A VIP antagonist distinguishes VIP receptors on spinal cord cells and lymphocytes

Vasoactive intestinal peptide (VIP) is a neuropeptide which also interacts with cells of the immune system. The paucity of specific VIP receptor antagonists has hampered studies of possible receptor heterogeneity and of VIP function. To aid in achieving these goals, a new VIP antagonist, a hybrid between neurotensin and VIP, has been synthesized. This peptide interacted with VIP receptors on spinal cord cells with an affinity 10-fold greater than VIP itself. In contrast, 1000-fold higher concentrations of the antagonist were required to displace labeled VIP from its receptor on lymphoid cells as compared to VIP itself, suggesting VIP receptor heterogeneity between immune and spinal cord cells.     

Soman intoxication-induced changes in serum acute phase protein levels,corticosterone concentration and immunosuppressive potency of the serum

We have studied the effect of soman intoxication on serum acute phase reactants (APR) levels, and the relationship of the APR and corticosterone concentrations and the immunosuppressive activity of the serum. One day after the injection of 1.8 LD₅₀ soman the concentrations of ₂-macroglobulin (₂-MG) and ₁-acid glycoprotein (AGP) in the serum of antidote protected rats increased 4- and 7-fold, respectively, whereas those of hemopexin (Hx), haptoglobin (Hp) and cysteine protease inhibitor (CPI) were two to three times higher than in the controls. A similar magnitude of increase of serum acute phase reactants levels was observed when 0.3 LD₅₀ soman was administered at 24-h intervals over the 5-day period. The relationship of changes in the APR concentration, corticosterone level and immunosuppressive activity of the serum was also comparable to that observed in the acute phase response to tissue injury.     

Evaluation and selection of candidates for renal transplantation at the Clinical Hospital Center in Rijeka

On December 31, 2001, 2486 patients with terminal renal failure received dialysis treatment in Croatia. Only one third of the patients are registered on the national waiting list for cadaveric kidney transplant. In most of the others, transplantation is impossible because of comorbidity. This is mainly due to the steadily growing age of the dialytic population and therefore a higher incidence of cardiovascular disease and diabetes. Still, evaluation of the potential recipients of cadaveric kidney transplant, registered on the waiting list, often reveals contraindications for transplantation. The aim of this study was to determine the incidence and type of contraindications in transplant candidates, found during immediate preoperative evaluation. Analysis of these data should help in determining how contraindications can be early detected and prevented. Before registering onto the national waiting list transplant candidates need to be thoroughly investigated including detailed history, physical examination, routine diagnostic procedures and additional examinations, if needed, to exclude or evaluate the possibly existing contraindications for transplantation. During the period from January 1997 until June 2002, 145 potential recipients from the national waiting list were referred to the Rijeka University Hospital Center and evaluated for kidney transplantation. Eighty-eight patients underwent transplantation. Preoperative evaluation revealed contraindications for transplantation in 52 (35.9%) candidates. Twenty-two (15.2%) patients had a positive cross-match with donor lymphocytes, 6 (4.1%) patients refused transplantation, and in 24 (16.6%) patients serious comorbidity was the reason for not being accepted for transplantation and for their withdrawal from the national waiting list. Comorbidity was mainly due to cardiovascular disease (12 patients--8.3%) and infection (8 patients--5.5%). These data show a high incidence of contraindications found during the immediate preoperative evaluation of potential kidney recipients. It was the case in more than one third of patients. During the evaluation of potential candidates for kidney transplantation special attention should be addressed to the presence of cardiovascular morbidity and infection. Peripheral vascular occlusive disease, cardiac status and/or cerebrovascular disease should be evaluated. Measures used to treat or reduce the development of complications include an optimal control of blood pressure, serum phosphate, hyperparathyroidism, dyslipidemia, and renal anemia. The sites of infection must be treated and eradicated, because immunosuppressive treatment is a threat to the transplant recipient's life. The second most common cause of refusal of potential candidates was a positive cross-match with donor lymphocytes. Sensitization to human leukocyte antigens can be prevented by the avoiding of blood transfusions and use of erythopoietin in treating renal anemia. To minimize the morbidity and mortality, the potential kidney recipients should undergo rigorous selection and thorough evaluation before including them into the waiting list for kidney transplantation. Afterwards, regular examinations are obligatory to reveal contraindications, proceed to medical interventions and treat concomitant diseases in time, which can influence the patient's survival. In case that contraindications for transplantation arise, the patient must be temporarily or definitely removed from the waiting list.     

Effect of creatine supplementation during rapid body mass reduction on metabolism and isokinetic muscle performance capacity

Well-trained subjects (n=6) were studied before and after losing a mean 3.0%–4.3% of body mass to determine whether muscle performance could be maintained or even enhanced by dietary creatine supplementation. During a 5-day period of loss of mass the subjects were randomly assigned to a creatine or placebo supplemented diet. All the subjects were measured before and after loss of mass on both supplements for isokinetic peak torque (PT) and work at peak torque (W _PT) of knee extensors, also for intermittent high intensity working capacity of the same muscle group. The latter test consisted of submaximal isokinetic knee extensions at an angular velocity of 1.57 rad?·?s^?1 for 45 s at the rate of 30 contractions each min (submaximal work, W _{s max} ) followed by 15-s maximal effort (maximal work, W _max ). Total duration of the test was 3 min. Haematocrit was measured and haemoglobin, ammonia, lactate, glucose and urea concentrations were analysed in blood samples obtained at rest and after cessation of muscle performance tests. The results indicated that creatine supplementation in comparison with placebo treatment during rapid body mass reduction may help to maintain muscle PT and W _PT at high angular velocities, not influencing W _max and the rate of fatigue development during W _max , but affecting adversely W _{s max} . Within the limitations of the present study the reasons for the partially detrimental effect of creatine administration remain obscure, but it is suggested that impaired creatine uptake in muscle during body mass loss as well as creatine induced changes in muscle glucose and glycogen metabolism may be involved.     

Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F,EA- 2R) along with Epstein–Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis

Introduction:Worldwide, breast cancer (BC) is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world’s population. Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India. Methodology:In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)– EBV PCR and Epstein–Barr virus latent membrane protein 1 (LMP1) IHC. Results:Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection. Conclusion:The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.Key Words: EBV, breast cancer, clinico-pathological variables, LMP1, viral oncogenesis     

Efficacy of acitretin in the treatment of reactive neutrophilic dermatoses in adult-onset immunodeficiency due to interferon-gamma autoantibody

Reactive neutrophilic dermatoses in adult-onset immunodeficiency due to interferon-γ autoantibody (AOID) are usually associated with concomitant active opportunistic infections. Data focusing on the treatment of these dermatoses with non-immunosuppressive drugs are still lacking. The aim of this study was to assess the efficacy and safety of acitretin treatment of reactive neutrophilic dermatoses in AOID. We conducted a retrospective review of all patients with AOID who had reactive neutrophilic dermatoses and had been treated with acitretin from January 2008 to December 2018. In total, 23 patients had been diagnosed with AOID, with 27 episodes of reactive neutrophilic dermatoses (20 episodes of Sweet syndrome and seven episodes of generalized pustular eruption) and treated with acitretin. The median effective dose of acitretin was 10 mg/day. The mean initial response was 5.6 ± 2.3 days. The rash had almost or completely cleared within 2 weeks in 70.4% of patients. One case had developed a reversible acitretin-induced liver injury with hepatocellular pattern. The median total duration of treatment was 3 months. In conclusion, this study demonstrates the potential role of acitretin as one of the treatments of choice for reactive neutrophilic dermatoses in AOID, attributable to its favorable response and good tolerability.     

The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. adult intensive care units

BACKGROUND: Patient-specific risk factors for acquisition of vancomycin-resistant enterococci (VRE) among hospitalized patients are becoming well defined. However, few studies have reported data on the institutional risk factors, including rates of antimicrobial use, that predict rates of VRE. Identifying modifiable institutional factors can advance quality-improvement efforts to minimize hospital-acquired infections with VRE. OBJECTIVE: To determine the independent importance of any association between antimicrobial use and risk factors for nosocomial infection on rates of VRE in intensive care units (ICUs). DESIGN: Prospective ecologic study. SETTING: 126 adult ICUs from 60 U.S. hospitals from January 1996 through July 1999. PATIENTS: All patients admitted to participating ICUs. MEASUREMENTS: Monthly use of antimicrobial agents (defined daily doses per 1000 patient-days), nosocomial infection rates, and susceptibilities of all tested enterococci isolated from clinical cultures. RESULTS: Prevalence of VRE (median, 10%; range, 0% to 59%) varied by type of ICU and by teaching status and size of the hospital. Prevalence of VRE was strongly associated with VRE prevalence among inpatient non-ICU areas and outpatient areas in the hospital, ventilator-days per 1000 patient-days, and rate of parenteral vancomycin use. In a weighted linear regression model controlling for type of ICU and rates of VRE among non-ICU inpatient areas, rates of vancomycin use (P < 0.001) and third-generation cephalosporin use (P = 0.02) were independently associated with VRE prevalence. CONCLUSIONS: Higher rates of vancomycin or third-generation cephalosporin use were associated with increased prevalence of VRE, independent of other ICU characteristics and the endemic VRE prevalence elsewhere in the hospital. Decreasing the use rates of these antimicrobial agents could reduce rates of VRE in ICUs.     

Vital Signs: Estimated Effects of a Coordinated Approach for Action to Reduce Antibiotic-Resistant Infections in Health Care Facilities — United States

BackgroundTreatments for health care–associated infections (HAIs) caused by antibiotic-resistant bacteria and Clostridium difficile are limited, and some patients have developed untreatable infections. Evidence-supported interventions are available, but coordinated approaches to interrupt the spread of HAIs could have a greater impact on reversing the increasing incidence of these infections than independent facility-based program efforts.MethodsData from CDC’s National Healthcare Safety Network and Emerging Infections Program were analyzed to project the number of health care–associated infections from antibiotic-resistant bacteria or C. difficile both with and without a large scale national intervention that would include interrupting transmission and improved antibiotic stewardship. As an example, the impact of reducing transmission of one antibiotic-resistant infection (carbapenem-resistant Enterobacteriaceae [CRE]) on cumulative prevalence and number of HAI transmission events within interconnected groups of health care facilities was modeled using two distinct approaches, a large scale and a smaller scale health care network.ResultsImmediate nationwide infection control and antibiotic stewardship interventions, over 5 years, could avert an estimated 619,000 HAIs resulting from CRE, multidrug-resistant Pseudomonas aeruginosa, invasive methicillin-resistant Staphylococcus aureus (MRSA), or C. difficile. Compared with independent efforts, a coordinated response to prevent CRE spread across a group of inter-connected health care facilities resulted in a cumulative 74% reduction in acquisitions over 5 years in a 10-facility network model, and 55% reduction over 15 years in a 102-facility network model.ConclusionsWith effective action now, more than half a million antibiotic-resistant health care–associated infections could be prevented over 5 years. Models representing both large and small groups of interconnected health care facilities illustrate that a coordinated approach to interrupting transmission is more effective than historical independent facility-based efforts.Implications for Public HealthPublic health–led coordinated prevention approaches have the potential to more completely address the emergence and dissemination of these antibiotic-resistant organisms and C. difficile than independent facility–based efforts.