bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinearity in Demographic and Behavioral Determinants of Morbidity
Authors: Norris Jean C. , Van der laan Mark J. , Lane Sylvia , Anderson James N. , Block Gladys
Published: December 2003

Objective. To examine nonlinearity of determinants of morbidity in the United States

Data Sources. A secondary analysis of data on individuals with dietary data from the Cancer Epidemiology Supplement and National Health Interview Survey (NHIS) 1987, a cross‐sectional, stratified random sample of the U.S. population (n=22,080).

Study Design. A statistical exploration using additive multiple regression models.

Methods. A Morbidity Index (0–30 points), derived from 1987 National Health Interview Survey data, combines number of conditions, hospitalizations, sick days, doctor visits, and degree of disability. Behavioral (health habits) variables were added to multivariate models containing demographic terms, with Morbidity Index and Self‐assessed Health outcomes (n=17,612). Tables and graphs compare models of morbidity with self‐assessed health models, with and without behavioral terms. Graphs illustrate curvilinear relationships.

Principal Findings. Morbidity and health are associated nonlinearly with age, race, education, and income, as well as alcohol, diet change, vitamin supplement use, body mass index (BMI), marital status/living arrangement, and smoking. Diet change and supplement use, education, income, race/ethnicity, and age relate differently to self‐assessed health status than to morbidity. Morbidity is strongly associated with income up to about $15,000 above poverty. Additional income predicts no further reduction in morbidity. Better health is strongly related to both higher income and education. After controlling for income, black race does not predict morbidity, but remains associated with lower self‐assessed health.

Conclusions. Good health habits, as captured in these models, are associated with a 10–20‐year delay in onset and progression of morbidity.
Socioeconomic Gradients and Low Birth‐Weight: Empirical and Policy Considerations
Authors: Finch Brian Karl
Published: December 2003

Objective.To examine whether socioeconomic status (SES) gradients emerge in health outcomes as early as birth and to examine the magnitude, potential sources, and explanations of any observed SES gradients.

Data Sources.The National Maternal and Infant Health Survey conducted in 1988.

Study Design.A multinomial logistic regression of trichotomized birth‐weight categories was conducted for normal birth‐weight (2,500–5,500 grams), low birth‐weight (LBWT; <2,500 grams), and heavy birth‐weight (>5,500 grams). Key variables included income, education, occupational grade, state‐level income inequality, and length of participation in Women‐Infants‐Children (WIC) for pregnant mothers.

Principal Findings.A socioeconomic gradient for low birth‐weight was discovered for an adjusted household income measure, net of all covariates in the unrestricted models. A gross effect of maternal education was explained by maternal smoking behaviors, while no effect of occupational grade was observed, net of household income. There were no significant state‐level income inequality effects (Gini coefficient) for any of the models. In addition, participation in WIC was discovered to substantially flatten income gradients for short‐term participants and virtually eliminate an income gradient among long‐term participants.

Conclusions.Although a materialist explanation for early‐life SES gradients seems the most plausible (vis‐à‐vis psychosocial and occupational explanations), more research is needed to discover potential interventions. In addition, the notion of a monotonic gradient in which income is salutary across the full range of the distribution is challenged by these data such that income may cease to be beneficial after a given threshold. Finally, the success of WIC participation in flattening SES gradients argues for either: (a) the experimental efficacy of WIC, or (b) the biasing selection characteristics of WIC participants; either conclusion suggests that interventions or characteristics of participants deserves further study as a potential remedy for socioeconomic disparities in early‐life health outcomes such as LBWT.
Social Determinants of Tooth Loss
Authors: Gilbert Gregg H. , Paul duncan R. , Shelton Brent J.
Published: December 2003

Objectives. To quantify racial and socioeconomic status (SES) disparities in oral health, as measured by tooth loss, and to determine the role of dental care use and other factors in explaining disparities.

Data Sources/Study Setting. The Florida Dental Care Study, comprising African Americans (AAs) and non‐Hispanic whites 45 years old or older who had at least one tooth.

Study Design. We used a prospective cohort design. Relevant population characteristics were grouped by predisposing, enabling, and need variables. The key outcome was tooth loss, a leading measure of a population's oral health, looked at before and after entering the dental care system. Tooth‐specific data were used to increase inferential power by relating the loss of individual teeth to the disease level on those teeth.

Data Collection Methods. In‐person interviews and clinical examinations were done at baseline, 24, and 48 months, with telephone interviews every 6 months.

Principal Findings. African Americans and persons of lower SES reported more new dental symptoms, but were less likely to obtain dental care. When they did receive care, they were more likely to experience tooth loss and less likely to report that dentists had discussed alternative treatments with them. At the first stage of analysis, differences in disease severity and new symptoms explained tooth loss disparities. Racial and SES differences in attitudes toward tooth loss and dental care were not contributory. Because almost all tooth loss occurs by means of dental extraction, the total effects of race and SES on tooth loss were artificially minimized unless disparities in dental care use were taken into account.

Conclusions. Race and SES are strong determinants of tooth loss. African Americans and lower SES persons had fewer teeth at baseline and still lost more teeth after baseline. Tooth‐specific case‐mix adjustment appears, statistically, to explain social disparity variation in tooth loss. However, when social disparities in dental care use are taken into account, social disparities in tooth loss that are not directly due to clinical circumstance become evident. This is because AAs and lower SES persons are more likely to receive a dental extraction once they enter the dental care system, given the same disease extent and severity. This phenomenon underscores the importance of understanding how disparities in health care use, dental insurance coverage, and service receipt contribute to disparities in health. Absent such understanding, the total effects of race and SES on health can be underestimated.
County‐Level Income Inequality and Depression among Older Americans
Authors: Muramatsu Naoko
Published: December 2003

Objectives. To examine (1) whether county‐level income inequality is associated with depression among Americans aged 70 and older, taking into consideration county‐level mean household income and individual‐level socioeconomic status (SES), demographic characteristics, and physical health, and (2) whether income inequality effects are stronger among people with lower SES and physical health.

Data Sources. The individual‐level data from the first wave of the Assets and Health Dynamics among the Oldest Old survey (1993–1994) were linked with the county‐level income inequality and mean household income data from the 1990 Census.

Study Design. Multilevel analysis was conducted to examine the association between income inequality (the Gini coefficient) and depression.

Principal Findings. Income inequality was significantly associated with depression among older Americans. Those living in counties with higher income inequality were more depressed, independent of their demographic characteristics, SES, and physical health. The association was stronger among those with more illnesses.

Conclusions. While previous empirical research on income inequality and physical health is equivocal, evidence for income inequality effects on mental health seems to be strong.
Racial Differences in the Receipt of Bowel Surveillance Following Potentially Curative Colorectal Cancer Surgery
Authors: Ellison Gary L. , Warren Joan L. , Knopf Kevin B. , Brown Martin L.
Published: December 2003

Objective. To investigate racial differences in posttreatment bowel surveillance after colorectal cancer surgery in a large population of Medicare patients.

Data Sources. We used a large population‐based dataset: Surveillance, Epidemiology, and End Results (SEER) linked to Medicare data.

Study Design. This is a retrospective cohort study. We analyzed data from 44,768 non‐Hispanic white, 2,921 black, and 4,416 patients from other racial/ethnic groups, aged 65 and older at diagnosis, who had a diagnosis of local or regional colorectal cancer between 1986 and 1996, and were followed through December 31, 1998. Cox Proportional Hazards models were used to investigate the relation of race and receipt of posttreatment bowel surveillance.

Data Collection. Sociodemographic, hospital, and clinical characteristics were collected at the time of diagnosis for all members of the cohort. Surgery and bowel surveillance with colonoscopy, sigmoidoscopy, and barium enema were obtained from Medicare claims using ICD‐9‐CM and CPT‐4 codes.

Principal Findings. The chance of surveillance within 18 months of surgery was 57 percent, 48 percent, and 45 percent for non‐Hispanic whites, blacks, and others, respectively. After adjusting for sociodemographic, hospital, and clinical characteristics, blacks were 25 percent less likely than whites to receive surveillance if diagnosed between 1991 and 1996 (RR=0.75, 95 percent CI=0.70–0.81).

Conclusions.

Elderly blacks were less likely than non‐Hispanic whites to receive posttreatment bowel surveillance and this result was not explained by measured racial differences in sociodemographic, hospital, and clinical characteristics. More research is needed to explore the influences of patient‐ and provider‐level factors on racial differences in posttreatment bowel surveillance.
Tackling Health Inequalities in the United Kingdom: The Progress and Pitfalls of Policy
Authors: Exworthy Mark , Blane David , Marmot Michael
Published: December 2003

Goal.Assess the progress and pitfalls of current United Kingdom (U.K.) policies to reduce health inequalities.

Objectives.(1) Describe the context enabling health inequalities to get onto the policy agenda in the United Kingdom. (2) Categorize and assess selected current U.K. policies that may affect health inequalities. (3) Apply the “policy windows” model to understand the issues faced in formulating and implementing such policies. (4) Examine the emerging policy challenges in the U.K. and elsewhere.

Data Sources.Official documents, secondary analyses, and interviews with policymakers.

Study Design.Qualitative, policy analysis.

Data Collection.2001–2002. The methods were divided into two stages. The first identified policies which were connected with individual inquiry recommendations. The second involved case‐studies of three policies areas which were thought to be crucial in tackling health inequalities. Both stages involved interviews with policy‐makers and documentary analysis.

Principal Findings.(1) The current U.K. government stated a commitment to reducing health inequalities. (2) The government has begun to implement policies that address the wider determinants. (3) Some progress is evident but many indicators remain stubborn. (4) Difficulties remain in terms of coordinating policies across government and measuring progress. (5) The “policy windows” model explains the limited extent of progress and highlights current and possible future pitfalls. (6) The U.K.'s experience has lessons for other governments involved in tackling health inequalities.

Conclusions.Health inequalities are on the agenda of U.K. government policy and steps have been made to address them. There are some signs of progress but much remains to be done including overcoming some of the perverse incentives at the national level, improving joint working, ensuring appropriate measures of performance/progress, and improving monitoring arrangements. A conceptual policy model aids understanding and points to ways of sustaining and extending the recent progress and overcoming pitfalls.
What New Knowledge Would Help Policymakers Better Balance Investments for Optimal Health Outcomes?
Authors: Kindig David , Day Patricia , Fox Daniel M. , Gibson Mark , Knickman James , Lomas Jonathan , Stoddart Gregory
Published: December 2003

Objective:Review the limitations in cross‐sectoral health outcomes research and suggest a future research agenda.

Data Sources, Study Design, Data Collection:Literature review and workshop discussion.

Principal Findings:The research evidence that would aid public and private policy makers in answering the question the title poses is quite limited.

Conclusions:Much more evidence from diverse disciplines is needed, and key areas are suggested. Criteria for progress by 2010 are proposed.
The Influence of Intraperitoneal Transplantation of Free and Encapsulated Langerhans Islets on the Second Set Phenomenon
Authors: Orłowski Tadeusz , Godlewska Ewa , Mościcka Maria , Sitarek Elżbieta
Published: December 2003

Abstract:  To protect the allografts or xenografts against transplant rejection special semipermeable membranes are applied. So far, there are only a few studies on the influence of an immunoisolated graft on the recipient immune system. Therefore, the possibility that an intraperitoneally grafted alginate/poly L‐lysine/alginate (APA) coated pancreatic islets graft can effectively sensitize the recipient and provoke second set phenomenon was studied. C3H male mice and male WAG rats were used as donors of full‐thickness skin and of free or encapsulated islet intraperitoneal grafts. Male BALB/c mice served as recipients. Skin grafts were performed following the method of Billingham and Medawar. The length of the second skin graft survival time served as the criterion for the sensitizing capacity of the primary graft. APA encapsulation of islets delayed but has not prevented the development of the second set phenomenon. However, the second skin graft rejection time was significantly longer after grafting of encapsulated islets than after free islets transplantation. APA microencapsulation of intraperitoneally transplanted islets delayed but did not prevent the development of the second set phenomenon. Encapsulation does not ensure complete immunoisolation, but only creates “an artificially immunoprivileged site of transplantation.”
Hemolysis in an Electromechanical Driven Pulsatile Total Artificial Heart
Authors: Ohashi Yukio , De Andrade Aron , Nosé Yukihiko
Published: December 2003

Abstract:  A motor rotation in an electromechanically‐driven pulsatile total artificial heart (TAH) may influence hemolysis. This study is designed to evaluate motor rotational conditions of the TAH and choose a suitable condition to obtain the least hemolytic characteristics. The TAH was driven in two motor rotational conditions: a constant motor rotational speed (rpm) mode (mode A) and a gradually increasing rpm mode (mode B). In these two modes, a maximum dP/dt value and a degree of hemolysis were measured and compared. The TAH was connected to an in vitro testing loop. In each mode, the TAH  was  driven  with  a  fixed pumping rate of 100 bpm. A preload and an afterload were held at 15 and 100 mm Hg, respectively. The outflow of the TAH was maintained at 4.0 L/min. The maximum dP/dt in mode A and mode B was 5914 ± 405 mm Hg/s and 2953 ± 191 mm Hg/s, respectively. The NIH value obtained from mode A and   mode B   was 0.063 ± 0.005 g/100 L and 0.026 ± 0.003 g/100 L, respectively. The results demonstrated that the TAH driven in a gradually increasing rpm mode reduces both a maximum dP/dt value and a degree of hemolysis. The gradually increasing rpm mode is a suitable driving condition to obtain the least hemolytic characteristics.
Improved Retention of Endothelial Cells Seeded on Polyurethane Small‐diameter Vascular Grafts Modified by a Recombinant RGD‐containing Protein
Authors: Hsu Shan‐hui , Sun Sung‐huan , Chen David Chanhen
Published: December 2003

Abstract:  Sponge‐type small‐diameter vascular grafts were fabricated from a medical‐grade polyurethane, Pellethane 2363–80A, by utilization of a salt casting technique. The grafts were compliance matched with a storage modulus of 0.53 ± 0.08 MPa. The luminal surface of grafts was modified with a thin layer (∼40 µm) of gelatin crosslinked by epoxide. Then a special Arg‐Gly‐Asp (RGD)‐containing recombinant protein, named CBD–RGD (cellulose binding domain RGD‐containing protein), was coated onto the gelatin layer. The platelet adhesion and activation on such a gelatin/CBD–RGD modified surface was significantly reduced. Human umbilical vein endothelial cells were seeded more efficiently onto the modified grafts. There was also a substantial reduction in the subsequent loss of cells from the graft surface following perfusion in vitro. The cell number retained on the modified graft was enhanced by three times after 1 h of perfusion, and by eight times after 3 h of perfusion (retention rate ∼63%). The retention after 3 h of perfusion could be further increased to nearly 100% if the lined endothelium on gelatin/CBD–RGD modified graft was cultured for another week before perfusion. The modified surface was also shown to help canine external jugular vein endothelial cells to maintain the round cell morphology in vitro.
Endotoxin Adsorption of Various Dialysis Membranes: In Vitro Study
Authors: Takemoto Yoshiaki , Nakatani Tatsuya , Sugimura Kazunobu , Yoshimura Rikio , Tsuchida Kenji
Published: December 2003

Abstract:  Endotoxin (ET) in the dialysate is known to adsorb on dialysis membranes made of polyether polymer alloy (PEPA) and polymethylmethacrylate (PMMA). In the present study, we investigated the adsorption of ET on dialysis membranes with a focus on PEPA membranes and polysulfone (PS) membranes that are extensively used in artificial kidneys or as ET‐removal filters. In the case of PEPA, the compounding of polyvinylpyrrolidone (PVP) was changed, and both a hydrophobic version and a hydrophilic version were used on the blood side. For the PS dialysis, commercial membranes (APS (Asahi), BSP (Toray), PSN (Fresenius), CLPS (Terumo)) were used. Adsorption was evaluated by exposing both sides of the membrane after it had been primed with physiological saline: the ET concentration on the blood side and dialysate side of the dialysis membrane was monitored during the 240 min from the start of the exposure. When the PEPA membrane was investigated, ET was significantly adsorbed on the hydrophobic version. For PS membranes, ET was adsorbed on the blood side or on both the blood and dialysate sides, depending on the membrane. PS dialysis membranes can adsorb ET but the power and site of adsorption are different even between membranes made of the same material. In addition to electrostatic action attributable to the compounding of hydrophilic agent PVP on the dialysis membrane, the distribution of PVP that was compounded and the potential of the membrane itself are considered to cause differences in adsorption.
Preservation of Human Saphenous Vein against Reactive Oxygen Species‐induced Oxidative Stress by Green Tea Polyphenol Pretreatment
Authors: Han Dong‐Wook , Suh Hwal , Park Young Hwan , Cho Bum Koo , Hyon Suong‐Hyu , Park Jong‐Chul
Published: December 2003

Abstract:  The injurious effects of reactive oxygen species on venous tissues and the potential protective role played by green tea polyphenol (GTPP) on human saphenous veins were investigated. Oxidative stress was induced exogenously in the vein segments, either by adding 0.8 or 1.6 M of H2O2, or by using 80 or 160 U/L of xanthine oxidase in the presence of xanthine (0.5 mM). After incubation, the viability of the endothelial cells dissociated from veins and the histology of the veins were evaluated. Due to both types of treatment, a significant decrease in cellular viability, severe morphological changes in the veins, and extracellular structural damage were induced. The H2O2‐induced alterations were prevented by preincubating the veins with either 0.5 or 1.0 mg/ml of GTPP for 1 h. When the oxidative stress was induced by xanthine oxidase, cellular viability and venous structure were preserved at the same polyphenol concentrations. These results demonstrate that GTPP can act as a biological antioxidant and protect veins from oxidative stress‐induced toxicity.
Vitamin E‐coated Membrane Dialyzer and β2‐microglobulin Removal
Authors: Mandolfo S. , Bucci R. , Imbasciati E.
Published: December 2003

Abstract:  This study was designed to test the removal of β2‐microglobulin (β2M) in a vitamin E‐modified membrane. We investigated in vivo the dialyzer (Excebrane, series EE, 1.8 m2) with respect to hydraulic permeability (Kuf), maximum ultrafiltration rate (UF max), sieving coefficient (Sc), and solute clearances in hemodialysis (HD) and in soft hemodiafiltration (HDF). Kuf was 18.4 ml/h/mmHg, UF max was 75 ml/min, and Sc for β2M was 0.45. Clearance values at 400 ml/min of Qb in HD were 258 ml/min for urea, 201 ml/min for creatinine, and 135 ml/min for phosphate. In soft HDF, clearances were slightly higher. β2M clearance was 26 ml/min in HD and 43 ml/min in soft HDF. In conclusion, Excebrane (series EE) procures a soft HDF with an amount of substitution fluid in post dilution mode of over 60 ml/min. Remarkable small solute clearances were obtained when the blood flow was raised to 400 ml/min. A significant reduction of β2M is demonstrated by HDF.
Unloading Effect of a Rotary Blood Pump Assessed by Mathematical Modeling
Authors: Vandenberghe Stijn , Segers Patrick , Meyns Bart , Verdonck Pascal
Published: December 2003

Abstract:  Due to the increased appeal of rotary blood pumps for long‐term cardiac assist, we conducted a study of their capacity to unload the left ventricle (LV). We used a validated mathematical model of the cardiovascular system and implemented the pump characteristics of an investigational microdiagonal pump (Medos). The influence of the pump on systemic hemodynamics, LV energetic parameters, and wall stress was evaluated in continuous and synchronous pulsatile modes of operation. For the continuous mode simulations, the influence of heart rate, LV contractility, and pump speed was assessed in a parametric study. For the pulsatile mode, different onsets of a synchronous time‐varying pump speed pattern were tested. Our data indicate that the effectiveness of unloading in continuous mode depends on the contractility of the native ventricle. Hypocontractile ventricles are most easily unloaded, while ventricles with moderate contractility require high continuous pump speeds to achieve notable unloading. In pulsatile mode, the pump timing is an important determinant of pump/cardiovascular system interaction, with a counterpulsation setting yielding the best unloading.
Efficacy and Safety of a New Whole‐blood Low‐density Lipoprotein Apheresis System (Liposorber D) in Severe Hypercholesterolemia
Authors: Otto Carsten , Kern Peter , Bambauer Rolf , Kallert Stefan , Schwandt Peter , Parhofer Klaus G.
Published: December 2003

Abstract:  Low‐density lipoprotein (LDL) apheresis is an extracorporeal modality to lower LDL cholesterol. While most of the devices eliminate LDL particles from plasma, a recently introduced whole‐blood perfusion column (DALI) adsorbs lipoproteins directly from whole blood. We investigated the efficacy and safety of a new whole‐blood LDL apheresis system (Liposorber D) in 10 patients with severe hypercholesterolemia in a multicenter trial. In 93 LDL aphereses, the mean reduction in LDL cholesterol and lipoprotein(a) was 62.2 ± 11.5% and 55.6 ± 16.9%, respectively (P < 0.01). If hemodilution during apheresis was considered, the reductions were 58.0 ± 10.9 and 55.3 ± 10.9%, respectively (P < 0.01), while high‐density lipoprotein (HDL) cholesterol did not change significantly. Three mild episodes of hypocalcemia and two mild episodes of arterial hypotension were observed; however, LDL apheresis could be continued in each case. In conclusion, the new whole‐blood LDL apheresis with Liposorber D is a safe, simple, and useful modality to reduce LDL cholesterol and lipoprotein(a) in cardiovascular high‐risk patients.
Diaphragm Motion Affects Flow Patterns in an Artificial Heart
Authors: Hochareon Pramote , Manning Keefe B. , Fontaine Arnold A. , Deutsch Steven , Tarbell John M.
Published: December 2003

Abstract:  In the sac‐driven artificial heart, the flow characteristics are coupled to the dynamics of the sac motion. The opening dynamics of the sac wall can, for example, strongly affect the chamber flow characteristics during diastole by directing or impeding the inflow. Poor sac motion can reduce the volume output of the pump and may increase the potential for thrombus formation within the ventricular chamber. It is particularly important for laboratory studies of the flow fields in artificial hearts that the diaphragm motion properly simulates the sac motion observed in vivo. In the present study, flow visualization was performed to investigate the relationship between the chamber flow characteristics of a Penn State artificial heart and the motion of the diaphragm during the filling phase during in vitro experimentation. The chamber flow pattern and diaphragm motion were recorded as a function of time, using high‐speed videography. Experiments were conducted to determine the influence of diaphragm motion on the flow characteristics by altering the filling pressure, diaphragm thickness, and fluid density. Diaphragm motion was quantified by tracking the position of three surface points over the cardiac cycle. The alignment of these three surface trajectories can be used to quantify the uniformity of diaphragm motion. As a result, diaphragm motion was determined to be nonuniform under most operating conditions with the diaphragm opening in a wave‐like pattern starting at the bottom of the chamber and propagating toward the inflow/outflow ports. This opening pattern simulates the opening pattern observed in an in vitro study of the clinical blood sac used in the Lionheart LVAD.
Development of a Nerve Scaffold Using a Tendon Chitosan Tube
Authors: Itoh Soichiro , Suzuki Masumi , Yamaguchi Isamu , Takakuda Kazuo , Kobayashi Hisatoshi , Shinomiya Kenichi , Tanaka Junzo
Published: December 2003

Abstract:  Bridge grafting (15 mm) into the sciatic nerve of SD rats was carried out using tendon chitosan tubes having either a circular or triangular cross‐section, as well as triangular tubes combined with laminin, CDPGYIGSR, or CSRARKQAASIKVAVSAD (n = 15 in each group). As a control, isografting (15 mm) was carried out in the SD rats (n = 7). Specimens were taken after 1, 2, 4, 6, and 8 weeks for histology, and nerve regeneration was evaluated electro‐physiologically and histologically after 12 weeks. The mechanical strength of triangular tubes was found to be higher than circular tubes, and the inner volume of a triangular tube tends to be larger than in circular tubes. Nerve tissue regeneration along the tube wall was found in both the laminin and laminin peptide groups. According to the result of percentage neural tissue in relation to evoked action potentials, the consecutive treatments of YIGSR and IKVAV was found to match the effectiveness of intact laminin.
Effects of sub‐antimicrobial dose doxycycline therapy on crevicular fluid MMP‐8, and gingival tissue MMP‐9, TIMP‐1 and IL‐6 levels in chronic periodontitis
Authors: Choi Dong‐Hoon , Moon Ik‐Sang , Choi Bong‐Kyu , Paik Jeong‐Won , Kim Yoon‐Sik , Choi Seong‐Ho , Kim Chong‐Kwan
Published: December 2003

Objective:  To investigate whether sub‐antimicrobial dose doxycycline (SDD) therapy for 120 d in chronic adult periodontitis patients had significant effects on gingival crevicular fluid (GCF) matrix metalloproteinase‐8 (MMP‐8) levels, and on gingival tissue MMP‐9, tissue inhibitor of matrix metalloproteinases‐1 (TIMP‐1) and interleukin‐6 (IL‐6) levels.

Background:  Tetracycline can significantly inhibit MMP activity in GCF and in gingival tissue, even in much lower dosage then a traditional antimicrobial dosage used in conventional therapy. Sub‐antimicrobial dose doxycycline (SDD) therapy has been shown to reduce periodontal disease activity to control MMP and pro‐inflammatory cytokines.

Methods:  A total of 32 patients with incipient to moderate (probing pocket depth ≈ 4–7 mm) chronic adult periodontitis were included in the study. Subjects were randomly assigned to two groups. After scaling and root planning (SRP), the SRP + SDD group received SDD, 20 mg bid, whereas the SRP + placebo group received placebo, 20 mg bid. In the follow‐up, efficacy measures included the change in probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and gingival crevicular fluid MMP‐8 levels, gingival tissue MMP‐9, TIMP‐1 and IL‐6 levels from baseline to 120 d.

Results:  After 120 d, PD and CAL improved significantly in the SRP + SDD group. Initial MMP‐8 levels for the SRP + SDD group and the SRP + placebo group were 407.13 ± 114.45 ng/ml and 378.71 ± 189.39 ng/ml, respectively, with no statistical difference between the two groups. MMP‐8 levels for the SRP + SDD group and the SRP + placebo group were: 235.35 ± 134.58 ng/ml and 364.04 ± 219.27 ng/ml at 30 d; 157.50 ± 95.95 ng/ml and 236.60 ± 186.16 ng/ml at 60 d; 102.70 ± 67.64 ng/ml and 208.56 ± 124.54 ng/ml at 90 d; and 63.77 ± 53.33 ng/ml and 229.13 ± 168.09 ng/ml at 120 d, respectively. The amount of decrease in MMP‐8 levels for the SRP + SDD group was statistically significant compared to that for the SRP + placebo group, especially apparent at 120 d (p < 0.05). TIMP‐1 levels in both groups increased from the baseline to 120 d with statistical significance (p‐value < 0.05), but there was no significant difference between the two groups. Changes in MMP‐9 and IL‐6 levels were not statistically significant.

Conclusion:  Adjunctive SDD therapy can improve the clinical parameters and this clinical improvement is reflected by controlled level of MMP‐8 in chronic adult periodontitis after the therapy.
Interaction of Porphyromonas gingivalis with low‐density lipoproteins: implications for a role for periodontitis in atherosclerosis
Authors: Miyakawa Hiroshi , Honma Kiyonobu , Qi Mingshan , Kuramitsu Howard K.
Published: December 2003

Objective:  The association of periodontitis with atherosclerosis has been suggested from epidemiological studies. Recently, we have reported that macrophages stimulated by Porphyromonas gingivalis formed foam cells in the presence of low‐density lipoproteins (LDL). In this study, we examined the direct interactions between LDL and P. gingivalis.

Methods:  We investigated the aggregation of LDL with P. gingivalis and its outer membrane vesicles (OMVs), degradation of the apo B‐100 protein of LDL by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and western blot analyses, as well as the effects of protease inhibitors or activators on the mobility of LDL by agarose gel shift assays. The binding of P. gingivalis or its OMVs with LDL was demonstrated by western blot analysis. We also examined whether or not the aggregated LDL induced foam cell formation from murine macrophages.

Results:  LDL was aggregated in a dose‐dependent manner with P. gingivalis and its OMVs. Moreover, degradation of the apo B‐100 protein of LDL was directly demonstrated in the presence of P. gingivalis or its OMVs. Furthermore, the gel shift assays indicated that the mobility of LDL was increased in the presence of P. gingivalis. This alteration was attenuated in the presence of the protease inhibitors TLCK and leupeptin and increased in the presence of reducing agents. Moreover, LDL was bound to specific proteins of P. gingivalis suggesting that these proteins may also play a role in aggregation. Finally, the aggregated LDL induced murine macrophages to form foam cells.

Conclusions:  These results suggest that P. gingivalis may stimulate foam cell formation, in part, by aggregating LDL by proteolysis of apo B‐100.
Expression of CD73/ecto‐5′‐nucleotidase on human gingival fibroblasts and contribution to the inhibition of interleukin‐1α‐induced granulocyte‐macrophage colony stimulating factor production
Authors: Nemoto Eiji , Kunii Ryotaro , Tada Hiroyuki , Tsubahara Taisuke , Ishihata Hiroshi , Shimauchi Hidetoshi
Published: December 2003

Background and objectives:  CD73/5′‐nucleotidase (5′‐NT) is an ectoenzyme that participates in immune/inflammatory reactions. We examined the possible expression of CD73/5′‐NT on human gingival fibroblasts (hGF), which are important to the immune/inflammatory system in periodontal tissue.

Methods and results:  We demonstrated that CD73/5′‐NT was expressed on hGF by flow cytometry. We found that pre‐treatment of hGF with 5′‐AMP induced marked inhibition of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) production from hGF upon stimulation with interleukin‐1α (IL‐1α) by enzyme‐linked immunosorbent assay (ELISA). A specific inhibitor of 5′‐NT, adenosine 5′‐[α,β‐methylene] diphosphate blocked the inhibition of GM‐CSF production, suggesting that adenosine converted from 5′‐AMP acts on the inhibitory effects. The GM‐CSF inhibition suggested that A3 receptor might be involved. The rank order of agonists was found to be (N6‐benzyl‐5′‐N‐ethylcarboxamidoadenosine) A3 receptor agonist ≥ (2‐chloroadenosine) non‐selective agonist > (CGS‐21680) A2A receptor agonist > adenosine ≥ (N6‐cyclohexyladenosine) A1 agonist. Further support for the main role of A3 receptor was the binding A3 antagonist [9‐chloro‐2‐(2‐furanyl)‐5‐([phenylacetyl]amino)[1,2,4]‐triazolo[1,5‐c]quinazdine] reversed the effect of adenosine, but no significant reverse was observed by A1 (1,3‐dipropyl‐8‐cyclopentylxanthine), A2 [3,7‐dimethyl‐1‐(2‐propargyl)xanthine], A2A[8‐(3‐chlorostyryl)caffeine], and A2B (alloxazine) antagonists. The CD73/5′‐NT expression was increased upon stimulation with gamma‐interferon, but not other stimulants such as tumor necrosis factor‐alpha, IL‐4, lipopolysaccharide from Porphyromonas gingivalis and Escherichia coli, and fimbriae from P. gingivalis, and this increase was correlated with the enhanced GM‐CSF inhibition by 5′‐AMP but not adenosine.

Conclusions:  These findings suggested that CD73/5′‐NT on hGF exerts an anti‐inflammatory effects in periodontal disease by conversion from 5′‐AMP to adenosine.
In situ expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts of rat periodontal tissue
Authors: Ogasawara T. , Yoshimine Y. , Kiyoshima T. , Kobayashi I. , Matsuo K. , Akamine A. , Sakai H.
Published: December 2003

Objectives:  This study examined the in situ expression of receptor activator of nuclear factor‐κB ligand (RANKL), receptor activator of nuclear factor‐κB (RANK), osteoprotegerin, interleukin‐1β (IL‐1β) and tumor necrosis factor α (TNFα) in the osteoclasts of rat periodontal tissue.

Background:  In periodontal disease, osteoclasts cause resorption of the alveolar bone. The function of osteoclasts is regulated by interaction with periodontal ligament cells (PDLs). Furthermore, various kinds of molecules such as RANKL, RANK, osteoprotegerin, IL‐1β and TNFα are known to be related to the osteoclasts differentiation and function. It is therefore important to observe the expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts and PDLs.

Methods:  Four‐week‐old Wistar rats were used. Tooth movement was performed by the Waldo method, and the pathological bone resorption was induced. The demineralized maxillae and mandiblae were embedded with paraffin. In situ hybridization was performed to detect RANKL, RANK, osteoprotegerin, IL‐1β, and TNFα mRNAs in osteoclasts and other cells using the specific RNA probes, respectively.

Results:  Both RANKL and RANK were concomitantly expressed in some osteoclasts. RANKL was also positive in osteoblasts and PDLs. No IL‐1β‐ and TNFα‐positive osteoclast was noted. The positive signals of osteoprotegerin were detected in almost all osteoblasts, PDLs and odontoblasts. No osteoprotegerin‐positive osteoclasts were observed. The number and the distribution pattern of RANKL‐ and RANK‐expressing osteoclasts changed when orthodontic excessive force was applied to periodontal tissue. In addition, IL‐1β and TNFα were shown to be expressed in osteoclasts under pathological status.

Conclusion:  These findings suggest that an autocrine mechanism of RANKL–RANK exists in osteoclast, which is heightened in the pathological conditions. Furthermore, the autocrine mechanism of IL‐1β and TNFα is also provided in osteoclast under pathological condition. These autocrine mechanisms therefore seem to regulate the osteoclast function in both physiological and pathological conditions.
The effect of centrifugal force on mRNA levels of collagenase, collagen type‐I, tissue inhibitors of metalloproteinases and β‐actin in cultured human periodontal ligament fibroblasts
Authors: Redlich M. , Roos H. , Reichenberg E. , Zaks B. , Grosskop A. , Bar Kana I. , Pitaru S. , Palmon A.
Published: December 2003

Background:  The aim of orthodontic treatment is to relocate teeth abnormally positioned in the jaws. This is achieved by application of continuous force on the tooth, which is immediately being sensed by the periodontal ligament (PDL), bone and the gingiva. Since the bony response is mediated by the PDL, tooth movement is primarily a PDL phenomenon.

Objectives:  Thus, the purpose of the present study was to evaluate the direct effect of force (excluding the in vivo tissue response) on the molecular level of matrix metalloproteinase‐1 (MMP‐1) and collagen type‐I (Col‐I) in human PDL fibroblasts.

Methods:  PDL cell culture flasks were centrifuged for 10, 20, 30, 60, 90 and 120 min by horizontal microplate rotor. The effect of force on mRNA levels of β‐actin, MMP‐1, Col‐I, tissue inhibitors‐1 and ‐2 (TIMPs) genes was analyzed by RT‐PCR.

Results:  The results showed that force had no effect on the mRNA levels of β‐actin during the first 90 min of application of force, indicating for the first time the use of β‐actin gene as an internal invariant control. It increased the mRNA levels of MMP‐1 while almost no effect on Col‐I and TIMPs was observed.

Conclusions:  The results indicate that PDL remodeling following application of orthodontic force could be partly attributed to the direct effect of the force on MMP‐1 gene expression in fibroblasts.
Accelerated alveolar bone loss in male HLA‐B27 transgenic rats: adult onset
Authors: May Natasha Y. , Tatakis Dimitris N.
Published: December 2003

Objective and background:  HLA‐B27 transgenic (TG) rats exhibit severe colitis, arthritis and other inflammatory lesions. Previous studies in female TG rats indicate that they develop severe alveolar bone loss (ABL). Lack of data on male TG rats has left open the question of possible hormonal/sex dependence for the observed ABL. The purpose of the present study was to assess the natural history of ABL in male HLA‐B27 rats, compared to age‐ and sex‐matched wild‐type Fischer 344 (WT) rats.

Materials and methods:  Fourteen WT and 11 TG male rats, aged 7–8 weeks, were used. Sacrifice times occurred at 10, 22 and 35 weeks. Animal heads were defleshed and treated to remove organic material, and skulls were stained to locate the cemento–enamel junction. ABL was measured as exposed molar root surface area (mm2) on the right maxilla and right mandible. Blinded measurements were performed using a computer‐assisted image analysis system.

Results:  ABL for the entire TG group was significantly different from the WT group (p < 0.05). There was no significant difference in ABL between WT and TG rats at 10 weeks of age. At 22 and 35 weeks of age TG rats experienced 23% and 37% greater ABL than WT rats, respectively; these differences were statistically significant (p < 0.015). For both TG and WT animals, ABL was significantly different between the three age groups.

Conclusions:  These results, consistent with previous findings in female TG rats, suggest that the accelerated ABL found in TG rats is an adult‐onset, age‐dependent, and sex‐independent process.
Mineralized bone loss in partially edentulous trabeculae of ovariectomized rabbit mandibles
Authors: Cao T. , Shirota T. , Ohno K. , Michi K. I.
Published: December 2003

Objective:  The purpose of this study was to evaluate trabeculae changes in partially edentulous bone in ovariectomized rabbits.

Background:  Numerous clinical studies have suggested that the greater risk for oral bone loss in females may be correlated with osteoporosis after menopause. Knowledge of trabecular changes in partially edentulous bone in animals with loss of ovarian function may be beneficial in the diagnosis and treatment of partially edentulous patients of postmenopausal women.

Methods:  Twelve adult female Japanese white rabbits were examined. The mandibular incisors were initially extracted to simulate the partially edentulous bone. Six animals were bilaterally ovariectomized and the other six sham‐ovariectomized 12 weeks after tooth extraction. The partially edentulous parts of distal mandibular bodies were processed undecalcified 12 weeks after ovariectomized or sham‐ovariectomized surgeries and examined by quantitative trabecular bone histomorphometry.

Results:  In ovariectomized rabbits, there were significant increases in trabecular separation, osteoid volume, osteoid thickness, osteoid width, eroded surface, and mineral apposition rate, and a significant decrease in trabecular number.

Conclusion:  The results of sparser trabecular structure, more trabecular osteoid, and increased trabecular bone turnover demonstrate mineralized bone loss in partially edentulous trabeculae of ovariectomized rabbit mandibles and suggest that the same loss may occur in postmenopausal women.
Vigabatrin‐induced modification of Ki‐67 expression in gingival epithelium: immunohistochemical study of a short series
Authors: Mesa F. , Aguilar M. , Gonzalez‐Moles M. A. , Guerrero A. , Sanchez‐Alvarez J. C. , Del Moral R. G. , O'Valle F.
Published: December 2003

Objective:  To study the expression and role in vigabatrin (VGB)‐induced gingival enlargement of Ki‐67 antigen and p27KIP1, p21WAF1, and p53, proteins that activate or inhibit cell‐cycle progression.

Materials and methods:  Six patients treated with VGB for partial epileptic seizures refractory to classic anticonvulsant treatment were studied. Gingival biopsies were taken from four of these patients for immunohistochemical studies; 10 control biopsies from individuals with healthy gingiva and 10 from patients with periodontal disease were also evaluated.

Results:  Four of the six patients presented some degree of gingival enlargement (mild or moderate). Nuclear expression of Ki‐67 was elevated (mean of 894 positive cells/mm2 in VGB‐induced gingival enlargement vs. 391 cells/mm2 in controls with healthy gingiva and 425 cells/mm2 in controls with periodontal disease) (p < 0.01, analysis of variance: anova), and nuclear expression of cyclin‐dependent kinase (cdk) inhibitors p27KIP1 and p21WAF1 was reduced. The patients with gingival enlargement presented inflammatory infiltrate in lamina propria, mainly composed of T lymphocytes (CD3+) and plasma cells (CD38+), which was even more intense than in the biopsies of patients with periodontal disease.

Conclusion:  The overexpression of antigen Ki‐67 and slight underexpression of cdk‐inhibitors p27KIP1 and p21WAF1 suggest that VGB induced an increase in cell proliferation and contributed, together with concomitant periodontal disease, to the gingival enlargement.
Detection of subgingival calculus and dentine caries by laser fluorescence
Authors: Kurihara Eriko , Koseki Takeyoshi , Gohara Kenjiro , Nishihara Tatsuji , Ansai Toshihiro , Takehara Tadamichi
Published: December 2003

Objectives:  Detection of subgingival calculus and dentine caries in the bottom of deep periodontal pockets is often difficult without visual observation. We thus examined the possibility of its detection using autofluorescence induced by laser irritation.

Methods:  Autofluorescence was measured at various excitation and emission wavelength settings in five specimens each of sound dentine and enamel, subgingival calculus, and root caries. Periodontopathic model teeth with bacterial cells and blood clots were also irritated by laser to obtain autofluorescent images.

Results:  Subgingival calculus and dentine caries showed a characteristic 700 nm emission when excited at 635 nm or a 720 nm emission when excited at 655 nm; sound dentine or enamel, however, did not. The calculus differentiation power, however, was higher with excitation at 635 nm than at 655 nm. The autofluorescent images photographed at an excitation of 633 nm provided clear calculus identification in periodontopathic model teeth when a 700 nm band‐pass filter or a 700 nm high‐pass filter was used. However, fluorescence intensity was masked when the calculus surface was covered by bacterial cells or blood clots. For clinical use, it would be important to remove subgingival plaque and debris from root surfaces before attempting to detect subgingival calculus and root caries with this manner.

Conclusion:  The autofluorescence method employing excitation of 633–635 nm was found to be a powerful tool for detecting subgingival calculus and root caries.
Parameterized Modeling of Thermomechanical Reliability for CSP Assemblies
Authors: Vandevelde Bart , Beyne Eric , Zhang Kouchi (G.Q.) , Caers Jo , Vandepitte Dirk , Baelmans Martine
Published: December 2003

Finite element modeling is widely used for estimating the solder joint reliability of electronic packages. In this study, the electronic package is a CSP mounted on a printed circuit board (PCB) using an area array of solder joints varying from 5×4 up to 7×7. An empirical model for estimating the reliability of CSP solder joints is derived by correlating the simulated strains to thermal cycling results for 20 different sample configurations. This empirical model translates the inelastic strains calculated by nonlinear three-dimensional (3D) finite element simulations into a reliability estimation (N50% or N100 ppm). By comparing with the results of reliability tests, it can be concluded that this model is accurate and consistent for analyzing the effect of solder joint geometry. Afterwards, parameter sensitivity analysis was conducted by integrating a design of experiment (DOE) analysis with the reliable solder fatigue prediction models, following the method of simulation-based optimization. Several parameters are analyzed: the PCB parameters (elastic modulus, coefficient of thermal expansion, thickness), the chip dimensions (area array configuration), and the parameters defining the solder joint geometry (substrate and chip pad diameter, solder volume). The first study analyzes how the solder joint geometry influences the CSP reliability. A second study is a tolerance analysis for six parameters. These parameters can have a tolerance (=accuracy) of their nominal value, and it is shown that these small tolerances can have a significant influence on the solder joint reliability.