Showing papers by "Veterans Health Administration published in 1989"

HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy

Abstract: The drug sensitivities of human immunodeficiency virus (HIV) isolates from a group of patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) who were receiving zidovudine (3'-azido-3'-deoythymidine, AZT) therapy were tested by means of a newly developed plaque assay in CD4+ HeLa cells. Fifty percent inhibitory dose (ID50) values of 18 isolates from untreated individuals ranged between 0.01 microM and 0.05 microM. In contrast, most isolates from patients who had received zidovudine for 6 months or more exhibited decreased sensitivity characterized by changes in ID50 or ID95 values (or both), with isolates from several patients (5/15) showing 100-fold increases in ID50. The latter isolates were also insensitive to 3'-azido-2',3'-dideoxyuridine; however, the isolates were still sensitive to 2',3'-dideoxycytidine, 2',3'-dideoxy-2',3'-didehydrothymidine, or phosphonoformate. It cannot be determined from this small sample of patients whether development of a less sensitive virus phenotype results in clinical resistance. Appearance of such variants was not associated with a consistent increase in viral p24 concentrations in patient plasma and did not herald any sudden deterioration in clinical status. More extensive studies are required to determine the clinical significance. Thus, it would be premature to alter any treatment protocols for HIV-infected individuals at present.

Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis.

Abstract: T CELLS expressing the αβ T-cell receptor (TCR) for antigen can elicit anti-idiotypic antibodies specific for the TCR that regulate T-cell function1–4. Defined sequences of the TCR, however, have not been used to elicit specific antibodies and the role of cellular immunity directed against TCR determinants has not been studied. We immunized Lewis rats with a synthetic peptide representing a hypervariable region of the TCR β8 molecule. Subsequent induction of experimental autoimmune encephalomyelitis, a paralytic disease of the central nervous system mediated primarily by Vβ8+ T cells specific for myelin basic protein5,6 was prevented. T cells specific for the TCR Vβ8 peptide conferred passive protection against the disease to naive rats, apparently by shifting the predominant T-cell response away from the major encephalitogenic epitope of basic protein. This is the first report demonstrating the use of a synthetic TCR V-region peptide to induce specific regulatory immunity and has important implications for the regulation of human disease characterized by common TCR V-gene usage.

Neuropsychological evidence for multiple implicit memory systems: a comparison of Alzheimer's, Huntington's, and Parkinson's disease patients

Abstract: The performances of patients with dementia of the Alzheimer type (DAT), patients with Huntington's disease (HD), and demented and nondemented patients with Parkinson's disease (PD) were compared on 2 tests of implicit memory that do not require the conscious recollection of prior study episodes: (1) a pursuit-rotor motor learning task and (2) a lexical priming test. The HD patients were found to be impaired on the motor learning but not the lexical priming task, whereas the DAT patients evidenced the opposite relationship on these tasks. The demented, but not the nondemented, PD patients were found to be impaired on both tests of implicit memory. For both the HD and PD patients, deficits on the motor learning task correlated significantly with severity of dementia but not with level of primary motor dysfunction. The noted double dissociation between HD and DAT patients indicates that different forms of implicit memory, all of which are intact in amnesia, are dependent upon distinct neuroanatomic systems. Motor skill learning may be mediated by a corticostriatal system, whereas verbal priming may depend upon the integrity of the neocortical association areas involved in the storage of semantic knowledge. The results for the PD patients suggest that the demented PD patients have endured damage to the neurologic systems subserving both motor learning and lexical priming.

Sleep Disturbance as the Hallmark of Posttraumatic Stress Disorder

Abstract: The reexperiencing ofa traumatic event in the form of repetitive dreams, memories, or flashbacks is one of the cardinal manifestations of posttraumatic stress disorder (PTSD). The dream disturbance associated with PTSD may be relatively specific for this disorder, and dysfunctional REM sleep mechanisms may be involved in the pathogenesis of the posttraumatic anxiety dream. Furthermore, the results of neurophysiological studies in animals suggest that CNS processes generating REM sleep may participate in the control of the classical startle response, which may be akin to the startle behavior commonly described in PTSD patients. Speculating that PTSD may be fundamentally a disorder of REM sleep mechanisms, the authors suggest several strategies for future research. (Am J Psychiatry 1989; 146:697-707)

Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure.

Abstract: To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, began between 24 to 48 h and reached a peak at 72 h after renal ischemia. As demonstrated by histoautoradiography, renal thymidine incorporation was essentially confined to tubule cells. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that the majority of labeled cells were found in renal cortex, but some labeled cells were also located in the inner stripe of the outer medulla, suggesting that injury to medullary thick ascending limbs also occurs in this ischemic model. Exogenous EGF administration produced increases in renal thymidine incorporation compared with non-treated animals at 24, 48, and 72 h after ischemic injury. This accelerated DNA replicative process was associated with significantly lower peak blood urea nitrogen (BUN) and serum creatinine levels, averaging 63 +/- 20 and 3.1 +/- 0.4 mg/dl in EGF-treated ischemic rats compared with 149 +/- 20 and 5.1 +/- 0.1 mg/dl, respectively, in nontreated ischemic rats, and was also associated with a return to near normal BUN and serum creatinine levels in EGF-treated animals approximately 4 d earlier than that observed in nontreated animals. This report is the first demonstration that EGF accelerates the repair process of a visceral organ after an injurious insult.

Segmentation of MR brain images into cerebrospinal fluid spaces, white and gray matter.

Abstract: An interactive computer method for quantifying CSF, white matter, and gray matter in magnetic resonance (MR) axial brain scans is presented. A stripping algorithm is used to remove the skull and scalp from each axial section. The images are then filtered to correct for radiofrequency inhomogeneity image artifacts. Late echo images are subtracted from or added to early echo images to enhance fluid/tissue and gray/white tissue contrast, respectively. Thresholds for fluid/tissue and gray/white separation are set interactively. A boundary pixel locking algorithm is used to handle ambiguities due to partial voluming between the fluid and tissue compartments. The MR brain scans from five healthy, young, normal men were obtained using a standard neuroanatomical reference technique. These data were processed and percentages computed for fluid, gray matter and white matter compartments. The gray/white ratios compare favorably with those determined in a published postmortem brain study.

Autoradiographic localization and characterization of tachykinin receptor binding sites in the rat brain and peripheral tissues

Abstract: Quantitative receptor autoradiography using several radiolabeled tachykinins was used to localize and characterize tachykinin peptide receptor binding sites in rat CNS and peripheral tissues Autoradiographic localization and displacement experiments using several radiolabeled tachykinins indicate that in the rat there are at least 3 distinct tachykinin receptor binding sites One of these is present in both the CNS and peripheral tissues, one is present only in the CNS, and one is present only in peripheral tissues The first tachykinin receptor binding site, which is detectable in both the CNS and peripheral tissues, appears to prefer substance P (SP) as an endogenous ligand Areas expressing high concentrations of this binding site include the medial septum, superior colliculus, inferior olive, inner plexiform layer of the retina, external muscle of the bladder, and the muscularis externa of the esophagus The second type of tachykinin receptor binding site, which is detectable only in the CNS appears to prefer either neuromedin K (NK) and/or substance K (SK) as the endogenous ligand This receptor binding site is labeled by Bolton- Hunter conjugates of NK, SK, eledoisin, or kassinin and is found in high concentrations in laminae 4 and 5 of the cerebral cortex, the ventral tegmental area, laminae 1 and 2 of the spinal cord, and the inner plexiform layer of the retina The third type of tachykinin receptor binding site is detectable only in peripheral tissues and appears to prefer SK as the endogenous ligand This receptor binding site is labeled by SK, eledoisin, or kassinin radioligands and tissues that express high concentrations include the muscularis mucosae of the esophagus, the circular muscle of the colon, and the external muscle of the bladder These data suggest that SP receptors are expressed in the brain and peripheral tissues, NK receptors are expressed in the CNS, and SK receptors are expressed in peripheral tissue These data fit well with radioimmunoassay data that suggest that, whereas in the CNS SP, SK and NK are present in high concentrations, in peripheral tissues only SP and SK are present in detectable concentrations The present classification of tachykinin receptors places a lower limit on the number of mammalian tachykinin receptor types and provides a functional/morphological framework for exploring the diverse actions of tachykinin peptides in both the CNS and peripheral tissues

High-pressure freezing for the preservation of biological structure: theory and practice.

Abstract: The two main advantages of cryofixation over chemical fixation methods are the simultaneous stabilization of all cellular components and the much faster rate of fixation The main drawback pertains to the limited depth (less than 20 microns surface layer) to which samples can be well frozen when freezing is carried out under atmospheric conditions High-pressure freezing increases the depth close to 06 mm to which samples can be frozen without the formation of structurally distorting ice crystals This review discusses the theory of high-pressure freezing, the design of the first commercial high-pressure freezing apparatus (the Balzers HPM 010), the operation of this instrument, the quality of freezing, and novel structural observations made on high-pressure-frozen cells and tissues

Behavioral disturbance, cognitive dysfunction, and functional skill. Prevalence and relationship in Alzheimer's disease.

Abstract: The nature and severity of behavioral problems, and their relationship to cognitive and functional abilities, was investigated in 56 community-residing patients with Alzheimer's disease. Measures evaluated three domains of function: behavior, cognition and activities of daily living. Problems of cognitive functioning, such as memory loss, confusion, and disorientation were most prevalent, reported to occur in 84%, 82%, and 64% of the sample, respectively. Problems with activity and emotional distress were next, affecting 20 to 43% of the sample. The mean number of problems reported was 10 per patient. Twenty-two percent of caregivers reported a minimum of 15 problems occurring at least twice a week and no caregiver reported an absence of problems. Male patients were reported to have more behavioral difficulties. Level of behavioral disturbance was largely unrelated to cognitive or functional ability. Age was unrelated to cognitive or behavioral disturbance but significantly related to activities of daily living. Results indicated that behavioral problems are prevalent and pervasive in even moderately impaired community-residing Alzheimer disease patients, and that age may be more important than level of cognitive dysfunction in predicting difficulties with activities of daily living.

Pretranslational suppression of an insulin-responsive glucose transporter in rats with diabetes mellitus.

Abstract: A prominent feature of diabetes mellitus is the inability of insulin to appropriately increase the transport of glucose into target tissues. The contributions of different glucose transport proteins to insulin resistance in rats with streptozotocin-induced diabetes was evaluated. A glucose transporter messenger RNA and its cognate protein that are exclusively expressed in muscle and adipose tissue were specifically depleted in diabetic animals, and these effects were reversed after insulin therapy; a different glucose transporter and its messenger RNA that exhibit a less restricted tissue distribution were not specifically modulated in this way. Depletion of the muscle- and adipose-specific glucose transporter species correlates with and may account for the major portion of cellular insulin resistance in diabetes in these animals.

Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia.

Abstract: Because CNS neuroleptic concentration cannot be directly measured in patients, the relation between clinical response and extent of dopamine receptor blockade is unknown. This relationship is critical in ascertaining whether nonresponse to neuroleptics is the result merely of inadequate CNS drug levels or of more basic biological differences in pathophysiology. Using ({sup 18}F)N-methylspiroperidol and positron emission tomography, the authors assessed dopamine receptor occupancy in 10 schizophrenic patients before and after treatment with haloperidol. Responders and nonresponders had virtually identical indices of ({sup 18}F)N-methylspiroperidol uptake after treatment, indicating that failure to respond clinically was not a function of neuroleptic uptake or binding in the CNS.

Increased Serum Levels of a Parathyroid Hormone-like Protein in Malignancy-Associated Hypercalcemia

Abstract: Study Objective:To measure the serum levels of a newly described parathyroid hormone-like protein (PLP), which was isolated from malignant tumors associated with hypercalcemia, and determi

DNA sequence of mip, a Legionella pneumophila gene associated with macrophage infectivity.

Abstract: In a previous study, a 24-kilodalton (kDa) protein surface antigen of Legionella pneumophila was cloned into Escherichia coli and found to be expressed on the host cell surface. Subsequently, a site-directed mutation in this gene (designated mip) in L. pneumophila was found to impair the capacity of this bacterium to initiate intracellular infection in human macrophages. The work presented here indicates that the antigenic gene product is distinct from the 24- to 29-kDa major outer membrane protein of L. pneumophila. In addition, the antigen was identified as a highly basic protein on two-dimensional nonequilibrium polyacrylamide gels and on two-dimensional monoclonal antibody immunoblots. When the DNA fragment encoding this protein was sequenced, a long open reading frame of 699 base pairs was identified within a region to which antigen expression was previously mapped. mip mRNA isolated from both L. pneumophila and transformed E. coli had the same 5' end, as determined by primer extension analysis, indicating that the same promoter sequences are used in both species. A likely factor-independent transcriptional terminator was found 20 residues downstream of the stop codon, suggesting that mip is encoded on a monocistronic message. The inferred polypeptide began with a possible 20- to 24-residue signal sequence, and, as predicted by two-dimensional electrophoresis, had a molecular weight of 24,868 and was a potent polycation with an estimated pI of 9.8.

Health science information management and continuing education of physicians. A survey of U.S. primary care practitioners and their opinion leaders.

Abstract: Purpose To identify self-perceived problems in managing science information needs of U.S. primary practitioners and their opinion leaders. Sample A two-stage random sample of the American Medical Association's "Masterlist of Physicians" to identify 625 office-based physicians, including general practice, family practice, internal medicine, obstetrics and gynecology, and pediatrics, and 100 physician opinion leaders. Data collection A formal telephone survey was completed for 79% of practitioners and 90% of opinion leaders sampled, using a pretested instrument applied by trained telephone surveyors. Results of data analysis Both practitioners and opinion leaders claimed that published reviews were the most useful means of identifying their information needs. When asked about use of six recent clinical advances, that is, "markers," for example, hemoglobin-A1C for diabetic control, as many as one fifth to one half were not using or were not aware of such an advance. Less than 1 in 3 practitioners personally searched the literature when information was needed; 2 in 3 claimed literature volume was unmanageable; 9 of 10 practitioners and opinion leaders assessed the scientific value of literature obtained, primarily from their own experience, with less than 1 in 10 contacting research methods specialists. Respondents suggested various innovations to better manage their science information needs in the future. Conclusions Primary practitioners require substantial help in meeting current science information needs. Increase in such resources as "validated reviews" or "expert networks" might help meet these needs.

Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology.

Abstract: Serotonin is released by activated platelets and may act as a mediator to initiate or sustain certain unstable syndromes of ischemic heart disease in humans. To determine whether or not serotonin concentration increases across the coronary bed in patients with severe, limiting angina, we measured central aortic and coronary sinus serotonin concentrations by a sensitive radioenzymatic assay in 39 patients with coronary artery disease and 13 patients with minimal or no coronary artery lesions as detected by arteriography. Although no difference existed in the mean aortic or coronary sinus serotonin concentrations between these two groups, elevated coronary sinus serotonin concentrations were detected in 23% of those with coronary artery disease. The coronary sinus and aortic serotonin concentration difference was greater in patients with significant coronary artery disease (0.6 +/- 6.62 ng/ml) compared with patients without significant coronary artery disease (-5.6 +/- 10.32 ng/ml) (mean +/- SD) (p less than 0.05). Further analysis revealed that patients with eccentric, irregular coronary artery lesions or intraluminal filling defects had a significantly elevated coronary sinus and aortic serotonin difference (3.1 +/- 5.54 ng/ml) compared with those with smooth concentric lesions (-1.9 +/- 6.61 ng/ml) (p less than 0.02). These data suggest that serotonin is released into the coronary circulation of some patients with coronary artery disease, especially those with frequent angina and complex coronary lesions. Although serotonin may be released in some patients with coronary artery disease, the specific pathophysiologic role of serotonin in the development or perpetuation of certain coronary syndromes in humans remains to be determined.

Peritoneovenous Shunting as Compared with Medical Treatment in Patients with Alcoholic Cirrhosis and Massive Ascites

Abstract: The optimal management of severe ascites in patients with alcoholic cirrhosis has not been defined. in a 5 1/2-year study, we randomly assigned 299 men with alcoholic cirrhosis, who had persistent or recurrent severe ascites despite a standard medical regimen, to receive either intensive medical treatment or peritoneovenous (LeVeen) shunting. We identified three risk groups: Group 1 had normal or mildly abnormal results on liver-function tests, Group 2 had more severe liver dysfunction or previous complications, and Group 3 had severe prerenal azotemia without kidney disease. For the patients who received the medical treatment and those who received the surgical treatment combined, the median survival times were 1093 days in Group 1, 222 days in Group 2, and 37 days in Group 3 (P less than or equal to 0.01) for all comparisons). For all the groups combined, the median time to the resolution of ascites was 5.4 weeks for medical patients and 3.0 weeks for surgical patients (P less than 0.01). Within each risk group, mortality during the initial hospitalization and median long-term survival were similar among patients receiving either treatment. However, the median time to the recurrence of ascites in Group 1 was 4 months in medical patients, as compared with 18 months in surgical patients (P = 0.01); in Group 2 it was 3 months in medical patients as compared with 12 months in surgical patients (P = 0.04). The median duration of hospitalization was longer in medical patients than in surgical patients (6.1 vs. 2.4 weeks in Group 1 [P less than 0.001] and 5.0 vs. 3.1 weeks in Group 2 [P less than 0.01]). Group 3 was too small to permit a meaningful comparison. During the initial hospitalization, the incidence of infections, gastrointestinal bleeding, and encephalopathy was similar among the medical and surgical patients. We conclude that peritoneovenous shunting alleviated disabling ascites more rapidly than medical management. However, survival was closely related to the severity of the illness at the time of randomization and was not altered by shunting.

The effects of muscle-building exercise on bone mineral density of the radius, spine, and hip in young men.

Abstract: We previously demonstrated that muscle-building exercise is associated with increases in serum Gla-protein, serum 1,25(OH)2D, and urinary cyclic AMP. These studies were interpreted to mean that this form of exercise increases bone formation and modifies the vitamin D-endocrine system to provide more calcium for bone. The present investigation was carried out in normal young adult white men to determine the effects of exercise on bone mineral density at weight-bearing and nonweight-bearing sites. Twelve men who had regularly engaged in muscle-building exercises (use of weights, exercise machines, or both) for at least 1 year and 50 age-matched controls (aged 19-40 years) were studied. The body weights of the two groups were not different from each other (78 +/- 2 vs. 74 +/- 1 kg, NS). Bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry, and BMD of the midradius was measured by single photon absorptiometry. It was found that muscle-building exercise was associated with increased BMD at the lumbar spine (1.35 +/- 0.03 vs. 1.22 +/- 0.02 g/cm2, P less than 0.01), trochanter (0.99 +/- 0.04 vs. 0.86 +/- 0.02 g/cm2, P less than 0.01), and femoral neck (1.18 +/- 0.03 vs. 1.02 +/- 0.02 g/cm2, P less than 0.001) but not at the midradius (0.77 +/- 0.02 vs. 0.77 +/- 0.01 g/cm2, NS). These studies provide additional evidence that muscle-building exercise is associated with increases in BMD at weight-bearing sites but not at nonweight-bearing sites.

Alterations in the Pulsatile Mode of Growth Hormone Release in Men and Women with Insulin-Dependent Diabetes Mellitus

Abstract: The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion time-series analysis. Compared to those in age-matched controls, integrated 24-h concentrations of GH were 2- to 3.5-fold higher in diabetic men (P = 0.002) and women (P = 0.0005). Both men and women with DM had over 50% more GH pulses per 24 h than their non-DM counterparts. In addition, maximal GH pulse amplitude was markedly elevated in the men and women with DM (P = 0.0019 and 0.0189, respectively). That the increase in maximal pulse amplitude was accounted for by greater baseline levels was documented by a higher interpulse valley mean GH concentration in the diabetics compared to the controls (P = 0.0437 and 0.0056, men and women, respectively) and the absence of any difference in incremental pulse amplitude for either sex (P greater than 0.05). DM men had larger GH pulse areas (P = 0.039) than control men, apparently accounted for by greater pulse width (P = 0.0037). Pulse areas in DM and non-DM women were indistinguishable. Time-series analysis revealed that the 24-h (circadian) rhythms of serum GH concentrations exhibited significantly increased amplitudes in the diabetic group as a whole (compared to the controls, P = 0.011). However, the times of maximal GH concentrations (acrophases) were not significantly different. As a group, serum insulin-like growth factor-I was lower in DM vs. non-DM individuals (P = 0.0014), although when separated by sex this difference did not reach statistical significance in women (P = 0.317). The present data confirm the higher circulating levels of GH previously reported to occur in individuals with poorly controlled DM. The altered frequency of GH pulses together with enhanced interpulse GH concentrations and an amplified circadian GH rhythm are compatible with hypothalamic dysfunction associated with dysregulation of somatostatin and/or GHRH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Prevalence of DSM-III personality disorders in the community.

Abstract: A community sample of adults with a standardized DSM-III, Axis II self-report instrument yielded an age adjusted community prevalence of 11.1% of DSM-111 personality disorders. When those with personality disorders (PDs) (n = 26) were compared to those without personality traits (n = 467) the PD group had less education 14.9 (3.0) years vs 16.5 (3.3) years,p = 0.02) and a greater percentage with difficulty with alcohol (19% vs 0.6%,p = 0.0001). Of those married, more 1 PDs reported marital difficulties (29% vs 3.5%,p = 0.002). There was a trend for the PD group to have longer unemployment (p = 0.07).

Load responsiveness of protein synthesis in adult mammalian myocardium: role of cardiac deformation linked to sodium influx.

Abstract: Exposure of adult mammalian myocardium to increased hemodynamic loads augments cardiac protein synthesis, ultimately leading to hypertrophy of the affected chamber. This established relationship between loading conditions and protein synthesis was examined in terms of two questions. First, is there a basic difference between the anabolic effect of a passive load imposed on diastolic myocardium and that of an active load generated by systolic myocardium? This issue was addressed by measuring [3H]phenylalanine incorporation into muscle protein in either quiescent or contracting ferret papillary muscles, set at known isometric lengths. Myocardial protein synthesis increased in proportion to total muscle tension in each case, with an equivalent relation describing both quiescent and contracting muscles. Synthesis of two contractile proteins, actin and myosin heavy chain, were enhanced by muscle loading. Thus, a quantitative rather than qualitative difference between the anabolic effects of diastolic and systolic loading was demonstrated. Second, since increased sodium influx is an initial cellular response requisite to the growth-inducing activity of many substances, and since sodium entry through stretch-activated ion channels is stimulated by deformation of the sarcolemma, does cardiac deformation during increased loading promote sodium influx as a signal to increase anabolic activity? In either quiescent or contracting papillary muscles, the rate of 24Na+ uptake was found to increase with load. Streptomycin, a cationic blocker of the mechanotransducer ion channels, was without effect on protein synthesis in stimulated but slack muscles; however, it inhibited, in a dose-related manner, the augmented protein synthesis otherwise observed in contracting muscles developing tension. At 500 microM, streptomycin did not reduce active tension, but it did reduce the synthesis of both actin and myosin heavy chain. In a second pharmacologic approach, inotropic agents were chosen which uniformly increased muscle tension development but which had contrasting effects on sodium influx. Protein synthesis increased in the presence of Na+ influx enhancers, monensin or veratridine; however, protein synthesis decreased in the presence of amiloride, a sodium influx inhibitor. Thus, myocardial protein synthesis varied directly with sodium influx despite the positive inotropic effect observed with each of these agents. In addition, inhibition of protein synthesis by ouabain demonstrated that activation of the Na+ pump is required for the anabolic effect of load.(ABSTRACT TRUNCATED AT 400 WORDS)

Can the provision of information to patients with osteoarthritis improve functional status? A randomized, controlled trial.

Abstract: After we assessed the functional status of 439 patients with osteoarthritis, we randomly assigned them to 1 of 3 intervention groups or to a control group. The interventions consisted of providing information, and differed only in the method of delivery: by phone, in person at the clinic, or both. Physical health improved (P = 0.02), pain was reduced (P = 0.02), and psychological health improved marginally (P = 0.10) in patients contacted by phone compared with those not contacted by phone. In those contacted only at the clinic, physical health worsened (P = 0.02), but neither pain (P = 0.80) nor psychological health (P = 0.90) differed from the values in patients not contacted at the clinic. We conclude that telephone contact is a useful intervention that can enhance the functional status of patients with osteoarthritis.

Posttraumatic stress disorder as a consequence of the POW experience.

Abstract: To estimate the relative contributions of trauma and premorbid disposition in the development and persistence of posttraumatic stress disorder (PTSD) symptoms, we conducted structured psychiatric interviews of 62 former World War II POWs. Half these men satisfied DSM-III criteria for PTSD in the year following repatriation. Eighteen (29%) continued to meet the criteria for PTSD 40 years later. Family history of mental illness and preexisting psychopathology were at best only weakly correlated with persistent PTSD symptoms. The strongest predictors of PTSD were proportion of body weight lost and the experience of torture during captivity. This study demonstrates that former POWs frequently develop posttraumatic stress disorder and that for one half of those who develop the symptoms, they persist for over 40 years. Familial risk factors and preexisting psychopathology are superseded by the overwhelming nature of the trauma. The persistence of the symptoms for many years is a reflection of the severity of the trauma.