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Biomedical subjects

C Caffarelli

Publications and source records attributed to C Caffarelli.

At least 19 recordsLinked to original sources

Changes in bone turnover and in bone mass in women with breast cancer switched from tamoxifen to exemestane.

Recently the third generation aromatase inhibitors have proved their efficacy and tolerability compared with tamoxifen in the adjuvant treatment of women with hormone responsive early breast cancer. However, there is some concern about the possible negative impact of these drugs on bone. The aim of the study was to evaluate the effects of the steroidal aromatase inactivator exemestane on bone turnover markers and on bone mineral density (BMD). Seventy postmenopausal women (62.0+/-8.9 years) with completely resected breast cancer and who were disease-free following 2-3 years on tamoxifen were randomly assigned to continue tamoxifen (n=36) or switch to exemestane (n=34). Sixty-one patients completed the 2-year study period. Bone alkaline phosphatase (B-ALP) and the carboxy-terminal telopeptide of type I collagen (CTX) were measured at baseline and after 3, 6, 9, 12, 18 and 24 months. BMD at lumbar spine (BMD-LS), at femoral neck (BMD-FN), at total hip (BMD-T) and at whole body (BMD-WB) were measured at 6-monthly intervals. Exemestane-treated women showed significant (p<0.01) increases with respect to baseline in both B-ALP and CTX. The difference between the 2 groups reached the statistical significance at month 6 for CTX (p<0.05) and at month 9 for B-ALP (p<0.01). Moreover, the exemestane-treated women showed an early decrease in PTH serum levels (-20.4%, p<0.01 at month 6). In the E group, the percentage changes were -2.37 (p<0.05) BMD-LS, -1.24 (p<0.05) BMD-FN, -1.1 (n.s.) BMD-T, -1.03 (n.s.) BMD-WB at month 12 and -2.99 (p<0.01) BMD-LS, -1.92 (p<0.01) BMD-FN, -2.01 (p<0.05) BMD-T, -1.3 (n.s.) BMD-WB at month 24. The tamoxifen group did not show significant changes in BMD. The differences between the two groups were significant at all skeletal sites except BMD-WB. Our data suggest that switching postmenopausal women from tamoxifen to exemestane causes a marked increase in bone turnover markers with a consequent reduction in BMD. These findings could be due to both the direct effect of exemestane and to the loss of the protective effect of tamoxifen. Therefore, the postmenopausal women switched from tamoxifen to exemestane should be monitored for bone loss especially if other risk factors for osteoporosis are present.

Alkaline Phosphatase↗

Teriparatide's effects on quantitative ultrasound parameters and bone density in women with established osteoporosis.

This study aimed to evaluate the effects of teriparatide [hPTH (1-34)] on quantitative ultrasound (QUS) parameters and bone mineral density (BMD) at the axial and appendicular (hand) skeleton in women with established osteoporosis who had been previously treated with antiresorptive drugs. Sixty postmenopausal women (age 71.1+/-6.8 years) were randomly assigned to either receive once-daily 20-mug subcutaneous teriparatide (n=30) or continue the antiresorptive treatment (n=30). At baseline and at 2-month intervals we measured QUS parameters at the calcaneus using the Achilles Plus (GE, Lunar), measuring speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index; QUS parameters at the phalanxes using the Bone Profiler (IGEA), measuring amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), and fast wave amplitude (FWA); and BMD values at the right hand using dual x-ray absorptiometry. BMD at the lumbar spine, femur, and whole body were measured on a 6-monthly basis. After 1 year of teriparatide treatment, the changes in BMD were 7.1% at the lumbar spine, 2.6% at the femoral neck, -0.8% at the total hip, and -0.6% for the whole body. Teriparatide induced a significant and persistent decrease in BMD at the hand (-3.6% at month 6 and -2.7% at month 12). In the teriparatide group at month 12, AD-SoS was slightly increased (0.7%; not significant), whereas BTT significantly decreased (-16.4%, p<0.001) and FWA significantly increased (17.5%, p<0.001). The FWA/BTT ratio increased by 26.6% and 32.9% at months 6 and 12, respectively, in the teriparatide group and remained unchanged in the antiresorptive group. In women with established osteoporosis who had previously been treated with various antiresorptive drugs, 1 year of teriparatide treatment determined the expected increase in BMD at the axial skeleton and a significant and prolonged decrease in BMD at the hand. Moreover, teriparatide determined important changes in BTT and FWA, two parameters obtained from the analysis of ultrasonographic trace at the phalanxes, which could be considered in monitoring for the early effect of teriparatide on bone.

Aged↗

Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis.

The mechanisms underlying the skeletal resistance to PTH in patients on chronic hemodialysis (CHD) are not yet fully clarified. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) modulate the genesis and activity of osteoclasts, however their role in renal osteodystrophy pathogenesis has not been clarified so far. The present study aimed to evaluate OPG and RANK-L serum levels in hemodialysis patients and whether OPG/RANK-L system could have a role in the skeletal resistance to PTH. In fasting blood samples obtained from 60 patients (36 males and 24 females) on CHD for at least 2 yr and from 40 healthy subjects of similar age and gender distribution as controls (CTRs), we measured serum OPG, RANK-L, bone alkaline phosphatase (B-ALP), N-terminal telopeptide of type I collagen (NTx), PTH(1-84), calcium and phosphate. In 30 of 60 hemodialysis patients, a blood sample was also drawn soon after the dialytic session. Serum levels of RANK-L, but not OPG, showed a slight but significant (p<0.05) decrease after the dialytic session. OPG resulted being about six times higher in CHD patients than in CTRs (38.7 +/- 16.2 vs 6.3 +/- 0.17 pg/ml), whereas RAN K-L serum levels were only slightly increased with respect to controls (0.88 +/- 0.47 vs 0.64 +/- 0.38 pmol/l). CHD patients showed serum PTH(1-84) and bone turnover higher than in CTRs. No correlation was found between OPG/RANK-L system and PTH or bone turnover markers. Instead, in the patients with high osteoclast activity (no.=21) OPG/RANK-L ratio was correlated (r=-0.41, p<0.01) with NTx serum levels, whereas in patients with decreased osteoclast activity (no.=39) no relationship was found. In conclusion, our findings showed that, although both OPG and RANK-L are accumulated in hemodialysis patients, only RANK-L and the balance between OPG and RANK-L seem to be related to osteoclast activity.

Aged↗

Bone ultrasonography in glucocorticoid-induced osteoporosis.

Osteoporosis is one of the major complications of glucocorticoid (GC) therapy. Few data are available on the usefulness of quantitative ultrasound (QUS), a technique that could also theoretically provide information on bone structure, in the management of glucocorticoid-induced osteoporosis (GIO). This study aimed (1) to evaluate the ability of QUS in detecting bone impairment and in being associated with the prevalence of fragility fracture in GC patients; and (2) to assess whether QUS parameters, and particularly the graphic trace analysis of QUS signal at phalanges, show any peculiar pattern of GIO. We studied 192 patients (136 women and 56 men, mean age 56.7 +/- 14.2 years) on treatment with GCs for at least 6 months, and 192 sex- and age-matched controls. In all subjects, we measured bone mineral density (BMD) at lumbar spine and at femur by DXA, and ultrasound parameters at calcaneus and phalanges. All DXA and QUS parameters were significantly lower in GC patients than in controls and in fracture than in nonfracture GC patients. BMD at lumbar spine showed the best ability in discriminating GC patients with or without fractures. Among QUS parameters, stiffness showed a discriminatory ability significantly better than AD-SoS. BMD at lumbar spine and total femur, stiffness, and AD-SoS are able to predict the odds of fragility fracture event. QUS parameters of the postmenopausal GC patients (n = 105) and of the postmenopausal healthy controls (n = 101) were also compared with those obtained in a separate sample of 90 postmenopausal osteoporotic women (PMO). All parameters were significantly lower in GC patients and in PMO than in controls, without any significant difference between GC and PMO. Our findings show that QUS can be useful in the assessment of glucocorticoid-induced bone impairment. In addition, in this study we found no alteration in QUS parameters or in the graphic trace analysis which could differentiate between GIO and PMO. Further longitudinal studies are needed to define the role of QUS in the prediction of fracture risk and in the clinical management of GIO.

Absorptiometry, Photon↗

Alendronate treatment in men with primary osteoporosis: a three-year longitudinal study.

Bisphosphonates have been widely used in the treatment of osteoporosis in women, whereas until now there have been few data on their use in men. The aim of this study was to evaluate the effect of a 3-year alendronate treatment on bone mineral density (BMD) and quantitative ultrasound (QUS) in men with primary osteoporosis. We studied 77 osteoporotic men (aged 57.1 +/- 10.8 yrs) who completed a 3-year treatment with alendronate (10 mg/day) plus calcium (1000 mg/day) (n = 39), or calcium alone (n = 38). At baseline and at a 12-month interval, we measured BMD at the lumbar spine and femur (femoral neck and total hip) by DXA (Hologic) and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness (S) at the os calcis by Achilles plus (Lunar). Alendronate treatment had significantly increased lumbar spine BMD by 4.2% at year 1, by 6.3% at year 2, and 8.8% at year 3. BMD at the femoral neck and total hip had increased by 2.1% and 1.6% at year 1, by 3.2% and 2.9% at year 2, and by 4.2% and 3.9% at year 3, respectively. BUA and Stiffness showed a significant increase in the alendronate-treated group at year 2 (3.2% and 4.9%, respectively) and at year 3 (3.8% and 6%, respectively). BMD at the lumbar spine showed the best longitudinal sensitivity whereas longitudinal sensitivity of both QUS at the heel and femur BMD were similar. In conclusion, this study confirms that alendronate represents an important therapeutic advance in the management of male osteoporosis. BMD at the lumbar spine appears to be the best method for monitoring the effect of alendronate on bone mass in osteoporotic men.

Absorptiometry, Photon↗

Determination of allergenicity to three cow's milk hydrolysates and an amino acid-derived formula in children with cow's milk allergy.

BACKGROUND: Products based on hydrolysed cow milk proteins or amino acid mixtures are recommended in children with cow's milk hypersensitivity. However, some children who are allergic to cow's milk and who clinically react to substitute milk formulas have been observed. OBJECTIVE: To determine the tolerance and allergenicity of protein hydrolysate or amino acid-derived formulas in children with IgE-mediated cow's milk allergy. METHODS: Twenty children with positive cow's milk challenges, positive skin prick tests and/or serum-specific IgE antibodies to cow's milk were selected. Oral challenges, skin prick tests and serum-specific IgE antibodies to extensively hydrolysed whey formula, partially hydrolysed whey formula, extensively hydrolysed casein formula and amino acid-derived formula were performed. RESULTS: Five out of 17 (5/17) children reacted to partially hydrolysed whey formula, (3/16) to extensively hydrolysed whey formula, (2/10) to amino acid-derived formula, (1/16) to extensively hydrolysed casein formula. Only extensively hydrolysed casein formula was tolerated by at least 90% (with 95% confidence intervals) of children. Hydrolysates provoked early and delayed clinical reactions, amino acid mixtures only delayed reactions. Partially hydrolysed whey formula elicited a significantly higher number of positive skin prick test reactions than other formulas. Two children had specific IgE antibodies to extensively hydrolysed whey formula, one to partially hydrolysed whey formula, one to extensively hydrolysed casein formula and none to amino acid-derived formula. CONCLUSION: In this study, none of the cow's milk substitutes has been found to be non-allergenic. Our results suggest that in children with IgE-mediated cow's milk allergy, the first ingestions of extensively hydrolysed cow's milk protein formulas require strict medical supervision because of immediate reactions. This is not the case for amino acid-derived formula. Moreover, our data suggest that treatment of children allergic to cow's milk with cow's milk substitutes should be monitored for several days to document tolerance.

Allergens↗

Low-dose local nasal immunotherapy in children with perennial allergic rhinitis due to Dermatophagoides.

BACKGROUND: Allergen specific immunotherapy was known to be useful in the treatment of respiratory allergic disease. Local nasal immunotherapy (LNIT) offers advantages such as a good efficacy/safety ratio and a more convenient allergen delivery. The aim of this study was to assess the safety and clinical efficacy of a modified scheduling of LNIT in 32 children with allergic rhinitis due to Dermatophagoides. METHODS: A multicentre, randomized, double-blind placebo controlled study carried out for two years, with a modified schedule of LNIT treatment: a build-up phase at increasing dosages from 2.5 AU to 80 AU and a maintenance period at low dosage (80 AU) once a week. Symptom and medication scores. threshold dose with specific nasal provocation test (NPT) and immunological parameters (IgE and IgG4) were evaluated. RESULTS: No important local or systemic side-effects were observed in children who completed the study. Compared to placebo, the active treatment group showed significant improvement in rhinitis symptoms and a reduction of drug consumption after 18 months of LNIT. These results were confirmed by a significant reduction of allergen specific nasal reactivity. Serum and nasal specific IgE and IgG4 did not show any difference in the two groups. CONCLUSIONS: The safety and clinical efficacy of low-dose LNIT suggests that this therapy may be useful in the treatment of allergic rhinitis disease in children.

Administration, Intranasal↗

False-negative food challenges in children with suspected food allergy.

Food allergy can be diagnosed from an immediate-onset reaction after oral food challenge. We administered 370 challenges in 242 children; five (3%) of the 193 children tolerating foods on challenges developed immediate symptoms when the same preparation of foods was ingested openly at home the next day. We confirmed the food allergy by subsequent double-blind challenges. All children had positive skin-prick test reactions and all, but one, specific IgE antibodies to the offending foods. Our findings suggest that open feedings under observation, the day after negative challenges, are useful to eliminate false-negative challenge results.

Adolescent↗

Duodenal IgE-positive cells and elimination diet responsiveness in children with atopic dermatitis.

BACKGROUND: Parameters for identifying eczematous children who could respond to an elimination diet are needed. In children with food allergy, duodenal IgE-containing cells are enhanced. OBJECTIVE: To determine the presence of duodenal mucosal IgE-positive cells in atopic dermatitis and to determine whether duodenal IgE-positive cells may identify eczematous children who will benefit from an elimination diet. METHODS: Thirty-one children with severe eczema underwent gastrointestinal endoscopy because of gastrointestinal symptoms and were treated with an elimination diet. A clinical score to skin lesions was given before and after diet. All subjects were skin-prick tested with food antigens and aeroallergens. Serum IgE levels were measured. Duodenal IgE-positive cells were investigated in 18 control subjects and in all eczematous children before diet. RESULTS: The number of duodenal IgE-positive cells in children with atopic dermatitis was significantly increased compared with that of control group (P < 0.001). Nineteen (61%) eczematous children improved on a few food diet. Diet-responsive children had significantly higher IgE-positive cells compared with both nondiet-responsive and controls. Positive predictive accuracy of duodenal IgE-positive cells was poor, whereas negative predictive accuracy was high at the cutoff level of 50 IgE-positive cells/10 visual fields. Diagnostic accuracy both of SPT reactions with foods and of food-specific serum IgE antibodies was poor. CONCLUSIONS: An intestinal IgE-mediated reaction occurred in children with severe atopic dermatitis who underwent intestinal endoscopy because of gastrointestinal symptoms. In these eczematous children, the number of IgE-positive cells in the duodenal mucosa might be helpful for excluding a positive response to the elimination diet.

Adolescent↗

Antibiotic resistance and antibiotic sensitivity based treatment in Helicobacter pylori infection: advantages and outcome.

AIMS: To compare two strategies for the eradication of Helicobacter pylori infection. METHODS: Groups 1 and 2 each consisted of 75 consecutive patients. Patients in group 1 were treated with two antibiotics based on antibiotic susceptibility testing; those in group 2 received amoxycillin and clarithromycin for eight days, together with either ranitidine or omeprazole. Eradication rate was assessed in both groups six months after treatment. RESULTS: In group 1, H pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63 isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and metronidazole. In group 1 the infection was eradicated in 96% of the initial 75 subjects, and in 98% of the subjects treated according to the antibiotic assay (62/63). As two patients were lost at follow up the overall eradication rate was 99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was significantly lower than the percentage of eradication observed in group 1 (81% versus 99%). CONCLUSIONS: Antibiotic susceptibility tests are useful in childhood as a very high percentage of subjects are cured. This approach is costly, but selective antibiotic treatment contributes to limit further development of antibiotic resistance, and money is saved in terms of reinvestigation and further repeated treatments.

Adolescent↗

Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. METHODS: We randomly assigned 24 children allergic to grass pollen to receive local allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. RESULTS: The active-treatment group had a statistically significant reduction of total symptoms (P<0.05), especially bronchial symptoms (P<0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EG1 increased significantly only in the placebo group during natural allergen exposure (P<0.01). CONCLUSIONS: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.

Administration, Oral↗

Treating asthma in children with beclomethasone dipropionate: Pulvinal versus Diskhaler.

Seventy-two children (mean age, 10.1 years) with stable moderate asthma who completed a 7-day run-in period were randomized to receive a 4-week treatment with beclomethasone dipropionate (200 micrograms twice daily) administered through two different powder inhalers (Pulvinal; Chiesi Farmaceutici S.p.A, Parma, Italy and Diskhaler; Glaxo-Wellcome, Evreux, France) in a parallel group design. Sixty-nine patients completed the study. Morning and evening peak expiratory flow values, the use of rescue salbutamol, and the severity of clinical symptoms were recorded daily on a diary card. Pulmonary function tests were performed at baseline and then after 2 and 4 weeks of treatment. Pulmonary function values, daily morning and evening peak expiratory flow, and most of the clinical symptoms significantly improved, although the use of rescue salbutamol significantly decreased from the second week of treatment until the end of the study in both groups. Equivalence of efficacy between groups was demonstrated for both pulmonary function and clinical parameters. We conclude that the Pulvinal inhaler is as efficacious as the Diskhaler in beclomethasone-based therapy of asthmatic children.

Administration, Inhalation↗

Gastrointestinal symptoms in patients with asthma.

AIMS: Minor gastrointestinal abnormalities have been reported in children with asthma, but the prevalence of gastrointestinal symptoms in these children has not been studied. METHODS: 75 children with bronchial asthma and an age and sex matched control group were recruited. Parents completed a questionnaire on gastrointestinal symptoms and on asthma. Weight and height were measured; a clinical evaluation of asthma was undertaken and skin prick tests were performed. RESULTS: Children with asthma had a significantly greater frequency of gastrointestinal symptoms, particularly diarrhoea, vomiting, and abdominal pain, than did controls. Gastrointestinal symptoms were slightly more common in children with atopic symptoms other than asthma, or with positive skin prick tests to foods. There was no association between current gastrointestinal symptoms and medications or attacks of asthma. CONCLUSIONS: The occurrence of gastrointestinal symptoms appears to be common in children with asthma. These symptoms might be caused by an atopic gastroenteropathy, which might play a part in the pathogenesis of asthma in some cases.

Adolescent↗

Cutaneous CD30+ cells in children with atopic dermatitis.

BACKGROUND: CD30 expression can be considered a marker of Th2 cells. We investigated the presence of CD30+ cells in the lesional skin of children with atopic dermatitis (AD). We also analyzed the possible relationship between CD30+ cells and serum soluble CD 30 (sCD30) levels, and IgE, soluble interleukin-2 (IL-2) receptor (sIL-2R) or soluble CD23 (sCD23) levels in the blood, and clinical score. METHODS: Ten eczematous children (4 males, 6 females; median age: 4 years and 5 months; range: 11 months to 14 years), 9 sex- and age-matched control children and an adult control group were studied. A clinical score (SCORAD index), was given to eczematous lesions. Blood was taken for the determination of IgE, sCD30, sIL-2R and sCD23 levels. Punch biopsies of lesional skin were stained with hematoxylin and eosin or incubated with anti-CD30 monoclonal antibodies. Skin prick tests (SPTs) were also performed. RESULTS: In the biopsy specimens, CD30 expression was observed in high proportions of infiltrating cells. In children with AD, total serum IgE, sCD30, sIL-2R, sCD23 and eosinophils were significantly elevated compared to controls. CD30+ cells were not associated with serum IgE, sCD30, sIL-2R, sCD23, or SPT results, score of inflammatory cells in lesional skin or clinical score. Children with AD who had high total IgE and specific IgE antibodies did not differ from those with normal total IgE and negative specific IgE in respect of age, clinical score, number of CD30+ cells, sCD30, sIL-2R and sCD23 levels, score of inflammatory cells in skin or clinical score. CONCLUSION: Our results showed remarkable numbers of CD30+ cells in the lesional skin and high sCD30 in the serum of children with AD. CD30+ cells did not correlate with systemic markers of IgE reaction.

Adolescent↗

[From atopic eczema to respiratory allergy].

The prevalence of atopic eczema in childhood is increasing. This is probably related with a deviation of immune system to Th2 directed to allergen instead of Th2 directed to microorganisms. Atopic eczema is genetically linked, but its expression is principally determined by environmental factors, allergens and infections. In children with atopic eczema, the immune system is altered. The number of Langheran's cells is augmented. Th2 cells infiltrate the skin and produce cytokines which mediate both immediate and late allergic reaction. Most of eczematous children is allergic to food. A IgE-mediated reaction take place at the mucosal intestinal site. The food challenge test is the most reliable mean to identify offending foods. Soy formula can be used in the treatment of cow milk allergy. The tolerance of formulae based on cow milk hydrolysed protein should be tested under medical supervision in children with cow milk allergy. Prevention of atopic disease with dietary interventions has not been successful. To prevent asthma, the administration of immunotherapy in children with allergic rhinitis seems to be promising. In eczematous children with elevated total IgE and specific IgE to inhalant allergens, cetarizine seems to prevent onset of asthmatic symptoms.

Asthma↗

Atopy in children with otitis media with effusion.

BACKGROUND: Contrasting data have been found on the prevalence of atopy in children with otitis media with effusion (OME). A major issue would be to determine whether screening for atopy should be recommended. Setting Centre for Study of Otitis Media with Effusion, Tabiano Terme, Parma, Italy. OBJECTIVE: The purpose of this study was to investigate the relation of OME to atopy. METHODS: The subjects were 172 children with OME and a control group of 200 children. The protocol included a questionnaire survey of diseases associated with atopy, a skin-prick test and a clinical evaluation of allergic symptoms and hypersensitivity to aeroallergens. RESULTS: No significant difference between patients and control group was observed for family history of atopy or positive skin-prick test reactions. Symptoms associated with atopy occurred significantly more frequently in the group with OME (P<0.001), though only the presence of rhinitis or atopic eczema was significantly associated with OME. CONCLUSIONS: Prevalence of positive skin-prick tests results is not enhanced in children with OME. Nevertheless, the association of OME with symptoms associated with atopy suggests that such concomitant diseases may play a part in the pathogenesis of the disorder. Children with allergic rhinitis or atopic eczema should be investigated by tympanometry for OME.

Acoustic Impedance Tests↗