Showing papers by "Jewish Hospital published in 1993"

A Comparison of Directional Atherectomy with Coronary Angioplasty in Patients with Coronary Artery Disease

Abstract: Background Directional coronary atherectomy is a new technique of coronary revascularization by which atherosclerotic plaque is excised and retrieved from target lesions. With respect to the rate of restenosis and clinical outcomes, it is not known how this procedure compares with balloon angioplasty, which relies on dilation of the plaque and vessel wall. We compared the rate of restenosis after angioplasty with that after atherectomy. Methods At 35 sites in the United States and Europe, 1012 patients were randomly assigned to either atherectomy (512 patients) or angioplasty (500 patients). The patients underwent coronary angiography at base line and again after six months; the paired angiograms were quantitatively assessed at one laboratory by investigators unaware of the treatment assignments. Results Stenosis was reduced to 50 percent or less more often with atherectomy than with angioplasty (89 percent vs. 80 percent, P<0.001), and there was a greater immediate increase in vessel caliber (1.05 vs. 0....

Clock Completion: An Objective Screening Test for Dementia

Abstract: Objective To develop a simple, readily administered and scored screening test for dementia utilizing the clock-drawing task. Design Retrospective analysis of clock-drawing errors and prospective validations. Setting Hospital-based outpatient geriatric assessment clinic, rehabilitation service, apartment building for older adults, and long-term care facility. Participants Convenience sample of patients attending the geriatric assessment clinic, patients on the rehabilitation service, or residents of the above sites. Measurements Sensitivity and specificity of a clock-scoring system in identifying patients with dementia and the comparison of this system with the Short Blessed Test (SBT) in the diagnosis of dementia and in the prospective validation of the test. Results Of the 10 clock-drawing errors evaluated, placement of digits in a pre-drawn circle had the greatest sensitivity and specificity in distinguishing patients with irreversible dementia from patients with other disorders who did not meet NINCDS-ADRDA criteria for probable dementia. The derived scoring system had a sensitivity of 87% and a specificity of 82%, compared with a sensitivity of 82% and a specificity of 88% for the SBT in identifying dementia. Test-retest reliability for the distinction between demented and non-demented was 82%, with a Kappa of 0.63 for the clock completion, and 82%, with a Kappa of 0.62 for the SBT. Inter-rater reliability for clock completion was 0.90 to 0.93. Conclusion A simple, completely objective scoring system for a clock completion test has been developed which involves only the number of digits placed in the fourth quadrant of a pre-drawn circle. This readily administered test is as effective in screening for dementia as the longer six-item SBT.

Connexin43 mediates direct intercellular communication in human osteoblastic cell networks.

Abstract: We have examined cell coupling and expression of gap junction proteins in monolayer cultures of cells derived from human bone marrow stromal cells (BMC) and trabecular bone osteoblasts (HOB), and in the human osteogenic sarcoma cell line, SaOS-2. Both HOB and BMC cells were functionally coupled, since microinjection of Lucifer yellow resulted in dye transfer to neighboring cells, with averages of 3.4 +/- 2.8 (n = 131) and 8.1 +/- 9.3 (n = 51) coupled cells per injection, respectively. In contrast, little diffusion of Lucifer yellow was observed in SaOS-2 monolayers (1.4 +/- 1.8 coupled cells per injection, n = 100). Dye diffusion was inhibited by octanol (3.8 mM), an inhibitor of gap junctional communication. All of the osteoblastic cells expressed mRNA for connexin43 and connexin45, but not for connexins 26, 32, 37, 40, or 46. Whereas all of the osteoblastic cells expressed similar quantities of mRNA for connexin43, the poorly coupled SaOS-2 cells produced significantly less Cx43 protein than either HOB or BMC, as assessed by immunofluorescence and immunoprecipitation. Conversely, more Cx45 mRNA was expressed by SaOS-2 cells than by HOB or BMC. Thus, intercellular coupling in normal and transformed human osteoblastic cells correlates with the level of expression of Cx43, which appears to mediate intercellular communication in these cells. Gap junctional communication may serve as a means by which osteoblasts can work in synchrony and propagate locally generated signals throughout the skeletal tissue.

Regional nodal management and patterns of failure following conservative surgery and radiation therapy for stage I and II breast cancer

Abstract: Purpose: To determine the incidence, pattern of regional nodal failure, and treatment sequelae as determined by the extent of lymphatic irradiation. Methods and Materials: The records of 511 patients with 519 Stage I and II breast cancers treated with breast conserving surgery with or without axillary dissection and irradiation were reviewed. The extent of nodal irradiation was at the discretion of the attending radiation oncologist and varied considerably over the years. Management of the axilla consisted of axillary dissection alone in 351, axillary dissection and supplemental irradiation in 74, irradiation alone in 75, and simply observation in 21 patients. Results: Overall, axillary recurrence was uncommon (1.2%), but was slightly more frequent after irradiation alone (2.7%) than after surgery alone (0.3%), p = 0.14. There was no benefit for supplemental axillary irradiation after an axillary dissection yielding negative or 1 to 3 positive nodes. In the 21 patients in whom the axilla was observed, axillary recurrence was not observed. Supraclavicular failures were rare in women with negative or 1 to 3 positive axillary lymph nodes (0.5%), and not significantly affected by elective irradiation. Internal mammary node recurrence was seen in only one patient, and was not significantly influenced by elective internal mammary irradiation. Both arm and breast edema were significantly more common in women having breast and nodal irradiation than after breast irradiation alone. These sequelae were not influenced significantly by the number of lymph nodes obtained in the axillary dissection specimen. Radiation pneumonitis was seen with increased frequency with more extensive nodal radiotherapy. Pneumonitis was not found to be affected by the administration or sequencing of chemotherapy. Conclusion: There is little justification for axillary or supraclavicular irradiation following an axillary dissection which yields negative or minimally involved (1 to 3 positive) lymp nodes. There were too few patients with extensive axillary node metastases (>- 4 positive) in our series to draw conclusions about the optimal extent of nodal irradiation in this subset. Elective internal mammary lymph node irradiation increases technical complexity, does not appear to be advantageous, and when combined with supraclavicular irradiation places the patient at highest risk for pneumonitis.

Accumulation of surfactant protein D in human pulmonary alveolar proteinosis.

Abstract: Surfactant protein D (SP-D) is a collagenous calcium-dependent carbohydrate-binding protein that is structurally related to the serum mannose-binding proteins and pulmonary surfactant protein A. SP-D was initially characterized as a biosynthetic product of freshly isolated rat type II cells and first purified in chemical amounts from bronchoalveolar lavage of rats with silica-induced alveolar lipoproteinosis. The present studies describe the characterization of human SP-D isolated from therapeutic bronchoalveolar lavage of patients with pulmonary alveolar proteinosis. Human proteinosis SP-D was extracted from the 10,000 x g pellet of bronchoalveolar lavage with 100 mmol/L glucose or ethylenediamine tetraacetic acid, and specifically bound to and eluted from maltosyl-agarose. The protein cross-reacted with monospecific antibodies to rat SP-D by enzyme-linked immunosorbent assay and immunoblot and eluted near the position of rat SP-D on reverse-phase high performance liquid chromatography. When chromatographed on 4% agarose (A-15M) in the presence of ethylenediamine tetraacetic acid, the solubilized human proteinosis SP-D eluted near the void volume and earlier than rat SP-D dodecamers or human SP-D multimers in the lavage supernatant. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting of proteins in the lavage pellet with antibodies to the carbohydrate-binding domain of proteinosis human SP-D demonstrated covalently cross-linked multimers of SP-D monomers (43 kd, reduced) and multimers of trimeric components stabilized by disulfide and non-disulfide bonds. These studies describe the isolation and biochemical characterization of human SP-D and demonstrate the abnormal accumulation of this protein in the air spaces of patients with alveolar proteinosis.

Relationships between lipoprotein(a), lipids, apolipoproteins, basal and stimulated fibrinolytic regulators, and D-dimer.

Abstract: In 191 newly referred hyperlipidemic patients, our specific aim was to assess relationships between levels of lipoprotein(a) [Lp(a)], lipids, apolipoproteins, regulators of basal and stimulated fibrinolytic activity, and D-dimer, a measure of in vivo fibrinolysis. Lp(a) levels correlated with none of the measures of basal fibrinolytic regulators or D-dimer. In 25 patients, levels of stimulated regulators of fibrinolytic activity and D-dimer were measured after 10-minute cuff venous occlusion. Lp(a) levels again correlated with none of the stimulated regulators of fibrinolytic activity or D-dimer. However, both basal and stimulated levels of fibrinolytic regulators and D-dimer were closely related to other major risk factors for coronary heart disease (CHD) including triglyceride, apolipoprotein (apo) A1, apo B, Quetelet index (QI), and sex. By stepwise regression in 191 patients, the following standardized partial regression coefficients were significant (P < or = .05), and model R2 and P values were as follows: basal tissue plasminogen activator (tPA) with apo B-.18, with time .17, with QI -.28, R2 = 17%, P < or = .0001; basal plasminogen activator inhibitor (PAI) with apo B..25, with time -.15, with QI .17, R2 = 14%, P < or = .0001; basal alpha 2-antiplasmin with apo A1.14, with apo B.24, with QI.17, with sex .30, R2 = 25%, P < .0001; basal plasminogen with A1.15, with apo B.21, with QI.17, with sex.17, R2 = 15%, P < or = .0001; basal fibrinogen with Lp(a).17, with QI.21, with sex.26, R2 = 14%, P < or = .0001; D-dimer with sex.15, R2 = 21%, P < or = .048. Given the absence of any relationship between Lp(a) levels and inhibition or stimulation of fibrinolysis regulators or D-dimer either in the basal or stimulated state, we postulate that Lp(a)'s major atherogenic effects are mediated by mechanisms other than reduction of fibrinolysis stimulation or in vivo fibrinolysis.

Regulation of paracellular permeability in Caco-2 cell monolayers by protein kinase C.

Abstract: Caco-2 cells are an enterocyte-like cell line derived from a human colonic adenocarcinoma. Paracellular permeability was assessed in monolayers of these cells by transmonolayer resistance and by the permeation of [3H]mannitol across the monolayer. Paracellular permeability was increased by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (50 nM), carbachol (500 microM), and the combination of carbachol (50 microM) and monolein (100 microM), an inhibitor of diacylglycerol kinase, as manifested by a decrease in transmonolayer resistance and an increase in mannitol permeation. The effects of all of these stimuli on transmonolayer resistance were inhibited by staurosporine (3 nM), an inhibitor of PKC. The effects of carbachol plus monolein were also inhibited by atropine (0.1 microM), a muscarinic antagonist. Treatment of the monolayers with each of the stimuli was associated with translocation of PKC activity from cytosol to a membrane-associated state. Stimulation of Caco-2 cell monolayers with phorbol myristate acetate or with the combination of carbachol and monolein was also associated with phosphorylation of the MARCKS protein, an endogenous substrate of PKC. These data support the hypothesis that intestinal paracellular permeability is regulated by the activity of enterocyte PKC and demonstrate that the increase in paracellular permeability induced by binding of carbachol to the muscarinic receptor is mediated by activation of PKC.

Familial high plasminogen activator inhibitor with hypofibrinolysis, a new pathophysiologic cause of osteonecrosis?

Abstract: In a 29 year old white male with osteonecrosis of both hips and a shoulder, and in his family, we measured basal and stimulated (10 min cuff venous occlusion at 100 mgHg) fibrinolytic activity to determine whether low fibrinolytic activity might be heritable and etiologically associated with osteonecrosis. The proband's basal tPA-Fx was low, 0.08 IU/ml (normal 0.11-1.94), tPA-Ag was normal (11.6 ng/ml), plasminogen activator inhibitor activity (PAI-Fx) was very high, 119 U/ml (normal 3.5-27), as was his plasminogen activator inhibitor antigen (PAI-Ag), 202 ng/ml (normal 3.2-37.1). The proband's basal PAI-Fx (119) and PAI-Ag (202) were respectively 6 and 13 standard deviations greater than the mean PAI-Fx (17 +/- 15 U/ml) and the mean PAI-Ag (25 +/- 13 ng/ml) in 172 concomitantly studied hyperlipidemic men. Alpha-2 antiplasmin, fibrinogen, plasminogen and Lp(a) were normal. Despite lowering TG to 301 mg/dl, basal tPA-Fx remained low, 0.05; PAI-Fx and PAI-Ag remained very high (109 and 191). Following venous occlusion, stimulated tPA-Fx remained very low, 0.1 (normal 2.3-11.3), but tPA-Ag rose normally to 17 (normal 8.4-31.4); stimulated PAI-Fx and PAI-Ag were very high, 134 and 223, (normal PAI-Fx 3.6-24, PAI-Ag 12-96). Stimulated D-dimer was < the 10th percentile, 0.084 micrograms/ml. With such high PAI-Fx available to bind tPA, occlusion-stimulated tPA-Fx could not rise, and fibrinolysis could not be initiated. Neither diseases nor drugs could explain the high PAI-Fx and PAI-Ag, low tPA-Fx; or osteonecrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucocorticoid Effects on Statural Growth

Abstract: Glucocorticoid use in children is not only associated with the side effects which are seen in adults, but also with severe adverse effects on statural growth. As little as 2.5-5.0 mg prednisolone/day can cause a retardation in statural growth. A direct relationship exists between the dose of glucocorticoid used and statural growth. The use of knemometry, a sensitive technique for measuring the growth of long bones in children has increased the accuracy of growth rate measurements. Many factors, such as disease process, sex, daily vs alternate day therapy, ethnic variations or whether the patient has been immobilized must be considered when evaluating the effects on stature of a particular glucocorticoid. Although alternate day therapy may benefit some patients (particularly those with juvenile chronic arthritis), not all patients respond beneficially to this type of regimen. New generations of glucocorticoids which may not be as detrimental to the growing child should now be considered.

Acid and base effects on avian osteoclast activity.

Abstract: Osteoclasts generate a massive acid flux to mobilize bone calcium. Local extracellular acidification by polarized vacuolar-type H(+)-ATPase, balanced by contralateral HCO3-(-)Cl- exchange to maintain physiological intracellular pH, is theorized to drive this process. It follows that extracellular pH, PCO2, or HCO3- concentration ([HCO3-]) should impact bone matrix dissolution. However, the effects on bone resorption of the concentrations of these ions or their transmembrane gradients are unknown. Furthermore, because bone management is a vital process, regulatory feedback may minimize such effects. Thus a complex relationship between bone resorption and pH, PCO2, and [HCO3-] is expected but requires experimental determination. We measured bone resorption by isolated avian osteoclasts while varying these parameters across the physiological range. Bone degradation increased 50% from pH 7.3 to 6.7, whether achieved by changing [HCO3-] (2.3-38 mM) at constant HCO3- or PCO2 (15-190 mmHg) at constant [HCO3-]. However, at constant pH, changing PCO2 and [HCO3-] within physiological limits did not affect bone resorption. In contrast, total HCO3- removal at pH 7.4 reduced bone degradation by rat or avian osteoclasts substantially, confirming that normal acid secretion requires HCO3-. These observations support a model coupling osteoclastic bone resorption to proton and HCO3- transport but indicate that [HCO3-] is not rate limiting under physiological conditions. Extracellular pH changes affect osteoclastic bone resorption measurably, but not dramatically, at physiological [HCO3-].

Inter-relationships between bone mineral content measures. Dual energy radiography (DER) and bitewing radiographs (BWX).

Abstract: In vitro periodontal alveolar bone mineral content (BMC) measurements obtained with dual-energy radiography (DER) were compared with assessments based on bitewing radiographs (BWX). In addition, in patients, the relationship between bitewing and several postcranial dual-energy-radiographic measures were evaluated. Dual-energy-radiographic and bitewing measurements were made on 2 cadaver mandibles initially and after 2 incremental bone reductions at 4 sites. Rank-order correlations between dual-energy-radiographic and bitewing measures for the 4 sites ranged from 0.7 to 1.00. Bitewing measures indicated true bone loss with a sensitivity of 1.00. For patients, correlations between bitewing measures and dual-energy-radiographic scans suggested the strongest relationships were in the distal sections of the radius and ulna and in the intertrochanteric and Ward's areas of the femur. Correlations, in the 0.5-0.6 range, were not statistically significant (p > 0.05), but were quite robust considering the small sample size and preliminary nature of this investigation. Results suggest that the bitewing measure is sufficiently sensitive to detect clinically meaningful (5% or greater) changes in alveolar BMC and, further, that alveolar bone mineral content may reflect postcranial BMC. The implications of postcranial bone mineral changes being reflected in alveolar bone would enhance both our understanding and treatment of alveolar bone loss. The use of bitewing measures to facilitate identification of patients with postcranial bone loss is discussed.

Retroperitoneal endoscopic adrenalectomy: an experimental study.

Abstract: Laparoscopic approaches to adrenalectomy have been limited by the retroperitoneal (RP) location of the adrenal glands and their relative inaccessibility transabdominally. We developed a technique for endoscopic adrenalectomy in a domestic swine model using insufflation of the RP space with CO2 and retroperitoneoscopy. The technique for retroperitoneal endoscopic adrenalectomy was first developed in an acute study of three animals. A chronic survival study was then undertaken in six pigs. Unilateral right (n = 3) or left (n = 3) adrenalectomy was performed. Mean RP insufflation time was 14.5 min (range, 7-30 min), and mean dissection time after insufflation was 100 min (range, 80-120 min). Two additional animals died under anesthesia after RP insufflation and placement of the trocars for retroperitoneoscopy but before dissection of the adrenal gland. One death was unexplained at autopsy. The other death was associated with a right-sided pneumothorax attributable to penetration of the diaphragm by a trocar. The remaining six pigs recovered uneventfully from the procedure. Autopsies performed 37 to 51 days postoperatively showed minimal scarring of the adrenalectomy bed. The results suggest that posterior adrenalectomy using RP CO2 insufflation and direct retroperitoneoscopy is potentially applicable to the treatment of small adrenal lesions in humans.

Blood flow and tissue survival in the rabbit venous flap.

Abstract: The extent of venous flow, revascularization, local fluid imbibition, and metabolic status was evaluated in an experimental venous flap model. Thirty-six rabbits divided into six groups of six rabbits each had a 3.5×2.5 cm venous flap elevated along the thoracoepigastric vein, connected only by its proximal and distal vein, and sutured back. A composite graft of the same size was created on the contralateral side. Venous flaps survived 14 days, while composite grafts consistently did not. The vascular network was partially filled with fluorescein tracer within an hour after flap creation, even with an underlying Silastic sheet

Mitoxantrone and 5−azacytidine for refractory/relapsed ANLL or CML in blast crisis : a leukemia intergroup study

Abstract: In an effort to determine if cell cycle active agents are augmented when given after non-cell cycle active agents, 104 patients with either multiply relapsed or refractory acute nonlymphocytic leukemia or blast crisis of chronic myelogenous leukemia were treated with mitoxantrone Patients whose bone marrow did not show significant cytoreduction received 5-azacytidine Twenty-seven of the 93 evaluable patients (23%) with ANLL achieved a complete remission A total of 28% of patients receiving mitoxantrone alone achieved remission compared to 15% for those receiving mitoxantrone and 5-azacytidine Relapsed patients had a higher CR rate (36%) than refractory patients (15%) Nausea, vomiting, and stomatitis were common but rarely severe The median duration of remission was 37 months and patients with abnormal karyotypes had longer remission durations than those with normal karyotypes In this patient population, there was no evidence that 5-azacytidine given after mitoxantrone increased the complete remission rate

Potency ratio--a brief synopsis.

Abstract: Deflazacort (DFZ) is a novel glucocorticoid with bone sparing properties, and there have been numerous studies investigating its potency relative to other glucocorticoids. As estimates of potency are difficult to evaluate in patients with disease, the concept of minimum effective dose is used. In double-blind, crossover studies, paired patient studies and between-patient studies, the potency of DFZ to prednisone (PDN) and to methylprednisolone was established as being 1.28:1 (1.17-1.38, 95% CI) and 1.6:1 (1.45-1.75, 95% CI), respectively. The bone wasting properties of DFZ have been determined using the concept of bone wasting ratio (ratio between bone loss velocity values observed in patients given the minimum effective doses of two glucocorticoids). The results of three studies which have evaluated the bone wasting ratio of PDN to DFZ indicate that this ratio is approximately 2.03:1 (1.84-2.23, 95% CI). That is, at therapeutically equivalent doses, twice as much bone loss occurs with PDN as with DFZ.

Prognostic Features of Ewing Sarcoma on Plain Radiograph and Computed Tomography Scan after Initial Treatment A Pediatric Oncology Group Study (8346)

Abstract: Background. The authors studied the short-term changes in the plain radiographic and computed tomography (CT) appearance of Ewing sarcoma for indicators of decreased survival or future disease progression. Methods. The authors evaluated CT scans and plain radiographs of the primary tumor site from 105 patients with Ewing sarcoma at diagnosis (prebiopsy), after induction chemotherapy (13 weeks), and after radiation therapy (20 weeks). Results. Data suggest an association between postinduction CT findings of medullary involvement, cortical destruction, lysis, permeation, and unhealed pathologic fracture and decreased survival. On the postradiation scans, only medullary involvement was associated with worsened survival. No plain radiographic features were significant at any time. Absolute greatest tumor dimension was not significantly related to survival or tumor progression. The Cox model suggested that fractional change in greatest tumor dimension on CT at the time points studied relative to the prebiopsy CT was correlated to survival. Log-rank testing did not corroborate this finding. All significant associations appeared to result from adverse outcomes in small subgroups. Conclusions. Our data suggest that CT obtained immediately after induction chemotherapy and radiation may have some limited use in predicting the long-term prognosis of patients with Ewing sarcoma.

Evidence against a role for alkaline phosphatase in the dephosphorylation of plasma membrane proteins : hypophosphatasia fibroblast study

Abstract: A major impasse to understanding the physiologic role(s) of alkaline phosphatase (ALP) is uncertainty as to its natural substrates. Various in vitro studies have led other investigators to suggest that ALP functions as a plasma membrane phosphoprotein phosphatase, consistent with our demonstration of ecto-topography of ALP in a variety of cell types. Thus, we compared the phosphorylation of plasma membrane proteins from control fibroblasts to those from profoundly ALP-deficient fibroblasts of hypophosphatasia patients. Fibroblasts from 3 controls and 3 hypophosphatasia patients (ALP activity < 4% of control) were biosynthetically labeled with 32Pi for 2 h. 32P incorporation into total trichloroacetic acid (TCA)-precipitable material was not significantly different in control and patient cells. Plasma membranes were prepared from these cells by hypotonic shock, solubilized, and subjected to two-dimensional (2-D) gel electrophoretic separation. Video densitometric analysis of silver-stained 2-D gels failed to reveal any consistent difference in the protein profile between patient vs. control fibroblasts (i.e., unique species, altered pls, or increased abundance). Autoradiography of individual 2-D gels demonstrated 63 plasma membrane phosphoproteins with molecular weights ranging from 15 to 152 kDa and predominantly acidic pls. Although several of these phosphoproteins appeared to have had donor-specific labeling, none was unique or especially abundant in the hypophosphatasia group. Thus, in ALP-deficient fibroblasts, normal incorporation of 32P into total cellular protein and into all identifiable plasma membrane phosphoproteins indicates that ALP does not modulate the phosphorylation of plasma membrane proteins.

Multiple personality disorder: scientific and medicolegal issues.

Abstract: Despite the intense study it has received since its inclusion in DSM-III, multiple personality disorder (MPD) largely remains an unvalidated construct. Definitional problems remain (there is not even agreement in the field as to whether a diagnosis of MPD truly means the existence of more than one personality), while the vagueness and liberality of existing criteria give the clinician little guidance in diagnosis. In forensic settings, diagnosis of MPD is even more problematic, since there is substantial evidence that the disorder cannot currently be phenomenologically distinguished from malingering. It also remains to be demonstrated that evaluators can determine whether alter personalities, if they exist, are truly unaware of each other, lack control over other alters' behavior, or are unable to know right from wrong.

Identifying nursing research priorities in an acute care hospital.

Abstract: The purpose of this study was to identify nursing research priorities for an acute care hospital. Using the Delphi technique, data were obtained from a panel of 52 nurses who held administrative, staff, or support positions. After three rounds of data collection, a prioritized listing of potential research topics was obtained. The study results have helped motivate and guide research efforts, stimulate formation of research interest groups, and attract local researchers to the facility.

Techniques of harvesting and cryopreservation of stem cells.

Abstract: Improved marrow processing techniques and in vitro marrow manipulations are revolutionizing the clinical application of both allogeneic and autologous bone marrow transplantation. The rapid evolution of clinically useful laboratory techniques now necessitates more sophisticated laboratory support of bone marrow transplantation.

Monitoring of drug utilization in public health surveillance activities: A conceptual framework

Abstract: The surveillance of individual and aggregate patterns of prescribed medication can potentially provide some very useful information to those involved in public health. At present however, this activity has attracted relatively little attention in Canada. This article will introduce a conceptual framework with which to examine the possibilities of prescription drug monitoring as a tool for public health surveillance. The sources of data available to undertake this activity as well as their limitations, will be presented along with some recent concrete applications.

1,25-Dihydroxyvitamin D3 increases type 1 interleukin-1 receptor expression in a murine T cell line.

Abstract: The biologically active metabolite of vitamin D3, 1,25 (OH)2 D3, exerts important immunoregulatory effects in addition to being a central mediator of calcium/phosphate metabolism. Utilizing an interleukin 1 responsive murine T cell line and 125I-interleukin 1α, we show that 1,25 (OH)2 D3 (5,50 nM) enhanced 125I-interleukin 1α binding up to almost 2-fold over control. This 1,25 (OH)2 D3 effect occurred in a dose-dependent manner and was detectable after 24 h but not before 7 h of culture. Scatchard analysis of 125I-interleukin 1α binding data demonstrated that 1,25 (OH)2 D3 enhanced interleukin 1 receptor number without a significant change in affinity. The biologically less potent metabolite of vitamin D3, 25 (OH) D3, also augmented 125I-interleukin 1α binding but at steroid levels 2–3 log orders greater than 1,25 (OH)2 D3. This observation, combined with the presence of high-affinity 3H-1,25 (OH)2 D3 receptors (88 sites/cell, K = 0.45 nM) in cytosolic extracts, strongly suggests that the nuclear vitamin D receptor mediates this steroid's effect on interleukin 1 receptor expression. Based on the capacity of an anti-type 1 interleukin 1 receptor monoclonal antibody (35F5) to block 1,25 (OH)2 D3-enhanced 125I-interleukin 1α binding, we conclude that this steroid augments type 1 interleukin 1 receptor expression. When combined with interleukin 1, a cytokine that also impacts MD10 interleukin 1 receptor expression, 1,25 (OH)2 D3 enhanced interleukin 1 receptor expression. Northern blots hybridized with a 32P-type 1 interleukin 1 receptor cDNA probe show that 1,25 (OH)2 D3 enhanced type 1 interleukin 1 receptor steady state mRNA levels. Functionally, 1,25 (OH)2 D3 pretreatment augmented the MD10 proliferative response to suboptimal levels of interleukin 1 (< 100 fM interleukin 1α). These findings further support 1,25 (OH)2 D3's role as an immunoregulatory molecule and provides a possible mechanism by which this steroid could potentiate certain immune activities.