Liver Histology Changes in Nonalcoholic Steatohepatitis after One Year of Treatment with Probucol

BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is effective in normalizing liver enzymes in patients with nonalcoholic steatohepatitis (NASH). We studied changes in the liver histology of patients with NASH after use of probucol for one year. METHODS: Ten patients with biopsy-proven NASH were included. Subjects were given 500 mg probucol daily. Liver biopsies were performed before treatment and after one year. RESULTS: Eight patients completed treatment. The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26, respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed. CONCLUSION: Probucol is effective in normalizing aminotransferase levels in patients with NASH. It also significantly reduces the histology grade of steatohepatitis after one year of treatment.     

The Effect of Enteric-Coated,Delayed-Release Peppermint Oil on Irritable Bowel Syndrome

Herbal remedies, particularly peppermint, have been reported to be helpful in controlling symptoms of irritable bowel syndrome (IBS). We conducted a randomized double-blind placebo-controlled study on 90 outpatients with IBS. Subjects took one capsule of enteric-coated, delayed-release peppermint oil (Colpermin) or placebo three times daily for 8 weeks. We visited patients after the first, fourth, and eighth weeks and evaluated their symptoms and quality of life. The number of subjects free from abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls (P < 0.001). The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls. Furthermore, Colpermin significantly improved the quality of life. There was no significant adverse reaction. Colpermin is effective and safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort.     

An Improved Method of Assessing Esophageal Emptying Using the Timed Barium Study Following Surgical Myotomy for Achalasia

Introduction  The timed barium study (TBS) is used to assess esophageal emptying in patients with achalasia. Improvement in emptying correlates with outcome after endoscopic therapy, but the results of the TBS have been variable after myotomy. Our aim was to evaluate a new method for assessing improvement in emptying after myotomy. Methods  A TBS was performed before and 3–6 months after myotomy in 30 patients. Emptying was assessed by measuring the percent difference in area of the barium column on films obtained 1 and 5 min after ingesting 150 ml of barium. Initial esophageal clearance was also assessed by comparing the area of the barium column on 1-min images obtained before and after therapy. Both measures were compared to clinical outcome. Results  After myotomy, 21 patients (70%) had no symptoms, four (13%) had mild, and five (17%) had moderate/severe symptoms. Using the standard method, esophageal emptying before and after surgery were not significantly different (25% vs. 37%; p = 0.22) and did not correlate with clinical outcome. In contrast, initial esophageal clearance improved significantly (median 81%) and correlated with clinical outcome. Conclusion  Esophageal emptying measured by the standard method is not useful to assess outcome after myotomy. However, initial esophageal clearance correlates well with clinical outcome. Previous presentations: 49th SSAT Annual Meeting at Digestive Disease Week, San Diego, 2008 and 23rd Annual SSAT Residents and Fellows Research Conference, San Diego, 2008     

Effect of a noninvasive ventilatory support during exercise of a program in pulmonary rehabilitation in patients with COPD

Background:

Breathlessness is the most common symptom limiting exercise in patients with chronic obstructive pulmonary disease (COPD). Exercise training can improve both exercise tolerance and health status in these patients, intensity of exercise being of key importance. Nevertheless, in these patients extreme breathlessness and/or peripheral muscle fatigue may prevent patients from reaching higher levels of intensity.

Study objective:

This study was to determine whether inspiratory pressure support (IPS) applied during sub maximal exercise could enable individuals with severe but stable COPD to increase their exercise tolerance.

Participants:

Twelve subjects with severe stable COPD (mean (SD): age = 63(8.2) years; FEV₁ = 0.89(0.42) L (34)% predicted; FEV₁/FVC = 0.31(0.07) only nine subjects completed the study.

Intervention:

Each subject completed ten sessions of cycling at 25%–50% of their maximum power without NIVS and another ten sessions using NIVS.

Measurements and results:

Dyspnea was measured using Borg scale. Subjects reached high levels of dyspnea 4.7 (1.81) during the sessions without NIVS vs low levels of dyspnea during the sessions using NIVS 1.3 (0.6). Exercise time during the sessions without NIVS and with NIVS was 19.37 (3.4) and 33.75 (9.5) min, respectively. Maximal workload during the sessions without NIVS and with NIVS was 27 (3.7) and 50 (10.5) watt, respectively.

Conclusion:

We conclude that IPS delivered by nasal mask can improve exercise tolerance and dyspnea in stable severe COPD patients and hence this mode of ventilatory support may be useful in respiratory rehabilitation programs.     

Antidepressant-like effect of magnetic resonance imaging-based stimulation in mice

INTRODUCTION: It has been reported that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) may show antidepressant effects. We examined whether the two routine diagnostic protocols of MRI [T1 and echo planar diffusion weighted imaging (EPI-DWI)], have antidepressant-like effects in an animal model of depression. METHODS: The effects of standard EPI-DWI and T1 MRI on immobility, swimming and climbing times in the modified forced swimming test (FST) in mice were examined. After exposure to the first session of modified forced swimming test, we randomly divided the mice into four groups. The first group (T1 MRI group, n=21) received a 15-minute stimulation of T1 sequence. The second group (EPI-DWI MRI group, n=21) received a 15-minute stimulation of EPI-DWI protocol. The third group (sham group, n=21) spent 15 min in a tunnel similar to the MRI gantry in terms of size, temperature and light intensity and received recorded sounds from a normal session of EPI-DWI with similar duration and intensity. The fourth group acted as controls (n=21).The second session of the modified FST was conducted twelve hours later. The mean of immobility, swimming and climbing times in this session were compared to the control group. RESULTS: T1 weighted and EPI-DWI MRI groups showed a reduction in immobility time compared to the control group (P value<0.002, P value<0.017 respectively). This effect is comparable to that seen in the FST after the administration of antidepressant agents. The climbing time in the group subjected to EPI-DWI MRI was longer than the control group (P value<0.035). Previous studies showed similar effects after the administration of antidepressant drugs affecting the catecholamine systems. The swimming time in the T1 MRI group was significantly longer than the control group (P value<0.037). Previous studies showed qualitatively similar effect to that of anti-depressant drugs affecting the serotoninergic systems. The swimming, climbing and immobility times in the sham and control groups showed no significant difference. CONCLUSIONS: Our findings raise the possibility that MRI-based stimulation may have antidepressant-like effects in mice. This is likely to be through different mechanisms in T1 weighted and EPI-DWI protocols. However the possible biological basis of this effect is not yet understood and we would advocate further studies of MRI-based stimulation effects on transmitters in the different organs in the body specially the brain.     

Infant morbidity, mortality, and breast milk immunologic profiles among breast-feeding HIV-infected and HIV-uninfected women in Botswana

BACKGROUND: Infants of human immunodeficiency virus (HIV)-infected women have high mortality, but the immunologic integrity and protection afforded by the breast milk of HIV-infected women is unknown. METHODS: We determined morbidity and mortality by 24 months among breast-fed infants of 588 HIV-infected and 137 HIV-uninfected women followed-up in a clinical trial in Botswana. A matched case-control study compared clinical, behavioral, and breast milk immunologic parameters among 120 HIV-infected women by infant outcome. Breast milk factors were also compared between HIV-infected and HIV-uninfected women. RESULTS: Twenty-four-month mortality was 29.5% among HIV-infected infants, 6.7% among HIV-exposed uninfected infants, and 1.6% among HIV-unexposed infants. No differences were detected in breast milk immunologic profiles of HIV-infected women whose infants were either ill or well. Discontinuation of breast-feeding was the strongest predictor of illness (P<.001). Levels in breast milk of pathogen-specific immunoglobulin (Ig) G and IgA to Haemophilus influenzae, Campylobacter jejuni, Helicobacter pylori, Streptococcus pneumoniae, and innate immune factors were not lower among HIV-infected women than among HIV-uninfected women. CONCLUSIONS: Mortality was higher among HIV-infected and HIV-exposed infants than among HIV-unexposed infants. However, the immunologic profiles of breast milk among HIV-infected women were intact, and discontinuation of breast-feeding was the primary risk for infant morbidity. Thus, the breast milk of HIV-infected women may confer protection against common infant pathogens. TRIAL REGISTRATION: (ClinicalTrials.Gov) identifiers: NCT00197691 and NCT00197652.     

Fistulous withers and eosinophilia in a horse

Fistulous withers is a chronic inflammatory disease of horses in the supraspinous bursa and associated tissues. The referred horse had a fistulous tract in the withers area with presence of purulent material accumulation under the ligamentum nuchae. The radiographic examination of the lesion showed an osteomyelitis involved area. The hematological examination revealed eosinophilia. Long-term antibiotic therapy reduced the eosinophilic reaction to normal. It was assumed that osteomyelitis was the cause of eosinophilia in this horse.     

Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1(+) leukemia

Imatinib has revolutionized the treatment of Bcr-Abl1(+) chronic myeloid leukemia (CML), but, in most patients, some leukemia cells persist despite continued therapy, while others become resistant. Here, we report that PlGF levels are elevated in CML and that PlGF produced by bone marrow stromal cells (BMSCs) aggravates disease severity. CML cells foster a soil for their own growth by inducing BMSCs to upregulate PlGF, which not only stimulates BM angiogenesis, but also promotes CML proliferation and metabolism, in part independently of Bcr-Abl1 signaling. Anti-PlGF treatment prolongs survival of imatinib-sensitive and -resistant CML mice and adds to the anti-CML activity of imatinib. These results may warrant further investigation of the therapeutic potential of PlGF inhibition for (imatinib-resistant) CML.     

Distinct functions of antigen-specific CD4 T cells during murine Mycobacterium tuberculosis infection

The immune response elicited after Mycobacterium tuberculosis (Mtb) infection is critically dependent on CD4 T cells during both acute and chronic infection. How CD4 T-cell responses are maintained throughout infection is not well understood, and evidence from other infection models has suggested that, under conditions of chronic antigen stimulation, T cells can undergo replicative exhaustion. These findings led us to determine whether subpopulations of CD4 T cells existed that displayed markers of terminal differentiation or exhaustion during murine Mtb infection. Analysis of antigen-specific effector CD4 T cells revealed that programmed death-1 (PD-1) and the killer cell lectin-like receptor G1 (KLRG1) delineated subpopulations of T cells. PD-1-expressing CD4 T cells were highly proliferative, whereas KLRG1 cells exhibited a short lifespan and secreted the cytokines IFNγ and TNFα. Adoptive transfer studies demonstrated that proliferating PD-1-positive CD4 T cells differentiated into cytokine-secreting KLRG1-positive T cells, but not vice versa. Thus, proliferating PD-1-positive cells are not exhausted, but appear to be central to maintaining antigen-specific effector T cells during chronic Mtb infection. Our findings suggest that antigen-specific T-cell responses are maintained during chronic mycobacterial infection through the continual production of terminal effector cells from a proliferating precursor population.