Equivalence of cell survival data for radiation dose and thermal dose in ablative treatments: analysis applied to essential tremor thalamotomy by focused ultrasound and gamma knife.

Thermal dose and absorbed radiation dose have historically been difficult to compare because different biological mechanisms are at work. Thermal dose denatures proteins and the radiation dose causes DNA damage in order to achieve ablation. The purpose of this paper is to use the proportion of cell survival as a potential common unit by which to measure the biological effect of each procedure. Survival curves for both thermal and radiation doses have been extracted from previously published data for three different cell types. Fits of these curves were used to convert both thermal and radiation dose into the same quantified biological effect: fraction of surviving cells. They have also been used to generate and compare survival profiles from the only indication for which clinical data are available for both focused ultrasound (FUS) thermal ablation and radiation ablation: essential tremor thalamotomy. All cell types could be fitted with coefficients of determination greater than 0.992. As an illustration, survival profiles of clinical thalamotomies performed by radiosurgery and FUS are plotted on a same graph for the same metric: fraction of surviving cells. FUS and Gamma Knife have the potential to be used in combination to deliver a more effective treatment (for example, FUS may be used to debulk the main tumour mass, and radiation to treat the surrounding tumour bed). In this case, a model which compares thermal and radiation treatments is valuable in order to adjust the dose between the two.

Imaging findings in MR imaging-guided focused ultrasound treatment for patients with essential tremor.

BACKGROUND AND PURPOSE: MR imaging-guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue. The goal of this study was to describe MR imaging findings pre- and post-ventralis intermedius nucleus lesioning by MR imaging-guided focused sonography as a treatment for essential tremor and to determine whether there was an association between these imaging features and the clinical response to MR imaging-guided focused sonography. MATERIALS AND METHODS: Fifteen patients with medication-refractory essential tremor prospectively gave consent; were enrolled in a single-site, FDA-approved pilot clinical trial; and were treated with transcranial MR imaging-guided focused sonography. MR imaging studies were obtained on a 3T scanner before the procedure and 24 hours, 1 week, 1 month, and 3 months following the procedure. RESULTS: On T2-weighted imaging, 3 time-dependent concentric zones were seen at the site of the focal spot. The inner 2 zones showed reduced ADC values at 24 hours in all patients except one. Diffusion had pseudonormalized by 1 month in all patients, when the cavity collapsed. Very mild postcontrast enhancement was seen at 24 hours and again at 1 month after MR imaging-guided focused sonography. The total lesion size and clinical response evolved inversely compared with each other (coefficient of correlation = 0.29, P value = .02). CONCLUSIONS: MR imaging-guided focused sonography can accurately ablate a precisely delineated target, with typical imaging findings seen in the days, weeks, and months following the treatment. Tremor control was optimal early when the lesion size and perilesional edema were maximal and was less later when the perilesional edema had resolved.

Distal biceps tendon anatomy: a cadaveric study.

BACKGROUND: The anatomy of the distal biceps tendon and aponeurosis has not been studied in detail. METHODS: Seventeen cadaver elbows were dissected with loupe magnification to identify the details of the distal biceps tendon and the lacertus fibrosus. RESULTS: In ten of the seventeen specimens, the distal biceps tendon was in two distinct parts, each a continuation of the long and short heads of the muscle. The remaining seven specimens showed interdigitation of the muscle distally. The tendon continued from each muscle belly. The short head inserted distal to the radial tuberosity and was positioned to be a more powerful flexor of the elbow, while the tendon of the long head inserted on the tuberosity further from the axis of rotation of the forearm and was positioned to be a stronger supinator. The bicipital aponeurosis consisted of three layers and completely encircled the ulnar forearm flexor muscles. The aponeurosis may be important in stabilizing the tendons distally. CONCLUSIONS: The double tendon insertion may allow an element of independent function of each portion of the biceps, and, during repair of an avulsion, the surgeon should ensure correct orientation of both tendon components.

Long term outcome of neonatal meningitis.

OBJECTIVES: To quantify long term impairment after neonatal meningitis. DESIGN: Longitudinal case-control study over 9-10 years. SUBJECTS AND METHODS: A total of 111 children who had suffered neonatal meningitis were seen and compared with 113 matched controls from their birth hospital and 49 controls from general practices. Assessments included the WISC III(UK), movement assessment battery for children (mABC), audiometry, vision testing, and social and medical data. Statistical analysis was by multiple regression, analysis of variance, and chi(2) tests. RESULTS: Some 10.8% of cases had a severe and 9% a moderate overall outcome compared with 0% and 1.8% for the hospital controls. The mean intelligence quotient (IQ) of the cases (88.8) was significantly less than that of the hospital controls (99.4) or the GP controls (99.6). The mABC score was significantly worse for the cases (7.08) than the hospital (5) or GP (4) controls. Some 3.6% of cases had sensorineural hearing loss, 2.7% had persisting hydrocephalus; no controls did. Some 5.4% of cases and 1.7% of hospital controls had treatment for seizures. CONCLUSIONS: Severe neurodisability and milder motor and psychometric impairment result from neonatal meningitis. Both clinical follow up and comprehensive developmental assessment are needed after this disease.

Loss of a prolyl oligopeptidase confers resistance to lithium by elevation of inositol (1,4,5) trisphosphate.

The therapeutic properties of lithium ions (Li+) are well known; however, the mechanism of their action remains unclear. To investigate this problem, we have isolated Li+-resistant mutants from Dictyostelium. Here, we describe the analysis of one of these mutants. This mutant lacks the Dictyostelium prolyl oligopeptidase gene (dpoA). We have examined the relationship between dpoA and the two major biological targets of lithium: glycogen synthase kinase 3 (GSK-3) and signal transduction via inositol (1,4,5) trisphosphate (IP3). We find no evidence for an interaction with GSK-3, but instead find that loss of dpoA causes an increased concentration of IP3. The same increase in IP3 is induced in wild-type cells by a prolyl oligopeptidase (POase) inhibitor. IP3 concentrations increase via an unconventional mechanism that involves enhanced dephosphorylation of inositol (1,3,4,5,6) pentakisphosphate. Loss of DpoA activity therefore counteracts the reduction in IP3 concentration caused by Li+ treatment. Abnormal POase activity is associated with both unipolar and bipolar depression; however, the function of POase in these conditions is unclear. Our results offer a novel mechanism that links POase activity to IP3 signalling and provides further clues for the action of Li+ in the treatment of depression.

A fractured peace: a changing pattern of violence.

Since the paramilitary cease-fire in Northern Ireland in August 1994 we have seen a change in the pattern of so called 'punishment attacks'. Shootings with low velocity handguns have been replaced by severe beatings to the extremities from multiple assailants using iron bars or similar weapons. In the 18 months prior to the cease-fire there were 177 punishment shootings, which were usually relatively minor and did not require any plastic surgical expertise. Between August 1994 and November 1996, however, there were 461 punishment beatings. These beatings result in much greater morbidity and require considerable orthopaedic and plastic surgical input. In the Northern Ireland Plastic and Maxillofacial Unit we have treated 18 patients with a mean age of 22.9 years (range 16-32 years) who have been the victims of punishment beatings. These patients sustained multiple injuries, all with severe soft tissue involvement; 70% had compound fractures. The majority of patients had multiple wounds. Four patients with compartment syndrome as a result of their injuries required fasciotomies. Soft tissue reconstruction included split skin grafting (4 patients), fasciocutaneous flaps (4 patients), adipofascial flaps (2 patients), local muscle flaps (2 patients) and free muscle transfers (2 patients). Six patients required more than one procedure for soft tissue reconstruction because of multiple injuries. Each patient had a cumulative mean time in theatre of 6.7 hours. The mean hospital stay was 22.2 days (range 2-52 days). This change in the pattern of injury has led to an increased use of plastic surgical resources. Patient morbidity is significantly greater than when guns are used, and permanent disability is often the result.

An audit of the combined non-operative and orthotic management of ruptured tendo Achillis.

At this institution we have introduced combined non-operative and orthotic treatment for ruptured tendo Achillis. An outcome audit was performed to assess this treatment. Patients were treated in a short-leg cast in the equinus position. After a cast period of 4 weeks, the patient was placed in orthoses for a further 4 weeks, after which they returned to normal activities as was appropriate. We performed a retrospective review including visual analogue scores of patient satisfaction and physical examination. Thirty-two patients were reviewed. The average time from injury to review was 2 years (range 6 months to 5.5 years). There were no significant complications following treatment with no re-ruptures to date. Average visual analogue scores (0-10) were for casts 5.9, orthoses 8.5 and overall outcome 8.3. Of those wishing to return to sporting activities 62 per cent did so within 6.6 months (average). Clinical examination showed no significant difference (P, 0.05) between normal and injured leg in terms of ankle range of movement, tone and subtalar movement. The maximum calf circumference was significantly reduced on the affected side (36.84 cm versus 38.2 cm) as was ankle plantar flexion power. This treatment was liked by patients and is at least as effective as other established methods. Calf power and muscle bulk were reduced in the affected leg and may be improved by including a physiotherapy protocol in the treatment.

Immunogenicity of oral poliovirus vaccine administered in mass campaigns versus routine immunization programmes.

Reported are the results of a study to investigate the immunogenicity of oral poliovirus vaccine (OPV) when administered in mass campaigns compared with that following routine immunization programmes. For this purpose, paired sera were collected from a cohort of children before and after a mass vaccination with OPV in Morocco in 1987. Serum samples and information on vaccination status and other confounding factors that could influence antibody responses to OPV were collected. Neutralizing antibody titres to poliovirus types 1, 2 and 3 were determined using a standardized assay. OPV doses administered exclusively during the mass campaign were consistently associated with higher type-specific seroprevalence rates than the same number of doses administered in the routine programme. These findings could not be attributed to differences in confounding factors. Enhanced secondary spread of vaccine virus may have occurred but could not be demonstrated because of limitations in the study design. Mass campaigns appear to be highly effective in raising the dose-related poliovirus type-specific immunity of the population above that achieved by the routine immunization programme. Our findings support the continued use of mass campaigns as an adjunct to routine programmes in order to both enhance and catalyse current efforts to achieve the global eradication of poliomyelitis by the year 2000.

PIP: Reported are the results of a study to investigate the immunogenicity of oral poliovirus vaccine (OPV) when administered in mass campaigns compared with that following routine immunization programs. For this purpose, paired sera were collected from a cohort of children before and after a mass vaccination with OPV in Morocco in 1987. Serum samples and information on vaccination status and other confounding factors that could influence antibody responses to OPV were collected. Neutralizing antibody titers to poliovirus types 1, 2, and 3 were determined using a standardized assay. OPV doses administered exclusively during the mass campaign were consistently associated with higher type-specific seroprevalence rates than the same number of doses administered in the routine program. These findings could not be attributed to differences in confounding factors. Enhanced secondary spread of vaccine virus may have occurred but could not be demonstrated because of limitations in the study design. Mass campaigns appear to be highly effective in raising the dose-related poliovirus type-specific immunity of the population above that achieved by the routine immunization program. These findings support the continued use of mass campaigns as an adjunct to routine programs in order to both enhance and catalyze current efforts to achieve the global eradication of poliomyelitis by the year 2000. (author's)

Social deprivation and premature mortality: regional comparison across England.

OBJECTIVE: To investigate the pattern and size of the relationship between social deprivation in electoral wards and premature mortality for each health region in England. DESIGN: Ecological study using 1981 census variables and data on mortality for 1981-5. SETTING: 14 regional health authorities in England. MAIN OUTCOME MEASURE: Mortality under the age of 65 years from all causes, coronary heart disease, and smoking related diseases in men and women. RESULTS: Increasing deprivation was significantly associated with mortality from all causes, coronary heart disease, and smoking related diseases. The relationship was linear with no apparent threshold. Correlation coefficients were generally greater for deaths from all causes and smoking related diseases and for men compared with women. The slope of the relationship between deprivation and mortality varied among regions. Variations in mortality still existed between regions for equal levels of deprivation. CONCLUSION: Deprivation of an area and premature mortality are strongly linked. The effects of deprivation can be seen throughout the range of affluence and are not limited to the poorest areas. Current targets for reducing coronary heart disease mortality may be achievable if the mortality in poor areas can be reduced to the rates in affluent areas.

Baby bottles and family rattles. Children and substance abuse.

Research shows that problem behaviors manifested early tend to persist into later life. Problem drinking does not necessarily commit the young adolescent to a life course of this behavior, but it does alter the probabilities. Conversely, early abstinence is a strong predictor of later healthful behavior. An important observation is that alcohol and other drug use tends to decrease along with smoking decreases. Young adolescents tend to believe that most of their peers engage in a particular type of behavior whether that is the actual case or not. There is a tendency across populations of adolescents to overestimate such behaviors by a factor of six or eight. In one study, school children estimated that about two-thirds of their peers smoked while the actual figure was about one-tenth. Adolescents tend to have weak orientation to the future, especially in regard to consequences of risk-taking behavior. College-bound adolescents tend to have a longer view of the future than those who do not pursue college, but in general adolescents think, "It can't happen to me," or, "It's so far off that I just can't think about it." They are focused on the here and now. Many youngsters when they think about it have a dismal view of the future. They are doubtful about their own ability to influence events in ways that build toward a rewarding life.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth status and the risk of contracting primary tuberculosis.

A case of open tuberculous infection in a member of staff at a primary school resulted in an outbreak in which nearly a quarter of the children in the school contracted a primary infection. The growth status of these children was compared with that in the non-infected children before the outbreak and on two occasions after the outbreak. The children with tuberculous infection were taller and fatter than the controls before and after the outbreak but differences were not always statistically significant. Among children with a good nutritional status the thin and small child is at no greater risk of contracting primary tuberculous infection than other children.