Monte Carlo calculation of single-beam dose profiles used in a gamma knife treatment planning system

The accuracy of single-beam dose profiles used in the algorithm of the Gamma Knife treatment planning system (Leksell GammaPlan) is verified. EGS4 Monte Carlo calculation was employed to calculate the dose distributions of single-beams in a spherical water phantom with diameter 160 mm. The beams were directed to the center of the phantom. Collimators of 4, 8, 14, and 18 mm sizes were studied. The single-beam dose profiles provided by Elekta (Manufacturer of Leksell Gamma Knife) were excellently consistent with the results of Monte Carlo for the 4, 14, and 18 mm collimators. The maximum discrepancy was less than 3% at all radial distances. For the 8 mm collimator, the maximum discrepancy was 8% in the relative dose in the radial distance range from 4.3 mm to 5.2 mm. Excellent agreement in dose profiles along x, y, and z axes for all collimator helmets by summing over all 201 sources was observed between the cases using the default single-beam dose profiles and the calculated Monte Carlo results, except for the 8 mm collimator helmet along z axis. Such difference may however be too small to give a clinical significance.     

The muscarinic acetylcholine antagonist scopolamine impairs short-distance homing pigeon navigation

The present study employed intramuscular (i.m.) injections of the acetylcholine (ACh) receptor antagonist scopolamine hydrobromide (0.10 mg/kg) to investigate the possible involvement of ACh in naturally occurring spatial navigation in homing pigeons (Columba livia). Control pigeons receiving injections of saline or scopolamine methylbromide, an ACh antagonist that does not cross the blood-brain barrier, were oriented in a homeward direction when released from a location 8 km from home. In contrast, pigeons injected with scopolamine hydrobromide (0.10 mg/kg, i.m.) were less well oriented and took more time to return home from the same location. These results suggest that homing pigeon navigation is regulated, in part, by central cholinergic mechanisms.     

Boundary layer drug delivery using a helical catheter

BACKGROUND: A catheter-based approach for local endovascular drug delivery has been developed. The catheter is deployed percutaneously, while the end of the catheter is in the form of a helix that is placed just proximal to the vascular site to be treated. The helices are in contact with the vessel wall. A number of small holes is drilled in the coils of the catheter through which drug is infused, so that the infused drug remains within the blood fluid 'boundary layer' adjacent to the vessel wall. This approach is expected to be highly efficient for administration of antithrombotic and antiproliferative agents that target processes leading to vascular occlusion, heart attacks, and strokes. METHODS: The helical catheter was qualitatively evaluated using optical dye density measurements of Evans blue dye infused using an in vitro steady flow system under a physiologic range of conditions. To further demonstrate the efficiency of the technique, its capacity to inhibit thrombosis was evaluated in a baboon thrombosis model. The catheter was inserted into a femoral arteriovenous shunt (blood flow rate = 100 ml/min) and placed proximal to a segment of highly thrombogenic Dacron vascular graft (4.0 mm i.d.). Integrelin (an inhibitor of platelet glycoprotein IIb/IIIa; doses: 0.25-1.0 microg/min) and hirudin (an antithrombin; doses: 10-100 microg/min) were used to inhibit thrombus formation. RESULTS: Experimental flow visualization studies demonstrated that high concentrations of the infused Evans blue dye were retained near the vessel wall. In the animal experiments, platelet deposition on the Dacron graft surface was reduced by 82-97% (Integrelin) and 68-92% (hirudin) over 1-2 h of blood exposure. The local antithrombotic effects produced were found to be 200-fold and 30-fold more efficient than systemic administration of the same agents. CONCLUSIONS: Local drug infusion using the helical catheter approach can achieve high drug concentration levels at target sites, may avoid systemic effects, and can reduce cost of therapy by reducing total drug requirements.     

Subcutaneous soft tissue tumours at the site of implanted microchips in mice

An experiment using 4279 CBA/J mice of two generations was carried out to investigate the influence of parental preconceptual exposure to X-ray radiation or to chemical carcinogens. Microchips were implanted subcutaneously in the dorsolateral back for unique identification of each animal. The animals were kept for lifespan under standard laboratory conditions. In 36 mice a circumscribed neoplasm occurred in the area of the implanted microchip. Females were significantly more frequently affected than male mice. An influence of age or different treatment on the s.c. tumour incidence in two mice generations could not be observed. Macroscopically, firm, pale white nodules up to 25 mm in diameter with the microchip in its center were found. Microscopically, soft tissue tumours such as fibrosarcoma and malignant fibrous histiocytoma were detected.     

A role for the cadherin family of cell adhesion molecules in hippocampal long-term potentiation

The cadherins are a family of cell-cell adhesion molecules that mediate Ca2+-dependent homophilic interactions between cells and transduce signals by interacting with cytoplasmic proteins. In the hippocampus, immunostaining combined with confocal microscopy revealed that both neural- (N-) and epithelial- (E-) cadherin are present at synaptic sites, implying a role in synaptic function. Pretreatment of hippocampal slices with antibodies (Abs) raised against the extracellular domain of either N-cad or E-cad had no effect on basal synaptic properties but significantly reduced long-term potentiation (LTP). Infusion of antagonistic peptides containing the His-Ala-Val (HAV) consensus sequence for cadherin dimerization also attenuated LTP induction without affecting previously established LTP. Because the intense synaptic stimulation associated with LTP induction might transiently deplete extracellular Ca2+ and hence potentially destabilize cadherin-cadherin interactions, we examined whether slices could be protected from inhibition by N-cad Abs or HAV peptides by raising the extracellular Ca2+ concentration. Indeed, we found that high extracellular Ca2+ prevented the block of LTP by these agents. Taken together, these results indicate that cadherins are involved in synaptic plasticity, and the stability of cadherin-cadherin bonds may be regulated by synaptic stimulation.     

Moisture sorption isotherms and isosteric heat of sorption of leaves and stems of lemon balm (Melissa officinalis L.) established by dynamic vapor sorption

The equilibrium moisture contents (MC) of leaves and stems of lemon balm (Melissa officinalis L.) were determined separately at temperatures of 25, 35 and 45 °C over a stepwise increase of relative humidity (RH) ranging from 3 to 90% by an automatic, gravimetric analyzer (DVS system). Equilibrium was achieved within 6 h for most of the target values of relative humidity. The equilibrium moisture content of leaves was significantly higher than that of stems (p < 0.05). Differences in moisture sorption capacity between the leaves and stems can be attributed to chemical composition and structure of the tissues. Five three-parameter moisture sorption models (modifications of Chung–Pfost, GAB, Halsey, Henderson and Oswin) were tested for their effectiveness to fit the experimental sorption data. The modified Oswin equation was found to be the best model to describe the adsorption isotherms of both leaves and stems of lemon balm. The recommended MC values of leaves and stems for microbial safe storage at 25 °C were 0.124 and 0.113 kg water per kg dry solids, respectively. The net isosteric heat of sorption was computed from the predicted sorption data by applying the integrated form of the Clausius–Clapeyron equation.     

Longitudinal changes in lung function associated with aspects of swine-confinement exposure

Several aspects of swine-confinement farming appear to be leading to adverse respiratory effects. This study was set up in a longitudinal design to study the association between certain characteristics of farms or the way they are run and a decline in lung function. A cohort of 171 pig farmers was observed for 3 years. Lung function was measured. Exposure to farm characteristics was determined at the start of the observation period, using data from standardized farm surveys and from diaries kept by the participants. Mean decline in lung function was 73 mL/year for forced expiratory volume in 1 second (FEV1) and 55 mL/year for forced vital capacity (FVC). A longitudinal decline in FEV1 was significantly associated with the use of quaternary ammonium compounds as disinfectants (an additional 43 mL/year) and also with the use of an automated dry feeding system (an additional 28 mL/year). The association with the use of wood shavings as bedding material was not statistically significant. The impact of these characteristics in a longitudinal study provides stronger evidence for causal inference than that shown in previous cross-sectional designs. This may be useful in promoting preventive measures.     

Influence of Neotyphodium coenophialum on copper concentration in tall fescue

Poor performance of livestock that graze tall fescue (Festuca arundinacea Schreb.) has been associated with the endophyte fungus Neotyphodium coenophialum [Morgan-Jones and Gams] Glenn, Bacon, and Hanlin). Recent evidence suggests lowered Cu status and a depression of Cu-related immune function in steers that graze endophyte-infected (E+) tall fescue. Greenhouse and field studies investigated relationships between the endophyte and Cu concentrations in tall fescue. Seventeen infected 'Kenhy' clones were divided, and one plant of each pair was treated three times with Benomyl to remove the endophyte (E-). Plants were watered with nutrient solution in a greenhouse for 6 mo before sampling. Copper concentrations were greater (P < .001) in E- than in E+ clones (3.4 vs 2.8 microg/g; SE, .06). In the second greenhouse experiment, genetically similar E+ and E- 'Kentucky'-31 (KY-31) and 'Georgia Jessup' were grown from seed and fertilized with nutrient solution to produce mature plants. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (8.6 vs 7.6 microg/g; SE, .3). In a field plot experiment in Texas, E+ and E- KY-31 were grown with 0, 50, and 100% replacement of potential evapotranspiration. By September, Cu concentrations were higher (P < .05) in E- than in E+ tall fescue (7.3 vs 6.6 microg/g; SE, .2). In pasture experiments, KY-31 E+ (> 70% infection level) and E- (< 5% infection level) tall fescue were grown in Virginia at two locations with three rates of N fertilizer. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (4.8 vs 4.5 microg/g; SE, .1) and increased (P < .01) linearly in response to N. Our data demonstrate that the presence of the endophyte is associated with lower Cu concentrations in tall fescue, which may contribute to lowered Cu status in animals and thus contribute to the etiology of fescue toxicity.     

Validation of the Applied Biosystems Prism 377 automated sequencer for the forensic short tandem repeat analysis

The Applied Biosystems (ABI) Prism 377 DNA sequencer has been evaluated in an attempt to increase the throughput of samples for short tandem repeat (STR) analysis, in both forensic casework and the UK National Criminal Intelligence DNA Database. The gel system assessed consisted of 0.2 mm, 4% acrylamide 6 M urea gels, with a well-to-read distance of 36 cm. Gels were run at a constant voltage of 3 kV and constant temperature of 51 degrees C. The run time of our second generation multiplex (SGM) STR system was achieved in less than 2 h. Rigorous validation has been performed on the instrument hardware and software. Complete resolution of 1 base differences was obtained, up to and beyond 350 bases; sizing precision across gels was more than 2-fold higher than the 373A and the sensitivity was increased by one third.     

Cardiac transplantation in perspective for the future. Survival, complications, rehabilitation, and cost

Two hundred twenty-seven cardiac transplant procedures have been performed in 206 patients from January, 1968, to April, 1981. Postoperative survival rates, calculated by the actuarial method for program years 1968 to 1973 (66 patients), are 44%, 33%, 27%, 21%, and 18% at 1, 2, 3, 4, and 5 years after transplantation, respectively. Postoperative survival rates for program years 1974 to 1981 (140 patients) are 63%, 55%, 51, 44%, and 39% at 1, 2, 3, 4, and 5 years after transplantation, respectively. This increase results primarily from improvement in survival achieved in the first 3 postoperative months (59% +/- 7%, 1968 to 1973, versus 80% +/- 40%, 1974 to 1980), reflecting improved patient management. Infection remains the primary cause of death following transplantation (76/131 patients, 58%), followed by acute rejection (24/181, 18.3%), graft arteriosclerosis (14/131, 10.7%), and malignancy (6/131, 4.6%). The development of graft arteriosclerosis has been examined in 85 one-year survivors studied by annual coronary arteriograms. Coronary lesions of varying severity have developed in 21 patients. HLA-A2 incompatibility was associated with a higher incidence of graft arteriosclerosis than was apparent for all other A locus incompatibilities (p less than 0.0003). Lymphoma has been shown to be associated with younger recipient age, a primary disease diagnosis of idiopathic cardiomyopathy, and retransplantation. One hundred six patients have survived at least 1 year after transplantation; 97% were in NYHA Class 1 at that time interval and 82% returned to employment or activity of choice. The longest survival time is new 11 years, 3 months. Cardiac transplantation can be considered "reasonable and therapeutic treatment to extend life" in selected individuals.