Quantification of circulating Epstein-Barr virus DNA in NK/T-cell lymphoma treated with the SMILE protocol: diagnostic and prognostic significance.

Circulating Epstein-Barr virus (EBV) DNA is a biomarker of EBV-associated malignancies. Its significance in natural killer/T-cell lymphoma treated with the novel regimen SMILE was investigated. EBV DNA was quantified with a World Health Organization EBV standard in 910 plasma samples collected during 230 courses of SMILE in 56 patients. Median presentation EBV DNA was 1900 (0-1.4 × 10(7)) IU/ml. Presentation EBV DNA was significantly associated with tumor load and treatment response. To examine lymphoma chemosensitivity, EBV DNA changes after SMILE were evaluated. EBV DNA after SMILE (I) significantly correlated with tumor load and treatment response. Two dynamic parameters were further analyzed: negative EBV DNA after SMILE (I) and EBV DNA change patterns during treatment (A: persistently undetectable; B: persistently detectablepresentation). Negative EBV DNA after SMILE (I) and pattern A EBV DNA change significantly correlated with lower tumor load and superior outcome. Multivariate analysis involving presentation features, international prognostic index (IPI), Korean prognostic score and EBV DNA parameters showed that negative EBV DNA after SMILE (I) had the most significant impact (P<0.001) on overall survival and pattern A EBV DNA change had the most significant impact (P=0.002) on disease-free survival. Presentation EBV DNA, IPI and Korean prognostic scores were not independent prognostic factors.

Prevalence of levator ani muscle injury in Chinese women after first delivery.

OBJECTIVES: To assess the prevalence of levator ani muscle injury in Chinese women after their first delivery and investigate associated factors. METHODS: A prospective observational study was conducted involving Chinese nulliparous women recruited in the first trimester of pregnancy. Translabial ultrasound was performed at 35-38 weeks' gestation and 8 weeks postpartum and three-dimensional volume datasets were obtained. Offline analysis to detect levator ani muscle injury was performed by investigators blinded to the delivery details. RESULTS: 339 women, with a mean age of 30.6 ± 3.9 years, completed the study. Overall, 201 (59.3%) had a spontaneous vaginal delivery, 62 (18.3%) an operative vaginal delivery (48 ventouse extraction and 14 forceps delivery), 14 (4.1%) an elective Cesarean section and 62 (18.3%) an emergency Cesarean section. No levator ani muscle injury was detected in any woman antenatally. After vaginal delivery, 57 (21.7% (95% CI, 16.7-26.7%)) women had levator ani muscle injury. The rates of injury for spontaneous vaginal delivery, ventouse extraction and forceps delivery were 15.4%, 33.3% and 71.4%, respectively. There was no levator ani muscle injury in the Cesarean section groups. Logistic regression analysis showed that only operative vaginal delivery (odds ratio, 3.09) was associated with an independent increase in the likelihood of levator ani muscle injury. Intrapartum epidural analgesics, duration of second stage of labor and infant birth weight were not independently associated with levator ani muscle injury. CONCLUSIONS: The prevalence of levator ani muscle injury in Chinese women after their first vaginal delivery was 21.7% (95% CI, 16.7-26.7%). Operative vaginal delivery was found to increase the likelihood of women suffering such injury. A longer follow-up of these women and future studies on the effects of episiotomy are proposed.

Indolent T-cell large granular lymphocyte leukaemia after haematopoietic SCT: a clinicopathologic and molecular analysis.

Four women and three men after allogeneic (n=4) and autologous (n=3) haematopoietic SCT (HSCT) were observed to have an increase in T-cell large granular lymphocytes (T-LGLs) of CD3+CD8+ phenotype for a median of 41 (15-118) months. Clonal rearrangement of the T-cell receptor gene was verified by two PCR techniques and direct DNA sequencing, confirming that the cases were neoplastic and therefore classifiable as T-LGL leukaemia. In the allogeneic HSCT cases, T-LGL leukaemia was derived from donor T cells in three patients, as shown by DNA chimerism analysis, and recipient T cells in one patient who had graft failure previously. None of the patients showed cytopenia, autoimmune phenomenon or organ infiltration, which were features typical of de novo T-LGL leukaemia. Six patients had remained asymptomatic with stable large granular lymphocyte counts. One patient died from cerebral relapse of the original lymphoma. T-LGL leukaemias occurring post-HSCT are distinct from de novo T-LGL leukaemia and may have a different pathogenesis and clinical course. Patients did not require specific treatment, and the disease remained stable for long periods.

Urinary symptoms and impaired quality of life in female ketamine users: persistence after cessation of use.

OBJECTIVE: To compare the urinary symptoms and quality of life in ex-ketamine abusers and controls. DESIGN: Prospective observational study. SETTING: A hospital in Hong Kong. PATIENTS: Female ex-ketamine abusers admitted to a local drug rehabilitation centre and age-matched controls attending a general gynaecology clinic between December 2009 and April 2010. MAIN OUTCOME MEASURES: Evaluation of urinary symptoms based on a 3-day bladder diary, and responses to the Urogenital Distress Inventory Short Form (UDI-6) and the Incontinence Impact Questionnaire Short Form (IIQ-7). The study group had repeat measurements 3 months later. RESULTS: Overall, 90% of ex-ketamine abusers had active urinary symptoms. On average, they had increased 24-hour urinary frequency (10.0 vs 5.8; P=0.001) and lower maximum voided volume (253.3 mL vs 401.9 mL; P<0.001) compared to controls. Correspondingly, the median functional bladder capacity was smaller (195.3 mL vs 261.2 mL; P=0.011) and the mean UDI-6 and IIQ-7 scores were higher (P<0.001). Among those who abused ketamine for 2 years or more, the mean UDI-6 and IIQ-7 scores were higher (P=0.03, P=0.02 respectively). When they stopped abusing ketamine for 3 months or more, their mean 24-hour urinary frequency had decreased (P=0.03), the maximum voided volume had increased (P=0.03) and the mean UDI-6 and IIQ-7 scores had decreased (P=0.04, P=0.02 respectively), although they were still higher than in controls. After 3 more months, in the ex-ketamine abusers there had been a further decrease in 24-hour urinary frequency (P=0.01) and a further improvement in quality of life based on mean UDI-6 scores (P=0.04) but nevertheless poorer than the control group (P<0.01). CONCLUSION: Female ex-ketamine abusers had significant urinary symptoms affecting their quality of life when studied at a mean of 8 (range, 0.5-48) months after cessation of use. The symptom severity was inversely correlated with the duration of cessation; though they improved with time, some still persisted.

Compensatory downregulation of myocardial Ca channel in SR from dogs with heart failure.

In this study we tested the hypothesis that the ryanodine-binding Ca-release channel activity and density of the sarcoplasmic reticulum (SR) terminal cisternae were decreased in congestive heart failure (CHF) that occurs spontaneously in doberman pinschers or experimentally with rapid ventricular pacing of mongrels. We used a novel, sensitive, and easy-to-perform microassay and demonstrated a 50% decrease in activity of the myocardial SR Ca pump and a 75% reduction in SR Ca-release channel activity in CHF. Decreases in Ca channel content were associated with increases in net Ca sequestration. 45Ca-release experiments from passively loaded SR terminal cisternae and ryanodine-binding studies confirmed a 53-68% downregulation of the Ca-release channel activity. As a consequence of release channel downregulation, there was partial restoration of net Ca sequestration activity in dogs with CHF and complete compensation in dogs with mild cardiac dysfunction. Deterioration of Ca cycling correlated with deterioration of myocardial performance, apparently due to decreased Ca-adenosinetriphosphatase (ATPase) pump and not Ca channel content. One-half the reduction in Ca-release activity could be attributed to decreased Ca sequestration and one-half to decreased Ca channel density. Downregulation of Ca channel content decreases the amplitude of the Ca cycle and maximizes the downregulation of Ca pumps that may occur. Although these adaptations may reduce cellular energy expenditure, they are likely to render the myocardium more susceptible to fatigue and failure.