Duration of antiviral immunity after smallpox vaccination.

Although naturally occurring smallpox was eliminated through the efforts of the World Health Organization Global Eradication Program, it remains possible that smallpox could be intentionally released. Here we examine the magnitude and duration of antiviral immunity induced by one or more smallpox vaccinations. We found that more than 90% of volunteers vaccinated 25-75 years ago still maintain substantial humoral or cellular immunity (or both) against vaccinia, the virus used to vaccinate against smallpox. Antiviral antibody responses remained stable between 1-75 years after vaccination, whereas antiviral T-cell responses declined slowly, with a half-life of 8-15 years. If these levels of immunity are considered to be at least partially protective, then the morbidity and mortality associated with an intentional smallpox outbreak would be substantially reduced because of pre-existing immunity in a large number of previously vaccinated individuals.

Neurotherapy of fibromyalgia?

OBJECTIVE: To evaluate the efficacy of a novel variant of electroencephalograph biofeedback, the Low Energy Neurofeedback System (LENS), that utilizes minute pulses of electromagnetic stimulation to change brainwave activity for the amelioration of fibromyalgia (FM) symptoms. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Tertiary referral academic medical center, outpatient. PATIENTS: Thirty-four patients diagnosed with FM according to 1990 American College of Rheumatology classification criteria. INTERVENTIONS: Active or sham LENS, depending on randomization, for 22 treatment sessions. OUTCOME MEASURES: Primary outcome measure was the Fibromyalgia Impact Questionnaire total score. Secondary outcome measures included number of tender points (TPs) and pressure required to elicit TPs on physical examination, quantitative sensory testing heat pain threshold, and self-reported cognitive dysfunction, fatigue, sleep problems, global psychological distress, and depression obtained at baseline, immediate post-treatment, and 3- and 6-month follow-up. RESULTS: Participants who received the active or sham interventions improved (Ps < 0.05) on the primary and a variety of secondary outcome measures, without statistically significant between group differences in evidence at post-treatment or 3- or 6-month follow-up. Individual session self-reported ratings of specific symptoms (cognitive dysfunction, fatigue, pain, and sleep, and overall activity level) over the course of the 22 intervention sessions indicated significant linear trends for improvement for the active intervention condition only (Ps < 0.05). CONCLUSION: LENS cannot be recommended as a single modality treatment for FM. However, further study is warranted to investigate the potential of LENS to interact synergistically with other pharmacologic and nonpharmacologic therapies for improving symptoms in FM.

Association of gammaA/gamma' fibrinogen levels and coronary artery disease.

GammaA/gamma' fibrinogen is a fibrinogen isoform that constitutes about 15% of total plasma fibrinogen. This isoform contains an additional binding site for zymogen factor XIII and for active thrombin, and forms fibrin clots that are resistant to fibrinolysis in vitro. Little is known about the variability of gammaA/gamma' fibrinogen levels in human populations, whereas total fibrinogen levels are known to increase with age and are higher in women than in men. In this report, evidence is presented that, in contrast to total fibrinogen levels, gammaA/gamma' fibrinogen levels showed no significant association with age or gender in a population of normal blood donors. A study of gammaA/gamma' fibrinogen levels in patients undergoing coronary angiography also showed that gammaA/gamma' fibrinogen levels were higher on average in coronary artery disease patients than in patients without coronary artery disease, and that this association was independent of total fibrinogen levels.

The dopamine transporter: importance in Parkinson's disease.

The dopamine transporter (DAT) may be the single most important determinant of extracellular dopamine concentrations. The importance of DAT in Parkinson's disease (PD) in which DAT may be reduced by 50 to 70% is unclear. We have examined the effects of methylphenidate (MPD), an inhibitor of DAT, administered alone or with levodopa, on parkinsonism measured with tapping and walking speeds, dyskinesia, subjective effects, and vital signs. MPD in oral doses of up to 0.4 mg/kg was well tolerated. Administered alone, MPD produced no objective improvement of parkinsonism. MPD, 0.4 mg/kg orally, coadministered with 2-hour levodopa infusions at 0.5 or 1.0mg/kg/hr increased the percentage of patients responding to the 0.5mg/kg/hr dose and prolonged the response to levodopa infusions as measured by tapping and walking speeds. Dyskinesia was prolonged in proportion to the increase in antiparkinson actions but severity was not increased. MPD decreased the hypotensive response to levodopa. In conclusion, MPD appeared to have no effect given alone but potentiated the effects of levodopa, particularly doses at threshold for clinical effects. These observations indicate that the residual DAT is functional in PD and is a potential target for symptomatic therapy of PD.

Evolution of the response to levodopa during the first 4 years of therapy.

The short-duration response, long-duration response, and dyskinetic response to levodopa change during long-term levodopa therapy. How these responses evolve, and which changes contribute to the emergence of motor fluctuations, remain unclear. We studied 18 subjects with Parkinson's disease before they began levodopa therapy and after 6, 12, 24, and 48 months of long-term levodopa therapy. The responses to 2-hour levodopa infusions after overnight and after 3 days of levodopa withdrawal were studied from 6 months onward. The mean magnitude of the short-duration response and the long-duration response measured after overnight without antiparkinsonian medications did not change during the 4 years. However, after 3 days without levodopa, it was apparent that the short-duration-response magnitude was progressively increasing (p < 0.0001) and that the long-duration response was decaying more rapidly (p = 0.0004). The short-duration-response magnitude at 4 years was inversely related to the long-duration-response magnitude (p = 0.022), suggesting that the long-duration response was one determinant of the short-duration-response magnitude. Dyskinesia increased progressively in severity during the study (p = 0.013). The duration of the short-duration response and dyskinesia did not change during the 4 years. Subject reports of motor fluctuations tended to be associated with a large short-duration response (p = 0.054). We suggest that a larger long-duration response, rather than a shortened one, is more important to the development of fluctuations. Improving the baseline or practical-off motor function to reduce the magnitude of the short-duration response may be a strategy to treat fluctuations.

Modifiable patient factors are associated with reverse vein graft occlusion in the era of duplex scan surveillance.

OBJECTIVE: Modifiable patient factors that contribute to graft occlusion may be addressed after surgery. To determine risk factors associated with reverse vein graft (RVG) occlusion, we examined the characteristics and duplex scan surveillance (DS) patterns of patients with RVGs. METHODS: Patients treated with RVG from January 1996 through December 2000 were identified from a prospective registry. The study population consisted of all patients with RVGs performed during the study period with grafts that subsequently occluded. Patients whose grafts remained patent served as age-matched and gender-matched control subjects. The prescribed DS regimen was every 3 months for the first postoperative year and every 6 months thereafter. Early DS failure was defined as having no DS within the first 3 months. Cox proportional hazards analysis was used to compare the two groups. Hazard ratios were calculated. RESULTS: During the study period, 674 patients underwent RVG. Fifty-five patients with occluded RVGs were compared with 118 with patent RVGs. The follow-up period for occluded grafts was 13.40 +/- 12.59 months and for patent grafts was 32.40 +/- 15.61 months. Dialysis therapy, a known hypercoagulable state, continued smoking, and DS failure were independent factors associated with RVG occlusion. The hazards ratio for dialysis was 6.45 (95% CI, 3.07 to 13.51; P <.001), for current smoking was 4.72 (95% CI, 2.5 to 8.85; P <.001), for hypercoagulable state was 2.99 (95% CI, 1.47 to 6.10; P =.003), and for early DS failure was 2.43 (95% CI, 1.29 to 4.59; P =.006). CONCLUSION: Continued smoking and failure to undergo DS within the first three postoperative months are modifiable factors associated with RVG occlusion. Smoking cessation and graft surveillance must be stressed to optimize patency of infrainguinal RVGs.

Relationship between site of initial symptoms and subsequent progression of disease in a prospective study of atherosclerosis progression in patients receiving long-term treatment for symptomatic peripheral arterial disease.

PURPOSE: There have been few studies of the natural history of peripheral arterial disease (PAD), and none have used serial noninvasive laboratory examinations for the objective quantification of disease progression. The relationship between the site of initial symptoms of PAD (lower-extremity disease [LED] vs cerebrovascular disease [CVD]) and the site of subsequent symptomatic progression (LED vs CVD vs coronary heart disease [CHD]) has not been examined. METHODS: This is a long-term, blinded prospective clinical research study of the relationship of PAD progression to multiple clinical, laboratory, and noninvasive vascular laboratory parameters. Patients with symptomatic LED, CVD, or both underwent comprehensive risk-factor assessment and were seen every 6 months for follow-up examinations. In addition to history and physical examination, all subjects underwent serial noninvasive lower-extremity and carotid artery testing. The relationship between the initial symptomatic site(s) and subsequent progression was examined by means of multivariate proportional hazards analysis, which was adjusted for age, diabetes mellitus, hypertension, smoking, cholesterol, homocysteine level, lowest initial ankle/brachial index (ABI), worst carotid stenosis, ABI progression, and carotid stenosis progression, because each of these factors was significantly associated with one or more aspects of progression. RESULTS: There were 397 study subjects (mean age, 66 years; 38% women) with a mean follow-up period of 48.5 months. LED was initially present in 88% of subjects and CVD in 37% of subjects (both were present in 25% of subjects). There were 78 deaths, 47 (60%) of which were caused by cardiovascular disease (18% mortality rate after 5 years by means of life table). Progression of disease as documented by means of vascular laboratory findings occurred in 90% of subjects by means of life table after 5 years (ABI progression, 31%; carotid stenosis progression, 40%). Symptomatic clinical progression of disease occurred in 52% of subjects by means of life table after 5 years (LED progression, 22%; CVD progression, 23%; CHD progression, 31%). By means of multivariate analysis, no significant relationship was found between the site of initial symptoms of PAD and the site(s) of subsequent symptomatic clinical progression (LED vs CVD vs CHD; P = not significant for all hazard ratios). CONCLUSION: Patients with symptomatic PAD experience symptoms of ongoing LED, CVD, and CHD with a frequency that is not influenced by the site(s) of their original symptoms. The hypothesis that lesions and resulting symptoms of systemic atherosclerosis occur at various anatomic sites as a matter of random chance should be tested with other studies.