Pharmacokinetics of amitriptyline and its demethylated metabolite in serum and specific brain regions of rats after acute and chronic administration of amitriptyline

The concentrations of amitriptyline (AMT) and its demethylated metabolite nortriptyline (NRT) in the serum and in specific brain regions were determined periodically after acute or chronic administration of 20 mg/kg of AMT in rats. Both AMT and NRT declined from the serum in a biexponential manner and were eliminated monoexponentially from the brain regions, with no significant difference in elimination among the eight brain regions examined. In the brain, both AMT and NRT were unevenly distributed after chronic administration, whereas an even distribution was observed after acute administration. The AUCbrain:AUCserum ratio of AMT was higher than that of NRT, indicating greater transport of AMT into the brain regions. The AUCAMT value in the serum increased 1.6 times after chronic administration, whereas no significant changes were observed in the brain regions. The AUCNRT values increased 9.0 times in the serum and 6.8 times in the brain, with the increase in the serum being greater. These results suggest inhibited distribution of the drugs into the tissues, including the brain regions, and enhanced metabolism of AMT.     

Growth fractions of transitional cell carcinomas of the bladder defined by the monoclonal antibody Ki-67

We used an immunohistochemical technique with the monoclonal antibody Ki-67, which recognizes nuclear antigen expressed in proliferating cells to determine the growth fractions of 5 normal mucosa specimens and 55 transitional cell carcinomas of the bladder. Normal mucosa had a mean value of 0.37 +/- 0.35% cells positive for Ki-67, whereas 9 histological grade 1 tumors showed 2.2 +/- 1.5%, 31 grade 2 tumors averaged 10.1 +/- 7.5% and 15 grade 3 tumors yielded 19.5 +/- 9.0%. These values were significantly different from each other (p less than 0.01), with Ki-67 indexes for grade 2 varying from 0.3 to 24.6%. Nonpapillary tumors had significantly higher indexes than papillary tumors (20.1 +/- 8.0 versus 6.7 +/- 5.9, p less than 0.01). The Ki-67 indexes were 4.6 +/- 4.5% for stage Ta (20 cases), 7.8 +/- 4.7% for stage T1 (14) and 20.2 +/- 7.8% for stages equal to or higher than T2 (21). Significant differences were noted between stages Ta and T1 (p less than 0.05) and between stages T1 and T2 or greater (p less than 0.01). Tumors with muscle layer invasion often showed more than 15% Ki-67 positive cells. Our results imply that Ki-67 indexes not only provide objective information to determine a malignant potential but also help to select the treatment.     

Diagnosis and characterization of non-Hodgkin's lymphoma in a patient with acute renal failure

This case illustrates the relatively rare occurrence of malignant lymphoma presenting as acute renal failure due to renal parenchymal infiltration. To our knowledge, it is the first report in which the phenotype of a non-Hodgkin's lymphoma was established using renal biopsy tissue. The dangers of treatment of renal lymphoma in the patient whose disease has not been adequately characterized have been noted by Coggins.     

IgG Anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in guillain-barré syndrome

To investigate the pathophysiological role of anti-GM1 antibody in Gullain-Barre syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patientsrpar;, or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathopsiological mechanisms in IgG anti-GM1)positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.     

Elective cesarean as a risk factor for transfusion after delivery of twins

We examined deliveries of twins to identify factors most strongly associated with an increased risk of transfusion. We reviewed the obstetric records of 511 twin deliveries at the Japanese Red Cross Katsushika Maternity Hospital from 2003 through 2007. After 18 (3.5%) of these deliveries, transfusions were required. Transfusion was significantly more likely after elective cesarean delivery at a gestational aged of 37 weeks or more (odds ratio, 4.85; 95% confidence interval, 1.87-12.61). Emergency cesarean delivery (at > or =37 weeks' gestation) was not associated with an increased risk of transfusion. The delivery mode of twins should be carefully considered because of the increased risk of transfusion after elective cesarean delivery at a gestational age of 37 weeks or more.     

Polymers containing stable free radicals, 6. Reactions of 2,4,6-triphenyl-3,4-dihydro-s-tetrazin-1 (2H)-yl (1,3,5-triphenylverdazyl) with organometallic compounds

2,4,6-Triphenyl-3,4-dihydro-s-tetrazin-1(2H)-yl ( 1 ) (1,3,5-triphenylverdazyl) was allowed to react with ethyl- and butyllithium, ethyl-, isopropyl-, and butylmagnesium bromide, as well as benzylmagnesium chloride to give the coupling products 2a–d . These results indicate that structures corresponding to 2 are present in the polymers resulting from vinyl monomers containing the verdazyl structure, if they are initiated with alkyllithium or a Grignard reagent. A reaction mechanism is discussed.