IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.     

Purine nucleoside phosphorylase deficiency: a new case report and identification of two novel mutations (Gly156A1a and Val217Ile), only one of which (Gly156A1a) is deleterious

Purine nucleoside phosphorylase (PNP) deficiency results in an autosomal recessive immunodeficiency disease characterized by initial involvement of cellular immunity and neurological manifestations with subsequent abnormalities of humoral immunity. The initial presentation and clinical course has varied widely in the relatively few published cases. The molecular basis has been reported in only 10 patients, precluding evaluation of phenotype-genotype relationships. We now report clinical, immunologic, and molecular findings in a new case of relatively early onset that emphasizes hypotonia and developmental delay as early manifestations. The patient carried two novel missense mutations (Gly56A1a and Val217Ile) on the same allele in apparent homozygosity. Expression of each of the mutant enzymes in vitro demonstrated that the Gly156A1a mutation abolished enzyme activity while the Val217Ile mutation was without obvious effect and is therefore a normal variant. Such "normal" polymorphisms might be associated with a variable response to the immunosuppressive PNP inhibitors currently in clinical trials.     

Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.     

Endoscopic features of smooth muscle tumors in children with AIDS

BACKGROUND: Smooth muscle tumors are the second most common malignancy encountered in children with acquired immunodeficiency syndrome (AIDS). This study reviewed the incidence and endoscopic appearance of smooth muscle tumors in the gastrointestinal tract of children with AIDS undergoing endoscopy. METHODS: Retrospective review of all endoscopic records (n = 70) of children with AIDS from August 1988 to December 1997 at a tertiary care inner city hospital. RESULTS: Three children with advanced AIDS (4%) were found to have smooth muscle tumors, all of which had the typical appearance of submucosal nodules with central ulceration. Some were hemorrhagic. They measured less than 1 to 4 cm in diameter. Two children had multiple tumors. All lesions except for one were located in the colon. Colonic biopsies revealed a leiomyoma in one patient and a smooth muscle tumor of uncertain malignant potential in another. The forceps biopsy of the single gastric mass was not deep enough to make the diagnosis of a smooth muscle tumor. A nonmalignant smooth muscle tumor grew from less than 5 mm to more than 4 cm in 1 year and was removed surgically. All three children are alive without any evidence of local spread or distant metastases despite no specific therapy for the smooth muscle tumor. CONCLUSIONS: Smooth muscle tumors in the GI tract of children with AIDS are relatively common. Further study of the long-term outcome for children infected with the human immunodeficiency virus who have these lesions are needed to establish prognosis and management guidelines.     

Sickle cell disease: the Lebanese experience

Sickle cell disease (SCD), the commonest single gene disorder worldwide, is an inherited disease that has different clinical and hematological manifestations in different populations. The objective of this study is to describe the characteristics of the Lebanese SCD population. This was a retrospective study that included information on 387 patients with either sickle cell anemia (SS) or sickle beta-thalassemia (ST). The mean (+/-SD) age was 17.9 years (+/-12.5), and the mean (+/-SD) follow-up was 9.3 +/- 6.9 years. Fifty percent of the patients were males and SS/ST distribution was 3 : 1. The disease was clustered in two geographic areas in North and South Lebanon. Nearly, all patients were Muslims and 56% were the offspring of consanguineous parents. The prevalence of splenomegaly beyond 6 years of age among SS patients was 28.9%. The prevalence rates of stroke, leg ulcers and priapism were 4.1%, 1.4%, and 0.8%, respectively. Comparing the SS and the ST patients, there were no statistically significant differences in the prevalence of all clinical manifestations except for splenomegaly (SS: 28.9%, ST: 54.9%, P-value < 0.001) and splenectomy (SS: 16.1%, ST: 35.7%, P-value < 0.001). In contrast to Northern American populations and similar to some Mediterranean populations, Lebanese SCD patients have a higher prevalence of persistent splenomegaly. The relatively low incidence of thrombotic complications deserves further investigation. The study's limitations include those of any other retrospective study and the fact that not all Lebanese centers caring for inherited hemoglobin disorders were included. However, the results of this first large scale national survey indicate that preventive efforts should target the Northern and Southern regions of Lebanon to decrease the number of new off springs afflicted with this disease similar to what has been successfully achieved with Thalassemia, another hemoglobinopathy that is highly prevalent in the country.     

Correlation between cathepsin D serum concentration and carotid intima-media thickness in hemodialysis patients

Aim  

Cardiovascular (CV) disease is the leading cause of death in hemodialysis (HD) patients, and approximately half of mortalities in HD patients are attributed to CV disease. Atherosclerosis is the most frequent cause of CV complications in patients with end-stage renal disease (ESRD). Based on recent studies, cathepsin D has been suggested as a potential marker of atherosclerosis, and we hypothesized that there is an association between serum concentration of cathepsin D and carotid intima-media thickness (CIMT) in hemodialysis patients.