Motilin induces gall bladder emptying and antral contractions in the fasted state in humans

BACKGROUND: Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying. AIMS: To explore the effect of increasing doses of exogenous motilin on gall bladder volume and antral contractility in the fasted state in humans. METHODS: After an overnight fast, eight healthy men received increasing intravenous doses of Leu13-motilin (KW-5139) or 0.9% NaCl in a double blind, randomised fashion. Gall bladder volume and antral contraction frequency were determined by ultrasonography. RESULTS: Infusion of motilin increased plasma motilin levels. Motilin induced a reduction in gall bladder volume of 8.0 (5.0)%, 17.1 (5.0)%, 18.5 (4.7)%, and 16.1 (4.9)% of baseline volume at the end of infusion of 2, 4, 8, and 16 pmol/kg/min respectively, compared with mean stable gall bladder volumes during placebo infusion (p < 0.05). Antral contraction frequency increased during motilin infusion, but not during placebo infusion (p < 0.05). CONCLUSIONS: Exogenous motilin reducted fasting gall bladder volume and increased antral contractions. After reaching maximal reduction, the gall bladder volume did not decrease further during continuous motilin infusion at higher doses and stayed at the same reduced volume. The degree of gall bladder volume reduction during motilin infusion mimicked gall bladder emptying preceding antral phase III activity of the migrating motor complex in humans. This study indicates that motilin may play a physiological role in the regulation of gall bladder emptying in the fasted state.     

Altered rhodopsin regeneration in diabetic mice caused by acid conditions within the rod photoreceptors

BACKGROUND: We sought to describe changes in spirometric variables and lung volume subdivisions in healthy subjects and patients with chronic obstructive pulmonary disease (COPD) during moderate acute hypobaric hypoxia as occurs during air travel. We further questioned whether changes in lung function may associate with reduced maximum ventilation or worsened arterial blood gases. METHODS: Ambulatory patients with COPD and healthy adults comprised the study populations (n = 27). We obtained baseline measurements of spirometry, lung volumes and arterial blood gases from each subject at sea level and repeated measurements during altitude exposure to 8000 ft (2438 m) above sea level in a man-rated hypobaric chamber. RESULTS: Six COPD patients and three healthy subjects had declines in FVC during altitude exposure greater than the 95% confidence interval (CI) for expected within day variability (p < 0.05). Average forced vital capacity (FVC) declined by 0.123 +/- 0.254 L (mean +/- SD; 95% CI = -0.255, -0.020; p < 0.05) for all subjects combined. The magnitude of decline in FVC did not differ between groups (p > 0.05) and correlated with increasing residual volume (r = -0.455; <0.05). Change in maximum voluntary ventilation (MVV) in the COPD patients equaled -1.244 +/- 4.797 L x min(-1) (95% CI = -3.71, 1.22; p = 0.301). Decline in maximum voluntary ventilation (MVV) in the COPD patients correlated with decreased FVC (r = 0.630) and increased RV (r = -0.546; p < 0.05). Changes in spirometric variables for patients and controls did not explain significant variability in the arterial blood gas variables PaO2, PaCO2 or pH at altitude. CONCLUSIONS: We observed a decline in forced vital capacity in some COPD patients and normal subjects greater than expected for within day variability. Spirometric changes correlated with changes in reduced maximum voluntary ventilation in the patients but not with changes in resting arterial blood gases.     

Factors that may increase morbidity in a model of intra-abdominal contamination caused by gallstones lost in the peritoneal cavity

OBJECTIVE: To assess the effect of intraperitoneal gallstones with and without Escherichia coli and sterile bile on the incidence of intraperitoneal complications in mice. DESIGN: Prospective randomised study. SETTING: Teaching hospital, Turkey. MATERIAL: 180 Swiss albino mice in five groups, n = 20 in the control group, and n = 40 in each of the experimental groups. INTERVENTIONS: Group A laparotomy alone (controls); group B, laparotomy amd intraperitoneal instillation of E. coli 4 x 10(6) 0.1 ml; group C, laparotomy and insertion of sterilised gallstones; group D, laparotomy, insertion of gallstones and instillation of E. coli 4 x 10(6) 0.1 ml; and group E, laparotomy, insertion of gallstones, and instillation of E. coli 4 x 10(6) 0.1 ml and sterile bile 0.1 ml. A quarter of each group was killed after 1, 2, 4, and 8 weeks. MAIN OUTCOME MEASURES: Intra-peritoneal abscesses, adhesions, perforations, fistula, or obstruction. RESULTS: No mice died. Adhesions were found in 3(15%), 7(18%), 30(75%), 25(63%), and 24(60%) in the five groups, respectively. No mice in groups A, B, or C developed an abscess, but 8 did in each of groups D and E (20%). One mouse in group D developed obstruction. Logistic regression showed that abscess formation was significantly increased by the addition of gallstones and E. coli to the peritoneal cavity (p < 0.001) but the addition of bile had no effect. Gallstones increased the rate of adhesions more than nine fold (p < 0.001) but E. coli with or without bile had no effect (p = 0.75). CONCLUSIONS: Free gallstones within the peritoneal cavity with or without E. coli or sterile bile, or both, increased the rate of formation of both abscesses and adhesions in mice. These results suggest that efforts should be made retrieve gallstones that are dropped into the peritoneal cavity during laparoscopic cholecystectomy, particularly in patients with acute cholecystitis.     

Psychiatric profiles and patterns of cerebral blood flow in focal epilepsy: interactions between depression, obsessionality, and perfusion related to the laterality of the epilepsy

For the purpose of shedding some light upon the possible mechanisms involved in gallstone formation in patients with Crohn's disease, we have investigated gallbladder emptying by means of ultrasonography in two groups of subjects: controls (n = 40) and Crohn's disease (n = 30). Diminished gallbladder emptying after a liquid fatty-meal stimulus was observed in patients with Crohn's disease when compared with controls (p < 0.001). Also, the values for the residual gallbladder volume (RGV) and maximal decrease in gallbladder volume (MDGV), both in milliliters and percentage were, respectively, increased (RGV = 9.6 ml) and diminished (MDGV = 14.8 ml; MDGV = 60.9%) in patients with Crohn's disease when compared with controls (RGV = 5.9 ml, p < 0.001; MDGV = 19.9 ml, p = 0.003; MDGV = 77.8%, p < 0.001). Hence, reduced gallbladder emptying with consequent stasis might be a contributory factor to the increased prevalence of gallstones in Crohn's disease.     

Inhibition of hypoxic pulmonary hypertension by heparins of differing in vitro antiproliferative potency

Heparin inhibits smooth-muscle cell (SMC) growth in vitro and inhibits the development of hypoxic pulmonary hypertension and vascular remodeling in vivo. We wondered whether preparations of heparin with different antiproliferative potency in vitro would differ in their ability to inhibit the development of hypoxic pulmonary hypertension in vivo. Two such heparins, a weakly antiproliferative lot of Elkins-Sinn (E-S) (% inhibition of SMC growth at 10 micrograms/ml = 13 +/- 9% [mean +/- SEM, n = 24]) and a more active lot from Upjohn (UJ) (% inhibition = 71 +/- 12% [n = 12, p < 0.05 versus E-S]), were infused subcutaneously (300 U.S.P. units/day; E-S 300 versus UJ 300) via an osmotic pump into guinea pigs exposed to hypoxia (10% O2) for 10 d, after which pulmonary artery pressure (PAP; mm Hg) and cardiac index (CI; ml/min/kg) were measured in room air. Hypoxic controls (HC) received saline. PAP increased from 11 +/- 1 mm Hg in normoxic controls (NC) (n = 5) to 24 +/- 1 mm Hg in HC (n = 8, p < 0.05). The PAP was lower in the E-S 300 (21 +/- 1; n = 7, p < 0.05 versus HC and NC) and even lower in the UJ 300-treated group (18 +/- 0.5; n = 7, p < 0.05 versus HC and NC). Total pulmonary vascular resistance (TPR; mm Hg/ml/min/kg) increased significantly from 0.038 +/- 0.002 in NC to 0.076 +/- 0.003 (p < 0.05) in HC. There was no difference in TPR between the HC and the E-S 300-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

MR guidance of laser disc decompression: preliminary in vivo experience

BACKGROUND: The mechanism of atrial natriuretic peptide (ANP) release has been difficult to demonstrate in patient studies because of inaccuracies in measuring atrial volumes using conventional techniques. METHODS: Magnetic resonance imaging was performed in 28 clinically stable patients (New York Heart Association class 3) with chronic heart failure to determine right atrial (RA), left atrial (LA), and ventricular volumes. In addition, right heart catheterization was serially performed and plasma ANP levels (in picograms per milliliter) were drawn from the right atrium. RESULTS: Five patients had to be excluded from data analysis for technical reasons. The remaining 23 patients had the following hemodynamic measurements (mean +/- SD): RA mean pressure 7+/-5 mm Hg, pulmonary artery mean pressure 28+/-10, pulmonary capillary wedge pressure 21+/-8 mm Hg, and cardiac index 2.9+/-1.4 (L/min/m2), respectively. Plasma ANP levels were significantly elevated at 162+/-117 (normal range 20 to 65 pg/ml, p < 0.05), as were LA and RA volumes compared with healthy controls (RA volume 128+/-64 ml vs 82+/-25 ml, p < 0.05; LA volume 157+/-54 ml vs 71+/-24 ml, p < 0.01, respectively). ANP showed a stronger relation with atrial volumes (RA volume, r = 0.91, p = 0.0001; LA volume, r = 0.80, p = 0.001) than with atrial pressures (RA mean pressure, r = 0.45, p = 0.03; pulmonary capillary wedge pressure, r = 0.67, p = 0.001). A subgroup analysis of patients with increased RA or LA volumes (>1 SD of mean of controls) revealed a stronger relation between ANP and RA volumes than between ANP and LA volumes. CONCLUSIONS: These data suggest that increased right heart volume with subsequent increased atrial stretch is the major determinant for ANP release in patients with stable CHF.     

Long-term extracellular matrix metabolism by cultured human osteogenesis imperfecta osteoblasts

BACKGROUND: While the side effects of oral glucocorticoids are well recognised there is debate about the systemic effects of high doses of inhaled glucocorticoids such as beclomethasone dipropionate and how these compare with the effects of oral prednisone. AIMS: To compare the effects of different doses of oral prednisone and inhaled beclomethasone dipropionate (BDP) on changes in circulating leukocytes. METHODS: Changes in different subsets of circulating leukocytes were measured as an index of the systemic effects of inhaled BDP and oral prednisone. We compared the effects of inhaled placebo and 500 and 1000 micrograms of inhaled BDP with oral placebo and 2.5, 5 and 10 mg of prednisone in eight healthy volunteers. Leukocyte numbers were measured before and four hours after each dose of medicine. RESULTS: Compared with inhaled placebo, 1000 micrograms of inhaled BDP led to a significant increase in neutrophils as a percentage of the total white count (p < 0.05) and a significant decrease in the total lymphocyte number (p < 0.05) and in the number of CD4 lymphocytes (p < 0.05). For 1000 micrograms BDP the increase in the % neutrophil count was 8.55% (95% CI 5.17 to 11.93) and the fall in lymphocyte numbers was -0.14 x 10(9)/L (95% CI 0.06 to -0.34) while 2.5 mg prednisone led to an increase in the % neutrophil count of 9.31% (95% CI 5.82 to 12.80) and a fall in lymphocyte numbers of -0.07 x 10(9)/L (95% CI 0.05 to -0.19). CONCLUSIONS: The systemic effects of 1000 micrograms inhaled BDP and 2.5 mg of prednisone are similar.     

Cultured astrocytes express functional receptors for galanin

OBJECTIVE: Inflammatory bowel disease (IBD) is characterized by T cell activation. Activated T cells shed interleukin-2 receptors (IL-2R) in a soluble form. A positive correlation between sIL-2Ralpha (CD25) and disease activity is well documented in IBD, whereas IL-2Rgamma (CD132) has not been investigated in this respect. Sera from 42 patients with ulcerative colitis (UC), 34 with Crohn's disease (CD), 31 healthy volunteers, and 12 patients with infectious enterocolitis were obtained. METHODS: Disease activity was scored according to a semiquantitative score for UC and CD. sIL-2R alpha chain and gamma chain were assessed by sandwich ELISA techniques using monoclonal antibodies specific for CD25 and CD132, respectively. RESULTS: The concentration of IL-2Ralpha chain (CD25) was found to be median 3.8 ng/ml in healthy volunteers versus 7.0 ng/ml in UC patients (p < 0.001), and 9.6 ng/ml in CD patients (p < 0.001). With respect to IL-2Rgamma (CD132), significantly higher amounts were found in CD patients: 6.6 ng/ml as compared with healthy controls <1.0 ng/ml (p < 0.004). A Kruskal-Wallis test revealed a significant correlation between alpha chain and disease activity in CD (p < 0.001), and further significantly higher gamma chain levels were found in active CD (p = 0.03). For UC patients, a statistically significant increase of the alpha chain with increasing disease activity (p < 0.01) was observed, whereas no significant changes of the gamma chain levels were found (p > 0.05). A difference of gamma chain levels were found between CD and UC in moderate and severe disease activity (p < 0.05). Further analyses revealed that mesalazine did not influence the IL-2Ralpha or -gamma concentration either in UC or in CD patients. CONCLUSION: An increased circulating level of the soluble common gamma chain (CD132) seems to be found in CD, and an overlap exists between CD and UC.     

Gallbladder dyskinesia in acalculous biliary colic

AIMS: To test the hypotheses that: 1) postprandial gallbladder emptying might be abnormal in patients with acalculous biliary colic; and 2) that hymecromone, a drug that increases bile flow and relaxes biliary muscle might improve symptoms. METHODS: Twenty-four women were studied. Twelve patients presented recurrent biliary type of pain in the absence of gallstones, and persistence of contrast in the gallbladder, 24 hours after an oral cholecystogram, suggesting cholesterolosis. Twelve healthy volunteers used as controls had no symptoms and the gallbladder was not visible the day after an oral cholecystogram. Gallbladder emptying induced by an oral meal was studied with ultrasound in both groups before and after the administration of hymecromone. RESULTS: Gallbladder volumes were similar in both groups (23 +/- 10 ml vs. 31 +/- 11 ml; NS). Gallbladder emptying in the control group was simple exponential (R2 = 0.948 +/- 0.059) with a rate of 32 +/- 16 minutes. Gallbladder emptying was bimodal in patients. Gallbladder volume increased to 120% in the first 10 minutes, to empty exponentially thereafter (R2 = 0.964 +/- 0.040. Rate: 29 +/- 22 minutes). This resulted in a marked reduction in gallbladder volume emptied at 40 minutes when compared to controls (30% +/- 27% vs. 54% +/- 14%; p = 0.012). Pretreatment of controls with hymecromone induced an emptying pattern similar to that of patients. In patients, emptying after hymecromone did not change but symptoms were improved. CONCLUSIONS: An abnormal emptying pattern of the gallbladder was identified in patients with acalculous biliary colic, and hymecromone was partly effective to reduce pain, despite a minor effect on gallbladder emptying pattern.     

Autistic disorder: a review for the pediatric dentist

A combined analysis of two polymorphic enzymes, glutathione S-transferase mu (GST M1) and q (GST T1) and their implication as cancer risk factors was performed in a case-control study of lung and bladder cancers. Using a multiplex polymerase chain reaction (PCR) based method, the frequency of the homozygous deleted GSTM1 and GSTT1 genotypes was examined in 117 lung cancer patients, 67 urinary bladder cancer patients, and in a community-based sample of 248 healthy, unrelated individuals. In both cancer groups the frequency of the GSTM1 null genotype was higher in comparison with that of the control group (59% and 59.7% vs. 49.6%), but this increase did not reach statistical significance (p > 0.05). After grouping by the smoking status, among smokers in both cancer groups (62.1% in lung cancer and 71.4% in the bladder cancer group, respectively) there were statistically significantly (p < 0.05) increased frequencies of the GSTM1 deletion genotype as compared to the control group (49.6%). Smokers with absence of the GSTM1 gene were at an approximately 1.7-fold higher risk for lung cancer (odds ratio--OR = 1.67, 95% confidence interval--CI 95% = 1.0-2.7, p = 0.04) and an approximately 2.5-fold higher risk for bladder cancer (OR = 2.54, CI 95% = 1.2-5.5, p = 0.02). As related to GSTT1, our study demonstrated an overall GSTT1 effect on bladder cancer risk. Individuals with absence of the GSTT1 gene were at an approximately 2.5-fold higher risk of developing bladder cancer. In the lung cancer cases, the frequency of the putatively high risk GSTT1 null genotype was not increased as compared with controls. No effect of smoking was found on risk of lung and bladder cancer associated with the GSTT1 0/0 genotype. In combined analysis, the obtained results suggested that individuals who were both GSTM1 null and GSTT1 null may be at increased risk because they lack both enzymes. The findings suggest that the GSTM1 null genotype may be associated with susceptibility to lung and urinary bladder cancer in dependence on the exposure to carcinogens in cigarette smoke and that the GSTT1 null genotype is not a critical factor in mediating the risk of lung cancer, but may be associated with an increased susceptibility to bladder cancer.     

Value of HIV-1 viral load and CD4 lymphocyte count as determinants of progression to AIDS and survival

BACKGROUND: HIV-1 viral load is regarded as a better surrogate marker for progression and death than CD4+ cell counts. Both markers are analysed in a cohort of patients with unknown seroconversion date and advanced HIV infection. PATIENTS AND METHODS: Retrospective cohort analysis of 421 patients, most on antiretroviral therapy, with a median initial CD4+ cell count of 209 x 10(6)/l and a median initial viral load of 4.7 log copies/ml. One thousand two hundred and eighty-six samples were analysed. Univariate and bivariate analysis were performed with initial and sequential CD4+ cell counts and viral load values to estimate the risk of progression and death by Cox regression models. RESULTS: After a median follow up of 763 days, 124 patients developed AIDS and 117 died. Relative risks of progression related to the group that maintained viral load values always < 35,000 copies/ml were: 5-fold (95% CI: 1.4-17.0; p < 0.05) for patients with any viral load value > 35,000 copies/ml but always < 200,000 copies/ml; and 13.6 fold (95% CI: 5.4-34.2; p < 0.0001) for patients who could not maintain viral load < 200.000 copies/ml. CD4+ counts = 100 x 10(6)/l and viral load = 220,000 copies/ml were the threshold values that best fitted to estimate the probability of survival by a bivariate analysis. CONCLUSIONS: The maintenance of sequential viral load values < 35.000 copies/ml is associated with a lower risk of progression. The maintenance of sequential viral load values < 150,000 copies/ml is associated with higher short-term survival rates.     

Asymmetry of the calves in the assessment of patients with suspected acute pulmonary embolism

PURPOSE: The purpose of this investigation was to evaluate measured asymmetry of the calves in the assessment of patients with suspected pulmonary embolism (PE). METHODS: Patients randomized for pulmonary angiography in the collaborative study of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) were evaluated. Only patients in whom the circumference of the calves was measured were included in this evaluation of PIOPED data. Among these, 232 had angiographically diagnosed PE and 446 had no PE by angiography. For purposes of comparison, measurements of the calves also were made in a nonrandomized current cohort of 101 healthy subjects. All calf measurements were made 10 cm below the tibial tuberosity. RESULTS: Asymmetry in the circumference of the calves of 1 cm or more was measured in 101 of 232 or 44% (95% confidence interval [CI], 37 to 51%) with PE, 176 of 446 or 39% (95% CI, 34 to 44%) without PE, and in 6 of 101 or 6% (95% CI, 1 to 11%) control subjects (PE vs control subjects, p < 0.001; subjects without PE vs control subjects, p < 0.001; PE vs no PE, p = NS). Among patients with PE, the addition of calf asymmetry of 1 cm or more to qualitative signs of deep venous thrombosis increased the prevalence of a detectable abnormality of the lower extremities from 62 of 232 or 27% (95% CI, 21 to 33%) to 129 of 232 or 56% (95% CI, 49 to 63% [p < 0.001]). CONCLUSION: Asymmetry of the calves of 1 cm or more is abnormal. Such asymmetry of the calves did not distinguish between patients with PE and those with no PE. When considered in proper perspective with other nonspecific signs and symptoms in patients with suspected acute PE, however, subtle calf asymmetry may call attention to the possibility of thromboembolic disease. The observation of subtle asymmetry may indicate a need for noninvasive diagnostic tests of the lower extremities to determine whether deep venous thrombosis is present.     

Nitric oxide is involved in the formation of learning and memory in rats: studies using passive avoidance response and Morris water maze task

Blood leukocytes of 16 patients with alcoholic liver cirrhosis and 18 healthy controls were induced for interferon (IFN) production by phytohemagglutinin (PHA) and concanavalin A (ConA) in the presence or absence of isoprinosine and levamisole at concentrations of 10 micrograms/ml and 1 ng/ml. This interferon was neutralized in 87-95% by anti-HuIFN-gamma monoclonal antibodies. In the presence of the drugs the IFN-gamma production was enhanced, however, IFN-gamma titers yielded from leukocytes of cirrhotic patients were still below the titers observed in stimulated and unstimulated blood leukocytes of healthy controls. For example, IFN titers induced by PHA in the presence of levamisole (1 ng/ml) in cirrhotic patients were 2.5 times lower (20.2 +/- 11.1 U/ml) in comparison to healthy subjects (50.6 +/- 27.3 U/ml).     

Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients

BACKGROUND: A high risk of developing sludge or gallstones has been associated with pregnancy. The aim of this study was to relate the prevalence of sludge and gallstones during and shortly after pregnancy to fasting gallbladder volume as an indicator of gallbladder motility. METHODS: The population included 114 apparently healthy pregnant women from the Outpatient Clinic of Obstetrics of a large regional hospital and from the practices of regional midwives. Ultrasonography of the gallbladder was performed at weeks 15, 25, and 35 of gestation and at week 3 and month 6 postpartum. RESULTS: At gestational week 15, 3 women had gallstones and 10 had sludge (mean volume, 33.8 ml), and 99 women had a normal gallbladder (mean volume, 30.5 ml). At week 25, 1 woman with a normal gallbladder formed gallstones and underwent cholecystectomy shortly after, and 22 women had sludge, of whom 13 had a normal gallbladder at first examination (mean volume, 33.2 ml). In 88 women with normal gallbladders (of whom 2 had sludge at week 15) mean volume was 31.9 ml. At week 35, 2 women had gallstones, and 21 had sludge (mean volume, 30.5 ml). In the remaining 79 women the gallbladders were clear (mean volume, 29.5 ml). Eight women developed sludge and two women gallstones in normal gallbladders at week 25. Seven women with sludge at week 25 had a normal gallbladder at week 35. Three weeks postpartum only 10 of 100 women had sludge (mean volume, 29.1 ml). Of these 10, 9 women had a normal gallbladder at week 35. Twenty of 21 women with sludge at week 35 had normal gallbladders week 3 postpartum. Gallstones found at week 35 had disappeared. In the women with a normal gallbladder the mean volume was decreased to 19.7 ml (P < 0.0001). Six months postpartum, sludge was found in 6 (mean volume, 18.4 ml) of 93 women (mean volume, 20.3 ml), of whom 5 had a normal gallbladder at week 3 postpartum. Only 61 women showed a normal gallbladder at each examination of the study. No differences in patient characteristics were found between women with normal gallbladders and those with sludge or gallstones. CONCLUSIONS: Fasting gallbladder volume was increased in all pregnant women. This could not explain the formation of sludge or gallstones during gestation. Decrement of gallbladder volumes after delivery was faster in normal, clear gallbladders. More than a prerequisite, increased fasting gallbladder volume seemed to be a permissive factor of pregnancy-associated gallstone formation.     

MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.

Objective: Brain MRI measures were correlated with neuropsychological function in 35 pediatric-onset multiple sclerosis (MS) patients and 33 age- and sex-matched healthy controls. Method: Mean age of MS patients was 16.3 ± 2.3 years with average disease duration of 4.3 ± 3.1 years. Cortical gray matter, thalamic, and global brain volumes were calculated for all participants using a scaling factor computed using normalization of atrophy method to normalize total and regional brain volumes for head size. T1- and T2-weighted lesion volumes were calculated for MS patients. Results: Cognitive impairment (CI) was identified in 29% of the MS cohort. Cognitive deficits predominantly involved attention and processing speed, expressive language, and visuomotor integration. Relative to controls, the MS group showed significantly lower thalamic volume (p p p p     

Effects of positive end-expiratory pressure on right ventricular function in COPD patients during acute ventilatory failure

OBJECTIVE: To examine the effects of external positive end-expiratory pressure (PEEP) on right ventricular function in chronic obstructive pulmonary disease (COPD) patients with intrinsic PEEP (PEEPi). DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: Seven mechanically ventilated flow-limited COPD patients (PEEPi = 9.7 +/- 1.3 cmH2O, mean +/- SD) with acute respiratory failure. INTERVENTION: Hemodynamic and respiratory mechanic data were collected at four different levels of PEEP (0-5-10-15 cmH2O). MEASUREMENTS AND RESULTS: Hemodynamic parameters were obtained by a Swan-Ganz catheter with a fast response thermistor. Cardiac index (CI) and end-expiratory lung volume (EELV) reductions started simultaneously when the applied PEEP was approximately 90% of PEEPi measured on 0 cmH2O (ZEEP). Changes in transmural intrathoracic pressure (PEEPi,cw) started only at a PEEP value much higher (120%) than PEEPi. The reduction in CI was related to a decrease in the right end-diastolic ventricular volume index (RVEDVI) (r = 0.61; p < 0.001). No correlation between CI and transmural right atrial pressure was observed. The RVEDVI was inversely correlated with PEEP-induced changes in EELV (r = -55; p < 0.001), but no with PEEPi,cw (r = -0.08; NS). The relationship between RVEDVI and right ventricular stroke work index, considered an index of contractility, was significant in three patients, i.e., PEEP did not change contractility. In the other patients, an increase in contractility seemed to occur. CONCLUSIONS: In COPD patients an external PEEP exceeding 90% of PEEPi causes lung hyperinflation and reduces the CI due to a preload effect. The reduction in RVEDVI seems related to changes in EELV, rather than to changes in transmural pressures, suggesting a lung/heart volume interaction in the cardiac fossa. Thus, in COPD patients, application of an external PEEP level lower than PEEPi may affect right ventricular function.     

Involvement of antizyme-like regulatory protein in polyamine-caused repression of ornithine decarboxylase in insect-derived Trichoplusia ni 5 cells

BACKGROUND: The diagnosis and classification of oesophageal motility disorders is currently based on assessment of the phasic contractile activity of the oesophagus. Tonic muscular contraction of the oesophageal body (oesophageal tone) has not been well characterised. AIM: To quantify oesophageal tonic activity in healthy subjects and in patients with achalasia. PATIENTS: Oesophageal tone was measured in 14 patients with untreated achalasia and in 14 healthy subjects. In eight patients with achalasia, oesophageal tone was again measured one month after either endoscopic or surgical treatment. METHODS: Tonic wall activity was quantified by means of a flaccid intraoesophageal bag, 5 cm long and of 120 ml maximal capacity, which was placed and maintained 5 cm above the lower oesophageal sphincter and connected to an external electronic barostat. The experimental design included measurement of oesophageal basal tone and compliance as well as the oesophageal tone response to a nitric oxide donor (0.5 ml amyl nitrite inhalation). RESULTS: Oesophageal basal tone, expressed as the intrabag (intraoesophageal) volume at a minimal distending pressure (2 mm Hg), did not differ significantly between patients with achalasia and healthy controls (6.6 (2.5) ml versus 4.1 (0.8) ml, respectively). Oesophageal compliance (volume/pressure relation during intraoesophageal distension) was significantly increased in achalasia (oesophageal extension ratio: 3.2 (0.4) ml/mm Hg versus 1.9 (0.2) ml/mm Hg; p < 0.01). Amyl nitrite inhalation induced oesophageal relaxation both in patients and in controls, but the magnitude of relaxation was greater in the latter (intrabag volume increase: 15.3 (2.4) ml versus 36.2 (7.1) ml; p < 0.01). CONCLUSION: In patients with achalasia, oesophageal tonic activity, and not only phasic activity, is impaired. Although oesophageal compliance is increased, residual oesophageal tone is maintained so that a significant relaxant response may occur after pharmacological stimulation.     

The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity

Glucocorticoid receptors (GR) and 3-O-methyl-D glucose (3-O-MG) transport were determined in mononuclear leukocytes (MNL) from 11 abdominal obese subjects, 10 pituitary-dependent Cushing's syndrome (Cushing's disease) and 10 healthy controls. Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer, MNL of abdominal obese subjects were found to have 4855 +/- 1389 sites/cell which was significantly lower (p < 0.05) than controls (6234 +/- 1568 sites/cell), although no significant difference was found in the mean serum cortisol level. Their mean Kd (affinity) was also significantly lower than that found in the healthy controls (obese Kd:2.92 +/- 0.84 nmol/l, control Kd: 4.55 +/- 0.67 nM, p < 0.05). On the other hand, the receptor characteristics in Cushing's disease patients were within the normal range. At the same time, 3-O-MG transport was determined in the same subjects. In Cushing's disease, 3-O-MG transport was within the normal range, whereas in abdominal obesity this value was significantly lower than the healthy controls (abdominal obese: 31.90 +/- 8.20; control: 46.26 +/- 12.91 fmol/10(6) cell, min, p < 0.05). We also found a positive correlation between 3-O-MG transport and GR binding capacity in abdominal subjects (r = 0.89, p < 0.001), however we did not find such a correlation in Cushing's disease (r = 0.60, p > 0.05). These results indicated that, in abdominal obesity, the GR binding capacity in MNL is influenced by the changes in glucose transport.     

Activity of renin-angiotensin-aldosterone system (RAAS) and vasopressin level in patients with primary pulmonary hypertension

AIM: Assessment of RAAS and vasopressin in patients with primary pulmonary hypertension (PPH). MATERIALS AND METHODS: Activity of plasma renin (APR), angiotensin-converting enzyme (ACE), plasma levels of angiotensin II (AII) and vasopressin (VP), serum concentration of aldosteron (AS) were measured by radioimmunoassay and enzyme immunoassay in 21 PPH patients with circulatory failure (age 34.7 +/- 2.1 years), 11 patients with NYHA functional class II-III, 10 with class IV, and 10 control subjects (age 29.8 +/- 1.5 years). RESULTS: Compared to controls, 21 PPH patients had elevated RAAS parameters: APR up to 3.52 ng/ml/h (p < 0.05), activity of ACE up to 43.13 units, AII level up to 33.93 ng/ml (p < 0.01), AS up to 468.86 ng/ml (p < 0.01), VP up to 5.26 ng/ml (p < 0.001). Circulatory failure progression resulted in activation of all the RAAS components. This and VP activation was the greatest in PPH patients with ACE > 5 ng/ml/h. PPH patients with mean pressure in the pulmonary artery higher than 60 mm Hg demonstrated higher ARP, AS, VP, AII, ACE than those who had this pressure under 60 mm Hg. CONCLUSION: PPH patients display a noticeable activation of RAAS and VP. This activation seems to be secondary as the changes increase with elevation of the pressure in the pulmonary artery and aggravation of circulatory insufficiency. Plasma renin activity determines the degree of RAAS activation as a whole. The discovered activation of RAAS in PPH gives grounds for doubts in the validity of using ACE inhibitors in the treatment of PPH.     

Altered migrating myoelectrical complex in an animal model of cholesterol gallstone disease: the effect of erythromycin

BACKGROUND: The ground squirrel on a high cholesterol diet exhibits prolonged intestinal transit, a pathogenetic factor in cholesterol gallstone formation. AIMS: To examine the effect of a high cholesterol diet on the characteristics of the migrating myoelectrical complex (MMC) and the potential benefit of erythromycin. METHODS: Twenty four animals received either a trace (controls) or a 1% (high) cholesterol diet. After four weeks, five bipolar jejunal and terminal ileal electrodes were implanted. Seven days later, myoelectric activity was measured in conscious, fasted animals before and after treatment with erythromycin. Biliary lipid composition was assessed. RESULTS: Compared with controls, animals fed the high cholesterol diet exhibited a prolonged MMC cycle period (70 (6) versus 83 (3) minutes; p<0.05), whereas MMC migration velocity and the proportions of the MMC represented by phases I, II, and III were unchanged. Oral erythromycin significantly shortened the MMC cycle period in animals on the control and high cholesterol diet by 59% and 54% respectively, and increased the proportion of the cycle period occupied by phase III of the MMC in both dietary groups. Gall bladder bile became saturated with cholesterol and crystals developed in nine of 12 animals on the high cholesterol diet; controls had none. CONCLUSION: Animals fed a high cholesterol diet had a prolonged MMC cycle period. This, along with diminished gall bladder motility, impairs the enterohepatic cycling of bile salts and reduces their hepatic secretion, contributing to the formation of abnormal bile. Erythromycin initiated more frequent cycling of the MMC. Its therapeutic value in cholesterol gallstone formation warrants further evaluation.