A case of perforative peritonitis complicated with lung and intestinal severe tuberculosis

A 27-year-old man was admitted to our hospital in September 18, 2000, complaining of fever, cough, appetite loss and body weight loss. He was diagnosed as advanced lung tuberculosis, because of chest X-ray findings and positive acid-fast bacilli in his sputum. He was administrated rifampicin (RFP), isoniazid (INH) and ethambutol (EB). Two days after starting treatment he complained of abdominal pain and the signs of perforating peritonitis. Emergency laparotomy was performed and we observed multiple ulcers and a perforation of ileum. We resected a part of distal ileum and ascending colon and made ileostomy. Histopathologic examination of resected ileum and colon showed multiple ulcers and epithelioid cell granulomas with caseous necrosis. Many acid bacilli were identified from the lesion by specially stained tissue sections. He was administrated streptomycin and INH by injection post-operatively while oral administration was impossible. Six days after the first operation, we found the signs of perforation in another part of the ileum. So we were obliged to perform second laparotomy and resect the part involved. Five days after the second operation, he was able to take RFP, INH, and levofloxacin per oral route. On February 8, 2001 we performed ileocolonal reconstruction with side to side anastomosis and closed ileostomy at the third laparotomy. He had continued chemotherapy and went back to Korea in April 7, 2001. Although intestinal tuberculosis has sharply declined in Japan thanks to development of effective antituberculous drugs, we should keep in mind that it could be a possible cause of the acute abdomen.     

EUS-Guided Biliary Drainage

Endoscopic ultrasonography (EUS) combines endoscopy and intraluminal ultrasonography, and allows imaging with a high-frequency transducer over a short distance to generate high-resolution ultrasonographic images. EUS is now a widely accepted modality for diagnosing pancreatobiliary diseases. EUS-guided fine-needle aspiration (EUS-FNA) using a curved linear-array echoendoscope was initially described more than 20 years ago, and since then many researchers have expanded its indications to sample diverse lesions and have also used it for various therapeutic purposes. EUS-guided biliary drainage (EUS-BD) is one of the therapeutic procedures that has been developed using a curved linear-array echoendoscope. Technically, EUS-BD includes rendezvous techniques via transesophageal, transgastric, and transduodenal routes, EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS). Published data have demonstrated a high success rate, albeit with a comparatively high rate of nonfatal complications for EUS-CDS and EUS-HGS, and a comparatively low success rate with a low complication rate for the rendezvous technique. At present, these procedures represent an alternative to surgery or percutaneous transhepatic biliary drainage (PTBD) for patients with obstructive jaundice when endoscopic biliary drainage (EBD) has failed. However, these procedures should be performed in centers with extensive experience in linear EUS and therapeutic biliary ERCP. Large prospective studies are needed in the near future to establish standardized EUS-BD procedures as well as to perform controlled comparative trials between EUS-BD and PTBD, between rendezvous techniques and direct-access techniques (EUS-CDS and EUS-HGS), and between EBD and EUS-BD.     

Potentially Reversible Resident Factors Associated with Rejection of Care Behaviors

OBJECTIVES: To identify the potentially modifiable resident‐level factors associated with rejection of care in nursing home (NH) residents. DESIGN: Secondary analysis of a 3.0 national field test to revise the Minimum Data Set (MDS). SETTING: Seventy‐one NHs in eight states. PARTICIPANTS: Three thousand two hundred thirty NH residents scheduled for MDS assessments from September 2006 through February 2007. MEASUREMENTS: The potentially mutable characteristics assessed were mood (Patient Health Questionnaire‐9), delirium (Confusion Assessment Method), delusions, hallucinations or illusions, hearing impairment, vision impairment, pain severity, and infection diagnoses. Characteristics considered as covariates were cognition, communication abilities, and impairment in activities of daily living. RESULTS: Of 3,230 residents assessed, 312 (9.7%) had demonstrated rejection of care in the preceding 5 days. In multiple regression analysis adjusted for covariates, rejection of care was associated with delusions (odds ratio (OR)=3.9; 95% confidence interval (CI)=2.5–6.0), delirium (OR=1.8, 95% CI=1.3–2.4), minor (OR=2.1, 95% CI=1.5–2.8) and major (OR=2.3, 95% CI=1.5–3.4) depression, and severe to horrible pain (OR=1.6, 95% CI=1.1–2.3). Infection diagnoses were not significant in bivariate analysis. Hallucinations or illusions, mild to moderate pain, and hearing and vision impairment were not significant in multiple regression analysis. CONCLUSION: In this population, delirium, delusions, depression, and severe pain were associated with rejection of care, suggesting that some care rejection behaviors may resolve with appropriate interventions for the identified target conditions if the associations observed are causal.     

Role of ghrelin in streptozotocin-induced diabetic hyperphagia

Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from the rat stomach. We have previously reported that central administration of ghrelin increases food intake and body weight. To investigate the role of ghrelin in the hyperphagic response to uncontrolled diabetes, adult male rats were studied 14 days after administration of streptozotocin (STZ) or vehicle. STZ-treated diabetic rats were markedly hyperphagic. This hyperphagia was accompanied by hyperglycemia, hypoinsulinemia, and reduced plasma GH levels. Treatment of diabetic rats with insulin reversed these changes. Plasma ghrelin concentrations in untreated diabetic rats were significantly higher than in control rats and were normalized by insulin treatment. The ghrelin gene expression in the stomach was also higher in STZ diabetic rats than in control rats, but this difference was not significant. In contrast, plasma leptin was markedly reduced in STZ diabetic rats. This reduction in plasma leptin levels was reversed by insulin treatment. In addition, hypothalamic NPY mRNA levels were increased in STZ-treated diabetic rats and were reversed by insulin treatment. Furthermore, the hyperphagia was partially reversed by the administration of a ghrelin-receptor antagonist. Therefore, we conclude that the elevated plasma ghrelin levels, along with decreased plasma leptin levels, could contribute to the diabetic hyperphagia in part by increasing hypothalamic NPY. This is the first report to show the pathophysiological significance of ghrelin in diabetes.     

Human chorionic gonadotropin (HCG) activates monocytes to produce interleukin-8 via a different pathway from luteinizing hormone/HCG receptor system

To investigate immune-endocrine interactions between the embryo and the mother early in pregnancy, we examined the effects of human chorionic gonadotropin (HCG) on IL-8 production by peripheral blood mononuclear cells (PBMC). Recombinant HCG promoted IL-8 secretion by PBMC derived from nonpregnant women. The induction of IL-8 mRNA expression was observed after 30 min of HCG stimulation. Adsorption of the HCG with anti-HCG antibodies confirmed the specificity of this effect. The translocation of nuclear factor kappaB into the nucleus and subsequent IL-8 production were observed mainly in monocytes, and IL-8 production was reduced when a proteasome inhibitor was added to inactivate nuclear factor kappaB. Although fluorescein isothiocyanate-labeled HCG was bound to the majority of monocytes, cell surface expression of HCG receptor was hardly detected. IL-8 production by HCG was not affected by inhibitors of protein kinases A and C. In contrast, this stimulation was attenuated by D-mannose, which inhibits binding to C-type lectins. The basal IL-8 production by PBMC from women early in pregnancy was significantly elevated, compared with that from nonpregnant women. This study showed that human monocytes respond to HCG and secrete IL-8 through a pathway different from the HCG receptor system, suggesting that this glycoprotein hormone can react with not only endocrine cells but also immune cells early in pregnancy, probably via primitive systems such as C-type lectins.     

Characterization of morphological and cytoskeletal changes in trophoblast cells induced by insulin-like growth factor-I

IGF-I and IGF-II were appeared to play major roles in the adhesive and migratory events that are considered to be crucial in the implantation process. The purpose of this study was to determine the effects of IGF-I on trophoblast adhesion to extracellular matrix. Trophoblast cells obtained from early gestation at artificial abortion were incubated with the indicated doses of IGF-I at the indicated times. Trophoblast cells were treated with IGF-I in the presence or absence of RGD peptide and an antibody against alpha-subunit of IGF-I receptor (alphaIR3). Morphometric and morphological changes were studied using light and electron microscopy. Furthermore, vinculin, actin stress fibers, phosphorylated focal adhesion kinase (FAK), phosphotyrosine, and paxillin were immunolocalized in trophoblast cells after IGF-I treatment in the presence or absence of alphaIR3. Immunoprecipitation and anti-phosphotyrosine immunoblotting were carried out to detect the phosphorylated FAK and phosphorylated paxillin contents of the IGF-I-treated and untreated trophoblast cells. The results showed that IGF-I promoted trophoblast adhesion to fibronectin substrate in a time- and dose-dependent manner, and addition of RGD peptide and alphaIR3 monoclonal antibody abolished the effects of IGF-I in these cells. Morphological studies exhibited an increase in the lamellipodia formation upon IGF-I treatment, and confocal images of immunofluorescent staining revealed localization of phosphorylated FAK, paxillin, and vinculin at focal adhesions as well as redistribution of actin microfilaments and formation of actin stress fibers inside the cell. Western blotting, using antiphosphotyrosine demonstrated proteins with molecular masses of 125 kDa (FAK) and 68 kDa (paxillin) present in the IGF-I-treated cells, which were lacking in the control groups. In conclusion, these findings suggest that IGF-I can stimulate lamellipodia formation and promote adhesion of trophoblast cells to extracellular matrix by activating their adhesion molecules that must be activated within the implantation window.     

Small guanosine triphospatase RhoA and Rho-associated kinase as regulators of trophoblast migration

The small guanosine triphosphatase Rho controls cell adhesion and motility through reorganization of the actin cyto-skeleton and regulation of actomyosin contractility. Among the putative target molecules of Rho, a Rho-associated coiled coil-forming protein kinase (ROCK) is thought to participate in Rho-mediated cell adhesion and motility. In the present study, we explored the expression and function of RhoA and ROCK in human trophoblast cells. The colocalization of RhoA, cytokeratin 8/18, and cytokeratin 7 in some cells located in the decidual stromal region indicated that extravillous trophoblast cells expressed RhoA. In double staining for RhoA and ROCK in human chorionic villi, RhoA staining was strongly positive in the cytoplasm of cytotrophoblasts, whereas ROCK stained in the cytoplasm of cytotrophoblasts and syncytiotrophoblasts. Both RhoA and ROCK were stained in cytoplasma of cultured human cytotrophoblast. Cultured human trophoblast cells contained actin stress fibers that were lost after treatment with C3, an exoenzyme produced by Clostridium botulinum. Y-27632, a selective ROCK inhibitor, suppressed RhoA-induced formation of actin stress fibers and formation of focal contact in trophoblast cells. The trophoblast reacquired actin stress fibers and focal contact after withdrawal of Y-27632. Cultured human cytotrophoblast cells from 7-9 wk of gestation migrated into a fibronectin-coated membrane. Both C3 exoenzyme and Y-27632 inhibited cytotrophoblast migration in a dose-dependent manner. In conclusion, cyto-trophoblasts express RhoA and ROCK in their cytoplasm, and RhoA-ROCK is involved in their assembly of actin stress fibers. Suppression of RhoA-ROCK reduces trophoblast migration. These findings suggest that RhoA-ROCK signaling is a key regulator of trophoblast cell migration.     

Secretory granules are recaptured largely intact after stimulated exocytosis in cultured endocrine cells

Classical cell biology teaches that exocytosis causes the membrane of exocytic vesicles to disperse into the cell surface and that a cell must later retrieve by molecular sorting whatever membrane components it wishes to keep inside. We have tested whether this view applies to secretory granules in intact PC-12 cells. Three granule proteins were labeled with fluorescent proteins in different colors, and two-color evanescent-field microscopy was used to view single granules during and after exocytosis. Whereas neuro-peptide Y was lost from granules in seconds, tissue plasminogen activator (tPA) and the membrane protein phogrin remained at the granule site for over 1 min, thus providing markers for postexocytic granules. When tPA was imaged simultaneously with cyan fluorescent protein (CFP) as a cytosolic marker, the volume occupied by the granule appeared as a dark spot where it excluded CFP. The spot remained even after tPA reported exocytosis, indicating that granules failed to flatten into the cell surface. Phogrin was labeled with GFP at its luminal end and used to sense the pH in granules. When exocytosis caused the acidic granule interior to neutralize, GFP-phogrin at first brightened and later dimmed again as the interior separated from the extracellular space and reacidified. Reacidification and dimming could be reversed by application of NH(4)Cl. We conclude that most granules reseal in <10 s after releasing cargo, and that these empty or partially empty granules are recaptured otherwise intact.