Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II.

Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 [MCP-1] induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production.     

Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.     

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans.

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but is also frequently demonstrated by children and adults with chronic obstructive lung diseases. AHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in children with post-infectious bronchiolitis obliterans (BO). Methacholine and adenosine 5'-monophosphate (AMP) challenges were used as tools for the evaluation of AHR to direct and indirect stimuli, respectively, in children with post-infectious BO (n = 28). These results were compared with those of asthmatic (n = 30) and control children (n = 25). Altogether, twenty-two patients (78.6%) with post-infectious BO were hyperreactive to methacholine with a provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) of <16 mg x mL(-1), but only six (21.4%) were hyperreactive to AMP with a PC20 of <200 mg x mL(-1). All patients with asthma responded positively to methacholine, and most (28, 93.3%) also responded positively to AMP. The majority of controls were insensitive to both challenges. Airway hyperresponsiveness to methacholine is a frequent, but by no means universal, finding in children with post-infectious bronchiolitis obliterans, but is usually not accompanied by airway hyperresponsiveness to adenosine 5'-monophosphate. This finding suggests that airway hyperresponsiveness in patients with post-infectious bronchiolitis obliterans has characteristics that differ from those of asthmatic subjects.     

Repeat operations in the management of clival chordomas: palliative surgery.

Some chordomas have a very poor prognosis because of their aggressive growth nature, but the efficacy of repeat operations for these cases has not been well documented. This report concerns 3 patients with aggressive chordoma of the clivus, who underwent operations 6 to 12 times over a period of 8 to 17 years because of symptomatic regrowth. Overall mean interval between repeat operations was 18 months with a range from 5 to 57 months and survival times were 9 to19 years after the first surgery. Main symptoms before each operation were diplopia and visual disturbance. Repeat palliative operations by intentional extradural debulking of the tumour to decompress offending neural structures, as well as maximal removal of the tumour, using appropriate skull base approaches, can mitigate progressive symptoms, and may result in better quality and some prolongation of life, although our patients gradually deteriorated neurologically throughout the clinical course.     

Accessory nerve neurotization in infants with brachial plexus birth palsy

We report the surgical results of 13 accessory nerve neurotizations in brachial plexus birth palsy. The mean age at operation was 5.9 months. The accessory nerve was transferred to three C5 roots, to three C6 roots, to four posterior division of the middle trunks, to one musculocutaneous nerve, and to two suprascapular nerves. Sixty-seven percent of the cases acquired M4 or more in the deltoid muscle, 88% in the infraspinatus muscle, and 100% in the biceps brachii muscle. Twenty-five percent of the cases acquired M4 or more in the triceps brachii muscle and the wrist extensor muscles. These results were much better than formerly reported for adult cases by other authors. No functional compromise of the trapezius muscle was noted. The accessory nerve neurotization can be used safely and effectively in neurosurgical reconstruction of the brachial plexus palsy in infants. © 1994 Wiley-Liss, Inc.     

Technique of intramedullary fixation for arthrodesis of the wrist in rheumatoid arthritis.

We did 18 arthrodeses of the wrist in 16 patients with rheumatoid arthritis using an intramedullary fixation technique. There were 15 women and one man, whose ages at operation ranged from 47 to 71 years (mean 58). Follow up ranged from 13 to 68 months (mean 27). The operative technique consists of a combination of intramedullary placement of two Kirschner (K)-wires and an autogenous bone graft. At follow up bony union was apparent in all cases. K-wires came out of the metacarpal joints in two cases. Paraesthesiae in the median nerve distribution occurred in two cases which both recovered within three months.     

Presence of circulating suppressive factor for muscarinic acetylcholine receptor in senile dementia

Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acetylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acetylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean +/- SD age of 77.5 +/- 8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic-subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (3H-QNB), an antagonist for muscarinic acetylcholine receptor, to the rat synaptic membrane, was 18.1 +/- 7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7 +/- 3.8%). However, that in the VD group (8.4 +/- 6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on 3H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r = 0.480, p less than 0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT.     

Report of a patient of primary Sj?gren syndrome, IgA nephropathy and chronic idiopathic thrombocytopenic purpura]

We describe the case of a 61-year-old woman diagnosed with primary Sj?gren's syndrome (SS) after an 8-year history of IgA nephropathy and a 3-year history of recurrent purpuric rashes. Her two daughters had previously been diagnosed with other autoimmune diseases. One daughter had Graves' disease and the other had Hashimoto's disease and systemic lupus erythematosus. The diagnosis of SS was made based on dryness of mucous membranes, Shirmer test, and parotid sialography. Thrombocytopenia, high platelet-aggregated IgG (PA-IgG) level, and normal megakaryocytes count in bone marrow suggested that her recurrent purpuric rashes were due to idiopathic thrombocytopenic purpura (ITP). Patients with SS may develop other autoimmune diseases. This case aids understanding of the immune pathogenesis and genetic background of SS.     

Late Effects of Childhood Acute Leukemia and Its Treatment

Late effects of childhood acute leukemia and its treatment were studied in 766 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.