NOS1 polymorphism is associated with atopy but not exhaled nitric oxide levels in healthy children

Exhaled nitric oxide (FE_NO) is raised in atopy. The mechanism for this is unclear. The aim of this study was to investigate whether the number of AAT repeats in intron 20 of the NOS1 gene, recently associated with variations in FE_NO in adults with asthma and cystic fibrosis, was associated with the raised FE_NO in healthy atopic children. Eighty-seven healthy children (44 girls, 42 atopic, age range 6–18 years) underwent measurements of FE_NO, spirometry, airway responsiveness and skin prick testing. Genotyping was carried out to determine the number of AAT repeats. There was no association between the number of AAT repeats and FE_NO in either the whole sample of healthy children (n = 87) or in the subsample of healthy atopics (n = 42). However, a greater number of atopic children had two high repeat alleles compared with non-atopic children (33.3% vs. 13.6%, respectively, p = 0.03). This suggests that variations in the NOS1 gene may contribute to atopy without this relationship being reflected by FE_NO.     

Serum measurements of soluble CD23 in HIV infection.

A gradual reduction in cell-mediated immunity is thought to occur with the progression of human immunodeficiency virus (HIV) infection. This suggests a selective attrition of the Th1 subset. The regulation of the soluble form of the low-affinity receptor for IgE (sCD23) by the opposing actions of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) allows the assessment of the overall balance of Th1 to Th2 activity in a given disease. In order to investigate this further we employed an enhanced chemiluminescent ELISA to analyse serum levels of sCD23 in male subjects with and without HIV infection. Serum levels of sCD23 were similar in 34 HIV seronegative homosexuals, 39 homosexuals with asymptomatic HIV infection, 27 homosexuals with acquired immune deficiency syndrome (AIDS) and 20 healthy controls. This suggests that HIV has no predilection for either the Th1 or Th2 subsets of CD4 T cells.     

Geometric indices of bone strength are associated with physical activity and dietary calcium intake in healthy older women.

A population-based study on 1008 postmenopausal women identified that the 24% of women achieving high levels of PA and CI had 3.4-4.4% higher femoral bone strength in axial compression and 1.7-5.2% in bending than those achieving low levels, indicating that lifestyle factors influence bone strength in the proximal femur. INTRODUCTION: Extensive research has shown that increased physical activity (PA) and calcium intake (CI) decrease the rate of bone loss; however, there is little research on how these lifestyle variables affect bone geometry. This study was designed to investigate the effects of modifiable lifestyle variables, habitual PA and dietary CI, on femoral geometry in older women. MATERIALS AND METHODS: Femoral geometry, habitual PA, and dietary CI were measured in a population-based sample of 1008 women (median age+/-interquartile range, 75+/-4years) enrolled in a randomized controlled trial (RCT) of calcium supplementation. Baseline PA and CI were assessed by validated questionnaires, and 1-year DXA scans (Hologic 4500A) were analyzed using the hip structural analysis technique. Section modulus (Z), an index of bending strength, cross-sectional area (CSA), an index of axial compression strength, subperiosteal width (SPW), and centroid position, the position of the center of mass, were measured at the femoral neck (NN), intertrochanter (IT), and femoral shaft (FS) sites. These data were divided into tertiles of PA and CI, and the results were compared using analysis of covariance (ANCOVA), with corrections for age, height, weight, and treatment (calcium/placebo). RESULTS AND CONCLUSIONS: PA showed a significant dose-response effect on CSA all hip sites (p<0.03) and Z at the narrow neck and intertrochanter sites (p<0.02). For CI, there was a dose-response effect for centroid position at the intertrochanter (p=0.03). These effects were additive, such that the women (n=240) with PA in excess of 65.5 kcal/day and CI in excess of 1039 mg/day had significantly greater CSA (NN, 4.4%; IT, 4.3%; FS, 3.4%) and Z (NN, 3.9%; IT, 5.2%). These data show a favorable association between PA and aspects of bone structural geometry consistent with better bone strength. Association between CI and bone structure was only evident in 1 of 15 variables tested. However, there was evidence that there may be additive effects, whereby women with high levels of PA and CI in excess of 1039 mg/day had significantly greater CSA (NN, 0.4%; FS, 2.1%) and Z (IT, 3.0%) than women with high PA but low CI. These data show that current public health guidelines for PA and dietary CI are not inappropriate where bone structure is the health component of interest.     

The adrenocorticotrophic hormone (4-9) analog ORG 2766 benefits autistic children: report on a second controlled clinical trial.

In a second controlled crossover trial, 20 autistic children received 40 mg/day of the neuropeptide ORG 2766, a synthetic analog of ACTH (4-9), for 8 weeks. Parents' checklist ratings (ABC) as well as clinicians' ratings (CGI) pointed to significant improvements after the course of treatment; improvements were clearest on the ABC social withdrawal subscale. The analysis of individual target symptoms and the parents' treatment preferences substantiated the beneficial effects of ORG 2766. In an ethologically analyzed playroom session, ORG 2766 treatment was associated with an improvement in the children's play behavior and a significant increase in the social interaction between child and experimenter. Gaze coordination between child and experimenter also was improved.     

Non-opiate effects of neuropeptides derived from beta-endorphin

Brain enzymes convert the opioid peptide beta-endorphin (beta E-(1-31)) to alpha- and gamma-endorphin and to several non-opioid fragments by further cleavage of the tyrosine residue or acetylation. Several of these peptides selectively affect brain functions. alpha-Endorphin (beta E-(1-16)) and relate non-opioid fragments (beta E-(2-16), beta E-(2-9) a.o.) like amphetamine, delay extinction of pole-jumping avoidance behavior and facilitate passive avoidance behavior. In addition these peptides enhance the stereotyped sniffing response induced by the injection of apomorphine into the nucleus caudatus. The fragment beta E-(10-16) inhibits, like serotonin and antidepressants, the behavioral effects of melatonin injected into the nucleus accumbens. gamma-Endorphin (beta E-(1-17)) has inherent opioid and neuroleptic-like properties, e.g. demonstrated by a naloxone reversible inhibition of hypermotility induced by apomorphine following injection into the nucleus accumbens. Also the non-opioid gamma-type endorphins (e.g. DT gamma E (beta E-(2-17) and DE gamma E (beta E-(6-17)) mimic certain effects of neuroleptics. These peptides facilitate extinction of pole-jumping avoidance behavior, attenuate passive avoidance behavior and antagonize the hypomotility and stereotyped sniffing induced by apomorphine injected into the nucleus accumbens and pyriform cortex respectively. These and other behavioral studies, including grasping responses, brain stimulation reward, food and other positively rewarded behavior, indicate that the action of alpha-type endorphins is in some aspects comparable to that of psychostimulants, while the effects of gamma-type endorphins are comparable to those of classical as well as atypical neuroleptics. Indeed, gamma-type endorphins have antipsychotic effects in a category of schizophrenic patients.     

Stromal macrophage-histiocytes in Hodgkin's disease. Their relation to fever

Morphologic variations of Concanavalin A-binding histiocytes were studied in biopsy specimens of 140 untreated patients with Hodgkin's disease (72 asymptomatic, and 68 with constitutional symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Three morphologic types of stromal histiocytes were recognized: medium-sized cells similar to those seen in reactive follicles, characterized by distinct cytoplasm and cell borders, and uniform nuclei (Type A); damaged-appearing Type A cells marked by rarefied or ragged cytoplasm, disrupted or indistinct cell borders, and varying sized nuclei (Type B); and large spindling or stellate cells (Type C). Type A cells were predominant in 52 patients; Type B cells in 51; Type C cells in seven; and Type A cells were mixed with Type B in 30. Fever was present in one of 52 patients (1.9%) with Type A predominance; 43 of 51 (84.3%) with Type B cell predominance; none of seven (0%) with Type C predominance; and 13 of 30 (43.3%) with mixed Type A and B cells. Logistic regression analysis of the data showed that the association of fever with Type B cell predominance was highly significant, and was not attributable to the known association of fever with other variables. Morphologic evidence suggests that fever in Hodgkin's disease may be a clinical manifestation of damaged macrophage-histiocytes rather than an acute-phase response of inflammatory or immune reaction.     

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.     

The pathogenicity of coagulase negative staphylococcus in the presence of silicone rubber implants

Coagulase negative staphylococci have long been thought to be harmless skin commensals. However they are now recognised as important pathogens in patients who have undergone insertion of prosthetic devices. We present three patients with infection following the insertion of silicone polymer prostheses, in whom a coagulase negative staphylococcus was the pathogen. All responded to antibiotic treatment. It is important to alert the bacteriologist to the presence of an implanted prosthesis when wound swabs are sent from an area showing clinical signs of infection. The coagulase negative staphylococci may otherwise be regarded falsely as merely skin contaminants.     

Severe hyponatraemia in malaria

We report a case of severe hyponatraemia and hypoglycaemia in a patient with complicated falciparum malaria. The use of large volumes of intravenous dextrose as a diluent for quinine may lead to fluid overload and exacerbate hyponatraemia.