Effect of angiotensin converting enzyme inhibition on myocardial phosphoinositide metabolism visualised with 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol in myocardial infarction in the rat

We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed predominantly in infarcted areas with active fibrogenesis rather than in non-infarcted regions, is involved in the upstream signalling systems of PI metabolism and plays an important role in the process of left ventricular (LV) remodelling after MI. We therefore hypothesised that the distribution of 11C-DAG after MI may be affected by the inhibition of angiotensin converting enzyme, which is one of the most important factors in the development of LV remodelling after MI. Rats were injected with 11C-DAG after 3 or 10 weeks of treatment with captopril or no treatment following coronary artery ligation, and quantitative autoradiography was performed. Cells occupying the infarcted region were identified by immunohistochemistry. Compared with untreated rats, treatment with captopril for 3 weeks after MI elicited a reduction in the 11C-DAG uptake in the infarcted region (P<0.05) but not in the non-infarcted region, and was associated with a 22% decrease in the heart weight/body weight ratio. The thallium-201 distribution in the infarcted area was similarly low in the rats with and rats without the 3-week captopril treatment after MI. Abundant macrophages and myofibroblasts occupied the infarcted area in both rats with and rats without the captopril treatment for 3 weeks after MI. The 11C-DAG radioactivity in the infarcted region in the untreated rats was lower 10 weeks after MI than 3 weeks after MI (P<0.01). This finding was in agreement with the results of immunohistochemistry demonstrating that the number and size of macrophages and myofibroblasts were remarkably reduced in rats 10 weeks after MI compared with 3 weeks after MI. Captopril treatment for 10 weeks after MI did not decrease the 11C-DAG radioactivity in the infarcted area further. These data suggest that 11C-DAG is useful for visually detecting regions with activated PI metabolism after MI, and that captopril reduces PI metabolism in the infarcted region in the relatively early phase of MI, which might contribute to the attenuation of ventricular remodelling.     

Relevance of tissue factor and tissue factor pathway inhibitor for hypercoagulable state in the lungs of patients with idiopathic pulmonary fibrosis

We investigated the role of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Bronchoalveolar lavage (BAL) fluid was obtained from 22 patients with IPF, and the levels of TF and TFPI antigen were measured by ELISA. The TF and TFPI levels in BAL fluid supernatant were significantly higher in IPF patients than in normal controls. In addition, both levels were significantly higher in advanced cases than in nonadvanced cases. There was a significant correlation between the TF and TFPI levels. Localization of TF and TFPI antigens was investigated by immunohistochemical staining. Both antigens were mainly localized in hyperplastic cuboidal epithelial cells, suggesting that the widespread distribution of these cells contributed to the increase of TF and TFPI antigen levels in the lungs of IPF patients. To assess whether TF activity is counterbalanced by TFPI in the lungs of IPF patients, we examined procoagulant activity and TF activity. It was found, however, that both procoagulant and TF activities were significantly higher in the BAL fluid supernatant of IPF patients than in that of normal controls, which suggested that TFPI was actually increased, but the increase was insufficient to counterbalance TF, leading to the development of a hypercoagulable state in the lungs of IPF patients.     

Stable microbubble test for predicting the risk of respiratory distress syndrome: II. Prospective evaluation of the test on amniotic fluid and gastric aspirate

We determined prospectively if the stable microbubble (SM) test on gastric aspirate obtained at birth was as useful as that on amniotic fluid in predicting respiratory distress syndrome (RDS). One hundred and five paired samples of amniotic fluid obtained at delivery from 105 consecutive women with gestation of 35 weeks or less and gastric aspirates from their neonates obtained within 30 min of birth were studied. The SM test with the predefined cut-off value of less than 5 bubbles/mm² for amniotic fluid and less than 10 bubbles/mm² for gastric aspirate signified the risk of RDS with the positive predictive value of 100% and 96% and with the negative predictive value of 91% and 84%, respectively. We conclude that the SM test on both amniotic fluid and gastric aspirate obtained at birth is a rapid (<10 min), simple and reliable procedure for predicting neonates who will develop RDS. It may be used as a bedside test to define a population of neonates with surfactant deficiency in clinical trials of prophylactic surfactant therapy.     

A case of large-cell lung cancer responding remarkably to combination chemotherapy with vinorelbine, mitomycin C and carboplatin

The patient was a male who started to show symptoms at age 59. He was a smoker until age 40. In October 1998 he came to the hospital complaining of hemosputum and hoarseness. There was already swelling of the supraclavicular lymph nodes. Through lymph node aspiration cytology and bronchofiberscopy, large-cell carcinoma (T2N3M0, stage IIIB) was diagnosed. Chemotherapy with vindesine (VDS, 3 mg/m2), mitomycin C (MMC, 8 mg/m2) and carboplatin (CBDCA, 300 mg/m2) was conducted in three stages. Thanks to a partial response (PR) the patient was released in January 1999. However, in September 1999 he was readmitted when dysphagia, loss of body weight and dyspnea appeared. After bronchoscopy, chemotherapy combining vinorelbine (VNB, 25 mg/m2), (MMC, 8 mg/m2), CBDCA and the Calbert method calculated at AUC = 4.5 (AUC = area under the concentration-time curve) was completed in 4 stages. Upon PR and an abatement of symptoms he was released from the hospital. It is thought that treatment combining VNB is effective.     

A case of acute autonomic, sensory and motor neuropathy (AASMN)--less favorable response of the autonomic dysfunctions to IVIg treatment]

We report a rare case of acute autonomic, sensory and motor neuropathy (AASMN). The patient, a 26-year-old woman, developed fever and common cold around January 20, 2001 and was admitted because of abdominal pain due to ileus on January 30. After admission, the patient complained of muscle weakness and numbness in the extremities, difficulty in seeing with the right eye, and dysuria. Neurologically, marked orthostatic hypotension, right tonic pupil, distal dominant moderate muscle weakness in extremities, areflexia in both lower limbs, glove and stocking type of paresthesia, and neurogenic atonic bladder were noted. Sensation to pin prick, light touch, temperature, and vibration were markedly impaired in upper limbs and below the level of the 5th thoracic cord. Cerebrospinal fluid examination revealed albumino-cytologic dissociation. Peripheral nerve conduction study revealed lower limb dominant axonal type impairment of sensory conduction and slight impairment of motor conduction velocity. Clinical autonomic testings revealed dysfunction of both sympathetic and parasympathetic systems. As having AASMN, she was given the intravenous high-dose immunoglobulin (IVIg) therapy twice. After IVIg, the sensory and motor symptoms improved remarkably, but pandysautonomia did not. To our knowledge, this is the first report of AASMN treated by IVIg, and the notable clinical feature in this case was the favorable motor and sensory recovery to IVIg, as opposed to poor autonomic outcome.     

Early postoperative evaluation of pylorus-preserving gastrectomy for gastric cancer

Early postoperative evaluation was prospectively performed in 35 gastric cancer patients after pylorus-preserving gastrectomy (PPG) between 1989 and 1991, comparing the results with those of 29 patients who underwent conventional distal gastrectomy (CDG). Surgical stress, including the duration of operation (149.0±4.3 minutes) and the total volume of bleeding at operation (97.0±11.2 g), was significantly less in the PPG patients. Early postoperative complications were seen in 31% after PPG and in 35% after CDG. The most frequent complication in PPG patients was remnant gastric stasis (23%). Endoscopy showed redness or erosion (or both) of the gastric remnant in 17% after PPG and in 81% after CDG. Bile regurgitation was demonstrated in 11% after PPG and in 62% after CDG. In PPG patients, the pyloric ring opened and closed during the examination. Gastric pH was 4.2±0.4 in PPG patients but was significantly lower in CDG patients. The resting gallbladder area, examined by ultrasonography, demonstrated no changes after PPG but was significantly enlarged after CDG (from 11.3±1.2 cm² to 15.8±1.5 cm² at 2 weeks). The percentage of the original resting gallbladder area at 20 minutes after injection of cerulein increased slightly in PPG patients but recovered thereafter, whereas in CDG patients it increased significantly (from 39.4±8.3% to 66.7±9.1% at 2 weeks). No gallstone formation was detected throughout the observation period after PPG, whereas after CDG it was detected in two patients at 1 year. These results indicated that PPG for gastric cancer has advantages over CDG in terms of surgical stress, the condition of the gastric remnant, and gallbladder function.

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Resumen Se hizo una evaluación prospectiva en el período postoperatorio temprano luego de gastrectomía con preservación del píloro (PPG) en 35 pacientes con cáncer gástrico entre 1989 y 1991, comparándolos con 29 pacientes sometidos a gastrectomía distal convencional (CDG). El estrés quirúrgico, incluyendo la duración de la operación (149±4.3 min) y el volumen total de hemorragia durante la operación (97±11.2 g) fueron significativamente menores en la PPG. Complicaciones postoperatorias tempranas aparecieron en 31% de los casos con PPG y en 35% de los casos con CDG. La complicación más frecuente en la PPG fue la estasis del remanente gástrico en 23% de los casos. La endoscopia demostró enrojecimiento y/o erosión del remanente gástrico en 17% de los pacientes luego de PPG, contra 81% luego de CDG. Se demostró regurgitación biliar en 11% luego de PPG, y en 62% luego de CDG. En los pacientes con PPG, el anillo pilórico se vio abrir y cerrar en el curso del examen. El pH gástrico fue 4.2±0.4 en PPG y significativamente más bajo que en los pacientes con CDG. La vesícula biliar en reposo estudiada mediante ultrasonografía señaló que no había cambios luego de PPG; sin embargo, apareció significativamente agrandada de tamaño luego de CDG, de 11.3±1.2 cm² a 15.8±1.5 cm² (2 semanas). El porcentaje del área original de la vesícula en reposo a los 20 minutos luego de la inyección de ceruleína aumentó levemente en la PPG pero luego se recuperó, en tanto que en la CDG aumentó significativamente de 39.4±8.3% a 66.7±9.1% (2 semanas). Luego de la PPG no se detectó formación de cálculos biliares durante el período de observación, pero sí se detectó en dos pacientes al año luego de CDG. Estos resultados indican que la PPG para cáncer gástrico tiene ventajas en cuanto a estrés quirúrgico, condición del remanente gástrico y función de la vesícula biliar, sobre la CDG.

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Résumé Les différentes formes de tolérance de la gastrectomie avec conservation du pylore (GCP) ont été évaluées chez 35 patients opérés de cancer gastrique entre 1989 et 1991, et comparées aux résultats observés chez 29 patients après une gastrectomie distale conventionnelle (GDC). Le stress chirurgical, défini par la durée de l'intervention (149±4.3 min.) et le volume total de saignement au cours de l'intervention (97±11.2 g), étaient statistiquement moindres en cas de GCP qu'en une de GDC. Il y ayait 31% de complications postopératoires après GCP et 35% après GDC. La complication la plus fréquente après GCP a été la stase du moignon gastrique, observée dans 23% des cas. L'endoscopie montrait chez 17% de ces patients opérés de GCP et chez 81% des patients après GDC, une rougeur et/ou des érosions du moignon gastrique. Un reflux bilieux a été constaté chez 11% des patients après GCP et chez 62% après GDC. Chez les patients ayant eu une GCP, on a pu mettre en évidence une ouverture et une fermeture de l'anneau pylorique pendant l'examen. Le pH gastrique était de 4.2±0.4 dans la GCP, significativement plus bas qu'après la GDC. L'échographie a montré une augmentation de la surface vésiculaire après GDC, allant de 11.3±2 cm² à 15.8±5 cm², statistiquement plus importante qu'après GCP. Après la GCP, la surface a augmenté légèrement 20 minutes après l'injection de céruléine, alors qu'après GDC, elle a augmenté significativement de 39.4±8.3% à 66.7±9.1% (à deux semaines). Après GCP, on n'a pas observé de formation de lithiase pendant toute la période d'observation alors qu'après GDC, deux cas de lithiase ont été observés à un an. Ces résultats indiquent que la GCP pour cancer gastrique a des avantages certains par rapport à la GDC surtout en ce qui concerne le fonctionnement et l'état du moignon gastrique et la fonction vésiculaire.

     

Comparison of the severity of atopic dermatitis lesions and the density ofStaphylococcus aureus on the lesions after antistaphylococcal treatment

We examined the relationship between atopic dermatitis (AD) andStaphylococcus aureus by comparing changes in AD lesions and the bacterial density on the lesions after antimicrobial treatment with cefdinir. We found that there was a greater density ofS. aureus on red erythemas and exudative lesions than in light/dark red erythemas and non-exudative lesions of AD. Forty-one of 59 cases (69%) showed a decrease in colony count following antimicrobial treatment. In 28 of 39 cases (72%) there was a decrease of erythema, and in 18 of 22 cases (82%) there was a decrease in the amount of exudate both associated with a decrease in colony density following antimicrobial treatment. Because acute phases of atopic dermatitis, such as red erythemas and exudative lesions, were closely related to the colonization ofS. aureus, dense colonization withS. aureus may be an important factor in the exacerbation of AD. We believe that staphylococcal products such as α-toxin, various enzymes, coagulase, and superantigenic exotoxins affect some aspect of the inflammatory process, resulting in exacerbation of AD.     

Magnetic resonance-guided percutaneous microwave coagulation therapy for liver metastases of breast cancer in a case

Real-time magnetic resonance (MR) imaging enables the application of percutaneous microwave coagulation for high-risk patients with metastatic liver tumours. The tumours, local vessels and bile ducts can be observed clearly in three-dimensional sections and a sufficient surgical margin can be confirmed on the MR image even during the coagulation procedure. MR-guided percutaneous microwave coagulation therapy is effective for treatment of not only primary liver tumours but also metastatic breast cancers in the liver, which are not diffuse but discrete, and difficult to treat with only chemo-and endocrine therapy. We report a 44-year-old Japanese woman who underwent modified radical mastectomy for right breast cancer (T1c N0 M0 Stage I). Three years after the operation, she developed two metastatic liver tumours and was treated by MR-guided percutaneous microwave coagulation, achieving a complete response (CR) without any recurrence for 15 months as of the present. The most beneficial aspect of MR-guided percutaneous microwave coagulation is its safety. It is only minimally invasive and can be repeated. This therapy, therefore promises to prolong the disease free period. Additional clinical trials will be valuable to delineate the effectiveness and safety of MR-guided percutaneous microwave coagulation therapy for controlling the liver metastases of breast cancer.     

Open-configuration MR-guided microwave thermocoagulation therapy for metastatic liver tumors from breast cancer

BACKGROUND: Liver metastases from breast cancer are associated with a poor prognosis, however, local control with microwave thermocoagulation therapy has been used in certain subgroups of these patients in the past decade. In this study, open-configuration magnetic resonance (MR) -guided microwave thermocoagulation therapy was used for metastatic liver tumors from breast cancer, and the efficacy of this treatment was assessed. METHODS: Between June 2000 and April 2004, we used MR-guided microwave thermocoagulation therapy on 11 nodules in 8 patients with metastatic liver tumors from breast cancer. The procedure was carried out under general anesthesia. A 0.5 T open-configuration MR system and a microwave coagulator were used. Near-real-time MR images and real-time temperature images were collected and displayed on the monitor. The MR-compatible thoracoscope was used and combined with MR imaging guidance. Navigation software, a 3D Slicer, was installed and customized. RESULTS: The customized navigation software displayed near-real-time MR images. The percutaneous puncture into the tumors was successful in all cases. No mortality or major complications occurred as a result of the procedures. Five of the 8 patients are alive with new metastatic foci with a mean observation period of 25.9 months. CONCLUSIONS: We developed several devices to allow safe, easy, and accurate MR-guided microwave thermocoagulation therapy of liver tumors. Open-configuration MR-guided microwave thermocoagulation therapy appears to be a feasible method for tumor ablation of metastatic liver tumors from breast cancer.     

Role of the ICOS-B7h costimulatory pathway in the pathophysiology of chronic allograft rejection

BACKGROUND: Inducible costimulator (ICOS) is the third member of the CD28 superfamily and has a unique role in T cell activation and function. Recent studies indicated that the ICOS-B7h pathway plays an important role in alloimmune responses. We further investigated the role of the ICOS pathway in the pathologic process of chronic rejection in vivo. METHODS: An established major histocompatibility complex class II disparate cardiac transplantation model was used. We treated mice with a blocking anti-B7h monoclonal antibody (mAb) either in the initiation phase (early blockade) or in the progression phase (delayed blockade) of disease. In addition, some mice received mAb in the entire period (whole blockade). At 6 weeks after transplantation, cardiac grafts were evaluated by histopathologic analysis in terms of vasculopathy, fibrosis, and cellular infiltration. The intragraft expressions of cytokines and chemokines were also examined by quantitative real-time polymerase chain reaction analysis. RESULTS: Early blockade of the ICOS-B7h pathway did not show any protective effect on chronic allograft rejection compared with untreated controls. In contrast, delayed blockade significantly inhibited the development of vasculopathy, fibrosis, and cellular infiltration (P=0.043, P=0.004, and P=0.03 vs. untreated control, respectively). Interestingly, whole blockade did not prevent the chronic rejection process. Furthermore, the inhibitory effect of delayed ICOS blockade on chronic rejection was associated with down-regulation of local intragraft expression of several cytokines and chemokines. CONCLUSIONS: These data suggest that the ICOS-B7h pathway is critical in the activation of effector/memory T cells that are necessary for the progression of chronic rejection and provide the rationale to develop novel and specific therapies to prevent this process.