Use of sterile gloves in the management of sutured hand wounds in the A&E department

In a single-blind, controlled, prospective trial of 242 sutured wounds of the hand in the A&E department there was increased late purulent infection in those treated without gloves. This difference is statistically significant. We recommend wearing of sterile gloves to suture all wounds in A&E departments.     

Survival after gastric adenocarcinoma resection: Eighteen-year experience at a single institution

Gastric adenocarcinoma is the second leading cause of cancer death worldwide. In Western series, survival rates vary widely and are generally lower than those reported from Eastern series. We performed a retrospective analysis of cases operated on at the Johns Hopkins Hospital over the past 18 years and collected data on demographics, tumor characteristics, pathologic stage, treatment methods, complications, survival time, and other relevant factors. Survival according to stage of disease, Lauren tumor type, tumorlocation,time period, andadministration of adjuvant therapy wasanalyzed, andresultswerecompared with those of other Western series. During this period, 436 patients with gastric adenocarcinoma underwent resection. We have shown a statistically significant association between survival and margin status, stage of disease, and Lauren tumor type. Overall 5-year survival was 26%, and 5-year survival after R0 resection was 33%. No significant difference was detected between survival and tumor location, time period of treatment, or administration of adjuvant therapy. Analysis of various Western series reveals major differences between the cohorts under study, such as stage of disease, extent of resection, tumor type, and tumor location. Many of the reported differences among Western series may be due to cohort differences, such as stage of disease, extent of resection, tumor type, and tumor location.     

Patient satisfaction in an urban accident and emergency department.

The aim of this study was to assess patients' opinions about their experience of attending an urban Accident and Emergency department. They were given a questionnaire designed to demonstrate any shortcomings in the delivery of care which required corrective actions. Just over half (50.8%) the patients responded, 411 (95%) of whom recorded satisfaction with the outcome of their visit (P = 0.0001). There was significant correlation between patient satisfaction and waiting time to see the doctor (P = 0.003), the doctor's explanation about management (P = 0.02), and total time spent in the department (P = 0.01). A total of 120 patients (27.8%) did not receive any explanation from the nurse about what was going to happen, and 267 (61.6%) received no information about possible delay. These factors did not significantly influence patients' satisfaction with the outcome, but they need to be addressed as they will obviously lead to an improved service.     

The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection

Somatic mitochondrial mutations are common in human cancers, and can be used as a tool for early detection of cancer. We have developed a mitochondrial Custom Reseq microarray as an array-based sequencing platform for rapid and high-throughput analysis of mitochondrial DNA. The MitoChip contains oligonucleotide probes synthesized using standard photolithography and solid-phase synthesis, and is able to sequence >29 kb of double-stranded DNA in a single assay. Both strands of the entire human mitochondrial coding sequence (15,451 bp) are arrayed on the MitoChip; both strands of an additional 12,935 bp (84% of coding DNA) are arrayed in duplicate. We used 300 ng of genomic DNA to amplify the mitochondrial coding sequence in three overlapping long PCR fragments. We then sequenced >2 million base pairs of mitochondrial DNA, and successfully assigned base calls at 96.0% of nucleotide positions. Replicate experiments demonstrated >99.99% reproducibility. In matched fluid samples (urine and pancreatic juice, respectively) obtained from five patients with bladder cancer and four with pancreatic cancer, the MitoChip detected at least one cancer-associated mitochondrial mutation in six (66%) of nine samples. The MitoChip is a high-throughput sequencing tool for the reliable identification of mitochondrial DNA mutations from primary tumors in clinical samples.     

Hepatocellular carcinomas show abnormal expression of fibronectin protein.

Fibronectin plays an important role in cell-to-cell adhesion, cell migration, and cell signaling. In the liver, fibronectin expression has been studied primarily as a component of the extracellular matrix, but little information is available on the expression of fibronectin protein in the neoplastic cells of hepatocellular carcinomas (HCCs). Twenty-four surgically resected HCCs were immunostained with fibronectin. Tumor and normal liver tissues were concurrently analyzed in all cases, and expression in the tumor was evaluated in comparison to the nonneoplastic liver. The average age at resection was 54 +/- 18 years for the 18 men and 6 women. Twenty-one of the cases were classic HCCs including 6 cases that were well differentiated, 12 cases moderately differentiated, and 3 cases poorly differentiated. The remaining 3 cases were moderately differentiated fibrolamellar carcinomas. In the normal liver, fibronectin labeled the sinusoids and weakly to moderately stained the cytoplasm of hepatocytes. In HCCs, 15/24 showed overexpression of fibronectin in the cytoplasm, 8/24 showed no change from the nonneoplastic liver, and one case showed decreased cytoplasmic staining. In addition, an abnormal membranous staining pattern was noted in 16/24 HCCs. In contrast to the HCCs, none of the three fibrolamellar carcinomas showed increased cytoplasmic or membranous staining. Excluding fibrolamellar carcinoma, increased cytoplasmic staining and/or an abnormal membranous staining was noted in 19/21 (90%) of HCCs. Fibronectin shows abnormal cytoplasmic and/or membranous staining in the majority of HCCs. The implications of fibronectin overexpression are uncertain but may reflect a critical step in tumor genesis.     

Epidemiology of chronic suppurative otitis media and deafness in a rural area and developing an intervention strategy

Of 613 children evaluated in a village in Haryana 94 (15.3%) were observed to have chronic suppurative otitis media (CSOM). Fifty eight (61.7%) children had hearing impairment. CSOM contributed to 71.6% of the hearing impaired (58/81). On analysis of association of CSOM with literacy and socio-economic status of mothers, and age, sex, and upper respiratory tract infections (URI) in children positive correlation was observed only with URIs (P<0.001). Literacy and socio-economic status of the mothers did not correlate significantly with knowledge about treatment seeking, and ear cleaning practices, probably due to the narrow range of incomes and literacy levels. An intervention program consisting of play, demonstrations, health charts and slogans, and aural cleaning and antibiotic drops was introduced.     

Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.

OBJECTIVES: Pancreatic adenocarcinoma is a deadly disease with an overall 5-year patient survival of less than 5%. This dismal prognosis of pancreatic cancer is largely due to the advanced stage of the disease at presentation. If pancreatic cancer could be diagnosed more readily and accurately using serum markers, patient survival could theoretically be improved by enabling more patients to avail of surgical resection. One candidate tumor marker recently identified by global gene expression analysis of pancreatic cancer is the secreted glycophosphoprotein osteopontin (OPN). In this study, we evaluate OPN as a serum marker of pancreatic adenocarcinoma. METHODS: In situ hybridization for OPN was performed on a pancreatic adenocarcinoma tissue microarray. Serum OPN levels were determined in preoperative sera from 50 patients with pancreatic cancer and 22 healthy control individuals by competitive ELISA. RESULTS: In situ hybridization for OPN performed on a tissue microarray revealed strong OPN mRNA signal in tumor-infiltrating macrophages in 8 of 14 pancreatic adenocarcinomas. In contrast, OPN expression was not seen in the pancreatic cancer cells themselves, nor was it seen in normal pancreatic tissue or in the macrophages distant from the infiltrating cancer. Serum OPN levels, as measured by ELISA, were elevated in the sera of 50 patients with resectable pancreatic adenocarcinoma compared to 22 healthy control individuals (mean +/- SD for OPN was 482 +/- 170 ng/ml and 204 +/- 65 ng/ml, respectively; P < 0.001). Using a cutoff level of 2 SD above the mean for healthy individuals, elevated OPN had sensitivity of 80% and specificity of 97% for pancreatic cancer. In contrast, only 62% of these patients with resectable pancreatic cancer had elevated CA19-9. CONCLUSIONS: Serum OPN may have utility as a diagnostic marker in patients with pancreatic cancer.     

Inherited medullary microcarcinoma of the thyroid: a study of 11 cases

The authors report 11 patients with genetically determined medullary microcarcinomas. Nine patients were either children or adolescents and two patients were young adults. The youngest patient was 7 years old and the oldest was 34 years of age (mean age, 15.4 yrs). The preoperative diagnosis was based on family history and elevated serum calcitonin levels. In addition, six patients had RET protooncogene mutations in exons 10, 11, and 16. Two patients who had the RET protooncogene mutations did not have serum calcitonin measurements. Nine patients had bilateral medullary microcarcinomas (<1.0 cm), whereas the two patients with unilateral tumors demonstrated multifocal disease. The principle microscopic differences between these genetically determined medullary microcarcinomas and larger sporadic (>1 cm) medullary carcinomas were the low incidence of stromal desmoplasia and amyloid deposition, the high incidence of C-cell hyperplasia, and the low incidence of lymph node metastases. Only one patient, a 34-year-old man, presented with lymph node metastases. All patients remain disease free 11 to 70 months after diagnosis. This small series of thyroid microcarcinomas illustrates the impact molecular diagnostics is having on the management and prognosis of genetically determined medullary carcinoma.     

Alterations in glucose-6-phosphatase gene expression in sepsis

BACKGROUND: The influence of sepsis on the expression and activity of hepatic glucose-6-phosphatase (Glu-6-Pase) was examined during the early hyperglycemic phase and the later hypoglycemic phase. METHODS: Sepsis was induced in anesthetized, fasted rats by cecal ligation and puncture, and liver samples were taken at 0, 0.5, 1, 1.5, and 20 hours after cecal ligation and puncture. RESULTS: The mRNA abundance of hepatic Glu-6-Pase increased fourfold at 0.5 hours over healthy control values, two-fold after 1 hour, and returned to normal after 1.5 hours. This finding was followed by a corresponding increase in Glu-6-Pase activity and was coincident with increased plasma glucose levels and decreased liver glucose-6-phosphate (Glu-6-P) at 0.5 and 1 hours. Plasma insulin and glucagon levels remained unchanged during this period, whereas corticosterone levels increased 2.5-fold over control values. At 20 hours cecal ligation and puncture, plasma glucose levels returned to normal, coincident with a 90% reduction in Glu-6-Pase mRNA abundance. Glu-6-Pase activity and Glu-6-P concentration returned to normal levels, while insulin, glucagon, and corticosterone levels increased significantly, i.e., 40-fold, 6.5-fold, and 6-fold, respectively. CONCLUSION: The initial rise and subsequent decline in blood glucose correlate very well with a corticosterone-dependent induction of hepatic Glu-6-Pase, mRNA, and protein, followed by an insulin-dependent suppression of its expression.     

HLA-G upregulation in pre-malignant and malignant lesions of the gastrointestinal tract

HLA-G belongs to the nonclassical MHC class Ib group of molecules and has been implicated in mediating immune-responsiveness in various cancerous and non-cancerous cell types. We have examined HLA-G expression in a number of human gastrointestinal malignancies, including pancreatic ductal adenocarcinoma, ampullary cancer, biliary cancer, and colorectal cancer by immunolabeling analysis. We used indices of <5% (negative), 6–25%, 26–50%, 51–75%, and >75% (diffuse) to subclassify lesions based on percentage of positive cell labeling. Across all cancer subtypes, 52–79% of lesions demonstrated expression of HLA-G, with up to 33% of lesions demonstrating diffuse (>75%) expression. In addition, we utilized the neoplastic progression model of colorectal cancer to evaluate HLA-G protein expression in normal colon, tubulovillous adenomas, invasive cancer, and liver metastases arising from colorectal cancer. Focal HLA-G expression was detected in regions of normal colon adjacent to sites of adenomatous and cancerous lesions, as well as in all stages of cancer progression. Overall, the percentage of diffusely (>75%) labeled lesions appeared increased in preneoplastic and neoplastic conditions, as compared to normal colon. Specifically, tubulovillous adnenomas demonstrated pronounced diffuse labeling in 58% of lesions examined. No correlation with HLA-G expression and CD4+ or CD8+ T cells was identified. We propose that HLA-G expression is upregulated in a large percentage of gastrointestinal lesions and may serve to mediate immuneresponsiveness in certain instances.