11Effect of an immune stress on prolactin secretion in early pregnancy

Problem:  Stress in early pregnancy has been linked to increased abortion rates. Immune stress in early pregnancy inhibits progesterone secretion in mice. As prolactin both mediates implantation and drives progesterone secretion, we hypothesised that stress would decrease prolactin secretion in early pregnancy.
Material and Methods:  Lipopolysaccharide (LPS; 12.5μg intraperitoneally) as an immune stress or vehicle were administered to day 5.5 early pregnant and virgin c57/Bl6J mice. They were killed by decapitation 60, 120 or 240 min later and trunk blood was collected and analysed for prolactin concentration (ELISA); corticosterone was also analysed (RIA).
Results:  LPS significantly decreased prolactin concentration in early pregnancy (P<0.001, 2-way ANOVA); however, there was no significant difference in the virgin groups. In contrast, LPS significantly elevated corticosterone concentration in all groups (P<0.001, 2-way ANOVA), confirming activation of the hypothalamo-pituitary-adrenal stress axis.
Conclusions:  Stress decreased prolactin secretion during early pregnancy, and might explain stress-disrupted implantation and progesterone secretion.     

InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers

BackgroundThere is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences.Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries.MethodsThis is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months.ResultsA total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %).Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments.ConclusionsThere is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.     

A national study of the availability and use of electrophysical agents by Australian physiotherapists

Electrophysical agents (EPAs) are a core part of physiotherapy practice and entry level education. With the increase in the number of EPAs over time, their availability and use in contemporary physiotherapy practice is an important consideration when determining entry level curricula. Thus, the aim of the study was to ascertain the current availability and usage of EPAs in Australian physiotherapy practice. A purpose-designed questionnaire was mailed to all registered physiotherapists in Australia. A response rate of 27% was obtained (n=3,538). Nonresponder analyses indicated that the results were representative of the total population of Australian physiotherapists. Over 70% of respondents had access to ultrasound, cold packs/ice, heat packs, electrical stimulation for sensory stimulation, and interferential therapy. Two main groups of EPAs were used relatively frequently. The first group was used daily or monthly by 60% of respondents (ultrasound, hot packs, and cold packs/ice), and a second group (electromyographic and pressure biofeedback, interferential therapy, and electrical stimulation for sensory stimulation) was used on a daily or monthly basis by between 30% and 45% of the sample. A group of EPAs, including ultraviolet light, microwave, and shortwave diathermy, was not used by over 90% of the sample. The study has provided contemporary national data on EPA availability and use in Australia.     

Trisomy 21 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study (8602)

Of 1,036 children with newly diagnosed non-T, non-B acute lymphoblastic leukemia (ALL) and a demonstrated cytogenetic abnormality treated on the frontline Pediatric Oncology Group (POG) therapeutic trial 8602, there were 33 patients with trisomy 21 as the sole abnormality. Of these 33, 14 had Down syndrome (DS). Although the non-DS (NDS) trisomy 21 cases tended to be older than the DS cases, there were no other significant differences in clinicobiologic features nor in treatment outcomes between the DS and NDS groups, nor between the entire trisomy 21 group and the other chromosome abnormality group. Among NDS patients with +21 and one additional abnormality, +X, +16, -20, and structural abnormalities involving 6q or 12p were common findings. Kaplan-Meier event-free survival (EFS) curves showed a 4-year EFS of 80% (SE, 12%) in NDS trisomy 21 cases, 71% (SE, 22%) in DS cases with trisomy 21 as the sole abnormality, and 69% (SE, 2%) in cases with other chromosome abnormalities. Trisomy 21 as a sole acquired abnormality in NDS patients suggests a good prognosis.     

Unusual deletions within the immunoglobulin heavy-chain locus in acute leukemias

We have investigated the structure of the Ig heavy (IGH) chain locus in 309 cases of acute leukemia. Seventy-one cases of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) were analyzed: in six cases deletion of joining (JH) segments in the presence of cytogenetically normal chromosome 14 was observed. Similar deletions were seen in 1 out of 8 cases of biphenotypic acute leukemia analyzed: this case exhibited t(9:22)(q34;q11) and coexpressed both myeloid and B cell differentiation antigens. Five of the 7 cases analyzed had deleted the JH segments from both chromosomes. Because these deletions may have contributed to the pathogenesis of the disease we have attempted to define their boundaries. Using probes that map both 5' and 3' of JH, the 3' (centromeric) boundary of the deletions was mapped to an approximately 30-kb central region of the 60 kb between C delta and C gamma 3 in 10 of the 12 deleted chromosomes. In the remaining two chromosomes, the 3' boundary mapped to S mu. The 5' (telomeric) boundary could not be defined. However, three cases with biallelic deletion of JH showed biallelic deletion of the most proximal variable (VH) (VH6 and VH5-B2) genes, indicating that the deletions spanned over 500 kb. VH5-B1 and VH5-B3 were retained in germline configuration and no gross deletions were observed using a VH3 subgroup-specific probe, indicating that the 5' boundary mapped within the VH locus. Unusual deletions of the portion of the IgH locus including JH segments and the C mu and C delta genes may occur in acute leukemias with immunophenotypic evidence of commitment to the B cell differentiation pathway. The possible consequences of the deletions remain to be determined. However, the clustering of the centromeric boundary of the deletions to S mu and to a region between the C delta-C gamma 3 genes, a known "hot spot" for recombination, may indicate the operation of a distinct pathogenic mechanism.     

Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia: retention of IRF1 on the 5q- chromosome in some patients with the 5q- syndrome

Acquired interstitial deletions of the long arm of chromosome 5 occur frequently in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Recently IRF1, a putative tumor suppressor gene localized to the long arm of chromosome 5, has been shown to be deleted from the 5q- chromosome in a group of patients with MDS and AML. It has been suggested that the loss of IRF1 may be critical to the development of the 5q- syndrome. We have investigated the allelic loss of IRF1 in a group of 12 patients with MDS and a 5q deletion and 2 patients with AML and a 5q deletion. Gene dosage experiments demonstrated that 12 of 14 patients had loss of one allele of the IRF1 gene but no evidence of homozygous loss and that 2 patients with 5q- syndrome retained both copies of the gene. The retention of IRF1 on the 5q- chromosome in these two cases has been confirmed by fluorescent in situ hybridization localization using an IRF1 cosmid. Pulsed field gel electrophoresis was used to determine whether there was any evidence for structural rearrangement in the region encompassing the IRF1 gene in these two patients. No aberrant bands were detected with a range of rare cutter enzyme digests. We conclude that IRF1 maps outside the commonly deleted segment of the 5q- chromosome and that loss of IRF1 is not solely responsible for the development of the 5q- syndrome.