bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental differences in the expression and modulation of extracellular matrix proteases and inhibitors in mouse skin fibroblasts
Authors: Island Eddie , Wu Huayang , Warburton David , Anderson Kathryn , Tuan Tai‐Lan
Published: March 2003

To investigate developmental differences in the wound repair process between fetal and adult skin fibroblasts, we studied the expression of plasminogen activator, plasminogen activator inhibitor, matrix metalloproteinase, and tissue inhibitor of metalloproteinase in E‐15, E‐17, newborn and adult mouse skin fibroblasts cultured within three dimensional matrices of either collagen or fibrin. Fibrin overlay and reverse overlay analyses revealed that mouse skin fibroblasts secreted tissue plasminogen activator and type1 plasminogen activator inhibitor. However, only E‐15 and E‐17 fibroblasts secreted the active form of tissue plasminogen activator, while in newborn and adult fibroblasts tissue plasminogen activator was conjugated to type1 plasminogen activator inhibitor. Only adult fibroblasts expressed a high level of active type1 plasminogen activator inhibitor. Gelatin zymography revealed that the predominant matrix metalloproteinase secreted by all the mouse fibroblasts was gelatinase A (matrix metalloproteinase ‐2). Matrix metalloproteinase ‐2 was partially activated in the adult fibroblasts cultured within a collagen matrix. The tissue inhibitor of metalloproteinase‐2 was expressed by all fibroblasts, but levels were highest in the newborn and adult fibroblasts. When E‐15 fibroblasts were cultured within a fibrin matrix, tissue plasminogen activator was downregulated. Transforming growth factor‐βdownregulated tissue plasminogen activator while upregulating type1 plasminogen activator inhibitor, and platelet‐derived growth factor enhanced tissue plasminogen activator expression in E‐15 fibroblasts. Therefore, plasminogen activator and its inhibitor, and matrix metalloproteinase and its associated tissue inhibitor are differentially expressed in fetal and adult fibroblasts, and their expression is controlled by extracellular matrix components and growth factors present in wounds.
The accuracy of using a wound care specialty clinic database to study diabetic neuropathic foot ulcers
Authors: Kantor Jonathan , Margolis David J
Published: March 2003

Few epidemiologic studies have examined the effect of clinical risk factors on the probability that a patient with a chronic wound will heal or develop another wound. Curative Health Services maintains one of the few databases that contain detailed patient record information on patients with chronic wounds. The purpose of this study was to evaluate the reliability and validity of using this database to study individuals with diabetic neuropathic foot ulcers. 154 patient medical records were randomly selected from the database and abstracted using a standardized questionnaire and protocol. We assessed three key variables: diagnosis of diabetic neuropathic foot ulcer, whether the patient healed, and if the patient received an autologous product called platelet releasate. These variables in the database very accurately agreed with the information in the patient medical records, with positive predictive values of 98% (95% confidence interval [0.89, 0.99]), 93% (95% confidence interval [0.68, 0.99]), and 100%, respectively. We have shown that, with respect to these three variables, the database is very accurate when compared to the medical record. It therefore represents a valuable tool with which to study patients with diabetic insensate foot ulcers.
Duration of surgery and patient age affect wound healing in children
Authors: Pajulo Olli T , Pulkki Kari J , Alanen Markku S , Reunanen Mikko S , Lertola Kalle K , Mattila‐Vuori Armi I , Viljanto Jouko A
Published: March 2003

The migration of inflammatory cells into a wound and their subsequent changes during wound healing are essential for the complex processes of tissue repair to occur. The aim of this work was to investigate the number of wound leukocytes during early wound healing at different time periods in children. Wound cells of 184 children aged 0–15 years, operated on for a benign disease in the lower abdominal region, were harvested with the Cellstick® device. The device was removed from the wound at 3, 6, or 24 hours after surgery and differential cell counts were performed. The cellular patterns were significantly influenced by the age of the patient and by the duration of the surgery. The proportions of neutrophils, lymphocytes, and monocytes changed significantly from 3–24 hours. Our results suggest that there is a distinct time‐related change in the pattern of inflammatory cells in the early phase of wound healing in children. This pattern is affected by the age of the child and by the duration of the surgery.
Interleukin‐8 levels and activity in delayed‐healing human thermal wounds
Authors: Iocono Joseph A , Colleran Kevin R , Remick Daniel G , Gillespie Brenda W , Ehrlich H. Paul , Garner Warren L
Published: March 2003

There are numerous causes for slow or delayed wound healing. Because slowly healing wounds are often inflamed, we quantitated the inflammatory chemokine, interleukin‐8, produced by slowly healing human burn wounds and compared this to interleukin‐8 from healed wounds and normal intact skin. Interleukin‐8 levels were increased significantly in unhealed wounds (19.7 ng/ml) compared to healed wounds (7.7 ng/ml) or normal skin (5.7 ng/ml). Interleukin‐8 in these ranges was added to adult human keratinocytes and fibroblasts. Interleukin‐8 significantly decreased keratinocyte replication but had no effect on fibroblast replication. The rate or final degree of fibroblast populated collagen lattice contraction was inhibited at interleukin‐8 concentrations between 10 and 30 ng/ml, but not altered at concentrations below 10 ng/ml and above 100 ng/ml. The concurrent application of indomethacin at 10 μg/ml reversed this interleukin‐8 induced inhibition. Interleukin‐8 inhibited myosin ATPase activity, apparently by reducing the phosphorylation of nonmuscle myosin light chain. We conclude that elevated levels of interleukin‐8 may be found during delayed healing, and these elevated interleukin‐8 levels may directly contribute to retarded wound closure.
Matrix‐enabled gene transfer for cutaneous wound repair
Authors: Chandler Lois A , Ma Chenglie , Gonzalez Ana Maria , Doukas John , Nguyen Thanh , Pierce Glenn F , Phillips M. Laurie
Published: March 2003

Several growth factor proteins have been evaluated as therapeutic agents for the treatment of chronic dermal wounds. Unfortunately, most have failed to produce significant improvements in wound healing, in part due to ineffective delivery and poor retention in the wound defect. It has been proposed that gene therapy might overcome the limitations of protein therapy via ongoing transcription and translation, thus prolonging the availability of the therapeutic protein. Reasoning that it would be of further benefit to ensure retention of the DNA vector as well as the therapeutic protein within the wound defect, we have evaluated matrix‐enabled gene transfer for cutaneous wound repair (Gene Activated Matrix). Formulations consisting of bovine type I collagen mixed with adenoviral or plasmid gene vectors have been evaluated in 3 in vivo models. The therapeutic transgenes employed encode human platelet‐derived growth factor‐A or ‐B, proteins key to each phase of normal wound repair. Increased granulation tissue formation, vascularization, and reepithelialization have been shown compared to controls treated with collagen alone or collagen containing a reporter gene vector. Further enhancements of the tissue repair response have been achieved by combining matrix‐enabled gene transfer with molecular targeting, in which the DNA vector is conjugated to a growth factor ligand (basic fibroblast growth factor). These promising results support the clinical evaluation of gene activated matrices for the treatment of chronic dermal wounds.
Use of the wound healing trajectory as an outcome determinant for acute wound healing
Authors: Franz Michael G , Kuhn M. Ann , Wright Terry E , Wachtel Thomas L , Robson Martin C
Published: March 2003

Accurate and clinically practical methods for measuring the progress of acute wound healing is necessary before interventions designed to optimize and even accelerate acute wound healing can be applied. Complete wound closure rates and operative wound closure severity are irrelevant to most acute wounds since most are closed at the time of primary tissue repair and remain closed throughout healing. Analogous to chronic wound closure, the rate of increase of incision tensile strength progressively decreases as time passes and 100% unwounded tissue strength is never achieved making the endpoint definition of “healed” vague. Conceptualizing acute wound healing in terms of its design elements with reintegration into a final outcome lends itself to the description of acute wound healing as a mathematical trajectory. Frequently such an equation is a rate expressing the change in an acute healing parameter, most often tensile strength, over time. Such an approach also normalizes misinterpretations in analysis or errors in theory developed by measuring healing parameters at fixed points in time. Distributions of fractional strength gain times (e.g., 85% normal strength) can be determined using statistical methodology similar that used for failure time of survival analysis. Preclinical studies show that acute wound healing trajectories can be shifted to the left from a “normal” or “impaired” curve to an accelerated or more “ideal” curve. A useful method for measuring acute wound healing outcomes is therefore required before the basic science of acute wound healing is inevitably applied to the problem of acute surgical wounds.
Role of glutathione redox dysfunction in diabetic wounds
Authors: MUDGE BRADLEY P. , HARRIS CRAIG , GILMONT ROBERT R. , ADAMSON BELINDA S. , REES RILEY S.
Published: March 2003

We propose that diabetic foot ulcers and diabetic mouse wounds have insufficient glutathione to maintain correct cellular redox potential. Therefore, tissue samples from the wound edge of diabetic foot ulcers, diabetic mice wounds and nondiabetic mice wounds were obtained. Levels of glutathione, cysteine, and mixed protein disulfide were determined and topical application of esterified glutathione in carboxymethylcellulose or carboxymethylcellulose alone was applied to the mice wounds. Diabetic foot ulcer mean glutathione levels were 150.6 pmol/mg in the controls and 53.4 pmol/mg at the wound edge (p < 0.05), while mean cysteine levels were 22.3 pmol/mg in the control and 10.5 pmol/mg at the wound edge (p < 0.05). The mixed protein disulfide levels were elevated in the wounds (14.6 pmol/mg), but not in the control (6.9 pmol/mg) (p < 0.05). The glutathione levels were lower in the diabetic mouse wounds (155 pmol/mg) than the nondiabetic mouse wounds (205 pmol/mg) (p=0.04). The diabetic mouse treated with carboxymethylcellulose alone healed slower (19.5 ± 2.2 days) than the nondiabetic mouse DM (11.5 ± 0.5 days) (p < 0.001). The diabetic mouse that received topical glutathione healed significantly faster (12.5 ± 0.8 days) than the carboxymethylcellulose‐treated mice (19.5 ± 2.2 days) (p < 0.001). Glutathione levels in the diabetic mouse (26.0 pmol/mg) were lower than in the nondiabetic mouse (311.7 pmol/mg) (p < 0.05) after glutathione treatment. In the glutathione‐treated diabetic mouse, the oxidized glutathione was higher (26.7%) than in the nondiabetic mouse (9.9%) (p=0.05). These data suggest that cellular redox dysfunction and lower glutathione levels are present in diabetic foot ulcers and diabetic mouse wounds.
Development, characterization, and wound healing of the keratin 14 promoted transforming growth factor‐β1 transgenic mouse
Authors: Chan Teddy , Ghahary Aziz , Demare Jack , Yang Liju , Iwashina Takashi , Scott PaulG. , Tredget Edward E.
Published: March 2003

Transforming growth factor‐β1 is a fibrogenic cytokine that is important in the development of fibroproliferative disorders of the skin after injury. To investigate the role of transforming growth factor‐β1 produced by keratinocytes during wound healing, a plasmid with the human transforming growth factor‐β1 gene coupled with the keratin 14 promoter (pG3Z: K14‐TGF‐β1) was constructed. The construct was tested successfully in vitro before being used to generate transgenic animals, which were subsequently bred into homozygous and heterozygous lines. Genotype screening of founders and progeny was performed by Southern blotting and targeting of the transgene to the epidermis by the keratin 14 promoter was shown by reverse transcription polymerase chain reaction. The major phenotypic change observed in the transgenic animals was “scruffiness” of the fur attributed to transgene expression in the skin, seen primarily in the homozygous line. A significant reduction in the rate of reepithelialization of full‐thickness excisional wounds of dorsal skin was seen in homozygous animals compared with normal litter‐mate controls at day 7 (p < 0.05, Fisher's Exact test) and day 9 (p < 0.01) postwounding. Wounds in heterozygous animals also healed more slowly at day 9 (p < 0.01). Northern analysis of mRNA extracted from the wounds showed increased human transforming growth factor‐β1 message levels in homozygous and heterozygous animals, maximal at day 5. Significant increases in transforming growth factor‐β1 activity in healing wounds measured using the plasminogen activator inhibitor‐1/luciferase assay were found in the transgenic strains at day 9 postinjury as compared with the normal litter‐mate control mice (p < 0.001, ANOVA). Type I procollagen mRNA expression was higher in the homozygous and heterozygous animals, with the highest levels reached at day 9. By day 5 postwounding, biopsies of both homozygous and heterozygous tissues were significantly higher in collagen as compared with wounds in control animals (p < 0.05, ANOVA). Based on these data, the K14‐TGF‐β1 transgenic mouse shows that excessive latent transforming growth factor‐β1 produced in the epidermal layer of the skin delays reepithelialization in excisional wounds but subsequently the cells of the epidermis stimulate dermal fibroblasts leading to fibrosis through a paracrine mechanism. (WOUND REP REG 2002;10:)
U–Pb isotopic constraints on diachronous metamorphism in the northern Monashee complex, southern Canadian Cordillera
Authors: Crowley  , Parrish
Published: March 2003

U–Pb isotopic data from the northern Monashee complex, one of the deepest structural exposures in the southern Canadian Cordillera, indicate that the age of metamorphism varies according to structural position in a 6 km thick section. This metamorphism resulted in an unusual sequence in which rocks with the lowest‐grade mineral assemblage (kyanite–sillimanite–staurolite–muscovite) are underlain and overlain by higher‐grade rocks. Xenotime and monazite U–Pb dates vary progressively from 64 Ma in the structurally highest rocks to 49 Ma in the deepest rocks. Discordant U–Pb ages from Proterozoic and Cretaceous monazite and titanite are used to interpret the thermal significance of the early Tertiary dates. The discordant analyses define linear arrays with lower intercepts that broadly overlap with early Tertiary, and the amount of discordance varies with structural level; it is least in the deeper rocks and greatest in higher rocks. Electron microprobe work showed that the monazite discordance in the deeper rocks resulted from Tertiary mineral overgrowth and recrystallization rather than Pb diffusion. We use previous studies of Pb diffusion and the fact that Proterozoic monazite and titanite suffered only negligible to moderate amounts of diffusive Pb loss to contend that elevated temperatures (c. 600–650 °C are inferred from pelitic mineral assemblages) existed in the deeper rocks for a short duration, perhaps a few million years. The downwards younging 64–49 Ma U–Pb dates are interpreted as closely reflecting xenotime and monazite growth ages rather than cooling ages or substantially reset ages based on the lack of Pb diffusion in monazite and the previously obtained 40Ar/39Ar data which suggest that rapid cooling occurred immediately after the U–Pb dates. In addition, growth ages are interpreted as thermal peak ages based on U–Pb dates from coeval kyanite‐bearing leucosomes, the consistent nature of the U–Pb dates throughout the study area, and petrographic relationships which suggest that monazite grew before or during development of the syn‐metamorphic foliation. These interpretations lead us to conclude that metamorphism was diachronous according to structural level, with higher rocks attaining peak temperatures and cooling rapidly while deeper rocks were heating towards a thermal peak that was attained a few million years later. This thermal scenario requires that higher rocks cannot have been the heat source for the deeper metamorphism, as was previously proposed.
Comparison of diagenetic and low‐grade metamorphic evolution of chlorite in associated metapelites and metabasites: an integrated TEM and XRD study
Authors: Árkai  , Mata M. P. , Giorgetti  , Peacor  , TÓth
Published: March 2003

Chlorite is a common sheet silicate that occurs in various lithologies over a wide grade range involving diagenesis and low‐grade metamorphism. Thus, the reaction progress of chlorite offers a unique opportunity for direct correlation of zonal classification of metasedimentary rocks based on illite crystallinity with metabasite mineral facies. To provide such correlation, chlorite crystallinity indices, apparent mean crystallite sizes and lattice strains, crystallite size distributions and compositions of chlorite from coexisting metapelites and metabasites were determined by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), analytical electron microscopy (AEM) and electron microprobe (EMP) methods. Samples were from Palaeozoic and Mesozoic formations of the Bükkium (innermost Western Carpathians, Hungary) that underwent Alpine (Cretaceous) orogenic metamorphism. Metapelites range in grade from late diagenesis to epizone, whereas metabasites vary from prehnite–pumpellyite through pumpellyite–actinolite to greenschist facies.

Despite significant differences in composition, mineral assemblages and textures, reaction progress, as measured in part by chlorite crystallinity, in metapelites paralleled that in metabasites. Chlorite crystallinity and mean crystallite size increase and the proportion of mixed layers in chlorite decreases, whereas the calculated lattice strain does not change significantly with increasing metamorphic grade. Similar trends, but (especially at higher grades) significant differences, were found in mean crystallite size values using various methods for XRD line profile analyses. The increase in crystallite size with increasing grade was demonstrated also by direct TEM measurements on ion‐milled whole‐rock samples, but with a larger scatter of data at higher grades. In spite of the different kinds of mixed layering in chlorite (Mg‐rich smectitic, mostly random, local corrensite‐like units in metabasites, and Fe‐rich berthierine and dioctahedral smectite in metapelites), XRD‐calculated and TEM‐measured parameters were found to be reliable tools for measuring reaction progress and metamorphic grade of the same degree in both lithotypes.
Contrasting pressure–temperature–deformation history across a vestigial craton–mobile belt boundary: the western margin of the Eastern Ghats Belt at Deobhog, India
Authors: Gupta S. , Bhattacharya A. , Raith M. , Nanda J.K.
Published: March 2003

At Deobhog, migmatitic gneisses and granulites of the Eastern Ghats Belt are juxtaposed against a cratonic ensemble of banded augen gneiss, amphibolite and calcsilicate gneiss, intruded by late hornblende granite and dolerite. In the migmatitic gneiss unit, early isoclinal folds (syn‐D1M and D2M) are reoriented along N–S‐trending and E‐dipping shear planes (S3M), with (S1M–S3M) intersection lineations having steep to moderate plunges. The near‐peak P–T  condition was syn‐D3M (≥900 °C, 9.5 kbar), as inferred from syn‐D3M Grt+Opx‐bearing leucosomes in mafic granulites, and from thermobarometry on Grt (corona)–Opx/Cpx–Pl–Qtz assemblages. The P–T  values are consistent with the occurrence of Opx–Spr–Crd assemblages in spatially associated high‐Mg–Al pelites. A subsequent period of cooling followed by isothermal decompression (800–850 °C, c. 7 kbar) is documented by the formation of coronal garnet and its decomposition to Opx+Pl symplectites in mafic granulites. Hydrous fluid infiltration accompanying the retrograde changes is manifested in biotite replacing Opx in some lithologies.

The cratonic banded gneiss–granite unit also documents two phases of isoclinal folding (D1B & D2B), with the L2B lineation girdle different from the lineation spread in the migmatitic gneiss unit. Calcsilicate gneiss (Hbl–Pl–Cpx–Scap–Cal) and amphibolite (Hbl–Pl±Grt±Cpx) within banded gneisses record syn‐D2B peak metamorphic conditions (c. 700 °C, 6.5 kbar), followed by cooling (to c. 500 °C) manifested in the stabilization of coronal clinozoisite–epidote. The D3B shear deformation post‐dates granite and dolerite intrusions and is characterized by top‐to‐the‐west movement along N–S‐trending, E‐dipping shear planes. Deformation mechanisms of quartz and feldspar in granites and banded gneisses and amphibole–plagioclase thermometry within shear bands in dolerites document an inverted syn‐D3B thermal gradient with temperature increasing from 350 to 550 °C in the west to ≥700 °C near the contact with the migmatitic gneiss unit. The thermal gradient is reflected in the stabilization of chlorite after hornblende in S3B shears to the west, and post‐D2B neosome segregation along D3B folds and shears to the east.

The contrasting lithologies, early structures and peak metamorphic conditions in the two units indicate unconnected pre‐D3P–T –deformation histories. The shared D3 deformation in the two units, the syn‐D3 inverted thermal gradient preserved in the footwall cratonic rocks and the complementary cooling and hydration of the hanging wall granulites across the contact are attributed to westward thrusting of ‘hot’ Eastern Ghats granulites on ‘cool’ cratonic crust. It is suggested that the Eastern Ghats migmatitic gneiss unit is not a reworked part of the craton, but a para‐autochthonous/allochthonous unit emplaced on and amalgamated to the craton.
Individualizing the Dialysate in the Hemodialysis Patient
Authors: Palmer Biff F.
Published: March 2003

In most outpatient centers the dialysate is prepared centrally such that the composition of the dialysate is the same for all patients. When delivered in this manner most patients tolerate the procedure well. However, there are patients who tolerate the procedure poorly, which has prompted a great deal of research focused on individualizing the composition of the dialysate in order to improve patient tolerability. Prescribing a patient‐specific dialysate will become increasingly important as the age of and number of comorbid conditions increase in the dialysis population.

Patients with end‐stage renal disease (ESRD) depend on dialysis to maintain fluid and electrolyte balance. Hemodialysis allows for solutes to diffuse between blood and dialysate such that, over the course of the procedure, plasma composition is restored toward normal values. The makeup of the dialysate is of paramount importance in accomplishing this goal. In most outpatient settings patients receive hemodialysis using dialysate prepared in bulk and delivered via a central delivery system so that the composition of the dialysate is the same for all patients. While most patients tolerate the procedure when administered in this fashion, many patients suffer from hemodynamic instability or symptoms of dialysis disequilibrium. One strategy to improve the clinical tolerance to dialysis is to adjust the dialysate composition according to the individual characteristics of the patient. This article reviews recent developments on how the dialysate can be manipulated in order to improve patient tolerance. Individualizing the dialysate composition is likely to gain increasing importance given the advancing age and increasing number of comorbid conditions found in ESRD patients.
Dialysis‐Induced Oxidative Stress: Biological Aspects, Clinical Consequences, and Therapy
Authors: Descamps‐Latscha Béatrice , Drüeke Tilman , Witko‐Sarsat Véronique
Published: March 2003

Oxidative stress, which results from a rupture in the natural balance between pro‐ and antioxidant systems, is considered as a major factor in dialysis‐associated morbidity and mortality. Emerging pharmacologic and dialytic antioxidant therapeutic and dialysis strategies should enable us to reduce the harmful consequences of oxidative stress in dialysis patients. Moreover, since there is increasing evidence of oxidative stress long before the initiation of maintenance dialysis, antioxidant therapeutic strategies should probably be developed very early in the course of renal failure.
Hyperkalemia in Dialysis Patients
Authors: Ahmed Junaid , Weisberg Lawrence S.
Published: March 2003

Serious hyperkalemia is common in patients with end‐stage renal disease (ESRD) and accounts for considerable morbidity and death. Mechanisms of extrarenal disposal of potassium (gastrointestinal excretion and cellular uptake) play a crucial role in the defense against hyperkalemia in this population. In this article we review extrarenal potassium homeostasis and its alteration in patients with ESRD. We pay particular attention to the factors that influence the movement of potassium across cell membranes. With that background we discuss the emergency treatment of hyperkalemia in patients with ESRD. We conclude with a review of strategies to reduce the risk of hyperkalemia in this population of patients.
Should Hemoglobin be Normalized in Patients with Chronic Kidney Disease?
Authors: Stevens Lesley , Stigant Caroline , Levin Adeera
Published: March 2003

In the last decade the nephrology community has learned much about the impact of anemia on patients with kidney disease. Therapy of anemia can correct many of the symptoms which seriously compromise patient function. Despite the obvious benefits, controversy continues regarding the optimal target hemoglobin concentration both in patients prior to dialysis and in dialysis populations. In this editorial we review the clinical data that contribute to this controversy and the physiologic concepts underlying the treatment of anemia. Furthermore, we discuss the need to individualize hemoglobin targets for specific patient populations and the importance of early identification and treatment of anemia in patients with kidney disease. The economic impact of normalizing hemoglobin with the use of erythropoietin and intravenous or oral iron has affected clinical practice over the last decade. Current guidelines published by Kidney Disease Outcomes and Quality Initiative (KDOQI), the European Working Group on Anemia Management, and the Canadian Society of Nephrology all recommend target hemoglobin concentrations and thresholds for initiation of therapy and also suggest the need for reevaluation of current targets in light of new evidence. This editorial supports those guidelines and challenges the reader to critically evaluate current practice in the context of the accumulating data and the physiologic principles discussed herein. The therapy of anemia in patients with chronic kidney disease (CKD) is becoming increasingly sophisticated and is an essential component of care in patients with CKD. However, the effects of therapy will be most impressive when accompanied by the optimal care of all hemodynamic and metabolic abnormalities that are associated with CKD.
Study Designs and Their Potential Influence on Conclusions
Authors: Szczech Lynda Anne , Coladonato Joseph A. , Owen William F.
Published: March 2003

Epidemiology is the basic medical science that focuses on the distribution and determinants of disease frequency in human populations. An understanding of the tools of epidemiology is helpful in defining the limitations of medical research and evaluating the conclusions of studies. This is the second in a series of three articles whose objective is to present the basic concepts of epidemiology and biostatistics, highlighted by examples of these concepts applied in the medical literature studying patients receiving dialysis. This article describes the study designs of case‐control, cohort, and randomized trials and issues in the conduct and analysis of each. Several studies examining the association between hematocrit and survival of dialysis patients are discussed. Their differences in design and methods are discussed in the context of their effect on study conclusions. The goal of this article is to present the reader with the issues of study design and the limitations they impose on study conclusions. Through the examination of these methods, the reader will be able to rigorously examine study methods and understand how design affects study conclusions and their application to patient care.
Automated Peritoneal Dialysis Symposium: Intra‐abdominal Pressure, Peritoneal Dialysis Exchange Volume, and Tolerance in APD
Authors: Enoch Christopher , Aslam Nabeel , Piraino Beth
Published: March 2003

Automated peritoneal dialysis (APD) is increasingly popular compared to continuous ambulatory peritoneal dialysis (CAPD). It not only can provide more solute clearance and ultrafiltration than its CAPD counterpart, but it is conducive to a more convenient lifestyle as well. Using relatively smaller‐volume daytime dwells, with the use of larger‐volume exchanges while the patient is recumbent during the night, is an attractive approach. Advantages of supine exchanges include greater small molecule clearances for equivalent flow rates and decreased intra‐abdominal pressure per volume of dialysate (as intraperitoneal pressure parallels intraperitoneal volume). Urea nitrogen clearance can be optimally increased on APD by increasing both the exchange volume and the frequency of exchanges at night. This is even true for anuric low transporters. This approach allows daytime exchanges and volumes to be minimized. Historic studies in peritoneal dialysis including flow rate analysis, clearance and adequacy studies, as well as tolerance have primarily involved CAPD. As a result, there is a paucity of investigations involving APD. More research is required in APD related to these subjects.
Disclosure of Misattributed Paternity: Issues Involved in the Discovery of Unsought Information
Authors: Wright Linda , MacRae Susan , Gordon Debra , Elliot Esther , Dixon David , Abbey Susan , Richardson Robert
Published: March 2003

Kidney transplantation from living donors is generally a safe, effective form of renal replacement therapy. When evaluating potential living donors and their intended recipients, a careful assessment process is followed in order to ensure that ethical standards are upheld. During this assessment, important medical information with serious consequences, which was not being sought as part of the donor/recipient evaluation, may be discovered. The information may or may not be relevant to the decision to donate. However, such a discovery raises the difficult questions of whether or not there is an obligation to disclose the information, to whom does the information belong, and what process should be used to resolve the issue? We present a case that forced us to confront these questions and raised issues of truth telling, autonomy, paternalism, confidentiality, and the nature of the relationship between patients and health care professionals.
Extended Follow‐Up of Patients with Stage T2a Prostate Adenocarcinoma After Outpatient Conformal Brachytherapy: Risk Stratification for Treatment Optimization
Authors: Sundararaman Srinath , Nori Dattatreyudu , Parikh Suhrid K. , Moni Janaki , Osian Adrian , Wilson Chester
Published: March 2003

Brachytherapy is an excellent definitive treatment modality for select patients with localized prostate cancer. Sixty‐four patients with Stage T2a prostate adenocarcinoma were identified from the series of prostate patients receiving conformal outpatient brachytherapy between 1990 and 1997. Pretreatment Gleason scores and prostate specific antigen (PSA) values ranged from 2 to 10 and 1.5 to 100, respectively. Median follow‐up was 48.5 months. The 5‐year overall survival rate was 82.5%, whereas the cause‐specific survival rate was 93.7%. The biochemical freedom‐from‐relapse (bFFR), defined as a PSA level of ≤ 1.0 for patients presenting with Gleason scores of ≤ 5, was 68%; 80% with Gleason scores of ≤ 5 and presenting PSA levels of ≤ 10. In patients with Gleason scores of 6 at presentation, the overall bFFrR was 67%; 87% with a Gleason scores of 6 and PSA levels of ≤ 10. The bFFR was maintained in more than half of patients with Gleason scores of 7 only if they presented with PSA levels of ≤ 10. All patients who presented with PSA levels of ≤ 10 had bFFRs of 75%, compared to 36% for those patients presenting with PSA levels of > 10. These data show that patients with Gleason scores of ≤ 5 can achieve very good PSA control with brachytherapy, especially if the presenting PSA level is ≤ 10. Consideration of PSA is of greater import when a Gleason score ≥ 6 is encountered at presentation. Our data show that durable bFFR can be achieved in patients presenting with Stage T2a disease, Gleason scores of 5–7, and PSA levels of ≤ 10. These results need to be confirmed with further follow‐up and other prospective data.
Pathologic Features of Occult Prostatic Carcinoma in Hypogonadal Men
Authors: Zhang Ping L. , Bubley Glenn , Upton Melissa , Morgentaler Abraham , DeWolf William C. , Rosen Seymour
Published: March 2003

Objectives: Androgen therapy in hypogonadal men with low free testosterone levels (< 1.5 ng/dl) is potentially dangerous because exogenous androgen may stimulate occult prostatic adenocarcinoma (PA). Our previous study reported occult PA (14% incidence) in hypogonadal men with normal prostate specific antigen (PSA) levels and normal findings on digital rectal examination (DRE). The purpose of the current study was to examine the extent and nature of PA in prostatectomy specimens of hypogonadal patients.

Materials and Methods: PA in these14 patients (the hypogonadal group) was compared to a control group of patients (n = 14). The two groups of patients were matched with similar mean ages, Gleason scores, and percentage of core involvement by PA. Subsequently, PA in prostatectomy specimens was analyzed in the two groups with additional comparison of immunohistochemical sections for androgen receptors, PSA, and prostatic acid phosphatase.

Results: As expected, patients in the hypogonadal group had significantly lower levels of PSA and free testosterone than those in the control group (PSA 2.32 ± 0.60 ng/ml versus 8.06 ± 1.17 ng/ml, respectively; free testosterone 1.17 ± 0.09 ng/dl versus 1.74 ± 0.20 ng/dl, respectively). Prostatectomy specimens in hypogonadal patients (n = 9) showed a less extensive PA (0% positive margins, 11% perineural invasion, 78% unilateral tumor, and 22% bilateral tumor) compared to control prostatectomy specimens (n = 14) (21% positive margins, 42% perineural invasion, 21% unilateral tumor, and 58% bilateral tumor). However, immunohistochemical studies using anti‐androgen receptor, anti‐PSA and anti‐prostatic acid phosphatase antibodies showed that carcinoma cells stained with equivalent intensity in both groups.

Conclusions: PA in hypogonadal patients who had normal DREs and PSA levels appears to be less extensive but otherwise is not morphologically different than usual and should be treated in the same manner. The high incidence of occult PA in these hypogonadal patients makes screening prostate biopsies important before the androgen replacement therapy.
Pilot Study of Oral Eniluracil/5‐FU in the Palliation of Hormone‐Refractory Prostate Cancer
Authors: Rosenthal Mark A. , Thomas David , Davis Ian , Toner Guy , Noordin Naeem , Zalcberg John
Published: March 2003

Objectives: Chemotherapy has an established role in the palliative therapy of patients with hormone‐refractory prostate cancer (HRPC). However, optimal chemotherapy for HRPC remains poorly defined. This pilot study examined the activity and toxicity of oral 5‐fluorouracil (5‐FU) in combination with eniluracil for the treatment of patients with HRPC.

Materials and Methods: Eighteen patients with HRPC and painful bone metastases were enrolled, although 1 patient was deemed ineligible because of incidental gastric cancer. The median age was 69 years (range, 57–82 years), median Eastern Cooperative Oncology Group performance status was 1 (range, 0–2) and median prostate specific antigen (PSA) level was 146 μg/l (range 4–2020 μg/l). Eniluracil (10 mg/m2) and 5‐FU (1 mg/m2) were given orally, twice daily, for 28 days in 35‐day cycles.

Results: Two patients (11%) had partial pain responses (95% confidence interval, 0–29%), and 6 patients (35%) had stable pain for a minimum of 8 weeks. A reduction in analgesic use occurred in four patients (23%), and five patients (29%) experienced stable analgesic use. A partial PSA response (>50% reduction on at least two occasions, 5 weeks apart) was achieved in three patients (18%), and eight patients (48%) had stable PSA responses (PSA was rising pretreatment). Grade 4 diarrhea occurred in one patient. Grade 3 toxicities were as follows: anemia, 1 patient; lethargy, 1 patient; and deterioration in liver function, 1 patient.

Conclusions: Oral eniluracil/5‐FU is well tolerated in this patient population but has only modest activity. Studies in combination with other active agents may be warranted in patients with HRPC.
The Effects of a Walking Exercise Program on Physical Function and Emotional State of Elderly Korean Women
Authors: Shin YunHee
Published: March 2003

Exercise is an important strategy for preventing chronic diseases and promoting the health of older adults. The purpose of this research was to evaluate the effects of an outdoor walking exercise program on the cardiorespiratory function, the flexibility, and the emotional state of elderly Korean women. A nonequivalent control group, pretest‐posttest design was used to measure the effects of the exercise program. The subjects were 27 females between the ages of 60 to 75 years. The intensity of the walking program was 40–60% of the target heart‐rate with a duration of 50–60 min, 3 times per week at an outdoor track for 8 weeks. The effects of the program were assessed by maximal oxygen uptake (VO2max), resting pulse rate, blood pressure, Forced Vital Capacity (FVC), Forced Expiratory Volume per 1 second (FEV1) for cardiorespiratory function, the “sit and reach test” for flexibility, and by the Profile of Mood States (POMS) for emotional state. The physical function and the emotional state of the experimental group improved significantly more than that of the control group except FEV1 and the anger factor of POMS. The VO2max and the flexibility of elderly women in the experimental group progressively improved as the duration of the exercise period continued. The results of this study suggest a practical and easy method of exercise to enhance the health of older women.
Use of the SF‐36 to Identify Community Dwelling Rural Elderly at Risk for Hospitalization
Authors: Benjamin‐Coleman Richardean , Alexy Betty
Published: March 2003

The SF‐36 has been identified as a generic measure of health‐related quality of life outcomes which is not age, disease, or treatment specific and is deemed appropriate for monitoring the results of care as well as a measure of outcomes from the patient's perspective. The purpose of this study was to use the SF‐36 to assess the general health status and health promotion activity of rural elderly 1 year following participation in a community‐based health promotion project. Eighty participants from the original sample of 222 (190 community‐based and 32 home‐based) were contacted by telephone and the SF‐36 was administered. Results found that 76% of the study participants were correctly predicted for past hospitalization. While this project studied elderly in a rural community, the administration of this instrument can be useful in identifying a variety of populations at risk for hospitalization.
Public Health Nurses' Responses to Domestic Violence: A Report from the Enhanced Domestic Abuse Intervention Project
Authors: Shepard Melanie F. , Elliott Barbara A. , Falk Dennis R. , Regal Ronald R.
Published: March 2003

Public health nurses (PHNs) can play an important role in the detection of domestic violence. This study examines whether the introduction of a domestic violence assessment protocol by public health nurses in a maternal and child health visiting program increases the identification and referral rates of women experiencing domestic violence. Data collected from case files during the baseline year prior to the initiation of the protocol were compared to case file information after the protocol had been implemented. When the protocol was used, there was a higher rate of identification, although the difference was not statistically significant. Significantly more women, however, were provided with information about domestic violence resources after the protocol was in place, and significantly more women were referred to services in the second year after the protocol had been implemented. This study provides support for the use of a domestic violence protocol to improve the public health nursing response to domestic violence.
Public Health Nursing Directors' Perceptions Regarding Interagency Collaboration with Community Mental Health Agencies
Authors: Chaudry Rosemary V , Polivka Barbara J , Kennedy Carol W
Published: March 2003

Involvement in collaborative interagency relationships is crucial to the future of public health nursing and public health agencies. The purpose of this study was to describe public health nursing directors' perceptions regarding relationships between public health agencies and mental health agencies in their communities. A secondary analysis was conducted of textual responses to open‐ended questions and unsolicited comments from 71 (55%) the of respondents to a larger survey of nursing directors of all public health agencies in Ohio. Data were analyzed inductively using content analysis for emergent themes and patterns, which were organized and classified deductively according to a community interagency collaboration framework. Public health nursing directors described environmental, situational, task, and interagency factors that impact collaboration between their agencies and local community mental health agencies. These descriptions provide a context for understanding impediments to collaboration between these two types of agencies, and have implications for designing interventions to enhance public health nursing directors' skills at marketing both their profession and their agencies. Collaborative relationships between public health and mental health agencies could improve care for community‐dwelling persons with severe mental disabilities and enhance the future of public health nursing in a changing, competitive health care system.
Death and Meaning in a Storefront Church
Authors: Abrums Mary
Published: March 2003

Nurses are often uncomfortable in addressing the needs of a spiritual family in times of death and grieving. They frequently find that scientific explanations and even emotional support fail to comfort individuals and families. This study, based in a small Black storefront church, explores the meaning of death and the experience of grieving among the deeply religious church members. Ethnographic description and analysis of life history interviews were employed to analyze these concepts. Church members had a particular way of managing the death of one of their members or the death of a child. They made an attempt to “go on,” and they had a strong belief in an afterlife. Church members sometimes experienced visions and visits from “the other side” that supported these beliefs. They had a spiritual manner of comforting those left behind, speaking often of the “homegoing” with acceptance, examining the purpose of the “journey” of one's life, trying to inspire hope, and yet simultaneously preparing for death. Members praised each other for doing all that they could for their loved one. The nurse who cares for a spiritual family needs to carefully assess each family individually, however, s/he may find that the approaches used by the church members in caring for one another are helpful to incorporate into her/his care.
Teleform: A Blessing or Burden?
Authors: Nies Mary A , Hein Laura
Published: March 2003

Burgeoning technology has created numerous alternatives for even the most mundane aspect of research, that is, data entry. Our research team is conducting a large NIH NINR clinical trial, and data entry and management are important aspects of this study. Our research team needed to decide whether to use manual data entry or a scannable form of data entry. This article describes some of the advantages and disadvantages related to our decision to use scannable data entry Teleform™.
Identification of Cardiovascular Risk: Use of a Cardiovascular‐Specific Genogram
Authors: Wimbush Frances B , Peters Rosalind M
Published: March 2003

Cardiovascular disease (CVD) affects nearly 50 million Americans of all ages, races, and educational levels. Many of the risk factors for CVD are modifiable and public health nurses (PHNs) are in unique position to impact this major health problem because of their access to individuals, families, and groups. Addressing this major health problem requires early identification of those at risk for CVD. This article describes the implementation of a cardiovascular‐specific genogram (CVSG) which can be used to identify persons at risk for CVD. Rationale for the development of this disease‐specific tool and suggestions for its clinical application are discussed. The genogram was distributed to the parents of 100 6th grade students. All of the respondents reported cardiovascular risk factors present in at least one of three generations examined. The risk factors in the two younger generations were at the primary and secondary levels of prevention and were modifiable with intervention. Only the older generation in this sample had tertiary level risk factors. The CVSG can easily be incorporated into all aspects of public health nursing practice, from assessment for case finding to planning and implementing disease management strategies. The CVSG can identify individuals, families, and groups at risk for CVD allowing the nurse to focus attention on those most at risk, and to implement proactive assessment, screening, and educational programs.
Breastfeeding Triplets: The At‐Home Experience
Authors: Leonard Linda G
Published: March 2003

The unprecedented rise in higher‐order multiple (HOM) births and the subsequent increase in parents who want to breastfeed their babies presents community health nurses (CHNs) with complex challenges. The extraordinary diversity of the triplet breastfeeding experience once all infants are settled at home is illustrated through findings from a survey of nine mothers of triplets. Parents revealed how they managed the feedings over the multiples' first year: type of feedings (breast, expressed breast milk [EBM], formula); scheduled and demand feedings; adequacy of milk supply; frequency and duration of feedings; consecutive and simultaneous feedings; nighttime with three; weaning; effects of breastfeeding on their bodies and well‐being; challenges and stresses; and spousal, family, and health professional attitudes and support. A number of strategies that CHNs can utilize are suggested. These include working with individual families as well as forming partnerships with parents of multiples' support groups, multiple birth associations, interested health professionals, and the community sector. It is through these actions that the accessibility, coordination, and quality of health, multiple birth education, and social support services can be strengthened and healthy public policies implemented which address the unique and enormous demands experienced by HOMs' families.