thalassaemia. DESIGN Recombinant human GH was given In a dose of 0-14IU/kg/day subcutaneously in an open study. PATIENTS Fifteen prepubertal Chinese children with β-thalassaemia major (ranging from 7.16 to 14.7 years In age) with height ?1.5 SD or more below the population mean for age and a growth velocity of less than 5 cm/year were treated with growth hormone for one year. All children had peak GH response >15mlU/l to insulin Induced hypoglycaemia and normal thyroid function and adrenal reserve. MEASUREMENTS Anthropometric measurements were performed every 3 months. Morning urine was tested twice weekly for glycosuria. Blood count, renal and liver function tests, fasting blood glucose, IGF-I and fructosa-mine levels were assessed at entry and every 3 months during treatment. Fasting Insulin was measured before and after 3 and 12 months of GH treatment. Skeletal maturity was assessed before and after one year of treatment. RESULTS Treatment was stopped in two children after 6 months because of poor growth response and noncompliance with treatment and In one child at 9 months because of bone marrow transplantation. In the 13 children, the growth velocity increased from 3.6±0.7 cm/year to 8±1.2 cm/year after one year of GH treatment (P<0.001). IGF-I was low before treatment (10.1±2.7nmol/l), rising significantly to 15.8±4.8, 18.4±4.6, 19.3±6.4 and 21.9±7.5nmol/l at 3, 6, 9 and 12 months of treatment (P<0.005). The mean pretreatment bone age in the 13 children was 9.58±1.41 years and increased to 10.53±1.43 years after one year of treatment (ΔBA/CA 0.95±0.3 years). None of the patients developed glycosuria or hypertension. There was no significant change in blood count, renal and liver function, thyroid function, fasting blood glucose or insulin concentrations during treatment. CONCLUSION Growth failure In these children with normal GH reserve and low serum IGF-I concentrations would suggest GH insensltlvity. Supraphyslologlcal doses of exogenous GH can cause a significant increase In serum IGF-I levels and a significant Improvement in short-term growth of short children with β-thalassaemia major.     

Single daily-dose ofloxacin monotherapy for Mycobacterium fortuitum sternotomy infection

Infection of sternotomy wounds due to Mycobacterium fortuitum-chelonei complex postoperatively was noted in ten patients in 1987 and six patients in 1988 in our hospital. The first ten patients were treated with a combination of ofloxacin and amikacin, successfully in nine. In the six later patients, five had M fortuitum infection and one had M chelonei infection. In those five we used single daily-dose ofloxacin, 600 mg, in three with rapid clinical response and bacteriologic cure. The MIC of ofloxacin for these three isolates ranged from 0.32 mg/L to 1.25 mg/L, and peak serum level of ofloxacin assessed by high-performance liquid chromatography ranged from 4.1 mg/L to 8.0 mg/L. Monotherapy with ofloxacin is recommended for M fortuitum infection of wound and soft tissue, with in vitro susceptibility studies as a guide, pending further reinforcing clinical evidence.     

Clinical significance of distal colon polyps for the prediction of an advanced proximal neoplasm: the KASID prospective multicenter study

Background/aims The possibility of proximal lesion without distal polyps is a weak point of sigmoidoscopic colon cancer screening, but the clinical significance of distal findings for advanced proximal neoplasm (APN) is uncertain. The aim of this study was to assess the significance of a distal finding as a predictor of APN. Materials and methods Asymptomatic patients ≥50 years old were enrolled from among patients who underwent polypectomy at 11 tertiary medical centers during the Korean Association for the Study of Intestinal Disease prospective study conducted between July 2003 and March 2004. Polyps located distal to the splenic flexure were defined as distal polyps. An advanced neoplasm was defined as a polyp of ≥10 mm in size, and/or with villous features, and/or with high-grade dysplasia, or invasive cancer. Age, gender, and distal polyp size, appearance, and histology were analyzed as risk factors of APN. The sensitivity and positive predictive value of distal polyps for APN were calculated. Results Data from 826 patients were analyzed. Mean patient age was 60.1 years (range 50–86), and 71.3% were men. APN was found in 98 patients, and 45 (45.9%) patients had no distal polyps. Risk factors of APN were a male gender, distal polyp size, and an advanced distal neoplasm. Sensitivities of a distal polyp of ≥10 mm and of an advanced distal neoplasm for APN were both 38.8% with positive predictive values of 13.3 and 14.4%, respectively. Conclusions Although distal colon findings were found to be helpful for predicting APN in asymptomatic patients aged ≥50 years, APN without distal polyps requires careful consideration.     

Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine

OBJECTIVE: To study the outcome and prognostic indicators of diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE) treated with sequential oral cyclophosphamide (CYC) and azathioprine (AZA). METHODS: SLE patients with biopsy-proven DPGN treated with sequential oral CYC and AZA were studied. Those who achieved renal remission at 12 months were identified, and the clinical predictors of complete remission were evaluated by regression analysis. All patients were followed up until a relapse of the nephritis or a doubling of the serum creatinine level occurred. The timing and risk factors for flares and creatinine doubling were evaluated by Kaplan-Meier analysis and with the Cox proportional hazards model. RESULTS: We studied 55 patients (47 women, 8 men; mean +/- SD age at renal biopsy 31.1 +/- 10.4 years); 25 (46%) had a serum creatinine level >106 micromoles/liter, and 29 (53%) had nephrotic syndrome. At 12 months posttreatment, 37 (67%) had complete remission and 12 (22%) had partial remission. The initial serum creatinine level was an independent predictor of complete remission. Excluding the 4 patients who were treatment- resistant or died, 21 patients (41%) had renal flares during a median followup of 4 years. The cumulative risk of renal flare was 6% at 1 year, 21% at 3 years, and 32% at 5 years. The median time to relapse was 43 months. The histologic activity score and the mean daily dose of CYC were multivariate predictors of renal flare, by Cox regression. At the last followup visit, 9 of 54 patients (17%) had a doubling of the creatinine level, 6 of whom (11%) underwent dialysis. The cumulative risk of creatinine doubling was 8.4% at 5 years and 18.2% at 10 years. An increasing chronicity index at the time of initial renal biopsy was an independent predictor of deterioration in renal function. CONCLUSION: Sequential therapy with oral CYC followed by AZA appears to be an effective treatment regimen for DPGN in patients with SLE, with 89% of patients achieving complete or partial remission at 12 months, 62.8% remaining in remission after 5 years, and 81.8% having stable renal function after 10 years. Predictors of treatment resistance and relapse include increasing serum creatinine level, higher histologic activity scores, and a lower dose of CYC. Increasing chronicity indices predict a deterioration of renal function.     

Inhaled corticosteroid prevents the thickening of airway smooth muscle in murine model of chronic asthma

Airway smooth muscle growth contributes to the mechanism of airway hyperresponsiveness (AHR) in asthma. Although current steroid use demonstrates anti-inflammatory activity, there is little reported on the action of corticosteroid on smooth muscle of the asthmatic airway. The present study investigated the effect of inhaled corticosteroid on the thickening of airway smooth muscle in bronchial asthma. We developed a mouse model of airway remodeling including smooth muscle thickening in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated intranasally with fluticasone during the OVA challenge. Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Intranasal administration of fluticasone inhibited the development of eosinophilic inflammation, and importantly, thickening of the smooth muscle layer. Moreover, intranasal fluticasone treatment reduced the transforming growth factor (TGF)-beta 1 level in bronchoalveolar lavage fluid and regulated active TGF-beta 1 signaling with a reduction in the expression of phospho-Smad2/3 and the concomitant up-regulation of Smad7 in lung tissue sections. These results suggest that intranasal administration of fluticasone can modulate the remodeling of airway smooth muscle via regulation of TGF-beta 1 production and active TGF-beta 1 signaling.     

Dry granular flows can generate surface features resembling those seen in Martian gullies

Over the past decade or more, contradictory evidence of Martian climate, indicating that surface temperatures seldom if ever approach the melting point of water at midlatitudes, and geomorphic features, consistent with liquid flows at these same latitudes, have proven difficult to reconcile. In this article, we demonstrate that several features of liquid-erosional flows can be produced by dry granular materials when individual particle settling is slower than characteristic debris flow speeds. Since the gravitational acceleration on Mars is about one-third that on Earth, and since particle settling speeds scale with gravity, we propose that some (although perhaps not all) Martian geomorphological features attributed to liquid flows may in fact be associated with dry granular flows in the presence of reduced gravity.