[Pain and neurocognitive disorders: current state of the art and remaining challenges]. / Pijn en neurocognitieve stoornissen: stand van zaken en de weg nog te gaan.

The detection and treatment of pain is hampered by cognitive disorders. In this review we discuss the epidemiology of pain in cognitive disorders, and elaborate further on the current state of the art on pain in these populations. We will specifically highlight current gaps and recommendations for the future for the following knowledge domains: 1) Biology and neuropathology,  2) Assessment and evaluation, 3) Treatment and management , and 4) Contextual factors such as the organization and education.  We identify the following knowledge gaps: 1) (Biology): Do pain experience and pain expressions change in different types of cognitive disorders, and how? 2) (Assessment): How to recognize, evaluate and assess pain, in case the self-report of pain is no longer reliable? 3) (Treatment): Which treatment possibilities are effective? How can we organize this in an interdisciplinary way? And how to monitor this? How can we ensure proper implementation of pain assessment and treatment in clinical practice? Specifically with regard to non-pharmacological treatment, how can we communicate observations from different disciplines, family members and clinicians to improve the detection of pain as well as treatment monitoring/evaluation? 4) (Contextual): How can we increase knowledge and skills on pain in cognitive impairment within educational training?

The first nocturnal home haemodialysis patient in Hong Kong.

We report our experience of the first use of nocturnal home haemodialysis in Hong Kong. The patient, a 40-year-old man with end-stage renal failure, was recruited into the Nocturnal Home Haemodialysis Programme at Princess Margaret Hospital in 2006. He received haemodialysis at home on alternate nights (3.5 sessions per week) for 5.5 to 6 hours per session. After 1 year of nocturnal home haemodialysis, his recombinant human erythropoietin requirement had been reduced by more than 50%. His serum phosphate level decreased by 35% and calcium phosphate product by 34%. After nocturnal home haemodialysis, his blood pressure control has been excellent and he was able to cease taking anti-hypertensive medications soon after commencing nocturnal home haemodialysis. Regression of his left ventricular hypertrophy has also been noted, with a 39% decrease in his left ventricular mass index. The haemodialysis adequacy index, weekly single-pool Kt/V, increased by 59% after switching to nocturnal home haemodialysis and his quality-of-life indices also showed significant improvement. Nocturnal home haemodialysis holds promise as an alternative dialytic therapy for patients on chronic haemodialysis in Hong Kong.

The MYCN oncogene is a direct target of miR-34a.

Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype. Database searches identified five microRNAs that map to the commonly deleted region of 1p36 and we hypothesized that the loss of one or more of these microRNAs contributes to the malignant phenotype of MYCN-amplified tumors. By bioinformatic analysis, we identified that three out of the five microRNAs target MYCN and of these miR-34a caused the most significant suppression of cell growth through increased apoptosis and decreased DNA synthesis in neuroblastoma cell lines with MYCN amplification. Quantitative RT-PCR showed that neuroblastoma tumors with 1p36 loss expressed lower level of miR-34a than those with normal copies of 1p36. Furthermore, we demonstrated that MYCN is a direct target of miR-34a. Finally, using a series of mRNA expression profiling experiments, we identified other potential direct targets of miR-34a, and pathway analysis demonstrated that miR-34a suppresses cell-cycle genes and induces several neural-related genes. This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma.

Minimal change disease following exposure to mercury-containing skin lightening cream.

A 34-year-old woman developed nephrotic syndrome after using a skin lightening cream that contained an extremely high level of mercury. Blood and urine mercury levels were elevated and a renal biopsy revealed minimal change disease. Membranous nephropathy was excluded using immunofluorescence and electron microscopy. Her proteinuria remitted 9 months after she stopped using the cosmetic cream. This is the first reported case in the English literature of proven minimal change disease secondary to mercury exposure. It is important that mercury poisoning due to cosmetic cream is considered in the differential diagnoses for any woman who presents with nephrotic syndrome.

Sodium ramping reduces hypotension and symptoms during haemodialysis.

OBJECTIVES: To evaluate the effectiveness of sodium ramping (profiling) in reducing hypotensive episodes and symptoms during haemodialysis. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Thirteen patients who experienced frequent episodes of hypotension and/or symptoms such as cramps, dizziness, chest pain, nausea, vomiting, and headache during haemodialysis in the preceding 4 weeks. INTERVENTIONS: Each patient was switched from standard haemodialysis with a constant dialysate sodium concentration of 135 to 140 mmol/L to a ramped sodium haemodialysis for a period of 4 weeks. During this time the dialysate sodium concentration was ramped linearly downwards from 150 mmol/L at the beginning of dialysis to 140 mmol/L at the end of dialysis. MAIN OUTCOME MEASURES: Intradialytic hypotensive episodes, intradialytic symptoms, nursing interventions, systolic and diastolic blood pressures, and interdialytic weight gain. RESULTS: A total of 248 haemodialysis sessions undertaken by 13 patients were analysed. Switching from constant sodium haemodialysis to ramped sodium haemodialysis resulted in a significant reduction in the number of intradialytic hypotensive episodes from 5.8 (standard deviation, 6.4) to 2.2 (3.3) [P<0.05], the total number of intradialytic symptoms from 7.1 (3.4) to 0.9 (1.3) [P<0.01], and nursing interventions from 11.3 (6.3) to 1.7 (3.9) [P<0.01]. Post-dialysis systolic and diastolic blood pressures were higher during ramped sodium haemodialysis compared with constant sodium haemodialysis (systolic blood pressure, 139 [standard deviation, 23] vs 133 [22] mm Hg, P<0.001; diastolic blood pressure, 77 [11] vs 74 [13] mm Hg, P<0.01), and there was a trend towards a smaller drop in blood pressure after dialysis. The interdialytic weight gain with sodium ramping haemodialysis was greater compared with constant sodium haemodialysis (3.1 [standard deviation, 1.0] vs 2.7 [1.1] kg, P<0.001). CONCLUSION: Sodium ramping during haemodialysis effectively reduces hypotensive episodes and intradialytic symptoms. Post-dialysis blood pressure is better maintained. A side-effect of sodium ramping is a greater interdialytic weight gain.

Renal tubular acidosis and severe hypophosphataemia due to toluene inhalation.

A 21-year-old woman developed severe muscle paralysis after sniffing toluene-containing thinner solution for 2 weeks. Her serum chemistries revealed severe hypokalaemia and a normal anion gap hyperchloraemic metabolic acidosis secondary to renal tubular acidosis. Her initial presentation mimicked hypokalaemic periodic paralysis, but toxicology screening of her blood and urine revealed the correct diagnosis of toluene poisoning. Her electrolyte and acid-base status returned to normal 4 days after cessation of toluene sniffing. On another occasion, apart from renal tubular acidosis, the patient also developed severe hypophosphataemia with the phosphate level decreasing to 0.15 mmol/L. Hypophosphataemia with such a low phosphate level after toluene poisoning has been rarely reported in the literature. Toluene inhalation can result in multiple electrolyte and acid-base abnormalities, and should be considered in the diagnosis of any young patient who presents with unexplained hypokalaemia and normal anion gap metabolic acidosis.

Characterization of additional genetic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion: a molecular cytogenetics study.

TEL/AML1 gene fusion that results from a cryptic t(12;21) is the most common genetic aberration in childhood B-lineage acute lymphoblastic leukemia (ALL). While the translocation may initiate the leukemic process, critical secondary genetic events are currently believed to be pivotal for leukemogenesis. We investigated 12 cases of childhood ALL with TEL/AML1 gene fusion by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) and documented additional or secondary genetic changes in seven patients (58%). Three patients showed extra copies of chromosome 21 including a case in which the trisomy 21 (+21) clone was distinct from the one harboring TEL/AML1 gene fusion. Interestingly, one patient without +21 showed amplification of the AML1 gene on chromosome 21q, supporting the contention that AML1 amplification may be an important additional genetic event. Gene expression study by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) in two of these four patients showed an increase in AML1 transcripts that paralleled the increase in gene copy number. Deletion of the normal TEL allele was detected in two patients, with one of them showing loss of chromosome 12 together with duplication of the der(12)t(12;21). Finally, one patient showed duplication of the fusion signal. Our findings confirm that additional or secondary genetic changes including AML1 amplification are commonly encountered in childhood ALL with TEL/AML1 gene fusion, which are envisaged to play significant roles in disease progression.