Multi-center analysis of calcinosis in children with juvenile dermatomyositis]

OBJECTIVES: To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed. METHOD: Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis. RESULTS: The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.     

Laparoscopic cholecystectomy and time-course changes in renal function

Background: Recently, the retraction method has been used to reduce intraabdominal pressure (IAP) during laparoscopic surgery. The purpose of this study was to determine the serial changes in renal function during laparoscopic cholecystectomy (LC) using the retraction method. Methods: Urine output, effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) were measured serially in seven patients who underwent LC with 12 mmHg pneumoperitoneum (High-IAP group) and five who underwent LC using the retraction method with 4 mmHg pneumoperitoneum (Low-IAP group). Results: Urine output, ERPF, and GFR were decreased during pneumoperitoneum in the High-IAP group, whereas no significant changes in any of these parameters were observed in the Low-IAP group. Conclusions: Our findings demonstrate that reduction of IAP to 4 mmHg using the retraction method prevents the transient renal dysfunction caused by prolonged 12 mmHg pneumoperitoneum during LC, suggesting that the retraction method reduces the risk of perioperative renal dysfunction during laparoscopic surgery. Received: 26 March 1996/Accepted: 27 July 1996     

Basic fibroblast growth factor prevents thalamic degeneration after cortical infarction

In the focal infarction model of the rat middle cerebral artery (MCA), the thalamus of the occluded side becomes gradually atrophic, mainly because of retrograde degeneration. We determined whether basic fibroblast growth factor (bFGF) administered intracisternally could prevent this thalamic atrophy. We occluded the left MCA through a small cranial opening, and animals were then divided into two groups. One group received intracisternal injections of recombinant bFGF (1 microgram dissolved in 0.1 ml of saline with 2% rat serum) starting 1 day after occlusion and repeated once a week to a total dose of 4 micrograms by four injections. The other group received vehicle solution by the same schedule. The animals were perfused and fixed at 28 days after occlusion, and histological examination was made at the level of the caudoputamen and thalamus. In the bFGF-treated rats, the area of the posterior ventral thalamus of the occluded side was 93% of that of the contralateral side, i.e., significantly larger than in the normal saline-treated rats (75%, p less than 0.01). The infarction size was not statistically different in the two groups. Microscopic observation indicated that normal-saline-treated animals showed shrinkage and disappearance of thalamic neurons, whereas bFGF-treated groups showed preservation of thalamic neurons. Computerized analysis of the cell size substantiated this observation. To assess the effect of bFGF on astrocytes, bFGF or vehicle solution was injected into normal rats, and their histology was evaluated at 1, 2, and 4 weeks after injection. The bFGF-injected group showed a significant increase in glial fibrillary acidic protein-positive astrocytes in the brain tissue facing the ventriculocisternal system.(ABSTRACT TRUNCATED AT 250 WORDS)     

A nationwide survey on transient hyperammonemia in newborn infants in Japan: prognosis of life and neurological outcome.

A nationwide survey of transient hyperammonemia in newborns was carried out in Japan. A total of 18 patients, consisting of 12 male and 6 female infants, were reported from 11 facilities. These neonates exhibited hyperammonemia with plasma ammonia levels in the range from 124 to 6256 micrograms/dl. Four newborn infants of the 18 died in the neonatal period, and an additional one died in the early infancy. Among the 13 infants who were alive at the time of this survey, 6 had neurological sequelae, including mental retardation, spastic quadriplegia and epilepsy. The multivariate analysis revealed that the Apgar score at 1 minute, peak plasma ammonia concentration, birth weight and sex were significant factors affecting the prognosis of life.     

A case of lung cancer with hypercalcemia which was incidentally complicated with primary hyperparathyroidism due to parathyroid adenoma.

In lung cancer patients, hypercalcemia is a fairly common metabolic problem associated with malignancy. However, the occurrence of hypercalcemia in lung cancer patients means an ominous prognostic sign. As hypercalcemia often causes early death, quick diagnosis and treatment for hypercalcemia are required. A 69-year-old woman was admitted to our hospital with anorexia caused by hypercalcemia. On admission, serum level of PTH was elevated and PTHrP was normal. From the results of CT findings and transbronchial lung biopsy, the cause of the hypercalcemia was determined as lung cancer incidentally complicated with primary hyperparathyroidism. First, serum calcium level was returned to normal through hydration with saline and bisphosphonates. Next, left hemithyroidectomy for primary hyperparathyroidism was performed. Histologically, the tumor was diagnosed as parathyroid adenoma. Fifteen days later, left lower lobectomy for primary lung cancer was performed under a video-assisted thoracoscopic approach. Histologically, the tumor was diagnosed as a moderately differentiated adenocarcinoma. Four years and three months after the operation, the patient is alive and well with no sign of recurrence. When a lung cancer patient is complicated with hypercalcemia, we need to consider that primary hyperparathyroidism is a possible cause of the hypercalcemia.     

Embolic myocardial infarction and left ventricular rupture due to mitral valve endocarditis.

A left ventricular rupture due to embolic myocardial infarction is extremely rare. A 72-year-old woman developed an acute embolic myocardial infarction and mitral regurgitation due to infective endocarditis. Two days after the infarction, a left ventricular free wall rupture occurred after transesophageal echo examination. She received an epicardial patch and mitral valve replacement. Perioperatively, an intra-aortic balloon pump and long-term antibiotics were used. The postoperative course was uneventful, and she is doing well 10 months after surgery.     

Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier.

In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water.