Toxic benzyl alcohol inhalation: Altered mental status with metabolic acidosis and hyperammonemia.

This report presents the case of a patient whose inhalation exposure to benzyl alcohol led to clinical manifestations similar to toluene intoxication, including sudden altered mental status, metabolic acidosis, hypokalemia, hypophosphatemia, and hyperammonemia. Toxicity from benzyl alcohol inhalation is quite rare, and hyperammonemia associated with renal tubular dysfunction in poisoning cases has not been reported in the past.

Simple pneumopericardium due to blunt trauma progressing to tension pneumopericardium during transportation.

Patients with simple pneumopericardium due to blunt thoracic trauma occasionally progressed to tension pneumopericardium, although pneumopericardium is believed to be benign in general. A 65-year-old man had both arms caught in a grinding machine and his face struck hard at work. He was diagnosed with bilateral degloving injuries of both arms and mediastinal emphysema on computed tomography. He required transfer to an advanced emergency medical service center for treatment. Although he was hemodynamically stable then, the patient's condition deteriorated during transportation. The patient returned to the local hospital as cardiopulmonary resuscitation continued, repeat computed tomography was performed, which showed a substantial pneumopericardium and exacerbation of mediastinal and subcutaneous emphysema. After then, cardiopulmonary resuscitation was discontinued because there was no response. For the patient to be rescued in this situation, thoracotomy is required, although it should be reserved for patients with evidence of hemodynamic compromise attributable to cardiac tamponade.

Hyperbaric oxygenation therapy for crush injuries reduces the risk of complications: research report.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has been adopted for crush injuries, but there are few studies supporting its use. We therefore investigated the effects of HBO2 on management of patients with complicated crush injuries. METHODS: This historic cohort study included patients with crush injuries and open fractures with severities greater than or equal to Gustilo class IIIA. We divided the patients into two groups: Control and HBO2. The control group received conventional treatment, while the HBO2 group received conventional treatment plus HBO2. We compared the groups with respect to the incidence of infection, need for additional surgery, and length of intensive care unit (ICU) and hospital stays. RESULTS: There were 16 patients in the HBO2 group and 13 in the control group. There were no patients with infections in the HBO2 group, whereas in the control group six patients had infections and five needed another drainage procedure. These incidences were significantly lower in the HBO2 group (p = 0.003 and 0.013). However, the durations of ICU and hospital stays were similar across the two groups. CONCLUSIONS: HBO2 is effective in the management of crush injuries from the viewpoint of reducing complications and reoperations. These observations should be verified in additional studies with larger sample sizes because the patient number is limited.

Epidemiology and outcomes of pregnant trauma patients in Japan: a nationwide descriptive study.

PURPOSE: Trauma during pregnancy is the leading indirect obstetric cause of death, and its management is challenging owing to its characteristics. We aimed to describe the epidemiology of pregnant trauma patients and explore their characteristics by comparing them with those of non-pregnant patients. METHODS: Using the Japan Trauma Data Bank data collected between January 2004 and May 2019, we identified pregnant and non-pregnant female trauma patients between the ages of 15-45 years. We described patient characteristics, prehospital information, in-hospital management, and clinical outcomes. We also investigated the differences in the information between pregnant and non-pregnant patients. RESULTS: In total, 165 pregnant trauma patients were identified (0.7%). Motor vehicle collisions were the most frequent mechanism of injury (64.6%) in pregnant patients. The time from call to the arrival of emergency medical services at the hospital was similar for both pregnant and non-pregnant patients. The use of abdominal computed tomography (CT) scans was lower and injury to the abdomen was more frequent in pregnant than non-pregnant patients. In-hospital mortality was 7.2% in pregnant patients and 10.9% in non-pregnant patients. No significant differences in mortality after adjustment for confounding factors were found (adjusted odds ratio: 0.78, 95% confidential interval: 0.35-1.75, p = 0.548). CONCLUSION: Transport time and mortality were similar between pregnant and non-pregnant trauma patients. Abdominal trauma and surgery were more common in pregnant relative to non-pregnant patients, while the number of CT scans was less. Further research is required to investigate the effects of trauma on the course of pregnancy and the fetus.

Massive expression of cysteine-containing proteins causes abnormal elongation of yeast cells by perturbing the proteasome.

The enhanced green fluorescent protein (EGFP) is considered to be a harmless protein because the critical expression level that causes growth defects is higher than that of other proteins. Here, we found that overexpression of EGFP, but not a glycolytic protein Gpm1, triggered the cell elongation phenotype in the budding yeast Saccharomyces cerevisiae. By the morphological analysis of the cell overexpressing fluorescent protein and glycolytic enzyme variants, we revealed that cysteine content was associated with the cell elongation phenotype. The abnormal cell morphology triggered by overexpression of EGFP was also observed in the fission yeast Schizosaccharomyces pombe. Overexpression of cysteine-containing protein was toxic, especially at high-temperature, while the toxicity could be modulated by additional protein characteristics. Investigation of protein aggregate formation, morphological abnormalities in mutants, and transcriptomic changes that occur upon overexpression of EGFP variants suggested that perturbation of the proteasome by the exposed cysteine of the overexpressed protein causes cell elongation. Overexpression of proteins with relatively low folding properties, such as EGFP, was also found to promote the formation of SHOTA (Seventy kDa Heat shock protein-containing, Overexpression-Triggered Aggregates), an intracellular aggregate that incorporates Hsp70/Ssa1, which induces a heat shock response, while it was unrelated to cell elongation. Evolutionary analysis of duplicated genes showed that cysteine toxicity may be an evolutionary bias to exclude cysteine from highly expressed proteins. The overexpression of cysteine-less moxGFP, the least toxic protein revealed in this study, would be a good model system to understand the physiological state of protein burden triggered by ultimate overexpression of harmless proteins.

[A case of drug-induced pneumonitis due to a cold remedy].

The patient was an 84-year-old woman who took a combination cold remedy, Shin-Rulu-A' for three days because of fever and cough. However, her symptoms worsened and she visited our hospital. Arterial blood gas analysis revealed severe hypoxemia and chest computed tomography showed diffuse ground glass opacities in both lungs. Analysis of bronchoalveolar lavage fluid disclosed an increased proportion of lymphocytes. The cold remedy was stopped, corticosteroids were administered, and she recovered. After positive results of lymphocyte stimulation testing to Shin-Rulu-A, a diagnosis of drug-induced pneumonitis was made. However the responsible ingredient was not established, because lymphocyte stimulation tests for each ingredient in Shin-Rulu-A were negative. To the best of our knowledge, this is the second report of Shin-Rulu-A-induced pneumonitis in Japan.

Genetic profiling of protein burden and nuclear export overload.

Overproduction (op) of proteins triggers cellular defects. One of the consequences of overproduction is the protein burden/cost, which is produced by an overloading of the protein synthesis process. However, the physiology of cells under a protein burden is not well characterized. We performed genetic profiling of protein burden by systematic analysis of genetic interactions between GFP-op, surveying both deletion and temperature-sensitive mutants in budding yeast. We also performed genetic profiling in cells with overproduction of triple-GFP (tGFP), and the nuclear export signal-containing tGFP (NES-tGFP). The mutants specifically interacted with GFP-op were suggestive of unexpected connections between actin-related processes like polarization and the protein burden, which was supported by morphological analysis. The tGFP-op interactions suggested that this protein probe overloads the proteasome, whereas those that interacted with NES-tGFP involved genes encoding components of the nuclear export process, providing a resource for further analysis of the protein burden and nuclear export overload.

Antithrombin III suppresses ADP-induced platelet granule secretion: inhibition of HSP27 phosphorylation.

Antithrombin III (AT-III), an anti-coagulant, has recently been reported to directly affect human platelet functions. However, the exact mechanism of AT-III in platelets remains to be clarified. We have previously shown that adenosine diphosphate (ADP)-induced phosphorylation of heat shock protein 27 (HSP27) via p44/p42 mitogen-activated protein kinase (MAPK) and p38 MAPK is correlated with platelet granule secretion. In the present study, we investigated the relationship between AT-III and the ADP-induced platelet granule secretion. The ADP-induced secretion of platelet-derived growth factor (PDGF)-AB and serotonin (5-HT) were significantly suppressed by AT-III. The ADP-induced soluble CD40 ligand (sCD40L) release was inhibited by either PD98059, a MEK inhibitor, or SB203580, a p38 MAPK inhibitor. AT-III also inhibited the sCD40L release. AT-III markedly attenuated the ADP-induced phosphorylation levels of p44/p42 MAPK and p38 MAPK. Furthermore, the ADP-induced HSP27 phosphorylation was suppressed by AT-III. These results strongly suggest that AT-III directly acts on platelets and suppresses ADP-induced platelet granule secretion due to inhibiting HSP27 phosphorylation via p44/p42 MAPK and p38 MAPK.

HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion.

Adenosine diphosphate (ADP) plays a crucial role in hemostasis and thrombosis by activating platelets. ADP has been reported to induce heat-shock protein (HSP) 27 phosphorylation in human platelets. However, the exact role of HSP27 phosphorylation in human platelets has not yet been clarified. In the present study, we investigated the mechanisms and the roles of ADP-induced HSP27 phosphorylation in human platelets. We showed for the first time that both of decreased phosphorylation levels of HSP27 by PD98059, a MEK1/2 inhibitor and SB203580, a p38 MAPK inhibitor were correlated with the suppressed levels of platelet granule secretion but not with platelet aggregation. Furthermore, the inhibition of either the p44/p42 MAPK or p38 MAPK pathways had no effect on ADP-induced platelet aggregation. These results strongly suggest that the ADP-induced phosphorylation of HSP27 via p44/p42 MAPK and/or p38 MAPK is therefore sufficient for platelet granule secretion but not for platelet aggregation in humans.

[Management of difficult-to-treat asthma using a flow sheet for systematic evaluation and therapeutic intervention].

BACKGROUND: Although most patients of asthma can be controlled by inhaled corticosteroid (ICS), some patients remain uncontrolled even after the introduction of ICS treatment. In management of such difficult-to-treat asthma, systematic review including additional differential diagnosis and avoidance of exacerbating factors is very important. METHODS: Here we postulate a flow sheet presenting an algorithm which intends to achieve better asthma control following ATS refractory asthma guidance. For patients with poor controlled asthma even after using ICS more than moderate dose, we used the sheet in our daily outpatient management and investigated whether we could improve the control in such patients. The sheet was constructed by an algorithm which included (1) reevaluation of inhalation technique of ICS; (2) additional differential diagnosis of COPD and other similar diseases; and (3) reevaluation of presence of exacerbating factors. RESULTS: In our outpatient department, seven clinicians managed 22 difficult-to-treat asthma patients using this sheet. Additional factors which might worsen asthma control could be detected in 21 patients (95.5%). Firstly, smoking was disclosed in 8 patients (36.4%). Secondly, keeping pets was identified in 7 patients (31.8%). 5 patients (22.7%) were diagnosed as COPD rather than asthma and 4 patients (18.2%) were diagnosed as having rhinosinusitis. Some improvement of asthma control was achieved in 9 patients (40.9%). CONCLUSIONS: Reevaluation of refractory asthma patients using our newly developed flow sheet is essential and it may facilitate understanding of management of difficult-to-treat asthma.

Negative regulation by p70 S6 kinase of FGF-2-stimulated VEGF release through stress-activated protein kinase/c-Jun N-terminal kinase in osteoblasts.

UNLABELLED: To clarify the mechanism of VEGF release in osteoblasts, we studied whether p70 S6 kinase is involved in basic FGF-2-stimulated VEGF release in osteoblast-like MC3T3-E1 cells. In this study, we show that p70 S6 kinase activated by FGF-2 negatively regulates VEGF release through SAPK/JNK in osteoblasts. INTRODUCTION: Vascular endothelial growth factor (VEGF) plays an important role in bone metabolism. We have previously reported that fibroblast growth factor-2 (FGF-2) stimulates the release of VEGF through p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates VEGF release. However, the mechanism behind VEGF release in osteoblasts is not precisely known. MATERIALS AND METHODS: The levels of VEGF released from MC3T3-E1 cells were measured by enzyme immunoassay. The phosphorylation of each protein kinase was analyzed by Western blotting. To knock down p70 S6 kinase in MC3T3-E1 cells, the cells were transfected with siRNA to target p70 S6 kinase. RESULTS: FGF-2 time-dependently induced the phosphorylation of p70 S6 kinase. Rapamycin significantly enhanced the FGF-2-stimulated VEGF release and VEGF mRNA expression. The FGF-2-induced phosphorylation of p70 S6 kinase was suppressed by rapamycin. Rapamycin markedly enhanced the FGF-2-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP kinase. SP600125, a specific inhibitor of SAPK/JNK, suppressed the amplification by rapamycin of the FGF-2-stimulated VEGF release similar to the levels of FGF-2 with SP600125. Finally, downregulation of p70 S6 kinase by siRNA significantly enhanced the FGF-2-stimulated VEGF release and phosphorylation of SAPK/JNK. CONCLUSIONS: These results strongly suggest that p70 S6 kinase limits FGF-2-stimulated VEGF release through self-regulation of SAPK/JNK, composing a negative feedback loop, in osteoblasts.

(-)-epigallocatechin gallate inhibits prostaglandin D2-stimulated HSP27 induction via suppression of the p44/p42 MAP kinase pathway in osteoblasts.

We previously reported that prostaglandin D2 (PGD2) stimulates heat shock protein 27 (HSP27) induction through p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), the major polyphenol found in green tea, affects the induction of HSP27 in these cells and the mechanism. EGCG significantly reduced the HSP27 induction stimulated by PGD2 without affecting the levels of HSP70. The PGD2-induced phosphorylation of p38 MAP kinase or SAPK/JNK was not affected by EGCG. On the contrary, EGCG markedly suppressed the PGD2-induced phosphorylation of p44/p42 MAP kinase and MEK1/2. However, the PGD2-induced phosphorylation of Raf-1 was not inhibited by EGCG. These results strongly suggest that EGCG suppresses the PGD2-stimulated induction of HSP27 at the point between Raf-1 and MEK1/2 in osteoblasts.

[Two metastatic colonic cancer patients successfully treated by combination therapy of tegafur/uracil (UFT) and oral Leucovorin].

Two metastatic colonic cancer patients were successfully treated by the combination therapy of UFT plus oral Leucovorin (UFT/LV). UFT was administered orally every eight hours at a dose of 300 mg/day in case of less than 1.20 m(2), 400 mg/day in case of between 1.20 and 1.70 m(2), 500 mg/day in case of over 1.70 m(2), and Leucovorin (75 mg/day) was simultaneously given for 28 consecutive days and stopped for seven days. This cycle was repeated until the patients requested the therapy be discontinued or a severe adverse reaction was observed. Case 1: A 79-year-old male had undergone sigmoidectomy for colonic cancer in 2001 and was diagnosed with pulmonary metastases in August, 2005. His performance status (PS) was grade 3. Case 2: A 61-year-old male with liver metastasis whose primary colonic lesion was surgically resected. After 2 cycles of UFT/LV therapy, a good partial response was achieved in both cases. Adverse effects were very mild, indicating that this therapy was very safe and recommendable for the treatment of metastatic colonic cancer patients with poor PS.

Sternoclavicular joint septic arthritis with chest wall abscess in a healthy adult: a case report.

BACKGROUND: Septic arthritis of the sternoclavicular joint is rare. It can be associated with serious complications such as osteomyelitis, chest wall abscess, and mediastinitis. In this report, we describe a case of an otherwise healthy adult with septic arthritis of the sternoclavicular joint with chest wall abscess. CASE PRESENTATION: A 68-year-old Japanese man presented to our hospital complaining of pain and erythema near the right sternoclavicular joint. Despite 1 week of oral antibiotics, his symptoms did not improve. Computed tomography revealed an abscess with air around the right pectoralis major muscle. After being transferred to a tertiary hospital, emergency surgery was performed. Operative findings included necrotic tissue around the right sternoclavicular joint and sternoclavicular joint destruction, which was debrided and packed open. Methicillin-susceptible Staphylococcus aureus was identified in blood and wound cultures. Negative pressure wound therapy and hyperbaric oxygen therapy were performed for infection control and wound healing. The patient's general condition improved, and good granulation tissue developed. The wound was closed using a V-Y flap on hospital day 48. The patient has been free of relapse for 3 years. CONCLUSIONS: Septic arthritis of the sternoclavicular joint is an unusual infection, especially in otherwise healthy adults. Because it is associated with serious complications such as chest wall abscess, prompt diagnosis and appropriate treatment are required.

Association between the severity of sepsis and the changes in hemostatic molecular markers and vascular endothelial damage markers.

It is well known that disorders of coagulation and fibrinolysis play a major role in the development of organ dysfunction during sepsis. Furthermore, the importance of the early initiation of anticoagulation therapy for severe cases has been emphasized based on the success of recent clinical trials. The purpose of this study is to search for useful markers for predicting organ dysfunction. Plasma samples were prospectively collected from 78 patients within 48 h after the onset of sepsis. Hemostatic markers and endothelial damage markers were compared between the patients with and without organ dysfunction. The WBC and platelet counts were not different between the groups. In contrast, fibrin/fibrinogen degradation products, D-dimer, thrombin-antithrombin complex, plasmin alpha2-antiplasmin complex, soluble fibrin, and total plasminogen activator inhibitor-1 were significantly higher, and the antithrombin activity and protein C levels were lower in the patients with organ dysfunction. Thus, the changes in the hemostatic molecular markers were associated with organ dysfunction from an early stage of sepsis, and antithrombin and protein C activities were found to be the most reliable markers.

Much caution does no harm! Organophosphate poisoning often causes pancreatitis.

Organophosphate poisoning (OP) results in various poisoning symptoms due to its strong inhibitory effect on cholinesterase. One of the occasional complications of OP is pancreatitis. A 62-year-old woman drank alcohol and went home at midnight. After she quarreled with her husband and drank 100 ml of malathion, a parasympathomimetic organophosphate that binds irreversibly to cholinesterase, she was transported to our hospital in an ambulance. On admission, activated charcoal, magnesium citrate, and pralidoxime methiodide (PAM) were used for decontamination after gastric lavage. Abdominal computed tomography detected edema of the small intestine and colon with doubtful bowel ischemia, and acute pancreatitis was suspected. Arterial blood gas analysis revealed severe lactic acidosis. The Ranson score was 6 and the APACHE II (Acute Physiology and Chronic Health Evaluation) score was 14. Based on these findings, severe acute pancreatitis was diagnosed. One day after admission, hemodiafiltration (HDF) was started for the treatment of acute pancreatitis. On the third hospital day, OP symptoms were exacerbated, with muscarinic manifestations including bradycardia and hypersalivation and decreased plasma cholinesterase activity. Atropine was given and the symptoms improved. The patient's general condition including hemodynamic status improved. Pancreatitis was attenuated by 5 days of HDF. Ultimately, it took 14 days for acute pancreatitis to improve, and the patient discharged on hospital day 32. Generally, acute pancreatitis associated with OP is mild. In fact, one previous report showed that the influence of organophosphates on the pancreas disappears in approximately 72 hours, and complicated acute pancreatitis often improves in 4-5 days. However, it was necessary to treat pancreatitis for more than 2 weeks in this case. Therefore, organophosphate-associated pancreatitis due to malathion is more severe. Although OP sometime causes severe necrotic pancreatitis or pancreatic pseudocysts, it was thought that the present patient had a good clinical course without these complications due to the appropriate intensive care including nafamostat, antibiotics, fluid resuscitation, and HDF. In conclusion, OP-associated pancreatitis requires careful assessment because it may be aggravated, as in this case.

An autopsy report of acute myocardial infarction with hypertrophic obstructive cardiomyopathy-like heart.

An 84-year-old woman, who was followed up as hypertrophic obstructive cardiomyopathy (HOCM) in a local hospital, was transferred to our center because of anterior chest pain and diagnosed with acute myocardial infarction (MI). Coronary angiography showed total occlusion of the mid-left anterior descending, and flow was restored after endovascular thrombectomy. An autopsy was performed after she died on hospital day 6. At autopsy, there was no significant stenosis in this vessel and the absence of plaque rupture was confirmed. Likewise, it was unclear asymmetric hypertrophy at autopsy, it could not deny that a sigmoid deformity of the basal septum occurs in elderly patients and can mimic the asymmetric septal hypertrophy of hypertrophic cardiomyopathy. MI was thought to be caused by coronary spasm or squeezing in HOCM-like heart. Therefore, it may be necessary antithrombosis therapy in HOCM-like patients with no history of paroxysmal atrial fibrillation.

Comparison of two pediatric flail chest cases.

Flail chest is a rare complication in pediatric patients with blunt chest trauma. There is no general consensus on which treatment is most appropriate for flail chest in pediatric patients, although it has been reported that surgical fixation is associated with beneficial outcomes for flail chest in adults. The present report described two pediatric cases of flail chest, which was rare in pediatric blunt trauma. In small children, functional residual capacity is smaller, and the thorax is pliable due to high thoracic compliance. Therefore, it is only advisable to select intubation and mechanical ventilation treatment. Likewise, in pediatric flail chest, the available evidence does not suggest that ventilator management protocols should be adopted routinely, and the treatment for pediatric flail chest was not established completely. There were not huge different between the described patients, including injury severity and ventilation setting. However, one had a relapse of flail chest after extubation and chest taping was required, while the other patient's condition was stable after decannulation. As described above, it is difficult to predict a recurrence of flail chest in pediatric patients even if treatment goes well. Therefore, T-piece trial should be considered prior to extubation.

Mechanism of collagen-induced release of 5-HT, PDGF-AB and sCD40L from human platelets: role of HSP27 phosphorylation via p44/p42 MAPK.

Collagen plays a crucial role in hemostasis and thrombosis by activating platelets and reportedly induces the phosphorylation of heat shock protein (HSP) 27 in human platelets. However, the exact role of HSP27 phosphorylation in human platelets has not yet been clarified. In the present study, we investigated the mechanism of collagen-induced HSP27 phosphorylation and the role in human platelets. The collagen-effect on the phospholylation of HSP27 was dose-dependent in the range between 0.03 and 1.0 microg/ml. The phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK) was also stimulated by collagen. PD98059, a specific inhibitor of MAPK kinase (MEK1/2), reduced collagen-induced HSP27 phosphorylation as well as p44/p42 MAPK phosphorylation. PD98059 significantly suppressed collagen-induced releases of serotonin (5-HT), platelet-derived growth factor (PDGF)-AB and soluble CD40 ligand (sCD40L) while it had little effect on the platelet aggregation. These results strongly suggest that the collagen-induced phosphorylation of HSP27 via p44/p42 MAPK is sufficient for releases of 5-HT, PDGF-AB and sCD40L from human platelets.

Antithrombin III reduces collagen-stimulated granule secretion of PDGF-AB and the release of soluble CD40 ligand from human platelets.

Although antithrombin-III (AT-III), an anti-coagulant, has been shown to affect human platelet functions, the direct effect of AT-III on platelets is still unknown. We recently reported that the collagen-induced phosphorylation of the heat shock protein 27 (HSP27) via the p44/p42 mitogen-activated protein (MAP) kinase is sufficient for granule secretion and the release of soluble CD40 ligand (sCD40L) from platelets but not platelet aggregation. In the present study, we investigated whether AT-III affects the collagen-induced secretion of the platelet-derived growth factor (PDGF)-AB and sCD40L release. AT-III inhibited collagen-stimulated platelet aggregation. The collagen-induced secretion of PDGF-AB was significantly suppressed by AT-III. AT-III also reduced sCD40L release. AT-III markedly attenuated the collagen-induced phosphorylated levels of p44/p42 MAP kinase. In addition, AT-III suppressed collagen-induced HSP27 phosphorylation. These results strongly suggest that AT-III reduced collagen-stimulated platelet granule secretion due to the inhibition of HSP27 phosphorylation via p44/p42 MAP kinase.