Reversible posterior leukoencephalopathy syndrome in a child treated with bevacizumab

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Hypertension is a well‐recognized, common side effect of VEGF blocking agents. The reversible posterior leukoencephalopathy syndrome (RPLS) has been described as a rare but serious consequence of bevacizumab administration. We present a case of a 6‐year‐old child with refractory hepatoblastoma who developed hypertensive crisis, seizures and MRI changes consistent with RPLS while receiving bevacizumab with gemcitabine and oxaliplatin. Findings completely resolved without neurologic sequelae with stringent blood‐pressure control. Better understanding of risk for RPLS, prompt recognition and aggressive management will be required as bevacizumab gains wider use in pediatrics. Pediatr Blood Cancer 2009;52:669–671. © 2008 Wiley‐Liss, Inc.     

Isolated chylopericardium due to mediastinal lymphangiomatous hamartoma;.

Isolated chylopericardium is a rare cause of pericardial effusion. Intrapericardial chyle was first noticed by Hasebroek (1888) at necropsy. Twenty years ago Groves and Effler (1954) first reported a clinical case of isolated chylopericardium. The present case is similar to theirs in several respects, and is the nineteenth case to be reported. To our knowledge this is the first British report of an isolated chylopericardium and is the fourth case of isolated chylopericardium due to a mediastinal lymphangiomatous hamartoma to be successfully treated.     

Production and characterization of a monoclonal antibody specific to Nef-associated factor 1 (Naf1)/A20-binding inhibitor of NF-kappaB activation (ABIN-1)

Cellular protein Naf1 (Nef-associated factor 1) or ABIN-1 (A20-binding inhibitor of NF-kappaB activation) is an important cellular protein, expressed in various human tissues and T-cell lines. Naf1 protein has two isoforms (Naf1alpha and Naf1beta) with different C-termini, produced by alternative splicing. Naf1alpha and Naf1beta have approximately 2800 and 2600 nucleotides, with an open reading frame of 1941 and 1781 nucleotides, encoding the 72-kDa Naf1alpha and 68-kDa Naf1beta proteins, respectively. In the present study, we generated a monoclonal antibody (MAb) against human Naf1, which recognizes full-length, endogenous Naf1 of both isotypes. For this purpose, recombinant 6xHis and myc-tagged N-terminal Naf1(38135), Naf1(N) protein was produced by using the baculovirus expression system. Recombinant Naf1(N) protein was used to immunize Balb/c mice, and a hybridoma cell line producing stable and highly specific MAb with strong affinity to Naf1 was established. We further characterized this antibody by immunofluorescent assay and Western blot analysis to confirm effectiveness in detecting recombinant and endogenous Naf1. By Western blot analysis of recombinant Naf1-N fusion proteins with overlapping N-terminal sequences, the epitope targeted by anti-Naf1 MAb was determined as the 81-88-amino acid region of human Naf1.     

Posttransplant lymphoproliferative disorder among renal transplant patients in relation to the use of mycophenolate mofetil

BACKGROUND: The introduction of increasingly effective immunosuppressants has raised the question of whether posttransplant lymphoproliferative disorder (PTLD), a complication of immunosuppression, would become more frequent. This study assessed the risk of PTLD in relation to immunosuppression during a period that saw the introduction and eventual market dominance of mycophenolate mofetil (MMF). METHODS: A case-control study was conducted at 23 U.S. transplant centers. All participants received a renal-only transplant on or after July 1, 1995. PTLD cases were reported by centers and confirmed by central review. The United Network for Organ Sharing (UNOS) supplemented case ascertainment and identified controls matched on center, transplant date, and age. Center personnel abstracted risk factor and therapy data for cases and up to four controls per case. Cases and controls were compared, using a matched multivariate analysis, to assess the impact of MMF as one component of triple-therapy adjusted for other drug therapies and known risk factors. RESULTS: Data were collected for 108 PTLD cases and 404 controls. PTLD risk for individuals on triple therapy with MMF was similar to the risk experienced by individuals on triple therapy with no MMF (adjusted odds ratio=1.19; 95% CI 0.55-2.55). There was no dose response relationship between MMF and PTLD risk. CONCLUSIONS: Use of MMF was not associated with an increase in PTLD among patients who received triple immunosuppressive therapy, but an excess in risk as large as 155% or a reduction in risk by as much as 45% cannot be ruled out.     

Anatomical basis of glial cell line-derived neurotrophic factor expression in the striatum and related basal ganglia during postnatal development of the rat

There is increasing evidence that glial cell line-derived neurotrophic factor (GDNF) plays a role as a limiting, striatal target-derived neurotrophic factor for dopamine neurons of the substantia nigra pars compacta (SNpc) by regulating the magnitude of the first phase of postnatal natural cell death which occurs in these neurons. While it has been shown that GDNF mRNA is relatively abundant in postnatal striatum, the cellular basis of its expression has been unknown. We therefore used nonradioactive in situ hybridization and immunohistochemistry to examine the cellular basis of GDNF mRNA and protein expression, respectively, in postnatal striatum and related structures. We found that GDNF mRNA is expressed within medium-sized striatal neurons. Expression in glia was not observed. At the protein level, regionally, GDNF expression in striatum was observed in striosomal patches, as previously described. At a cellular level a few neurons were observed, but they do not account for the striosomal pattern. This pattern is predominantly due to GDNF-positive neuropil. Some of this neuropil arises from tyrosine hydroxylase-positive nigro-striatal dopaminergic afferents. Astrocytic processes do not appear to contribute to the striosomal pattern. GDNF-positive fibers are identified not only within intrinsic striatal neuropil, but also in fibers within the major striatal efferent targets: the globus pallidus, the entopeduncular nucleus, and the SN pars reticulata. We conclude that during normal postnatal development, medium-sized neurons are the principal source of GDNF within the striatum.     

Pseudo-tumours of the urinary tract in patients with spinal cord injury/spina bifida

OBJECTIVE: To raise awareness of pseudo-tumours of urinary tract, as pseudo-tumours represent benign mass lesions simulating malignant neoplasms. Accurate diagnosis helps to avoid unnecessary surgery in spinal cord injury patients. SETTING: Regional Spinal Injuries Centre, Southport, UK CASE REPORTS: Pseudo-tumour of kidney: A 58-year-old man with tetraplegia developed a right perirenal haematoma while taking warfarin; ultrasound and CT scanning showed no evidence of tumour in the right kidney. The haematoma was drained percutaneously. After 8 months, during investigation of a urine infection, ultrasound and CT scan revealed a space-occupying lesion in the mid-pole of the right kidney. CT-guided biopsy showed features suggestive of an organising haematoma; the lesion decreased in size over the next 13 months, thus supporting the diagnosis. Pseudo-tumour of urinary bladder: A frail, 34-year-old woman, who had spina bifida, marked spinal curvature and pelvic tilt, had been managing her neuropathic bladder with pads. She had recurrent vesical calculi and renal calculi. CT scan was performed, as CT would be the better means of evaluating the urinary tract in this patient with severe spinal deformity. CT scan showed a filling defect in the base of the bladder, and ultrasound revealed a sessile space-occupying lesion arising from the left bladder wall posteriorly. Flexible and, later, rigid cystoscopy and biopsy demonstrated necrotic slough and debris but no tumour. Ultrasound scan after 2 weeks showed a similar lesion, but ultrasound-guided biopsy was normal with nothing to explain the ultrasound appearances. A follow-up ultrasound scan about 7 weeks later again showed an echogenic mass, but the echogenic mass was seen to move from the left to the right side of the bladder on turning the patient, always maintaining a dependent position. The echogenic bladder mass thus represented a collection of debris, which had accumulated as a result of chronic retention of urine and physical immobility. CONCLUSION: Recognising the true, non-neoplastic nature of these lesions enabled us to avoid unnecessary surgical procedures in these patients, who were at high risk of surgical complications because of severely compromised cardiac and respiratory function.     

Prepayment was superior to postpayment cash incentives in a randomized postal survey among physicians

OBJECTIVE: Improving response rates, particularly among physicians, is important to minimize nonresponder bias and increase the effective sample size in epidemiologic research. We conducted a randomized trial to examine the impact of prepayment vs. postpayment incentives on response rates. STUDY DESIGN AND SETTING: Self-completion postal questionnaires were mailed to 949 physicians who were respondents to an earlier survey and representative of the general physician population in Hong Kong. These physicians were randomly allocated to receive a HK dollar 20 cash prepayment incentive that accompanied the survey (n=474) or a postpayment reward of the same amount on receipt of the completed questionnaire (n=475). RESULTS: The final prepayment response rate was 82.9%, compared with 72.5% in the postpayment arm (P < .001). Of the eight alternative incentive and follow-up strategies evaluated, three lie on the efficiency frontier (i.e., not dominated), including postpayment with three mailings at HK dollar 42.7, prepayment with three mailings at HK dollar 66.5 and prepayment with three mailings and telephone follow-up at HK dollar 112.1 per responder recruited (US dollar 1=HK dollar 7.8). CONCLUSION: The findings demonstrate that prepayment cash incentives are superior to postpayment of the equivalent amount in improving response rates among a representative sample of Hong Kong physicians. Further research should concentrate on confirming the generalizability of these findings in other health care occupation groups and settings.     

A comparative study of three warming interventions to determine the most effective in maintaining perioperative normothermia

Perioperative hypothermia poses a challenge because of its deleterious effects on patient recovery. The current practice of applying two cotton blankets on patients during surgery is thought to be less ideal than using reflective insulation or forced-air warming. We studied 300 patients who underwent unilateral total knee replacement and were randomized equally to three groups: (a) the two-cotton-blanket group, (b) the one-reflective-blanket with one-cotton-blanket group, and (c) the forced-air-warming with one-cotton-blanket group. Tympanic temperature readings were taken before surgery in the induction room, on arrival at the recovery room, and at 10-min intervals until discharge from the recovery room. On arrival at the recovery room, the forced-air-warming group had significantly higher temperatures (adjusted for sex, age, and patient's induction room temperature) of 0.577 degrees C +/- 0.079 degrees C (95% confidence interval [CI], 0.427-0.726; P < 0.001) and 0.510 degrees C +/- 0.08 degrees C (95% CI, 0.349-0.672; P < 0.001) more than the reflective-blanket and two-cot-ton-blanket groups, respectively. The forced-air-warming group took a significantly (P < 0.001) shorter time of 18.75 min (95% CI, 13.88-23.62) to achieve a temperature of 36.5 degrees C in the recovery room as compared with 41.78 min (95% CI, 36.86-46.58) and 36.43 min (95% CI, 31.23-41.62) for the reflective-blanket and two-cotton-blanket groups, respectively. The reflective technology was less effective than using two cotton blankets, and the forced-air warming was most efficient in maintaining perioperative normothermia. IMPLICATIONS: Perioperative hypothermia has deleterious effects on patient recovery. We found in patients having knee surgery that reflective technology was less effective than using two cotton blankets, whereas active surface warming with the forced-air method was most effective in maintaining normothermia.