Showing papers by "University of Tennessee Health Science Center published in 1997"

A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST)

Abstract: Objective. —To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis. Setting and Degign. —A randomized, single-blind clinical trial lasting 18 months conducted at 2 academic medical centers. Participants. —A total of 439 community-dwelling adults, aged 60 years or older, with radiographically evident knee osteoarthritis, pain, and self-reported physical disability. Invervention. —An aerobic exercise program, a resistance exercise program, and a health education program. Main Outcome Measures. —The primary outcome was self-reported disability score (range, 1-5). The secondary outcomes were knee pain score (range, 1-6), performance measures of physical function, x-ray score, aerobic capacity, and knee muscle strength. Results. —A total of 365 (83%) participants completed the trial. Overall compliance with the exercise prescription was 68% in the aerobic training group and 70% in the resistance training group. Postrandomization, participants in the aerobic exercise group had a 10% lower adjusted mean (±SE) score on the physical disability questionnaire (1.71 ±0.03 vs 1.90±0.04 units; P Conclusions. —Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability, physical performance, and pain from participating in either an aerobic or a resistance exercise program. These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis.

Molecular diagnosis of thiopurine S-methyltransferase deficiency: Genetic basis for azathioprine and mercaptopurine intolerance

Abstract: Background: Thiopurine S-methyltransferase (TPM) catalyzes the S-methylation (that is, inactivation) of mercaptopurine, azathioprine, and thioguanine and exhibits genetic polymorphism. About 10% of...

Prospective study of blunt aortic injury: Multicenter trial of the American Association for the Surgery of Trauma

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.

Molecular and Physiological Diversity of Cortical Nonpyramidal Cells

Abstract: The physiological and molecular features of nonpyramidal cells were investigated in acute slices of sensory-motor cortex using whole-cell recordings combined with single-cell RT-PCR to detect simultaneously the mRNAs of three calcium binding proteins (calbindin D28k, parvalbumin, and calretinin) and four neuropeptides (neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, and cholecystokinin). In the 97 neurons analyzed, all expressed mRNAs of at least one calcium binding protein, and the majority (n = 73) contained mRNAs of at least one neuropeptide. Three groups of nonpyramidal cells were defined according to their firing pattern. (1) Fast spiking cells (n = 34) displayed tonic discharges of fast action potentials with no accommodation. They expressed parvalbumin (n = 30) and/or calbindin (n = 19) mRNAs, and half of them also contained transcripts of at least one of the four neuropeptides. (2) Regular spiking nonpyramidal cells (n = 48) displayed a firing behavior characterized by a marked accommodation and presented a large diversity of expression patterns of the seven biochemical markers. (3) Finally, a small population of vertically oriented bipolar cells, termed irregular spiking cells (n = 15), fired bursts of action potentials at an irregular frequency. They consistently co-expressed calretinin and vasoactive intestinal polypeptide. Additional investigations of these cells showed that they also co-expressed glutamic acid decarboxylase and choline acetyl transferase. Our results indicate that neocortical nonpyramidal neurons display a large diversity in their firing properties and biochemical patterns of co-expression and that both characteristics could be correlated to define discrete subpopulations.

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

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

Scrambler and yotari disrupt the disabled gene and produce a reeler -like phenotype in mice

Abstract: Formation of the mammalian brain requires choreographed migration of neurons to generate highly ordered laminar structures such as those in the cortices of the forebrain and the cerebellum. These processes are severely disrupted by mutations in reelin1 which cause widespread misplacement of neurons and associated ataxia in reeler mice2,3. Reelin is a large extracellular protein secreted by pioneer neurons that coordinates cell positioning during neurodevelopment1,4,5,6,7,8. Two new autosomal recessive mouse mutations, scrambler9 and yotari10 have been described that exhibit a phenotype identical to reeler9,10,11. Here we report that scrambler and yotari arise from mutations in mdab1 (ref. 12), a mouse gene related to the Drosophila gene disabled ( dab )13. Both scrambler and yotari mice express mutated forms of mdab1 messenger RNA and little or no mDab1 protein. mDab1 is a phosphoprotein that appears to function as an intracellular adaptor in protein kinase pathways. Expression analysis indicates that mdab1 is expressed in neuronal populations exposed to Reelin. The similar phenotypes of reeler, scrambler, yotari and mdab1 null mice14 indicate that Reelin and mDab1 function as signalling molecules that regulate cell positioning in the developing brain.

The Possibilities and Pitfalls of Doing a Secondary Analysis of a Qualitative Data Set

Abstract: The purpose of this article is to identify the general methodologic and data set-specific challenges that must be overcome when attempting a secondary analysis of qualitative data Two separate examples of secondary analyses of qualitative data sets are also described, including one unsuccessful beginning

Trial of Calcium to Prevent Preeclampsia

Abstract: Background Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. Methods We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. Results Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 wome...

D1 Receptor Activation Enhances Evoked Discharge in Neostriatal Medium Spiny Neurons by Modulating an L-Type Ca2+ Conductance

Abstract: Most in vitro studies of D1 dopaminergic modulation of excitability in neostriatal medium spiny neurons have revealed inhibitory effects. Yet studies made in more intact preparations have shown that D1 receptors can enhance or inhibit the responses to excitatory stimuli. One explanation for these differences is that the effects of D1 receptors on excitability are dependent on changes in the membrane potential occurring in response to cortical inputs that are seen only in intact preparations. To test this hypothesis, we obtained voltage recordings from medium spiny neurons in slices and examined the impact of D1 receptor stimulation at depolarized and hyperpolarized membrane potentials. As previously reported, evoked discharge was inhibited by D1 agonists when holding at negative membrane potentials (approximately -80 mV). However, at more depolarized potentials (approximately -55 mV), D1 agonists enhanced evoked activity. At these potentials, D1 agonists or cAMP analogs prolonged or induced slow subthreshold depolarizations and increased the duration of barium- or TEA-induced Ca2+-dependent action potentials. Both effects were blocked by L-type Ca2+ channel antagonists (nicardipine, calciseptine) and were occluded by the L-type channel agonist BayK 8644-arguing that the D1 receptor-mediated effects on evoked activity at depolarized membrane potential were mediated by enhancement of L-type Ca2+ currents. These results reconcile previous in vitro and in vivo studies by showing that D1 dopamine receptor activation can either inhibit or enhance evoked activity, depending on the level of membrane depolarization.

Antibiotic Therapy for Reduction of Infant Morbidity After Preterm Premature Rupture of the Membranes: A Randomized Controlled Trial

Abstract: Context. —Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent. Objective. —To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity. Design. —Randomized, double-blind, placebo-controlled trial. Setting. —University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Patients. —A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization. Intervention. —Interavenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization. Main Outcome Measures. —The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed. Results. —In the total study population, the primary outcome (44.1% vs 52.9%;P=.04), respiratory distress (40.5% vs 48.7%;P=.04), and necrotizing enterocolitis (2.3% vs 5.8%;P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%;P=.03), respiratory distress (40.8% vs 50.6%;P=.03), overall sepsis (8.4% vs 15.6%;P=.01), pneumonia (2.9% vs 7.0%;P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P Conclusions. —We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.

Spontaneous Subthreshold Membrane Potential Fluctuations and Action Potential Variability of Rat Corticostriatal and Striatal Neurons In Vivo

Abstract: Stern, Edward A., Anthony E. Kincaid, and Charles J. Wilson. Spontaneous subthreshold membrane potential fluctuations and action potential variability of rat corticostriatal and striatal neurons in...

p55 Tumor Necrosis Factor Receptor Fusion Protein in the Treatment of Patients With Severe Sepsis and Septic Shock: A Randomized Controlled Multicenter Trial

Abstract: Objective. —To evaluate the safety and efficacy of p55 tumor necrosis factor receptor fusion protein, a recombinant chimeric protein of human p55 (type I) tumor necrosis factor receptor (CD120a) extracellular domain and lgG1 sequences (referred to as p55-lgG), in the treatment of patients with severe sepsis or septic shock. Design. —Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. Setting. —Forty-four community and university-affiliated hospitals in the United States and Europe. patients. —There were 498 patients enrolled in this clinical trial. Intervention. —Patients prospectively stratified within each site into refractory shock or severe sepsis groups were randomized to receive a single infusion of p55IgG, 0.083 mg/kg, 0.042 mg/kg, or 0.008 mg/kg, or placebo. Patients received standard aggressive medical/surgical care during the 28-day postinfusion period. Outcome Measure. —Twenty-eight—day all-cause mortality. Results. —The distribution of variables describing demographics, organ system dysfunction or failure, infecting microorganisms, predicted mortality, plasma interleukin 6 levels, and plasma tumor necrosis factor α (TNF-α) levels were similar among patients in the p55-lgG and placebo treatment arms. A planned interim analysis was performed after 201 patients were enrolled. Because a statistically nonsignificant trend toward increased mortality was present in patients who had received 0.008 mg/kg, this treatment arm was discontinued, and the study continued with 3 arms. Among all infused patients, there was a statistically nonsignificant trend toward reduced 28-day all-cause mortality in those who received p55-lgG compared with placebo-treated patients (5% reduction, 0.042 mg/kg vs placebo; 15% reduction, 0.083 mg/kg vs placebo;P=.30). However, in patients with severe sepsis and early septic shock (n=247), therapy with p55-lgG, 0.083 mg/kg, was associated with a 36% reduction in 28-day all-cause mortality compared with placebo (P=.07): 20 (23%) of 87 patients died among those treated with p55-lgG, 0.083 mg/kg; 30 (37%) of 82 among those treated with p55-lgG, 0.042 mg/kg; and 28 (36%) of 78 in the placebo group. A prospectively planned logistic regression analysis to assess treatment effect on 28-day all-cause mortality by means of predicted mortality and serum interleukin 6 levels as continuous covariates demonstrated a significant improvement in outcome for the patients with severe sepsis treated with p55-lgG, 0.083 mg/kg, compared with placebo (P=.01). Serious adverse events, including death and the development of new organ system dysfunction, were reported in 65% of patients infused with placebo, with no increased frequency (56%) present in the 2 p55-lgG treatment arms. There were no reports of immediate hypersensitivity reactions caused by p55-lgG. Conclusions. —In this dose-finding study, there was no decrease in mortality between placebo and p55-lgG in all infused patients. In the prospectively defined population of patients with severe sepsis who received p55-lgG, 0.083 mg/kg, there was a trend toward reduced mortality at day 28 that became significant when predicted mortality and plasma interleukin 6 levels were included in a logistic regression analysis.

A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.

Abstract: The underlying basis of many forms of syndromic craniosynostosis has been defined on a molecular level However, many patients with familial or sporadic craniosynostosis do not have the classical findings of those craniosynostosis syndromes Here we present 61 individuals from 20 unrelated families where coronal synostosis is due to an amino acid substitution (Pro250Arg) that results from a single point mutation in the fibroblast growth factor receptor 3 gene on chromosome 4p In this instance, a new clinical syndrome is being defined on the basis of the molecular finding In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe Sensorineural hearing loss was present in some, and developmental delay was seen in a minority While the radiological findings of hands and feet can be very helpful in diagnosing this syndrome, it is not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes Therefore, this mutation should be tested for in patients with coronal synostosis

Osteoarthritic lesions: involvement of three different collagenases.

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

Prooxidant-Antioxidant Shift Induced by Androgen Treatment of Human Prostate Carcinoma Cells

Abstract: Background: Prostate cancer is a disease associated with aging. Also commonly associated with increasing age is a shift in the prooxidant‐antioxidant balance of many tissues toward a more oxidative state, i.e., increased oxidative stress. We hypothesize that androgen exposure, which has long been associated with the development of prostate cancer, may be a means by which the prooxidant‐antioxidant balance of prostate cells is altered. Purpose: Using established prostate carcinoma cell lines, we studied the effect of androgens on various parameters of oxidative state (e.g., generation of hydrogen peroxide and hydroxyl radicals, lipid peroxidation, and oxygen consumption) and antioxidant defense mechanisms (e.g., the glutathione system and catalase). Methods: The androgen-responsive LNCaP and the androgen-independent DU145 prostate carcinoma cell lines were exposed to 5a-dihydrotestosterone (DHT) and to the synthetic androgen R1881. The cellular proliferation responses were measured by use of a fluorometric assay to quantitate the amount of DNA. The generation of reactive oxygen species was measured by use of 2*,7*-dichlorofluorescin diacetate, a dye that fluoresces in the presence of hydrogen peroxide or hydroxyl radicals. Lipid peroxidation was quantitated by use of a chromogen specific for malonaldehyde and 4-hydroxy-2(E)-nonenal. General mitochondrial activity was determined by assaying 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) reduction. A Clarktype electrode was used to assess oxygen consumption per cell. Intracellular glutathione concentrations and the activities of catalase and g-glutamyl transpeptidase were measured spectrophotometrically. All P values resulted from two-sided tests. Results: DHT at less than 1 to 100 nM (a concentration range encompassing the physiologic levels of DHT considering all ages) and R1881 at 0.1-1 nM concentrations were effective in inducing in LNCaP cells comparable proliferative responses and changes in oxidative stress. In contrast, neither DHT nor R1881 had any effect on the oxidative stress in DU145 cells. The mitochondrial activity in LNCaP cells, as measured by MTT reduction, was significantly elevated above the levels of the untreated controls by DHT (0.1-1000 nM) and R1881 (0.05-1 nM )( P<.001 in both). Oxygen consumption and catalase activity were increased in LNCaP cells in the presence of 1 nM R1881 by 60% and 40%, respectively, over the values in the untreated control cells (P<.03 and P<.01, respectively). The same concentration of R1881 resulted in a decrease in intracellular glutathione concentrations and an increase in g-glutamyl transpeptidase activity in LNCaP ells. Treatment with the oxidizing agents H2O2 and menadione produced an increase in g-glutamyl transpeptidase activity in LNCaP cells, whereas treatment with the antioxidant compound ascorbic acid (100 mM) reduced the oxidative stress produced in LNCaP cells by 1 nM R1881 and completely blocked the g-glutamyl transpeptidase activity. Conclusions: Physiologic levels of androgens are capable of increasing oxidative stress in androgenresponsive LNCaP prostate carcinoma cells. The evidence suggests that this result is due in part to increased mitochondrial activity. Androgens also alter intracellular glutathione levels and the activity of certain detoxification enzymes, such as g-glutamyl transpeptidase, that are important for maintenance of the cellular prooxidant‐antioxidant balance. [J Natl Cancer Inst 1997;89:40-8]

Improved Success in Nonoperative Management of Blunt Splenic Injuries: Embolization of Splenic Artery Pseudoaneurysms

Abstract: Objectives: By using abdominal computed tomographic scans in the evaluation of blunt splenic trauma, we previously identified the presence of vascular blush as a predictor of failure, with a failure of nonoperative management of 13% in that series. This finding led to an alteration in our management scheme, which now includes the aggressive identification and embolization of splenic artery pseudoaneurysms. Methods: The medical records of 524 consecutive patients with blunt splenic injury managed over a 4.5-year period were reviewed for the following information: age, Injury Severity Score (ISS), American Association for the Surgery of Trauma splenic injury grade (SIG), method and outcome of management. Results: Of the patients, 66% were male with a mean age of 32± 16, and mean ISS of 25 ± 13. A total of 180 patients (34%) were managed with urgent operation on admission (81% splenectomy (SIG 4.0), 19% splenorrhaphy (SIG 2.6)). The remaining 344 patients (66%) were hemodynamically stable and underwent computed tomographic scan and planned nonoperative management. Of these patients, 322 patients (94%) were successfully managed nonoperatively (61% of total splenic injuries). In 26 patients (8%), a contrast blush identified on computed tomographic scan was confirmed as a parenchymal pseudoaneurysm on arteriography. Twenty patients (SIG, 2.8) were successfully embolized. In six patients, technical failure precluded embolization; all required splenectomy (SIG, 4.0). A total of 22 patients (6%) failed nonoperative management, including the six with unsuccessful embolization attempts. Sixteen patients (SIG, 3.0) who had no evidence of pseudoaneurysm were explored for a falling hematocrit, hemodynamic instability, or a worsening follow-up computed tomography: 13 patients had splenectomy, and three patients had splenorrhaphy. Conclusions: Aggressive surveillance for and embolization of posttraumatic splenic artery pseudoaneurysms improved the rate of successful nonoperative management of blunt splenic trauma to 61%, with a nonoperative failure rate of only 6%. In comparison with our previous work, this reduction in failure of nonoperative management is a significant improvement (p < 0.03).

Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled.

Abstract: Objective. —To characterize hospital diagnoses, procedures and charges, and nursing home admissions in the year when older persons become severely disabled, comparing those in whom severe disability develops rapidly with those in whom disability develops gradually. Design. —A prospective, population-based cohort study with at least 6 annual interviews beginning in 1982. Setting. —A total of 3 communities: East Boston, Mass, New Haven, Conn, and Iowa and Washington counties in Iowa. Subjects. —A total of 6070 persons at least 70 years old with at least 1 interview after the fourth annual follow-up and without evidence of previous severe disability, defined as disability in 3 or more activities of daily living (ADLs). Main Outcome Measures. —Characteristics associated with development of severe disability after the fourth annual follow-up, in which the disability is classified as catastrophic disability if the individual did not report any ADL disability in the 2 interviews prior to severe disability onset or as progressive disability if the individual had previous disability in 1 or 2 ADLs. Results. —In the year during which severe disability developed, hospitalizations were documented for 72.1% of those developing catastrophic disability and for 48.6% of those developing progressive disability. In the corresponding year, only 14.7% of those who were stable with no disability and 22.3% of those with some disability were hospitalized. The 6 most frequent principal discharge diagnoses included stroke, hip fracture, congestive heart failure, and pneumonia in both severe disability subsets; coronary heart disease and cancer in catastrophic disability; and diabetes and dehydration in progressive disability. These diagnoses occurred in 49% of those with catastrophic disability and 25% of those with progressive disability. In both severe disability subsets, the oldest patients received less intensive hospital care as indicated by charges for surgery, diagnostics, and rehabilitation and by the percentage who received major diagnostic procedures; they were also more often admitted to nursing homes. Conclusions. —In the year when they become severely disabled, a large proportion of older persons are hospitalized for a small group of diseases. Hospital-based interventions aimed at reducing the severity and functional consequences of these diseases could have a large impact on reduction of severe disability.

D2 Dopamine Receptors Reduce N-Type Ca2+ Currents in Rat Neostriatal Cholinergic Interneurons Through a Membrane-Delimited, Protein-Kinase-C-Insensitive Pathway

Abstract: Yan, Zhen, Wen-Jie Song, and D. James Surmeier. D2 dopamine receptors reduce N-type Ca2+ currents in rat neostriatal cholinergic interneurons through a membrane-delimited, protein-kinase-C-insensit...

STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interferon receptor.

Abstract: STAT (signal transducers and activators of transcription) proteins undergo cytokine-dependent phosphorylation on serine and tyrosine. STAT3, a transcription factor for acute phase response genes, was found to act as an adapter molecule in signal transduction from the type I interferon receptor. STAT3 bound to a conserved sequence in the cytoplasmic tail of the IFNAR1 chain of the receptor and underwent interferon-dependent tyrosine phosphorylation. The p85 regulatory subunit of phosphatidylinositol 3-kinase, which activates a series of serine kinases, bound to phosphorylated STAT3 and subsequently underwent tyrosine phosphorylation. Thus, STAT3 acts as an adapter to couple another signaling pathway to the interferon receptor.

Trends in sun exposure knowledge, attitudes, and behaviors : 1986 to 1996

Abstract: Background: The American Academy of Dermatology's national program Melanoma/Skin Cancer Detection and Prevention, developed in response to the rising incidence of invasive melanoma in the United States, has annually during the past decade produced extensive print, radio, and television coverage about the dangers of sun exposure and benefits of sun protection. Objective: We measured the progress achieved in increasing the awareness and knowledge of skin cancer and changing the attitudes, beliefs, and behaviors that affect skin cancer risk. We also describe current sun-related behavior including sunburning, assess the likelihood of practicing sun protection strategies, and provide a baseline against which future changes in sun protection behavior may be evaluated. Methods: A 1996 telephone survey repeated questions used in 1986 to evaluate change and used classifying questions to better define attitudes and behaviors. Results: From 1986 to 1996, the knowledge of the perceived harmful effects of the sun significantly broadened, but the UV exposure behavior as measured by sunburning (30% to 39%) and regular use of a tanning booth (2% to 6%) also increased. There was a decline in the attitude that having a tan was healthy; however, in 1996 having a tan was still considered to enhance appearance, particularly by men. Sunscreen use increased (35% to 53%). Women, younger persons, persons residing in areas with fewer sunny days, and whites were more likely to tan intentionally, but men who lived in the South were more likely to sunburn. Conclusion: During the past decade, the early process of change involving cognitive and emotional activities began. With this study, high-risk population subsets performing specific adverse behavior were identified. In the future, they can be targeted with messages that promote attitudinal and behavioral change. (J Am Acad Dermatol 1997;37:179-86.)

Risk Factors for Violent Death of Women in the Home

Abstract: Objectives: To determine risk factors for violent death of women in the home, and particularly, to assess the strength and direction of any association between domestic violence or keeping firearms and homicide or suicide in the home. Methods: Subgroup analysis of a large population-based case-control study database was performed, defining cases as all homicides and suicides occurring in the homes of female victims in 3 metropolitan counties: Shelby County, Tennessee; King County, Washington; and Cuyahoga County, Ohio. Randomly selected control subjects were matched to the victims by neighborhood, sex, race, and age range. Exposures to potential risk factors were ascertained by interviewing a proxy for the victim 3 to 6 weeks after the violent death occurred. These answers were compared with those obtained from controls using matched-pairs methods. Results: All cases (n=266) were identified in the 3-county area, including 143 homicides and 123 suicides, during a 5-year period. Matching controls (n=266) were also identified. Firearms were involved in 46% of the homicides and 42% of the suicides. Independent risk factors for suicide in the home included a history of mental illness (odds ratio [OR], 258.8; 95% confidence interval [CI], 18.2-3679.8), living alone (OR, 13.4; 95% CI, 2.0-87.8), and having 1 or more guns in the home (OR, 4.6; 95% CI, 1.2-17.5). Independent risk factors for homicide included living alone (OR, 5.1; 95% CI, 2.0-13.2), illicit drug use by any member of the household (OR, 4.9; 95% CI, 1.3-15.9), prior domestic violence (OR, 4.0; 95% CI, 1.5-10.5), 1 or more guns in the home (OR, 3.4; 95% CI, 1.6- 7.1), and previous arrest of any member of the household (OR, 3.0; 95% CI, 1.3-6.6). The increased risk of homicide associated with domestic violence, firearms, or illicit drugs was attributable to the homicides at the hands of a spouse, intimate acquaintance, or close relative. Conclusions: Among women, mental illness and living alone increase the risk of suicide in the home, and household use of illicit drugs and prior domestic violence increase the risk of homicide. Instead of conferring protection, keeping a gun in the home is associated with increased risk of both suicide and homicide of women. Household use of illicit drugs, domestic violence, and readily available firearms place women at particularly high risk of homicide at the hands of a spouse, an intimate acquaintance, or a close relative. Many factors place women at increased risk of violent death in the home. Community- and clinic-based interventions should target those with identifiable risk factors. Arch Intern Med. 1997;157:777-782

An HLA-DR1 Transgene Confers Susceptibility to Collagen-induced Arthritis Elicited with Human Type II Collagen

Abstract: Rheumatoid arthritis (RA) is an autoimmune disease that is strongly associated with the expression of several HLA-DR haplotypes, including DR1 (DRB1*0101). Although the antigen that initiates RA remains elusive, it has been shown that many patients have autoimmunity directed to type II collagen (CII). To test the hypothesis that HLA-DR1 is capable of mediating an immune response to CII, we have generated transgenic mice expressing chimeric (human/ mouse) HLA-DR1. When the DR1 transgenic mice were immunized with human CII (hCII), they developed a severe autoimmune arthritis, evidenced by severe swelling and erythema of the limbs and marked inflammation and erosion of articular joints. The development of the autoimmune arthritis was accompanied by strong DR1-restricted T and B cell responses to hCII. The T cell response was focused on a dominant determinant contained within CII(259–273) from which an eight amino acid core was defined. The B cell response was characterized by high titers of antibody specific for hCII, and a high degree of cross-reactivity with murine type II collagen. These data demonstrate that HLA-DR1 is capable of presenting peptides derived from hCII, and suggest that this DR1 transgenic model will be useful in the development of DR1-specific therapies for RA.

MR imaging differentiation of benign and malignant peripheral nerve sheath tumors: use of the target sign

Abstract: T2-weighted MR imaging of soft tissue tumors of neural origin may show round lesions with a central hypointensity and a hyperintense rim resembling a target. We define the “target sign” as a mass consisting of a solitary target, or a multicompartmental mass in which the largest component consists of multiple targets. The objective of this study was to determine whether the target sign can differentiate benign neurofibromas and their malignant counterparts, malignant peripheral nerve sheath tumors. Preoperative T2-weighted MR images of 23 neurofibromas or malignant peripheral nerve sheath tumors were retrospectively reviewed in 16 patients, aged 3 weeks to 20 years (median 15 years), without knowledge of the pathologic diagnosis. The presence or absence of a target sign was noted. The target sign was seen in all 12 neurofibromas and 1 of the 11 malignant peripheral nerve sheath tumors. Statistical analysis showed good differentiation of benign and malignant tumors using this sign (x = 0.91). The target sign on T2-weighted MR imaging is helpful in differentiating neurofibromas from malignant peripheral nerve sheath tumors.

Mammalian cells express two differently localized Bag-1 isoforms generated by alternative translation initiation.

Abstract: The Bcl-2 oncoprotein is a key regulator of apoptosis and the Bag-1 protein interacts with Bcl-2 and cooperates with Bcl-2 to suppress apoptosis. The human Bag-1 cDNA is essentially identical with a previously described cDNA encoding RAP46, which interacts with activated steroid hormone receptors. However, there is considerable confusion over the structure of Bag-1/RAP46 proteins and their relationship to endogenous Bag-1 proteins. Here we have characterized Bag-1 expression in mammalian cells. We demonstrate that, in addition to the previously identified 32 kDa murine and 36 kDa human Bag-1 proteins, cells express a second 50 kDa Bag-1 isoform. In some murine cell lines p50 is expressed at the same level as p32 Bag-1, and p50 and p32 Bag-1 proteins have distinct subcellular localizations, suggesting that they are functionally distinct. The published mouse Bag-1 cDNA is partial, and sequencing of additional murine Bag-1 RNA 5' sequences demonstrated that human and murine Bag-1 cDNAs contain longer open reading frames than originally suspected. We determined which open reading frames gave rise to the Bag-1 isoforms in human cells. Surprisingly, translation of neither protein initiated at the first in-frame methionine, and cells do not express Bag-1/RAP46 proteins with the previously proposed structures; p50 Bag-1 initiates at an upstream CUG codon, whereas p36 Bag-1 initiates at a downstream AUG codon. Therefore, cells express two differently localized Bag-1 isoforms generated by alternative translation initiation, and Bag-1 proteins may play a dual role in regulating apoptosis and steroid hormone-dependent transcription.