Alteration in myelin-associated proteins following spinal cord irradiation in guinea pigs.

The aim of this study was to investigate the pathological and cellular basis for radiation-induced myelopathy in guinea pigs by monitoring biochemical alterations in levels of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Guinea pigs were irradiated to the lumbar region with various doses of neutrons or cobalt gamma irradiation. The ED50s for paralysis were 17.2 Gy and 67.5 Gy for neutron and cobalt irradiation, respectively, and was histologically associated with demyelination. In spinal cords taken from animals at the onset of paralysis myelin basic protein levels were decreased in direct relationship to the radiation dose. The lowest doses to cause paralysis led to a 25% decrease in MBP levels. In a separate experiment, alterations in MBP were measured in the spinal cords over the time period leading up to paralysis. Surprisingly, decreases in MBP were found immediately after the end of the 4 week irradiation period. These early changes in MBP were not markedly dose dependent and occurred with nonparalyzing doses. Dose-dependent decreases were found only just before the onset of paralysis. CNPase activity measured in the same specimens showed changes that were essentially similar to those for MBP. In the CSF, MBP levels were essentially constant until onset of paralysis. This study showed that demyelination, as assessed by the levels of the myelin-associated proteins MBP and CNPase, can occur soon after spinal cord irradiation but that profound dose-dependent changes are seen only immediately preceding the onset of paralysis. Although increases in MBP in the CSF were associated with the onset of radiation-induced myelopathy, its assay is unlikely to predict this complication of irradiation.     

The significance of a rapid cold hemagglutination test for detecting mycoplasma infections in children with asthma exacerbation.

BACKGROUND AND PURPOSE: Mycoplasma pneumoniae infection is a frequent cause of community-acquired respiratory infections in children and adults. However, standardized, rapid, specific methods for its diagnosis are lacking. The relationship between M. pneumoniae infection and asthma exacerbation has been recently discussed in the literature. We investigated the accuracy of rapid detection of mycoplasma infection by cold hemagglutination test compared to conventional enzyme immunoassays. The clinical characteristics of mycoplasma infection seen during emergent visits in asthmatic children were reviewed. METHODS: We retrospectively reviewed medical records of patients with asthma exacerbation visiting the Department of Pediatric Emergency, National Taiwan University Hospital, over a 12-month period. Subjects 2-18 years of age diagnosed with asthma at our outpatient clinic were included in this study. Patients with immunodeficiency, congenital anomalies, neurological diseases and irregular follow-up were excluded. RESULTS: A total of 269 children (174 males and 95 females) with a mean (+/- standard deviation) age of 6.15 +/- 3.08 years were included. The prevalence of asthma exacerbation in regular follow-up patients was 13.4%, and as many as 19.6% of cases (74/378 person-times) required hospitalization. Asthma attacks were most prevalent during December. 126 patients had both rapid cold hemagglutination testing and mycoplasma immunoglobulin M titers determined using acute blood samples drawn in the emergency room; 46 (36.5%) of these patients demonstrated mycoplasma infection. Sensitivity and specificity of the rapid cold hemagglutination test was 78.3% and 41.3%, respectively. The positive predictive value was 43.4%. Comparison of patients with or without mycoplasma infection revealed no differences in gender, age, chest X-ray findings, and most symptoms/signs and laboratory data, except that more signs of fever and auscultatory rales were seen in the non-mycoplasma infection group. CONCLUSIONS: Mycoplasma infections could be an exacerbating factor for asthma, and the rapid cold hemagglutination test should not be a guideline for prescribing macrolides in the emergency room.     

Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides.

We have investigated the use of a cationic lipid preparation to enhance antisense oligonucleotide activity in human umbilical vein endothelial cells. A liposomal preparation containing the cationic lipid N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) was found to increase by at least 1000-fold the potency of an antisense oligonucleotide (ISIS 1570) that hybridizes to the AUG translation initiation codon of human intercellular adhesion molecule-1. In the presence of 8 microM DOTMA, 6-15-fold more 35S-ISIS 1570 associated with cells, at oligonucleotide concentrations from 0.01 to 5 microM, than did in the absence of DOTMA. Both 35S-ISIS 1570 association with cells and antisense activity were increased as a function of DOTMA concentration and with increasing time of incubation with the cationic lipid. Fluorescein-labeled ISIS 1570 was used to assess the intracellular distribution of the oligonucleotide in the presence and absence of DOTMA. In the absence of DOTMA, the oligonucleotide localized to discrete structures in the cytoplasm of the cell, resulting in a punctate fluorescence pattern. In the presence of DOTMA, cellular fluorescence markedly increased and the oligonucleotide localized within the nucleus, as well as to discrete structures in the cytoplasm. Accumulation of the oligonucleotide in the nucleus in the presence of DOTMA was time and temperature dependent. Nuclear accumulation was inhibited by preincubation of the cells with monensin but not chloroquine, NH4Cl, nocodazole, colcemid, or brefeldin A. These data demonstrate that cationic lipids increase antisense activity by increasing the amount of oligonucleotide associated with cells and altering intracellular distribution of the oligonucleotide.     

Patient satisfaction with and recommendation of a hospital: effects of interpersonal and technical aspects of hospital care.

OBJECTIVES: To examine patient satisfaction with and recommendation of a hospital, with a special focus on the correlation of these measures to patient ratings of interpersonal and technical performance of the hospital. DESIGN: Telephone survey of patients with four specific conditions after their discharge from hospitals. SETTING: Accredited district teaching hospitals and above, nationwide in Taiwan. PARTICIPANTS: A total of 4945 patients from 126 hospitals diagnosed with or undergoing procedures related to stroke, diabetes mellitus, Caesarean section, or appendectomy were interviewed by telephone. MAIN OUTCOME MEASURES: Overall patient satisfaction and recommendation were measured by single-item questions. Interpersonal skills were measured by three items: doctors' explanation, attitude, and caring. Technical skills were measured by another three items: hospital equipment, clinical competence, and outcome of treatment. RESULTS: Interpersonal skills were as influential or more influential than clinical competence on patient satisfaction for three of the four disease categories. In contrast, technical competence was a more influential predictor for recommendation for patients in all four disease categories. CONCLUSION: The preliminary results imply that a hospital with high percentage of patient satisfaction does not necessarily receive a high level of recommendation. This finding provides new insights for researchers and for hospital managers who devote resources exclusively for achieving the highest possible levels of patient satisfaction.     

Microencapsulated pancreatic islets: a pathologic study.

Dog pancreatic islets isolated by an enzymatic digestion method were encapsulated in an alginate-poly L-lysine-alginate membrane. These microencapsulated pancreatic islets were cultured in vitro to study their ability of insulin secretion. Portions of these in vitro-cultured microencapsulated pancreatic islets were taken out for a viability dye exclusion study as well as for pathologic studies to correlate them with insulin secretion ability. We found that there was a strong correlation between them. Good insulin-secreting microcapsules showed well-preserved cell membranes and beta-cell granules. An in vitro culture for one to two days in RPMI-1640 made the islets more stable, the cellular surface became smoother and the beta-granules were in better shape. The microencapsulated pancreatic islets were also injected into the peritoneum of streptozotocin-induced diabetic CDF1 mice. Blood glucose levels dropped and stayed low for up to 60 days. But, when non-encapsulated dog pancreatic islets were used, the blood glucose levels remained low for only about 14 days. A small portion of the injected microcapsules were washed out at specific times for pathologic study. Up to 28 days after injection, only a few of the injected microcapsules showed pericapsular cellular infiltrate. However, after 56 days, most of the microcapsules showed dense pericapsular cellular infiltrate. Immunohistochemical analysis of these infiltrates showed that the majority of cells were fibroblasts and macrophages. Most of the cells located in the inner portion of the infiltrate were fibroblasts, while the macrophages were located mainly on the outer portion. Both scanning and transmission electron microscopy showed that the surface of the microcapsule outer wall was much smoother than the inner wall. The size of the microcapsules was approximately 0.6-0.8 mm and the thickness of the wall measured around 10 nm. The smaller the microcapsule is, the less chance there is of rupture with release of the xenographic islets. Once the wall of the transplanted microcapsules was ruptured, the inner surface showed more increased inflammatory cell and fibroblast infiltration than the outer surface.     

Sirolimus-induced interstitial pneumonitis in a renal transplant recipient.

Sirolimus is a recently licensed immunosuppressant for organ transplantation that has been used as basic, adjuvant, or maintenance therapy for prevention of organ rejection. Well-known side effects of this agent are hyperlipidemia and bone marrow suppression. Interstitial pneumonitis is a relatively newly described adverse effect of the drug. A 43-year-old female recipient of a cadaveric kidney developed cough with blood-tinged sputum while receiving sirolimus immunosuppressive therapy. High-resolution computed tomographic scan and chest radiograph revealed interstitial infiltrations over bilateral lower lungs. No evidence of bacterial, fungal, mycobacterial, or viral infection was found and all tests for collagen vascular diseases were negative. Discontinuation of sirolimus resulted in a significant improvement of the lung disease.     

Isokinetic eccentric exercise can induce skeletal muscle injury within the physiologic excursion of muscle-tendon unit: a rabbit model

Background and Purpose  

Intensive eccentric exercise can cause muscle damage. We simulated an animal model of isokinetic eccentric exercise by repetitively stretching stimulated triceps surae muscle-tendon units to determine if such exercise affects the mechanical properties of the unit within its physiologic excursion.     

Sustained-release theophylline-uniphyllin in nocturnal asthmatics

For a period of six months, we collected 12 cases of nocturnal asthmatics (7 males, 5 females); their ages ranged from 20 to 66 (the average age is 49). We found that administration of Uniphyllin (10 mg/kg) once a day at 6 PM could maintain the blood level of theophylline within therapeutic range at least 12 to 24 hrs. The peak expiratory flow rate of the 6 cases we collected, were significantly improved. The result of pharmokinetic parameters: 1) The average of a single dose (12 cases) is AUC (ug. hr/ml) 275.1 +/- 62. k; Kel (hr-1) 0.068 +/- 0.019; Ka (hr-1) 0.33 +/- 0.07); Tmax (hr) 6.3 +/- 1.4; T 1/2 (hr) 11.2 +/- 4.4; Clearance/F (ml/kg/hr) 37.9 +/- 9.0.2). The average of steady state (12 cases) is Css (mg/L) 5. 7 +/- 2.6; Cmax-Cmin (mg/L) 10.09 +/- 1.46.3). The average of relative bioavailability (3 cases) is 82%, 83%, 102%. However, the extent of absorption data is available for only 3 subjects. There are too few subjects to draw any meaningful conclusions about this relative bioavailability. Four cases show slight symptoms, including 1 case of dizziness, 2 cases of nausea, and 1 case gaseousness. It is suggested that the drug be administered at about 6-8 PM to coincide peak levels in the early morning in nocturnal asthmatics.