OBJECTIVETo evaluate the response rate and adverse reactions of exemestane (a new aromatase inactivator) in the treatment of postmenopausal women with advanced breast cancer.

METHODSOne hundred and seventy-three patients with advanced breast cancer entered this study with two patients excluded because of postmenopausal time being less than one year. Therefore, 173 patients could be evaluated for adverse events and 171 patients could be evaluated for efficacy. Exemestane, 25 mg orally daily for 4 weeks as one cycle was given.

RESULTSIn the 171 patients evaluated for efficacy, 4 (2.3%) experienced a complete response (CR) and 40 (23.4%) a partial response (PR), with the overall response rate of 25.7%. Ninety patients (52.6%) had stable disease (SD), with 25 having SD for at least 24 weeks. The clinical benefit (CR + PR + SD > or = 24 weeks) was shown in 69 (40.4%) patients. Progressive disease (PD) was shown in 37 (21.6%) patients. The untreated patients had a higher objective response rate (33.8%) than the retreated ones (18.1%) with significant difference (P = 0.019 7). The response rates for soft-tissue, bone involvement and visceral metastasis were 32.8%, 23.9%, and 12.4% (P = 0.002). There was no significant difference in different ages, time of menopause, disease-free interval or receptor status (P > 0.05). Drug-related adverse events were gastric discomfort (17.9%), malaise (17.9%), nausea (13.9%), hot flushes (11.0%) and dysphoria (5.8%). Other side reactions and abnormal laboratory parameters were observed occasionally which were irrelevant.

CONCLUSIONExemestane can be used to treat postmenopausal women with advanced breast cancer giving only mild adverse reactions which are well tolerated.

Adult ; Aged ; Androstadienes ; adverse effects ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Aromatase Inhibitors ; Breast Neoplasms ; drug therapy ; Enzyme Inhibitors ; therapeutic use ; Female ; Humans ; Middle Aged ; Postmenopause

The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated. Medline, Embase, the Cochrane Library, some databases of clinical trial registries, grey literatures, other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved. RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected. Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration's RevMan 4.2 software package. The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs. control: RD=0.03, 95% CI=-0.13-0.18, Z=0.34, P=0.73; ARBs vs. control: RD=-0.02, 95% CI=-0.07-0.03, Z=0.75, P=0.45). However, there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs. control: WMD=0.10, 95% CI=0.06-0.15, Z=4.64, P<0.00001; ARBs vs. control: WMD=-0.24, 95% CI=-0.37-0.11, Z=3.58, P=0.0003). The use of ACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients, however the serum potassium could be increased with use of ACEIs in HD patients. Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.
Aged ; Angiotensin Receptor Antagonists ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Female ; Humans ; Hyperkalemia ; chemically induced ; Male ; Middle Aged ; Renal Dialysis

OBJECTIVE: To evaluate the efficacy and safety of combined treatment with angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on diabetic kidney disease. METHODS: Randomized controlled trials (RCTs) were identified from CoChrane library, PubMed, EMbase, CNKI and VIP. Eleven RCTs involving 602 patients were included and analyzed with Rev Man 5.1 software. RESULTS: Compared with ACEI alone, combined treatment with ARB and ACEI was more effective on decreasing 24 h albuminuria, systolic pressure, average 24 h systolic pressure, diastolic pressure, and average 24 h diastolic pressure but with a high level of serum potassium. Compared with ARB alone, combined treatment with ARB and ACEI was more effective on decreasing systolic pressure and diastolic pressure. Compared with ACEI or ARB alone, we didn't get a definite conclusion that whether combined treatment with ARB and ACEI was more effective on decreasing 24 h proteinuria. CONCLUSION Based on this Meta analysis, combined treatment with ARB and ACEI is safer and has positive effect on diabetic kidney disease. However, small sample size and low methodological quality appeared in most of the trials included in this systematic review. Therefore, available evidence is insufficient to recommend a routine clinical application of combined treatment with ARB and ACEI on diabetic kidney disease.
Angiotensin Receptor Antagonists ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Diabetic Nephropathies ; drug therapy ; Drug Therapy, Combination ; Humans ; Randomized Controlled Trials as Topic

OBJECTIVETo evaluate the effects of W-7, a calmodulin inhibitor, on transmural dispersion of repolarization (TDR), early after depolarization (EAD) and torsade de pointes (TdP) induction after administration of d-sotalol in isolated rabbit heart.

METHODSTdP was induced by d-sotalol (30 micromol/L), bradycardia, and hypokalemic (1.5 mmol/L)/hypomagnesaemic (0.35 mmol/L) solution in isolated female rabbit hearts. Thirty six rabbit hearts were divided into 4 groups (n = 9 each): d-sotalol alone, d-sotalol + W-7 (20 micromol/L), d-sotalol + W-7 (50 micromol/L), and d-sotalol + W-7 (100 micromol/L). Monophasic action potentials (MAPs) of the left ventricular epimyocardium (Epi), midmyocardium (M), and endomyocardium (Endo) were recorded simultaneously with ECG. The incidence of EAD and TdP were observed as well.

RESULTSTreatment with d-sotalol alone prolonged ventricular MAP duration and QT interval, increased TDR, and evoked high incidence of EAD (9/9) and spontaneous TdP (7/9) in hypokalemic/hypomagnesaemic solution in female rabbit heart. W-7 concentration-dependently decreased incidence of TdP (4/9 in 20 micromol/L; 2/9 in 50 micromol/L; 1/9 in 100 micromol/L). This effect of W-7 coincided with the decreased incidence of EAD (5/9 in 20 micromol/L; 4/9 in 50 micromol/L; 1/9 in 100 micromol/L). However, the d-sotalol-induced prolongation of QT interval and TDR was not significantly altered by W-7 at the three concentration used.

CONCLUSIONSIn isolated female rabbit hearts, calmodulin antagonist W-7 suppresses d-sotalol-induced TdP without altering TDR but does suppress EAD. The effects observed with W-7 also suggest a possible important role for calmodulin-activated enzymes in the induction of TdP.

Animals ; Calmodulin ; antagonists & inhibitors ; Enzyme Inhibitors ; therapeutic use ; Female ; In Vitro Techniques ; Rabbits ; Sotalol ; adverse effects ; Sulfonamides ; therapeutic use ; Torsades de Pointes ; chemically induced ; prevention & control

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% +/- 0.71% to 7.71% +/- 0.93%) and voglibose groups (from 8.38% +/- 0.73% to 7.68% +/- 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 +/- 69.38 to 176.80 +/- 46.63 mg/dL) compared with the voglibose group (from 224.18 +/- 70.07 to 193.01 +/- 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528)
Acarbose/adverse effects/*therapeutic use ; Blood Glucose ; Diabetes Mellitus, Type 2/blood/*drug therapy ; Enzyme Inhibitors/adverse effects/therapeutic use ; Female ; Hemoglobin A, Glycosylated/analysis ; Humans ; Hypoglycemic Agents/adverse effects/therapeutic use ; Inositol/adverse effects/*analogs & derivatives/therapeutic use ; Insulin/*blood/therapeutic use ; Male ; Metformin/therapeutic use ; Middle Aged ; Prospective Studies ; alpha-Glucosidases/antagonists & inhibitors

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFalpha) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFalpha inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFalpha therapy in patients with TNFalpha-associated TB. We used data of 1,012 patients with RA or AS treated with TNFalpha inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-gamma releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFalpha therapy. All patients discontinued TNFalpha inhibitors with starting the treatment of TB. Eight patients were re-administered TNFalpha inhibitors due to disease flares and promptly improved without recurrence of TB. TNFalpha inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Antirheumatic Agents/adverse effects/therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Enzyme Inhibitors/adverse effects/therapeutic use ; Female ; Humans ; Hydroxychloroquine/adverse effects/therapeutic use ; Immunoglobulin G/adverse effects/therapeutic use ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Interferon-gamma Release Tests ; Male ; Methotrexate/adverse effects/therapeutic use ; Middle Aged ; Mycobacterium tuberculosis/isolation & purification ; Receptors, Tumor Necrosis Factor/therapeutic use ; Retrospective Studies ; Spondylitis, Ankylosing/*drug therapy ; Tuberculin Test ; Tuberculosis/*chemically induced/microbiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.
Adult ; Aged ; Antibiotics, Antineoplastic/adverse effects/therapeutic use ; Antimetabolites, Antineoplastic/adverse effects/therapeutic use ; Antineoplastic Agents/*adverse effects/therapeutic use ; Antineoplastic Agents, Alkylating/adverse effects/therapeutic use ; Drug-Induced Liver Injury/etiology/radiography ; Enzyme Inhibitors/adverse effects/therapeutic use ; Fatty Liver/etiology/radiography ; Female ; Humans ; Immunotherapy ; Liver Cirrhosis/etiology/radiography ; Liver Diseases/etiology/*radiography ; Male ; Middle Aged ; Neoplasms/therapy ; Tomography, X-Ray Computed

OBJECTIVETo evaluate the efficacy and safety of oseltamivir phosphate as treatment for naturally acquired influenza infection.

METHODSThis study was conducted as a double-blind, randomized, placebo-controlled, multicenter trial during the influenza epidemic season from January to April 2001 at 7 centers in China. A total of 478 adults without other medical history, aged 18 to 65 years, were enrolled into the study. All subjects demonstrated febrile respiratory illness of no more than 36 hours' duration with a temperature of 37.8 degrees C or more plus at least two of the following symptoms: coryza/nasal congestion, sore throat, cough, myalgia/muscles aches and pain, fatigue, headache or chills/sweats. Individuals were randomized into either the oseltamivir phosphate or placebo group with identical-looking capsules. Either oral oseltamivir phosphate, 75 mg twice daily, or placebo was administered to the subjects for 5 days.

RESULTSA total of 451 individuals were analyzed for efficacy as the intent-to-treat population (ITT) (216 oseltamivir and 235 placebo) and 273 individuals were identified as influenza-infected through laboratory test, who were then defined as the intent-to-treat infected population (ITTI) (134 oseltamivir and 139 placebo). Four hundred and fifty nine individuals were included in the safety analysis. In the ITTI population, the cumulative alleviation proportion of oseltamivir group was significantly higher than that of the placebo group (P = 0.0466)). The median duration of illness was 91.6 h [95% confidence interval (CI) = 80.2 - 101.3 h] in the oseltamivir group and 95 h (95% CI = 84.5 - 105.3 h) in the placebo group. The median area under the curve of decreased total score was significantly higher in the oseltamivir group than in the placebo group, 1382.9 and 1236.7 score-hours, respectively (P = 0.0196). For the ITT population, similar results were observed. Adverse events (AE) were similarly reported in both the oseltamivir group and the placebo group. The main adverse events following test drug were gastrointestinal symptoms, neurological symptoms and rashes.

CONCLUSIONOseltamivir was effective and well tolerated as treatment of early naturally acquired influenza.

Acetamides ; adverse effects ; therapeutic use ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Enzyme Inhibitors ; therapeutic use ; Female ; Humans ; Influenza, Human ; drug therapy ; Male ; Middle Aged ; Neuraminidase ; antagonists & inhibitors ; Oseltamivir

BACKGROUNDPostprandial hypotension (PPH) occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate at which glucose enters the small intestine. We hypothesized that acarbose (alpha-glucosidase inhibitor), a hypoglycemic agent that decreases the rate of glucose absorption in the small intestine, would attenuate PPH in the elderly, and would be safe in the treatment.

METHODSForty-three elderly in-patients with PPH were recruited. All of them were in relatively stable conditions. They had semi-liquid standard meals without and with acarbose for the two following days: screening day and intervention day. Blood pressure and heart rate (HR) were recorded at baseline and every 15 minutes for 120 minutes using a non-invasive ambulatory blood pressure monitoring system during the study, and ejection fraction (EF) and fractional shortening (FS) were measured by two dimensional echocardiography.

RESULTSCompared with the screening day, the falls in systolic, diastolic and mean arterial blood pressure (SBP, DBP, MAP) (all P < 0.05) were significantly attenuated after taking acarbose during breakfast, so were MAP (P < 0.05) during lunch, DBP (P < 0.05) and MAP (P < 0.05) during supper. The change of HR was not statistically significant after taking acarbose in three meals. EF and FS were positively correlated with the relief rate. The effective power was 63%, and the incidence of adverse drug reaction (ADR) was 9%.

CONCLUSIONAcarbose is effective and safe in the treatment of elderly patients with PPH.

Acarbose ; adverse effects ; therapeutic use ; Aged ; Aged, 80 and over ; Blood Pressure ; drug effects ; Enzyme Inhibitors ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Hypoglycemic Agents ; therapeutic use ; Hypotension ; drug therapy ; Male ; Postprandial Period ; physiology

BACKGROUNDThe results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure in high-risk patients, and telmisartan was associated with slightly superior tolerability. The combination of the two drugs was associated with more adverse events without an increase in benefit. This study aimed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics, the compliance, efficacy, and safety of the different treatment strategies in randomized patients in China.

METHODSA total of 1159 high-risk patients were randomized into three treatment groups: with 390 assigned to receive 80 mg of telmisartan, 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications. The median follow-up period was 4.3 years.

RESULTSThe mean age of Chinese patients was 65.6 years, 73.6% of patients were male. The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population (47.7% vs. 20.9%). In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5% in the telmisartan group, which was much less than that in the combination or the ramipril group. There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients. More strokes occurred in Chinese patients than in the entire study population (8.5% vs. 4.5%). Greater systolic blood pressure reduction (-9.8 mmHg), and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group (2.6% vs. 1.6% and 1.0%).

CONCLUSIONSThere was no evidence that the results of ONTARGET differed between Chinese patients and the entire study population with respect to the incidence of primary outcome, particularly safety. Compliance with study medications was good. The evidence from ONTARGET indicated that the treatment strategies in ONTARGET were applicable to patients in China.

Aged ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Benzimidazoles ; administration & dosage ; adverse effects ; therapeutic use ; Benzoates ; administration & dosage ; adverse effects ; therapeutic use ; China ; Drug Therapy, Combination ; Female ; Heart Failure ; drug therapy ; Humans ; Male ; Middle Aged ; Ramipril ; administration & dosage ; adverse effects ; therapeutic use