Immunologie der Tuberkulose

Zusammenfassung: Die Infektion mit M.tuberculosis (Mtb) ist nach wie vor weit verbreitete, aber nur bei bestimmten Menschen wird aus der primären Infektion eine Erkrankung. Nur Patienten mit einer Immunschwäche oder einer reduzierten Immunität erkranken. Das sind pro Jahr weltweit ca. 8-10Mio. Menschen. Ein gutes Verständnis der Mtb-Immunität ist wichtig, wenn man Mtb verhindern, Immunmodulatoren für bestimmte Krankheiten einsetzen oder neue Impfstoffe auf der Grundlage des durch die Entschlüsselung der Genomstruktur von Mtb gewonnenen Wissens entwickeln wil

Fat-free mass change to weightchange ratio during refeeding following lungtransplantation

Abstract. : Malnutrition occurs frequently prior to lung transplantation (LTR), but patients gain weight after LTR. The study aimed to determine the ratio changes of fat-free mass (ΔFFM): changes of body weight (ΔBW) during refeeding. A total of 37 LTR patients were measured for weight and FFM and body fat by bioimpedance analysis at 1 month post-LTR, then annually for 3 years. Linear regressions determined the ratio ΔFFM:ΔBW during refeeding. ΔFFM was: year- 1=1.822+0.389* ΔBW, r 2=0.397; yr-2=0.611+0.246* ΔBW, r 2=0.441; yr-3=-0.17+0.208 * ΔBW, r 2=0.319. Refeeding during year-1 in thin subjects resulted in a ratio ΔFFM:ΔBW of 0.389, whereas the change in ratio ΔFFM:ΔBW during year- 2 and 3 was 0.246 and 0.208, respectively. Refeeding resulted in a larger ratio ΔFFM:ΔBW in thin subjects versus normal and overweight subjects. Thus, refeeding in underweight LTR patients is geared to normalizing depleted FFM, whereas later FFM gains were similar to FFM gains in normal and overweight subject

Prevalence of low fat-free massindex and high and very high body fat mass index following lungtransplantation

Abstract. : The aim of this study was to determine the prevalence of low fat-free mass index (FFMI) and high and very high body fat mass index (BFMI) after lung transplantation (LTR). A total of 37 LTR patients were assessed prior to and at 1 month, 1 year and 2 years for FFM and compared to 37 matched volunteers (VOL). FFM was calculated by the Geneva equation and normalized for height (kg/m2). Subjects were classified as FFMI "low”, ≤17.4 in men and ≤15.0 in women; BFMI ”high”, 5.2-8.1 in men and 8.3-11.7 in women; or "very high” >8.2 kg/m2 in men and >11.8 kg/m2 in women. In 23 M/14 F, body mass index (BMI) was 22.3±4.4 and 20.1±4.9 kg/m2, respectively. The prevalence of low FFMI was 80% at 1 month and 33% at 2 years after LTR. Prevalence of very high BFMI increased and was higher in patients than VOL after LTR. The prevalence of low FFMI was high prior to and remained important 2 years after LTR, whereas BFMI was lower prior to and higher 2 years after LT

Suppression of alcohol-induced hypertension by dexamethasone

BACKGROUND. Alcohol consumption is associated with an increased incidence of hypertension and stroke, but the triggering mechanisms are unclear. In animals, alcohol causes activation of the sympathetic nervous system and also stimulates the release of corticotropin-releasing hormone (CRH), which has sympatho-excitatory effects when administered centrally. METHODS. To determine whether alcohol evokes sympathetic activation and whether such activation is attenuated by the inhibition of CRH release, we measured blood pressure, heart rate, and sympathetic-nerve action potentials (using intraneural microelectrodes) in nine normal subjects before and during an intravenous infusion of alcohol (0.5 g per kilogram of body weight over a period of 45 minutes) and for 75 minutes after the infusion. Each subject received two infusions, one after the administration of dexamethasone (2 mg per day) and one after the administration of a placebo for 48 hours. RESULTS. The infusion of alcohol alone evoked a marked (P < 0.001) and progressive increase in the mean (+/- SD) rate of sympathetic discharge, from 16 +/- 3 bursts per minute at base line to 30 +/- 8 bursts per minute at the end of the two-hour period. This sympathetic activation was accompanied during the second hour by an increase in mean arterial pressure of 10 +/- 5 mm Hg (P < 0.001). After the administration of dexamethasone, the alcohol infusion had no detectable sympathetic effect. The dexamethasone-induced suppression of sympathetic activation was associated with a decrease in mean arterial pressure of 7 +/- 6 mm Hg (P < 0.001) during the alcohol infusion and with suppression of the pressor effect during the second hour. CONCLUSIONS. Alcohol induces pressor effects by sympathetic activation that appear to be centrally mediated. It is possible that these alcohol-induced hemodynamic and sympathetic actions could participate in triggering cardiovascular events

Added diagnostic value of 16S rRNA gene pan-mycobacterial PCR for nontuberculous mycobacterial infections: a 10-year retrospective study.

The diagnosis of mycobacterial infections has been dramatically improved by the introduction of molecular methods aimed to reduce the time to diagnosis as compared with culture. The broad range pan-mycobacterial PCR can detect all the mycobacterial species directly from clinical specimens. We aimed to evaluate its usefulness and its clinical added value for the diagnosis of nontuberculous mycobacterial (NTM) infections. We performed a retrospective study (2003-2013) including 952 samples taken from 639 patients with clinical suspicion of NTM infection. The performance of smear microscopy, PCR and culture was established using clinical data to investigate discrepant results. We also compared the time to microbial diagnosis between the direct PCR and culture. The sensitivity, specificity, positive and negative predictive values of the PCR were 61.6% (53.5-69.1), 99.1% (98.2-99.6), 92.8% (85.8-96.5) and 93.4% (91.6-94.9), respectively, when considering all specimens. When considering smear-positive specimens and smear-negative specimens, the sensitivity was 81.6% and 40%, respectively. The sensitivity for pulmonary and extra-pulmonary smear-positive specimens was 85.2% versus 72.7%. The median time to identification at species level was 35 days (SD, 17.67) for culture and 6 days (SD, 2.67) for the PCR (when positive), which represents a 29-day shorter time to results (p < 0.0001). The 16S rRNA gene pan-mycobacterial PCR displays a substantial benefit in terms of time to diagnose NTM infections when compared with culture. Despite an excellent specificity, its sensitivity is yet limited in particular for smear-negative specimens, which might be improved by relying onto real-time PCRs

Pars plana vitrectomy for diabetic macular edema: a systematic review, meta-analysis, and synthesis of safety literature

Purpose. To assess the risk and benefit of pars plana vitrectomy for diabetic macular edema (DME). Methods. We conducted a systematic literature review using PubMed, EMBASE, Web of Science, and Cochrane Central Database of Controlled Trials until September 2014. The population was patients with DME, intervention vitrectomy, comparator macular laser or observation, and efficacy outcome visual acuity and central retinal thickness (CRT). Safety outcomes were intra- and postoperative surgical complications. The efficacy meta-analysis included only randomized controlled trials. The safety analysis included prospective, retrospective, controlled and uncontrolled studies. Results. Five studies were eligible for the efficacy meta-analysis (n = 127 eyes) and 40 for the safety analysis (n = 1,562 eyes). Combining follow up intervals from 6 to 12 months, the meta-analysis found a non-significant 2 letter visual acuity difference favoring vitrectomy, and a significant 102 micron greater reduction in CRT favoring vitrectomy, but a post-hoc subgroup analysis found that a 6 month CRT benefit reversed by 12 months. The most frequent complications were retinal break (7.1%), elevated intraocular pressure (5.2%), epiretinal membrane (3.3%), and vitreous hemorrhage (2.4%). Cataract developed in 68.6% of 121 phakic eyes. Conclusions. Vitrectomy produces structural and functional improvements in select eyes with DME, but the visual gains are not significantly better than with laser or observation. No major safety concerns were identified

Randomized placebo-controlled trial of amlodipine in vasospastic angina

AbstractObjectives. This study was designed to assess the efficacy and safety of amlodipine, a long-acting calcium channel blocker, in patients with vasospastic angina.Background. Previous studies have established the value of short-acting calcium channel blockers in the treatment of coronary spasm.Methods. Fifty-two patients with well documented vasospastic angina were entered into the present study. After a single-blind placebo run-in period, patients were randomized (in a double-blind protocol) to receive either amlodipine (10 mg) or placebo every morning for 4 weeks. Twenty-four patients received amlodipine and 28 received placebo. All patients were given diaries in which to record both the frequency, severity, duration and circumstances of anginal episodes and their intake of sublingual nitroglycerin tablets.Results. The rate of anginal episodes decreased significantly (p = 0.009) with amlodipine treatment compared with placebo and the intake of nitroglycerin tablets showed a similar trend. Peripheral edema was the only adverse event seen more frequently in amlodipine-treated patients. No patient was withdrawn from the double-blind phase of the study because of an adverse event. Patients who completed the double-blind phase as responders to amlodipine or as nonresponders to placebo were offered the option of receiving amlodipine in a long-term, open label extension phase. During the extension, the daily dose of amlodipine was adjusted to 5 or 15 mg if needed and the rate of both anginal episodes and nitroglycerin tablet consumption showed statistically significant decreases between baseline and final assessment.Conclusion. This study suggests that amlodipine given once daily is efficacious and safe in the treatment of vasospastic angina

Direct cost of pars plana vitrectomy for the treatment of macular hole, epiretinal membrane and vitreomacular traction: a bottom-up approach

Purpose The direct cost to the National Health Service (NHS) in England of pars plana vitrectomy (PPV) is unknown since a bottom-up costing exercise has not been undertaken. Healthcare resource group (HRG) costing relies on a top-down approach. We aimed to quantify the direct cost of intermediate complexity PPV. Methods Five NHS vitreoretinal units prospectively recorded all consumables, equipment and staff salaries during PPV undertaken for vitreomacular traction, epiretinal membrane and macular hole. Out-of-surgery costs between admission and discharge were estimated using a representative accounting method. Results The average patient time in theatre for 57 PPVs was 72 min. The average in-surgery cost for staff was £297, consumables £619, and equipment £82 (total £997). The average out-of-surgery costs were £260, including nursing and medical staff, other consumables, eye drops and hospitalisation. The total cost was therefore £1634, including 30 % overheads. This cost estimate was an under-estimate because it did not include out-of-theatre consumables or equipment. The average reimbursed HRG tariff was £1701. Conclusions The cost of undertaking PPV of intermediate complexity is likely to be higher than the reimbursed tariff, except for hospitals with high throughput, where amortisation costs benefit from economies of scale. Although this research was set in England, the methodology may provide a useful template for other countries