A part-randomized study of intravenous oseltamivir in adolescents and adults.

Seriously ill patients with influenza may be unable to take oral medication. The safety of intravenous oseltamivir was evaluated in adults and adolescents. This prospective, part-randomized study enrolled hospitalized patients aged ≥13 years with clinical or laboratory-confirmed influenza, who started study medication within 144 h of illness onset. Patients with normal renal function received oseltamivir 100 or 200 mg every 12 h for 5 days by slow intravenous infusion. Patients with renal impairment received lower doses, appropriate to the degree of impairment. Blood samples were taken for pharmacokinetics, and nasal swabs were taken to monitor viral shedding and resistance [reverse transcription polymerase chain reaction (RT-PCR) and culture]. Adverse events (AEs) were monitored for 30 days from treatment initiation. Of the 118 patients enrolled, 103 had normal renal function. On day 1, 64 patients had laboratory-confirmed influenza. Ninety-four (80 %) patients completed 5 days of oseltamivir treatment (32 intravenous only). Sixty-eight and 13 patients reported on-treatment AEs and serious AEs (SAEs), respectively (62 and nine during intravenous dosing, respectively). For 33 and six patients, these AEs and SAEs were considered treatment-related (31 and five during intravenous dosing, respectively); 11 patients had AEs causing treatment withdrawal. Five patients died. Adequate systemic exposure to oseltamivir carboxylate (OC) was achieved at the intravenous doses tested. Oseltamivir-resistant viruses (H275Y) were detected in two patients. In seriously ill, hospitalized patients with/without renal impairment, intravenous oseltamivir was not associated with adverse safety findings at the dosages tested and achieved systemic OC exposures at least as high as the approved oral dose.

Findings of a hospital surveillance-based outcome evaluation study for Clostridium difficile-associated colitis.

We completed a prospective study of 164 patients involved in a Clostridium difficile surveillance programme, evaluating a range of variables such as disease severity, treatment regimen and known clinical risk factors, for their effect on case lethality. The aim of this study was to determine if there are any additional clinical variables worth considering for inclusion in the therapeutic decision-making process. Beyond common risk factors, secondary immunodeficiencies such as diabetes mellitus, malignancy, autoimmune disease, immunosuppressive therapy and chronic hepatitis were assessed. Overall case lethality was 23%. There was a suggestion that regular proton pump inhibitor use in past medical history might be associated with greater lethality. Immunosuppressive therapy within 1 month before the onset of diarrhoea was associated with a significant four-fold lethality increase. This last finding may have the potential to further improve therapeutic judgement if used as an explicit component of a revised scoring system. In relation to Clostridium difficile-associated colitis, immunosuppressive therapy as a red flag entity, as described here, has not been previously published.

Clinical, radiological and pathological correlates of leukoaraiosis.

INTRODUCTION: Leukoaraiosis is characterized by an abnormal appearance of the brain white matter on imaging. Its pathogenesis is still a matter of investigation. The purpose of this study was to investigate the radiological, clinical and pathological correlates of leukoaraiosis. METHODS: The study population consisted of 93 deceased patients. The pre-mortem T2W magnetic resonance images were evaluated for the presence and grading of leukoaraiosis. The clinical and pathological characteristics based on the clinical charts and autopsy reports were evaluated. Tissue specimens of the blocks of 19 brains that demonstrated severe leukoaraiosis and those of five control brains were excised and stained. RESULTS: The variables found to be significantly associated with leukoaraiosis were age and a clinical history of Parkinson's disease. Other risk factors and pathological markers of atherosclerosis were not significantly correlated with leukoaraiosis. No significant difference was found between the scoring of the myelin integrity, glial fibrillary acidic protein, cluster of differentiation 68 and smooth muscle actin. There was a significant difference with respect to thickening of vessels walls. CONCLUSIONS: Our pathological results indicate that structural vascular abnormalities characterized by vessel wall thickening are associated with leukoaraiosis, supporting the assertion that vascular changes and ischemia generate leukoaraiosis. The relations between parkinsonism and leukoaraiosis may be explicable through vascular effects on the circuitry of the basal ganglia.

Meconium periorchitis: case report and literature review.

Meconium periorchitis (MPO) is an uncommon entity associated with healed meconium peritonitis. The typical presentation is soft hydrocele at birth which becomes harder in weeks as the meconium calcifies. It mimics a scrotal mass, and, without knowledge of this rare disease, this may lead to unnecessary surgery. Both the masses and the calcifications have the tendency to resolve spontaneously without compromising the testicle. Sonographic features together with an abdominal plain film are diagnostic, and visualization of the normal testicle may be helpful in differentiating this tumor-like lesion from scrotal tumors. A case of a meconium periorchitis is reported on and the radiological and histological features are discussed with a literature review on the subject.

Changes of urinary enzyme activity after endoscopic treatment of vesico-ureteric reflux.

The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP), Leucine-Arylamidase (LAS), and Dipeptidyl-Peptidase-IV (DPP-IV) were measured before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two groups of twenty children. Ten patients had undergone successful endoscopic corrective surgery for VUR, another 10 patients had unsuccessful endoscopic intervention. After successful treatment the activity of LAS in the urine did not change, but GGT, ALP and DPP-IV activity in the urine was 2-5 times higher than before treatment (P < 0.03 for all three enzymes). Considerable changes of urinary enzyme activity were not observed following unsuccessful endoscopic treatment. Our data and the literature are contradictory. However, this contradiction might be explained by the differences in urine sampling methods. Our patients received the same chemoprophylactic drug at the time of both urine samplings, a point not considered by other researchers. The extent of increase of enzyme activity after endoscopic treatment of VUR did not reach the level that would permit the use of investigated enzymes for screening, because the observed changes did not exceed the limits of the normal range.

[Usefulness of ultrasound in the diagnosis of vesico-ureteral reflux in neonates and infants]. / Az ultrahangvizsgálat alkalmazhatósága újszülött- és csecsemökori vesicoureteralis reflux gyanúja esetében.

PURPOSE: Postnatal ultrasound (US) findings were assessed in an infant population with primary vesicoureteral reflux (VUR) and the findings of voiding cystourethrography (VCUG) were compared with those of sonography. MATERIALS AND METHODS: Between 1988 and 1997 55 babies (43 boys and 12 girls) with primary VUR were diagnosed. US criteria for suspected VUR included unexplained or transient fullness of the collecting system, pelvic wall thickening and signs of renal dysplasia. RESULTS: Among 55 patients reflux was unilateral in 32 cases, and bilateral in 23 patients, altogether 78 refluxing units were investigated. VUR Grade III-V, were detected in 62 units (79%). At least one US anomaly was present in 66 units (85%). No ultrasound anomaly was found in 12 renal units (15%). In 34 cases (44%) conservative treatment was performed, 40 renal units (51%) underwent ureteric reimplantation, and in 4 (5%) cases nephrectomy was carried out. CONCLUSIONS: The correct detection and grading of reflux is not reliable by sonography, although with careful US examination of the neonatal urinary tract in 85% of VUR cases at least one sonographic abnormality has been found. However, the US negative group, (15%) showed severe reflux on VCUG in a few cases. Therefore, all neonates with ultrasound pathology of unknown origin detected prenatal or postnatal, should undergo VCUG to exclude VUR.

[Changes in urinary enzyme activity following silicon therapy of vesico-ureteral reflux]. / A vizeletenzimek aktivitásváltozása vesicoureteralis reflux szilikonnal végzett kezelésében.

The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP), Leucine-Arylamidase (LAS) and Dipeptidyl-Peptidase-IV (DPP-IV) were measured before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two groups of twenty children's. Ten patients had undergone successful endoscopic corrective surgery for VUR, another 10 patients had unsuccessful endoscopic intervention. After successful treatment the activity of LAS in the urine did not change, but that of GGT, ALP and DDP-IV activity in the urine was 2-5 times higher than before treatment (P < 0.03 for all three enzymes). Considerable changes of urinary enzymes' activity were not observed following unsuccessful endoscopic treatment. Our data and the literature are contradictory. However this contradiction might be explained by the differences in urine sampling methods. Our patients received the same chemoprofilactic drug at the time of both urine sampling, a point not considered by other researchers. The extent of increase of enzyme activity after endoscopic treatment of VUR did not reach the level that would permit the use of investigated enzymes for screening, because the observed changes did not exceed the limits of the normal range.

[Diagnosis of neonatal liver hemangioma]. / Az újszülöttkori májhaemangioma diagnosztikája.

The hepatic hemangiomas of infancy are rare, benign vascular tumours, differentiated in their morphologic and clinical appearances. They may manifest either as asymptomatic liver masses, or with the potentially fatal complication of congestive heart failure. They can be large in infancy, act as arteriovenous fistulas and may result in massive arteriovenous shunt. Multiple imaging modalities have been employed in the diagnosis, including ultrasonography (US), computed tomography (CT), radionuclide studies, angiography, magnetic resonance (MR) imaging. Generally the US, Doppler and CT appearances of hepatic hemangiomas may be diagnostic. Biopsy in often needed for diagnosis, especially if classic signs and symptoms are lacking. The diagnostic possibilities and difficulties in three patients are discussed. Different US images were present in all three cases, with atypical CT appearance in one. Doppler signals were lacking in two cases. Sonographic appearance of infantile hepatic hemangioma is variable, non-specific, but Doppler US is useful as a non-invasive method in the follow-up of hemangiomas.