Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.     

High concentrations of soluble tumor necrosis factor receptors in ascites.

Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy-related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor-alpha concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy-related (p55: 26.0 +/- 8.6 ng/ml; p75: 20.5 +/- 17.4 ng/ml; mean +/- S.D.) and infected ascites (p55: 25.1 +/- 10.9 ng/ml, p75: 22.6 +/- 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 +/- 4.4 ng/ml; p75: 6.0 +/- 2.6 ng/ml). Patients with infected or malignancy-related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 +/- 15.2 ng/ml to 10.7 +/- 1.9 ng/ml and from 20.2 +/- 14.4 ng/ml to 7.5 +/- 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective localisation of neuro-specific T lymphocytes in the central nervous system

Using experimental autoimmune encephalomyelitis (EAE) in the rat as a model of central nervous system (CNS) inflammation, activated and quiescent T lymphocytes with different antigen specificities were labelled with the fluorescent dye Hoechst 33342 and tested by fluorescence microscopy for their ability to accumulate in different regions of the spinal cord and in other organs at varying times post inoculation. With this highly sensitive assay it was found that activated myelin basic protein (MBP)-specific T cell lines accumulated in the spinal cord (a 1000-fold increase in the lumbar/sacral region by day 4) and caused clinical signs of EAE. In contrast, interleukin-2 (IL-2)-maintained (quiescent) MBP-specific T cell lines failed to accumulate in the CNS and cause disease. Activated ovalbumin (OA)-specific and purified protein derivative of tuberculin (PPD)-specific T cell lines were also found at significantly higher levels in the spinal cord than non-activated cells although they failed to accumulate to a substantial degree when injected alone. When injected with activated MBP-specific T cells the activated OA- and PPD-specific cell lines accumulated in the spinal cord following initial accumulation of the MBP-specific cells, demonstrating that during the inflammatory process there is considerable non-specific recruitment of cells into the inflammatory site. CNS accumulation of activated MBP-specific T cell lines occurred 1-2 days later in irradiated animals than in non-irradiated recipients. This was consistent with irradiated animals also exhibiting a later onset of disease and suggests that irradiation may directly affect the endothelium in a way that makes it less adhesive. In conclusion, this study demonstrates that activated lymphocytes of any specificity enter the spinal cord, and that the neuro-antigen specific cells accumulate there and lead to the recruitment of other cells. Non-activated cells, even those with neural antigen specificity fail to enter the cord. Understanding the nature of what an 'activated' lymphocyte is may allow us to design strategies to inhibit such immune-mediated inflammation.     

An experience of renal replacement therapy in a combined neonatal and paediatric intensive care unit of Hong Kong

Intensive care services are expensive. The experience of developing a combined paediatric and neonatal intensive care unit (ICU) in a regional hospital is reported with reference to the provision of renal support for the critically ill patients. The combined unit is staffed by a team of paediatric intensivists, each of whom has special interest in a subspecialty, including cardiology, respiratory medicine, nephrology and neonatology. In the past 7 years, renal replacement therapy (peritoneal dialysis and haemofiltration) was provided to 40 patients, with comparable mortality and complication rates to other reports. This arrangement has been feasible and might be more efficient than running separate paediatric and neonatal ICUs or combining the paediatric ICU with the adult ICU.     

Rotational ablation of coronary artery lesions using single,large burrs

Previous clinical use of the Rotablator^(TM) In coronary artery disease has involved a sequential increase in burr sizes up to 2 mm in diameter and has often utilized balloon adjunct to achieve an optimal result. We report our experience and describe our technique using a single, large burr (2.25, 2.5, or 2.75 mm diameter) without balloon assistance. The burr size was selected to approximate 70–90 percent of the apparent normal lumen diameter. Thirty-one patients with 36 lesions of complex morphology (eccentric, irregular, calcified, ulcerated, at bends, at bifurcations, completely occluded, as well as balloon failures) were successfully treated with the Rotablator^(TM). Results were assessed by computerized quantitative angiography. The percent diameter stenosis (mean ± SD) for the group was reduced from 69.8 ± 11.3% to 30.9 ± 10% (p < 0.001). The mean absolute diameter stenosis increased from 0.9 ± 0.3 mm to 2.2 ± 0.3 mm (p < 0.001). Angiographically visible dissections were seen in 4 patients and were uncomplicated in 2. One patient had a non-Q-wave myocardial infarction. A fourth patient had a presumed acute occlusion 36 hr after the procedure, necessitating emergency bypass surgery, but without Q waves on the electrocardiogram or wall-motion abnormalities on the echocar-diogram. Nitroglycerin was infused through the Rotablator^(TM) catheter and has considerably lowered the degree and frequency of spasm. No other acute complications occurred. The mean procedure time using a single burr was shorter than when multiple burrs were used: 56.5 vs. 97.3 min, respectively (p < 0.05). The use of a single, large-size Rotablator^(TM) burr is an effective method of treating complex coronary stenoses without balloon assistance and has an encouragingly low complication rate and short procedure time. © 1992 Wiley-Liss, Inc.     

Percutaneous transluminal angioplasty of tibial arteries for limb salvage

Percutaneous transluminal balloon angioplasty (PTA) was performed in 17 tibial arteries with an average cross-sectional area stenosis of 92% (range 75–99%) in 13 patients (14 limbs) for limb salvage. In 4 of 14 lower extremities, PTA of femoropopliteal arteries was also performed. Technical success with 50% or less residual stenosis was achieved in all 17 tibial vessels. At approximately 2 months after PTA, clinical improvement had occurred in 10 of 14 limbs; no patient was made worse. Most recent follow-up (mean 19 months, range 8–34 months) revealed continued satisfactory clinical success with no further vascular intervention in 9 of these 10 limbs (one patient died). Short segmental stenoses, residual stenoses less than 40% following PTA, and absence of diabetes or gangrene appear to be predictors of favorable clinical outcomes. Our results suggest that PTA of focal tibial stenosis is an effective and safe treatment modality in properly selected patients and that wider use of PTA may be justified.     

Relaxation Therapy and Compliance in the Treatment of Adolescent Headache

SYNOPSIS
Few controlled studies have examined the effectiveness of relaxation therapy for the treatment of adolescent headaches. In this study, ten chronic headache sufferers (migraine or muscle contraction), ranging in age from 12 to 17 years (M = 13.5 SD = 1.3), were sequentially assigned to either a relaxation therapy or waiting-list control group. Following treatment, subjects in the treatment group demonstrated significantly lower Headache Index scores than subjects in the control group (U = 0, p £ .004). Group differences in Headache Free Days, Peak Headache Rating, and Medication Index scores were not significant; differences in Medication Index scores approached significance at U = 3, p £ .03. Objective compliance to treatment data indicated subjects overreported their actual practice time, on average, by 70%. Results and implications for future research are discussed.     

Spinal dysraphism and cavovarus foot deformity: a case report

Neurological impairment secondary to spinal dysraphism most commonly presents as unilateral cavovarus foot in children. The deformity usually develops in the growing child around the age of five or six. The presence of a cavovarus foot of unknown origin in a child should lead to a complete neurological examination, including an assessment of the spine for spinal dysraphism. The early recognition of pathology may prevent severe neurological sequelae. A case of lipomyelomeningocele is presented to illustrate that cord damage in children with spinal dysraphism can present initially as a cavovarus foot.