Showing papers by "Mayo Clinic published in 1997"
TL;DR: Single-molecule atomic force microscopy was used to investigate the mechanical properties of titin, the giant sarcomeric protein of striated muscle, and refolding of immunoglobulin domains was observed.
Abstract: Single-molecule atomic force microscopy (AFM) was used to investigate the mechanical properties of titin, the giant sarcomeric protein of striated muscle. Individual titin molecules were repeatedly stretched, and the applied force was recorded as a function of the elongation. At large extensions, the restoring force exhibited a sawtoothlike pattern, with a periodicity that varied between 25 and 28 nanometers. Measurements of recombinant titin immunoglobulin segments of two different lengths exhibited the same pattern and allowed attribution of the discontinuities to the unfolding of individual immunoglobulin domains. The forces required to unfold individual domains ranged from 150 to 300 piconewtons and depended on the pulling speed. Upon relaxation, refolding of immunoglobulin domains was observed.
2,959 citations
TL;DR: Symptoms of reflux are common among white men and women who are 25-74 years of age and heartburn and acid regurgitation are significantly associated with chest pain, dysphagia, dyspepsia, and globus sensation.
2,034 citations
TL;DR: It is argued that genetic and molecular biological data provide strong support for the veracity of the 'amyloid cascade hypothesis' for disease pathogenesis, and that this hypothesis offers a coherent framework for drug discovery.
1,474 citations
TL;DR: Concerns are raised that fenfluramine-phentermine therapy may be associated with valvular heart disease, which is arouse concern about serious potential adverse effects, including pulmonary hypertension and valvULAR heart disease.
Abstract: Background Fenfluramine and phentermine have been individually approved as anorectic agents by the Food and Drug Administration (FDA). When used in combination the drugs may be just as effective as either drug alone, with the added advantages of the need for lower doses of each agent and perhaps fewer side effects. Although the combination has not been approved by the FDA, in 1996 the total number of prescriptions in the United States for fenfluramine and phentermine exceeded 18 million. Methods We identified valvular heart disease in 24 women treated with fenfluramine–phentermine who had no history of cardiac disease. The women presented with cardiovascular symptoms or a heart murmur. As increasing numbers of these patients with similar clinical features were identified, there appeared to be an association between these features and fenfluramine–phentermine therapy. Results Twenty-four women (mean [±SD] age, 44±8 years) were evaluated 12.3±7.1 months after the initiation of fenfluramine–phentermine thera...
1,464 citations
TL;DR: Dual‐energy X‐ray absorptiometry measurements of femoral bone mineral density (BMD) from the third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) are used to estimate the overall scope of the disease in the older U.S. population and explore different approaches for defining low BMD in older men in that age range.
Abstract: Data on the number of U.S. women with low femoral bone mineral density (BMD) are currently available only from indirect estimates. We used dual-energy X-ray absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) to estimate prevalences of low femoral BMD in women ages 50 years and older using an approach proposed recently by an expert panel of the World Health Organization (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white (NHW) women aged 20-29 years from the NHANES III dataset. The prevalence of older U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5 SD below the mean of young NHW women) ranged from 34-50% in four different femur regions, which corresponds to approximately 12-17 million women. The prevalence with osteoporosis (BMD > 2.5 SD below the mean of young NHW women) ranged from 17-20%, or approximately 6-7 million women. Prevalences were 1.3-2.4 times higher in NHW women than non-Hispanic black women (NHB), and 0.8-1.2 times higher in NHW versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA women with osteopenia were 10-15 million, 800,000-1.2 million, and 300,000-400,000, respectively; corresponding figures for osteoporosis were 5-6 million, 200,000-300,000, and 100,000 respectively. Thus, the first data on BMD from a nationally representative sample of older women show a substantial number with low femoral BMD.(ABSTRACT TRUNCATED AT 250 WORDS)
1,396 citations
TL;DR: It is suggested that neuronal loss in association areas such as the superior temporal sulcus contributes directly to cognitive impairment in AD.
Abstract: To assess the relationship between dementia, neuronal loss, and neuropathological findings in Alzheimer's disease (AD), we counted the number of neurons, senile plaques, and neurofibrillary tangles in a high-order association cortex. We studied the superior temporal sulcus of 34 individuals with AD and 17 nondemented control subjects, using statistically unbiased, stereological counting techniques. The number of superior temporal sulcus neurons in nondemented control subjects was stable across the sixth to ninth decades. In AD, more than 50% of the neurons were lost. Both neuronal loss and neurofibrillary tangles increased in parallel with the duration and severity of illness, but the amount of neuronal loss exceeded by manyfold the amount of neurofibrillary tangles accumulated. In contrast to the correlation between neurofibrillary tangles and neuronal loss, the number of senile plaques and the percentage of the superior temporal sulcus that was covered by Abeta (amyloid burden) were not related to neuronal loss, number of neurofibrillary tangles, or duration of disease. Neither the amount nor the rate of neuronal loss in the superior temporal sulcus in AD correlated with apolipoprotein E genotype. These data suggest that neuronal loss in association areas such as the superior temporal sulcus contributes directly to cognitive impairment in AD.
1,382 citations
TL;DR: Although the majority of U.S. health care expenditures for the treatment of osteoporotic fractures were for white women, one‐fourth of the total was borne by other population subgroups.
Abstract: Osteoporotic fractures are a significant public health problem, resulting in substantial morbidity and mortality. Previous estimates of the economic burden of osteoporosis, however, have not fully accounted for the costs associated with treatment of nonhip fractures, minority populations, or men. Accordingly, the 1995 total direct medical expenditures for the treatment of osteoporotic fractures were estimated for all persons aged 45 years or older in the United States by age group, sex, race, type of fracture, and site of service (inpatient hospital, nursing home, and outpatient). Osteoporosis attribution probabilities were used to estimate the proportion of health service utilization and expenditures for fractures that resulted from osteoporosis. Health care expenditures attributable to osteoporotic fractures in 1995 were estimated at $13.8 billion, of which $10.3 billion (75.1%) was for the treatment of white women, $2.5 billion (18.4%) for white men, $0.7 billion (5.3%) for nonwhite women, and $0.2 billion (1.3%) for nonwhite men. Although the majority of U.S. health care expenditures for the treatment of osteoporotic fractures were for white women, one-fourth of the total was borne by other population subgroups. By site-of-service, $8.6 billion (62.4%) was spent for inpatient care, $3.9 billion (28.2%) for nursing home care, and $1.3 billion (9.4%) for outpatient services. Importantly, fractures at skeletal sites other than the hip accounted for 36.9% of the total attributed health care expenditures nationally. The contribution of nonhip fractures to the substantial morbidity and expenditures associated with osteoporosis has been underestimated by previous researchers.
1,321 citations
TL;DR: A simplified approach to understanding the process of diastolic filling of the left ventricle and interpreting the Doppler flow velocity curves as they relate to this process is presented.
1,264 citations
TL;DR: A double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation, which excluded smokers with current depression, but not those with a history of major depression.
Abstract: Background and Methods Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or “target quit date”) was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less. Results At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg gro...
1,163 citations
TL;DR: Age- and gender-adjusted, normalized MRI-based hippocampal volumetric measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process.
Abstract: Magnetic resonance imaging (MRI)-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly control subjects and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly control subjects and AD patients with the very mildest form of the disease. We performed MRI-based volumetric measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly control subjects and 94 patients with probable AD. The diagnosis of AD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR 0.5 were classified as very mild, CDR 1 as mild, and CDR 2 as moderate disease severity. Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women. The volume of each measured MTL structure also declined with age in patients with AD. The volume of each MTL structure was significantly smaller in AD patients than control subjects (p < 0.001). Of the several MTL measures, the total hippocampal volumetric measurements were best at discriminating control subjects from AD patients. The mean hippocampal volumes for AD patients relative to control subjects by severity of disease were as follows: very mild AD (CDR 0.5) -1.75 SD below the control mean, mild AD (CDR 1) -1.99 SD, and moderate AD (CDR 2) -2.22 SD. Age- and gender-adjusted, normalized MRI-based hippocampal volumetric measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process.
1,056 citations
TL;DR: A role for mTOR in translational control is defined and further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells are offered.
Abstract: The immunosuppressant rapamycin interferes with G1-phase progression in lymphoid and other cell types by inhibiting the function of the mammalian target of rapamycin (mTOR). mTOR was determined to be a terminal kinase in a signaling pathway that couples mitogenic stimulation to the phosphorylation of the eukaryotic initiation factor (eIF)-4E-binding protein, PHAS-I. The rapamycin-sensitive protein kinase activity of mTOR was required for phosphorylation of PHAS-I in insulin-stimulated human embryonic kidney cells. mTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells.
TL;DR: The frequency and clinical significance of incidentally discovered, nonpalpable thyroid nodules are reviewed and a practical approach to their treatment is offered and the recommendations for treating thyroid incidentalomas are offered.
Abstract: Background: The introduction of highly sensitive imaging techniques has made it possible to detect many nonpalpable nodules, or “incidentalomas,” in the thyroid. Discovery of these lesions raises c...
TL;DR: The aim of this study was to assess the frequency of pancreatic cancer and other tumors in patients with hereditary form of pancreatitis and to determine the natural history of hereditary pancreatitis.
Abstract: BACKGROUND Hereditary pancreatitis is an autosomal-dominant disease, with a variable expression and an estimated penetrance of 80%. The gene for this disease has recently been mapped to chromosome 7q35, and the defect is believed to be caused by a mutation in the cationic trypsinogen gene. Acute attacks of abdominal pain begin early in life and the disease often progresses to chronic pancreatitis. Although the risk of pancreatic cancer is thought to be increased in more common types of chronic pancreatitis, the frequency of pancreatic cancer in the inherited type of pancreatitis is uncertain. PURPOSE The aim of this study was to assess the frequency of pancreatic cancer and other tumors in patients with hereditary form of pancreatitis. METHODS To determine the natural history of hereditary pancreatitis, we invited all members of the American Pancreatic Association and the International Association of Pancreatology to participate in a longitudinal study of this rare form of pancreatitis. The initial criteria for patient eligibility were as follows: early age (< or = 30 years) at onset of symptoms, positive family history, and absence of other causes. From April 1995 through February 1996, 37 physicians from 10 countries contributed medical records of 246 (125 males and 121 females) patients thought to have hereditary pancreatitis as the most likely diagnosis. This group included 218 patients where the diagnosis appeared to be highly probable and 28 additional patients where the diagnosis of hereditary pancreatitis was less certain: 25 patients who had relatively late onset of disease and a positive family history and three patients with onset of disease before age 30 years but with an uncertain family history. We reviewed all causes of death and compared the observed to the expected frequency of cancer in this historical cohort of patients with hereditary pancreatitis. The strength of the association between pancreatitis and pancreatic cancer was estimated by the standardized incidence ratio (SIR), which is the ratio of observed pancreatic cancer cases in the cohort to the expected pancreatic cancers in the background population, adjusted for age, sex, and country. RESULTS The mean age (+/- standard deviation [SD]) at onset of symptoms of pancreatitis was 13.9 +/- 12.2 years. Compared with an expected number of 0.150, eight pancreatic adenocarcinomas developed (mean age +/- SD at diagnosis of pancreatic cancer: 56.9 +/- 11.2 years) during 8531 person-years of follow-up, yielding an SIR of 53 (95% confidence interval [CI] = 23-105). The frequency of other tumors was not increased: SIR = 0.7 (95% CI = 0.3-1.6). Eight of 20 reported deaths in the cohort were from pancreatic cancer. Thirty members of the cohort have already been tested for the defective hereditary pancreatitis gene: all 30 carry a mutated copy of the trypsinogen gene. The transmission pattern of hereditary pancreatitis was known for 168 of 238 patients without pancreatic cancer and six of eight with pancreatic cancer. Ninety-nine of the 238 patients without pancreatic cancer and six of the patients with pancreatic cancer inherited the disease through the paternal side of the family. The estimated cumulative risk of pancreatic cancer to age 70 years in patients with hereditary pancreatitis approaches 40%. For patients with a paternal inheritance pattern, the cumulative risk of pancreatic cancer is approximately 75%. CONCLUSIONS Patients with hereditary pancreatitis have a high risk of pancreatic cancer several decades after the initial onset of pancreatitis. A paternal inheritance pattern increases the probability of developing pancreatic cancer.
TL;DR: Using radioligand binding assays, the equilibrium dissociation constants (KD's) for 37 antidepressants, three of their metabolites, some mood stabilizers, and assorted other compounds for the human serotonin, norepinephrine, and dopamine transporters are determined to help predict some possible adverse effects and drug-drug interactions of antidepressants and related compounds.
TL;DR: Microalbuminuria is a strong predictor of total and cardiovascular mortality and cardiovascular morbidity in patients with NIDDM and to quantify the risk.
Abstract: Objectives: To critically analyze the literature linking microalbuminuria with total and cardiovascular mortality and cardiovascular morbidity in non—insulin— dependent diabetes mellitus (NIDDM) and to quantify the risk. Methods: A combination of retrieval techniques (MEDLINE, SCISEARCH, and handsearching published bibliographies) was used to find all relevant articles based on title and abstract and "Methods" sections. Unpublished data on albumin excretion rate were sought from large NIDDM cohort studies. Results: A total of 264 citations were retrieved, of which 11 cohort studies were selected for inclusion in the overview, representing a total of 2138 patients followed up for a mean of 6.4 years. Patient age was similar across cohorts. Duration of NIDDM ranged from newly diagnosed to 13 years. The prevalence of microalbuminuria ranged from 20% to 36% in the 8 cohorts that excluded patients with clinical proteinuria. All studies reported either a trend or a significant association between microalbuminuria and total mortality or cardiovascular morbidity or mortality; the overall odds ratio for death was 2.4 (95% confidence interval, 1.8-3.1) and for cardiovascular morbidity or mortality, 2.0 (95% confidence interval, 1.4-2.7). We found no evidence of reporting bias. Conclusion: Microalbuminuria is a strong predictor of total and cardiovascular mortality and cardiovascular morbidity in patients with NIDDM. Arch Intern Med. 1997;157:1413-1418
TL;DR: Evaluated the cognitive profiles of patients with mild cognitive impairment at the time of their initial diagnosis in an attempt to predict who would remain stable and who would evolve to AD, and results indicate that diagnostic criteria can be defined for patients who are likely to convert to AD.
Abstract: In recent years, patients who are at high risk for developing Alzheimer's disease (AD) have become a focus of study. Several research groups have identified these patients, developed diagnostic criteria, and followed the patients longitudinally. These patients therefore constitute a clinical entity that is suitable for therapeutic interventions. In this article, we report our 5-year experience at the Mayo Clinic in characterizing a group of patients with mild cognitive impairment. These subjects were recruited from community-dwelling individuals who were receiving general medical care in the Department of Internal Medicine. They received the diagnosis of mild cognitive impairment if they met the following criteria: (a) complaint of defective memory, (b) normal activities of daily living, (c) normal general cognitive function, (d) abnormal memory function for age, and (e) absence of dementia. In following more than 75 of these patients, some of whom have been studied for as long as 5 years, it appears that approximately 10% to 15% of the subjects evolve to AD each year. We therefore evaluated the cognitive profiles of these patients at the time of their initial diagnosis in an attempt to predict who would remain stable and who would evolve to AD. Certain features of learning and memory performance indicated patients who were more likely to progress, but the strongest predictor was their apolipoprotein E status. The patients who possessed an epsilon 4 allele were more likely to convert to AD at a more rapid rate then those who were not carriers. Our results and similar data from other study groups indicate that diagnostic criteria can be defined for patients who are likely to convert to AD; the natural history of these patients is becoming apparent, and variables that predict ultimate conversion can be defined. Consequently, patients with mild cognitive impairment constitute an important group for study, particularly form the aspect of therapeutic interventions.
TL;DR: The present study demonstrates that prolonged exposure to high glucose increases eNOS gene expression, protein expression, and NO release, however, upregulation of eNos andNO release is associated with a marked concomitant increase of O2- production.
Abstract: Background Hyperglycemia is a primary cause of premature vascular disease. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxations is likely to be involved. Little is known about the molecular mechanisms of hyperglycemia-induced endothelial dysfunction. Methods and Results This study was designed to determine the effect of hyperglycemia on the l-arginine/nitric oxide (NO) pathway. Expression of endothelial nitric oxide synthase (eNOS) mRNA and production of NO were studied in human aortic endothelial cells exposed to control levels (5.5 mmol/L) and high levels (22.2 mmol/L) of glucose for 5 days. We examined the effect of glucose on NO release by measuring changes in nitrite (NO2−) levels by Griess reaction. Superoxide anion (O2−) production was also examined by the ferrocytochrome c assay. NOS mRNA and protein expression, which were evaluated by reverse transcription–polymerase chain reaction and Western blotting, were approximately twofold greater in endothelial cells ...
University of Tennessee Health Science Center1, University of Louisville2, Pennsylvania State University3, Houston Methodist Hospital4, University of Kentucky5, Erie County Medical Center6, University of Arkansas at Little Rock7, University of Cincinnati8, University of California, Davis9, Ohio State University10, Harvard University11, St. John's Hospital12, University of California, San Diego13, Vanderbilt University14, MedStar Washington Hospital Center15, University Medical Center16, University of South Carolina17, Allegheny General Hospital18, Baylor College of Medicine19, University of Southern California20, Wright State University21, University of Western Ontario22, University of Alberta23, Gundersen Health System24, Medical College of Wisconsin25, Dartmouth College26, Boston University27, Sparrow Health System28, State University of New York Upstate Medical University29, Saint Louis University30, University of Missouri31, University of Texas Medical Branch32, University of North Carolina at Chapel Hill33, Mayo Clinic34, Carolinas Medical Center35, Cedars-Sinai Medical Center36, Rutgers University37, Henry Ford Health System38, University of Manitoba39, University of Texas Southwestern Medical Center40, University of California, San Francisco41, University of South Alabama42, University of Tennessee43
TL;DR: Although newer diagnostic techniques are being applied, at this time aortography remains the diagnostic standard; bypass techniques, which provide distal aortic perfusion, produced significantly lower paraplegia rates than the clamp and sew approach.
Abstract: Background: Blunt aortic injury is a major cause of death from blunt trauma. Evolution of diagnostic techniques and methods of operative repair have altered the management and posed new questions in recent years. Methods: This study was a prospectively conducted multicenter trial involving 50 trauma centers in North America under the direction of the Multi-institutional Trial Committee of the American Association for the Surgery of Trauma. Results: There were 274 blunt aortic injury cases studied over 2.5 years, of which 81% were caused by automobile crashes. Chest computed tomography and transesophageal echocardiography were applied in 88 and 30 cases, respectively, and were 75 and 80% diagnostic, respectively. Two hundred seven stable patients underwent planned thoracotomy and repair. Clamp and sew technique was used in 73 (35%) and bypass techniques in 134 (65%). Overall mortality was 31%, with 63% of deaths being attributable to aortic rupture; mortality was not affected by method of repair. Paraplegia occurred postoperatively in 8.7%. Logistic regression analysis demonstrated clamp and sew (p = 0.002) and aortic cross clamp time of 30 minutes (p = 0.01) to be associated with development of postoperative paraplegia. Conclusions: Rupture after hospital admission remains a major problem. Although newer diagnostic techniques are being applied, at this time aortography remains the diagnostic standard. Aortic cross clamp time beyond 30 minutes was associated with paraplegia; bypass techniques, which provide distal aortic perfusion, produced significantly lower paraplegia rates than the clamp and sew approach.
TL;DR: People with AODM exhibited significantly increased risk of all dementia, and risk of Alzheimer's disease was also elevated, highlighting the importance of AodM prevention and prompt additional investigation of the relation between AODm and dementia.
Abstract: It is unclear whether persons with diabetes are at increased risk for dementia, including Alzheimer's disease. Existing studies are limited by small sample size, selection bias, and case-control designs. This population-based historical cohort study provides estimates of the risk of dementia and Alzheimer's disease associated with adult onset diabetes mellitus (AODM). The sample included all persons with AODM residing in Rochester, Minnesota, on January 1, 1970, plus all persons diagnosed in Rochester or who moved to Rochester with the diagnosis between January 1, 1970, and December 31, 1984. Individuals were followed through review of their complete medical records from AODM diagnosis until dementia onset, emigration, death, or January 1, 1985. Standardized morbidity ratios for dementia and Alzheimer's disease were calculated, using an expected incidence based on age- and sex-specific rates for the Rochester population. Poisson regression was used to estimate risks for persons with AODM relative to those without. Of the 1,455 cases of AODM followed for 9,981 person-years, 101 developed dementia, including 77 who met criteria for Alzheimer's disease. Persons with AODM exhibited significantly increased risk of all dementia (Poisson regression relative risk (RR) = 1.66, 95% confidence interval (Cl) 1.34-2.05). Risk of Alzheimer's disease was also elevated (for men, RR = 2.27, 95% Cl 1.55-3.31; for women, RR = 1.37, 95% Cl 0.94-2.01). These findings emphasize the importance of AODM prevention and prompt additional investigation of the relation between AODM and dementia.
TL;DR: The electrodiagnosis of carpal tunnel syndrome is reviewed, including discussions of old and new techniques of motor and sensory nerve conduction, anomalous innervation, and needle electrode examination.
Abstract: The electrodiagnosis of carpal tunnel syndrome is reviewed, including discussions of old and new techniques of motor and sensory nerve conduction, anomalous innervation, needle electrode examination, and one method of examining a patient with suspected carpal tunnel syndrome. The results of electromyographic testing of 505 patients with carpal tunnel syndrome in Rochester, Minnesota, from 1961 to 1980 are compared with results from previous studies. In the appendixes, a method of performing median motor and sensory nerve conduction studies and Mayo Clinic normal values are provided.
TL;DR: Three clinical and 3 radiographic characteristics predicted the malignancy in radiologically indeterminate solitary pulmonary nodules (SPNs) in a clinically relevant subset of patients with SPNs that measured between 4 and 30 mm in diameter.
Abstract: Background: A clinical prediction model to identify malignant nodules based on clinical data and radiological characteristics of lung nodules was derived using logistic regression from a random sample of patients (n=419) and tested on data from a separate group of patients (n=210). Objective: To use multivariate logistic regression to estimate the probability of malignancy in radiologically indeterminate solitary pulmonary nodules (SPNs) in a clinically relevant subset of patients with SPNs that measured between 4 and 30 mm in diameter. Patients and Methods: A retrospective cohort study at a multispecialty group practice included 629 patients (320 men, 309 women) with newly discovered (between January 1, 1984, and May 1, 1986) 4- to 30-mm radiologically indeterminate SPNs on chest radiography. Patients with a diagnosis of cancer within 5 years prior to the discovery of the nodule were excluded. Clinical data included age, sex, cigarette-smoking status, and history of extrathoracic malignant neoplasm, asbestos exposure, and chronic interstitial or obstructive lung disease; chest radiological data included the diameter, location, edge characteristics (eg, lobulation, spiculation, and shagginess), and other characteristics (eg, cavitation) of the SPNs. Predictors were identified in a random sample of two thirds of the patients and tested in the remaining one third. Results: Sixty-five percent of the nodules were benign, 23% were malignant, and 12% were indeterminate. Three clinical characteristics (age, cigarette-smoking status, and history of cancer [diagnosis, ≥5 years ago]) and 3 radiological characteristics (diameter, spiculation, and upper lobe location of the SPNs) were independent predictors of malignancy. The area (±SE) under the evaluated receiver operating characteristic curve was 0.8328±0.0226. Conclusion: Three clinical and 3 radiographic characteristics predicted the malignancy in radiologically indeterminate SPNs. Arch Intern Med. 1997;157:849-855
Rutgers University1, National Institutes of Health2, University of Minnesota3, Mayo Clinic4, Washington University in St. Louis5, Yeshiva University6, Rush University Medical Center7, University of Chicago8, SRI International9, University of Pittsburgh10, University of Tennessee Health Science Center11
TL;DR: In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure, and among patients with prior MI, an 80% risk reduction was observed.
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.
TL;DR: Therapy with melphalan and prednisone results in objective responses and prolonged survival as compared with colchicine in patients with primary amyloidosis.
Abstract: Background Primary systemic amyloidosis is an uncommon disease characterized by the accumulation in vital organs of a fibrillar protein consisting of monoclonal light chains. Methods We treated 220 patients with biopsy-proved amyloidosis. The patients were randomly assigned to receive colchicine (72 patients), melphalan and prednisone (77), or melphalan, prednisone, and colchicine (71). They were stratified according to their chief clinical manifestations: renal disease (105 patients), cardiac involvement (46), peripheral neuropathy (19), or other (50). Results The median duration of survival after randomization was 8.5 months in the colchicine group, 18 months in the group assigned to melphalan and prednisone, and 17 months in the group assigned to melphalan, prednisone, and colchicine (P Conclusions Therapy with melphalan and prednisone results in objective responses and prolonged survival as compared with colchicine in patients with primary amyloidosis.
TL;DR: Fungal infections, caused by both yeasts and mycelial fungi, are associated with the highest mortality rates, and mycobacterial, pneumocystis, and parasitic diseases may also occur.
Abstract: Solid-organ transplantation is a therapeutic option for many human diseases. Infections are a major complication of solid-organ transplantation. All candidates should undergo a thorough infectious-disease screening prior to transplantation. There are three time frames, influenced by surgical factors, the level of immunosuppression, and environmental exposures, during which infections of specific types most frequently occur posttransplantation. Most infections during the first month are related to surgical complications. Opportunistic infections typically occur from the second to the sixth month. During the late posttransplant period (beyond 6 months), transplantation recipients suffer from the same infections seen in the general community. Opportunistic bacterial infections seen in transplant recipients include those caused by Legionella spp., Nocardia spp., Salmonella spp., and Listeria monocytogenes. Cytomegalovirus is the most common cause of viral infections. Herpes simplex virus, varicella-zoster virus, Epstein-Barr virus and others are also significant pathogens. Fungal infections, caused by both yeasts and mycelial fungi, are associated with the highest mortality rates. Mycobacterial, pneumocystis, and parasitic diseases may also occur.
TL;DR: Lower urinary tract symptoms, depressed peak urinary flow rates, enlarged prostates and older age are associated with an increased risk of acute urinary retention in community dwelling men.
TL;DR: The two classes of caspases, the reasons why humans may have so many caspase genes, the growing list of cispase substrates, and viral and pharmacological casp enzyme inhibitors are discussed.
TL;DR: Brain invasion and an increased mitotic index are the most powerful histologic factors prognostic for recurrence in meningiomas and an objective definition for atypicalMeningioma is proposed based on data.
Abstract: Histologic grading of meningiomas has prognostic and sometimes therapeutic implications, but diagnostic criteria for atypical meningioma are vague, and the significance of brain invasion in the determination of malignancy remains controversial. We reviewed our experience with 581 patients whose meningiomas were resected at Mayo Clinic during the years 1978 through 1988. All patients were followed until death or a median of 9.0 years. Ten histologic parameters were assessed and compared with recurrence-free survival. On univariate analysis, six variables were associated with recurrence, although most were statistically significant only in the subset of patients having undergone gross total tumor resection. On multivariate analyses, the most significant parameters were histologic brain invasion (when assessable) and maximal mitotic rate of at least four per 10 high-power fields (HPF). Also significant were combinations of at least three of the following four parameters: hypercellularity, architectural sheeting, macronucleoli, and small cell formation. Proposed grading criteria based on these findings yielded 81% classic, 15% atypical, and 4% brain invasive meningiomas with respective 5-year recurrence rates of 12%, 41%, and 56%. There was no association between histologic grade and either extent of surgical resection or patient age. However, male sex was associated with high-grade (atypical/brain invasive) tumors. Too few frankly anaplastic meningiomas were encountered for statistical analysis. Brain invasion and an increased mitotic index (at least four per 10 HPF) are the most powerful histologic factors prognostic for recurrence in meningiomas. We propose an objective definition for atypical meningioma based on our data. Because the difference in recurrence rates for brain invasive and atypical meningiomas was not statistically significant, it could not be determined whether brain invasion alone warrants a designation of malignancy. Likewise, we were unable to determine what constitutes histologic anaplasia due to the rarity of such cases.
Journal Article•
TL;DR: Data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas, and it is interesting that all three mutations occur in exon 17 of the PTCH gene.
Abstract: Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin's syndrome, is an autosomal dominant disorder that predisposes to developmental defects and various forms of cancer. PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome. Another NBCCS-associated cancer is medulloblastoma, a common central nervous system tumor in children. Most medulloblastomas, however, occur without indication of an inherited predisposition. We have examined 24 sporadic medulloblastomas for loss of heterozygosity (LOH) at loci flanking as well as within PTCH. In cases with LOH, single-strand conformational polymorphism and sequencing analysis were performed to determine the status of the remaining PTCH allele. Microsatellite analysis indicated LOH of PTCH in 5 of 24 tumors, and in three of these cases a mutation of the remaining allele was identified. Two of the mutations were duplication insertions, and the third consisted of a single base deletion. It is interesting that all three mutations occur in exon 17 of the PTCH gene. These data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas.
TL;DR: In this paper, the authors rephotographed the central corneal endothelium of 52 normal subjects with the same contact specular microscope and found that the mean endothelial cell density decreased during the 10.6-year interval from 2715 +/- 301 cells/mm2 to 2539 +/- 284 cells/m2 (P < 0.001).
TL;DR: A decline in the synthesis rate of myosin heavy chain implies a decreased ability to remodel this important muscle contractile protein and likely contributes to the declining muscle mass and contractile function in the elderly.
Abstract: A decline in muscle mass and contractile function are prominent features of the sarcopenia of old age. Because myosin heavy chain is an important contractile protein, it was hypothesized that synth...