Absence of Meissner corpuscles in the digital pads of mice lacking functional TrkB

The TrkB-expressing sensory neurons seem to be involved in touch and other discriminative sensibilities. Thus, several slowly and rapidly adapting cutaneous mechanoreceptors, as well as muscle spindles, are reduced or absent in the territory of the trigeminal nerve in functionally TrkB-deficient mice. Whether this also occurs in the cutaneous or muscular territories of dorsal root ganglia has not been analyzed. Here we used immunohistochemistry and transmission-electron microscopy to analyze the impact of a mutation in the gene coding for TrkB on Meissner and Pacinian corpuscles, and muscle spindles. The animals were studied at the post-natal days 15 and 25, because at this time all the mechanoreceptors examined are fully developed. Typical Meissner's corpuscles, displaying S-100 protein immunoreactivity, were found in the digital pads of wild-type and TrkB+/- mice whereas they were absent in the TrkB-/- animals. Regarding Pacinian corpuscles, the mutation in the trkB gene does not alter either the immunohistochemical or the ultrastructural characteristics. Finally, in muscle spindles the arrangement of the intrafusal muscle fibers and nerve fibers was unchanged in the mutated animals. Nevertheless, about 10% of muscle spindles showed increased number of the intrafusal cells (between 6 and 12) and were supplied by more than one large myelinic nerve fiber. The present results strongly suggest that TrkB-expressing sensory neurons in dorsal root ganglia, like those of the trigeminal ganglion, are responsible for the development and maintenance of several rapidly adapting cutaneous mechanoreceptors, i.e. Meissner's corpuscles.     

Phase II study of irinotecan (CPT-11) administered every 2 weeks as treatment for patients with colorectal cancer resistant to previous treatment with 5-fluorouracil-based therapies: comparison of two different dose schedules (250 and 200 mg/m2) according to toxicity prognostic factors

Our objective was to assess the antitumoral activity and toxicity of irinotecan (CPT-11) 60-min i.v. infusion every 2 weeks as second-line monotherapy of advanced colorectal cancer. Two doses were studied (250 and 200 mg/m) according to the risk of developing toxicity. Two groups of patients were studied: high-risk group (HR, 200 mg/m, n = 45; Karnofsky score 60-80% and/or the record of prior pelvic irradiation) and low-risk-group (LR, 250 mg/m, n = 51; Karnofsky score >80% and without prior pelvic irradiation). The mean number of cycles per patient was 7: 6.6 (HR group) and 8.3 (LR group). Median RDI was 0.96. The overall response rate was 8.9% [95% confidence interval (CI) 2.5-21.2%; HR group] and 15.7% (95% CI 7.0-28.5%; LR group), respectively. The LR group showed two complete responses and a higher percentage of stable disease (56.9 versus 33.3% in HR group). The median survival was 7.1 months (95% CI 5.2-8.9 months, HR group) and 11.7 months (95% CI 8.4-15.1 months, LR group). The median time to disease progression was 3.2 months (95% CI 1.0-5.4 months, HR group) and 5.3 months (95% CI 3.8-6.7 months, LR group). Both CPT-11 treatments were well tolerated. Grade 3/4 toxicity incidence was low, e.g. granulocytopenia (7% of patients in HR group and 9% in LR group) and delayed diarrhea (18% of patients in HR group and 14% in LR group). We conclude that the treatment of patients with the adjusted dose of CPT-11 according to prognostic factors for toxicity resulted in the improved toxicity profile, but showed poorer efficacy outcome. Therefore, the dose reduction in patients with low performance and treated with radiotherapy needs further investigation to provide some new insights on the benefit:risk ratio of such treatment.     

Purging behaviors and comorbidity as predictive factors of quality of life in anorexia nervosa

OBJECTIVE: This study examined the predictive factors for the physical and mental summary components (PCS and MCS) of quality of life (SF-36) in patients with anorexia nervosa. METHOD: Forty-seven patients with anorexia nervosa were studied. Assessment comprised psychiatric diagnosis by a clinical structured interview for Axis I disorders (SCID-I) and personality disorders (SCID-II), Clinical Global Impression (CGI), and Quality of Life (SF-36). RESULTS: Anorexia nervosa, restrictive type, was diagnosed in 73.9% of the patients and 51% of the patients presented with comorbidity on Axis I or Axis II or both. The predictive variables for the PCS were poor outcome in previous year, comorbidity on Axes I and II, and female gender. The predictive variables for the MCS were the presence of comorbidity in one or the other of the Axis I or II disorders and purging behaviors. DISCUSSION: The current study suggests the importance of comorbidity and purging behaviors in the quality of life of these patients with anorexia nervosa.     

Telomerase is frequently activated in tumors with microsatellite instability

Telomeres are specialized structures at the ends of eukaryotic chromosomes that are required for the complete replication and stability of naturally occurring chromosome ends. Telomere stabilization is critical for the unlimited cellular proliferation that is necessary for tumor formation. While most tumors achieve telomere stabilization through activation of telomerase, a subset of tumors utilize a recombination-based mechanism termed Alternative Lengthening of Telomeres (ALT) to maintain chromosome termini. Tumors utilizing ALT for telomere preservation will likely be refractory to treatment with telomerase inhibitors. Furthermore, tumors carrying mutations that predispose a cell to utilize ALT may activate this pathway when challenged by telomerase inhibition. Mutation of the mismatch repair (MMR) pathway enhances telomerase independent survival in yeast, with the survivors using recombination-based pathways for telomere maintenance. One possibility is that mutation of the MMR pathways alleviates suppression of recombination, thereby abrogating the need for telomerase activation. If true, one might predict an increased frequency of tumors harboring MMR mutation to use ALT for telomere maintenance. Here we characterized tumors with and without MMR mutation for the presence of telomerase activity versus ALT. We found similarly frequent activation of telomerase in tumors with and without MMR mutation, suggesting that human tumors with MMR mutation may respond favorably to treatment with telomerase inhibitors.     

Acquired and inherited thrombophilia in women with unexplained fetal losses

OBJECTIVE: The purpose of this study was to investigate the possible role of inherited and acquired thrombophilia in women with unexplained abortions and intrauterine fetal death. STUDY DESIGN: We included 75 women with >/=1 unexplained fetal loss, and 75 control subjects with at least 1 healthy term infant and without gestational complications. All of these women were tested for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; deficiencies of antithrombin-III, protein C, and protein S; and the presence of antiphospholipid antibodies and fasting homocysteine concentration. A placental histologic study was also carried out. RESULTS: Thirty-five percent of the 75 patients had thrombophilia (control subjects, 16%; P =.008; odds ratio, 2.78). This prevalence was more prominent in second and third trimesters (P =.0002; odds ratio, 6.3), and the presence of combined genetic defects was associated with intrauterine fetal death (P =.04; odds ratio, 12; 95% CI, 1.44-102). When we analyzed the overall gestations of the patients, we observed an increase of intrauterine fetal death in patients with thrombophilia (P =.01) and early pregnancy loss in patients without thrombophilia (P =.02). The analysis of the correlation between extensive placental infarctions and thrombophilic defects rendered values in the boundaries of significance (P =.05). CONCLUSION: The significant high prevalence of biologic causes in patients with late fetal loss suggests that a study of thrombophilia should be carried out, together with an assessment of a preventive treatment.     

Disparity in total hip replacement affecting Hispanic Medicare beneficiaries

OBJECTIVE: To compare the utilization of total hip replacement (THR) between Hispanic persons and non-Hispanic persons in a sample with health insurance. RESEARCH DESIGN: Case-control study using Medicare claims data. PATIENTS: The cases were Medicare beneficiaries from Arizona, Illinois, New Mexico, or Texas who underwent a primary THR. The controls were Medicare beneficiaries who did not receive a THR, matched by age, sex, and county of residence. MEASURES: Beneficiary surnames and the race indicator in Medicare records were used to classify beneficiaries' probability of being Hispanic. Conditional logistic regression was used to estimate the odds of receiving of THR, adjusting for Medicaid eligibility. RESULTS: Six thousand four hundred thirty-seven recipients of a primary THR were matched to 12,874 controls. According to the Medicare race indicator, 1% of recipients of THR and 3.3% of controls were Hispanic (P < or =0.001). The odds of THR decreased as the probability of Hispanic ethnicity increased, from an odds ratio (OR) of 1.00 among beneficiaries with non-Hispanic surnames, to an OR of 0.36 among those with heavily Hispanic surnames (95% CI, 0.31, 0.43). Poverty, as reflected by eligibility for Medicaid, did not modify the low odds of THR among Hispanic persons (OR, 0.25 among Medicaid-eligible Hispanic persons; 95% CI, 0.19, 0.33; and OR, 0.30 among Hispanic persons not Medicaid eligible; 95% CI, 0.24, 0.38). CONCLUSION: Hispanic persons with Medicare receive THR at lower rates than do non-Hispanic persons. Because Medicare covers THR, our findings suggest that under utilization of THR by Hispanic persons cannot be attributed to lack of health insurance alone.     

Portal vein thrombosis: an emergency solution for blood flow in liver transplantation

Recipient portal vein thrombosis in liver transplantation is a contingency that increases surgical difficulty as well as patient morbidity and mortality. The aim of this paper is to demonstrate a surgical technique for reconstruction of portal blood flow in emergency situations of portal vein thrombosis with inadequate blood flow and a poor vascular bed for re-vascularization.     

Molecular analysis of echovirus 13 isolates and aseptic meningitis,Spain

Echovirus 13 (EV13), considered rare, was reported worldwide in 2000, mostly related to aseptic meningitis outbreaks. In Spain, 135 EV13 isolates were identified. The genetic relationships between 64 representative strains from Spain and other reported isolates from the United States, Germany, Italy, Japan, and Sweden were described by analyzing the partial sequence of the major capsid protein (VP1) gene. The strains from Spain were clearly identified as EV13 (79.5% similarity with the EV13 reference strain) and were grouped phylogenetically into two different clusters (by origination on either the Iberian Peninsula or Canary Islands). Isolates from Germany from 2000 clustered with the Canary Islands group. The isolates from other countries obtained before 2000 were genetically distant. Changes in EV13 coding sequence involved several differences in the C-terminal extreme of the VP1 protein. Part of the neutralizing antigenic site III has been described in this genome region in poliovirus and swine vesicular disease virus.