Monte Carlo and analytical calculation of proton pencil beams for computerized treatment plan optimization

Proton pencil beams in water, in a format suitable for treatment planning algorithms and covering the radiotherapy energy range (50-250 MeV), have been calculated using a modified version of the Monte Carlo code PTRAN. A simple analytical model has also been developed for calculating proton broad-beam dose distributions which is in excellent agreement with the Monte Carlo calculations. Radial dose distributions are also calculated analytically and narrow proton pencil-beam dose distributions derived. The physical approximations in the Monte Carlo code and in the analytical model together with their limitations are discussed. Examples showing the use of the calculated set of proton pencil beams as input to an existing photon treatment planning algorithm based on biological optimization are given for fully 3D scanned proton pencil beams; these include intensity modulated beams with range shift and scanning in the transversal plane.     

The incidence, morbidity, and mortality of surgical procedures after orthotopic heart transplantation

OBJECTIVE: The authors present their experience with patients having undergone orthotopic heart transplantation (OHT) in whom surgical conditions subsequently developed that required operative intervention. The incidence, morbidity, and mortality of these procedures are reported. SUMMARY BACKGROUND DATA: Several studies have evaluated the management options of biliary tract disease after OHT. Multiple reports of patients having undergone OHT who subsequently underwent peripheral vascular reconstructions, plastic reconstructive, and thoracic procedures also have been published. METHODS: A chart review of 349 patients who underwent OHT between 1985 and 1996 was conducted to identify surgical procedures that were required in the post-transplant period. Their outcomes are reported. RESULTS: Of 349 patients who underwent OHT, conditions requiring 94 surgical procedures developed in 54 patients (15%). Biliary tract disease developed in 17 patients (5%) who required cholecystectomy, 2 of the 5 patients with acute cholecystitis died. Eight patients (2%) underwent orthopedic procedures with no operative mortality. Flap advancements for sternal wound infections were performed in five patients and four deaths occurred. Seventeen thoracic procedures were performed in 11 patients with an overall mortality of 45%. Twenty-one vascular procedures were performed on 17 patients with 1 delayed death due to a malignancy. Seven patients underwent procedures of the colon and rectum with no mortality. Seven patients underwent repair of inguinal or incisional hernias with no mortality. Various infections occurred with one resultant death after operative intervention. Six procedures were performed for diseases of the small intestine with no resultant mortalities. CONCLUSIONS: Patients having undergone OHT and chronic immunosuppression are at increased risk of having complications develop from infection. Acute cholecystitis and sternal wound infection caused an inordinate risk of complications and death. Malignancies developed in four patients who required surgical intervention. A heightened awareness of coexisting peripheral vascular disease in patients transplanted for ischemic cardiomyopathy should exist. Close screening before surgery and surveillance after surgery to identify risk factors for infection and vascular disease and to screen for malignancies are essential.     

Inhibition of androgen action by dehydroepiandrosterone sulfotransferase transfected in PC-3 prostate cancer cells

Age-dependent loss of androgen sensitivity of the rat liver is associated with a marked increase in dehydroepiandrosterone/hydroxysteroid sulfotransferase (rStd) activity. Sulfonated steroid hormones are known to be ineffective in binding receptor proteins. These observations suggest that intracellular androgen sulfonation can physiologically influence androgen action. We have examined the inhibitory effect of rStd on androgen action in the human prostate cancer-derived PC-3 cells transfected with the rat androgen receptor (AR) expression plasmid and two androgen-responsive promoter reporter constructs (murine mammary tumor long-terminal repeat ligated to chloramphenicol acetyltransferase (CAT) gene and rat probasin androgen response element (ARE) ligated to firefly luciferase (LUC) gene). These transfected cells were dependent on 5alpha-dihydrotestosterone (DHT) for the activation of both reporter genes and showed about a 200- and a 800-fold increase of CAT and LUC activity, respectively, at 10(-10) M DHT over the no-hormone control. Expression of the sulfonating enzyme in this cell transfection system via the rStd expression plasmid caused a dose-dependent decline in the reporter activity with approximately 90% inhibition of androgen action at a rStd:AR plasmid ratio of 100. From these results we conclude that irrespective of a high level of AR, changes in the Std expression can markedly alter the androgen sensitivity of target cells.     

Molecular and immunologic characterization of group A bovine rotavirus field isolates with P8[11] spike protein

Bovine rotavirus strain B223 is the North American prototype for group A P8[11] serotype/genotype rotaviruses. Rotaviruses with this serotype/genotype are a prevalent cause of neonatal calf diarrhea and have also been isolated from asymptomatic human infants. On the basis of deduced amino acid sequence of the outer capsid viral protein 4 (VP4), strain B223 lacks a cysteine at position 318 that is conserved among all other rotavirus strains. It has been speculated that this may result in the loss of disulfide bond and a change in the structure of the VP4 that may affect the infectivity and antigenicity of the virus. This paper describes partial sequences of the VP4 gene (nucleotides 613 to 1016 coding for amino acid positions 202 to 335) of 16 bovine rotavirus field isolates with P8[11] that were obtained from calves in Nebraska and Indiana. All the isolates lack a cystein at position 203 and had a conserved valine residue at position 318, thus indicating that the prototype strain B223 is representative of group A rotaviruses with P8[11] serotype/genotype.     

Familial Mondini dysplasia

OBJECTIVES/HYPOTHESIS: To determine the mode of inheritance of familial nonsyndromic Mondini dysplasia. Study Design: Correlative clinical genetic analysis of a single kindred. METHODS: Clinical history, physical examination, audiologic analysis, computed tomography of the temporal bones, and cytogenetic analysis. RESULTS: The male proband, three affected sisters, and an affected brother are offspring of unaffected parents. The mother and an unaffected brother have audiologic findings suggestive of heterozygous carrier status for a recessive hearing loss gene. CONCLUSIONS: Pedigree analysis indicates autosomal recessive inheritance in this family. The observed inheritance and clinical, audiologic, and radiologic findings are different from those previously described for another family with nonsyndromic Mondini dysplasia. The phenotype in this study family therefore represents a distinct subtype, indicating clinical and genetic heterogeneity of this disorder. This information should facilitate future molecular linkage analyses and genetic counselling of patients with inner ear malformations.     

Biomechanical and histologic alteration of facial recipient bone after reconstruction with autogenous bone grafts and alloplastic implants: a 1-year study

Potential alteration of the underlying recipient bone resulting from a graft or implant has significant clinical relevance. The present study was designed to evaluate the biomechanical and histologic alteration of facial recipient bone with autogenous bone graft and alloplastic implants over a 1-year period. The bilateral arches of 15 rabbits were randomized between four groups: (1) control (n = 6), subperiosteal exposure of the zygomatic arch was made; (2) onlay (n = 12), bone graft was placed as an onlay to the zygomatic arch; (3) inlay (n = 6), bone graft was placed as an inlay within the zygomatic arch; (4) implant (n = 6), a stainless steel plate was placed as an onlay to the zygomatic arch. Animals were killed 1 year after grafting. In the onlay groups, all steel implants and half of the onlay bone grafts (n = 6) were separated from the zygomatic arch; the remaining onlay bone grafts (n = 6) were left on the zygomatic arch. Three-point breaking strength was measured through the center of the graft/implant site on the zygomatic arch, followed by histologic evaluation and histometric assessment of residual bone density. The findings demonstrated no difference in the breaking strength per unit bone area between the control zygomatic arch group and the onlay group in which the bone graft was left in place. Breaking strength of the zygomatic arch in the former two groups was significantly greater than that in either group in which the onlay bone graft or implant had been removed, and was also greater than the breaking strength in that group in which inlay bone had been placed (p < 0.05). Histologic assessment showed full-thickness conversion in architecture of the zygomatic arch from compact to woven bone beneath onlays of either autogenous bone graft or steel implant; histometric assessment demonstrated an accompanying decrease in bone density in the latter groups relative to the control zygoma (p < 0.05). We conclude that onlay autogenous bone graft and alloplastic implants to the facial skeleton induce transformation of both graft and recipient bone from compact to woven architecture, accompanied by a reduction in bone density. The biomechanical strength of recipient facial bone is significantly weakened if an onlay bone graft or implant is removed. Weakening occurs per unit area of remaining bone, and is therefore independent of any thinning that may occur within the recipient bone because of graft/implant placement. These findings may impact upon decisions to augment stress-bearing regions of the facial skeleton with bone graft or implants, particularly if the graft/implant may eventually require removal.     

Specific binding of L-triiodothyronine modulates Na(+)-K(+)-ATPase activity in adult rat cerebrocortical synaptosomes

Interactions of L-triiodothyronine (T3) in adult rat cerebrocortical synaptosomes were studied in vitro. Scatchard plot analysis revealed two sets of T3 binding sites. The degree of saturation of T3 binding sites (putative receptor) correlated well with the dose-dependent inhibition of Na(+)-K(+)-ATPase activity in synaptosomes. The relative binding affinities and relative inhibition of enzyme activities for different TH analogues were L-T3 > T3-amine > TRIAC = L-T4 > r-T3 > T2 and L-T3 > T3-amine > TRIAC > L-T4 > r-T3 > T2, respectively. The present study demonstrates the nature of inhibition of synaptosomal Na(+)-K(+)-ATPase activity may be as a function of T3 occupancy of synaptosomal receptor sites in adult mammalian brain.