Calcitonin gene-related peptide mediates acid-induced lung injury in mice

BACKGROUND AND OBJECTIVE: Acid-induced lung injury from aspiration is one of the most important causes of ARDS. Calcitonin gene-related peptide (CGRP) is a neuropeptide that has various biological actions. The current study investigated whether CGRP might have pathophysiological roles in acid-induced lung injury. METHODS: The investigations employed CGRP gene-disrupted mice--mutant mice (CGRP(-/-)) and their littermate controls (CGRP(+/+)). Anaesthetized and mechanically ventilated mice received 2 mL/kg HCl (pH = 1.5) intratracheally. Lung wet-to-dry weight ratios were calculated to assess pulmonary oedema, total and differential cell counts of the BALF were determined, and measurements of myeloperoxidase activity were performed. RESULTS: Acid-induced lung injury was characterized by an increase in lung permeability and respiratory failure. Disruption of the CGRP gene significantly attenuated acid-induced injury, oedema and respiratory failure. CONCLUSIONS: This study suggests that CGRP is involved in the pathogenesis of acute lung injury caused by acid aspiration and CGRP mutant mice may provide an appropriate model to study molecular mechanisms in this context.     

Postoperative outcome in aortic stenosis with diastolic heart failure compared to one with depressed systolic function

BACKGROUND: In patients with aortic stenosis (AS), the clinical outcome worsens after the development of angina, syncope, and heart failure. This study was performed to elucidate whether the outcome with AS was also poor in patients with diastolic heart failure. METHODS AND RESULTS: Fifty-two patients who had undergone aortic valve replacement (AVR) for AS were retrospectively classified into 3 groups (G) on the basis of LV ejection fraction (EF) and pulmonary wedge pressure (PWP): G-1) normal LVEF, low PWP (EF > or = 45% and PWP < 16 mmHg; n = 35), G-2) normal LVEF, high PWP (EF > or = 45% and PWP > or = 16 mmHg; n = 8), and G-3) low LVEF (EF < 45%; n = 9). Among these 3 groups, we compared the outcome after AVR. None of the patients died after the operation in AS with preserved LVEF irrespective of the PWP, whereas there were 3 cardiac deaths in AS with low EF irrespective of the PWP. CONCLUSIONS: In patients with AS, diastolic heart failure developed in addition to systolic heart failure. The development of LV systolic dysfunction in AS was regarded as poor during the postoperative course, but diastolic heart failure did not affect the outcome. The occurrence of heart failure with preserved systolic function may have a slightly better prognosis and may still be suitable for AVR.     

The present situation of children with psycho-motor disabilities and their parents

We examined the present situation of children and adolescents with psycho-motor disabilities, and their parents by means of a questionnaire survey. The survey was conducted on the family members of outpatients, 116 males and 86 females. About half the patients were older than 15 years of age. The families of 128 patients did not use a home help service such as home nursing or a regional care service. Many family members had chronic ailments. The families of only 45 patients expressed that it would be better if their children would live in a care home in the future. We must develop a versatile system with social support and medical care for such cases.     

Thioredoxin may exert a protective effect against tissue damage caused by oxidative stress in salivary glands of patients with Sjögren's syndrome

OBJECTIVE: To demonstrate the existence of oxidative stress and the role of the antioxidant thioredoxin (TRX) in Sj?gren's syndrome (SS). METHODS: Labial biopsy specimens from patients with SS were analyzed immunohistochemically to detect 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), nitrotyrosine, and TRX. Levels of TRX in saliva and plasma were quantified by ELISA. To analyze the effect of TRX on human salivary gland (HSG) cells, recombinant TRX (rTRX)-treated HSG cells were stimulated by interferon-gamma (IFN-gamma) for detecting interleukin 6 (IL-6) with ELISA and RT-PCR, or stimulated with IFN-gamma and anti-Fas antibody for analyzing Fas-induced apoptosis with PI/annexin V staining. RESULTS: Large amounts of 8-OHdG, 4-HNE, nitrotyrosine, and TRX were produced in salivary duct cells of SS patients, whether there was periductal lymphocytic infiltration or not. Strong TRX expression was detected in acinar cells from 13 of 19 SS specimens. Levels of salivary TRX were significantly higher in SS patients than in controls (p < 0.05), and were inversely related to the salivary flow rates in SS patients. Patients who showed acinar TRX expression had higher salivary TRX levels than those who did not (p < 0.05). Interferon-gamma-induced expression of IL-6 and Fas-mediated apoptosis in HSG cells were significantly suppressed by pretreating cells with rTRX. CONCLUSION: Parallel production of oxidative stress markers together with massive secretion of TRX suggests that oxidative stress induces TRX in the salivary gland. Moreover, suppression of IL-6 production and apoptosis by rTRX in HSG cells suggests TRX acts to protect the salivary glands of SS patients from tissue damage.     

Percutaneous ultrasound-guided radiofrequency ablation of hepatocellular carcinoma with artificially induced pleural effusion and ascites

Background Ultrasound-guided procedures are sometimes of limited use because the tumor is located under the diaphragm or near the surface of the liver. We investigated the safety and efficacy of radiofrequency ablation (RFA) with artificial pleural effusion and/or artificial ascites. Methods Between January 2002 and May 2006, 43 lesions in 36 patients with hepatocellular carcinoma (HCC) were treated by RFA with artificial pleural effusion and/or artificial ascites. Results Artificial pleural effusion allowed visualization of the whole tumor for 36 (83.7%) of the 43 lesions that were otherwise not detectable or poorly visible. Artificial ascites was also helpful in visualizing whole tumors that could not be visualized with only artificial pleural effusion. In all lesions, artificial pleural effusion and/or artificial ascites were helpful in performing percutaneous RFA. Artificial ascites was useful for creating a space between the liver's surface and the skin or diaphragm to avoid burns. Adverse effects after the induction of artificial pleural effusion included pneumonia in one patient and temporary atelectasis in another patient. Severe side effects were not observed. Complete necrosis after RFA was obtained in 43 (100%) of the 43 lesions. During a mean follow-up period of 31.8 ± 5.8 months, local recurrence at the ablation site was found in none of the 43 lesions. Conclusions Percutaneous RFA with artificial pleural effusion and/or artificial ascites was a safe and useful treatment that resulted in good local control of HCC.     

Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid

Insulin Autoimmune Syndrome (IAS) is a rare disease characterized by hypoglycemia and autoantibodies to insulin without prior insulin administration. Here, we report a case of IAS associated with alpha lipoic acid (ALA). The patient is a 55-year-old man. He began to complain of hypoglycemic symptoms after taking ALA. He lost consciousness in the late postprandial period and blood glucose was found to be 27 mg/dl. A high insulin level and high titers of insulin antibodies were detected. His HLA genotype contains DRB1* 0406. As ALA comes to be used widely, the incidence of IAS due to ALA might increase.     

Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa

High serum level of GH in the presence of low plasma level of insulin-like growth factor-I (IGF-I) is one of the endocrinological features of anorexia nervosa (AN). Whether the amount of endogenous GH is not enough to increase IGF-I is not certain. We studied the effect of recombinant human growth hormone (rhGH) on the GH-IGF-I axis and on malnutrition-related disorders in this syndrome. Twenty patients with AN were divided into two groups; one (N = 13) was given rhGH (0.33 mg/day), and the other (N = 7) was given placebo for 6 or 12 months, respectively. During each treatment, levels of serum GH, plasma IGF-I, serum thyroid hormones, serum cholesterol, fasting plasma glucose and cardiac function were monitored. Changes in body mass index (BMI) and calorie taken were also evaluated. Plasma IGF-I level increased from 74.4 +/- 41.9 to 269.0 +/- 31.2 microg/L (P<0.001) during administration of rhGH, which associated with a decrease in serum GH level from 17.0 +/- 15.0 to 1.6 +/- 0.8 microg/L (P<0.001). Administration of rhGH increased BMI, body temperature, fasting plasma glucose level, and food intake. Serum level of triiodothyronine, but not thyroxine, increased during treatment with rhGH. The treatment decreased serum levels of both total and HDL-cholesterol. Studies with echocardiography showed an increase in cardiac output during the treatment with rhGH. These improvements were not observed in patients treated with placebo. Administration of rhGH is recommended as one of the methods of managing the patients with AN.     

A case of sigmoid colon cancer with temporary dysarthria associated with irinotecan

A40 -year-old woman visited our hospital with adenocaricinoma of the sigmoid colon with multiple liver metastases and ovarian metastasis. Because of a stenosis of the primary tumor, she underwent a colostomy before chemotherapy. 5-fluorouracil and irinotecan and leucovorin(FOLFIRI)was selected as first-line chemotherapy. At the start of chemotherapy, just after the end of irinotecan and leucovorin administration, the patient developed dysarthria. There were no neurological abnormalities or hematological abnormalities. The treatment was temporarily discontinued, and the dysarthria completely disappeared within 90 minutes. 5-fluorouracil was administered after the disappearance of dysarthria. Within 60 minutes of the administration of irinotecan and leucovorin at the second chemotherapy treatment, the patient developed dysarthria again. The patient had no neurological or hematological abnormalities. Magnetic resonance imaging(MRI)showed no abnormalities. The treatment was stopped and dysarthria disappeared within 60 minutes as it did the first time. At each time, no treatment for dysarthria was performed. This patient refused to continue irinotecan because of dysarthria. Therefore, chemotherapy without irinotecan was continued for the third time onward. In the previous literature, 8 cases of dysarthria caused by irinotecan were reported as a rare toxicity. In all cases, dysarthria was temporary and reversible. Because the mechanism of dysarthria is unclear, specific treatment and precaution for dysarthria is not recommended. Since dysarthria is reversible, however, irinotecan might be continued until progression.