bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated Bone-Targeted Therapy for Hormone-Refractory Prostate Carcinoma: Randomized Phase II Trial With the New, High-Energy Radiopharmaceutical Rhenium-188 Hydroxyethylidenediphosphonate
Authors: Palmedo Holger , Manka-Waluch Agnieska , Albers Peter , Schmidt-Wolf Ingo G.H. , Reinhardt Michael , Ezziddin Samer , Joe Alexius , Roedel Roland , Fimmers Rolf , Knapp F.F. , Guhlke Stefan , Biersack Hans-Jürgen
Published: July 2003

Purpose: We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments.

Patients and Methods: Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death.

Results: In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P = .006 and P = .001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P = .0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P = .043).

Conclusion: Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.
Problèmes de ruine en théorie du risque à temps discret avec horizon fini
Authors: Picard Philippe , Lefèvre Claude , Coulibaly Ibrahim
Published: July 2003

We consider a discrete-time risk model which describes the evolution of the reserves of an insurance company at periodic dates fixed in advance. The amount of loss per unit of time corresponds to independent and identically distributed random variables with arithmetic distribution, and the process of the receipt of premiums is assumed to be deterministic, nonnegative but not uniform (instead of being constant and equal to 1 as in the standard, compound binomial model). For this model, we determine the probability of ruin (or of non-ruin), as well as the distribution of the severity of the eventual ruin, with some finite horizon. A compact and efficient exact expression is found by bringing up-to-date a generalised family of Appell polynomials. The method used is illustrated with some numerical examples.
Probabilité de ruine éventuelle dans un modèle de risque à temps discret
Authors: Picard Philippe , Lefèvre Claude
Published: July 2003

We continue the study of the discrete-time risk model introduced by Picard et al. (2003). The cumulative loss process (St)t∊ℕ has independent and stationary increments, the increments per unit of time having nonnegative integer values with distribution {ai, i ∊ ℕ and mean ā. The premium receipt process (ck)k∊ℕ is deterministic, nonnegative and nonuniform; in addition, we assume it to be regular in order for there to exist a constant c > ā such that the deviation is bounded as the time t varies. We are interested in whether or not ruin occurs within a finite time. If T is the time of ruin, we obtain P(T = ∞) as the limit of P(T > t) as t → ∞, firstly in the particular case where c = 1/d for some positive d ∊ ℕ, and then in the general case for positive c under the condition that a0 > ½.
Biased movement at a boundary and conditional occupancy times for diffusion processes
Authors: Ovaskainen Otso , Cornell Stephen J.
Published: July 2003

Motivated by edge behaviour reported for biological organisms, we show that random walks with a bias at a boundary lead to a discontinuous probability density across the boundary. We continue by studying more general diffusion processes with such a discontinuity across an interior boundary. We show how hitting probabilities, occupancy times and conditional occupancy times may be solved from problems that are adjoint to the original diffusion problem. We highlight our results with a biologically motivated example, where we analyze the movement behaviour of an individual in a network of habitat patches surrounded by dispersal habitat.
Buffer content of a leaky-bucket system with long-range dependent input traffic
Authors: González-Arévalo Bárbara , Samorodnitsky Gennady
Published: July 2003

The leaky bucket is a flow control mechanism that is designed to reduce the effect of the inevitable variability in the input stream into a node of a communication network. In this paper we study what happens when an input stream with heavy-tailed work sessions arrives to a server protected by such a leaky bucket. Heavy-tailed sessions produce long-range dependence in the input stream. Previous studies of single server fluid queues without flow control suggested that such long-range dependence can have a dramatic effect on the system performance. By concentrating on the expected time till overflow of a large finite buffer we show that leaky-bucket flow control does make the system overflow less often, but long-range dependence still makes its presence felt.
Carousel system performance
Authors: Park Byung Chun , Park Jae Young , Foley Robert D.
Published: July 2003

We analyse the performance of a material handling system consisting of two carousels and one picker. We derive expressions for the system throughput and picker utilization. We work out the throughput and picker utilization for two different pick-time distributions: deterministic, which might be a reasonable model when a robot is picking, and exponential, which might be a reasonable model when a person is picking.
On the structure of value functions for threshold policies in queueing models
Authors: Bhulai Sandjai , Koole Ger
Published: July 2003

We study the multiserver queue with Poisson arrivals and identical independent servers with exponentially distributed service times. Customers arriving at the system are admitted or rejected according to a fixed threshold policy. Moreover, the system is subject to holding, waiting, and rejection costs. We give a closed-form expression for the average costs and the value function for this multiserver queue. The result will then be used in a single step of policy iteration in the model where a controller has to route to several finite-buffer queues with multiple servers. We numerically show that the improved policy has a close to optimal value.
On ordered series and later waiting time distributions in a sequence of Markov dependent multistate trials
Authors: Fu James C. , Chang Yung-Ming
Published: July 2003

The sooner and later waiting time problems have been extensively studied and applied in various areas of statistics and applied probability. In this paper, we give a comprehensive study of ordered series and later waiting time distributions of a number of simple patterns with respect to nonoverlapping and overlapping counting schemes in a sequence of Markov dependent multistate trials. Exact distributions and probability generating functions are derived by using the finite Markov chain imbedding technique. Examples are given to illustrate our results.
A method for computing total downtime distributions in repairable systems
Authors: Suyono  , van der Weide J. A. M.
Published: July 2003

In this paper we derive the distribution of the total downtime of a repairable system during a given time interval. We allow dependence of the failure time and the repair time. The results are presented in the form of Laplace transforms which can be inverted numerically. We also discuss asymptotic properties of the total downtime.
One-sided variations on interval trees
Authors: Itoh Yoshiaki , Mahmoud Hosam M.
Published: July 2003

The binary interval tree is a random structure that underlies interval division and parking problems. Five incomplete one-sided variants of binary interval trees are considered, providing additional flavors and variations on the main applications. The size of each variant is studied, and a Gaussian tendency is proved in each case via an analytic approach. Differential equations on half scale and delayed differential equations arise and can be solved asymptotically by local expansions and Tauberian theorems. Unlike the binary case, in an incomplete interval tree the size determines most other parameters of interest, such as the height or the internal path length.
Ladder variables, internal structure of Galton–Watson trees and finite branching random walks
Authors: Marckert Jean-François , Mokkadem Abdelkader
Published: July 2003

In this paper, we consider Galton–Watson trees conditioned by size. We show that the number ofk-ancestors (ancestors that havekchildren) of a nodeuis (almost) proportional to its depth. Thek,j-ancestors are also studied. The methods rely on the study of ladder variables on an associated random walk. We also give an application to finite branching random walks.
Power-law correlations and other models with long-range dependence on a lattice
Authors: Ma Chunsheng
Published: July 2003

This paper introduces long-range dependence for a stationary random field on a plane lattice, derives an exact power-law correlation model and other models with long-range dependence on the lattice, and explores the close connection between short-range dependent correlation functions and absolutely summable double sequences.
Exact overflow asymptotics for queues with many Gaussian inputs
Authors: Dębicki Krzysztof , Mandjes Michel
Published: July 2003

In this paper we consider a queue fed by a large number of independent continuous-time Gaussian processes with stationary increments. After scaling the buffer exceedance threshold and the (constant) service capacity by the number of sources, we present asymptotically exact results for the probability that the buffer threshold is exceeded. We consider both the stationary overflow probability and the (transient) probability of overflow at a finite time horizon. We give detailed results for the practically important cases in which the inputs are fractional Brownian motion processes or integrated Gaussian processes.
Initial and final behaviour of failure rate functions for mixtures and systems
Authors: Block Henry W. , Li Yulin , Savits Thomas H.
Published: July 2003

In this paper we consider the initial and asymptotic behaviour of the failure rate function resulting from mixtures of subpopulations and formation of coherent systems. In particular, it is shown that the failure rate of a mixture has the same limiting behaviour as the failure rate of the strongest subpopulation. A similar result holds for systems except the role of strongest subpopulation is replaced by strongest min path set.
Convergence theorems for the lengths of consecutive successes of Markov Bernoulli sequences
Authors: Wang Y. H. , Chang Hsiao-Fen , Chen Shun-Yi
Published: July 2003

The limiting distributions of the sums of the lengths of four different kinds of runs of consecutive successes of Markov Bernoulli sequences are derived. It is shown that the limits are convolutions of several distributions involving the Bernoulli, the geometric and the Poisson or compound Poisson distributions.
Asymptotic inference for nearly unstable INAR(1) models
Authors: Ispány M. , Pap G. , van Zuijlen M. C. A.
Published: July 2003

A sequence of first-order integer-valued autoregressive (INAR(1)) processes is investigated, where the autoregressive-type coefficient converges to 1. It is shown that the limiting distribution of the conditional least squares estimator for this coefficient is normal and the rate of convergence is n3/2. Nearly critical Galton–Watson processes with unobservable immigration are also discussed.
Statistical properties of a system reliability estimator using the Littlewood software reliability model
Authors: Agustin Marcus A.
Published: July 2003

This paper considers a competing risks system with p pieces of software where each piece follows the model by Littlewood (1980) described as follows. The failure rate of a piece of software relies on the residual number of bugs remaining in the software where each bug produces failures at varying rates. In effect, bugs with higher failure rates tend to be observed earlier in the testing period. Tasks are assigned to the system and the task completion times as well as the software failure times are assumed to be independent of each other. The system is observed over a fixed testing period and the system reliability upon test termination is examined. An estimator of the system reliability is presented and its asymptotic properties as well as finite-sample properties are obtained.
SIR epidemics on a Bernoulli random graph
Authors: Neal Peter
Published: July 2003

We consider a generalized stochastic epidemic on a Bernoulli random graph. By constructing the epidemic and graph in unison, the epidemic is shown to be a randomized Reed–Frost epidemic. Hence, the exact final-size distribution and extensive asymptotic results can be derived.
Perpetual American put options in a level-dependent volatility model
Authors: Ekström Erik
Published: July 2003

We find the explicit value of perpetual American put options in the constant elasticity of variance model using the concept of smooth fit. We show that the price is increasing in the volatility and convex in the underlying stock price. Moreover, as the model converges to the standard Black and Scholes model, the value of the put is shown to approach the ‘correct’ limit.
Mixed distributions in Sattolo's algorithm for cyclic permutations via randomization and derandomization
Authors: Mahmoud Hosam M.
Published: July 2003

We investigate the limit distributions associated with cost measures in Sattolo's algorithm for generating random cyclic permutations. The number of moves made by an element turns out to be a mixture of 1 and 1 plus a geometric distribution with parameter ½, where the mixing probability is the limiting ratio of the rank of the element being moved to the size of the permutation. On the other hand, the raw distance traveled by an element to its final destination does not converge in distribution without norming. Linearly scaled, the distance converges to a mixture of a uniform and a shifted product of a pair of independent uniforms. The results are obtained via randomization as a transform, followed by derandomization as an inverse transform. The work extends analysis by Prodinger.
On the moment problem for random sums
Authors: Gut Allan
Published: July 2003

A recent paper by Lin and Stoyanov is devoted to the moment problem for geometrically compounded sums. The aim of this note is to provide affirmative answers to their conjectures.
From the central limit theorem to heavy-tailed distributions
Authors: Chen Jinwen
Published: July 2003

It has been observed that in many practical situations randomly stopped products of random variables have power law distributions. In this note we show that, in order for such a product to have a power law distribution, the only random indices are the exponentially distributed ones. We also consider a more general problem, which is closely related to problems concerning transformation from the central limit theorem to heavy-tailed distributions.
Time spent below a random threshold by a Poisson driven sequence of observations
Authors: Kirmani S. N. U. A. , Wesołowski Jacek
Published: July 2003

The mean and the variance of the time S(t) spent by a system below a random threshold until t are obtained when the system level is modelled by the current value of a sequence of independent and identically distributed random variables appearing at the epochs of a nonhomogeneous Poisson process. In the case of the homogeneous Poisson process, the asymptotic distribution of S(t)/t as t → ∞ is derived.
Nonstationarity in ℝnis second-order stationarity in ℝ2n
Authors: Perrin Olivier , Meiring Wendy
Published: July 2003

We prove that a nonstationary random field indexed by ℝnwith moments at least of order 2 can always be viewed as second-order stationary in ℝ2n.
A note on quasi-stationary distributions of birth–death processes and the SIS logistic epidemic
Authors: Clancy Damian , Pollett Philip K.
Published: July 2003

For Markov processes on the positive integers with the origin as an absorbing state, Ferrari, Kesten, Martínez and Picco studied the existence of quasi-stationary and limiting conditional distributions by characterizing quasi-stationary distributions as fixed points of a transformation Φ on the space of probability distributions on {1, 2, …}. In the case of a birth–death process, the components of Φ(ν) can be written down explicitly for any given distribution ν. Using this explicit representation, we will show that Φ preserves likelihood ratio ordering between distributions. A conjecture of Kryscio and Lefèvre concerning the quasi-stationary distribution of the SIS logistic epidemic follows as a corollary.
Characterizations using record moments in a random record model and applications
Authors: Nagaraja H. N. , Barlevy Gadi
Published: July 2003

We consider a random record model from a continuous parent X with cumulative distribution function F, where the number of available observations is geometrically distributed. We show that, if E(|X|) is finite, then so is E(|Rn|) whenever Rn, the nth upper record value, exists. We prove that appropriately chosen subsequences of E(Rn) characterize F and subsequences of E(Rn − Rn−1) identify F up to a location shift. We discuss some applications to the identification of wage-offer distributions in job search models.
Dermatologic and Nondermatologic Uses of Thalidomide
Authors: Nasca Maria R , Micali Giuseppe , Cheigh Nina H , West Lee E , West Dennis P
Published: July 2003

OBJECTIVE:

To review published data on thalidomide, with emphasis on current knowledge about mechanism of action, new and/or potential dermatologic and nondermatologic therapeutic applications, well-known and emerging adverse effects, and current indications for its safe use.

DATA SOURCES:

Review articles, in vitro research studies, references from retrieved articles, case reports, and clinical trials were identified from a computerized literature search using MEDLINE and OVID (1966—January 2003) and on the Cochrane Clinical Trials Register (January 2003). Information available from meetings' abstract books, Internet, or pharmaceutical companies was also considered.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified as relevant, including those from non-English literature, were considered in an attempt to provide to the reader both the theoretical basis and practical guidelines for thalidomide pharmacotherapy.

DATA SYNTHESIS:

Thalidomide has hypnosedative, antiangiogenic, antiinflammatory, and immunomodulatory properties. Moreover, it has been shown to selectively inhibit the production of tumor necrosis factor-α and reduce the expression of various integrin receptors on the membrane of leukocytes and other cell types in a dose-dependent fashion. Controlled trials demonstrated the efficacy of thalidomide in a number of diseases, including erythema nodosum leprosum, lupus erythematosus, aphthosis, graft-versus-host disease, prurigo nodularis, and actinic prurigo. Single case reports or studies in small series have also suggested a possible role for thalidomide in numerous other dermatologic and nondermatologic disorders. Possibly severe and sometimes irreversible risks related to the clinical use of thalidomide include teratogenicity and neurotoxicity.

CONCLUSIONS:

Although teratogenicity and neurotoxicity are significant adverse effects requiring cautious use, thalidomide is an effective therapeutic modality in a variety of difficult-to-treat disorders and, providing careful selection of patients, should offer an acceptable risk-to-benefit ratio.
Outcomes with Changes in Prescribing of Glycoprotein IIb/IIIa Inhibitors in PCI
Authors: Dobesh Paul P , Lanfear Sara L , Abu-Shanab Joy R , Lakamp Jonathan E , Gowda Siddhesh , Haikal Maged Y
Published: July 2003

Background

Glycoprotein IIb/IIIa receptor antagonists have been shown to have an impact on the outcomes of death/myocardial infarction (MI) in patients undergoing percutaneous coronary intervention. At our institution, tirofiban has largely replaced abciximab in an attempt to decrease costs.

Objective

To assess the impact of this change on patient outcomes in the absence of head-to-head trials.

Methods

Medical records were reviewed and telephone follow-ups were conducted on patients receiving tirofiban (n = 83) at our facility between February and November 1999. Death/MI at 30 days and 6 months after infusion were recorded. Safety and length of stay (LOS) were also assessed. These data were compared using χ2 analysis with results obtained from a previous review of abciximab use (n = 83) collected between May 1997 and November 1998.

Results

There was no difference in the baseline incidence of (1) cardiovascular risk factors, (2) prior revascularization, (3) prior MI, (4) the number of vessels with atherosclerotic disease assessed by angiography, and (5) the number of vessels receiving procedures. Death/MI trended to be worse with tirofiban versus abciximab at our institution at 30 days (4.8% abciximab vs. 12% tirofiban; p = 0.163) and 6 months (6% abciximab vs. 18.1% tirofiban; p = 0.032). Bleeding and median LOS (3 d abciximab vs. 3 d tirofiban) were not different. Despite an increase in pharmacy cost, the use of abciximab provided these outcomes without an increase in total hospital cost.

Conclusions

The perceived economically driven change in medication selection from abciximab to tirofiban may not have been appropriate based on the negative trends seen in this review. To maintain optimal patient outcomes, this change should be reevaluated.
Use and Definition of Herbal Medicines Differ by Ethnicity
Authors: Bharucha Diana X , Morling Beth A , Niesenbaum Richard A
Published: July 2003

Background

While past studies have investigated uses of and attitudes toward herbal medicines by different ethnic groups, none have assessed how people may define them.

Objective

To determine definitions of and attitudes toward herbal medicines in different ethnic groups.

Methods

Surveys were distributed to 300 people of different professions and ethnic backgrounds in northern Pennsylvania. We quantified Latino/non-Latino group similarities and differences in the following variables: which of a list of 26 substances people categorized as herbal medicines, people's intent to use herbal medicines in the future, people's attitudes toward herbal medicine use, how people described their doctors' and friends' attitudes toward herbal medicines, and people's ability to use herbal medicines. These variables were based on the Theory of Planned Behavior.

Results

The Latino sample compared with the non-Latino white sample was more likely to categorize certain foods (e.g., garlic, carrots) as herbal medicines. Non-Latinos had more negative attitudes toward herbal medicines and were less likely to intend to use them in the future. Non-Latinos were more likely to base their attitudes on those of their health professionals, whereas Latinos were more likely to base their attitudes on their ability to buy and use herbal medicines.

Conclusions

Our results suggest that pharmacists have greater potential to educate and consult with the non-Latino population regarding the use of herbal medicines, and the Latino population may be at greater risk of adverse effects from herbal medicines. Our results also suggest that, because of the ways that different groups define herbal medicines, health professionals should clarify what their clients mean when they use this term.
Potentially Inappropriate Medication Use by Elderly Mexican Americans
Authors: Raji Mukaila A , Ostir Glenn V , Markides Kyriakos S , Espino David V , Goodwin James S
Published: July 2003

BACKGROUND:

Use of inappropriate medications by the elderly is a public health concern with potentially serious health consequences. Research indicates relatively high rates of inappropriate prescription drug usage for older whites and African Americans. However, rates for older Mexican Americans are unknown.

OBJECTIVE:

To examine the prevalence and predictors of inappropriate prescription medication use by older Mexican Americans.

METHODS:

A cross-sectional study of 3050 Mexican Americans aged ≥65 years living in the southwestern US was conducted. In-home interviews in 1993 and 1994 assessed prescription medication use. Descriptive statistics and logistic regression models were used to estimate prevalence and risk of inappropriate prescription drug use.

RESULTS:

Approximately 12% (n = 365) of the sample had used at least 1 of 32 potentially inappropriate prescription medications within 2 weeks of the baseline assessment. Four drugs, chlorpropamide, propoxyphene, amitriptyline, and dipyridamole, accounted for 54% of all inappropriate prescribing. Unmarried subjects, those with ≥1 chronic diseases, high depressive symptoms, frequent physician visits, and combined Medicaid and Medicare insurance were more likely to have used at least 1 of the 32 potentially inappropriate drugs.

CONCLUSIONS:

The prevalence of inappropriate medication use is lower in older Mexican Americans than in similar white and African American populations. More studies are needed on the pattern of inappropriate prescribing over time and on intervention programs to reduce potentially adverse health outcomes in older Mexican Americans most at risk.
Dapsone-Induced Acute Pancreatitis
Authors: Jha Shivkumar H , Reddy Jyothi A , Dave Jatin K
Published: July 2003

Objective

To report a case of acute pancreatitis associated with dapsone use.

Case Summary

An 87-year-old white man was prescribed dapsone for dermatitis herpetiformis. Four weeks later, he developed acute abdominal pain requiring hospitalization. The patient had elevated serum amylase and lipase levels. Laboratory test results for other possible etiologies were negative. His symptoms resolved when dapsone was discontinued. Dapsone was reintroduced for exacerbation of dermatitis herpetiformis 4 months later. The patient again had severe abdominal pain with high amylase and lipase levels. Again, symptoms resolved following dapsone discontinuation.

Discussion

Only 1 other case of pancreatitis associated with dapsone was found in a MEDLINE search of the literature (1966–June 2003) using the key terms dapsone and pancreatitis. An objective causality assessment revealed dapsone to be a probable cause of acute pancreatitis, based on the Naranjo probability scale. Drugs should always be considered as causative factors for pancreatitis in patients without known risk factors. Dapsone is increasingly used as a second line of treatment of Pneumocystis carinii pneumonia (PCP). The recognition of dapsone-induced pancreatitis is of particular importance in these patients.

Conclusions

While dapsone is traditionally used for the treatment of leprosy and dermatitis herpetiformis, its use for PCP prophylaxis, malaria, brown recluse spider bites, and acne is not uncommon. Pancreatitis is an uncommon adverse effect of dapsone, and greater awareness of this association will prompt a high index of suspicion in an appropriate clinical setting. Further reporting of cases and clinical research of drug-induced pancreatitis is indicated.
Venous Thromboembolism Prophylaxis in a South Australian Teaching Hospital
Authors: Learhinan Elizabeth R , Alderman Christopher P
Published: July 2003

Background

Venous thromboembolism (VTE) is relatively common among hospitalized patients, is often clinically silent, and is associated with substantial morbidity and mortality. Risk stratification and routine use of thromboprophylaxis for patients at moderate to high risk for VTE are key strategies that can be used to prevent VTE.

Objective

To assess the appropriateness of the selection and implementation of thromboprophylactic measures for prevention of VTE within a South Australian teaching hospital.

Methods

Guidelines for risk stratification and prophylaxis were compiled from a range of studies, consensus statements, and tertiary references. Using prospective, observational methodology, data collection was performed through case note audit for 130 inpatient admissions over a 4-week period.

Results

The decisions regarding the usage of thromboprophylaxis were considered inappropriate in 32% of cases in the study cohort. Suboptimal practices were also observed with respect to factors including the choice between mechanical and pharmacologic methods and the timing of initiation and cessation of thromboprophylaxis.

Conclusions

These findings provide evidence suggesting that the selection and implementation of thromboprophylaxis require improvement and that appropriate means to facilitate this improvement need to be developed and evaluated through future research.
White Coat Ceremonies in US Schools of Pharmacy
Authors: Brown Daniel L , Ferrill Mary J , Pankaskie Marvin C
Published: July 2003

Background

Pharmacy and medical schools share similar concerns regarding the need to place greater emphasis on professional socialization. Many academic institutions of both professions have elected to establish a white coat ceremony to initiate the process of inculcating professional values. However, a recent literature search revealed little published information on pharmacy white coat ceremonies.

Objective

To determine the prevalence of white coat ceremonies in US schools of pharmacy and identify commonalities between ceremonies conducted at different schools.

Methods

In April 2002, a 25-question survey was sent via E-mail to the deans of the 83 accredited schools of pharmacy in the US. The survey solicited details about the nature of each school's white coat ceremony or reasons why the school does not conduct a ceremony.

Results

The first ceremony in pharmacy was held at the University of Kentucky in 1995. As of May 2002, 51 of the 83 schools had already conducted a white coat ceremony and another 10 indicated plans to initiate a ceremony by the end of the year. Telephone follow-up confirmed that, as of May 2003, the number had risen to 61 schools. Most schools conduct the ceremony during the first professional year. Common features include presentation of the coat, recitation of an oath, a speech by an honored guest, a class photograph, and a reception.

Conclusions

The white coat ceremony is a growing phenomenon in pharmacy education that could play a pivotal role in the quest to better achieve professional socialization among students.
Triclonal gammopathy in an extranodal non‐Hodgkin lymphoma patient
Authors: Tirelli Angelo , Guastafierro Salvatore , Cava Benedetto , Lucivero Giacomo
Published: July 2003

The case of a patient with an extranodal non‐Hodgkin lymphoma and three M‐components (IgGκ + IgGλ + IgMλ) in the serum is described. Three separate populations of M‐component producing cells have been identified. Since a κ→λ chain switch is not demonstrated, the synthesis of IgGκ and IgGλ by two distinct clones is obvious. IgMλ and IgGλ M‐components are synthesized by two different plasma cell populations that could represent two unrelated cell clones or, alternatively, two subclones originated by a common precursor. After chemotherapy the IgGλ M‐component is replaced by heavy γ chains without evidence of λ light chains. Am. J. Hematol. 73:273–275, 2003. © 2003 Wiley‐Liss, Inc.
Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft‐versus‐host disease
Authors: Hirayama Yasuo , Sakamaki Sumio , Tsuji Yasushi , Sagawa Tamotsu , Chiba Hiroki , Matsunaga Takuya , Kuroda Hiroyuki , Kusakabe Toshiro , Akiyama Takehide , Kato Junji , Niitsu Yoshiro
Published: July 2003

Thrombocytopenia is well known to be one of the clinical manifestations of chronic graft‐versus‐host disease (cGVHD). However, there exist cases in which the cause of thrombocytopenia has been unexplained. Recently, thrombopoietin (TPO) from bone marrow (BM) stromal cells and transforming growth factor (TGF)‐β from platelets and megakaryocytes have been identified as strong positive and negative regulators of megakaryopoiesis in vivo. We hypothesized that the decreased TPO production from BM could be one of the causes of thrombocytopenia in the patients with cGVHD. In the present study, therefore, TPO and TGF‐β concentrations in peripheral blood (PB) and BM were measured serially in two patients with acute leukemia who had received fully matched stem cell transplantation from relatives and subsequently developed extensive cGVHD with thrombocytopenia. The results showed that platelet numbers correlated well with the TPO concentrations, which were consistently higher in BM than in PB. The difference in TPO concentrations between BM and PB was decreased when the platelet levels were low, indicating that the amount of TPO production from BM decreased throughout the duration of thrombocytopenia. TGF‐β concentrations were normal during all periods in which measurements were carried out. Thus, our results suggest that one mechanism of thrombocytopenia in patients with cGVHD is low TPO production by BM cells. Am. J. Hematol. 73:285–289, 2003. © 2003 Wiley‐Liss, Inc.
Acquired and reversible Pelger‐Huët anomaly of polymorphonuclear neutrophils in three transplant patients receiving mycophenolate mofetil therapy
Authors: Asmis Lars M. , Hadaya Karine , Majno Pietro , Toso Christian , Triponez Frédéric , Starobinski Michel
Published: July 2003

Deficient nuclear segmentation and abnormal chromatin condensation define Pelger‐Huët anomaly of polymorphonuclear neutrophils. Next to the hereditary irreversible form, acquired forms both reversible and irreversible have been described. We describe three transplant patients who were all investigated for a left shift in the absence of symptoms or signs of infection and in whom acquired reversible Pelger‐Huët anomaly was discovered. The abnormal PMN phenotype was induced by mycophenolate mofetil (MMF). MMF is a necessary but not sufficient condition for the development of the anomaly. In our three patients a dose–response effect was observed regarding plasma MMF concentration and severity of neutrophil dysplasia. Except for one slightly elevated value, the patients' plasma MMF levels were within the therapeutic range. None of the patients, one who was neutropenic at presentation and two who were non‐neutropenic, developed infectious complications. From our three cases as well as those of other authors, we identify previous graft rejection episodes as a potential predisposing factor for the development of PHA. In the first patient, drug withdrawal led to normalization of PMN morphology. In the other two patients, the left shift disappeared after dose reduction. In these latter two patients, a form of desensitization to the effect of MMF on neutro‐ phils was observed following re‐augmentation of MMF dose. Am. J. Hematol. 73:244–248, 2003. © 2003 Wiley‐Liss, Inc.
Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions
Authors: Walmet Paula S. , Eckman James R. , Wick Timothy M.
Published: July 2003

Adherence of sickle erythrocytes to endothelium in venules is thought to initiate or propagate vaso‐occlusive episodes. Because of blood shear forces with normal microvascular flow, adherence in post‐capillary venules requires binding via high‐affinity receptor‐mediated pathways. Microvascular flow in sickle patients is episodic, even in asymptomatic patients, so adherence may also occur at low shear not requiring high‐affinity binding. Sickle cell binding to endothelium was quantified under flow or static incubation with unusually large vWF, thrombospondin, α4β1/VCAM‐1 or α4β1/fibronectin (FN). Adherence under flow at 0.5 dyne/cm2 shear stress leads to the greatest number of adherent sickle cells. Adherence under flow at 1.0 dyne/cm2 leads to the strongest adherence. Static incubation conditions promote weak adherence of low numbers of sickle cells to endothelium. Following attachment at 1.0 dyne/cm2, adherence strength was 2.5 ± 0.1 or 2.6 ± 0.2 dynes/cm2 for α4β1/VCAM‐1 or α4β1/FN pathways, a level 50% greater than adherence strength mediated by thrombospondin or ULvWF (1.7 ± 0.08 or 1.6 ± 0.07 dynes/cm2, respectively). Sickle cell adhesion promoted by simultaneous activation of α4β1/VCAM‐1 and α4β1/FN pathways is the strongest at 6.2 ± 0.2 dynes/cm2 and adherent red cells resist detachment shear stresses up to 10 dynes/cm2. These data demonstrate that sickle cell adhesion to endothelium is regulated both by receptor/ligand affinity and flow conditions. Thus, both microvascular flow conditions and receptor–ligand interactions may regulate sickle cell adherence in vivo. Am. J. Hematol. 73:215–224, 2003. © 2003 Wiley‐Liss, Inc.
D‐dimer assay in Gaucher disease: Correlation with severity of bone and lung involvement
Authors: Shitrit David , Rudensky Bernard , Zimran Ari , Elstein Deborah
Published: July 2003

The D‐dimer assay as a marker of cross‐linked fibrin may also be an indicator of active microvascular thrombosis, even in patients without overt hypercoagulation. In type I Gaucher disease, there is tremendous phenotypic variability that cannot be ascribed solely to different genotypes. Thus, there are no predictive tests to ascertain patients at risk for bone involvement, such as avascular necrosis, or lung disease, particularly pulmonary hypertension, which are two of the major causes of morbidity in Gaucher disease and which are slow to respond to enzyme replacement therapy. Previous studies to correlate these parameters with thrombophilic profiles have not been conclusive. Levels of D‐dimers were assayed and compared to the presence of avascular necrosis and abnormally elevated TI gradient among other variables, in 118 unselected adult patients (52 males) with Gaucher disease. Of these, 19 patients had very mild Gaucher disease (Severity Score Index, SSI < 5) and 23 had severe disease (SSI > 15); 29 had avascular necrosis; 37 were splenectomized (due to massive splenomegaly and hypersplenism). As an indirect measure of pulmonary hypertension, TI gradient was used: 90 patients had normal TI gradients (<25 mmHg), and 12 patients had abnormal TI gradients (>30 mmHg). There were significant correlations between D‐dimers and avascular necrosis, splenectomy, and elevated TI gradient. Thus, the D‐dimer assay may be potentially predictive of bone and lung involvement in Gaucher disease. Am. J. Hematol. 73:236–239, 2003. © 2003 Wiley‐Liss, Inc.
Early lymphopenia as a risk factor for chemotherapy‐induced febrile neutropenia
Authors: Choi Chul Won , Sung Hwa Jung , Park Kyong Hwa , Yoon So Young , Kim Seok Jin , Oh Sang Cheul , Seo Jae Hong , Kim Byung Soo , Shin Sang Won , Kim Yeul Hong , Kim Jun Suk
Published: July 2003

Febrile neutropenia (FN) is a frequent complication of cancer chemotherapy, which causes death in 4–21% of patients and worsens the quality of life of patients. As a simple and accurate way of identifying patients who are at risk of FN, a lymphocyte count on post‐chemotherapy day 5 was suggested. To confirm the feasibility of this method and to define the incidence of FN among our own patient group, we conducted this prospective study. From September 2001 to February 2002, patients who received cytotoxic chemotherapy at Guro Hospital, Korea University, were enrolled. Blood sampling for a complete blood count was done on the starting day of chemotherapy and on day 3 and day 5 post‐chemotherapy. The prospective results of the CBC were compared between the FN group and non‐FN group. During the study period, 82 patients were enrolled. The male to female ratio was 52:30, and the median age was 56 years old (range: 14–78). Underlying malignancies were non‐Hodgkin's lymphoma (14 patients), stomach cancer (17), breast cancer (11), NSCLC (7), hepatobiliary cancer (10), sarcoma (3), colorectal cancer (3), and others (17). The incidence of FN was 18% (15/82 patients), and ANC at the time of FN was 275 ± 327/μl. Duration of fever was 3.9 ± 3.5 days. The incidence of FN was significantly higher in patients with lymphocyte counts at day 3 ≤ 500/μl (P = 0.06), day 5 ≤ 500/μl (P = 0.023), day 3 ≤ 700/μl (P = 0.01), and day 5 ≤ 700/μl (P = 0.0001). As a result of a logistic regression test, a day‐5 lymphocyte count ≤ 700/μl was identified as an independent risk factor for FN.

In conclusion, a day‐5 lymphocyte count <700/μl was a risk factor for FN. To strengthen our result, we are planning to validate in a larger patient group. Am. J. Hematol. 73:263–266, 2003. © 2003 Wiley‐Liss, Inc.
Imatinib in Philadelphia chromosome‐positive chronic phase CML patients: Molecular and cytogenetic response rates and prediction of clinical outcome
Authors: le Coutre Philipp , Kreuzer Karl‐Anton , Na Il‐Kang , Schwarz Michaela , Lupberger Joachim , Holdhoff Matthias , Baskaynak Gökben , Gschaidmeier Harald , Platzbecker Uwe , Ehninger Gerhard , Prejzner Witold , Huhn Dieter , Schmidt Christian A.
Published: July 2003

Previous clinical trials with the tyrosine kinase inhibitor imatinib in chronic‐phase Philadelphia chromosome‐positive chronic myelogenous leukemia (CML) resulted in 95% of hematologic and 60% major cytogenetic remissions in patients who failed a previous interferon‐α‐containing regimen. In an identical clinical trial setting with 39 chronic‐phase CML patients we achieved comparable cytogenetic response rates after a median follow up of 30.1 weeks, with an almost identical toxicity profile. In order to identify predictive markers for the therapeutical use of imatinib, we monitored apart from standard hematology parameters bcr/abl fusion transcripts by quantitative real‐time fluorescence RT‐PCR. As previous investigations demonstrated that the plasma protein α‐1 acid glycoprotein might inactivate circulating levels of free imatinib by protein binding with high affinity, we assessed plasma α‐1 acid glycoprotein concentrations in our study cohort as well. Median bcr/abl fusion transcripts declined gradually over the entire treatment period and became significantly lowered at month 3 after initiation of imatinib therapy. Further, we observed elevated pretreatment levels of α‐1 acid glycoprotein in patients who relapsed with leukemia, whereas initial bcr/abl mRNA copy numbers were not of predictive value. In addition, we provide data showing molecular response to this therapy in the vast majority of patients. Finally, our results support the hypothesis, that initially elevated plasma levels of α‐1 acid glycoprotein might serve as a predictive marker for the clinical outcome of treatment with imatinib. Am. J. Hematol. 73:249–255, 2003. © 2003 Wiley‐Liss, Inc.
HLA system affects the age‐at‐onset in chronic myeloid leukemia
Authors: Oguz Fatma Savran , Kalayoglu Sevgi , Diler A. Sarper , Tozkir Hilmi , Sargin Deniz , Carin Mahmut , Dorak M. Tevfik
Published: July 2003

Chronic myeloid leukemia (CML) occurs from childhood to old age. The adult form is characterized by the presence of Philadelphia chromosome resulting from bcr/abl translocation. The BCR–ABL fusion proteins are immunogenic, and the junctional sequences show unique HLA class I and class II restriction patterns in vitro. A previous study in the west of Scotland showed an influence of several HLA genotypes on the age‐at‐onset of CML. In the present study, we examined the HLA‐A, ‐B, and ‐DRB1/3/4/5 allele and haplotype distributions in Turkish CML patients diagnosed in a single center where they are routinely HLA‐typed by PCR‐SSP analysis as a preparation for stem cell transplantation. The patients were 169 subjects of age 17–60 years. The older patients were not HLA typed and missing from the study group. The age‐matched control group (n = 213) was healthy blood donors from the same geographical area. HLA‐B*37 showed a risk association with CML [P = 0.02; odds ratio (OR) = 5.35]. The DRB1*10 association at similar magnitude was due to its linkage disequilibrium (LD) with B*37. HLA‐B*35 and DRB1*11 showed independent protective effects (P = 0.007 and 0.017; OR = 0.54 and 0.60, respectively). The protective association of DRB1*11 may be due to its involvement in the presentation of the common (b3a2) fusion gene. HLA‐B*14 and DRB1*01 showed strong LD, and all 5 patients who were positive for the presumed haplotype B*14‐DRB1*01 were of age 43 years old or older (P = 0.003), suggesting a delay effect. We also examined the influence of homozygosity for DRB3 (DR52) and DRB4 (DR53) haplotypes on susceptibility. As previously shown in CML and CLL, DRB4 homozygosity was a risk marker (P = 0.01; OR = 3.36), and DRB3 homozygosity was protective (P = 0.007; OR = 0.51). Despite the lack of elderly patients in the study group, the opposite accelerating (DRB4) and delaying (DRB3) effects of homozygous genotypes on the age‐at‐onset were evident. Besides replicating previously found associations in a different population, this study also suggested new, and probably population‐specific associations in CML. The mechanisms by which the HLA system modifies susceptibility to CML are unknown, likely to include immune and nonimmune ones, and worthy of further studies. Am. J. Hematol. 73:256–262, 2003. © 2003 Wiley‐Liss, Inc.
Deep vein thrombosis followed by internal jugular vein thrombosis as a complication of in vitro fertilization in a woman heterozygous for the prothrombin 3′ UTR and factor V Leiden mutations
Authors: McGowan B.M.C. , Kay L.A. , Perry D.J.
Published: July 2003

Thrombosis of the internal jugular vein is a rare event but one that can have serious consequences. Most cases reported in the literature have occurred in patients with indwelling central venous catheters, in association with head and neck sepsis, or in hypercoagulable states. However, a small number of cases have been associated with in vitro fertilization and more often with the ovarian hyperstimulation syndrome (OHSS). We report the case of a 30‐year‐old woman heterozygous for both the prothrombin 3′ UTR mutation and for the factor V Leiden mutation who presented with a proximal deep vein thrombosis following in vitro fertilization. She subsequently developed an internal jugular vein thrombosis extending into the subclavian and axillary vein despite therapeutic anticoagulation with a low molecular weight heparin. Thromboembolic events can occur in the absence of other clinical features of OHSS, especially in patients with underlying prothrombotic abnormalities. Neck pain and swelling in a pregnant woman, especially one that has undergone in vitro fertilization, should be taken seriously and investigated with duplex scanning and/or MRI. Women with a personal or family history of thrombosis undergoing in vitro fertilization should be made fully aware of the potential thrombotic risks and should be considered for a thrombophilia screen. Am. J. Hematol. 73:276–278, 2003. © 2003 Wiley‐Liss, Inc.