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J Aronson

Publications and source records attributed to J Aronson.

At least 19 recordsLinked to original sources
PubMed2001

Phenol derivatives accelerate inactivation kinetics in one inactivation-deficient mutant human skeletal muscle Na(+) channel.

Altered inactivation kinetics in skeletal muscle Na(+) channels due to mutations in the encoding gene are causal for the alterations in muscle excitability in nondystrophic myotonia. Na(+) channel blockers like lidocaine and mexiletine, suggested for therapy of myotonia, do not reconstitute inactivation in channels with defective inactivation in vitro. We examined the effects of four methylated and/or halogenated phenol derivatives on one heterologously expressed inactivation-deficient Paramyotonia congenita-mutant (R1448H) muscle Na(+) channel in vitro. All these compounds accelerated delayed inactivation of R1448H-whole-cell currents during a depolarization and delayed accelerated recovery from inactivation. The potency of these effects paralleled the potency of the drugs to block the peak current amplitude. We conclude that the investigated phenol derivatives affect inactivation-deficient Na(+) channels more specifically than lidocaine and mexiletine. However, for all compounds, the effect on inactivation was accompanied by a substantial block of the peak current amplitude.

Cell Line↗
PubMed2001

Development of tensile strength during distraction osteogenesis in a rat model.

These studies were designed to determine the reliability of in vitro tensile testing to measure the temporal development of regenerate bone strength in rats during limb lengthening (distraction osteogenesis, DO). External fixators were placed on the right tibiae of 36 virus-free, 400-450 g male Sprague Dawley rats, and osteotomies (n = 33) were performed. Distraction was initiated the following morning (0 day latency) at 0.4 mm/day and continued to day 20. The 8 mm gap was allowed to consolidate for up to 50 days (day 70 postop). Contralateral unoperated and operated (fixator only) controls were included. On days 20, 30, 50 and 70 postop, the rats were anesthetized, and their tibiae were radiographed prior to undergoing sacrifice for histological or tensile analysis. On day 70, an additional group was tested by three-point bending. Radiodensity measurements demonstrated progressive mineralization of the DO gap, and histology confirmed typical intramembranous ossification of collagen bundles oriented parallel to the distraction force. Tensile stiffness increased significantly between days 20 and 30 postop, this increase correlated with initial radiographic and histologic bridging of the DO gap. Energy to failure and ultimate tensile strength increased progressively to day 70. At day 70, the force to failure for three-point bending was 65% of control tibiae. In conclusion, in vitro tensile testing provides a reliable method to test the development of structural integrity during the early stages of DO. Therefore, the biomechanical effects of postulated modulators of bone repair can be measured during early stages (bone formation, bridging, early consolidation) of DO in a rat model.

Animals↗
PubMed2001

The effect of aging on distraction osteogenesis in the rat.

The effect of age on bone formation in the limb lengthening model of distraction osteogenesis (DO) was investigated in two studies using Sprague-Dawley (SD) rats from two colonies at various ages (CAMM: 9 vs 24 months, Harlan: 4 vs 24 months). External fixators were placed on the right tibiae of 30 male SD rats (20 CAMM, 10 Harlan) and mid-diaphyseal osteotomies were performed. Distraction was performed at 0.2 mm bid for 20 days (CAMM) or 14 days (Harlan). The experimental (DO) and control (contra-lateral) tibiae were removed for high-resolution radiography and decalcified histology. Videomicroscopy was used to quantitate radiodensity, histology (matrix type) and relative areas of cell proliferation, which was identified by proliferating cell nuclear antigen (PCNA) immunochemistry. Both studies demonstrated an age-related decrease in the percent mineralized bone (radiodensity) in the distraction gap (CAMM 9 vs 24 months: 68% vs 51%, P < 0.003; Harlan 4 vs 24 months: 95% vs 36%, P < 0.001) and no significant colony or distraction time-specific difference was seen between the two colonies of 24-month-old rats. Histology was performed on the Harlan rats. The DO gaps in the 24-month-old rats demonstrated less endosteal new bone compared to the 4-month-old rats (P < 0.01), but equivalent periosteal new bone. In 4-month-old rats, PCNA-immunostained cells were organized along the primary matrix front (where the first deposition of osteoid occurs) extending across both periosteal and endosteal surfaces. In 24-month-old rats, PCNA+ cells were organized in zones along the periosteal new bone fronts only and irregularly scattered throughout the endosteal gap within a fibrovascular non-ossifying matrix. These results indicate that 24-month-old rats have a relative deficit in endosteal bone formation which may not be related to cell proliferation but rather to cell organization. This model reflects the clinical situation where radiographic findings in older patients demonstrate significant delays in mineralization during DO. We believe this model of DO in aged rats presents unique in vivo opportunities to test hypotheses concerning (1) the effects of aging on bone repair, (2) the effects of pharmacological agents on bone repair in a geriatric setting, and (3) to study the mechanisms underlying DO.

Aging↗
PubMed2001

Skeletal effects of developmental lead exposure in rats.

To identify possible direct and indirect mechanisms underlying the effects of lead on skeletal growth, 3 studies were conducted. In the first study, 1 male and 1 female pup/litter (n = 5 litters), were exposed ad libitum to 0, 825, or 2475 ppm lead acetate in the drinking water from gestational day 4 to euthanasia on day 55. Tibial strength was tested by 3-point bending and plasma levels of vitamin D metabolites were measured. A dose-dependent decrease of the load to failure was demonstrated but only in male pups. No differences in plasma levels of vitamin D metabolites were observed. In the second study, conducted to test if hormone treatment would attenuate the lead deficits, male and female pups were exposed to 0 or 2475 ppm lead acetate and then, from 30-60 days of age, received either saline vehicle, L-dopa, testosterone (males only), dihydrotestosterone (DHT, males only), or estradiol (females only). Lead exposure significantly reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period. Sex steroid replacement did not restore skeletal parameters in lead-exposed rats. L-Dopa increased plasma insulin-like growth factor 1 (IGF(1)) concentrations, rates of bone growth, and bone strength measures in controls while having no effect in lead-exposed pups. The third study was conducted at 100 days of age, when endocrine parameters have been shown to be normalized, to test for effects of lead exposure on bone formation during tibial limb lengthening (distraction osteogenesis, DO). Both DO gap x-ray density and proximal new endosteal bone formation were decreased in the distraction gaps of the lead-treated animals (p < 0.01). In conclusion, lead exposure reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period, and these effects could not be reversed by a growth hormone (GH) axis stimulator or by sex-appropriate hormones. Finally, lead exposure appears to specifically inhibit osteoblastogenesis in vivo in adult animals.

Animals↗
PubMed2001

Prevalence of infectious diseases among internationally adopted children.

OBJECTIVE: Internationally adopted children are at increased risk of infections acquired in their country of origin. Ongoing surveillance of this unique population is needed to detect changing epidemiology and provide appropriate care. METHODS: We performed a retrospective cohort study of 504 children adopted from abroad and evaluated from 1997 to 1998 to determine the prevalence of and factors associated with various infectious diseases. RESULTS: The mean age of the study participants at medical evaluation was 1.6 years; 71% were girls, and they were adopted from 16 countries, including China (48%), Russia (31%), Southeast Asia (8%), Eastern Europe (8%), and Latin America (5%). Overall, 75 (19%) of 404 children tested had tuberculin skin tests >/=10 mm, but all had normal chest radiographs. BCG vaccination (odds ratio [OR]: 7.37; 95% confidence interval [CI]: 3.29, 17.16) and being Russian born (OR: 2.90; 95% CI: 1.68, 5.00) were risk factors for latent tuberculosis infection. Fourteen (2.8%) children had detectable hepatitis B surface antigen, but no child had active hepatitis C, human immunodeficiency virus, or syphilis. Giardia lamblia antigen was detected in 87 (19%) of 461 tested children, and such children were older (mean: 22 months vs 15.5 months) and more likely to have been born in Eastern Europe (OR: 2.82; 95% CI: 1.70, 4.68). CONCLUSIONS: We demonstrated increased rates of latent tuberculosis infection and G lamblia infection than previously reported. Thus, ongoing surveillance of internationally adopted children, international trends in infectious diseases, and appropriate screening will ensure the long-term health of adopted children as well as their families.

Adoption↗
PubMed2000

A medical alphabet

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Journal Article↗
PubMed2000

An/atomy

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Journal Article↗
PubMed2000

Chickenpox

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Journal Article↗
PubMed2000

Say cee

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Journal Article↗
PubMed2000

Monthly injections

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Journal Article↗
PubMed2000

Overate?

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Journal Article↗
PubMed2000

Induction of oxidative stress and TNF-alpha secretion by dichloroacetonitrile, a water disinfectant by-product, as possible mediators of apoptosis or necrosis in a murine macrophage cell line (RAW).

The water disinfectant by-product dichloroacetonitrile (DCAN) is a direct-acting mutagen and induces DNA strand breaks in cultured human lymphoblastic cells. Cellular activation by environmental agents may exert detrimental effects to the cells. Activated macrophages produce reactive oxygen intermediates such as H(2)O(2), (-)OH and O(2). Therefore, the effect of various concentrations of DCAN (100-400 microM) on the activity macrophage cells (RAW 264.7) was studied. In these cells, DCAN-induced oxidative stress was characterized by the production of reactive oxygen intermediates (ROI). Also, the ratios of intracellular GSH/GSSG was assessed and used as a biomarker for oxidative stress. The secretion of TNF-alpha was assessed since macrophages are known to secrete TNF-alpha as a result of cellular oxidative stress. Electrophoretic detection of DNA degradation and light microscopy was utilized for the characterization of DCAN-induced apoptosis. Lactate dehydrogenase (LDH) leakage and trypan blue exclusion were used as markers of cellular necrosis. Following exposure to DCAN (200 microM and 400 microM), intracellular GSSG was increased (2.5-fold of control, P<0. 05). DCAN activation of RAW cells was detected by elevated levels of intracellular ROI (1.9-2.5-fold than control, P<0.05) and increased secretion of TNF-alpha (4.5 fold-than control, P <0.05). Elecrophoresis of genomic DNA of treated cells indicated a dose-dependent increase in degradation of genomic DNA. Morphological studies also indicated that exposure of RAW cells to 100 microM or 200 microM DCAN incites apoptotic cell death. At higher concentrations (400 microM), however, significant (P<0.05) increase in LDH leakage and decrease in cell viability (55% of control) indicative of cellular necrosis, were observed. These studies indicate that DCAN induces dose-dependent apoptosis or necrosis in RAW cells that could be due to the disturbance in intracellular redox status and initiation of ROI-mediated oxidative mechanisms of cellular damage.

Acetonitriles↗
PubMed2000

Home care users' experiences of fiscal constraints. Challenges and opportunities for case management.

With mounting fiscal constraints in home care, case managers find themselves increasingly confined in rationing roles and pressed into a narrow focus on the individual case. These pressures frustrate case management's potential to inform and contribute to more broadly-based improvements in service systems, policy formulation, and resource development. A study of home care users' perspectives in a jurisdiction where fiscal pressures have been rapidly increased reveals how rationing and service reduction affect service recipients and shape their relationships with case managers. The study sheds light on the challenges and opportunities for case managers of practicing in such straitened circumstances. Combined with their own detailed understanding of front-line service delivery, case managers can build on the knowledge of service users' perspectives to make critical contributions to both the well-being of the generally jeopardized populations who need home care and to the broadening of case management practice in keeping with its commitments to advocacy and systems level change.

Adult↗