[CHANGE IN BCL-2 PROTEIN EXPRESSION IN NEURONS OF THE HIPPOCAMPAL AREAS AFTER THE APPLICATION OF ISCHEMIC CEREBRAL POSTCONDITIONING].

Bcl-2 protein expression was studied in hippocampal CA1, CA2, CA3 and CA4 pyramidal neurons in Mongolian gerbils (Meriones unguiculatus), of the in in the early (Day 2) and late (Day 7) reperfusion period after a 7-minute forebrain ischemia and following ischemic postconditioning (IPostC), as well as in sham-operated animals (n=60). In the latter, the highest level, of Bcl-2-expression was found in CA4 neurons, while the lowest--in-CA1 neurons (P<0.01). Reversible ischemic brain damage led to the increasing deficit of morphologically unchanged hippocampal neurons with the increasing duration of reperfusion period. This was accompanied by a significant decrease in expression of Bcl-2 in the early reperfusion period, but in the late reperfu- sion period this decrease largely disappeared. IPostC, applied as three episodes of ischemia-reperfusion lasting 15/15 seconds, contributed to significant increase in the number of morphologically unchanged CA1 and CA3 neurons in the early reperfusion period, while the expression of Bel-2 was increased in morphologically unchanged neurons in all the hippocampal areas. In the late reperfusion period after IPostC, the number of unchanged neurons was increased in hippocampal areas CA1, CA3 and CA4 (P<0.05), while a significant increase in Bcl-2 expression (by 12.7%, P<0.01) was detected only in CA1 neurons. The results suggest that the cytoprotective effect of IPostC in hippocampal CA1 area is realized through a mechanism leading to increased expression of Bcl-2 protein, i.e., by blocking apoptosis.

Whole-body MRI with diffusion-weighted sequences compared with 18 FDG PET-CT, CT and superficial lymph node ultrasonography in the staging of advanced cutaneous melanoma: a prospective study.

OBJECTIVES: The aim of our study was to compare the diagnostic performances of non-radiating whole-body magnetic resonance imaging (wbMRI), either volumetric, with Volumetric interpolated breath-hold examination (VIBE) or metabolic, with diffusion-weighted sequences (wbMRI), with classical irradiating techniques such as PET-CT, CT and with lymph node ultrasonography (US) for the staging of advanced melanoma. PATIENTS AND METHODS: Thirty-seven melanoma AJCC stage IV patients were prospectively included. All images were independently interpreted without prior knowledge of the results of studies performed with concurrent techniques, and all imaging techniques were scheduled within a mean interval of 7 days. The overall and site-specific diagnosis performances of each imaging modality were studied, as well as the interest of combined MRI VIBE and diffusion sequences. RESULTS: The number of visceral or lymph node metastases spotted was, respectively, 218, with 125 metastases for wbMRI, 191/103 for PET-CT, 209/115 for CT and 33/13 for lymph node US. No statistically significant difference (P < 0.05) of overall diagnostic performances between wbMRI (Se 84%, Sp 87.1%, PPV 89.8%, NPV 80.2%) and PET-CT (Se 79.8%, Sp 93.1%, PPV 93.2%, NPV 79.4%) was observed. No statistically significant difference was found between wbMRI and PET-CT with two channels for CT with respect to different metastatic sites. Compared with the CT, wbMRI had significantly better overall specificity (P = 0.0011) and PPV (P = 0.02). For lung exploration, sensitivity of wbMRI (51.6%) was inferior to CT (71.4%). To detect superficial metastatic lymph nodes, wbMRI and US both showed high diagnostic accuracy with no statistically significant difference. Intra-observer agreement was almost perfect for all imaging modalities considering the overall staging. Inter-observer agreement for wbMRI and diffusion alone was almost perfect except for bone and lymphatic sites. Overall diagnostic performance of diffusion alone was significantly inferior to those of combined VIBE and diffusion sequences. CONCLUSIONS: Whole-body MRI, using diffusion weighted sequences, was a reliable non-radiating imaging for staging of melanoma and offers the same diagnostic performances than combined CT, PET-CT and lymph node US.

Management of abdominal emergencies in adults using telemedicine and artificial intelligence.

The terms "telemedicine" and "artificial intelligence" (AI) are used today throughout all fields of medicine, with varying degrees of relevance. If telemedicine corresponds to practices currently being developed to supply a high quality response to medical provider shortages in the general provision of healthcare and to specific regional challenges. Through the possibilities of "scalability" and the "augmented physician" that it has helped to create, AI may also constitute a revolution in our practices. In the management of surgical emergencies, abdominal pain is one of the most frequent complaints of patients who present for emergency consultation, and up to 20% of patients prove to have an organic lesion that will require surgical management. In view of the very large number of patients concerned, the variety of clinical presentations, the potential seriousness of the etiological pathology that sometimes involves a life-threatening prognosis, healthcare workers responsible for these patients have logically been led to regularly rely on imaging examinations, which remain the critical key to subsequent management. Therefore, it is not surprising that articles have been published in recent years concerning the potential contributions of telemedicine (and teleradiology) to the diagnostic management of these patients, and also concerning the contribution of AI (albeit still in its infancy) to aid in diagnosis and treatment, including surgery. This review article presents the existing data and proposes a collaborative vision of an optimized patient pathway, giving medical meaning to the use of these tools.

Primary aorto-enteric fistula: a rare complication of abdominal aortic aneurysm.

A 70-year-old lady presented with recurrent gastrointestinal bleeding and septicemia caused by multiple enteric pathogens. She was diagnosed to have primary aorto-enteric fistula (PAEF) complicating abdominal aortic aneurysm. Endovascular aneurysm repair was carried out that arrested gastrointestinal bleeding, but despite prolonged antibiotic therapy the patient died a month later of probable sepsis. PAEF refers to abnormal communication between the aorta and the intestine resulting from disease at either site; this rare condition should be suspected in patients with abdominal aortic aneurysm who present with unexplained life-threatening gastrointestinal bleeding. Computerized tomography is the most sensitive investigation. Presence of ectopic gas adjacent to or within the aorta and of contrast within the gastrointestinal tract is the pathognomonic finding. Definitive treatment consists of surgical intervention, but it is associated with high risk in the acute setting. Endovascular therapy using stent-grafts is safe and effective in arresting gastrointestinal bleeding. However, it is frequently associated with recurrent sepsis even with continued antibiotic therapy, and should be considered as a bridge to more definitive surgical repair at a later time, after optimization of the patient's condition.

Aspirin resistance in Indian patients with coronary artery disease and cardiovascular events.

BACKGROUND: Aspirin resistance is a major problem and its incidence and clinical significance in Indian patients with documented coronary artery disease are not known. AIM: We sought to study the incidence of aspirin resistance and its clinical significance in a cohort of Indian patients with coronary heart disease on therapy with aspirin using urinary 11-Dehydrothromboxane B2 levels as a surrogate marker for antiplatelet efficacy. SETTING AND DESIGN: Non randomized single center prospective study in cohort of patients with stable cardiovascular disease on chronic aspirin therapy attending the cardiology outpatient clinic of a tertiary care hospital. MATERIALS AND METHODS: Urinary dehydrothromboxane levels were analyzed in a cohort of 63 patients with stable documented coronary artery disease and in 21 healthy volunteers. The cases were followed up prospectively for a median period of 36 (1-53) months. The clinical endpoint was a composite of acute coronary syndrome, stroke, revascularization and death. STATISTICAL ANALYSIS: Comparison of urinary dehydrothromboxane concentration values between various risk factors was done using Mann Whitney U test, a non parametric alternative of independent t test. All statistical analyses were done using SPSS 11.0 (Chicago, USA) software. RESULTS: The median (range) absolute values of urinary11- dehydrothromboxane B2 levels for the healthy volunteers and cases were 440 (286-2050) pg/ml and 320 (72-2600) pg/ml (P=0.007). The corresponding normalized values were 87.3 (43-143) and 60.8 (16.7-943) ng/mmol of creatinine (P=0.131). Among the various vascular risk factors, patients who were overweight had higher absolute levels of 11- urinary dehydrothomboxane B2 levels (P=0.016). There were significantly more clinical events in patients with absolute urinary 11-dehydrothromboxane B2 levels in the upper two quartiles compared to the lower two quartiles (P=0.04). CONCLUSION: The incidence of aspirin resistance in the cohort of patients with documented heart disease was 38.1%. Patients with elevated absolute urinary dehydrothomboxane levels (>320 pg/ml) on chronic aspirin therapy constitute a high risk subset for recurrent vascular events.

Molecular evidence for the first records of facultative parthenogenesis in elapid snakes.

Parthenogenesis is a form of asexual reproduction by which embryos develop from unfertilized eggs. Parthenogenesis occurs in reptiles; however, it is not yet known to occur in the widespread elapid snakes (Elapidae), which include well-known taxa such as cobras, mambas, taipans and sea snakes. Here, we describe the production of viable parthenogens in two species of Australo-Papuan elapids with divergent reproductive modes: the oviparous coastal/Papuan taipan (Oxyuranus scutellatus) and the viviparous southern death adder (Acanthophis antarcticus). Analyses of nuclear SNP data excluded paternity for putative fathers and convincingly demonstrated asexual reproduction, thus representing the first evidence of facultative parthenogenesis in Elapidae. Our finding has broad implications for understanding the evolution of reproductive diversity in snakes, as well as managing the conservation of genetic diversity in wild and captive populations.

Predicting susceptibility and incubation time of human-to-human transmission of vCJD.

BACKGROUND: Identification of possible transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion has caused concern over spread of the disease within the human population. We aimed to model iatrogenic spread to enable a comparison of transmission efficiencies of vCJD and bovine spongiform encephalopathy (BSE) and an assessment of the effect of the codon-129 polymorphism on human susceptibility. METHODS: Mice were produced to express human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene. Since the human PrP gene has variation at codon 129, with MM, VV, and MV genotypes, three inbred lines with an identical genetic background were produced to express human PrP with the codon-129 MM, MV, and VV genotypes. Mice were inoculated with BSE or vCJD and assessed for clinical and pathological signs of disease. FINDINGS: BSE was transmitted to the bovine line but did not transmit to the human lines. By contrast, vCJD was transmitted to all three human lines with different pathological characteristics for each genotype and a gradation of transmission efficiency from MM to MV to VV. INTERPRETATION: Transmission of BSE to human beings is probably restricted by the presence of a significant species barrier. However, there seems to be a substantially reduced barrier for human-to-human transmission of vCJD. Moreover, all individuals, irrespective of codon-129 genotype, could be susceptible to secondary transmission of vCJD through routes such as blood transfusion. A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public-health issue.

The birth bed: A qualitative study on the views of midwives regarding the use of the bed in the birth space.

BACKGROUND: There is a growing body of evidence to show that the birth environment can influence women's experiences of labour and birth as well as midwifery practice. A common feature of the modern birth space is the bed. Knowledge about how the use of the bed shapes clinicians' perceptions and attitudes is limited. AIM: The aim of this paper is to describe midwives' perceptions of the birth bed. METHOD: Qualitative descriptive design. Fourteen midwives from one Queensland maternity unit participated in digitally recorded and transcribed interviews. Thematic analysis was used to analyse the data set. FINDINGS: Four themes were identified. The first, described beliefs that using the bed formed part of women's childbirth expectations. A second theme, captured midwives' perceptions that the bed was also an object required to safely undertake their work. The third theme described how others commonly worked to ensure the woman stayed off the bed. Lastly, there was evidence that whilst wanting to avoid the use of the bed, some were reluctant, fearing potential reprimand. CONCLUSION: The themes highlight differences in how the midwives conceptualised the use of a bed within a birth space. While some avoided the use of the bed altogether others would only conceive of women moving off the bed if everything was 'normal'. How the bed was culturally constructed appeared to dictate clinical practice. Reflecting on the meaning of an object, such as the bed, is important if clinicians are to fully understand how the birth environment influences their practice and thus women's experiences of labour and birth.

Precise deletions in large bacterial genomes by vector-mediated excision (VEX). The trfA gene of promiscuous plasmid RK2 is essential for replication in several gram-negative hosts.

We have developed a simple and efficient method of vector-mediated excision (VEX) for in vivo generation of precisely defined deletions in large bacterial genomes. The system uses homologous recombination with small cloned fragments on specialized pVEX plasmids to insert directly repeated bacteriophage P1 loxP sites at positions flanking the region to be deleted. In the presence of Cre recombinase, the loxP sites are efficiently recombined to produce the deletion. Deletion endpoints can be directed to specific nucleotides because they are defined by the termini of small homology-bearing fragments cloned into the pVEX plasmids. We have used VEX to delete trfA, the only known replication initiator gene of the 56.4 kb broad host-range plasmid RK2. The RK2 delta trfA mutant was found to be conjugation proficient, but unable to replicate in the RK2 hosts Acinetobacter calcoaceticus, Caulobacter crescentus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas putida, Rhizobium meliloti, or Rhodobacter sphaeroides. These results show that trfA is essential for replication in these hosts and indicate that the broad host-range of RK2 does not involve multiple replicons.

Herbivory differentially affects male and female reproductive traits of Cucumis sativus.

Herbivory is an important selection pressure in the life history of plants. Most studies use seed or fruit production as an indication of plant fitness, but the impact of herbivory on male reproductive success is usually ignored. It is possible that plants compensate for resources lost to herbivory by shifting the allocation from seed production to pollen production and export, or vice versa. This study examined the impact of herbivory by Helix aspersa on both male and female reproductive traits of a monoecious plant, Cucumis sativus. The effects of herbivory on the relative allocation to male and female flowers were assessed through measurements of the number and size of flowers of both sexes, and the amount of pollinator visitation. We performed two glasshouse experiments; the first looked at the impact of three levels of pre-flowering herbivory, and the second looked at four levels of herbivory after the plants had started to flower. We found that herbivory during the flowering phase led to a significant increase in the number of plants without male flowers. As a consequence there was significantly less pollen export from this population, as estimated by movement of a pollen analog. The size of female flowers was reduced by severe herbivory, but there was no affect on pollen receipt by the female flowers of damaged plants. The decrease in allocation to male function after severe herbivory may be adaptive when male reproductive success is very unpredictable.

Induction of sister-chromatid exchanges in human lymphocytes and Chinese hamster cells exposed to aflatoxin B1 and N-methyl-N-nitrosourea.

The effect of a 1-h exposure to aflatoxin B1 (AFB1) in inducing sister-chromatid exchange in Chinese hamster ovary (CHO) cells and human lymphocytes in the presence or absence of mixed function oxidase ("S9 mix") was compared. CHO cells were also exposed to a graded series of doses of N-methyl-N-nitrosourea, a powerful inducer of SCE whose action was independent of the presence or absence of S9 mix. CHO and human cells showed a close correlation in response to SCE induction by AFB1 and in both cell systems the additon of mixed function oxidases in the S9 mix resulted in a marked enhancement of action of AFB1.

The Colorado Newborn Hearing Screening Project: effects on speech and language development for children with hearing loss.

OBJECTIVE: To compare the speech and language development of children with bilateral hearing loss and normal cognition who were born in hospitals with universal newborn hearing screening to that of their peers who were born in hospitals without this screening program. STUDY DESIGN: Subjects for the major analyses are 50 Colorado children (25 matched pairs) from 9 to 61 months old who are participants in a study of the development of children birth to six with bilateral hearing loss. Analyses included parametric dependent t-tests and analysis of covariance, nonparametric chi-squared and Wilcoxon signed rank tests, descriptive statistics and odds ratios. RESULTS: Newborn screening programs for hearing loss are positively related to scores in expressive and receptive language (p < 0.001) and vocabulary production (p < 0.001) on standardized inventories; speech intelligibility (p = 0.015) from independent ratings; number of different simple consonants (p < 0.01) and consonant blends (p = 0.026) from phonological transcripts; and total number of intelligible words (p < 0.01) and number of different words produced (p < 0.01) from computer analysis of videotaped language samples. CONCLUSION: Hospital-based newborn hearing screening programs are positively related to language and speech performance for children in early intervention programs who are deaf and hard of hearing.

Universal newborn hearing screening with automated auditory brainstem response: a multisite investigation.

OBJECTIVE: The purpose of the study was to assess the feasibility of performing universal newborn hearing screening in different clinical settings and tracking the infants who did not pass initial screening through their confirmatory testing. STUDY DESIGN: Between December 1996 and December 1997, a total of 11,711 infants were enrolled from five clinically different study sites. Universal newborn hearing screening was performed using automated auditory brainstem response (AABR) testing. Infants who did not pass the initial screening were tested again prior to discharge. Data regarding the rate of referral for follow-up testing, age of infant at screening, the duration of time required for screening, and type of personnel performing the test were collected. Formal audiology appointments were made prior to discharge for infants who required follow-up testing, and letters were sent with phone calls made to those who failed to keep their appointments for repeat testing. Outpatient testing consisted of a repeat AABR and, if necessary, a diagnostic auditory brainstem-evoked response, otoacoustic emission testing, and tympanometry. RESULTS: At the time of hospital discharge, the refer rate was < 2% (215 of 11,711 newborns) using AABR screening. Sensorineural hearing loss (SNHL) was confirmed in 32 of these infants, resulting in an overall incidence of confirmed SNHL of 2.7 per thousand newborns. The false-positive rate ranged from 0.3% to 2.5%, with a cumulative false-positive rate of 0.9% (1.5% if all infants lost to follow-up are included as false-positives). No false-negatives were identified. The average time of testing was 7.1 minutes independent of the personnel performing the testing and the age of testing was < 24 hours in 70% of the infants tested. The total number of infants lost to follow-up was 61 (29% of patients referred or 0.5% of the study population). CONCLUSION: This study demonstrated that the refer rate for universal hearing screening with the AABR was acceptably low when performed by a variety of personnel in typical nursery settings within the first 24 hours after birth. A low rate of screening failures with the AABR minimizes costs associated with subsequent follow-up assessments and lessens any potential impact of false-positive screening on the parent-newborn relationship.

The Marion Downs National Center for Infant Hearing: developing comprehensive state systems.

The Marion Downs National Center for Infant Hearing was established in 1996 through a Maternal and Child Health Grant awarded to the University of Colorado. The goals of the grant are to implement statewide systems of newborn hearing screening, audiologic assessment, and early intervention in 19 states. Newborn hearing screening alone will not assure early identification or positive outcomes for the development of communication and language. Therefore, the staff at the Marion Downs National Center developed comprehensive goals for all participating states. These goals are described in this article.

Breastfeeding and mothering one-handed.

This case study describes how a mother with a congenital below-elbow limb absence manages breastfeeding and child care. Information for the case study was gained from direct observation, detailed interviews, and the subject's written reflections. Literature review revealed that, worldwide, many women have upper limb deficiencies. Such deficits may occur congenitally from teratogens or other causes, or they may occur as a result of disease or trauma. In spite of recent technological advances, prostheses are restricted in their efficiency and are not frequently used. Support from others is a critical factor in enabling those with limb deficiencies to achieve an optimal quality of life, including during childbearing and childrearing. No published data to assist breastfeeding mothers with limb deficiencies was revealed. Specific practices are mentioned that promote self-confidence and capability with breastfeeding and fulfilling children's needs.

Superinfection of focal liver lesions after bile duct procedures.

OBJECTIVES: Pyogenic liver abscess is a rare condition in the general population. The source of infection is most often biliary, and more rarely gastrointestinal via the portal tract, or even hematogenic. Other than in special contexts (scarring after radiofrequency ablation), focal liver lesions are not a usual risk factor for hepatic abscesses in patients with a history of bile duct procedures (sphincterotomy, biliary stenting, biliary enteric anastomosis). MATERIALS AND METHOD - RESULTS: We report four cases of focal liver lesions (two patients with benign lesions of the biliary cyst type and two other patients with lesions due to pancreatic cancer) complicated by a superinfection in patients with a history of bile duct procedures. There were no predisposing factors other than a context of cancer or diabetes. CONCLUSION: Superinfection of a focal liver lesion should be considered when there is a suggestive clinical picture and a change in the appearance of the lesion in patients with a history of bile duct procedures in a context of cancer or diabetes.

[Diagnosis of cardiac amyloidosis using magnetic resonance imaging: a new reliable, non-invasive technique to be validated]. / Diagnostic de l'amylose cardiaque par imagerie par résonnance magnétique nucléaire : une nouvelle méthode fiable, non invasive, en cours de validation.

INTRODUCTION: Amyloidosis is characterised by extracellular tissue deposition of insoluble fibrillar protein in various organs. Cardiac involvement is associated with the worse prognosis and the main cause of death. It needs a prompt diagnosis, which could be sometimes difficult to obtain. Endomyocardial biopsy remains the gold standard diagnostic technique, but recent studies on cardiac magnetic resonance imaging (MRI) indicate that this imaging procedure may be useful to the diagnosis of amyloidosis. CASE REPORTS: We report three patients with systemic amyloidosis who underwent cardiac MRI for the diagnosis or the follow-up of their disease. In addition to poorly specific signs of restrictive cardiomyopathy, cardiac MRI showed, after gadolinium enhancement that was considered characteristic of amyloidosis. CONCLUSION: Cardiac MRI is a useful diagnostic tool in cardiac amyloidosis, as it was shown in recent studies. Compared to endomyocardial biopsy it is a non-invasive technique that is now more readily accessible and that seems to have an acceptable specificity.

[Diabetes and hypokinetic cardiopathy : when to consider mitochondrial disease?]. / Diabète et cardiopathie hypokinétique, quand évoquer une cytopathie mitochondriale ?

The association between diabetes mellitus and hypokinetic cardiomyopathy is frequent. We report a case of diabetes and hypokinetic cardiopathy in a 40-year-old man which led to the hypothesis of maternally inherited diabetes and deafness (MIDD) due to a mitochondrial disease. This diagnosis was confirmed by genetic testing which showed a DNA A3243G mutation in the mitochondria, the prevalence of which is 1-2% in diabetes mellitus. Cardiac abnormalities are frequent (18-34% of patients depending on the series) and the co-existence of left ventricular hypertrophy and systolic dysfunction is suggestive of this disease. Some authors have proposed co-enzyme Q as a treatment to improve the left ventricular ejection fraction and insulin secretion.