11 research outputs found
Xanthogranulomatous Pyelonephritis in a male child with renal vein thrombus extending into the inferior vena cava: a Case Report
<p>Abstract</p> <p>Background</p> <p>We present a case of Xanthogranulomatous pyelonephritis (XGPN) in a male child with renal vein thrombus extending into the inferior vena cava. This is a rare presentation. XGPN is a rare type of renal infection characterised by granulomatous inflammation with giant cells and foamy histiocytes. The peak incidence is in the sixth to seventh decade with a female predominance. XGPN is rare in children.</p> <p>Case presentation</p> <p>An 11 year old male child presented with a history of high grade fever and chills, right flank pain and progressive pyuria for two months. He had a history of vesical calculus for which he was operated four years back. In our case, a subcapsular right nephrectomy was performed. The surgical specimens were formalin fixed and paraffin embedded. The sections were stained with routine Hematoxylin & Eosin stain. Grossly; the kidney was enlarged with adherent capsule and thickening of the perinephric tissue. The pelvicalyceal system was dilated and was filled with a cast of pus. Histological evaluation revealed diffuse necrosis of the renal parenchyma and perinephric fat. Neutrophils, plasma cells, sheets of foamy macrophages and occasional multinucleate giant cells were seen. The renal vein was partially occluded by an inflammatory thrombus with fibrin, platelets and mixed inflammatory cells. The thrombus was focally adherent to the vein wall with organization.</p> <p>Conclusions</p> <p>The clinical presentation and the macroscopic aspect, together with the histological pattern, the cytological characteristics addressed the diagnosis towards XGPN with a vena caval thrombus. Our case illustrates that the diagnosis of XGPN should be considered even in paediatric age group when renal vein and vena caval thrombi are present.</p
Control of Herpesvirus Infection in Organ Transplant Recipients
The most important causes of infectious disease morbidity and
mortality in organ transplant recipients are the herpesviruses, particularly cytomegalovirus (CMV) and
Epstein-Barrvirus (EBV). Because of their properties of latency, cell association, and potential oncogenicity,
they are particularly well suited to causing disease in the transplant patient. Antilymphocyte antibody
therapies are potent reactivators of these viruses, and cyclosporine, by inhibiting the critical host defense
(virus specific cytotoxic T cells) in a dose-dependent fashion, amplifies the extent and effects of the viral
replication. This in turn is translated into clinical disease: fever; pneumonia; gastrointestinal ulcerations;
broad-based suppression of host defences leading to opportunistic superinfection and, perhaps, allograft
injury in the case of CMV; and B cell lymphoproliferative disease in the case of EBV. New approaches to
controlling these viruses in which pre-emptive therapy is linked to immunosuppressive therapy, and new
diagnostic techniques for viral monitoring, hold promise for limiting clinical disease due to these viruses
Psychiatric disease and cytomegalovirus viremia in renal transplant recipients
Although cytomegalovirus (CMV) is rarely cultured from peripheral-blood leukocytes of immunocompetent patients, it may be cultured from up to 60% of renal transplant recipients, 1 to 4 months after transplantation. During this same period, renal transplant recipients are often referred for psychiatric evaluation. Since CMV may infect the central nervous system, the relationship between isolation of CMV from peripheral-blood leukocytes (viremia) and psychiatric evaluation was investigated in 80 renal allograft recipients at the Massachusetts General Hospital. Five of 16 (31%) patients with viremia and 7 of 64 (11%) patients without viremia required psychiatric consultation (P = 0.04, two-tailed Fisher exact test). CMV viremia may be an important but treatable contributor to psychiatric symptoms in the transplant recipient
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Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial
BackgroundGlutamate excitotoxicity might contribute to the pathophysiology of amyotrophic lateral sclerosis. In animal models, decreased excitatory aminoacid transporter 2 (EAAT2) overexpression delays disease onset and prolongs survival, and ceftriaxone increases EAAT2 activity. We aimed to assess the safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis in a combined phase 1, 2, and 3 clinical trial.MethodsThis three-stage randomised, double-blind, placebo-controlled study was done at 59 clinical sites in the USA and Canada between Sept 4, 2006, and July 30, 2012. Eligible adult patients had amyotrophic lateral sclerosis, a vital capacity of more than 60% of that predicted for age and height, and symptom duration of less than 3 years. In stages 1 (pharmacokinetics) and 2 (safety), participants were randomly allocated (2:1) to ceftriaxone (2 g or 4 g per day) or placebo. In stage 3 (efficacy), participants assigned to ceftriaxone in stage 2 received 4 g ceftriaxone, participants assigned to placebo in stage 2 received placebo, and new participants were randomly assigned (2:1) to 4 g ceftriaxone or placebo. Participants, family members, and site staff were masked to treatment assignment. Randomisation was done by a computerised randomisation sequence with permuted blocks of 3. Participants received 2 g ceftriaxone or placebo twice daily through a central venous catheter administered at home by a trained caregiver. To minimise biliary side-effects, participants assigned to ceftriaxone also received 300 mg ursodeoxycholic acid twice daily and those assigned to placebo received matched placebo capsules. The coprimary efficacy outcomes were survival and functional decline, measured as the slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00349622.FindingsStage 3 included 66 participants from stages 1 and 2 and 448 new participants. In total, 340 participants were randomly allocated to ceftriaxone and 173 to placebo. During stages 1 and 2, mean ALSFRS-R declined more slowly in participants who received 4 g ceftriaxone than in those on placebo (difference 0·51 units per month, 95% CI 0·02 to 1·00; p=0·0416), but in stage 3 functional decline between the treatment groups did not differ (0·09, -0·06 to 0·24; p=0·2370). No significant differences in survival between the groups were recorded in stage 3 (HR 0·90, 95% CI 0·71 to 1·15; p=0·4146). Gastrointestinal adverse events and hepatobiliary adverse events were more common in the ceftriaxone group than in the placebo group (gastrointestinal, 245 of 340 [72%] ceftriaxone vs 97 of 173 [56%] placebo, p=0·0004; hepatobiliary, 211 [62%] vs 19 [11%], p<0·0001). Significantly more participants who received ceftriaxone had serious hepatobiliary serious adverse events (41 participants [12%]) than did those who received placebo (0 participants).InterpretationDespite promising stage 2 data, stage 3 of this trial of ceftriaxone in amyotrophic lateral sclerosis did not show clinical efficacy. The adaptive design allowed for seamless transition from one phase to another, and central venous catheter use in the home setting was shown to be feasible.FundingNational Institute of Neurological Disorders and Stroke
Biomarkers of immunosuppressant organ toxicity after transplantation: status, concepts and misconceptions
Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation.
It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field
Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial
BACKGROUND: Glutamate excitotoxicity may contribute to the pathophysiology of amyotrophic lateral sclerosis (ALS). Studies in ALS animal models show decreased excitatory amino acid transporter 2 (EAAT2) overexpression delays onset and prolongs survival, and that ceftriaxone increases EAAT2 activity in rodent brains. Phase 1, 2, and 3 clinical studies of ceftriaxone for ALS were combined into a three-stage, nonstop study. METHODS: 514 participants were randomised to ceftriaxone (n=341) or placebo (n=173); 66 participants were enrolled in stages 1 (pharmacokinetics) and 2 (safety) to determine cerebrospinal fluid and blood pharmacokinetics and safety of two dosages: 2 grams and 4 grams/day of ceftriaxone. All participants continued into stage 3 (efficacy) in blinded fashion with participants who began treatment on the discontinued dose analysed in the same group as those on the dose that that was continued. In stage 3, 44 participants previously assigned to 2 or 4 g ceftriaxone in stage 2 received 4 g ceftriaxone; 21 participants assigned to placebo in stage 2 continued on placebo. 448 new participants were randomized in stage 3 to 4 g ceftriaxone or placebo (2:1). Participants, family members and all site staff were blinded to treatment assignment. Computerized randomisation sequence using permuted blocks of 3 was stratified by riluzole use and blocked by site. Participants received 2g ceftriaxone or placebo BID via a central venous catheter (CVC) administered in the home setting by a trained caregiver. To minimize biliary side effects, participants assigned to ceftriaxone also received 300 mg ursodiol BID in a blinded manner; those assigned to placebo received matched placebo capsules BID. The co-primary efficacy outcomes were survival and functional decline, using the slope of scores on the ALS Functional Rating Scale-Revised (ALSFRS-R). The first participant entered the trial on September 4, 2006 (stage 1); the first stage-3 participant entered on June 4, 2009. The trial was stopped in July 2012. FINDINGS: During stages 1 and 2, ALSFRS-R functional decline was 0.5076±0.2440 units per month slower in participants taking 4 g ceftriaxone versus those taking placebo (95% CI 0.0196, 0.9956, p=0.0416), yet in stage 3, functional decline differed only by 0.08975±0.07581 units per month (95% CI −0.05919, 0.2387; p=0.2370). No significant differences were seen in stage 3 survival (hazard ratio, 0.904 [95% CI 0.710, 1.152]; p=0.4146). Adverse events rates were higher in the ceftriaxone versus placebo group for gastrointestinal (72% [245/340] vs 56% [97/173]; p=0.0004) and hepatobiliary events (62% [211/340] vs 11% [19/173]; p<0.0001). Add-on ursodiol reduced these events in participants taking ceftriaxone. A significantly larger percentage of ceftriaxone versus placebo participants experienced hepatobiliary serious adverse events (12% [41/340] vs 0% [0/173]). INTERPRETATION: Despite promising stage-2 efficacy data, the stage-3 ceftriaxone in ALS study failed to show clinical efficacy. The adaptive design approach allowed for seamless movement from one phase to another obviating the need for multiple grant submissions. CVC use in the home setting was shown to be not only possible, but also safe