Peripheral neuropathy and myonecrosis following hyperthermia and radiation therapy for recurrent prostatic cancer: correlation of damage with predicted SAR pattern.

During the past 10 years, numerous phase I-II studies were conducted and provided clinical experience with combined radiation therapy and hyperthermia treatments. Among the rare complications reported in these combined radiation therapy-hyperthermia trials were myonecrosis and peripheral neuropathy which were felt, mainly on a clinical basis, to be caused by local heat damage. Recently, such complications were noted in two patients with recurrent prostatic cancer treated in our department with radiation therapy combined with deep regional hyperthermia delivered by the Sigma-60 applicator of the BSD 2000 hyperthermia system (Salt Lake City, UT, USA). Analysis of the results of three-dimensional modelling of the SAR (specific absorption rate, W/kg) pattern in these patients indicated high SAR at the sites of the complications. Pretreatment three-dimensional modelling or other methods of predicting potential areas of high power deposition may have a role for future hyperthermia treatment planning aiding in the prevention of possible local heat damage and providing improved delivery of heat to the target volume.     

Quantitative Magnetic Resonance Imaging of Human Brain Development: Ages 4-18

Brain magnetic resonance images (MRI) of 104 healthy childrenand adolescents, aged 4–18, showed significant effectsof age and gender on brain morphometry. Males had larger cerebral(9%) and cerebellar (8%) volumes (P < 0.0001 and P = 0.008.respectively), which remained significant even after correctionfor height and weight After adjusting for cerebral size, theputamen and globus pallidus remained larger in males, whilerelative caudate size was larger in females. Neither cerebralnor cerebellar volume changed significantly across this agerange. Lateral ventricular volume increased significantly inmales (trend for females), with males showing an increase inslope after age 11. In males only, caudate and putamen decreasedwith age (P = 0.007 and 0.05, respectively). The left lateralventricles and putamen were significantly greater than the rightP = 0.01 and 0.0001, respectively). In contrast, the cerebralhemispheres and caudate showed a highly consistent right greater-than-leftasymmetry (P < 0.0001 for both). All volumes demonstrateda high degree of variability. These findings highlight gender-specificmaturational changes of the developing brain and the need forlarge gender-matched samples in pediatric neuropsychiatric studies.     

Congenital defects of lower limbs and associated malformations: A population based study

As part of a detailed study of limb defects and associated patterns of congenital malformations, cases with lower limb deficiencies were analysed separately. We identified a total of 130 cases with deficiencies of the lower limbs without defects of the upper limbs. This gives an incidence of 1.07/10,000 livebirths, or 1/9,337 for this group of limb defects. Most common were femur deficiencies and deficiencies of the foot. A preponderance of males was found in the group of transverse defects of the leg (fibula/tibia deficiencies) and central axis deficiencies, while females had significantly more often longitudinal tibia defects and preaxial ray defects. © 1993 Wiley-Liss, Inc.     

Quantitative assessment of variables that influence soft-tissue electrovaporization in a fluid environment

Objectives. To evaluate the process of soft-tissue electrovaporization and to study variables that affect tissue clearance rates in a laboratory setting, in order to identify parameters that can optimize transurethral electrovaporization of the prostate.Methods. Fresh bovine skeletal muscle, equivalent in impedance and surface properties to the human prostate, was submerged in 3.3% sorbitol solution and electrovaporized with a grooved monopolar electrode attached to the weighted arm of a linear actuator. The effects of excursion rate, applied mechanical load, power setting, electrode configuration, and generator performance on the volume of tissue removed, were assessed.Results. Tissue removal increased significantly when electrode excursion rate was slowed from 25 to 15 mm/s (P <0.05) and then to 10 mm/s (P <0.05); when the load was increased from 20 to 50 g (P <0.005); and when dial power was increased from 120 to 150 W (P <0.01). Tissue removal was generator dependent. There was no significant difference between the Force 40 and the Force 2 (P > 0.4), but a new computer-controlled constant power output generator (Force FX) did significantly improve tissue vaporization at an equivalent power setting (P <0.005 and P <0.01, respectively). Tissue removal was also dependent upon electrode configuration, with the VaporTrode-Grooved Bar removing significantly more tissue than either an ungrooved roller bar of equivalent size or 2-mm smooth roller ball, respectively, both after a single pass (P <0.001 and P <0.05) and after five repeated passes (P <0.05 and P <0.005). The histologic depth of tissue thermal effect was less than 1 mm, but it was 38% greater for the VaporTrode-Grooved Bar (0.68 mm) than for the standard cutting loop (0.5 mm, P <0.01).Conclusions. Using a novel method to quantify tissue removal, we have demonstrated that electrode configuration, excursion rate, applied load, power setting, and generator performance are interdependent factors that influence the efficacy of the electrovaporization process in a fluid environment.     

Interaction of HPV-18 and nitrosomethylurea in the induction of squamous cell carcinoma

A strong correlation exists between the presence of specifictypes of human papillomavirus (HPV) and the development of anogenitalcancer, as well as significant epidemiologic evidence suggestingsmokers are at increased risk of developing cervical, vulvarand/or anal carcinomas. Primary and human papillomavirus type18 (HPV-8)-immortalized human keratinocytes were used to addressthe co-carcinogenic potential of HPV and nitrosomethylurea (NMU)in tumorigenesis. Only cells containing HPV-18 and treated withNMU and the tumor-promoting phorbol ester, TPA, were transformedto a malignant phenotype. An in vitro system is described whichinitiates studies involving the mechanisms of HPV and chemicalcarcinogen co-operation in the etiology of squamous cell carcinomas.     

Increase in brain cerebrospinal fluid volume is greater in older than in younger alcoholic patients: A replication study and CT/MRI comparison

This cross-sectional study used a semi-automated analysis technique to quantify regional brain cerebrospinal fluid (CSF) volumes derived from computed tomography (CT) in 84 healthy men ranging from 21 to 82 years of age and 28 patients meeting Research Diagnostic Criteria for alcohol dependence. The goals were to replicate an earlier CT study of an independent sample of alcoholic and control subjects (Pfefferbaum et al., 1988a; Zipursky et al., 1988) and to compare CT assessments of brain changes with magnetic resonance imaging (MRI) assessments made in the same alcoholic patients (Pfefferbaum et al., 1992). Regional brain changes associated with normal aging were derived by regression analysis, using CT data collected from the healthy control subjects. As in the earlier CT study and in the concurrent MRI study, ventricular and sulcal CSF volumes in alcoholic patients were greater than would be expected for their age. Furthermore, the present CT study replicated the previous CT and MRI findings of a positive relationship between age and CSF volume enlargement in alcoholic patients over and above the normal age-related increase in CSF volume, suggesting greater vulnerability of the aging brain to alcohol. Comparison of CT-and MRI-derived estimates of ventricular and cortical sulcal volume revealed high correlations (>0.80). MRI and CT produced similar absolute ventricular volumes, while MRI produced larger sulcal volume estimates than did CT. The difference in sulcal volume estimate may be due to differences between CT and MRI in slice thickness and sensitivity to partial volume effects.     

Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine

A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine.     

The epidemiology of severe injuries to children in northern Manhattan: methods and incidence rates

The epidemiology of injury incidence in inner-city children has not previously been described. This study presents the methods used and the incidence rates found for severe injury (causing hospitalisation or death) in a population of 89,000 children under age 17 years in northern Manhattan, a largely poor area of New York City. The average annual incidence rate (measured from 1983 to 1987) for severe injuries to children under 17 was 846/100,000 a year. The vast majority (79%) were classified as unintentional. Nine per cent were due to assault, 3% were self-inflicted and in an additional 9% the intention was unclear. Classified by cause, the highest incidence (per 100,000/year) was found for falls (218), vehicle-related (141, primarily pedestrian), ingestion (119) and burns (110). Guns caused 3% of the injuries (27). The death rate from injury was 18.7/100,000, 36% of which was due to homicide. In an additional 28%, intentional injury was suspected. The suicide rate was 0.4/100,000. The leading causes of injury death included guns and burns (both 2.7/100,000). Compared with childhood injury rates in predominantly rural and suburban populations, the rates reported here for northern Manhattan are higher for overall injury incidence (fatal and non-fatal) and for homicide, but lower for injury mortality not due to homicide.