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Biomedical subjects

J Geller

Publications and source records attributed to J Geller.

At least 19 recordsLinked to original sources

Monitoring of skeletal progression of prostate cancer by GFP imaging, X-ray, and serum OPG and PTHrP.

BACKGROUND: Prostate cancers (PCas) produce factors that can serve as biomarkers for tumor metastasis and bone progression. Transduced GFP expression by cancer cells can be imaged to monitor therapy. We exploited both concepts by developing a GFP-expressing PCa cell line that expresses PTHrP and studying it in an animal model of malignancy with methods that assess the skeletal progression of this tumor. METHODS: We developed a GFP-producing PCa cell line by stable transduction of PC-3 PCa cells. This PC-3 variant was used to study tumor progression in an immunocompromised mouse model. Skeletal progression of the PCa cells and the effects of pamidronate administration were evaluated radiologically, fluorometrically, and by measurement of serum tumor markers. RESULTS: The PC-3 cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3 cells could be monitored by GFP optical imaging, X-ray, and by measurements of tumor products in serum, notably PTHrP and OPG. Pamidronate treatment reduced tumor burden as assessed at autopsy by imaging and biomarkers. CONCLUSIONS: Pamidronate treatment exhibited anti-tumor effects that were reflected by decreases in serum PTHrP, OPG, and by GFP and radiological imaging procedures. Imaging of GFP expression enables real-time monitoring of tumor growth in the bone. PTHrP and OPG may be useful as tumor biomarkers for PCa that has metastasized to bone. This novel human PCa model can be used to study the clinical potential of diagnostic and therapeutic modalities in the skeletal progression of PCas.

Adenocarcinoma↗

Caloric requirement for refeeding inpatients with anorexia nervosa: the contribution of anxiety exercise, and cigarette smoking.

BACKGROUND: Refeeding inpatients with anorexia nervosa (AN) is costly, stressful, and can precipitate the refeeding syndrome. Caloric intake is usually increased gradually from a low starting point until a steady weight gain is achieved. There is no reliable equation that predicts the number of calories required for a weight gain. It was our clinical suspicion that anxiety, exercise, and cigarette smoking might increase the caloric need for refeeding. METHOD: We conducted an observational cohort study of 17 females with AN admitted to an inpatient eating disorder unit for refeeding. We estimated the energy intake by observation, the caloric expenditure due to exercise with a triaxial accelerometer, the number of cigarettes smoked by history, and the anxiety by the Beck Anxiety Inventory (BAI). RESULTS: Neither anxiety, exercise, or cigarette smoking predicted the caloric requirement for refeeding, individually or in combination. DISCUSSION: Our data suggest that the caloric requirement for weight gain during refeeding is not predicted by the patient's anxiety, exercise or smoking habits. The standard methods of estimating caloric requirements for refeeding remain indirect calorimetry and previous history.

Adult↗

Assessing readiness for change in the eating disorders: the psychometric properties of the readiness and motivation interview.

This study examined the psychometric properties of the Readiness and Motivation Interview (RMI), a symptom-specific measure of readiness and motivation for change in the eating disorders. For 4 symptom domains, the RMI assesses the extent to which individuals are in precontemplation, contemplation, and action/maintenance, and the extent to which change is made for internal versus external reasons. Ninety-nine individuals with eating disorders completed the RMI and measures to assess convergent, divergent, and criterion validity. RMI profiles revealed differences in readiness and motivation across symptom domains. The RMI demonstrated good reliability and construct validity, and RMI scores predicted anticipated difficulty of recovery activities, completion of recovery activities, decision to enroll in an intensive symptom-reduction program, and treatment dropout. The RMI may have important clinical applications by providing much-needed information on client readiness for action-oriented treatment.

Adolescent↗

Partitioning an object-oriented terminology schema.

Controlled medical terminologies are increasingly becoming strategic components of various healthcare enterprises. However, the typical medical terminology can be difficult to exploit due to its extensive size and high density. The schema of a medical terminology offered by an object-oriented representation is a valuable tool in providing an abstract view of the terminology, enhancing comprehensibility and making it more usable. However, schemas themselves can be large and unwieldy. We present a methodology for partitioning a medical terminology schema into manageably sized fragments that promote increased comprehension. Our methodology has a refinement process for the subclass hierarchy of the terminology schema. The methodology is carried out by a medical domain expert in conjunction with a computer. The expert is guided by a set of three modeling rules, which guarantee that the resulting partitioned schema consists of a forest of trees. This makes it easier to understand and consequently use the medical terminology. The application of our methodology to the schema of the Medical Entities Dictionary (MED) is presented.

Humans↗

A metaschema of the UMLS based on a partition of its semantic network.

The Unified Medical Language System's (UMLS's) Semantic Network (SN) provides an important conceptual abstraction that helps orient users to the vast knowledge content of its Metathesaurus. However, the SN is itself large and complex, and can also benefit from an additional abstract view of its own. In this paper, we present a metaschema that serves such a purpose. This metaschema is derived from a previously developed partitioning methodology for the SN. The metaschema is formally defined, and used to provide partial compact views of the SN.

Semantics↗

Inhibited expression of negative emotions and interpersonal orientation in anorexia nervosa.

OBJECTIVE: This study examined inhibited expression of negative feelings and interpersonal orientation in women with anorexia nervosa. METHOD: Twenty-one women meeting DSM-IV criteria for anorexia nervosa were compared with 21 psychiatric and 21 normal control women matched on education. Two measures were used to assess inhibited expression of negative feelings and interpersonal orientation: the State-Trait Anger Expression Inventory assesses the suppression and expression of anger and the Silencing the Self Scale assesses four cognitive schemas involving the repression of needs and feelings to protect interpersonal relationships. RESULTS: Women with anorexia nervosa reported significantly higher scores on the four Silencing the Self schemas and on suppressed anger after controlling for age. These group differences were maintained for two of the cognitive schemas (Care and Silence) after controlling for depression, self-esteem, and global assessment of functioning. Inhibited expression of negative emotion and interpersonal orientation scores were also significantly related to cognitive and affective components of body image dissatisfaction and to trait and self-presentational dimensions of perfectionism. DISCUSSION: These findings are reviewed in the context of health psychology, as well as feminist and temperament theories. Implications for treatment are addressed.

Adolescent↗

Assessment of shape- and weight-based self-esteem in adolescents.

OBJECTIVES: The Adolescent version of the Shape and Weight-Based Self-Esteem (SAWBS-A) Inventory provides a contextual measure of the importance of shape and weight to overall feelings of self-worth. The psychometric properties of the adult SAWBS Inventory have been previously established. The present research examined the psychometric properties of this measure in adolescent females, and compared structural aspects of self-concept in symptomatic and nonsymptomatic individuals. METHOD: A school sample of 197 adolescents completed the SAWBS-A Inventory and measures to assess concurrent and discriminant validity. A subsample completed the SAWBS-A Inventory a second time, 1 week later. RESULTS: SAWBS-A scores were stable over 1 week and correlated with measures of eating disorder symptomatology. The scores also discriminated between adolescents reporting few or no disturbed eating symptoms and possible/probable cases. Comparison of self-esteem profiles in these two groups revealed that in addition to body, the groups differed in the extent to which facial appearance contributed to feelings of self-worth. CONCLUSIONS: The SAWBS-A Inventory may be useful in examining structural dimensions of self-esteem in adolescents.

Adolescent↗

Comparison of shoplifting behaviours in patients with eating disorders, psychiatric control subjects, and undergraduate control subjects.

Shoplifting behaviours were examined in an eating disorder group (EDG, n = 48), a psychiatric control group (PCG, n = 46), and an undergraduate control group (UCG, n = 82). They were examined in relation to self-esteem, depression, and eating disorder symptomatology. The 3 groups did not differ in overall history of shoplifting, but EDG women were more likely to have shoplifted in the past 6 months (current shoplifting) and to have shoplifted often than were women from the PCG or UCG. Across all 3 groups, current shoplifting was associated with low self-esteem, elevated depression, and purging behaviours at the time of the assessment. The implications of these findings with regard to the relationship between shoplifting and eating disorder symptomatology will be addressed.

Adolescent↗

Characteristics of substance-abusing persons with schizophrenia: the paradox of the dually diagnosed.

Previous studies have noted the paradox of the dually-diagnosed (serious mental illness and substance abuse) in which the dually-diagnosed are judged to be both behaviorally more disorganized and simultaneously more socially competent. This study sought to further assess this paradox with a large sample size and a comprehensive assessment approach. In this study, the dually-diagnosed (N = 233) differed significantly from the non-dually-diagnosed (N = 262) in the symptom paradox. The dually-diagnosed were judged both more behaviorally disorganized and socially intact. The comprehensive assessment approach yielded empirical data in support of three possible hypotheses to explain the paradox. The implications of the findings and the three possible hypotheses are discussed.

Activities of Daily Living↗

An orthotopic mouse model of remetastasis of human colon cancer liver metastasis.

Whether liver metastases from colon cancer are capable of metastasizing to other sites is an important question in surgical oncology. To answer this question, we have developed a highly metastatic orthotopic transplant model of a liver metastasis from a human colon cancer patient in nude mice that targets the liver and lymph nodes. The metastatic human tumor was transplanted in athymic nude mice by surgical orthotopic implantation (SOI) of a liver metastasis from a colon cancer patient. The human colon tumor was then subsequently implanted in the colon by SOI or, in an additional series of nude mice, in the liver by surgical hepatic implantation (SHI). The mice were then explored over time for lymph node involvement beginning 10 days after implantation. After SOI, 100% of the animals had liver metastasis within 10 days, and subsequently, 19 days after SOI, all lymph nodes draining the liver were involved with metastasis without any retroperitoneal or lung tissue involvement. After SHI, all sites of lymphatic drainage of the liver, including portal, celiac, and mediastinal lymph nodes, were massively involved by metastasis in 100% of the animals as early as 10 days after tumor implantation on the liver. The results of this study demonstrate that liver metastases from colon cancer are capable of remetastasizing to other sites. This study thus suggests that in colon cancer patients with liver metastasis, mediastinal, celiac, and portal lymph node metastases originate from the liver metastasis and not, as previously thought, from primary colon cancer.

Adenocarcinoma↗

High-malignancy orthotopic nude mouse model of human prostate cancer LNCaP.

BACKGROUND: An animal model of human prostate cancer LNCaP demonstrating high rates of spontaneous metastasis from the orthotopic site after tumor implantation would be very valuable for mechanistic and drug discovery studies. We previously developed microsurgical techniques to implant histologically intact tumor tissues orthotopically in nude mice in order to develop high metastatic mouse models of human cancer. METHODS: Intact tissue of the androgen-dependent human prostate cancer cell line, LNCaP, was implanted on the ventral lateral lobes of the prostate gland by surgical orthotopic implantation (SOI) in a series of 20 nude mice. Mice were autopsied, and histopathological examination of primary tumors and relevant organs was done to identify and quantitate micrometastasis. RESULTS: Eighteen of 20 animals transplanted with LNCaP by SOI had tumor growth. Mean primary tumor weight in the prostate was 9.24 g at time of necropsy. Sixty-one percent of the transplanted animals had lymph node metastasis. Forty-four percent had lung metastasis. Mean survival time was 72 days, indicating a high degree of malignancy of the tumor. CONCLUSIONS: The extensive and widespread lung metastasis as well as lymph node metastasis following orthotopic implantation of LNCaP in nude mice and the short survival time provide a high-malignancy nude model of the LNCaP human prostate tumor.

Animals↗

Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group.

OBJECTIVES: Prostate-specific antigen (PSA) is produced exclusively in the prostate gland and is currently the most useful clinical marker for the detection of prostate cancer. In this report, we examine whether serum PSA is also a predictor of important benign prostatic hyperplasia (BPH)-related outcomes, acute urinary retention (AUR), and the need for BPH-related surgery. METHODS: Three thousand forty men were treated with either placebo or finasteride in a double-blind, randomized study of 4-year duration. Serum PSA was measured at baseline, and baseline prostate volume was measured in a 10% subset of 312 men. Probabilities and cumulative incidences of AUR and BPH-related surgery, as well as reduction in risk of events with finasteride, were calculated for the entire patient population, stratified by treatment assignment, baseline serum PSA, and prostate volume. RESULTS: The risk of either needing BPH-related surgery or developing AUR ranged from 8.9% to 22.0% during the 4 years in placebo-treated patients stratified by increasing prostate volume and from 7.8% to 19.9% when stratified by increasing serum PSA. In comparison with symptom scores, flow rates, and residual urine volume, receiver operating characteristic curve analyses showed that serum PSA and prostate volume were the most powerful predictors of spontaneous AUR in placebo-treated patients (area under the curve 0.70 and 0.81, respectively). Finasteride treatment reduced the relative risk of needing surgery or developing AUR by 50% to 74% and by 43% to 60% when stratified by increasing prostate volume and serum PSA, respectively. CONCLUSIONS: Serum PSA and prostate volume are powerful predictors of the risk of AUR and the need for BPH-related surgery in men with BPH. Knowledge of baseline serum PSA and/or prostate volume are useful tools to aid physicians and decision makers in predicting the risk of BPH-related outcomes and choosing therapy for BPH.

Acute Disease↗

Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group.

OBJECTIVES: The purpose of this open-label study extension was to assess the long-term safety and efficacy of finasteride in the treatment of men with benign prostatic hyperplasia (BPH). METHODS: A Phase III North American BPH trial originally enrolled 895 men, 297 of whom were randomized to receive finasteride 5 mg. An enlarged prostate gland by digital rectal examination, symptoms of urinary obstruction, and a maximal urinary flow rate of less than 15 mL/s were required for entry. Patients who completed the initial 12-month, double-blind, placebo-controlled study were invited to participate in an open-label extension for 4 additional years. RESULTS: Of the 297 patients initially randomized to receive finasteride 5 mg, 259 completed 12 months in the double-blind period and 186 completed 48 months of open-label therapy. Prostate volume reached a nadir of -24.6% at month 24, and the effect was maintained through month 60. Compared with baseline values, month 60 prostate volume was decreased by 22.7% (P<0.001), the quasi-American Urological Association symptom score was decreased by 4.3 points, and maximal urinary flow was increased by 2.3 mL/s (P<0.001) on average. Finasteride was well tolerated, with no significant increase in the prevalence of sexual adverse events over time. CONCLUSIONS: Patients treated with finasteride 5 mg maintained an initial decrease in prostate volume and improvement in symptom score and maximal urinary flow rate over 5 years.

Double-Blind Method↗

Immobilization of the mallet finger. Effects on the extensor tendon.

Since the mallet finger that is treated with isolated splinting of the distal interphalangeal (DIP) joint can be moved freely proximal to the DIP joint, we sought to determine whether such motion might cause a tendon gap that could explain the extensor lag that often follows treatment. Experiments were performed on 32 cadaveric fingers with open mallet finger lesions, immobilizing either the DIP joint alone or both the DIP and PIP joints, while repeatedly flexing and extending the more proximal finger and wrist joints. For each experiment, the gap in the extensor tendon was measured. Joint motion proximal to the DIP joint and retraction of the intrinsics did not cause a tendon gap in a finger with a mallet lesion, supporting the convention that only the DIP joint needs to be immobilized.

Bone Wires↗

A methodology for partitioning a vocabulary hierarchy into trees.

Controlled medical vocabularies are useful in application areas such as medical information systems and decision-support systems. However, such vocabularies are large and complex, and working with them can be daunting. It is important to provide a means for orienting vocabulary designers and users to the vocabulary's contents. We describe a methodology for partitioning a vocabulary based on an IS-A hierarchy into small meaningful pieces. The methodology uses our disciplined modeling framework to refine the IS-A hierarchy according to prescribed rules in a process carried out by a user in conjunction with the computer. The partitioning of the hierarchy implies a partitioning of the vocabulary. We demonstrate the methodology with respect to a complex sample of the MED, an existing medical vocabulary.

Models, Theoretical↗

Intraarticular anatomic risks of tibial nailing.

OBJECTIVE: To identify the risks to intraarticular structures of the knee during tibial portal creation and to identify the safe zone for tibial nail placement. STUDY DESIGN: Cadaveric anatomic. LOCATION: University trauma center. METHODS: Forty fresh frozen cadaveric knees were studied to elaborate the risks of tibial portal creation and nail placement to the intraarticular structures of the knee. Nails were placed through medial and lateral parapatellar approaches, and the distance from the nail portal to the intraarticular structures of the knee was measured. A safe zone for portal placement was determined. RESULTS: The tibial portal location averaged 4.4+/-3 millimeters lateral to the midline of the plateau. Actual intraarticular structural damage occurred in 20 percent of the specimens; however, an additional 30 percent demonstrated the nail to be subjacent to one of the menisci. A lateral paratendinous approach placed the lateral articular surface at most risk, and a medial paratendinous approach placed the medial meniscus at most risk. The safe zone for nail placement was identified and is located 9.1+/-5 millimeters lateral to the midline of the plateau and three millimeters lateral to the center of the tibial tubercle. The width of the safe zone averaged 22.9 millimeters and was as narrow as 12.6 millimeters. CONCLUSION: Damage to the intraarticular structures of the knee is possible during tibial nailing with a superior portal. The safe zone for nail placement is small and can be exceeded if a reamed nail is used. The safest starting point for tibial nailing should be slightly lateral to the center of the tibial tubercle.

Bone Nails↗

Morbidity and mortality in elderly trauma patients.

BACKGROUND: Despite an increasing incidence, relatively few studies have examined the factors that predict morbidity and mortality in older patients and several reports have found standard predictors such as the Injury Severity Score to be less useful in this patient population. Similarly, the effect of skeletal injury has not been examined with regard to complications and mortality. The purpose of this study was to review a large multicenter experience with elderly trauma patients to isolate factors that might predict morbidity and mortality. The potential effect of skeletal long-bone injury was of particular interest. METHODS: The charts of all patients older than 60 years who were admitted to one of four Level I trauma centers after sustaining blunt trauma were reviewed. Mechanisms of injury included in the study were motor vehicle crash, pedestrian struck, fall from a height, and crush injury. Slip-and-fall injuries were excluded. A total of 326 patients met inclusion criteria. Variables studied included age, sex, mechanism of injury, Injury Severity Score (ISS), Revised Trauma Score, Glasgow Coma Scale (GCS) score, blood transfusion, fluid resuscitation, surgery performed (laparotomy, long-bone fracture stabilization, both), and timing of surgery. Outcome variables measured included incidence of adult respiratory distress syndrome, pneumonia, sepsis, myocardial infarction, deep venous thromboembolism, gastrointestinal complications, and death. chi2, logistic regression, t test, and nonparametric analyses were done as appropriate for the type of variable. RESULTS: The average age of the patients was 72.2+/-8 years. Overall, 59 patients (18.1%) died, of whom 52 of 59 survived at least 24 hours. Statistical significance for continuous variables (p < 0.05) using univariate analysis was reached for the following factors for the patients who died: higher ISS (33.1 vs. 16.4), lower GCS score (11.5 vs. 13.9), greater transfusion requirement (10.9 vs. 2.9 U), and more fluid infused (12.4 vs. 4.9 L). Logistic regression analysis was performed to determine the factors that predicted mortality. They included (odds ratios and p values in parentheses) transfusion (1.11, p = 0.01), ISS (1.04, p = 0.008), GCS score (0.87, p = 0.007), and fluid requirement (1.06, p = 0.06). Regarding surgery, orthopedic surgery alone had an odds ratio of 0.53, indicating that orthopedic patients was less likely to die than patients who did not undergo any surgery. Patients who underwent only a general surgical procedure were 2.5 times more likely to die (p = 0.03) and patients who underwent both general and orthopedic procedures were 1.5 times more likely to die (p = 0.32) than patients who did not require surgery. Early (< or =24 hours) versus late (>24 hours) surgery for bony stabilization did not have a statistical effect on mortality (11% early vs. 18% late). Two patients in need of bony stabilization, however, died before these procedures were performed. With regard to complications, regression analysis revealed that ISS predicted adult respiratory distress syndrome, pneumonia, sepsis, and gastrointestinal complications; fluid transfusion predicted myocardial infusion; and need for surgery and transfusion requirements predicted sepsis. These complications, in turn, were significant risk factors for mortality. This large series of elderly patients demonstrates that mortality correlates closely with ISS and is influenced by blood and fluid requirements and by GCS score. The institution-specific mortality was the same when adjusted for ISS. The need for orthopedic surgery and the timing of the surgery was not a risk factor for systemic complications or mortality in this series. CONCLUSION: Mortality is predicted by ISS and by complications in older patients. Seventy-seven percent of the orthopedic injuries were stabilized early, but the timing of surgery did not have any statistical effect on the incidence of complications or mortality. (ABSTRACT TRUNCA

Aged↗