Showing papers by "Mayo Clinic published in 1995"
TL;DR: The results indicate that displacement patterns corresponding to cyclic displacements smaller than 200 nanometers can be measured and suggest the feasibility of a medical imaging technique for delineating elasticity and other mechanical properties of tissue.
Abstract: A nuclear magnetic resonance imaging (MRI) method is presented for quantitatively mapping the physical response of a material to harmonic mechanical excitation. The resulting images allow calculation of regional mechanical properties. Measurements of shear modulus obtained with the MRI technique in gel materials correlate with independent measurements of static shear modulus. The results indicate that displacement patterns corresponding to cyclic displacements smaller than 200 nanometers can be measured. The findings suggest the feasibility of a medical imaging technique for delineating elasticity and other mechanical properties of tissue.
2,015 citations
Journal Article•
TL;DR: (ICT+IRT)/ET is a conceptually new, simple and reproducible Doppler index of combined systolic and diastolic myocardial performance in patients with primarymyocardial systols dysfunction and was easily measured, reproducible, and had a narrow range in normals.
1,565 citations
TL;DR: This histopathologic study confirms an intimate relation between whole heart, coronary artery, and segmental coronary atherosclerotic plaque area and EBCT coronary calcium area but suggests that there is a threshold value for plaque area below which coronary calcium is either absent or not detectable by this methodology.
Abstract: Background Coronary calcium identified by electron-beam computed tomography (EBCT) correlates poorly with luminal atherosclerotic narrowing, but calcium, an intimate part of coronary plaque, may be more directly related to atheromatous plaque area. Methods and Results Thirty-eight coronary arteries from 13 autopsy hearts were dissected, straightened, and scanned with EBCT in 3-mm contiguous increments. Coronary calcium area was defined as one or more pixels with a density >130 Hounsfield units (0.18 mm 2 /pixel). Each artery was divided into corresponding 3-mm segments, representative histological sections were stained, and atherosclerotic plaque area per segment (mm 2 ) was quantified. Coronary artery calcium and coronary artery plaque areas were correlated for the hearts as a whole, for individual coronary arteries, and for individual coronary artery segments. The sums of histological plaque areas versus the sums of calcium areas were highly correlated for each heart and for each coronary artery. However, coronary plaque area was on the order of five times greater than calcium area. Furthermore, minimal diffuse segmental coronary plaque could be present despite the absence of coronary calcium detectable by EBCT. Conclusions This histopathologic study confirms an intimate relation between whole heart, coronary artery, and segmental coronary atherosclerotic plaque area and EBCT coronary calcium area but suggests that there is a threshold value for plaque area below which coronary calcium is either absent or not detectable by this methodology.
1,435 citations
TL;DR: The incidence of hip fracture, and, presumably, other osteoporotic fractures will increase four-fold worldwide during the next 50 years and the attendant costs will threaten the viability of the healthcare systems of many countries.
1,345 citations
Journal Article•
1,125 citations
TL;DR: A revised taxonomic system for disorders previously called reflex sympathetic dystrophy (RSD) and causalgia is presented and these revised categories have been included in the 2nd edition of the IASP Classification of Chronic Pain Syndromes.
Abstract: We present a revised taxonomic system for disorders previously called reflex sympathetic dystrophy (RSD) and causalgia. The system resulted from a special consensus conference that was convened on this topic and is based upon the patient's history, presenting symptoms, and findings at the time of diagnosis. The disorders are grouped under the umbrella term CRPS: complex regional pain syndrome. This overall term, CRPS, requires the presence of regional pain and sensory changes following a noxious event. Further, the pain is associated with findings such as abnormal skin color, temperature change, abnormal sudomotor activity, or edema. The combination of these findings exceeds their expected magnitude in response to known physical damage during and following the inciting event. Two types of CRPS have been recognized: type I, corresponds to RSD and occurs without a definable nerve lesion, and type II, formerly called causalgia refers to cases where a definable nerve lesion is present. The term sympathetically maintained pain (SMP) was also evaluated and considered to be a variable phenomenon associated with a variety of disorders, including CRPS types I and II. These revised categories have been included in the 2nd edition of the IASP Classification of Chronic Pain Syndromes.
1,025 citations
TL;DR: For the reporting practice of pathologists, it is recommended that the pathologist routinely sign out biopsy samples with features of chronic hepatitis by indicating etiology, grade, and stage, which eliminates ambiguous terminology and avoids the risk of inappropriate treatment.
Abstract: The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and chronic lobular hepatitis (CLH) have become obsolete, and their use without further specifications should be discontinued. This recommendation has become necessary because these names have changed from descriptive term
998 citations
TL;DR: Functional studies are in progress both in vitro using cDNAs and cell lines and in vivo utilizing mutant mice in which a particular mucin gene has been inactivated or overexpressed to help determine whether the functions of mucins are restricted to protection and lubrication, or if they are involved in the adhesion of tumor cells to other cells or tissue components or in modulation of the immune system.
Abstract: The last seven years have been exciting in the world of mucin biology. Molecular analyses of mucin genes and deduced protein structures have provided insight into structural features of mucins and tools with which to examine expression, secretion, and glycosylation, thereby enabling a better understanding of the role of mucins in normal physiological processes and in disease. Functional studies are in progress both in vitro using cDNAs and cell lines and in vivo utilizing mutant mice in which a particular mucin gene has been inactivated or overexpressed. These studies should help determine whether the functions of mucins are restricted to protection and lubrication, or if they are involved in the adhesion of tumor cells to other cells or tissue components or in modulation of the immune system.
970 citations
TL;DR: The data suggest that actigraphy, despite its limitations, may be a useful, cost-effective method for assessing specific sleep disorders, such as insomnia and schedule disorders, and for monitoring their treatment process.
Abstract: This paper, which has been reviewed and approved by the Board of Directors of the American Sleep Disorders Association, provides the background for the Standards of Practice Committee's parameters for the practice of sleep medicine in North America The growing use of activity-based monitoring (actigraphy) in sleep medicine and sleep research has enriched and challenged traditional sleep-monitoring techniques This review summarizes the empirical data on the validity of actigraphy in assessing sleep-wake patterns and assessing clinical and control groups ranging in age from infancy to elderly An overview of sleep-related actigraphic studies is also included Actigraphy provides useful measures of sleep-wake schedule and sleep quality The data also suggest that actigraphy, despite its limitations, may be a useful, cost-effective method for assessing specific sleep disorders, such as insomnia and schedule disorders, and for monitoring their treatment process Methodological issues such as the proper use of actigraphy and possible artifacts have not been systematically addressed in clinical research and practice
917 citations
TL;DR: It is shown that this ER degradation is sensitive to inhibitors of the cytosolic proteasome, including lactacystin and certain peptide aldehydes, which completely blocks the ATP-dependent conversion of the wild-type precursor to the native folded form that enables escape from degradation.
891 citations
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TL;DR: Treatment of osteoporosis in men consists both of nonpharmacological (lifestyle factors, calcium and vitamin D supplementation) and pharmacological approaches, with efficacy similar to that seen in women.
Abstract: With the aging of the population, there is a growing recognition that osteoporosis and fractures in men are a significant public health problem, and both hip and vertebral fractures are associated with increased morbidity and mortality in men. Osteoporosis in men is a heterogeneous clinical entity: whereas most men experience bone loss with aging, some men develop osteoporosis at a relatively young age, often for unexplained reasons (idiopathic osteoporosis). Declining sex steroid levels and other hormonal changes likely contribute to age-related bone loss, as do impairments in osteoblast number and/or activity. Secondary causes of osteoporosis also play a significant role in pathogenesis. Although there is ongoing controversy regarding whether osteoporosis in men should be diagnosed based on female- or male-specific reference ranges (because some evidence indicates that the risk of fracture is similar in women and men for a given level of bone mineral density), a diagnosis of osteoporosis in men is generally made based on male-specific reference ranges. Treatment consists both of nonpharmacological (lifestyle factors, calcium and vitamin D supplementation) and pharmacological (most commonly bisphosphonates or PTH) approaches, with efficacy similar to that seen in women. Increasing awareness of osteoporosis in men among physicians and the lay public is critical for the prevention of fractures in our aging male population.
TL;DR: This is a mature study with all patients able to be followed for more than 5 years, and the evidence for therapeutic benefit was strong, but it was possible that the authors were only prolonging the interval to cancer recurrence and death rather than actually improving cure rates.
Abstract: Objective: To determine the effectiveness of two adjuvant therapy regimens in improving surgical cure rates in stage III (Dukes stage C) colon cancer. Design: Randomized, concurrently controlled cl...
TL;DR: The results strongly suggest that the FKBP12-rapamycin complex interacts with homologous ligands in yeast and mammalian cells and that the loss of mTOR function is directly related to the inhibitory effect of rapamycin on G1- to S-phase progression in T-lymphocytes and other sensitive cell types.
TL;DR: Patients with mild cognitive impairment can be clinically defined, many members of this group progress to Alzheimer's disease, and APOE epsilon 4 allele status appears to be a strong predictor of clinical progression.
Abstract: Objective. —The outcome of patients with mild cognitive impairment is not known, yet these patients present a difficult dilemma for the clinician. This study was designed to characterize the outcome of a group of patients with mild cognitive impairment and to determine whether the presence of the e4 allele on the apolipoprotein E gene (APOE) is a predictor of that outcome. Design. —A prospective, longitudinal inception cohort. Setting. —General community clinic. Participants. —A consecutive sample of 66 patients who met criteria for a diagnosis of a mild cognitive impairment and who had at least one clinical reevaluation was identified from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry. Interventions. —We evaluated patients initially and at 12- to 18-month intervals up to 54 months using standard neurological and neuropsychological measures such as the Mini-Mental State Examination, the Dementia Rating Scale, the Wechsler Adult Intelligence Scale—Revised, the Wechsler Memory Scale—Revised, and the Free and Cued Selective Reminding Test. TheAPOEstatus of study patients was determined. Main Outcome Measure. —The development of dementia as determined by theDiagnostic and Statistical Manual of Mental Disorders, Revised Third Editionand the National Institute of Neurological and Communicative Disorders and Stroke/ Alzheimer's Disease and Related Disorders Association criteria. Results. —Sixty-six individuals had been reevaluated once (mean of 18 months), 36 individuals twice (mean of 36 months), and 22 individuals on three occasions (mean of 54 months), with conversion rates to dementia at these intervals of 24%, 44%, and 55%, respectively. A multivariate Cox regression model demonstrated that possession of anAPOEe4 allele was the strongest predictor of clinical outcome. Conclusions. —These data suggest the following: (1) patients with mild cognitive impairment can be clinically defined, (2) many members of this group progress to Alzheimer's disease, and (3)APOEe4 allele status appears to be a strong predictor of clinical progression. (JAMA. 1995;273:1274-1278)
TL;DR: Valve repair significantly improves postoperative outcome in patients with mitral regurgitation and should be the preferred mode of surgical correction.
Abstract: Background Mitral valve repair has been suggested as providing a better postoperative outcome than valve replacement for mitral regurgitation, but this impression has been obscured by differences in baseline characteristics and has not been confirmed in multivariate analyses. Methods and Results The outcomes in 195 patients with valve repair and 214 with replacement for organic mitral regurgitation were compared using multivariate analysis. All patients had preoperative echocardiographic assessment of left ventricular function. Before surgery, patients with valve repair were less symptomatic than those with replacement (42% in New York Heart Association functional class I or II versus 24%, respectively; P=.001), had less atrial fibrillation (41% versus 53%; P=.017), and had a better ejection fraction (63±9% versus 60±12%, P=.016). After valve repair, compared with valve replacement, overall survival at 10 years was 68±6% versus 52±4% (P=.0004), overall operative mortality was 2.6% versus 10.3% (P=.002), o...
TL;DR: Newest approaches to diagnosis and pathogenesis of sporadic inclusion-body myositis and hereditary inclusion- body myopathies, including molecular-pathologic similarities to Alzheimer disease are introduced.
Abstract: Preface Part I. Overview of Pathologic and Pathogenic Comparison Between Sporadic Inclusion-Body Myositis and Hereditary Inclusion-Body Myopathies: 1. Newest approaches to diagnosis and pathogenesis of sporadic inclusion-body myositis and hereditary inclusion-body myopathies, including molecular-pathologic similarities to Alzheimer disease Part II. Historical Perspective: 2: Evolving concepts of inclusion-body myositis Part III. Sporadic Inclusion-Body Myositis - Clinical and Diagnostic Considerations: 3: Sporadic inclusion-body myositis: Clinical and laboratory features and diagnostic criteria 4: Inclusion-body myositis: natural history 5: Uncommon clinico-pathological forms of sporadic inclusion-body myositis: Report of four cases 6: Inclusion-body myositis: pathological changes 7: Unusual pathological forms of inclusion-body myositis, and neuromuscular disorders with IBM-like changes 8: Electrophysiological findings in inclusion-body myositis 9: Genetic factors in sporadic inclusion-body myositis Part IV. Hereditary Inclusion-Body Myopathies - Clinical and Diagnostic Considerations: 10: Hereditary inclusion-body myopathy in Jews of Persian origin: Clinical and laboratory data 11. Hereditary inclusion-body myopathy (h-IBM) with quadriceps sparing: epidemiology and genetics 12: Familial autosomal-recessive inclusion-body myositis with asymptomatic leukoencephalopathy 13: Welander distal myopathy - clinical, pathophysiological, and molecular aspects 14. Tibial muscular dystrophy - clinical, genetic, and morphological characteristics 15. Distal myopathy with rimmed vacuoles, inclusion-body myositis and related disorders in Japan 16. Inclusion-body myopathies 17. Is the muscle fiber in inclusion body-myositis an antigen-presenting cell of an innocent bystander? 18. Viruses, immunodeficiency and inclusion-body myositis 19. Myonuclear abnormalities may play a central role in the pathogenesis of muscle fiber damage in inclusion-body myositis 20. Nuclear degeneration and rimmed vacuole formation in neuromuscular disorders 21. Mitochondrial alterations in sporadic inclusion-body myositis 22. mtDNA analysis in muscle of patients with sporadic inclusion-body myopathy Part V. Treatment: 23. Evaluation of treatment for sporadic inclusion-body myositis 24. Personal experience in treating sporadic inclusion-body myositis Subject index.
TL;DR: The outcome of 113 total shoulder replacement arthroplasties performed with a Neer prosthesis between 1975 and 1981 for the treatment of osteoarthritis, rheumatoid arthritis, and old fractures or dislocations with traumatic arthritis was determined.
TL;DR: It is found that small homozygous deletions represent the predominant mechanism of inactivation at 9p21 in bladder tumours and are present in other tumour types, including breast and prostate cancer.
Abstract: Many tumour types have been reported to have deletion of 9p21 (refs 1-6). A candidate target suppressor gene, p16 (p16INK4a/MTS-1/CDKN2), was recently identified within the commonly deleted region in tumour cell lines. An increasing and sometimes conflicting body of data has accumulated regarding the frequency of homozygous deletion and the importance of p16 in primary tumours. We tested 545 primary tumours by microsatellite analysis with existing and newly cloned markers around the p16 locus. We have now found that small homozygous deletions represent the predominant mechanism of inactivation at 9p21 in bladder tumours and are present in other tumour types, including breast and prostate cancer. Moreover, fine mapping of these deletions implicates a 170 kb minimal region that includes p16 and excludes p15.
TL;DR: Five-year survival for patients undergoing pancreatic resection for lesions deemed to be clinically “curable” intraoperatively and histologically reviewed/confirmed to be ductal adenocarcinoma of the pancreas is approximately 7%.
Abstract: OBJECTIVE: The authors review their recent experience with resected pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Ductal adenocarcinoma of the pancreas has traditionally had a 5-year survival rate less than 10% after curative resection. Recently, several groups have reported markedly improved 5-year survival rates (approaching 25%) for patients undergoing curative resection. METHODS: Institutional experience with 186 consecutive patients (1981-1991) with pathologic diagnoses of ductal adenocarcinoma undergoing pancreatic resection was reviewed. Histologic specimens of all 3-year survivors (n = 31) were re-reviewed by two pathologists, one internal and one external; nonductal pancreatic cancers then were excluded. RESULTS: After histologic re-review, 12 patients did not have ductal adenocarcinoma, leaving a total of 174 patients for analysis (102 men, 72 women; mean age 63 years, range 34-82 years). Mean follow-up was 22 months (range 4-109). Classical pancreaticoduodenectomy was performed in 71%, pylorus-preserving resection in 9%, and total pancreatectomy in 20%. Hospital mortality was 3%. Twenty-eight patients (16%) had macroscopically incomplete resections; 98 (56%) had lymph node metastases within the resected specimens, and 21 patients (12%) had extensive perineural invasion. Overall actuarial 5-year survival was 6.8%. Five-year survival was greater for node-negative versus node-positive patients (14% vs. 1%, p < 0.001), and for smaller (< 2 cm) versus larger tumors (20% vs. 1%, p < 0.001). The 5-year survival for the subset of patients with negative nodes and no perineural or duodenal invasion (69 patients) was 23% (p < 0.001). Mean survival of the 12 excluded patients was 53 +/- 7 months compared with 17.5 +/- 1 months in the 174 patients with ductal pancreatic cancer. CONCLUSIONS: Five-year survival for patients undergoing pancreatic resection for lesions deemed to be clinically "curable" intraoperatively and histologically reviewed/confirmed to be ductal adenocarcinoma of the pancreas is approximately 7%. Survival is greater (23%) in the subset of patients with negative nodes and no duodenal or perineural invasions. Pathologic review of all patients with pancreatic ductal cancer adenocarcinoma is mandatory if survival data are to be meaningful.
TL;DR: It is concluded that the rapid PTH-induced rise in bone formation did not require cell proliferation and was most likely due to activation of preexisting bone lining cells to osteoblasts.
Abstract: Previous studies demonstrated that intermittent treatment with PTH increases osteoblast number and bone formation in growing and adult rats. The cellular mechanism for this increase in osteoblast number was investigated in 16-month-old female rats. Continuous [3H]thymidine infusion over a 1-week intermittent PTH [human PTH-(1-34)] treatment period was performed to determine the percentage of newly formed osteoblasts that originate from progenitor cells. To verify increases in bone formation, we performed histomorphometry and Northern blot analysis of selected bone matrix proteins. PTH treatment resulted in dramatic increases in fluorochrome-labeled perimeter (727%), osteoid perimeter (735%), osteoblast number (626%), and steady state mRNA levels of osteocalcin (946%) and type 1 collagen (> 1000%). Autoradiographic analysis of metaphyseal sections revealed no difference in the percentage of [3H]thymidine-labeled osteoblasts between PTH- and vehicle-treated groups (4.3 +/- 1.3% vs. 5.7 +/- 2.7%, respectively). Similar changes were observed in PTH-treated ovariectomized rats. As the PTH-induced increase in osteoblast number did not require proliferation of progenitor cells we carried out an additional experiment in adult ovariectomized rats to determine the onset of PTH action. Incorporation of [3H]proline in the distal femoral epiphysis of PTH-treated adult ovariectomized rats was increased within 24 h. We conclude that the rapid PTH-induced rise in bone formation did not require cell proliferation and was most likely due to activation of preexisting bone lining cells to osteoblasts.
TL;DR: Transgenic FVB/N mice overexpressing human and mouse Alzheimer amyloid precursor protein die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum.
TL;DR: A population-based, retrospective cohort study to determine whether the incidence of aortic aneurysm is increased in patients with previously diagnosed giant cell arteritis, and to identify clinical features of giantcell arteritis that could be associated with an increased risk for aneurYSm formation.
Abstract: Objective: To determine the frequency of aneurysm and dissection of the aorta in patients with giant cell arteritis and to assess the effects of these events on these patients. Design: Population-b...
TL;DR: The high frequency of P/Q-type calcium-channel antibodies found in patients with Lambert-Eaton syndrome implies that antibodies of this specificity have a role in the presynaptic pathophysiology of this disorder.
Abstract: Background Voltage-gated calcium channels in small-cell lung carcinomas may initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert–Eaton syndrome. The calcium-channel subtype that is responsible is not known. Methods We compared the effects of antagonists of L-type, N-type, and P/Q-type neuronal calcium channels on the depolarization-dependent influx of calcium-45 in cultured carcinoma cells. Serum samples from patients with various disorders were tested for reactivity with P/Q-type channels solubilized from carcinoma and cerebellar membranes and N-type channels from cerebral cortex. Results P/Q-type calcium-channel antagonists were the most potent inhibitors of depolarization-induced 45Ca influx in cultured small-cell carcinoma cell lines. Anti–P/Q-type calcium-channel antibodies were found in serum from all 32 patients with the Lambert–Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with the Lambert–Eaton syndrome without cancer. Anti–N-type calcium-chan...
TL;DR: These studies reveal that the lamin proteinase and the fragmentation nuclease function in independent parallel pathways during the final stages of apoptotic execution, and neither pathway alone is sufficient for completion of nuclear apoptosis.
Abstract: Although specific proteinases play a critical role in the active phase of apoptosis, their substrates are largely unknown. We previously identified poly(ADP-ribose) polymerase (PARP) as an apoptosis-associated substrate for proteinase(s) related to interleukin 1 beta-converting enzyme (ICE). Now we have used a cell-free system to characterize proteinase(s) that cleave the nuclear lamins during apoptosis. Lamin cleavage during apoptosis requires the action of a second ICE-like enyzme, which exhibits kinetics of cleavage and a profile of sensitivity to specific inhibitors that is distinct from the PARP proteinase. Thus, multiple ICE-like enzymes are required for apoptotic events in these cell-free extracts. Inhibition of the lamin proteinase with tosyllysine "chloromethyl ketone" blocks nuclear apoptosis prior to the packaging of condensed chromatin into apoptotic bodies. Under these conditions, the nuclear DNA is fully cleaved to a nucleosomal ladder. Our studies reveal that the lamin proteinase and the fragmentation nuclease function in independent parallel pathways during the final stages of apoptotic execution. Neither pathway alone is sufficient for completion of nuclear apoptosis. Instead, the various activities cooperate to drive the disassembly of the nucleus.
TL;DR: It was found that during tidal breathing the movement of the heart due to respiration is dominated by superior‐inferior (SI) motion, which is linearly related to the SI motion of the diaphragm.
Abstract: Respiratory motion is a major limiting factor in improving image resolution and signal-to-noise ratio in MR coronary imaging. In this work the effects of respiration on the cardiac position were studied quantitively by imaging the heart during diastole at various positions of tidal respiration with a breath-hold segmented fast gradient echo technique. It was found that during tidal breathing the movement of the heart due to respiration is dominated by superior-inferior (SI) motion, which is linearly related to the SI motion of the diaphragm. The motion of the heart due to respiration is approximately a global translation. These results provide motivation for employing adaptive motion correction techniques to reduce image blurring in nonbreath-hold coronary MR imaging.
01 Jul 1995
TL;DR: This study of the incidence and natural history of AA in a community shows that this disorder is fairly common and can be seen at all ages and may evolve into severe and chronic hair loss, which may be psychosocially devastating for affected persons.
Abstract: Objective To assess the incidence and natural history of alopecia areata (AA) among unselected patients from a community. Design We conducted a retrospective population-based descriptive study of AA among residents of Olmsted County, Minnesota, for the period from 1975 through 1989. Material and Methods After identifying 292 Olmsted County residents first diagnosed with AA during the 15-year study period, we reviewed their complete (inpatient and outpatient) medical records in the community and statistically analyzed the effects of gender and age-group. Results The overall incidence of AA was 20.2 per 100,000 person-years and did not change with time. Rates were similar in the two genders and over all ages, and lifetime risk was estimated at 1.7%. Eighty-seven percent of patients were examined by a dermatologist who diagnosed AA, and 29% of cases were confirmed by biopsy. Most patients had mild or moderate disease, but alopecia totalis or universalis developed at some point during the clinical course in 21 patients. Conclusion This study of the incidence and natural history of AA in a community shows that this disorder is fairly common and can be seen at all ages. Although spontaneous resolution is expected in most patients, a small but significant proportion of cases (probably approximately 7%) may evolve into severe and chronic hair loss, which may be psychosocially devastating for affected persons.
TL;DR: It is suggested that activated G protein subunits can interact directly with ion channels to elicit regulation, and this is the working hypothesis for the most-studied G protein-regulated ion channels.
Abstract: Ion channels are poised uniquely to initiate, mediate, or regulate such distinct cellular activities as action potential propagation, secretion, and gene transcription. In retrospect, it is not surprising that studies of ion channels have revealed considerable diversities in their primary structures, regulation, and expression. From a functional standpoint, the various mechanisms coopted by cells to regulate channel activity are particularly fascinating. Extracellular ligands, membrane potential, phosphorylation, ions themselves, and diffusible second messengers are all well-established regulators of ion channel activity. Heterotrimeric GTP-binding proteins (G proteins) mediate many of these types of ion channel regulation by stimulating or inhibiting phosphorylation pathways, initiating intracellular cascades leading to elevation of cytosolic Ca2+ or adenosine 3',5'-cyclic monophosphate levels, or by generating various lipid-derived compounds. In some cases, it seems that activated G protein subunits can interact directly with ion channels to elicit regulation. Although there is currently little direct biochemical evidence to support such a mechanism, it is the working hypothesis for the most-studied G protein-regulated ion channels.
TL;DR: The economic impact of IBS is significant and a better understanding of the determinants of these costs is needed so that cost-saving strategies can be implemented.
TL;DR: Aneurysmal bone cyst is the result of a specific pathophysiologic change, which is probably a result of trauma or a tumor-induced anomalous vascular process as mentioned in this paper.
Abstract: The aneurysmal bone cyst is the result of a specific pathophysiologic change, which is probably the result of trauma or a tumor-induced anomalous vascular process. In approximately one third of cases, the preexisting lesion can be clearly identified. The most common of these is the giant cell tumor, which accounts for 19-39% of cases in which the preceding lesion is found. Other common precursor lesions include osteoblastoma, angioma, and chondroblastoma. Less common lesions include fibrous dysplasia, fibroxanthoma (nonossifying fibroma), chondromyxoid fibroma, solitary bone cyst, fibrous histiocytoma, eosinophilic granuloma, and even osteosarcoma. Interestingly, some of the controversy surrounding this lesion may be the result of a change in how the lesion was defined by Lichtenstein in 1953, when intramedullary lesions were added to the previously described juxtacortical (superficial) lesions. Members of the AFIP have suggested that many of the intramedullary lesions in which no previous lesion can be identified may represent giant cell tumors of bone. Their similarity to proved giant cell tumors in skeletally immature patients can be striking and seems more than coincidental. Appropriate treatment of an aneurysmal bone cyst requires the realization that it results from a specific pathophysiologic process, and identification of the preexisting lesion, if possible, is essential. Clearly an osteosarcoma with superimposed secondary aneurysmal bone cyst change must be treated as an osteosarcoma, and giant cell tumor with secondary features of aneurysmal bone cyst would be expected to be more likely to recur locally. The vast majority (approximately 80%) of patients presenting with aneurysmal bone cystlike findings are less than 20 years old. More than half of all such lesions occur in long bones, with approximately 12-30% of cases occurring in the spine. The pelvis accounts for about half of all flat bone lesions. Most patients present with pain and/or swelling, with symptoms usually present for less than 6 months. The imaging appearance of aneurysmal bone cyst reflects the underlying pathophysiologic change. Radiographs show an eccentric, lytic lesion with an expanded, remodeled "blown-out" or "ballooned" bony contour of the host bone, frequently with a delicate trabeculated appearance. Radiographs may rarely show flocculent densities within the lesion, which may mimic chondroid matrix. CT scanning will define the lesion and is especially valuable for those lesions located in areas in which the bony anatomy is complex, and which are not adequately evaluated by plain films. Fluid-fluid levels are common and may be seen on CT scans and MR images.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Predicted quality survival at home for several months, rather than a specific diagnosis, seems to be the soundest justification for HPEN and its role in terminal conditions and patients without primary gastrointestinal diseases needs further evaluations.