Pharmacokinetics of oral alminoprofen (Minalfen) in elderly patients with rheumatoid arthritis and spondylosis deformans]

The pharmacokinetics of oral Alminoprofen, a nonsteroidal anti-inflammatory drug, were studied in five elderly patients with rheumatoid arthritis and spondylosis deformans after 200 mg (three times a day) repeated dose for 5 days. The pharmacokinetic parameters after oral administration of Alminoprofen were analyzed by the one-compartment open model method. The maximum plasma concentrations (Cmax) were 16.1 +/- 2.5 micrograms/ml, after dosing on day 1, 25.2 +/- 1.6 micrograms/ml on day 3 and 21.6 +/- 2.7 micrograms/ml on day 5. The maximum time (Tmax) were about 2 hours after the medication in al cases. The area under the curve in drug concentration in plasma versus time (AUC) were 58.5 +/- 6.3 micrograms hr/ml on day 1, 58.5 +/- 3.1 micrograms hr/ml on day 3 and 58.1 +/- 8.5 micrograms hr/ml on day 5. The biological half-lives (t1/2) were 2.45 +/- 0.35, 2.09 +/- 0.82 and 2.49 +/- 0.63 hours, after dosing on day 1, day 3 and day 5, respectively. The analysis of moment in pharmacokinetics revealed that the mean residence time (MRT) on day 1, day 3 and day 5 observed were 2.31 +/- 0.03, 2.15 +/- 0.09 and 2.15 +/- 0.07 hours, respectively. The variance residence times (VRT) observed were 0.95 +/- 0.05 hour2 on day 1, 0.88 +/- 0.09 hour2 on day 3 and 1.06 +/- 0.07 hour2 on day 5. The ratios of accumulation calculated were 1.16 +/- 0.05 in both the morning medication on day 3 day 5, and it therefore appears that the steady-state equilibrium is established within 3 days after commencement of dosage.(ABSTRACT TRUNCATED AT 250 WORDS)     

A Case of Fibrous Histiocytoma Associated with Xanthogranulomatous Alteration

We report here an unusual case of fibrous histiocytoma in which an area of xanthogranuloma was observed histologically. Our case suggests that adult xanthogranuloma is a variant of fibrous histiocytoma.     

A case of bilateral panophthalmoplegia caused by paranasal malignant lymphoma extending into the skull base]

A case of bilateral panophthalmoplegia developed after paranasal malignant lymphoma is described, and previously reported cases are reviewed. A 74-year-old female was hospitalized with the chief complaints of bilateral ptosis and bilateral deep orbital pain that had developed over a 10-day period. Neurological examination revealed bilateral dilated pupils, panophthalmoplegia, and hypalgesia in the area of the ophthalmic nerve on both sides. Laboratory studies and endocrinological examination were free from abnormal findings. Skull X-ray films showed a soft tissue lesion in the sphenoidal and ethmoidal sinus and this was associated with bony structure destruction in the surrounding area. Computed tomography demonstrated a heterogeneously enhanced mass lesion in the paranasal sinus extending into the intrasellar region and bilateral cavernous sinus. Meticulous investigation has so far revealed no distant lesions either in the thoracic or abdominal lesions. Subtotal tumor resection was undergone via the transsphenoidal route at which time tumor extension into the nasal cavity and sellar floor destruction were confirmed. Diffuse and mixed B-cell type malignant lymphoma was the pathological diagnosis. Postoperatively, improvement of abnormalities of pupils, panophthalmoplegia, and ptosis was achieved but this was only transient. Despite focal radiation therapy and repeated chemotherapy, the patient died 14-months after the diagnosis was made. On reviewing the literature, it is shown that the incidence of bilateral panophthalmoplegia among patients who develop disturbance of ocular movement is extremely low (0.4%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hypertension on asymmetrical septal hypertrophy: an echocardiographic study

The effect of hypertension on asymmetrical septal hypertrophy was studied by echocardiography to differentiate idiopathic asymmetrical septal hypertrophy (ASH) from ASH with hypertension. One hundred eight patients with ASH proven by echocardiography were categorized in two groups; 53 patients with hypertension (greater than 160 systolic, greater than 95 diastolic) (hypertensive group: HT) and 55 patients with normal blood pressure (normotensive group: NT). Septal hypertrophy was classified as mid-portion (M-type), diffuse (D-type), and basal (B-type) hypertrophy by the long-axis view, and also diffuse (I-type), anterolateral (II-type), anteroseptal (III-type), and anterior septal (IV-type) by the short-axis view, respectively. Endomyocardial biopsy and left ventriculography were performed in 50 patients (18 hypertensives and 32 normotensives). In the hypertensive group, 45%, 30%, and 25% of cases had diffuse, basal and mid-portion hypertrophy, respectively. There was no case in the basal hypertrophy whose biopsy findings were compatible with hypertrophic cardiomyopathy. In the normotensive group, 78% and 22% of patients had midportion and diffuse hypertrophy, respectively, but none of them had the basal hypertrophy. Type IV was seen in only six patients in the normotensive group.     

Single photon emission computerized tomography in childhood hydrocephalus

Single photon emission computerized tomography (SPECT) is now widely used as one of the tools in evaluating cerebral blood flow (CBF). The authors report the CBF changes in childhood hydrocephalus. Five pediatric cases studied by ¹²³I-IM SPECT in children are presented. The authors counted radioactivities both in early and delayed images in each patient, and calculated the reabsorption ratio (RR). Two negative-RR cases and three positive-RR cases were found. All of the negative-RR patients had a poor prognosis, while all of the positive-RR patients had a favorable outcome.     

Local cerebral blood flow responses in rats to hypercapnia and hypoxia in the rostral ventrolateral medulla and in the cortex.

The effects of hypercapnia and hypoxia on two local cerebral blood flows in the parietal cortex (PC-BF) and rostral ventrolateral medulla (RVLM-BF) were examined using laser Doppler flowmetry in anesthetized rats. Hypercapnia for 45 s duration at the end-tidal CO2 between 5% and 10%, induced by increasing inspiratory CO2, increased both cerebral blood flows and systemic blood pressure in a degree-dependent manner. The response of RVLM-BF was significantly stronger than that of PC-BF. Both cerebral blood flow responses to hypercapnia were not influenced by cutting peripheral chemoreceptor afferent nerves. Hypoxia for 45 s duration at the end-tidal O2 between 12% and 6%, induced by decreasing inspiratory O2, produced an increase of similar magnitude in both RVLM and PC local blood flows in a degree-dependent manner and a decrease in systemic blood pressure. The responses of both PC-BF and RVLM-BF to hypoxia were significantly diminished after cutting peripheral chemoreceptor afferent nerves. It is concluded that: (1) the RVLM-BF is much more sensitive to hypercapnia than the PC-BF; and (2) activation of peripheral arterial chemoreceptors possibly contributes to hypoxia-induced increase in the RVLM-BF and PC-BF.     

Effect of lipopolysaccharide on transport and metabolism of arginine in mouse peritoneal macrophages.

The transport activity of arginine in mouse peritoneal macrophages was strongly induced when they were cultured with 1 ng/ml bacterial lipopolysaccharide (LPS) for 12 h. Arginine in the medium decreased whereas ornithine in the medium increased during the culture. This time-dependent change of arginine to ornithine was accelerated by LPS. However, the activity of arginase in the macrophages did not change during the culture with or without LPS and release of arginase from the cells to the medium was not detected. It is suggested that the transport of arginine and ornithine was a rate-limiting step in arginine-to-ornithine conversion in the macrophage culture medium. A possible role of the induction of arginine transport activity in the macrophage cytocidal activity due to arginine depletion and nitric oxide production is discussed.     

Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma

BACKGROUND: Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) are thought to contribute to the airway inflammation and airway hyper-responsiveness (AHR) of allergic asthma. Some differences from allergic asthma have been noted, including airway neutrophilia, and the involvement of ICAM-1 in toluene diisocyanate (TDI) asthma is currently unclear. OBJECTIVE: We utilized mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in airway inflammation and AHR in TDI-induced asthma. METHODS: Male C57BL/6J mice (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed 24 h after challenge by TDI or solvent. The production of antigen-specific IgG and IgE by TDI sensitized and non-sensitized mice was determined. RESULTS: TDI challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein-2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable. CONCLUSION: These results suggest that ICAM-1 plays an essential role in airway inflammation and AHR in TDI-induced asthma.