Evaluation of the pathogenesis of flatulence and abdominal cramps in patients with lactose malabsorption

Aim of this study was to assess whether the interindividual differences in the development of flatulence and cramps in patients with lactose malabsorption are due to the quantity of malabsorbed lactose or gas accumulation, or if accelerated intestinal transit or increased perception of gas might play a role. Hydrogen breath tests were performed in 43 patients with lactose malabsorption after ingestion of 50 g lactose and, on a separate day, 25 g lactulose. The unabsorbed amount of lactose, small bowel transit time and colonic hydrogen accumulation were assessed in patients who did and did not develop flatulence and cramps after ingestion of lactose. The unabsorbed amount of lactose, small bowel transit time and volume and rate of colonic hydrogen accumulation were the same in patients who did or did not have symptoms after lactose. Patients with flatulence and cramps had a significantly longer time interval between the onset of the increase and peak breath hydrogen concentration (p < 0.05) and a significant correlation between the time of occurrence of peak symptoms and the time of peak breath hydrogen concentration (r = 0.75, p < 0.001). Our data suggest that subjective symptoms of lactose intolerance are not due to the amount of malabsorbed lactose or to the volume or rate of gas accumulation per se, but are related to increased perception of gas.     

Neuromuscular function in HIV infection: analysis of a placebo-controlled combination antiretroviral trial. AIDS Clinical Group 175/801 Study Team

OBJECTIVE: To determine the frequency of peripheral neuropathy and myopathy in HIV-infected subjects enrolled in a combination antiretroviral treatment trial. DESIGN AND METHODS: AIDS Clinical Trial Group (ACTG) protocol 175 was a multicenter, double-blind, placebo-controlled, clinical trial. A total of 2467 subjects were randomized to one of four single or combination regimens, containing zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), and their respective placebos. Site investigators reported peripheral neuropathy, and the diagnosis of distal symmetrical neuropathy (DSP) was established by the study authors. Myalgia, muscle weakness and creatine phosphokinase (CPK) were prospectively assessed in a subset of the antiretroviral-naive cohort (n = 1067). RESULTS: Of 222 site diagnoses of neuropathy, 109 (49%) were DSP. There was a significant difference between treatment arms for rate of DSP and time to first grade 2 or higher DSP (ZDV-ddC, 6%; ZDV, 4%; ZDV-ddl, 4%; ddl, 3%; P = 0.029). Age and Karnofsky score were significant predictors of DSP. Fifty-six (54%) out of 104 patients with DSP remained on study medication at full (n = 29) or reduced (n = 27) dose within 6 months of developing neuropathy. There was no significant difference between treatment arms in the rate of myalgia or muscle weakness. The median CPK of subjects on ZDV-ddC was significantly higher than other study treatments, although CPK levels did not correlate with symptoms of myopathy. Only six subjects were diagnosed with myopathy during the study (one ZDV-ddl, one ZDV-ddC, and four ddl). CONCLUSIONS: DSP and myopathy may occur with current dosing regimens of combination antiretroviral therapy, and should be diagnosed using stringent criteria. ZDV-ddC was associated with the highest rate of DSP, although features of myopathy were not significantly different between treatment regimens.     

Pneumatic retinopexy failures. Cause, prevention, timing, and management

BACKGROUND: Pneumatic retinopexy is a procedure for reattaching the retina by injecting an expanding gas bubble and using either laser or cryopexy. The procedure is controversial because there may be a lower initial success rate, and intraocular gas may increase the risk of proliferative vitreoretinopathy. METHODS: The authors performed a retrospective review of 107 unpublished consecutive cases of pneumatic retinopexy together with a literature review of 25 statistical series with primary attention to failures. Univariate and multivariate analyses were carried out on the data set, and adjusted odds ratios for risk factors associated with failure were calculated using logistic regression. RESULTS: Initially, 74 (69%) of 107 patients had successful results, and with re-operations the success rate increased to 98%. Failure of the procedure to achieve retinal reattachment occurred soon after the initial procedure, with 86% of recorded failures occurring within the first month. The initial cause of failure was new or missed breaks in 14.9%, reopened initial breaks in 11.2%, and breaks never closed in 4.6%. Risk factors that showed a correlation with failure were patients being male (adjusted odds ratio = 2.65), eyes with preoperative visual acuity worse than 20/50 (adjusted odds ratio = 1.21), eyes with four quadrants of retinal detachment or total detachment (adjusted odds ratio = 2.03), aphakic or pseudophakic eyes (adjusted odds ratio = 1.91), and eyes with additional pathologic findings (adjusted odds ratio = 3.14). Poor visual outcome was associated with initial visual acuity less than 20/50 (adjusted odds ratio = 15.7) and eyes with four quadrants of retinal detachment or total detachment (adjusted odds ratio = 5.01). CONCLUSIONS: Failures of pneumatic retinopexy occur early in the postoperative course. Factors known to be associated with failure of retinal reattachment using scleral buckling also were associated with failure in pneumatic retinopexy. A higher success rate in females was noted, suggesting that educational efforts may need to be greater in males. Poorer visual results occurred in patients with poor initial vision and in eyes with four quadrants of retinal detachment or total detachments.     

Micropipette manipulation technique for the monitoring of pH-dependent membrane lysis as induced by the fusion peptide of influenza virus

We have assembled a micropipette aspiration assay to measure membrane destabilization events in which large (20-30 microns diameter) unilamellar vesicles are manipulated and exposed to membrane destabilizing agents. Single events can be seen with a light microscope and are recorded using both a video camera and a photomultiplier tube. We have performed experiments with a wild-type fusion peptide from influenza virus (X31) and found that it induces pH-dependent, stochastic lysis of large unilamellar vesicles. The rate and extent of lysis are both maximum at pH 5; the maximum rate of lysis is 0.018 s-1 at pH 5. An analysis of our data indicates that the lysis is not correlated either to the size of the vesicles or to the tension created in the vesicle membranes by aspiration.     

Sialyl Lewis(x)/E-selectin-mediated rolling in a cell-free system

Selections mediate transient adhesion of neutrophils to stimulated endothelial cells at sites of inflammation by binding counter-receptors that present carbohydrates such as sialyl Lewis(x). We have developed a cell-free adhesion assay using sialyl Lewis(x)-coated microspheres and E-selection-IgG chimera-coated substrates to investigate the premise that rolling primarily results from functional properties of selection-carbohydrate bonds, whereas cellular morphology and signaling act as secondary effects. Sialyl Lewis(x)-coated microspheres attach to and roll over E-selectin-IgG chimera-coated substrates between the physiological wall shear stresses of 0.7 and 2 dynes/cm2. Rolling velocities vary with time and depend on E-selectin-IgG chimera site density and wall shear stress. Our results show that sialyl Lewis(x) is a minimal functional recognition element required for rolling on E-selectin under flow.