The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs

We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methylformamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5–5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 μg/kg, i.v.) or substance P (6.5 μg/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5–5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 μg/kg, i.v.)- or substance P (6.5 μg/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge. Received: 29 April 1996 / Accepted: 10 October 1996     

Local muscimol disinhibits mesolimbic dopaminergic activity as examined by brain microdialysis and Fos immunohistochemistry

Infusion of muscimol (5×10⁻⁵ M, 60 min) into the nucleus accumbens (NAC) through a dialysis membrane caused a significant increase in extracellular dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC). Fos-like immunoreactivity induced by intra-NAC infusion of muscimol was seen ipsilaterally in many accumbofugal target areas, but no Fos-positive neurons were seen in the vicinity of the dialysis membrane in the NAC. Sequential staining of Fos and tyrosine hydroxylase (TH) immunoreactivities revealed that a portion of A10 dopaminergic neurons were double-labelled. These results suggest that muscimol in the NAC disinhibits mesolimbic DA neuronal activity possibly through activity of the accumbofugal GABA neuron system.     

Clinical evaluation of cefmenoxime in internal medicine, with special reference to infection associated with hematological disorders

Clinical evaluation of cefmenoxime (CMX, Bestcall) was performed against infections associated with hematological, respiratory tract and other disorders. Clinical effectiveness of CMX against severe infections with hematological disorders including sepsis, pneumonia, pyelitis and so on was 74.4% for good responses and against the respiratory tract infections, 96.2% for good responses was obtained. Neither objective or subjective side effects nor extreme abnormalities in laboratory tests were observed in these patients. It can be concluded, therefore, that CMX is one of the most useful drugs against infectious diseases associated with hematological disorders, respiratory tract and other disorders.     

Primary Adenocarcinoma in the Urethrorectal Fistula

A 60-year-old Japanese man was hospitalized because of urinary leakage from the anus on October 3, 1994. Retrograde urethrography detected a fistula between the bulbous urethra and the rectum. Urethrocystoscopy revealed a tumor on the urethrorectal fistula. Tumor biopsy showed a well differentiated adenocarcinoma. Cystourethrectomy with fistulectomy, and ileal conduit urinary diversion were performed. Pathological examination revealed primary adenocarcinoma in the fistula with invasion to the prostatic urethra and bladder wall. The patient showed no evidence of a recurrence as of August, 1996.     

Small Cell Carcinoma of the Prostate: A Case Report

A case of small cell carcinoma of the prostate without a primary lesion in the lung was reported. The cancer was diagnosed after the patient complained of lumbago caused by bone metastasis. The tumor was 5.9 times 5.0 times 4.6cm. The patient was treated with 4 courses of chemotherapy using cisplatin and etoposide. The tumor diminished to 4.0 times 4.0 times 3.5 cm after completion of the 4 courses of treatment. Prostatic antigen levels were less than 1.0ng/mL during the therapy. Neuron-specific enolase levels were 35.9ng/mL at the beginning of therapy, and decreased to 7.4 ng/mL after completion of 4 courses of treatment. The patient died 3 months after the completion of treatment. This regimen had some value for inhibiting the growth of small cell carcinoma.     

Measurement of quality of life in rheumatoid arthritis]

This study was designed to explore the health status or quality of life (QOL) in 366 patients with rheumatoid arthritis in Japan. Physical, social, and emotional functions of the patients, namely the QOL, were measured by the modified health assessment questionnaire, the quality of well-being score, and the face scale, respectively. These functions were also evaluated by the new methods using visual analogue scales. The longer the duration of rheumatoid arthritis, the worse the QOL measures in these patients. A similar result was observed in the relationship between the stage classification of progression of rheumatoid arthritis and the QOL measures. In contrast, the traditional medical process measures, such as Lansbury activity index, sedimentation rate, and serum CRP concentration did not correlate with the duration of the disease. We conclude that the QOL measures in this study are useful for evaluation of the functional status and well-being of patients with rheumatoid arthritis. However, the clinical usefulness of these measures for evaluation of effectiveness and/or side effects of anti-rheumatic drugs still remains unknown.     

Present situations and problems of sampling and transportation

Quality control of laboratory testings has been markedly improved. However, the importance of preanalytical quality control seems to have been poorly recognized by most medical staff members. In order to improve the present preanalytical situation, a round table discussion on sampling and transportation was held together by doctors, nurses and laboratory staff to know the present situation and to recognize the current problems. It was stressed that better communication among medical staffs and also between medical staff and patients are essential to obtain more precise data.     

Efficacy of continuous cleansing with teicoplanin on post-CABG methicillin-resistant staphylococcus aureus (MRSA) mediastinitis: report of a case.

The patient was a 48-year-old male who was diagnosed with unstable angina. He had worsening cardiogenic shock during coronary angiography. Emergency coronary artery bypass grafting (CABG) was performed. He had a methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis on day 22 after CABG. Drains were placed in the anterior mediastinum, left thoracic cavity, and abscess cavity, and another drain was placed in the mediastinal space for continuous cleansing with povidone iodine, oxydol. For antibiotics, teicoplanin (TEIC) was administered intravenously and to the local site via the cleansing drain for about one month. No MRSA was detected by culture in discharges from the mediastinal drain. Inflammatory findings were improved, and the patient was discharged and resumed everyday life without recurrence of inflammation as of eight months. Although the number of cases of MRSA mediastinitis is small and accumulation of cases is necessary to investigate therapeutic methods and selection of antibiotics, our department will select closed continuous cleansing and TEIC for antibiotics as the first choice for MRSA mediastinitis, and accumulate cases to investigate its efficacy.     

Cyclic mechanical stretching and interleukin-1alpha synergistically up-regulate prostacyclin secretion in cultured human uterine myometrial cells.

Prostacyclin (PGI2), a potent uterine smooth muscle relaxant, is postulated to be a major prostaglandin (PG) secreted from the human myometrium. PGI2 metabolite concentrations in the maternal plasma were reported to be elevated during pregnancy, especially during labor. Recently, we developed cultured human myometrial cells from pregnant women and reported that cyclic mechanical stretching mimicking labor increased PGI2 secretion from these cells by up-regulating PGI2 synthase promoter activities. Since elevation of cervical/vaginal interleukin-1alpha (IL-1alpha) concentrations is also a characteristic feature of delivery, and IL-1alpha is a known stimulator of PG synthesis, we investigated a possible synergistic effect of cyclic mechanical stretching and IL-1alpha on PGI2 production in cultured human myometrial cells. Treatment with IL-1alpha (10 ng/ml) significantly augmented (4- to 60-fold) the secretion of PGI2, prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha) and thromboxane A2 (TXA2) from cultured human myometrial cells obtained from non-pregnant and pregnant women as well as in cultured human umbilical artery and cultured human coronary artery smooth muscle cells (p < 0.05 for all comparisons). However, labor-like cyclic mechanical stretching up-regulated IL-1alpha-augmented PGI2 secretion from myometrial cells obtained from non-pregnant and pregnant women 2.1- to 2.8-fold (p < 0.05 for all comparisons), but not PGE2, PGF2alpha nor TXA2. Moreover, such an augumentation of PGI2 secretion by cyclic mechanical stretching was not observed in cultured human umbilical artery nor in cultured human coronary artery smooth muscle cells. These results suggest that cyclic mechanical stretching by labor, in concert with IL-1alpha stimulation, contributes to the increase in myometrial PGI2 secretion during delivery.     

Preliminary study on the effects of bar placement on the thorax after the nuss procedure for pectus excavatum using bone scintigraphy.

AIM: Bone scintigraphy was performed to elucidate the effects of the Nuss procedure for pectus excavatum on the bony thorax. METHODS: Eight boys and 6 girls (5 - 24 years of age) underwent bone scintigraphy, using (99m)Tc-HMDP. Eleven patients were studied 5 to 21 days after the Nuss procedure; 6 were studied 20 to 24 months after the operation before bar removal. Three of 14 were studied twice after the Nuss procedure and before bar removal. RESULTS: In the early postoperative phase, RI accumulation was found at the sternum and ribs in only 1 of 6 patients under 9 years of age, whereas in all 5 older patients, RI had accumulated at the sternum. Scintigrams before bar removal revealed, regardless of age, hot spots at the lateral ribs in contact with the bar and at the costochondral junctions where the bar passed through the intercostal spaces. Furthermore, chest roentgenograms showed the deformed lateral ribs in contact with the bar. CONCLUSIONS: The Nuss procedure creates minute fractures at the sternum and the ribs, especially in older patients. The bar deforms the ribs and restrains the growth of the thorax. Furthermore, it constantly rubs against the ribs and can therefore cause late complications. Bone scintigraphy may determine the appropriate timing for bar removal.