A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether tricuspid valve (TV) repair with an annuloplasty ring leads to an improved outcome over a conventional suture annuloplasty for patients with severe tricuspid incompetence. Altogether, 306 papers were found using the reported search, of which 14 presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. We found seven studies supporting the use of ring annuloplasty over De Vega's suture annuloplasty. Five studies found no significant difference in outcome between the two techniques. We found only two studies supporting the use of De Vega's suture annuloplasty over ring annuloplasty. Therefore, most of the tabulated studies show good evidence in support of ring annuloplasty compared with De Vega's suture repair for treatment of moderate to severe TV regurgitation. One cohort study identified a 20.4% postoperative failure rate for tricuspid regurgitation (TR) repair and concluded non-application of ring as a predictor for reoperation. One cohort study with a mean follow-up of 17 months reported success rates as high as 97% with ring annuloplasty for TV regurgitation. One large cohort study of 2277 patients with TR who had undergone repair reported a sustained reduction in TR and the rate of recurrence in a 5-year echocardiographic follow-up. One cohort study of 129 patients concluded that ring annuloplasty has the lowest rate of recurrence compared with De Vega's suture repair. An old randomized controlled trial (RCT) on the subject also reported a similar result to the mentioned studies. In contrast, we reviewed one recent study and four older studies and found no significant difference between the two techniques. We reviewed one study that reported De Vega's suture repair as a superior technique to ring annuloplasty. We conclude that there is good evidence supporting ring annuloplasty over conventional De Vega's suture annuloplasty.
Tricuspid valve; Suture; Cardiac valve annuloplasty
Hashimoto encephalopathy remains a Rubik's cube for the present generation of clinical research. Myriad presentations have been noted, and observations recorded in few subgroups of patients have gone on only to be trashed by a second group of patients with a completely different clinical profile. Steroids have been traditionally held to be the treatment for this condition, but long-term side effects associated with it limits its use. Although multiple drugs have been tried, yet there exists no data for their long-term efficacy in maintaining remission. No radiological findings have been consistently associated with this condition. We report the use of azathioprine in maintaining long-term remission in one such patient with Hashimoto encephalopathy and the presence of lactate peak in magnetic resonance spectroscopy of the patient, which showed dramatic regression with institution of immunosuppression.
Anti-thyreoperoxidase; azathioprine; encephalopathy; lactate peak; methylprednisolone; MRI-spectroscopy
Cyanide (CN) toxicity is a serious clinical problem and can occur with sodium nitroprusside (SNP), accidental smoke inhalation, industrial mishaps and bio-terrorism. In this study we induced severe CN toxicity independently with SNP or sodium cyanide (NaCN) in a juvenile pig model to demonstrate reversal of severe CN toxicity with a new antidote, sulfanegen sodium, a prodrug of 3-mercaptopyruvate.
SNP study: A pilot study in eleven anesthetized, mechanically ventilated juvenile pigs allowed us to determine the dose of SNP to induce CN toxicity. Blood CN, serum lactates and blood gases were monitored. CN toxicity was defined as the occurrence of severe lactic acidosis accompanied by significant elevation in blood CN levels. Based on this pilot study, eight anesthetized pigs received a high-dose IV infusion of SNP (100mg/hr) for 2 hours to induce CN toxicity. They were then randomized to receive either sulfanegen sodium or placebo. Four pigs received 3 doses of sulfanegen sodium (2.5g IV) every hour after induction of severe CN toxicity, while 4 pigs received placebo.
A pilot study was conducted in four spontaneously ventilating pigs sedated with propofol plus ketamine to demonstrate hemodynamic and metabolic stability for several hours. After this, 6 pigs were similarly sedated and given NaCN in bolus aliquots to produce CN toxicity ultimately resulting in death. Hemodynamics and metabolic variables were followed to define peak CN toxicity. In another group of six pigs, severe CN toxicity was induced by this method, and at peak toxicity, the animals were given sulfanegen sodium (2.5 g IV) followed by a repeat dose 60 minutes later in surviving animals.
SNP study: The pilot study demonstrated the occurrence of a significant increase in blood CN levels (p<0.05) accompanied by severe lactic acidemia (p<0.05) in all pigs receiving a high dose of SNP. Administration of the sulfanegen antidote resulted in progressive significant reduction in blood lactate and CN levels with 100% survival (p<0.05), whereas the placebo-treated pigs deteriorated and did not survive (p<0.05).
NaCN injection resulted in CN toxicity accompanied by severe lactic acidosis and mortality in all the pigs. Sulfanegen sodium reversed this toxicity and prevented mortality in all the pigs treated with this antidote.
CN toxicity can be successfully induced in a juvenile pig model with SNP or NaCN. The prodrug, sulfanegen sodium, is effective in reversing CN toxicity induced by SNP or NaCN.
The visualization and quantification of mitochondria-associated proteins with high power microscopy methods is of particular interest to investigate protein architecture in this organelle. We report the usage of a custom-made STimulated Emission Depletion (STED) fluorescence nanoscope with ~20 nm lateral resolution for protein mapping of Percoll-purified viable mitochondria from murine heart. Using this approach, we were able to quantify and resolve distinct protein clusters within mitochondria; specifically, cytochrome c oxidase subunit 2 is distributed in clusters of ~20 and ~28 nm; whereas the voltage dependent anion channel 1 displays four size distributions of ~22, ~33, ~55 and ~83 nm.
STED; mitochondria; subdiffraction-resolution; imaging; VDAC1; Cox2
Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that targets vascular endothelial growth factor-A, and is indicated in the treatment of various tumors (colon, lung, renal, and glioblastoma). It has been recently approved for the treatment of ovarian cancer in various countries. This review summarizes the activity and toxicity of bevacizumab in the treatment of ovarian cancer, both as single-agent drug and in combination with cytotoxic chemotherapy. As a single-agent drug, it has shown response rates of 16–21% in the treatment of recurrent ovarian cancer. Two phase III randomized trials have been published evaluating the addition of bevacizumab to standard chemotherapy as front-line treatment of advanced ovarian cancer. In addition, trials evaluating the combination with chemotherapy in recurrent ovarian cancer (platinum-sensitive and platinum-resistant disease) have also been reported. All these trials showed a statistically significant improvement in progression-free survival although no improvement in overall survival has been reported. The main adverse event is hypertension. Other serious, but uncommon adverse events include gastrointestinal perforation as well as renal and central nervous system toxicity.
bevacizumab; combination therapy; single-agent therapy; ovarian cancer; progression-free survival
Mutations of the orphan transporter ABCC6 (ATP-binding cassette, subfamily C, member 6) cause the connective tissue disorder pseudoxanthoma elasticum. ABCC6 was thought to be located on the plasma membrane of liver and kidney cells.
Mouse systems genetics and bioinformatics suggested that ABCC6 deficiency affects mitochondrial gene expression. We therefore tested whether ABCC6 associates with mitochondria.
Methods and Results
We found ABCC6 in crude mitochondrial fractions and subsequently pinpointed its localization to the purified mitochondria-associated membrane fraction. Cell-surface biotinylation in hepatocytes confirmed that ABCC6 is intracellular. Abcc6-knockout mice demonstrated mitochondrial abnormalities and decreased respiration reserve capacity.
Our finding that ABCC6 localizes to the mitochondria-associated membrane has implications for its mechanism of action in normal and diseased states.
PXE; vascular calcification; ABCC6/MRP6; MAM; mitochondria; cardiovascular disease
The emergency department of every tertiary care teaching hospital is the backbone of community health care service.
This study was undertaken to identify the pattern of emergencies in the hospital, and to identify the risk factors associated with these emergencies.
Materials and Methods:
This was a retrospective record analysis of the emergency department from Jan 2010 to Dec 2010. The data were analyzed for various types of medical emergencies presented at the hospital at Guru Gobind Singh Medical College and Hospital, Faridkot.
A total of 2310 patients presented in the emergency department of which nearly half were males; a great majority were in the age group of 15–40 years. The diseases related to the cardiovascular system, 367 (15.89%), topped the list of which hypertension was noted in 267 (11.56%) cases. This was followed by morbidities related to the neurological system, diabetes, hepatobiliary, respiratory, renal 168 (7.27%), poisoning, pyrexia of unknown origin, and multi-organ involvement. With regard to the specific diseases, the majority were contributed by coronary artery disease 217 (9.39%), stroke 178 (7.71%), alcoholic liver disease 160 (6.93%), and chronic obstructive lung diseases 90 (3.90%). In our series, we noted that a great majority of cases were in the 41–60 age groups except poisoning (majority less than 40 years). The age groups were significantly related with selected morbidities.
There are transparent evidence that we need an organized emergency care system in India as relatively the younger age group (15–40 years) comprised nearly half cases.
Emergencies; emergency department; fever
There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing inter-individual differences in angiogenic capacity and resistance to anti-angiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and –independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer patients (mCRC) treated with bevacizumab (BV) and oxaliplatin-based chemotherapy.
A total of 132 patients treated with first-line BV and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole blood samples by PCR-RFLP or direct DNA-sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS) and response rate (RR).
The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate COX regression analysis (HR 0.52; 95%CI 0.31–0.87; adjusted-P=0.012 and HR 0.60; 95%CI 0.36–0.99; adjusted-P=0.046, respectively). The minor allele of HIF1α rs11549465 C>T was significantly associated with increased PFS, but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (Pact=0.003).
In this study we identified common germline variants in VEGF-dependent and – independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line BV and oxaliplatin-based chemotherapy.
bevacizumab; oxaliplatin; colorectal cancer; angiogenesis; polymorphisms
To study the effect of intravenous magnesium sulfate infusion on clinical outcome of patients of acute stroke.
Materials and Methods:
Sixty consecutive cases of acute ischemic stroke hospitalised within 24 h of an episode of stroke were taken as subjects. All subjects underwent a computed tomography head, and those found to have evidence of bleed/space-occupying lesions were excluded from the study. The subjects taken up for the study were divided into two groups of 30 subjects each. Both the groups received the standard protocol management for acute ischemic stroke. Subjects of Group 1 additionally received intravenous magnesium sulfate as initial 4 g bolus dose over 15 min followed by 16 g as slow infusion over the next 24 h. In all the subjects of the two study groups, serum magnesium levels were estimated at the time of admission (Day 0), Day 1 and Day 2 of hospitalization using an atomic absorption spectrometer.
Statistical Analysis Used:
Scandinavian stroke scores were calculated on Day 3, day of discharge and Day 28. Paired t-test was employed for comparison of stroke scores on Day 3, day of discharge and Day 28 within the same group and the unpaired t-test was used for the intergroup comparison, i.e. comparison of stroke scores of control group with corresponding stroke scores of magnesium group.
Comparison of stroke scores on Day 3 and day of discharge, on the day of discharge and Day 28 and on Day 3 and Day 28 in the magnesium group produced a t-value of 5.000 and P <0.001, which was highly significant. However, the comparison of the mean stroke scores between the magnesium and the control groups on Day 3, day of discharge and Day 28 yielded a P-value of >0.05, which was not significant.
The study failed to document a statistical significant stroke recovery in spite of achieving a significant rise in serum magnesium level, more than that necessary for neuroprotection, with an intravenous magnesium sulfate regime.
Ischemic stroke; magnesium sulfate; neuroprotection
The biomedical research community relies on a diverse set of resources, both within their own institutions and at other research centers. In addition, an increasing number of shared electronic resources have been developed. Without effective means to locate and query these resources, it is challenging, if not impossible, for investigators to be aware of the myriad resources available, or to effectively perform resource discovery when the need arises. In this paper, we describe the development and use of the Biomedical Resource Ontology (BRO) to enable semantic annotation and discovery of biomedical resources. We also describe the Resource Discovery System (RDS) which is a federated, inter-institutional pilot project that uses the BRO to facilitate resource discovery on the Internet. Through the RDS framework and its associated Biositemaps infrastructure, the BRO facilitates semantic search and discovery of biomedical resources, breaking down barriers and streamlining scientific research that will improve human health.
Ontology; Biositemaps; Resources; Biomedical research; Resource annotation; Resource discovery; Search; Semantic web; Web 2.0; Clinical and Translational Science Awards
A number of techniques have been described to reattach the torn distal biceps tendon to the bicipital tuberosity. We report a retrospective analysis of single incision technique using an endobutton fixation in sports persons.
Materials and Methods:
The present series include nine torn distal biceps tendons in eight patients, fixed anatomically to the radial tuberosity with an endobutton by using a single incision surgical technique; seven patients had suffered the injuries during contact sports. The passage of the endobutton was facilitated by using a blunt tipped pin in order to avoid injury to the posterior interosseous nerve. The patients were evaluated by Disabilities of the Arm, Shoulder and Hand (DASH) score and Mayo elbow score.
The average age of the patients was 27.35 years (range 21–42 years). Average follow-up was 41.5 months (range 24–102 months). The final average flexion extension arc was 0°–143°, while the average pronation and supination angles were 77° (range 70°–82°) and 81° (range 78°–85°), respectively at the last followup. All the patients had a Disabilities of the Arm, Shoulder and Hand (DASH) score of 0 and a Mayo elbow score of 100 each. All the seven active sports persons were able to get back to their respective game. There was no nerve injury or any other complication.
The surgical procedure used by us is a simple, safe and reproducible technique giving minimal morbidity and better cosmetic results.
Autograft; biceps tendon; elbow; tendon repair; tendon rupture
From time immemorial, fear and anxiety have been associated with dental treatment. Coping with this fear and anxiety has been one of the most vexing problems with which the individual dentist, as well as the profession has had to contend. Hence this study was undertaken to evaluate a new technique for management of such anxious patients.
The aim of this study is to evaluate the efficacy of using ‘Perceived control’ for the management of anxious patients undergoing endodontic therapy.
Settings and Design:
‘A communication device designed by the author and named as “Touch N’ Tell” (Patent no: 234291, Government of India) was installed on the dental chair which helps to create an effective communiqué between the patient and dentist during the dental procedure.
Materials and Methods:
Sixty anxious patients were selected using Modified Dental Anxiety Scale (MDAS), and were divided into two groups. For group A, the patients were treated along with the use of ‘communication system’ installed on the dental chair, whereas the patients were managed in a routine manner for Group B. The post operative MDAS scores were recorded for both the groups.
The mean change in anxiety levels was calculated for both the groups. Statistical analysis was done using unpaired t-test.
Result and Conclusion:
A significant decrease in the mean anxiety levels was observed in the group where ‘communication system’ was used as a measure of perceived control.
Anxiety; dental treatment; perceived control
Living liver donation is becoming a more common means to treat patients with liver failure because of a shortage of cadaveric organs and tissues. There is a potential for morbidity and mortality, however, in patients who donate a portion of their liver. The purpose of this study is to identify anesthetic complications and morbidity resulting from living liver donor surgery.
Patients and Methods:
The anesthetic records of all patients who donated a segment of their liver between January 1997 and January 2006 at University of Minnesota Medical Center-Fairview were retrospectively reviewed. The surgical and anesthesia time, blood loss, hospitalization length, complications, morbidity, and mortality were recorded. Data were reported as absolute values, mean ± SD, or percentage. Significance (P < 0.05) was determined using Student's paired t tests.
Seventy-four patients (34 male, 40 female, mean age = 35.5 ± 9.8 years) donated a portion of their liver and were reviewed in the study. Fifty-seven patients (77%) donated the right hepatic lobe, while 17 (23%) donated a left hepatic segment. The average surgical time for all patients was 7.8 ± 1.5 hours, the anesthesia time was 9.0 ± 1.3 hours, and the blood loss was 423 ± 253 ml. Forty-six patients (62.2%) received autologous blood either from a cell saver or at the end of surgery following acute, normovolemic hemodilution, but none required an allogenic transfusion. Two patients were admitted to the intensive care unit due to respiratory depression. Both patients donated their right hepatic lobe. One required reintubation in the recovery room and remained intubated overnight. The other was extubated but required observation in the intensive care unit for a low respiratory rate. Twelve patients (16.2%) had complaints of nausea, and two reported nausea with vomiting during their hospital stay. There were four patients who developed complications related to positioning during the surgery: Two patients complained of numbness and tingling in the hands which resolved within two days, one patient reported a blister on the hand, and one patient complained of right elbow pain that resolved quickly. Postoperative hospitalization averaged 7.4 ± 1.5 days. There was no patient mortality.
Living liver donation can be performed with low morbidity. However, postoperative respiratory depression is a concern and is perhaps due to altered metabolism of administered narcotics and anesthetic agents.
Anesthesia; complications; living liver donor surgery; respiratory depression
Ligand-gated ion channels underlie synaptic communication in the nervous system1. In mammals there are three families of ligand-gated channels: the cys loop, the glutamate-gated and the P2X receptor channels2. In each case binding of transmitter leads to the opening of a pore through which ions flow down their electrochemical gradients. Many ligand-gated channels are also permeable to calcium ions3, 4, which have downstream signaling roles5 (e.g. gene regulation) that may exceed the duration of channel opening. Thus ligand-gated channels can signal over broad time scales ranging from a few milliseconds to days. Given these important roles it is necessary to understand how ligand-gated ion channels themselves are regulated by proteins, and how these proteins may tune signaling. Recent studies suggest that many, if not all, channels may be part of protein signaling complexes6. In this article we explain how to identify the proteins that bind to the C-terminal aspects of the P2X2 receptor cytosolic domain.
P2X receptors are ATP-gated cation channels and consist of seven subunits (P2X1-P2X7). P2X receptors are widely expressed in the brain, where they mediate excitatory synaptic transmission and presynaptic facilitation of neurotransmitter release7. P2X receptors are found in excitable and non-excitable cells and mediate key roles in neuronal signaling, inflammation and cardiovascular function8. P2X2 receptors are abundant in the nervous system9 and are the focus of this study. Each P2X subunit is thought to possess two membrane spanning segments (TM1 & TM2) separated by an extracellular region7 and intracellular N and C termini (Fig 1a)7. P2X subunits10 (P2X1-P2X7) show 30-50% sequence homology at the amino acid level11. P2X receptors contain only three subunits, which is the simplest stoichiometry among ionotropic receptors. The P2X2 C-terminus consists of 120 amino acids (Fig 1b) and contains several protein docking consensus sites, supporting the hypothesis that P2X2 receptor may be part of signaling complexes. However, although several functions have been attributed to the C-terminus of P2X2 receptors9 no study has described the molecular partners that couple to the intracellular side of this protein via the full length C-terminus. In this methods paper we describe a proteomic approach to identify the proteins which interact with the full length C-terminus of P2X2 receptors.
Early childhood caries (ECC) is a serious and preventable disease which pediatric clinicians can help address by counseling to reduce risk.
We implemented a multifaceted practice-based intervention in a pediatric outpatient clinic treating children vulnerable to ECC (N = 635), comparing results to those from a similar nearby clinic providing usual care (N = 452).
We provided communication skills training using the approach of patient centered counseling, edited the electronic medical record to prompt counseling, and provided parents/caregivers with an educational brochure.
We assessed changes in provider knowledge about ECC after the intervention, and examined providers' counseling practices and incidence of ECC over time by site, controlling for baseline ECC, patient sociodemographics and parents'/caregivers' practice of risk factors (diet, oral hygiene, tooth-monitoring), among 1045 children with complete data.
Provider knowledge about ECC increased after the intervention training (percentage correct answers improved from 66% to 79%). Providers at the intervention site used more counseling strategies, which persisted after adjustment for sociodemographic characteristics. Children at the intervention site had a 77% reduction in risk for developing ECC at follow up, after controlling for age and race/ethnicity, sociodemographics and ECC risk factors; P ≤ 0.004.
The multifaceted intervention was associated with increased provider knowledge and counseling, and significantly attenuated incidence of ECC. If validated by additional studies, similar interventions could have the potential to make a significant public health impact on reducing ECC among young children.
early childhood caries; physician-patient relations; physicians'; practice patterns; intervention studies
The radiological diagnosis of osteolytic lesions of the long bones in pediatric population constitutes a challenge when the case history and clinical data are uncharacteristic. We believe that the description of few clinically and histologically proven cases to verify the existence of radiological signs useful for diagnosis may be of interest. Here, we describe a case of Langerhans' cell histiocytosis (LCH) presenting as unifocal eosinophilic granuloma of femur along with a brief review of the literature.
In this paper, we present a novel method for the classification of mammograms using a unique weighted association rule based classifier. Images are preprocessed to reveal regions of interest. Texture components are extracted from segmented parts of the image and discretized for rule discovery. Association rules are derived between various texture components extracted from segments of images, and employed for classification based on their intra- and inter-class dependencies. These rules are then employed for the classification of a commonly used mammography dataset, and rigorous experimentation is performed to evaluate the rules’ efficacy under different classification scenarios. The experimental results show that this method works well for such datasets, incurring accuracies as high as 89%, which surpasses the accuracy rates of other rule based classification techniques.
Image classification; association rule; mammograms
Lung cancer is the leading cause of cancer death for both men and women in the United States, and similar trends are seen world wide. The lack of early diagnosis is one of the primary reasons for the high mortality rate. A number of biomarkers have been evaluated in lung cancer patients, however, their specificity and early stage diagnostic values are limited. Using traditional protein chemistry and proteomics tool we have demonstrated higher serum haptoglobin levels in small cell lung cancer (SCLC). Similar findings have been reported for other cancers including ovarian cancer and glioblastoma. Haptoglobin is an acute phase protein with at least six possible phenotypes. The six phenotypes, in combination with two post translational modifications, glycosylation and deamidation, lead to large numbers of possible haptoglobin isoforms. Recent studies indicate a possible correlation between specific haptoglobin glycosylation and particular disease conditions. In our current study, we have fractionated control and SCLC patient serum by 2-D gel electrophoresis to identify differentially expressed haptoglobin isoforms in SCLC serum samples.
Serum; Haptoglobin; Isoforms; Small cell lung cancer
The aims of this study were to compare prevalence of early childhood caries (ECC) in 1- to 3-year-old children seeing primary-care pediatricians at two urban medical centers in Boston to the prevalence of ECC in similarly aged US children surveyed as part of the Third National Health and Nutrition Examination Survey (NHANES III) and to assess risk factors for ECC among this cohort of children compared with risk factors among similarly aged US children.
Characteristics of 787 1- to 3-year-old children from two urban Boston medical centers were compared with those of 3,644 similarly aged US children surveyed as part of NHANES III. Demographic and social characteristics and ECC prevalence by putative risk factors were compared. A multiple logistic regression model was fit to assess putative risk factors and difference between groups simultaneously.
Race, age, previous dental visit, parents’ education, and household income were significantly associated with ECC prevalence. Parents’ place of birth was a significant effect modifier with lower ECC among Boston children of immigrants than among US children of immigrants.
Lower ECC prevalence among urban Boston children of immigrant parents compared with US children of immigrant parents may reflect changing immigrant composition in the United States since NHANES III or a different immigrant composition in the Boston area compared with the United States. This finding reinforces the need for further research of immigrants in order to understand cultural practices that may affect oral health. Finally, low ECC prevalence among very young children reinforces the importance of early intervention in reducing ECC.
early childhood caries; oral health disparities
Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models.
Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 220.127.116.11 server tools and software applications and the model-driven architecture is implemented in a J2EE framework.
The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet.
These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems.
Tissue banking informatics; information models for translational research
The Early Detection Research Network (EDRN) colorectal and pancreatic neoplasm virtual biorepository is a bioinformatics-driven system that provides high-quality clinicopathology-rich information for clinical biospecimens. This NCI-sponsored EDRN resource supports translational cancer research. The information model of this biorepository is based on three components: (a) development of common data elements (CDE), (b) a robust data entry tool and (c) comprehensive data query tools.
The aim of the EDRN initiative is to develop and sustain a virtual biorepository for support of translational research. High-quality biospecimens were accrued and annotated with pertinent clinical, epidemiologic, molecular and genomic information. A user-friendly annotation tool and query tool was developed for this purpose. The various components of this annotation tool include: CDEs are developed from the College of American Pathologists (CAP) Cancer Checklists and North American Association of Central Cancer Registries (NAACR) standards. The CDEs provides semantic and syntactic interoperability of the data sets by describing them in the form of metadata or data descriptor. The data entry tool is a portable and flexible Oracle-based data entry application, which is an easily mastered, web-based tool. The data query tool facilitates investigators to search deidentified information within the warehouse through a “point and click” interface thus enabling only the selected data elements to be essentially copied into a data mart using a dimensional-modeled structure from the warehouse’s relational structure.
The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository database contains multimodal datasets that are available to investigators via a web-based query tool. At present, the database holds 2,405 cases and 2,068 tumor accessions. The data disclosure is strictly regulated by user’s authorization. The high-quality and well-characterized biospecimens have been used in different translational science research projects as well as to further various epidemiologic and genomics studies.
The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository with a tangible translational biomedical informatics infrastructure facilitates translational research. The data query tool acts as a central source and provides a mechanism for researchers to efficiently query clinically annotated datasets and biospecimens that are pertinent to their research areas. The tool ensures patient health information protection by disclosing only deidentified data with Institutional Review Board and Health Insurance Portability and Accountability Act protocols.
Colorectal and pancreatic neoplasm; tissue banking informatics
Beta-lactamases are one of the most serious threats to public health. In order to combat this threat we need to study the molecular and functional diversity of these enzymes and identify signatures specific to these enzymes. These signatures will enable us to develop inhibitors and diagnostic probes specific to lactamases. The existing classification of beta-lactamases was developed nearly 30 years ago when few lactamases were available. DLact database contain more than 2000 beta-lactamase, which can be used to study the molecular diversity and to identify signatures specific to this family.
A set of 2020 beta-lactamase proteins available in the DLact database http://18.104.22.168/DLact were classified using graph-based clustering of Best Bi-Directional Hits. Non-redundant (> 90 percent identical) protein sequences from each group were aligned using T-Coffee and annotated using information available in literature. Motifs specific to each group were predicted using PRATT program.
The graph-based classification of beta-lactamase proteins resulted in the formation of six groups (Four major groups containing 191, 726, 774 and 73 proteins while two minor groups containing 50 and 8 proteins). Based on the information available in literature, we found that each of the four major groups correspond to the four classes proposed by Ambler. The two minor groups were novel and do not contain molecular signatures of beta-lactamase proteins reported in literature. The group-specific motifs showed high sensitivity (> 70%) and very high specificity (> 90%). The motifs from three groups (corresponding to class A, C and D) had a high level of conservation at DNA as well as protein level whereas the motifs from the fourth group (corresponding to class B) showed conservation at only protein level.
The graph-based classification of beta-lactamase proteins corresponds with the classification proposed by Ambler, thus there is no need for formulating a new classification. However, further characterization of two small groups may require updating the existing classification scheme. Better sensitivity and specificity of group-specific motifs identified in this study, as compared to PROSITE motifs, and their proximity to the active site indicates that these motifs represents group-specific signature of beta-lactamases and can be further developed into diagnostics and therapeutics.
The Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer neoplasm virtual biorepository is a bioinformatics-supported system to incorporate data from various clinical, pathological, and molecular systems into a single architecture based on a set of common data elements (CDEs) that provides semantic and syntactic interoperability of data sets.
The various components of this annotation tool include the Development of Common Data Elements (CDEs) that are derived from College of American Pathologists (CAP) Checklist and North American Association of Central Cancer Registries (NAACR) standards. The Data Entry Tool is a portable and flexible Oracle-based data entry device, which is an easily mastered web-based tool. The Data Query Tool helps investigators and researchers to search de-identified information within the warehouse/resource through a "point and click" interface, thus enabling only the selected data elements to be essentially copied into a data mart using a multi dimensional model from the warehouse's relational structure.
The SPORE Head and Neck Neoplasm Database contains multimodal datasets that are accessible to investigators via an easy to use query tool. The database currently holds 6553 cases and 10607 tumor accessions. Among these, there are 965 metastatic, 4227 primary, 1369 recurrent, and 483 new primary cases. The data disclosure is strictly regulated by user's authorization.
The SPORE Head and Neck Neoplasm Virtual Biorepository is a robust translational biomedical informatics tool that can facilitate basic science, clinical, and translational research. The Data Query Tool acts as a central source providing a mechanism for researchers to efficiently find clinically annotated datasets and biospecimens that are relevant to their research areas. The tool protects patient privacy by revealing only de-identified data in accordance with regulations and approvals of the IRB and scientific review committee.
Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women. the symptomatic patients should receive standard therapy for heart failure, managed by a multidisciplinary team. The diagnosis of PPCM rests on the echocardiographic identification of new left ventricular systolic dysfunction during a limited period surrounding parturition. Diagnostic criteria include an ejection fraction of less than 45%, fractional shortening of less than 30%, or both, and end-diastolic dimension of greater than 2.7 cm/m2 body surface-area. This entity presents a diagnostic challenge because many women in the last month of a normal pregnancy experience dyspnea, fatigue, and pedal edema, symptoms identical to early congestive heart failure. There are no specific criteria for differentiating subtle symptoms of heart failure from normal late pregnancy. Therefore, it is important that a high index of suspicion be maintained to identify the rare case of PPCM as general examination showing symptoms of heart failure with pulmonary edema. PPCM remains a diagnosis of exclusion. No additional specific criteria have been identified to allow distinction between a peripartum patient with new onset heart failure and left ventricular systolic dysfunction as PPCM and another form of dilated cardiomyopathy. Therefore, all other causes of dilated cardiomyopathy with heart failure must be systematically excluded before accepting the designation of PPCM. Recent observations from Haiti suggest that a latent form of PPCM without clinical symptoms might exist. The investigators identified four clinically normal postpartum women with asymptomatic systolic dysfunction on echocardiography, who subsequently either developed clinically detectable dilated cardiomyopathy or improved and completely recovered heart function.
Heart failure; peripartum cardiomyopathy; pre-eclamptic toxemia; pregnancy; pulmonary edema
Eventration of the diaphragm is an abnormal elevation of the dome of diaphragm. It is a condition in which all or part of the diaphragm is largely composed of fibrous tissue with only a few or no interspersed muscle fibers. It can be complete or partial. Complete eventration of the right diaphragm, as seen in this adult patient, is relatively rare.
Diaphragm; eventration; sniff test; fluoroscopy