Buprenorphine and midazolam act in combination to depress respiration in rats.

High dose buprenorphine is used as substitution treatment in human heroin addiction. Deaths have been reported in addicts using buprenorphine, frequently in association with benzodiazepines. In the current study, we observed the effects of buprenorphine and midazolam alone and in combination on arterial blood gases. Four groups of 10 male Sprague-Dawley rats received a parenteral injection of aqueous solvent, buprenorphine (30 mg/kg, iv), midazolam (160 mg/kg, ip), or buprenorphine (30 mg/kg, iv) plus midazolam (160 mg/kg, ip). Serial blood gases were obtained over 3 hours. There was a mild but significant effect of buprenorphine alone in comparison with the aqueous solvent on PaCO2 at 60 min (6.24 vs. 5.65 kPa, p< 0.01). There was also a mild but significant effect of midazolam alone in comparison with aqueous solvent on arterial pH at 90 min (7.33 vs. 7.41,p< 0.001) and PaCO2 at 60 min (6.52 vs. 5.65 kPa,p< 0.01). The combination of midazolam and buprenorphine produces a rapid, profound, and prolonged respiratory depression, as demonstrated by an increase in PaCO2 at 7.65 +/- 0.12 kPa at 20 min and a decrease in arterial pH at 7.25 +/- 0.02 at 20 min, with appearance of delayed hypoxia with a decrease in PaO2 at 8.74 +/- 0.20 kPa at 120 min. These data show that high doses of midazolam and buprenorphine alone have limited effects on arterial blood gases in rats while midazolam and buprenorphine appear to act in an additive or synergistic fashion to depress ventilation in rats.     

Hepatitis B, C seroprevalence and delta viruses in HIV-1 Senegalese patients at HAART initiation (retrospective study)

The aim of this study was to determine hepatitis co-infection in a cohort of HIV infected patients at their inclusion in the Senegalese Initiative of ART Access. B, C, and D Hepatitis viruses serological markers were checked retrospectively on 363 stored plasma. For HBV, the Abbott laboratories equipment IMx was used to detect HBs Ag and anti Core Ab on negative HBs Ag samples. For HDV, anti Delta Ab was performed using the Abbott Murex Kit on all HBs Ag positive samples. For HCV, anti HCV Ab was detected by IMx as double screening test and confirmed by INNO-LIA(TM) HCV Core of Innogenetics laboratories. The statistical analysis was done with STATA V8. The study population was composed of 164 men and 199 women aged between 16 and 66 years. The immune and virological markers averages at their enrollment were 154 cell/mm(3) for TLCD4+ (n = 355 patients) and 4.9 log for viral load (n = 277 patients). HBs Ag was found in 61 patients or 16.8% and the prevalence of anti-HBc Ab was 83.2% (252/295). 2 patients or 3% on HBs Ag positive sample presents HBV/HDV co-infection Ab anti HCV was detects in 6 patients or 1.6% after confirmation and 2 patients had triple infection with HBV. These results showed that the prevalence of HBV and HCV in the population of persons living with HIV/AIDS in Senegal is similar to that found in the general population. Our data indicated that hepatitis pathology in the PLwHIV was essentially due to HBV. Further studies are needed to diagnose occult hepatitis in order to set up therapeutic strategies taking into account co-infections by hepatitis viruses in the ART programmes.     

Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes

The cellular dynamics underlying activation of CD8+ T cells by dendritic cells (DCs) in the lymph node are not known. Here we have tracked the behavior of T cells and DCs by subjecting intact lymph nodes to real-time two-photon microscopy. We show that DCs scan at least 500 different T cells per hour in the absence of antigen. Antigen-bearing DCs are highly efficient in recruiting peptide-specific T cells and can engage more than ten T cells simultaneously. The duration of these interactions is of the order of hours, not minutes. The overall avidity of the interaction influences the probability that T cells will be stably captured by DCs, providing a possible basis for T cell competition. Taken together, our results identify the cellular behaviors that promote an efficient CD8+ T cell response in the lymph node.     

Epidermoid cyst of the cerebellar vermis: Case report of a rare medial topography

Intracranial epidermoid cysts are very rare benign tumors representing less than 2% of intracranial tumors. They are located preferentially in the cerebellopontine angles, parasellar, and temporal regions. We report here the case of an epidermoid cyst of very uncommon medial location in the cerebellar vermis, in a 61-year-old female patient complicated with tumor protrusion into the foramen magnum and active hydrocephalus.     

The family's experience of the child and/or teenager in palliative care: fluctuating between hope and hopelessness in a world changed by losses

OBJECTIVES:

to understand the family''s experience of the child and/or teenager in palliative care and building a representative theoretical model of the process experienced by the family.

METHODOLOGY:

for this purpose the Symbolic Interactionism and the Theory Based on Data were used. Fifteen families with kids and/or teenagers in palliative care were interviewed, and data were collected through semi-structured interviews.

RESULTS:

after the comparative analysis of the data, a substantive theory was formed "fluctuating between hope and hopelessness in a world changed by losses", composed by: "having a life shattered ", "managing the new condition", "recognizing the palliative care" and "relearning how to live". Hope, perseverance and spiritual beliefs are determining factors for the family to continue fighting for the life of their child in a context of uncertainty, anguish and suffering, due to the medical condition of the child. Along the way, the family redefines values and integrates palliative care in their lives.

CONCLUSION:

staying with the child at home is what was set and kept hope of dreaming about the recovery and support of the child''s life, but above all, what takes it away even though temporarily is the possibility of their child''s death when staying within the context of the family.     

Snake bites by the jararacucu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in Sao Paulo State, Brazil

The jararacucu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in Sao Paulo State, Brazil. We examined 29 cases of proven jararacucu bites recruited over a 20-year period in two Sao Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care- unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination.      

Dynamical malaria models reveal how immunity buffers effect of climate variability

Assessing the influence of climate on the incidence of Plasmodium falciparum malaria worldwide and how it might impact local malaria dynamics is complex and extrapolation to other settings or future times is controversial. This is especially true in the light of the particularities of the short- and long-term immune responses to infection. In sites of epidemic malaria transmission, it is widely accepted that climate plays an important role in driving malaria outbreaks. However, little is known about the role of climate in endemic settings where clinical immunity develops early in life. To disentangle these differences among high- and low-transmission settings we applied a dynamical model to two unique adjacent cohorts of mesoendemic seasonal and holoendemic perennial malaria transmission in Senegal followed for two decades, recording daily P. falciparum cases. As both cohorts are subject to similar meteorological conditions, we were able to analyze the relevance of different immunological mechanisms compared with climatic forcing in malaria transmission. Transmission was first modeled by using similarly unique datasets of entomological inoculation rate. A stochastic nonlinear human–mosquito model that includes rainfall and temperature covariates, drug treatment periods, and population variability is capable of simulating the complete dynamics of reported malaria cases for both villages. We found that under moderate transmission intensity climate is crucial; however, under high endemicity the development of clinical immunity buffers any effect of climate. Our models open the possibility of forecasting malaria from climate in endemic regions but only after accounting for the interaction between climate and immunity.Climate plays a key role in driving the seasonal outbreaks of malaria in areas of low or unstable malaria transmission (1–4). Recent studies have shown the possibility of forecasting malaria outbreaks on the basis of climate information and disease features in these low-transmission settings (3, 5). For instance, in highland malaria the role of warming temperatures is vividly debated (4, 6–8) and in desert-epidemic fringes early studies reported predictions of a widespread increase in malaria transmission (9–12). Recent malaria models also predict a global net increase of the population at risk (13); however, others suggest a shift in spatial distribution rather than a large net increase in total malaria incidence worldwide (14, 15). In epidemic fringes, variation in the incidence of disease is largely determined by the seasonal variation of the mosquito population’s occurrence and density, which are essentially modulated by local rainfall [e.g., if water limited (3, 16)] or temperature [e.g., if altitude limited (2, 4, 8)]. This is not the case in holoendemic transmission settings, where incidence of disease is determined not only by external forces, but also by the development of clinical and antiparasite immunity. Under intense transmission, clinical immunity develops during childhood after many infections (17, 18), whereby the individual can tolerate nonnegligible parasite densities without showing symptoms. Subsequently, antiparasite immunity, which enables control of parasite density, develops much more slowly (19), leading to a state of premunition, whereby individuals harbor chronic, potentially subpatent infections (20). Continued exposure to the parasite is seemingly required to maintain such premunition (21). Complete protection from further infections is rarely, if ever, achieved. In such high-transmission regions, the relationship between local climate and disease is difficult to disentangle.In this study, two unique long-term cohort datasets from villages separated by 5 km but with markedly different malaria transmission intensity (Fig. 1, Upper) enable us to showcase the relative roles of internal and external factors in malaria epidemiology, assess the potential degree of predictability emanating from climatic variability, and generate estimates of key parameters in determining malaria population dynamics. To this end, we use a recently developed inference methodology for nonlinear stochastic dynamical systems, successfully applied to epidemic dynamics (3, 16) but never applied to endemic settings. A general coupled mosquito–human compartment model that includes possible key mechanisms common to both villages serves our aim of disentangling differences related to immunity, infectivity, superinfection, and asymptomatic infections as well as to measure the relevance of local climate for each village.Open in a separate windowFig. 1.(Upper) P. falciparum malaria incidence for Dielmo (red) and Ndiop (green). Vertical dotted black lines separate the four different drug regimes (from left to right: Quinine, Chloroquine, Fansidar, and ACT). Incidence units are episodes per person per month. (Lower) Average annual cycles computed as the average month by month for the whole time series of P. falciparum monthly incidence for Dielmo (red) and Ndiop (green), local rainfall (blue), and temperature (orange). Shaded regions correspond to the SD.