Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.      

The relation between mean platelet volume and coronary collateral vessels in patients with acute coronary syndromes

ObjectiveElevated mean platelet volume (MPV) has been proposed as a risk factor for coronary artery disease (CAD) and is associated with poor clinical outcome in acute coronary syndrome (ACS). We aimed to evaluate the association of MPV with presence of coronary collateral vessel (CCV) in patients with ACS.MethodsA total of 417 patients with ACS were included in the study. All patients underwent coronary angiography on the first day after admission and patients with a greater than or equal to 80% obstruction in at least one epicardial coronary artery were included in the study. The CCVs are graded according to the Rentrop scoring system and a Rentrop grade 0 was accepted as no CCV development (Group 1), Rentrop Grade 1–2–3 were accepted as presence of CCV development (Group 2).ResultsThe median of MPV was 9.1 ± 1.4 fl. Mean age was 60 ± 12 year. Group 1 consisted of 233 (55.9%) patients and Group 2 consisted of 184 (44.1%) patients. Presence of CCV was significantly associated with high levels of MPV (p = 0.005). Presence of CCV was also associated with presence of diabetes and systolic blood pressure.ConclusionHigh MPV on admission was associated with presence of CCV in patients with ACS.     

Impaired aortic elastic properties in patients with chronic graft-versus-host disease

Objectives: Graft‐versus‐host disease (GVHD), which develops as a result of the immunologic response that donor T‐lymphocytes generate against host tissue following hematopoietic stem cell transplantation (HSCT), is the leading cause of morbidity and mortality in these patients. The aim of this study is the investigate relation between aortic wall stiffness and duration of the disease in patients with chronic GVHD. Methods: The study population included 32 patients (18 men; mean age, 36.9 ± 12.5 years, and mean disease duration = 14.7 ± 2.9 months) who received HSCT and was diagnosed with GVHD and 44 patients (23 men; mean age, 35.2 ± 9.6 years, and mean disease duration = 13.5 ± 2.4 months) who did not develop GVHD following HSCT. All patients underwent baseline echocardiography before HSCT and were followed. After approximately 10–14 months following HSCT, these patients were divided into two groups based on whether they had developed chronic GVHD, and were compared to aortic stiffness parameters and cardiac functions. Results: There was no change in basal characteristics, laboratory and echocardiographic findings, and aortic stiffness parameters in both groups before HSCT (P > 0.05). After HSCT, the mean aortic strain and distensibility values of the chronic GVHD patients were significantly lower, compared with the non‐GVHD patients (9.8 ± 3.2% vs. 12.9 ± 5.0%, P = 0.002 and 4.1 ± 1.5 × 10^?6 cm²/dyn vs. 5.3 ± 2.1 × 10^?6 cm²/dyn; P = 0.005, respectively). In addition, aortic stiffness index was increased in the chronic GVHD group compared with non‐GVHD group (2.7 ± 1.7 vs. 2.0 ± 0.8, P = 0.03). Conclusion: Aortic stiffness measurements were significantly different in chronic GVHD group compared to non‐GVHD group and these findings suggested useful explanation for the potential mechanism about the development of disease. (Echocardiography 2011;28:1011‐1018)     

The relationship between Helicobacter pylori IgG titre and coronary atherosclerosis

OBJECTIVES: The role of Helicobacter pylori (HP) in the progression of atherosclerosis is controversial. We investigated the relation between HP IgG antibody titres and severity and intensity of coronary atherosclerosis and also clinical presentation of coronary artery disease (CAD). METHODS: The patient group consisted of 353 patients with angiographically proven CAD, which contains 3 different subgroups: 163 patients with myocardial infarction (MI), 106 patients with unstable angina (USAP) and 84 patients with stable angina (SAP). Control group included 163 subjects with angiographically proven normal coronary arteries. Helicobacter pylori IgG antibody titres were measured by an enzyme immunoassay method in all patients. Gensini and Extent scores were used to evaluate the angiographic severity and extent of atherosclerosis. C-reactive protein levels were measured by Behring nephelometry system kits. RESULTS: Seropositivity rates for HP were similar between groups (82.7% in the patient group and 86.6% in the control group (P > 0.05)). Also HP-IgG levels were similar among the MI, USAP and SAP groups. No significant correlation was observed between CRP levels and HP-LgG level titres. There was no significant correlation between HP-IgG level (r = 0.086, P = 0.2) and Gensini score but a significant poor correlation was observed between HP-IgG level and Extent score (r = + 0.156, P = 0.03). CONCLUSIONS: Helicobacter pylori IgG titres do not play an important role in the presentation of CAD and do not increase systemic inflammatory response. However, Helicobacter pylori IgG antibody titres may be correlated with the extent of CAD.     

Intracervical versus vaginal misoprostol for cervical dilatation prior to operative hysteroscopy—a comparative study

Background

Hysteroscopic surgery requires pre-operative cervical ripening to facilitate adequate dilatation of the cervix for insertion of operative hysteroscope. This study was conducted to compare the efficacy of intracervical misoprostol with vaginal misoprostol in achieving cervical ripening before operative hysteroscopy.

Methods

In this randomised comparative study conducted at a tertiary care teaching hospital, 56 patients needing operative hysteroscopy were divided into two groups of 28 patients, one for intracervical misoprostol and the other for vaginal misoprostol. Four hundred microgram of misoprostol was inserted on the night before and in the morning of operative hysteroscopy intracervically in group I and vaginally in group II.

Results

Primary outcome measure was number of patients achieving 7 mm preoperative dilatation of cervix. Largest Hegar dilator that could be passed into the uterine cavity past the internal optic sheath without resistance was noted in each case. Mean cervical dilatation prior to operative hysteroscopy was calculated. In addition, incidence of slipping of vulsellum and cervical laceration was also noted. Time to achieve full cervical dilatation was recorded. In 23/28 cases of group I and 5/28 in group II, size 7 Hegar dilator could be passed without effort. Mean cervical dilatation was 7.5 mm in group I and 5.7 mm in group II. Slipping of the vulsellum and cervical lacerations were seen in significantly less patients in group I. Mean time to achieve cervical dilatation to 10 mm was 43.39 seconds in group I and 103.96 seconds in group II (P<0.0001).

Conclusion

Intracervical administration of misoprostol is an effective method of achieving cervical ripening for easy cervical dilatation up to 10 mm prior to operative hysteroscopy.     

硬骨凌霄叶对伤口愈合的促进作用(英文)

The aim of the present study was to evaluate the potential wound healing activity of Tecomaria capensis leaves extract (TCLE) using different models in rats. (a) Excision wound model, (b) Incision wound model and (c) Dead space wound model. TCLE (100, 300, 1 000 and 2 000 mg·kg-1) was given to rats to observe acute toxicity. No toxicity was found in animals till 14 days. TCLE 5% and 10% ointment were applied topically in excision wound model and incision wound model. TCLE 200 and 400 mg·kg-1 were given orally in dead space wound model. It improved healing in excision wound model, increased breaking strength of tissue in incision wound model, and increased granuloma breaking strength and hydroxyproline content in dead space wound model. These results showed that TCLE presents significant wound healing activity.     

Polymorphisms in CYP2A13 and UGT1A7 genes and head and neck cancer susceptibility in North Indians

Oral Diseases (2010) 16 , 760–768 Objectives: To examine role of genetic variants of CYP2A13 and UGT1A7 genes, involved in activation and detoxification of tobacco carcinogens, with risk of head and neck cancer as well as to assess the potential modifying role of gene‐gene and gene‐environment interactions. Methods: 203 head and neck cancer patients and 201 healthy controls were genotyped for functional polymorphisms of CYP2A13 and UGT1A7 genes using polymerase chain reaction‐restriction fragment length polymorphism, denaturing high‐performance liquid chromatography and sequencing. Results: We identified two novel polymorphisms T478C and T494C in CYP2A13 gene which were associated with significantly reduced risk of cancer (OR 0.37; 95% CI 0.19–0.71; P < 0.05). A CYP2A13 haplotype carrying variant alleles of T478C/T494C was found to be associated with reduced risk of head and neck cancer (OR 0.42; 95% CI 0.22–0.78; P = 0. 005). Mutant ‘T’ allele of CYP2A13 C578T polymorphism was found to be present in cancer patients only. A sevenfold increased risk of cancer was observed in smokers with UGT1A7 low activity genotypes (OR 7.01; 95% CI 1.02–48.37; P < 0.05). UGT1A7 haplotype carrying C allele (T622C) showed 10‐fold increased risk of cancer (OR 10.12; 95% CI 1.29–79.4; P < 0.05). Conclusion: Interplay between genetic variants of CYP2A13 and UGT1A7 genes and smoking may modulate susceptibility to head and neck cancer.     

High-dose cytosine arabinoside and fractionated total-body irradiation: an improved preparative regimen for bone marrow transplantation of children with acute lymphoblastic leukemia in remission

Twenty children with acute lymphoblastic leukemia in second (18 patients) or third (two patients) complete remission after bone marrow relapse received allogeneic bone marrow transplants from histocompatible sibling donors. The preparative regimen for marrow transplantation consisted of 12 doses of 3,000 mg/m2 cytosine arabinoside twice daily for six days followed by 1,200 cGy total-body irradiation (six doses of 200 cGy twice daily for three days). The preparative regimen was well tolerated, and all patients showed marrow engraftment promptly. Twelve patients are alive in complete remission 12+ to 79+ months posttransplant; eight patients are over 48 months posttransplant. Six patients died 1 to 9 months posttransplant of nonleukemic causes: (two each of graft-v-host disease, interstitial pneumonitis, and infection). Two patients developed recurrent leukemia at 15 and 30 months posttransplant. Both have died at 19 and 36 months posttransplant. Life table analysis reveals an actuarial survival and event-free survival rate of 58% and a marrow relapse rate of 17%. These results suggest that high-dose cytosine arabinoside and fractionated total-body irradiation is a relatively nontoxic and highly effective preparative regimen for allogeneic bone marrow transplantation for acute lymphoblastic leukemia that deserves further evaluation.