Molecular epidemiologic analysis of a Pneumocystis pneumonia outbreak among renal transplant patients.

Between 18 November and 3 December 2011, five renal transplant patients at the Department of Nephrology, Toho University Omori Medical Centre, Tokyo, were diagnosed with Pneumocystis pneumonia (PCP). We used molecular epidemiologic methods to determine whether the patients were infected with the same strain of Pneumocystis jirovecii. DNA extracted from the residual bronchoalveolar lavage fluid from the five outbreak cases and from another 20 cases of PCP between 2007 and 2014 were used for multilocus sequence typing to compare the genetic similarity of the P. jirovecii. DNA base sequencing by the Sanger method showed some regions where two bases overlapped and could not be defined. A next-generation sequencer was used to analyse the types and ratios of these overlapping bases. DNA base sequences of P. jirovecii in the bronchoalveolar lavage fluid from four of the five PCP patients in the 2011 outbreak and from another two renal transplant patients who developed PCP in 2013 were highly homologous. The Sanger method revealed 14 genomic regions where two differing DNA bases overlapped and could not be identified. Analyses of the overlapping bases by a next-generation sequencer revealed that the differing types of base were present in almost identical ratios. There is a strong possibility that the PCP outbreak at the Toho University Omori Medical Centre was caused by the same strain of P. jirovecii. Two different types of base present in some regions may be due to P. jirovecii's being a diploid species.

Chronic atherosclerotic mesenteric ischemia that started to develop symptoms just after anaphylaxis.

An 83-year-old woman was referred to our emergency department with acute urticaria and sudden shortness of breath approximately 30 min after taking rectal diclofenac potassium for lumbago. After treatment with adrenaline and corticosteroids, the patient became hemodynamically stable and left the hospital on the next day. She attended our hospital 1 week after the onset of anaphylaxis because of repeated postprandial epigastric pain. No abnormal lesions were found in endoscopy. Radiographic selective catheter angiography revealed chronic mesenteric ischemia caused by atherosclerosis and abundant collateral arteries between the celiac trunk, the superior mesenteric artery and the inferior mesenteric artery. Patients with chronic mesenteric ischemia usually present with a clinical syndrome characterized by painful abdominal cramps and colic occurring typically during the postprandial phase. Fear of eating resulted in malnutrition. She was prescribed proton pump inhibitor, digestants, anticholinergic agents, serine protease inhibitors, prokinetics, antiplatelet agents and transdermal nitroglycerin intermittently, but these had no beneficial effects. It was most probable that this patient with chronic atherosclerotic mesenteric ischemia was suffering from functional abdominal pain syndrome induced by anaphylaxis. Since psychiatric disorders were associated with alterations in the processing of visceral sensation, we facilitated the patient's understanding of functional abdominal pain syndrome with the psychologist. Postprandial abdominal pain gradually faded after administration of these drugs and the patient left the hospital. Developing a satisfactory patient-physician relationship was considered more effective for the management of persistent abdominal pain caused by complicated mechanisms.

[The relation between the frequency of exercise oxygen desaturation following major lung resection and the predictions of postoperative pulmonary function].

The predictors of oxygen desaturation during exercise in patients submitted to major pulmonary resection for lung cancer are to be determined. We analyzed retrospectively the relation between the oxygen saturation by pulse oxymetry (Spo2) during exercise and the predictions of postoperative pulmonary function. A hundred twenty-two patients with lung cancer who underwent lung resection from January 1999 to May 2004 were included (79 men, 43 women, average age 66.9 +/- 9.2). A fall over 5% in Spo2 during exercise was termed 'desaturation'. Twenty-eight patients developed desaturation [group D(+)] and 94 patients did not [group D(-)]. We compared the predictions of postoperative pulmonary function (%ppoVC, %ppoFEV1.0, %ppoDLco) between these 2 groups. As a result, only %ppoDLco was significantly different between 2 groups [D(+) 68.7 +/- 19.1%, D(-) 83.8 +/- 24.9%]. Patients with poor %ppoDLco are at increased risk to develop a postoperative exercise oxygen desaturation.

[The last period of surgical site infection after pulmonary resection for lung cancer with hemodialysis; report of a case].

An 80-year-old man had been on maintenance hemodialysis for nondiabetic chronic renal failure from June 1996. He underwent investigation of an abnormal chest X-ray and was referred to our hospital with a diagnosis of squamous cell carcinoma in the upper lobe of the right lung. On February 20, 2003, right upper lobectomy was performed. The postoperative course was uneventful and he was discharged on postoperative day 13. Two weeks later he was readmitted with a wound infection. Although he received antibiotics, drainage, and wound lavage, his fever persisted and chest X-ray showed inflammatory changes in the right lower lung field. He was placed on mechanical ventilation for dyspnea. After this, his respiratory function became stable and he could be weaned from the ventilator within 2 weeks. The subsequent course was uneventful and he was discharged 1 month after re-admission. This patient needed ventilation due to weakness caused by wound infection. Such infection is uncommon but can be fatal for a compromised host, so we administered antibiotics for 3 days until the wound closed.

[Tension hemopneumothorax complicated by severe hepatic and renal disorder; report of a case].

A 46-year-old man was admitted to our hospital because of dyspnea and chest pain. We diagnosed tension hemopneumothorax and chest tube drainage was performed. A large volume of bloody pleural fluid (1,200 ml) was removed, but severe liver and renal dysfunction were then recognized. He was treated conservatively because there was no more bleeding. Despite administration of methylprednisolone, re-expansion pulmonary edema occurred after 6 hours of drainage, but this was also treated conservatively. After 3 days, his pneumothorax recurrenced. It was successfully managed by video-assisted thoracoscopic surgery (VATS).

The effect of postoperative ataralgesia by manual therapy after pulmonary resection.

Muscle therapy, a form of manual therapy, was applied to control pain persisting for more than 1 week following posterolateral thoracotomy, and its efficacy for the alleviation of pain was investigated. Eight patients who underwent posterolateral thoracotomy and lung resection for cancer (n=7) or emphysema (n=1) received manual therapy to incised muscles and the muscles inserting into the ribs in the affected area for an average of 17 days postoperatively. Pressure-friction and stretching techniques were used. Treatment was continued until the intensity of the pressure-friction technique reached a level at which the patient complained of pain and a decrease in muscle tone was detected. Treatment was performed once a week for 3 weeks. Pain severity was measured using a visual analog scale (VAS) (0-10). Before the first treatment, the VAS was set at 10, and changes of the score were observed before and after the treatment as well as over time. After three sessions, all patients showed a decrease in pain from 10 to an average of 1.9 (range 1.3-2.6).

Proliferating cell nuclear antigen positive cells in the hippocampal subgranular zone decline after irradiation in a rodent model.

Four-week-old ICR mice were systemically exposed to 18Gy X-rays. Afterwards, the expression of proliferating cell nuclear antigen (PCNA) in the cerebrum was observed with time using Western blot analysis and immunohistochemical staining. As a result, PCNA-positive cells were observed in the subgranular zone (SGZ) of the hippocampus and subventricular zone (SVZ) of the lateral ventricles in unirradiated mice. The number of PCNA-positive cells decreased with time in all zones after irradiation, but the decrease was more marked in the hippocampal SGZ. We think that PCNA-positive cells are stem cells. The selective vulnerability to radiation in the hippocampus is considered to be attributed to the fact that stem cells in the SGZ selectively undergo radiation-induced apoptosis.

Thiopental enhances human platelet aggregation by increasing arachidonic acid release.

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30-300 microM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5-15 microM), epinephrine (0.1-20 microM) arachidonic acid (0.5-1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30-500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 microM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental (> or = 100 microM). Thiopental (> or = 100 microM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 microM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 microM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.

[Two cases of patch closure of pericardial defects using fascia lata after pulmonary resection with pericardiectomy].

We reported two cases of patch closure of pericardial defects using fascia lata after pulmonary resection with pericardiectomy. We confirm many advantages of this method-cheap, low risk of infection, tight tissue and easy technique in a short time with no skilled hand.

Utilization of the walking oximetry test to allow safe ambulation after pulmonary resection.

Supplemental oxygen therapy after pulmonary resection can generally be tapered according to arterial blood gases at rest or pulse oximetry (SpO2). However, detecting exercise-induced oxygen desaturation can be difficult. We developed the walking oximetry test (WOT) so that thoracotomy patients could be rehabilitated without the risk of undetected ambulatory hypoxemia. The subjects were 58 patients who had undergone pulmonary resection and could walk at the bedside, with oxygen at 3 l/min via a nasal cannula. Patients with a value of more than 100 torr were allowed to walk with assistance for 6 min in the corridor. The oxygen flow rate was kept at 3 l/min and the walking pace was less than 50 m/min. SpO2 was determined using a wristwatch pulse oximeter. The test was stopped if the SpO2 fell below 90% or there was a score of 5 or more on the Borg scale (range 1-10). Oxygen desaturation occurred in six patients (10%) during the WOT. These patients underwent ambulatory training with sufficient oxygen supplementation and were then tested again. Patients whose SpO2 values remained higher than 90% and who showed no more than 5% desaturation were permitted to walk in the corridor with oxygen at 3 l/min via a nasal cannula. All these patients had a Borg score of 4 or lower. The WOT is a reliable, nonvasive method for detecting exercise-induced oxygen desaturation during ambulation after pulmonary resection.

[Two surgical cases of pulmonary dirofilariasis].

Two surgical cases of pulmonary dilofilariasis (women aged 80 and 54 years old) were reported. They, who had no history of keeping dogs, were admitted to our hospital with complaining of cough and coin lesion on chest X-ray. On investigation, it was difficult to distinguish between pulmonary dilofilariasis and lung cancer. Wedge resection was performed by video-assisted thoracic surgery (VATS), and a definite diagnosis of pulmonary dilofilariasis was made. Nodes 2-3 cm in diameter are formed beneath the pleura in many cases of pulmonary dilofilariasis. Therefore, VATS is useful owing to its minimal invasiveness.

[Bronchopleural fistula after pneumonectomy following induction therapy for cT4N0M0 squamous cell lung cancer].

A 69-year-old man developed after thoracotomy for lung cancer. He had centrally located cT4N0M0 squamous cell lung cancer that was downstaged to cTxN0M0 by induction chemoradiotherapy with grade 3 hematologic toxicity. Two months after the finish of chemotherapy, right pneumonectomy with concomitant resection of the superior vena cava was performed. Three weeks later, he developed with a bronchopleural fistula and died of ARDS. This demonstrates increased risk of surgery following induction chemoradiotherapy.

[Experience with induction chemoradiotherapy for cT4N2M0 lung cancer].

The 42-year-old man with cT4N2M0 adenocarcinoma is reported. The primary tumor showed no change in size on chest X-ray film after chemoradiotherapy, but chest computed tomography revealed necrosis of the lesion and was supposed to be down staging to cT3N0M0. Right upper lobectomy and lymph node dissection (R 2) was performed. Pathological examination revealed histological CR, and he is still alive 34 months after the start of induction therapy.

Propofol has both enhancing and suppressing effects on human platelet aggregation in vitro.

BACKGROUND: Volatile anesthetics are known to suppress platelet aggregation. In contrast, there is conflicting information regarding the effect of propofol on platelet function. The present study was designed to clarify the effects of propofol on platelet function and the mechanisms underlying these effects. METHODS: Propofol or an equivalent volume of 10% Intralipos (as a control) was added to test tubes 5 min before the induction of each reaction. Platelet aggregation induced by epinephrine, arachidonic acid (AA), prostaglandin G2 (PGG2), or STA2 (a thromboxane A2 [TXA2] analog) was measured using an eight-channel aggregometer. To determine type 1 cyclooxygenase activity, AA (0.5 mM) was added to an assay mixture containing type 1 cyclooxygenase, and the concentration of the final product, malonaldehyde, was measured by spectrophotometry. Epinephrine-, adenosine diphosphate-, AA-, and PGG2-induced TXA2 formation was measured using a commercially available radioimmunoassay kit. To estimate TXA2 receptor-binding affinity, 3H-S145, a specific TXA2 receptor antagonist, was added, and the radioactivity of receptor-bound 3H-S145 was determined using a liquid scintillation analyzer. Inositol 1,4,5-triphosphate formation was measured in STA2-stimulated platelets using a commercially available inositol 1,4,5-triphosphate assay kit. RESULTS: Propofol (40 microM) enhanced, whereas 100 microM suppressed, adenosine diphosphate- and epinephrine-induced secondary aggregation without affecting primary aggregation. Propofol (40 microM) also enhanced, but 100 microM suppressed, AA-induced aggregation. Propofol (100 microM) enhanced PGG2- and STA2-induced aggregation. Propofol (100 microM) suppressed AA-induced TXA2 formation but did not alter that induced by PGG2. Propofol (30-100 microM) suppressed AA-induced malonaldehyde formation, indicating inhibition of type 1 cyclooxygenase activity. Propofol did not alter TXA2 receptor-binding affinity. Propofol (30 and 100 microM) augmented inositol 1,4,5-triphosphate formation in STA2-stimulated platelets. CONCLUSIONS: The present findings clearly indicate that high concentrations of propofol suppress the activity of type 1 cyclooxygenase, the enzyme that converts AA to PGG2. Furthermore, propofol also enhanced STA2-induced inositol 1,4,5-triphosphate formation. These results may explain the inconsistent findings of previous investigators.

Anesthesia with sevoflurane, but not isoflurane, prolongs bleeding time in humans.

PURPOSE: Halothane has been shown to suppress platelet aggregation in vitro and ex vivo and to prolong bleeding time. In a previous in vitro study, we demonstrated that sevoflurane had a stronger suppressive effect on platelet aggregation than halothane. The present study investigated whether clinical use of sevoflurane affects bleeding time in vivo. METHODS: Thirty-four patients undergoing minor elective surgery were randomly assigned to sevoflurane or isoflurane. Anesthesia was induced with intravenous thiopental and maintained with sevoflurane or isoflurane with nitrous oxide. Bleeding time was measured by the Duke method. An initial (control) measurement was obtained in the operating room before the induction of anesthesia, and a second was obtained 5-10 min after endotracheal intubation but before starting the operation, when the end-expiratory concentration of sevoflurane or isoflurane had been stabilized at 1-1.5 times the minimum alveolar concentration (MAC), and the mean arterial pressures were between 80% and 120% of the preanesthetic values. RESULTS: Bleeding time was increased from the preanesthetic value of 2.07 +/- 0.82 min to 2.83 +/- 0.93 min (n = 15) in the sevoflurane group (P < 0.01) but was not significantly altered in the isoflurane group. CONCLUSION: Sevoflurane alters bleeding time in the clinical situation.

Platelet aggregation is impaired during anaesthesia with sevoflurane but not with isoflurane.

PURPOSE: Halothane suppresses platelet aggregation in vitro and ex vivo, and prolongs bleeding time. In a previous in vitro study we demonstrated that sevoflurane had a more suppressive effect on platelet aggregation than did halothane. The present study investigated whether the clinical use of sevoflurane affected platelet aggregation ex vivo. METHODS: Thirty-eight patients undergoing minor elective surgery were divided randomly into sevoflurane and isoflurane groups. Anaesthesia was induced with thiopentone i.v., and was maintained with sevoflurane or isoflurane with nitrous oxide. Blood was collected to measure platelet aggregation induced by adenosine diphosphate (ADP) and epinephrine. The first (control) blood collection was performed in the operating room before induction of anaesthesia, and the second 5-10 min after tracheal intubation but before the start of surgery, when the end-expiratory sevoflurane or isoflurane concentrations had stabilised at 1-1.5 times the minimum alveolar concentration (MAC) and mean arterial pressures were between 80-120% of preanaesthetic values. RESULTS: In all samples obtained during sevoflurane anaesthesia (n = 15), ADP and epinephrine could not induce secondary aggregation, although they did induce primary aggregation. In contrast, in the isoflurane group, both primary and secondary aggregation were observed in 14 out of 15 patients, and secondary aggregation was abolished in only one of the samples obtained during anaesthesia. CONCLUSIONS: Sevoflurane, but not isoflurane, alters platelet aggregation in the clinical situation, possibly by suppression of thromboxane A2 formation.

Donor-specific cytotoxic lymphocyte activity from bronchoalveolar lavage during acute canine lung allograft rejection.

OBJECTIVE: We investigated the relationship between acute lung rejection and donor-specific cytotoxic activity (DSCA) in recipient's lymphocytes obtained from bronchoalveolar lavage (BAL). METHODS: A total of 26 mongrel dogs underwent left lung allotransplantation. Dogs received either no immunosuppressive treatment (group I), cyclosporine (group II), or cyclosporine and methylprednisolone for evidence of acute rejection (group III). DSCA was measured by a 51Cr release assay, using lymphocytes from BAL samples as effector cells and 51Cr-labeled donor skin fibroblasts as target cells. The pathologic findings of the transplanted lungs were classified according to the working formulation for classification and grading of pulmonary rejection. In addition, the degree of cellular infiltration in the perivascular, peribronchial, interstitial, and intraalveolar areas was determined based on an infiltration score. RESULTS: DSCA in BAL samples was elevated during mild, moderate and severe acute rejection. The accuracy of the diagnosis of mild or moderate rejection was 92.3% at effector:target (E:T) ratios of 100:1 and 50:1. The DSCA in the BAL fluid and the total infiltration score were correlated closely with correlation coefficients of 0.859 and 0.828 at E:T ratios of 100:1 in group I and group II dogs, respectively. Lung aeration improved and DSCA decreased with methylprednisolone therapy in three of four dogs with grade 2 rejection. CONCLUSION: There is a direct relationship between the DSCA in BAL fluid and the degree of tissue damage caused by acute rejection. The DSCA can be detected by a 51Cr release assay which may hold promise for future clinical applications.

[Are we legally allowed to administer blood for lifesaving to a patient who refuses it?].

We surveyed the literatures and discussed the legal issues whether we should administer blood for lifesaving to a patient who refuses it. The valid refusal of the transfusion requires the distinct intention of a competent patient. Minors below fifteen years of age are incompetent and their parents make a substituted judgement. Anyone must not give priority to the parents' belief and blood ought to be transfused if necessary for the children's benefits. We could evade liability for withholding blood only when we manage an operation arranged to succeed without blood transfusion, undergoing the sufficient treatments to avoid the risks, as well as on the basis of the valid refusal of a patient. The release deed and the intervention of hospital directors, ethics committees and courts are invalid for the immunity from liability. Anesthesiologists have to take the responsibility on themselves of administering blood or not. A statute law should be established to define what is a patient's valid intention and who is responsible.

[An adult case of Williams-Campbell syndrome associated with pulmonary hypertension and a severe decrease in ventilatory response].

Williams-Campbell syndrome is a unique form of bronchiectasis caused by a congenital defect in bronchial cartilage, and is rare in Japan. A 34-year-old man was admitted to our hospital with a fever, and a productive cough. Arterial blood gas analysis revealed severe type II-respiratory failure. Many thin-walled cystic shadows (5-60 mm in diameter) were present in the entire lung field. Pulmonary function tests revealed obstructive impairment. Bronchograms demonstrated cystic bronchiectasis, with ballooning on inspiration and collapse on expiration, characteristic of Williams-Campbell syndrome. Despite severe hypoxia, he did not suffer from dyspnea. We examined ventilatory response to hypercapnea (HCVR) and hypoxia (HVR), and both HCVR and HVR were abnormal. In addition, the mean pulmonary artery pressure was 26 mmHg, indicating pulmonary hypertension.

Sevoflurane inhibits human platelet aggregation and thromboxane A2 formation, possibly by suppression of cyclooxygenase activity.

BACKGROUND: Halothane increases bleeding time and suppresses platelet aggregation in vivo and in vitro. A previous study by the authors suggests that halothane inhibits platelet aggregation by reducing thromboxane (TX) A2 receptor-binding affinity. However, no studies of the effects of sevoflurane on platelet aggregation have been published. METHODS: The effects of sevoflurane, halothane, and isoflurane were examined at doses of 0.13-1.4 mM. Human platelet aggregation was induced by adenosine diphosphate, epinephrine, arachidonic acid, prostaglandin G2, and a TXA2 agonist ([+]-9, 11-epithia-11, 12-methano-TXA2, STA2) and measured by aggregometry. Platelet TXB2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA2 receptors were examined by Scatchard analysis using a [3H]-labeled TXA2 receptor antagonist (5Z-7-(3-endo-([ring-4-[3H] phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [3H]S145). RESULTS: Isoflurane (0.28-0.84 mM) did not significantly affect platelet aggregation induced by adenosine diphosphate and epinephrine. Sevoflurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondary platelet aggregation induced by adenosine diphosphate (1-10 microM) and epinephrine (1-10 microM) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G2 or STA2, although halothane (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect the binding of [3H]S145 to platelets, whereas halothane (3.3 mM) suppressed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strongly suppressed TXB2 formation by arachidonic acid-stimulated platelets. CONCLUSIONS: The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.