A retrospective observational study to assess adverse transfusion reactions of patients with and without prior transfusion history.

BACKGROUND AND OBJECTIVES: This study compares the frequency of adverse transfusion reactions (ATRs) after first transfusions with the frequency of ATRs for subsequent (non-first) transfusions. MATERIALS AND METHODS: Five hospitals agreed to systematically collect and share 2 years of data. This was a retrospective observational analysis of data including the number of transfusion episodes and ATRs for red blood cells (RBCs), fresh frozen plasma (FFP) and platelet concentrates (PCs) given to first-time transfusion recipients and to those previously transfused. RESULTS: First transfusion ATRs to RBCs, FFP and PCs were 1.08%, 2.84% and 3.34%, respectively. These are higher than ATR incidences to RBCs (0.69%), FFP (1.91%) and PCs (2.75%) on subsequent transfusions. Specifically, first transfusion incidences of febrile non-haemolytic transfusion reactions (FNHTRs) to RBCs (0.43%) and allergic reactions to FFP (2.51%) were higher than on subsequent transfusions (RBCs: 0.23%, FFP: 1.65%). CONCLUSION: There are risks of ATRs on the first transfusion as well as transfusions of patients with transfusion history.

Persistent parvovirus B19 infection resulting in red cell aplasia after allogeneic hematopoietic stem cell transplantation.

Persistent parvovirus B19 (PVB) infection has been reported sporadically in immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients. However, the pathogenesis of persistent infection has yet to be fully elucidated. We report here a patient with multiple myeloma developing red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic stem cell transplantation (HSCT) caused by PVB. The patient had already had PVB viremia before transplantation and remained asymptomatic. The route of PVB transmission was considered to be direct contact with the patient's family member with primary PVB infection 1 month before transplantation. Treatment with intravenous immunoglobulin resulted in prompt resolution of anemia. These findings suggest that monitoring of PVB DNA is recommended for patients undergoing HSCT and having contact with individuals with documented PVB infection, even if they are asymptomatic.

[Techniques and arts of mediastinal lymph nodes dissection for lung cancer].

The outcomes ofhe operations for the lung cancer depends on the quality of the hilar and mediastinal lymph nodes dissection. Especially in the mediastinal lymph nodes dissection, techniques and arts are indispensable for reliable and promising results in the lung cancer surgery. The essence of procedures of mediastinal lymph nodes dissection are as follows, ( ystematic and sharp lymph nodes dissection as a group, precise and perfect removal of lymph nodes with adjacent fatty tissues based on the anatomical structures, retrograde lymph nodes dissection from the view point of prevention of lymph node metastasis and consequent distant metastasis. Satisfactory and confidential lymph nodes dissection requires attentive assistance of the coworker-surgeons providing good fields of vision. Nowadays minimally invasive approaches by means of thoracoscopic techniques are considered to be smart and welcomed widely in the current thoracic surgery. However, essential for the lung cancer surgery is trying to choose between the operability of radical operation and the degree of minimal invasion. According to a standard rule of ND2a lymph nodes dissection, procedures of upper and middle mediastinal lymph nodes dissection under postero-lateral thoracotomy are summarized.

[Radical surgery using modified open door method for anterior apical tumor].

The approach that should be used for an anterior apical tumor still remains controversial. Since a modified open door method was very useful for the widening of the surgical field in a recent patient with an anterior apical tumor, an outline of this case is reported. The patient was a 66-year-old male with squamous cell carcinoma of the anterior apical region of the right lung (suspected to be invading the thoracic wall, cT3N1M0). After a midline sternal incision with a right unilateral collar incision, the medial half of the right clavicle and a few cm of the right 1st rib on the sternal side were resected to sufficiently expose the area from the right brachiocephalic trunk to around the subclavicular artery and vein, where invasion was suspected. This treatment facilitated widening of the visual field around the site of tumor invasion and made safe right upper lobectomy + combined thoracic wall resection + ND2a possible. In this patient, anterolateral incision at the 4th intercostal level, which is made using the original open door method, could be avoided, probably minimizing surgical invasion.

Haemostatic effects of polymerized albumin particles carrying fibrinogen gamma-chain dodecapeptide as platelet substitutes in severely thrombocytopenic rabbits.

Our purpose was to produce a platelet substitute that could enhance haemostatic ability using rabbits with severe thrombocytopenia. We have developed polymerized albumin particles (polyAlb) for treatment of bleeding and focused on a dodecapeptide, HHLGGAKQAGDV (H12), as a useful ligand for activated platelet. This sequence occurs only at the carboxy-terminus of the fibrinogen gamma-chain (gamma 400-411). H12 was conjugated to the surface of polyAlb modified with poly(ethylene glycol) (PEG) chains to produce blood-compatible particles (H12-PEG-polyAlb) that had prolonged blood residence time and enhanced stability in vitro and in vivo. The H12-PEG-polyAlb was administered intravenously to rabbits with severe thrombocytopenia, and the ear bleeding time was measured in order to evaluate the haemostatic effect. The H12-PEG-polyAlb significantly shortened the ear bleeding time of severely thrombocytopenic rabbits and showed no effect on the inhibition or promotion of endogenous and exogenous coagulation activities. Furthermore, we could assess the haemostatic capacity of the H12-PEG-polyAlb, based on the relationship between transfused platelet count and the bleeding time. The H12-PEG-polyAlb may be a suitable candidate for an alternative to human platelet concentrates infused to treat bleeding in patients with severe thrombocytopenia.

[Congenital bronchoesophageal fistula in an adult; an undiscribed mechanism of symptom tolerance].

We present a case of a congenital bronchoesophageal fistula in a 61-year-old woman. She was referred to hospital because of postprandial heart burn. Three-dimensional (3D) computed tomography (CT) demonstrated an anastomosis between her right intermediate bronchus and esophagus. In spite of direct communication between her bronchus and esophagus, she has never suffered severe infection. We visualized the orifice of fistula closed with mucosal flap in swallowing by means of a bronchofiberscope. The delay of a diagnosis was explained by symptom tolerance. Some theories as to the symptom tolerance are found in literatures, but we supposed to find an undiscribed mechanism; closure of the orifice in swallowing. The fistula was surgically closed.

[Pulmonary staple granuloma mimicking lung cancer; report of a case].

A 67-year-old man was referred to our hospital with chief complaints of bloody sputum and an abnormal chest shadow. He had a history of chronic renal failure and surgery for right pneumothorax. During dialysis treatment 2 years ago, an examination revealed a mass shadow with spiculation in the apex of the right lung. Subsequently, he noted bloody sputum, and the shadow became larger. Serum Progastrin-releasing-peptide (GRP) levels remained within the range of 70-80 pg/ml at the previous clinic, but were elevated to 109 pg/ml on admission to our hospital. These findings suggested lung cancer developing around the scar due to pneumothorax surgery, and we performed an operation. The resected tumor was a granuloma formed around a staple with a polytetra-fluoroethylene (PTFE) sheet, showing no evidence of malignancy. The patient's postoperative course was uneventful, and the serum Pro-GRP level fell to 60 pg/ml.

[Median approach for the right upper lobe lung cancer patient with impaired pulmonary function].

We report the usefulness of a median approach to the right upper lobe lung cancer with impaired pulmonary function. Patient was a 68-year-old man with chronic obstructive pulmonary disease and primary right upper lobe (S1) lung cancer with suspected anterior mediastinal invasion (cT4N0M0). Thoracoscopy excluded mediastinal invasion, but a median sternal incision was made to avoid injuring respiratory muscles and postoperative respiratory complications. We successfully performed systematic mediastinal lymph node dissection (ND2a) after right upper lobectomy. The patient was discharged on the 10th postoperative day without any events. He eventually underwent additional chemotherapy because of the liver metastasis confirmed at 8 months after the operation. In right upper lobe lung cancer patients with impaired pulmonary function, a median approach seems useful for intraoperative respiratory management and the sparing of respiratory muscles which will reduce the possibility of postoperative respiratory complications.

[Surgical approach for histopathological determination of anterior mediastinal malignant lymphoma].

In a retrospective review of all patients who admitted our hospital between January 1992 and December 2006, we identified 9 with anterior mediastinal malignant lymphoma. They represented 6.8% of the 133 patients with mediastinal tumor. Histology revealed 3 cases of primary mediastinal large B-cell lymphoma, 2 of Hodgkin lymphoma, 2 of precursor T-lymphoblastic lymphoma and 2 of thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma. Careful attention should be paid to the relatively high incidence of malignant lymphoma in the anterior mediastinal tumors. It is highly important to differentiate of malignant lymphoma from other diseases that shape anterior mediastinal tumor to avoid unnecessary operation. Early and accurate diagnosis of these tumors is also important because some of these patients require immediate treatment by hematology specialists.

[Reoperation for left main bronchial stump fistula developing after pneumonectomy].

We report the case of a 71-year-old male patient who underwent reoperation for bronchial stump fistula developing after left pneumonectomy for adenocarcinoma of the left lung (clinical stage IIB). After surgery, he developed persistent, severe cough and chest X-ray films taken on the 23rd postoperative day showed a drop in the air-fluid level in the left lung field, which, along with bronchoscopic findings, strongly suggested the bronchial stump fistula and subsequent reoperation was performed. Both superior pulmonary vein and main pulmonary artery were dissected again proximally in pericardium, and the left main bronchus was separated from the surrounding tissue. Bronchial stump was closed with a stapler as close to the carina as possible, and additional resection was performed. After reoperation, the patient had an uneventful course, and was discharged in the second postoperative week. Shorter length of bronchial stump may be the most important factor to prevent the bronchial stump fistula developing after pneumonectomy.

[Median approach for upper lobe lung cancer patients with suspected anterior mediastinal invasion].

We report the usefulness of a median approach to the mediastinum for the treatment of lung cancer with possible mediastinal invasion. Patient was a 74-year-old man with left S3 squamous cell carcinoma suspected of anterior mediastinal invasion (cT4N0M0) because of hoarseness before surgery. A median sternotomy with partial collar incision was chosen for surgery. The tumor was widely adherent to the anterior mediastinum, invading the common carotid artery and the origin of the left subclavian artery. Left upper lobectomy with ND2a by incomplete resection of the invading portion followed by postoperative radiotherapy was performed. For upper lobe lung cancer with possible mediastinal invasion, a median approach seems to be useful, because it facilitates both easy approach to the anterior mediastinum and the management of invasion of large vessels.

The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.

Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]o), platelet aggregation can be induced under low shear force (12 dyn/cm2) and is mediated by fibrinogen binding to the glycoprotein IIb-IIIa complex. Aggregates formed under these conditions are not stable, and when shear force is increased to 68 dyn/cm2, disaggregation results. By contrast, platelets from blood collected with hirudin as anticoagulant, wherein [Ca2+]o is within normal plasma levels, do not undergo low shear-induced aggregation; however, after exposure to a shear force above 80 dyn/cm2, aggregation is observed but only when von Willebrand factor is present and can interact with both its platelet binding sites, glycoprotein Ib-IX and glycoprotein IIb-IIIa. Fibrinogen is not involved in high shear-induced aggregation which, in fact, occurs normally in patients with severe afibrinogenemia. Thus, von Willebrand factor in the absence of exogenous agonists can mediate platelet aggregation in experimental conditions that may mimic the hemorheological situation of partially occluded arteries. This pathway of platelet aggregation involving only one adhesive ligand and two membrane adhesion receptors may play a relevant role in thrombogenesis.

Low shear stress can initiate von Willebrand factor-dependent platelet aggregation in patients with type IIB and platelet-type von Willebrand disease.

Platelets exposed to shear stress aggregate in the absence of exogenously added agonists, utilizing distinct platelet membrane receptors and ligands depending upon the level of shear stress applied. Using a modified cone and plate type viscometer, we previously demonstrated that, under low shear stress (18 dyn/cm2), aggregation is mediated by platelet membrane glycoprotein (GP) IIb-IIIa and fibrinogen, whereas aggregation induced by high shear stress (108 dyn/cm2) requires the binding of von Willebrand factor (vWF) to both GPIb-IX and GPIIb-IIIa (Ikeda, Y., M. Handa, K. Kawano, T. Kamata, M. Murata, Y. Araki, H. Anbo, Y. Kawai, K. Watanabe, I. Itagaki, et al. 1991. J. Clin. Invest. 87:1234-1240). Here we report that vWF-dependent aggregation occurs under low shear stress in citrated platelet-rich plasma (PRP) from two types of congenital bleeding disorders, platelet-type von Willebrand disease (vWD) and type IIB vWD, in both of which ristocetin-induced aggregation is known to be heightened. Aggregation induced by low shear stress was enhanced in both types of disorders compared to normal controls, and the enhancement was completely abolished by anti-vWF monoclonal antibody NMC-4, which blocks the GPIb-binding site on vWF. Under high shear stress, the extent of maximal aggregation was not different between controls and the patient groups although maximal aggregation was reached much more quickly in the latter. When citrated PRP was exposed to a gradient of shear stress (6 to 108 dyn/cm2 over a 5-min period), vWF-dependent aggregation, as judged from the inhibitory effect of NMC-4, first occurred at 14 dyn/cm2 in platelet-type vWD and at 10-12 dyn/cm2 in type IIB vWD, as compared with more than 81 +/- 20.1 dyn/cm2 in control platelets. These results suggest that an abnormality in either vWF or GPIb-IX triggers the aggregation-inducing interaction of the two molecules under low shear stress, which might explain the intravascular platelet clumping, that presumably underlies the thrombocytopenia observed in these bleeding disorders.

A role for glycosphingolipid-enriched microdomains in platelet glycoprotein Ib-mediated platelet activation.

BACKGROUND: Glycoprotein (GP) Ib, a platelet von Willebrand factor (VWF) receptor, plays a crucial role in thrombosis and hemostasis. As recent reports have suggested that GPIb partially locates in a particular region, designated as glycosphingolipid-enriched microdomains (GEMs), we hypothesized that GEMs play a central role in GPIb-mediated platelet activation. METHODS: Platelets were stimulated by VWF/botrocetin to activate platelets through GPIb. GEMs and non-GEMs were isolated by sucrose density gradient ultracentrifugation and the location of signaling molecules characterized. The role of GEMs-mediated signaling in platelet behavior was tested by platelet aggregation and by platelet interaction with immobilized VWF under flow conditions when GEMs were disrupted by methyl-beta-cyclodextrin (MbetaCD). RESULTS: GPIb was partially translocated to GEMs upon VWF/botrocetin stimulation. Immunoprecipitation of GPIb in GEMs and non-GEMs revealed that the tyrosine kinases, Src and Lyn, were associated with GPIb only in GEMs after GPIb-stimulation, and not in non-GEMs. Activation of PLCgamma2 was more intense in GEMs than non-GEMs. Disruption of GEMs by MbetaCD strongly inhibited tyrosine phosphorylation of Syk and PLCgamma2. Functional studies revealed that stable adhesion of platelets to a VWF-coated surface under flow was impaired by GEM disruption by MbetaCD. CONCLUSION: The combined results suggest that GEMs play an important role in GPIb-mediated platelet activation.

Neuroanatomical and pharmacological assessment of Fos expression induced in the rat brain by the phosphodiesterase-4 inhibitor 6-(4-pyridylmethyl)-8-(3-nitrophenyl) quinoline.

A major obstacle in the therapeutic development of phosphodiesterase-4 (PDE4) inhibitors is the production of adverse side effects such as nausea and vomiting. Immunohistochemical detection of Fos-like immunoreactivity (FLI) was used to address the neuroanatomical basis for the pharmacological actions of PDE4 inhibitors. The potent and selective PDE4 inhibitors 6-(4-pyridylmethyl)-8-(3-nitrophenyl) quinoline (PMNPQ) and rolipram elevated FLI in brain regions potentially relevant to the anti-depressant and emetic effects of PDE4 inhibition. PMNPQ and rolipram elevated FLI in the locus coeruleus, habenula, paraventricular nucleus of the thalamus, amygdala and nucleus accumbens, all structures with strong limbic connectivity implicated in arousal, memory and affective aspects of behaviour. Consistent with the emetic effects of PDE4 inhibitors such as PMNPQ and rolipram, these compounds elevated FLI in caudal brainstem nuclei such as the area postrema and nucleus of the solitary tract. Administration of the NK(1) antagonist RP 67580 prior to PMNPQ reversed increases in FLI produced by PMNPQ in these regions. RP 67580 did not, however, reduce PMNPQ-induced FLI in limbic structures. These findings suggest that PDE4 inhibitors produce emesis by increasing NK(1) receptor activation in the AP/NTS and implicate brain regions associated with reward and mood such as the amygdala, paraventricular nucleus of the thalamus, habenula and nucleus accumbens in the anti-depressant activity of such compounds.

Immunoneutralization of glycoprotein Ibalpha attenuates endotoxin-induced interactions of platelets and leukocytes with rat venular endothelium in vivo.

This study aimed to examine molecular mechanisms for endotoxin-induced adhesive changes in platelets in vivo. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester were visualized in rat mesenteric venules through intravital microscopy assisted by a high-speed fluorescence video imager at 1000 frames per second or by a normal-speed intensifier under monitoring of erythrocyte velocity. Leukocyte rolling was examined by normal-speed transmission video images. The velocity of platelets traveling along the centerline of venules followed that of erythrocytes, whereas that measured at the periendothelial space was significantly smaller than the erythrocyte velocity; a majority of these cells exhibited transient but notable rolling with endothelium. Administration of endotoxin increased the density of periendothelial platelets and reduced the rolling velocities of platelets and leukocytes in venules: All events were attenuated by anti-rat P-selectin monoclonal antibody s789G or by anti-human glycoprotein (GP) Ibalpha monoclonal antibody GUR83/35, which blocks ristocetin-induced aggregation of rat platelets. Isolated rat platelets injected into endotoxin-pretreated rats were able to roll on the venules. This event was attenuated by pretreatment of platelets in vitro with GUR83/35 but not with s789G, suggesting involvement of endothelial P-selectin and platelet GP Ibalpha in the endotoxin-induced responses. Furthermore, isolated human platelets showed similar rolling interactions with endotoxin-preexposed rat venules, and pretreatment of the platelets with GUR83/35, but not with s789G, significantly reduced such interactions. Our results provide the first evidence for involvement of GP Ibalpha in endotoxin-induced microvascular rolling of platelets and leukocytes, and this system serves as a potentially useful tool to examine GP Ibalpha-associated function of human platelets in vivo.

[Pulmonary actinomycosis developing diffuse phregmone after pneumonectomy].

The patient was a 75-year-old male who consulted the department of respiratory tract internal medicine in our hospital for left chest pain occurring from the beginning of December 2003. Chest X-ray indicated a tumorous shadow in the left lower lung field. A chest CT also revealed an irregularly shaped mass shadow in the left lower lobe. Since bronchoscopy failed to establish a definitive diagnosis, the patient was referred to our department for surgery to undertake thoracotomy. After left pneumonectomy being performed based on a suspicion of lung abscess, pathological examination of specimen from the resected left lung showed sulfur granules which led to the diagnosis of pulmonary actinomycosis. Because of the diffuse phregmone developing around the surgical wound, benzylpenicillin potassium administration was started, and was continued for a further 6 months on an outpatient basis. Pulmonary actinomycosis is a relatively rare chronic pulmonary infection. It is often difficult to distinguish pulmonary actinomycosis from other pulmonary disease such as lung cancer because of the similarity of their appearance on X-ray or CT, and almost all cases of pulmonary actinomycosis are diagnosed by thoracotomy.

[Large cell carcinoma with chest wall infiltration combined with contralateral giant bulla].

A 48-year-old male consulted the department of respiratory medicine for right precordial pain occurring from the beginning of May 2004. Chest X-ray indicated a tumorous shadow in the right upper lung field and a large left lung cyst. Although chest wall infiltration was suspected based on computed tomography (CT) demonstrating a mass lesion in the right S2, there was no significant swelling of the mediastinal lymph node. On the left side, the lung was markedly compressed by a large cyst in the left upper lobe. Since bronchoscopy failed to establish a definitive diagnosis, the patient was referred to our department for surgery based on a suspicion of malignant pulmonary tumor. Considering both the risk of perioperative complications due to the left cystic lesion at surgery for right lung lesion and the improvement of respiratory function by removing cystic lesion of the left lung, the left side operation was preceded by the right side. Although postoperative examinations of respiratory function did not demonstrate any particular improvement, the results of selective right pulmonary artery obstruction test supported the possibility of pulmonary lobectomy. Therefore, the right upper lobectomy and ND 2a mediastinal dissection combined with chest wall resection was subsequently performed. Postoperative pathological diagnosis revealed that the tumor was a stage IIB large cell carcinoma of pT3N0M0 with costal infiltration.

[Surgical strategy for critical aoritc stenosis with small aortic annulus in the elderly patients].

BACKGROUND: There are an increasing number of elderly patients with critical aortic stenosis. This study was performed to evaluate the surgical outcome of aortic valve surgery for elderly patients with aortic stenosis. METHODS: Eleven patients aged over 75 years old (mean 79.7 +/- 4.4) underwent aortic valve replacement with stented bioprosthesis from May 2001 to August 2004. All of the patients had a history of congestive heart failure, syncope, or angina pectoris with multiple medical problems including renal dysfunction, diabetes mellitus, cerebral infarction, or coronary artery disease. The New York Heart Association (NYHA) classification ranged II to IV (mean 2.8 +/- 0.7). Their logistic Euro score ranged from 2.56 to 41.61 (mean 8.6 +/- 10.9). The concomitant procedures were annular enlargement in 2 and coronary artery bypass grafting (CABG) in 3 patients. RESULTS: All patients tolerated these procedures well and were discharged except 1 patient who died from arrhythmia on the postoperative day 14. Postoperative echocardiogram after 3 months showed satisfactory decrease in peak left ventricular-aortic pressure gradient as well as left ventricular mass regression. All surviving patients are in NYHA class I. CONCLUSIONS: Aortic valve replacement provided satisfactory results for elderly patients. Surgical treatment should be considered even for the elderly patients with critical aortic stenosis under meticulous perioperative management.