Interleukin-12/T cell stimulating factor,a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells

At least two subsets of CD4⁺ T helper cell lymphocytes termed T_h1 and T _h, 2 exist in the mouse and probably in humans. They are characterized by the secretion of different lymphokines and by their functional behavior. Dysregulated expansion of one or the other subset may be one reason for the development of certain diseases. Thus, it is of importance to define the signals involved in the differentiation and activation of the two T_h cell subsets. It is known and has been confirmed in this report that the cytokine interleukin (IL)-1 acts onT_h2 cells but not on T_h1 cells. We now report that a previously identified cytokine which was provisionally termed T cell stimulating factor is identical with IL-12 and exhibits a reciprocal behaviour to IL-1. IL-12 has several effects on T_h1 cells. It can induce the proliferation of certain T_h1 cells in combination with IL-2. Synthesis of interferon (IFN)-γ by T_h1 cells can be triggered by IL-2 plus IL-12. In contrast to the IFN-γ production observed after T cell receptor (TcR) CD3 stimulation of T_h1 cells with lectin Concanavalin A the IFN-γ production induced by IL-12+IL-2 is insensitive to the immunosuppressive drug cyclosporin A. Furthermore, IL-12 enhances the TcR/CD3-induced synthesis of IFN-γ of several T_h1 clones. Finally, IL-12 (+ IL-2) induces homotypic cell aggregation of T_h1 clones. This type of cell aggregation depends on the participation of LFA-1 and ICAM-1 molecules. In all activation systems with T_h1 cells no effect of IL-1 was demonstrable. In contrast, only IL-1 but not IL-12 served as a co-stimulatory signal for several T_h2 cell lines activated via the TcR/CD3 complex.     

„Breast implant illness“ – Fakt oder Fiktion?

Journal für Ästhetische Chirurgie - Brustvergrößerungen mit Implantaten gehören zu den häufigsten ästhetisch chirurgischen Eingriffen. Trotz jahrzehntelanger...     

Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS

BACKGROUND: Nitric oxide-dependent factors (serotonin, activated platelets, acetylcholine) cause vasodilation in normal coronary arteries but vasoconstrict atherosclerotic vessels. This experiment tested the hypothesis that intravenous systemic infusions of L-arginine, a precursor for nitric oxide production, dilate the coronary vascular bed of patients undergoing coronary artery bypass graft surgery. METHODS: Twenty patients scheduled for coronary artery bypass graft surgery surgery were studied in a prospective, blinded, randomized clinical trial. Saphenous vein graft blood flow was measured with a transit time flow probe, and coronary vascular resistance was calculated. After weaning from bypass, patients were given a venous infusion (placebo or 10% arginine hydrochloride [30 g]) over 15 min. Arterial blood samples for the determination of L-arginine and L-citrulline levels were drawn before, 10 min after starting infusion, and 10 min after end of infusion. RESULTS: The placebo group experienced an increase in mean arterial pressure and coronary vascular resistance and a decrease in graft blood flow. Patients in the L-arginine group maintained their baseline values. Mean arterial pressure (L-arginine, 88+/-17 to 92+/-13 mmHg vs. placebo, 80+/-12 to 92+/-9 mmHg, P = 0.021), coronary vascular resistance (L-arginine, 97,000+/-60,000 to 99,600+/-51,000 dynes x s x cm(-5) vs. placebo, 81,000+/-69,000 to 117,000+/-64,000 dynes x s x cm(-5), P = 0.05), and graft blood flow (L-arginine, 55+/-25 to 50+/-19 ml/min vs. placebo, 60+/-34 to 46+/-18, P = 0.05) remained more stable in the L-arginine-treated patients. CONCLUSIONS: Systemic L-arginine infusion reduced postbypass coronary vasoconstriction. There were no adverse events associated with the drug infusion.     

Bilateral subcapital loss of arms following high-voltage electrical injury in the child: a new method for stump distalisation

Summary Bilateral loss of arms following high-voltage electrical injury results in severe problems for prosthetic replacement. To allow a unilateral myoelectric prosthetic fitting directed by contralateral contact switches, stump construction was achieved by bilateral tissue expansion and free non-vascularized double-fibula transplantation. Indications, technical details and functional results are presented.     

Cultured epithelial autografts: three years of clinical experience with eighteen patients.

Eighteen patients with major burns (mean total body surface area burned was 49% and mean total body surface area with full-thickness burns was 38%) had cultured epithelial autografts applied to 2% to 35% of the body surface area. In six patients successful "take" of greater than 65% occurred, and in 12 patients less than 40% "take" occurred. Most wounds underwent early excision to subcutaneous fat or fascia, and the wounds of 16 patients had been treated previously with homograft. Cultured epithelial autografts were covered with either single or multilayered dressings. Perioperative wound cultures showed that all patients had microorganisms, and appropriate perioperative antibiotic coverage of Staphylococcus epidermidis and Pseudomonas aeruginosa was noted less frequently in the poor take group, which may have influenced subsequent cultured epithelial allograft take. Adherence and stability of cultured epithelial allografts lag behind adherence and stability of meshed split-thickness autograft. The anterior trunk and thighs are the best recipient sites. The number of autograft harvests that were required to close wounds and the length of hospital stay were not significantly decreased by the use of cultured epithelial allografts as compared with comparable full-thickness burns that were treated previously without cultured epithelial allografts. Presently, grafting with cultured epithelial allografts is an adjunct but not an alternative to conventional burn-wound coverage with split-thickness autograft, because engraftment is inconsistent.     

Operative Behandlungsmöglichkeiten bei fortgeschrittenem karpalen Kollaps (SNAC/SLAC wrist)

Longstanding and untreated scaphoid fractures and scapholunate dissociations lead to painful destruction of the wrist with carpal collapse. The severity of degenerative arthrosis is classified in three stages and can be treated adequate operatively. SNAC wrist (scaphoid nonunion advanced collapse) after failed fusion of the scaphoid and SLAC wrist (scapholunate advanced collapse) after scapholunate dissociation should be differentiated. The reconstruction of the scaphoid or scapholunate ligament in stage II and III is no reasonable option. Motion preserving procedures such as proximal row carpectomy or midcarpal arthrodesis are preferable in this situation. Thirty-one male patients (average 41 years) were treated for SNAC or SLAC wrist with midcarpal arthrodesis. All patients were reexamined, the mean follow-up was 15 months. Grip strength was measured with the Dexter-System, pain was evaluated by a visual analogue scale (VAS 0-100). Patients' daily activities and general quality of life were estimated with the DASH-questionnaire. Pain was reduced to 50% compared to the preoperative situation. Grip strength improved to 60% of the opposite side. Active range of motion reached 50% of the contralateral wrist. Total DASH-score reached 39.0. Nonunion at the fusion site necessitated additional surgery in four patients resulting in total wrist arthrodesis. 80% of the patients returned to their original occupation. Midcarpal fusion is a reliable procedure for treating the difficult condition of advanced carpal collapse if proper realignment of the carpus is performed. The DASH-score reflects the subjective impressions of the patients in daily life and justifies the choice of a salvage procedure preserving wrist mobility. Total wrist fusion represents the last line of defense.     

NT-proBNP to exclude heart failure in primary care – a pragmatic,cluster-randomized study

Abstract

Heart failure (HF) is difficult to recognize in primary care. N-terminal pro B-type natriuretic peptide (NT-proBNP) can be used as a rule-out test in HF due to its high negative predictive value. We aim to determine whether the number per 1000 patients of HF diagnoses increase among patients referred from primary care to an outpatient HF clinic, if general practitioners (GPs) were offered NT-proBNP in a real-life setting. All GP practices covered by Randers Regional Hospital were randomized to an intervention group (34 GP practices) and a control group (35 GP practices) in this pragmatic, cluster-randomized controlled trial. The main outcome was the number of patients referred to echocardiography and diagnosed with HF in each group. The number of patients per 1000 diagnosed with HF in the two groups was the same (0.09 (0.02–0.16) vs. 0.14 (0.07–0.21), p?=?.3541). A total of 700?NT-proBNP analyses, of which 611 were unique, were requested from 31 GP practices in 17.5?months. A total of 184 patients were referred to echocardiography on suspicion of HF. The number of patients per 1000 referred in the intervention group was significantly higher (p?p?=?.019). Hence, increased diagnostic effectiveness could not be shown in this real-life setting.