Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. METHODS: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The kappa statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. RESULTS: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The kappa statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The kappa statistic for the margins of the EMR specimens was 0.80 (excellent agreement). CONCLUSIONS: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign-appearing lesions.     

Surgical management of massive cerebellar infarction.

Massive cerebellar infarction accounts for less than 2% of strokes. Unlike massive hemispherical infarctions, in pure cerebellar infarctions, the prognosis is better. This case report discusses, a 61 year old lady who presented with atrial fibrillation and a massive cerebellar infarction. Timely surgical intervention reversed the deterioration in neurological status. The indications for surgical management, based on review of the literature, is presented.     

Interaction of fluoxetine with the human placental serotonin transporter

The interaction of fluoxetine, a non-tricyclic antidepressant, with the human placental serotonin transporter was investigated by studying its influence on [3H]paroxetine binding to the transporter and on [3H]serotonin uptake via the transporter. These studies were done using brush-border membrane vesicles purified from normal term human placentas. Fluoxetine inhibited binding of paroxetine to the membrane vesicles in a concentration-dependent manner, with a Ki value of 3 nM. Kinetic analysis revealed that the inhibition was competitive because the presence of 10 nM fluoxetine increased the Kd for paroxetine from 72 to 461 pM, but had no effect on the Bmax. Fluoxetine also caused a time-dependent dissociation of paroxetine already bound to the transporter. The dissociation followed first-order kinetics. Uptake of serotonin in these membrane vesicles was also inhibited by fluoxetine. The inhibition was concentration dependent with a Ki value of 66 nM at pH 7.5 and 80 nM at pH 6.5. The effect of fluoxetine on the uptake kinetics was to increase the apparent dissociation constant (Kt) for serotonin without influencing the maximal transport capacity (Vmax). The results demonstrate that fluoxetine is a high-affinity ligand and a potent inhibitor of the serotonin transporter found in the human placental brush-border membrane.     

Voltage-dependent priming of rat vanilloid receptor: effects of agonist and protein kinase C activation

The responses of vanilloid receptor (VR) channels to changing membrane potential were studied in Xenopus oocytes and rat dorsal root ganglion (DRG) neurons. In oocytes, capsaicin-evoked VR currents increased instantaneously upon a step depolarization and thereafter rose biexponentially with time constants of ≈20 and 1000 ms. Similarly, upon repolarization the current abruptly decreased, followed by a biexponential decay with time constants of ≈4 and 200 ms. Qualitatively similar effects were observed in single channel recordings of native VR channels from DRG neurons and with endogenous VR activators, including heat (43 °C), H⁺, anandamide and protein kinase C (PKC). The magnitude of the time-dependent current rise increased with membrane depolarization. This effect was accompanied by an increase in the relative proportion of the fast kinetic component, A ₁. In contrast, the time constants of the activation and deactivation processes were not strongly voltage dependent. Increasing the agonist concentration both reduced the magnitude of the current rise and increased its overall rate, without significantly altering the deactivation rate. In contrast, PKC both speeded the current rise and slowed its decay. These results suggest that voltage interacts with agonists in a synergistic manner to augment VR current and this mechanism will be enhanced under conditions of inflammation when VRs are likely to be phosphorylated.     

Effect of Solanum trilobatum on hepatic drug metabolising enzymes during diethylnitrosamine-induced hepatocarcinogenesis promoted by Phenobarbital in rat

The present study was aimed to investigate the chemopreventive effects of Solanum trilobatum (ST) extract against diethylnitrosamine (DEN)-induced hepatocarcinogenesis promoted by Phenobarbital (PB) in Wistar rats. Hepatocarcinogenesis was initiated by a single intraperitoneal injection of DEN (200 mg/kg b.w.) and promoted with PB (0.05%) in basal diet. The experimental study extended for periods of 13 and 26 weeks. Alcoholic extract of ST was orally administered for the entire experimental period after initiation along with commencement of promotion. The chemopreventive effect of ST was assessed from the incidence of nodules, drug metabolizing phase I components such as contents of cytochrome P450, cytochrome b(5), activities of NADPH cytochrome c reductase, NADH - cytochrome b(5) reductase and phase II components such as levels of glutathione, activities of UDP-glucuronyl transferase, glutathione S-transferase and gamma-glutamyl transpeptidase in the liver. Lipid peroxidation at basal and prooxidants-induced (NADPH + ADP + Fe and Ascorbate + Fe) states was assessed in the microsomes. Animals administered with ST extract evidenced significant inhibition of tumor nodular incidence in DEN + PB + ST animals compared to DEN + PB animals, with favorable alterations in the hepatic drug-metabolizing phase I and phase II components. Administration of ST inhibited basal and pro-oxidant-induced lipid peroxidation. The present result suggests the probable mediation of chemoprevention by ST against DEN-induced carcinogenesis by the modulation of drug metabolizing components in the liver of treated animals.     

Analysis of the butyrylcholinesterase gene and nearby chromosome 3 markers in Alzheimer disease

The K-variant of butyrylcholinesterase (BCHE-K) recently has been reported to be associated with Alzheimer disease (AD) in carriers of the epsilon4 allele of the apolipoprotein E (APOE) gene. We have re- examined the frequency of the BCHE-K allele in a large data set of both sporadic and familial cases of AD disease, and we have also examined the segregation of three genetic markers on chromosome 3 near BCHE . Our data neither support an association of BCHE-K with sporadic or familial AD, nor do they suggest the existence of another gene nearby on chromosome 3 as a common cause of familial AD.      

Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency

Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of carnitine. CDSP may present with acute metabolic derangement simulating Reye's syndrome within the first 2 years of life. After 3 years of age, patients with CDSP may present with cardiomyopathy and muscle weakness. A linkage with D5S436 in 5q was reported in a family. A recently cloned homologue of the organic cation transporter, OCTN2, which has sodium-dependent carnitine uptake properties, was also mapped to the same locus. We screened for mutation in OCTN2 in a confirmed CDSP family. One truncating mutation (Trp132Stop) and one missense mutation (Pro478Leu) of OCTN2 were identified together with two silent polymorphisms. Expression of the mutant cDNAs revealed virtually no uptake activity for both mutations. Our data indicate that mutations in OCTN2 are responsible for CDSP. Identification of the underlying gene in this disease will allow rapid detection of carriers and postnatal diagnosis of affected patients.     

Interaction between a live avian pneumovirus vaccine and two different Newcastle disease virus vaccines in broiler chickens with maternal antibodies to Newcastle disease virus.

Broiler chicks with maternal antibodies to Newcastle disease virus (NDV) but none to avian metapneumovirus (APV) were divided into six groups. One group was kept as an unvaccinated control group. Three of the other groups were vaccinated at 1 day old with live APV vaccine or one of two live NDV vaccines (VG/GA or HB1). The remaining two groups received the APV vaccine in combination with either of the two NDV vaccines at 1 day old. At intervals after vaccination for up to 42 days, distribution of the viruses in the tissues was monitored, together with humoral antibody responses. Few NDV isolations were made from any NDV-vaccinated chicks, probably due to the presence of NDV maternal antibodies. In both dual-vaccinated groups, APV persisted longer (up to 21 days post vaccination (d.p.v.)) than in the single vaccinates (up to 14 d.p.v.). After 14 d.p.v., antibody titres against APV in both dual-vaccinated groups remained higher than the single APV vaccinates. For NDV haemagglutination inhibition antibodies, similar titres were found in the single and dual NDV VG/GA vaccinates. However, for chickens dually vaccinated with NDV HB1 and APV, the haemagglutination inhibition titres were significantly higher at 21 and 28 d.p.v. than the single HB1 vaccinates. These differences reflect the fact that NDV haemagglutination inhibition titres may depend on the NDV vaccine used.