Factors associated with provision of depot medroxyprogesterone acetate to adolescents by US health care providers

ObjectiveIdentify factors associated with healthcare providers' frequency of depot medroxyprogesterone acetate (DMPA) provision to adolescents.Study designWe analyzed data from surveys mailed to a nationally representative sample of public-sector providers and office-based physicians (n=1984). We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with frequent DMPA provision to adolescents in the past year.ResultsAlthough most providers (>95%) considered DMPA safe for adolescents, fewer reported frequent provision (89% of public-sector providers; 64% of office-based physicians). Among public-sector providers, factors associated with lower odds of frequent provision included working in settings without Title X funding (aOR 0.44, 95% CI 0.30–0.64), reporting primary care as their primary clinical focus versus reproductive or adolescent health (aOR 0.42, 95% CI 0.28–0.61), and providing fewer patients with family planning services. Among office-based physicians, factors associated with lower odds of frequent provision included specializing in obstetrics/gynecology (aOR 0.50, 95% CI 0.27–0.91) and family medicine (aOR 0.21, 95% CI 0.09–0.47) versus adolescent medicine, completing training ≥15 versus <5 years ago (aOR 0.27, 95% CI 0.09–0.83), and reporting that 0–24% of patients pay with Medicaid or other government healthcare assistance versus ≥50% (aOR 0.23, 95% CI 0.09–0.61). The reason most commonly reported by providers for infrequent DMPA provision was patient preference for another method.ConclusionsWhile most providers reported frequently providing DMPA to adolescents, training on evidence-based recommendations for contraception, focused on subgroups of providers with lower odds of frequent DMPA provision, may increase adolescents' access to contraception.ImplicationsAlthough >95% of providers considered depot medroxyprogesterone (DMPA) a safe contraceptive for adolescents, only 89% of public-sector providers and 64% of office-based physicians reported frequently providing DMPA to adolescents. Provider training on evidence-based recommendations for contraception counseling and provision may increase adolescents' access to DMPA and all methods of contraception.     

Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.     

Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that C_max and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.

The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.

The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.     

A variant of the HL-60 cell line expressing a high level of PTP1C exhibits increased susceptibility to differentiation by phorbol 12-myristate 13-acetate

A variant of the HL-60 cell line, HL-60/MCSFR4D2, has been found to express twice the amount of PTP1C as compared to the parental HL-60 cell line by immunoblotting and immunoprecipitation. Differentiation of the variant cells after phorbol 12-myristate 13-acetate (PMA) treatment was examined by the appearance of adherence. In 1% fetal calf serum (FCS), 20% of HL-60/MCSFR4D2 cells exhibited adherence after treatment with 0.5 ng/ml PMA for 48 h, 60% exhibited adherence after treatment with 1.0 ng/ml PMA and 80% exhibited adherence after treatment with 5.0 ng/ml PMA, while HL-60 cells exhibited only a slight response. Furthermore, antisense PTP1C oligonucleotides decreased the PMA-induced adherence of HL-60/MCSFR4D2 cells. These results suggest that the high-expression of PTP1C in HL-60 cells may be involved in the enhancement of susceptibility to macrophage-like differentiation by PMA.     

新肩三针穴位注射为主治疗肩手综合征的临床研究

目的评价新肩三针穴位注射治疗脑卒中后肩手综合征的临床疗效。方法采用随机对照的方法,将72例符合纳入标准的患者分为治疗组(针刺 新肩三针穴位注射)和对照组(单纯用针刺)。用脑卒中临床神经功能缺损程度评分量表,肩关节疾患治疗成绩判定标准和手掌手指功能评价进行临床疗效评定。结果治疗组疗效明显优于对照组,差异有统计学意义(P<0.05)。结论新肩三针穴位注射是治疗脑卒中后肩手综合征的有效治疗方法。     

Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: Implications for immunoadjuvant potential

Ethnopharmacological relevance

Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations.

Aim of the study

To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals.

Materials and methods

We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside^®) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls.

Results

Treatment with ARE (100 mg/(kg b.w. p.o.)) resulted in significant increase of CD3⁺ and CD4/CD8⁺ percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes.

Conclusion

The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential.     

Loss of heterozygosity alterations associated with progesterone therapy in endometrial hyperplasia and adenocarcinoma

Loss of heterozygosity (LOH) was analyzed in four patients with endometrial hyperplasia (EH) with atypia (two patients) and without atypia (two patients) and in five patients with endometrial adenocarcinoma (EAC) to clarify the clinicopathologic relationship between genetic alterations and hormone therapy. Each patient was initially administered high-dose medroxyprogesterone acetate (MPA) as a uterine-sparing treatment. The five microsatellite markers used to analyze LOH were at chromosomal loci 8p22.1, 8p21, 8p21.3, 8p22, and 8p22. DNA was extracted from paraffin-embedded sections before, during, and after MPA therapy using laser capture microdissection. As a result, LOH was more frequently detected after MPA therapy (overall ratios were 16, 17, and 29% before, during, and after MPA therapy, respectively). LOH is more easily detected in EH loci than in EAC loci before MPA. For EAC, initial LOH detection on chromosome 8 may be related to an incomplete response to MPA, but negative LOH does not guarantee a favorable treatment outcome. For EH or atypical endometrial hyperplasia, it is unknown whether LOH alteration associated with MPA therapy is related to atypia of the disease.     

复方醋酸环丙孕酮和罗格列酮序贯用药对氯米芬抵抗的多囊卵巢综合征患者内分泌及生育功能的影响

目的探讨复方醋酸环丙孕酮和罗格列酮序贯用药对改善多囊卵巢综合征（PCOS）患者生育功能的临床疗效。方法30例氯米芬抵抗的PCOS胰岛素抵抗患者，口服复方醋酸环丙孕酮3个月后，罗格列酮联合氯米芬用药6个月，比较用药前后体重指数、月经周期、生殖激素水平、排卵率、妊娠率、血糖和胰岛素水平的变化。结果与用药前相比，服用复方醋酸环丙孕酮后，雄激素水平和LH／FSH值明显降低（P〈0．05），服用罗格列酮后，胰岛素抵抗指数（Homa IR）、胰岛素分泌指数（Homa β）以及β细胞功能评定指数（MBCI）均较用药前降低（P〈0．05）。结论复方醋酸环丙孕酮和罗格列酮序贯用药可有效地抑制氯米芬抵抗的PCOS患者的高雄激素血症，改善胰岛素抵抗及生育功能。     

子宫腺肌症病变中雌激素、孕激素、癌基因、凋亡抑制基因的表达研究

目的 研究雌激素（ER）、孕激素（PR）及癌基因（cerbB-2）、凋亡抑制基因（Bcl-2）在子宫腺肌症病变中的表达和子宫腺肌症发病的相关性。方法 用免疫组化方法检测40例子宫腺肌症病变组织中ER及其他生物学指标的表达。结果 ER、PR与CerbB．2、Bcl-2在子宫腺肌症病变中均有不同程度的阳性表达，子宫肌层异位内膜ER阳性表达率97．5％，PR阳性率97．5％，cerbB-2阳性率82．5％，Bcl-2阳性率62．5％。在位内膜和异位内膜ER、PR均呈阳性，阳性率比较差异无统计学意义（P〉0．05）。异位内膜cerbB-2的强阳性率高于在位内膜，差异有统计学意义（P〈0．05）。ER、PR与cerbB-2、Bcl-2阳性率相比具有相关性（P〈0．05）。结论 ER、PR与cerbB．2、Bcl-2在异位内膜高表达，提示这些生物学指标在子宫腺肌症发生发展中发挥作用。