Showing papers by "Rush University Medical Center published in 1997"

Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument.

Abstract: PURPOSEThis is the first published report on the validation of the Functional Assessment of Cancer Therapy-Breast (FACT-B), a 44-item self-report instrument designed to measure multidimensional quality of life (QL) in patients with breast cancer. The FACT-B consists of the FACT-General (FACT-G) plus the Breast Cancer Subscale (BCS), which complements the general scale with items specific to QL in breast cancer. The FACT-B was developed with an emphasis on patients' values and brevity and is available in nine languages.METHODS AND RESULTSTwo validation samples were used for this report. The first (n = 47) was tested twice over a 2-month period to assess sensitivity to change. Significant sensitivity to change in performance status rating (PSR) was demonstrated for the FACT-B total score, the Physical Well-Being (PWB) subscale, the Functional Well-Being (FWB) subscale, and the BCS. Sensitivity to change in QL as measured by the Functional Living Index-Cancer (FLIC) was documented in the FACT-B total score, ...

Prevention of Heart Failure by Antihypertensive Drug Treatment in Older Persons With Isolated Systolic Hypertension

Abstract: Context. —Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. Objective. —To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. Design. —Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Participants. —A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). Intervention. —Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. Main Outcome Measures. —Fatal and nonfatal heart failure. Results. —During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71;P Conclusion. —In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.

Education and Other Measures of Socioeconomic Status and Risk of Incident Alzheimer Disease in a Defined Population of Older Persons

Abstract: Objective: To assess the relations of 3 measures of socioeconomic status (education, occupational prestige, and income) to risk of incident clinically diagnosed Alzheimer disease (AD). Design: Cohort study with an average observation of 4.3 years. Setting: East Boston, Mass, a geographically defined community. Participants: A stratified random sample of 642 community residents 65 years of age and older who were free of AD at baseline. Main Outcome Measure: Clinical diagnosis of probable AD according to standard criteria, using structured uniform evaluation. Results: The relations of the 3 measures of socioeconomic status to risk of disease were assessed using logistic regression analyses. In individual analyses, fewer years of formal schooling, lower income, and lower occupational status each predicted risk of incident AD; risk of disease decreased by approximately 17% for each year of education. In an analysis including all 3 measures, the effect of education on risk for disease remained approximately the same, but the effects of the other 2 measures were somewhat less and did not attain formal statistical significance, compared with separate analysis of each measure. Conclusions: Markers of lower socioeconomic status predict risk of developing incident AD. The mechanism of this relation is uncertain, but the possibility that it reflects unidentified and potentially reversible risk factors for the disease deserves careful investigation.

Lymph Node Micrometastases from Breast Carcinoma Reviewing the Dilemma

Abstract: BACKGROUND The presence or absence of regional lymph node metastases has been one of the most important determining factors in recommending adjuvant chemotherapy for patients with breast carcinoma. However, because of the 15-20% failure rate at 5 years for lymph node negative patients, other tumor-related prognostic factors have gained greater significance in this decision-making process. Many investigators have reported finding micrometastases that were not detected by routine sectioning of the lymph nodes but were identified by multiple sectioning and additional staining. This review attempts to evaluate the role of occult lymph node micrometastases and their relevance to disease recurrence. METHODS A literature search of the entire MEDLINE data base was conducted. All relevant articles were reviewed for the criteria they used to define micrometastases. The frequency of detection of micrometastases by various methodologies and the prognostic significance of such deposits were examined. RESULTS Tumor deposits involving the lymph nodes were found to be arbitrarily categorized as either micrometastases or macrometastases, with the cutoff point ranging from 0.2-2.0 mm. The detection rate of such deposits by conventional techniques was inadequate. Serial sectioning and immunohistochemistry appeared to increase the detection rate by 9-33%. A definite survival disadvantage was noted for patients with such occult metastases. CONCLUSIONS Current routine histologic examination of regional lymph nodes underestimates breast carcinoma metastases. Serial sectioning and immunohistochemistry increase the yield but are too labor-intensive and expensive for routine use. However, the introduction of the sentinel lymph node biopsy in lieu of axillary lymph node dissection in cases of breast carcinoma holds promise for making these methods practical and cost-effective. Cancer 1997; 80:1188-97. © 1997 American Cancer Society.

Validity of a verbally administered numeric rating scale to measure cancer pain intensity

Abstract: The ability to quantify pain intensity is essential when caring for individuals in pain in order to monitor patient progress and analgesic effectiveness. Three scales are commonly employed: the simple descriptor scale (SDS), the visual analog scale (VAS), and the numeric (pain intensity) rating scale (NRS). Patients with English as a second language may not be able to complete the SDS without translation, and visually, cognitively, or physically impaired patients may have difficulty using the VAS. The NRS has been found to be a simple and valid alternative in some disease states; however, the validity of this scale administered verbally, without visual cues, to oncology patients has not yet been established. The present study examined validity of a verbally administered 0-10 NRS using convergence methods. The correlation between the VAS and the NRS was strong and statistically significant (r = 0.847, p < 0.001), supporting the validity of the verbally administered NRS. Although all subjects were able to complete the NRS and SDS without apparent difficulty, 11 subjects (20%) were unable to complete the VAS. The mean opioid intake was significantly higher for the group that was unable to complete the VAS (mean 170.8 mg, median 120.0 mg, SD = 135.8) compared to the group that had no difficulty with the scale (mean 65.6 mg, 33.0 mg, SD = 99.7) (Mann-Whitney test, p = 0.0065). The verbally administered 0-10 NRS provides a useful alternative to the VAS, particularly as more contact with patients is established via telephone and patients within the hospital are more acutely ill.

Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale

Abstract: We developed a 12-item bone marrow transplant subscale (BMTS) for the general Functional Assessment of Cancer Therapy (FACT) measure. The subscale combined with the FACT, (FACT-BMT) is a 47-item, valid and reliable measure of five dimensions of quality of life in bone marrow transplant patients. The three-step validation process involved the generation and selection of BMT-specific items and the testing of the overall measure. Items were selected from a list produced by seven oncology experts and 15 patients and were designed to assess content not represented in the general FACT items. A total of 182 patients completed the FACT-BMT at baseline, prior to BMT. An analysis measuring sensitivity to change was performed with 74 patients after transplantation and 60 patients over the three time-points of baseline, hospital discharge and 100 days. The FACT-BMT and all subscales were correlated, sensitivity to change was measured, and the internal consistency for each scale was calculated. Coefficients of reliability and validity ranged from 0.86 to 0.89 for the entire FACT-BMT and 0.54 to 0.63 for the BMTS. The BMTS was able to discriminate patients on the basis of performance status rating and also demonstrated sensitivity to change over time. The FACT-BMT has good psychometric properties for use in assessing quality of life in bone marrow transplant patients. The addition of the bone marrow transplant subscale to the general FACT measure makes it an excellent choice for use in BMT clinical trials.

Protective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease.

Abstract: Huntington's disease is a genetic disorder that results from degeneration of striatal neurons, particularly those containing GABA (γ-aminobutyric acid)1. There is no effective treatment for preventing or slowing this neuronal degeneration. Ciliary neurotrophic factor (CNTF) is a trophic factor for striatal neurons2,3 and therefore a potential therapeutic agent for Huntington's disease. Here we evaluate CNTF as a neuroprotective agent in a non-human primate model of Huntington's disease. We gave cyno-molgus monkeys intrastriatal implants of polymer-encapsulated baby hamster kidney fibroblasts that had been genetically modified to secrete human CNTF. One week later, monkeys received unilateral injections of quinolinic acid into the previously implanted striatum to reproduce the neuropathology seen in Huntington's disease4,5. Human CNTF was found to exert a neuroprotective effect on several populations of striatal cells, including GABAergic, cholinergic and diaphorase-positive neurons which were all destined to die following administration of quinolinic acid. Human CNTF also prevented the retrograde atrophy of layer V neurons in motor cortex and exerted a significant protective effect on the GABAergic innervation of the two important target fields of the striatal output neurons (the globus pallidus and pars reticulata of the substantia nigra). Our results show that human CNTF has a trophic influence on degenerating striatal neurons as well as on critical non-striatal regions such as the cerebral cortex, supporting the idea that human CNTF may help to prevent the degeneration of vulnerable striatal populations and cortical–striatal basal ganglia circuits in Huntington's disease.

Costs of an Emergency Department-Based Accelerated Diagnostic Protocol vs Hospitalization in Patients With Chest Pain A Randomized Controlled Trial

Abstract: Context. —More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units. Objective. —To determine whether use of an emergency department (ED)—based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain. Design. —Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques. Setting. —A large urban public teaching hospital serving a predominantly African American and Hispanic population. Patients. —A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm. Main Outcome Measures. —Primary outcomes measured for each subject were LOS and total cost of treatment. Results. —The hospital admission rate for ADP vs control patients was 45.2% vs 100% ( P P P Conclusions. —In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACI.

Osteoarthritic lesions: involvement of three different collagenases.

Abstract: Objective. To assess the presence of fibroblast collagenase (MMP-1), neutrophil collagenase (MMP-8), and collagenase 3 (MMP-13) in osteoarthritic (OA) cartilage, with particular emphasis on areas of macroscopic cartilage erosion. Methods. Messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, and Northern blot analysis. Results. MMP-1 and MMP-13 were expressed at higher levels by OA chondrocytes than by normal chondrocytes. In addition, mRNA for MMP-8 was present in OA cartilage but not normal cartilage by PCR and Northern blot analyses. Chondrocytes from areas surrounding the OA lesion expressed greater quantities of MMP-1 and MMP-13 compared with normal chondrocytes, suggesting local modulation by mechanical and inflammatory factors. Tumor necrosis factor α stimulated the expression of all 3 collagenases. Retinoic acid, an agent which induces autodigestion of cartilage in vitro, stimulated only the expression of MMP-13. Conclusion. These findings suggest a key role of MMP-13 and MMP-8, as well as MMP-1 in osteoarthritis.

Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain a randomized controlled trial

Abstract: Context.-More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units. Objective.-To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain. Design.-Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques. Setting.-A large urban public teaching hospital serving a predominantly African American and Hispanic population. Patients.-A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm. Main Outcome Measures.-Primary outcomes measured for each subject were LOS and total cost of treatment. Results.-The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01). Conclusions.-In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACl.

Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease

Abstract: A total of 335 patients with early Parkinson's disease (PD) were enrolled in a multicenter, randomized, double-blind trial designed to assess the efficacy and safety of pramipexole. Entry was restricted to patients with idiopathic PD who were not receiving levodopa. Pramipexole was administered according to an ascending dose schedule up to 4.5 mg/d. During the 7-week dose-escalation phase, each subject was titrated to his or her maximally tolerated dose of study medication. This was followed by a 24-week period of maintenance therapy. The mean daily dose during the maintenance period was 3.8 mg. Pramipexole significantly reduced the severity of PD symptoms and signs compared with placebo, as measured by decreases in parts II (Activities of Daily Living) and III (Motor Examination) of the Unified Parkinson's Disease Rating Scale at week 24 compared with baseline (p < or = 0.0001). Differences between the active drug and placebo groups emerged at week 3 (1.5 mg/d) in the ascending-dose interval and persisted throughout the maintenance phase (p < or = 0.0001). The majority of patients completed the study (pramipexole 83%, placebo 80%). In the assessment of adverse events, nausea, insomnia, constipation, somnolence, and visual hallucinations occurred more frequently in the pramipexole treatment group compared with placebo patients. No clinically significant changes were noted in blood pressure or pulse rate. Overall, these results indicate that pramipexole is safe and effective in the treatment of early PD.

Rotatory Instability of the Elbow. The Anatomy and Role of the Lateral Stabilizers

Abstract: Posterolateral rotatory instability of the elbow has been attributed to disruption of the ulnar part of the lateral collateral ligament. Forty fresh cadavera were studied to define the ligamentous anatomy of the lateral aspect of the elbow specifically as it relates to rotatory instability. The dissections revealed a broad conjoined insertion of the lateral collateral and annular ligaments onto the proximal aspect of the ulna. This insertion was bilobed (type I) in twenty-two specimens and broad (type II) in eighteen specimens. Serial sectioning studies revealed primary and secondary stabilizers of the lateral aspect of the elbow. In addition to the lateral collateral ligament and the annular ligament, the extensor muscle origins provide stability through fascial bands and intermuscular septa. CLINICAL RELEVANCE: The findings of this study suggest that post-traumatic posterolateral rotatory instability of the elbow is the result of attenuation or disruption of both the ligamentous and the muscular origins from the lateral epicondyle of the humerus. Injury to these structures should be avoided during operative exposures for procedures such as debridement of the elbow for recalcitrant lateral epicondylitis, resection of the radial head, or capsular release for a stiff elbow. If immobilization is necessary postoperatively, the forearm should be held in pronation.

Monitoring Plasma HIV-1 RNA Levels in Addition to CD4+ Lymphocyte Count Improves Assessment of Antiretroviral Therapeutic Response

Abstract: Background: CD4+ lymphocyte counts and plasma HIV-1 RNA levels predict progression of HIV-related disease, but the relative importance of these and other virological factors in defining response to...

Tramadol: a new centrally acting analgesic

Abstract: The pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of tramadol are reviewed. Tramadol is a synthetic analogue of codeine that binds to mu opiate receptors and inhibits norepinephrine and serotonin reuptake. It is rapidly and extensively absorbed after oral doses and is metabolized in the liver. Analgesia begins within one hour and starts to peak in two hours. In patients with moderate postoperative pain, i.v. or i.m. tramadol is roughly equal in efficacy to meperidine or morphine; for severe acute pain, tramadol is less effective than morphine. Oral tramadol can also be effective after certain types of surgery. Tramadol and meperidine are equally effective in postoperative patient-controlled analgesia. In epidural administration for pain after abdominal surgery, tramadol is more effective than bupivacaine but less effective than morphine. In patients with ureteral calculi, both dipyrone and butylscopolamine are more effective than tramadol. For labor pain, i.m. tramadol works as well as meperidine and is less likely to cause neonatal respiratory depression. Oral tramadol is as effective as codeine for acute dental pain. In several types of severe or refractory cancer pain, tramadol is effective, but less so than morphine; for other types of chronic pain, such as low-back pain, oral tramadol works as well as acetaminophen-codeine. Common adverse effects of tramadol include dizziness, nausea, dry mouth, and sedation. The abuse potential seems low. The recommended oral dosage is 50-100 mg every four to six hours. Tramadol is an effective, if expensive, alternative to other analgesics in some clinical situations.

The use of mesh in gynecologic surgery.

Abstract: The aim of this review was to compare properties of the most commonly used synthetic meshes and describe their use in gynecologic procedures An Ovid search of the English literature from 1966 to the present was carried out, together with a hand search ofIndex Medicus from 1950 to 1965 Articles involving the use of mesh in surgical procedures or comparative studies of the different mechanical properties of mesh are included Overviews from urogynecologic texts and surgical texts are also included All studies in this review consisted of retrospective case series (21 suburethral sling articles, 15 sacrocolpopexy articles, and five pelvic sling articles) No randomized prospective trials were available Outcome variables, including cure rates and mesh-related complications, are reviewed and compared Conclusions show that long-term success of the suburethral sling with synthetic mesh ranges from 61% to 100%, and the success rate of the abdominal sacrocolpopexies using mesh ranges from 68% to 100% Mesh-related complications rates are frequent, with up to a 35% removal rate and 10% sinus tract formation for suburethral slings and 9% erosion rate for sacrocolpopexy The ideal synthetic mesh material for pelvic surgery, one that induces minimal foreign-body reaction with minimal risk of infection, rejection and erosion, has yet to be developed

Local Control Model of Excitation–Contraction Coupling in Skeletal Muscle

Abstract: This is a quantitative model of control of Ca2+ release from the sarcoplasmic reticulum in skeletal muscle, based on dual control of release channels (ryanodine receptors), primarily by voltage, secondarily by Ca2+ (Rios, E., and G. Pizarro. 1988. NIPS. 3:223–227). Channels are positioned in a double row array of between 10 and 60 channels, where exactly half face voltage sensors (dihydropyridine receptors) in the transverse (t) tubule membrane (Block, B.A., T. Imagawa, K.P. Campbell, and C. Franzini-Armstrong. 1988. J. Cell Biol. 107:2587–2600). We calculate the flux of Ca2+ release upon different patterns of pulsed t-tubule depolarization by explicit stochastic simulation of the states of all channels in the array. Channels are initially opened by voltage sensors, according to an allosteric prescription (Rios, E., M. Karhanek, J. Ma, A. Gonzalez. 1993. J. Gen. Physiol. 102:449–482). Ca2+ permeating the open channels, diffusing in the junctional gap space, and interacting with fixed and mobile buffers produces defined and changing distributions of Ca2+ concentration. These concentrations interact with activating and inactivating channel sites to determine the propagation of activation and inactivation within the array. The model satisfactorily simulates several whole-cell observations, including kinetics and voltage dependence of release flux, the “paradox of control,” whereby Ca2+-activated release remains under voltage control, and, most surprisingly, the “quantal” aspects of activation and inactivation (Pizarro, G., N. Shirokova, A. Tsugorka, and E. Rios. 1997. J. Physiol. 501:289–303). Additionally, the model produces discrete events of activation that resemble Ca2+ sparks (Cheng, H., M.B. Cannell, and W.J. Lederer. 1993. Science (Wash. DC). 262:740–744). All these properties result from the intersection of stochastic channel properties, control by local Ca2+, and, most importantly, the one dimensional geometry of the array and its mesoscopic scale. Our calculations support the concept that the release channels associated with one face of one junctional t-tubule segment, with its voltage sensor, constitute a functional unit, termed the “couplon.” This unit is fundamental: the whole cell behavior can be synthesized as that of a set of couplons, rather than a set of independent channels.

A Phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma

Abstract: BACKGROUND Anastrozole is a new oral aromatase inhibitor with highly potent and selective activity for the aromatase enzyme. In a Phase III trial, the efficacy and tolerability of anastrozole, given in doses of 1 and 10 mg orally once daily, and megestrol acetate, given in doses of 40 mg orally 4 times daily, were compared in 386 postmenopausal women with advanced breast carcinoma who progressed after tamoxifen therapy. METHODS The trial was randomized, double blind for anastrozole, open label for megestrol acetate, parallel group, and multicenter. Patients were randomly assigned to receive anastrozole, 1 mg (n = 128); anastrozole, 10 mg (n = 130); or megestrol acetate (n = 128). The primary efficacy measures were time to progression and tumor response; secondary measures were time to treatment failure, duration of response, quality of life, and time to death. RESULTS With a median duration of follow-up of 6 months, there was no statistical evidence of a difference between either 1 or 10 mg doses of anastrozole and megestrol acetate for any efficacy endpoint. According to rigid response criteria, 10%, 6%, and 6% of patients in the anastrozole 1 mg, anastrozole 10 mg, and megestrol acetate groups, respectively, had an objective response (complete response or partial response) and 27%, 24%, and 30% of patients in the respective groups had stable disease for a duration of 24 weeks or longer. Quality-of-life assessments revealed that anastrozole in a 1-mg dose was associated with better physical scores and anastrozole in a 10-mg dose with better psychologic scores than megestrol acetate. Both anastrozole and megestrol acetate were generally well tolerated. Among anticipated adverse events, gastrointestinal disturbance was more common among patients in the anastrozole groups, whereas weight gain occurred more frequently among patients in the megestrol acetate groups. Weight increases of 5% or more and 10% or more were more common among megestrol acetate-treated patients; moreover, patients in this group continued to gain weight over time. CONCLUSIONS Anastrozole, given in doses of 1 and 10 mg once daily, represents a well tolerated and effective therapeutic option for the treatment of postmenopausal women with advanced breast carcinoma who progress after tamoxifen treatment. Cancer 1997; 79:730-9. © 1997 American Cancer Society.

Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the Treatment of Mild Hypertension Study

Abstract: Objectives: To compare 5 antihypertensive drugs and placebo for changes in quality of life (QL). To assess the relationship of lifestyle factors and change in lifestyle factors to QL in participants with stage I diastolic hypertension. Methods: The Treatment of Mild Hypertension Study (TOMHS) was a randomized, double-blind, placebocontrolled clinical trial with minimum participant follow-up of 4 years. It was conducted at 4 hypertension screening and treatment academic centers in the United States. The cohort consisted of 902 men and women with hypertension, aged 45 to 69 years, with diastolic blood pressures less than 100 mm Hg. Informed consent was obtained from each participant after the nature of the procedures had been fully explained. Sustained nutritional-hygienic intervention was administered to all participants to reduce weight, to reduce dietary sodium and alcohol intake, and to increase physical activity. Participants were randomized to take (1) acebutolol (n=132); (2) amlodipine maleate (n=131); (3) chlorthalidone (n=126); (4) doxazosin mesylate (n=134); (5) enalapril maleate (n=135); or placebo (n=234). Changes in 7 QL indexes were assessed based on a 35-item questionnaire: (1) general health; (2) energy or fatigue; (3) mental health; (4) general functioning; (5) satisfaction with physical abilities; (6) social functioning; and (7) social contacts. Results: At baseline, higher QL was associated with older age, more physical activity, lower obesity level, male gender, non-African American race, and higher educational level. Improvements in QL were observed in all randomized groups, including the placebo group during follow-up; greater improvements were observed in the acebutolol and chlorthalidone groups and were evident throughout follow-up. The amount of weight loss, increase in physical activity, and level of attained blood pressure control during follow-up were related to greater improvements in QL. Conclusions: In patients with stage I hypertension, antihypertensive treatment with any of 5 agents used in TOMHS does not impair QL. The diuretic chlorthalidone and the cardioselective β-blocker acebutolol appear to improve QL the most. Success with lifestyle changes affecting weight loss and increase in physical activity relate to greater improvements in QL and show that these interventions, in addition to contributing to blood pressure control, have positive effects on the general well-being of the individual. Arch Intern Med. 1997;157:638-648

5- to 13-year follow-up study on cementless femoral components in revision surgery.

Abstract: The 5- to 13-year follow-up data on 297 cementless revision arthroplasties with extensively coated components (Anatomic Medullary Locking femoral component, DePuy, Warsaw, IN) are reported. A basic classification of the femoral defects was developed. All patients were evaluated clinically and radiographically at a minimum of 60 months. Clinically, the average Postel-d'Aubigne score improved from 4.8 before to a 10.2 after surgery. Definite radiographic instability was noted in seven hips. Five patients were symptomatic and were revised. The mechanical failure rate was 2.4%. The overall complication rate was 5.7%, with a 2.6% dislocation rate. In the presence of bone loss in the proximal metaphyseal region of the femur, fixation of the femoral component is best achieved in the diaphyseal region of the femur using an extensively coated femoral component.

Metabolism of the extracellular matrix formed by intervertebral disc cells cultured in alginate

Abstract: Study design Cells from normal rabbit nucleus pulposus (NP) and anulus fibrosus (AF) were cultured in alginate beads for as long as 14 days to allow them to reform a matrix made up of two compartments: the cell-associated matrix (CM) and further removed matrix (FRM). At different time points, the CM and FRM made by each cell population were analyzed using histologic, biochemical, and immunologic assays. Objectives To study the metabolism of normal rabbit NP and AF cells in alginate by characterizing the CM and FRM formed by each cell population, and to identify metabolic properties that may shed light on mechanisms at play in disc degeneration. Summary of background data Little is known about the metabolism of intervertebral disc cells, in part because of the lack of microculture systems appropriate for the study of these cells in vitro. In recent studies from our laboratories, it was suggested that articular chondrocytes cultured in alginate beads remain phenotypically stable and reform a matrix similar to the one they populate in vivo. This culture system appears ideally suited for the study of intervertebral cells available only in limited numbers. Methods Rabbit NP and AF cells released from the matrix by sequential enzyme digestion were encapsulated in alginate beads (20,000 cells/bead) and cultured for as long as 14 days. At selected time points, beads were solubilized with calcium chelating agents, and the CM and FRM were isolated. The rate of 35S-sulfate incorporation into proteoglycans, and the contents of various extracellular matrix molecules (total sulfated proteoglycans, antigenic keratan sulfate, hyaluronan, collagen, and pyridinium crosslinks) were measured. Results Both NP and AF cells remained phenotypically stable in the alginate gel throughout the culture period and reestablished a matrix composed of CM and FRM compartments. The two cell populations exhibited numerous differences in their metabolic activities in vitro. Nucleus pulposus cells synthesized fewer proteoglycan and collagen molecules and were less effective in incorporating these into the CM than AF cells. Conclusions Intervertebral disc cells, especially NP cells, are extremely sluggish in reforming a CM, a protective shell rich in proteoglycans and collagen molecules. This may help explain why damage to the NP often is accompanied by progressive degeneration of the disc in vivo.

Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons

Abstract: Objective. —To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the ϵ4 allele. Design. —Community-based cohort study. Setting. —East Boston, Mass. Participants. —A random sample of 578 community residents aged 65 years and older free of AD. Main Outcome Measure. —Clinical diagnosis of AD by uniform, structured evaluation. Results. —The increased risk of AD associated with the presence of the ϵ4 allele was less than that found in most family and case-control studies. Persons with the ϵ4/ϵ4 or ϵ3/ϵ4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the ϵ3/ϵ3 genotype. The ϵ4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the ϵ4 allele on risk of AD did not appear to vary with age. Conclusions. —The apolipoprotein E ϵ4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.

Joint loading with valgus bracing in patients with varus gonarthrosis.

Abstract: The purpose of this study was to determine whether a brace designed to unload varus degenerative knees actually alters medial compartment loads by decreasing the adduction moment. Eleven patients who had arthrosis confined to the medial compartment were fitted with a valgus brace and tested before and after brace wear with pain and function scoring instruments and by automated gait analysis. The biomechanical data from these patients were compared with those from 11 healthy control subjects. Scores from an analog pain scale decreased 48% with brace wear, and function with activities of daily living increased 79%. Mean adduction moment without the brace measured 4.0 +/- 0.8% body weight times height versus 3.6 +/- 0.8% body weight times height when wearing the brace (10% decrease). The mean adduction moment for control subjects was 3.5 +/- 0.6% body weight times height. Thus, the mean adduction moment decreased from approximately one standard deviation from the normal mean to a value that is similar to the control value. Nine of 11 patients had a decrease in the adduction moment with the brace, five of 11 patients had a reduction higher than 10%, and decreases in this moment were as high as 32%. This study shows that pain, function, and biomechanical knee loading can be altered by a brace designed to unload the medial compartment of the knee.

Patterns of Meniscal Injury in the Anterior Cruciate-Deficient Knee: A Review of the Literature

Abstract: The importance of addressing meniscal pathology associated with anterior cruciate ligament (ACL) insufficiency stems from the increased incidence of meniscal tears with chronic instability The combined effect of instability and meniscal lesions can lead to the development of knee arthrosis A predominance of lateral meniscal tears has been demonstrated with acute ACL rupture, whereas the incidence of medial meniscal tears increases significantly with chronic ACL insufficiency The percentage of repairable meniscal tears is higher on the medial than the lateral side and decreases overall with the chronicity of ACL insufficiency The likelihood of a successful meniscal repair is enhanced significantly when combined with ACL reconstruction This review suggests that maximal meniscal preservation is best achieved with ACL reconstruction This review suggests that maximal meniscal preservation is best achieved with ACL reconstruction shortly after injury and simultaneous repair of coexisting peripheral meniscus tears