Human immunodeficiency virus-related conditions in children and adults with hemophilia: rates, relationship to CD4 counts, and predictive value

To further elucidate the natural history of human immunodeficiency virus (HIV) infection, we studied intermediate HIV-related conditions occurring before acquired immunodeficiency syndrome (AIDS) in a prospectively observed multicenter cohort of 738 HIV-infected persons with hemophilia. We analyzed the frequency in adults and children of common HIV-related conditions and the relative risk of AIDS after occurrence of these conditions, controlling for age at seroconversion and the percentage of CD4+ lymphocytes. Thrombocytopenia was the most frequently observed condition with cumulative incidences of 43% +/- 7% in adults and 27% +/- 6% in children and adolescents by 10 years after seroconversion. Oral candidiasis, fever, weight loss, and non-AIDS pneumonia were two to four times more common in adults than children, whereas herpes zoster risk was similar in the two age groups. HIV- related conditions were infrequent during the first 4 years of infection, particularly in children. With the exception of thrombocytopenia, mean CD4 counts were less than 350 cells/microL at the onset of the conditions. The relative hazard of AIDS after oral candidiasis was 18 in children and 3.8 in adults. Relative hazard in adults was also increased after persistent fever (10), weight loss (3.2), and non-AIDS pneumonia (2.2). Herpes zoster and thrombocytopenia were not significantly associated with AIDS in either age group. We conclude that intermediate HIV-related conditions occur more frequently in adults than in children with hemophilia. Persistent fever is the strongest predictor of AIDS in adults, whereas oral candidiasis is the strongest predictor in children. These findings should facilitate the design and conduct of clinical trials as well as the management of HIV- infected children and adults.     

Constructive (obliterative) bronchiolitis

Constrictive bronchiolitis (CB), also termed in lung transplant patients obliterative bronchiolitis, is inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles with resultant narrowing of their lumens. CB is found in a variety of settings, most often as a complication of lung and heart-lung transplantation (affecting 34% to 39% of patients, usually in the first 2 years after transplantation) and bone marrow transplantation, but also in rheumatoid arthritis, after inhalation of toxic agents such as nitrogen dioxide, after ingestion of certain drugs such as penicillamine and ingestion of the East Asian vegetable Sauropus androgynous, and as a rare complication of adenovirus, influenza type A, measles, and Mycoplasma pneumoniae infections in children. In lung transplants, CB is the single most important factor leading to death thereafter. In one study, the overall mortality rate was 25%. However, at the same time, 87% of patients who were asymptomatic and diagnosed solely by transbronchial biopsy had resolution or stabilization of disease. Decreases in FEV1 from baseline can be used to clinically support CB in transplant patients; the term bronchiolitis obliterans syndrome is used to denote this clinical dysfunction, and a grading system has been established for it that is now widely used in the literature. Significant risk factors for the development of CB in lung transplants include alloantigen-dependent and -independent mechanisms. In the former group are late acute rejection and HLA mismatches at the A loci; in the latter are ischemia/reperfusion injuries to airways that result from the transplantation surgery and cytomegalovirus infection.     

Intentional donor lymphocyte-induced limited acute graft-versus-host disease is essential for long-term survival of relapsed acute myeloid leukemia after allogeneic stem cell transplantation

The prognosis of patients with relapsed acute myeloid leukemia after allogeneic transplantation is poor. We hypothesized that initial disease control by effective cytoreduction, followed by rapid induction of a profound allo-immune response by donor-lymphocyte infusion during the neutropenic phase, is essential for long-term survival. Additional interferon-α was administered when no acute graft-versus-host-disease occurred within 3 weeks after donor-lymphocyte infusion. Overall, 44 patients with relapsed acute myeloid leukemia were assessed; 26 had relapsed after myeloablative conditioning and 18 after reduced-intensity conditioning. Of these 44 patients, seven were not eligible for cytoreductive treatment because of poor performance status (n=3) or severe graft-versus-host-disease (n=4) at the time of relapse. Patients with smoldering relapses (n=5) received donor-lymphocyte infusion only. Thirty-two patients received cytoreductive treatment, followed by donor-lymphocyte infusion in 22 patients. Reasons for not receiving donor-lymphocyte infusion were chemotherapy-related death (n=1) and chemotherapy-refractory disease (n=9). The 2-year overall survival rate after donor-lymphocyte infusion was 36% (95% confidence-interval: 16–57%). The impact of acute graft-versus-host-disease on survival was calculated with a Cox-regression model including onset of acute graft-versus-host-disease as a time-dependent variable. Development of grade 1–3, but not grade 4, acute graft-versus-host-disease was associated with superior survival as compared to absence of graft-versus-host-disease (hazard ratio 0.22, P=0.03). In conclusion, efficient cytoreduction followed by donor-lymphocyte infusion and subsequent interferon-α leading to limited acute graft-versus-host-disease represents a potentially curative option for patients with relapsed acute myeloid leukemia after allogeneic transplantation.     

Dendritic remodeling in the adolescent medial prefrontal cortex and the basolateral amygdala of male and female rats

There is recent evidence of continuing development throughout adolescence in two neural areas involved in emotion and cognition, the basolateral amygdala (BLN) and the medial prefrontal cortex (mPFC). Previous research from our laboratory has demonstrated a cellular loss in both of these brain regions in rats between postnatal day (P) 35 and 90. This study investigates dendritic changes in pyramidal neurons of the BLN and Layer 5 of the mPFC at P20 (juvenile), 35 (puberty), and 90 (adulthood) in hooded rats of both sexes. Dendritic branching and dendritic spines were quantified in Golgi‐Cox impregnated tissue. Between P20 and 35, dendritic length and complexity, as well as the density of dendritic spines, increased in both structures. Between P35 and 90, dendritic spines in the mPFC neurons significantly decreased in both sexes, while a loss of basilar dendrites was only detected in females. In the BLN, there was an increase in the number of branches between P35 and 90 without an increase in the total length of the dendritic tree. BLN spine density also remained stable during this period. These results show that the dendritic tree grows prior to puberty while dendritic remodeling and pruning occurs after puberty in both of these neural areas. This late development may lead to susceptibilities to psychopathologies and addictions that often develop at this time. Synapse 68:61–72, 2014 . © 2013 Wiley Periodicals, Inc.     

Treatment of acute uncomplicated diverticulitis without antibiotics: risk factors for treatment failure

Purpose

Conservative treatment strategy without antibiotics in patients with uncomplicated diverticulitis (UD) has proven to be safe. The aim of the current study is to assess the clinical course of UD patients who were initially treated without antibiotics and to identify risk factors for treatment failure.

Methods

A retrospective cohort study was performed including all patients with a CT-proven episode of UD (defined as modified Hinchey 1A). Only non-immunocompromised patients who presented without signs of sepsis were included. Patients that received antibiotics within 24 h after or 2 weeks prior to presentation were excluded from analysis. Patient characteristics, clinical signs, and laboratory parameters were collected. Treatment failure was defined as (re)admittance, mortality, complications (perforation, abscess, colonic obstruction, urinary tract infection, pneumonia) or need for antibiotics, operative intervention, or percutaneous abscess drainage within 30 days after initial presentation. Multivariable logistic regression analyses were used to quantify which variables are independently related to treatment failure.

Results

Between January 2005 and January 2017, 751 patients presented at the emergency department with a CT-proven UD. Of these, 186 (25%) patients were excluded from analysis because of antibiotic treatment. A total of 565 patients with UD were included. Forty-six (8%) patients experienced treatment failure. In the multivariable analysis, a high CRP level (>?170 mg/L) was a significant predictive factor for treatment failure.

Conclusion

UD patients with a CRP level >?170 mg/L are at higher risk for non-antibiotic treatment failure. Clinical physicians should take this finding in consideration when selecting patients for non-antibiotic treatment.

     

Effect of promoter and intron 2 polymorphisms on murine lung K-ras gene expression

Differences in tumor formation among inbred mouse strains with high (A/J) and low (C3H) susceptibility for lung cancer have been linked to a repetitive element within the second intron of the K-ras gene. The purpose of this investigation was to determine whether differences within the K-ras gene promoter region or the intron 2 polymorphism affect K-ras gene expression in lung tumors and target alveolar type II cells isolated from A/J and C3H mice. Ribonuclease protection assays were performed using RNA isolated from 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK)-induced lung tumors from each mouse strain and alveolar type II cells isolated from A/J and C3H mice. An 838 bp fragment of the murine K-ras gene promoter region was amplified by PCR, cloned and sequenced from both mouse strains. Promoter regions from both mouse strains were inserted into a luciferase reporter gene vector, with and without the second intron polymorphism, and transfected into sensitive, intermediate and resistant lung tumor cell lines. No significant differences in K-ras gene promoter activity was found between the two strains using these specific reporter gene constructs. Consistent with these results, levels of K-ras expression did not differ between alveolar type II cells, whole lung or tumors induced by NNK in A/J or C3H mice. Moreover, in lung tumor cell lines derived from mice with differing susceptibility for lung cancer, K-ras expression did not correlate with the growth rate of tumors induced in nude mice from these cell lines. These results indicate that factors involved in modulating the rapid clonal expansion of the mutated K-ras allele from A/J mice are not directly linked to expression of this gene. Other genetic changes or losses in conjunction with hypothesized modifier loci, such as the Par1 locus, must play a significant role in establishing the phenotypic strain differences for lung tumor formation.      

血浆Adropin水平与急性心肌梗死患者心功能关系的相关性研究

目的探讨急性心肌梗死（AMI）患者血浆Adropin水平与心功能的关系。方法选择108例AMI患者（AMI组）及60例健康对照者（对照组）。使用Killip心功能分级标准评价AMI患者的心功能,采用超声心动图测量AMI患者的左心室射血分数（LVEF）,使用ELISA法测定两组的血浆Adropin水平。结果AMI组患者血浆Adropin水平（11．46±159）ng／mI,较对照组（628±072）ng／ml明显增高（P〈0．01）。血浆Adropin水平随Killip心功能分级的增加而增高（r=0318,P〈005）,而与LVEF值呈负相关（r=-0．225,P〈0．01）。结论血浆Adropin水平越高的AMI患者心功能越差,Adropin是预测AMI患者心功能的一个潜在的生物学标记物。     

22400例手部皮肤病情况调查

本文叙述了22400例在手部的11种皮肤病，并讨论其原因。