Endoscopy in Asymptomatic Minidose Aspirin Consumers

Aspirin is widely used for its antiplatelet activity, but it harbors a risk of severe adverse gastrointestinal effects, such as bleeding and perforation, especially in elderly people. Our aim to assess the prevalence of upper gastrointestinal lesions and the effect of aspirin on the gastrointestinal mucosa in asymptomatic subjects taking minidose aspirin (100 to 325 mg per day) for more than 3 months. A prospective, open design was used. Patients attending the ophthalmology and cardiology outpatient clinics who had a medical history of more than 3 months of regular aspirin consumption were referred for esophagogastroduodenoscopy (EGD). Of the 90 patients referred for EGD, 44 were symptomatic (epigastric pain or dyspepsia) and were excluded from the study. The 46 asymptomatic patients included 22 men and 24 women of mean age 70 ± 10 years (range, 36 to 87 years); 32% were current or former smokers. Mean daily aspirin dose was 129.34 ± 76.61 mg. Only 24% were taking a gastroprotective agent. EGD revealed ulcer or erosions in 47.83% of the patients: erosive gastroduodenitis in 13 patients, gastric ulcer in 14, duodenal ulcer in 2, and gastric and duodenal ulcers in 2. Urease test for Helicobacter pylori infection was positive in 26%. Univariate and multivariate analysis revealed no factor other than aspirin predictive of a positive endoscopy. Minidose aspirin treatment is associated with a high prevalence of ulcerations of the stomach and duodenum.     

Serologic Testing for Celiac Disease in Young Adults—A Cost–Effect Analysis

In recent years, there has been a marked increase in the diagnostic workups for celiac disease among military personnel, thereby significantly increasing overall laboratory testing expenditures and burden. We evaluated the serologic testing procedure in symptomatic young adults, using a cost–effect approach. We evaluated the serologic screening policy for celiac disease among serologically tested military personnel. The study population was divided into subgroups according to the clinical presentation prior to screening: isolated (low-risk) and combined complaints (high-risk). Sensitivity, specificity, and predictive values of serologic markers for celiac disease were evaluated. Cost analyses were based on diagnostic expenditures. Cost–effect ratio is expressed as cost per newly diagnosed patients, and cost minimization as cost per screened individuals. Five hundred thirty-eight military personnel were serologically tested for celiac disease. Eight new cases of celiac were diagnosed, all of whom belonged to the high-risk subgroup and tested positive for at least two positive serologic tests (tTG + EMA or tTG + AGA IgG + EMA). EMA Ab measured the highest sensitivity, specificity, and predictive values. Average screening expenditure was U.S. $287 per patient. The lowest cost–effect and cost minimization ratios were achieved by implementing a two-step single-marker screening protocol for high-risk subjects and one-step follow-up for low-risk subjects. Among patient population of young adults, selective diagnostic workup could result in cost-minimization without risking quality of diagnosis. From a cost–effect perspective, implemented screening procedures need to be dependent on subgroup: low-risk, clinical follow-up; and high-risk, serological testing for EMA and, only if positive, possibly a small-bowel biopsy.     

Preimplantation genetic diagnosis of Canavan disease

OBJECTIVE: Canavan disease is an autosomal recessive disorder which is relatively common in Ashkenazi Jews. It is characterized by developmental delay, severe hypotonia and early death, and is caused by a deficiency of aspartoacylase which is encoded by the ASPA gene. In Ashkenazi Jews, one major mutation (E285A) and one minor mutation (Y231X) account for the majority of cases. The objective of this study was to develop a preimplantation genetic diagnosis (PGD) protocol for Canavan disease. METHODS: Two carrier couples requested PGD for Canavan disease. In 1 couple each was a carrier of a different ASPA mutation (Y231X and E285A). In the other couple both were carriers of the minor mutation (Y231X). A single-cell duplex nested polymerase chain reaction (PCR) protocol was first developed on single leukocytes obtained from the known carrier parents. Following verification in single leukocytes, clinical PGD was offered to both couples. RESULTS: We evaluated 115 single leukocytes from known carriers and found an allele drop out rate of 1.7% for the fragment harboring the Y231X mutation and 0% for the fragment harboring the E285A mutation. One cycle of PGD was performed in each family. In the first, 11 embryos were successfully analyzed and 4 were found to be affected. Two unaffected embryos were transferred, but no pregnancy resulted. In the other family, 4 embryos were analyzed, 1 was affected, 2 were heterozygotes and 1 was homozygous normal. Following transfer of 2 unaffected embryos, a singleton pregnancy resulted, currently ongoing at 18 weeks gestational age. Amniocentesis performed at 16 weeks confirmed the diagnosis. CONCLUSION: Reliable PGD for Canavan disease is possible using a single-cell nested PCR approach.     

To Test or Not To Test? Moderators of the Relationship Between Risk Perceptions and Interest in Predictive Genetic Testing

The moderating effects of motivational factors (illness prevention vs. emotional reassurance), regulatory focus (health vs. illness orientations), and cancer anxiety on the relationship between risk perceptions and women's interest in predictive genetic testing for breast cancer were studied among 102 women with no history of breast cancer. Risk perceptions per se were unrelated to testing interests. Perceptions of higher personal risk for developing breast cancer were positively related to women's interest in testing only among women whose dominant motivation was not emotional reassurance, who were not oriented towards ruling-out disease, and who were not highly anxious about breast cancer. These findings pointed to conditions under which risk perceptions may enhance screening behaviors, and other conditions under which they may not. This study was done in partial fulfillment of the M.A. thesis of the second author.     

Beta-adrenergic hyperresponsiveness in compensated hypothyroidism associated with Down syndrome

Although compensated hypothyroidism (CH) is the most common thyroid impairment in Down syndrome (DS), its pathogenesis remains elusive. Because primary gonadal failure is another DS-associated endocrinopathy, we hypothesized that an impaired signal-transduction pathway shared by several organs may provide a unifying explanation for both endocrinopathies. We assessed two possible transduction-pathway components associated with CH in DS: the G-protein adenylate-cyclase (AC) system and beta-adrenergic responsiveness, previously reported to be enhanced in DS fibroblasts. Twenty-one DS patients and 14 control subjects were studied. Peripheral mononuclear cells (PMCs) were incubated with G-protein modulators [prostaglandin E1 (PGE1) and cholera toxin (CTx)], an AC stimulator (forskolin), and a beta-adrenergic agonist (isoproterenol), and cAMP levels were determined. All participants had normal plasma thyroid hormone levels, but 11 of the DS patients had elevated TSH levels (hTSH), whereas in the 10 others, they were normal (nTSH). cAMP levels in response to forskolin, PGE1, and CTx were similar in all groups, whereas isoproterenol-stimulated cAMP levels were significantly higher in the hTSH group than in the nTSH group and control subjects (45 +/- 30 versus 22 +/- 9 and 21 +/- 9 pmol . 10(6) cells(-1) . 10 min(-1), respectively; p = 0.02). Four patients in the DS hTSH subgroup had impaired sexual development. We found hyperresponsiveness of PMCs to a beta-adrenergic agonist in a subgroup of DS patients with CH. If this observation is applicable to the thyroid gland, then it may reflect a mechanism in which negative effects on cell growth or responsiveness to TSH lead to CH.     

Effect of white-colored mineral trioxide aggregate in different concentrations on Candida albicans in vitro

The antifungal action of different concentrations of white-colored mineral trioxide aggregate (MTA) against Candida albicans was assessed in vitro. Fresh mix of MTA was prepared at concentrations varying from 0.78 mg/ml to 50 mg/ml by dilution with 10 ml molten agar at 45 degrees C. The MTA-agar compound was thoroughly mixed and the uniform mix was then poured into sterile Petri dishes and allowed to set. A total of 348 agar plates were prepared and divided into experimental groups of 11 plates each and control groups of 5 plates each. Plates of agar without MTA served as positive control and plates without C. albicans served as negative control. Fresh inoculate of C. albicans was prepared by growing an overnight culture from a stock culture. Aliquots of C. albicans were then taken from the stock culture and plated on the agar compound of the experimental and positive control groups. All plates were incubated at 37 degrees C for 1, 24, 48, and 72-h periods. At each time period, the presence of C. albicans colonies was assessed and recorded. A direct correlation was found between MTA concentration and its inhibition effect on C. albicans growth. Plates containing MTA in concentration of 50 mg/ml showed significantly better killing action against C. albicans in all of the time periods tested (p < 0.001). Plates containing MTA in concentration of 25 mg/ml showed antifungal activity only at 1 and 24-h time periods. Plates containing lower concentrations of MTA did not show any antifungal activity. It appears that under the conditions of this study, white-colored MTA in concentration of 50 mg/ml is effective in killing C. albicans for periods of up to 3 days. Lower MTA concentrations may not be effective.     

Assessment of psychomotor skills acquisition during laparoscopic cholecystectomy courses

BACKGROUND: Standardized short courses in laparoscopic cholecystectomy aim to teach laparoscopic skills to surgical trainees, although end-of-course assessments of performance remain subjective. The current study aims to objectively assess psychomotor skills acquisition of trainees attending laparoscopic cholecystectomy courses. METHODS: Thirty-seven junior surgical trainees had their laparoscopic skills assessed before and after attending 1 of 3 separate 2-day courses (A, B, and C), all with identical format. Assessments were comprised of a standardized simulated laparoscopic task, with performance measured using a valid electromagnetic hand-motion tracking device. RESULTS: Overall, trainees made significant improvements in path length (P=.006), number of movements (P<.001), and time taken (P<.001). Analyzing the 3 courses separately, only trainees attending courses A and C made significant improvements. DISCUSSION: Objective validated methods can be used to assess learning of psychomotor skills on courses. In addition to providing participants with an insight into their skills, these data can be used to demonstrate course efficacy.     

Photodynamic therapy induced esophageal stricture--an animal model: from mouse to pig

INTRODUCTION: A major limitation of photodynamic therapy (PDT) for Barrett's esophagus is the development of esophageal stricture. We developed an animal model of PDT-induced esophageal stricture to elucidate the mechanism of stricture development. Our studies began in a mouse but, due to its limitations, we advanced to a porcine model. MATERIALS AND METHODS: In the mouse model, 62 mice were injected with Photofrin (2-10 mg/kg) 48 h prior to photoactivation. Light energy (20-400 Joules/cm (J)) was delivered with a laser probe as a single dose, or fractionated doses (20-150 J). Animals were sacrificed when showing signs of distress or 6 to 18 weeks post-illumination. Esophagus was removed, with gross and microscopic examination performed on frozen specimens. To develop a pig model, six pigs were injected with Photofrin (2 mg/kg) 48 h prior to photoactivation. Light energy (400 J) was delivered via an endoscope using a laser probe as a single dose or repeated at 48 h. Animals were sacrificed if they could not eat soft food or lost more than 10% of their original weight according to the University of Pittsburgh Institutional Animal Care and Use Committee. RESULTS: Exposure of mice to doses of 400 J x 1, 125 J x 3, or 150 J x 3 fractions resulted in severe lung damage and death in 90% of the mice without any evidence of esophageal stricture. Lower energy levels caused minor lung damage and no change in the endothelial layer or a stricture. In pigs, exposure of 400 J as one or two fractions resulted in weight loss of 10% within 3 weeks. Endoscopy, upper GI, contrast swallow, and pathological and histological examination showed evidence of esophageal stricture at the exposed area. CONCLUSIONS: In the mouse model, pulmonary toxicity is the limiting factor following esophageal PDT exposure. In the pig model we induced esophageal stricture following PDT. This is the first animal model created to study esophageal strictures resulting from PDT.     

Sudden cardiac death without structural heart disease: Update on the long QT and brugada syndromes

The long QT syndrome (LQTS) and the Brugada syndrome (BrS) are the most common genetic causes of malignant ventricular arrhythmias and sudden cardiac death in young patients with normal cardiac morphology. To date, more than 250 different mutations in seven genes have been identified as causing LQTS, whereas the only gene identified to be linked to BrS is SCN5A. In both syndromes, genespecific mutations have been shown to be associated with specific phenotypic expressions. Risk stratification in LQTS and BrS is based mainly upon a constellation of electrocardiographic findings and a history of prior symptoms. In patients identified as high risk for arrhythmic mortality, the implantable cardioverter defibrillator is the most effective treatment and has been shown to provide near-complete protection during long-term follow-up.