Evidence that oxidative stress is higher in replacement gilts than in multiparous sows.

The recent success obtained in term of increasing the litter size of sows has not correlated with a reduction of replacement rate. There is thus an increased economic demand for gilts with optimal reproductive potential and longevity. Unfortunately, replacement gilts are known to be more susceptible to diseases and less productive than multiparous sows. Interestingly, reproductive performance, resistance to diseases and longevity could all be largely affected by oxidative stress. To investigate whether oxidative stress conditions could account for the poor longevity of gilts, three distinct groups of conventional Yorkshire × Landrace sows were formed based on their similar age and parity (gilts, second parity sows as well as fourth to fifth parity sows). All animals were slaughtered during the post-ovulatory period, and blood as well as tissue samples were collected. Biomarkers of oxidative damage to proteins (carbonyls) and DNA (8-OHdG) were analysed in samples. Specific mRNA expression of major antioxidants such as glutathione peroxidases 1, 3 and 4 (GPx1, GPx3, GPx4) as well as superoxide dismutases 1 and 2 (Sod1, Sod2) were monitored in liver and kidney samples by quantitative RT-PCR. Specific enzymatic activities of both GPx and SOD were measured by spectrophotometric assays. The plasma concentration of protein carbonyls was significantly different between the three groups with the highest concentration being observed in gilts (p ≤ 0.001). The mRNA expression levels of GPx1 and GPx4 were also significantly increased in the liver of gilts when compared to multiparous sows (p ≤ 0.05). SOD2 enzymatic activity was found to be higher in the liver of gilts than multiparous sows (p ≤ 0.05). Taken together, these results indicate that replacement gilts sustain significantly higher oxidative conditions than multiparous sows. Current findings may contribute to the design of nutritional regimens that will increase the productivity of gilts by counteracting oxidative stress.

Epsilon-near-zero mode for active optoelectronic devices.

The electromagnetic modes of a GaAs quantum well between two AlGaAs barriers are studied. At the longitudinal optical phonon frequency, the system supports a phonon polariton mode confined in the thickness of the quantum well that we call epsilon-near-zero mode. This epsilon-near-zero mode can be resonantly excited through a grating resulting in a very large absorption localized in the single quantum well. We show that the reflectivity can be modulated by applying a voltage. This paves the way to a new class of active optoelectronic devices working in the midinfrared and far infrared at ambient temperature.

Huygens-Fresnel principle for surface plasmons.

We present an explicit form of the surface plasmon propagator. Its form has the structure of a vectorial Huygens-Fresnel principle. The propagator appears to be a powerful tool to deal with diffraction, interference and focusing of surface plasmons. In contrast with the scalar approximation used so far, the vectorial propagator accounts for near-field and polarization effects. We illustrate the potential of the propagator by studying diffraction of surface plasmons by a slit and focusing of surface plasmons by a Fresnel lens.

Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared to 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial.

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline. RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated. CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day.

[In vitro fertilization and smoking: use of urinary cotinine and expired air carbon monoxide measurements]. / Fécondation in vitro et tabac: intérêt de la cotininurie et de l'analyseur de monoxyde de carbone expiré.

OBJECTIVE: To study the correlation between expired air carbon (EACO) and urinary cotinine, and to determine the impact of tobacco smoking on in vitro fertilization (IVF) results. PATIENTS AND METHODS: We studied prospectively 221 patients in our ART center from October 2002 to October 2004: 51 active smokers, 85 passive smokers, and 85 non-smokers. Patients were classified into active, passive smokers, or non-smokers, based on a questionnaire. We measured urinary cotinine and EACO on the embryo transfer day and we recorded the IVF parameters. RESULTS: Two hundred and twenty-one patients were included. We observed a 17.2% reduction of estradiolemy (P=0.05), a 1.5% reduction of pregnancies (NS), a 7.8% reduction of infants born alive (NS), a 28.5% reduction of twin pregnancies (P=0.06), as well as a 10% increase of miscarriages (NS) in the active smokers in comparison with non-smokers (the same trends were observed between active and passive smokers). EACO and urinary cotinine were well correlated. There was a negative correlation between estradiolemy and urinary cotinine (R=-0.15, P=0.02). DISCUSSION AND CONCLUSION: Tobacco smoking intensity may be dilatory on IVF results. There is a high correlation between EACO and urinary cotinine. Other larger studies would probably obtain results more statistically significant.

A randomized, double-blind, placebo-controlled trial of CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, in patients with corticosteroid-dependent Crohn's disease.

AIM: To evaluate CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for the treatment of corticosteroid-dependent Crohn's disease. METHODS: Patients with corticosteroid-dependent Crohn's disease (use of prednisolone 15-40 mg/day or budesonide 9 mg/day for at least 8 weeks, a previous failed attempt to discontinue corticosteroids within 8 weeks, and Crohn's Disease Activity Index score 150 points or less) were enrolled in a 16-week, randomized, double-blind, placebo-controlled trial. The patients received intravenous CDP571 (20 mg/kg at week 0 and 10 mg/kg at week 8) or placebo. Corticosteroid therapy was decreased following a predefined schedule. The primary efficacy end-point was the percentage of patients with corticosteroid-sparing [i.e. no disease flare (Crohn's Disease Activity Index score > or =220 points) and no longer requiring corticosteroid therapy] at week 10. The major secondary efficacy end-point was corticosteroid-sparing at week 16. RESULTS: Seventy-one patients received treatment. Corticosteroid-sparing was achieved by 19 of 39 (48.7%) CDP571 patients and 13 of 42 (40.6%) placebo patients (P = 0.452) at week 10, and by 18 of 39 (46.2%) CDP571 patients and seven of 32 (21.9%) placebo patients (P = 0.032) at week 16. CDP571 therapy was well-tolerated and the incidence of serious adverse events was similar to placebo. CONCLUSIONS: The CDP571 was effective for corticosteroid-sparing at week 16 but not week 10, and was well-tolerated in patients with corticosteroid-dependent Crohn's disease.

Vascular endothelial growth factor production by isolated rat hepatocytes after cold ischemia-warm reoxygenation.

Inflammatory disturbances in the liver microcirculation have been associated with preservation injury of hepatic grafts. Vascular endothelial growth factor (VEGF), a proinflammatory growth factor released by hepatocytes, acts on sinusoidal endothelial cells, but its implication in graft injury is still unclear. We studied VEGF production by rat hepatocytes after cold ischemia and warm reoxygenation and compared the capacity of University of Wisconsin (UW) and sodium-lactobionate-sucrose (SLS) preservation solutions to maintain this hepatocellular function. Isolated hepatocytes were kept for 0, 24, and 48 hours at 4 degrees C in either solution (cold ischemia), then incubated for 1 to 24 hours at 37 degrees C (warm reoxygenation). We assessed cell viability and production of VEGF messenger RNA (mRNA) and protein. Cell viability decreased in a linear time-dependent fashion by 10% after 48 hours of cold preservation and by an additional 40% after 24 hours of warm culture. Very little VEGF mRNA could be detected after up to 48 hours of simple cold preservation in either solution. However, subsequent warm culture led to a robust and rapid increase in VEGF mRNA expression within the first hour, which declined to close to background levels within 8 to 12 hours in culture. This effect was more important in cells preserved in SLS than UW solution. Similarly, cold preservation alone did not trigger VEGF secretion. VEGF secretion was detected after culturing hepatocytes at 37 degrees C and reached a maximal secretion rate within 12 to 15 hours. However, VEGF production by preserved cells was reduced compared with unstored cells. In conclusion, cold ischemia and warm reoxygenation triggers VEGF mRNA expression by hepatocytes, but subsequent VEGF secretion is partially impaired, suggesting posttranslational defects.

Bismuth-based quadruple therapy with bismuth subcitrate, metronidazole, tetracycline and omeprazole in the eradication of Helicobacter pylori.

BACKGROUND: A previous study showed that 14 days of qid bismuth-based triple therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth subcitrate 120 mg resulted in excellent Helicobacter pylori eradication rates (89.5%). The present study looked at a shorter treatment period by adding omeprazole and by reducing the dose of tetracycline. METHODS: One hundred sixty-one patients with H pylori confirmed by histology and (13)carbon urea breath test were included in the study. They were treated for seven days with bismuth subcitrate 120 mg plus metronidazole 250 mg plus tetracycline 250 mg qid plus omeprazole 20 mg bid (OBMT). Patients were 18 to 75 years of age and had dyspepsia with or without a history of peptic ulcer. Patients with irritable bowel syndrome, active ulcer or previous attempt at eradication, or those who had used antibiotics or antiulcer drugs in the previous 30 days were excluded. Eradication was determined by two (13)carbon urea breath tests done one and three months, respectively, after treatment. Strains with minimal inhibitory concentrations of 8 microg/mL or higher were considered to be resistant to metronidazole. RESULTS: The overall per protocol eradication rate was 84%-89.5% in metronidazole-sensitive and 70.8% in metronidazole-resistant strains. Modified intent-to-treat analysis resulted in a 80% eradication rate--82.5% in metronidazole-sensitive and 66.7% in metronidazole-resistant strains. Only one patient discontinued treatment because of adverse events. CONCLUSIONS: The OBMT regimen used in this study is safe and effective against metronidazole-sensitive H pylori strains.

An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial.

BACKGROUND & AIMS: We evaluated CDP571, a humanized antibody to tumor necrosis factor, for the treatment of active Crohn's disease. METHODS: One hundred sixty-nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week placebo-controlled trial. Patients were initially randomized to a single dose of 10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess subsequent dosing intervals. The primary endpoint was clinical response at week 2, defined as a decrease in the Crohn's Disease Activity Index score > or = 70 points. RESULTS: At week 2, clinical response occurred in 45% of CDP571-treated patients compared with 27% of patients in the placebo group (P = 0.023). Patients appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of the results for secondary endpoints were statistically significant. The frequency of severe or serious adverse events was similar among all groups. CONCLUSIONS: CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment of patients with moderate-to-severe Crohn's disease. Preliminary evidence suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks may also be beneficial, but additional studies are needed.

STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation.

To investigate the role of signal transducer and activator of transcription (STAT) proteins in granulocyte colony-stimulating factor (G-CSF)-regulated biological responses, we generated transgenic mice with a targeted mutation of their G-CSF receptor (termed d715F) that abolishes G-CSF-dependent STAT-3 activation and attenuates STAT-5 activation. Homozygous mutant mice are severely neutropenic with an accumulation of immature myeloid precursors in their bone marrow. G-CSF-induced proliferation and granulocytic differentiation of hematopoietic progenitors is severely impaired. Expression of a constitutively active form of STAT-3 in d715F progenitors nearly completely rescued these defects. Conversely, expression of a dominant-negative form of STAT-3 in wild-type progenitors results in impaired G-CSF-induced proliferation and differentiation. These data suggest that STAT-3 activation by the G-CSFR is critical for the transduction of normal proliferative signals and contributes to differentiative signals.

Bismuth-based triple therapy with bismuth subcitrate, metronidazole and tetracycline in the eradication of Helicobacter pylori: a randomized, placebo controlled, double-blind study.

OBJECTIVE: To determine the rate of Helicobacter pylori eradication following bismuth-based triple therapy with colloidal bismuth subcitrate, tetracycline hydrochloride and metronidazole. PATIENTS AND METHODS: One hundred and eleven patients were randomly assigned, in a two to one ratio, to colloidal bismuth subcitrate 120 mg qid plus metronidazole 250 mg qid plus tetracycline 500 mg qid (Gastrostat), or matching placebo tablets and capsules for 14 days. Presence or absence of H pylori was documented by histology at entry and at least 28 days after treatment. Patients had dyspeptic symptoms with or without a history of peptic ulcer. Patients with any previous attempt(s) at eradication of H pylori, who used bismuth, antibiotics, H2 receptor antagonists or proton pump inhibitors in the previous four weeks were excluded. RESULTS: Fifty-three of 59 (90%) patients on bismuth-based treatment and only one of 35 (3%) on placebo achieved eradication by per protocol analysis. Fifty-three of 65 (82%) patients on bismuth-based treatment achieved eradication, while only two of 34 (5%) achieved eradication on placebo by intention to treat analysis. Eradication rates for bismuth-based treatment across sites ranged from 83% to 100%. Only two patients in the bismuth-based treatment group (4%) and one in the placebo group (3%) discontinued treatment because of adverse events. CONCLUSIONS: Colloidal bismuth subcitrate plus metronidazole plus tetracycline, given in the doses studied for 14 days, is safe and highly effective against H pylori infection and would be appropriate as a first-line therapy for eradication.

Rate and cost of hospitalizations for asthma in Quebec: An analysis of 1988/89, 1989/90 and 1994/95 data.

The objectives of this study were to evaluate recent trends in the frequency and length of stay of hospitalization for asthma in the province of Quebec and to estimate the costs of asthma hospitalizations. Data were extracted for persons hospitalized for 30 days or less with a primary diagnosis of asthma in all Quebec short-stay hospitals during the years 1988/89, 1989/90 and 1994/95. There were 1.76 asthma hospitalizations per 1000 persons in Quebec in 1988/89, down to 1.44 in 1989/90 and up again to 1.75 in 1994/95. There was a small decrease in mean length of stay when the three data years were compared. In all three years, the rate of hospitalization was particularly high among young boys. In 1994/95, more hospitalizations occurred during the fall months. We estimated the total cost for asthma hospitalization that year to be $18 to $21 million.

Omeprazole and ranitidine in the prevention of relapse in patients with duodenal ulcer disease.

BACKGROUND: Although the eradication of Helicobacter pylori is of primary importance when initiating treatment, it is also important to have a strategy for patients who are H pylori-negative, fail to demonstrate eradication or have a tendency to become re-infected or relapse. PATIENTS AND METHODS: In a double-blind, parallel-group clinical trial of 928 patients (from 70 centres in 16 countries) with duodenal ulcers who after a short term study had relief of symptoms and healed ulcers proved endoscopically, 308 were randomly assigned to receive omeprazole 10 mg in the morning, 308 to receive omeprazole 20 mg in the morning and 312 to receive ranitidine 150 mg at bedtime for up to 12 months. Symptoms were assessed every three months and endoscopy repeated at three, six and 12 months, or more often if indicated by recurrence of symptoms. The safety screening included basal serum gastrin concentrations and gastric mucosal histopathology. RESULTS: The remission rates up to 12 months were 87% for the omeprazole 20 mg group, 71% for the omeprazole 10 mg group and 63% for the ranitidine group. Omeprazole 20 mg differed significantly from both omeprazole 10 mg (P=0.0001, 95% CI 9 to 23) and ranitidine (P=0.0001, 95% CI 17 to 31). There was no statistically significant difference between omeprazole 10 mg and ranitidine over the 12-month period, but the 95% confidence interval allowed differences between 0% and 16% in favour of omeprazole at 12 months. A Cox regression analysis revealed that longer treatment courses to heal, smoking, a long ulcer history and young age negatively contributed to the odds of staying in remission. The treatments were well tolerated. There was a slight increase in basal serum gastrin concentrations, reflecting the different degrees of acid inhibition induced by the three treatments. No dysplastic or neoplastic lesions were found in any biopsies. CONCLUSIONS: More duodenal ulcer patients are maintained in remission with omeprazole 20 mg daily than with omeprazole 10 mg daily or with ranitidine 150 mg at bedtime.

Short-course therapy with amoxycillin-clarithromycin triple therapy for 10 days (ACT-10) eradicates Helicobacter pylori and heals duodenal ulcer. ACT-10 Study Group.

BACKGROUND: Whilst the role of Helicobacter pylori eradication in managing duodenal ulcers has been established, consensus regarding the ideal regimen has not been achieved. METHODS: Patients with H. pylori-positive active duodenal ulcer were randomly assigned to receive triple therapy with amoxycillin 1000 mg b.d. + clarithromycin 500 mg b.d. + omeprazole 20 mg daily for 10 days (ACT-10) or dual therapy with clarithromycin 500 mg t.d.s. + omeprazole 40 mg daily for 14 days (Dual). No additional acid suppression was provided following eradication therapy. Endoscopy, with biopsy for culture and histology, as well as 13C-urea breath testing (13C-UBT) were performed pre-treatment to assess H. pylori infection. H. pylori eradication was established at 4-6 weeks follow-up with culture (2 antral, 1 corpus biopsies), histology (2 antral biopsies), and 13C-UBT. Ulcer healing by endoscopy and change in clinical symptoms were also assessed at 4-6 weeks. RESULTS: Two hundred and sixty-seven (267) patients were randomized to ACT-10 (n = 137) or Dual therapy (n = 130). By per-protocol and intention-to-treat analyses, H. pylori eradication at 4-6 weeks follow-up was 91% (115/127) and 88% (120/136), respectively, for ACT-10 patients and 59% (68/115) and 55% (72/130), respectively, for Dual therapy patients (P < 0.001 for both analyses). Ulcer healing was high in both treatment groups: ACT-10, 93% (118/127) and 90% (122/136), respectively; and Dual therapy, 91% (104/114) and 85% (111/130), respectively. Pre-treatment resistance to clarithromycin was low (4%, 8/214) as compared to metronidazole resistance which was over 40%. Emergence of resistance to clarithromycin was observed in 2% of patients receiving ACT-10 and in 25% of those receiving Dual therapy. ACT-10 and Dual therapy patients experienced similar rates of drug-related adverse events (33% vs. 32%, respectively) and discontinuation from therapy due to an adverse event (1.5% vs. 5%, respectively). More than 90% of patients were compliant with each prescribed medication. CONCLUSION: In patients with active duodenal ulcer, a 10-day course of amoxycillin-clarithromycin-based triple therapy without additional acid suppression is highly effective in eradicating H. pylori and healing duodenal ulcer.

A double-blind randomized study of cisapride in the treatment of nonulcer dyspepsia. The Canadian Cisapride Nud Study Group.

Cisapride is a substituted benzamide with gastrointestinal prokinetic effects presumed to be due to the enhancement of the physiological release of acetylcholine at the myenteric plexus. In a multicentre study, 189 patients with nonulcer dyspepsia (NUD) received single-blind placebo treatment for two weeks. A total of 123 patients with no or minimal response to placebo and epigastric pain of at least moderate severity and frequency were randomly assigned to one of the three parallel double-blind treatments for six weeks: cisapride 10 mg tid, cisapride 20 mg tid or placebo. The severity and frequency of individual symptoms (epigastric pain, heartburn, nausea, vomiting anorexia, postprandial discomfort, regurgitation, lower abdominal pain, bloating and constipation) were assessed on a four- and five-point categorical scale, respectively, by the investigator at three on treatment visits and by patients in a daily diary. Analysis of investigator and patient assessments for differences in symptom severity x frequency composite scores among the three treatment groups showed no statistically significant differences for individual symptoms or symptom clusters. As assessed by the investigator, and compared with baseline, cisapride 20 mg tid significantly (P < 0.05) improved epigastric pain, bloating and early satiety as well as improved the total symptom cluster. Investigator evaluation of the five most severe and frequent symptoms for each patient showed statistically significant improvement in each treatment group. For patient diary assessments, statistically significant within-treatment improvement of the total symptom cluster, the five most severe symptoms cluster, bloating and early satiety was observed for both cisapride 20 mg and placebo, whereas epigastric pain significantly (P < 0.05) improved in all three treatment groups. Investigator evaluation of global response (good+excellent) rate at the end of the six week treatment period was 38% for cisapride 20 mg, 47% for cisapride 10 mg and 33% for placebo. No statistically significant difference in this parameter among treatments was noted. Cisapride was well tolerated at both doses with a side effect profile comparable with that of placebo. It is concluded that in this double-blind multicentre study with a single-blind two-week placebo run in phase, cisapride 10 mg tid and 20 mg tid were not effective compared with placebo in improving symptoms in NUD patients. This study re-emphasizes the good prognosis of patients with NUD, with 14% of patients improving in the two-week placebo run-in phase and a further 33% improving in the next six weeks while on placebo. Within-treatment analysis of investigator assessments showed improvement for cisapride 20 mg tid suggesting a trend of efficacy at this dose.

Utilization of anti-asthma medications in two Quebec populations of anti-asthma medication users: a prescription database analysis.

This study describes the utilization of anti-asthma medications in two groups of users of such medications in the province of Quebec, Canada, during the year from June 1, 1990, to May 31, 1991. It is based on a secondary analysis of existing data banks recording the medications reimbursed by two government-funded ambulatory drug reimbursement programs that cover individuals aged 65 and over (seniors) and income security (welfare) recipients (ISRs). The study analyzed the use of the anti-asthma medications included in the list of medications eligible for reimbursement for program beneficiaries. Use was studied in two random samples of individuals who had at least one prescription filled for an anti-asthma medication (2566 seniors and 3695 ISRs). The most commonly used medication in both groups was inhaled salbutamol 100 mcg. Various forms of theophylline tablets were also used by a high proportion of the sample studied. Over 75% of the seniors and 68% of the ISR group used at least one form of theophylline during the course of the year. Inhaled corticosteroids were used by 43% of the seniors and by 36% of the ISR group, and sympathomimetics (beta 2-agonists), by 63% of seniors and 68% of ISRs.

Treatment of acute lead ingestion in a juvenile macaw.

A juvenile domestic green-winged macaw was admitted to the veterinary clinic within an hour of ingestion of lead drapery weights. Radiopaque objects were evident in the crop and ventriculus. The bird was anesthetized, and the crop was lavaged to remove lead fragments. Because lead fragments remained in the ventriculus after lavage, chelation treatment was instituted. Serial radiography was done on days 2, 5, 9, and 14 to determine passage of the lead. By day 14, lead fragments were not visible radiographically. The macaw did not have ill effects from the lead ingestion or from medical treatments. Because this bird had been observed ingesting the lead weights, treatment was for foreign body ingestion initially and for lead ingestion secondarily.

Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators.

BACKGROUND: Long-term corticosteroid therapy for Crohn's disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohn's disease has been suggested, the long-term safety and efficacy of this treatment have not been established. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of the effect of 18 months of low-dose cyclosporine treatment on the course of Crohn's disease. Adult patients whose disease had been active within the previous two years were randomly assigned to receive cyclosporine (151 patients) or placebo (154 patients) in addition to their usual therapy. Randomization was stratified according to center and score on the Crohn's Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 150). The primary outcome measure was clinically important worsening of Crohn's disease, defined as a 100-point increase in the Crohn's Disease Activity Index from the patient's base-line value. Secondary outcomes were the use of prednisone and 5-amino-salicylates, mean score on the Crohn's Disease Activity Index and mean quality-of-life score, and the need for surgery. RESULTS: The condition of more patients worsened with cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of disease in patients receiving cyclosporine was 338 days, as compared with 492 days in patients receiving placebo (P = 0.25; relative risk, 1.22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mean Crohn's Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate benefit. CONCLUSIONS: In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy.

Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial Study Group.

BACKGROUND/AIMS: Quality of life (QOL), a subjective index of health perception and function, embraces physical, social, and emotional performance but has not had a prominent role in clinical trials of inflammatory bowel disease (IBD). To test the robustness of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific QOL index, this study assessed its validity, reliability, and responsiveness during a multicenter trial. METHODS: Three hundred five patients with stable Crohn's disease received cyclosporin or placebo for 18 months. IBDQ and dimensional scores (bowel, social, systemic, and emotional) were correlated with disease activity (Crohn's disease activity index [CDAI] and Harvey-Bradshaw index). Concordance of IBDQ scores was tested in 280 stable subjects. Linear regression evaluated change in IBDQ scores over time. RESULTS: IBDQ scores correlated highly with CDAI (r = -0.67; P < 0.0001). The reliability coefficient for IBDQ score was 0.70 vs. 0.66 for CDAI and 0.55 for Harvey-Bradshaw index. Regression line slopes of IBDQ scores were significantly different in patients who deteriorated from those who remained stable ([b] < 0.15; P < 0.0001). QOL scores were lower in patients who required surgery. CONCLUSIONS: The IBDQ is a valid reliable assessment tool that reflects important changes in the health status of patients with IBD. The IBDQ is a robust measure of therapeutic efficacy and should be used in future clinical trials in IBD.

Medication Compliance in a Family Practice: Testimg a self-report questionnaire in a primary care setting.

For the physician in a primary care setting, a self-report questionnaire on medication compliance can help to determine whether a lack of hypertension control is due to a drug-taking behavior problem or inadequate medication. Such a questionnaire can easily be implemented as a part of routine care and can help clinicians increase the efficiency of medical care dispensed to hypertensive patients.