Multiple primary malignant neoplasms: a case of colonic adenocarcinoma and non-Hodgkin's lymphoma on a background of ulcerative colitis.

The presence of an adenocarcinoma and non-Hodgkin's lymphoma in an individual is an uncommon finding. In this case report, we discuss the case of an elderly man presenting with a synchronous moderately differentiated colonic adenocarcinoma alongside a distal ileal extranodal marginal zone lymphoma, on a background of ulcerative colitis. He underwent an elective open panproctocolectomy with an end ileostomy for the management of his malignancy.

Multiple primary malignant neoplasms: a case of colonic adenocarcinoma and non-Hodgkin's lymphoma on a background of ulcerative colitis.

The presence of an adenocarcinoma and non-Hodgkin's lymphoma in an individual is an uncommon finding. In this case report, we discuss the case of an elderly man presenting with a synchronous moderately differentiated colonic adenocarcinoma alongside a distal ileal extranodal marginal zone lymphoma, on a background of ulcerative colitis. He underwent an elective open panproctocolectomy with an end ileostomy for the management of his malignancy.

Laparoscopic surgery reduces the incidence of surgical site infections compared to the open approach for colorectal procedures: a meta-analysis.

BACKGROUND: Surgical site infections (SSI) are the commonest healthcare associated infections. They severely compromise patient safety, are a significant burden on healthcare resources and have an adverse impact on patient quality of life. The incidence of SSIs can be as high as 10% after colorectal procedures. The laparoscopic approach is being increasingly used to undertake colorectal procedures. It provides advantages over the traditional open approach with smaller incisions, shorter hospital stay and equal oncological outcomes. The aim of this meta-analysis was to evaluate whether the laparoscopic approach for colorectal procedures reduces the incidence of SSI compared to the open approach. METHODS: Randomised controlled trials (RCTs) comparing the two approaches published since 2000 were included in the review. Revman 5.3 software was used to carry out the review. Data were pooled and the results were shown as risk ratios with 95% confidence intervals using the fixed effects model. RESULTS: Sixteen RCT's were included in the analysis comprising 5797 patients. These covered a range of colorectal pathologies including colon cancer, rectal cancer, inflammatory bowel disease and familial adenomatous polyposis syndrome. Analysis showed significantly lower wound infection rates (RR: 0.72, 95% confidence interval: 0.60-0.88, p = 0.001) and lower abdominal abscess rates (RR: 0.88, 95% CI 0.62-1.27, p = 0.51). The combined SSI rate was significantly lower in laparoscopic compared to open surgery (RR: 0.76, 95% CI 0.64-0.90, p = 0.001). CONCLUSIONS: Laparoscopic colorectal surgery significantly lowers the incidence of SSI compared to open surgery.

Perinuclear Antineutrophil Cytoplasmic Antibody Positive Glomerulonephritis in a Case of Limited Cutaneous Scleroderma.

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis in a patient of scleroderma is very rare. Very few cases have been reported in English literature. We report a case of a 58-year-old male with long-standing limited cutaneous scleroderma (Scl-70 positive) presenting with normotensive scleroderma renal crisis. Perinuclear ANCA with antimyeloperoxidase antibody was found to be strongly positive. Renal biopsy showed pauci immune-necrotizing crescentic glomerulonephritis. We believe that this case report will be helpful in understanding clinical features of normotensive ANCA-associated glomerulonephritis in scleroderma patients.

Endoscopic Myringoplasty Versus Microscopic Myringoplasty in Tubotympanic CSOM: A Comparative Study of 120 Cases.

Myringoplasty is one of the commonest operations performed on the middle ear. Our aim was to compare the results of endoscopic permeatal myringoplasty with that of conventional myringoplasty by post aural approach using operating microscope. A total of 120 patients having central perforation of tympanic membrane were randomly divided into two equal groups of 60 patients each. In the first group, endoscope was used and in the second group microscope was used to do myringoplasty. Temporalis fascia was used as a graft material. The patients were kept in follow-up for 1 year. The pre-operative and post-operative audiograms, post-operative pain, graft uptake and time taken for surgery were compared in both the groups. The graft uptake rate was 91.67% in the endoscopic group, whereas it was 93.3% in the microscopic group. Post-operative pain was significantly less in the endoscopic group as compared with microscopic group and not much difference was found in the gain in A-B gap in either group. The mean ABG gain was 16.16 dB (SD = 4.68) in endoscopic group and 19.54 dB (SD = 3.45) in microscopic group. On applying the Mann-Whitney U test, this finding was statistically significant (p value = 0.0001). In our study success rate was equal between endoscopic and microscopic technique. In terms of morbidity and postoperative recovery endoscope produced better results. Endoscopic tympanoplasty can be a good alternative of microscopic tympanoplasty.

Extracranial Head and Neck Schwannomas: Our Experience.

Schwannomas are benign neoplasms of the peripheral nerves originating in the Schwann cells. They are rare and usually solitary, with clearly delimited capsules. They occur in the head and neck region in only 25 % of the cases, and may be associated with Von Recklinghausen's disease. Schwannomas are always a diagnostic dilemma as they are asymptomatic for long time and histopathology is the gold standard for diagnosis. The present study retrospectively analysed data of 4 patients with schwannomas and reviewed the literature on the subject. Retrospective study at ENT & Head and Neck Surgery Department of Navodaya Medical College, Raichur. Data of 4 patients between 2008 and 2014 were reviewed. The sites of cervical schwannomas and the intraoperative, histopathological and postoperative clinical status of these cases were studied. Diagnostic methods, type of surgery and associated nerve of origin (NOO) were evaluated. The patients' age ranged from 18 to 50 years. None of them had type I neurofibromatosis or Von Recklinghausen's disease. The nerves affected included the brachial plexus, vagus nerve, sympathetic chain and lingual nerve. The nerve of origin was identified based on intra-operative findings and post-operative neurological deficits. Tumour was removed by debulk operation with the preservation of NOO method. Schwannomas are generally benign, and rarely recur. An accurate preoperative workup with the identification of NOO is very important not only for a correct diagnosis, but also for surgical planning and informing the patient about the possible complications.

Isolation of filamentous fungi from sputum in asthma is associated with reduced post-bronchodilator FEV1.

BACKGROUND: Fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown. OBJECTIVE: To provide a comprehensive analysis on the range of filamentous fungi isolated in sputum from people with asthma and report the relationship with their clinico-immunological features of their disease. METHODS: We recruited 126 subjects with a diagnosis of asthma, 94% with moderate-severe disease, and 18 healthy volunteers. At a single stable visit, subjects underwent spirometry; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel; specific IgE to Aspergillus fumigatus. Fungi were identified by morphology and species identity was confirmed by sequencing. Four patients had allergic bronchopulmonary aspergillosis. RESULTS: Forty-eight percent of asthma subjects were IgE-sensitized to one fungal allergen and 22% to ≥ 2. Twenty-seven different taxa of filamentous fungi were isolated from 54% of their sputa, more than one species being detected in 17%. This compared with 3 (17%) healthy controls culturing any fungus (P < 0.01). Aspergillus species were most frequently cultured in isolation followed by Penicillium species. Post-bronchodilator FEV (1) (% predicted) in the subjects with asthma was 71(± 25) in those with a positive fungal culture vs. 83 (± 25) in those culture-negative, (P < 0.01). CONCLUSION AND CLINICAL RELEVANCE: Numerous thermotolerant fungi other than A. fumigatus can be cultured from sputum of people with moderate-to-severe asthma; a positive culture is associated with an impaired post-bronchodilator FEV (1) , which might be partly responsible for the development of fixed airflow obstruction in asthma. Sensitization to these fungi is also common.

Analysis of early changes in the articular cartilage transcriptisome in the rat meniscal tear model of osteoarthritis: pathway comparisons with the rat anterior cruciate transection model and with human osteoarthritic cartilage.

OBJECTIVE: The purpose of this study was to use microarray technology to: (1) understand the early molecular events underlying the damage of articular cartilage initiated by this surgical procedure, and (2) determine whether these changes mimic those that are occurring in human osteoarthritic (OA) cartilage. DESIGN: Cartilage was harvested from both medial and lateral sides of the tibial plateaus and femoral condyles of both meniscal tear (MT) and sham surgery groups on days 3, 7 and 21 post-surgery. mRNA prepared from these rat cartilage samples was used for microarray analysis. RESULTS: Statistical analysis identified 475 genes that were differentially expressed between the sham and MT groups, at one or more of the time points that were analyzed. By integrating these genes with OA-related genes reported previously in a rat OA model and in human OA array studies, we identified 20 commonly changed genes. Six out of these 20 genes (Col5A1, Col6A2, INHBA, LTBP2, NBL1 and SERPINA1) were differentially expressed in two animal models and in human OA. Pathway analysis identified some key features of OA pathology, namely cartilage extracellular matrix remodeling, angiogenesis, and chondrocyte cell death that were recapitulated in the animal models. The rat models suggested increased inflammation and cholesterol metabolic pathways may play important role in early cartilage degeneration. CONCLUSION: We identified a large number of differentially expressed genes in the articular cartilage of the MT model. While there was lack of overall identity in cartilage gene expression between the rat models and human OA, several key biological processes were recapitulated in the rat MT OA model.

Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes.

The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administration, we administered a low dose of the transient osteoclast inhibitor salmon calcitonin (sCT) to young rats receiving an anabolic PTH regimen. Co-administration of sCT significantly blunted the anabolic effect of PTH as measured by peripheral quantitative computer tomography (pQCT) and histomorphometry in the femur and tibia, respectively. To determine gene targets of sCT, we carried out quantitative real time PCR and microarray analysis of metaphyseal samples 1.5, 4 and 6.5h after administration of a single injection of PTH, sCT or PTH+sCT. Known targets of PTH action, IL-6, ephrinB2 and RANKL, were not modified by co-administration with sCT. Surprisingly, at all time points, we noted a significant upregulation of sclerostin mRNA by sCT treatment, as well as down-regulation of two other osteocyte gene products, MEPE and DMP1. Immunohistochemistry confirmed that sCT administration increased the percentage of osteocytes expressing sclerostin, suggesting a mechanism by which sCT reduced the anabolic effect of PTH. Neither mRNA for CT receptor (Calcr) nor labeled CT binding could be detected in sclerostin-enriched cells differentiated from primary calvarial osteoblasts. In contrast, osteocytes freshly isolated from calvariae expressed a high level of Calcr mRNA. Furthermore immunohistochemistry revealed co-localization of CT receptor (CTR) and sclerostin in some osteocytes in calvarial sections. Taken together these data indicate that co-treatment with sCT can blunt the anabolic effect of PTH and this may involve direct stimulation of sclerostin production by osteocytes. These data directly implicate calcitonin as a negative regulator of bone formation through a previously unsuspected mechanism.

Data-driven analysis approach for biomarker discovery using molecular-profiling technologies.

High-throughput molecular-profiling technologies provide rapid, efficient and systematic approaches to search for biomarkers. Supervised learning algorithms are naturally suited to analyse a large amount of data generated using these technologies in biomarker discovery efforts. The study demonstrates with two examples a data-driven analysis approach to analysis of large complicated datasets collected in high-throughput technologies in the context of biomarker discovery. The approach consists of two analytic steps: an initial unsupervised analysis to obtain accurate knowledge about sample clustering, followed by a second supervised analysis to identify a small set of putative biomarkers for further experimental characterization. By comparing the most widely applied clustering algorithms using a leukaemia DNA microarray dataset, it was established that principal component analysis-assisted projections of samples from a high-dimensional molecular feature space into a few low dimensional subspaces provides a more effective and accurate way to explore visually and identify data structures that confirm intended experimental effects based on expected group membership. A supervised analysis method, shrunken centroid algorithm, was chosen to take knowledge of sample clustering gained or confirmed by the first step of the analysis to identify a small set of molecules as candidate biomarkers for further experimentation. The approach was applied to two molecular-profiling studies. In the first study, PCA-assisted analysis of DNA microarray data revealed that discrete data structures exist in rat liver gene expression and correlated with blood clinical chemistry and liver pathological damage in response to a chemical toxicant diethylhexylphthalate, a peroxisome-proliferator-activator receptor agonist. Sixteen genes were then identified by shrunken centroid algorithm as the best candidate biomarkers for liver damage. Functional annotations of these genes revealed roles in acute phase response, lipid and fatty acid metabolism and they are functionally relevant to the observed toxicities. In the second study, 26 urine ions identified from a GC/MS spectrum, two of which were glucose fragment ions included as positive controls, showed robust changes with the development of diabetes in Zucker diabetic fatty rats. Further experiments are needed to define their chemical identities and establish functional relevancy to disease development.

Effects of parathyroid hormone on Wnt signaling pathway in bone.

The Wnt signaling pathway has recently been demonstrated to play an important role in bone cell function. In previous studies using DNA microarray analyses, we observed a change in some of the molecular components of the canonical Wnt pathway namely, frizzled-1 (FZD-1) and axil, in response to continuous parathyroid hormone (PTH) treatment in rats. In the present study, we further explored other components of the Wnt signaling pathway in rat distal metaphyseal bone in vivo, and rat osteoblastic osteosarcoma cells (UMR 106) in culture. Several Wnt pathway components, including low-density lipoprotein-receptor-related protein 5 (LRP5), LRP6, FZD-1, Dickkopf-1 (Dkk-1), and Kremen-1 (KRM-1), were expressed in bone in vivo and in osteoblasts in vitro. Continuous exposure to PTH (1-38) both in vivo and in vitro upregulated the mRNA expression of LRP6 and FZD-1 and decreased LRP5 and Dkk-1. These effects in UMR 106 cells were associated with an increase in beta-catenin as measured by Western blots and resulted in functional activation (three to six-fold) of a downstream Wnt responsive TBE6-luciferase (TCF/LEF-binding element) reporter gene. Activation of the TBE6-luciferase reporter gene by PTH (1-38) in UMR 106 cells was inhibited by the protein kinase A (PKA) inhibitor, H89. Activation was mimicked by PTH (1-31), PTH-related protein (1-34), and forskolin, but both PTH (3-34) and (7-34) had no effect. These findings suggest that the effect of PTH on the canonical Wnt signaling pathway occurs at least in part via the cAMP-PKA pathway through the differential regulation of the receptor complex proteins (FZD-1/LRP5 or LRP6) and the antagonist (Dkk-1). Taken together, these results reveal a possible role for the Wnt signaling pathway in PTH actions in bone.

Rhinocerebral mucormycosis: An analysis of probable mode of spread and its implication in an early diagnosis and treatment.

The study was done in two parts:Analysis of CT scan findings of 17 cases of mucormycosis to determine paranasal sinus, orbital and intra-cranial involvement.Cadaveric dissections of the ethmoid complex anatomy to correlate the probable mode of spread. Ethmoidal sinus was found to be the most commonly involved. The disease probably appears first here, spreads to orbit through the lamina papyracea and then through the retro-orbital region, intra-cranially. Our aim would be to diagnose the disease at the stage of ethmoid involvement. In immuno-compromised patients, if headache, peri- or retro-orbital pain or blood stained nasal discharge occur; a CT scan of the paranasal sinuses and a nasal endoscopy with biopsy from anterior ethmoids, if this area shows pathology then CT scan must be performed. If this is positive for mucormycosis, surgical debridement of the involved sinuses is to be done and Amphotericin B as intra-venous infusion and treatment of underlying condition is started.

Isolated uvulitis: An uncommon but not a rare clinical entity.

Infections of uvula have been described in association with group A streptococcal pharyngitis (Rapkin, JAMI, 43, 1980, 1843), or Haemolytic influenzae type b epiglottitis. Medicine (Gorjinkel HJ, 58, 1979, 80) however, to our knowledge, only two cases of isolated uvulitis are reported in world literature. We report five cases of isolated uvulitis in adults.

Postoperative resolution of urinary retention in patients with advanced pelvic organ prolapse.

OBJECTIVE: This study was undertaken to determine whether surgery for advanced pelvic organ prolapse corrects the voiding dysfunction commonly associated with this condition and if so to evaluate the ability of preoperative voiding studies to predict such correction. STUDY DESIGN: We reviewed the records of all women who underwent surgery at our center between January 1996 and June 1999 for stage 3 or 4 pelvic organ prolapse. Patients were included in this review if they had a postvoid residual volume of >100 mL documented by catheterization on at least 2 occasions, had no normal postvoid residual volumes documented, and had undergone preoperative multichannel urodynamic testing that included an instrumented voiding study. Demographic and urodynamic data were analyzed for the ability to predict whether the elevated postvoid residual volume would be resolved after surgery. RESULTS: Thirty-five patients satisfied the criteria for inclusion in the review. Twenty-six had stage 3 pelvic organ prolapse and 9 had stage 4 pelvic organ prolapse. The mean preoperative postvoid residual volume was 226 mL (range, 105-600 mL). Thirty-one patients (89%) had normal postvoid residual volumes after surgery. As a predictor of elevated postoperative postvoid residual volumes, the preoperative voiding study (performed with the prolapse reduced) had a sensitivity of 66%, a specificity of 46%, a positive predictive value of 12%, and a negative predictive value of 93%. CONCLUSION: In our center a preoperative voiding study performed with the pelvic organ prolapse reduced most accurately predicted postoperative voiding function when results of the voiding study were normal. Most patients with advanced pelvic organ prolapse and elevated postvoid residual volume had normalization of the postvoid residual volume after surgical correction of the pelvic organ prolapse.

Xylanase II from an alkaliphilic thermophilic Bacillus with a distinctly different structure from other xylanases: evolutionary relationship to alkaliphilic xylanases.

A 1.0 kilobase gene fragment from the genomic DNA of an alkaliphilic thermophilic Bacillus was found to code for a functional xylanase (XynII). The complete nucleotide sequence including the structural gene and the 5' and 3' flanking sequences of the xylanase gene have been determined. An open reading frame starting from ATG initiator codon comprising 402 nucleotides gave a preprotein of 133 amino acids of calculated molecular mass 14.090 kDa. The occurrence of three potential N-glycosylation sites in XynII gene is a unique feature for a gene of bacterial origin. The stop codon was followed by hairpin loop structures indicating the presence of transcription termination signals. The secondary structure analysis of XynII predicted that the polypeptide was primarily formed of beta-sheets. XynII appeared to be a member of family G/11 of xylanases based on its molecular weight and basic pI (8.0). However, sequence homology revealed similar identity with families 10 and 11 of xylanases. The conserved triad (Val-Val-Xaa, where Xaa is Asn or Asp) was identified only in the xylanases from alkaliphilic organisms. Our results implicate for the first time the concept of convergent evolution for XynII and provide a basis for research in evolutionary relationship among the xylanases from alkaliphilic and neutrophilic organisms.

Severe spasm of a radial artery coronary bypass graft during coronary intervention.

Coronary spasm is a well-recognized observation during coronary angiography. This report describes a patient who developed spasm of a radial artery bypass graft during coronary intervention. There are many reports on the angiographic follow-up to confirm the surgical results for patency in radial arterial conduits. We share our experience with this first case in the literature noted to have severe vasospasm during PTCA. Cathet. Cardiovasc. Intervent. 47:331-335, 1999.

Synapse formation and establishment of neuronal polarity by P19 embryonic carcinoma cells and embryonic stem cells.

A number of different cell lines that exhibit a partial neuronal phenotype have been identified, but in many cases the full extent of their neuronal differentiation has not been directly addressed by functional studies. We have used electrophysiology and immunofluorescence to examine the formation of synapses and the development of neuronal polarity by murine embryonic stem (ES) cells and the mouse P19 embryonic carcinoma cell line. Within 2-3 weeks after induction by retinoic acid, subsets of P19 and ES cells formed excitatory synapses, mediated by glutamate receptors, or inhibitory synapses, mediated by receptors for GABA or glycine. In ES-cell cultures, both NMDA and non-NMDA receptors contributed to the excitatory postsynaptic response. Staining with antibodies to growth-associated protein-43 and microtubule-associated protein-2 revealed segregation of immunoreactivity into separate axonal and somato-dendritic compartments, respectively. Consistent with our physiological evidence for synapse formation, intense punctate staining was observed with antibodies to the synaptic vesicle proteins synapsin, SV2, and synaptophysin. These results demonstrate the in vitro acquisition by pluri-potent cell lines of neuronal polarity and functional synaptic transmission that is characteristic of CNS neurons.

Diffusion in Fe(II/III) radiation dosimetry gels measured by magnetic resonance imaging.

We analyse the diffusion problem in the traditional Fe(II/III) agarose gel system employed in MRI studies of radiation dosimetry. The diffusion coefficient is measured using an inversion recovery null-point imaging method in a model gel/water phantom. The diffusion coefficient of Fe(III) in 1% agarose gel at pH 1.1 is D = 2.7 +/- 0.3 x 10(-6) cm2 s-1. The diffusion coefficient of Fe(II) is D = 3.3 +/- 0.5 x 10(-6) cm2 s-1. Measurement of the diffusion coefficients permits simulation of the MRI signal intensity from phantoms with model radiation dose distributions. We allow for diffusion of both Fe(II) and Fe(III) in our simulations as well as the effect of both relaxation agents on the local spin-lattice relaxation time T1. We also analyse the effects of the physical penumbra on the diffusion problem.

Autopsy study of infant kidneys in cases of urinary tract anomalies.

The infant autopsies were scrutinised to find the incidence, etiology & significance in terms of fatality of urinary tract anomalies. On analysing 1329 infant autopsies, 24 cases (1.8%) of significant urinary tract anomalies were found. There was marked male predominance. Intrauterine obstruction of urinary tract was the main etiological factor leading to dysplastic changes in the renal tissue. Dysplasia is severe in extent and may be associated with persistent blastemal zones when the obstruction is complete & bilateral in nature.