Influence of CYP2C19 on Helicobacter pylori eradication in Brazilian patients with functional dyspepsia.

The aim of this study was to examine the effect of polymorphisms in the cytochrome P450 (CYP) 2C19 gene (CYP2C19) on the Helicobacter pylori eradication rate in Brazilian patients with functional dyspepsia. Adults diagnosed with functional dyspepsia based on the ROME III criteria and infected with H. pylori were recruited to this study. The patients were subjected to gastrointestinal endoscopy and the H. pylori status was defined when both urease test and histopathology results were negative or positive. The patients were treated with proton pump inhibitor-based triple therapy (omeprazole, amoxicillin, and clarithromycin). CYP2C19*2 and CYP2C19*3 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. One hundred and forty-eight patients (81.8% women) with a mean (± SD) age of 46.1 (12.2) years were included in this study. Based on the CYP2C19 genotypes, the patients were classified as homozygous extensive metabolizer (HomEM; 67.6%), heterozygous extensive metabolizer (HetEM; 26.3%), or poor metabolizer (PM; 6.1%). The H. pylori eradication rates in patients with HomEM, HetEM, and PM were 85.0, 89.7, and 100.0% (P = 0.376), respectively. The included study population comprised a high frequency of patients carrying the HomEM genotype. Although the genotypes of CYP2C19 variants were not statistically significant, the results of this study suggest a possible effect of the PM genotype on the efficacy of H. pylori eradication.

Association between medication use and adverse gastroenterologic events in patients receiving enteral nutrition therapy at a University Hospital.

INTRODUCTION: Enteral Nutrition Therapy (ENT) is considered an important tool for the appropriate maintenance of nutritional conditions. ENT tolerance may be limited due to gastrointestinal (GI) events resulting from formula composition and/or simultaneously administered drug therapies. AIMS: To verify the possible association between GI events and drug therapies being administered to patients receiving ENT at a university hospital. METHODS: A prospective observational cohort study was conducted. Medical records from 95 patients requiring ENT at the Hospital de Clínicas de Porto Alegre (HCPA) were randomly evaluated until discharge, death, or initiation of oral or parenteral diet occurred. Details of the administered medications and enteral formula, together with the presenting patient disease and digestive manifestations, were recorded by the medical team. Three experienced gastroenterologists evaluated the possible association between the digestive symptoms and the medications employed. The study protocol was approved by the HCPA Research Ethics Committee and patient consent forms were signed. RESULTS: Mean patient age: 65±17 (24-95) years; 94.70% presented with GI events: constipation 70.50%, diarrhea 38.90%, abdominal distension 18.90%, vomiting 16.80%, and pulmonary aspiration 1.10%. ENT was most indicated in neurologic (50.50%) and neoplastic (25.30%) disease. Medications given to the patients showed a positive relation: 63.20% to 86.70% of GI symptoms could be attributed to the drugs being administered. CONCLUSIONS: GI complications during ENT are common; they are frequently linked to administered drug therapy. Health care teams should consider all risk factors present, specifically those related to prescribed medication, before modifying/suspending ENT.

Acute myopathy in a type 2 diabetic patient on combination therapy with metformin, fenofibrate and rosiglitazone.

AIMS/HYPOTHESIS: This report describes the case of a 75-year-old male type 2 diabetic Caucasian who was admitted to the clinical ward because of acute pain and cramps in both calf muscles. MATERIALS AND METHODS: Neuromuscular function was assessed by electromyography and electroneurography of the right leg. An open biopsy was taken from the left vastus lateralis muscle for histological and histochemical analyses. Southern blotting was performed to detect defects in mitochondrial DNA and tRNA. Cytochrome P450 (CYP-P450) polymorphisms were analysed in blood cells. RESULTS: Fifteen weeks before admission, the patient's lipid-lowering medication was switched from simvastatin to fenofibrate because of predominant hypertriglyceridaemia; this did not affect creatine kinase levels. Three weeks before admission, rosiglitazone was added to his existing metformin therapy because of worsening metabolic control. Upon admission, serum enzymes indicating myopathy were elevated (creatine kinase 6897 U/l, myoglobin 902 ng/ml) and kidney function was impaired (creatinine 0.116 mmol/l, blood urea nitrogen 2.3 mmol/l). Electrophysiology revealed myopathy and sensory polyneuropathy. Histology showed multiple damage of the myofibrillar architecture. There was no evidence of defects in mitochondrial DNA or tRNA. Furthermore, no functional limitations in CYP2C9, CYP2C19 and CYP2D6 were detected. Following withdrawal of the oral medication and intravenous hydration, clinical symptoms and laboratory parameters gradually decreased. CONCLUSIONS/INTERPRETATION: Until more data from controlled trials are available, we recommend that combination therapy with fibrates and thiazolidinediones should be monitored frequently by measurements of serum creatine kinase and creatinine, specifically in patients with pre-existing nephropathy and polyneuropathy.

Helicobacter pylori eradication does not cause reflux oesophagitis in functional dyspeptic patients: a randomized, investigator-blinded, placebo-controlled trial.

BACKGROUND: The protective role of Helicobacter pylori in gastro-oesophageal reflux disease has been widely discussed. AIM: To assess the risk of reflux oesophagitis in patients with functional dyspepsia after treatment for H. pylori infection. METHODS: A randomized, placebo-controlled, investigator-blinded trial was carried out on 157 functional dyspeptic patients. Patients were randomized to receive lansoprazole, amoxicillin and clarithromycin (antibiotic group) or lansoprazole and identical antibiotic placebos (control group). Upper gastrointestinal endoscopy was performed at baseline, 3 and 12 months after randomization. The primary aim was to detect the presence of reflux oesophagitis. Analyses were performed on an intention-to-treat basis. RESULTS: A total of 147 patients (94%) and 133 (85%) completed 3 months and 12 months follow-up, respectively. The eradication rate of H. pylori was 90% in the antibiotic group (74 of 82) and 1% (one of 75) in the control group. At 3 months, reflux oesophagitis was diagnosed in 3.7% (three of 82) in the antibiotic group and 4% (three of 75) in the control group (P > 0.2). At 12 months, diagnosis was established in five new cases within the first group and in four within the second (P > 0.2). No difference was found in heartburn symptoms. CONCLUSIONS: H. pylori eradication does not cause reflux oesophagitis in this western population of functional dyspeptic patients.

Symptoms of depression and anxiety, and screening for mental disorders in migrainous patients.

The purpose of this clinic-based study was the assessment of symptoms of depression, anxiety, and non-specific psychiatric disorders amongst patients with migraine, compared with healthy subjects and with individuals with a non-neurological chronic disease. A cross-sectional study was carried out in which 178 individuals (migraine 51; psoriasis 35; healthy 92) were submitted to three scales: MADRS (depression), STAI-T (anxiety) and SRQ (screening for mental disorders). The subjects with migraine and psoriasis were from the Out-patient Clinics of Headache and of Dermatology, and the healthy volunteers were persons who were accompanying out-patients in the same hospital. Scores were analysed by manova and by association analysis and logistic regression. Scores of all instruments were higher in the migrainous group, but the univariate analysis of association (using cut-offs) showed significance only for suspicion of mental disorders (SRQ). By logistic regression, variables with strongest association to migraine were gender, education, and SRQ in decreasing order.

Health related quality of life in patients with long-standing insulin dependent (type 1) diabetes mellitus: benefits of regular physical training.

BACKGROUND AND AIMS: Regular exercise is recommended to diabetic patients in addition to dietary restrictions and drug therapy. We have studied whether health related quality of life (HRQOL) can be improved by a regular physical training program. METHODS: 23 otherwise healthy patients with history of type 1 diabetes for 20 +/- 10 years were included. 15 patients (age: 41 +/- 2 years) participated in an aerobic physical training program over 4 months and 8 patients (33 +/- 11 years) served as a control group. HRQOL was assessed by a validated questionnaire (MOS SF-36). Tests were carried out at baseline and after 4 months. RESULTS: Physical training increased peak oxygen uptake (VO2max) by 27 +/- 13% after 4 months (p = 0.04) in the training group. There was no significant change in hand or leg isometric muscle strength. All HRQOL scales improved in the training group with significantly higher (p < 0.04) Social Functioning and Vitality scores, respectively. Moreover, insulin requirements decreased during physical training program (p < 0.05). CONCLUSIONS: Our data indicate that physical exercise training in patients with type I diabetes mellitus improves metabolic control and various aspects of HRQOL. Besides enhanced cardiorespiratory capacity, this is an important subjective benefit in patients with longstanding insulin dependent (type 1) diabetes mellitus.

Moyamoya disease associated with renovascular disease in a young African-Brazilian patient.

Moyamoya is a rare disease characterized by fibrous dysplasia of the internal carotid and proximal cerebral arteries, which has been described mainly in young Japanese. We present a case of Moyamoya disease with renal artery involvement in a young male patient with an African origin. A 15-year-old boy was referred to our hospital due to uncontrolled blood pressure, headache, somnolence, cognitive deficit and multiple lacunar infarcts in the computed tomography. Cerebral arteriography showed the absence of the normal vascular anatomy at the level of the circle of Willis. The intracranial vessels presented severe stenosis or were occluded and replaced by an extensive network of ectasic collateral vessels. Abdominal ultrasound examination identified asymmetric kidneys, and renal arteriography showed a tight stenosis of the ostium and proximal segment of right main artery, which was only partially relieved by balloon angioplasty. A saphenous bypass from aorta to the right renal artery re-established the renal blood flow. Blood pressure dropped after surgery and was controlled with low doses of diuretic and beta-blocker. After arteriography he presented right hemiplegia, with partial recovering in the following months. In conclusion, we described the first case of Moyamoya disease with concomitant renovascular disease in a young adult of African origin, an association that may be more frequent than usually suspected in clinical practice.

Expression patterns of retinoblastoma and E2F family proteins during corneal development.

PURPOSE: To determine the expression patterns of the retinoblastoma protein and the E2F transcription factor families in limbal and corneal epithelia and in corneal keratocytes in situ during corneal development and differentiation. METHODS: Retinoblastoma protein (pRb) and its family members p107 and p130; E2F-1, -2, and -4, members of the E2F family of transcription factors; and Ki67, a marker of actively cycling cells, were localized by indirect immunofluorescence microscopy, in corneas of neonatal, juvenile, and adult rats. Presence of mRNA for pRb, p107, p130, and E2F types 1 to 5 in adult corneal epithelium was determined by reverse transcription-polymerase chain reaction. RESULTS: mRNA for all members of pRb and E2F families was present in adult corneal epithelium. The greatest number of Ki67-positive corneal and limbal epithelial cells were present at days 13 to 19, and Ki67-positive stromal keratocytes at day 2. pRb and E2F-2 were localized to all cells in neonatal, juvenile, and adult corneas. With age, p130 localization became more intense and nuclear in stromal keratocytes and suprabasal cells of corneal and limbal epithelia; p107, initially nuclear in limbal and corneal epithelia, became increasingly cytoplasmic in corneal epithelium. E2F-1 was initially nuclear in keratocytes and diminished after day 10. E2F-1 was localized in the basal cell layer of limbal and corneal epithelia after day 10. E2F4 was always nuclear in limbal epithelium and cytoplasmic in corneal epithelium. CONCLUSIONS: Expression patterns of pRb and E2F family proteins vary with corneal cell differentiation, but are most apparent with p130 and p107. Nuclear localization of p130 appears to correlate with terminal differentiation in epithelium and entrance into a quiescent state by keratocytes. In contrast, p107 is nuclear in the undifferentiated limbal basal cells and is cytoplasmic in the remainder of the corneal epithelial cells.

Laser in situ keratomileusis for undercorrection after radial keratotomy.

PURPOSE: To assess the safety and efficacy of excimer laser in situ keratomileusis (LASIK) in treating residual myopia and/or astigmatism following refractive keratotomy. METHODS: Fourteen eyes that had previously undergone radial and/or arcuate keratotomy were included. The surgeries were performed using the Chiron Automated Microkeratome and the VISX 20/20B excimer laser. RESULTS: Average follow-up was 12.64+/-5.02 months. Mean spherical equivalent refraction was reduced from -3.48+/-3.52 D preoperatively to -0.04+/-0.87 D postoperatively. At the last follow-up examination there were 8 eyes (57.1%) with a refraction within+/-0.50 D, and 10 eyes (71.4%) within +/-1.00 D of emmetropia. Uncorrected visual acuity was 20/20 or better in 4 eyes (28.6%) and 20/40 or better in 10 eyes (71.4%). Vector analysis of the astigmatic correction showed an index of success of 80%. There was no significant loss (> or = or =2 lines) of spectacle-corrected visual acuity. We observed interface epithelial ingrowth in one eye. CONCLUSIONS: The correction of residual myopia and/or astigmatism with LASIK in eyes with prior refractive keratotomy proved to be safe and effective. Careful preoperative evaluation may help to avoid complications such as reopening of incisions during surgery or postoperative ingrowth of epithelium beneath the corneal flap.

Laser in situ keratomileusis to correct refractive errors after keratoplasty.

PURPOSE: To assess the safety and effectiveness of excimer laser in situ keratomileusis (LASIK) to correct refractive myopia, astigmatism, or both after keratoplasty. SETTING: Eye Clinic Day Hospital, São Paulo, Brazil. METHODS: Twenty-two eyes that had previously had corneal transplantation were studied. Laser in situ keratomileusis was performed using the Chiron automated microkeratome and the VISX Twenty-Twenty B excimer laser. RESULTS: Mean follow-up after LASIK was 10.09 months +/- 3.87 (SD). The spherical equivalent refraction dropped from -4.55 +/- 3.66 D before LASIK to -0.67 +/- 1.24 D after surgery. At the last examination, 72.7% of patients had a refractive error within +/- 1.00 D of emmetropia and 54.5% had uncorrected visual acuity of 20/40 or better. Vector analysis of astigmatic correction showed an index of success of 54.0%. Best spectacle-corrected visual acuity was unchanged in 8 cases, improved in 9, and decreased in 5. Significant endothelial cell loss, keratoplasty wound dehiscence, and other serious complications did not develop in any eye. CONCLUSION: The correction of refractive error with LASIK in postkeratoplasty patients proved to be safe, effective, and predictable. Further studies with longer follow-up are needed to determine the method's clinical value.

Evaluation of pentoxifylline in the prevention of haze after photorefractive keratectomy in the rabbit.

BACKGROUND: Pentoxifylline (PTX) is a methylxanthine derivative that, besides its hemorrheologic properties, possesses multiple physiologic effects at the cellular level. It has been used in keloid prevention due to its ability to inhibit the secretion of collagen and glycosaminoglycans from activated fibroblasts. METHODS: Ten New Zealand White (NZW) rabbits underwent a -7.00 diopters, 6.0 mm diameter photorefractive keratectomy after laser ablation of the epithelium with a VISX 20/20 excimer laser. The bare stroma was stained with fresh 0.5% dichlorotriazinyl aminofluorescein (DTAF). The procedure was performed on both eyes, 4 days apart. One eye received 1% Pentoxifylline qid and the other balanced salt solution qid as a control for 4 weeks, starting the same day of surgery. Two masked observers graded the amount of haze at 2, 4, 6, and 8 weeks after surgery using slit-lamp biomicroscopy. Three rabbits were sacrificed at 2 and 4 weeks followed by two rabbits at 6 and 8 weeks. The area between the DTAF-stained collagen to the base of the epithelium was measured using a digital image analyzer. RESULTS: There was no statistically significant difference in the amount of haze either by slit-lamp microscopy or by histological analysis between the pentoxifylline-treated eyes and the controls at any time interval (Student's t-test: 0.16 to 0.92) CONCLUSION: Pentoxifylline did not seem to affect haze formation in a PRK rabbit model. As no signs of toxicity were observed, further studies might examine higher concentrations or dose frequencies.