Immunologic events in pigeon breeders'' disease

The immunologic and physiologic status of a group of symptomatic and asymptomatic pigeon breeders was studied in an attempt to define the immunologic events occurring in pigeon breeders' disease. Antibody activity to antigen(s) present in pigeon dropping extract (PDE) and pigeon serum (PS) was detected in the serum of both symptomatic and asymptomatic breeders. Antibody activity, however, tended to be greater in the symptomatic pigeon breeders. When subjects were challenged with PS via aerosol, serum complement activity became depressed only in asymptomatic patients. Cellular hypersensitivity to antigens present in PDE was detected in vitro in peripheral lymphocyte populations of 4 of 5 symptomatic breeders and in none of the asymptomatic breeders; cellular hypersensitivity to antigens in PS was not demonstrated in any of the individuals tested. These findings indicate that cell-mediated hypersensitivity, as well as humoral immunologic processes, may be involved in the pathogenesis of the hypersensitivity pneumonitis found in pigeon breeders.     

Tardive dyskinesia successfully treated with alprazolam

Tardive dyskinesia is a disorder secondary to prolonged treatment (from 18 months to 3 years) with antipsychotic agents, affecting approximately 15% to 20% of patients. Tardive dyskinesia is characterized by difficulty controlling involuntary movements of the small muscle groups, producing tic-like reactions, muscle rigidity, and difficulty maintaining muscle tone. It is a chronic and unrelenting disorder which may be permanent if not successfully treated. The mechanism of action is thought to be secondary to dopamine hypersensitivity resulting from prolonged deprivation of dopamine on the part of dopamine-sensitive receptors. Theoretically, these receptors have been deprived of the neurotransmitter by chronic treatment with antipsychotic drugs, which are recognized as dopamine-blocking agents. We present a case in which alprazolam was successfully used in treating tardive dyskinesia.     

1,25-Dihydroxyvitamin-D3 regulation of interleukin-2 and interleukin-2 receptor levels and gene expression in human T cells

1,25-Dihydroxyvitamin-D3 (1,25-D3) is known to inhibit DNA synthesis, immunoglobulin and lymphokine production [interleukin-2 (IL-2), gamma interferon (G-IFN), and granulocyte-monocyte colony-stimulating factor (GM-CSF)] by mitogen-stimulated human peripheral blood mononuclear cells (PBMCs). Recent data suggest these inhibitory effects are mediated at the gene level through inhibition of mRNA accumulation of specific lymphokines in the activated cells. In previous studies, we have demonstrated the CD8+ T cell population was less sensitive to the anti-proliferative actions of 1,25-D3 than CD4+ T cells. The purpose of this investigation was to further assess ability of 1,25-D3 to regulate CD4+ and CD8+ T cell functions. Initial experiments showed that 1,25-D3 inhibited both IL-2 production and mRNA accumulation in mitogen-stimulated PBMC. However, IL-2 receptor (IL-2R) expression and mRNA accumulation in stimulated PBMC was not affected by 1,25-D3. Both FACS sorted CD4+ and CD8+ T cells expressed IL-2R equally upon stimulation and neither showed an inhibitory effect on this expression by 1,25-D3. Human CD4+ and CD8+ T cells showed a stimulus-specific production of IL-2. CD4+ cells stimulated with mitogen and HLA-DR positive accessory cells produced measurable levels of IL-2 that were completely inhibited by 1,25-D3. CD8+ T cells did not generate measurable amounts of IL-2 in this system. However, CD4+ and CD8+ T cells produced large amounts of IL-2 when stimulated with mitogen and a protein kinase C activator, phorbol myristate acetate (PMA). Under these circumstances, both CD4+ and CD8+ T cell IL-2 production was inhibited completely by 1,25-D3. These data suggest that IL-2R expression in PBMCs and T cell subsets is equal and unaffected by 1,25-D3 while IL-2 production in T cell subsets is stimulus-specific and completely inhibited by 1,25-D3.     

LPS binding protein is important in the airway response to inhaled endotoxin

BACKGROUND: Inhaled endotoxin is a risk factor for asthma exacerbation, and endotoxin inhalation by itself recapitulates many of the classical features of asthma in mice, including reversible airflow obstruction and inflammation, airways hyperresponsiveness, and airway remodeling. OBJECTIVE: Our objective was to determine the importance of LPS binding protein (LBP) in the response to inhaled LPS. METHODS: We challenged LBP-deficient mice (C57BL/6(LBP-/-)) and C57BL/6 mice with inhaled endotoxin for 4 hours, 5 days, or 4 weeks, followed by 3 days of recovery. RESULTS: LBP in the lung was significantly increased in LPS-exposed C57BL/6 mice from all 3 groups. Only LPS-exposed C57BL/6 mice had significantly enhanced airway responsiveness to inhaled methacholine. Total lavage cells in LPS-exposed C57BL/6(LBP-/-) mice were significantly reduced compared with those seen in LPS-exposed C57BL/6 mice; however, the percentage of PMNs was similarly increased in both the C57BL/6 and C57BL/6(LBP-/-) mice. TNF-alpha, IL-1 beta, and IL-6 protein concentrations in whole-lung lavage fluid from C57BL/6(LBP-/-) mice were also significantly reduced when compared with those seen in C57BL/6 mice. In C57BL/6(LBP-/-) mice submucosal cell proliferation was significantly reduced in the 1-week group when compared with that seen in similarly exposed C57BL/6 mice. The 4-week exposed C57BL/6 mice had significantly thickened airway submucosa and significantly increased lavaged TGF-beta(1) protein compared with that seen in C57BL/6(LBP-/-) mice. CONCLUSIONS: These findings indicate that LBP is one of the critical molecules regulating the acute and chronic airway response to inhaled LPS.     

Single-stage methods of hypospadias repair

Summary The repair of all hypospadias in one stage represents state of the art in virtually all instances. Implicit in the repair of hypospadias is the correction of chordee, the construction of the neourethra such that the meatus is located on the tip of the glans, and the creation of a penis which is cosmetically appropriate. Described in this paper are most of the currently employed methods utilized for the repair of hypospadias in a single stage. The techniques described herein, in skilled hands, yield good results in 85–90% of cases. Repairs of hypospadias which have been designed and which are recommended for the occasional operator have no place in today's surgical therapy.     

Elevated sperm DNA fragmentation does not predict recurrent implantation failure

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9–105.5] million. Overall median DFI% and HDS% was 12 [7.1–18.9] and 9.6 [6.5–14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98–1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94–1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99–1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99–1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.     

Damage control orthopaedics in polytraumatized patients- current concepts

The principles of fracture management in patients with multiple injuries continue to be of crucial importance. Early treatment of unstable polytraumatized patients with head, chest, abdomen or pelvic injuries, with blood loss followed by immediate fracture fixation (Early Total Care -ETC) may be associated with secondary life threatening posttraumatic systemic inflammatory response syndrome (SIRS). Development of SIRS is typically a function of the type and severity of the initial injury (the “first hit”). Immediate Fracture fixation, using reamed nails or plates, in such unstable patients with multiple injuries is subsequently defined as the “second hit” and may be associated with development of acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF), with relatively high morbidity and mortality.The other alternative for long bone fracture fixation in unstable polytraumatized patients is based on immediate treatment of life threatening conditions related to the injuries, followed by the initial use of minimally invasive modular external frames for long bone fractures and is called Damage Control Orthopedics (DCO) and is widely accepted. In order to refine the DCO concept and to avoid an overuse of external fixation, the “Safe Definitive Surgery” (SDS) concept has been introduced, which is a dynamic synthesis of both strategies (ETC and DCO). The SDS strategy employs clinical parameters and includes repeated assessment of patients. The following paper is going to summarize historical backgrounds and recent concepts in treatment of polytraumatized patients.     

The association of Hospital Medicare beneficiary payer-mix,national quality rankings and outcomes following hepatopancreatic surgery

IntroductionWe sought to determine the impact of payer-mix on post-operative outcomes among Medicare beneficiaries following hepatopancreatic surgery.MethodsMedicare beneficiaries who underwent hepatopancreatic surgery were identified. Hospital quality markers were obtained from the Hospital General Information dataset. Hospitals were dichotomized (low/average vs. high) based on Medicare patient days versus all patient days irrespective of payer type.ResultsHigh Medicare patient-mix hospitals were more likely to be ranked higher than the national average relative to safety of care (29.4% vs. 38.1%) and timeliness of care (15.4% vs. 26.3%) versus low burden Medicare hospitals (both p < 0.001). However, Medicare beneficiaries who had hepatopancreatic surgery at a high Medicare patient-mix hospital were at higher risk of a complication (OR = 1.13, 95%CI 1.04–1.22), and death within 30-days (OR = 1.37, 95%CI 1.23–1.53) following surgery.ConclusionWhile hospitals caring for higher numbers of Medicare beneficiaries generally performed better on CMS quality indicators, these rankings did not equate to improved post-operative outcomes.