Showing papers by "Medical University of South Carolina published in 1999"

Predictors of Recurrence After Deep Vein Thrombosis and Pulmonary Embolism: A Population-Based Cohort Study

Abstract: Background The appropriate duration of oral anticoagulation after a first episode of venous thromboembolism (VTE) is uncertain and depends upon VTE recurrence rates. Objective To estimate VTE recurrence rates and determine predictors of recurrence. Methods Patients in Olmsted County, Minnesota, with a first lifetime deep vein thrombosis or pulmonary embolism diagnosed during the 25-year period from 1966 through 1990 (N = 1719) were followed forward in time through their complete medical records in the community for first VTE recurrence. Results Four hundred four patients developed recurrent VTE during 10 198 person-years of follow-up. The overall (probable/definite) cumulative percentages of VTE recurrence at 7, 30, and 180 days and 1 and 10 years were 1.6% (0.2%), 5.2% (1.4%), 10.1% (4.1%), 12.9% (5.6%), and 30.4% (17.6%), respectively. The risk of recurrence was greatest in the first 6 to 12 months after the initial event but never fell to zero. Independent predictors of first overall VTE recurrence included increasing age and body mass index, neurologic disease with paresis, malignant neoplasm, and neurosurgery during the period from 1966 through 1980. Independent predictors of first probable/definite recurrence included diagnostic certainty of the incident event and neurologic disease in patients with hospital-acquired VTE. Recurrence risk was increased by malignant neoplasm but varied with concomitant chemotherapy, patient age and sex, and study year. Conclusions Venous thromboembolism recurs frequently, especially within the first 6 to 12 months, and continues to recur for at least 10 years after the initial VTE. Patients with VTE with neurologic disease and paresis or with malignant neoplasm are at increased risk for recurrence, while VTE patients with transient or reversible risk factors are at less risk.

Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide

Abstract: Background For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. Methods We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. Results Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rat...

Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways

Abstract: Heterozygous mutations in NKX2.5, a homeobox transcription factor, were reported to cause secundum atrial septal defects and result in atrioventricular (AV) conduction block during postnatal life. To further characterize the role of NKX2.5 in cardiac morphogenesis, we sought additional mutations in groups of probands with cardiac anomalies and first-degree AV block, idiopathic AV block, or tetralogy of Fallot. We identified 7 novel mutations by sequence analysis of the NKX2.5-coding region in 26 individuals. Associated phenotypes included AV block, which was the primary manifestation of cardiac disease in nearly a quarter of affected individuals, as well as atrial septal defect and ventricular septal defect. Ventricular septal defect was associated with tetralogy of Fallot or double-outlet right ventricle in 3 individuals. Ebstein’s anomaly and other tricuspid valve abnormalities were also present. Mutations in human NKX2.5 cause a variety of cardiac anomalies and may account for a clinically significant portion of tetralogy of Fallot and idiopathic AV block. The coinheritance of NKX2.5 mutations with various congenital heart defects suggests that this transcription factor contributes to diverse cardiac developmental pathways. J. Clin. Invest. 104:1567–1573 (1999).

Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience.

Abstract: BACKGROUND Endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) is a recent innovation in the evaluation of gastrointestinal and pulmonary malignancies. AIMS To review the experience with EUS-FNA of a large single centre. METHODS 333 consecutive patients underwent EUS-FNA. Follow up data were available on 327 lesions in 317 patients, including 160 lymph nodes, 144 pancreatic lesions, 15 extraintestinal masses, and eight intramural tumours. RESULTS A primary diagnosis of malignancy was obtained by EUS-FNA in 62% of patients with clinically suspicious lesions. The overall accuracy of EUS-FNA for the diagnosis of malignancy was 86%, with sensitivity of 84% and specificity of 96%. With respect to lesion types, the sensitivity, specificity, and accuracy were 85%, 100%, and 89% for lymph nodes; 82%, 100%, and 85% for pancreatic lesions; 88%, 100%, and 90% for perirectal masses; and 50%, 25%, and 38% for intramural lesions, respectively. Compared with size and sonographic criteria, EUS-FNA in the evaluation of lymph nodes provided superior accuracy and specificity, without compromising sensitivity. Inadequate specimens were obtained from only six patients, including 3/5 with stromal tumors. Only one complication occurred. CONCLUSIONS EUS-FNA is safe and can readily obtain tissue specimens adequate for cytopathological diagnoses. Compared with size and sonographic criteria, it is a superior modality for the detection of nodal metastases. While providing accurate diagnosis of pancreatic and perirectal malignancies, results suggest the technique is less useful for intramural lesions.

Effects of tissue plasminogen activator for acute ischemic stroke at one year

Abstract: Background In 1995, the two-part National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Study found that patients who were treated with tissue plasminogen activator (t-PA) within three hours after the onset of symptoms of acute ischemic stroke were at least 30 percent more likely than patients given placebo to have minimal or no disability three months after the stroke. It was unknown, however, whether the benefit would be sustained for longer periods. Methods In the NINDS trial, a total of 624 patients with stroke were randomly assigned to receive either t-PA or placebo. We collected outcome data over a period of 12 months after the occurrence of stroke. The primary outcome measure was a “favorable outcome,” defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. Results Using an intention-to-treat analysis for the comb...

Transcranial magnetic stimulation: applications in neuropsychiatry.

Abstract: In the 1990s, it is difficult to open a newspaper or watch television and not find someone claiming that magnets promote healing. Rarely do these claims stem from double-blind, peer-reviewed studies, making it difficult to separate the wheat from the chaff. The current fads resemble those at the end of the last century, when many were falsely touting the benefits of direct electrical and weak magnetic stimulation. Yet in the midst of this popular interest in magnetic therapy, a new neuroscience field has developed that uses powerful magnetic fields to alter brain activity—transcranial magnetic stimulation. This review examines the basic principles underlying transcranial magnetic stimulation, and describes how it differs from electrical stimulation or other uses of magnets. Initial studies in this field are critically summarized, particularly as they pertain to the pathophysiology and treatment of neuropsychiatric disorders. Transcranial magnetic stimulation is a promising new research and, perhaps, therapeutic tool, but more work remains before it can be fully integrated in psychiatry's diagnostic and therapeutic armamentarium.

Constipation in infants and children: evaluation and treatment. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition.

Abstract: Background Constipation, defined as a delay or difficulty in defecation, present for 2 or more weeks, is a common pediatric problem encountered by both primary and specialty medical providers. Methods The Constipation Subcommittee of the Clinical Guidelines Committee of the North American Society for Pediatric Gastroenterology and Nutrition has formulated clinical practice guidelines for the management of pediatric constipation. The Constipation Subcommittee, consisting of two primary care pediatricians, a clinical epidemiologist, and pediatric gastroenterologists, based its recommendations on an integration of a comprehensive and systematic review of the medical literature combined with expert opinion. Consensus was achieved through Nominal Group Technique, a structured quantitative method. Results The Subcommittee developed two algorithms to assist with medical management, one for older infants and children and the second for infants less than 1 year of age. The guidelines provide recommendations for management by the primary care provider, including evaluation, initial treatment, follow-up management, and indications for consultation by a specialist. The Constipation Subcommittee also provided recommendations for management by the pediatric gastroenterologist. Conclusions This report, which has been endorsed by the Executive Council of the North American Society for Pediatric Gastroenterology and Nutrition, has been prepared as a general guideline to assist providers of medical care in the evaluation and treatment of constipation in children. It is not intended as a substitute for clinical judgment or as a protocol for the management of all patients with this problem.

Naltrexone and Cognitive Behavioral Therapy for the Treatment of Outpatient Alcoholics: Results of a Placebo-Controlled Trial

Abstract: OBJECTIVE: The opiate antagonist drug naltrexone has been shown in a few studies with limited sample sizes to be effective when combined with psychosocial therapies for the treatment of alcohol dependence. The goal of this study was to obtain additional information regarding its efficacy in pertinent alcoholic populations and with a well-defined therapy. METHOD: In this study, 131 recently abstinent alcohol-dependent outpatients were treated with 12 weekly sessions of manual-guided cognitive behavioral therapy and either 50 mg/day of naltrexone (N=68) or placebo (N=63) (with riboflavin added as a marker of compliance) in a double-blind, randomized clinical trial. Alcohol consumption, craving, adverse events, and urinary riboflavin levels were assessed weekly. Levels of blood markers of alcohol abuse were also ascertained during the trial. RESULTS: The study completion, therapy participation, and medication compliance rates in the trial were high, with no differences between treatment groups. Naltrexone-tr...

Multisystemic treatment of substance-abusing and dependent delinquents: outcomes, treatment fidelity, and transportability.

Abstract: The effectiveness and transportability of multisystemic therapy (MST) were examined in a study that included 118 juvenile offenders meeting DSM-III-R criteria for substance abuse or dependence and their families. Participants were randomly assigned to receive MST versus usual community services. Outcome measures assessed drug use, criminal activity, and days in out-of-home placement at posttreatment (T2) and at a 6-month posttreatment follow-up (T3); also treatment adherence was examined from multiple perspectives (i.e., caregiver, youth, and therapist). MST reduced alcohol, marijuana, and other drug use at T2 and total days in out-of-home placement by 50% at T3. Reductions in criminal activity, however, were not as large as have been obtained previously for MST. Examination of treatment adherence measures suggests that the modest results of MST were due, at least in part, to difficulty in transporting this complex treatment model from the direct control of its developers. Increased emphasis on quality assurance mechanisms to enhance treatment fidelity may help overcome barriers to transportability.

Matrix Metalloproteinase Inhibition During the Development of Congestive Heart Failure Effects on Left Ventricular Dimensions and Function

Abstract: —The development of congestive heart failure (CHF) is associated with left ventricle (LV) dilation and myocardial remodeling. The matrix metalloproteinases (MMPs) play a significant role in...

Home-based multisystemic therapy as an alternative to the hospitalization of youths in psychiatric crisis: clinical outcomes.

Abstract: Objective The primary purpose of this study was to determine whether multisystemic therapy (MST), modified for use with youths presenting psychiatric emergencies, can serve as a clinically viable alternative to inpatient psychiatric hospitalization. Method One hundred sixteen children and adolescents approved for emergency psychiatric hospitalization were randomly assigned to home-based MST or inpatient hospitalization. Assessments examining symptomatology antisocial behavior, self-esteem, family relations, peer relations, school attendance, and consumer satisfaction were conducted at 3 times: within 24 hours of recruitment into the project shortly after the hospitalized youth was released from the hospital (1–2 weeks after recruitment), and at the completion of MST home-based services (average of 4 months postrecruitment). Results MST was more effective than emergency hospitalization at decreasing youths' externalizing symptoms and improving their family functioning and school attendance. Hospitalization was more effective than MST at improving youths' self-esteem. Consumer satisfaction scores were higher in the MST condition. Conclusions The findings support the view that an intensive, well-specified, and empirically supported treatment model, with judicious access to placement, can effectively serve as a family-and community-based alternative to the emergency psychiatric hospitalization of children and adolescents.

The role of stress in alcohol use, alcoholism treatment, and relapse.

Abstract: Addiction to alcohol or other drugs (AODs) is a complex problem determined by multiple factors, including psychological and physiological components. Stress is considered a major contributor to the initiation and continuation of AOD use as well as to relapse. Many studies that have demonstrated an association between AOD use and stress have been unable to establish a causal relationship between the two. However, stress and the body’s response to it most likely play a role in the vulnerability to initial AOD use, initiation of AOD abuse treatment, and relapse in recovering AOD users. This relationship probably is mediated, at least in part, by common neurochemical systems, such as the serotonin, dopamine, and opiate peptide systems, as well as the hypothalamic-pituitary-adrenal (HPA) axis. Further exploration of these connections should lead to important pharmacological developments in the prevention and treatment of AOD abuse. Studies indicate that treatment techniques which foster coping skills, problem-solving skills, and social support play a pivotal role in successful treatment. In the future, individualized treatment approaches that emphasize stress management strategies in those patients in whom a clear

Telescoping of landmark events associated with drinking: a gender comparison.

Abstract: Objective: The literature suggests that women exhibit "telescoped" development of (i.e., faster progression to) alcoholism, with fewer years drinking than men. The purpose of this study was to use data gathered in the course of a large clinical trial to further examine this issue. Method: Subjects in this retrospective study were from a pool of 1,307 men and 419 women enrolled in Project MATCH, a multisite alcohol treatment matching study. MATCH subjects were recruited from both outpatient and aftercare settings over a 2-year period. Age-of-onset for landmark events in the development of alcoholism were determined from self-report and clinical interviews given at baseline entry into the study. Gender differences in age-of-onset variables were assessed within both outpatient and aftercare settings. Gender differences in progression times between successive landmarks were also examined. Differences were tested with both multivariate and univariate ANOVA techniques. Results: Women generally began getting dru...

Thymoma: State of the Art

Abstract: Thymoma is the most common tumor of the anterior mediastinum. This tumor is associated with unique paraneoplastic syndromes, such as myasthenia gravis, hypogammaglobulinemia, and pure red cell aplasia. The rarity of this tumor, however, has somewhat obscured the optimal treatment for this disease. For the majority of patients who present with localized tumor, surgical extirpation remains the standard of choice. Adjuvant radiotherapy seems to improve local control and survival. In more advanced disease, systemic therapy has been demonstrated to produce a 50% to 80% objective response rate. These observations have led to the development of multimodality therapy for the treatment of patients with advanced thymoma. In this article, we will review the current perspectives on the management of early stage and advanced thymoma.

Defining organ involvement in sarcoidosis: the ACCESS proposed instrument. ACCESS Research Group. A Case Control Etiologic Study of Sarcoidosis.

Abstract: Background Sarcoidosis is a multiorgan granulomatous disease of unknown cause. Lack of an objective system for assessment of sarcoidosis to evaluate disease course and effectiveness of therapy is a major problem. Methods The sarcoidosis assessment instrument was developed by the Steering Committee of A Case Control Etiologic Study of Sarcoidosis (ACCESS) which included investigators at the ten ACCESS Clinical Centers, the Clinical Coordinating Center, and representatives of the National Heart, Blood, and Lung Institute. This system was developed to assess sarcoidosis organ involvement in ACCESS patients who would be followed over a two-year period. The system represents a consensus of opinions of members of the Steering Committee based on review of their experience and the medical literature. Results Criteria for involvement in patients with biopsy-confirmed sarcoidosis are presented for organs and systems that are commonly involved (lung, skin, eyes, liver, calcium metabolism), unusual but clinically important (nervous system, kidney, heart) and other sites (non-thoracic lymph nodes, bone marrow, spleen, bone/joint, ear/nose/throat, parotid/salivary glands, muscles). Conclusion The proposed instrument is partially subjective in that it depends upon the clinician's diligence in pursuing evidence for sarcoidosis involvement of various organs. It is hoped that this instrument will lead to increased standardization in the definition of sarcoidosis organ involvement to help clinicians and researchers better characterize patients with sarcoidosis.

Successful strategies for improving operating room efficiency at academic institutions.

Abstract: UNLABELLED In this prospective study, we evaluated the etiology of operating room (OR) delays in an academic institution, examined the impact of multidisciplinary strategies to improve OR efficiency, and established OR timing benchmarks for use in future OR efficiency studies. OR times and delay etiologies were collected for 94 cases during the initial phase of the study. Timing data and delay etiologies were analyzed, and 2 wk of multidisciplinary OR efficiency awareness education was conducted for the nursing, surgical, and anesthesia staff. After the education period, timing data were collected from 1787 cases, and monthly reports listing individual case delays and timing data were sent to the Chiefs of Service. For the first case of the day, patient in room, anesthesia ready, surgical preparation start, and procedure start time were significantly earlier (P < 0.01) in the posteducation period compared with the preeducation period, and the procedure start time for the first case of the day occurred, on average, 22 min earlier than all other procedures. For all cases combined, turnover time decreased, on average, by 16 min. Unavailability of surgeons, anesthesiologists, and residents decreased significantly (P < 0.05) as causes of OR delays. Anesthesia induction times were consistently longer for the vascular and cardiothoracic services, whereas surgical preparation time was increased for the neurosurgical and orthopedic services (P < 0.05). Identification of the etiology of OR inefficiency, combined with multidisciplinary awareness training and personal accountability, can improve OR efficiency. The time savings realized are probably most cost-effective when combined with more flexible OR staffing and improved OR scheduling. IMPLICATIONS We achieved significant improvements in operating room efficiency by analyzing operating room data on causes of delays, devising strategies for minimizing the most common delays, and subsequently measuring delay data. Personal accountability, streamlining of procedures, interdisciplinary team work, and accurate data collection were all important contributors to improved efficiency.

Hydrogen peroxide activation of multiple mitogen-activated protein kinases in an oligodendrocyte cell line: role of extracellular signal-regulated kinase in hydrogen peroxide-induced cell death.

Abstract: Oxidative stress is known to induce cell death in a wide variety of cell types, apparently by modulating intracellular signaling pathways. In this study, we have examined the activation of mitogen-activated protein kinase (MAPK) cascades in relation to oxidant-induced cell death in an oligodendrocyte cell line, central glia-4 (CG4). Exposure of CG4 cells to hydrogen peroxide (H2O2) resulted in an increased tyrosine phosphorylation of several protein species, including the abundantly expressed platelet-derived growth factor (PDGF) receptor and the activation of the three MAPK subgroups, i.e., extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK). Dose-response studies showed differential sensitivities of PDGF receptor phosphorylation (>1 mM) and ERK/p38 MAPK (>0.5 mM) and JNK (>0.1 mM) activation by H2O2. The activation of ERK was inhibited by PD98059, a specific inhibitor of the upstream kinase, MAPK or ERK kinase (MEK). H2O2 also activated MAPK-activated protein kinase-2, and this activation was blocked by SB203580, a specific inhibitor of p38 MAPK. The oxidant-induced cell death was indicated by morphological changes, decreased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, and DNA fragmentation. These effects were suppressed dose-dependently by the MEK inhibitor PD98059. The results demonstrate that H2O2 induces the activation of multiple MAPKs in oligodendrocyte progenitors and that the activation of ERK is associated with oxidant-mediated cytotoxicity.