Low dose epidural morphine does not affect non-nociceptive spinal reflexes in patients with postoperative pain

In order to determine the selectivity of the antinociceptive effect of epidural morphine, the electrophysiological features of a monosynaptic reflex were investigated before and after epidural morphine (2-3 mg) required for pain relief, in 4 patients suffering from postoperative pain. The reflex tested was the H reflex from the soleus muscle. Not only the classical Hmax/Mmax ratio, but also the threshold and the slope of the rising phase of the recruitment curve of H and M responses were analyzed. It was found that epidural morphine did not change significantly any of these parameters, at least during the 60 min post-injection period. By contrast, as usually observed clinically, epidural morphine produced an onset of pain relief by the 25th-30th min following injection. These data support the hypothesis that epidural morphine produced a 'selective spinal analgesia in man.'     

Usefulness of the hepatitis C virus core antigen assay for screening of a population undergoing routine medical checkup

We studied the usefulness of the recently designed Trak-C assay for the detection and quantification of the hepatitis C virus (HCV) core antigen (Ag) for the screening of HCV infection in 4,201 subjects selected from 74,150 consecutive volunteers undergoing routine medical checkups. Subjects were selected for screening because they had risk factors (group II, n = 321) and/or elevated alanine transaminase activity (group I, n = 3847). Initially, the anti-HCV antibody assay and the Trak-C assay were performed on each patient. Subsequently, the Trak-C assay was performed only when the anti-HCV enzyme immune assay (EIA) was positive. Positive samples were further evaluated for anti-HCV antibodies by a third-generation strip immunoblot assay and for HCV RNA. Four samples (1.2%) from group II and 113 (2.9%) from group I were anti-HCV EIA positive. We also tested 33 subjects who previously tested positive for anti-HCV in our medical center. Among the 150 anti-HCV EIA-positive samples, the HCV core Ag result was in accord with the HCV RNA result in 146 cases (97.3%). When the EIA result was positive, the HCV core Ag concentration and the HCV RNA load were correlated (r(2) = 0.78; P < 0.001). Four samples with low viral loads were Trak-C negative but HCV RNA positive. Among the 2,395 anti-HCV EIA-negative serum samples collected during the first part of the study, 17 (0.7%) were found to contain very low levels of HCV core Ag (<8.5 pg/ml, the cutoff value being 1.5 pg/ml). All these samples were HCV RNA negative and considered to be false positives. This was confirmed by HCV core Ag neutralization analysis. The HCV core Ag assay is a useful method in the screening strategy of HCV infection and provides a reliable means of distinguishing between current and cleared HCV infections that is well correlated with HCV RNA testing.     

Effets de l’halothane sur les gaz du sang et l’équilibre acido-basique artériels chez le rat intact et chez le rat chémodénervé

L’halothane diminue la réponse ventilatoire à l’hypoxie et l’activité des chémorécepteurs artériels périphériques, réalisant une «chémodénervation chimique». Afin d’évaluer le rôle de cette «chémodénervation chimique» dans les modifications de l’équilibre acido-basique et des gaz du sang artériel provoquées par l’halothane, ces paramètres ont été mesurés chez des rats intacts éveillés, puis anesthésiés, et chez des rats chémodénervés, éveillés puis anesthésiés. Le niveau de l’anesthésie pouvant être modifié par la chémodénervation anatomique, l’ED₅₀ inspirée d’halothane a été mesurée chez six rats avant et après chémodénervation anatomique. D’éventuelles modifications hémodynamiques dues à l’halothane et /ou à la chémodénervation anatomique pouvant interférer avec les résultats, la pression artérielle systémique et la fréquence cardiaque ont été mesurées chez six rats intacts éveillés, puis anesthésiés, et chez les six mêmes rats chémodénervés, éveillés puis anesthésiés. Chez neuf rats intacts et chez 19 rats chémodénervés, le pH artériel, la concentration artérielle de bicarbonates, et les gaz du sang artériel (PaO₂ et PaCO₂) ont été mesurés avant et après administration d’halothane. La chémodénervation anatomique ne modifia ni l’ED₅₀ inspirée (1,1%), ni la pression artérielle moyenne et la fréquence cardiaque. Les effets hémodynamiques de l’halothane furent comparables chez les rats intacts et chez les rats chémodénervés. Les modifications des gaz du sang et de l’équilibre acido-basique provoquees par l’halothane chez les rats intacts, et par la chémodénervation anatomique chez les rats éveillés, ne furent pas significativement différentes: diminution significative de PaO₂ et de pHa, augmentation significative de PaCO₂ Chez les rats chémodénervés, l’halothane provoqua une diminution supplémental de PaO₂ et une augmentation supplémentaire de PaCO₂. Le fait que l’halothane et que la chémodénervation anatomique modifient de la même manière les gaz du sang et l’équilibre acido-basique est en faveur de l’action «chémodénervatrice chimique» de l’halothane. Mais les effets additionnels de l’halothane chez l’animal chémodénervé anatomiquement confirment que les effets de l’halothane sur les gaz du sang et l’équilibre acido-basique résultent de multiples points d’impact sur le système respiratoire.     

Effets de l’halothane sur la ventilation et les gaz du sang artériel chez le rat avec ou sans paralysie diaphragmatique

Certains patients atteints de paralysie diaphragmatique ou de dysfonctionnement diaphragmatique maintiennent leur ventilation par la mise en jeu d’autres muscles que le diaphragme. L’anesthésie, modifiant le fonctionnement de ces muscles, représente un risque potentiel chez ces patients. Afin d’évaluer ce risque, nous avons étudié les effets de l’halothane sur la ventilation et sur les gaz du sang artériel sur un modèle de paralysie diaphragmatique bilatérale, le rat phrénicectomisé. L’étude a été réalisée sur 43 rats. L’efficacité de la phrénicectomie a été contrôlée par l’observation directe, après laparotomie. La laparotomie n’entraine pas de modification des gaz du sang. Chez 23 rats, une laparotomie a été effectuée et une artère carotide a été cathétérisée. Chez 11 rats témoins, les nerfs phréniques ont été abordés, sans être sectionnés. Chez 12 rats, les phréniques ont été sectionnés. La ventilation a été mesurée par une technique pléthysmographique, chez les rats éveillés, avant et après l’opération, puis chez les mêmes rats anesthésiés avec 1,1%, d’halothane inspiré. Les gaz du sang ont été mesurés après l’opération chez les rats éveillés, puis anesthésiés. Chez les 23 rats opérés on observe, après l’opération, une diminution du poids et de la température centrale, plus importante chez les phrénicectomisés que chez les témoins. Chez les 11 rats témoins, après l’opération, la ventilation augmente, sans modification des gaz du sang. Chez ces rats, l’halothane provoque une diminution de la ventilation minute et de la PaO₂ et une augmentation de la PaCO₂. La phrénicectomie entraine chez les 12 rats, éveillés, une augmentation de la ventilation minute, une hypoxémie et une hypercapnie. Chez ces rats, l’halothane entraine le décès dans trois cas, une diminution de la ventilation minute et une hypercapnie et une hypoxémie importantes chez les neuf autres rats. Les modifications des gaz du sang sont plus importantes que chez les témoins anesthésiés. Chez le rat intact, l’halothane provoque des modifications des gaz du sang comparables à celles observées chez d’autres espèces et chez l’homme. La présente étude confirme les effets de l’halothane sur les muscles respiratoires autres que le diaphragme. Elle met en évidence le risque respiratoire majeur que l’anesthésie peut fair courir aux patients dont la ventilation est maintenue par d’autres muscles que le diaphragme.     

Younger donor's age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Background

How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Design and Methods

This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure.

Results

Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2–132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39–57 %) and 27% (95% CI 19–36), respectively. Eighteen patients (12%) experienced grade III–IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10–22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor’s age ≤50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor’s age ≤50 years and full chimerism were independent prognostic factors for better outcome.

Conclusions

We confirmed the feasibility of tandem autologour-allogeneic transplantation in heavily treated patients with multiple myeloma. We identified younger donor’s age and upfront tandem transplantation as two independent prognostic factors for survival which could be further explored in prospective studies.     

Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m²), mitoxantrone (MXR, 12 mg/m²), or idarubicin (IDA, 10 mg/m²) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients.     

Navigated anterior cruciate ligament replacement: an experimental validation study

We wanted to test the following hypothesis: the location of the tibial and femoral ACL attachments measured by a navigation system differs from their actual anatomic location. A total of 10 gross specimens were studied. The standard navigated procedure was used. Metallic reference pins were implanted around the tibial and femoral ACL attachments and palpated with a navigated stylus. Their position was recorded in comparison with the same tibial or femoral reference point. All measurements were repeated with a caliper. Caliper and navigated measurements were compared with appropriate statistical tests at a 0.05 level of significance. There was a significant difference between caliper and navigated measurements at the tibia in absolute value (maximal range of 4 mm, mean difference about 2 mm), but the difference ratio was low (about 3%); there was no significant difference between caliper and navigated measurements at the femur. There was a strong correlation and a good agreement between caliper and navigated measurements. It is likely that these differences have few, if any, clinical relevance. We demonstrated that the navigation system used during the present study has the potential to enhance the precision of the intra-operative measurement of the tunnel placement during ACL replacement.