This investigation uses a system for inducing and detecting anti-tetanus toxoid antibody (anti-TT) synthesis to study specific antibody (Ab) synthesis by bone marrow mononuclear cells (MC). We ...measured the amounts of anti-TT secreted and the number of B cells secreting antibody (Ab). The ELISA plaque detects single B cells secreting specific Ab. The results show that (1) spontaneous anti-TT secretion by MC is higher than spontaneous anti-TT secretion by peripheral blood lymphocytes (PBL) using an ELISA plaque (P less than 0.01); (2) spontaneous anti-TT production by MC correlated with the serum anti-TT titers as measured by an ELISA (r = 0.75, P = 0.005); (3) two types of marrow B cells were identified--one that spontaneously secretes anti-TT and another that produces anti-TT after TT-stimulation; (4) the frequency of anti-TT-secreting B cells is higher in MC than in PBL; (5) the amount of Ab secreted per marrow B cell is not different from that secreted by a peripheral B cell; and (6) marrow B cells could be induced to produce anti-TT in vitro up to 10 months without added cytokines. These results show that bone marrow is a major repository for differentiated B cells that spontaneously produce Abs to maintain circulating Abs titers and for memory B cells that can be induced to produce specific Ab.
Background Few studies have investigated the long-term association between inhaled corticosteroids (ICSs) and lung function decline in asthma. Objective To evaluate whether prolonged treatment with ...ICSs is associated with FEV1 decline in adults with asthma. Methods An international cohort of 667 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1999 to 2002. Spirometry was performed on both occasions. FEV1 decline was analyzed according to age, sex, height, body mass index, total IgE, time of ICS use, and smoking, while adjusting for potential confounders. Results As ICS use increased, the decline in FEV1 was lower ( P trend = .025): on average, decline passed from 34 mL/y in nonusers (half of the sample) to 20 mL/y in subjects treated for 48 months or more (18%). When adjusting for all covariates, there was an interaction ( P = .02) between ICS use and total IgE: in subjects with high (>100 kU/L) IgE, ICS use for 4 years or more was associated with a lower FEV1 decline (23 mL/y; 95% CI, 8-38 compared with nonusers). This association was not seen in those with lower IgE. Conclusion Although confirming a beneficial long-term association between ICSs and lung function in asthma, our study suggests that subjects with high IgE could maximally benefit from a prolonged ICS treatment. Clinical implications This study adds further evidence to the beneficial effect of inhaled steroids on lung function in asthma; future studies will clarify whether calibrating the corticosteroid dose according to the level of total IgE is a feasible approach in asthma management.
The upper cervical component of the spinomesencephalic tract and cranial nerves V, VII (nervus intermedius), IX, and X are involved in mechanisms of acute and chronic pain from head and neck ...structures. To date there is no reliable method for relief of refractory pain (i.e., pain that cannot be relieved by conventional pharmacologic therapies) from these structures. Therefore, we explored continuous intracisternal infusion of bupivacaine for the treatment of refractory pain of the head and neck.
Intracisternal catheters were inserted in 13 adults with refractory nonmalignant (n = 4) and malignant (n = 9) pain from the head, face, mouth, neck, and upper extremities; 0.5% plain bupivacaine was infused continuously at rates of 1-7 (median 1.5) mg/h with optional bolus doses of 0.5-2.0 mg 4-2 times/h. The efficacy was assessed from pain relief (daily VAS(max), VAS(min), and VAS(mean) scores 0-10), daily doses of intracisternal bupivacaine and total opioid (expressed as mg parenteral morphine-eq), amount of nocturnal sleep, and rates of adverse effects.
The 13 patients were treated for 3-182 days (median 37, total 712 days), 3 patients being treated at home for 10-112 days (median 88, total 210 days). In one patient, the efficacy of the treatment could not be estimated because of advanced senility. Eleven of the remaining 12 patients obtained acceptable pain relief with daily doses of intracisternal bupivacaine ranging from 20 to 118 mg (median 37 mg): VAS(mean) scores decreased from 7 to 2, mean pain relief increased for 30% to 80%, total opioid daily dose decreased from 53 to 36 mg parenteral morphine-eq, and nocturnal sleep increased from 2 to >6h (all figures are median values). Speech, eating, walking, and natural functions were generally not affected. Side effects such as tiredness and malaise, somnolence and sleep, feeling of coldness in the neck and skull base, transient post-spinal puncture headache, paresthesias, hoarseness, dysphagia, transient paresis of the upper/lower extremities, episodic miosis and conjunctival hyperemia, and transient orthostatic arterial hypotension were each observed in one or two patients. No patient presented clinical evidence of phrenic nerve paralysis. There was no nausea or vomiting. No persistent neurologic deficit or death could be attributed to the intracisternal pain treatment.
Continuous intracisternal infusion of bupivacaine may be a useful method in exceptional, well selected patients with refractory pain from the head and neck structures. Further studies are necessary to establish the indications and the safety of the method.
Background It has been suggested that sleep-disordered breathing (SDB) is a risk factor for diabetes, but long-term follow-up studies are lacking. The aim of this community-based study was to analyze ...the influence of SDB on glucose metabolism after > 10 years. Methods Men without diabetes (N = 141; mean age, 57.5 years) were investigated at baseline, including whole-night respiratory monitoring. After a mean period of 11 years and 4 months, they were followed up with an interview, anthropometric measurements, and blood sampling. Insulin resistance was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). ΔHOMA-IR was calculated as (HOMA-IR at follow-up − HOMA-IR at baseline). An oral glucose tolerance test was performed on 113 men to calculate the insulin sensitivity index. Results The mean apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) at baseline were 4.7 and 3.3, respectively. At follow-up, 23 men had diabetes. An ODI > 5 was a predictor of developing diabetes (OR, 4.4; 95% CI, 1.1-18.1, after adjusting for age, BMI, and hypertension at baseline and ΔBMI and years with CPAP during follow-up). The ODI was inversely related to the insulin sensitivity index at follow-up ( r = −0.27, P = .003). A deterioration in HOMA-IR was significantly related to all variables of SDB (AHI, AHI > 5; ODI, ODI > 5; minimum arterial oxygen saturation), even when adjusting for confounders. When excluding the variable years with CPAP from the multivariate model, all associations weakened. Conclusions SDB is independently related to the development of insulin resistance and, thereby, the risk of manifest diabetes mellitus.
Virtually all known exoplanets reside around stars with \(M<2.3~M_\odot\); to clarify if the dearth of planets around more massive stars is real, we launched the direct-imaging B-star Exoplanet ...Abundance STudy (BEAST) survey targeting B stars (\(M>2.4~M_\odot\)) in the young (5-20 Myr) Scorpius-Centaurus association (Sco-Cen). Here we present the case of a massive (\(M \sim 9~M_\odot\)) BEAST target, \(\mu^2\) Sco. Based on kinematic information, we found that \(\mu^2\) Sco is a member of a small group which we label Eastern Lower Scorpius, refining in turn the precision on stellar parameters. Around this star we identified a robustly detected substellar companion (\(14.4\pm 0.8 M_J\)) at a projected separation of \(290\pm 10\) au, and a probable second object (\(18.5\pm 1.5 M_J\)) at \(21\pm 1\) au. The planet-to-star mass ratios of these objects are similar to that of Jupiter to the Sun, and their irradiation is similar to those of Jupiter and Mercury, respectively. The two companions of \(\mu^2\) Sco are naturally added to the giant planet b Cen b recently discovered by BEAST; although slightly more massive than the deuterium burning limit, their properties resemble those of giant planets around less massive stars and they are better reproduced by a formation under a planet-like, rather than a star-like scenario. Irrespective of the (needed) confirmation of the inner companion, \(\mu^2\) Sco is the first star that would end its life as a supernova that hosts such a system. The tentative high frequency of BEAST discoveries shows that giant planets or small-mass brown dwarfs can form around B stars. When putting this finding in the context of core accretion and gravitational instability, we conclude that the current modeling of both mechanisms is not able to produce this kind of companion. BEAST will pave the way for the first time to an extension of these models to intermediate and massive stars. (abridged)
The present results demonstrate that chronic nicotine treatment can in part protect against mechanically-induced and neurotoxin-induced degeneration of nigrostriatal DA neurons. These results ...indicate that in sufficient doses chronic treatment with nicotine may be considered in the pharmacological treatment of Parkinson's disease. It remains to be demonstrated whether these protective actions can be extended to include also other injured neurons such as the cholinergic neurons, known to be severely affected in Alzheimer's disease.
Highlights • More men than women report habitual snoring. • Women are more likely than men to report daytime sleepiness. • Self-reported exposure to traffic pollution and noise is associated with ...daytime sleepiness. • Self-reported exposure to traffic noise increase the risk of habitual snoring.
The recognition of 16 mycobacterial Ags by a panel of T cell lines from leprosy patients and healthy exposed individuals from an endemic population was examined within the context of expressed HLA-DR ...molecules. Although overall no significant differences were found between the frequencies of Ag recognition in the different subject groups, when Ag-specific T cell responses were examined within the context of HLA-DR, a highly significant difference was found in the recognition of the 30/31-kDa Ag. HLA-DR3 appeared to be associated with high T cell responsiveness to the 30/31-kDa Ag in healthy contacts (p = 0.01), but, conversely, with low T cell responsiveness to this Ag in tuberculoid patients (p = 0.005). Within the group of HLA-DR3-positive individuals, differences in 30/31-kDa directed T cell responsiveness were highly significant not only between healthy individuals and tuberculoid patients (p < 0. 0001), but also between healthy individuals and lepromatous patients (p = 0.009), and consequently between healthy individuals compared with leprosy patients as a group (p < 0.0001). A dominant HLA-DR3-restricted epitope was recognized by healthy contacts in this population. It has been proposed that secreted Ags may dominate acquired immunity early in infection. The low T cell response to the secreted, immunodominant 30/31-kDa Ag in HLA-DR3-positive leprosy patients in this population may result in retarded macrophage activation and delayed bacillary clearance, which in turn may lead to enhanced Ag load followed by T cell-mediated immunopathology.
IntroductionDevice implantation requires fluoroscopic guidance, which carries inherent risks of ionizing radiation to patients and staff. We evaluated the impact of a novel low-dose fluoroscopic ...protocol on radiation exposure during pediatric and adult congenital device implantation.MethodsAll patients who underwent pacemaker or ICD implantation with new transvenous leads from 7/11 - 01/18 were included. A novel ALARA protocol consisting of ultra-low frame rates (2-3 frames/s), low dose/frame (6-18 mGy/frame), proper collimation and use of the “air-gap” technique for children < 20kg (including removal of the anti-scatter grid) was employed in all cases. Fluoroscopy save was utilized for axillary/subclavian venography as an additional method to decrease radiation exposure. Demographics, procedural data and radiation exposure levels were collected and analyzed.ResultsThirty patients underwent device implantation without additional catheterization, electrophysiology study or ablation procedure (median age 15 years; range 5-50, median weight 55 kg; range 19-138) with a total of 43 leads placed. 47% of patients had a primary rhythm disturbance, 33% had cardiomyopathy and 20% had congenital heart disease. 50% were pacemakers (53% dual-chamber, 27% single-chamber ventricle, 20% single-chamber atrial) and 50% of devices implanted were ICDs (87% single chamber). All implants were acutely successful with acceptable atrial and ventricular sensing and capture thresholds. The median fluoroscopy time was 11.5 minutes (inter-quartile range (IQR) 8.0 - 18.2), median air kerma dose 4.0 mGy (IQR 2.5 - 19.5) and median dose-area product 27.8 μGy/m (IQR 17.1 - 106.5). Median implant procedure time was 133 minutes (IQR 108 - 167). One patient required revision secondary to device migration without lead derangement 2 days post-procedure. There were no other complications related to the device implantation procedures.ConclusionsThe use of a novel fluoroscopic protocol may help decrease radiation exposure to patients and staff without affecting efficacy or risk. These data may represent benchmarks against which future device implantation procedures can be compared.
PDF
