硫酸多糖对体外人脐静脉内皮细胞损伤的保护作用

研究表明,硫酸多糖体外对多聚阳离子和氧自由基损伤的人脐静脉内皮细胞有保护作用。肝素、硫酸软骨素A抗多聚阳离子损伤作用比同浓度低分子肝素和甘糖酯强。肝素、硫酸软骨素A、甘糖酯抗氧自由基损伤作用优于同浓度低分子肝素。结果显示硫酸多糖有保护血管内皮的作用,其作用可能与所带阴离子基团有关。     

105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Does the addition of recombinant LH in WHO group II anovulatory women over-responding to FSH treatment reduce the number of developing follicles? A dose-finding study

BACKGROUND: In anovulatory women undergoing ovulation induction, addition of recombinant human LH (rLH) to FSH treatment may promote the dominance of a leading follicle when administered in the late follicular phase. The objective of this study was to find the optimal dose of rLH that can maintain the growth of a dominant follicle, whilst causing atresia of secondary follicles. METHODS: Women with infertility due to anovulation and over-responding to FSH treatment were randomized to receive, in addition to 37.5 IU recombinant human FSH (rFSH), either placebo or different doses of rLH (6.8, 13.6, 30 or 60 microg) daily for a maximum of 7 days. The primary efficacy endpoint was the proportion of patients who had exactly one follicle > or = 16 mm on hCG day. RESULTS: Among 153 enrolled patients, the five treatment groups were similar in terms of baseline characteristics. The proportion of patients with exactly one follicle > or = 16 mm ranged from 13.3% in the placebo group to 32.1% in the 30 microg rLH group (P = 0.048). The pregnancy rate ranged from 10.3% in the 60 microg group to 28.6% in the 30 microg rLH group. Adverse events were similar between groups. CONCLUSIONS: In patients over-responding to FSH during ovulation induction, doses of up to 30 microg rLH/day appear to increase the proportion of patients developing a single dominant follicle (> or = 16 mm). Our data support the 'LH ceiling' concept whereby addition of rLH is able to control development of the follicular cohort.     

Perioperative Blood Transfusions Are Associated with a Higher Incidence of Thromboembolic Events After TKA: An Analysis of 333,463 TKAs

BackgroundGiven the morbidity, mortality, and financial burden associated with venous thromboembolism (VTE) after TKA, orthopaedic providers continually seek to identify risk factors associated with this devastating complication. The association between perioperative transfusion status and VTE risk has not been thoroughly explored, with previous studies evaluating this relationship being limited in both generalizability and power.Questions/purposesTherefore, we sought to determine whether perioperative transfusions were associated with an increased risk of (1) pulmonary embolism (PE) or (2) deep vein thrombosis (DVT) after primary TKA in a large, multi-institutional sample.MethodsThe American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was implemented for our analysis. The definitions of complications, such as DVT and PE, and risk adjustment validation is monitored by the central ACS NSQIP office to ensure participating hospitals are adhering to the same guidelines to log patients. Additionally, both preoperative and intraoperative/72 hour postoperative transfusion status is included for all patients. Therefore, ACS NSQIP was determined to be the most appropriate database for our analysis. All patients who underwent primary TKA between 2011 and 2018 were identified using Current Procedural Terminology code 27447. Primary TKAs designated as “non-elective” were excluded, thereby providing a cohort composed solely of patients undergoing unilateral primary elective TKA for further analysis. The final analysis included 333,463 patients undergoing TKA (mean age 67 ± 9 years, 62% female). Preoperative transfusions were received by < 0.01% (48 of 333,463) of the patients, while 4% (14,590 of 333,463) received a transfusion within the interim between the start of surgery up to 72 hours postoperatively. All missing values were imputed through multiple imputation by chained equation to avoid variable availability-based selection and the subsequent listwise deletion-associated bias in the estimate of parameters. A multivariable logistic regression analysis was conducted using variables identified in a univariate model to calculate adjusted odds ratios and 95% confidence intervals for risk factors associated with symptomatic DVT and/or PE. For variables that maintained significance in the multivariable model, an additional model without confounders was used to generate fully adjusted ORs and 95% CIs. A propensity score matched comparison between recipients versus nonrecipients (1:1) of transfusion (preoperative and intraoperative/72 hours postoperative) was then conducted to evaluate the independent association between DVT/PE development and patients’ transfusion status. Significance was determined at a p value < 0.05.ResultsAdjusted multivariable regression analysis accounting for patient age, sex, race, BMI, American Society of Anesthesiologists (ASA) class and baseline comorbidities demonstrated the absence of an association between preoperative (OR 1.75 [95% CI 0.24 to 12.7]; p = 0.58) or intraoperative/72 hours postoperative (OR 1.12 [95% CI 0.93 to 1.35]; p = 0.23) transfusions and higher odds of developing PE. Similar findings were demonstrated after propensity score matching. Although multivariable regression demonstrated the absence of an association between preoperative transfusion and the odds of developing DVT within the 30-day postoperative period (OR 1.85 [95% CI 0.43 to 8.05]; p = 0.41), intraoperative/postoperative transfusion was associated with higher odds of DVT development (OR 3.68 [95% CI 1.14 to 1.53]; p < 0.001) relative to transfusion naïve patients. However, this significance was lost after propensity score matching.ConclusionAfter controlling for various potential confounding variables such as ASA Class, age, anesthesia type, and BMI, the receipt of an intra- or postoperative transfusion was found to be associated with an increased risk of DVT. Our findings should encourage orthopaedic providers to strictly adhere to blood management protocols, further tighten transfusion eligibility, and adjust surgical approach and implant type to reduce the incidence of transfusion among patients with other DVT risk factors. Additionally, our findings should encourage a multidisciplinary approach to VTE prophylaxis and prevention, as well as to blood transfusion guideline adherence, among all providers of the care team.Level of EvidenceLevel III, therapeutic study.     

Inclusion complexation of furosemide in cyclodextrins. Part 2: Implication on bioavailability

The effect of inclusion complexation of furosemide in cyclodextrins (CyD) on the bioavailability of the drug was studied on normal human volunteers. The excretion rate of the drug was determined by HPLC for a period of 24 h. post dosing. Several pharmacokinetic parameters were calculated and statistically analyzed. viz., peak excretion rate, peak excretion time, half peak time, elimination rate constant, area under the excretion rate time-curve as well as the total amount of drug excreted. The obtained results show that on administration of furosemide in the form of an inclusion complex in CyDs particularly beta-CyD or its dimethyl derivative may improve its biological performance, taking into consideration that furosemide is characterized by a rapid onset and a short duration of action. Inclusion complexation of furosemide in CyDs leads to a more or less delay in its onset of action, a significant increase in its duration of action as well as significant augmentation in its overall biological availability.     

Headache and family history

In two headache questionnaire surveys we inquired about the occurrence of headache in the mothers, fathers, siblings and children of the respondents. In total, 633 people completed valid questionnaires, 260 in the first survey and 373 in the second. The hypothesis was that familial headache occurrence would be positively associated with headache frequency. In each survey, the regression of headache frequency on the number of parents having headache was highly significant. Neither sex nor the sibling and children variables were significant predictors. In the cross-tabulations of the parental occurrence of headache with headache frequency we saw a clear "break-point" between the "no headache" and the headache frequency categories studied. For the final analyses the dichotomy "headache/no headache" was related in fourfold tables to headache occurrence in the father and the mother separately, and to the number of headache parents. The positive associations were not simply due to the large number of migraine cases since they remained after removing the migraineurs.