Hemodynamic and autonomic response to acute hemorrhage in streptozotocin-induced diabetic rats

<p>Abstract</p> <p>Background</p> <p>The various autonomic control systems lead to characteristic changes in heart rate (HR) and blood pressure (BP) during acute hemorrhage. However, cardiovascular autonomic neuropathy due to diabetes mellitus may interfere with the normal compensation for hemorrhage.</p> <p>Materials and methods</p> <p>A controlled graded bleeding (6 - 36% loss of estimated total blood volume: ETBV) was performed in streptozotocin-induced diabetic rats (STZ rats) under a conscious state. Hemodynamic and autonomic responses to acute hemorrhage were examined using analysis of BP-HR variability. The effects of dextran treatment after hemorrhage were also examined.</p> <p>Results</p> <p>A significant reduction in mean arterial pressure began at 12% ETBV loss in STZ rats and 18% in the control rats, respectively. When blood loss reached 18% of TEBV, the decrease in HR was prominent in STD rats due to the activation of a parasympathetic drive, as indicated by the increase in high frequency (HF; 0.75~3.0 Hz) power in HR variability, while in the control rats this response was not observed. The administration of dextran prevented the activation of the parasympathetic drive in STZ rats during hemorrhaging. In the control rats, the dextran treatment sustained the initial increase in HR with reduced HF power in HR variability.</p> <p>Conclusion</p> <p>STZ rats showed different hemodynamic and autonomic responses to acute hemorrhage from the control rats. STZ rats were prone to develop bradycardiac hypotension characterized by marked parasympathetic activation during hemorrhaging. This finding suggests enhancement of the Bezold-Jarisch reflex in STZ rats. Dextran treatment to maintain a normovolemic hemorrhage state inhibits this reflex.</p

Premedication with midazolam in intellectually disabled dental patients: intramuscular or oral administration? A retrospective study

Background: The use of midazolam for dental care in patients with intellectual disability is poorly documented. The purpose of this study was to determine which method of premedication is more effective for these patients, 0.15 mg/kg of intramuscular midazolam or 0.3 mg/kg of oral midazolam. Material and Methods: This study was designed and implemented as a non-randomized retrospective study. The study population was composed of patients with intellectual disability who required dental treatment under ambulatory general anesthesia from August 2009 through April 2013. Patients were administered 0.15 mg/kg of midazolam intramuscularly (Group IM) or 0.3 mg/kg orally (Group PO). The predictor variable was the method of midazolam administration. The outcome variables measured were Observer’s Assessment of Alertness/ Sedation (OAA/S) Scale scores, the level of cooperation when entering the operation room and for venous cannulation, post-anesthetic agitation and recovery time. Results: Midazolam was administered intramuscularly in 23 patients and orally in 21 patients. More patients were successfully sedated with no resistance behavior during venous cannulation in Group PO than in Group IM ( p =0.034). There were no differences in demographic data and other variables between the groups. Conclusions: The results of this study suggest that oral premedication with 0.3 mg/kg of midazolam is more effective than 0.15 mg/kg of midazolam administered intramuscularly, in terms of patient resistance to venous cannulation. If both oral and intramuscular routes of midazolam are acceptable in intellectually disabled patients, the oral route is recommended

〈Cases Reports〉Successful treatment with intravenous colistin of sepsis caused by metallo-beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa in a patient with acute myeloid leukemia

[Abstract] In recent years, multidrug-resistant Pseudomonas aeruginosa (MDRP) has been detected in patients undergoing chemotherapy for hematological malignancies. MDRP can cause life-threatening infections such as sepsis and pneumonia, being a major concern for physiciansand patients. Here, we report the case of a patient with acute myeloid leukemia (AML ; FAB classification M2) who developed septic shock from MDRP infection during leukopenia induced by the first cycle of consolidation therapy, and in whom the combination of colistin administration and steroid pulse therapy promptly improved the septic shock symptoms and cleared MDRP from the blood. Although a transient nephrotoxic effect was observed, itsubsided rapidly on discontinuation of treatment. MDRP in stool samples fell to undetectable levels following oral doses of polymyxin B sulfate. The patient could continue consolidation chemotherapy and has remained in remission

Real-world effectiveness and safety analysis of carfilzomib-lenalidomide-dexamethasone and carfilzomib-dexamethasone in relapsed/refractory multiple myeloma: a multicenter retrospective analysis

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered

Monocyte or white blood cell counts and β₂ microglobulin predict the durable efficacy of daratumumab with lenalidomide

BACKGROUND: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. OBJECTIVES: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. DESIGN: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. METHODS: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. RESULTS: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. CONCLUSION: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts

〈Originals〉Trib1 and Trib2 inhibit granulocytic differentiation by suppressing Akt pathway

[Abstract] Background :Overexpression of Tribbles homolog 1 (Tribl) and Tribbles homolog 2 (Trib2) in hematopoietic stem/progenitor cells evokes acute myeloid leukemia (AML) in murine transplantation models. Degradation of CCAAT-enhancer-binding-protein α (C/EBPα) plays a crucial role in Trib1 or Trib2-induced AML. However, because C/EBPα knockout mice do not develop AML, it is likely that Trib1 and Trib2 influence other signaling pathways besides C/EBPα. Elevated Akt phosphorylation is considered to contribute to the development of AML. In contrast, two groups recently reported that reduced Akt activity is involved in the pathogenesis of leukemia. We performed this study to reveal the role of Akt signaling in Trib family-induced AML.Methods : G-CSF-induced granulocytic differentiation of 32D cells was assessed morphologically and phenotypically. G-CSF-induced signaling wasassessed by Westernblotting. Results : Overexpression of Trib1 or Trib2 inhibited GCSF-induced granulocytic differentiation of 32D cells, which was accompanied by reduced Akt phosphorylation. Also, an Akt inhibitor API-2 blocked G-CSF-induced granulocytic differentiation independently of C/EBPα degradation.　Furthermore, retroviral C/EBPα restoration did not completely abolish the differentiation block caused by Trib1 and Trib2. Conclusion :Trib1 and Trib2 block granulocytic differentiation, at least partially, by suppressing Akt phosphorylation

Bilateral Parkinson's disease model rats exhibit hyperalgesia to subcutaneous formalin administration into the vibrissa pad.

We bilaterally injected 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of rats and developed bilateral Parkinson's disease (PD) model rats in order to experimentally investigate the neural mechanisms underlying the alteration of nociception in the orofacial region of patients with PD. We explored the effects of dopamine depletion on nociception by investigating behavioral responses (face rubbing) triggered by subcutaneous administration of formalin into the vibrissa pad. We also assessed the number of c-Fos-immunoreactive (c-Fos-IR) cells in the superficial layers of the trigeminal spinal subnucleus caudalis (Vc). Subcutaneous formalin administration evoked a two-phase increase in face rubbing. We observed the first increase 0-5 min after formalin administration (first phase) and the second increase 10-60 min after administration (second phase). The number of face rubbing behaviors of 6OHDA-injected rats did not significantly change compared with saline-injected rats in both phases. Significant increase of c-Fos-IR cells in the Vc was found in 6-OHDA-injected rats after formalin administration compared with those in saline-injected rats after formalin administration. We also assessed expression of c-Fos-IR cells in the paraventricular nucleus (PVN), and significant decrease of c-Fos-IR cells in the PVN of 6-OHDA-injected rats was found. Taken together, these findings suggest that bilateral dopaminergic denervation evoked by 6-OHDA administration causes hyperalgesia in the trigeminal region and the PVN may be involved in the hyperalgesia

Effectiveness of dexmedetomidine for emergence agitation in infants undergoing palatoplasty: a randomized controlled trial

OBJECTIVES: In infants, there is a high incidence of emergence agitation (EA) after sevoflurane (Sev) anesthesia. This study aimed to test the hypothesis that dexmedetomidine (Dex) administration would reduce the incidence and severity of EA after Sev-based anesthesia in infants undergoing palatoplasty. METHODS: A prospective randomized clinical trial was conducted with 70 patients undergoing palatoplasty, aged 10-14 months. Infants were randomly allocated into two groups: Dex (n = 35) and saline (n = 35). In the Dex group, Dex (6 µg/kg/h) was administered approximately 10 min before the end of the surgery for 10 min, followed by 0.4 µg/kg/h until 5 min after extubation. In the saline group, an equivalent amount of saline was administered in a similar manner. After the surgery, patients were transferred to the postanesthetic care unit (PACU). The infant's behavior and pain were assessed with scoring system for EA (5-point rating scale) and pain scale (PS; 10-point rating scale), respectively. EA and PS were estimated at six time points (after extubation, leaving the operating room, 0, 30, 60, and 120 min after arrival in PACU). RESULTS: EA and PS scores were significantly lower in the Dex group than in the saline group from extubation to 120 min after arrival in PACU. CONCLUSIONS: Dex administration has the advantage of a reduced EA and PS without any adverse effects. Dex provided satisfactory recovery in infants undergoing palatoplasty