Strontium ranelate as an adjuvant for fracture healing: clinical, radiological, and ultrasound findings in a randomized controlled study on wrist fractures.

UNLABELLED: This randomized and controlled study evaluated the effect of therapy with strontium ranelate on callus formation in wrist fractures and its incidence in wrist recovery. Radiographic healing, progression of clinical recovery, and callus quality with ultrasound were evaluated. No statistically significant benefit of therapy was found. INTRODUCTION: Fracture prevention is the main goal of any therapy for osteoporosis. Various drugs used in osteoporosis treatment have the theoretical premises to promote fracture healing and osseointegration. In this study, the effect of strontium ranelate on callus formation in wrist fractures was evaluated and whether it could lead to clinically relevant modification of wrist recovery; having strontium ranelate osteoinductive properties, it could be used, if effective, as an adjunct in fracture healing for a faster and functionally better recovery and, at the same time, in starting proper therapy in osteoporotic patients with fragility fractures. METHODS: We considered only patients older than 60 years who had suffered wrist fracture and received nonoperative treatment with manual reduction of the fracture and cast for 35 days. Forty patients were included and randomly assigned to one of two groups: group A [patients treated with calcium (1200 mg/day) and vitamin D (800 IU/day)] and group B [patients treated with calcium (1200 mg/day) and vitamin D (800 IU/day) associated with strontium ranelate 2 g daily]. Radiographic healing was evaluated through the bone callus formation, cortical continuity, and density of the callus. A clinical evaluation using Castaing's criteria was carried out 2 and 3 months following the fracture together with an ultrasound study of callus density and vessels. RESULTS: A parametric analysis of the X-ray data, clinical evaluation, and ultrasonography results showed that there were no statistically significant differences in the two groups (p > 0.05 for all data). CONCLUSION: In analyzing the data obtained, we concluded that strontium ranelate administered in acute phase did not improve nor accelerate wrist fracture healing in our population.

Forensic application of ESEM and XRF-EDS techniques to a fatal case of sodium phosphate enema intoxication.

Sodium phosphate enemas and laxatives are widely used for the treatment of constipation, even if a number of cases of significant toxicity due to alterations of the fluid and electrolyte equilibria (hypernatremia, hyperphosphatemia, and hypocalcemia) have been reported. We present the case of an 83-year-old man who died of fecal and chemical peritonitis secondary to an iatrogenic colon perforation (produced performing a Fleet enema through the patient's iliac colostomy) with peritoneal absorption of sodium phosphate. Environmental scanning electron microscopy coupled with an X-ray fluorescence energy dispersive spectrometry discovered multiple bright crystals formed of calcium, phosphorus, and oxygen in the brain, heart, lung, and kidney sections of the victim. The absence of these kinds of precipitates in two control samples chronically treated with Fleet enemas led us to assume that the deceased had adsorbed a great quantity of phosphorus ions from the peritoneal cavity with subsequent systemic dissemination and precipitation of calcium phosphate bindings.

Intestinal metabolism of weaned piglets fed a typical United States or European diet with or without supplementation of tributyrin and lactitol.

The aim of the study was to investigate the effects of supplementation of a microencapsulated blend of tributyrin and lactitol (TL) to a standard European (EU) diet without antibiotic growth promoters on intestinal metabolism and mucosa development of weaned piglets and to compare it with a standard US diet containing animal proteins, zinc oxide, copper sulfate, and carbadox. Ninety piglets weaned at 21 d were divided into 3 dietary groups consisting of 5 replicates each: 1) US diet supplemented with 55 mg/kg of carbadox, and 2.5% each of plasma proteins and spray-dried blood cells in the first phase, 3,055 mg/kg of Zn in the first and second phases, and 180 mg/kg of Cu in the third phase; 2) EU diet based on vegetable proteins and no antibiotics; and 3) the same EU diet supplemented with 3,000 mg/kg of microencapsulated TL. The study was divided into 3 phases: 0 to 7, 8 to 21, and 22 to 35 d. On d 7, 21, and 35, animals were weighed, and feed consumption and efficiency were determined. On d 14 and 35, one pig per pen was killed, and the intestinal contents and mucosa from the proximal, middle, distal jejunum and the ileum were sampled. Intestinal wall sections were fixed for histological analysis, and intestinal content was used for VFA, ammonia, and polyamine analysis. Throughout the study (d 0 to 35), the US diet had greater ADG and ADFI than the EU diet (P < 0.05). The EU diet supplemented with TL tended to have 11% greater ADG (P = 0.17). Feeding the EU diet caused a reduction in proximal and middle jejunum villi length by 10% (P < 0.05) and an increase in crypt size in proximal jejunum (P < 0.05) compared with the US diet, probably due to an increased rate of cell loss and crypt cell production. The TL supplementation resulted in longer villi along the jejunum and less deep crypts in the proximal jejunum (+15.9 and -8.9%, respectively; P < 0.05) than the unsupplemented EU diet. The TL diet increased the concentrations of cadaverine and putrescine in the small intestine (P < 0.05) and seemed to increase cadaverine, histamine, putrescine, and spermine in the large intestine by 1.5- to 10-fold compared with the US or EU diet. In conclusion, although the US diet had a greater effect on growth performance and mucosal trophic status than the EU diets, the supplementation with slowly released TL seemed to be an effective tool to partially overcome the adverse effects of vegetable protein diets.

Summary of recommendations for the design of clinical trials and the registration of drugs used in the treatment of asthma.

With new drugs being introduced to treat asthma it is timely to review criteria that can be used to assess efficacy in clinical trials. Anti-asthma drugs are classified into symptoms-modifying, symptom preventers and disease modifying agents. Attention is drawn to the types of experimental evidence required in preclinical studies to support further clinical development of a new therapy. Clinical trials demand careful selection of patients to maximise the strength of the efficacy signal according to the type of trial being designed. While provocation tests are useful in suggesting efficacy, negative tests do not necessarily indicate lack of anti-asthma activity. Therapeutic trial designs need to take account of duration of treatment, dose-response relationships and confirmatory trials. Outcome measures include symptoms, lung function, reduction in concomitant medication, exacerbations, quality of life and measures of inflammation. Interpretation of results need to include the clinical relevance of any changes as well as statistical significance. Special consideration needs to be given to the evaluation of drugs for acute severe asthma, asthma in children and older people, co-morbidity such as rhinitis, and inhaler devices. As with all drugs introduced into practice, careful attention needs to be paid to both short- and long-term safety.

Clinical use of Levofloxacin in the long-term treatment of drug resistant tuberculosis.

Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease recurrence, as well as with higher mortality than forms of TB sensitive to first-line drugs. Levofloxacin (LFX) represents one of the few second-line drugs recently introduced in the therapeutic regimens for MDR TB. We report our experience concerning in vitro activity and clinical safety of LFX in long term second-line regimens for MDR TB. IN VITRO ACTIVITY ON MYCOBACTERIA: The in vitro activity of ciprofloxacin, ofloxacin and LFX was studied on 28 strains belonging to different species of Mycobacteria. In Dubos medium, LFX inhibited the growth of both library and MDR clinical Mycobacteria strains in a range of 0.25-1 mcg/ml. In International Union Tuberculosis Medium (IUTM) the minimum inhibitory concentrations (MIC) were slightly higher, but LFX activity was not affected by the higher complexity of the medium. CLINICAL EXPERIENCE: Four patients with MDR TB were treated with a second-line regimen comprising oral LFX 500 mg twice daily, for at least 9 months. Two isolates obtained from the patients reported here showed multi resistance to isoniazid and rifampin, one to rifampin and streptomycin and one to isoniazid and ethambutol. During therapy, no significant alteration of either liver function tests, blood tests or any other described side effect of the fluoroquinolone class was observed. The 3 patients with pulmonary MDR TB showed radiologic and clinical improvement. CONCLUSION: We confirm the higher in vitro activity of LFX compared to older fluoroquinolones. Furthermore, in a limited number of MDR TB patients, second-line regimens comprising LFX 500 mg b.i.d. administered in a range of 9-24 months were well tolerated and safe.

Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rationale of a randomized, double-blind comparative study (the IMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial).

Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids represent a management challenge. Leukotrienes play a key role in asthma pathophysiology, and since pro-inflammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add a leukotriene receptor antagonist (LTRA) when a low to moderate dose of inhaled corticosteroids does not provide sufficient disease control. Long acting beta2-agonist (LABA) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment. To compare the relative clinical benefits of adding either a LTRA or a LABA to asthma patients inadequately controlled by inhaled corticosteroids, a randomized, double-blind, multi-centre, 48-week study will be initiated at approximately 120 centres throughout Europe, Latin America, Middle East, Africa and the Asia-Pacific region in early 2000. The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol, each administered on a background of inhaled fluticasone, on asthma attacks, quality of life, lung function, eosinophil levels, healthcare utilization, and safety, in approximately 1200 adult asthmatic patients. The requirements for study enrollment include a history of asthma, FEV1 or PEFR values between 50% and 90% of the predicted value together with > or = 12% improvement in FEV1 after beta-agonist administration, a minimum pre-determined level of asthma symptoms and daily beta-agonist medication. The study will include a 4-week run-in period, during which patients previously taking inhaled corticosteroids are switched to open-label fluticasone (200 microg daily), followed by a 48-week double-blind, treatment period in which patients continuing to experience abnormal pulmonary function and daytime symptoms are randomized to receive montelukast (10 mg once daily) and salmeterol placebo, or inhaled salmeterol (100 microg daily) and montelukast placebo. All patients will continue with inhaled fluticasone (200 microg daily). During the study, asthma attacks, overnight asthma symptoms, and morning peak expiratory flow rate will be assessed using patient diary cards; quality of life will also be assessed using an asthma-specific quality-of life questionnaire. The results of this study are expected to provide physicians with important clinical evidence to help them make a rational and logical treatment choice for asthmatic patients experiencing breakthrough symptoms on inhaled corticosteroids.

[The therapy of bronchial asthma]. / Terapia dell'asma bronchiale.

Asthma (Greek word that means "breathlessness" or "open-mouth breath") is a chronic inflammatory disorder of the airways, with extensive infiltration of the airway lumen and wall with eosinophils, mast cells, activated T-lymphocytes. Airway inflammation is associated with airway hyperresponsiveness, recurrent episodes of reversible airflow limitation and respiratory symptoms such as wheezing, chest tightness, breathlessness and cough with mucus production. Curiously, asthma worsens particularly at night and in the early hours of the morning. The current consensus on asthma therapy suggests that pharmacological control of asthma can be achieved with antiinflammatory "controller" medications such as inhaled glucocorticoids and cromones. Short-acting bronchodilators act as "reliever" medications and rapidly reverse acute manifestations of asthma. Asthmatic exacerbations require the repetitive administration of inhaled short-acting beta-2-agonist and the early introduction of oral glucocorticoids. Rarely the severity of exacerbation requires the administration of oxygen (that, if available, is not contraindicated), intravenous bronchodilators, glucocorticoids and epinephryne and mechanical ventilation.

Chemotherapy with 5-fluorouracil and streptozotocin in carcinoid tumors of gastrointestinal origin: experiences with 13 patients.

The Authors report their experiences on the treatment of 13 consecutive cases of gastro-intestinal carcinoid tumors observed over the last 11 years. The primary sites were as follows: intestine (5 cases), appendix (3 cases), colon (1 case) and peritoneum (4 cases); only 3 patients presented systemic signs. Ten patients in advanced phase were treated with a chemotherapeutic regimen containing 5-fluorouracil (5-Fu) and streptozotocin (STZ). One case was excluded from the study because of a concomitant gastric carcinoma. Of the 9 evaluable patients, two achieved partial remission (22%) with a duration of 18+ and 66 months respectively; 4 (44.5%) had stable disease for periods ranging from 7 to 40 months and 3 cases progressed. Severe toxicity (thrombocytopenia and diarrhea) occurred in 2 cases and disappeared with the suspension of therapy. The systemic signs disappeared with treatment and did not appear in 2 cases out of 3. The prospective of the employment of new drugs such as alpha-interferon and, above all, somatostatin provides hope that this uncommon disease may have an improved response rate to treatment in the future.

Venous blood platelets decrease during allergen-induced asthmatic reactions.

To determine whether circulating platelets alter during asthmatic reactions induced by allergens, we studied nine subjects previously shown to develop an early or dual asthmatic reaction after inhalation challenge with extracts of house dust mite or grass pollen. In each subject, FEV1, circulating platelets and leucocytes were measured before, 15, 30 and 60 min, and 2, 4, 6 and 8 hr after inhalation of allergen and diluent control administered in a single-blind, randomized fashion. The same procedure was repeated in six of the nine subjects after bronchoconstriction induced by methacholine. Each subject developed an early asthmatic reaction after allergen inhalation challenge, which was followed by a late asthmatic reaction in six subjects and by an equivocal late asthmatic reaction in two of them (fall in FEV1 of 15 and 17% respectively). Compared with the control day, circulating platelets significantly decreased during the allergen-induced early asthmatic reaction (P less than 0.025, at 30 min). Platelet counts returned to baseline values within 4 hr and remained steady thereafter both in subjects who did and did not develop a late asthmatic reaction. No changes in platelet counts occurred after bronchoconstriction induced by methacholine. Diurnal increase of leucocyte numbers occurred after challenge with both allergen and diluent control. These results suggest that platelets may be involved in the pathogenesis of allergen-induced asthmatic reactions.

Renal osteodystrophy in CAPD patients.

To assess the influence of continuous ambulatory peritoneal dialysis (CAPD) on the evolution of renal osteodystrophy, we studied 36 adult patients with end-stage renal failure before starting dialysis and after 7-30 months. 17 patients (12 males and 5 females) were treated by CAPD as first treatment and 19 (14 males and 5 females) received maintenance hemodialysis. The two groups were age- and sex-matched and no patient received vitamin D. All patients had adequate clinical and metabolic follow-up with a radiological survey and quantitative bone histology at the start of dialysis and at the end of the study. Serum phosphate concentrations were much easier to control in CAPD than in hemodialysis patients. There was no difference in the evolutive pattern of vascular and periarticular calcifications in the two groups. The 25-hydroxyvitamin D3 levels were frequently lower in CAPD than in hemodialysis patients. In some CAPD patients, there was a significant loss of trabecular bone volume at the end of the study. The radiological and histological appearances of secondary hyperparathyroidism improved or seemed to worsen to a lesser degree in CAPD compared to hemodialysis patients.

[Periaticular metastatic calcifications in uremic patients]. / Le calcificazioni metastatiche periarticolari nel paziente uremico

Metastatic periarticular calcification was observed in 18 per cent of a series of 61 patients receiving haemodialytic treatment for from 3 months to over 5 yr. Calcium deposits occurred more frequently in the 1st and 2nd yr of treatment. The factors responsible included the plasma calcium-phosphorus product, non-optimal calcium and magnesium ion concentration in the dialysis bath, and secondary hyperparathyroidism. Tests for the diagnosis of parathyroid hyperfunction in the uraemic subject are described. The therapeutic criteria adopted in the prevention and management of calcification are also discussed.