Emergency repair of lacrimal canaliculus

Twenty-three patients with canalicular injuries who underwent emergency treatment are presented. A round-tipped pigtail probe was used to position the silicone tube for canalicular intubation. Four patients had the injury in the common lacrimal canaliculus. After tubing both canaliculi, the silicone tube ends were retrieved from the inferior meatus. The rest of the patients had inferior canalicular injury. In those cases, a circle was formed by a silicone tube between the upper and lower canaliculi. The silicone tube was held in place for 4–6 months. After removal of the silicone tube, the lacrimal drainage system was evaluated by the dye disappearance test and radiological methods. The drainage system was patent in all cases with a consequent lack of epiphora.This study was partly presented at the European Appointed 20th National Congress of the Turkish Society of Plastic Surgeons on 5 September 1998.     

Emergence of the metabolic syndrome in childhood: an epidemiological overview and mechanistic link to dyslipidemia

Insulin resistance and type 2 diabetes are rapidly emerging as major disorders of childhood and adolescence. This appears to be closely linked to a rapid rise in the prevalence of obesity in the pediatric population. The development of insulin resistance appears to lead to a "metabolic syndrome" which includes a number of major complications such as dyslipidemia and hypertension. Childhood metabolic syndrome promotes the development of premature atherosclerosis and significantly increases cardiovascular disease risk early in life. The mechanisms linking obesity, insulin resistance, and metabolic dyslipidemia are not fully understood. This review will attempt to discuss some of the key mechanistic issues surrounding insulin resistance and its association with metabolic dyslipidemia. Most of the recent progress in this field has come from the use of genetic and diet-induced animal models of insulin resistance. New data from these animal studies particularly the fructose-fed hamster, a model of metabolic syndrome and dyslipidemia, will be reviewed. Evidence from both animal and human studies suggest a key role for insulin sensitive tissues such as adipose tissue, liver, and intestine in the development of an insulin resistant state and its associated lipid and lipoprotein disorders. The critical interaction of metabolic signals among these tissues appears to govern the transition from an insulin sensitive to an insulin resistant state that underlies dyslipidemic conditions.     

NOSH-Aspirin: A Novel Nitric Oxide-Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals

A series of new hybrids of aspirin (ASA), bearing both nitric oxide (NO) and hydrogen sulfide (H(2)S)-releasing moieties were synthesized and designated as NOSH compounds (1-4). NOSH-1 (4-(3-thioxo-3H-1,2-dithiol-5-yl) phenyl 2-((4-(nitrooxy)-butanoyl)oxy) benzoate); NOSH-2 (4-(nitrooxy)butyl (2-((4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)carbonyl)phenyl)); NOSH-3 (4-carbamothioylphenyl 2-((4-(nitrooxy)butanoyl)-oxy)benzoate); and NOSH-4 (4-(nitrooxy)butyl 2-(5-((R)-1,2-dithiolan-3-yl)pentanoyloxy)-benzoate). The cell growth inhibitory properties of compounds 1-4 were evaluated in eleven different human cancer cell lines of six different tissue origins. These cell lines are of adenomatous (colon, pancreatic, lung, prostate), epithelial (breast), and lymphocytic (leukemia) origin. All NOSH compounds were extremely effective in inhibiting the growth of these cell lines. NOSH-1 was the most potent, with an IC(50) of 48 ± 3 nM in HT-29 colon cancer cells. This is the first NSAID-based compound with such potency. This compound was also devoid of any cellular toxicity, as determined by LDH release. NOSH-1 was comparable to aspirin in its anti-inflammatory properties, using the carrageenan rat paw edema model.     

Evaluation of Alum-Naltrexone Adjuvant Activity,on Efficacy of Anti-Leishmania Immunization with Autoclaved Leishmania major (MRHO/IR/75/ER) Antigens in BALB/C Mice

Background

Naltrexone, an opioid receptor antagonist shifts the immune response toward a Th1 profile. In the current study, we evaluated the efficacy of the mixture of NTX and alum, as a new adjuvant, to enhance immune response and induce protection against Leishmania major in a mouse model.

Methods

BALB/c mice were immunized three times either autoclaved L. major promastigotes’ antigens alone or in combination with the adjuvant alum, naltrexone or the alum–naltrexone mixture. Both humoral and cellular immune responses were assessed two weeks after the last immunization and compared with control mice.

Results

The administration of alum- NTX in combination with the parasite antigen, significantly increased production of IFN-γ IFN-γ /IL-5 ratio, lymphocyte proliferation and improved DTH response against L. major. There was no significant difference in survival following challenge among groups.

Conclusion

Immunization with the alum– naltrexone mixture as an adjuvant, in combination with the autoclaved L. major promastigotes antigens, can enhance cellular immunity and shift the immune responses to a Th1 pattern.     

Comparison among Ocular Response Analyzer, Corvis ST and Goldmann applanation tonometry in healthy children

AIM: To explore the relationship between different parameters of Ocular Response Analyzer (ORA) and Corvis ST (CST) in a sample of healthy Iranian school-aged children and the relationship between parameters of these 2 instruments against intraocular pressure (IOP), measured by the Goldmann applanation tonometer (GAT-IOP), age and gender, and find possible correlation between ORA and CST with GAT. METHODS: This cross-sectional study included 90 healthy children. A general interview and complete eye examination were performed. Following successful GAT-IOP measurement, ORA and CST were conducted. The CST parameters were A 1/2 length (A1L, A2L), A 1/2 velocity (A1V, A2V), highest concavity deformation amplitude (HCDA), radius of curvature (RoC), peak distance (PD), central corneal thickness (CCT) and IOP. The ORA parameters were corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated IOP (IOP-G) and corneal compensated IOP (IOP-CC). Extracted data was analyzed using the Statistical Package for Social Science software. RESULTS: Totally 39 males with age of 9.08±1.60 (6-12)y and 51 females with age of 8.96±1.55 (6-13)y were included. Many CST parameters were significantly correlated with CH, CRF, IOP-G and IOP-CC. Some CST parameters had a significant correlation with GAT-IOP, including IOP-CST in both eyes and HCDA, A2L, PD, and RoC in the left eye, but none with age, except A2L in the right eye. The CRF measurement showed a significant correlation with GAT-IOP in both eyes and CH in the right eye, yet, none with age. Among all CST and ORA parameters, CCT-CST in both eyes and A1L in right eye had a significant correlation with gender, although this was a negligible negative correlation. Comparison of mean IOP values by different devices showed a significantly highest IOP overestimation by CST and lowest by IOP-CC compared with GAT. Also, IOP-G versus IOP-CST significantly had the lowest IOP overestimation among others. Overall, either low positive correlation or negligible correlation was found between IOP measurements by 3 instruments. CONCLUSION: The study finds the highest IOP overestimation by CST and lowest by IOP-CC compared with GAT. Overall, either low positive correlation or negligible correlation is found between IOP measurements by the 3 instruments.     

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population.

BACKGROUND: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene has been variably associated with insulin resistance, obesity and type 2 diabetes in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that this variation might be associated with insulin resistance, type 2 diabetes and related metabolic traits in this population. METHODS: The Pro12Ala genotypes were determined by PCR-restriction fragment length polymorphism in 696 unrelated subjects including 412 non-diabetic controls and 284 type 2 diabetic patients. RESULTS: The frequency of the Ala allele was 9.4% and 5.9% in controls and type 2 diabetic subjects, respectively [adjusted odds ratio (OR) 0.457, p=0.005]. The Ala allele did not show a significant effect on anthropometric and biochemical parameters in the type 2 diabetic group, whereas in non-diabetic subjects, carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels compared to Pro/Pro subjects. Multivariate logistic regression analysis showed that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in this population. CONCLUSIONS: Our results for a sample of Iranian type 2 diabetes cases and controls provide evidence that the Pro/Ala genotype of the PPARgamma-2 gene is associated with insulin sensitivity and may also have protective role against type 2 diabetes.     

The Ubiquitin–Proteasome System Regulates the Stability of Neuronal Nicotinic Acetylcholine Receptors

Ubiquitination is a key event for protein degradation by the proteasome system, membrane protein internalization, and protein trafficking among cellular compartments. Few data are available on the role of the ubiquitin–proteasome system (UPS) in the trafficking of neuronal nicotinic acetylcholine receptors (nAChRs). Experiments conducted in neuron-like differentiated rat pheochromocytoma cells (PC12 cells) show that the α3, β2, and β4 nAChR subunits are ubiquitinated and that their ubiquitination is necessary for degradation. A 24-h treatment with the proteasome inhibitor PS-341 increased the total levels of α3 and the two β subunits in both whole cell lysates and fractions enriched for the ER/Golgi compartment. nAChR subunit upregulation was also detected in plasma membrane-enriched fractions. Inhibition of the lysosomal degradation machinery by E-64 had a significantly smaller effect on nAChR turnover. The present data, together with previous results showing that the α7 nAChR subunit is a target of the UPS, point to a prominent role of the proteasome in nAChR trafficking.     

In-Hospital Outcomes of Delayed Sternal Closure after Open Cardiac Surgery

Abstract   Background: The purpose of this prospective study was to evaluate the current incidence, survival, morbidity, and predictors of mortality for open sternotomy at our center. Methods: Prolonged open chest was used in 126 of 2485 cardiac operations (5.0%) between June 2006 and January 2008. The indications were hemodynamic instability (98), bleeding (14), arrhythmia (five), cardiac edema (three), tamponade (three), and cardiac arrest (three). Delayed sternal closure (DSC) was performed in 81 of 126 patients at a mean of 2.35 ± 1.73 days (range: 0.5 to 10 days). Results: Sixty-five of the 81 who had DSC (81.4%) survived. Forty-five patients (35.7%) died before DSC and 16 after this method. The 65 survivors (51.6%) were discharged from the hospital at a mean of 15.6 ± 8.4 days (range: 7 to 50 days). The most common causes of death included low cardiac output (67.2%) and multiorgan failure (26.2%). Superficial sternal wound infection occurred in one of 81 (1.2%) patients after DSC, mediastinitis in four (4.9%), and sternal dehiscence in two (2.4%) patients. New onset of acute renal failure and the presence of intraaortic balloon pump (IABP) were predictive of in-hospital death. Conclusions: This study shows that open chest with DSC is useful in the treatment of postoperatively impaired cardiac function, intractable bleeding, and persistent arrhythmias. It can be carried out with a relatively low incidence of sternal complications. Patients with new onset acute renal failure and who require IABP continue to have a high mortality rate.     

Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic renal cell cancer?

Interleukin-2 (IL-2) was the preferred treatment for medically fit patients with advanced kidney cancer, but recently, several targeted therapies have been approved for metastatic renal cell carcinoma. We wished to determine the long-term survival rate for patients with kidney cancer treated with IL-2 and whether the use of intense inpatient IL-2 has declined since the introduction of targeted therapies. Patients who received IL-2 were identified from clinical trial enrollment, pharmacy logs, and financial billing records. Survival was determined from the earliest date of IL-2 therapy. There were 79 patients hospitalized for high-dose infusional IL-2 between March 1989 and March 2009. Median age was 58 years, and 27% were older than 65 years at the time of treatment. At the time of this analysis, 72 patients had deceased. Median survival was 9.9 months, but 5-year survival was 19.4%. The average number of patients with IL-2 increased from 2.2 per year during 1989-1992 to 5.6 during 1993-2001 after FDA approval, but dropped to 2.0 during 2002-2009. High-dose IL-2 is associated with a 5-year survival rate that is higher than objective response rates, suggesting a delayed immunotherapy benefit for some patients. The use of intensive IL-2 has declined dramatically in recent years, but unless a long-term survival benefit can be shown for these new targeted products, we feel that inpatient IL-2 remains the preferred initial treatment.