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Biomedical subjects

S Zimmerman

Publications and source records attributed to S Zimmerman.

At least 19 recordsLinked to original sources
PubMed2007

The U.S. Thrombosis and Hemostasis Centers pilot sites program.

Venous thromboembolism (VTE) is a common disorder associated with significant morbidity and mortality. Despite important advances in understanding the etiology of VTE, delivery of care to patients with thrombosis and thrombophilia is frequently incomplete and highly variable. A comprehensive model of health care has been used successfully to treat and prevent complications for people with hemophilia and other chronic disorders. The effectiveness of an integrated healthcare model for patients with all coagulation disorders has yet to be evaluated. The Division of Hereditary Blood Disorders of the Centers for Disease Control and Prevention (CDC) is collaborating with eight Thrombosis and Hemostasis Centers (pilot sites) to provide health-related services and conduct research directed toward the reduction or prevention of complications of thrombosis and thrombophilia. The initial objectives of the collaboration are to (1) determine the efficacy of integrated multidisciplinary care and prevention services for people with hemostatic disorders, (2) assess unmet needs for service delivery and identify outreach strategies to improve access to care, (3) develop effective messages aimed at disease management and prevention, and (4) foster the development of training programs to enhance provider skills for the delivery of patient care. To address these objectives, the investigators and CDC have developed and implemented a web-based patient registry to follow prospectively service allocation and patient outcomes. Funding for the program began in October 2001. All eight funded centers are affiliated with U.S. medical schools. Principal investigators at the centers are hematologists (five adult, two pediatric) or cardiologists. Faculty in obstetrics-gynecology, surgery, and multiple other specialties are integral to the model of care at the centers. Other critical components at the centers are clinical laboratory services, training programs, research networks, and education and outreach programs. From August 2003 to March 2006, over 2,600 patients were enrolled in the registry, accounting for a total of more than 5,000 visits to the centers. Immediate goals of the data collection at the centers are to characterize patients receiving care at centers and document the state of health services provided. Long-term goals are to evaluate prospectively clinical outcomes for patients receiving multidisciplinary care and prevention services at centers. The network of data collection across centers will facilitate future collaborative clinical and epidemiologic investigations and enhance collective expertise in hemostasis and coagulation disorders.

Academic Medical Centers↗
PubMed2006

Women with hip fracture have a greater rate of decline in bone mineral density than expected: another significant consequence of a common geriatric problem.

INTRODUCTION: Hip fracture is a major public health problem, annually affecting over 350,000 persons in the United States and 1.6 million worldwide. Consequences include decreased survival, loss of independence, and increased risk of subsequent fractures. A substantial decline in bone mineral density (BMD) also occurs, yet the magnitude of the decline specifically attributable to hip fracture has not been documented. METHODS: To determine the amount of BMD decline attributable to hip fracture, the rate of decline in BMD in a cohort of hip fracture patients was compared with that in a cohort of women of similar age and BMD but without hip fracture. All subjects were community dwelling when enrolled. Hip fracture patients in the Baltimore Hip Studies (BHS) came from two hospitals in Baltimore, Maryland, from 1992 through 1995; comparison subjects came from the Study of Osteoporotic Fracture (SOF) enrolled in four areas of the United States during the same period. Eighty-four white, female hip fracture patients 65 years and older from the BHS were compared with 168 SOF participants matched on age, race, and BMD at baseline. BMD of the femoral neck and total hip was measured by dual-energy x-ray absorptiometry. RESULTS: Hip fracture patients had a greater decline in BMD during the 12-month postfracture follow-up than that expected on the basis of the nonfracture cohort: 4.9% vs. 0.4% at the femoral neck and 3.5% vs. 0.7% for the total hip. The decline in BMD in hip fracture patients was 11.8 times the amount expected at the femoral neck (matched on age and baseline BMD and adjusted for between-cohort differences in smoking prevalence) and 4.9 times that expected for the total hip at the end of 1 year after the hip fracture. CONCLUSION: In this sample of older women, bone loss over the year following hip fracture far exceeded that expected and is an important clinical management concern.

Activities of Daily Living↗
PubMed2006

Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS).

BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response.

Acute Disease↗
PubMed2004

A clinically meaningful difference was generated for a performance measure of recovery from hip fracture.

BACKGROUND AND OBJECTIVE: The Lower Extremity Gain Scale (LEGS) is a performance measure of tasks that are often impaired in hip fracture patients. This study was designed to determine a clinically meaningful difference in LEGS. METHODS: The population was 139 female patients (age >65 years) admitted to Baltimore hospitals. Recovery levels were estimated by fitting trajectory curves for the cohort for the 12 months post fracture. The clinically meaningful difference was evaluated using an anchor-based approach, examining the relationship between the LEGS recovery level and age. A second, distribution-based method used an effect size of .20. RESULTS: According to our model, a difference of 5 years in age corresponded to a difference of 1.6-3.6 points in LEGS scores. The standard deviation for LEGS at 12 months was 8.0; thus, Cohen's effect size of 0.2 would equate to a difference of 1.6 points. CONCLUSION: This suggests that a clinically meaningful difference in the LEGS scores for a population in this age range would be 2-3 points.

Activities of Daily Living↗
PubMed2003

Kinetics of cell death in T lymphocytes genetically modified with two novel suicide fusion genes.

Donor lymphocyte infusions (DLI) following allogeneic stem cell transplantation are known to mediate graft-versus-leukemia effect (GVL). A major side effect of these immunotherapies is the development of graft-versus-host diseases (GVHD). One promising approach to prevent GVHD is to genetically modify donor T cells with a suicide mechanism that can be induced in the case of GVHD. Here we report on a retroviral vector containing the death effector domain (DED) of the human Fas-associated protein with death domain (FADD). The DED was fused to two copies of an FKBP506-binding protein and a truncated version of the human low-affinity receptor for nerve growth factor (LNGFR). Activation of the death signal pathway can be triggered upon the addition of chemical inducers of dimerization. This construct was functionally compared to an optimized HSV-TK vector in which a hypersensitive mutant of the herpes simplex virus thymidine kinase gene (TK39) was fused to a cytoplasmic truncated version of the cell surface antigen CD34. A direct comparison between both vectors in primary T lymphocytes showed that the number of T cells transduced with vectors containing the DED was significantly reduced within 24 h of drug administration whereas ganciclovir treatment of TK39-transduced T cells showed a delay in cell death of approximately 3-4 days. Our results indicate that constructs containing the DED may prove to be the most efficient mechanism to quickly eliminate alloreactive T cells.

Antiviral Agents↗
PubMed2002

A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis.

BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors (non-steroidal anti-inflammatory drugs) inhibit large bowel carcinogenesis in patients with familial adenomatous polyposis (FAP). Their role in the duodenum of these patients is less certain. The disease modifying activity of specific COX-2 inhibitors has not been explored in humans. PATIENTS AND METHODS: This was a randomised, double blind, placebo controlled study of celecoxib (100 mg twice daily (n=34) or 400 mg twice daily (n=32)) versus placebo (n=17), given orally twice daily for six months to patients with FAP. Efficacy was assessed qualitatively by blinded review of shuffled endoscopy videotapes comparing the extent of duodenal polyposis at entry and at six months and quantitatively by measurement of the percentage change in duodenal area covered by discrete and plaque-like adenomas from photographs of high and low density polyposis. RESULTS: Shuffled and blinded video review showed a statistically significant effect of 400 mg twice daily celecoxib compared with placebo treatment (p=0.033) with all five independent observers scoring a beneficial effect. Overall, patients taking celecoxib 400 mg twice daily showed a 14.5% reduction in involved areas compared with a 1.4% for placebo (p=0.436). However, patients with clinically significant disease at baseline (greater than 5% covered by polyps) showed a 31% reduction in involved areas with celecoxib 400 mg twice daily compared with 8% on placebo (p=0.049). CONCLUSIONS: A panel of five endoscopists found a significant reduction in duodenal polyposis after six months of treatment with celecoxib 400 mg twice daily. COX-2 inhibition may help this otherwise untreatable condition.

Adenomatous Polyposis Coli↗
PubMed2001

The effects of hydrostatic pressure-induced changes on the cytoskeleton and on the regulation of gene expression in pheochromocytoma (PC-12) cells.

The purpose of this investigation was to determine the relationship of hydrostatic pressure-induced changes in the cytoarchitecture to regulation of gene expression in PC-12 cells. Hydrostatic pressure disrupts the cytoskeleton, decreases tubulin and actin mRNA levels and causes changes in the localization of tubulin and actin mRNA. Actin mRNA levels, at 6000 and 10,000 psi for 20 min, were reduced to 78% and 64%, respectively, in undifferentiated cells and to 81% and 72%, respectively, in 4-day differentiating cells, relative to untreated controls. Tubulin mRNA levels, at 6000 and 10,000 psi for 20 min, were reduced to 75% and 67%, respectively, in undifferentiated cells and to 84% and 74%, respectively, in 4-day differentiating cells. Changes in the localization of mRNA in the soluble and cytoskeletal fractions were determined by measuring the pressure level where the mRNA level in the cytoskeletal fraction equals the mRNA level in the soluble fraction. This measurement was designated the cytoskeletal/soluble fraction index (CSFI(50)). CSFI(50)measurements indicated that following hydrostatic pressure, actin mRNA cytoskeletal association was more stable than tubulin mRNA cytoskeletal association. The addition of chemicals which stabilize or destabilize microtubules and microfilaments to pressure treatment resulted in additional changes in the CSFI(50).

Actin Cytoskeleton↗
PubMed2001

Hydrostatic pressure induced changes in the cytoarchitecture of pheochromocytoma (PC-12) cells.

Confocal microscopy, in association with three-dimensional reconstruction, revealed that microtubules and microfilaments in differentiating PC-12 cells were disrupted in a dose-dependent manner following pressure treatment. Hydrostatic pressure caused cell rounding, microtubule and microfilament disorganization, neurite retraction and the formation of a microtubule ring adjacent to the cell surface. Volume analysis from computer-generated reconstructed cells, at atmospheric pressure, showed that the apparent volume of microtubules and microfilaments, normalized to 100 units, was 22 and 11 respectively. At 4000 and 8000 psi, the apparent microtubule volume was reduced to 16 and 12 units, respectively, and the apparent microfilament volume was reduced to 8 and 5 units, respectively. Thus, the apparent microtubule and microfilament volumes in PC-12 cells decreased as pressure increased. In the presence of taxol and phalloidin which stabilize the cytoarchitecture, cells resist the effects of hydrostatic pressure. In the presence of colchicine and cytochalasin D compounds which destabilize the cytoarchitecture, cells are more susceptible to the disrupting effects of hydrostatic pressure. The effects of hydrostatic pressure on cell morphology were reversible.

Actin Cytoskeleton↗
PubMed2001

Medical care for nursing home residents: differences by dementia status. Epidemiology of Dementia in Nursing Homes Research Group.

OBJECTIVE: To understand the use of medical services by nursing home residents. DESIGN: Descriptive, longitudinal study comparing medical service use of residents by dementia status and describing the use of medical services following detection of fever or infection. SETTING: Fifty-nine randomly selected nursing homes in Maryland from 1992 to 1995. PARTICIPANTS: 2,153 residents admitted to one of 59 randomly selected nursing homes. MEASUREMENT: A panel of psychiatrists and neurologists ascertained dementia based on review of medical records, interview data with significant others and nursing staff, and results of a cognitive exam. Medical service use was abstracted from medical records. BACKGROUND: Understanding the use of medical services by nursing home residents as distinct from services provided by the nursing home is important, particularly as new medical care models are tested. This study compares the medical service use of residents by dementia status and describes the use of medical services following detection of fever or infection. RESULTS: Residents with dementia compared with those without dementia had lower annual rates of physician visits (10.2 vs 12.7, P < .001) and hospitalizations (0.9 vs 1.2, P < .001), virtually the same rate of emergency department visits, and similar lengths of stay in the hospital. Subsequent to infection, a lower proportion of residents with dementia had either a physician visit, an emergency department visit, or a hospital admission compared with residents without dementia (27.2% vs 32.2%, P < .001). In 87% of infections, an antibiotic was used, implying meaningful contact with a physician. Residents with dementia compared with those without dementia had fewer physician visits subsequent to fevers (20.6% vs 29.9%, P < .001) and infections (21.8% vs 27.5%, P < .001). CONCLUSIONS: The association of less medical service use by individuals with dementia compared with those without dementia may reflect differences in health status or implicit end-of-life decision-making and a proclivity toward less-aggressive treatment for these individuals.

Aged↗
PubMed2001

Hyperleptinemia in pregnant bats is characterized by increased placental leptin secretion in vitro.

Hyperleptinemia is a common feature of pregnancy in mammals. The source of increased plasma leptin is uncertain. We examined leptin secretory rates in vitro to test the hypothesis that leptin secretion is upregulated during pregnancy. Two species of insectivorous bats were examined, Myotis lucifugus and Eptesicus fuscus, because of their unique reproductive cycle. Body mass and plasma leptin significantly increased with gestation and decreased during lactation. Adiposity increased in midgestation, then decreased in late gestation and lactation and was not significantly correlated with plasma leptin in pregnant or early lactating individuals. Leptin secretion in vitro per gram of adipose tissue tended to increase with gestation but was not significantly correlated with plasma leptin in the same individuals. Leptin secretion from placentae, however, increased with gestation and was significantly correlated with plasma leptin from the same individuals. In suckling pups, plasma leptin was high shortly after birth, then decreased to low levels that were not correlated with adiposity thereafter. We conclude that in bats, the placenta is a major source of circulating leptin during pregnancy, and that adiposity and plasma leptin levels are decoupled during three different periods of intense metabolic demand (pregnancy, early lactation, and neonatal growth).

Adipose Tissue↗
PubMed2000

The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.

Adenomatous Polyposis Coli↗
PubMed2000

Steroid-dependent up-regulation of adipose leptin secretion in vitro during pregnancy in mice.

Circulating leptin levels are elevated during the later stages of pregnancy in mammals, suggesting that maternal leptin may play a role in maintenance of pregnancy and/or preparation for parturition and lactation. The regulation and source of circulating leptin during pregnancy remains undetermined, but leptin mRNA levels increase in adipose tissue during this time in some species. Considerable controversy exists whether placenta is also a leptin-secreting tissue during pregnancy. Here, we directly demonstrate that leptin secretion rates from mouse adipose tissue in vitro are decreased during early pregnancy and up-regulated during late pregnancy and lactation. Changes in leptin secretion rates in vitro paralleled those of circulating leptin in vivo during gestation. Subcutaneous implants of estradiol or corticosterone into lactating mice for 48 h stimulated adipose leptin secretion rates in vitro to the level of that in pregnant mice. However, corticosterone, but not estradiol, increased leptin secretion when added to isolated adipose tissue in vitro. Placentae obtained at two stages of pregnancy did not secrete leptin in vitro, either when acutely isolated or when dissociated into cells for long-term cultures. Placental tissue (or cells) secreted progesterone, however, demonstrating placental viability. We conclude that hyperleptinemia during late pregnancy in mice primarily results from corticosterone-dependent up-regulation of leptin secretion from adipose tissue, and that the placenta does not contribute to leptin secretion. The initial decrease in leptin secretory rates from adipose tissue during early pregnancy may facilitate energy storage for the subsequent, increased metabolic demands of later pregnancy and lactation.

Adipose Tissue↗
PubMed2000

To decentralize or not to decentralize, is that the question? Nicaraguan health policy under structural adjustment in the 1990s.

Since 1990, health services decentralization in Nicaragua has been accompanied by structural adjustment, resulting in reduced equity and accountability. Sandinista efforts in the 1980s to extend access to primary care and reduce class and regional disparities in the delivery of health services were accompanied by modest attempts to increase local-level accountability and responsiveness. The escalation of war in the late 1980s transformed this effort into greater de facto decentralization. Over the past decade, Nicaragua has used decentralization policy to restructure the health system through health spending cuts and the favoring of curative over preventive services; privatization and the promotion of user fees; and confusion of lines of accountability. The authors analyze the 1990s' health policies in Nicaragua, paying particular attention to the blending of decentralization policy with the fiscal and administrative reforms advanced by the International Monetary Fund, World Bank, and other international agencies. They conclude that analyzing decentralization as a sector-specific reform that can be ameliorated through technocratic modifications is insufficient. A full understanding of the problems and possibilities of decentralization requires an analysis of the political and economic context that conditions these policies.

Delivery of Health Care↗
PubMed2000

Neurologial interpretations and the information in the cognitive pupillary response.

It has been known for 70 years that the human pupil dilates when a person responds to a cognitive task. Further, it is known that parasympathetic pupillary innervation decreases with raised attention state while sympathetic innervation increases. But the information the pupil transmits during elevated attention states about such neurological dynamics and a quantitative measure of this information have defied statistical modelling. Now we describe experiments using a short-term memory task called an acoustic impulse test in which the pupillary dynamics in response to random acoustic impulses are recorded with a high resolution (0.01 mm) pupillometer with the result that parasympathetic and sympathetic pupillary dilation components are quantifiable, as is the information transmitted by these components.

Arousal↗
PubMed1999

Measurement of distal forearm bone mineral density: can different forearm segments be used interchangeably ?

Many different forearm sites have been used for the measurement of bone mineral density (BMD) and prediction of risk of future fracture among community dwelling populations. In populations where bone densitometry of peripheral sites may be the most cost effective and practical means of measuring BMD, such as the nursing home population, knowing the characteristics of forearm BMD measures would be beneficial. The purpose of this study was to assess the relationship of four common commercially available measures to each other and to estimate the inter- and intrarater reliability of the measures in a sample of nursing home residents as a first step toward identifying appropriate forearm measurement sites. These sites were the distal radius, the distal ulna, a composite of the distal radius and distal ulna, and the ultra distal radius. BMD measurements on 48 nursing home patients were obtained using single X-ray absorptiometry. Inter- and intrarater reliability was excellent at all four sites (interclass correlation coefficients > 0. 85). Moderate to high correlations (0.84-0.91) between the distal radius and ultra distal radius sites of the forearm suggest that these measures may be interchangeable. Although not directly assessed here, differences in bone composition among forearm sites may partially explain moderate rather than high correlations between sites and may affect the ability of each site to predict future fractures. Thus, different forearm sites may be used interchangeably for diagnostic purposes; however, the prognostic value of each site remains unknown.

Absorptiometry, Photon↗
PubMed1999

Miniaturized FRET assays and microfluidics: key components for ultra-high-throughput screening.

Assay miniaturization applicable across a wide range of target classes, along with automation and process integration, are well-recognized goals for ultra-high-throughput screening on an industrial scale. This report summarizes the implementation of fluorescence resonance energy transfer (FRET)-based biochemical and cell-based assays in 3456-well NanoWelltrade mark assay plates using key components of Aurora's ultra-high-throughput screening system.

Journal Article↗
PubMed1998

Treatment of malnutrition with 1.1% amino acid peritoneal dialysis solution: results of a multicenter outpatient study.

A peritoneal dialysis (PD) solution containing 1.1% amino acids as the osmotic agent was evaluated in a 3-month randomized, prospective, open-label study in malnourished PD patients. Patients in the treatment group (DAA) received one or two exchanges daily with the amino acid solution, depending on tolerance, in place of glucose solutions. Controls (DD) received their usual therapy with glucose dialysate. Fifty-four DAA and 51 DD patients completed the study. In DAA, but not in DD patients, there was a significant increase at month 3 in serum insulin-like growth factor-1 (IGF-1) levels and significant decreases in serum potassium (all 3 months) and inorganic phosphorus levels (months 1 and 3), indicating a general anabolic response. Prealbumin and transferrin levels were significantly increased in DAA but not in DD patients at month 1, but the groups did not differ at months 2 and 3. In patients with baseline albumin levels less than 3.5 g/dL (bromcresol green [BCG] method), DAA patients showed increases in albumin, transferrin (months 1 and 2), and prealbumin levels (all 3 months) relative to baseline values, whereas these serum protein levels were unchanged in DD patients, although the changes from baseline did not differ between groups. In this subgroup, midarm muscle circumference (MAMC) did not change in DD or DAA patients. In patients with baseline albumin levels of 3.5 g/dL or greater, DD patients had decreases in albumin and total protein levels at all 3 months and in prealbumin levels at months 1 and 2, relative to baseline. In DAA patients, there were fewer changes in serum proteins. MAMC increased significantly from baseline in DAA but not in DD patients, although changes from baseline did not differ between DAA and DD groups. DAA patients showed no changes in peritoneal membrane transport characteristics. The results indicate that treatment with one or two exchanges daily of this amino acid-based PD solution is safe and provides nutritional benefit for malnourished PD patients.

Amino Acids↗