The BDNF Val66Met polymorphism is not associated with late onset Alzheimer's disease in three case-control samples.
Explore the source record for details and available documents.
Age of Onset↗
Biomedical subjects
C Rowland
Publications and source records attributed to C Rowland.
Investigation of fatigue crack growth in acrylic bone cement using the acoustic emission technique.
Failure of the bone cement mantle has been implicated in the loosening process of cemented hip stems. Current methods of investigating degradation of the cement mantle in vitro often require sectioning of the sample to confirm failure paths. The present research investigates acoustic emission as a passive experimental method for the assessment of bone cement failure. Damage in bone cement was monitored during four point bending fatigue tests through an analysis of the peak amplitude, duration, rise time (RT) and energy of the events emitted from the damage sections. A difference in AE trends was observed during failure for specimens aged and tested in (i) air and (ii) Ringer's solution at 37 degrees C. It was noted that the acoustic behaviour varied according to applied load level; events of higher duration and RT were emitted during fatigue at lower stresses. A good correlation was observed between crack location and source of acoustic emission, and the nature of the acoustic parameters that were most suited to bone cement failure characterisation was identified. The methodology employed in this study could potentially be used as a pre-clinical assessment tool for the integrity of cemented load bearing implants.
Acoustics↗
Adrenocortical carcinoma: surgical progress or status quo?
HYPOTHESIS: Outcome of patients with adrenocortical carcinoma (ACC) has improved with the advent of more widely available and higher quality imaging. Operative management strategies and use of adjuvant therapy have not changed. DESIGN: Retrospective review of patient histories, imaging studies, operative data, adjuvant therapy, and outcomes at a single institution. Follow-up was complete for a mean of 53 months. Data was compared with prior institutional experience. SETTING: Tertiary care referral center. PATIENTS: All patients undergoing operative management for ACC during the period from 1980 to 1996. MAIN OUTCOME MEASURES: Determinants of recurrence, survival, and the effect of adjuvant therapy on overall outcome. RESULTS: Fifty-eight patients (30 men, 28 women) with a mean age of 53 years underwent primary operative management for ACC. Functional tumors were identified in 27 patients (47%). Mean tumor size was 12.5 cm. Stage according to the TNM staging system (AJCC Cancer Staging Manual) at presentation was I (n = 0), II (n = 30), III (n = 7), and IV (n = 21). Surgical management included curative resection in 41 (71%), noncurative resection in 14 (24%), and open biopsy in 3 (5%). Perioperative mortality was 5%. Recurrence occurred in 30 patients (73%) with a median time to recurrence of 17 months. Five-year survival by the Kaplan-Meier method was 37%. Prognostic factors (P<.05) included functional status, stage, and chemotherapy in stage III/IV patients. When compared with our prior institutional experience (1960-1980), current patients were more likely to present with stages I to II (52% vs. 34%), have curative resections (71% vs. 50%), and have improved 5-year survival (37% vs. 16%). CONCLUSIONS: (1) Surgical resection remains the principal treatment for stage I to III disease. (2) Adjuvant therapy may improve survival in patients with stage III or IV disease. (3) Current patients were more likely to present at an earlier stage, undergo curative resections, and have improved 5-year survival than institutional historical comparisons.
Adolescent↗
Primary uncemented total hip arthroplasty in patients <40 years old: 10- to 14-year results using first-generation proximally porous-coated implants.
Eighty-two consecutive primary first-generation uncemented total hip arthroplasties (72 patients) performed in patients <40 years old were reviewed with minimum follow-up of 10 years. Of 82 hips, 24 (29.3%) have been revised to date. The estimated survival free of aseptic revision or radiographic failure was 81.3% at 10 years for the acetabular components. The estimated survival free of aseptic revision or radiographic failure was 84.9% at 10 years for the femoral component. In this exclusively young patient cohort, there was a high failure rate of the acetabular component and the femoral component. The data in this report can serve as a baseline for comparison of newer implants and operative methods.
Adolescent↗
Thirty-day mortality after elective total hip arthroplasty.
BACKGROUND: Previous reports on perioperative mortality associated with hip arthroplasty have not documented, to our knowledge, patient characteristics and surgical factors that increase the likelihood of death. The purpose of this study was to determine the prevalence of and associated risk factors for perioperative death after elective hip arthroplasty. METHODS: The records of 30,714 consecutive patients who had undergone elective hip arthroplasty at our institution from 1969 to 1997 were retrospectively reviewed to identify patients who had died within thirty days after the procedure. Mortality rates were determined according to age, gender, diagnosis, implant type, and fixation mode. RESULTS: Ninety deaths occurred within thirty days after elective total hip arthroplasty, for an overall mortality rate of 0.29% (ninety of 30,714). The thirty-day mortality rate was significantly higher for patients with preexisting cardiovascular disease (p < 0.0001), male patients (p < 0.0001), and patients who were seventy years of age or older (p < 0.0002). The mortality rate was slightly, but not significantly, higher for patients with an underlying diagnosis of rheumatoid arthritis (p < 0.36) and those receiving cemented implants (p < 0.57). There was no difference in the thirty-day mortality rate for revision as compared with primary hip arthroplasty (p < 0.92). CONCLUSIONS: Factors that are associated with an increased risk of mortality within thirty days after elective hip arthroplasty include an older age, male gender, and a history of cardiorespiratory disease. There has been a significant decline in the thirty-day mortality rate after elective hip arthroplasty in the last decade (p < 0.0002); during the 1990s, the overall rate at our institution was 0.15% (twenty-three of 14,989).
Aged↗
Retention of all-polyethylene acetabular components after femoral revision of a cemented total hip replacement.
BACKGROUND: This study was undertaken to provide a basis for decision-making when a well-fixed cemented cup is encountered at the time of a revision of a femoral component of a total hip replacement. It may be beneficial to retain the cup in some instances and thus reduce morbidity, complications, blood loss, operative time, and cost. METHODS: All patients who had a revision of the femoral component and retention of an all-polyethylene acetabular component from 1971 to 1996 were identified. Three hundred and seventy-four patients with a total of 395 cemented total hip replacements fit the inclusion criteria. The gender, date of and age at the index surgery, type of acetabular implant, and time of and reason for the revision of the femoral component were reviewed. The time to subsequent cup revision or latest surveillance was noted. The average age (and standard deviation) was 66.5 +/- 11.8 years at the time of the femoral revision, which was performed at an average of 8.0 +/- 4.4 years after the primary arthroplasty. For the purposes of this study, the end point for survival of the acetabular component was cup revision for any reason. RESULTS: At the time of the latest follow-up, at an average of nine years after the femoral revision and 17.3 years after the primary arthroplasty, 342 (86.6%) of the 395 cups remained in situ. Fifty-three cups (13.4%) in fifty-two patients had been revised, at an average of 10.0 +/- 5.7 years after the femoral revision and 16.7 +/- 5.3 years after the primary arthroplasty. The rate of survival of the retained acetabular components was 96.9% at five years, 89.3% at ten years, and 78.7% at fifteen years after the femoral revision and was 95.1% at fifteen years and 87.1% at twenty years after the primary arthroplasty. Increased age (p < 0.0001) and a shorter time-interval (less than 7.5 years) between the primary arthroplasty and the femoral revision (p = 0.05) were significantly associated with an increased likelihood of survival free of cup revision. Femoral head size, acetabular component design, gender, and primary diagnosis did not affect prosthetic survival in this sample of patients. CONCLUSIONS: The likelihood of survival of the unrevised cup was associated with patient age and duration of implantation, with the age of the patient being the more dominant factor predicting failure of the acetabular component.
Acetabulum↗
Assembly of very low density lipoproteins in mouse liver: evidence of heterogeneity of particle density in the Golgi apparatus.
The assembly of very low density lipoproteins (VLDL) by hepatocytes is believed to occur via a two-step process. The first step is the formation of a dense phospholipid and protein-rich particle that is believed to be converted to VLDL by the addition of bulk triglyceride in a second step. Previous studies in our laboratory led us to hypothesize a third assembly step that occurs in route to or in the Golgi apparatus. To investigate this hypothesis, nascent lipoproteins were recovered from Golgi apparatus-rich fractions isolated from mouse liver. The Golgi fractions were enriched 125-fold in galactosyltransferase and contained lipoprotein particles averaging approximately 35 nm in diameter. These lipoproteins were separated by ultracentrifugation into two fractions: d < 1.006 g/ml and d1.006;-1.210 g/ml. The d < 1.006 g/ml fraction contained apolipoprotein B-100 (apoB-100), apoB-48, and apoE, while the d1.006;-1.210 g/ml fraction contained these three apoproteins as well as apoA-I and apoA-IV. Both fractions contained a 21-kDa protein that was isolated and sequenced and identified as major urinary protein. Approximately 50% of the apoB was recovered with the denser fraction. To determine if these small, dense lipoproteins were secreted without further addition of lipid, mice were injected with Triton WR1339 and [(3)H]leucine, and the secretion of apoB-100 and apoB-48 into serum VLDL (d < 1.006 g/ml) and d1.006;-1.210 g/ml fractions was monitored over a 2-h period. More than 80% of the newly synthesized apoB-48 and nearly 100% of the apoB-100 were secreted with VLDL. These studies provide the first characterization of nascent lipoproteins recovered from the Golgi apparatus of mouse liver. We conclude that these nascent hepatic Golgi lipoproteins represent a heterogeneous population of particles including VLDL as well as a population of small, dense lipoproteins. The finding of the latter particles, coupled with the demonstration that the primary secretory product of mouse liver is VLDL, suggests that lipid may be added to nascent lipoproteins within the Golgi apparatus.
Animals↗
Thermal balloon and rollerball ablation to treat menorrhagia: two-year results of a multicenter, prospective, randomized, clinical trial.
STUDY OBJECTIVE: To evaluate 2-year follow-up results in patients participating in a randomized, clinical trial comparing uterine balloon therapy with rollerball endometrial ablation. STUDY DESIGN: Prospective, randomized, clinical trial (Canadian Task Force classification I). SETTING: Fourteen university-affiliated and private practice sites. PATIENTS: Two hundred fifty-five women with menorrhagia. INTERVENTIONS: Patients were randomized to rollerball or uterine balloon endometrial ablation. MEASUREMENTS AND MAIN RESULTS: Patient satisfaction with both treatments was consistently high. Only 15 hysterectomies had been performed (6 for menorrhagia) at the end of 2 years, 11 in the rollerball group, 4 in the balloon therapy group. CONCLUSION: Endometrial ablation by both procedures was highly successful in avoiding hysterectomy and relieving symptoms of menorrhagia. Additional benefits were reduction in dysmenorrhea and premenstrual syndrome.
Adult↗
Surgical treatment of adult primary hepatic sarcoma.
BACKGROUND: Primary sarcomas of the liver are extremely rare in adults. Optimal therapeutic approaches remain unclear. METHODS: Twenty consecutive adult patients who had surgical treatment for primary hepatic sarcomas were reviewed. Patient age ranged from 23 to 80 years. Other than one patient with primary hepatic angiosarcoma who had a history of thorium dioxide colloid (Thorotrast) exposure 23 years before diagnosis, no predisposing causes were apparent. Nineteen patients had hepatic resection and one patient had an orthotopic liver transplant. No patient received neoadjuvant chemotherapy or radiotherapy but radiotherapy was delivered intraoperatively in one patient. RESULTS: Leiomyosarcoma was the most common histological type of sarcoma diagnosed (five of 20 patients), followed by malignant solitary fibrous tumour (four) and epithelioid haemangioendothelioma (three). Fourteen tumours were high-grade sarcomas and six were low grade malignancies. Thirteen patients developed a recurrence. Distant metastases (ten patients) and intrahepatic recurrence (six) were the predominant sites of initial treatment failure. Six patients received salvage chemotherapy. Histological grade was the only factor significantly associated with overall patient survival (P= 0.03). With complete resection, patients with high-grade tumours had a 5-year survival rate of 18 (95 per cent confidence interval 5-62) per cent compared with 80 (52-100) per cent for patients with low-grade tumours. The 5-year survival rate for all 20 patients was 37 (20-60) per cent. CONCLUSION: Surgical resection is the only effective therapy for primary hepatic sarcomas at present. Better adjuvant therapy is necessary, especially for high-grade malignancies, owing to the high failure rate with operation alone.
Adult↗
Is calciphylaxis best treated surgically or medically?
BACKGROUND: Calciphylaxis is a rare, painful, life-threatening problem of cutaneous necrosis and refractory healing in patients with uremia and secondary hyperparathyroidism. The pathogenesis involves abnormalities in calcium and phosphorus metabolism and acute deposition of calcium in tissues. METHOD: The clinical course of 16 patients who were diagnosed with calciphylaxis at our institution from 1994 through 1998 was reviewed. RESULTS: Fourteen female patients and 2 male patients had chronic renal disease, secondary hyperparathyroidism, and characteristic skin necrosis (mean age, 56 years; range, 39-70 years). All patients underwent intensive medical therapy, including ongoing hemodialysis (n = 16 patients), parathyroidectomy (n = 7 patients), and debridement of cutaneous lesions (n = 8 patients). Mean serum values in surgical and nonsurgical patients were significantly different for phosphorus, calcium-phosphorus product, and parathormone levels. Median survival was 9.4 months; 15 patients (93%) have died. The median survival time for parathyroidectomy versus nonparathyroidectomy was 14.8 and 6.3 months (P =.22), for skin debridement versus nondebridement was 14.1 and 6.1 months (P =.08), and for diabetic versus nondiabetic patients was 6.5 and 13.9 months (P =.11). CONCLUSIONS: Calciphylaxis has a female preponderance, with a dismal prognosis. A multidisciplinary approach that uses frequent hemodialysis to normalize calcium and phosphorus levels and local debridement of skin lesions seems prudent. Parathyroidectomy cannot be recommended routinely in all patients, unless severe hyperparathyroidism mandates intervention.
Adult↗
The impact of antidepressant use on social functioning: reboxetine versus fluoxetine.
Depression compromises affected individuals' functional well-being and impairs their level of social and workplace performance. Improved social functioning in depressed patients may improve their work productivity. This study evaluated the differential effects of two antidepressants on social functioning outcomes for patients with major depression comparing reboxetine, a non-tricyclic, selective noradrenaline reuptake inhibitor and fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor. A model using data from 284 depressed patients (138 reboxetine, 146 fluoxetine) in two 8-week clinical trials was developed to predict the percentage change over time in continuous outcome assessments as measured by a 21-item self-rating scale called the Social Adaptation Self-evaluation Scale (SASS). The percentage change from baseline SASS score was modelled as a function of both time-invariant and time-varying covariates. Results suggest that, by mid-study, the more severely ill subjects benefitted more from reboxetine treatment in terms of the outcome improvement rate and, by study-end, this effect also extended into the less severely ill population. In addition, a significant relationship was identified between the change in depression symptom severity as measured by the standard Hamilton Depression Rating Scale score and the change in social functioning per the SASS.
Adrenergic Uptake Inhibitors↗
Effects of transdermal nicotine treatment on structure and function of coronary artery bypass grafts.
Smoking is a major risk factor for failure of coronary artery bypass grafts (CABG). Experiments were designed to determine effects of transdermal nicotine, independent of smoking, on structure and function of CABG. Saphenous veins were placed as CABG in untreated dogs (control) or in dogs treated with transdermal nicotine (one 11-mg or two 22-mg patches/day) for 5 wk. Serum nicotine and plasma nitric oxide were measured. Grafts were removed and prepared for organ chamber studies and histology. Serum nicotine averaged 12.1 and 118.7 ng/ml in the 11 mg/day and 44 mg/day groups, respectively. Plasma nitric oxide was higher in dogs treated with 11 mg/day doses compared with controls. In organ chamber studies, endothelium-dependent relaxations to thrombin and A-23187 and endothelium-independent relaxations to nitric oxide were greatest in grafts from dogs treated with 11 mg/day doses. Intimal thickness of the grafts were similar among groups. However, staining for bone sialoprotein was increased in the media of grafts from the 11 mg/day treatment group. These data suggest that transdermal nicotine in doses comparable and double to those used for conventional smoking cessation treatment in humans does not adversely affect early patency of canine CABG up to 4 wk postoperatively. Transdermal nicotine, however, may increase production of and response to nitric oxide in bypass grafts.
Actins↗
Treatment of invasive thymoma with single-agent ifosfamide.
PURPOSE: To evaluate single-agent ifosfamide in the treatment of invasive thymoma. PATIENTS AND METHODS: Fifteen patients (eight male and seven female) with histologically confirmed invasive thymoma were treated. The median age was 48 years (range, 23 to 76 years). Four patients had stage III disease, seven patients had stage IVa disease, and four patients had stage IVb disease. The most common histologic type was lymphoepithelial. Seven patients had received prior treatment, including one patient who received chemotherapy. Ifosfamide 1.5 g/m(2) was given on days 1 to 5, with mesna as a uroprotector. RESULTS: Thirteen patients were assessable for response. Five complete responses (38.5%; 95% confidence interval [CI], 17.7% to 64.5%) and one partial response (7.7%; 95% CI, 1.4% to 33.3%) were seen. The median duration of complete response was 66+ months (range, 25 to 87 months), and the estimated survival rate 5 years after ifosfamide treatment was 57% (SE, 32% to 79%). The most frequent toxicities were nausea, vomiting, and leucopenia, but these were well tolerated. CONCLUSION: Single-agent ifosfamide possesses significant activity against invasive thymoma and is comparable to currently used combination regimens. The inclusion of ifosfamide in combination therapy, particularly in place of cyclophosphamide in regimens such as cisplatin, doxorubicin, and cyclophosphamide, needs to be evaluated.
Adult↗
Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience.
Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver. It is, though, a rare tumor and little is known regarding its natural history, clinicopathologic characteristics, or the outcomes of surgical therapy. We reviewed the experience of 61 patients with ICC seen by the surgical service at the Mayo Clinic over a 31-year period. Patient demographic and clinical data were recorded, as were survival statistics. Pathologic data were also obtained and patients stratified according to the TNM classification. Twenty-eight patients were resected for cure. Overall, 45 patients died of ICC. Of the patients resected for cure, survival at 3 years was 60%. No pathologic condition was found to be associated with the development of ICC. Overall survival correlated with stage of the tumor. Among patients resected for cure, stage did not correlate with survival. Prognosis for patients with ICC remains poor; resection, though, appears to prolong survival.
Adult↗
Use of parents, sibs, and unrelated controls for detection of associations between genetic markers and disease.
Detecting the association between genetic markers and complex diseases can be a critical first step toward identification of the genetic basis of disease. Misleading associations can be avoided by choosing as controls the parents of diseased cases, but the availability of parents often limits this design to early-onset disease. Alternatively, sib controls offer a valid design. A general multivariate score statistic is presented, to detect the association between a multiallelic genetic marker locus and affection status; this general approach is applicable to designs that use parents as controls, sibs as controls, or even unrelated controls whose genotypes do not fit Hardy-Weinberg proportions or that pool any combination of these different designs. The benefit of this multivariate score statistic is that it will tend to be the most powerful method when multiple marker alleles are associated with affection status. To plan these types of studies, we present methods to compute sample size and power, allowing for varying sibship sizes, ascertainment criteria, and genetic models of risk. The results indicate that sib controls have less power than parental controls and that the power of sib controls can be increased by increasing either the number of affected sibs per sibship or the number of unaffected control sibs. The sample-size results indicate that the use of sib controls to test for associations, by use of either a single-marker locus or a genomewide screen, will be feasible for markers that have a dominant effect and for common alleles having a recessive effect. The results presented will be useful for investigators planning studies using sibs as controls.
Female↗
Cost effectiveness of pramipexole in Parkinson's disease in the US.
OBJECTIVE: Pramipexole was recently approved in the US for treatment of the symptoms of idiopathic Parkinson's disease (PD). Although pramipexole has been found to be safe and efficacious when compared with placebo, little data are yet available on its cost effectiveness when compared with baseline treatment. The aim of this study was to estimate the costs and cost effectiveness (cost utility) of pramipexole compared with baseline treatment in patients with early and advanced PD. DESIGN AND SETTING: We developed a cost-effectiveness (CE) model in the US setting that linked Unified Parkinson's Disease Rating Scale (UPDRS) Part II (activities of daily life) and III (motor) scores to disease progression, costs and patient utility. Data for the model were obtained from clinical trials, a literature review and a survey of 193 patients' health resource use and utility. We used cost and quality-adjusted life-year (QALY) estimates from the model to estimate the incremental cost effectiveness of pramipexole relative to baseline treatment patterns. We performed separate analyses for patients with early and advanced PD. We also performed extensive sensitivity analyses by adding other dopamine agonists to the no-pramipexole treatment regimen and varying disease progression parameters. The study was conducted from the societal perspective, although data presentation allows interpretation of cost effectiveness from either the societal or payer perspective. MAIN OUTCOME MEASURES AND RESULTS: For patients with both early and advanced PD, treatment with pramipexole had higher costs but was more effective than baseline treatment. For patients with early onset of PD, the incremental total CE ratio for pramipexole was $US8837/QALY. For patients with advanced PD, the incremental CE ratio was $US12 294/QALY (1997 costs). These ratios were lower than the CE ratios of many widely used medical treatments. CONCLUSIONS: Subject to the inherent limitations of modelling chronic disease progression and subsequent healthcare costs and patient utility, the results suggested that pramipexole was a cost effective treatment for patients with early and advanced PD in the US.
Antiparkinson Agents↗
The impact on unemployment of an intervention to increase recognition of previously untreated anxiety among primary care physicians.
Anxiety is a common, though often unrecognized, problem in primary care settings. This study examines the effect on employment of an intervention designed to attune primary care physicians to previously unrecognized and untreated anxiety. Primary care physicians in a mixed-model health maintenance organization (HMO) were randomized by practice site to groups with (intervention) and without (usual care) intensive one-on-one education about anxiety and periodic feedback about their patients with anxiety. All persons 21-65 years of age presenting to the offices of these primary care providers were screened for anxiety with the SCL-90-R on two occasions. Those meeting the SCL-90-R cutpoints for anxiety and whose medical records provided no evidence of recognition or treatment for a mental health condition within the last 6 months were eligible for the study (n = 637). Of these, 573 (90%) completed two follow-up assessments. The present study evaluates the impact of the intervention aimed at the primary care physicians on the labor force participation rate of the persons with anxiety after 5 months of follow-up. The study also evaluates the impact of the intervention on hours of work and the presence of days spent in bed among the persons with anxiety working at the baseline interview and after 5 months. At baseline, the patients of intervention and usual care physicians with previously unrecognized and untreated anxiety did not differ in labor force participation rates. At the conclusion of the study, the patients of the intervention group physicians had significantly lower rates of labor force participation than those of the usual care group physicians. Among those working both at the beginning and conclusion of the study, the intervention had no impact on hours of work or the presence of days spent in bed. We conclude that attuning physicians may reduce labor force participation rates.
Absenteeism↗
Quality of life and pharmaco-economic aspects of obsessive-compulsive disorder. A South African survey.
OBJECTIVE: The quality of life and pharmaco-economic aspects of obsessive-compulsive disorder (OCD) have received relatively little research attention to date. We aimed to gather preliminary data on these in a South African patient sample. DESIGN: A survey of members of the Obsessive-Compulsive Disorder Association of South Africa was undertaken by means of a detailed self-report questionnaire. RESULTS: Results of the survey suggest that OCD causes significant morbidity, leading to clear distress and Interference with academic, occupational, social and family function. Unfortunately, correct diagnosis and appropriate treatment have been delayed in many patients, and the financial costs of such incorrect management are likely to be considerable. CONCLUSION: Much further work needs to be done by the medical profession and by interested consumers to raise awareness about OCD and to provide information about its management. In South Africa, it is particularly Important to undertake such psycho-education at a primary health care level and to impact on patients of low socio-economic status.
Activities of Daily Living↗