Hypovitaminosis D-induced pain

Vitamin D deficiency is a problem of considerable magnitude that has reemerged as a major public health issue in the United States and several other developed countries. Vitamin D plays a crucial role in calcium homeostasis in the body. Hypovitaminosis D leads to osteomalacia and increased risk of fractures, especially in the elderly. Preliminary research suggests that vitamin D can prevent certain types of cancer and autoimmune diseases. A recent large study has shown the association between severe hypovitaminosis D and persistent, non-specific musculoskeletal pain, further suggesting that patients with no apparent cause of pain should be assessed and possibly treated for vitamin D deficiency.     

Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.     

Amotosalen-treated donor T cells have polyclonal antigen-specific long-term function without graft-versus-host disease after allogeneic bone marrow transplantation.

We have previously shown that amotosalen HCl (S-59 psoralen)-treated donor splenocytes, which have limited proliferative capacity in vitro, can protect major histocompatibility complex-mismatched bone marrow transplant (BMT) recipients from lethal murine cytomegalovirus infection without causing graft-versus-host disease. In this study, we further investigated the effects of amotosalen-treated donor T cells on immune reconstitution after allogeneic BMT. We were surprised to find that amotosalen-treated donor T cells persisted long-term in vivo, comprising 6% to 10% on average of the T-cell compartment of transplant recipients at 4 months after transplantation. Donor T cells derived from amotosalen-treated splenocytes were predominantly polyclonal CD44 hi/int CD8 + memory T cells and were functionally active, synthesizing interferon gamma in response to stimulation with murine cytomegalovirus antigen. Amotosalen-treated donor T cells, reisolated from BMT recipients' spleens >/=4 months after transplantation, proliferated in vitro, thus indicating repair of amotosalen-mediated DNA cross-links. Compared with infusion of untreated donor splenocytes, amotosalen-treated cells enhanced thymopoiesis by bone marrow-derived stem cells in BMT recipients. However, amotosalen treatment abrogated the thymopoietic activity of lymphoid progenitor cells among the donor splenocytes. Thus, infusion of amotosalen-treated donor T cells produced rapid immune reconstitution after major histocompatibility complex-mismatched BMT by transferring long-lived polyclonal memory T cells with antiviral activity and also by enhancing bone marrow-derived thymopoiesis. This is a novel approach to adoptive immunotherapy in allogeneic BMT.     

Could human papillomaviruses be spread through blood?

The human papillomaviruses (HPVs) are epitheliotropic viruses that require the environment of a differentiating squamous epithelium for their life cycle. HPV infection through abrasion of the skin or sexual intercourse causes benign warts and sometimes cancer. HPV DNA detected in the blood has been interpreted as having originated from metastasized cancer cells. The present study examined HPV DNA in banked, frozen peripheral blood mononuclear cells (PBMCs) from 57 U.S. human immunodeficiency virus (HIV)-infected pediatric patients collected between 1987 and 1996 and in fresh PBMCs from 19 healthy blood donors collected in 2002 to 2003. Eight patients and three blood donors were positive mostly for two subgroups of the HPV type 16 genome. The HPV genome detected in all 11 PBMC samples existed as an episomal form, albeit at a low DNA copy number. Among the eight patients, seven acquired HIV from transfusion (three associated with hemophilia) and one acquired HIV through vertical transmission; this patient also had received a transfusion before sampling. Our data suggest that PBMCs may be HPV carriers and might spread the virus through blood.     

Effectiveness of oral desmopressin therapy in posterior urethral valve patients with polyuria and detection of factors affecting the therapy

OBJECTIVES: The present study aims to evaluate the effect of desmopressin treatment on urine output, density and glomerular filtration rate (GFR) in patients with posterior urethral valve (PUV) and the factors affecting the response to this treatment. METHODS: A total of 68 PUV patients who were followed-up after valve ablation were examined with the fluid intake, urine output and GFR. Sixteen patients who were polyuric (a urine output more than 30 ml/kg/day) and had hypoosmolar urine (urinary density of 1015 or lower) included in the study. Blood chemistry and serum ADH level were studied. Following 5 days of observation, patients were given DDAVP perorally with a dosage of 0.4 mg/day, two equal doses per day. After 7 days and after a 3 month period of treatment, voiding characteristics, day-time and night-time urine densities and also GFR have been re-evaluated. RESULTS: The mean age was 6.8 years (range 2 to 11 years). The mean age at valve ablation was 20.7 months (range 5 months to 6 years). The mean daily urine output during first week and at the third month of the treatment had decreased significantly (p=0.004 and p=0.006). There was increase in night-time and day-time urine density in 10 patients (62%) and in 13 patients (81%) respectively at the third month evaluation. Increments in urine density were statistically significant for the third month evaluation. Nine (56%) patients had ADH levels within normal (<7 pcg/ml) levels and 7 patients had higher levels. There was no statistically significant difference between pretreatment and posttreatment micturation characteristics. However patients with voiding dysfunction responded better to DDAVP treatment. CONCLUSIONS: Desmopressin treatment improves polyuria in PUV patients. The responses are better particularly in PUV patients with significant bladder dysfunction. This supports the harmful role of polyuria on bladder dysfunction. The DDAVP treatment improves the day-time and night-time in PUV patients. Combination of DDAVP treatment with overnight catheterization may be a good alternative that needs to be evaluated by further prospective randomized studies.     

Impact of pneumococcal polysaccharide vaccine (Prevnar) on middle ear fluid in children undergoing tympanostomy tube insertion

OBJECTIVES: The purpose of this study was to describe the bacteriology of middle ear effusions in children who have received the pneumococcal polysaccharide vaccine (Prevnar) compared with unvaccinated children. METHODS: A prospective review of medical records from July 2001 to July 2002 was conducted on children with middle ear effusion at time of tympanostomy tube insertion. Middle ear fluid was plated onto culture media immediately after acquisition, and antimicrobial resistance of cultured organisms along with serotyping of Streptococcus pneumoniae was examined. Vaccination status, demographics, and risk factors were determined from patients' medical records, parent interviews, or contact with their primary care physicians. RESULTS: After adjusting for age and number of previous infections, children vaccinated with Prevnar are two times less likely to have non-S. pneumoniae pathogenic bacteria isolated than children not vaccinated. Of those with growth, vaccinated children were almost three times more likely than nonvaccinated children to have the presence of H. influenzae. Vaccinated children with H. influenzae were 7.5 times less likely to have beta-lactamase producing H. influenzae than nonvaccinated children with H. influenzae. CONCLUSION: Because the incidence of S. pneumoniae was low, no inference could be made whether Prevnar decreased otitis media with effusion or recurrent acute otitis caused by the S. pneumoniae serotypes covered by the vaccine. However, vaccinated children did appear to have the unexpected benefit of having a certain level of protection to growth of typical acute otitis media pathogens.