Dayton VA Medical Center

BACKGROUND: Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed. METHODS: We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy. RESULTS: Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004). CONCLUSIONS: Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).

BACKGROUND: Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1β, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit. METHODS: We conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revascularization was added to the primary end point. RESULTS: The trial was stopped after a median follow-up of 2.3 years. Methotrexate did not result in lower interleukin-1β, interleukin-6, or C-reactive protein levels than placebo. The final primary end point occurred in 201 patients in the methotrexate group and in 207 in the placebo group (incidence rate, 4.13 vs. 4.31 per 100 person-years; hazard ratio, 0.96; 95% confidence interval [CI], 0.79 to 1.16). The original primary end point occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs. 3.43 per 100 person-years; hazard ratio, 1.01; 95% CI, 0.82 to 1.25). Methotrexate was associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non-basal-cell skin cancers than placebo. CONCLUSIONS: Among patients with stable atherosclerosis, low-dose methotrexate did not reduce levels of interleukin-1β, interleukin-6, or C-reactive protein and did not result in fewer cardiovascular events than placebo. (Funded by the National Heart, Lung, and Blood Institute; CIRT ClinicalTrials.gov number, NCT01594333.).

Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC.

Importance: More than half of patients with acute ischemic stroke have minor neurologic deficits (National Institutes of Health Stroke Scale [NIHSS] score of 0-5) at presentation. Although prior major trials of alteplase included patients with low NIHSS scores, few without clearly disabling deficits were enrolled. Objective: To evaluate the efficacy and safety of alteplase in patients with NIHSS scores of 0 to 5 whose deficits are not clearly disabling. Design, Setting, and Participants: The PRISMS trial was designed as a 948-patient, phase 3b, double-blind, double-placebo, multicenter randomized clinical trial of alteplase compared with aspirin for emergent stroke at 75 stroke hospital networks in the United States. Patients with acute ischemic stroke whose deficits were scored as 0 to 5 on the NIHSS and judged not clearly disabling and in whom study treatment could be initiated within 3 hours of onset were eligible and enrolled from May 30, 2014, to December 20, 2016, with final follow-up on March 22, 2017. Interventions: Participants were randomized to receive intravenous alteplase at the standard dose (0.9 mg/kg) with oral placebo (n = 156) or oral aspirin, 325 mg, with intravenous placebo (n = 157). Main Outcomes and Measures: The primary outcome was the difference in favorable functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days via Cochran-Mantel-Haenszel test stratified by pretreatment NIHSS score, age, and time from onset to treatment. Because of early termination of the trial, prior to unblinding or interim analyses, the plan was revised to examine the risk difference of the primary outcome by a linear model adjusted for the same factors. The primary safety end point was symptomatic intracranial hemorrhage (sICH) within 36 hours of intravenous study treatment. Results: Among 313 patients enrolled at 53 stroke networks (mean age, 62 [SD, 13] years; 144 [46%] women; median NIHSS score, 2 [interquartile range {IQR}, 1-3]; median time to treatment, 2.7 hours [IQR, 2.1-2.9]), 281 (89.8%) completed the trial. At 90 days, 122 patients (78.2%) in the alteplase group vs 128 (81.5%) in the aspirin group achieved a favorable outcome (adjusted risk difference, -1.1%; 95% CI, -9.4% to 7.3%). Five alteplase-treated patients (3.2%) vs 0 aspirin-treated patients had sICH (risk difference, 3.3%; 95% CI, 0.8%-7.4%). Conclusions and Relevance: Among patients with minor nondisabling acute ischemic stroke, treatment with alteplase vs aspirin did not increase the likelihood of favorable functional outcome at 90 days. However, the very early study termination precludes any definitive conclusions, and additional research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02072226.

Fatigue and workplace sleepiness are consequences of modern industrial society. Fatigue is a complex biological phenomenon that occurs as a function of time awake, time-of-day, workload, health, and off-duty lifestyle. Fatigue is a function of two major biological factors - the homeostatic drive for sleep and circadian rhythm of sleepiness. The greatest cause of fatigue is insufficient or disrupted sleep. Excessive sleepiness in the workplace and on highways is a serious safety hazard, and insufficient or disrupted sleep results in numerous accidents and adverse mental and physical health outcomes. Evidence-based strategies that promote better sleep and optimize work/rest schedules can mitigate the impact of fatigue and sleep loss. Proper nap and sleep scheduling, work breaks, modeling and monitoring tools, fatigue detection technologies, and pharmacological countermeasures can be implemented at home and/or in the workplace to reduce performance and safety hazards. Education about obtaining adequate sleep, the dangers of fatigue in terms of both health and cognitive consequences, and the availability of scientifically-proven sleep-enhancement and alertness-management strategies is essential.

PURPOSE: To evaluate the accuracy, safety, and clinical utility of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) of pancreatic masses. METHODS: Forty-seven patients were referred for EUS with a pancreatic mass and suspicion of pancreatic cancer based upon painless obstructive jaundice, epigastric abdominal pain plus weight loss/anorexia, or idiopathic pancreatitis. All patients underwent EUS with both radial (Olympus UM20) and linear array (Pentax FG32-UA) systems. After TNM staging by EUS, ultrasound directed FNA of the pancreatic mass was performed using a 23 gauge, 4 cm long needle. RESULTS: EUS-guided FNA was performed in all 47 patients. Results: successful targeting = 100%, adequate cellularity = 100%, FINDINGS: adeno Ca = 25, squamous cell Ca = 1, lymphoma = 1, poorly differentiated Ca= 1, atypical cytology or suspicious for carcinoma = 9, no malignant cells = 10. The sensitivity, specificity, positive predictive value and negative predictive value of EUS-guided pancreatic FNA for the diagnosis of malignancy was 64%, 100%, 100% and 16% respectively. CONCLUSIONS: EUS with FNA is useful for detection of malignancy in a pancreatic mass. The procedure appears to have a complication rate of 2%. Impact of this technique on clinical management of patients needs further evaluation.

It was hypothesized that the metabolic effects of caffeine, which can be objectively measured (i.e. physiological, “arousal”), could be used to develop a physiological arousal model of chronic insomnia in a group of normal young adults. Twelve normal young adult males participated for 11 nights after laboratory adaptation. Subjects received 400 mg of caffeine three times a day for 7 nights and days. As predicted, the use of caffeine resulted in increased metabolic rate. Sleep efficiency was significantly reduced by caffeine and multiple sleep latency tests (MSLTs) were significantly increased. Some adaptation to the metabolic, sleep efficiency, and MSLT effects of caffeine was seen over the week of administration. Withdrawal effects (i.e. rebound sleep or sleepiness) were not seen for metabolic, MSLT or sleep variables. The data indicated that caffeine was effective in producing significant metabolic and sleep effects and that those effects were related. The results were consistent with the interpretation that a chronic decrease in sleep efficiency associated with increased physiological arousal, although producing subjective dysphoria, does not produce a physiological sleep debt.

Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification).

BACKGROUND: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease. METHODS: We conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≥4 weeks in adults. RESULTS: Nineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (-5.7 [-9.0, -2.3] mmHg), diastolic blood pressure (-1.7 [-3.4, -0.1] mmHg) and glomerular filtration rate (-3.2 [-5.4, -1.0] mL/min/1.73 m(2)). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse. CONCLUSIONS: Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit.

OBJECTIVE: Sleep State Misperception insomnia has been commonly viewed as a perceptual or psychological problem. It was hypothesized that Sleep State Misperception insomnia, like psychophysiological insomnia, could be associated with increased physiological activation, here indexed by whole body metabolic rate. METHOD: Groups of nine patients with Sleep State Misperception insomnia and age-, sex-, and weight-matched normal sleepers were evaluated on sleep, performance, mood, personality, and metabolic measures over a 36-hour sleep laboratory stay. RESULTS: Sleep State Misperception insomniacs had a subjective history of poor sleep and perceived their laboratory sleep as poor but had electroencephalogram (EEG) parameters that did not differ statistically from matched normal controls. Sleep State Misperception insomniacs had abnormal MMPI values and were subjectively more confused, tense, depressed, and angry than matched normals. Sleep State Misperception insomniacs also had a significantly increased 24-hour metabolic rate, compared with matched normals. CONCLUSIONS: The overall increase in whole body oxygen use was less than that seen in psychophysiological insomniacs but was consistent with the view that Sleep State Misperception insomnia may be a mild version or a precursor to psychophysiological insomnia.

BACKGROUND: Health risks associated with smoking have been exhaustively documented and include increased incidence of periodontal disease, greater risk of osteitis following oral surgery, and compromised wound healing due to hypoxia. Information related directly to dental implants, although limited, points to higher rates of implant failures among smokers than non-smokers. This paper reports on long-term clinical outcomes of osseointegrated dental implants placed in smokers and non-smokers in a longitudinal clinical study of endosseous dental implants. METHODS: In 1990, the Dental Implant Clinical Research Group (DICRG) of the Department of Veterans Affairs (DVA) launched an 8-year, randomized, prospective clinical study of more than 2,900 endosseous dental implants in more than 800 patients at 32 study centers. Confounding variables, including smoking patterns, were recorded. For this report, new follow-up data were analyzed for two groups: 1) current smokers and 2) those who never smoked combined with those who quit. Most of the variables recorded for each implant were screened on a univariate basis as possible predictors associated with implant survival/failure. Those with P values less than 0.15 and those likely to be a factor of clinical importance were placed in a logistic regression equation and analyzed for a simultaneous effect on survival. A step-wise procedure was used to eliminate those variables that showed the least significance, until only those variables with a Wald chi-square of significance in the presence of others remained. The effects of clustering within patients and of unbalanced distribution within hospitals were standardized to facilitate analysis of influence of demographic variables. The GEE analysis was performed with the patient as the primary cluster. RESULTS: Current data do not support earlier findings that smoking contributes to early implant failure (placement to uncovering). A trend of greater failures in smokers appeared between the time after uncovering and before insertion of the prosthesis. Hydroxyapatite (HA)-coated implants had significantly lower failure rates. For the entire 3-year period, overall failures were significantly higher for smokers than non-smokers. CONCLUSIONS: Results suggest that increased implant failures in smokers are not the result of poor healing or osseointegration, but of exposure of peri-implant tissues to tobacco smoke. Data also suggest that detrimental effects may be reduced by: 1) cessation of smoking; 2) the use of preoperative antibiotics; and 3) the use of HA-coated implants.

The growing incidence of melanoma is a serious public health issue that merits a thorough understanding of potential causative risk factors, which includes exposure to ultraviolet radiation (UVR). Though UVR has been classified as a complete carcinogen and has long been recognized for its ability to damage genomic DNA through both direct and indirect means, the precise mechanisms by which the UVA and UVB components of UVR contribute to the pathogenesis of melanoma have not been clearly defined. In this review, we therefore highlight recent studies that have addressed roles for UVA radiation in the generation of DNA damage and in modulating the subsequent cellular responses to DNA damage in melanocytes, which are the cell type that gives rise to melanoma. Recent research suggests that UVA not only contributes to the direct formation of DNA lesions but also impairs the removal of UV photoproducts from genomic DNA through oxidation and damage to DNA repair proteins. Moreover, the melanocyte microenvironment within the epidermis of the skin is also expected to impact melanomagenesis, and we therefore discuss several paracrine signaling pathways that have been shown to impact the DNA damage response in UV-irradiated melanocytes. Lastly, we examine how alterations to the immune microenvironment by UVA-associated DNA damage responses may contribute to melanoma development. Thus, there appear to be multiple avenues by which UVA may elevate the risk of melanoma. Protective strategies against excess exposure to UVA wavelengths of light therefore have the potential to decrease the incidence of melanoma. Environ. Mol. Mutagen. 59:438-460, 2018. © 2018 Wiley Periodicals, Inc.

A yoked control study used sleep recordings from 10 insomniacs to produce similar sleep patterns in a group of matched normal sleepers for 7 nights to determine if specific electroencephalographic (EEG) sleep patterns were responsible for the secondary insomnia symptoms reported by the insomniacs. Specifically, it was found that insomniacs display increased tension/confusion, decreased vigor, personality disturbance, subjective over-estimation of poor sleep, increased body temperature, increased 24-hour whole body metabolic rate, and increased multiple sleep latency test (MSLT) values. Normal sleepers given the nocturnal EEG parameters of insomniacs displayed decreased tension, decreased vigor, decreased body temperature, and decreased MSLT values. The spectrum of changes seen in the normal sleepers given an insomniac sleep pattern was characteristic of mild partial sleep deprivation and not consistent with symptoms found in patients with primary insomnia. It was concluded that the secondary symptoms reported by patients with primary insomnia are probably not related to their poor sleep per se. Data from previous studies that varied physiological arousal were used to support the contention that the secondary symptoms of insomnia, including poor sleep, occur secondary to central nervous system hyperarousal.

OBJECTIVE: Hospital-acquired Legionella pneumonia has a fatality rate of 28%, and the source is the water distribution system. Two prevention strategies have been advocated. One approach to prevention is clinical surveillance for disease without routine environmental monitoring. Another approach recommends environmental monitoring even in the absence of known cases of Legionella pneumonia. We determined the Legionella colonization status of water systems in hospitals to establish whether the results of environmental surveillance correlated with discovery of disease. None of these hospitals had previously experienced endemic hospital-acquired Legionella pneumonia. DESIGN: Cohort study. SETTING: Twenty US hospitals in 13 states. INTERVENTIONS: Hospitals performed clinical and environmental surveillance for Legionella from 2000 through 2002. All specimens were shipped to the Special Pathogens Laboratory at the Veterans Affairs Pittsburgh Medical Center. RESULTS: Legionella pneumophila and Legionella anisa were isolated from 14 (70%) of 20 hospital water systems. Of 676 environmental samples, 198 (29%) were positive for Legionella species. High-level colonization of the water system (30% or more of the distal outlets were positive for L. pneumophila) was demonstrated for 6 (43%) of the 14 hospitals with positive findings. L. pneumophila serogroup 1 was detected in 5 of these 6 hospitals, whereas 1 hospital was colonized with L. pneumophila serogroup 5. A total of 633 patients were evaluated for Legionella pneumonia from 12 (60%) of the 20 hospitals: 377 by urinary antigen testing and 577 by sputum culture. Hospital-acquired Legionella pneumonia was identified in 4 hospitals, all of which were hospitals with L. pneumophila serogroup 1 found in 30% or more of the distal outlets. No cases of disease due to other serogroups or species (L. anisa) were identified. CONCLUSION: Environmental monitoring followed by clinical surveillance was successful in uncovering previously unrecognized cases of hospital-acquired Legionella pneumonia.

The purpose of this paper is to review the exercise physiology literature on spinal cord injured individuals with quadriplegia performing voluntary arm exercise and/or electrically stimulated leg exercise. The effects of level of injury, active muscle mass, and sympathetic dysfunction on acute physiologic adjustments during exercise testing and chronic training adaptations are discussed. Several topics for future research are suggested, including methods to achieve higher aerobic/cardiovascular fitness, reduce secondary cardiovascular/pulmonary disabilities and related health care costs, and promote health, wellness, and an active lifestyle.

Many patients with chronic obstructive pulmonary disease (COPD) receiving supplemental oxygen state that this treatment makes them less short of breath at rest. We postulated that this phenomenon may be related to improved arterial oxygenation, reduced ventilation, or stimulation of nasal receptors caused by the flow of gas. Eight patients who reported this phenomenon were studied in a quiet room. Each patient received zero flow, 2, or 4 L/min of air or oxygen through nasal cannula for 5 min at each level in random order in a single blind manner. At the end of each period, arterial blood gas composition was measured, and breathlessness was assessed with a visual analog scale. The scale was calibrated to read from zero (not at all breathless) to 100 (extremely short of breath). The entire protocol was repeated after application of topical lidocaine to the nasal passages. Results were assessed by analysis of variance. We found no significant effect of inspired oxygen concentration, gas flow, arterial oxygen tension, or arterial carbon dioxide tension on breathlessness. There was, however, a significant increase in breathlessness after nasal anesthesia from 44 +/- 3 SEM to 52 +/- 4 SEM (p less than 0.005). We suggest that the reduction of breathlessness in these patients by nasal oxygen is a placebo effect caused by wearing the nasal cannulas and is unrelated to gas flow or the increased arterial oxygen tension.

Previous studies have shown that performance during sleep loss is improved by prophylactic naps as a function of varying nap length. Based on single-dose caffeine studies, a similar dose-response effect has been hypothesized on performance, alertness and mood during sleep loss. The present study compared the effects of repeated versus single-dose administration of caffeine and varying amounts of sleep taken prior to sleep loss on performance, mood and physiological measures during 2 nights and days of sleep loss. A total of 140 normal, young adult males participated at one of two study sites. Ninety-eight subjects at one site were randomly assigned to one of four nap conditions (0, 2, 4 or 8 hours) and 42 subjects at the second site were assigned to one of four caffeine conditions. After a normal baseline night of sleep and morning baseline tests of performance, mood and nap latency, subjects in the nap groups returned to bed at noon, 1600 hours, 1800 hours or not at all. Bedtimes were varied so that all naps ended at 2000 hours. Subjects in the caffeine groups received either a single 400-mg dose of caffeine at 0130 hours each night or repeated doses of 150 or 300 mg every 6 hours starting at 0130 hours on the 1st night of sleep loss. A placebo control group (no nap and placebo administered every 6 hours on the repeated caffeine schedule) was run at both sites. Subjects remained awake and followed the same schedule of computer-administered performance tests, mood scales, multiple sleep latency test observations and meals/breaks for 52 hours before being allowed a recovery night of sleep at their normal sleep time. Results are consistent with previous findings and suggest that performance, mood and alertness are directly proportional to prophylactic nap length. Furthermore, an 8-hour nap is superior in maintaining performance, mood and alertness to either single or repeated caffeine administrations. Naps, in general, provided longer and less graded changes in performance, mood and alertness than did caffeine, which displayed peak effectiveness and loss of effect within about 6 hours. Shorter prophylactic naps and small repetitive doses of caffeine, however, did maintain performance, mood and alertness during sleep loss significantly better than no naps or large single doses of caffeine. Neither nap nor caffeine conditions could preserve performance, mood and alertness near baseline levels beyond 24 hours, after which levels approached those of placebo.

Multiple sclerosis (MS) is a neurological disease characterized by a variety of potentially debilitating symptoms. The manner in which the disease affects each individual is unique; however, many individuals with MS have a normal life expectancy and remain ambulatory throughout their lives. Very little research has focused on understanding how MS affects basic physiologic responses during exercise. Four general topics have been addressed: autonomic control of heart rate (HR) and arterial blood pressure (BP), cardiorespiratory fitness, skeletal muscle function, and symptom instability under thermal stress. Abnormalities in cardiovascular reflexes have been observed in some MS individuals during quiescent testing; however, HR and BP responses during exercise have not confirmed such findings. Deficits in cardio-respiratory fitness appear to be present in moderately impaired individuals, which are not always present in minimally impaired persons. Similarly, abnormalities in skeletal muscle function have been reported in some individuals with MS, while absent in others. Training appears to improve both cardiorespiratory fitness and skeletal muscle function. Findings appear to be indirectly influenced by the level of physical impairment of the experimental sample. This factor needs to be considered in sample selection, as well as in analyzing and reporting data. Elicitation of symptoms in response to thermal stressors has been documented by several investigators using unreliable techniques to measure core temperature. The use of more valid methods during rest and exercise have not confirmed the relationship between symptoms and core temperature changes. It may be that thermal sensitivity, although typically reported by most MS individuals, is a symptom that is very unique to each individual and sample selection may have indirectly contaminated results in past research. Considerations for future research are discussed.

Smoking has been reported to have a deleterious effect on the oral cavity. Research has associated smoking with oral cancer, periodontal disease, leukoplakia, stomatitis nicotina, and impaired gingival bleeding. In 1991 the Dental Implant Clinical Research Group initiated a prospective, randomized clinical study in cooperation with the Department of Veterans Affairs to investigate the influence of implant design, application, and site of placement on long-term clinical performance and crestal bone height. Over 70 dental and medical history variables and exclusion factors were analyzed to determine relationships, if any, with implant failure at the time of second-stage surgery. The variables were analyzed separately for individual implants, cases (prostheses), and patients. The cases ranged from one to five implants each, and more than one case from a single patient could be included in the investigation. At this interim analysis, 2,066 implants have been placed representing 433 cases in 310 patients. With regard to implant failure rates, possible exclusion variable (9) and medical history variables (39) were not found to be statistically significant. For the dental history variables (23), only the question related to smoking was statistically significant on an implant, case, and patient basis (P < 0.007). Results of this interim analysis suggest that smoking is detrimental to implant success.

This study was conducted to evaluate a newly designed functional neuromuscular stimulation (FNS)-induced knee extension (KE) exercise system that incorporates the most desired features of previously described systems by determining the musculoskeletal responses of spinal cord injured (SCI) individuals to training. A specially designed chair and electrical stimulator were fabricated for FNS-induced KE resistance exercise. Surface electrodes were placed over motor points of the quadriceps muscles, and KE was alternated between legs at an average rate of 6 KE/min/leg. KE testing protocols were developed for pre- and post-training evaluations of performance, and 12 SCI subjects exercise-trained up to three times per week for 36 sessions using a progressive resistance load at ankle level. Pre- and post-training evaluation data were statistically compared using a 0.05 level for significance. Quadriceps muscle performance (strength x repetitions) improved for both legs in all subjects as indicated by significant increases in load resistance and repetitions over the 36-session training period (right leg mean = 1156.0 versus 1624.8 kg.reps, left leg mean = 1127.3 versus 1721.1 kg.reps). In addition, knee range of motion significantly increased (right leg mean = 134 versus 146 degrees, left leg mean = 133 versus 144 degrees). Thigh skinfold, thigh girth, body weight and bone density were not significantly changed. The lack of decrease in bone density in some subjects suggests that the training may retard the rate of bone loss which typically occurs with SCI. No injuries or problems were encountered during testing and training.(ABSTRACT TRUNCATED AT 250 WORDS)