Impact of patient-prosthesis mismatch and aortic valve design on coronary flow reserve after aortic valve replacement.

OBJECTIVES: This prospective-randomized study investigated the effect of aortic valve design and patient-prosthesis mismatch (PPM) on coronary flow reserve (CFR) after mechanical or biological aortic valve replacement (AVR) in patients with aortic stenosis (AS). BACKGROUND: Coronary flow reserve may be an important parameter of long-term survival after AVR in patients with AS. Reduced CFR may contribute to more cardiovascular events and greater rates of mortality. METHODS: A total of 48 patients undergoing AVR underwent magnetic resonance imaging for the measurement of coronary flow preoperatively, 5 days postoperatively, and at 6-month follow-up with measurement of CFR. Patients scheduled for mechanical AVR were randomized to a tilting disc or bileaflet prosthesis (n = 12 in each group). For biological AVR, patients were scheduled to receive a stented (n = 12) or stentless (n = 12) valve. Patients also underwent echocardiography with measurement of transvalvular pressure gradients and left ventricular mass regression. RESULTS: Postoperatively, coronary flow increased significantly in all groups (p < 0.001). Only stentless valves demonstrated a normal CFR (3.4 +/- 0.3 vs. 2.3 +/- 0.1 for stented biological valves, 2.1 +/- 0.2 for tilting disc, and 2.2 +/- 0.3 for bileaflet mechanical valves). Patient-prosthesis mismatch with an indexed effective orifice area <0.85 cm2/m2 led to decreased rates of CFR in the tilting disc, stentless, and stented groups. Pressure gradients were 14 +/- 3 mm Hg for tilting disc, 12 +/- 4 mm Hg for bileaflet, 19 +/- 6 mm Hg for stented, and 10 +/- 4 mm Hg for stentless valves. CONCLUSIONS: Normalization of CFR after AVR in patients with AS was observed only for stentless valves. Coronary flow reserve might explain the excellent long-term results for stentless valves. (Impact of Patient-Prosthesis Mismatch on Coronary Flow Reserve; http://www.clinicaltrials.gov/ct/show/NCT00310947?order=1; NCT00310947).     

Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease: an effective second-line treatment

Transsphenoidal surgery (TSS) is considered first-line treatment for Cushing's disease (CD). Options for treatment of postoperative persisting hypercortisolemia are pituitary radiotherapy (RT), repeat TSS, or bilateral adrenalectomy. From 1983 to 2001, we treated 18 pediatric patients (age, 6.4-17.8 yr) with CD. All underwent TSS, and 11 were cured (postoperative serum cortisol, <50 nM). Seven (39%) had 0900-h serum cortisol of 269-900 nM during the immediate postoperative period (2-20 d), indicating lack of cure. These patients (6 males and 1 female; mean age, 12.8 yr; range, 6.4-17.8 yr; 4 prepubertal; 3 pubertal) received external beam RT to the pituitary gland, using a 6-MV linear accelerator, with a dose of 45 Gy in 25 fractions over 35 d. Until the RT became effective, hypercortisolemia was controlled with ketoconazole (dose, 200-600 mg/d) (n = 4) and metyrapone (750 mg-3 g/d) +/- aminoglutethimide (1 g/d) or o'p'DDD (mitotane, 3 mg/d) (n = 3). All patients were cured after pituitary RT. The mean interval from RT to cure (mean serum cortisol on 5-point day curve, <150 nM) was 0.94 yr (0.25-2.86 yr). Recovery of pituitary-adrenal function (mean cortisol, 150-300 nM) occurred at mean 1.16 yr (0.40-2.86 yr) post RT. At 2 yr post RT, puberty occurred early in one male patient (age, 9.8 yr) but was normal in the others. GH secretion was assessed at 0.6-2.5 yr post RT in all patients: six had GH deficiency (peak on glucagon/insulin provocation, <1.0-17.9 mU/liter) and received human GH replacement. Follow-up of pituitary function 7.6 and 9.5 yr post RT in two patients showed normal gonadotropin secretion and recovery of GH peak to 29.7 and 19.2 mU/liter. The seven patients were followed for mean 6.9 yr (1.4-12.0 yr), with no evidence of recurrence of CD. In conclusion, pituitary RT is an effective and relatively rapid-onset treatment for pediatric CD after failure of TSS. GH deficiency occurred in 86% patients. Long-term follow-up suggests some recovery of GH secretion and preservation of other anterior pituitary function.     

Warfarin sensitivity: be aware of genetic influence

BACKGROUND: avoidance of over anticoagulation in response to warfarin therapy would reduce risk of associated bleeding. SUBJECTS: two elderly patients with venous thromboembolism exhibited extreme anticoagulant response to warfarin. Both were noted to have variant CYP2C9 alleles, which reduce the metabolic capacity of cytochrome P450 2C9. DISCUSSION: adverse outcomes with warfarin therapy could be explained and possibly avoided by identifying patients with variant alleles for CYP2C9 before initiation of therapy.     

Tobacco consumption,opium use,alcohol drinking and the risk of esophageal cancer in North Khorasan,Iran

Background: There are some unique epidemiological characteristics of esophageal cancer in Iran. The objective of this study was finding the association between tobacco, substance and alcohol using with the risk of esophageal cancer in North Khorasan, Iran.

Methods: This Case-Control study was carried out on 96 patients with esophageal cancer and 187 controls. Controls were matched to cases by age and sex. Data were collected through structured interview. Data were analyzed by using chi-square test, T-test and logistic regression, in Stata software version 12.

Results: Our findings show Hookah smoking [OR = 6.1(CI_95%:1.2–13.1)] and opium consumption [OR = 2.1(CI_95%:1.2–3.5)] were associated with esophageal cancer. Cigarette and pipe smoking, age of onset of smoking, duration of smoking, number of smoking per day, leaving history of smoking, years of leaving smoking, drug withdrawal, number of times of drug withdrawal, a history of drug relapse, alcohol consumption and alcohol dose–response were not related to esophageal cancer.

Conclusion: According to our results, hookah smoking and opium consumption enhance the risk of esophageal cancer in North Khorasan of Iran. We suggest appropriate planning to prevent the esophageal cancer in this district.     

Efficacy of immunization with outer membrane proteins for induction of pulmonary clearance of nontypeable Haemophilus influenzae in a rat respiratory model

Three strains of nontypeable Haemophilus influenzae namely NTHi-I, NTHi-II and NTHi-III were isolated from the sputum of patients with bronchitis and identified by biochemical, serological and electron microscopy. The polypeptide patterns of isolates were compared and found to have similar sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) polypeptide patterns, although some of the bands were specific in some strains. A similar comparison was made on extracted outer membrane proteins (OMPs) on the above mentioned strains, using Triton X-100 and sodium dodecyle sulphate (SDS). It was found that the polypeptides with molecular weights of 70, 42, 33 and 27 KDa were identified as P1, P2, P4 and P5 respectively. The protein estimation of crude OMPs from the three strains were calculated, and OPM-I prepared from NTHi-I showed the highest amount of protein and was chosen for its immunogenicity in a rat respiratory model. The efficacy of immunization with OMP was determined by enhancement of pulmonary clearance of live bacteria in the rat lung. A significant protective immune response induced by OMP was observed by enhanced respiratory clearance of nontypeable H. influenzae following mucosal immunization.     

Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older

Outcome of patients with acute myeloid leukemia (AML) who are older than 60 years of age remains unsatisfactory, with low remission rates and poor overall survival. We have previously established the activity of clofarabine plus cytarabine in AML relapse. We have now conducted a phase 2 study of clofarabine plus cytarabine in patients aged 50 years or older with previously untreated AML. Clofarabine was given at 40 mg/m2 as a 1-hour intravenous infusion for 5 days (days 2 to 6) followed 4 hours later by cytarabine at 1 g/m2/d as a 2-hour intravenous infusion for 5 days (days 1 to 5). Of 60 patients, 29 (48%) had secondary AML, 30 (50%) had abnormal karyotypes (monosomy 5 and/or 7 in 15 [25%]), and 11 (21%) showed FLT3 abnormalities. The overall response (OR) rate was 60% (52% CR, 8% CRp). Four patients (7%) died during induction. Adverse events were mainly grade 2 or lower and included diarrhea, nausea, vomiting, mucositis, skin reactions, liver test abnormalities, and infusion-related facial flushing and headaches. Myelosuppression was common. Clofarabine plus cytarabine has activity in adult AML, achieving a good CR rate. However, survival does not appear to be improved compared with other regimens. Modifications of this combination in AML therapy of older patients warrant further evaluation.     

Comparative analysis of Behcet's disease in the APLAR region

Aims: Behcet's disease (BD) was originally a disease of the Silk Road. Some authors think that BD from the Silk Road is different from those seen in other countries. The aim of this study was to analyze the clinical manifestations of BD in APLAR countries, where some of them are in the Silk Road (SR) and some others not (NSR). Methods: Data from Australia (NSR), Hong Kong (NSR), India (SR), Iran (SR), and Singapore (SR) were selected and analyzed under the same protocol. Prior published data from China (SR) Japan (SR) and Korea (SR) were included in the analysis. Results: The mean age at the onset of the disease was under 30 for all countries except Japan and Singapore. The male gender was more frequent except in Australia and Korea. Oral aphthosis was the most frequent manifestation (90–100%). Genital aphthosis was less frequent (57–82%). Skin manifestations were also frequent (61–87%). Ocular manifestations were reported from 21–69% of patients. The difference was mainly due to patients’ selection bias and the low number of patients in some reports. The same was true for joint (30–87%), gastrointestinal (6–38%), neurological (2.5–29%) and vascular manifestations (5–28%). Conclusion: Despite the percentage difference among some countries, the general pattern of the disease was the same, suggesting that the minor differences seen in different parts of the world were not enough to call the disease a syndrome, or to differentiate Behcet's disease of the Silk Road from those seen in Western countries.     

Predictive factors for outcome and response in patients treated with second-generation tyrosine kinase inhibitors for chronic myeloid leukemia in chronic phase after imatinib failure

We assessed the predictive factors for outcome and response in 123 patients with chronic myeloid leukemia in chronic phase treated with second-generation tyrosine kinase inhibitors (TKIs) after imatinib failure. Better event-free survival rates with second-generation TKI therapy were associated with a previous cytogenetic response to imatinib (P < .001) and a performance status of 0 (P = .001). Patients with 0, 1, or 2 adverse factors had 2-year event-free survival rates of 78%, 49%, and 20% (P < .001), respectively; 2-year overall survival rates of 95%, 85%, and 40%, (P = .002), respectively; and a 12-month probability of achieving a major cytogenetic response of 64%, 36%, and 20% (P = .007), respectively. In conclusion, patients with poor performance status and no previous cytogenetic response to imatinib therapy have a low likelihood of responding to second-generation TKI with poor event-free survival and therefore should be offered additional treatment options. This scoring system could serve to advise patients of their prognosis and treatment options, as well as to evaluate the benefit of newer alternate options.     

DMARD combination therapy in rheumatoid arthritis: 5‐year follow‐up results in a daily practice setting

Aim: To evaluate the overall effect of disease modifying anti‐rheumatic drug (DMARD) combination therapy in daily practice. Methods: In a retrospective study, 161 consecutive files of patients who attended regular follow‐up sessions, seen from 1998, were analysed. Their data were extracted at baseline, 6 months, 1, 2, 3, 4 and 5 years. American College of Rheumatology ACR70 criteria was chosen for the evaluation of the global result. DMARD combination was methotrexate (7.5–15 mg weekly) and chloroquine (150 mg daily), with low‐dose prednisolone (less than 10 mg daily). In cases of remission, methotrexate was gradually tapered, then prednisolone. Chloroquine was discontinued after 1 year if no recurrence occurred at low‐dose (150 mg every other day). In cases of recurrence at any stage, the treatment scheme was stepped back. Results: The data of 161 patients were analysed. One hundred and six were rheumatoid factor positive (RF+) (66%). ACR 70 for all patients at 6 months follow‐up was 72.5% (95% CI = 7.0); at 1 year, 75.8% (95% CI = 6.7); at 2 years, 72.2% (95% CI = 7.2); at 3 years, 78.9% (95% CI = 6.6); at 4 years, 78.4% (95% CI = 6.9); and at 5 years, 70.6% (95% CI = 8.5). Conclusion: The classical DMARD combination therapy, when used with adequate low‐dose prednisolone, gave an ACR70 response from 71–79%. The efficacy of the treatment did not fade over time. RF– patients did better than RF+ patients, but the difference was not statistically significant.