Calcitonin gene-related peptide in rat spinal cord motoneurons: subcellular distribution and changes induced by axotomy.

Using light and electron microscopy, a study has been made of the changes of calcitonin gene-related peptide-like immunoreactivity in rat lumbar spinal cord motoneurons during cell body response to sciatic nerve injury. At light microscopy level, calcitonin gene-related peptide-like immunoreactivity was evaluated using an indirect immunofluorescence technique combined with Fast Blue retrograde tracing and a peroxidase-antiperoxidase procedure. The calcitonin gene-related peptide changes to sciatic nerve transection and crushing were compared. Calcitonin gene-related peptide-like immunoreactivity was transiently increased after the peripheral nerve lesion, but the response was sustained for a longer period when the peripheral nerve was transected and nerve regeneration prevented. The first changes in calcitonin gene-related peptide-like immunoreactivity were detected four days after nerve crush or transection. In animal spinal cords to which nerve crush had been applied, the maximal enhancement of immunoreactivity was found 11 days after lesion. This was followed by a gradual decline, normal levels being attained 45 days after nerve crushing. When the nerve was transected, the response was similar, but the maximal calcitonin gene-related peptide-like immunoreactivity was maintained over a period of between 11 and 30 days. As with crushing, an important decrease was observed after 45 days. The ultrastructural compartmentation of calcitonin gene-related peptide-like immunoreactivity was studied using either peroxidase-antiperoxidase method or immunogold labelling. Calcitonin gene-related peptide-like immuno-reactivity was located in restricted sacs of the Golgi complex, multivesicular bodies, small vesicles and tubulo-vesicular structures. Large, strongly labelled vesicles resembling secretory granules were also observed in neuronal bodies. Our results reveal that the increase of calcitonin gene-related peptide in motoneurons is a relevant change the cell body undergoes in response to peripheral injury. The ultrastructural location of the peptide distribution suggests specific compartmentation on tubulo-vesicular structures connected with the Golgi complex which form a network in the neuronal cytoplasm. The distribution pattern observed may be related to the sorting and delivery of calcitonin gene-related peptide to secretory vesicles.     

Is there a benefit to adding rituximab to CHOP in the overall survival of patients with B-cell non-Hodgkin's lymphoma in a developing country?

Rituximab (R) has changed the prognosis of patients with non-Hodgkin's lymphoma (NHL) in developed countries, but its role has not been analyzed in underprivileged circumstances. One hundred and two patients with NHL treated in a developing country were analyzed: 28 patients with follicular lymphoma (FL) and 74 with diffuse large B-cell lymphoma (DLCL). Patients were treated upfront with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or R-CHOP; the decision to employ R depending solely on the ability of patients to defray it. In DLCL, 42 were given CHOP and 32 R-CHOP, whereas in FL, 19 were given CHOP and 9 R-CHOP. The impact of the addition of R was found to be clearer in FL than in DLCL. In patients with DLCL, the overall survival (OS) was 87% at 80 months for those treated with R-CHOP and 84% at 145 months for those treated with CHOP (not significant). In patients with FL, the OS was 89% at 88 months for those treated with R-CHOP and 71% at 92 months for those treated with CHOP (P = 0··05). In a multivariate analysis, other variables which were identified to be associated with the OS were IPI and number of cycles in DLCL. It is concluded that R produced a mild positive impact in the OS of patients with FL, but not in those with DLCL. Since the addition of R results in a 36-fold increase in treatment costs, these observations may be important to decide therapeutic approaches in NHL patients living in underprivileged circumstances.     

Anti-acetylcholine receptor antibodies induced in mice by syngeneic receptor without adjuvants.

Acetylcholine receptor (AChR)-bearing membranes from the BC3H-1 cell lines were injected, without adjuvant, either intrathymically (i.t.) followed by intraperitoneal (i.p.) booster doses, or i.p. alone, into (C57BL X BALB/c)F1 mice. Over 75% of the animals developed serum anti-AChRs which reacted with the cell-line AChR and with normal mouse endplate AChR. The titres were within the lower range of those of myasthenia gravis patients, and some mice showed reduced miniature endplate potential (m.e.p.p) amplitudes. these results indicate that loss of tolerance to acetylcholine receptors can result from immunization against syngeneic AChR without adjuvant. This approach may provide a useful model for studying mechanisms of autoimmunity against acetylcholine receptor.     

Prospective epidemiological study of invasiveHaemophilus influenzae disease in adults

The incidence and characteristics of invasiveHaemophilus influenzae disease were studied in 43 adult patients admitted to the acute care hospitals in El Vallés County (Barcelona, Spain) between January 1987 and June 1992. The annual incidence ofHaemophilus influenzae disease was 1.2 per 100,000 inhabitants. Pneumonia occurred in 24 patients, meningitis in five, intraabdominal infections in three, obstetric infections in two, epiglottitis in two and cellulitis in one. In six patients the source of infection was unknown. Ten (23 %) of the infections were hospital acquired. Underlying conditions were diagnosed in 30 (70 %) patients. NontypeableHaemophilus influenzae strains predominated in all adult age groups. Sixty-one percent of type b and 34 % of nontypeable strains were ampicillin resistant (p=0.08). Multiple antibiotic resistance was also high among type b (53 %) and nontypeable (18 %) strains. The mortality rate was significantly higher in patients with pneumonia, bactaeremia from an unidentified focus or shock at presentation.     

DNQX blockade of amphetamine behavioral sensitization

The role of the N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid (EAA) receptors in the mechanism of behavioral sensitization to amphetamine-induced sterotypy was investigated in mice. The results confirm previous observations that NMDA antagonists can block the induction of the phenomenon but not the expression; in contrast, DNQX, a non-NMDA receptor antagonist, can block both the induction and the expression of the sensitization. The differential effects of the two classes of antagonists suggest that the induction and the expression are the result of different mechanisms, both of which involve the EAA system. The DNQX results differ from those of haloperidol, which can also block both the induction and expression, because haloperidol can completely block the amphetamine-induced responses in naive and in sensitized animals; whereas DNQX is without effect on the amphetamine activity in naive animals and, in the sensitized animal, can block only that portion of the response that is derived from the sensitization phenomenon. The effects of the EAA antagonists support the hypothesis that the enhanced responsiveness in the sensitized animals is derived from the activation of EAA receptors, which, in turn, increases the release of dopamine in the striatum. Finally, the involvement of the non-NMDA receptors in the expression of the behavioral sensitization further substantiates the postulate that the amphetamine-induced sensitization is a behavioral manifestation of long-term potentiation (LTP).     

Diabetic ketoacidosis in adult patients: an audit of factors influencing time to normalisation of metabolic parameters

Background

Diabetic ketoacidosis (DKA) is an acute life‐threatening metabolic complication of diabetes that imposes substantial burden on our healthcare system. There is a paucity of published data in Australia assessing factors influencing time to resolution of DKA and length of stay (LOS).

Aims

To identify factors that predict a slower time to resolution of DKA in adults with diabetes.

Methods

Retrospective audit of patients admitted to St Vincent's Hospital Melbourne between 2010 to 2014 coded with a diagnosis of ‘Diabetic Ketoacidosis’. The primary outcome was time to resolution of DKA based on normalisation of biochemical markers. Episodes of DKA within the wider Victorian hospital network were also explored.

Results

Seventy‐one patients met biochemical criteria for DKA; median age 31 years (26–45 years), 59% were male and 23% had newly diagnosed diabetes. Insulin omission was the most common precipitant (42%). Median time to resolution of DKA was 11 h (6.5–16.5 h). Individual factors associated with slower resolution of DKA were lower admission pH (P < 0.001) and higher admission serum potassium level (P = 0.03). Median LOS was 3 days (2–5 days), compared to a Victorian state‐wide LOS of 2 days. Higher comorbidity scores were associated with longer LOS (P < 0.001).

Conclusions

Lower admission pH levels and higher admission serum potassium levels are independent predictors of slower time to resolution of DKA. This may assist to stratify patients with DKA using markers of severity to determine who may benefit from closer monitoring and to predict LOS.     

Guidelines of the Spanish Society of Cardiology for clinical practice in exercise testing

Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain.This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.     

Limited novel influenza A (H1N1) 09 infection in travelling high-school tour group

Please cite this paper as: Mardani et al. (2011) Limited novel influenza A (H1N1) 09 infection in travelling high‐school tour group. Influenza and Other Respiratory Viruses 5(1), 47–51. Background A single case of novel influenza A (H1N1) 09 infection was identified by PCR among a New Zealand high‐school group that toured California in April 2009. Close monitoring of the tour group and their New Zealand contacts identified 11 other tour members with respiratory symptoms who were investigated. In all nine instances where nasopharyngeal swabs were indicated, tests were negative for novel influenza A (H1N1) 09 by PCR. Objective To determine whether serology could identify any cases of novel influenza A (H1N1) 09 that had not been detected by PCR. Methods Acute and convalescent serological testing for antibodies against pandemic (H1N1) 2009 and seasonal A (H1N1) influenza viruses using haemagglutination inhibition assays and microneutralisation assays. Results Serological analysis of symptomatic tour members identified a further possible case of novel influenza A (H1N1) 09 infection. The possible case had not been tested by PCR because he or she had already received prophylaxis with oseltamivir. Conclusions These findings suggest infection among tour group members was limited despite prolonged periods of close contact during travel. Furthermore, multiple public health interventions are likely to have effectively prevented an outbreak following the tour group’s return.     

Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia

Elevated numbers of primitive Philadelphia chromosome-positive (Ph+) progenitors, including long-term culture-initiating cells (LTC-IC) as well as colony-forming cells (CFC), have been previously described in the blood of patients with chronic myeloid leukemia (CML) in chronic phase with high white blood cell counts. In the present study, which focused primarily on an analysis of circulating progenitors present in such patients at diagnosis, we discovered the frequent and occasionally exclusive presence of circulating normal (Ph-) LTC-IC, often at levels above those seen for LTC-IC in the blood of normal individuals. The presence of detectable numbers of circulating Ph- LTC-IC was independent of the fact that the same peripheral blood samples also contained elevated numbers of predominantly or exclusively Ph+ CFC. Interestingly, both the Ph+ and Ph- LTC-IC in these samples were CD34+CD71- and variably CD38- and Thy-1+, as previously documented for LTC-IC in normal marrow. Thus, neither CD38 nor Thy-1 expression was useful for discriminating between Ph+ and Ph- LTC-IC in mixed populations. Nevertheless, an association of these phenotypes with LTC- IC function did allow highly enriched (> 5% pure) suspensions of either Ph+ or Ph- LTC-IC to be obtained from selected samples of CML blood in which the initial LTC-IC population was either predominantly Ph+ or Ph- , respectively. These findings suggest that the mechanisms causing mobilization of leukemic stem cells in untreated CML patients may affect their normal counterparts. They also indicate a possible new source of autologous cells for the support of intensive therapy of CML patients. Finally, they provide a method for obtaining the most highly purified populations of Ph+ LTC-IC described to date. This method should be useful for further analyses of the molecular activities of these very primitive neoplastic cells.