University of Miami Hospital

Brand equity is very important to marketers of consumer goods and services. Brand equity facilitates in the effectiveness of brand extensions and brand introductions. This is because consumers who trust and display loyalty toward a brand are willing to try to adopt brand extensions. While there have been methods to measure the financial value of brand equity, measurement of customer‐based brand equity has been lacking. Presents a scale to measure customer‐based brand equity. The customer‐based brand equity scale is developed based on the five underlying dimensions of brand equity: performance, value, social image, trustworthiness and commitment. In empirical tests, brands that scored higher on the customer‐based brand equity scale generally had higher prices. Discusses the implications for managers.

Magnetic resonance images of the shoulders of ninety-six asymptomatic individuals were evaluated to determine the prevalence of findings consistent with a tear of the rotator cuff. The scans were reviewed independently by two diagnostic radiologists who are experienced in the interpretation of magnetic resonance images of the shoulder. The over-all prevalence of tears of the rotator cuff in all age-groups was 34 per cent (thirty-three). There were fourteen full-thickness tears (15 per cent) and nineteen partial-thickness tears (20 per cent). The frequency of full-thickness and partial-thickness tears increased significantly with age (p < 0.001 and 0.05, respectively). Twenty-five (54 per cent) of the forty-six individuals who were more than sixty years old had a tear of the rotator cuff: thirteen (28 per cent) had a full-thickness tear and twelve (26 per cent) had a partial-thickness tear. Of the twenty-five individuals who were forty to sixty years old, one (4 per cent) had a full-thickness tear and six (24 per cent) had a partial-thickness tear. Of the twenty-five individuals who were nineteen to thirty-nine years old, none had a full-thickness tear and one (4 per cent) had a partial-thickness tear. Magnetic resonance imaging identified a high prevalence of tears of the rotator cuff in asymptomatic individuals. These tears were increasingly frequent with advancing age and were compatible with normal, painless, functional activity. The results of the present study emphasize the potential hazards of the use of magnetic resonance imaging scans alone as a basis for the determination of operative intervention in the absence of associated clinical findings.

Department of Anesthesiology, University of Colorado Medical Center and the Veterans Administration Hospital, Denver, Colorado. Dr. Aldrete's present address: University of Miami Medical School, Miami, Florida 33136. Read at the 44th Congress of the International Anesthesia Research Society, March 15–19, 1970, Palm Springs, California.

UNLABELLED: One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores > or =2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized alanine aminotransferase level. Histological improvement (> or =2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96% of patients, and a > or =1-point improvement in the Ishak fibrosis score was found in 88% of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline. CONCLUSION: The majority of nucleoside-naive patients with CHB who were treated with entecavir in this long-term cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis.

We measured the in situ biomechanical properties of knee joint cartilage from five species (bovine, canine, human, monkey, and rabbit) to examine the biomechanical relevance of animal models of human knee joint injuries and osteoarthritis. In situ biphasic creep indentation experiments were performed to simultaneously determine all three intrinsic material coefficients (aggregate modulus, Poisson's ratio, and permeability) of the cartilage as represented by the linear KLM biphasic model. In addition, we also assessed the effects of load bearing on these intrinsic properties at "high" and "low" weight-bearing regions on the distal femur. Our results indicate that significant differences exist in some of these material properties among species and sites. The aggregate modulus of the anterior patellar groove within each species is the lowest among all sites tested, and the permeability of the patellar groove cartilage is the highest and does not vary among species. Similarly, the Poison's ratio in the patellar groove is the lowest in all species, except in the rabbit. These results lead to the conclusion that patellar groove cartilage can undergo greater and faster compression. Thus, under high compressive loads, the cartilage of the patellar groove surface can more rapidly compress to create a congruent patellofemoral joint articulation. For any given location, no differences were found in the aggregate modulus among all the species, and no correlation was found between aggregate modulus and thickness at the test site. Thus, in the process of selecting a suitable experimental animal model of human articular cartilage, it is essential to consider the significant interspecies differences of the mechanical properties.

BACKGROUND: Mitral regurgitation (MR) may complicate acute myocardial infarction (MI). However, it is not known whether mild MR is an independent predictor of post-MI outcome. METHODS AND RESULTS: The study cohort consisted of 727 Survival and Ventricular Enlargement Study patients who underwent cardiac catheterization, including left ventriculography, up to 16 days after MI. Left ventriculograms were analyzed for diastolic and systolic volumes, global left ventricular sphericity, extent of wall motion abnormality, and endocardial curvature. The presence of MR was related to the risk of developing a cardiovascular event during 3.5 years of follow-up. MR was present in 141 patients (19.4%). Severe (3+) MR was present in only 2 patients. Patients with MR were more likely to have a persistently occluded infarct artery (MR versus no MR, 27.3% versus 15.2%; P=.001). Although the ejection fractions were similar, MR patients had larger end-systolic and end-diastolic volumes and more spherical ventricles than patients without MR. Sphericity change from diastole to systole was also significantly reduced in MR patients. Patients with MR were more likely to experience cardiovascular mortality (29% versus 12%; P<.001), severe heart failure (24% versus 16%; P=.0153), and the combined end point of cardiovascular mortality, severe heart failure, or recurrent myocardial infarction (47% versus 29%; P<.001). The presence of MR was an independent predictor of cardiovascular mortality (relative risk, 2.00; 95% CI, 1.28 to 3.04). CONCLUSIONS: Mild MR is an independent predictor of post-MI mortality. As such, it adds important information for risk stratification of post-MI patients.

BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter)--the primary end point--or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

Until now oligonephropathy to indicate "too few nephrons" has been associated with intrauterine growth restriction and experimentally induced abnormalities of renal development. The purpose of this study was to determine whether there is evidence of abnormal postnatal glomerulogenesis in extremely low birth weight preterm infants. Renal autopsy tissue was studied by computer-assisted morphometry from 56 extremely premature infants (birth weight < or = 1000 g) and 10 fullterm infants as controls. Preterm infants were divided into two groups (short survival < or = 40 days vs. long survival > or = 40 days). Each group was subdivided into those with renal failure (RF) and those with normal renal function. Forty-two of 56 preterm infants (75%) were adequate for gestational age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly decreased in all preterm infants as compared to term controls and correlated significantly with gestational age (r = 0.87; P < 0.001). Active glomerulogenesis with "basophilic S-shaped bodies" was absent in longer surviving preterm and all term infants. RGC of preterm infants surviving > or =40 days with RF were significantly less than RGC of those with long survival and no RF (P < 0.001). Only this latter group demonstrated increased glomerular size as measured by mesangial tuft area and Bowman's capsule area compared to all other groups (P < 0.001). The kidney continues to form postnatally in preterm neonates, but glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF. Compensatory mechanisms in longer surviving preterm infants include glomerular hypertrophy and mesangial proliferation that could lead to hyperfiltration.

Carbonate sediments are prone to rapid and pervasive diagenetic alterations that change the mineralogy and pore structure within carbonate rocks. In particular, cementation and dissolution processes continuously modify the pore structure to create or destroy porosity. In extreme cases these modifications can completely change the mineralogy from aragonite/calcite to dolomite, or reverse the pore distribution whereby original grains are dissolved to produce pores as the original pore space is filled with cement to form the rock (Figure 1). All these modifications alter the elastic properties of the rock and, therefore, the sonic velocity. The result is a dynamic relationship among diagenesis, porosity, pore-type, and sonic velocity. The result is a wide range of sonic velocity in carbonates, in which compressional-wave velocity (VP) ranges from 1700 to 6600 m/s and shear-wave velocity (VS) from 600 to 3500 m/s.

BACKGROUND: Current information on the epidemiology and outcomes of hypertrophic cardiomyopathy (HCM) in children is limited by disease diversity and small case series. METHODS AND RESULTS: The Pediatric Cardiomyopathy Registry has collected prospective and retrospective data on children diagnosed with HCM since 1990. We identified the various causes of HCM in childhood and determined the relationship between outcomes, cause, and age at presentation. Of 855 patients <18 years of age with HCM, 8.7% (n=74) had inborn errors of metabolism, 9.0% (n=77) had malformation syndromes, 7.5% (n=64) had neuromuscular disorders, and 74.2% (n=634) had idiopathic HCM. Children with HCM associated with inborn errors of metabolism and malformation syndromes have significantly worse survival than the other 2 groups. Patients with idiopathic HCM diagnosed before 1 year of age (n=227) had worse survival from the time of diagnosis than those diagnosed after 1 year of age (n=407). Patients with idiopathic HCM who survived to at least 1 year of age, however, had an annual mortality rate of 1% that was similar regardless of whether they were diagnosed before or after 1 year of age. CONCLUSIONS: In children, HCM is a diverse disorder with outcomes that depend largely on cause and age. Patients presenting before 1 year of age have the broadest spectrum of causes and the poorest outcome. In those children with idiopathic HCM who survive beyond age 1, however, survival is independent of age at diagnosis, with an annual mortality rate (1%) that is much lower than previously reported in children and is not different from has been found in population-based studies in adults.

CD44 is a facultative proteoglycan implicated in cell adhesion and trafficking, as well as in tumor survival and progression. We demonstrate here that CD44 heparan sulfate proteoglycan (CD44HSPG) recruits proteolytically active matrix metalloproteinase 7 (matrilysin, MMP-7) and heparin-binding epidermal growth factor precursor (pro-HB-EGF) to form a complex on the surface of tumor cell lines, postpartum uterine and lactating mammary gland epithelium, and uterine smooth muscle. The HB-EGF precursor within this complex is processed by MMP-7, and the resulting mature HB-EGF engages and activates its receptor, ErbB4, leading to, among other events, cell survival. In CD44(-/-) mice, postpartum uterine involution is accelerated and maintenance of lactation is impaired. In both uterine and mammary epithelia of these mice, MMP-7 localization is altered and pro-HB-EGF processing as well as ErbB4 activation are decreased. Our observations provide a mechanism for the assembly and function of a cell surface complex composed of CD44HSPG, MMP 7, HB-EGF, and ErbB4 that may play an important role in the regulation of physiological tissue remodeling.

BACKGROUND: Radial access for percutaneous coronary intervention (r-PCI) is associated with reduced vascular complications; however, previous reports have shown that <2% of percutaneous coronary intervention (PCI) procedures in the United States are performed via the radial approach. Our aims were to evaluate temporal trends in r-PCI and compare procedural outcomes between r-PCI and transfemoral PCI. METHODS AND RESULTS: We conducted a retrospective cohort study from the CathPCI registry (n=2 820 874 procedures from 1381 sites) between January 2007 and September 2012. Multivariable logistic regression models were used to evaluate the adjusted association between r-PCI and bleeding, vascular complications, and procedural success, using transfemoral PCI as the reference. Outcomes in high-risk subgroups such as age ≥75 years, women, and patients with acute coronary syndrome were also examined. The proportion of r-PCI procedures increased from 1.2% in quarter 1 2007 to 16.1% in quarter 3 2012 and accounted for 6.3% of total procedures from 2007 to 2012 (n=178 643). After multivariable adjustment, r-PCI use in the studied cohort of patients was associated with lower risk of bleeding (adjusted odds ratio, 0.51; 95% confidence interval, 0.49-0.54) and lower risk of vascular complications (adjusted odds ratio, 0.39; 95% confidence interval, 0.31-0.50) in comparison with transfemoral PCI. The reduction in bleeding and vascular complications was consistent across important subgroups of age, sex, and clinical presentation. CONCLUSIONS: There has been increasing adoption of r-PCI in the United States. Transradial PCI now accounts for 1 of 6 PCIs performed in contemporary clinical practice. In comparison with traditional femoral access, transradial PCI is associated with lower vascular and bleeding complication rates.

The phenomenon of postpacing depression of cardiac pacemakers was utilized to evaluate the sinus-node function in 56 patients by analyzing the sinus-node recovery time (SRT), that is, the interval between the last paced P wave and the following sinus P wave. Corrected SRT (CSRT) is defined as the recovery interval in excess of the sinus cycle (SRT — sinus cycle length). The SRT was measured following sinus-node suppression by (1) isolated premature beats (PABs) and (2) atrial pacing (AP) at rates of 100 to 140/min for periods of 2 to 5 min at each level. Twenty-eight patients had normal heart rates (group A), and 28 patients had sinus bradycardia (SB; group B). Ten of the 28 patients with SB were restudied after receiving atropine (2 mg intravenously). The CSRT with PABs was similar in both group A and group B patients and remained essentially unchanged after atropine despite a decrease in sinus cycle length. The phenomenon of interpolated PABs was demonstrated in seven of the 56 patients. In 27 of the 28 patients with normal heart rates (group A), the CSRT with AP ranged from 110 to 525 msec and was essentially independent of the rate and duration of AP. In the remaining one patient of group A, despite a normal heart rate, the CSRT was prolonged (1810 msec) and directly dependent on the rate and duration of AP. In 12 of the 28 patients with SB, the CSRT was comparable to that in group A (≦525 msec). In the remaining 16 patients with SB (group B), the CSRT ranged from 560 to 3740 msec and was usually directly proportional to the rate and duration of AP. After atropine in most of the patients with a prolonged CSRT, the CSRT remained abnormal whereas in others junctional escape beats appeared first, followed eventually by normal sinus rhythm. In a single patient with SB and an abnormal CSRT, restudy 7½ months later again showed a prolonged CSRT indicating the reproducibility of the measurement. The CSRT with AP provides a potentially useful clinical means of assessing the sinus-node function and thereby aids in the diagnosis of the "sick sinus syndrome." It is stressed that AP was found to be more reliable than PABs in eliciting an abnormal response. Furthermore, a normal sinus (atrial) rate does not necessarily provide assurance of a normal sinus-node response to AP, that is, normal sinus-node function.

The development of effective antineoplastic therapies for childhood cancer is a great success in modern medicine. Five year survival rates of children diagnosed with cancer in the USA and Western Europe in excess of 70% make long term survivors of childhood cancer a steadily increasing population. Although there is much to celebrate, new challenges lie ahead in treating the systemic sequelae of chemotherapy.1 Results from the Childhood Cancer Survivor Study (CCSS) showed that 30 years after treatment, the cumulative incidence of chronic health conditions in long term survivors reaches 73%, with a cumulative incidence of 42% for severe, disabling, or life threatening conditions or death.2 Severe conditions, that are significantly more common in childhood cancer survivors than in their siblings, include: major joint replacement (relative risk (RR) 54.0), congestive heart failure (RR 15.1), second malignant neoplasm (RR 14.8), severe cognitive dysfunction (RR 10.5), coronary artery disease (RR 10.4), cerebrovascular accident (RR 9.3), and renal failure (RR 8.9).2 Previous CCSS results found that patients who had survived at least 5 years after diagnosis had 10.8-fold increased rates of all cause mortality.3 The standardised mortality ratio for cardiac causes was 8.2 times higher than expected and the cumulative probability of cardiac death increased 15–25 years after cancer diagnosis. A similar study in a large Nordic cohort documented a standardised mortality ratio of 5.8 for cardiac death and elevated rates of sudden, presumed arrhythmic, deaths.4 Chief among adverse late effects is the cardiovascular toxicity of anthracyclines.5–11 Unfortunately, despite well documented dose related toxicity, the superior disease-free survival rates of regimens including anthracyclines leave limited viable treatment alternatives and the majority of long term paediatric cancer survivors in the Pediatric Oncology Group received an anthracycline during treatment.12 ### Mechanism of cardiotoxicity Several cytotoxic biochemical changes follow anthracycline exposure in …

PURPOSE: We evaluated the ability of an immunoassay for nuclear matrix protein 22 (NMP22 test kit) to predict the subsequent disease status of patients with transitional cell carcinoma of the urinary tract at approximately 10 days after transurethral resection of bladder tumor. MATERIALS AND METHODS: A total of 90 patients with transitional cell carcinoma provided voided urine samples at least 5 days postoperatively. NMP22 was determined using a commercial test kit. At initial cystoscopic examination 3 to 6 months later the disease status was recorded, and the NMP22 values before and after transurethral resection of bladder tumor were compared. RESULTS: Of 125 followup cystoscopic examinations (60 patients had 1, 26 had 2, 3 had 3 and 1 had 4 recurrences) transitional cell carcinoma was pathologically confirmed in 33. No malignancy was present at 79 examinations (if tumor was seen endoscopically, pathological evaluation indicated atypia, dysplasia or no abnormality). NMP22 values in these 2 populations were significantly different (malignancy median 20.81 units per ml. and no malignancy median 5.72 units per ml., Mann-Whitney U test for differences between 2 medians p = 0.00005). Of the 33 recurrences 23 (70%) had NMP22 values greater than the reference range (10 units per ml.). Additionally, NMP22 identified all 6 subjects (100%) who had invasive disease 3 to 6 months later. Of 72 patients with NMP22 less than 10 units per ml. 62 (86%) had no malignancy at subsequent cystoscopy. CONCLUSIONS: NMP22 was highly predictive of tumor status at followup cystoscopy. This quantitative, noninvasive assay, with high negative predictive value (86%) and sensitivity to detect malignancy (100% for invasive disease and 70% overall), may be a helpful adjunct to cytology and endoscopy for monitoring disease status after endoscopic tumor resection.

Using a monoclonal antibody to bromodeoxyuridine (BUdR) and immunohistochemistry, we measured the incorporation of this thymidine analogue into the DNA of human normal and malignant cells exposed in vivo. BUdR given as a constant intravenous infusion for 12 or 24 h daily for up to 13 d resulted in a steady-state plasma level of 10(-6) M during the infusion. We demonstrated extensive incorporation of BUdR into both normal skin, normal bone marrow, and malignant melanoma cells. In addition, this infusion of BUdR was adequate to identify sister chromatid exchanges from human marrow chromosomes exposed in vivo. Using this constant infusion, significant but reversible (acute) toxicity was observed with myelosuppression and skin photosensitivity. These techniques, which are considerably less cumbersome and time-consuming than the use of radioactive isotopes of thymidine, can be used for further human studies of cell kinetics and chromosomal replication in both normal and malignant cells.

BACKGROUND: Aspiration pneumonia is common among frail elderly persons with dysphagia. Although interventions to prevent aspiration are routinely used in these patients, little is known about the effectiveness of those interventions. OBJECTIVE: To compare the effectiveness of chin-down posture and 2 consistencies (nectar or honey) of thickened liquids on the 3-month cumulative incidence of pneumonia in patients with dementia or Parkinson disease. DESIGN: Randomized, controlled, parallel-design trial in which patients were enrolled for 3-month periods from 9 June 1998 to 19 September 2005. SETTING: 47 hospitals and 79 subacute care facilities. PATIENTS: 515 patients age 50 years or older with dementia or Parkinson disease who aspirated thin liquids (demonstrated videofluoroscopically). Of these, 504 were followed until death or for 3 months. INTERVENTION: Participants were randomly assigned to drink all liquids in a chin-down posture (n = 259) or to drink nectar-thick (n = 133) or honey-thick (n = 123) liquids in a head-neutral position. MEASUREMENTS: The primary outcome was pneumonia diagnosed by chest radiography or by the presence of 3 respiratory indicators. RESULTS: 52 participants had pneumonia, yielding an overall estimated 3-month cumulative incidence of 11%. The 3-month cumulative incidence of pneumonia was 0.098 and 0.116 in the chin-down posture and thickened-liquid groups, respectively (hazard ratio, 0.84 [95% CI, 0.49 to 1.45]; P = 0.53). The 3-month cumulative incidence of pneumonia was 0.084 in the nectar-thick liquid group compared with 0.150 in the honey-thick liquid group (hazard ratio, 0.50 [CI, 0.23 to 1.09]; P = 0.083). More patients assigned to thickened liquids than those assigned to the chin-down posture intervention had dehydration (6% vs. 2%), urinary tract infection (6% vs. 3%), and fever (4% vs. 2%). LIMITATIONS: A no-treatment control group was not included. Follow-up was limited to 3 months. Care providers were not blinded, and differences in cumulative pneumonia incidence between interventions had wide CIs. CONCLUSION: No definitive conclusions about the superiority of any of the tested interventions can be made. The 3-month cumulative incidence of pneumonia was much lower than expected in this frail elderly population. Future investigation of chin-down posture combined with nectar-thick liquid may be warranted to determine whether this combination better prevents pneumonia than either intervention independently.

Although effective anti-neoplastic agents, anthracyclines are limited by their well recognized and pervasive cardiotoxic effects. The incidence of late progressive cardiovascular disease in long-term survivors of cancer is established and may contribute to heart failure and death. To maximize the benefits of these drugs, a high-risk population has been identified and new strategies have been investigated to minimize toxic effects, including limiting the cumulative dose, controlling the rate of administration and using liposomal preparations and novel anthracycline analogues. Dexrazoxane also shows promise as a cardioprotectant during treatment. This paper reviews these strategies, as well as medications used to manage anthracycline-induced cardiotoxicity, and functional and biochemical means of monitoring cardiotoxicity, including echocardiography, radionuclide scans and biomarker analysis. The treatment of adult cancer survivors who have had anthracycline-related cardiotoxicity has not been systematically studied. Empirically, anthracycline-associated cardiac dysfunction is treated very similarly to other forms of heart failure. These treatments include avoiding additional cardiotoxic regimens, controlling hypertension, lifestyle changes, medications and heart transplantation.

BACKGROUND: Silent infarcts have been reported in 17% of young patients with sickle cell disease and are associated with impaired performance on standardized psychometric tests. Risk factors for the development of these lesions have not been identified. METHODS: Investigators in the Cooperative Study of Sickle Cell Disease performed a brain magnetic resonance imaging scan on sickle cell anemia patients age 5.9 years and older who had been followed according to the protocols of the Cooperative Study since birth. Individuals with a known history of cerebrovascular accident were excluded from this analysis. Patients with and without silent infarctions were compared with regard to clinical and laboratory parameters. RESULTS: The study sample included 42 patients (18.3%) with silent infarcts. Patients who had silent infarcts were significantly more likely to have a clinical history of seizure and a lower painful event rate. Lower hemoglobin level, increased leukocyte count, elevated pocked red blood cell count, and SEN betaS globin gene haplotype were associated also with the presence of silent infarcts. There was no relationship between silent infarcts and platelet count, fetal hemoglobin level, reticulocyte percentage, serum aspartate aminotransferase level, total bilirubin concentration, blood pressure, growth parameters, or presence of alpha-thalassemia. A multivariate model for silent infarction identified the following as risk factors: low pain event rate, history of seizure, leukocyte count >/=11.8 x 10(9)/L, and the SEN betaS globin gene haplotype. CONCLUSIONS: Patients with risk factors for silent infarcts should be evaluated for cerebrovascular disease. If evidence of infarction is found, consideration must be given to therapeutic intervention. At present, the appropriate treatment has not been determined.

Previous classification systems of failure of limb salvage focused primarily on endoprosthetic failures and lacked sufficient depth for the effective study of the causes of failure. In order to address these inadequacies, the International Society of Limb Salvage (ISOLS) formed a committee to recommend revisions of the previous systems. The purpose of this study was to report on their recommendations. The modifications were prepared using an earlier, evidence-based model with subclassification based on the existing medical literature. Subclassification for all five primary types of failure of limb salvage following endoprosthetic reconstruction were formulated and a complementary system was derived for the failure of biological reconstruction. An additional classification of failure in paediatric patients was also described. Limb salvage surgery presents a complex array of potential mechanisms of failure, and a complete and precise classification of types of failure is required. Earlier classification systems lacked specificity, and the evidence-based system outlined here is designed to correct these weaknesses and to provide a means of reporting failures of limb salvage in order to allow the interpretation of outcome following reconstructive surgery.