Are hip hemiarthroplasty and total hip arthroplasty infections different entities? The importance of hip fractures.

Hip hemiarthroplasty (HHA) and total hip arthroplasty (THA) infections are usually considered as one entity; however, they may show important differences. We analyze these differences, as well as predictors of treatment failure (TF) and poor functional status among patients with prosthetic hip infections (PHIs). A multicenter cohort study of consecutive patients with PHIs was performed. The main outcome variable was TF after the first surgical treatment performed to treat the infection. Multivariate analysis was used to identify predictors of TF. A total of 127 patients with PHI were included (43 HHA, 84 THA). Patients with HHA infections were more frequently women (88% vs. 54%; p < 0.001), had comorbidities (86% vs. 67%, p = 0.02), and were older (median age 79 vs. 65 years, p < 0.001), and the reason for arthroplasty was more frequently a fracture (100% vs. 18%, p < 0.001). Failure of initial treatment and crude mortality were more frequent among HHA patients (44% vs. 23%, p = 0.01 and 28% vs. 7%, p = 0.001, respectively). However, HHA was not associated with TF in the multivariate analysis when hip fracture was considered; thus, variables independently associated with TF were hip fracture, inadequate surgical management, prosthesis retention, and higher C-reactive protein level. Failure of the first surgical treatment was associated with poorer functional status. HHA and THA infections showed significant differences in epidemiology, clinical features, and outcome. Although patients with HHA infections had a higher risk of TF, this was related to the reason for hip implant: a hip fracture. Success of the initial management of infection is a predictor of better clinical and functional outcome.

Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis. / Evaluación prospectiva del perfil emético y la eficacia analgésica del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la apendicitis aguda pediátrica.

BACKGROUND: Literature comparing different alternatives for pain control in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce. MATERIALS AND METHODS: We prospectively compared the analgesic and emetogenic profile of intravenous ibuprofen and metamizole in the immediate postoperative period of PAA. For this purpose, we used a sample of patients operated on in 2021 in our center. Participants were recruited on arrival at the Emergency Department and histopathological confirmation of the diagnosis was obtained in all of them. Pain was evaluated every 8 hours after the surgery with validated visual analog scales ranging from 0 to 10 points. Repeated measures ANOVA was used to compare the evolution of pain in the 48 hours after surgery between the two groups. RESULTS: The sample included 95 patients (65% males) with a mean age of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen (group 1) and 54 with metamizole (group 2). No significant differences were found in the level of pain either in the comparisons of point measurements or in its evolution in the 48 hours after surgery (p= 0.58). After adjusting for the received fluid therapy, children in the metamizole group had significantly more emetic episodes and needed significantly more doses of ondansetron. CONCLUSIONS: In our cohort, ibuprofen had a similar analgesic efficacy and a better emetogenic profile than metamizole in the immediate postoperative period of PAA. Future prospective, adequately controlled studies with larger sample sizes are needed to validate these findings.

INTRODUCCION: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor en el postoperatorio inmediato de la apendicitis aguda pediátrica (AAP). MATERIAL Y METODOS: Comparación prospectiva del perfil analgésico y emético del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la AAP, para lo cual se recurre a una muestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndose confirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía mediante escalas analógicas visuales validadas, con valoraciones entre los 0 y los 10 puntos. Se realizó un ANOVA de las medidas repetidas entre los dos grupos para comparar la evolución del dolor en las 48 horas posteriores a la cirugía. RESULTADOS: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT: 3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 con metamizol (grupo 2). No se hallaron diferencias significativas en lo que respecta al dolor, ni en las comparaciones de las mediciones puntuales, ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Una vez realizado el ajuste correspondiente a la terapia de fluidos recibida, los niños del grupo metamizol tuvieron significativamente más episodios eméticos y necesitaron significativamente más dosis de ondansetrón. CONCLUSIONES: En nuestra cohorte, el ibuprofeno tuvo una eficacia analgésica similar y un mejor perfil emético que el metamizol en el postoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudios prospectivos, adecuadamente controlados y con mayor tamaño muestral que validen estos hallazgos.

[Comparison between VAMA(®) and Berman(®) cannulas for fibroscopic orotracheal intubation in anaesthetised patients]. / Comparación de las cánulas VAMA(®) y Berman(®) para la intubación fibroscópica orotraqueal en pacientes anestesiados.

OBJECTIVES: In fibroscopic intubation, the fact of achieving a direct view in real time does not guarantee the correct advance of the endotracheal tube (ET) to its intratracheal position. The use of oral cannulas helps in achieving a free airway in order to pass the fibroscope and the ET. This study compares the VAMA(®) (V) and Berman(®) (B) cannulas as regards the time required for the intubation, fibroscopic view, and the ease in positioning the ET. PATIENTS AND METHODS: 90 patients with no signs of difficult airway were randomised into 2 groups, Berman(®) (B) and VAMA(®) (V), depending on the type of cannula employed. After inducing general anaesthesia, they were intubated using a flexible fibroscope. The fibroscope and intubation times were recorded, as well as the quality of the fibroscopic view, and the level of difficulty in positioning the ET. RESULTS: No statistically significant differences were observed between the cannulas, although the intubation time (P=.292) and the difficulty found in positioning the ET were slightly less (P=.447) in the VAMA(®) group compared to the Berman(®) group. The vision quality was good with both devices, with only some degree of obstruction being encountered in only 22% of the patients. In no case was there complete obstruction, thus all the patients could be intubated correctly. CONCLUSIONS: The VAMA(®) cannula is an effective alternative to the classic cannulas for fibreoptic assisted intubation. Furthermore, the novel design provides advantages for the correct orientation of the fiberscope and the withdrawal of the cannula after intubation.

Acute Carbon Monoxide Poisoning in a Filipino Household: A Case Report.

There are multiple reports already regarding acute carbon monoxide (CO) poisoning in the Philippines secondary to the misuse of portable generators, especially during times of typhoons. We present a case of unintentional carbon monoxide poisoning in a Filipino household wherein our index patient is among the five members who were unconscious before they were rushed to the hospital. Three of the household members, on the other hand, were found dead. The index patient had an increased serum fraction percentage of carboxyhemoglobin level and presented with rhabdomyolysis during admission. Neuroimaging confirmed a hypoxic-ischemic encephalopathy secondary to carbon monoxide intoxication. Even without hyperbaric oxygen therapy, the patient improved with adequate hydration, early rehabilitation, and trauma-focused psychotherapy.

Reinforcement learning for patient-specific optimal stenting of intracranial aneurysms.

Developing new capabilities to predict the risk of intracranial aneurysm rupture and to improve treatment outcomes in the follow-up of endovascular repair is of tremendous medical and societal interest, both to support decision-making and assessment of treatment options by medical doctors, and to improve the life quality and expectancy of patients. This study aims at identifying and characterizing novel flow-deviator stent devices through a high-fidelity computational framework that combines state-of-the-art numerical methods to accurately describe the mechanical exchanges between the blood flow, the aneurysm, and the flow-deviator and deep reinforcement learning algorithms to identify a new stent concepts enabling patient-specific treatment via accurate adjustment of the functional parameters in the implanted state.

Single free anterolateral thigh flap for simultaneous reconstruction of composite hypopharyngeal and external neck skin defect after head and neck cancer ablation.

Single flap for complex hypopharyngoesophageal and anterior neck skin defect reconstruction is still a challenge for reconstructive surgeons. Herein, we present five patients, with advanced hypopharyngeal cancer and anterior neck skin invasion, which received a single anterolateral thigh (ALT) fasciocutaneous flap for composite inner pharyngeal and outer skin defect reconstruction after wide composite resection. Two ALT flaps were divided into two distinct paddles supplied by two or more separate perforators, one part for reconstructing the inner pharyngeal defect and another for neck skin coverage. Three ALT flaps only supplied by one sizable perforator could not be divided and de-epithelization of mid-part had to be done to reconstruct both defects with the single flap. The results revealed survival of all flaps. There were no flap loss, fistulas, or bleeding complications. All patients recovered uneventfully and could eat a soft diet to regular diet postoperatively. In conclusion, one-staged reconstruction of complex pharyngoesophageal and external skin defects after extensive oncological resection is feasible using a single ALT fasciocutaneous free flap.

MC3T3-E1 cell response to microporous tantalum oxide surfaces enriched with Ca, P and Mg.

The formation of a porous oxide surface doped with osteoconductive elements, Ca, P and Mg, to enhance osseointegration, was achieved through micro arc oxidation. Micro arc oxidation parameters, such as electrolyte composition, concentration and applied voltage, were studied to understand their effect on the morphology and chemical composition of the samples surface. Considering the optimum atomic concentration reported in literature for each osteoconductive element, microporous Ta anodic oxide samples treated with calcium acetate (CaA) and ß-glycerophosphate (ß-GP) revealed that an increase of ß-GP molarity in the electrolyte boosts Ca incorporation, as well as, increasing the porosity. In adding magnesium acetate (MgA) to the electrolyte, when composed by CaA + ß-GP, both addition and variation of MgA did not affect the surface morphology along the samples, being incorporated into the oxide layer for 0.1 M. Finally, in vitro tests were carried out to study the biocompatibility of Ta, to verify the cytotoxicity of the samples and their behavior towards cells, by performing adhesion and differentiation tests with the MC3T3-E1 cell line. Cytotoxicity tests revealed that the samples were non-toxic. Despite none of the samples having been raised up through cell adhesion tests, cell differentiation revealed promising results for the Ta-CaP.

The effect of daily repeated sedation using ketamine or ketamine combined with medetomidine on physiology and anesthetic characteristics in rhesus macaques.

BACKGROUND: Non-human primates are frequently sedated to permit handling that can alter physiological values. The purpose of this study was to identify the effects of daily serial sedation using ketamine (K) or ketamine combined with medetomidine (KM). We hypothesized KM would reduce observed effects of repeated sedation. METHODS: Eight rhesus macaques were anesthetized for three consecutive days. Physiological data were recorded daily at 5-minute intervals. Time intervals from injection to ataxia, recumbency, first movement and recovery were recorded. Depth of anesthesia was evaluated. RESULTS: Data showed an 11.7% increased heart rate at 5 minutes between the first and third day of injection with K and 17.9% with KM. Time from injection to ataxia increased 13.7% with K and 14.3% with KM. Time to recumbency increased 34.7% with K and 37.1% with KM. CONCLUSION: These findings demonstrate repeated anesthesia with ketamine can initiate changes suggesting a tolerance effect.

Effects of serial anesthesia using ketamine or ketamine/medetomidine on hematology and serum biochemistry values in rhesus macaques (Macaca mulatta).

BACKGROUND: This study aimed at determining the cumulative effect of daily anesthesia, using two drug regimens, over hematological and biochemical parameters. METHODS: Blood samples were obtained from rhesus monkeys 20 minutes after intramuscular administration of ketamine or ketamine/medetomidine combination for three consecutive days and results were evaluated to determine their effect on hematological and serum biochemistry values. Statistical significance of drug, day, and interaction of these two variables were evaluated. RESULTS: Drug effect resulted in a dramatic increase of aspartate aminotransferase and creatine kinase values. Day effect resulted in decreases of RBC, HCT, Hgb, and alkaline phosphatase but an increase of other biochemical parameters evaluated. The drug/day interaction effect was found to be -significant for RBC, platelets, aspartate aminotransferase, alanine aminotransferase, and creatine kinase values. CONCLUSION: The results of our study suggest a cumulative effect of serial anesthesia and should be an important consideration when interpreting hematology and serum biochemistry in rhesus macaques.

Sublingual immunotherapy in peach allergy: monitoring molecular sensitizations and reactivity to apple fruit and Platanus pollen.

BACKGROUND: Peach allergy is prevalent, persistent, and potentially severe and as such is a target for immunotherapy. Our aims were to evaluate the profile of sensitization to Rosaceae allergens and the effects of sublingual peach immunotherapy on immunoglobulin (Ig) E levels to these allergens, to monitor for neosensitizations, and to check if this treatment modified other Rosaceae fruit and pollen-related sensitizations. METHODS: A double-blind placebo-controlled trial was conducted on 56 peach-allergic patients who received, sublingually, a standardized peach extract quantified in mass units of Pru p 3, or placebo for 6 months. IgE to recombinant (r) Mal d 1, rMal d 4, rPru p 3, and natural (n) Art v 3 and skin prick test (SPT) reactivity to Platanus pollen and apple extracts evaluated before treatment (T0), after 1 month (T1) and after and 6 months (T6) were recorded. RESULTS: In total, 18.5% of patients recognized rMal d 1, 83.3%, rPru p 3, 24.1%, rMal d 4, and 25.9% nArt v 3. IgE to Pru p 3 rose from T0 to T1 in both the active group (P = .003) and the placebo group (P = .022), and remained elevated at T6 in the active group (P = .001). IgE to other purified allergens did not change significantly and no relevant neosensitizations were detected. SPT reactions to peach decreased from T0 to T6 in the active group (P < 0.05). Reactivity to peach (T1 and T6) and apple (T6) was lower in the active group than in the control group. CONCLUSIONS: The main allergen was Pru p 3. Changes in rPru p 3 IgE levels and in peach and apple extract SPT were induced by sublingual immunotherapy.

Structure, morphology, adhesion and in vitro biological evaluation of antibacterial multi-layer HA-Ag/SiO2/TiN/Ti coatings obtained by RF magnetron sputtering for biomedical applications.

Biocompatible and antibacterial multi-layer coatings of hydroxyapatite (HA)-Ag/SiO2/TiN/Ti were obtained on the Ti-6Al-4V alloy, by means of the magnetron sputtering technique. During characterization of the coatings, the chemical composition was evaluated by energy dispersive X-ray spectroscopy and the phase analysis was carried out by X-ray diffraction. The morphology of the coatings was observed by field emission scanning electron microscopy, while transmission electron microscopy was used to appreciate their structure. The adhesion of the coatings to the substrate was evaluated by micro scratch test. The in vitro biological response was evaluated in terms of cytotoxicity, adhesion and differentiation of mouse mesenchymal stem cells, as well as adhesion and bacterial viability of Staphylococcus aureus strain. Through the compositional study carried out, the deposition of the HA phase was verified, with a Ca/P ratio close to 1.67 and the characteristic diffraction peaks of this compound. The structural study of the coatings evidenced the obtention of multi-layer architectures. The use of an intermediate SiO2/TiN/Ti trilayer was found to improve adhesion between HA-Ag and the substrate by 84%. Finally, the in vitro biological tests carried out indicated a potentially non-toxic character in the coatings. Additionally, an antibacterial effect was registered at low concentrations of Ag (<0.25 mg/L).

Characterization of the subgenomic RNAs produced by Pelargonium flower break virus: Identification of two novel RNAs species.

Pelargonium flower break virus (PFBV), a member of the genus Carmovirus, has a single-stranded positive-sense genomic RNA (gRNA) of 3.9kb. The 5' half of the gRNA encodes two proteins involved in replication, the p27 and its readthrough product, p86 (the viral RNA dependent-RNA polymerase, RdRp), and the 3' half encodes two small movement proteins, p7 and p12, and the coat protein (CP). As other members of the family Tombusviridae, carmoviruses express ORFs that are not 5'-proximal from subgenomic RNAs (sgRNAs). Analysis of double-stranded RNAs extracted from PFBV-infected leaves and Northern blot hybridizations of total RNA from infected plants or protoplasts revealed than PFBV produces four 3'-coterminal sgRNAs of 3.2, 2.9, 1.7 and 1.4kb, respectively. The 5' termini of the 1.7 and 1.4kb sgRNAs mapped 26 and 143 nt upstream of the initiation codons of the p7 and CP genes, respectively, whereas the 5'-ends of the 3.2 and 2.9kb sgRNAs were located within the readthrough portion of the RdRp gene. The PFBV sgRNAs begin with a motif which is also present at the 5' terminus of the gRNA and the minus polarity of the regions preceding their corresponding start sites (in the gRNA) may be folded into hairpin structures resembling those found for the sgRNA promoters of other carmoviruses. The results indicate that, besides the sgRNAs involved in the translation of the movement proteins and the CP identified in most carmoviral infections, PFBV produces two additional sgRNAs whose biological significance is currently unknown. The possible participation of the 3.2 and 2.9kb PFBV sgRNAs in the expression of readthrough portions of the RdRp is discussed.

Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract.

BACKGROUND: Peach allergy is highly prevalent in the Mediterranean area; it is persistent and potentially severe, and therefore a prime target for immunotherapy. We aimed to study the efficacy and safety of sublingual immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3, the peach lipid transfer protein. METHODS: Randomized, double-blind, placebo-controlled (DBPC) clinical trial. The main efficacy outcome was the change in the response to a DBPC food challenge (DBPCFC) with peach. Secondary efficacy outcomes were the changes in skin prick test (SPT), and in specific immunoglobulin E (IgE) and IgG(4) to Pru p 3. Tolerance was assessed with a careful recording of adverse events. RESULTS: After 6 months of SLIT, the active group tolerated a significantly higher amount of peach (three- to ninefold), presented a significant decrease (5.3 times) in SPT, and a significant increase in IgE and IgG(4) to Pru p 3. No significant changes were observed within the placebo group. Statistically significant inter-group differences were only observed in the SPT and IgG(4) responses. No serious adverse events were reported. Systemic reactions were mild, and observed with a similar frequency in both groups. Local reactions were significantly more frequent in the active group (three times) and 95% of them restricted to the oral cavity. CONCLUSION: In this first exploratory clinical trial, SLIT for peach allergy seems to be a promising therapeutic option that could modify the clinical reactivity of the patients to peach intake and the underlying immunological response with a good tolerance.

Interrelationship between skin sensitization, rhinitis, and asthma in patients with allergic rhinitis: a study of Spain and Portugal.

OBJECTIVE: Allergic rhinitis can determine the presence and type of asthma. The main aim of this study was to evaluate the link between allergic rhinitis, asthma, and skin test sensitization in patients with allergic rhinitis. METHODS: Patients with allergic rhinitis, aged 10 to 50 years, were consecutively enrolled at different allergy centers in Spain and Portugal. All the patients underwent skin prick tests with a panel of 20 biologically standardized aeroallergens. Allergic rhinitis was classified according to etiology and the Allergic Rhinitis and its Impact on Asthma guidelines and asthma was classified according to the Global Initiative for Asthma guidelines. RESULTS: A total of 3225 patients, with a mean age of 27 years, were evaluated. House dust mites and grass and olive tree pollens were the most common aeroallergens. The mean (SD) number of positive skin tests per patient was 6.5 (4), the mean wheal size was 42.3 (28) mm2, and the mean atopy index was 6.5 (2). Forty-nine percent of the patients had concomitant asthma. Asthma severity was associated with a longer time since onset (P < .04) and allergic rhinitis severity (P < .001). Patients with concomitant asthma had a significantly higher number of aeroallergens and sensitization intensity than those without asthma (P < .001). CONCLUSIONS: In this broad population sample, the presence and type of asthma was influenced by skin sensitization and both time since onset and severity of allergic rhinitis.

[Management of the easy or complicated airway by nonexperts using the AirTraq optical laryngoscope]. / Manejo de la vía aérea fácil y complicada con el laringoscopio optico AirTraq en manos inexpertas.

OBJECTIVES: To evaluate the utility of the AirTraq optical laryngoscope in a retrospective case series, assessing indications for use and benefits as well as possible limitations. PATIENTS AND METHODS: Retrospective study of the first 124 patients in whom we used the AirTraq for tracheal intubation. Anatomical and demographic variables were recorded in addition to preoperative findings on examination of the airway. Ease in accomplishing the maneuver and quality of the procedure were assessed after intubation with the AirTraq. RESULTS: The trachea was correctly intubated in 97.6% of the patients. Intubation failed in only 3 (2.4%) patients. Laryngoscopic quality was optimal in over 95% of the cases. There were few complications or other events. CONCLUSIONS: The AirTraq laryngoscope has been shown to facilitate intubation even when nonexpert staff perform the maneuver in cases in which previous attempts at laryngoscopy have failed and in which a difficult airway is anticipated. Ease of use and relative safety make the AirTraq a practical device for a variety of patient types and clinical settings.

Evaluación prospectiva del perfil emético y la eficacia analgésica del ibuprofeno y el metamizol intravenososen el postoperatorio inmediato de la apendicitis agudapediátrica / Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis

Introducción: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor enel postoperatorio inmediato de la apendicitis aguda pediátrica (AAP).Material y métodos: Comparación prospectiva del perfil anal-gésico y emético del ibuprofeno y el metamizol intravenosos en elpostoperatorio inmediato de la AAP, para lo cual se recurre a unamuestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndoseconfirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía medianteescalas analógicas visuales validadas, con valoraciones entre los 0 ylos 10 puntos. Se realizó un ANOVA de las medidas repetidas entrelos dos grupos para comparar la evolución del dolor en las 48 horasposteriores a la cirugía.Resultados: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT:3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 conmetamizol (grupo 2). No se hallaron diferencias significativas en lo querespecta al dolor, ni en las comparaciones de las mediciones puntuales,ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Unavez realizado el ajuste correspondiente a la terapia de fluidos recibida,los niños del grupo metamizol tuvieron significativamente más episodioseméticos y necesitaron significativamente más dosis de ondansetrón.Conclusiones: En nuestra cohorte, el ibuprofeno tuvo una eficaciaanalgésica similar y un mejor perfil emético que el metamizol en elpostoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudiosprospectivos, adecuadamente controlados y con mayor tamaño muestralque validen estos hallazgos.(AU)

Background: Literature comparing different alternatives for paincontrol in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce.Materials and methods: We prospectively compared the analgesicand emetogenic profile of intravenous ibuprofen and metamizole in theimmediate postoperative period of PAA. For this purpose, we used asample of patients operated on in 2021 in our center. Participants wererecruited on arrival at the Emergency Department and histopathologi-cal confirmation of the diagnosis was obtained in all of them. Pain wasevaluated every 8 hours after the surgery with validated visual analogscales ranging from 0 to 10 points. Repeated measures ANOVA wasused to compare the evolution of pain in the 48 hours after surgerybetween the two groups. Results: The sample included 95 patients (65% males) with a meanage of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen(group 1) and 54 with metamizole (group 2). No significant differ-ences were found in the level of pain either in the comparisons of pointmeasurements or in its evolution in the 48 hours after surgery (p= 0.58).After adjusting for the received fluid therapy, children in the metamizolegroup had significantly more emetic episodes and needed significantlymore doses of ondansetron. Conclusions: In our cohort, ibuprofen had a similar analgesic ef-ficacy and a better emetogenic profile than metamizole in the immediatepostoperative period of PAA. Future prospective, adequately controlledstudies with larger sample sizes are needed to validate these findings.(AU)

Inhibition of Hsp90 function by ansamycins causes downregulation of cdc2 and cdc25c and G(2)/M arrest in glioblastoma cell lines.

Ansamycins exert their effects by binding heat shock protein 90 (Hsp90) and targeting important signalling molecules for degradation via the proteasome pathway. We wanted to study the effect of geldanamycin (GA) and its derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) on glioblastoma cell lines. We show that these cells are growth inhibited by ansamycins by being arrested in G(2)/M and, subsequently, cells undergo apoptosis. The protein levels of cell division cycle 2 (cdc2) kinase and cell division cycle 25c (cdc25c) were downregulated upon GA and 17-AAG treatment and cdc2 kinase activity was inhibited. However, other proteins involved in the G(2)/M checkpoint were not affected. The cdc2 and cdc25c mRNA levels did not show significant differences upon ansamycin treatment, but the stability of cdc2 protein was reduced. The association of cdc2 and cdc25c with p50(cdc37), an Hsp90 co-chaperone, decreased, but the interaction of cdc2 and cdc25c with the Hsp70 co-chaperone increased after ansamycin treatment. Proteasome inhibitors were able to rescue the cdc2 downregulation, but not the cdc25c reduction. However, calpain inhibitors were able to rescue the cdc25c downregulation, suggesting that cdc25c is proteolysed by calpains in the presence of ansamycins, and not by the proteasome. We conclude that ansamycins downregulate cdc2 and cdc25c by two different mechanisms.

Bispectral index monitoring for early detection of brain death.

OBJECTIVE: We sought to determine the utility of the bispectral index (BIS) as a tool for clinical evaluation of the moment of brain death (BD). MATERIALS AND METHODS: During a period of 12 months, 54 BDs were registered in our unit, of which 28 were included in the organ donation protocol; 24 fulfilled the requirements of our retrospective observational study. Continuous BIS monitoring was performed using an XP BIS monitor and BIS Quatro sensor evaluating the BIS and the suppression ratio (SR). In almost all cases, sonographic monitoring with transcranial Doppler ultrasound (TCD) was performed every 8 to 12 hours until the diagnosis of BD. RESULTS: We detected a gradual decrease in BIS and increase in SR when the patients underwent clinical progression to BD. At the moment of BD diagnosis, all cases showed BIS 0 and SR 100. In 9 cases the follow-up TCD showed a BD pattern, moments before a BIS 0 and SR 100 appeared. In 18 cases, at the moment of BIS 0/SR 100, TCD showed BD. In all 24 cases, BD diagnosis was confirmed by means of neurological examination and electroencephalogram (EEG). CONCLUSIONS: BIS monitoring is a continuous, simple method that is easy to interpret. It can help in clinical evolution and the decision of the BD moment. In our series, cerebral circulatory cessation (TCD) preceded BIS 0 and SR 100 values. The BIS prematurely detected the start of cerebral circulatory cessation, alerting us of BD.