A randomised controlled trial of pectoral nerve-2 (PECS 2) block vs. serratus plane block for chronic pain after mastectomy.

Thoracic interfascial plane blocks are effective for post-mastectomy acute analgesia. However, their effects on chronic pain are uncertain. We randomly allocated 80 women equally to pectoral nerve-2 (PECS 2) block or serratus plane block. The pectoral nerve-2 block reduced the rate of moderate or severe chronic pain from 13/40 (33%) with the serratus plane block to 4/40 (10%), p = 0.03, adjusted odds ratio (95%CI) 0.23 (0.07-0.80), p = 0.02. The rates of pain-free women at six postoperative months were indeterminate, 10/40 (25%) after serratus plane block vs. 19/40 (48%) after pectoral nerve-2 block, p = 0.06, adjusted odds ratio (95%CI) 2.9 (1.1-7.5), p = 0.03. Health-related quality of life at six postoperative months was similar after serratus plane and pectoral nerve-2 blocks, mean (SD) EQ-5D-3L scores 0.87 (0.15) vs. 0.91 (0.14), respectively, p = 0.21. The pectoral nerve-2 block reduced median (IQR [range]) morphine consumption in the first 24 postoperative hours from 6 (3-9 [1-25]) mg to 4 (2-7 [0-37]) mg, p = 0.04. However, acute pain scores after serratus plane and pectoral nerve-2 blocks were similar, median (IQR [range]) 23 (11-35 [0-70]) mm vs. 18 (11-27 [0-61]) mm, respectively, p = 0.44. Pectoral nerve-2 block reduced chronic pain 6 months after mastectomy compared with serratus plane block.

Evaluation of the predictive performance of a pharmacokinetic model for propofol in Japanese macaques (Macaca fuscata fuscata).

Propofol is a short-acting intravenous anesthetic used for induction/maintenance anesthesia. The objective of this study was to assess a population pharmacokinetic (PPK) model for Japanese macaques during a step-down infusion of propofol. Five male Japanese macaques were immobilized with ketamine (10 mg/kg) and atropine (0.02 mg/kg). A bolus dose of propofol (5 mg/kg) was administrated intravenously (360 mg/kg/h) followed by step-down infusion at 40 mg/kg/h for 10 min, 20 mg/kg/h for 10 min, and then 15 mg/kg/h for 100 min. Venous blood samples were repeatedly collected following the administration. The plasma concentration of propofol (Cp) was measured by high-speed LC-FL. PPK analyses were performed using NONMEM VII. Median absolute prediction error and median prediction error (MDPE), the indices of prediction inaccuracy and bias, respectively, were calculated, and PE - individual MDPE vs. time was depicted to show the variability of prediction errors. In addition, we developed another population pharmacokinetic model using previous and current datasets. The previous PK model achieved stable prediction of propofol Cp throughout the study period, although it underestimates Cp. The step-down infusion regimen described in this study would be feasible in macaques during noninvasive procedures.

Mosaic and polymorphic imprinting of the WT1 gene in humans.

We have examined the imprinting of the Wilms' tumour suppressor gene (WT1) in human tissues. We confirm that WT1 is biallelically expressed in the kidney, however, in five of nine preterm placentae WT1 was expressed largely or exclusively from the maternal allele. Monoallelic expression of WT1 was also found in two fetal brains. These data demonstrate that WT1 can undergo tissue specific imprinting. Furthermore, because monoallelic expression of WT1 was not found in all placentae examined, WT1 imprinting may be genetically polymorphic within the human population.

Predictive performance of Shock Index for postpartum hemorrhage during cesarean delivery.

BACKGROUND: The Shock Index (SI), defined as heart rate divided by systolic blood pressure, is reportedly an early surrogate indicator for postpartum hemorrhage (PPH). However, most previous studies have used clinical data of women who delivered vaginally. Therefore, we aimed to evaluate the SI pattern during cesarean delivery and determine its usefulness in detecting PPH. METHODS: This was a single-center retrospective study using the clinical data of women (n = 331) who underwent cesarean delivery under spinal anesthesia at term between 2018 and 2021. We assessed the SI pattern stratified by total blood loss and evaluated the predictive performance of each vital sign in detecting PPH (total blood loss ≥1000 mL) based on the area under the receiver operating characteristic curve (AUROC). RESULTS: At 10-15 min after delivery, the mean SI peaked between 0.84 and 0.90 and then decreased to a level between 0.72 and 0.77, which was similar to that upon entering the operating room. Among 331 women, 91 (27.5%) were diagnosed with PPH. There was no correlation between SI and total blood loss (rs = 0.02). The SI had low ability to detect PPH (AUROC 0.54, 95% confidence interval 0.47 to 0.61), which was similar to other vital signs (AUROCs 0.53-0.56). CONCLUSION: We determined the pattern of SI during cesarean delivery. We found no correlation between SI and total blood loss. Unlike in vaginal delivery, the prognostic accuracy of SI for PPH detection in cesarean delivery was low.

Tetraparesis resembling acute transverse myelitis in a captive chimpanzee (Pan troglodytes): long-term care and recovery.

BACKGROUND: A 24-year-old, male chimpanzee (Pan troglodytes) developed acute tetraparesis. Magnetic resonance imaging showed a diffuse T2-weighted hyperintensive lesion, indicating inflammation at the C1-2 level. All infective, autoimmune, and vascular investigations were unremarkable. RESULTS AND CONCLUSIONS: The chimpanzee's condition most resembled acute transverse myelitis (ATM) in humans. The chimpanzee was in severe incapacitated neurological condition with bedridden status and required 24-hour attention for 2 months followed by special care for over a year. Initially, corticosteroid therapy was performed, and his neurological symptoms improved to some extent; however, the general condition of the chimpanzee deteriorated in the first 6 months after onset. Pressure ulcers had developed at various areas on the animal's body, as the bedridden status was protracted. Supportive therapy was continued, and the general condition, appetite, mobility, and pressure ulcers have slowly but synergistically recovered over the course of 2 years.

Mutations in a protein kinase C homolog confer phorbol ester resistance on Caenorhabditis elegans.

The tpa-1 gene mediates the action of tumor-promoting phorbol esters in the nematode Caenorhabditis elegans. A genomic fragment that constitutes a portion of the tpa-1 gene was cloned by Tc1 transposon tagging and was used as a probe to screen a nematode complementary DNA library. One of the isolated complementary DNA clones had a nucleotide sequence that predicts a polypeptide of 526 amino acids. The predicted amino acid sequence revealed that the predicted tpa-1 protein sequence is highly similar to protein kinase C molecules from various animals, including man.

A metalloprotease disintegrin that controls cell migration in Caenorhabditis elegans.

In Caenorhabditis elegans, the gonad acquires two U-shaped arms by the directed migration of its distal tip cells (DTCs) along the body wall basement membranes. Correct migration of DTCs requires the mig-17 gene, which encodes a member of the metalloprotease-disintegrin protein family. The MIG-17 protein is secreted from muscle cells of the body wall and localizes in the basement membranes of gonad. This localization is dependent on the disintegrin-like domain of MIG-17 and its catalytic activity. These results suggest that the MIG-17 metalloprotease directs migration of DTCs by remodeling the basement membrane.

A triple-blinded randomized trial comparing spinal morphine with posterior quadratus lumborum block after cesarean section.

BACKGROUND: This study aimed to compare the postoperative analgesic effects of ultrasound-guided posterior quadratus lumborum block with spinal morphine, after cesarean section, using the visual analogue scale pain score. METHODS: One-hundred-and-seventy-six pregnant women scheduled for elective cesarean section with spinal anesthesia were randomly allocated into four groups to receive spinal morphine 0.1 mg (group M+); spinal saline (M-); posterior quadratus lumborum block using either 0.3% ropivacaine (0.45 mL/kg each side, maximum 150 mg) group pQ+); or saline (pQ-). All patients received 11-13 mg hyperbaric bupivacaine 0.5% and 10 µg fentanyl. Intravenous droperidol, fentanyl and acetaminophen were administered during surgery. Bilateral posterior quadratus lumborum block was performed immediately after surgery. Postoperative pain was assessed at 0.5, 1, 2, 4, 6, 18 and 24 h after surgery, and the pain score 6 h after surgery was the primary endpoint. RESULTS: One-hundred-and-forty-six patients were included in the final analysis. Pain scores 6 h after surgery, both at rest and when moving, were significantly different when comparing the M+pQ+ group with the M-pQ+ or M-pQ- groups, and when comparing the M+pQ- group with the M- pQ+ or M- pQ- groups (all P <0.05). There was no significant difference between the M+pQ+ and M+pQ- groups, or between the M-pQ+ and M-pQ- groups. CONCLUSION: Spinal morphine improved postoperative analgesia but the combination of posterior quadratus lumborum block with spinal morphine did not lead to further improvement.

The C. elegans unc-18 gene encodes a protein expressed in motor neurons.

The C. elegans unc-18 gene is required to maintain normal acetylcholine levels. We determined the complete structure of an unc-18 cDNA that encodes a protein of 591 highly charged and hydrophilic amino acids. The protein shows sequence similarity with elements of the secretory pathway in the yeast S. cerevisiae. Antibodies raised against a portion of the unc-18-encoded protein (UNC-18) detected a 68 kd soluble antigen on immunoblots and intensely stained all vertical cord motor neurons in situ. These findings suggest that UNC-18 participates in the axonal transport system and influences the acetylcholine flow in motor neurons.

Catheterization in an ultrasound-guided thoracic paravertebral block using thoracoscopy.

Thoracic paravertebral block (TPVB) is an efficient alternative to epidural anesthesia. The location of a catheter within the thoracic paravertebral space (TPVS) has been examined in the human cadaver studies, but it is unclear how it goes into the TPVS during catheterization. In this report, thoracoscopy was used to observe the thoracic cavity in real-time during a parasagittal in-plane approach of ultrasound-guided TPVB. During thoracoscopy, we observed whether a paravertebral catheter could be advanced caudally beyond the ribs into the neighboring TPVS. Our result demonstrated that the catheter was difficult to be advanced beyond the ribs and confined within the same level of TPVS as where it was inserted. In the previous thoracoscopic observation of the paravertebral spread, we assumed that the local anesthetic acts most strongly at the intercostal level of the injection. Therefore, we recommend to insert the catheter for TPVB at the level corresponding to the incision site of thoracotomy.

GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia.

To investigate better GVHD prophylaxis in reduced intensity conditioning umbilical cord blood transplantation (RIC-UCBT), we compared transplant outcomes after UCBT among GvHD prophylaxes using the registry data. We selected patients transplanted for AML or ALL with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 748 first RIC-UCBT between 2000 and 2012 (MTX+ group, 446, MMF+ group, 302) were included. The cumulative incidence of neutrophil and platelet counts higher than 50 000/µL was significantly better in the MMF+ group (relative risk (RR), 1.55; P<0.001: RR, 1.34; P=0.003, respectively). In multivariate analyses, the risk of grade II-IV and III-IV acute GvHD was significantly higher in the MMF+ group than in the MTX+ group (RR, 1.75; P<0.001: RR, 1.97; P=0.004, respectively). In disease-specific analyses of AML, the risk of relapse of high-risk disease was significantly lower in the MMF+ group (RR, 0.69; P=0.009), whereas no significant difference was observed in the risk of relapse-free and overall survival in high-risk disease. In patients with standard-risk disease, no significant differences were noted in the risk of relapse or survival between the MTX+ and MMF+ groups. Collectively, these results suggest that MMF-containing prophylaxis may be preferable in RIC-UCBT, particularly for high-risk disease.

The tpa-1 gene of Caenorhabditis elegans encodes two proteins similar to Ca(2+)-independent protein kinase Cs: evidence by complete genomic and complementary DNA sequences of the tpa-1 gene.

The gene tpa-1 on chromosome IV of the nematode Caenorhabditis elegans plays a major and definitive role in the adversary action of tumour-promoting phorbol esters, which induce growth arrest and locomotory distress in the animal. The gene was deduced to code for a protein kinase C (PKC) homologue by molecular cloning. We have now sequenced the complete genomic and complementary DNAs for tpa-1 and have analysed their structural features in detail: (1) tpa-1 spans over 20 kb consisting of eleven exons and ten introns; (2) two different-sized mRNAs are generated from the tpa-1 locus; (3) both mRNAs are trans-spliced to the trans-spliced leader SL1; (4) both mRNAs encode PKC isoforms, which are most similar to Ca(2+)-independent novel PKC0; (5) the two PKC isoforms differ from each other in that the smaller lacks the amino-terminal region of the larger corresponding to the first four exons and a portion of the fifth exon; and (6) three introns are located at; identical positions in the polypeptide sequences aligned between the C. elegans tpa-1 product and a PKC of the fruit fly Drosophila melanogaster.

Mutations affecting symmetrical migration of distal tip cells in Caenorhabditis elegans.

The rotational symmetry of the Caenorhabditis elegans gonad arms is generated by the symmetrical migration of two distal tip cells (DTCs), located on the anterior and posterior ends of the gonad primordium. Mutations that cause asymmetrical migration of the two DTCs were isolated. All seven mutations were recessive and assigned to six different complementation groups. vab-3(k121) and vab-3(k143) affected anterior DTC migration more frequently than posterior, although null mutants showed no bias. The other five mutations, mig-14(k124), mig-17(k113), mig-18(k140), mig-19(k142), and mig-20(k148), affected posterior DTC migration more frequently than anterior. These observations imply that the migration of each DTC is regulated differently. mig-14 and mig-19 also affected the migration of other cells in the posterior body region. Four distinct types of DTC migration abnormalities were defined on the basis of the mutant phenotypes. vab-3; mig-14 double mutants exhibited the types of DTC migration defects seen for vab-3 single mutants. Combination of mig-17 and mig-18 or mig-19, which are characterized by the same types of posterior DTC migration defects, exhibited strong enhancement of anterior DTC migration defects, suggesting that they affect the same or parallel pathways regulating anterior DTC migration.

Animal model of depression. III. Mechanism of action of tetrabenazine.

A study was undertaken to gain an understanding of the biochemical mechanism whereby tetrabenazine (TBZ) produces a sedative effect on the locomotor activity of rats. Rats injected with L-5-hydroxytryptophan (L-5-HTP, 30 mg/kg), the immediate precursor of 5-hydroxytryptamine (5-HT), showed the characteristic bison appearance, pitosis, and catalepsy normally observed after injecting TBZ (30 mg/kg). The treatment of rats with low doses of L-5-HTP (9 mg/kg) plus TBZ (2 mg/kg) significantly decreased locomotor activity, whereas low doses of either one of these drugs given alone had no significant effect on locomotor activity. The level of 5-hydroxyindoleacetic acid (5-HIAA) was elevated in the brain of rats sacrificed 3 hr after treatment with low doses of either L-5-HTP or TBZ alone. Treatment of rats with p-chlorophenylalanine to inhibit the synthesis of 5-HT had an inhibitory effect on the duration of sedation following an injection of TBZ (30 mg/kg). The results of the biochemical and pharmacological studies as reflected by changes in locomotor activity were interpreted to indicate that the sedative action of TBZ was due to an excess of functional 5-HT.

Determination of the optimal pressure support level evaluated by measuring transdiaphragmatic pressure.

The purpose of this study was to determine the optimum pressure support (PS) in six patients with respiratory failure. Esophageal pressure (Pe), gastric pressure (Pg), airway pressure, and transdiaphragmatic pressure (Pdi), obtained by subtracting Pe from Pg, were measured using a newly developed multiluminal nasogastric catheter. For each patient, different PS levels were selected every 20 minutes, and measurements were made at each PS level. We defined the optimum PS level as the level that showed the minimum Pe value. Respiratory rate (RR) decreased and tidal volume (VT) increased with an increase in PS level. RR and VT at the optimum PS were 19.7 +/- 5.5 breaths per minute and 11.7 +/- 4.5 ml/kg, respectively. Pdi decreased linearly with increasing PS level in all patients. Mean Pdi at the optimum Ps was 4.2 +/- 1.2 cm H2O. Based on the relationship between Pdi and PS level, we constructed an equation to estimate the optimum PS level as follows: Optimum PS level = [( Pdi during T-piece mode] - 4)/0.8. We conclude that Pdi measurement is helpful for titrating the required PS level.

Comparison of inspiratory work of breathing in T-piece breathing, PSV, and pleural pressure support ventilation (PPSV).

We have compared the inspiratory work of breathing during T-piece breathing, pressure support ventilation (PSV), and pleural pressure support ventilation (PPSV) by using a lung model with variable compliance and resistance, under simulated spontaneous breathing. Our lung model consists of two spring-loaded bellows, representing the lung and diaphragm, placed in an airtight container. Inspiration begins with the withdrawal of air from the diaphragm bellows by a time-cycled jet-flow-creating Venturi mechanism. Expiration occurs by opening the diaphragm bellows to the atmosphere. Work of breathing (WOB) is calculated by plotting the pressure-volume curve, with pressure corresponding to intrabox pressure and volume corresponding to the tidal volume; PPSV is a new mode of mechanical ventilatory support accomplished by setting the ventilator (Servo 900C) into the PSV mode with a level of 0 cm H2O, using the pleural pressure as the input and target signal. The PPSV maximally reduces WOB under any circumstances. The PSV sufficiently reduced WOB only in the normal lung and the lung with low compliance; however, a pressure supporting time is diminished in the lung with low compliance. The serious limitations of PSV remain in its application to the lung with high resistance. It is concluded that PPSV is closer to the actual patient's signal and has a potential advantage in reducing WOB in the lung with low compliance or high resistance (or both). The lung with flow limitation is still a challenging issue for mechanical ventilatory assistance.

Fatal GVHD demonstrating an involvement of respiratory muscle following donor leukocyte transfusion (DLT).

A 41-year-old female patient with AML, who relapsed after an allogeneic BMT from her HLA-identical sister, was treated by a donor leukocyte transfusion (DLT). Thereafter, bone marrow aplasia accompanied by the disappearance of leukemic blasts following the GVHD was observed. The patient died of chronic GVHD with respiratory muscle involvement 19 months after the DLT. Although the DLT was considered helpful in suppressing the proliferation of the leukemic cells, it might also have caused the severe GVHD observed in this case. Efforts to separate the lymphocyte clones responsible for GVL from those for the GVHD thus appear to be necessary for the further development of the therapeutic approach, so-called DLT.