Quantitative studies on the postnatal growth of the spinal cord and the vertebral column of the albino mouse

The rate of growth of the various regions of the spinal cord and the vertebral column of the albino mouse aged, 1, 10, 20, 30 and 120 days was studied. It was found that:

• (1) There is more rapid growth in the length of the vertebral column than that of the spinal cord. The lower regions of the vertebral column grow more rapidly than the upper regions but the reverse was found in the spinal cord resulting in regression of the spinal cord. The cord ends at one day opposite the fifth sacral vertebra and then receded to the fifth lumbar vertebra till 120 days.
• (2) The white matter has a more rapid rate of growth in volume than the gray matter. So the process of myelination and the growth of the fibers in diameter exceed the rate of growth of the neurons and their dendrites.
• (3) The packing density of the neurons is nearly the same in all regions of the cord with the exception of the cervical region which showed less packing density due to more branching of their dendrites.
• (4) The total number of neurons at each region is fixed from birth till maturity. The thoracic region contains the highest number of neurons followed by the cervical then the lumbar and the least number is in the sacral region.

     

Long-term controlled immortalization of a primate hepatic progenitor cell line after Simian virus 40 T-Antigen gene transfer

Hepatoblasts are bipotent progenitors of both hepatocytes and cholangiocytes. The lack of stable in vitro culture systems for such cells makes it necessary to generate liver progenitor cell lines by means of immortalization. In this study, we describe the long-term behaviour of a clone of simian foetal hepatic progenitor cells immortalized by Simian virus 40 (SV40) large T-antigen (T-Ag) flanked by loxP sites. Immortalization was associated with the re-expression of telomerase activity, which decreased at late passages (population doubling 120) after more than a year in culture. This decrease was concomitant to telomere shortening and karyotypic instability. However, the chromosomes carrying the p53 gene remained intact and long-term immortalized progenitor cells maintained contact inhibition and proliferative properties. They also displayed the features of a normal bipotent phenotype. We constructed a retroviral vector expressing an inducible Cre recombinase and transferred it into the immortalized progenitors. Activation of the Cre recombinase by 4-hydroxy-tamoxifen induced SV40 T-Ag excision, leading to the death of cells expressing Cre recombinase. Immortalized progenitors at late passages stopped growing and eventually disappeared after transplantation into the livers of immunocompromised mice. These cells provide a novel model to study hepatic differentiation and carcinogenesis.     

The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene

Several tyrosine kinase genes are involved in chromosomal translocations in chronic myeloproliferative disorders, but there are still uncharacterized translocations in some cases. We report two such cases corresponding to atypical chronic myeloid leukaemia with a t(8;9)(p22;p24) translocation. By fluorescence in situ hybridisation (FISH) on the corresponding metaphases with a bacterial artificial chromosome probe encompassing the janus kinase 2 (JAK2) gene at 9p24, we observed a split for both patients, suggesting that this gene was rearranged. The locus at 8p22 contains different candidate genes including the pericentriolar material 1 gene (PCM1), already implicated in reciprocal translocations. The rearrangement of the PCM1 gene was demonstrated by FISH, for both patients. By RT-PCR, we confirmed the fusion of 3' part of JAK2 with the 5' part of PCM1. Sequence analysis of the chimeric PCM1-JAK2 mRNA suggests that the putative protein displays the coiled-coil domains of PCM1 and the tyrosine kinase domain of JAK2. This new translocation identifies JAK2 as a possible therapeutic target for compounds with anti-tyrosine kinase activity.     

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.     

Evaluation of peracetic acid permeation during flash sterilization through pharmaceutical plastic polymers used in cytotoxic reconstitution units

Peracetic acid (PAA) permeation in flash sterilization was studied using three different plastic infusion bags made of polypropylene and polyethylene, filled with glucose 5% or NaCl 0.9%. The pH was measured and acetic acid (AA) and PAA concentrations were made by reverse phase high-performance liquid chromatography (RP-HPLC). PAA was derivatized by oxidation of methyl tolyl sulfide (MTS) into methyl tolyl sulfoxide (MTSO) detected by ultraviolet (UV) absorbance at 230 nm. The technique has a sensitivity of 0.3 microg x L(-1) and was highly specific. Results showed that pH measurements remain constant and demonstrated the absence of PAA permeation, which was confirmed by the absence of AA permeation regardless of the brand tested, with both unwrapped and overwrapped infusion bags, when flash sterilization is applied. These results allow flash sterilization to be performed with unwrapped infusion bags without any risk of drug degradation by PAA. This makes compounding safer and easier, which improves productivity.     

Adolescent substance-use assessment: methodological issues in the use of the ADAD (Adolescent Drug Abuse Diagnosis)

During the past twenty years, various instruments have been developed for the assessment of substance use in adolescents, mainly in the United States. However, few of them have been adapted to, and validated in, French-speaking populations. Consequently, although increasing alcohol and drug use among teenagers has become a major concern, the various health and social programs developed in response to this specific problem have received little attention with regard to follow-up and outcome assessment. A standardized multidimensional assessment instrument adapted for adolescents is needed to assess the individual needs of adolescents and assign them to the most appropriate treatment setting, to provide a single measurement within and across health and social systems, and to conduct treatment outcome evaluations. Moreover, having an available instrument makes it possible to develop longitudinal and trans-cultural research studies. For this reason, a French version of the Adolescent Drug Abuse Diagnosis (ADAD) was developed and validated at the University Child and Adolescent Psychiatric Clinic in Lausanne, Switzerland. This paper aims to discuss the methodological issues that we faced when using the ADAD instrument in a 4-year longitudinal study including adolescent substance users. Methodological aspects relating to the content and format of the instrument, the assessment administration and the statistical analyses are discussed.     

Causes of syncope in patients with Alzheimer's disease treated with donepezil

INTRODUCTION: Treatment of Alzheimer's disease (AD) with cholinesterase inhibitors carries a theoretical risk of precipitating bradycardia. Though syncope occurs in patients with AD, its aetiology is unclear. The aim of this study was to determine the causes of syncope in patients with AD who were treated with donepezil and hospitalised for evaluation of syncope. METHODS: We studied 16 consecutive patients (12 women, 4 men) with AD aged 80 +/- 4 years who were hospitalised for evaluation of syncope. All patients underwent staged evaluation, ranging from physical examination to electrophysiological testing. RESULTS: The mean dose of donepezil administered was 7.8 mg/day, and the mean duration of donepezil treatment at the time of syncope was 12 +/- 8 months. A cause of syncope was identified in 69% of patients. Carotid sinus syndrome was observed in three patients, complete atrioventricular block in two patients, sinus node dysfunction in two patients, severe orthostatic hypotension in two patients and paroxysmal atrial fibrillation in one patient. A brain tumour was discovered in one patient. No cause of syncope was found in 31% of patients despite comprehensive investigation. Repetition of the investigations after discontinuation of donepezil was noncontributory. CONCLUSION: In patients with AD treated with donepezil, a noninvasive evaluation identified a probable cause of syncope in over two-thirds of patients. Cardiovascular abnormalities were predominant. Noninvasive evaluation is recommended before discontinuing treatment with cholinesterase inhibitors in patients with AD and unexplained syncope.     

Cost-benefit analysis of vaccination against tick-borne encephalitis among French troops

BACKGROUND: French troops are exposed to tick-borne encephalitis (TBE) during their tours of duty in the Balkans. This disease, potentially serious because of its lethality and morbidity, has an effective vaccination. The epidemiological characteristics of TBE in the Balkans are not well known. OBJECTIVE: In order to provide the French Department of Defence with arguments on the utility of vaccinating troops on missions in this area of Europe, we conducted a cost-benefit study. DESIGN AND SETTING: Through a decision analysis, we estimated the net benefit of a three-injection vaccination programme for all French military personnel in the Balkans versus no vaccination during a period from 2004 to 2014. We used a review of the literature to estimate the parameters necessary for the present study: the disease's morbidity and death incidence rate; the disease's sequelae; and the adverse effects of the vaccination. The initial hypothesis of the seroconversion rate of TBE in the Balkans was 834 per 100,000 person-years. Human life was valued in Euro (year 2004 values) by calculating the amounts paid by the French Department of Defence to military personnel in case of disabling sequelae and to their heirs in case of death. MAIN RESULTS: The net benefit was negative: -5.68 million Euro. The vaccination programme's cost was 10.05 million Euro. 121 cases of TBE could be prevented by this vaccination; however, the sensitivity analysis showed that the results are closely related to the incidence of the disease. CONCLUSION: Very high incidence rates of TBE were initially hypothesised compared with what has actually been reported. As a result, the vaccination programme against TBE for French military personnel should not be implemented unless the objective of the armed forces is to prevent all cases of TBE and they are willing to assume the cost of doing so.