Outcomes of Surgical Management of Familial Intrahepatic Cholestasis 1 and Bile Salt Export Protein Deficiencies

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations.Peer reviewe

Clinical and Immunologic Features of Ultra-short Celiac Disease

BACKGROUND & AIMS: The clinical effects of gluten-sensitive enteropathy with villous atrophy limited to the duodenal bulb (D1) have not been delineated in adults with celiac disease. We investigated the sensitivity of D1 biopsy analysis in the detection of celiac disease, the number and sites of biopsies required to detect ultra-short celiac disease (USCD, villous atrophy limited to D1), and the clinical phenotype of USCD. METHODS: We performed a prospective study of 1378 patients (mean age, 50.3 y; 62% female) who underwent endoscopy at a tertiary medical center in the United Kingdom from 2008 through 2014; routine duodenal biopsy specimens were collected from D1 and the second part of the duodenum (D2). Quadrantic D1 biopsy specimens were collected from 171 consecutive patients with a high suspicion of celiac disease (mean age, 46.5 y; 64% female). Clinical data from patients diagnosed with USCD, based on biopsy analysis, were compared with those from patients with conventional celiac disease (CCD) (villous atrophy beyond D1) and individuals without celiac disease (controls). The number of intraepithelial lymphocytes (IELs) and immune phenotypes were compared between D1 vs D2 in patients with celiac disease. RESULTS: Of the 1378 patients assessed, 268 (19.4%) were diagnosed with celiac disease; 9.7% of these patients had villous atrophy confined to D1 (USCD; P < .0001). Collection of a single additional biopsy specimen from any D1 site increased the sensitivity of celiac disease detection by 9.3%–10.8% (P < .0001). Patients with USCD were younger (P ¼ .03), had lower titers of tissue transglutaminase antibody (P ¼ .001), and less frequently presented with diarrhea (P ¼ .001) than patients with CCD. Higher proportions of patients with CCD had ferritin deficiency (P ¼ .007) or folate deficiency (P ¼ .003) than patients with USCD or controls. Patients with celiac disease had a median of 50 IELs/100 enterocytes in D1 and a median of 48 IELs/100 enterocytes (P ¼ .7) in D2. The phenotype of IELs from patients with D1 celiac disease was indistinguishable from those of patients with D2 celiac disease. CONCLUSIONS: Collection of a single additional biopsy specimen from any site in the D1 intestine increases the sensitivity of detection for celiac disease. Patients with USCD may have early stage or limited celiac disease, with a mild clinical phenotype and infrequent nutritional deficiencies

GRB 171010A/SN 2017htp: a GRB-SN at z = 0.33

The number of supernovae known to be connected with long-duration gamma-ray bursts (GRBs) is increasing and the link between these events is no longer exclusively found at low redshift (z ≲ 0.3) but is well established also at larger distances. We present a new case of such a liaison at z = 0.33 between GRB 171010A and SN 2017htp. It is the second closest GRB with an associated supernova of only three events detected by Fermi-LAT. The supernova is one of the few higher redshift cases where spectroscopic observations were possible and shows spectral similarities with the well-studied SN 1998bw, having produced a similar Ni mass (⁠ M Ni =0.33±0.02 M ⊙ MNi=0.33±0.02 M⊙ ⁠) with slightly lower ejected mass (⁠ M ej =4.1±0.7 M ⊙ Mej=4.1±0.7 M⊙ ⁠) and kinetic energy (⁠ E K =8.1±2.5× 10 51 erg EK=8.1±2.5×1051 erg ⁠). The host-galaxy is bigger in size than typical GRB host galaxies, but the analysis of the region hosting the GRB revealed spectral properties typically observed in GRB hosts and showed that the progenitor of this event was located in a very bright H ii region of its face-on host galaxy, at a projected distance of ∼ 10 kpc from its galactic centre. The star-formation rate (SFRGRB ∼ 0.2 M⊙ yr−1) and metallicity (12 + log(O/H) ∼8.15 ± 0.10) of the GRB star-forming region are consistent with those of the host galaxies of previously studied GRB–SN systems

the prevention of chronic diseases through ehealth a practical overview

Disease prevention is an umbrella term embracing individual-based or population-based interventions aimed at preventing the manifestation of diseases (primary prevention), reducing the impact of a disease that has arisen (secondary prevention), or mitigating the impact of an ongoing illness (tertiary prevention). Digital health has the potential to improve prevention of chronic diseases. Its application ranges from effective mHealth weight-loss intervention to prevent or delay the onset of diabetes in overweight adults to the cost-effective intervention on the provision of mental-health care via mobile-based or Internet-based programs to reduce the incidence or the severity of anxiety. The present contribution focuses on the effectiveness of eHealth preventive interventions and on the role of digital health in improving health promotion and disease prevention. We also give a practical overview on how eHealth interventions have been effectively implemented, developed, and delivered for the primary, secondary, and tertiary prevention of chronic diseases

Growth hormone and prolactin are paracrine growth and differentiation factors in the haemopoietic system

The pituitary secretory proteins growth hormone (GH) and prolactin (PRL) do not, as yet, have major roles in haematology or immunology. Recent evidence indicates that these hormones are haemopoietic growth factors and exert immunomodulatory functions at physiological concentrations. Here Robert Hooghe and colleagues discuss the significance of these hormones on different aspects of the immune system. © 1993.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The transcription factor Pit-1/GHF-1 is expressed in hemopoietic and lymphoid tissues

The expression of the Pit-1/GHF-1 transcription factor (hereafter Pit-1), which controls the expression of growth hormone (GH) and prolactin (PRL) in the pituitary gland, has been documented in human and rat hemopoietic and lymphoid tissues and cell lines. Pit-1 mRNA was detected by in situ hybridization in about 1 % of rat bone marrow cells and in the spleen red pulp and marginal zone. Pit-1 was also expressed in human tonsils (mantle zone), in the thymus (rat and human, non-lymphoid cells), in lipopolysaccharide-stimulated rat peritoneal cells and in non-hepatocyte cells in the liver (rat and human). A detailed investigation of the rat spleen showed a very similar distribution for Pit-1, GH and PRL mRNA and Pit-1, GH and PRL proteins (detected by immunocytochemistry). Using polymerase chain reaction followed by Southern hybridization, the expression of Pit-1 could be confirmed in human and rat spleen, bone marrow and thymus. HL60 and RAJI leukemic cells were also positive. The sequence of fragments amplified from rat spleen and from human bone marrow completely matched published sequences of rat and human pituitary Pit-1, respectively. Expression of GH and PRL in lymphoid tissues has been documented. The straightforward hypothesis would therefore be that Pit-1's main function in lymphoid tissues is controlling GH and PRL expression, as in the pituitary gland. GH and PRL may be hemopoietic and lymphoid growth and differentiation factors.SCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

Growth hormone and prolactin are paracrine growth and differentiation factors in the haemopoietic system

The pituitary secretory proteins growth hormone (GH) and prolactin (PRL) do not, as yet, have major roles in haematology or immunology. Recent evidence indicates that these hormones are haemopoietic growth factors and exert immunomodulatory functions at physiological concentrations. Here Robert Hooghe and colleagues discuss the significance of these hormones on different aspects of the immune system.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Pit-1/GHF-1 expression in pituitary adenomas: Further analogy between human adenomas and rat SMtTW tumours

Adenomas can develop from each cell type of the anterior pituitary. In the normal pituitary, three of these cell types, the GH-, prolactin- and TSH-secreting cells, express the transcription factor Pit-1/GHF-1 which is responsible for prolactin and GH (and probably TSH) cell commitment, differentiation, probably proliferation and gene expression. We have analysed the expression of Pit-1/GHF-1 in a panel of human pituitary adenomas. All GH-, prolactin- and TSH-expressing adenomas studied expressed the Pit-1/GHF-1 factor, as demonstrated by in-situ hybridization and immunocytochemistry. The expression was higher in adenomas than in normal human pituitary. In contrast, ACTH- adn LH-FSH-secreting and non-secreting adenomas were negative. Seven transplants of the spontaneous rat prolactinoma SMtTW were also investigated and all were found to be positive. This further stresses the analogy between these tumours and human prolactinomas. Taken together, the data confirm that Pit-1/GHF-1 expression is restricted to GH-, prolactin- and TSH-expressing cells, and the increased expression in adenomas is compatible with a role of Pit-1/GHF-1 in cell proliferation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The relationship between semaphorin 3C and microvessel density in the progression of breast and oral neoplasia

This study aimed to identify the expression of semaphorin 3C (SEMA3C) in the normal-metastatic spectrum of breast and oral cancers, and correlate expression with microvessel density (MVD, CD31), a surrogate marker of angiogenesis. Histological analysis revealed that SEMA3C expression was reduced in the development of oral cancer from normal oral tissue (P. <. 0.0001) and expression was inversely correlated with MVD (r. =. -. 0.394, P. =. 0.05). In contrast, SEMA3C expression increased in the transition from normal to invasive breast disease in epithelial/tumour cells (P. =. 0.001) and endothelial cells (P. =. 0.006), with both correlating weakly with MVD (r. =. 0.35, p. =. 0.03 and r. =. 0.243, p. =. 0.041 respectively). Furthermore, histological analysis of a breast cancer tissue microarray revealed a weak positive correlation with tumour grade (r. =. 0.305, P. =. <. 0.001) and biological phenotype (r. =. 0.237, p. =. 0.004) with tumour cell expression of SEMA3C highest in triple negative and ER. -, PR. -, HER2. + subtypes. These data suggest that SEMA3C expression is differentially regulated in the development and progression of breast versus oral neoplasia, and that increased expression of SEMA3C may be modulating breast cancer progression and angiogenesis, and could represent a biomarker of metastatic disease. © 2015 Elsevier Inc

Receptors for pituitary adenylate cyclase activating peptides in human pituitary adenomas

SCOPUS: ar.jinfo:eu-repo/semantics/publishe