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Biomedical subjects

R S Weinstein

Publications and source records attributed to R S Weinstein.

At least 37 records · Page 2Linked to original sources

Differential parental treatment predicts achievement and self-perceptions in two cultural contexts.

This study examined 148 Asian American and European American late adolescents' perceptions of differential affection and control by mothers and fathers as predictors of academic achievement and self-perceptions of intellectual ability and global self-worth. Overall, analyses generally confirmed the hypotheses that the more differentially favorable the treatment (more affection or less control) or the less differential treatment (above and beyond which sibling was favored) reported in the home, the more positive late adolescents' outcomes. Perceptions of differential parental treatment predicted up to 13% of the variance in achievement and self-perceptions. Several findings were moderated by ethnicity or gender. Finally, and perhaps most importantly, perceptions of differential parental treatment predicted a significant and unique amount of variance in outcomes beyond that predicted by perceptions of absolute levels of affection and control.

Achievement↗

Evaluation of a digital camera for acquiring radiographic images for telemedicine applications.

Many rural sites cannot afford a digitizer to digitize radiographic films and transmit them via a telemedicine network for review by a radiology specialist. This project tested the feasibility of using a consumer digital still camera to photograph radiographic images and transmit them via a telemedicine network to a consulting hub site. In this study, the feasibility of using a digital camera to photograph plain film radiographs of 40 bone trauma cases from a rural health center in Arizona was tested. The cases were transmitted to the Arizona Telemedicine Program hub site using a private asynchronous transfer mode network based on T1 carriers. Two orthopedic surgeons and two radiologists reviewed the cases on a color monitor and the original film images. The readers also rated image quality. There were no significant differences in diagnostic accuracy between conventional film and telemedicine reading. Diagnostic agreement between film and monitor viewing was quite high, as was agreement in confidence ratings. Image quality was generally rated as excellent to good in both viewing conditions. Cases that did not correlate well were judged to have poor image quality, or diagnoses were based on photographs that had part of the diagnostic region of interest cropped off. It was determined that a digital still camera can be used effectively in many cases to photograph radiographic images for transmission and viewing via a telemedicine network, as long as adequate views, zoomed in regions of interest, and good quality original films are used in the acquisition process.

Arizona↗

Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip.

An increase in osteoblast and osteocyte apoptosis has been demonstrated in mice and humans receiving glucocorticoids and may be involved in the pathogenesis of the associated osteonecrosis. To examine the spatial relationship between osteocyte apoptosis and glucocorticoid-induced osteonecrosis, we determined the prevalence of osteocyte apoptosis in whole femoral heads obtained from patients who underwent prosthetic hip replacement because of osteonecrosis due to chronic glucocorticoid treatment (n = 5), alcoholism (n = 3), and trauma (n = 1) as well as in femoral neck cores from patients with sickle cell disease (n = 5). Abundant apoptotic osteocytes and cells lining cancellous bone were found juxtaposed to the subchondral fracture crescent in femurs from the patients with glucocorticoid excess. In contrast, apoptotic bone cells were absent from the specimens taken from patients with trauma or sickle cell disease and were rare with alcohol abuse. These results indicate that glucocorticoid-induced osteonecrosis is a misnomer. The bone is not necrotic; instead, it shows prominent apoptosis of cancellous lining cells and osteocytes. Glucocorticoid-induced osteocyte apoptosis, a cumulative and irreparable defect, could uniquely disrupt the mechanosensory function of the osteocyte network and thus start the inexorable sequence of events leading to collapse of the femoral head.

Adult↗

True strength.

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Animals↗

Chromosomal mapping of osteopenia-associated quantitative trait loci using closely related mouse strains.

Peak bone mineral density (BMD) is a highly heritable trait in humans and is currently the best predictor of skeletal fragility underlying osteoporosis. The SAMP6 mouse strain displays unusually low BMD at maturity, and age-dependent osteopenia associated with defective osteoblastogenesis. To identify quantitative trait loci (QTLs) influencing bone density, we constructed crosses between SAMP6 and either AKR/J or SAMP6, two related mouse strains of higher peak BMD. Due to common ancestry of these strains, intercross parents differed at only 39-40% of 227 highly-polymorphic genotyping markers, thus restricting our search to this informative portion of the genome and reducing the number of mice required for QTL significance. Using dual energy X-ray absorptiometry (DEXA), we measured spinal BMD in F2 cross progeny at 4 months of age, and selectively genotyped those in the highest and lowest quartiles for BMD. Based on linear regression of bone density on genotype, including Composite Interval Mapping to enhance mapping precision while adjusting for effects of distal markers, we identified multiple QTLs significantly affecting spinal BMD; these were mapped to regions of chromosomes 2 (two sites, one confirmed in both crosses), 7, 11, 13 and 16. One of these loci had been previously identified as a significant bone-density QTL, while 3 substantiate QTLs suggested by a low-power study of 24 recombinant-inbred mouse lines. Such recurrent appearance of QTLs, especially in crosses involving distantly-related strains, implies that polymorphism at these loci may be favored by evolution and might underlie variation in peak bone density among humans.

Absorptiometry, Photon↗

Routine surgical telepathology in the Department of Veterans Affairs: experience-related improvements in pathologist performance in 2200 cases.

OBJECTIVE: To determine whether diagnostic concordance, case deferral rate, and/or time required to review slides changed significantly as telepathologists gained additional experience using a hybrid dynamic/store-and-forward (HDSF) telepathology (TP) system on the 2000 cases following an initial 200 consecutive surgical cases, previously reported. MATERIALS AND METHODS: Gross surgical pathology specimens were prepared by specially trained personnel in Iron Mountain, Michigan. For TP, glass slides were placed on the stage of a robotic microscope at the Iron Mountain VAMC (remote site); control of the motorized microscope was then transferred to a pathologist located 220 miles away at the Milwaukee, Wisconsin, VAMC (host site). For each case, a telepathologist had the option of either rendering a diagnosis or deferring the case for later analysis by conventional light microscopy (LM). After the slides were read by TP and a surgical pathology report had been generated (for nondeferred cases), the slides were transported to Milwaukee, where they were reexamined by the same pathologist, now using LM. When there was disagreement between the TP and LM diagnosis, a supplemental or revised report was issued, and the referring physician was notified by telephone immediately. All supplemental and revised reports were reviewed by a third pathologist in the group. The slides were then reviewed by the pathology group practice or, when there was no consensus, by the Armed Forces Institute of Pathology to establish a "truth" diagnosis. To determine changes in telepathologist performance with experience after the initial start-up of the service, their performance in handling 10 consecutive sets of 200 surgical pathology cases was analyzed. RESULTS: Concordance rates for clinically significant TP and LM diagnoses were high for all 10 sets, ranging from 99% to 100%. Comparing the first set (Cases 201-400) with the last set (Cases 2001-2200), viewing times per case were reduced from 10.26 min to 3. 58 min. Viewing times per slide were reduced from 3.44 min to 1.13 min per slide, comparing the first and last sets. Case turnaround times (TAT) decreased from 2.46 days to < or =1.5 days. CONCLUSION: Thes results demonstrate that improvements in TP services occur over time as the result of additional experience using the TP system. The high diagnostic concordance and low rate of case deferral lend additional support to the proposal that a host-site pathologist using HDSF TP can substitute effectively for an on-site pathologist as a service provider.

Clinical Competence↗

Diagnostic accuracy and image quality using a digital camera for teledermatology.

OBJECTIVE: The study was designed to evaluate the effectiveness of digital photography for dermatologic diagnoses and compare it with in-person diagnoses. MATERIALS AND METHODS: Patients referred for specialty consultations (n = 308) were recruited from a university dermatology clinic. Patients were examined in-person by one of three board-certified dermatologists who provided clinical diagnoses. Digital photos were obtained on all patients and were evaluated as computer images by a panel of dermatologists. RESULTS: There was 83% concordance between in-person versus digital photo diagnoses. Intradermatologist concordance averaged 84%, and interdermatologist concordance averaged 81%. Decision confidence was rated as "very definite" to "definite" 62% of the time. Concordance with biopsy results was achieved in 76% of the cases. Image sharpness and color quality were rated "good" to "excellent" 83% and 93% of the time, respectively. CONCLUSION: Digital photography for store-and-forward teledermatology produces high-quality images and diagnostic concordance rates that compare favorably with in-person clinical diagnoses.

Arizona↗

Efficiency analysis of a multi-specialty telemedicine service.

OBJECTIVE: The goal of this project was to assess case turn-around times for store-and-forward and real-time video consultations in the Arizona Telemedicine Program. MATERIALS AND METHODS: Five components contributing to total case turn-around time were analyzed. Each parameter was submitted to statistical analysis and compared for store-and-forward and real-time sessions. RESULTS: Turn-around for real-time are longer than for store-and-forward sessions. Real-time sessions take longer, from when the consulting clinician is contacted to the time the case is reviewed. This is compounded by the fact that real-time sessions sometimes need to be rescheduled. For both types of consults, the time to deliver the final report is the longest segment of the total turn-around time. CONCLUSION: Several factors contribute to case turn-around times. By identifying and analyzing each contributing factor, it is possible to revise consult protocols to improve efficiency.

Arizona↗

Cost minimization analysis of telepathology.

Telepathology is gaining acceptance as a mode of providing pathology services to remote sites, but its economic feasibility is unknown. A dynamic robotic telepathology service between the Veterans Affairs Medical Center, Iron Mountain, MI, and the Veterans Affairs Medical Center, Milwaukee, WI, provides diagnostic services for routine and frozen section surgical pathology cases at Iron Mountain. We conducted a cost minimization analysis of this service by building a model to compare telepathology and on-site pathology in Iron Mountain and a courier method of transporting specimens from Iron Mountain to Milwaukee for diagnosis. Base case analysis showed the courier method to be the most economic; telepathology was less costly than on-site pathology. If the costs of telepathology equipment and telecommunication are lowered to reflect current cost, then telepathology becomes the favored option. Telepathology can be an economic mode of providing pathology services to a remote site.

Costs and Cost Analysis↗

Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone.

The mass of regenerating tissues, such as bone, is critically dependent on the number of executive cells, which in turn is determined by the rate of replication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. Bone mass can be increased by intermittent parathyroid hormone (PTH) administration, but the mechanism of this phenomenon has remained unknown. We report that daily PTH injections in mice with either normal bone mass or osteopenia due to defective osteoblastogenesis increased bone formation without affecting the generation of new osteoblasts. Instead, PTH increased the life-span of mature osteoblasts by preventing their apoptosis - the fate of the majority of these cells under normal conditions. The antiapoptotic effect of PTH was sufficient to account for the increase in bone mass, and was confirmed in vitro using rodent and human osteoblasts and osteocytes. This evidence provides proof of the basic principle that the work performed by a cell population can be increased by suppression of apoptosis. Moreover, it suggests novel pharmacotherapeutic strategies for osteoporosis and, perhaps, other pathologic conditions in which tissue mass diminution has compromised functional integrity.

Animals↗

Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin.

Glucocorticoid-induced osteoporosis may be due, in part, to increased apoptosis of osteocytes and osteoblasts, and bisphosphonates (BPs) are effective in the management of this condition. We have tested the hypothesis that BPs suppress apoptosis in these cell types. Etidronate, alendronate, pamidronate, olpadronate, or amino-olpadronate (IG9402, a bisphosphonate that lacks antiresorptive activity) at 10(-9) to 10(-6) M prevented apoptosis of murine osteocytic MLO-Y4 cells, whether it was induced by etoposide, TNF-alpha, or the synthetic glucocorticoid dexamethasone. BPs also inhibited apoptosis of primary murine osteoblastic cells isolated from calvaria. Similar antiapoptotic effects on MLO-Y4 and osteoblastic cells were seen with nanomolar concentrations of the peptide hormone calcitonin. The antiapoptotic effect of BPs and calcitonin was associated with a rapid increase in the phosphorylated fraction of extracellular signal regulated kinases (ERKs) and was blocked by specific inhibitors of ERK activation. Consistent with these in vitro results, alendronate abolished the increased prevalence of apoptosis in vertebral cancellous bone osteocytes and osteoblasts that follows prednisolone administration to mice. These results suggest that the therapeutic efficacy of BPs or calcitonin in diseases such as glucocorticoid-induced osteoporosis may be due, in part, to their ability to prevent osteocyte and osteoblast apoptosis.

Alendronate↗

Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia.

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization of cartilage and bone matrix. We investigated two independently generated TNSALP gene knock-out mouse strains as potential models for hypophosphatasia. Homozygous mice (-/-) had < 1% of wild-type plasma TNSALP activity; heterozygotes had the predicted mean of approximately 50%. Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate are putative natural substrates for TNSALP and all were increased endogenously in the knock-out mice. Skeletal disease first appeared radiographically at approximately 10 days of age and featured worsening rachitic changes, osteopenia, and fracture. Histologic studies revealed developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones. Progressive osteoidosis from defective skeletal matrix mineralization was noted but not associated with features of secondary hyperparathyroidism. Plasma and urine calcium and phosphate levels were unremarkable. Our findings demonstrate that TNSALP knock-out mice are a good model for the infantile form of hypophosphatasia and provide compelling evidence for an important role for TNSALP in postnatal development and mineralization of the murine skeleton.

Age Factors↗

Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.

Glucocorticoid-induced bone disease is characterized by decreased bone formation and in situ death of isolated segments of bone (osteonecrosis) suggesting that glucocorticoid excess, the third most common cause of osteoporosis, may affect the birth or death rate of bone cells, thus reducing their numbers. To test this hypothesis, we administered prednisolone to 7-mo-old mice for 27 d and found decreased bone density, serum osteocalcin, and cancellous bone area along with trabecular narrowing. These changes were accompanied by diminished bone formation and turnover, as determined by histomorphometric analysis of tetracycline-labeled vertebrae, and impaired osteoblastogenesis and osteoclastogenesis, as determined by ex vivo bone marrow cell cultures. In addition, the mice exhibited a threefold increase in osteoblast apoptosis in vertebrae and showed apoptosis in 28% of the osteocytes in metaphyseal cortical bone. As in mice, an increase in osteoblast and osteocyte apoptosis was documented in patients with glucocorticoid-induced osteoporosis. Decreased production of osteoclasts explains the reduction in bone turnover, whereas decreased production and apoptosis of osteoblasts would account for the decline in bone formation and trabecular width. Furthermore, accumulation of apoptotic osteocytes may contribute to osteonecrosis. These findings provide evidence that glucocorticoid-induced bone disease arises from changes in the numbers of bone cells.

Adult↗

Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group.

BACKGROUND: Preventing bone loss associated with menopause and aging and maintaining the normal micro-architecture of bone provide important opportunities for the prevention of osteoporosis and fractures. OBJECTIVE: To determine the safety and efficacy of alendronate, an aminobisphosphonate, for preventing postmenopausal bone loss. DESIGN: 3-year double-blind, randomized, placebo-controlled trial. SETTING: 15 osteoporosis centers throughout the world. PARTICIPANTS: 447 women who had recently experienced menopause (6 to 36 months before study entry). INTERVENTION: Participants were randomly assigned to one of five regimens: oral placebo; oral alendronate, 1, 5, or 10 mg/d; or oral alendronate, 20 mg/d for 2 years followed by placebo during the third year (20/0 mg/d). MEASUREMENTS: Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover and bone quality were assessed with biochemical markers and bone histomorphometry. RESULTS: Alendronate at 5, 10, and 20/0 mg/d increased bone mineral density from baseline at the lumbar spine, femoral neck, and trochanter by 1% to 4% and in the total body by 0.3% to 1.0%; placebo led to losses of 2% to 4% at these sites. Alendronate, 1 mg/d, attenuated losses relative to those seen with placebo. Alendronate decreased markers of bone resorption to a new steady state by 3 months and decreased markers of bone formation by 6 to 12 months. Bone quality remained normal. At all dosages studied, alendronate had a safety and tolerability profile similar to that of placebo. CONCLUSIONS: In early postmenopausal women, alendronate given for 3 years at dosages of 5 mg/d or greater prevented the loss of bone mineral density at the spine and hip and in the total body. Alendronate seems to be a safe and effective nonhormonal option for prevention of postmenopausal bone loss.

Adult↗

Telemicrobiology: feasibility study.

BACKGROUND: Rural hospitals generally lack staffing with infectious disease specialists or pathologists. Without on-site pathologists, the range of microbiology services offered by clinical laboratories may be limited as well. OBJECTIVE: To study the feasibility of using static-image telepathology to evaluate Gram stains of microbiologic preparations. MATERIALS AND METHODS: In this retrospective feasibility study, three pathologists evaluated Gram stains of slides from 50 cases by two viewing modalities: static-image telepathology and conventional light microscopy. Digital video images of slides were captured at two magnifications (using 40x and 100x objective lenses) at 1024 x 768 x 24-bit color and transmitted over standard telephone lines at 14,400 kbps. Pathology reports and culture results served as "truth diagnoses." Categories of interpretations were correct, minor discrepancy, or major discrepancy with regard to the implications for patient care. RESULTS: The diagnostic accuracy of video image readings and conventional light microscopy readings were nearly identical, with no statistically significant differences in the performances of specialty and nonspecialty pathologists (P > 0.05). The mean accuracies of readings of the video images and light microscopy images were 95.3% and 95.4%, respectively. Taking into account the time required by a referring pathologist to capture video digital images, telemicrobiology was somewhat less efficient than conventional light microscopy. CONCLUSIONS: Pathologists can accurately evaluate digital video images of preselected fields on Gram-stained slides. In clinical practice, however, a limiting factor may be the availability of local personnel qualified to select the microscopic fields for evaluation by telepathologists. The adequacy of the video images suggests that telepathology may also be used for remote supervision of quality assurance programs in microbiology laboratories, as well as for remote proficiency training of laboratory personnel.

Arizona↗