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Biomedical subjects

F Castello

Publications and source records attributed to F Castello.

At least 19 recordsLinked to original sources

Statins and osteoporosis: myth or reality?

Several beneficial effects produced by statins over and above the reduction in plasma cholesterol levels, the so-called ''pleiotropic effects'' of statins, have been described. Recent clinical and experimental data have suggested a potential new effect of these drugs, namely a reduction in the risk of osteoporotic fractures. In 1999 the role of statins in bone formation was shown and, after that, observations of large groups of patients have pointed to a reduction in the risk of osteoporotic fractures with the use of statins compared to those using other lipid-lowering drugs or to the control group. The first prospective studies have produced contrasting results as to the effects of therapy with several statins (atorvastatin, fluvastatin, simvastatin) at different doses on biochemical markers of bone remodelling. To date only one randomised trial has been published. This compares the effects of treatment with simvastatin and atorvastatin on the levels of biochemical markers of bone remodelling, but still with non-univocal results: only therapy with simvastatin (but not atorvastatin) reduced the levels of bone-specific alkaline phosphatase. To conclude, observational studies have shown a reduction in the risk of osteoporotic fractures with the use of statins, but it is not yet known whether using these drugs may have a beneficial effect on bone turnover. We must therefore await larger prospective randomised clinical trials before prescribing these drugs in osteoporotic patients.

Anticholesteremic Agents↗

Treatment of hydrops fetalis with hemofiltration.

The treatment of hydrops fetalis, a critical state of extravascular fluid overload in the newborn, poses a great medical challenge. The aim of this study was to investigate the use of continuous arteriovenous hemofiltration (CAVH) in the treatment of five critically ill newborns with hydrops fetalis of different etiology. All patients had anasarca, oliguria not responsive to diuretics, were on mechanical ventilation, and were treated with inotropic drugs and sedation. The duration of treatment ranged from 42 to 114 h and all patients, except one who died from congenital heart disease, achieved the clinical goals of weight loss and restoration of diuresis. Regular clinical and neurological follow-up to the age of 2 years was normal for the four surviving patients. In conclusion, CAVH appears to be a safe treatment of fluid overload in newborns with hydrops fetalis.

Body Weight↗

Monitoring of brain spiking activity and autoantibodies to N-terminus domain of GluR1 subunit of AMPA receptors in blood serum of rats with cobalt-induced epilepsy.

We have monitored EEG spontaneous spiking activity and analyzed serum from rats with cobalt-induced epilepsy for the presence of autoreactive antibodies to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptide specific to the N-terminus domain of the GluR1 subunit of the AMPA receptor. Rats with cobalt-induced epilepsy exhibited strong GluR1 immunoreactivity at the end of the first week after surgery compared with vehicle-treated rats. We showed that GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy preceded the spiking activity maximum in the EEG. Levels of autoantibodies to GluR1 detected in blood of these rats remained elevated when EEG spiking activity was significantly reduced and seizures disappeared. The EEG monitoring of spiking activity showed a correlation with accumulation of GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy.

Animals↗

Lessons learned from autopsies at a pediatric teaching hospital.

Twenty-six percent of pediatric patients had discrepant major diagnoses revealed at autopsy. A printed form used to document permission for autopsies improved the autopsy rate. No variables were found to predict the success rate for obtaining autopsies.

Autopsy↗

Attitudes of pediatricians and pediatric residents toward obtaining permission for autopsy.

OBJECTIVE: To investigate attending physician and resident attitudes and factors affecting autopsy consent. METHODS: A validated, self-report, multiple-choice questionnaire was administered to 158 physicians. RESULTS: The overall response rate was 113 (72%), with 57 (85%) of 67 pediatric residents and 51 (56%) of 91 attending physicians responding. The status of five respondents was unknown. Most respondents (98%) believed autopsies provide valuable information; physicians who had graduated before 1980 were more likely to believe that the benefits of autopsy should be taught (P < or = .002). Autopsy was considered unnecessary by 20% (22/112) when the disease was known before death and by 11% (12/112) when the patient was designated "do not resuscitate." Physicians who did not attend an autopsy while in training were less likely to believe in the benefits of autopsy (P < or = .02). Factors that influenced the failure to obtain consent for an autopsy were physician belief that the family felt the body would be desecrated (30/81 [37%]); physician belief that the family would be upset (36/104 [35%]); and physician belief that little information would be obtained (19/104 [18%]). Fourteen (17%) of 81 physicians indicated that they do not ask permission for autopsy if the family is upset. CONCLUSION: Most physicians believe autopsies have benefit. If the autopsy rate is to improve, physicians in training will require increased exposure to autopsies, education regarding the potential benefits, and enhancement of interpersonal skills for successful communication with families in crisis.

Attitude of Health Personnel↗

[Considerations regarding the treatment of non-aganglionic congenital intestinal neuropathies].

Hyperganglionosis or neuronal intestinal dysplasias (NID) and hypoganglionosis (HO) are intestinal diseases of difficult diagnosis and treatment and diverse evolution, despite identical histologic findings. The aim of this study was to discuss the therapeutic problems derived from the patients differing clinical course. Retrospective review of 14 patients with regard to diagnosis, manometry and histology (hematoxylin-eosin, acetylcholinesterase activity, immunohistochemistry and Smith's silver stain) was done. Six patients presented intestinal occlusion or sub-occlusion from the first months of life with impeded oral feeding. Ileostomy was performed in 5 and total colectomy with anastomosis in 1. All patients required parenteral nutrition; cisapride was added in 2. Three died from sepsis (3 NID). Of the 3 survivors, 2 have ileostomies (2 NID) and the other ileo-rectal anastomosis (NID). Of the remaining patients, two presented aganglionism and the finding of proximal hyperganglionism occurred post-surgery. Surgery was repeated in one patient. The remaining 6 (1 HO, 5 NID) were diagnosed between 3 and 10 years of age because of constipation. Four are under treatment with cisapride and 2 required partial colic resection. No relationship can be established between histologic findings and clinical manifestations. In chronic clinical courses, treatment with cisapride and cleaning enemas should be tried first. Acute clinical pictures (occlusion-sub occlusion) should be treated by decompressive ileostomy. Partial colic resection may lead to new intestinal failure.

Anastomosis, Surgical↗

Dose-related effect of beclomethasone dipropionate on airway responsiveness in asthma.

The effects of twice daily inhaled beclomethasone dipropionate (BDP) at two dose levels (500 and 1,000 micrograms daily) on the airway responsiveness to inhaled histamine was evaluated by a randomized, single-blind, cross-over study in 10 patients with stable asthma. The 12-week study began with a 3-week run-in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a 3-week placebo period. Patients attended the laboratory every 3 weeks for spirometry and histamine inhalation tests to determine the provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 s (PC20 of FEV1). There was a similar significant improvement (p less than 0.05) in mean FEV1 after both treatments. There was no significant change in PC20 after treatment with 500 micrograms daily, the geometric mean being 0.587 mg/ml after the placebo period and 0.860 mg/ml after BDP treatment. There was a significant improvement in PC20 (1.930 mg/ml) after treatment with 1,000 micrograms BDP daily in comparison with the placebo and treatment periods with 500 micrograms BDP daily (p less than 0.001). These results suggest that higher doses than usual of inhaled BDP must be used to control airway responsiveness in asthmatics.

Adult↗

Effect of beclomethasone dipropionate on the bronchial responsiveness to propranolol in asthmatics.

The effect of four weeks of treatment with beclomethasone dipropionate (BDP, 500 micrograms twice daily) on the bronchial responsiveness to propranolol was examined in 16 patients with mild asthma in a placebo-controlled, double-blind crossover study. Propranolol was inhaled in doubling concentrations and the results were expressed as the cumulative dose producing a 20 percent fall in FEV1 (PC20). After four weeks of treatment with BDP, the mean FEV1 increased from 82.0 percent predicted to 88.1 percent predicted. The difference was significant (p less than 0.001). Treatment with BDP did not significantly change the responsiveness to propranolol, the geometric mean PC20 being 3.17 mg/ml before and 3.64 mg/ml after BDP treatment. The recovery of FEV1 was faster after 60 minutes of BDP treatment in comparison with placebo treatment (beyond 90 minutes). This study suggests that BDP treatment is unable to reduce bronchial responsiveness to propranolol but can accelerate the recovery of bronchoconstriction induced by propranolol in asthmatic patients.

Administration, Inhalation↗

Increased responsiveness to histamine after propranolol in subjects with asthma nonresponsive to the bronchoconstrictive effect of propranolol.

Eight nonsmoking subjects with asthma, nonresponsive to the bronchoconstrictive effect of oral propranolol, were studied. The airway response to increasing concentrations of histamine aerosol was assessed by measuring FEV1. The threshold provocative dose of histamine needed to cause a 20% fall in starting FEV1 (PD20) was measured by log dose-response curve. Histamine challenge was performed in duplicate after premedication with placebo or 40 mg of propranolol on separate days. The mean starting FEV1 did not change significantly after placebo and after propranolol administration. The mean PD20 values after propranolol (0.37 mg/ml and 0.32 mg/ml, respectively, for the first and the second challenge) were significantly lower (p less than 0.01) than mean control PD20 values (1.36 mg/ml and 1.48 mg/ml, respectively, for the first and the second challenge). These results indicate that propranolol increases airway responsiveness to histamine, even in those subjects with asthma in whom propranolol has little bronchoconstrictive effect.

Adult↗

Effect of ketotifen on the bronchodilation induced by salbutamol.

Twelve subjects with stable asthma each inhaled two puffs (200 micrograms) of salbutamol on 2 separate days 3 h after double-blind oral administration of ketotifen (two 1-mg capsules) or identical placebo. FEV1 was recorded before and at intervals for 4 h after inhalation of salbutamol. Overall, the FEV1 was significantly greater during the 4-hour period after premedication with ketotifen (p less than 0.02) and the difference between the effect of placebo and ketotifen was statistically significant at 120, 180 and 240 min after salbutamol (p less than 0.05).

Adult↗

Airway responsiveness to histamine in patients refractory to repeated exercise.

To investigate the mechanisms contributing to refractoriness in exercise-induced asthma (EIA), airway responsiveness to histamine was studied in eight asthmatic patients. Patients were included in the study on the basis of their refractory response to multiple exercise challenges. Incremental challenges with inhaled histamine were performed at rest and 40 minutes after single and paired exercise tests. The geometric mean histamine concentration required to produce a 20 percent fall in FEV1 (PC20) for the challenge after paired exercise test (4.34 mg/ml) was significantly higher (p greater than 0.001) than those for the challenges after a single exercise (1.05 mg/ml) and for the challenge at rest (0.67 mg/ml). There was no significant difference between PC20 values at rest and after a single exercise test (p greater than 0.05). The results show that the response to histamine is reduced during the refractory period following paired exercise test.

Adult↗

Effect throughout the day of inhaled fenoterol on the bronchial responsiveness to histamine in asthmatic patients.

The effect throughout the day of inhaled fenoterol on the bronchial responsiveness to inhaled histamine was evaluated in 8 asthmatic patients. The airway response to increasing concentration of histamine aerosol was assessed by measurement of forced expiratory volume in one second (FEV1). The provocative dose of histamine needed to cause a 20% fall in starting FEV1 was calculated from the cumulative log dose response curves. Histamine challenges were performed in duplicate, on separate days, after premedication with placebo or fenoterol given by metered dose inhalers in the morning and in the afternoon. The mean starting FEV1 in the morning and in the afternoon did not change significantly after placebo inhaler, but fenoterol caused a mean increase in FEV1 of 11.11% in the morning and 4.92% in the afternoon. Geometric mean histamine PC20 was significantly higher after fenoterol than after placebo. After fenoterol there was no significant difference between morning and afternoon geometric mean histamine PC20. No relation was found between bronchodilatation achieved by fenoterol and increase in the geometric mean histamine PC20 (p greater than 0.05). There was instead a significant relationship between starting FEV1 and histamine PC20 in the morning and in the afternoon both after placebo and fenoterol.

Adolescent↗

Oral sustained-release aminophylline and bronchodilator response to inhaled fenoterol in patients with chronic airflow obstruction.

The bronchodilator response to inhaled fenoterol (400 micrograms) was examined in the morning and in the afternoon before and during oral sustained-release aminophylline treatment in eight patients with chronic reversible airway obstruction. Bronchodilatation was evaluated by measuring serial peak expiratory flow rates (PEFR) for eight hours after inhaled fenoterol and calculating the area under the time-response curves and the percentage increment from the baseline values. The patients showed an enhancement of the bronchodilatation achieved with fenoterol in the morning during aminophylline treatment. In the afternoon, instead, the effect of the fenoterol was not improved by oral aminophylline. This different effect of oral aminophylline might depend on the variable degree of potential reversibility present or diurnal variation in the bronchial response.

Aerosols↗

Influence of the administration time on the antihypertensive and hypokalaemic effects of chlorthalidone in patients with primary hypertension.

A double-blind crossover study was designed to compare the antihypertensive and hypokalaemic effects of chlorthalidone administered at 10h00 and 22h00 to sixteen patients with primary hypertension. Blood pressure values during chlorthalidone treatment at 10h00 did not differ significantly from those at 22h00. Significant correlation (r = 0.8987) was seen, however, only between the patients' blood pressure during the placebo period and the fall in blood pressure obtained by administration of chlorthalidone at 22h00. The serum potassium level fell significantly (p less than 0.01) during morning treatment while a slight, insignificant fall was found during evening treatment. No correlation was seen between decrease in blood pressure and decrease in serum potassium level.

Adult↗