Comparison of azithromycin and clarithromycin in triple therapy regimens for the eradication of Helicobacter pylori

OBJECTIVE: We sought to compare an azithromycin-based regimen with an already established clarithromycin-based regimen in the eradication of Helicobacter pylori infection. METHODS: A prospective, randomized, blinded comparative analysis was performed on 56 patients with upper GI symptoms who presented to the Gastroenterology Department at the Naval Medical Center Portsmouth. All patients had documented H. pylori infection on endoscopy via rapid urease test and histopathology. Patients were randomized to a treatment arm, which consisted of bismuth, clarithromycin, amoxicillin, and lansoprazole (B-LAC) or one consisting of bismuth, azithromycin, amoxicillin, and lansoprazole (B-LAA). To assess eradication, patients then received repeat endoscopy at 8 wk from entrance into the study. Rapid urease test and histopathology were again used to evaluate infection. Patients recorded all side effects. Comparison between the two groups was made using the chi2 method. RESULTS: Of the 56 patients included in the study, 27 went on to receive B-LAC, whereas 29 received B-LAA. The per protocol eradication rate was 84.6% with B-LAC and 55.5% with B-LAA (p = 0.021). Under intention to treat analysis, the eradication rates for B-LAC and B-LAA were 81% and 52%, respectively (p = 0.019). There was a significant difference between the two groups in number of subjects using nonsteroidal anti-inflammatory drugs (NSAIDs) (p = 0.013) and a trend toward a difference in histamine-2 (H2) blocker use (p = 0.066). Taking these two variables into account, a logistical regression was performed and continued to show a significant superiority in the B-LAC regimen (p = 0.03). CONCLUSIONS: The results of our study suggest that B-LAC is superior to B-LAA in the eradication of Helicobacter pylori. Our results also suggest that B-LAA is not a suitable regimen in the treatment of H. pylori because of its substandard eradication rate.     

Inhibition of matrix metalloproteinases by lung TIMP-1 gene transfer or doxycycline aggravates pulmonary hypertension in rats

Chronic hypoxic pulmonary hypertension (PH) results from persistent vasoconstriction, excess muscularization, and extracellular matrix remodeling of pulmonary arteries. The matrix metalloproteinases (MMPs) are a family of proteinases implicated in extracellular matrix turnover and hence in smooth muscle and endothelial cell migration and proliferation. Because MMP expression and activity are increased in PH, we designed the present study to investigate whether inhibition of lung MMPs in rats subjected to chronic hypoxia (CH) contributes to or protects against vascular remodeling and PH. To achieve lung MMP inhibition, rats exposed to 10% O(2) for 15 days were treated with either doxycycline (20 mg/kg per day by gavage starting 2 days before and continuing throughout the CH period) or a single dose of recombinant adenovirus (Ad) for the human tissue inhibitors of metalloproteinases-1 (hTIMP-1) gene (Ad.hTIMP-1, 10(8) plaque-forming units given intratracheally 2 days before CH initiation). Control groups either received no treatment or were treated with an adenovirus containing no gene in the expression cassette (Ad.Null). Efficacy of hTIMP-1 gene transfer was assessed both by ELISA on bronchoalveolar lavages and by hTIMP-1 immunofluorescence on lung sections. MMP inhibition in lungs was evaluated by in situ zymography and gelatinolytic activity assessment using [(3)H]gelatin. Rats treated with either doxycycline or Ad.hTIMP-1 had higher pulmonary artery pressure and right heart ventricular hypertrophy more severe than their respective controls. Worsening of PH was associated with increased muscularization and periadventitial collagen accumulation in distal arteries. In conclusion, our study provides compelling evidence that MMPs play a pivotal role in protecting against pulmonary artery remodeling.     

Bacterial infection as a complication of liver transplantation: epidemiology and risk factors

A retrospective survey was undertaken to characterize the epidemiology of bacterial infection in 79 patients who underwent 103 operations for orthotopic liver transplantation. Fifty-four patients (68%) developed 115 bacterial infections (1.46 episodes per patient), and seven patients died as a result of these infections. Fifty-three percent of bacterial infections occurred within 2 weeks after transplantation and were designated as early infections. The most common sites of infection were the abdomen (35 cases), the bloodstream (31 cases), and the surgical wound (19 cases). Aerobic enteric gram-negative bacilli were the predominant pathogens, and other pathogenic organisms were enterococci, staphylococci, and Pseudomonas bacteria. Logistic regression analysis identified prolonged duration of surgery (greater than or equal to 8 hours) and an elevated bilirubin level (greater than or equal to 12 mg/dL) as risk factors for early bacterial infection at any site; risk factors for abdominal or wound infection were prolonged duration of surgery, increased operative transfusion requirement (greater than or equal to 2 blood volumes), and prior hepatobiliary surgery. Awareness of the sites, pathogens, and time of onset of bacterial infection provides a basis for improved prophylaxis and empiric therapy.     

Donor cell expansion is delayed following nonablative in utero transplantation to treat murine mucopolysaccharidosis type VII

To block development of progressive childhood diseases, in utero transplantation (IUTx) requires immediate and significant donor peripheral blood (PB) cell amplification. To date, negligible and nontherapeutic donor PB cell levels have been observed postnatally, except in patients with immunodeficiency diseases. Donor cell fate in utero still is not clear. Ease of identifying and quantifying beta-glucuronidase (GUSB)-expressing donor cells in GUSB-null mucopolysaccharidosis type VII (MPSVII) mouse recipients allowed us to evaluate temporal donor cell engraftment and amplification post-IUTx. Like humans, MPSVII mice are unable to catabolize lysosomal glycosaminoglycans and progressively develop severe storage disease unless they are treated early in life.IUTx recipients were nonablated MPSVII fetuses and genetically stem cell-deficient, and hence myeloablated, W(41)/W(41) MPSVII fetuses. Donor GUSB+ cells were identified and counted in histochemical tissue sections. Quantitative results were confirmed by flow cytometry, enzyme analysis, and histopathology.Whereas GUSB+ cells engraft in most tissues in utero, significant amplification does not occur until the first postnatal week in the nonablated MPSVII hosts. In contrast, genetically myeloablated MPSVII recipients display widely distributed donor cell replacement accompanied by extensive amplification in utero. In both models, storage is alleviated in adult tissues with significant donor cell repopulation.To become therapeutic, IUTx must overcome the limitations of donor cell expansion in the highly competitive fetal environment. Fortunately, nonablative mechanisms to amplify cells in utero are coming on line.     

Morbidity of hypoglycemia in type 1 diabetes

Hypoglycemia is a common side effect of intensive insulin therapy in patients with type 1 diabetes. Mild hypoglycemia is any episode that can be self-treated, while a severe episode requires external help for recovery. Acute hypoglycemia produces autonomic and neuroglycopenic symptoms, including cognitive impairment and mood changes, while sympathoadrenal stimulation can provoke acute hemodynamic changes with alterations in regional vascular perfusion and a risk of cardiac dysrhythmias. Neurological manifestations include coma, convulsions and focal abnormalities. Long-term morbidities associated with hypoglycemia include impaired awareness of hypoglycemia, counterregulatory hormonal deficiencies, hypoglycemia-associated autonomic failure, and, in rare cases, permanent cognitive impairment. Hypoglycemia affects all aspects of life for the person with type 1 diabetes, including employment, social interactions, driving, sport and leisure activities, and sleep. Appreciation of the potential morbidities of hypoglycemia should encourage physicians to utilize therapeutic regimens that decrease the risk of severe hypoglycemia.     

Occlusion of the Modified Blalock–Taussig Shunt: Unique Methods of Treatment and Review of Catheter‐based Intervention

Objective. To report unique methods of treatment and review catheter‐based intervention for occluded modified Blalock–Taussig shunts (BTS). Methods. Case reports and articles involving children undergoing catheter‐based treatment for occluded modified BTS were reviewed. Results. Literature review detailed 38 patients in whom occluded modified BTS were treated with 39 catheter‐based interventions. Thrombolytics alone were delivered by catheter in 13 cases. Balloon angioplasty was performed in 23 cases, 5 with stent implantation. Both thrombolytic delivery and angioplasty were performed in 3 cases, 2 with stent implantation. Intervention was initially successful at re‐establishing modified BTS patency in 35/39 (90%) of cases. Patency could not be established in 2 patients who then proceeded to the operating for surgical shunt revision. Two deaths occurred during the procedures. Three cases at Emory University demonstrate uncommon or unique instances of catheter‐based intervention: (1) declotting of a shunt in a patient supported by extracorporeal membrane oxygenation (ECMO); (2) declotting of a shunt via a right axillary arterial approach; and (3) declotting of a shunt using a carotid arterial (ECMO) cannula for percutaneous access. Conclusions. The use of catheter‐based techniques for the treatment of BTS occlusion is highly successful, and potentially avoids high‐risk re‐operative intervention. ECMO can provide for a stable patient during the procedure. Hopefully, with improved technology and innovative procedures, more children in the future with BTS occlusion can be served by successful percutaneous intervention.     

Variation of the genetic expression pattern after exposure to estradiol-17beta and 4-nonylphenol in male zebrafish (Danio rerio)

There is much concern about the increasing presence in the environment of synthetic chemicals that are able to disrupt the endocrine system. Among these compounds, 4-nonylphenol (4-NP) is one of the most studied xenoestrogens, due to its widespread accumulation in water sediment and consequent presence in fatty acid of aquatic organisms. Here, we have used a zebrafish microarray representing 16,399 genes to study the effects of 4-NP and estradiol-17β (E2) in adult male zebrafish in order to elucidate the mechanism of action of 4-NP compared with that of E2. The microarray results showed that both 4-NP and E2 induced a strong expression of vitellogenin (VTG), the sex related precursor of the yolk proteins in oviparous vertebrates. Both treatments induced elevated protein turnover upregulating genes involved in proteolysis and those that are constituents of the ribosome. Many genes regulated by 4-NP and E2 are involved in energy metabolism, oxidative stress defense mechanisms, xenobiotic metabolism, and lipid metabolism. A different pattern of expression in the two treatments was found for genes involved in oxidative stress, since E2 seems to induce the mechanism of detoxification, while 4-NP seems to inhibit this protective mechanism of the cell.Overall, these findings demonstrate that the microarray approach can contribute significantly to the understanding of expression patterns induced by E2 and 4-NP in male zebrafish. The results also demonstrate that 4-NP is able to act through an alternative pattern to that of estradiol-17β, modulating the expression of the same genes in a different manner.