Evaluation of efficacy and indications of surgical fixation for multiple rib fractures: a propensity-score matched analysis.

PURPOSE: The purpose of this study was to assess the effects of recent surgical rib fixation and establish its indications not only for flail chest but also for multiple rib fractures. METHODS: Between 2007 and 2015, 187 patients were diagnosed as having multiple rib fractures in our institution. After the propensity score matching was performed, ten patients who had performed surgical rib fixation and ten patients who had treated with non-operative management were included. Categorical variables were analyzed with Fischer's exact test and non-parametric numerical data were compared using the Mann-Whitney U test. Wilcoxon signed-rank test was performed for comparison of pre- and postoperative variables. All statistical data are presented as median (25-75 % interquartile range [IQR]) or number. RESULTS: The surgically treated patients extubated significantly earlier than non-operative management patients (5.5 [1-8] vs 9 [7-12] days: p = 0.019). The duration of continuous intravenous narcotic agents infusion days (4.5 [3-6] vs 12 [9-14] days: p = 0.002) and the duration of intensive care unit stay (6.5 [3-9] vs 12 [8-14] days: p = 0.008) were also significantly shorter in surgically treated patients. Under the same ventilating conditions, the postoperative values of tidal volume and respiratory rate improved significantly compared to those values measured just before the surgery. The incidence of pneumonia as a complication was significantly higher in non-operative management group (p = 0.05). CONCLUSIONS: From the viewpoints of early respiratory stabilization and intensive care unit disposition without any complications, surgical rib fixation is a sufficiently acceptable procedure not only for flail chest but also for repair of severe multiple rib fractures.

Stress response of prolactin-releasing peptide knockout mice as to glucocorticoid secretion.

Prolactin-releasing peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP-knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP-KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP-KO mice. As we reported previously, PrRP stimulates corticotrophin-releasing factor and regulates the hypothalamic-pituitary-adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP-KO mice, and found that PrRP-KO mice showed higher concentrations of blood glucose and corticosterone compared to wild-type mice after restraint stress. By contrast, there were no difference in c-Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild-type and PrRP-KO mice. Thus, we conclude that PrRP-KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion.

[Aortic valve replacement and repeat coronary artery bypass grafting in a patient with a patent internal thoracic artery bypass graft; report of a case].

We report a case of aortic valve replacement and repeat coronary artery bypass grafting in a patient with a patent internal thoracic artery bypass graft. A 77-year-old man, who underwent coronary artery bypass grafting (CABG) 10 years ago, was admitted to the hospital for aortic stenosis and angina pectoris. Transthoracic echocardiography demonstrated severe aortic calcification with an 86 mmHg gradient across the aortic valve. Coronary angiography demonstrated the patency of all grafts and 90% stenosis of the left circumflex coronary artery. At surgery, a full median sternotomy was performed. The adhesions around the heart and great vessels were severe and the left internal thoracic artery (LITA) was found adherent to the heart and sternum. The LITA and saphenous vein graft (SVG) graft were dissected carefully. Retrograde coronary sinus (CS) perfusion was performed with antegrade myocardial protection for cardiac arrest. We performed aortic valve replacement (AVR) with a 17 mm St. Jude Medical Regent Valve and CABG to the circumflex artery with the saphenous vein under cardiopulmonary bypass. His postoperative course was uneventful. He was discharged from our hospital without major complications.

[Recurrent cardiac myxoma that developed rapidly in a short period].

A 55-year-old woman, who had undergone extirpation of left atrial myxoma 3-years before, was admitted to our hospital with dyspnea. Chest computed tomography revealed a low density mass in the left atrium (LA) with a diameter of 54 mm. Transthoracic echocardiography showed that the mass was attached to the left atrial septal wall and had a pendulum-like movement. We urgently performed an operation for recurrent left atrial myxoma. Through atrial transseptal approach, a huge myxomatus tumor was observed in the LA. The stalk was on the endocardium at the cranial side of the previous autologous pericardial patch. The tumor was completely excised along with the patch. We repaired the disrupted endocardium and performed Dacron patch repair of the atrial septal defect. The patient recovered uneventfully and was discharged 14 days after surgery. The excised tumor was found to be myxoma on pathological examination similar to the previous tumor. We report a case of recurrent left atrial myxoma with rapid growth in a short time period.

Partial left ventriculectomy in a 3-year-old boy with dilated cardiomyopathy.

A 3-year-old boy suffered severe heart failure 2 months after ventricular septal defect repair. The cardiothoracic ratio was 67% and the ejection fraction 13%. Echocardiography showed a dilated left ventricle and thin myocardium. After thorough study, we made a diagnosis of dilated cardiomyopathy. Because conventional therapy was unsuccessful, we conducted partial left ventriculectomy with Alfieri repair of the mitral valve. The postoperative cardiothoracic ratio was 57% at 1 year of follow-up and the ejection fraction 40%. The New York Heart Association functional class improved from IV to I. In conclusion, the role of partial left ventriculectomy is both as a bridge to transplantation and as a definitive repair in dilated cardiomyopathy during childhood.

[Surgical treatment of 2 cases of irradiation induced constrictive pericarditis].

A 72-years-old man underwent radiation therapy (62 Gy) for esophageal carcinoma. Twelve months later, symptoms of heart failure such as syncope, cough and hepatomegaly manifested. On catheter study, a dip and plateau pattern of right ventricular pressure curve was evident. Pericardiectomy without extracorporeal circulation was performed. Operative findings and pathological results were compatible with radiation-induced constrictive pericarditis. He recovered from the heart failure, and has been doing well 3 months after the surgery. A 54-years-old man underwent thymectomy for malignant thymoma. He underwent a radiation therapy (52 Gy) postoperatively. After 12 months from the irradiation, syncope and dyspnea manifested. On catheter study, a dip and plateau pattern of right ventricular pressure curve was observed. Pericardiectomy with extracorporeal circulation was performed. He recovered from the heart failure after pericardiectomy, however he died of radiation-induced pneumonitis 6 months later.

Retrocaval ureter and preaortic iliac venous confluence in a patient with an abdominal aortic aneurysm.

Anomalous anatomic location of a large venous system poses a potential hazard in aortic operations. We encountered a patient with an infrarenal abdominal aortic aneurysm who was also found at preoperative contrast-enhanced computed tomography to have a retrocaval right ureter and a preaortic iliac vein confluence. This combined anomaly has not previously been reported except for one postmortem case. As abdominal aortic surgery is currently performed routinely, care must be taken to avoid injury to surrounding organs due to rare anatomic anomalies.

[A case report of selective IgA deficiency in rheumatoid arthritis and anti-IgA antibody induced anaphylactic transfusion].

We described a case of rheumatoid arthritis (RA) with selective IgA deficiency. A 69 year-old female with RA was admitted because of gall bladder cancer, and also had selective IgA deficiency which serum IgA level was less than 5.0 mg/dl, and IgA 1 and IgA 2 subclasses were not detected. Prior to the operation, she was given red cell compatible blood transfusion because of severe anemia. After 30 min of transfusion, she developed chill, nausea, vomiting and hypotension. These anaphylactic reactions might be induced by the presence of anti-IgA antibody, since the level of this antibody titers in her serum was elevated, assessed by the methods of ELISA and Western blotting. Although a case of RA associated with selective IgA deficiency, and also with elevated serum anti-IgA antibody level is extremely uncommon, attention should be paid to the presence of anti-IgA antibody in patients with selective IgA deficiency to avoid any unexpected anaphylactic reactions.

The mitogen-activated protein kinase pathway inhibits ceramide-induced terminal differentiation of a human monoblastic leukemia cell line, U937.

This communication describes an extracellular signal-regulated kinase kinase (MEK)-dependent signal transduction pathway that prevents the terminal differentiation of a hemopoietic cell line. Both PMA and the cell-permeable ceramide, C2-ceramide, caused differentiation of U937 cells, but with distinct cell morphology and CD11b/CD14 surface expression. While PMA activated extracellular signal-regulated kinase (ERK), a downstream kinase of Raf-MEK signaling, C2-ceramide activated c-Jun NH2-terminal kinase (JNK), an anchor kinase of stress-induced signaling. Furthermore, only C2-ceramide stimulated an induction of cell cycle arrest that was associated with stable expression of p21CIP1 and retinoblastoma nuclear phosphoprotein dephosphorylation. Expression of p21CIP1 and JNK activation were also observed in sphingosine-treated cells, whereas sphingosine did not induce detectable differentiation. Concomitant stimulation with C2-ceramide and PMA resulted in the PMA phenotype, and cell cycle arrest was absent. ERK activation was enhanced by C2-ceramide plus PMA stimulation, whereas the activation of JNK was aborted. Strikingly, the inhibition of MEK with PD98059 altered the phenotype of C2-ceramide- and PMA-stimulated U937 cells to that of cells treated with C2-ceramide alone. Thus, ERK and JNK pathways deliver distinct signals, and the ERK pathway is dominant to the JNK cascade. Furthermore, differentiation and cell cycle arrest caused by C2-ceramide rely on independent signaling pathways, and JNK is an unlikely signaling element for this differentiation. Importantly, during C2-ceramide and PMA costimulation, the JNK pathway is not simply blocked by ERK activation; rather, cross-talk between these MAP kinase pathways acts to simultaneously augment ERK activity and down-regulate JNK activity.

Activation of p21-CDC42/Rac-activated kinases by CD28 signaling: p21-activated kinase (PAK) and MEK kinase 1 (MEKK1) may mediate the interplay between CD3 and CD28 signals.

CD28, a T cell costimulatory receptor, provides a signal that induces both optimal proliferation and the production of IL-2 by TCR-activated T cells. We show that the stimulation of CD28 leads to the activation of p21-activated kinase and MEK kinase 1. The same pathway was also stimulated in T cells treated with the cell-permeable ceramide analogue, C2-ceramide. The combined stimulation of either CD3 and CD28 or CD3 concurrently with C2-ceramide largely enhanced the activity of p21-activated kinase and MEK kinase 1. Therefore the Rac1/CDC42-coupled pathway(s) is a candidate that transduces and facilitates cross-talk between the CD28 costimulatory signal and the TCR signal.

Stimulation of CD28 with B7-2 promotes focal adhesion-like cell contacts where Rho family small G proteins accumulate in T cells.

Unless a costimulatory signal is provided, TCR recognition of Ag bound to the MHC is insufficient to induce optimal T cell proliferation or the production of IL-2. Here we show that the stimulation of CD28, a T cell costimulatory receptor, by a specific Ab increases F-actin contents in T cells. The interaction between T cells and B7-2-transfected Chinese hamster ovary cells expressing the CD28 ligand leads to the rearrangement of the actin cytoskelton in the region of cell-cell contact. Within the Rho family of G proteins, Rac1, but not Rho, translocates to the sites of cell-cell contact where Tailin also accumulates. These results indicate that the interaction between B7-2 and CD28 establishes a focal adhesion-like cell contact between T cell and APCs. The results also suggest that CD28 signaling is primarily transduced by a cytoskeletal rearrangement/signaling pathway mediated by the Rho family G proteins.

Phase transitions of CdS microcrystals under high pressure.

The experiment under high pressure using a diamond anvil cell (DAC) requires the utilization of synchrotron radiation. High-pressure experiments were performed using a DAC on CdS microcrystals, both in the far-IR and in the X-ray regions, in order to study the lattice dynamics and lattice stability concerned with the phase transitions. From these experiments, experimental evidence is presented indicating that a CdS microcrystal of smaller diameter shows a higher transition pressure for lattice transformation under pressure. The origin of such an increase in the transition pressure in the microcrystals is discussed in relation to the surface tension.

[A case of gastric cancer completely responding to sequential methotrexate and 5-fluorouracil therapy].

A case of an 81-year-old male with Borrmann II type was reported. The lesion was diagnosed histologically as undifferentiated adenocarcinoma. Biochemically modulated chemotherapy preceded by administration of Methotrexate (MTX) and followed by 5-fluorouracil (5-FU) was given to him. The procedure was weekly intermediate-dose therapy consisting of MTX 100 mg (i.v.) followed 3 hours later by 5-FU 600 mg (i.v.) with leucovorin rescue in the following 2 days. After this treatment was repeated 6 times, advanced gastric cancer disappeared on endoscopic and histological findings, so the patient was regarded as showing a complete response. Ths, this biochemically modulated chemotherapy was thought to be in effective method against gastric cancer.

[A case of rheumatoid arthritis associated with agranulocytosis during bucillamine treatment].

Bucillamine has been reported to have beneficial effects in rheumatoid arthritis. This report concerns a case of RA in which agranulocytosis developed while on a course of bucillamine. A 52-year-old female with RA developed a rapid fall in white blood cell count after 4 weeks of bucillamine treatment at daily dose of 50 mg. Agranulocytosis was diagnosed (WBC 1300/mm3, granulocytes 5%). The administration of bucillamine was halted and she was treated with only prophylactic antibiotic regime. The peripheral granulocyte count result rapidly reversed within 3 days after discontinuation of the bucilamine treatment. Anti-leukocyte antibody was detected by the leukocyte lysis phenomenon method during the period of agranulocytosis. And high intrinsic G-CSF activities were detected in the patient serum before the recovery period of agranulocytosis. Agranulocytosis is a rare side effect of bucillamine but it is potentially more harmful than other side effects. In treatment with bucillamine, therefore, the drug should be carefully administered and regular blood examinations carried out to prevent the occurrence of this side effect.

[Lung injury associated with bucillamine therapy].

We have reported previously a first case of interstitial pneumonitis in rheumatoid arthritis treated with bucillamine in 1989. Thereafter, a dozen cases with lung injury associated with bucillamine therapy have been reported. To explore the similarities among these patients, we tried to carry out a survey concerning the lung injuries in these cases in the present study. We obtained the following results. (1) Patients with lung injury consisted of 7 females and 3 males, aged 65 years on average (59-72). (2) The total amount of bucillamine used was 20-40 g on average (5.1-144 g) during approximately 100 days. (3) Serum rheumatoid factor was positive in 9 of 10 cases. (4) HLA-DR4 was significantly (p less than 0.01) detected in all cases of lung injury associated with bucillamine. (5) Interestingly the effect of bucillamine on rheumatoid disease activity was excellent in most cases. (6) Drug lymphocyte stimulation test (DLST) using bucillamine was performed in 6 cases. Positive DLST was found in 3 of 6 cases. These results suggest that cell-mediated hypersensitivity reaction (Coombs & Gell type IV) may contribute to the development of lung injury associated with bucillamine therapy.

Lysosomal enzyme activities in experimental granulomatous inflammation.

Foreign-body (dextran beads) and hypersensitivity (antigen-coupled agarose beads) lung granulomas were induced in BALB/c mice by the intratracheal injection of beads. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous extracts of both granulomas contained high levels of lysosomal enzymes N-acetyl-beta-D-glucosaminidase (NAG) and lysozyme. Lysosomal enzyme activities in the extracts correlated with granuloma sizes. Dispersed granuloma cells were able to produce these enzymes. These results suggest that lysosomal enzymes may reflect the activity/size of granulomatous inflammation.

Involvement of interleukin-1-like factor(s) in type II collagen-induced arthritis in mice.

To explore the role of interleukins in development of arthritis, we induced collagen-induced arthritis in mice and examined interleukin activities in the inflamed joints. Arthritis developed in 90% of mice 4-5 weeks after primary immunization with type II collagen. Joint extracts from mice with collagen-induced arthritis contained high levels of interleukin 1 (IL-1)-like activity but not interleukin 2 (IL-2) or interleukin 4 (IL-4) activity. IL-1-like activities in the lesions were correlated with development of arthritis assessed by joint swelling and erythema. These results suggest that IL-1-like factor(s) may participate in the etiopathogenesis of collagen-induced arthritis in mice.