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A case of severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection is described. To further understand the molecular mechanism of this adverse reaction, analyses of the genetic variants of human leukocyte antigen (HLA) and of the epoxide hydrolase gene (EPHX1), previously associated with carbamazepine hypersensitivity, were performed. A lymphocyte transformation test (LTT) was conducted in order to detect drug-specific lymphocytes. In the hypersensitive patient, 2 genetic factors previously associated with intolerance to carbamazepine were detected: the allele HLA-A*3101 and homozygosity for the variant allele of SNP rs1051740 in EPHX1. Drug-specific lymphocytes could be detected by LTT when the HHV was active (positive PCR for viral DNA and increased anti-HHV 6 IgG titer), but not when it was no longer active. In conclusion, we document a case of severe carbamazepine hypersensitivity triggered by viral reactivation in a patient presenting the interaction of 2 unfavorable genetic factors., (Copyright 2009 S. Karger AG, Basel.)

The recommendation of statin treatment to younger patients too, as recently issued by the American Academy of Pediatrics, appeared to be controversial, especially looking at the lack of evidence in term of efficacy on primary end-point and long term safety data.

Colchicine is the treatment of choice in familial Mediterranean fever (FMF) for the prevention of both attacks and secondary amyloidosis. The overall nonresponder rate is about 5-10%. Anakinra is known to have good effectiveness in a severe autoinflammatory syndrome [chronic infantile neurological cutaneous and articular (CINCA) syndrome] and other recurrent hereditary periodic fevers. Pyrin--the protein involved in FMF--has a role in activating the proinflammatory cytokine interleukin (IL)-1beta. We report the effectiveness of the addition of an IL-1-receptor inhibitor (anakinra) to colchicine in controlling the febrile attacks and acute phase response in an adolescent with FMF resistant to colchicine.

Objective: To investigate paediatricians' perception and awareness of off-label (OL) and unlicensed drug usage in clinical practice., Methods: We conducted a questionnaire-based, observational study involving 28 departments/specialty units of four tertiary paediatrics Italian hospitals. The questionnaire was sent to a designated paediatrician in each department/specialty unit with the request that they summarise their awareness of OL prescriptions after a group discussion with all paediatricians working in the same department/unit., Results: A total of 95 drugs were identified. The most common perceived reasons detected for OL use were age and formulation. Corticosteroids, ACE-inhibitors, beta-blockers and calcium-antagonists were most frequently indicated as OL for formulation, while ACE-inhibitors, new generation anti-epilepsy drugs, immunosuppressants, ketorolac and propofol as OL for age. Adrenaline, midazolam and ACE-inhibitors were indicated as unlicensed for route of administration. We found a high concordance between the OL drugs identified by physicians and those reported in the "Italian Summary Product Characteristics"., Conclusions: Italian paediatricians perceived different drugs as unlicensed/OL from those identified by existing prescriptions studies. These perceived drugs may represent a priority in tackling the problem of OL usage in the hospital practice. The review of the Italian Summary Product Characteristics of some of the drugs identified, together with the monitoring of permanent clinical practice and with new clinical research, may be a step forward to reduce OL use in children.

Objectives: To compare the sequential therapy with levofloxacin with a standard treatment in the management of urosepsis., Materials and Methods: It was a multicenter, randomized, open label, pilot trial in community acquired urosepsis carried out in 7 hospitals. Levofloxacin administered 500 mg twice a day intravenously and then orally was compared to piperacillin/tazobactam 4 g/0.5 g three times a day, both in combination with amikacin 7.5 mg/Kg twice a day, for a maximum of 14 days. Amikacin could be suspended between day 3-7., Results: Both treatments were efficacious and well tolerated in the 47 enrolled patients, even tough the time to clinical stability was shorter in the levofloxacin treated patients (3.9 vs. 4.9 days). In the levofloxacin group the sequential therapy was performed in 19 (82.6%) cases, after 4.8 +/- 1.7 days of parenteral administration (100% in the per-protocol population after 5.1 +/- 1.9 days)., Conclusions: The implementation of the sequential therapy in the levofloxacin group allowed an early hospital discharge in patients with urosepsis and a cost saving in the hospital perspective.

We describe a 12-year-old white girl with granuloma annulare localized to both ankles since she was five, necrobiosis lipoidica in the left pretibial region since she was ten, and a recent history of weakness, migraine, and weight loss. After initial evaluation, high fasting blood glucose levels and high hemoglobin A1c were found. The family history for non-insulin-dependent diabetes was suggestive of maturity-onset diabetes of the young. Coexistence of necrobiosis lipoidica and granuloma annulare, together with a family history of non-insulin-dependent diabetes, the age of onset, and the absence of ketosis, are specific features making possible, a clinical diagnosis. Genetic confirmation may not be so easily accessible or necessary.

Objective: Hyper-IgD syndrome (HIDS) is a rare autosomal recessive disease characterized by recurrent fever, lymphadenopathy, diarrhoea, abdominal pain, headache, arthralgia and skin rash. Abdominal symptomatology may mimic inflammatory bowel disease. We report on four patients with HIDS who had been previously investigated for Crohn's disease (CD). The levels of IgD were measured in a series of patients with CD to evaluate the specificity of this assay in the differential diagnosis between the two conditions., Material and Methods: Diagnosis of HIDS was based on clinical criteria as well as immunological or genetic data. IgD levels were measured in the four subjects affected by HIDS, in 59 patients with CD and in a group of 160 healthy controls., Result: All patients underwent a variety of gastroenterological investigations because inflammatory bowel disease was suspected. Ultrasonography was pathologic in all the patients, showing enlargement of mesenteric lymph nodes. Abdominal leucocyte scintigraphy displayed diffuse signals of mild to moderate degree. IgD and IgA levels were elevated in three out of four patients. No difference in IgD values was found in CD patients as compared to the control group., Conclusions: Gastrointestinal complaints associated with recurrent fever and mesenteric adenopathy warrant genetic investigation for HIDS, in order to avoid unnecessary invasive investigations and treatment.

Rotaviruses (RV) are the most common etiological agents in acute gastroenteritis (GE) in children in the first years of life. Data from the national scientific literature show that RV is responsible of 26% of all cases of hospitalisation for diarrea in children, resulting the most frequently identified agent. The Italian database of hospital discharge, freely available from the web site of the national Ministry of Health, was searched to investigate the epidemiology of RV gastroenteritis. The mean number of hospitalisation for RV enteritis in children in the first 4 years of live was 4.758 in the years 2001, 2002 and 2003, representing 84% of viral enteritis. RV was identified as agent in 17% of all intestinal infectious diseases in this age group. This percentage shows the important role of RV in severe gastrointestinal infections; it is however much lower than the value expected from specifically performed surveys. This underestimation may be attributed to the high number of undefined gastroenteritis found in the database (54%), to the scarce sensitivity of the hospital discharge code, and to the fact that the analysis was performed using only the principal diagnosis. A specific immunisation strategy, safe, effective, cost-effective and easy to perform, could have a great impact on the incidence of the disease and on the associated costs.

Procedural sedation is generally recommended for children requiring repeated painful diagnostic or therapeutic procedures. A child with leukemia undergoes an average of 20 procedures such as lumbar puncture and bone marrow aspiration through the course of illness. No data are currently available about the psychological impact of repeated sedations on children. The objective of this study was to evaluate the attitudes of patients with leukemia toward repeated deep sedations using propofol. A questionnaire addressing sedation-related distress was given to 30 children with leukemia. Procedure-related distress was evaluated using the Amended Observational Scale of Behavioural Distress. Another questionnaire concerning the same issues was given to an historical group of 39 children who had undergone painful procedures without sedation in previous years. Fear and distress were significantly reduced in the sedation group compared with the historical one. Fear of sedation was reported by 17% of children of this group. Distressed behavior was observed in 27%. In conclusion, sedation-related distress was observed in a subgroup of patients; in these cases, specific strategies could be considered to reduce sedation-related distress.

The synergistic potential of ceftazidime plus amikacin or levofloxacin was assessed against 61 Pseudomonas aeruginosa isolates with variable susceptibility patterns to the 3 antibiotics. A checkerboard broth method and a disk diffusion method were used and compared. The latter, also easy to perform as a triple-disk assay, could be a helpful laboratory screening tool for drug synergism to drive possible combination treatments.

Study Objectives: Levofloxacin is a fluoroquinolone antimicrobial agent for which pharmacodynamic relationships between the maximum serum antibiotic concentration (Cmax)/minimum inhibitory concentration (MIC) ratio and/or the area under the serum concentration-time curve during a 24-h dosing period (AUC(0-24))/MIC ratio and clinical and/or microbiological outcomes have been developed. In this study we examined the relationship between the in vitro bacterial susceptibility to levofloxacin, the achieved levofloxacin serum and sputum concentrations, and the in vivo bacterial eradication in patients with acute exacerbations of chronic bronchitis., Patients and Interventions: Thirty patients received levofloxacin, 500 mg/d po for 7 days. Samples of venous blood and sputum for the determination of levofloxacin concentrations were collected on day 1 immediately prior to dosing, and then at 1, 4, 8, 12, and 24 h., Results: The mean peak concentration in serum (6.5 mg/L) was found 1 h after administration, and at 4 h after administration in sputum (5.1 mg/L). Levofloxacin was always detectable 24 h after administration from both samples. Successful treatment occurred in 90% (27 of 30 patients) when assessed both clinically and bacteriologically. Treatment was successful in eight patients when the AUC(0-24)/MIC ratio was > 40 for serum, and in nine patients when it was > 30 for sputum. Treatment was also successful in seven patients when the Cmax/MIC ratio was > 5.01 for serum, and in nine patients when the Cmax/MIC ratio was > 4.01 for sputum. Treatment was successful in 90% (27 of 30 patients) when the AUC(0-24)/MIC ratio was > 125 for serum and > 100 for sputum, and when Cmax/MIC was > 10.01 for serum and > 8.01 for sputum following the first dose., Conclusions: The pharmacodynamics values that we have obtained in sputum with levofloxacin may be used as predictors of therapy outcomes.

A 1.5-year-old girl developed high frequency tremors and chorea after receiving a dose of 120 mg/kg/d trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of Pneumocystis pneumonia. The child was human immunodeficiency virus-negative but immunocompromised because of prolonged immunosuppressive therapy. These symptoms disappeared 3 days after TMP-SMX was discontinued. Pediatricians should be aware of tremors and chorea among the potential adverse effects of high doses of TMP-SMX.

Objectives: To evaluate the applicability and the effectiveness of practice guidelines based on a wait-and-see strategy for children with acute otitis media (AOM)., Population: Children from 1 to 14 years old having AOM who were referred to primary care pediatric practices., Study Design: Prospective observational study., Main Outcome Measure: Proportion of children having a diagnosis of AOM and eligible for symptomatic treatment who, at 72 hours from enrollment, recovered from their symptoms (fever and earache) without receiving antibiotic treatment., Results: One hundred sixty-nine pediatricians participated in the study and enrolled 1672 children. One thousand two hundred seventy-seven children were included in the analysis. One hundred seventy-eight children received antibiotic treatment at first contact according to the practice guidelines criteria (presence of otorrhea or recurrent AOM). Of the 1099 children who were eligible for symptomatic treatment only, 743 (67.6%) recovered without antibiotic treatment at 3 days and 716 (65.1%) at 30 days. No complications were observed. Coexistence of a high fever (temperature > or = 38.4 degrees C) and red and bulging tympanic membrane as well as male sex were significantly associated with antibiotic use., Conclusions: Practice guidelines based on a wait-and-see strategy for children with AOM are applicable and effective in primary care. This strategy was able to avoid the administration of antibiotic treatment in 2 of 3 children.

A prospective multi-center Italian urology outpatient survey, undertaken to determine the prevalence of prostatitis in Italy, provided an ideal opportunity to identify and characterize the typical prostatitis patient presenting to Italian urologists. A total of 70 urologists, representing a cross section of urologic centers in Italy, counted and recorded the overall total male patients reported in the clinic and the overall total patients diagnosed with prostatitis over a 5 week period in late 2001. Data on demographics, previous diagnoses, symptoms (frequency and severity), quality of life, physical examination and laboratory data were prospectively collected. A total of 1,148 patients were identified with prostatitis (12.8%). Of these, 1,074 patients had complete data and could be included in this characterization analysis. The mean age of the prostatitis patients was 47.1 years (range 16-83); two thirds had experienced their first symptom within the last year. A family history of prostatitis was reported by 20.4%. The most common urinary diseases were benign prostatic hyperplasia (17.4%), recurrent urinary tract infection (11.2%) and urinary calculogenesis (11.1%), while the most common concurrent diseases were diabetes (7.2%) and depression (6.8%). The most frequently reported and most severe symptoms at the time of evaluation were irritative voiding symptoms, perineal and suprapubic pain and discomfort. Over three quarters of the patients were dissatisfied with their quality of life. Bacteria were cultured in 15.6%, 17.7% and 14.0% of expressed prostatic secretions, urine specimens after prostatic massage and semen specimens, respectively. Prostatitis is a common outpatient diagnosis, comprising over 10% of male outpatient visits to urologists in Italy. This comprehensive characterization of the typical prostatitis patient diagnosed in routine urological outpatient practice can be employed to generate hypothesis-driven studies in diagnosis and treatment.

Nephropathic cystinosis is a severe autosomal recessive inherited metabolic disease characterized by accumulation of free cystine in lysosomes. Cystinosis can lead to renal failure and multiorgan impairment. Only five cases of cystinosis with associated Bartter syndrome are reported in the literature, and no genetic evaluation has been reported. We describe two siblings with nephropathic cystinosis presenting with features of Bartter syndrome and their genetic pattern.

Aim: To assess the evidence supporting early antibiotic treatment in asymptomatic cystic fibrosis (CF) patients colonised by Pseudomonas aeruginosa (PA)., Methods: We carried out a computerised (Medline, Embase) and hand search of journals for suitable publications. All English-language clinical studies regarding the efficacy of early antibiotic treatment on PA colonisation in asymptomatic patients were considered. Each eligible publications fitting these criteria were assessed for the following outcome measures: frequency of positive PA cultures; serum level of precipitating antibodies; lung function; survival; number of hospitalisations; adverse effects and resistance to antibiotics., Results: Of the 11 studies eventually considered, 3 were randomised-2 versus placebo- and 8 were cohort studies-2 of which had historical controls. Overall, 309 patients (population range 7-91 patients) were recruited. There was a high variability between the individual studies for age, outcome measures, duration of follow-up (1 to 44 months) and treatment (three studies used only aerosol tobramycin, one colistin, four aerosol colistin plus oral ciprofloxacin, one used intravenous treatment and two miscellaneous therapy). An overall evaluation indicated that early antibiotic treatment can reduce the number of positive cultures and the anti-PA antibody titre. In one study, FEV1 was better in the treated group (oral ciprofloxacin and nebulised colistin) than in historical controls, while in one placebo-controlled trial, no effect on lung function was shown after 1 year of tobramycin inhalation. Collateral effects and bacterial resistance were not increased. The short follow-up did not allow definite conclusions with regard to the long-term progression of respiratory insufficiency or survival., Conclusions: Evidence was found that antibiotic treatment can reduce the rate of positive cultures and of anti-PA antibody titres in asymptomatic CF patients with newly isolated PA. Different therapeutic options have not been directly compared: a multi-centre comparative study needs to be carried out.

Background/aims: Ultrasound (US) and color Doppler are not sensitive enough to detect anomalies in cortical perfusion, which is affected in most graft dysfunctions. The renal cortical ratio (RCR) is a variation in the resistive index (RI) values from the renal artery to cortical vessels, expressed in percent. The aim of this study was to compare the RI and RCR in the differentiation of normal and pathological grafts, to assess the positive predictive value of RCR and show that RCR enables earlier diagnosis than RI., Methods: Based on clinical, biochemical and histological examinations, 494 renal allografts were divided into 3 groups (normal grafts, acute and chronic pathologies). All patients underwent US color Doppler. RI was measured and RCR calculated. Follow-up confirmed the initial division in groups. Statistical significance was calculated using the two-tailed Student's t test. The positive predictive value was calculated for each group., Results: 24 h after transplant, RCR differentiated normal grafts from acute dysfunctions despite confusing biochemical values and clinical symptoms. In chronic patients, RCR variations occurred later but always before the serum creatinine level increased., Conclusion: RCR presented a higher positive predictive value than RI. RCR curves were already altered in the early stages of transplant pathologies. RCR calculation is easy and makes a significant contribution towards a correct early diagnosis., (Copyright (c) 2004 S. Karger AG, Basel.)

In recent years there has been an increase in the use of ACE inhibitors in the paediatric population. We describe a case of hyperchloraemic metabolic acidosis with hypoaldosteronism in a 4-year-old boy with nephrotic syndrome who was receiving ACE inhibitors.

Background: The need to perform procedural sedation for children has increased in recent years, and so has the experience of nonanesthesiologists in this field. The use of propofol increases the success of satisfactory deep sedation, but it can produce rapid and profound decreases in level of consciousness and cardiorespiratory function. Data are needed to assess the safety of this drug outside an anesthesiology setting., Objective: To assess safety and efficacy of procedural sedation with propofol in a pediatric ward of a tertiary-care pediatric teaching hospital with trained personnel and monitoring facilities., Methods: Patients admitted to the hospital who needed invasive procedures underwent procedural sedation by the pediatric sedation unit with intravenous propofol. A training protocol was developed to educate nurses and residents., Results: We performed 1059 procedures. Sedation was achieved in all procedures, and all but 1 were successfully performed. No patient required intubation. Transient desaturation resolving spontaneously occurred in 134 (12.7%) of 1059 patients. Major desaturation requiring a short course of ventilation occurred in 4 (0.8%) of 483 patients undergoing upper endoscopies, in 1 (0.3%) of 287 patients undergoing painful procedures, and in none of the 289 patients undergoing colonoscopies. Laryngospasm occurred in 10 (2.1%) of 483 patients undergoing upper endoscopies., Conclusions: In this experience, the use of propofol with concurrent oxygen administration allowed sedations in children with no significant complications for colonoscopies and painful procedures. Complications in the group of upper endoscopies appear too high for recommending propofol in a sedation unit with residents in attendance. This protocol of procedural sedation by nonanesthesiologists allowed a significant increase in the number of procedures performed with sedation and saved anesthesiology resources.

Objectives: The aim of this prospective descriptive study was to draw the picture of the diagnostic and therapeutic pathways of general practitioners (GPs) in the practice of management of urinary tract infections (UTIs) in Italy. The study results are published in two separate papers. We report here the epidemiological data collected on the prevalence of UTIs and their etiology., Materials and Methods: A total of 2.696 GPs were requested to fulfill a questionnaire on their perception of the prevalence of UTIs and their habits in the management of patients either before (IVU1 study, 1.111 GPs) or after (IVU2 study, 1.585 GPs) a specific training course. Epidemiological data from both studies were merged and analyzed., Results: The perceived prevalence of UTIs among the GPs was 1.7% ambulatory-related patients/GP/month, leading to an average of 18.7 UTIs cases/GP/month. UTIs were higher among women (75%) with respect to men (25%), being acute uncomplicated cystitis in women the more prevalent (nearly 50% of female ambulatory-related patients). E. coli was considered the most frequently isolated bacterial pathogen in urine., Conclusion: The epidemiological results of this study contribute to assess the prevalence and etiology of UTIs among Italian outpatients. These data may be helpful for urologists in the management of community-acquired UTIs.

Objectives: The aim of this prospective, descriptive study was to draw the picture of the diagnostic and therapeutic pathways of general practitioners (GPs) in the practice of management of urinary tract infections (UTIs) in Italy. The study results are published in two separate papers. We report here the clinical pathways followed by GPs to diagnose and treat UTIs., Materials and Methods: A total of 2.696 GPs were requested to fulfill a questionnaire on their perception of the prevalence of UTIs and their habits in the management of patients either before (IVU1 study, 1.111 GPs) or after (IVU2 study, 1.585 GPs) a specific training course. The clinical management pathway was analysed., Results: GPs turned out to share an appropriate management of UTIs, even though some discrepancies between the clinical habits and UTIs guidelines were focused. After the training course the discrepancies were partly amended (IVU2 study). Urinalysis and urine culture are nearly always requested by GPs, frequently including blood examinations. Older and newer fluoroquinolones are mostly prescribed for UTIs, followed by fosfomycin tromoetamol. Lifestyle recommendations for UTIs containment and prevention are released to patients by GPs., Conclusion: The clinical results of this study contribute to assess the habits of Italian GPs in diagnosing and treating UTIs. These data may be helpful for urologists in the management of community-acquired UTIs.

Objectives: The objective of this open-label, single-arm, multicenter study was to assess the efficacy and safety of levofloxacin in the treatment of complicated urinary tract infections., Materials and Methods: A total of 72 outpatients with symptoms/signs of urinary tract infection and underlying anatomic or functional abnormality of the urinary tract was enrolled to receive levofloxacin 250 mg orally once daily for 10 days. Return visits were scheduled at 3-5 days (early follow-up visit) and 4-6 weeks after completion of therapy (long-term follow-up). At each visit symptoms and signs were assessed, possible adverse events were recorded and a urine specimen was obtained for culture., Results: At 3-5 days post-therapy clinical success rate was 94% and the overall microbiological eradication rate of pathogens was 94%. Microbiological eradication rate with respect to patients was 86%. Treatment failed in 4 patients and 2 patients had superinfections with pathogens still susceptible to levofloxacin. At long-term follow-up visit 3 reinfections were observed in patients previously cured at early follow-up. Drug-related adverse events were reported by 2 patients., Conclusion: These study results indicate that levofloxacin 250 mg orally once daily for 10 days is an effective and well tolerated treatment of complicated urinary tract infections.

Levofloxacin showed comparable in vitro susceptibility to ciprofloxacin among Enterobacteriaceae, Pseudomonas aeruginosa, enterococci, and Staphylococcus aureus, while greater susceptibility was observed in Stenotrophomonas maltophilia and Staphylococcus epidermidis, mainly when oxacillin resistant. The susceptibility of Streptococcus pneumoniae to levofloxacin reached 99%.