Reversal of diuretic-induced hepatic encephalopathy with infusion of albumin but not colloid

In patients with cirrhosis, dehydration induced by diuretics is a common precipitant of hepatic encephalopathy (HE), which may respond to volume expansion. The mechanism of HE in this situation is not fully understood. The present study evaluates the effect of plasma volume expansion on the severity of HE, plasma and urinary ammonia in patients with diuretic-induced HE. Fifteen patients with alcoholic cirrhosis and diuretic-induced HE of Grade 2 or more were enrolled. In eight patients, 4.5% human albumin solution (HAS) was used for volume expansion and in seven patients colloid (Gelofusine) was used. Significant improvement of HE Grade was observed at 24 h and was sustained at 72 h ( P <0.05) only in the group treated with HAS. There were similar and statistically significant reductions in plasma ammonia concentration, plasma renin activity and angiotensin II and an increase in mean arterial pressure, renal plasma flow and urinary ammonia excretion in both groups. Plasma malondialdehyde was elevated in both groups, but was reduced significantly only in the group treated with HAS. The findings of the present study show that plasma volume expansion results in significant reduction in plasma ammonia concentration, possibly through an increase in urinary ammonia excretion. This reduction in ammonia concentration translates into an improvement in mental state only in those patients treated with HAS in whom concomitant reduction in oxidative stress was observed. These data support the notion that other factors, such as oxidative stress, act as adjuncts to ammonia in the pathogenesis of diuretic-induced HE and suggest a possible role for albumin infusion in its treatment.     

Comparison of the predictive value of exercise-induced ST depression versus exercise technetium-99m sestamibi single-photon emission computed tomographic imaging for detection of coronary artery disease in patients with left ventricular hypertrophy

Scant knowledge exists regarding the significance of either additional ST depression in the presence of baseline depression or new stress-induced ST depression in patients with left ventricular (LV) hypertrophy. Accordingly, the purpose of this investigation is to determine whether the appearance and/or severity of ST abnormalities during exercise stress testing can accurately predict the prevalence of ischemic burden as measured by quantitative technetium-99m-sestamibi single-photon emission computed tomographic imaging in patients with LV hypertrophy. The results show that the presence of exercise ST-segment depression, as well as its magnitude, are not accurate predictors for identifying patients with coronary artery disease in the presence of electrocardiographic criteria for LV hypertrophy.     

Overexpression of calbindin D(28k) in dentate gyrus granule cells alters mossy fiber presynaptic function and impairs hippocampal-dependent memory

Calcium is a key signaling ion for induction of synaptic plasticity processes that are believed to influence cognition. Mechanisms regulating activity-induced increases in neuronal calcium and related synaptic modifications are not fully understood. Moreover, involvement of specific synapses in discrete aspects of spatial learning remains to be elucidated. We used herpes simplex amplicons to overexpress calbindin D(28k) (CaBP) selectively in dentate gyrus (DG) granule cells. We then examined the effects on hippocampal network activity by recording evoked synaptic responses in vivo and in vitro and analyzing hippocampal-dependent behavior. Relative to Lac-Z- and sham-infected controls, CaBP overexpression increased mossy fiber (MF-CA3) excitatory postsynaptic potentials and reduced paired-pulse facilitation (PPF), suggesting an increase in presynaptic strength. Additionally, CaBP overexpression reduced long-term potentiation (LTP), caused a frequency-dependent inhibition of post-tetanic potentiation (PTP), and impaired spatial navigation. Thus, increasing CaBP levels selectively in the DG disrupts MF-CA3 presynaptic function and impairs spatial cognition. The results demonstrate the power of gene delivery in the study of the neural substrates of learning and memory and suggest that mossy fiber synaptic plasticity is critical for long-term spatial memory.     

Activities of daily living in patients with dementia: clinical relevance, methods of assessment and effects of treatment

Disability, characterised by the loss of ability to perform activities of daily living (ADL), is a defining feature of dementia that results in growing caregiver burden and the eventual need for alternative care or nursing home placement. Functional decline in patients with dementia can also result from causes other than dementia, such as comorbid medical and psychiatric illnesses and sensory impairment. ADL consists of instrumental ADL (IADL) [complex higher order skills, such as managing finances] and basic ADL (BADL) [self-maintenance skills, such as bathing]. Assessment of IADL and BADL is recommended to establish a diagnosis of dementia. Functional assessment also helps the healthcare provider to offer appropriate counselling regarding safety concerns and need for custodial care. Functional capacity measures have been used increasingly in pharmacological trials of patients with Alzheimer's disease (AD) and related dementias, although at the present time these measures are generally not primary outcome measures. Functional impairment is not a uniform construct; rather, it is multifaceted and can be measured with various clinical instruments. Many scales have been validated for use in patients with AD for characterising functional impairment and evaluating the efficacy of treatment. Research to date indicates that cholinesterase inhibitors have the potential for modest but meaningful beneficial effects on ADL in patients with mild-to-moderate AD. Memantine also has promising beneficial effects on functional abilities in persons with moderate-to-severe AD. Assessment of ADL as a primary efficacy measure using a validated scale that is non-gender biased and cross-nationally relevant is recommended in new treatment trials of patients with AD and related dementias.     

Management of unscarred ruptured uterus

AIMS AND OBJECTIVES: Rupture of an unscarred gravid uterus is a rare and dangerous event. We carried out a postal questionnaire survey of the Fellows of the Royal College of Obstetricians and Gynaecologists (United Kingdom), to ascertain the past and present management policies in such an event. 210 Fellows responded (43.5%) and 85 of them managed at least one case of uterine rupture in previously unscarred gravid uterus. RESULTS: A total of 108 cases were reported of which 74 (68.5%) were diagnosed during labor. The tear was repaired and the uterus conserved in 56.5% cases. Maternal mortality was 10.2% (95% CI 5.2, 17.5) and perinatal mortality was 34.3% (95% CI 25.4, 44). When asked how they would manage such a case in the absence of life threatening circumstances in future, 80.8% of Fellows would opt for uterine repair. Fellows with previous hands-on experience of uterine rupture would involve urologists more often in operative management (22% v 8%, OR 3.4, 95% CI 1.2, 10.1). 48% of Fellows felt that in-patient management is indicated in subsequent pregnancies and 91% would perform an elective cesarean section in subsequent pregnancy.     

Phase behavior and oral bioavailability of amorphous Curcumin

Amorphous form has been used as a means to improve aqueous solubility and oral bioavailability of poorly water soluble drugs. The objective of present study was to characterize thermodynamic and kinetic parameters of amorphous form of Curcumin (CRM-A). CRM-A was found to be a good glass former with glass transition temperature (T(g)) of 342.64K and critical cooling rate below 1K/min. CRM-A had a moderate tendency of crystallization and exhibited Kauzmann temperature (T(KS)) of 294.23 K. CRM-A was found to be fragile in nature as determined by T(m)/T(g) (1.32), C(p)(1 iq):C(p)(glass) (1.22), strength parameter (D<10), fragility index (m>75), T(K)/T(g) (0.85), and T(g)-T(K) (48.41). Theoretically predicted aqueous solubility advantage of 43.15-folds, was reduced to 17-folds under practical conditions. This reduction in solubility was attributed to water induced devitrification, as evident through PXRD and SEM analysis. Further, oral bioavailability study of CRM-A was undertaken to investigate bioavailability benefits, if any. C(max) was improved by 1.97-folds (statistically significant difference over control). However, oral bioavailability (AUC(0-)(∞)) was improved by 1.45-folds (statistically non significant difference over control). These observations pointed towards role of rapid devitrification of CRM-A in GIT milieu, thus limiting its oral bioavailability advantage.     

Conservative versus surgical management of prolapse: what dictates patient choice?

Introduction and hypothesis  

The aim of this study is to establish whether the presence of severe symptoms influences women’s choice of pessaries or surgery for uterovaginal prolapse.