八项肝纤维化血清标志物比较研究

目的比较血清血小板衍生生长因子-BB(PDGF-BB)、转化生长因子-β1(TGF-B1)、基质金属蛋白酶抑制剂-1(TIMP-1)、基质金属蛋白酶-1(MMP-1)、透明质酸(HA)、Ⅲ型前胶原(PC Ⅲ)、Ⅳ型胶原(C Ⅳ)和层黏连蛋白(LN)及外周血单个核细胞(PBMC)内TIMP-1 mRNA、MMP-1 mRNA在肝纤维化中的诊断价值。方法常规肝穿活检、组织病理学诊断；RT-PCR检测PBMCs中MMP-1 mRNA、TIMP-1 mRNA水平；酶标法检测血清PDGF-BB、TGF-β1、TIMP-1和MMP-1含量；放射免疫法检测血清HA、PC Ⅲ、C-Ⅳ和LN含量。结果经ROC曲线分析，血清PDGF-BB、TIMP-1、HA、PC Ⅲ、C-Ⅳ、LN和TIMP-1 mRNA的AUC分别为0．985、0．726、0．318、0．728、0．727、0．583、0．463、0．876；血清PDGF-BB和PBMCs中TIMP-1 mRNA的灵敏度和特异度分别为90％、95％，73．7％、100％；两者联合检测的灵敏度为97．4％，特异度为95．0％。结论八项指标中，血清PDGF-BB的诊断价值最大。在筛选肝纤维化患者时，以血清PDGF-BB、PBMC中TIMP-1 mRNA联合检测最佳。     

Envelope sequence variation and phylogenetic relations of human T cell lymphotropic virus type 1 from endemic areas of Colombia

The HTLV-1 envelope gene of 12 TSP/HAM patients from two endemic areas of southwest Colombia (Tumaco and Buenaventura) was amplified by nested PCR, sequenced, and compared with previously reported HTLV-1 envelope sequences from isolates worldwide. In general, the sequence divergences among all Colombian samples ranged from 0.1 to 1.6%. Some amino acid substitutions, referring to the ATK-1 prototype strain in the surface domain gp46 and in p21, were highly prevalent in southwest Colombia, suggesting a geographical clustering of mutations in the envelope gene. The phylogenetic analysis showed that the Colombian isolates belong to the HTLV-1a lineage with minor subgroups. The genetic distance between Colombian and Japanese isolates ranged from 0.1 to 1.8%; in comparison, the genetic distance between Colombian and Caribbean isolates ranged from 0.4 to 2.2%. Our results strongly suggest that the actual quasispecies populations in southwest Colombia have been generated by separate, differently timed introductions of virus.     

Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization

Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.     

Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.     

Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

Prevalence of cardiac amyloidosis among elderly patients with systolic heart failure or conduction disorders

Objective: Cardiac amyloid infiltration can lead to systolic heart failure (HF) or to conduction disorders (CD). Patients with transthyretin (ATTR) amyloidosis are particularly exposed. We sought to determine the prevalence of ATTR and AL among patients >60?years admitted with CD or unexplained systolic HF and increased wall thickness.

Materials and Methods: We studied 143 patients (57% males, 79?±?9?years) with HF (N?=?28) or CD requiring pacemaker implantation (N?=?115). In total, 139 (97%) patients (28 with HF and 111 with CD) underwent ^99mTc-DPD scintigraphy to detect ATTR, and 105 (73%; 19 HF and 86?CD) underwent AL screening.

Results: Five patients (4%; 95%CI:0–7%) exhibited wild-type ATTR (ATTRwt) amyloidosis, 2 (2%; 95%CI:0–4%) had CD and 3 (11%; 95%CI:0–23%) HF. No patient showed AL. The 2 ATTRwt patients with CD were previously asymptomatic, did not show classical ECG signs and exhibited mild LV hypertrophy with preserved LVEF. By contrast, all ATTRwt patients with HF had ECG and echocardiographic signs of amyloid. During a mean follow-up of 18?±?11?months, 3(60%) patients with ATTRwt amyloidosis (1?CD and 2 HF) and 14(10.4%) without died.

Conclusion: Prevalence of ATTRwt amyloidosis in patients with CD requiring pacemaker is low. Although, additional studies are needed, prevalence seems to be higher in elderly patients with systolic HF.     

Giant retroperitoneal leiomyosarcoma. Multiorgan block removal

INTRODUCTION

Retroperitoneal tumors are rare, mostly malignant. Locally aggressive, and more frequent in women in their 5th decade of life. Its symptoms are nonspecific, including abdominal pain and palpable mass. To diagnosis is helpful computed tomography and biopsy. It needs surgery for absolute healing.

PRESENTATION OF CASE

67 years old man was admitted with back pain and fever. Abdominal imaging tests showed a 15 cm abdominal mass without clear organodependencia. Endoscopy with biopsies evidenced mesenchymal neoplasia of undetermined origin. In surgery we confirm its resecability and was necessary multiorgan resection. Pathologic diagnosis: well differentiated retroperitoneal leiomyosarcoma. Started adjuvant radiotherapy. In subsequent tests showed the presence of liver metastases.

DISCUSSION

Retroperitoneal tumors are developed from nerve, vascular, muscular, connective, supportive and fibroareolar tissue from this space. Its size does not modificate survival or resectability. We used TC and biopsy for its diagnose. Adjuvant therapy does not affect survival or quality of life, surgery remains the only curative option. Locoregional recurrence is the most influential figure in the prognosis. A large percentage of patients required a second surgery (between 45 and 82%).

CONCLUSION

The only curative option of retroperitoneal sarcomas is surgery, which usually requires multiple organ resection. Chemotherapy and radiotherapy are mostly a surgical supplement. Chemotherapy has not shown significant increase in survival.     

Baseline glycated hemoglobin levels are associated with duodenal-jejunal bypass liner-induced weight loss in obese patients

Introduction

Endoscopic treatment with the duodenal-jejunal bypass liner (DJBL) leads to significant weight loss in obese patients. We sought to identify clinical factors associated with weight loss in obese patients treated with the DJBL for 1 year.

Methods

Subjects with morbid obesity were enrolled in a single-arm, open-label, prospective trial and implanted with the DJBL. Patient demographics along with baseline comorbidities, anthropometrics, and biochemical variables were selected for univariate and multivariate analysis.

Results

The DJBL was implanted in 79 subjects and 61 completed 12 months of follow-up. There were 18 early removals. Baseline mean age and body mass index (BMI) were 35.4 ± 9.7 years and 43 ± 5.6 kg/m², respectively. Forty-four (72 %) were women. This population included 22 subjects with type 2 diabetes (T2DM). Twelve months after treatment, patients had a mean excess body weight loss (%EBWL) of 46 ± 18 %. Univariate analysis identified that fasting glycemia (r ² = ?0.303, p < 0.013), insulin-resistance determined by HOMA-IR (r ² = ?0.457, p < 0.019), and glycated hemoglobin (HbA1c) (r ² = ?0.471, p < 0.013) were associated inversely with %EBWL at 1 year. In this cohort of patients, the multivariate analysis indicated that only baseline HbA1c levels were associated inversely with %EBWL after 1 year of treatment (β adjusted coefficient ?0.758, p < 0.016). Importantly, no differences at 1 year in %EBWL were observed between patients with or without T2DM (%EBWL T2D 46.7 ± 20 % vs. non-T2DM 46.8 ± 18.6 %, p = 0.988).

Conclusions

This analysis indicates that higher baseline HbA1c levels are associated independently with diminished body weight loss in obese patients treated with the DJBL independent of their diabetic status. These results show that DJBL induces clinically significant weight loss in both T2DM and non-T2DM patients.