Medical management of carotid artery disease

It is estimated that more than 700,000 strokes occur in the United States annually, and stroke remains the third leading cause of death. As many as 20% of strokes are due to carotid artery disease. Approaches to therapy include surgery and stenting in appropriate settings, but medical therapy is a critical aspect of management of carotid artery disease. Best medical therapy for carotid stenosis has evolved in recent years and clinicians can now employ newer antiplatelet agents, aggressive use of statins, and targeted blood pressure reduction. Application of this multimodal cocktail holds promise for reducing vascular events in patients with carotid artery disease and may reduce the need for revascularization procedures.     

Successful surgical management of a prenatally diagnosed intrapericardial teratoma

Congenital intrapericardial teratoma is a rare, usually benign tumour frequently associated with massive pericardial effusion, cardiac compression, and severe cardiorespiratory distress shortly after birth. Surgical removal is not only curative but also potentially lifesaving because these lesions often become fatal if not promptly excised. We present a case of a newborn with a huge intrapericardial teratoma diagnosed in utero. After normal delivery the infant underwent surgical removal and has had clinical follow-up for more than 11 months.     

Myeloperoxidase-positive inflammatory cells participate in bile duct damage in primary biliary cirrhosis through nitric oxide-mediated reactions

Previous studies have suggested that increased nitric oxide (NO)-mediated products are found in the livers of subjects with primary biliary cirrhosis (PBC), but the mechanisms involved remain enigmatic. We took advantage of immunohistochemistry and several unique monoclonal antibodies to study inflammatory cells responsible for the generation of NO, the enzymes responsible for NO production, the expression of 3-nitrotyrosine, and the presence of CD68(+) and/or myeloperoxidase (MPO)(+) cells. We examined a total of 113 liver specimens, including 64 with PBC, 19 with primary sclerosing cholangitis (PSC), 6 with non-A, non-B hepatitis, 6 with alcoholic liver disease, 4 with cryptogenic cirrhosis, 4 with biliary atresia, and 10 normal subjects. Twenty-two percent of PBC had elevated expression of 3-nitrotyrosine in their bile duct epithelial cells (BECs) (P =.0316). Furthermore, the BECs in PBC also demonstrated apoptotic changes. MPO-positive inflammatory cells were also noted adjacent to the basement membrane. In contrast, the liver of normal subjects showed few apoptotic changes in the bile ducts, with no evidence of MPO staining in the portal area. Furthermore, sections from livers of subjects with stage I or stage II PBC demonstrated significantly increased inflammatory cell infiltration (P =.0064) and elevated 3-nitrotyrosine expression in BECs (P =.0246) compared with stage III and IV. The presence of 3-nitrotyrosine was closely associated with infiltrating CD68- and/or MPO-positive cells. There was also a stage-associated difference in the presence of bile duct infiltrating cells and 3-nitrotyrosine in PBC with an increase dominant in early stage disease. In conclusion, NO and reactive oxygen species, collectively determined as 3-nitrotyrosine, are associated with bile duct destruction in PBC and are particularly prevalent in early stage disease.     

Outcome of large angle exotropia treated by single stage adjustable strabismus surgery with monitored conscious anesthesia

Purpose:To evaluate the outcomes of large-angle exotropia by single-stage adjustable strabismus surgery (SSASS) under monitored conscious anesthesia.Methods:A prospective study was done in 33 patients above 14 years with ≥40 prism diopters (PD) of exotropia. All patients underwent SSASS under monitored conscious anesthesia (topical anesthesia plus intravenous sedation). For deviations of ≤55 PD, two horizontal rectus muscles, and for >55 PD, three rectus muscles were operated and a decision on adjustment/operating on an additional rectus muscle was taken after assessing the alignment. Monitored conscious anesthesia allowed us to check our results after surgery and plan further surgery/adjustment to achieve the desired alignment.Results:Mean preoperative deviation for distance was 52 ± 11.1 PD. The target alignment was achieved with the initial surgical plan in 10/21 patients with <55 PD exotropia and 4/12 patients with >55 PD exotropia, and one patient in each group needed adjustment. The remaining patients needed additional rectus muscle surgery. One patient with >55 PD exotropia needed both adjustment and additional rectus surgery. The success rate for distance correction was 85% at 6 months and 1 year. The overall success rate was 71% at 6 months. Percentage of patients with binocular single vision improved from 31% preoperatively to 78% by 6 months. Incidence of oculocardiac reflex was 6.1%.Conclusion:SSASS under monitored conscious anesthesia is a viable option for large-angle strabismus correction with good patient comfort and safety.     

Tumor necrosis factor allelic polymorphism with diabetic retinopathy in India

The association of tumor necrosis factor (TNF) with diabetic retinopathy (DR) has been described previously. A total of 207 Asian Indian patients of 15-year duration of type 2 diabetes were identified. This group included (i) 100 patients with DR and (ii) 107 patients without retinopathy (DNR). In this study, we correlated the length of the (GT)n microsatellite di-nucleotide repeat upstream to the promoter region of TNF gene with susceptibility for the development of retinopathy. The microsatellite was polymerase chain reaction amplified and electrophoresed on polyacrylamide gel and silver stained. In our study population, there were 18 alleles ranging from 97 to 131 base pairs (bp). Allele 4 (103 bp) had a higher prevalence (9.81%) in the DNR group compared to that (2.5%) in the DR group (P=0.002). Patients with retinopathy and allele 8 (111 bp) had a tendency to develop proliferative diabetic retinopathy (PDR). In this study of Indian subjects, it is suggested that allele 4 is a low risk allele for developing retinopathy and allele 8 (111 bp) shows an association with PDR.     

Molecular genetic analysis of a consanguineous south Indian family with congenital glaucoma: relevance of genetic testing and counseling

The genetic background of congenital glaucoma in a consanguineous south Indian family was examined by homozygosity analyses. Significant evidence for the homozygosity of alleles was detected for markers D2S177 and D2S1346 that are tightly linked to the CYP1B1 gene, and further involvement of this gene was confirmed by the co-segregation of a novel truncating mutation (Q110X) in exon 2 with the disease in all affected members. Newborn genetic screening and carrier identification were also performed in the family. The role of consanguinity and the risk of autosomal recessive disease were discussed and genetic counseling was given.     

Increasing rates of hospitalization due to septicemia in the US elderly population, 1986-1997

Rates of hospitalization due to septicemia (International Classification of Diseases, Ninth Revision, Clinical Modification, code 038) in the US elderly population for 1986-1997 were examined, using Medicare administrative data. Age group-, sex-, and race-adjusted rates more than doubled from 1986 through 1997, from 3.42 to 7.42 per 1000 beneficiaries. The 1997 rates of septicemia increased with age, from 4.47 per 1000 beneficiaries among persons 65-74 years old to 18.1 per 1000 beneficiaries among persons > or =85 years old. The rates of septicemia were slightly greater among men (7.46 per 1000 beneficiaries) than among women (7.39 per 1000 beneficiaries) and were higher among blacks (13.61 per 1000 beneficiaries) than among whites (6.89 per 1000 beneficiaries). The most likely sites of the origin of the septicemia were the urinary tract (40.1%) and lungs (15.3%). Escherichia coli and Staphylococcus species were the most frequently reported organisms. Diabetes was listed as a comorbidity in 24.5% of the hospitalizations. We estimate that the cost to Medicare for septicemia hospitalizations in 1997 was >$1.8 billion.     

Mutations in SCN10A Are Responsible for a Large Fraction of Cases of Brugada Syndrome

Background

BrS is an inherited sudden cardiac death syndrome. Less than 35% of BrS probands have genetically identified pathogenic variants. Recent evidence has implicated SCN10A, a neuronal sodium channel gene encoding Na_v1.8, in the electrical function of the heart.

Objectives

The purpose of this study was to test the hypothesis that SCN10A variants contribute to the development of Brugada syndrome (BrS).

Methods

Clinical analysis and direct sequencing of BrS susceptibility genes were performed for 150 probands and family members as well as >200 healthy controls. Expression and coimmunoprecipitation studies were performed to functionally characterize the putative pathogenic mutations.

Results

We identified 17 SCN10A mutations in 25 probands (20 male and 5 female); 23 of the 25 probands (92.0%) displayed overlapping phenotypes. SCN10A mutations were found in 16.7% of BrS probands, approaching our yield for SCN5A mutations (20.1%). Patients with BrS who had SCN10A mutations were more symptomatic and displayed significantly longer PR and QRS intervals compared with SCN10A-negative BrS probands. The majority of mutations localized to the transmembrane-spanning regions. Heterologous coexpression of wild-type (WT) SCN10A with WT-SCN5A in HEK cells caused a near doubling of sodium channel current compared with WT-SCN5A alone. In contrast, coexpression of SCN10A mutants (R14L and R1268Q) with WT-SCN5A caused a 79.4% and 84.4% reduction in sodium channel current, respectively. The coimmunoprecipitation studies provided evidence for the coassociation of Na_v1.8 and Na_v1.5 in the plasma membrane.

Conclusions

Our study identified SCN10A as a major susceptibility gene for BrS, thus greatly enhancing our ability to genotype and risk stratify probands and family members.