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Stephen Lewis

Publications and source records attributed to Stephen Lewis.

At least 19 recordsLinked to original sources

Alteration of sulfate and hydrogen metabolism in the human colon by changing intestinal transit rate.

OBJECTIVES: Changes in intestinal transit rate are also implicated in the etiology of many colonic diseases and strongly influence many metabolic processes in the colon. We set out to investigate whether intestinal transit time could influence the activity of the hydrogen-consuming bacterial flora and sulfate metabolism. METHODS: Normal volunteers underwent four interventions while taking a low-sulfate diet: placebo, sulfate supplements, or sulfate supplements with either senna or loperamide. Stools were cultured and analyzed for sulfate, sulfide, methionine, sulfate reduction rates, methionine reduction rates, acetic acid production rates, methane production rates, short-chain fatty acids, and bile acids. Urine was analyzed for sulfate. RESULTS: The addition of sulfate alone increased fecal and urinary excretion of sulfate, fecal sulfide, sulfate reduction rates, and acetic acid production rates; it reduced fecal methanogenic bacterial concentrations. Faster intestinal transit increased fecal sulfate, sulfide, bile acids, the reduction rates of sulfate, and methionine and the production rates of acetic acid. Reduction in fecal methanogens and methane production was seen. The reverse effects were seen with loperamide. CONCLUSIONS: Both sulfate supplements and changes in intestinal transit rate markedly alter the activity of the colonic bacterial flora with respect to sulfate metabolism and hydrogen disposal. Dietary influences on intestinal transit and sulfate consumption may influence disease processes. While a variety of processes govern sulfate metabolism and hydrogen disposal, our knowledge is far from complete. How far the observed changes in sulfate metabolism seen in certain diseases are relevant to the pathogenesis of the disease or secondary to the disease itself is unclear.

Acetic Acid↗

Vector-based spatial-temporal minimum L1-norm solution for MEG.

Minimum L1-norm solutions have been used by many investigators to analyze MEG responses because they provide high spatial resolution images. However, conventional minimum L1-norm approaches suffer from instability in spatial construction, and poor smoothness of the reconstructed source time-courses. Activity commonly "jumps" from one grid point to (usually) the neighboring grid points. Equivalently, the time-course of one specific grid point can show substantial "spiky-looking" discontinuity. In the present study, we present a new vector-based spatial-temporal analysis using a L1-minimum-norm (VESTAL). This approach is based on a principle of MEG physics: the magnetic waveforms in sensor-space are linear functions of the source time-courses in the imaging-space. Our computer simulations showed that VESTAL provides good reconstruction of the source amplitude and orientation, with high stability and resolution in both the spatial and temporal domains. "Spiky-looking" discontinuity was not observed in the source time-courses. Importantly, the simulations also showed that VESTAL can resolve sources that are 100% correlated. We then examined the performance of VESTAL in the analysis of human median-nerve MEG responses. The results demonstrated that this method easily distinguishes sources very spatially close to each other, including individual primary somatosensory areas (BA 1, 2, 3b), primary motor area (BA 4), and other regions in the somatosensory system (e.g., BA 5, 7, SII, SMA, and temporal-parietal junction) with high temporal stability and resolution. VESTAL's potential for obtaining information on source extent was also examined.

Adult↗

Efficacy of olanzapine and risperidone in schizophrenia: a randomized double-blind crossover design.

This article compares the efficacy of olanzapine and risperidone for positive and negative symptoms using an 18-week, randomized, double-blind, crossover design. The hypotheses were that olanzapine would be more efficacious for treating negative symptoms, and that risperidone would be superior in treating positive symptoms. Positive and negative symptoms scores improved throughout treatment, regardless of medication type. Differences between the medications were found for negative and general psychopathology rating scales. Overall, olanzapine led to greater improvements in negative symptoms than did risperidone. When each scale was analyzed individually, greater improvements were found for olanzapine on Positive and Negative Symptoms Scale (PANSS) General,PANSS total, and Scale for the Assessment of Negative Symptoms (SANS)attention. A nearly significant trend favoring olanzapine was found for the Calgary Depression Scale. Several negative symptom subscales followed a nonsignificant trend toward olanzapine being more efficacious than risperidone.Thus, there was a very consistent pattern of greater efficacy for olanzapine, particularly for negative symptoms. Despite the small number of subjects, this study shows the potential of a within-subject design to elucidate differences in efficacy.

Adult↗

Effect of the prebiotic oligofructose on relapse of Clostridium difficile-associated diarrhea: a randomized, controlled study.

BACKGROUND & AIMS: Ten percent to 20% of patients relapse after successful treatment of their Clostridium difficile -associated diarrhea. We set out to determine if the prebiotic oligofructose could alter the fecal bacterial flora and, in addition to antibiotic treatment, reduce the rate of relapse from C difficile infection. METHODS: Consecutive inpatients with C difficile -associated diarrhea were randomly allocated to receive oligofructose or placebo for 30 days in addition to specific antibiotic treatment. Patients were followed up for an additional 30 days. The main end point was the development of further diarrhea. Stools were collected for bacterial culture and C difficile toxin measurement. RESULTS: One hundred forty-two patients were recruited. Stool culture confirmed the probiotic effect of oligofructose with an increase in fecal bifidobacteria from baseline 8.68 log(10) colony-forming units (cfu)/g to 9.37 log(10) cfu/g at discharge (P < .0001; 95% confidence interval [CI], 0.45-0.94), 9.64 log(10) cfu/g at 30 days (P < .0001; 95% CI, 0.74-1.18), and 9.42 log(10) cfu/g at 60 days (P < .0001; 95% CI, 0.56-0.93). Thirty patients experienced a relapse of diarrhea after a median of 18 days (range, 8-34 days). Relapse of diarrhea was more common in those taking placebo (8.3% oligofructose vs 34.3% placebo, P < .001, chi(2) = 14.35). Patients who relapsed stayed in the hospital longer than those who did not (53 vs 26 days, P = .021; 95% CI, 2-28), and there was a longer period of time from commencing metronidazole or vancomycin and their diarrhea settling (6 vs 3 days; P = .007; 95% CI, 1.0-5.0). CONCLUSIONS: Fecal cultures confirmed the prebiotic effect of oligofructose. Patients taking oligofructose were less likely to develop further diarrhea than those taking the placebo.

Aged↗

Effects of metronidazole and oligofructose on faecal concentrations of sulphate-reducing bacteria and their activity in human volunteers.

OBJECTIVE: Sulphate-reducing bacteria (SRB) have been implicated in the aetiology of ulcerative colitis. Sulphide produced from reduction of sulphate by SRB is highly toxic to colonocytes and can impair their metabolic function. The aim of this study was to investigate the modulation of the colonic bacterial flora using metronidazole and the prebiotic oligofructose on the concentration and activity of SRB. MATERIAL AND METHODS: Healthy volunteers were randomly allocated to take metronidazole (5 days), oligofructose (12 days) or both metronidazole (5 days) and oligofructose (12 days). At days 0, 5, 12 and 19, stool samples were cultured, and their pH measured; concentrations of sulphate, hydrogen sulphide, short-chain fatty acids (SCFAs) were measured and the sulphate reduction rates (SRRs) determined. RESULTS: In SRB-positive volunteers (n=16) faecal SRB concentrations fell with metronidazole (95% CI, 2.19, 3.36 p<0.0001) even when combined with oligofructose (95% CI 2.32, 4.01 p<0.0001). Faecal anaerobe concentrations fell with metronidazole and bifidobacterial concentrations rose with oligofructose irrespective of SRB status. Faecal SRRs fell with metronidazole irrespective of the presence of faecal SRB (95% CI 29.0, 56.1 p<0.0001). No changes in faecal sulphate concentrations were seen. Faecal hydrogen sulphide concentrations fell with oligofructose in SRB-positive volunteers (95% CI 0.14, 0.53 p=0.002). Faecal SCFA concentrations fell with metronidazole (-103.7, -19.6, p=0.007) and rose with oligofructose (9.9, 83.1 p=0.016). CONCLUSIONS: The study shows that metronidazole, but not oligofructose, reduced the concentration and activity of faecal SRB. This reduction had no impact on faecal concentrations of sulphate and hydrogen sulphide, suggesting that other methods of hydrogen sulphide production are more important. Oligofructose causes a reduction in faecal hydrogen sulphide, and an increase in SCFA concentrations may thus have a therapeutic role in patients with ulcerative colitis.

Adult↗

Women and HIV.

Explore the source record for details and available documents.

Female↗

Perioperative and postoperative nutrition.

Nutritional deficiency among hospitalized patients is common, and is often unrecognized and untreated. Perioperative starvation is detrimental to recovery. Nutritional support can reduce morbidity, mortality and length of hospital stay. This article reviews the evidence for parenteral, enteral and oral nutritional support in the perioperative and postoperative period.

Eating↗

Visual processing of facial affect.

To evaluate the role of the fusiform gyrus in identifying and processing facial emotional expression in humans, MEG data were collected while six healthy subjects judged whether photographs of faces displayed emotion (happiness or disgust) compared to neutral faces and equiluminant scrambled faces. For all six subjects, a magnetic source localizing to right fusiform gyrus was evident approximately 150 ms following presentation of face stimuli, but not following non-face stimuli. MEG source strength for this component was greatest for happy, intermediate for disgust, and lowest for neutral facial expressions, suggesting that activity in fusiform gyrus is sensitive to both face-specific stimuli and to the affective content of the face. These findings are considered in the context of a specialized neural face-dependent information system.

Adult↗

Time-dependent inhibitory effects of indomethacin on spinal fusion.

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs following spine arthrodesis is discouraged because of the negative effects on bone-healing. We are not aware of any data regarding when nonsteroidal anti-inflammatory drugs may be safely resumed postoperatively. We hypothesized that these drugs have a time-dependent deleterious effect on fusion, with the greatest inhibition during the early phases of fusion. METHODS: Seventy New Zealand White rabbits underwent posterior intertransverse process arthrodesis at L5-L6 with use of iliac autograft. Rabbits randomly received indomethacin (10 mg/kg orally) starting at two weeks after surgery (twenty-four animals), indomethacin starting at four weeks postoperatively (twenty-three), or saline starting at two weeks postoperatively (twenty-three) (the control group). The animals were killed at six weeks, and the spines were denuded of soft tissues and palpated for L5-L6 motion. Fusion was defined as the complete absence of motion. RESULTS: Sixty-five percent (fifteen) of the twenty-three spines in the control group and 48% (eleven) of the twenty-three in the four-week group fused. However, only 21% (five) of the twenty-four spines in the two-week group fused. The difference between the two-week and control groups was significant (p < 0.002), as was the difference between the two and four-week groups (p = 0.05). The difference between the four-week and control groups was not significant (p = 0.2). CONCLUSIONS: The earlier that indomethacin was resumed postoperatively, the greater was its negative effect on fusion. Indomethacin appears to play a significant inhibitory role in the early phase of healing. Initiating indomethacin treatment in the latter phase of healing does not appear to significantly affect fusion rates, although there was a nonsignificant trend toward inhibition. To our knowledge, this is the first investigation of the time-dependent nature of indomethacin's effect on bone-healing.

Animals↗

The effect of cyclooxygenase-2 inhibitors on spinal fusion.

BACKGROUND: Spine surgeons discourage the use of nonsteroidal anti-inflammatory drugs following spine arthrodesis because of their inhibitory effect on bone-healing. To our knowledge, there are no data on the effects of the new cyclooxygenase-2 inhibitors on bone-healing. We undertook this study to determine the effects of these more selective nonsteroidal anti-inflammatory drugs on spinal fusion in a rabbit model. METHODS: Seventy-two New Zealand White rabbits underwent a posterolateral intertransverse process arthrodesis with use of autologous iliac crest bone. Sixty-six rabbits survived the surgical procedure and the perioperative period and had an uneventful postoperative course. These rabbits were randomly divided into three groups. One group received 10 mg/kg of celecoxib orally, the second group received 10 mg/kg of indomethacin orally, and the third group (the control group) received 1 cm (3) of saline solution orally. The rabbits received the treatment daily for eight weeks, after which they were killed and the lumbar spine was harvested. The specimens were palpated for motion, radiographed, and prepared for histological analysis. The quality of the fusion was graded at each level by assigning a histological score of 0 to 7. RESULTS: Gross inspection and palpation revealed that 64% (fourteen) of the twenty-two control spines and 45% (ten) of the twenty-two spines in the rabbits treated with celecoxib were fused. With the numbers available, this difference was not significant (p = 0.224). Of the twenty-two spines in the indomethacin-treated rabbits, 18% (four) were fused, and this percentage was significantly different from the control value (p = 0.002). On radiographic assessment, the spine segment was deemed to be fused in 82% (eighteen) of the twenty-two controls, 86% (nineteen) of the twenty-two rabbits treated with celecoxib, and 41% (nine) of the twenty-two indomethacin-treated animals. Only the difference between the indomethacin-treated and control groups was significant (p = 0.004). The histological scores averaged 5.2, 4.8, and 3.5 for the control, celecoxib, and indomethacin groups, respectively. There was a significant difference between the control and indomethacin groups (p = 0.002) but not between the celecoxib and control groups (p = 0.161). CONCLUSIONS: These results suggest that celecoxib does not significantly inhibit the rate of spinal fusion in rabbits. They also suggest that the inhibitory effects of nonsteroidal anti-inflammatory drugs on bone-healing are likely mediated by inhibition of cyclooxygenase-1 and that celecoxib is the better choice if treatment with nonsteroidal anti-inflammatory drugs is deemed necessary following spinal arthrodesis.

Administration, Oral↗