Anorectal Anomalies in Adults-Laparoscopic Management and Review of Literature

Anorectal malformations (ARMs) are one of the most common congenital anomalies dealt by surgeons. The reported incidence of ARMs range between 1:3,300 and 1:5,000 live births. These defects are invariably detected and treated in infancy or early childhood. There is a group of patients among these who have fistulous external opening from the rectum. These may not present in child hood and may continue to live with fecal incontinence till adult hood. One of such anomalies is rectovaginal fistulas which comprises of only 4% of all anomalies. Delayed management in such cases increases surgical and functional complications. Traditionally high and intermediate anorectal anomalies are treated by posterior sagittal anorectoplasty (PSARP). This involves cutting of sphincter muscles in the midline and then placement of rectum in the sphincter complex. The continence results of this operation are less than ideal. Laparoscopically assisted anorectal pull-through (LAARP) has potential advantage of precise placement of the rectum inside the sphincter complex without dividing and weakening the muscles, diminished soft tissue scarring around the rectum leading to improved rectal compliance. Three adult female patients with ARMs were managed through LAARP procedure. It involves dissection around rectum, identification and ligation of fistula tract, creation of neoanus and pull through of rectum into neoanus. Results-Continence was good in all our patients which they regained after 3 to 4?days of surgery. On follow up which ranged from 6?months to 2?years all were passing well formed stools 1?C2 times a day and have symmetric anal contraction with strong squeeze on digital rectal examination. Conclusion-LAARP offers an excellent option to the patients of ARM over conventional posterior sagittal anorectal approach because if its theoretical advantages of early recovery and better continence. Long term followup is needed to substantiate these results.     

Matrix-protein-specific regulation of Cx43 expression in cardiac myocytes subjected to mechanical load

To elucidate mechanisms responsible for mechanotransduction in the heart and define the effects of remodeling of the extracellular matrix, we cultured neonatal rat ventricular myocytes on native type I collagen, fibronectin, or denatured collagen and subjected them to uniaxial, pulsatile stretch. Changes in expression of the cardiac gap junction protein, Cx43, were measured by confocal microscopy and immunoblotting. Cells grown on fibronectin or denatured collagen exhibited significantly greater Cx43 expression than cells grown on native collagen. Stretch induced a approximately 2-fold increase in Cx43 expression in cells grown on native collagen but no increase in cells grown on fibronectin or denatured collagen. Incubation of cells on native collagen with a peptide containing the arginine-glycine-aspartate (RGD) motif upregulated Cx43 expression equivalent to that induced by stretch. Nonselective activation of integrin signaling with MnCl2 also upregulated Cx43 expression in cells grown on native collagen. This effect was blocked completely by pretreatment with anti-beta1 integrin antibody but not by anti-beta3 integrin antibody. Stretch led to a marked increase in beta1 integrin immunofluorescent signal in cells grown on native collagen but not in cells grown on fibronectin or denatured collagen. Stretch-induced upregulation of Cx43 was also blocked by anti-beta1 integrin antibody. Thus, matrix protein-myocyte interactions regulate Cx43 expression via beta1 integrin signaling initiated by mechanical stimulation in cells grown on native type I collagen, or by RGD-integrin signaling independent of mechanical stress in cells grown on fibronectin or denatured collagen. Changes in the composition of the extracellular matrix may affect electrical coupling in cardiac myocytes.     

Novel protein kinase, AUT-PK 85, isolated from adrenocortical carcinoma: purification and characterization.

We describe the purification to apparent homogeneity of a protein kinase (designated AUT-PK 85) from adrenocortical carcinoma 494, as evidenced by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The enzyme binds cyclic AMP (cAMP) and autophosphorylates but does not use histone, casein, or polysomes as substrates in the presence or absence of cAMP. Stoichiometry of phosphate incorporation was 0.71 mol/mol of enzyme. The enzyme was found to have a molecular weight of 85,000 based on gel filtration. The protein was composed of polypeptides having the same molecular weight 42,000, and thus it appears to consist of two subunits of equal size. The enzyme bound two cAMP molecules, indicating that each subunit binds one molecule of cAMP. The homogeneous enzyme did not inhibit the protein kinase activity of the free catalytic subunit of normal adrenal cAMP-dependent protein kinase under conditions such that recombination with the free regulatory subunit occurred. cAMP bound specifically to the enzyme with an apparent dissociation constant (cfKd) of 1.2 X 10(-8) M. Scatchard plot data indicated one type of binding sites for cAMP. The enzyme did not bind adenosine. This novel autophosphorylating, cAMP-binding, protein kinase may be a characteristic of certain adrenal neoplasms.     

Microalbuminuria: A marker of severe disease activity in rheumatoid arthritis

ObjectiveMicroalbuminuria is associated with increased risk for renal and cardiovascular mortality and morbidity in diabetes mellitus, hypertension, patients with acute myocardial infarction and elderly patients but the significance of microalbuminuria in rheumatoid arthritis and its correlation with disease activity is not well studied. The present study is therefore aimed to determine the microalbuminuria in rheumatoid arthritis patients and to correlate it with indicators of disease activity like CRP and ESR.MethodsHundred confirmed cases of Rheumatoid arthritis (2010 ACR-EULAR criteria) and hundred age and sex matched controls were taken. Those suffering from hypertension, diabetes mellitus and renal disease were excluded. Microalbumin was assessed by immunoturbidimetric method on Delta nephelometer. Disease activity was assessed by CRP and ESR.ResultsThe relative frequency of microalbuminuria in patients with rheumatoid arthritis was 26% as compared to 4% in controls. The median level of microalbuminuria in rheumatoid arthritis patients was significantly greater than in the controls (17 vs. 3.29, p < 0.01). Microalbuminuria significantly correlated with CRP (p < 0.001, r = 0.457) and ESR (p < 0.001, r = 0.361). A significant correlation was found with duration of disease (p < 0.05, r = 0.231) and number of joints involved (p < 0.05, r = 0.240).ConclusionsWe found increased prevalence of microalbuminuria in rheumatoid arthritis patients and it correlated with acute phase reactants.     

Health screening for people with Down's syndrome

All adults over the age of 18 years with Down's syndrome living in a borough of London, England, were identified through a case register. A questionnaire seeking information on health status and screening was sent to their carers. The reply rate was 70%. The attendance for general health care is reasonable, but there are some gaps in screening. The implications for primary health care and health promotion are discussed.     

Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies.

PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed primary brain tumors for the presence of hypoxia, as indicated by the uptake of 18F-fluoromisonidazole (18F-FMISO) and to examine the relationship of hypoxia to the uptake of 18F-FDG and molecular markers of hypoxia. METHODS: Seventeen patients with suspected primary glioma were enrolled prospectively in this study. Sixteen patients had histology, with 2 having metastatic disease. All patients had PET studies with 18F-FMISO and 18F-FDG and MRI studies. Immunohistochemistry was undertaken with tumor markers of angiogenesis and hypoxia. Patients were monitored for disease progression and statistical analysis of data was performed. RESULTS: Of the 14 patients with histology, 8 died with a median time of 16 mo (range, 2-30 mo) until death. Of those who died, 7 had positive and 1 had negative 18F-FMISO uptake. 18F-FMISO uptake was observed in all high-grade gliomas but not in low-grade gliomas. A significant relationship was found between 18F-FDG or 18F-FMISO uptake and expression of VEGF-R1 and Ki67 expression. Other immunohistochemical markers demonstrated a trend toward increased uptake but none was significant. CONCLUSION: 18F-FMISO PET provides a noninvasive assessment of hypoxia in glioma and was prognostic for treatment outcomes in the majority of patients. 18F-FMISO PET may have a role not only in directing patients toward targeted hypoxic therapies but also in monitoring response to such therapies.     

Immunomodulation Due to Coexposure to Styrene and Dioctyl Phthalate in Mice

Pathomorphological and immunological alterations caused by a mixture of styrene and dioctyl phthalate were studied in albino mice following oral administration of 0.02, 0.03, 0.05±LD50 of the mixture. The chemicals were mixed together proportionate to their respective LD50 values and fed in ground nut oil, 5d/wk for 4 weeks. Histological examination of spleen revealed considerable depletion of cellular population of lymphoid follicles which corresponded to the dose dependent decrease in splenic mononuclear cell population count. The thymic lobules revealed slight atrophy but accompanied by a significant increase in thymocyte population. Correspondingly few significant histological changes were observed in mesenteric and peripheral lymph nodes. The treatment caused impairment of primary humoral immune response to SRBC (IgM) but there was a significant increase in response of splenocytes to B-cell mitogen LPS. There was a suppression of cutaneous delayed type hypersensitivity and increase in splenic lymphocyte response to T-cell mitogen PHA. Simultaneously, indirect immunity represented by decreased phagocytosis and enhanced metabolic function of reducing NBT by peritoneal exudate cells was observed. The in vitro exposure of vero cells to the mixture caused dose dependent protective effect. The results of present study indicate that subchronic exposure to low doses of mixture of styrene and dioctyl phthalate under certain conditions may modulate some of the immune functions as compared to exposure to either chemicals alone.