Economic costs of functional dyspepsia

Dyspepsia is defined as chronic or recurrent symptoms believed to originate in the upper gastrointestinal tract. When routine investigation results in no identifiable explanation for those symptoms patients are labelled as having functional dyspepsia. In community-based surveys, approximately 30% of the otherwise apparently healthy population report dyspeptic symptoms and the majority are believed to have functional dyspepsia. Although only 1 in 4 or 5 patients make use of healthcare resources, this patient category is one of the largest in ambulatory care (1.6 to 5% of all consultations in general practice). The annual frequency of consultations for functional dyspepsia in Sweden has been estimated at 47 per 1000 population. In consequence of its high prevalence and associated absenteeism, the total costs of functional dyspepsia are considerable. In Sweden in 1981, the costs were estimated at $US55 000 per 1000 population ($US113 630 in 1991 dollars). The most cost-effective management strategy remains to be defined. Evidence is accumulating that the traditional 'wait-and-see' policy with initial empirical therapeutic trials without investigation may not be the most cost conserving strategy.     

Effect of pregnancy, menopause and hormone substitution therapy on disseminated systemic lupus erythematosus

EXACERBATIONS DURING PREGNANCY: Clinical and experimental data have clearly evidenced the influence of hormones on the course of systemic lupus erythematosus. In prospective studies of pregnant women, an exacerbation is observed in 57% to 60% of the cases. It can be severe in 10% of the cases and occur in the post partum in 7%. For most patients, the exacerbation is moderate and has no unfavorable effect on the outcome of pregnancy. In case of renal involvement, it is difficult to differentiate an intricated HELPP syndrome. MARKERS AND RISK FACTORS: Low complement and elevated anti-DNA levels are distinctive markers. Earlier renal involvement and hypertension are important prognostic factors, particularly when the lupus begins during pregnancy. However, when serum creatinine is lower than 100 mumol/l at pregnancy onset in patients in remission, pregnancy does not alter renal function. An association with antiphospholipid antibodies increases the risk for the fetus and the kidney function. TREATMENT: Optimal treatment remains to be defined. Commonly, patients are given aspirin, heparin in case of a history of thromboembolism, or both. The rate of success currently exceeds 70%. The risk of thromboembolism in the peri or post partum period requires anticoagulant treatment. Outside pregnancy: Ovulation induction raises two risks: triggering a lupus flare-up and thrombosis, particularly for patients with antiphospholipid antibodies. The influence of menopause and hormone replacement therapy remains poorly understood.     

Involvement of the proliferating cell nuclear antigen (PCNA) in DNA repair induced by alkylating agents and oxidative damage in human fibroblasts

The involvement of the proliferating cell nuclear antigen (PCNA) in the process of DNA repair induced by alkylating agents or by oxidative damage was investigated in human quiescent fibroblasts by immunofluorescence and flow cytometry. Transition from soluble to the DNA-bound form of PCNA, was taken as the parameter to determine its involvement in repair DNA synthesis. Treatment with the alkylating agents methylmethane sulfonate and N-methyl-N'-nitro-N-nitrosoguanidine resulted in the rapid and dose-dependent increase in the nuclear binding of PCNA. Similar results were obtained with compounds such as hydrogen peroxide or tert-butyl hydroperoxide, which are known to induce oxidative DNA damage. Tert-butyl hydroperoxide may also generate malondialdehyde through a reaction of lipid peroxidation. This mutagenic and carcinogenic product has been previously shown to form adducts with DNA. Therefore, the possibility that tert-butyl hydroperoxide could induce DNA damage through this pathway was investigated by incubating cells directly in the presence of malondialdehyde. Such treatment resulted in an increase in immunofluorescence associated with nuclear-bound PCNA. The ability of oxidative and alkylating agents to induce the nuclear binding of PCNA was also assessed in proliferating cells. In these conditions, treatment with hydrogen peroxide or methylmethane sulfonate, resulted in an increase in nuclear-bound PCNA in the G1 and in the G2 + M compartments, but not in S phase. At longer times after treatment, PCNA immunostaining was reduced to basal levels, while an increase in nuclear binding of p21(waf1/cip1) protein was found in concomitance with cell-cycle arrest. These results indicate that agents inducing DNA base alterations in vivo, promote the nuclear binding of PCNA. These lines of evidence support the role of a PCNA-dependent reaction in the base excision repair system.      

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.      

宫颈病变液基细胞学筛查与组织病理学对照观察

目的　探讨液基薄层细胞学(ThinPrepCytologyTest, TCT)技术在妇科门诊人群宫颈病变筛查的准确性。方法　回顾性分析10 980例TCT,与组织学对比观察。结果　　TCTLSIL以上阳性率45. 7% ( 373 /817),组织学检查阳性率50. 1% ( 409 /817 ),两者统计学比较无显著性差异(P>0. 05 )。TCT诊断符合率LSIL75. 8% (191 /252),HSIL98. 1% (101 /103),SCC90. 9% (10 /11),AC85. 7% (6 /7)。鳞状上皮内病变诊断符合率HSIL与LSIL统计学比较有显著性差异(P<0. 01)。结论　液基细胞学检查是宫颈癌早期筛查的有效手段,加强制片技术及诊断质量控制对提高诊断的准确性有重要意义。     

Predictors of men's acceptance of modern contraceptive practice: study in rural Vietnam.

Studies have shown family planning adoption is likely to be more effective for women when men are actively involved. The transtheoretical model of behavior change was used to examine men's involvement in general contraception and intrauterine device (IUD) use by their wives. The study was carried out in rural Vietnam with 651 eligible participants. Cons of IUD use for men in precontemplation and contemplation/preparation were significantly higher than those in the action/maintenance stages, whereas the reverse was true for pros of IUD. The self-efficacy for convincing wife to have IUD in precontemplation was significantly lower than for those in higher stages. Women's education and ages, spontaneous recall of modern contraceptive method, cons for IUD, and self-efficacy for contraception and for convincing wives to get IUD inserted (or continue use) were significant predictors of men's readiness to accept IUD. Interventions are targeted to reduce cons and increase self-efficacy for IUD use.     

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2^neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2^neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2^neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2^neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2^neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2^neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2^neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2^neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.