Effects Of Different Regimens Research Articles

EFFECTIVENESS OF MAINTENANCE THERAPY AFTER THE END OF THE FIRST LINE OF TREATMENT FOR PATIENTS WITH METASTATIC COLORECTAL CANCER – THE RESULTS OF A POPULATION-BASED STUDY

Aim.To evaluate the effectiveness of different regimens of maintenance chemotherapy after the first line of treatment for patients with metastatic colorectal cancer.Materials and methods.We performed retrospective analyses of the data from 432 patients from 17 clinics in 14 regions of the Russian Federation who started systemic therapy for metastatic cancer in 2013. The main inclusion criterion was objective response or stabilization after the first 16 weeks of first-line therapy. Four groups of patients were compared, depending on the nature of maintenance therapy: those receiving fluoropyrimidines, a combination of fluoropyrimidines with bevacizumab, monotherapy of bevacizumab and monotherapy of anti-EGFR antibodies. The main criteria for assesment of the effectiveness of treatment were progression-free survival and overall survival. The statistical analysis was performed with the SPSS 20.0 sof tware package.Results.Maintenance therapy after completion of the first 16 weeks of the 1st line of chemotherapy was administered in 126 patients, most of them were treated with fluoropyrimidines (53.1 %). The median overall survival in the maintenance group was 27 versus 21 months in the observation group, p=0.01, HR=0.78 (95 % CI 0.6–1.02) Median progression-free survival in the maintenance group was 11 vs 7 months in the observation group (p<0.001, HR=0.6, 95 % CI 0.5–0.8). The worst results of progression-free survival were observed in the group with monotherapy of bevacizumab – median was 10 months versus 12 months in the fluoropyrimidine monotherapy group, 10 months for the combination of fluoropyrimidine with bevacizumab and 14 months for monotherapy of the anti-EGFR (p=0,9, HR=1.0, 95 % CI 0.9–1.2).Conclusions.There were no statistical differences in survival with different regimens of maintenance therapy. Monotherapy of bevacizumab in maintenance treatment was associated with the worst sur vival rates.

Intrauterine insemination with controlled ovarian hyperstimulation in the treatment of subfertility.

To determine the success rate of intrauterine insemination (IUI), following controlled ovarian hyperstimulation (COH) and to identify the prognostic factors associated with successful outcome in couples undergoing this form of assisted reproduction. Case series. Concept Fertility Centre, Karachi, Pakistan from January - December 2004. A total of 290 IUI procedures carried out for the treatment of unexplained and male factor subfertility were included. The age of women ranged from 20 to 44 years and the duration of subfertility were variable. All women had tubal patency confirmed before undergoing COH with one of the three regimens. IUI was performed at follicular maturity of > 16 mm and endometrial thickness of > 7 mm. Main outcome measures analyzed were pregnancy rate per cycle of IUI, miscarriage rate and ongoing pregnancy rate. Other variables observed were the various prognostic factors associated with successful outcome in IUI, such as maternal age, effect of different regimen of COH, motile sperm count and numbers of pre-ovulatory mature follicles > 16 mm. Data was collected and entered in SPSS version 10. Chi- square test of significance was applied and p-value determined. The cycle pregnancy rate (CPR), miscarriage rate and ongoing pregnancy rate was 10%, 13.8% and 8.6% respectively. CPR was 12% in women <35 years compared to 3% in >35 years (p-value 0.03). Significant difference was not observed in the CPR with three different COH regimes. CPR increased dramatically with motile sperm count of >10 millions/ml compared with < 10 millions/ml (12.3% vs. 2.8%, p-value 0.02). Significantly higher pregnancy rate was observed with increasing number of mature follicles >16 mm (6.2%, 12.9% and 30% with one, two and three follicles, p-value 0.0019). There was no case of OHSS and only one case of twin gestation. The overall CPR in patients undergoing IUI following COH at our clinic is comparable to the pregnancy rates as shown in different studies. Younger age, motile sperm count of > 10 millions/ml and two or three mature follicles >16 mm are good prognostic factors for successful outcome. However, no significant difference was observed in CPR with different COH regimes.

Effectiveness of Different Treatment Regimens on Eradication of Helicobacter Pylori Infection (A Single Center Experience in Kuwait)

AbstractBackground: Helicobacter pylori treatment still remains a challenge for physicians, and no current first-line therapies are able to cure the infection in all treated patients, recent studies reported declining in eradication rate with commonly usedclarithromycin based triple therapy and high cure rate was observed in patients treated by other regimens such as bismuth based therapy.Aim of the Study: To evaluate the effectiveness of the different regimens (Clarithromycin based triple therapy, bismuth based therapy and levofloxacin based therapy) on eradication of H.pylori infection.Methods: The data of 510H. pylori-infected treatment-naive subjects (215 males, 295 female) were collected retro-spectively through period between January 2014 and Decem-ber 2016. Patients treated at Gastroenterology Clinic Al-Sabah Hospital Kuwait. Four hundred and twenty nine patients treated by clarithromycin based triple therapy, 75 patients treated by bismuth containing quadruple therapy. C13 urea breath test was used for confirm eradication.Results: Eradication rate was significantly higher in 10 days bismuth based quadruple regimen than 14 days clarithro-mycin based triple regimen (96%, 77% respectively) (p<0.001). Levofloxacin based triple therapy and bismuth based quadruple therapy were effective 2nd line therapy (³90% cure rate).Conclusion: Bismuth based quadruple regimen more effective therapy for H.pylori infection than clarithromycin based triple regimen. Levofloxacin based triple and bismuth based quadruple regimens are effective 2nd line therapy with high cure rate.

НОВЫЕ АСПЕКТЫ ЭРАДИКАЦИОННОЙ ТЕРАПИИ ИНФЕКЦИИ HELICOBACTER PYLORI У БОЛЬНЫХ ХРОНИЧЕСКИМИ ГАСТРОДУОДЕНАЛЬНЫМИ ЗАБОЛЕВАНИЯМИ И САХАРНЫМ ДИАБЕТОМ 2 ТИПА

The aim of the study was to analyze the effectiveness of different regimens of anti-Helicobacter pylori therapy and their influence on the small intestinal overgrowth syndrome (SIBOS) in type 2 diabetic patients with chronic gastroduodenal disorders. For this purpose an open comparative randomized study was performed in 138 type 2 diabetic patients with chronic gastroduodenal disorders, aged 54.4±5.2 on average. Gastroduodenal pathology was confirmed by gastroduodenoscopy, the H.pylori contamination by use of the unease method or finding bacterial antigen in excrements. The SIBOS was recognized by a respiratory hydrogen method with lactulose. Depending on the type of anti-H.pylori regimen all the patients were divided into 3 groups. Optimization 14-days triple therapy by use of Rabeprazol instead of Omeprazol was found to be effective with 80.6% of H.pylori eradication. Addition of both vismuth and probiotic resulted in increased eradication up to 94.1%, while the optimized triple regimen with Metronidazol and probiotic (intensified combined therapy) proved to be the most effective (97.2%) in H.pylori eradication. All 3 regimens of anti-H.pylori therapy resulted in the decreased number of SIBOS cases, but the best results in comparison with the initial data were obtained in the groups on the triple optimized and intensive combined therapy – up to 60 and 78.3%, respectively. The positive influence of anti-H.pylori therapy on SIBOS seen in the study allows the authors to propose one more indication for anti-H.pylori therapy.

Analysis for the effect of different regimens on ocular myasthenia gravis in children

To evaluate the efficacy, recurrent risk factors and transferable ratio of treatments with 3 different regiments on children with systematic myasthenia gravis (MG). Methods: The data of 104 children with ocular MG from June 2010 to March 2014 were collected from Department of Pediatric Neurology of Xiangya Hospital and they were retrospectively studied. The patients were divided into 3 groups: a methylprednisolone group (n=44), a prednisone group (n=48) and a bromine pyridostigmine group (n=12). Evaluative system from American MG foundation was used to evaluate the efficacy of treatment and the ratio of ocular MG transformed into systematic MG. Results: The efficacy in the methylprednisolone group was better than that in the prednisone group, and both of them were better than that in the bromine pyridostigmine group (both P<0.05).Methylprednisolone, prednisone combined with bromine pyridostigmine could reach a better long-term efficacy in children with ocular MG. Early treatment with glucocorticoid could reduce clinical relapse. Conclusion: A treatment with high-dose methylprednisolone pulse can improve early clinical remission in children with ocular MG. However, there is a similar efficacy in the long run of different glucocorticoid therapeutic regiments. A relatively order onset age, infection and thyroid dysfunction are recurrent risk factors in children with ocular MG.

Effects of different regimens of PGF2α treatment during postpartum on reproductive performance in dairy cows

O objetivo do presente trabalho foi avaliar os efeitos do tratamento pós-parto precoce com PGF2α sobre o desempenho reprodutivo de vacas leiteiras sincronizadas para reprodução controlada por monta natural após o período de espera voluntário. Neste experimento, 120 vacas foram distribuídas em três grupos independentes da presença ou ausência de corpo lúteo. Vacas no grupo PG-14 foram tratadas com PGF2α a partir do 14o dia pós-parto, vacas do grupo PG-28 foram tratadas com PGF2α a partir do 28o dia pós-parto e as vacas do grupo PG-42 não foram tratadas com PGF2α até o final do período de espera voluntário (d42). Após o 42o dia pós-parto as vacas dos três grupos foram tratadas com PGF2α com intervalos de 14 dias até a monta natural após o período de espera voluntário. Os registros dos parâmetros reprodutivos incluíram: dias para o primeiro estro, dias para a primeira cobertura, dias em aberto, serviços por concepção, taxa de concepção, percentagem de animais repetidores de cios e as perdas de gestações. O tratamento precoce com PGF2α, a partir do 14o dia pós-parto reduziu significativamente os dias para o primeiro estro (34,9 ± 0,74, P &lt; 0,003), dias para a primeira cobertura (62,35 ± 1,53, P &lt; 0,04), dias em aberto (117,23 ± 3,1, P&lt;0,001) e o número de serviços por concepção (1,9 ± 0,009, P &lt; 0,02); e o grupo PG-14 apresentou um acréscimo na taxa de concepção (52,5%, P &lt; 0,05). A proporção da síndrome de vacas repetidoras de cios tendeu a ser afetada pelo tratamento com PGF2α a partir do 14o dia pós-parto. A conclusão obtida foi que o tratamento das vacas com PGF2α a partir do 14o dia pós-parto melhorou o desempenho reprodutivo dos animais.

Effects of different regimens of iron prophylaxis on maternal iron status and pregnancy outcome: a randomized control trial

Purpose: Iron supplementation is associated with side effects and overload risk. We compared different regimens of iron supplementation on maternal hematological status and pregnancy outcome in a cohort of healthy pregnant women.Materials and methods: Eighty non-anemic women with a normal singleton pregnancy were recruited at 11–13 weeks and randomized into controls (C; n = 20) and groups supplemented with ferrous iron 30 mg (FI; n = 20), liposomal iron 14 mg (Sideral® Pharmanutra, Pisa PI, Italy) (LI14; n = 20) and liposomal iron 28 mg/daily (LI28; n = 20) up to 6 weeks post-partum. Longitudinal maternal blood samples for iron markers were collected. Data on birth outcome were recorded. The treatment effect was evaluated using a mixed-effect regression model.Results: Both LI28 and LI14 groups showed significantly higher hemoglobin and ferritin concentrations compared with controls. Birth weight showed a trend to increase with supplementation, resulting in higher birth weight in the LI28 group compared with controls (3499 ± 464.1 g and 3092 ± 469.5 g, respectively, p < 0.01).Conclusions: Our data show the effectiveness of 28 mg and 14 mg LI on maternal anemia prevention, as previously reported with FI 40 mg. LI has similar effects of higher doses of ferrous iron on maternal hematological parameters, thus allowing to reduce iron doses and side effects.

Sitagliptin/Metformin Versus Insulin Glargine Combined With Metformin in Obese Subjects With Newly Diagnosed Type 2 Diabetes.

To compare the therapeutic effects of different regimens in Chinese obese type 2 diabetic mellitus (T2DM) patients.From October 2013 to July 2014, a total of 166 T2DM outpatients who attended the Shanghai Changhai Hospital and the Yijishan Hospital of Wannan Medical College were randomly assigned into an experimental sitagliptin/metformin combined with low caloric diet group (n = 115) and an insulin glargine combined with metformin control group (n = 51). Inclusion criteria were body mass index (BMI) ≥ 25 kg/m2 and diagnosed with T2DM with glycosylated hemoglobin (glycated hemoglobin A1C [HbA1c]) >9%. Main outcome parameters were fasting plasma glucose, postprandial plasma glucose, BMI, HbA1c, fasting C-peptide, 2-h postprandial C-peptide, triglyceride (TG), total cholesterol (TC), high-density cholesterol (HDL-C), and low-density cholesterol (LDL-C), which were determined by the 75 g steamed-bun meal tolerance test before and 4, 8, 12, and 24 weeks after the treatment started. Treatment costs and life quality were also assessed.BMI, HbA1C, TG, TC, and LDL were significantly more reduced (P < 0.000) and HbA1c significantly better improved in the experimental group than in the control group (<6.5% in 24 [20.87%] vs 2 [3.92%], P < 0.001; <7% in 65 [56.52%] vs 12 [23.53%], P < 0.001). Quality of life scores in the experimental group increased more than in the control group (P < 0.001). The costs for the experimental group medication were less than for other regimens.For obese T2DM patients diagnosed with a glycosylated hemoglobin level >9%, oral sitagliptin/metformin combined with a low caloric diet effectively and economically maintained glycemic control and significantly improved life quality.

Comparative study of hyoscine doses as antisialagogue for patients receiving ketofol sedation undergoing colonoscopy procedures.

Objective:To compare the effects of different regimens of hyoscine as antisialagogue in patients undergoing ketofol sedation for colonoscopy procedures.Patients and Methods:In this prospective double-blind randomized controlled trial 200 American Society of Anesthesiologists I-II aged 20–60-year-old undergoing colonoscopy were randomly assigned into four equal groups, group A received 5 mg hyoscine intravenous, group B received 10 mg, group C received 20 mg intravenous, and control group (D) that was received saline. All patients were sedated using ketofol titrated to achieve Ramsey Sedation Score 4, hemodynamic variables and occurrence of increased secretions were evaluated and recorded.Results:Hyoscine in a dose of 10 mg was the optimum dose to achieve least salivation with the least side effect while hyoscine 5 mg was not efficient to achieve dry field or good surgical conditions. However, hyoscine 20 mg achieved dry field and fair surgical conditions in expenses of tachycardia.Conclusion:Hyoscine 10 mg was the least effective dose that significantly reduced hypersalivation in patients receiving ketofol sedation for colonoscopy procedures, this dose was as effective as 20 mg in draying secretion but with significantly less tachycardia.

Mortality and Other Outcomes in Relation to First Hour Fluid Resuscitation Rate: A Systematic Review.

To determine the effect of different regimen of first hour fluid administration rates on mortality and severe consequences of impaired circulation in 2 to 60 months old children with impaired circulation. Systematic review of randomized controlled trials. Various databases including PubMed, Cochrane Library and EMBASE were searched. We found only two relevant trials; one was excluded as there was no comparator arm. Only one study (The FEAST Trial) compared boluses with maintenance fluid alone in children with severe febrile illness and one or more signs of impaired perfusion. The 48 hour mortality was more in the bolus group (RR 1.45, 95% CI 1.13,1.86). The quality of evidence is rated as moderate. For the children who met the WHO criteria for shock (severely impaired circulation) (n=65 children), those receiving boluses had higher mortality (RR 2.40, 95% CI 0.84, 6.88); the quality of evidence was rated as very low. A single large randomized controlled trial conducted in low-resource settings indicates that administration of fluid bolus is associated with higher mortality in comparison to the maintenance fluids alone in children with severe febrile illness and one or more signs of impaired perfusion. The findings are not generalizable to contexts with different severity of and different causes of shock and in centers with better facilities. There is urgent need for research in different settings to determine the optimal rate of fluid resuscitation in the first hour in children presenting with impaired circulation, particularly with severely impaired circulation.

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Objective: To observe the reverse effect of different combined regimens on blood pressure and microalbuminuria(MAU) in hypertensive patients. Design and method: Ninety-four hypertensive patients with blood pressure > 140/90 mmHg (1 mmHg = 0.133 kPa) and positive MAU after treatment with inhibitors of angiotensin invertase and antagonists of angiotensin receptor were included in this study. The patients were randomly divided into L-amlodipine group (n = 52) and diuretics (HCTZ) group (n = 42). After the patients were treated with L-amlodipine(2.5–5 mg/d) and HCTZ(12.5–25 mg/d) respectively for 12 weeks, the reverse effect of different regimens on blood pressure and MAU was observed. Results: The normal blood pressure was achieved in 35(67.3%)and 27 patients(64.3%) respectively(P > 0.05), the negative MAU rate was 53.8% and 19.0% respectively (P < 0.01), the blood pressure was < 140/90 mmHg and the MAU was no less than30% in 80.8% and 64.3% of the patients in the two groups 12 weeks after treatment(P < 0.05). Conclusions: The effect of renin and angiotensin blocking agents in combination with calcium antagonists or HCTZ is similar to that of other regimens on blood pressure and other parameters, and is better than that of renin and angiotensin blocking agents in combination with HCTZ on MAU.

A 24-month prospective study on the efficacy and safety of two different monthly regimens of vitamin D supplementation in pre-menopausal women with systemic lupus erythematosus.

Low vitamin D (vit.D) serum levels are common in patients with systemic lupus erythematosus (SLE) and seem to correlate with higher disease activity. We investigated the effects of different regimens of vit.D supplementation in SLE patients with inactive disease. This 24-month prospective study included 34 SLE women who were randomized to receive, together with their ongoing treatment, a standard regimen (SR) of cholecalcipherol (25,000 UI monthly) or an intensive regimen (IR) (300,000 UI initial bolus followed by 50,000 UI monthly) for one year and then were switched to the other regimen in the second year. Patients were seen quarterly for assessment of 25-OH vit.D levels, disease activity, SLE serology and bone metabolism markers. By intra-patient comparison, only the IR was found able to significantly raise vit.D serum levels. After 12 months, values above 30 ng/ml were found in 75% of patients in IR while in only 28% in SR. No significant differences in disease activity and SLE serology were found at any time point between SR and IR. No changes in the mineral metabolism were observed. The IR was safe and effective in obtaining sufficient levels of vit.D in most SLE patients. However, both regimens of supplementation did not differently affect disease activity nor SLE serology.

Treatment of IgA nephropathy based on the severity of clinical and histological features.

Immunoglobulin A (IgA) nephropathy (IgAN) represents a common glomerular disease treated by various therapeutic regimens. We studied 50 IgAN patients to determine the effect of different regimens selected according to severity of the disease on the clinical outcome of patients over a follow-up period of five years. Patients with normal renal function and proteinuria <1 g/24-h received no treatment (Group A, n = 6). Thοse with normal renal function, proteinuria >1 g/24-h and mild to moderate histological lesions received angiotensin-converting enzyme inhibitors (ACEi) and corticosteroids (Group B, n = 23). Patients with baseline serum creatinine (Scr) <2.5 mg/dL, proteinuria >3.5 g/24-h and severe histological lesions received ACEi, corticosteroids and other immunosuppressive drugs (Group C, n = 18). Finally, patients with Scr >2.5 mg/dL, glomerulosclerosis and tubulointerstitial fibrosis received ACEi and fish oil (Group D, n = 3). Doubling of baseline Scr was observed in nine (18%) patients; two (8.7%) patients from Group B, five (27.7%) patients from Group C and two (66.7%) patients from Group D. Of the seven (14%) patients who reached end-stage renal disease, one (4.3%) patient was from Group B, four (21.0%) patients were from Group C and two (66.7%) patients were from Group D. Reduction of proteinuria was observed in all (100%) patients from Group B and in 15 (83.3%) patients from Group C. Adverse reactions occurred in three of 18 (16%) patients treated with immunosuppressive drugs. The choice of therapeutic regimen used in the treatment of patients with IgAN could be based on the severity of clinical and histological involvement in order to achieve the maximum effect with the least of adverse reactions.

Effect of rifampicin and gentamicin on Shiga toxin 2 expression level and the SOS response in Escherichia coli O104:H4.

A novel pathotype, Shiga toxin-producing Escherichia coli O104:H4, was the cause of a severe outbreak that affected European countries, mainly Germany, in 2011. The effect of different regimens of rifampicin and gentamicin were evaluated to determine possible treatment modes for the novel strain, and to evaluate the SOS response and its effect on toxin release. Pulsed-field gel electrophoresis (PFGE) was performed on the novel E. coli O104:H4 pathotype and two pre-outbreak E. coli O104:H4 CDC strains. Transcript levels of the stx2 and recA gene (SOS response inducer) were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in the novel E. coli O104:H4 samples subjected to different regimens of rifampicin and gentamicin. Consequently, reverse passive latex agglutination (RPLA) was used to determine the Stx2 titers in these samples. Western blot was performed to determine the LexA levels (SOS response repressor) in E. coli O104:H4. The efficacy of treatment with antimicrobial agents was assessed in BALB/c mice. The outbreak and pre-outbreak strains are closely related as shown by PFGE, which demonstrated slight genomic differences between the three strains. The transcription level of the stx2 gene in the new pathotype was 1.41- and 1.75-fold that of the 2009 EL-2050 and 2009 EL-2071 pre-outbreak strains, respectively. Moreover, the transcription level of the stx2 gene in the new pathotype was substantially decreased as a result of treatment with the different concentrations of the antimicrobial agents, but was enhanced when the antibiotics were administered at two subinhibitory levels. RPLA data were in accordance with the qRT-PCR results. E. coli O104:H4 exposed to gentamicin at both sub-minimum inhibitory concentration (MIC) levels led to high transcription levels of the recA gene and lack of expression of the LexA protein, implying that the SOS response was activated. Rifampicin at both sub-MIC levels resulted in low transcript levels of the recA gene, indicating that the SOS response was not induced. In vivo, the highest survival rate in BALB/c mice was observed in the group that was treated with the minimum bactericidal concentration (MBC) of gentamicin. The use of antimicrobial agents in E. coli O104:H4 infection seems to be effective at the MIC and MBC levels. This provides a promising ground for treatment of E. coli O104:H4.

Dose/Time-Dependent Modulation of the Endothelial Function Through Induction Agents: Non-Depleting Versus Depleting Agents

BackgroundPolyclonal anti-thymocyte globulins (ATGs) and anti-CD25 antibodies are agents used for induction of immunosuppression in solid-organ transplantation. We aimed to investigate the effect of different regimens of these immunosuppressive induction agents on transendothelial migration of peripheral blood mononuclear cells (PBMC) and evaluated the endothelial apoptosis after treatment. MethodsHuman microvascular endothelial cells were either activated with tumor necrosis factor-α/interferon-γ or not and further treated with 25 or 125 μg/mL ATG (Thymoglobulin, Sanofi-Aventis, Germany) for 2 hours or 24 hours, or with 5 μg/mL Basiliximab (Simulect, Novartis, Germany) for 2 hours or 24 hours. PBMC were either activated with phytohaemagglutinin (PHA) or not and further treated with 25 or 125 μg/mL ATG or with 5 μg/mL Basiliximab for 2 h and then used for transendothelial migration assays. Apoptosis of endothelial cells was detected by means of Annexin-V staining after 2-hour incubation with either 25 or 125 μg/mL ATG or 5 μg/mL Basiliximab. ResultsProphylactic 24-hour administration of ATG to naive endothelial cells without PBMC treatment reduced transendothelial migration. Prophylactic 24-hour administration of ATG and Basiliximab to naive endothelial cells after PBMC treatment with the same agents reduced the transendothelial migration after 24 hours. In both cases, no effect could be observed after 2-hour treatment. Basiliximab but not ATG showed a reduction of transmigration after 2-hour treatment of PBMCs without naive EC treatment. Apoptosis of endothelial cells after treatment increased in both cases, being in case of ATG dose-dependent, increasing from 1.2% after either 25 μg/mL ATG to 8.7% after 125 μg/mL ATG. ConclusionsImmunosuppressive induction agents modulate the endothelial activity in a dose- and time-dependent manner. Our results suggest that administration of induction agents over longer time periods could provide a potential benefit regarding endothelial immunomodulation. Increased doses may, however, show a deleterious effect on endothelial survival.

Long-term therapeutic effects of mesenchymal stem cells compared to dexamethasone on recurrent experimental autoimmune uveitis of rats.

We tested the long-term effects of different regimens of mesenchymal stem cell (MSC) administration in a recurrent experimental autoimmune uveitis (rEAU) model in rats, and compared the efficacy of MSC to that of dexamethasone (DEX). One or two courses of MSC treatments were applied to R16-specific T cell-induced rEAU rats before or after disease onsets. The DEX injections were given for 7 or 50 days continuously after disease onsets. Clinical appearances were observed until the 50th day after transfer. On the 10th day, T cells from control and MSC groups were analyzed by flow cytometry. Supernatants from the proliferation assay and aqueous humor were collected for cytokine detection. Functions of T cells and APCs in spleens also were studied by lymphocyte proliferation assays. One course of MSC therapy, administered after disease onset, led to a lasting therapeutic effect, with a decreased incidence, reduced mean clinical score, and reduced retinal impairment after 50 days of observation, while multiple courses of treatment did not improve the therapeutic benefit. Although DEX and MSCs equally reduced the severity of the first episode of rEAU, the effect of DEX was shorter lasting, and DEX therapy failed to control the disease even with long periods of treatment. The MSCs significantly decreased T helper 1 (Th1) and Th17 responses, suppressed the function of antigen-presenting cells, and upregulated T regulatory cells. These results suggested that MSCs might be new corticosteroid spring agents, while providing fewer side effects and longer lasting suppressive effects for recurrent uveitis.

Anti-Müllerian hormone screening to assess ovarian reserve among female survivors of childhood cancer

Anti-Müllerian hormone (AMH) is an indicator of oocyte reserve in healthy females. The role of AMH testing in oncology remains investigational, although its sensitivity and stability over the menstrual cycle make it an attractive screening test for fertility assessment among female cancer survivors. We measured AMH level in survivors of childhood cancer and evaluated its association with treatment and patient factors. Participants were adult female survivors of childhood malignancy treated with chemotherapy. Serum AMH was measured at a random day of the menstrual cycle. Multivariate analysis was used to evaluate the association between AMH level, alkylating agent exposure using the cyclophosphamide equivalent dose (CED), and other covariates. Sixty-six females with a median attained age of 23.3 years were eligible for analysis. Median AMH was 25.5 pM (range 0.5-108.0), at a median time of 11.5 years (range 1.4-25.1) since cancer diagnosis. Twenty-three patients (34.8%) had low AMH, including a significant proportion that reported normal menstrual cycles. Compared to ALL survivors, sarcoma survivors had significantly lower AMH levels. Among alkylating agents evaluated, procarbazine had the greatest adverse effect on AMH. In multivariate analysis, higher CED (p = 0.001), older age at diagnosis (p < 0.001), and use of oral contraceptive pills (p = 0.04) remained significantly associated with lower AMH. Random AMH can reveal evidence of oocyte depletion among female survivors reporting normal cycles, although low AMH should be interpreted cautiously among those taking oral contraception. Age at exposure and CED can aid identification of those more likely to have low AMH, although CED may underestimate the effect of procarbazine on oocyte reserve. Measurement of AMH can reveal apparent depletion of ovarian reserve in female childhood cancer survivors reporting normal menstrual cycles. Sarcoma survivors and those exposed to procarbazine may benefit from targeted AMH evaluation in an outpatient setting, and thereby allow appropriate fertility counseling before the onset of premature ovarian failure. The cyclophosphamide equivalent dose may facilitate comparison of the potential effect of different regimens on fertility.

Different regimens of intravenous sedatives or hypnotics for electroconvulsive therapy (ECT) in adult patients with depression.

Depression is a common mental disorder. It affects millions of people worldwide and is considered by the World Health Organization (WHO) to be one of the leading causes of disability. Electroconvulsive therapy (ECT) is a well-established treatment for severe depression. Intravenous anaesthetic medication is used to minimize subjective unpleasantness and adverse side effects of the induced tonic-clonic seizure. The influence of different anaesthetic medications on the successful reduction of depressive symptoms and adverse effects is unclear. This review evaluated the effects of different regimens of intravenous sedatives and hypnotics on anti-depression efficacy, recovery and seizure duration in depressed adults undergoing ECT. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE via Ovid SP (from 1966 to 31 December 2012); and EMBASE via Ovid SP (from 1966 to 31 December 2012). We handsearched related journals and applied no language restrictions. We included randomized controlled trials (RCTs) and cross-over trials evaluating the effects of different intravenous sedatives and hypnotics for ECT. We excluded studies and trials using placebo or inhalational anaesthetics and studies that used no anaesthetic. Two review authors independently assessed trial quality and extracted data. When possible, data were pooled and risk ratios (RRs) and mean differences (MDs), each with 95% confidence intervals (CIs), were computed using the Cochrane Review Manager statistical package (RevMan). We included in the review 18 RCTs (599 participants; published between 1994 and 2012). Most of the included trials were at high risk of bias.We analysed the results of studies comparing six different intravenous anaesthetics.Only a few studies comparing propofol with methohexital (four studies) and with thiopental (three studies) could be pooled.No difference was noted in the reduction of depression scores observed in participants treated with propofol compared with methohexital (low-quality evidence). These four studies were not designed to detect differences in depression scores.The duration of electroencephalograph (EEG) and of motor seizures was shorter in the propofol group compared with the methohexital group (low-quality evidence). No difference was seen in EEG seizure duration when propofol was compared with thiopental (low-quality evidence).Time to recovery (following commands) was longer among participants after anaesthesia with thiopental compared with propofol (low-quality evidence).For the remaining comparisons of anaesthetics, only single studies or insufficient data were available. Adverse events were inadequately reported in eligible trials, and none of the included trials reported anaesthesia-related mortality. Most of the included studies were at high risk of bias, and the quality of evidence was generally low. The studies were not designed to detect clinically relevant differences in depression scores. Anaesthetic agents should be chosen on the basis of adverse effect profile, emergence and how these medications affect seizure duration. If it is difficult to elicit an adequately long seizure, methohexital may be superior to propofol (low-quality evidence). If a patient is slow to recover from anaesthesia, propofol may allow a faster time to follow commands than thiopental (low-quality evidence). A factor of clinical concern that was not addressed by any study was adrenal suppression from etomidate. Optimal dosages of intravenous sedatives or hypnotics have not yet been determined.Larger well-designed randomized studies are needed to determine which intravenous anaesthetic medication leads to the greatest improvement in depression scores with minimal adverse effects.

Weight change trajectory in women with breast cancer receiving chemotherapy and the effect of different regimens

To investigate the trajectory of weight change in Taiwanese women with breast cancer after starting chemotherapy and the impact of chemotherapy regimens on weight change while controlling for age, menopausal status, body mass index, lymph node involvement and changes in habits of dietary fat intake and exercise. Weight gain after adjuvant chemotherapy in women with breast cancer has negative impact on health outcomes. Longitudinal, clinical observational study. Weights were repeatedly measured in 147 women with breast cancer stages I-III. Hierarchical linear modelling was used to analyse these longitudinal data. The overall pattern of weight change was a cubic form beginning with a mean of 56·9 kg before chemotherapy. It gradually increased to 59·4 kg at 8·5 months after the first chemotherapy followed by a decrease to 58·5 kg at 21·5 months. During the last 2·5 months, weight increased slightly and never returned to the initial level. After controlling for confounders, steeper weight change was observed among women receiving cyclophosphamide, methotrexate and fluorouracil. The highest weight gain in the cyclophosphamide, methotrexate and fluorouracil group was 2·9 kg (5%) vs. 0·9 kg (1%) in the anthracycline-based group. The trajectory of body weight change within two years after chemotherapy shows a trend of gradual ascent, followed by a small decline and a slight increase in the last 2·5 months. The chemotherapy regimen can predict the trend after controlling for other confounders; women on cyclophosphamide, methotrexate and fluorouracil have a steeper weight change. Nurses can inform women with breast cancer about the expected changes in body weight after chemotherapy to reduce their uncertainty. Future studies on effective interventions to minimise chemotherapy-induced weight gain are needed.

Drugs of abuse as memory modulators: a study of cocaine in rats

It has been proposed that drugs of abuse reinforce behavior partly, or wholly, because they facilitate learning by enhancing memory consolidation. Cocaine can clearly serve as a reinforcer, but its effect on learning has not been fully characterized. To explore the effects of different regimens of pre- and post-training cocaine administration on win-stay and object learning. Cocaine naïve and cocaine pre-exposed (30 mg/kg/day, × 5 days followed by 7 days drug-free) male Sprague-Dawley rats received cocaine (0, 1, 2.5, 7.5, or 20 mg/kg, i.p.) immediately following training on a win-stay task in a radial maze or following the sample phase of an object learning task. Win-stay performance was also assessed in tests of extinction and after a set shift. Post-training cocaine did not improve accuracy on the win-stay task and produced performance deficits at 20 mg/kg. These deficits were attenuated by prior cocaine exposure. There was indirect evidence of facilitated learning in extinction and set shift tests, but the effective dosage was different (2.5 and 7.5 mg/kg, respectively). Post-training cocaine produced dose-dependent improvements in object learning. Post-training cocaine administration can facilitate learning, but this effect is highly dependent on the dose and the type of task employed.