Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass

BACKGROUND: It has been suggested that cyclic adenosine monophosphate-elevating agents suppress cytokine production. To evaluate the effects of milrinone, a phosphodiesterase III inhibitor, on cytokine production after cardiopulmonary bypass, we conducted a prospective randomized study. METHODS: Twenty-four patients undergoing coronary artery bypass grafting were randomized to receive either milrinone treatment (milrinone, n = 12) or no milrinone treatment (control, n = 12). Administration of milrinone (0.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and was continued for 24 hours. Blood samples for determination of plasma cyclic adenosine monophosphate, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 levels were collected perioperatively. RESULTS: No significant differences were observed in tumor necrosis factor-alpha and interleukin-8 levels between the groups. Interleukin-1beta and interleukin-6 levels after cardiopulmonary bypass were significantly (p < 0.05) lower in the milrinone group than in the control group. Plasma levels of cyclic adenosine monophosphate increased significantly (p < 0.05) after the administration of milrinone and the levels correlated inversely (r = -0.55, p < 0.01) with interleukin-6 levels. CONCLUSIONS: The results indicate that milrinone suppresses cytokine production by elevating cyclic adenosine monophosphate levels in patients undergoing cardiopulmonary bypass. With its positive inotropic and vasodilator activities, milrinone may have antiinflammatory effects.     

Preoperative serum carbohydrate antigen 19-9 levels predict early recurrence after the resection of early-stage pancreatic ductal adenocarcinoma

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is a serious disease with a poor prognosis. Only a minority of patients undergo surgery due to the advanced stage of the disease, and patients with early-stage disease, who are expected to have a better prognosis, often experience recurrence. Thus, it is important to identify the risk factors for early recurrence and to develop an adequate treatment plan.AIMTo evaluate the predictive factors associated with the early recurrence of early-stage PDAC.METHODSThis study enrolled 407 patients with stage I PDAC undergoing upfront surgical resection between January 2000 and April 2016. Early recurrence was defined as a diagnosis of recurrence within 6 mo of surgery. The optimal cutoff values were determined by receiver operating characteristic (ROC) analyses. Univariate and multivariate analyses were performed to identify the risk factors for early recurrence.RESULTSOf the 407 patients, 98 patients (24.1%) experienced early disease recurrence: 26 (26.5%) local and 72 (73.5%) distant sites. In total, 253 (62.2%) patients received adjuvant chemotherapy. On ROC curve analysis, the optimal cutoff values for early recurrence were 70 U/mL and 2.85 cm for carbohydrate antigen 19-9 (CA 19-9) levels and tumor size, respectively. Of the 181 patients with CA 19-9 level > 70 U/mL, 59 (32.6%) had early recurrence, compared to 39 (17.4%) of 226 patients with CA 19-9 level ≤ 70 U/mL (P < 0.001). Multivariate analysis revealed that CA 19-9 level > 70 U/mL (P = 0.006), tumor size > 2.85 cm (P = 0.004), poor differentiation (P = 0.008), and non-adjuvant chemotherapy (P = 0.025) were significant risk factors for early recurrence in early-stage PDAC.CONCLUSIONElevated CA 19-9 level (cutoff value > 70 U/mL) can be a reliable predictive factor for early recurrence in early-stage PDAC. As adjuvant chemotherapy can prevent early recurrence, it should be recommended for patients susceptible to early recurrence.     

Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome?

AIM: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age. It is associated with hyperinsulinemia and insulin resistance which is further aggravated during pregnancy. This mechanism has a pivotal role in the development of various complications during pregnancy. In the past few years, metformin, an insulin sensitizer, has been extensively evaluated for induction of ovulation. Its therapeutic use during pregnancy is, however, a recent strategy and is a debatable issue. At present, evidence is inadequate to support the long-term use of insulin-sensitizing agents during pregnancy. It is a challenge for both clinicians and researchers to provide good evidence of the safety of metformin for long-term use and during pregnancy. This study aimed to evaluate pregnancy outcomes in women with PCOS who conceived while on metformin treatment, and continued the medication for a variable length of time during pregnancy. METHODS: This case-control study was conducted from January 2005 to December 2006 at the antenatal clinics of the Department of Obstetrics and Gynecology, Aga Khan University, Karachi, Pakistan. The sample included 137 infertile women with PCOS; of these, 105 conceived while taking metformin (cases), while 32 conceived spontaneously without metformin (controls). Outcomes were measured in three groups of cases which were formed according to the duration of use of metformin during pregnancy. Comparison was made between these groups and women with PCOS who conceived spontaneously. RESULTS: All 137 women in this study had a confirmed diagnosis of PCOS (Rotterdam criteria). These women were followed up during their course of pregnancy; data forms were completed once they had delivered. Cases were divided into three groups: group A, 40 women who stopped metformin between 4-16 weeks of pregnancy; group B, 20 women who received metformin up until 32 weeks of gestation; and group C; 45 women who continued metformin throughout pregnancy. All the groups were matched by age, height and weight. Comparison was in terms of early and late pregnancy complications, intrauterine growth restriction and live birth rates. In groups A, B and C the rate of pregnancy-induced hypertension/pre-eclampsia was 43.7%, 33% and 13.9% respectively (P<0.020). Rates of gestational diabetes requiring insulin treatment in groups A and B were 18.7% and 33.3% compared to 2.5% in group C (P<0.004). The rate of intrauterine growth restriction was significantly low in group C: 2.5% compared to 19.2% and 16.6% in groups A and B respectively (P<0.046). Frequency of preterm labor and live birth rate was significantly better in group C compared to groups A and B. Overall rate of miscarriages was 7.8%. Controls were comparable to group A in terms of early and late pregnancy complications. CONCLUSION: In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction. No congenital anomaly, intrauterine death or stillbirth was reported in this study.     

氟-羟基磷灰石对骨肉瘤MG63细胞生物学性能的影响

目的 评价氟取代比例为20％的氟-羟基磷灰石(fluor-hydroxyapatite,FHA)对骨肉瘤MG63细胞增殖和成骨分化的影响,以期为FHA的临床应用提供依据.方法 采用化学沉淀法合成FHA,扫描电镜、X射线衍射仪、傅里叶红外光谱仪观察结构并表征.设置FHA组(培养基中加入FHA)、羟基磷灰石(hydroxyapatite,HA)组(培养基中加入HA)和空白对照组(单纯培养基),每组样本量为3,共培养骨肉瘤MG63细胞.甲基噻唑基四唑法检测3组细胞增殖能力,检测3组细胞碱性磷酸酶(alkaline phosphatese,ALP)活性.反转录PCR检测3组细胞成骨分化相关基因(Ⅰ型胶原、ALP、骨钙素和核心结合因子)mRNA表达情况.结果 FHA的X射线衍射图谱主晶相与HA标准图谱一致.培养3d后FHA组细胞增殖(A值为1.87±0.06)显著高于空白对照组(1.25±0.02)(P＜0.05),FHA组与HA组(1.84±0.03)差异无统计学意义(P＞0.05).培养3d后FHA组ALP活性(4.62±0.09)显著高于空白对照组(1.92±0.05)(P＜0.05).与空白对照组相比,FHA上调细胞Ⅰ型胶原、ALP、骨钙素mRNA表达,下调核心结合因子mRNA表达.结论 FHA对MG63细胞增殖和成骨分化相关基因mRNA的表达有促进作用,具有良好的生物相容性.     

Caregiver report of prevalence and appearance order of linguistic symptoms in Alzheimer's patients

We interviewed primary caregivers of 99 Alzheimer's disease patients about the existence and appearance order of linguistic symptoms in a longitudinal study of disease effects on communication. The most prevalent linguistic symptom was difficulty finding the correct word and the least prevalent was increased talkativeness. The prevalence of linguistic symptoms was strongly correlated with order of symptom appearance, with difficulty writing a meaningful letter appearing first and word finding difficulty appearing second. Based on caregiver perceptions, symptom prevalence and order of appearance are specified and discussed in relation to onset of nonlinguistic memory deficit, dementia severity, and performance on a linguistic communication test battery.     

ATS prosthetic valve motion: an in vitro analysis

BACKGROUND AND AIM OF THE STUDY: We have reported clinical findings that normally functioning open pivot ATS valves did not open completely. In order to analyze features of the ATS valve motion more precisely, in vitro tests were conducted. METHODS: Opening angles and pressure gradients of the ATS valve were measured and compared with those of the St. Jude Medical (SJM) valve under steady flow, but with various outlet configurations. Second, opening angles of the two valves were measured under pulsatile conditions in two different outflow configurations: (i) a 'straight outlet' where the leaflets did not extend into the tapering outflow chamber, and (ii) an 'abrupt enlargement outlet' where the leaflets extended directly into the enlarged outflow space. Third, flow visualization studies were made under steady flow conditions in the straight and abrupt enlargement outlet conduits, respectively. RESULTS: Under steady flow conditions, opening of the ATS valve was restricted in most outflow configurations; only when the outlet angle was 0 degrees did the valve open fully. The SJM valve opened completely in all downstream configurations. Despite restricted opening in the ATS valve, the pressure gradient was similar in both valves. Under pulsatile conditions, both valves opened fully in the straight outlet; however, in the abrupt enlargement outlet the ATS valve opened incompletely and the SJM valve completely. Substantial turbulent flow was observed at the outside of the leaflet and corners of the conduit, notably with the ATS valve. CONCLUSION: This study showed that the ATS valve did not open fully except when the outflow was straight, and the leaflet did not extend into an enlarged downstream chamber. Structural features of the ATS, such as its axis being located close to the straight edge and its leaflets extending further downstream from the ring orifice, may cause this unique valve behavior.     

Surgical repair of genital fistulae

OBJECTIVE: Genital fistula is one of the serious childbirth injuries that can occur among women in the developing countries. Complex fistulae still represent a challenging management problem. We report our experience of managing genital fistulae at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. METHODS: Eighty-seven women with genital fistulae were managed between January 1988 and December 2002. Sixty-eight cases were urogenital and 19 were rectovaginal fistulae. Three women had concomitant urogenital and rectovaginal fistulae. The position of patients for surgery and the route of repair were individualized according to the appropriate access to the fistulae. RESULTS: Of the 68 cases of urogenital fistulae, 54 were successfully repaired at first attempt. Three patients were cured at second repair. A success rate of 83.8% was achieved. Four patient with ureterosigmoid anastomosis and seven patients who were lost to follow-up, were considered as failures. All of the 19 rectovaginal fistulae (100%) closed after single repair. CONCLUSION: With an experienced uro-gynecologic team using conventional approach and meticulous repair, a high percentage of patients with genital fistulae can be rendered dry and continent.