Bone Mineral Density Determinations by Dual-Energy x-ray Absorptiometry in the Management of Patients with Marfan Syndrome—Some Factors Which Affect the Measurement

Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex.     

Abnormal sensorimotor integration is related to disease severity in Parkinson's disease: a TMS study.

Hyperexcitability of the motor system has been reported in Parkinson's disease (PD). We evaluate how cutaneous afferents modulate motor excitability in PD patients and whether abnormal modulation is correlated to parkinsonian symptoms. Digital stimulation causes abnormal enhancement of motor responses in patients. This effect may be one of the features of motor hyperexcitability in PD. Cutaneomotor hyperexcitability correlates with clinical scores, suggesting that abnormal processing of cutaneous inputs might contribute to the pathogenesis of parkinsonian symptoms.     

Hypoxemia after heart surgery. An exception or a normal development?]

The course of respiratory exchange through arterial blood gas analysis after coronary bypass-grafting and valvular replacement has been investigated in a cohort of 62 patients. Arterial blood gases were measured at baseline (the day before surgery), and then 1, 2, 3 and 9 days after surgery; in a subset of 18 patients, randomly selected from the same population, pulmonary function tests were also performed at baseline and repeated on day 9. Arterial blood gases showed a remarkable prevalence of hypoxaemia (as defined as arterial PaO2 less than 60 mmHg): 31% on the first, 50% on the second, and 40% on the third post-operative day; anemia and desaturated mixed venous blood were also prominent findings during the first two days. Arterial PO2 resulted higher afterward, although its mean value then was significantly lower than baseline (81.5 +/- 8.8 vs 93.1 +/- 9 mmHg, p less than 0.005). Pulmonary function tests evidenced widespread restrictive changes, with alterated thoraco-pulmonary mechanics (loss of more than 40% of vital capacity and one second forced expiratory flow) and parenchimal lung damage (residual volume and CO diffusion capacity decrease). Some differences in PaO2 course between coronary patients and valvular patients have been releaved; the mean basal PaO2 value of valvular was significantly lower then the other one (86.7 +/- 10.8 vs 94.7 +/- 10.9, p less than 0.05).     

Caffeine restores regional brain activation in acute hypoglycaemia in healthy volunteers.

AIMS: Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our aim was to explore its effects on cortical function, which are not known at present. METHODS: Regional brain activation during performance of the four-choice reaction time (4CRT) at different levels of complexity was measured using functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy right-handed men. RESULTS: During hypoglycaemia, caffeine enhanced adrenaline responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01) and restored the brain activation response to the non-cued 4CRT, the linear increases in regional brain activation associated with increased task complexity and the ability to respond to a cue that were lost in hypoglycaemia alone. CONCLUSIONS: Caffeine can sustain regional brain activation patterns lost in acute hypoglycaemia, with some restoration of cortical function and enhanced adrenaline responsiveness. A methodology has been established that may help in the development of therapies to protect against severe hypoglycaemia in insulin therapy for patients with diabetes and problematic hypoglycaemia.     

Transglutaminase in cell proliferation and transformation

Transglutaminase (TGase) activity was reduced in intact mitogen-stimulated human peripheral blood lymphocytes (PBL) when compared to intact resting PBL. Moreover, a treatment of the same quiescent immunocompetent cells with purified liver TGase and Ca²⁺ completely suppressed the mitogen-induced blast transformation. A decrease in TGase activity in neoplastically transformed seminal vesicle epithelial cells with respect to their normal parent counterpart was also observed. Our data support the notion of a possible implication of TGase in cell proliferation and transformation.     

Alteration of acylphosphatase levels in familial Alzheimer''s disease fibroblasts with presenilin gene mutations

Acylphosphatase (ATPase), an enzyme that modulates the activity of Ca²⁺-ATPase by hydrolysing its phosphorylated moiety, has been found to be significantly higher in cultured skin fibroblasts from donors affected by early onset familial Alzheimer's disease (EOFAD) with PS-1 and PS-2 gene mutations. Of the two known isoenzymes of acylphosphatase, only the erythrocyte one accounts for the total increase in activity. No relevant alteration was observed in phosphotyrosine phosphatase activity (PTPase), in Ca²⁺-ATPase and Na⁺,K⁺-ATPase activities of the same cells as compared to age-matched controls. This finding could suggest a possible explanation for the calcium-dependent biochemical alterations previously described in Alzheimer's disease fibroblasts.     

Allergenicity of goat’s milk in children with cow’s milk allergy

BACKGROUND: Cow's milk allergy (CMA) is a common disease of infancy and childhood. An appropriate cow's milk (CM) substitute is necessary for feeding babies with CMA. CM substitutes are soy formulas and casein- or whey-based extensively hydrolyzed formulas. In several countries, including Italy, goat's milk (GM) formulas are available, and some physicians recommend them for feeding babies with CMA. OBJECTIVE: We sought to investigate, in vitro and in vivo, the allergenicity of GM in 26 children with proven IgE-mediated CMA. METHODS: All the children underwent skin tests with CM and GM; detection of specific serum IgE to CM and GM; and double-blind, placebo-controlled, oral food challenges (DBPCOFCs) with fresh CM, GM, and, as placebo, a soy formula (Isomil, Abbott, Italy). CAP inhibition and immunoblotting inhibition assays were also carried out in 1 of 26 and 4 of 26 children with positive RAST results to both CM and GM, respectively. RESULTS: All the children had positive skin test responses and CAP results to both CM and GM, all had positive DBPCOFC results to CM, and 24 of 26 had positive DBPCOFCs to GM. In CAP inhibition tests, preincubation of serum with CM or GM strongly inhibited IgE either to CM or to GM. In immunoblotting inhibition assays, preincubation with CM completely extinguished reactivity to GM, whereas GM partially inhibited reactivity to CM. CONCLUSIONS: These data strongly indicate that GM is not an appropriate CM substitute for children with IgE-mediated CMA. A warning on the lack of safety of GM for children with CMA should be on the label of GM formulas to prevent severe allergic reactions in babies with CMA.     

Relative value of selective group A streptococcal agar incubated under different atmospheres.

A commercially available selective group A streptococcal agar (ssA) was evaluated for the recovery of group A streptococci (GAS) in comparison with recovery from simultaneous cultures on conventional sheep blood agar (SBA). Both sets of plates were incubated in air, 5% CO2, and anaerobically for 48 h, with a first reading taken at 24 h. A total of 402 (67.0%) GAS were isolated from the 600 specimens that were submitted. Recovery of GAS was significantly greater after 48 h of incubation than after 24 h of incubation for each medium-atmosphere combination. After 48 h of incubation, the sensitivities of GAS detection obtained by each culture technique were as follows: ssA-anaerobic atmosphere, 98.5%; SBA-anaerobic atmosphere, 89.5%; ssA-CO2 atmosphere, 88.0%; SBA-air, 86.5%; SBA-CO2 atmosphere, 82.0%; and ssA-air, 74.6%. There were no cultures positive in air or CO2 which were not positive anaerobically on either medium. The increased sensitivity of detecting positive GAS cultures when incubation was done in an ssA-anaerobic atmosphere for 48 h uncovered patients truly infected with the organisms.     

Allergenicity of mare's milk in children with cow's milk allergy

BACKGROUND: Cow's milk allergy is a common disease of infancy and early childhood. If the baby is not breast-fed, a substitute for cow's milk formula is necessary. OBJECTIVE: The aim of this study was to investigate, in vitro and in vivo, the allergenicity of mare's milk in a population of selected children with severe IgE-mediated cow's milk allergy. METHODS: Twenty-five children (17 male and 8 female) aged 19 to 72 months (median age 34 months) with IgE-mediated cow's milk allergy were selected for this study. All the children underwent skin prick tests with cow's milk and mare's milk and double-blind placebo-controlled oral food challenge (DBPCOFC) with fresh cow's milk, fresh mare's milk, and, as placebo, a soy formula (Isomil, Abbott, Campoverde, Italy). We performed immunoblotting of cow's and mare's milk developed with IgE from allergic children. RESULTS: All the children showed strong positive skin test responses to cow's milk (4+); 2 children had positive skin test responses to mare's milk (2+). All children had positive DBPCOFCs to cow's milk; one child had a positive DBPCOFC to mare's milk. No children reacted to the placebo (Isomil). In the cow's milk, some proteins are able to strongly react with human IgE; when the sera are tested with mare's milk, the bands corresponding to the same proteins are recognized by a lower percentage of sera. CONCLUSION: These data suggest that mare's milk can be regarded as a good substitute of cow's milk in most children with severe IgE-mediated cow's milk allergy. It would be prudent, however, to confirm its tolerability by a supervised titrated oral challenge test.     

The set of naturally processed peptides displayed by DR molecules is tuned by polymorphism of residue 86

The response to tetanus toxoid (TT) was studied in immune donors that carry two alleles of DR5 that differ only at DRβ residue 86: DRB1*1101 (G86, abbreviated 1101) and DRB1*1104 (V86, abbreviated 1104). A large number of TT-specific T cell clones was isolated and the epitopes recognized in association with 1101 and 1104 were mapped. We found that two epitopes (p2 and p32) can be recognized in association with both 1101 and 1104 while three epitopes (p23, p27 and p30) are recognized in association with 1101, but never in association with 1104. The sets of naturally processed self peptides displayed by 1101 and 1104 were characterized using alloreactive T cell clones. We found that all 1104 alloreactive clones recognize both 1104 and 1101, while ?30% of the alloreactive 1101 clones fail to recognize 1104. Thus it is apparent that both naturally processed TTand self peptides displayed on 1104 molecules represent a fraction of those displayed on 1101 molecules. The mechanism responsible for this differential presentation was investigated by comparing the capacity of 1101 and 1104 antigen-presenting cells to present TTor synthetic peptides to specific T cells and by measuring the binding of these peptides to DR molecules. Three sets of results suggest that V86 acts as a constraint to the binding of naturally processed peptides: (i) all 1104-restricted or alloreactive T cell clones recognize TT- or allo-epitopes presented by 1101 as well, thus ruling out a major effect of V86 as a residue determining T cell restriction specificity; (ii) presentation of naturally processed peptides correlates in general with the capacity of long synthetic peptides to bind to 1101 or 1104 and (iii) while the naturally processed p30 epitope discriminates between 1101 and 1104, a short synthetic peptide binds equally well to and is comparably recognized in association with both 1101 and 1104. Taken together these results suggest that the natural polymorphism at residue 86 might be a molecular switch that finely tunes the complexity of the peptide collection presented on DR molecules.