Successful treatment with methylprednisolone pulse therapy for a life-threatening pulmonary insufficiency in a patient with chronic granulomatous disease following pulmonary invasive aspergillosis and Burkholderia cepacia infection.

A 14-year-old boy with X-linked chronic granulomatous disease developed severe invasive pulmonary aspergillosis. He was treated with itraconazole and amphotericin B. However, he deteriorated with progressive pulmonary lesions. Burkholderia cepacia was isolated from his bronchoalveolar lavage. Finally, he was given granulocyte transfusions. Following this procedure, his condition rapidly worsened leading to respiratory failure. His lung biopsy demonstrated organizing pneumonia at his right middle lobe. Then, a methylprednisolone pulse therapy was initiated together with the administration of appropriate antibiotics and adequate amounts of amphotericin B. Dramatically, his condition improved. Therefore, a methylprednisolone pulse therapy with appropriate antimicrobial drugs seems to be beneficial for severe pulmonary insufficiency in this type of patients.

Therapeutic strategy of perioperative use of percutaneous cardiopulmonary bypass support (PCPS) for adult cardiac surgery.

SUBJECT AND METHOD: Percutaneous cardiopulmonary bypass support is beneficial for patients with circulatory collapse. However, therapeutic strategies of percutaneous cardiopulmonary bypass support for post-cardiotomy LOS have not been determined. We reviewed 9 patients undergoing cardiac surgery and treated with percutaneous cardiopulmonary bypass support to determine an adequate strategy for perioperative use of percutaneous cardiopulmonary bypass support. Patients included 8 males and 1 female with a mean age of 56.4 +/- 3.9 years. Six patients with IHD underwent CABG for 5 and CABG + MVR for 1 patient and 3 patients with valvular disease underwent AVR, AVR + MVR, and Ross operation respectively. Indication for percutaneous cardiopulmonary bypass support was post-cardiotomy LOS in 7 and preoperative cardiogenic shock in 2 patients. All patients underwent IABP associated with percutaneous cardiopulmonary bypass support. Systemic blood pressure was regulated to 100-120 mmHg by percutaneous cardiopulmonary bypass support flow and with minimum inotropic supports. RESULTS: Six of 9 patients (66.7%) were weaned from percutaneous cardiopulmonary bypass support and 5 patients were discharged. Five of 6 patients (83.3%) with IHD were weaned from percutaneous cardiopulmonary bypass support compared to 1 of 3 patients (33.3%) (p = 0.134) with valvular disease. Hemodynamic conditions in patients weaned from percutaneous cardiopulmonary bypass support were markedly improved within 40 hours of the introduction of percutaneous cardiopulmonary bypass support (mean percutaneous cardiopulmonary bypass support running time: 23.9 +/- 5.5 hrs). In contrast, those unable to be weaned from percutaneous cardiopulmonary bypass support (mean percutaneous cardiopulmonary bypass support running time: 84.3 +/- 6.3 hrs) showed no improvement and developed major complications such as cerebral damage or multiorgan failure. CONCLUSIONS: Perioperative use of percutaneous cardiopulmonary bypass support may be more effective for patients undergoing coronary artery surgery. Limited use of percutaneous cardiopulmonary bypass support within 48 hours may be applicable for post-cardiotomy patients.

Chitin-graft-poly(2-methyl-2-oxazoline) enhanced solubility and activity of catalase in organic solvent.

Catalase from bovine liver was lyophilized from an aqueous solution containing chitin-graft-poly(2-methyl-2-oxazoline) (3), which was synthesized by the reaction of 52% deacetylated chitin (1) with living poly(2-methyl-2-oxazoline) (2). The rate of consumption of H2O2 in chloroform catalyzed by the lyophilized catalase with 3 was enhanced more than 10 times that by catalase without 3. The dispersibility and solubility of lyophilized catalase with 3 in chloroform were improved in comparison with catalase itself.

Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock.

OBJECTIVES: To obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis. DESIGN: Prospective observational study. SETTING: General intensive care unit. PATIENTS: Nineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2=.236, p< .0001) and the number of dysfunctioning organs (r2=.229, p=.035). CONCLUSIONS: We systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III.

Determination of the degree of acetylation of chitin/chitosan by pyrolysis-gas chromatography in the presence of oxalic Acid.

A new method to determine directly and rapidly the degree of acetylation of chitin/chitosan was developed based on reactive pyrolysis-gas chromatography in the presence of an oxalic acid aqueous solution. The degree of acetylation was precisely evaluated on the basis of peak intensities of the characteristic products such as acetonitrile, acetic acid, and acetamide originating from the N-acetyl group of N-acetyl-d-glucosamine units of chitin/chitosan. The observed values were in good agreement with those obtained by (1)H NMR and the other methods. Moreover, the proposed technique was applicable to any kinds of chitin/chitosan samples over the whole range of acetylation including insoluble chitin/chitosan and perfectly acetylated artificial chitin having higher crystallinity to which (1)H NMR had been inapplicable.

Role of pulmonary intravascular macrophages in anti-platelet serum-induced pulmonary hypertension in sheep.

It has been reported that an injection of anti-sheep platelet serum (AsPS) induces transient pulmonary hypertension in sheep, but the mechanism by which this occurs has not been well explained. To examine the hypothesis that pulmonary intravascular macrophages (PIMs) are involved in this phenomenon, we investigated the morphological features of PIMs from sheep that received three different kinds of AsPS injections. The pulmonary arterial pressure response was examined not only in sheep that have many PIMs in the lung and had received AsPS, but also in rats that reportedly have few PIMs and had received an injection of anti-rat platelet serum. The pulmonary arterial pressure responses of the two species were quite different in quality and quantity. In sheep whose pressure response was definitely positive in association with production of thromboxane in the pulmonary circulation, PIMs were found by fluorescent microscopy and electron microscopy to phagocytize aggregated platelets that bound AsPS. These results suggest that PIMs significantly contribute to AsPS-induced transient pulmonary hypertension in sheep.

[Cyclophosphamide-responsive subclinical Sjögren's syndrome in a patient with initial peripheral and central nervous system involvement].

A 36-year old woman was admitted because of painful dysesthesia of her extremities, suggesting the presence of mononeuritis multiplex. Laboratory data was almost within normal limits, with the exception of lupus anticoagulant positivity and increase of IgM level. We considered the possibility of connective tissue diseases and examined the patient accordingly. Keratoconjunctivitis sicca without dry eye symptoms, identified by rose-bengal and fluorescence testing, was the only recognizable abnormality. Oral sicca symptoms were not revealed although lip biopsy showed infiltration by a moderate number of plasma cells and lymphocytes. Under the diagnosis of subclinical Sjögren's syndrome, the following examination was carried out. Sural nerve biopsy specimens revealed wallerian degeneration and perivascular mononuclear cell infiltration of the vasa nervorum. We therefore concluded that the peripheral neuropathy was caused by subclinical Sjögren's syndrome. Magnetic resonance imaging (MRI) of the brain demonstrated multiple small lesions with increased spin echo images (T2 weighted) in the white matter. So, this patient was suffered from not only peripheral but also central nervous system complications. The mechanism of nervous system involvement was considered to be mononuclear cell-dependent ischemic damage caused by infiltration of the vasa nervorum. Both steroid pulse therapy and oral corticosteroid administration were ineffective in treatment of the peripheral neuropathy. Alternative use of cyclophosphamide (75 mg per day) was dramatically effective in relieving peripheral nervous system disorders. This was evident in the remarkable improvement of painful dysesthesia, grip strength and motor nerve conduction velocities. This case could be considered valuable for understanding the pathophysiology of Sjögren's syndrome and associated nervous system complications.

[Protein-losing enteropathy and cerebral infarction associated with systemic lupus erythematosus].

A 26-year old woman, who was diagnosed as having systemic lupus erythematosus at the age of 23 year old, presented diarrhea and headache. She showed severe hypoproteinemia (serum total protein 3.7 g/dl, serum albumin 1.4 g/dl) and hyperlipidemia. She revealed to have protein-losing enteropathy with the result of alpha-1-antitrypsin clearance test using stool. Increase of prednisolone improved the loss of albumin into the bowel and abnormal laboratory findings. She also showed watershed infarction in the area of middle cerebral artery and posterior cerebral artery. Protein-losing enteropathy is a rare complication of SLE, only 18 cases are available on literature. No case is found to have cerebral infarction in patients with protein-losing enteropathy associated with SLE. It is known that blood levels of anticoagulation factors decrease in protein-losing enteropathy due to the leakage of plasma protein into intestinal lumen. Serum antithrombin III was decreased in this case. Hyperlipidemia found in this case seems to be caused by same mechanism in nephrotic syndrome. Lupus anticoagulant was also positive in this patient. These factors seems to be related to the occurrence of cerebral infarction. This case suggests the possibility of cerebral infarction in patients with protein-losing enteropathy in SLE.

[A case of chronic hepatitis C complicated by ischemia-like changes seen on the electrocardiogram during interferon treatment].

A 53-year-old woman was admitted to the hospital for chest pain with headache, nausea and vomiting, two and a half hours after an intramuscular injection of 6 x 10(6) units of IFN (interferon) alpha 2a, in the 11th week of IFN treatment for chronic hepatitis C. The electrocardiogram (ECG) showed ST depression and T inversion in leads II, III, aVF and V3-V6, as commonly seen in myocardial ischemia. However, emergency coronary angiography (CAG) did not show stenosis or spasms clearly, serum CPK was always within the normal limits, Tc-99m PYP scintigraphy and T1-201 scintigraphy did not show any abnormal uptake or defect, and the echocardiogram did not show any abnormality. She recovered from chest pain and the ischemia-like changes seen on the ECG, after IFN treatment was stopped, and she rested for 7 days from this treatment and other treatment using nitrites and a calcium-antagonist. After recovery, the ECG during exercise and hyperventilation showed changes similar to those seen on admission. From these findings, this case was considered to be precipitated by spasms of coronary microvessels, which were not noticeable in CAG. The cause was thought to be complicated by IFN treatment, because this episode appeared after IFN injection, and improved after stopping IFN treatment.

[Two cases of RA-like and SLE-like features similar to remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome)].

In 1985, McCarty et al reported 10 patients with a symmetrical synovitis affecting predominately the wrists and flexor digitorum tendon sheaths associated with marked pitting edema of the dorsum of both hands and both feet. It was insisted on the clinical entity as remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome). These patients were mostly elderly men whose sera revealed negative rheumatoid factor and had a benign clinical course. Patients with RS3PE syndrome remitted completely within 3-36 months and the remission was maintained even after all medications were discontinued. We experienced 2 interesting cases which were similar to RS3PE syndrome. One case with SLE-like conditions evolved into RA-like conditions. On the contrary, the other which had been effectively treated as RA developed into SLE-like conditions. Both cases were seronegative and had the characteristic pitting edema of both hands and feet demonstrating the symmetrical synovitis without bony erosions. They went into complete remission by corticosteroid therapy, although it did not continue for a long time. We should consider that such cases are similar to RS3PE syndrome and must be distinct from it.

Liver cirrhosis with severe hypoxemia and paradoxic pulmonary vascular response to graded inspiratory oxygen tension.

We present the findings in a patient with liver cirrhosis who showed oppositional pulmonary vascular responses to various alveolar oxygen tensions. In this case the pulmonary artery constricted on exposure to hyperoxia and then gradually dilated during progressive hypoxic inhalation. Such a paradoxic response must result in severe arterial hypoxemia because of severe V/Q mismatching.

[Efficacy of conventional CT in diagnosis of pulmonary emphysema: evaluation of low attenuation area by multiple observers].

The efficacy of conventional CT in the diagnosis of pulmonary emphysema (PE) was studied in 122 patients with miscellaneous diseases including 26 patients with PE. The density and the distribution of low attenuation area (LAA) were evaluated by six independent physicians. Analysis with kappa statistics showed a good inter-observer agreement in the detection of LAA. The grading of LAA correlated well with FEV1/FVC, DLCO/VA, and lung volumes, which indicated that PE could be detected by conventional CT by the evaluation of LAA. The agreement was poor, however, for the detection of low grade LAA and there were some false positives, and there was no specific pattern in the distribution of LAA in PE compared to other pulmonary diseases. We conclude that the evaluation of LAA by conventional CT is simple and effective in the screening of PE.

[A case of cyclosporin A-induced myopathy].

A 40-year old man with Behçet's disease was admitted for severe decrease of visual acuity. Since 1987, he had suffered from oral aphtha, retinitis, erythema nodosum, genital ulcer and epididymitis. He was diagnosed as complete Behçet's disease and has been administered cyclosporin A (CYA) and colchicine (Col). Because of repeated ocular attacks and reduced visual acuity, CYA was increased from 3.49 mg/kg/day (220 mg/day) to 6.35 mg/kg/day (400 mg/day) and Col, 0.5 mg/day to 1.0 mg/day. 2 weeks later, he revealed fever, generalized myalgia, muscle weakness and general fatigue, accompanying marked elevation of creatine kinase (4962 IU/l). CYA was discontinued and Col was diminished to 0.5 mg/day. The myalgia disappeared in 4 days and general conditions including creatine kinase were normalized within 2 weeks. We concluded that CYA was highly suspected of the cause of myopathy considering his clinical course.

[Effect of home oxygen therapy on prognosis of patients with chronic pulmonary disease associated with pulmonary hypertension].

We prospectively elucidated the effect of home oxygen therapy (HOT) on the prognosis of patients with chronic pulmonary disease associated with pulmonary hypertension. One hundred and twenty-seven patients with pulmonary hypertension (mean pulmonary arterial pressure > or = 20 Torr) participated in this study. Fifty-four patients had chronic pulmonary emphysema, 5 chronic bronchitis, 19 diffuse panbronchiolitis, 29 old tuberculosis, 8 pulmonary fibrosis, and 12 other diseases. Fifty-one patients died of respiratory failure. The survival curve of patients who received HOT was not different from that of patients who did not receive HOT, although FEV1 and PaO2, both prognostic factors, were significantly worse in the patients who received HOT than in the patients who did not receive HOT. In the patients with COPD, the survival rate of patients who received HOT was significantly higher than that of those who did not receive HOT. The mean survival time of the patients who received HOT was significantly longer than that of the patients who did not received HOT (1971 +/- 217 SEM days and 978 +/- 156 days, respectively). From these data, we conclude that HOT improves the survival of patients with chronic pulmonary disease, especially COPD, associated with pulmonary hypertension.

[Gold-induced severe cholestatic jaundice in rheumatoid arthritis patient and effect of repeated steroid pulse therapy].

A 32-year-old female with early stage of rheumatoid arthritis (RA) developed anorexia, pruritus, dark urine, pale stool and jaundice 3 weeks after initiation of chrysotherapy. She was administered a total of 35mg of gold sodium thiomalate (GST) intramuscularly and auranofin 6mg per day orally. Liver function tests and biopsy specimens showed severe cholestatic jaundice. Prednisolone 30mg per day and plasma exchange were started. No response however was obtained and the total bilirubin level gradually increased. Steroid pulse therapy, 1000mg methylprednisolone for successive 3 days as one therapy unit, was repeated 4 times. Liver functions were then gradually improved. Gold induced hepatotoxicity is a rare complication. We concluded that the hepatotoxicity in this case was caused by allergic reaction against GST and repeated steroid pulse therapy was very effective to these conditions.

Diurnal monoamine variation in young and old rats: a microdialysis study.

The levels of striatal extracellular DA, DOPAC, HVA and 5-HIAA significantly decreased in aged rats compared to young adults. The magnitude of age-related reduction was greater in dopaminergic than serotonergic substances. The levels of striatal extracellular monoamines in young adult rats showed significant diurnal variations. On the other hand, these substances of aged rats, except for HVA, did not exhibit significant diurnal variations. Enriched environment housing increased levels of striatal extracellular DOPAC in aged rats, but did not influence on the age-related changes of diurnal variations in the striatal extracellular monoamines.

[Effects of differently composed liposomes on pulmonary arterial pressure in sheep--involvement of pulmonary intravascular macrophages].

The authors previously reported that liposomes, when injected intravenously, produce transitory pulmonary hypertension with increased secretions of thromboxane A2 from activated intravascular macrophages that phagocytize liposomes in sheep. In the present study, we attempted to determine whether such responses were modified by the lipid compositions of the liposomes. Five different types of liposomes were prepared by reverse-phase evaporation. The liposomes used were composed of phosphatidylcholine (PC), cholesterol (CHOL), and either phosphatidylglycerol (PG-liposomes), phosphatidylserine (PS-liposomes), phosphatidylethanolamine (PE-liposomes), stearlyamine (SA-liposomes) or none (PC-liposomes). The net charges of PG and PS-liposomes were negative, SA-liposomes were positive, PE- and PC-liposomes were neutral. Each liposome was injected intravenously to obtain a pulmonary arterial pressure response. Arterial blood was sampled before and after liposome injections to measure thromboxane B2 concentrations. All liposomes, but not PC-liposomes, produced pulmonary arterial hypertension associated with increased arterial thromboxane B2 concentrations, irrespective of the net surface charge of the liposome. PG and PS-liposomes, both of which were negatively charged, showed different dose-response curves, the two different types of neutral liposomes showed different responses, and PC-liposomes produced a small increase in pulmonary arterial pressure. PE-liposomes produced marked increases in the pulmonary arterial pressure. From these results, the authors concluded that pulmonary arterial pressure responses to the liposomes are modified by the lipid compositions of the liposomes, and that this is not caused by the difference in the net charge of each liposome.

[A case of hypereosinophilic syndrome followed by bronchial asthma, intraventricular thrombus, and duodenitis].

We report a 43-year-old male with hypereosinophilic syndrome. The patient has had eosinophilia since the age of 25. He developed bronchial asthma at 41 years of age. In the following year, he consulted a gastroenterologist because of fever and abdominal discomfort. Upper gastrointestinal study showed duodenitis. At the age of 43 years, there was slight fever, watery diarrhea, and eosinophilia. Examination in our department disclosed hypereosinophilic syndrome associated with duodenitis, endomyocarditis with an intraventricular thrombus, and bronchial asthma caused by house dust. Both prednisolone and aspirin were administered with improvement of eosinophilia and partial thrombolysis. Assays of IL-3, GM-CSF, and IL-5 revealed increased activity of IL-5, GM-CSF, and IL-3 in this order. Especially IL-5 has by far the strongest activity in these cytokines. IL-5 may play an important role in the development of hypereosinophilic syndrome.

[Effects of antiplatelet serum on the pulmonary intravascular macrophage].

Antiplatelet serum (APS) has been used to investigate the role of platelets in lung injury. However, the effect of APS on pulmonary intravascular macrophages (PIMs) is unknown. Therefore we investigated the effects of APS on PIMs. A bolus injection of APS raised pulmonary arterial pressure with the production of thromboxane. Fluorescence- and electronmicroscopy revealed that PIMs engulfed APS-platelets complexes after the APS injection. Repeated injections of APS increased the ratio of PIMs which engulfed platelets and the number of platelets in a PIM, but attenuated phagocytosis of liposomes by PIMs to decrease liposome-induced pulmonary hypertension and production of thromboxane. From the above data it was concluded that APS injection causes PIMs to engulf APS-platelets complexes, and that APS injection attenuates the phagocytosis of liposomes by PIMs, and thereby diminishes liposome-induced pulmonary hypertension and production of thromboxane.

Pineal microdialysis in freely moving rats.

We describe a surgical technique to implant the guide cannula for in vivo microdialysis in the rat pineal gland. This technique has the following features and advantages: (a) does not require ligation of the superior or transverse sinus, (b) minimizes bleeding from the dural veins, (c) does not disturb the sympathetic innervation originating from superior cervical ganglia, which is essential for pineal function. This new technique makes it possible to carry out chronic pineal microdialysis of freely moving rats.