Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability

The colorectum and uterine endometrium are the two most commonly affected organs in hereditary nonpolyposis colon cancer (HNPCC), but the genetic basis of organ selection is poorly understood. As tumorigenesis in HNPCC is driven by deficient DNA mismatch repair (MMR), we compared its typical consequence, instability at microsatellite sequences, in colorectal and endometrial cancers from patients with identical predisposing mutations in the MMR genes MLH1 or MSH2. Analysis of non-coding (BAT25, BAT26, and BAT40) and coding mononucleotide repeats (MSH6, MSH3, MLH3, BAX, IGF2R, TGF beta RII, and PTEN), as well as MLH1- and MSH2-linked dinucleotide repeats (D3S1611 and CA7) revealed significant differences, both quantitative and qualitative, between the two tumor types. Whereas colorectal cancers displayed a predominant pattern consisting of instability at the BAT loci (in 89% of tumors), TGF beta RII (73%), dinucleotide repeats (70%), MSH3 (43%), and BAX (30%), no such single pattern was discernible in endometrial cancers. Instead, the pattern was more heterogeneous and involved a lower proportion of unstable markers per tumor (mean 0.27 for endometrial cancers versus 0.45 for colorectal cancers, P < 0.001) and shorter allelic shifts for BAT markers (average 5.1 bp for unstable endometrial cancers versus 9.3 bp for colorectal cancers, P < 0.001). Among the individual putative "target" loci, PTEN instability was associated with endometrial cancers and TGF beta RII instability with colon cancers. The different instability profiles in endometrial and colorectal cancers despite identical genetic predisposition underlines organ-specific differences that may be important determinants of the HNPCC tumor spectrum.     

Effect of Different Respirator Adjustments on Central Haemodynamics in Open-Heart Surgery Patients

Changes in cardiac index (CI) mean pulmonary artery pressure (PAP), mean pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and pulmonary artery vascular resistance (PVR), associated with spontaneous respiration (SR) and two different types of intermittent positive pressure ventilation (IPPPV and IPNPV) were studied in a total of 17 patients undergoing aortic valve replacement or myocardial revascularization. Swan-Ganz thermodilution pulmonary artery cardiac output catheters were used and the aim was to determine: whether postoperative cardiac output may paradoxically be greater during IPPPV than during IPNPV or SR; whether the use of "negative" pressure in the expiratory phase during controlled ventilation may be responsible for bringing about the central haemodynamic conditions prevailing during spontaneous respiration; and whether, in weaning from postoperative IPPPV to SR, there is a risk of pulmonary congestion as a consequence of possible autotransfusion. IPPPV connected with anaesthesia induction caused a highly significant deterioration central haemodynamics. The use of positive end-expiratory pressure (PEEP) is not to be recommended for such patients at this stage. On the first postoperative day, the mean CI was lower during IPPPV than during IPNPV (P less than 0.1) or during SR (P less than 0.05). The changes observed in CI, were, however, so slight that the authors consider the routine use of PEEP to be beneficial during controlled ventilation following major open-heart surgery. In some patients, the CI was paradoxically higher during IPPPV than during IPNPV or SR. The mean CI was nearly the same during IPNPV (3.32) as during SR (3.38). However, PAP, PCWP and PVR values were significantly higher during SR than during IPNPV. Thus, according to this study, the use of "negative" end-expiratory pressure during controlled ventilation did not in these patients produce central pressure conditions corresponding to spontaneous respiration. The present study supports the finding that in weaning from controlled ventilation with PEEP to SR there is a danger of pulmonary congestion. This could be predicted by measurement of pulmonary wedge pressure, but not by measurement of central venous pressure.     

Dental primer and adhesive containing a new antibacterial quaternary ammonium monomer dimethylaminododecyl methacrylate

ObjectivesThe main reason for restoration failure is secondary caries caused by biofilm acids. Replacing the failed restorations accounts for 50–70% of all operative work. The objectives of this study were to incorporate a new quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) and nanoparticles of silver (NAg) into a primer and an adhesive, and to investigate their effects on antibacterial and dentin bonding properties.MethodsScotchbond Multi-Purpose (SBMP) served as control. DMADDM was synthesized and incorporated with NAg into primer/adhesive. A dental plaque microcosm biofilm model with human saliva was used to investigate metabolic activity, colony-forming units (CFU), and lactic acid. Dentin shear bond strengths were measured.ResultsMinimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the new DMADDM were orders of magnitude lower than those of a previous quaternary ammonium dimethacrylate (QADM). Uncured primer with DMADDM had much larger inhibition zones than QADM (p < 0.05). Cured primer/adhesive with DMADDM-NAg greatly reduced biofilm metabolic activity (p < 0.05). Combining DMADDM with NAg in primer/adhesive resulted in less CFU than DMADDM alone (p < 0.05). Lactic acid production by biofilms was reduced by 20-fold via DMADDM-NAg, compared to control. Incorporation of DMADDM and NAg into primer/adhesive did not adversely affect dentin bond strength.ConclusionsA new antibacterial monomer DMADDM was synthesized and incorporated into primer/adhesive for the first time. The bonding agents are promising to combat residual bacteria in tooth cavity and invading bacteria at tooth-restoration margins to inhibit caries. DMADDM and NAg are promising for use into a wide range of dental adhesive systems and restoratives.     

Viewing oneself as a capable person – experiences of professionals working with older Finnish immigrants

The proportion of older immigrants in the population is expected to increase in Sweden. Research indicates that older immigrants face the double burden of frailty, caused by a weaker health status, and the immigration process. Health promotion interventions can be used to prevent frailty and support healthy ageing in this population. Healthcare professionals are a crucial part of health promotion and the present study aimed to explore healthcare professionals’ experiences of health in context of daily life among older immigrants to and provide a basis for the development of a health promotion intervention targeted at older immigrants. Four focus group discussions were conducted with professionals who worked with home‐dwelling older people from Finland, currently living in Sweden. Participants represented a variety of healthcare professions. Data were analysed using qualitative content analysis. The healthcare professionals perceived that health in daily life was (i) connected to the view of oneself as a capable person and (ii) participants strove to maintain their own origin. The findings highlighted that when planning for health promotion interventions for older immigrants, the point of departure should be to recognise the person as a person and the background of immigration is not the first issue to address. Therefore, a person‐centred health promotion intervention is recommended to open a dialogue between healthcare professionals and older immigrants, so that a common view of the intervention can be reached.     

Spontaneous rupture of a hepatic cystadenoma and cystadenocarcinoma: report of two cases

Hepatobiliary cystadenomas and cystadenocarcinomas are rare tumors. Differentiating between these tumors and benign hepatic cysts may be difficult. Because of their rarity, diagnosis is often delayed and may result in inaccurate treatment, resulting in unnecessary morbidity and mortality. The purpose of this report is to draw attention to these entities and their complications. We report on two cases with spontaneous rupture of hepatobiliary cystadenoma and cystadenocarcinoma cysts, initially treated as simple hepatic cysts by aspiration, or by aspiration combined with sclerotherapy. The spontaneous rupture of the cysts appeared years after the initial treatment of the cysts, leading in one case to a prolonged stay in an intensive care unit. In both cases, a formal liver resection was carried out and microscopic investigations revealed a mucinous cystadenocarcinoma and cystadenoma. In conclusion, although hepatobiliary cystadenomas and cystadenocarcinomas are rare findings, they should not be forgotten in the diagnostic workshop when examining patients with hepatic cysts. If hepatobiliary cystadenomas and cystadenocarcinomas cannot be excluded following radiological imaging, surgery is recommended.     

Expression of vascular endothelial growth factor in human adrenals

Angiogenesis is an important component in many biological processes and also in pathologic conditions including neoplastic diseases. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific growth factor, which is induced by tissue hypoxia and is angiogenic in vivo. Adrenal gland is a well-vascularized organ, and the roles of VEGF in normal adrenal and in adrenal tumorigenesis is not well characterized. We therefore investigated VEGF mRNA expression in normal human adrenals and in cultured adrenocortical cells. VEGF mRNA was constantly expressed in normal adrenals as well as in cultured adrenocortical cells. The mRNA levels were increased after 24h stimulation with either ACTH or cAMP. The effect of cAMP was dose-dependent. This suggests that ACTH-induced VEGF mRNA expression is mediated via protein kinase A dependent pathway.     

Recurrent Acute-Onset Cushing’s Syndrome 6 Years after Removal of a Thymic Neuroendocrine Carcinoma: From Ectopic ACTH to CRH

We describe a rare case of ectopic Cushing’s syndrome that recurred 6 years after resection of a thymic neuroendocrine carcinoma. We discuss reasons for the differing clinical presentations, management, hormone profiles, as well as immunopathology. A 41-year-old male developed acute-onset Cushing’s syndrome. Clinical presentation and laboratory results were compatible with ectopic adrenocorticotropin hormone (ACTH) production. Computerized tomography (CT) showed a 3.6 cm thymic tumor which was successfully resected. Plasma ACTH (P-ACTH) normalized the first postoperative day. Histopathology demonstrated a well-differentiated neuroendocrine carcinoma with diffuse positivity for ACTH and focal corticotropin-releasing hormone (CRH) reactivity in a few scattered cells. The patient was in remission for 6 years. He then again presented with acute-onset Cushing’s syndrome. Fluorine-labeled dihydroxyphenylalanine (¹⁸F-DOPA) PET/CT showed local uptake in the mediastinum and he underwent repeat resection. However, P-ACTH remained increased (613 ng/l) and 24-h urinary cortisol was 36,720 nmol, suggesting incomplete tumor removal or metastatic spread. Metyrapone treatment was initiated but then withdrawn because the patient spontaneously recovered and cortisol metabolism gradually normalized within 3 weeks. Histopathology demonstrated a recurrent neuroendocrine carcinoma with the same features as the previous lesion but this time CRH was strongly positive in more numerous cells. Normalization of P-ACTH after primary surgery was compatible with ectopic ACTH production. However, the delayed fall in P-ACTH and serum cortisol is compatible with ectopic CRH production and stimulation of pituitary ACTH secretion, which gradually resolved. Although ectopic CRH production is very rare, the unusual dynamics illustrated here should raise the possibility of CRH production by a neuroendocrine tumor.     

Comparison of indirect diagnostic methods for hypolactasia

The aim of this study was to continue our previously published work and to compare the different indirect diagnostic methods for hypolactasia with the lactase to sucrase ratio obtained by jejunal biopsy. The following tests were performed in 63 adult patients: the breath hydrogen test, the lactose tolerance test with ethanol (serum galactose measurement after oral lactose load with ethanol), the urinary lactose tolerance test (urinary galactose measurement after oral lactose load with ethanol), and the strip test (like the former but using a special test strip for urinary galactose). Specificities of all these tests were good (96-98%). The 3-h breath hydrogen test was less sensitive (69%) than the other methods (81-94%). The strip test is recommended for the general practitioner for the diagnosis of this common cause of abdominal complaints.     

Value of posttransplant protocol biopsies in 2 biliary autoimmune liver diseases: A step toward personalized immunosuppressive treatment

The value of protocol liver graft biopsies with good liver function was evaluated in patients with primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC).A total of 250 protocol liver biopsy reports from 182 PSC and PBC patients were compared. Overall histopathological findings and those leading to changes in immunosuppression therapy were retrospectively analyzed.The mean time to first protocol biopsy after transplantation was 5.5 (±4.5) years for PSC patients and 9.3 (±6.6) years for PBC patients. More than 1 abnormal histopathological parameter was found in 43% and 62% of PSC and PBC patients, respectively. However, the histology was interpreted as normal by the pathologist in 78% of PSC and 60% of PBC patients. Immunosuppression therapy was reduced in 10% and increased in 6% patients due to protocol biopsy findings. Biopsies leading to increased immunosuppression therapy had more portal (P = .004), endothelial (P = .008), interphase (P = .021), and lobular (P = .000) inflammation.Mild histopathological findings were frequently found in the protocol biopsies despite the normal biochemistry. PBC patients had more histological abnormalities than those transplanted due to PSC; however, PBC patients had longer follow-up times. Immunosuppression therapy could be safely increased or decreased according to protocol biopsy findings after multidisciplinary meeting discussions.