Deletion of 7p or monosomy 7 in pediatric acute lymphoblastic leukemia is an adverse prognostic factor: a report from the Children's Cancer Group.

Monosomy 7 or deletions of 7q are associated with many myeloid disorders; however, the significance of such abnormalities in childhood acute lymphoblastic leukemia (ALL) is unknown. Among 1880 children with ALL, 75 (4%) had losses involving chromosome 7, 16 (21%) with monosomy 7, 41 (55%) with losses of 7p (del(7p)), 16 (21%) with losses of 7q (del(7q)), and two (3%) with losses involving both arms. Patients with losses involving chromosome 7 were more likely to be > or =10 years old, National Cancer Institute (NCI) poor risk, and hypodiploid than patients lacking this abnormality. Patients with or without these abnormalities had similar early response to induction therapy. Event-free survival (EFS) and survival for patients with monosomy 7 (P<0.0001 and P=0.0007, respectively) or del(7p) (P<0.0001 and P=0.0001, respectively), but not of patients with del(7q), were significantly worse than those of patients lacking these abnormalities. The poorer EFS was maintained after adjustment for a Philadelphia (Ph) chromosome, NCI risk status, ploidy, or an abnormal 9p. However, the impact on survival was not maintained for monosomy 7 after adjustment for a Ph. These results indicate that the critical region of loss of chromosome 7 in pediatric ALL may be on the p-arm.     

The effect of polymorphisms in tumor necrosis factor-alpha, interleukin-10, and transforming growth factor-beta1 genes in acute hepatic allograft rejection

BACKGROUND: The occurrence of acute rejection in orthotopic liver transplantation is unpredictable. The role of cytokines in the process of rejection is not entirely clear. We investigated polymorphisms in the genes encoding tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, and transforming growth factor (TGF)-beta1, which affect the amount of cytokine produced in vitro, in a liver transplant population to determine any association with acute rejection. METHOD: DNA was extracted from whole blood of liver transplant patients. After amplification with polymerase chain reactions, the polymorphisms at TNF-alpha -308, IL-10 -1082, and TGF-beta1 +869 and +915 were determined using sequence-specific oligonucleotide probes. Acute cellular rejection was a clinical and histological diagnosis. RESULTS: Acute cellular rejection requiring treatment occurred in 68 (48%) of 144 patients. Acute cellular rejection was significantly associated with the TNF-alpha -308 A/A genotype (P<0.02). There was no significant association with either IL-10 or TGF-beta1 polymorphisms in acute rejection. CONCLUSION: Patients with a homozygous TNF-alpha -308 genotype A/A are more likely to suffer from acute cellular rejection after liver transplantation.     

A new cranial access device for cerebral monitoring

We report the design and clinical application of a new cranial access device (triple bolt) designed to transmit intracranial pressure monitors, multiparameter sensors, microdialysis catheters and laser doppler probes into the cerebral parenchyma. The objective was to achieve insertion on the Neuro-Critical Care Unit, imaging compatibility, angled trajectories and versatility of monitor application. The bolt has been successfully applied to 100 patients with severe head injury and subarachnoid haemorrhage.     

Assessing outcome in lumbar disc surgery using patient completed measures

Measuring outcome after spinal surgery is difficult. The objective of this study was to assess the use of four measures in establishing outcome in patients undergoing lumbar discectomy. Forty-six consecutive patients who had undergone two operations for lumbar disc prolapse and 54 patients who had undergone one operation for the same condition over the same period were identified. The SF-36 questionnaire was used to assess general health. The Roland-Morris questionnaire and a simple modification of the Roland-Morris questionnaire were used to assess back and leg related disability, respectively. Analogue pain scales were used to measure back pain and sciatica. The SF-36 scores revealed significantly worse health status in the two operation compared with the one operation patients and in all patients compared with the normal population. Using the Roland-Morris and the leg disability questionnaires, patients who had undergone two operations reported significantly worse disability (Roland-Morris, 53%, poor outcome) than those who had undergone one operation (Roland-Morris, 19%, poor outcome). There was significantly greater back disability than leg disability in both groups of patients and this was confirmed by the analogue pain scales. In patients who had undergone two operations, 25% classified their back pain as very bad or unbearable, and 22.5% described very bad or unbearable leg pain. For the one operation patients these figures were 9.5 and 2.4%, respectively. The results demonstrate that both generic and condition specific patient completed measures have the potential to detect differences in outcome between patients who have undergone either one or two lumbar disc operations. The study provides support for the use of these patient completed measures in assessing outcome in lumbar disc surgery.     

Current concepts in triple arthrodesis

When performed appropriately, good to excellent results may be obtained with triple arthrodesis in about 80% of patients. Postoperative pain relief, a plantigrade foot, and improved ambulatory ability are the desired surgical goals. Although there is a significant incidence of degenerative or compensatory arthritis in the remaining articulations, it is rarely of clinical significance. The surgical technique of triple arthrodesis is technically demanding. Rigid attention to detail is important to reduce surgical complications. It is important to understand the local anatomy to avoid injury to nerves, vessels, and tendons. Proper exposure of the joints facilitates cartilage removal and lowers the incidence of nonunion. Rigid compression fixation in an appropriate position provides the best possibility of a successful outcome. It is crucial to remember that a triple arthrodesis is an end-stage salvage procedure. With realistic expectations, the level of satisfaction will be higher for both patient and surgeon.     

Ocular microtremor (OMT): a new neurophysiological approach to multiple sclerosis

Using a piezoelectric transducer, the frequency and pattern of ocular microtremor (OMT) between 50 normal subjects and 50 patients with multiple sclerosis were compared. Controls were age matched. All records were analysed blindly. The frequency of OMT in the normal group was 86 (SD 6) Hz, which was significantly different from that of the multiple sclerosis group (71 (SD) 10 Hz, p<0.001). Those in the multiple sclerosis group with clinical evidence of brain stem or cerebellar disease (n=36) had an average OMT frequency of 67 (SD 9) Hz (p<0.001) compared with normal (n=86), whereas those with no evidence of brain stem or cerebellar involvement (n=14) had a frequency of 81.2 (SD 6) Hz (p<0.05, n=64). The differences between the two multiple sclerosis groups were also significant (p<0. 001, n=50). At least one abnormality (frequency and pattern) of OMT activity was seen in 78% of patients with multiple sclerosis. In the presence of brain stem or cerebellar disease 89% had abnormal records whereas in the absence of such disease 50% had abnormal records. This is the first report of the application of this technique to patients with multiple sclerosis. The results suggest that OMT activity may be of value in the assessment of multiple sclerosis.     

Clinical cerebral microdialysis: a methodological study

OBJECT: Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC). METHODS: A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at -70 degrees C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations. CONCLUSIONS: Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and 30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.