bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor angiogenesis in the bone marrow of multiple myeloma patients and its alteration by thalidomide treatment
Authors: Du Wenlin , Hattori Yutaka , Hashiguchi Akinori , Kondoh Kensuke , Hozumi Nobumichi , Ikeda Yasuo , Sakamoto Michiie , Hata Jun‐ichi , Yamada Taketo
Published: April 2004

Angiogenesis in solid tumors is important to tumor growth, invasion and metastasis. Recently, it has been suggested that angiogenesis plays a certain role in the development of hematopoietic malignancies, including leukemia and multiple myeloma. We evaluated tumor angiogenesis in the bone marrow (BM) of multiple myeloma (MM) patients by calculating microvessel density (MVD) in needle‐biopsy specimens obtained from 51 cases of untreated MM or monoclonal gammopathy of undetermined significance (MGUS). The MVD in the BM of donors for transplantation and patients with non‐hematological diseases was calculated as a control. There was an obvious increase in MVD in the BM of MM patients, and the MVD correlated with the grade of myeloma cell invasion of the BM in the untreated MM cases. It was recently reported that thalidomide might be effective for the treatment of MM. We assessed the effect of thalidomide on angiogenesis in BM treatment of 11 patients with refractory MM. The concentration of M‐protein in the serum or urine of seven of the 11 patients was reduced by at least 30% after thalidomide treatment, and MVD in the BM decreased in three of these seven cases in response to thalidomide. Increased plasma concentrations of basic fibroblast growth factor (FGF‐2) and vascular endothelial growth factor (VEGF) were observed in all 11 cases before thalidomide administration and both levels were reduced after treatment with thalidomide. Augmented angiogenesis in the bone marrow of MM patients was confirmed in the present study. It seems that thalidomide is effective in the treatment of MM through the impairment of angiogenesis by decreasing FGF‐2 and VEGF production. This is the first report on pathological evidence in the bone marrow of MM before and after thalidomide treatment, in Japan.
Re‐evaluation of mucin phenotypes of gastric minute well‐differentiated‐type adenocarcinomas using a series of HGM, MUC5AC, MUC6, M‐GGMC, MUC2 and CD10 stains
Authors: Shiroshita Hidefumi , Watanabe Hidenobu , Ajioka Yoichi , Watanabe Gen , Nishikura Ken , Kitano Seigo
Published: April 2004

We examined which, and how many, mucin markers are necessary to define the phenotypes of gastric cancers, and re‐evaluated the incidence of their mucin phenotypes and whether minute gastric carcinomas arise as unclassified type. Well‐differentiated‐type minute gastric carcinomas (n = 33) measuring ≤5 mm were examined using human gastric mucin (HGM) and MUC5AC, MUC6 and M‐GGMC‐1 (or paradoxical concanavalin A type III mucin (Con A)), MUC2 and CD10 stains, and a new method to separate the previous intestinal type into intestinal type and small intestinal type. The phenotypes of carcinomas were classified into gastric, gastrointestinal, intestinal, small intestinal, and unclassified types. MUC5AC or HGM, MUC6, MUC2, and CD10 stains were all necessary to define gastric cancer phenotypes. The incidence of gastric, gastrointestinal, intestinal, small intestinal, and unclassified type was 6%, 49%, 0%, 45%, and 0%, respectively, when the percentage of positive mucin phenotype was set at >0%, and was 33%, 33%, 3%, 30%, and 0%, respe‐ctively, when the percentage of positive mucin phenotype was set at ≥10%. Thus, a panel of MUC5AC (or HGM), MUC6, MUC2 and CD10 stains is indispensable for accurately determining the mucin phenotypes of gastric carcinomas, and the above‐mentioned classification is important for studying changes in the histological types of well‐differentiated‐type adenocarcinomas during change to the poorly differentiated type, as well as corresponding genetic abnormalities.
Inflammatory response and cathepsins in silica‐exposed Hermansky–Pudlak syndrome model pale ear mice
Authors: Yoshioka Yasuko , Kumasaka Toshio , Ishidoh Kazumi , Kominami Eiki , Mitani Keiko , Hosokawa Yoshinori , Fukuchi Yoshinosuke
Published: April 2004

Hermansky–Pudlak syndrome (HPS) is a hereditary disorder involving the sorting processes of intracellular organelles such as lysosomes of reticuloendothelial cells. Pale ear (ep) mouse is known to have the HPS1 gene mutation, which is seen in patients with HPS and pulmonary fibrosis. As pulmonary fibrosis is not spontaneously observed in ep mice, we hypothesized that external stimuli are necessary for the genetic predisposition of its development. We used silica as the external stimulus to induce the alveolar macrophage‐mediated inflammatory response and evaluated the pathological changes of the lung and biochemical analysis of collagenolytic lysosomal enzymes cathepsins L and B in ep mice. Treatment with silica induced the following: persistent accumulation of activated macrophages; delayed clearance of silica from alveolar spaces; and increased collagen fibers in alveolar tissues, which were shown with trichrome staining in ep mice. The comparison of bronchoalveolar lavage cells between the naïve ep and control mice revealed: decreased enzymatic activities but increased antigenic levels of cathepsins L and B, resulting in significantly lower ratios of activity to antigen; increased ceroid deposits and cathepsin L antigens in lysosomes; and no abnormal forms of cathepsins were detected. After silica instillation, activities of cathepsin L in the ep mice increased but ratios of activity to antigen were still significantly low. These phenomena induced by silica suggest that external stimuli bring forth fibrogenesis in the animal models or humans that have HPS1 gene mutation.
Towards Administrative Human Rights in the EU. Impact of the Charter of Fundamental Rights
Authors: Ka´nska Klara
Published: April 2004

Abstract:  This article analyses the development of administrative human rights in the EU. It demonstrates that the new right to good administration enshrined in Article 41 of the Charter of Fundamental Rights crowns a long process of constitutionalisation of basic administrative rights in the Community. The article discusses the meaning, content, and possible impact of Article 41 of the Charter. It explains, inter alia, the doctrinal basis of a ‘right to good administration’, and its more immediate origins. It also offers a textual analysis and commentary of Article 41. Other rights, which possibly come within the concept of ‘good administration’ but are not included in Article 41, are also suggested. The article concludes with an evaluation of Article 41 of the Charter. It argues that although Article 41 is a significant development in terms of individual administrative rights, it offers a one‐sided vision of the function of administrative law.
Dominant Rail Undertakings under European Competition Policy
Authors: Stehmann Oliver , Zellhofer Georg
Published: April 2004

Abstract:  For the last 30 years, railway transport has been in steep decline within the Community. It is argued that such a decline is not inevitable, but it is partly due to regulatory distortions that favour other transport modes. As a result of the delay in liberalisation, railways lose out in comparison to air and road transport where market opening triggered a restructuring process of the industry much earlier. An important step towards more competition has been taken with a new ‘railway package’, which liberalises rail freight transport from 2003 on. This article gives an overview of recent developments in the sector, including the status quo of liberalisation and the recently adopted legislation. Taking into account recent jurisprudence, it then analyses competition policy issues with a focus on obligations that arise for dominant railway companies under Article 82 EC. The article lastly discusses what structural changes are required to deal with structural obstacles to a competitive European railway market. It is argued that a complete separation of infrastructure operation and transport services would be the solution most compatible with the railway directives and Article 86 EC.
Oskar Rosenfeld and the Realism of Holocaust‐History: On Sex, Shit, and Status
Authors: Lang Berel
Published: April 2004

In the Beginning was the Ghetto: 890 Days in Lodz. By Oskar Rosenfeld. Edited and with an Introduction by Hanno Loewy; Translated by Brigitte M. Goldstein
The use of pyruvic acid in the treatment of acne
Authors: Cotellessa C , Manunta T , Ghersetich I , Brazzini B , Peris K
Published: April 2004

Background  Acne is one of the most common dermatological diseases, affecting about 50% of adolescents. Different chemical peelings are used in local treatment, either alone or in association with other therapies.

Objective  To evaluate the efficacy and tolerability of chemical peeling with pyruvic acid for treatment of mild to moderate papulo‐pustular acne.

Methods  We conducted an open‐label study in which patients affected by mild to moderate papulo‐pustular acne were treated with 40–50% pyruvic acid every 2 weeks for a total of 3–4 months. Forty patients (26 women and 14 men), ranging in age from 18 to 30 years, were enrolled in the study. Evaluations of sebum production and skin hydration were performed before and after treatment in 24 patients.

Results  Complete remission was observed in 16 patients (40%), partial remission was detected in 20 patients (50%), and no improvement was seen in four patients (10%). No side‐effects were observed during or after treatment. Post‐treatment evaluation of sebum production in 24 patients revealed a reduction in sebum levels in all patients. Post‐treatment values of cutaneous hydration did not vary significantly from pretreatment values in the 24 patients evaluated.

Conclusions  The results of our study indicate that peeling with pyruvic acid can be considered an effective, safe and well‐tolerated procedure in the treatment of patients affected by mild to moderate papulo‐pustular acne.
The effect of extracorporeal photopheresis on intracellular cytokine expression in chronic cutaneous graft‐versus‐host disease
Authors: Darvay A , Salooja N , Russell‐Jones R
Published: April 2004

Background  Cytokines derived from T helper (Th)1 lymphocytes are thought to be involved in the pathogenesis of graft‐versus‐host disease (GVHD) and extracorporeal photopheresis (ECP) has been reported to affect Th1/Th2 lymphocyte ratios. It may also influence the balance of cytotoxic Tcells (Tc1/Tc2).

Objectives  This study was formulated to assess the effect of ECP on the cytokine profiles of peripheral blood (PB) lymphocytes from patients with chronic GVHD.

Patients and methods  Nine patients were studied. Peripheral blood was sampled at baseline and between 3 and 4 months of therapy when clinical effects are demonstrable. Intracellular cytokine production was assessed in vitro by stimulating PB lymphocytes with phorbol‐12‐myristate 13‐acetate (PMA), inhibiting cytokine release and staining with fluorescein‐labelled monoclonal antibodies to interleukin (IL)‐2, interferon gamma (IFN‐γ) and IL‐4. Flow cytometry analysis gave the absolute number and the percentage of cells expressing a particular cytokine within each lymphocyte subset.

Results  Absolute counts of CD3, CD4, CD8, CD19 and CD16+ cells per microlitre were recorded before and after ECP. There was a small but non‐significant reduction in all subsets after 3 months of ECP. The percentage of cells expressing IL‐2 and IFN‐γ rose following ECP in both the CD4 and CD8 subsets. However, only the percentage of CD4 cells expressing IFN‐γ reached statistical significance (P = 0.02; 95% confidence interval, CI 0.6–15.6). There were no significant changes in the percentage of CD4 cells expressing IL‐4.

Conclusions  Our findings appear to be inconsistent with current theories regarding the pathogenesis of GVHD as increased production of Th1 or Tc1 cytokines might be expected to exacerbate GVHD. However, chronic GVHD is characterized by a relative deficiency of IL‐2 and IFN‐γ producing cells compared with other patients post‐bone marrow transplantation (BMT). This indicates that Th1 and Tc1 cytokines are depleted in chronic GVHD. Thus, by reducing disease activity, ECP could allow cytokine production by these cells to recover. This indicates that the therapeutic effect of ECP is mediated by a different mechanism, and that the changes observed in this study are epiphenomena.
Pyogenic granulomas following topical application of tretinoin
Authors: Teknetzis A , Ioannides D , Vakali G , Lefaki I , Minas A
Published: April 2004

Topical tretinoin is used in the treatment of acne and other dermatoses. The most common side‐effects are itching, dryness and reddening of the skin. We report an additional cutaneous reaction, which occurred in patients using topical tretinoin. Pyogenic granulomas developed in two patients with acne and in one with dermatofibroma following application of tretinoin. The granulomas grew on the lesions after 2–3 weeks of therapy initiation. All patients were men and the granulomas developed in their trunk. The lesions resolved when topical tretinoin was ceased. Although the number of patients reported is too small to estimate the true incidence of this reaction, it is likely that dermatologists will encounter similar reactions in patients treated with topical tretinoin for acne or other reasons.
Cutaneous basosquamous carcinoma infiltrating cerebral tissue
Authors: Şendur N , Karaman G , Dikicioglu E , Karaman CZ , Savk E
Published: April 2004

Basosquamous carcinoma of the skin is a rare malignancy with specific histopathological features of both basal cell carcinoma and squamous cell carcinoma. Some authors believe that basosquamous carcinoma is a variant of basal cell carcinoma, while others suggest that this tumour may behave more aggressively.

 We present a 44‐year‐old female patient who was diagnosed with a basosquamous carcinoma histopathologically. She had extensive ulcero‐vegetative lesions, involving the anterior half of the scalp, the left orbit and the left side of the face. With this case we aim to emphasize the aggressive nature of basosquamous carcinoma and review the literature.
Serum interleukin‐6, procalcitonin and C‐reactive protein levels in subjects with active Behçet's disease
Authors: Adam B , Calikoglu E
Published: April 2004

Background  Erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) and cytokines, including serum interleukin (IL)‐6, IL‐8 and IL‐10, and tumour necrosis factor‐alpha (TNF‐α) have been proposed as disease activity markers in Behçet's disease (BD), although studies have shown conflicting results for IL‐6. Serum procalcitonin (PCT) levels in active BD have not yet been investigated.

Objective  The aim of the present study was to determine the reliability of serum IL‐6 and PCT levels as well as CRP as biological markers for activity of BD.

Methods  Serum PCT, IL‐6 and CRP protein levels were measured in patients with active BD (n = 15) and in healthy control subjects (n = 15). IL‐6 and PCT levels were measured in serum by chemiluminescent assay. In addition, a nephelometric method was used to analyse CRP concentrations in serum.

Results  Serum CRP and IL‐6 values were significantly higher in the subjects with active disease than in the healthy controls (P < 0.05), but there was no significant difference in the levels of PCT in the two groups.

Conclusion  The results of our study suggest that serum CRP and IL‐6 levels are elevated in patients with active BD, but that serum PCT values are not elevated in these patients.
Closing the feedback loop: an audit of the use of imiquimod for the treatment of genital warts
Authors: Brady S , Wilson JD
Published: April 2004

A retrospective case‐note audit of 74 patients with 81 treatment episodes of anogenital warts with imiquimod from April 1999 until July 2000 was performed. The majority of patients had failed to clear their warts with other treatments, had recurrences after other treatments, or had other medical problems complicating their genital wart treatment.

 The overall clinically confirmed complete clearance rate was 33%. This is lower than other published data, but may be so because it includes patients with immunosuppression and difficult‐to‐treat warts. The complete clearance rate in immunocompetent patients was 37%. In addition, in this audit of clinical practice 17% of the patients did not return for full response to be assessed. The complete clearance rate in those who were able to tolerate treatment and who returned for follow‐up was 45%.

 Based on the results of the audit we have extended the indications for the use of imiquimod in the clinic treatment guidelines. Patients are now offered imiquimod if six or more episodes of other treatments fail to give a good response. Earlier treatment with imiquimod is also offered to those patients with recurrent anogenital warts, and it is recommended as a first‐line therapy for patients with multiple keratinized warts.
What Determines Corporate Transparency?
Authors: BUSHMAN ROBERT M. , PIOTROSKI JOSEPH D. , SMITH ABBIE J.
Published: April 2004

We investigate corporate transparency, defined as the availability of firm‐specific information to those outside publicly traded firms. We conceptualize corporate transparency within a country as output from a multifaceted system whose components collectively produce, gather, validate, and disseminate information. We factor analyze a range of measures capturing countries' firm‐specific information environments, isolating two distinct factors. The first factor, interpreted as financial transparency, captures the intensity and timeliness of financial disclosures, and their interpretation and dissemination by analysts and the media. The second factor, interpreted as governance transparency, captures the intensity of governance disclosures used by outside investors to hold officers and directors accountable. We investigate whether these factors vary with countries' legal/judicial regimes and political economies. Our main multivariate result is that the governance transparency factor is primarily related to a country's legal/judicial regime, whereas the financial transparency factor is primarily related to political economy.
Investor Protection and Corporate Governance: Evidence from Worldwide CEO Turnover
Authors: DEFOND MARK L. , HUNG MINGYI
Published: April 2004

Recent research asserts that an essential feature of good corporate governance is strong investor protection, where investor protection is defined as the extent of the laws that protect investors' rights and the strength of the legal institutions that facilitate law enforcement. The purpose of this study is to test this assertion by investigating whether these measures of investor protection are associated with an important role of good corporate governance: identifying and terminating poorly performing CEOs. Our tests indicate that strong law enforcement institutions significantly improve the association between CEO turnover and poor performance, whereas extensive investor protection laws do not. In addition, we find that in countries with strong law enforcement, CEO turnover is more likely to be associated with poor stock returns when stock prices are more informative. Finding that strong law enforcement institutions are associated with improved CEO turnover‐performance sensitivity is consistent with good corporate governance requiring law enforcement institutions capable of protecting shareholders' property rights (i.e., protecting shareholders from expropriation by insiders). Finding that investor  protection laws are not associated with improved CEO turnover‐performance sensitivity is open to several explanations. For example, investor protection laws may not be as important as strong law enforcement in fostering good governance, the set of laws we examine may not be the set that are most important in promoting good governance, or measurement error in our surrogate for extensive investor protection laws may reduce the power of our test of this variable.
Transitional Care of Older Adults Hospitalized with Heart Failure: A Randomized, Controlled Trial
Authors: Naylor Mary D. , Brooten Dorothy A. , Campbell Roberta L. , Maislin Greg , McCauley Kathleen M. , Schwartz J. Sanford
Published: April 2004

Objectives: To examine the effectiveness of a transitional care intervention delivered by advanced practice nurses (APNs) to elders hospitalized with heart failure.

Design: Randomized, controlled trial with follow‐up through 52 weeks postindex hospital discharge.

Setting: Six Philadelphia academic and community hospitals.

Participants: Two hundred thirty‐nine eligible patients were aged 65 and older and hospitalized with heart failure.

Intervention: A 3‐month APN‐directed discharge planning and home follow‐up protocol.

Measurements: Time to first rehospitalization or death, number of rehospitalizations, quality of life, functional status, costs, and satisfaction with care.

Results: Mean age of patients (control n=121; intervention n=118) enrolled was 76; 43% were male, and 36% were African American. Time to first readmission or death was longer in intervention patients (log rank χ2=5.0, P=.026; Cox regression incidence density ratio=1.65, 95% confidence interval=1.13–2.40). At 52 weeks, intervention group patients had fewer readmissions (104 vs 162, P=.047) and lower mean total costs ($7,636 vs $12,481, P=.002). For intervention patients, only short‐term improvements were demonstrated in overall quality of life (12 weeks, P<.05), physical dimension of quality of life (2 weeks, P<.01; 12 weeks, P<.05) and patient satisfaction (assessed at 2 and 6 weeks, P<.001).

Conclusion: A comprehensive transitional care intervention for elders hospitalized with heart failure increased the length of time between hospital discharge and readmission or death, reduced total number of rehospitalizations, and decreased healthcare costs, thus demonstrating great promise for improving clinical and economic outcomes.
Effect of Hip Fracture on Mortality in Elderly Women: The EPIDOS Prospective Study
Authors: Empana Jean‐Philippe , Dargent‐Molina Patricia , Bréart Gérard ,   for the EPIDOS Group
Published: April 2004

Objectives: To assess whether the occurrence of a hip fracture is associated with an increased risk of mortality even after taking into account age and prefracture health status and whether this increased risk of mortality persists beyond the first 6 months after the fracture.

Design: A prospective study of risk factors for hip fracture.

Setting: Five French areas: Amiens, Lyon, Montpellier, Paris, and Toulouse.

Participants: The cohort consisted of 7,512 volunteer ambulatory women aged 75 and older who were recruited from voter registration lists. Women who had a history of hip fracture or bilateral hip replacement were excluded.

Measurements: The baseline examination included a functional and clinical examination and a questionnaire on life style and treatments. Thereafter, women were followed every 4 months for 4 years to record the occurrence of fractures and deaths. A multivariable proportional hazards model was used to determine the association between hip fracture (treated as a time‐dependent variable) and mortality, after adjustment for age and baseline health status.

Results: During a mean±standard deviation follow‐up of 3.9±0.9 years, 338 women had a first hip fracture, and their postfracture mortality rate was 112.4 per 1,000 woman‐years, compared with 27.3 per 1,000 woman‐years for the 6,115 women who did not have any fracture (P<.001). After adjusting for age and baseline health status, women with hip fracture were more than twice as likely to die (95% confidence interval (CI)=1.6–2.8). This increased risk appeared more pronounced in the first 6 months (relative risk (RR)=3.0, 95% CI=1.9–4.7) than after (RR=1.9, 95% CI=1.6–2.2) (P=.09).

Conclusion: In ambulatory elderly women, the occurrence of a hip fracture is associated with an increased risk of death, even after prefracture health status is taken into account. Although the effect of the fracture is stronger in the first 6 months, it persists for several years thereafter, which suggests that prevention of hip fracture and improved care after the fracture may contribute to increase life expectancy in addition to preserving quality of life.
Infections and Functional Impairment in Nursing Home Residents: A Reciprocal Relationship
Authors: Büla Christophe J. , Ghilardi Giuseppe , Wietlisbach Vincent , Petignat Christiane , Francioli Patrick
Published: April 2004

Objectives: To determine the relationship between infections and functional impairment in nursing home residents.

Design: Prospective cohort study (follow‐up period, 6 months).

Setting: Thirty‐nine nursing homes in western Switzerland.

Participants: A total of 1,324 residents aged 65 and older (mean age 85.7; 76.6% female) who agreed to participate, or their proxies, by oral informed consent.

Measurements: Functional status measured every 3 months. Two different outcomes were used: (a) functional decline defined as death or decreased function at follow‐up and (b) functional status score using a standardized measure.

Results: At the end of follow‐up, mortality was 14.6%, not different for those with and without infection (16.2% vs 13.1%, P=.11). During both 3‐month periods, subjects with infection had higher odds of functional decline, even after adjustment for baseline characteristics and occurrence of a new illness (adjusted odds ratio (AOR)=1.6, 95% confidence interval (CI)=1.2–2.2, P=.002, and AOR=1.5, 95% CI=1.1–2.0, P=.008, respectively). The odds of decline increased in a stepwise fashion in patients with zero, one, and two or more infections. The analyses predicting functional status score (restricted to subjects who survived) gave similar results. A survival analysis predicting time to first infection confirmed a stepwise greater likelihood of infection in subjects with moderate and severe impairment at baseline than in subjects with no or mild functional impairment at baseline.

Conclusion: Infections appear to be both a cause and a consequence of functional impairment in nursing home residents. Further studies should be undertaken to investigate whether effective infection control programs can also contribute to preventing functional decline, an important component of these residents' quality of life.
Hospice Admission Practices: Where Does Hospice Fit in the Continuum of Care?
Authors: Lorenz Karl A. , Asch Steven M. , Rosenfeld Kenneth E. , Liu Hui , Ettner Susan L.
Published: April 2004

Objectives: To evaluate selected hospice admission practices that could represent barriers to hospice use and the association between these admission practices and organizational characteristics.

Design: From December 1999 to March 2000, hospices were surveyed about selected admission practices, and their responses were linked to the 1999 California Office of Statewide Health Planning and Development's Home and Hospice Care Survey that describes organizational characteristics of California hospices.

Setting: California statewide.

Participants: One hundred of 149 (67%) operational licensed hospices.

Measurements: Whether hospices admit patients who lack a caregiver; would not forgo hospital admissions; or are receiving total parenteral nutrition (TPN), tube feedings, radiotherapy, chemotherapy, or transfusions.

Results: Sixty‐three percent of hospices restricted admission on at least one criterion. A significant minority of hospices would not admit patients lacking a caregiver (26%). Patients unwilling to forgo hospitalization could not be admitted to 29% of hospices. Receipt of complex medical care, including TPN (38%), tube feedings (3%), transfusions (25%), radiotherapy (36%), and chemotherapy (48%), precluded admission. Larger program size was significantly associated with a lower likelihood of all admission practices except restricting the admission of patients receiving TPN or tube feedings. Hospice programs that were part of a hospice chain were less likely to restrict the admission of patients using TPN, radiotherapy, or chemotherapy than were freestanding programs.

Conclusion: Patients who are receiving complex palliative treatments could face barriers to hospice enrollment. Policy makers should consider the clinical capacity of hospice providers in efforts to improve access to palliative care and more closely incorporate palliation with other healthcare services.
Neuroleptic Drug Therapy in Older Adults Newly Admitted to Nursing Homes: Incidence, Dose, and Specialist Contact
Authors: Bronskill Susan E. , Anderson Geoffrey M. , Sykora Kathy , Wodchis Walter P. , Gill Sudeep , Shulman Kenneth I. , Rochon Paula A.
Published: April 2004

Objectives:  To describe the incidence and dose of neuroleptic drug therapy newly dispensed for behavioral disorders to older adults admitted to nursing homes and to determine whether this use is associated with patient characteristics and contact with specialists.

Design:  A retrospective cohort study using administrative data from a comprehensive and universal drug program.

Setting:  All licensed nursing homes in Ontario, Canada.

Participants:  All 19,780 adults aged 66 and older who had no evidence of neuroleptic drug use in the previous year and no history of major psychosis and were newly admitted to a nursing home between April 1, 1998, and March 31, 2000.

Measurements:  Exposure to neuroleptic drug therapy and initial dose were measured using claims submitted to the Ontario Drug Benefit Program.

Results:  A prescription for a neuroleptic therapy was dispensed to 17% of older adults with no previous neuroleptic exposure within 100 days and to 24% within 1 year of their nursing home admission. New exposure to a neuroleptic therapy was less likely in women (odds ratio (OR)=0.7, 95% confidence interval (CI)=0.6–0.8) and more likely in residents with dementia (OR=3.5, 95% CI=3.2–3.8). Almost 10% of nursing home residents received an initial dose that exceeded recommended thresholds. Only 14% of those newly exposed had prior contact with a geriatrician or psychiatrist.

Conclusion:  Incident use of neuroleptics in Ontario nursing homes is substantial. Use of high doses suggests that some physicians may need better information about using these agents, particularly given the rapid adoption of atypical neuroleptic drug therapies.
Evaluation of the Mini‐Mental State Examination's Internal Consistency in a Community‐Based Sample of Mexican‐American and European‐American Elders: Results from the San Antonio Longitudinal Study of Aging
Authors: Espino David V. , Lichtenstein Michael J. , Palmer Raymond F. , Hazuda Helen P.
Published: April 2004

This study examined the effect of scoring method, education, and language usage on internal consistency of the Folstein Mini‐Mental State Examination (MMSE). Trained bilingual staff administered the MMSE in participants' homes as part of the San Antonio Longitudinal Study of Aging home‐based assessment battery. Subjects included 833 community‐dwelling Mexican‐American (MA) and European‐American (EA) elders, aged 65 and older, residing in three socioculturally distinct neighborhoods in San Antonio, Texas. Three methods of scoring the MMSE were examined: serial sevens only, spelling only, and serial sevens or spelling, whichever was higher. Mean MMSE scores±standard deviation ranged from 27.7±2.4 to 28.5±1.9 for EAs, from 25.6±3.2 to 27.2±2.9 for MAs interviewed in English, and from 22.5±4.5 to 25.5±3.5 for MAs interviewed in Spanish, depending on scoring method. Across the three ethnic‐language subgroups, the lowest mean scores, largest coefficients of variation, and highest alpha coefficients were observed using serial sevens only. Stratification by educational level showed that alpha coefficients for all three scoring methods were consistently lower in high school graduates than in less‐educated groups. Serial sevens only was the only scoring method that yielded acceptably high alpha coefficients across all ethnic, language, and education subgroups. Thus, clinicians should use the serial sevens–only method when administering the MMSE and be alert to the increased potential for false‐negatives in more highly educated EA and MA elders, particularly in EAs and MAs proficient in English.
Right Ventricular Outflow Tract Placement of Defibrillation Leads:
Authors: GIUDICI MICHAEL C. , BAROLD S. SERGE , PAUL DEBORAH L. , SCHRUMPF PHILLIP E. , VAN WHY KENT J. , ORIAS DAVID W.
Published: April 2004

Over a 5‐year period, 112 patients (89 male/23 female, mean age 65 years) underwent right ventricular outflow tract (RVOT) placement of permanent active‐fixation transvenous pacing/defibrillating leads. At implantation, the pacing threshold was 0.6 ± 0.3 V at 0.5 ms pulse duration and R wave amplitude was 10.9 ± 4.9 mV. The defibrillation threshold (DFT) of right‐sided implants was 17.7 ± 3.4 J while that of left‐sided implants was 16.1 ± 3.3 J. Patients were followed at 1 and 3 month postimplant and at six‐month intervals thereafter. At mean follow‐up of 22.5 ± 17.5 months (range 1–47 months) there were no lead dislodgments, unsuccessful shock therapies, or failure to sense or pace for bradycardia or tachycardia. Death was not sudden in the 17 patients who died. We conclude that RVOT pacing‐defibrillation lead implantation is safe, efficacious, and potentially attractive because preliminary evidence suggests that it may not be associated with the adverse hemodynamic effects of pacing at the right ventricular apex. (PACE 2004; 27:443–446)
Noncontact and Electroanatomic Mapping of Atrial Flutter in Surgically Repaired Sinus Venosus Atrial Septal Defect and Rerouting of Anomalous Pulmonary Venous Drainage
Authors: KUMARASWAMY NATARAJAN , KUMBAR CHANDRASHEKAR , DHALA ANWER , SRA JASBIR
Published: April 2004

Atypical atrial flutter with two prior failed ablations, complicating surgically repaired sinus venosus atrial septal defect and partial anomalous pulmonary venous connection, mapped by noncontact and electroanatomic mapping, is described. Electroanatomic and noncontact mapping clearly identified a narrow zone of normal voltage and activation which was targeted, with successful termination of the arrhythmia. (PACE 2004; 27:526–529)
Asymptomatic Brugada Syndrome Associated with Postural Orthostatic Tachycardia Syndrome:
Authors: MORISHIMA ITSURO , SONE TAKAHITO , TSUBOI HIDEYUKI , MUKAWA HIROAKI , SATODA MASAHIKO , UESUGI MICHITAKA
Published: April 2004

Autonomic imbalance may work as a modifying factor for initiating lethal arrhythmia in patients with Brugada syndrome. A 26‐year‐old man with episodes of near syncope was given a diagnosis of an autonomic disorder, postural orthostatic tachycardia syndrome (POTS). The patient spontaneously showed typical Brugada‐type ECG, and ventricular fibrillation was induced by programmed electrical stimulation, which allowed the further diagnosis of Brugada syndrome. Although it seems that Brugada syndrome is asymptomatic, its uncommon association of POTS may increase the risk for future arrhythmic events in this patient. (PACE 2004; 27:537–540)
P Wave Separation After Atrial Compartment Operation for Atrial Fibrillation
Authors: LO HUEY‐MING , LIN FANG‐YUE , TSENG YUNG‐ZU
Published: April 2004

Surgically induced abnormalities in atrial conduction could result in unusual P wave changes. A 31‐year‐old woman underwent concomitant mitral valve surgery and atrial compartment operation for mitral stenosis and atrial fibrillation (AF). After operation, the AF was successfully converted to sinus rhythm, whereas an unusual electrocardiogram (ECG) with a discrete negative deflection before the T wave in V1 was noted. Electrophysiological study showed a marked conduction delay from the high right atrium (HRA) to the right atrial appendage (RAA) compartment, which resulted in a separation of P waves. The P wave preceding the QRS complex represented the activation of sinus node and the left atrial compartments, and the P at the vicinity of T wave represented the activation of RAA compartment. The conduction from HRA to RAA was worsened on HRA pacing at a faster rate, and improved after isoproterenol infusion. This report demonstrated that conduction across a surgically created isthmus in the atrium could be severely impaired and result in unusual P wave separation. (PACE 2004; 27:547–550)
Prophylactic Implantable Cardioverter Defibrillator Placement in a Sporadic Desmin Related Myopathy and Cardiomyopathy
Authors: LUETHJE LARS G. C. , BOENNEMANN CARSTEN , GOLDFARB LEV , GOEBEL HANS H. , HALLE MARTIN
Published: April 2004

Desminopathy is a neuromuscular disorder associated with the accumulation of the protein desmin. This article reports a case of a man with a mutation in the desmin gene suffering from cardiomyopathy and skeletal myopathy. This patient underwent implantable cardioverter defibrillator (ICD) implantation for prognostic considerations and subsequently developed a sustained ventricular tachycardia (SVT). While nonsustained VTs (NSVT) have previously been reported, this is the first time that a SVT could be seen in a patient with this disease. (PACE 2004; 27:559–560)
Compact Fluorescent Lamp Observed Through a Diffraction Grating
Authors: Gratton L. M. , Perini M. , Zanetti V.
Published: April 2004

This paper describes the use of a compact fluorescent lamp and a diffraction grating to introduce some basic concepts connected with the perception of colors. If a spherical compact fluorescent lamp is observed through a diffraction grating from a distance of 3 m or more, some interesting and perhaps unexpected features (Fig. 1) may be noticed: interesting, because of the many images having the shape of disks with different brilliant colors (corresponding to the wavelengths of emission lines in the discharge spectrum of the gas mixture in the lamp). There are unexpected features because when we get closer to the lamp it is possible to see that some of the different colored images become superimposed. Colors seen in the overlapping areas are quite different from those of the original disks. The appearance of these new colors has to do with how we perceive color.
Migrating Songbirds Recalibrate Their Magnetic Compass Daily from Twilight Cues
Authors: Cochran William W. , Mouritsen Henrik , Wikelski Martin
Published: April 2004

Night migratory songbirds can use stars, sun, geomagnetic field, and polarized light for orientation when tested in captivity. We studied the interaction of magnetic, stellar, and twilight orientation cues in free-flying songbirds. We exposed
Catharus
thrushes to eastward-turned magnetic fields during the twilight period before takeoff and then followed them for up to 1100 kilometers. Instead of heading north, experimental birds flew westward. On subsequent nights, the same individuals migrated northward again. We suggest that birds orient with a magnetic compass calibrated daily from twilight cues. This could explain how birds cross the magnetic equator and deal with declination.
A Functional Protein Chip for Pathway Optimization and in Vitro Metabolic Engineering
Authors: Jung Gyoo Yeol , Stephanopoulos Gregory
Published: April 2004

Pathway optimization is difficult to achieve owing to complex, nonlinear, and largely unknown interactions of enzymes, regulators, and metabolites. We report a pathway reconstruction using RNA display–derived messenger RNA–enzyme fusion molecules. These chimeras are immobilized by hybridization of their messenger RNA end with homologous capture DNA spotted on a substrate surface. Enzymes thus immobilized retain activity proportional to the amount of capture DNA, allowing modulation of the relative activity of pathway enzymes. Entire pathways can thus be reconstructed and optimized in vitro from genomic information. We provide concept validation with the sequential reactions catalyzed by luciferase and nucleoside diphosphate kinase and further illustrate this method with the optimization of the five-step pathway for trehalose synthesis.
Surface Glycans ofCandida albicansand Other Pathogenic Fungi: Physiological Roles, Clinical Uses, and Experimental Challenges
Authors: Masuoka James
Published: April 2004

Although fungi have always been with us as commensals and pathogens, fungal infections have been increasing in frequency over the past few decades. There is a growing body of literature describing the involvement of carbohydrate groups in various aspects of fungal disease. Carbohydrates comprising the cell wall or capsule, or as a component of glycoproteins, are the fungal cell surface entities most likely to be exposed to the surrounding environment. Thus, the fungus-host interaction is likely to involve carbohydrates before DNA, RNA, or even protein. The interaction between fungal and host cells is also complex, and early studies using whole cells or crude cell fractions often produced seemingly conflicting results. What was needed, and what has been developing, is the ability to identify specific glycan structures and determine how they interact with immune system components. Carbohydrate analysis is complicated by the complexity of glycan structures and by the challenges of separating and detecting carbohydrates experimentally. Advances in carbohydrate chemistry have enabled us to move from the foundation of composition analysis to more rapid characterization of specific structures. This, in turn, will lead to a greater understanding of how fungi coexist with their hosts as commensals or exist in conflict as pathogens.
Salmonella entericaSerotype Choleraesuis: Epidemiology, Pathogenesis, Clinical Disease, and Treatment
Authors: Chiu Cheng-Hsun , Su Lin-Hui , Chu Chishih
Published: April 2004

NontyphoidSalmonellastrains are important causes of reportable food-borne infection. Among more than 2,000 serotypes,Salmonella entericaserotype Choleraesuis shows the highest predilection to cause systemic infections in humans. The most feared complication of serotype Cholearesuis bacteremia in adults is the development of mycotic aneurysm, which previously was almost uniformally fatal. The advances in diagnostic techniques, surgical care, and antimicrobial therapy have greatly improved the survival of these patients. However, the recent emergence of serotype Choleraesuis that is resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and, notably, fluoroquinolone antibiotics has aroused concern about the use of these agents for the empirical treatment of systemic infection caused by this organism. In view of the serious implications of the situation, the chain of transmission and mechanism of resistance should be carefully studied to reduce the spread of infection and threat to human health. To date, there are no vaccines available to prevent serotype Choleraesuis infections in humans. The availability, in the near future, of the genome sequence of serotype Cholearesuis will facilitate the development of effective vaccines as well as the discovery of new targets for novel antimicrobial agents.
Invasion of the Central Nervous System by Intracellular Bacteria
Authors: Drevets Douglas A. , Leenen Pieter J. M. , Greenfield Ronald A.
Published: April 2004

Infection of the central nervous system (CNS) is a severe and frequently fatal event during the course of many diseases caused by microbes with predominantly intracellular life cycles. Examples of these include the facultative intracellular bacteriaListeria monocytogenes,Mycobacterium tuberculosis, andBrucellaandSalmonellaspp. and obligate intracellular microbes of the Rickettsiaceae family andTropheryma whipplei. Unfortunately, the mechanisms used by intracellular bacterial pathogens to enter the CNS are less well known than those used by bacterial pathogens with an extracellular life cycle. The goal of this review is to elaborate on the means by which intracellular bacterial pathogens establish infection within the CNS. This review encompasses the clinical and pathological findings that pertain to the CNS infection in humans and includes experimental data from animal models that illuminate how these microbes enter the CNS. Recent experimental data showing thatL. monocytogenescan invade the CNS by more than one mechanism make it a useful model for discussing the various routes for neuroinvasion used by intracellular bacterial pathogens.
DNA Vaccines against Human Immunodeficiency Virus Type 1 in the Past Decade
Authors: Giri Malavika , Ugen Kenneth E. , Weiner David B.
Published: April 2004

This article reviews advances in the field of human immunodeficiency virus type 1 (HIV-1) and AIDS vaccine development over the last decade, with an emphasis on the DNA vaccination approach. Despite the discovery of HIV-1 and AIDS in humans nearly 20 years ago, there is no vaccine yet that can prevent HIV-1 infection. The focus has shifted toward developing vaccines that can control virus replication and disease progression by eliciting broadly cross-reactive T-cell responses. Among several approaches evaluated, the DNA-based modality has shown considerable promise in terms of its ability to elicit cellular immune responses in primate studies. Of great importance are efforts aimed at improvement of the potency of this modality in the clinic. The review discusses principles of DNA vaccine design and the various mechanisms of plasmid-encoded antigen presentation. The review also outlines current DNA-based vaccine strategies and vectors that have successfully been shown to control virus replication and slow disease progression in animal models. Finally, it lists recent strategies that have been developed as well as novel approaches under consideration to enhance the immunogenicity of plasmid-encoded HIV-1 antigen in various animal models.
Animal Pneumoviruses: Molecular Genetics and Pathogenesis
Authors: Easton Andrew J. , Domachowske Joseph B. , Rosenberg Helene F.
Published: April 2004

Pneumoviruses are single-stranded, negative-sense, nonsegmented RNA viruses of the familyParamyxoviridae, subfamilyPneumovirinae, and include pathogens that infect humans (respiratory syncytial virus and human metapneumovirus), domestic mammals (bovine, ovine, and caprine respiratory syncytial viruses), rodents (pneumonia virus of mice), and birds (avian metapneumovirus). Among the topics considered in this review are recent studies focused on the roles of the individual virus-encoded components in promoting virus replication as well as in altering and evading innate antiviral host defenses. Advances in the molecular technology of pneumoviruses and the emergence of recombinant pneumoviruses that are leading to improved virus-based vaccine formulations are also discussed. Since pneumovirus infection in natural hosts is associated with a profound inflammatory response that persists despite adequate antiviral therapy, we also review the recent experimental treatment strategies that have focused on combined antiviral, anti-inflammatory, and immunomodulatory approaches.
Intraspecific Diversity ofYersinia pestis
Authors: Anisimov Andrey P. , Lindler Luther E. , Pier Gerald B.
Published: April 2004

Increased interest in the pathogenic potential ofYersinia pestishas emerged because of the potential threats from bioterrorism. Pathogenic potential is based on genetic factors present in a population of microbes, yet most studies evaluating the role of specific genes in virulence have used a limited number of strains. ForY. pestisthis issue is complicated by the fact that most strains available for study in the Americas are clonally derived and thus genetically restricted, emanating from a strain ofY. pestisintroduced into the United States in 1902 via marine shipping and subsequent spread of this strain throughout North and South America. In countries from the former Soviet Union (FSU), Mongolia, and China there are large areas of enzootic foci ofY. pestisinfection containing genetically diverse strains that have been intensely studied by scientists in these countries. However, the results of these investigations are not generally known outside of these countries. Here we describe the variety of methods used in the FSU to classifyY. pestisstrains based on genetic and phenotypic variation and show that there is a high level of diversity in these strains not reflected by ones obtained from sylvatic areas and patients in the Americas.