Extruded and protruded lumbar discs: combined clinical, histopathological, histochemical, immunopathological, histochemical, immunopathological and ultrastructural studies.

A total number of selected 252 patients with prolapsed lumbar intervertebral discs (92 extruded and 160 protruded) were operated upon in Neurosurgery Department Zagazig University Hospital during the period extended from January, 1988, to October 1990. In this study we reviewed their clinical and operative data. Surgical biopsies were taken from randomly selected 120 patients of them (50 extruded and 70 protruded discs) and were subjected to histopathological, histochemical and immunopathological studies. Ultrastructural study was performed for randomly selected 14 cases (7 extruded and 7 protruded discs). The results were compared with 7 normal intervertebral discs obtained from these studies showed that there were no differences between extruded and protruded discs at the histochemical level. Cell mediated immunity could be added as a factor in the pathogenesis of the degenerative process that lead to disc prolapse (in 20% of cases with extruded discs and 57.1% of cases with protruded discs). At the ultrastructural level 85.3% of extruded discs were prolapsed nucleus pulposus while 14.7% were prolapsed annulus fibrosus alone or with nucleus pulposus. All protruded discs were prolapsed annulus fibrosus with nucleus pulposus. These findings may have an impact on the management of this common problem.     

Hypercalcaemia: a clue to Mycobacterium avium intracellulare infection in a patient with AIDS

Hypercalcaemia is uncommon in HIV-infected patients and should suggest a different priority for differential diagnosis than would be considered in other settings. Although hypercalcaemia has long been associated with granulomatous diseases including tuberculosis, it has only recently been recognised that patients with illness due to Mycobacterium avium intracellulare (MAI) may develop it. We report a patient with AIDS in whom unexplained hypercalcaemia was the harbinger of clinically significant MAI infection. Patients with AIDS who develop hypercalcaemia should be closely evaluated for underlying MAI infection.     

Laparoscopic Colorectal Surgery: Summary of the Current Evidence

INTRODUCTION

Laparoscopic colectomy has not been accepted as quickly as laparoscopic cholecystectomy. This is because of its steep learning curve, concerns with oncological outcomes, lack of randomised controlled trials (RCTs) and initial reports on port-site recurrence after curative resection. The aim of this review is to summarise current evidence on laparoscopic colorectal surgery.

PATIENTS AND METHODS

Review of literature following Medline search using key words ‘laparoscopic’, ‘colorectal’ and ‘surgery’.

CONCLUSIONS

Laparoscopic colorectal surgery proved to be safe, cost-effective and with improved short-term outcomes. However, further studies are needed to assess the role of laparoscopic rectal cancer surgery and the value of enhanced recovery protocols in patients undergoing laparoscopic colorectal resections.     

Fusion of nearby inverted repeats by a replication-based mechanism leads to formation of dicentric and acentric chromosomes that cause genome instability in budding yeast

Large-scale changes (gross chromosomal rearrangements [GCRs]) are common in genomes, and are often associated with pathological disorders. We report here that a specific pair of nearby inverted repeats in budding yeast fuse to form a dicentric chromosome intermediate, which then rearranges to form a translocation and other GCRs. We next show that fusion of nearby inverted repeats is general; we found that many nearby inverted repeats that are present in the yeast genome also fuse, as does a pair of synthetically constructed inverted repeats. Fusion occurs between inverted repeats that are separated by several kilobases of DNA and share >20 base pairs of homology. Finally, we show that fusion of inverted repeats, surprisingly, does not require genes involved in double-strand break (DSB) repair or genes involved in other repeat recombination events. We therefore propose that fusion may occur by a DSB-independent, DNA replication-based mechanism (which we term “faulty template switching”). Fusion of nearby inverted repeats to form dicentrics may be a major cause of instability in yeast and in other organisms.     

Necrotizing panniculitis: a skin condition associated with acinar cell carcinoma of the pancreas

Pancreatic panniculitis (PP) is a rare cutaneous eruption that is associated with severe pancreatic disease. A patient presented with a fever, joint pains, and an erythematous rash with draining pustules that had spread from his legs to his arms over 4 months. Thorough investigation revealed stage IV acinar cell carcinoma of the pancreas. The rash was a result of necrotizing PP. The variable cutaneous manifestations of internal malignancies may challenge primary care physicians and dermatologists when patients present without findings associated with malignancy. Panniculitis should be kept in mind in the differential diagnosis of inflamed appearing nodules and pustules with an erythematous base, particularly when they are progressive and unrelenting.     

Factors associated with adverse neurodevelopmental outcomes in infants with congenital heart disease

OBJECTIVE: To review reported neurodevelopmental outcome data for patients with congenital heart disease, identify risk factors for adverse neurodevelopmental sequelae and summarize potential neuromonitoring strategies that have been described. METHODS: A Medline search was performed utilizing combinations of the keywords congenital heart, cardiac, neurologic, neurodevelopment, neuromonitoring, quality of life, and outcome. All prospective and longitudinal follow-up studies of patients with congenital heart disease were included. Additionally, studies that examined neuroimaging, neuromonitoring, and clinical factors in relation to outcome were examined. Case reports and editorials were excluded. Additional references were retrieved from selected articles if the abstract described an evaluation of neurodevelopmental outcomes and/or predictors of outcome in patients with congenital heart disease. RESULTS: Overall, patients with CHD have increased rates of neurodevelopmental impairments, although intelligence appears to be in the normal range. Preoperative risk stratification, intraoperative techniques, postoperative care, and neuromonitoring strategies may all contribute to ultimate long-term neurodevelopmental outcomes in patients with CHD postsurgical repair. CONCLUSIONS: As advances in the medical and surgical management improves survival in patients with CHD, increasing knowledge about neurodevelopmental outcomes and the factors that affect them will provide for strategies to optimize long-term outcome in this high-risk population.     

Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: potential for rapid screening

OBJECTIVE—People with the HLA genotype DRB1*0301-DQA1*0501-DQB1*0201/DRB1*04-DQA1*0301-DQB1*0302 (DR3/4-DQ8) are at the highest risk of developing type 1 diabetes. We sought to find an inexpensive, rapid test to identify DR3/4-DQ8 subjects using two single nucleotide polymorphisms (SNPs).RESEARCH DESIGN AND METHODS—SNPs rs2040410 and rs7454108 were associated with DR3-DQB1*0201 and DR4-DQB1*0302. We correlated these SNPs with HLA genotypes and with publicly available data on 5,019 subjects from the Type 1 Diabetes Genetic Consortium (T1DGC). Additionally, we analyzed these SNPs in samples from 143 HLA-typed children who participated in the Diabetes Autoimmunity Study of the Young (DAISY) using Taqman probes (rs7454108) and restriction digest analysis (rs2040410).RESULTS—With a simple combinatorial rule, the SNPs of interest identified the presence or absence of the DR3/4-DQ8 genotype. A wide variety of genotypes were tested for both SNPs. In T1DGC samples, the two SNPs were 98.5% (1,173 of 1,191) sensitive and 99.7% (3,815 of 3,828) specific for DR3/4-DQ8. In the DAISY population, the test was 100% (69 of 69) sensitive and 100% (74 of 74) specific. Overall, the sensitivity and specificity for the test were 98.57 and 99.67%, respectively.CONCLUSIONS—A two-SNP screening test can identify the highest risk heterozygous genotype for type 1 diabetes in a time- and cost-effective manner.We have the ability to identify subjects with a greater than 50% risk of developing anti-islet autoimmunity and type 1 diabetes on the basis of family history and HLA genotype (1,2). Siblings with the highest type 1 diabetes risk HLA genotype DRB1*0301-DQA1*0501-DQB1*0201/DRB1*04-DQA1*0301-DQB1*0302 (DR3/4-DQ8) who are identical by descent for the major histocompatibility complex region with a type 1 diabetic sibling have an 85% risk of developing diabetes-related autoimmunity by age 15 years and a 55% risk of developing type 1 diabetes by age 12 years (1). Children with multiple first-degree relatives with type 1 diabetes and high–or moderate–diabetes risk HLA genotypes are reported to have a 50% risk for the development of multiple diabetes-related autoantibodies and type 1 diabetes (2).Prevention trials, including the Trial to Reduce Type 1 Diabetes in the Genetically at Risk (TRIGR) (3), the Nutritional Intervention to Prevent Diabetes (NIP-Diabetes) trial (4), and the Primary Oral and Intranasal Trial (Pre-POINT) are currently underway in genetically at-risk children. Many of these trials include first-degree relatives of people with diabetes as well as individuals with high-risk HLA genotypes, including DR3/4-DQ8. The identification of subjects for these trials requires large-scale HLA screening, with many children tested who do not have the highest type 1 diabetes risk. Current typing techniques for DR3/4-DQ8 often utilize coamplification of the DQA1 and DQB1 genes followed by multiple probe hybridization or direct sequencing. This technique uses sequence-specific oligonucleotides in a linear assay for hybridization with amplified product from DNA samples (5). Alleles are called with a customized typing program. Sequence-based typing techniques use PCR to amplify DRB1 genes that are sequenced, with HLA type determined using special software (6). High-throughput screening systems that employ asymmetric PCR and hybridization of allele-specific probes as a first screening step to identify samples with specified HLA genotypes have been developed. Samples identified via these programs can be identified for further HLA genotyping (7). This method is cost and time consuming, as it may cost up to $31.44 to genotype 1 sample and takes up to 9 h to perform and analyze a set of 50 samples.Several studies have examined the possibility of predicting HLA alleles from existing single nucleotide polymorphism (SNP) data (8–10); however, only one article has provided data on predicting specific HLA alleles from individual SNPs. de Bakker et al. (8) reported an association between HLA types and SNPs. SNP rs2040410 A allele was associated with DRB1*0301, and rs7454108 C allele with DQB1*0302. We have developed and tested the ability of these two SNPs to identify individuals with the DR3/4-DQ8 genotype in subjects within the Type 1 Diabetes Genetics Consortium (T1DGC) and the Diabetes Autoimmunity Study in the Young (DAISY). This novel method adds to existing knowledge by utilizing SNP technology to quickly identify individuals with the DR3/4-DQ8 genotype and may be beneficial to prevention trials because it provides high-throughput screening in a time- and cost-effective manner.