Range verification in heavy-ion therapy using a hadron tumour marker.

Objective.A new method to estimate the range of an ion beam in a patient during heavy-ion therapy was investigated, which was previously verified for application in proton therapy.Approach.The method consists of placing a hadron tumour marker (HTM) close to the tumour. As the treatment beam impinges on the HTM, the marker undergoes nuclear reactions. When the HTM material is carefully chosen, the activation results in the emission of several delayed, characteristicγrays, whose intensities are correlated with the remaining range inside the patient. When not just one but two reaction channels are investigated, the ratio between these twoγray emissions can be measured, and the ratio is independent of any beam delivery uncertainties.Main results.A proof-of-principle experiment with an16O ion beam and Ag foils as HTM was successfully executed. The107Ag(16O,x)112Sb and the107Ag(16O,x)114Sb reaction channels were identified as suitable for the HTM technique. When only oneγ-ray emission is measured, the resulting range-uncertainty estimation is at the 0.5 mm scale. When both channels are considered, a theoretical limit on the range uncertainty of a clinical fiducal marker was found to be ±290µm.Significance.Range uncertainty of a heavy-ion beam limits the prescribed treatment plan for cancer patients, especially the direction of the ion beam in relation to any organ at risk. An easy to implement range-verification technique which can be utilized during clinical treatment would allow treatment plans to take full advantage of the sharp fall-off of the Bragg peak without the risk of depositing excessive dose into healthy tissue.

Treatment of subchondral lucencies in the medial proximal radius with a bone screw in 8 horses.

OBJECTIVE: To describe the results of screw placement through subchondral lucencies (SCL) of the proximal radius in 8 horses. STUDY DESIGN: Retrospective clinical study. ANIMALS: Horses with cubital SCL causing lameness (n=8). METHODS: Medical record review and clinical follow-up. RESULTS: Eight horses with SCL in the proximal radius causing lameness were treated with a screw placed across the lucency. The horses range in age from 1 to 20 years. In 4 of 8 horses, the lameness had been intermittently severe (apparent at the walk). Lameness was isolated to the cubital joint by intra-articular anesthesia in 5 horses and diagnosed radiographically in all 8. All horses had a 4.5 mm cortical bone screw placed from medial to lateral (6 lag, 2 neutral) across the SCL using fluoroscopic or radiographic control. Postoperative care included stall confinement with hand walking for 30-60 days, followed by an additional 30-60 days of pasture turnout. Radiographic SCL healing (reduction in SCL size) was demonstrated at 3-4 months after surgery in all horses, and 7/8 horses (87.5%) were used as intended (4 performance, 3 pasture turn-out) within 6 months. Lameness in the remaining horse improved initially (dressage) but returned. CONCLUSIONS: A screw placed through the SCL of the proximal-medial radius was effective in reducing or resolving lameness associated with the elbow joint in 7/8 horses (88%). Screw placement in the proximal radius should be considered for horses with lameness caused by an SCL when a quick return to exercise is desired or conservative therapy is ineffective.

Compressor optimization with compressor-based multiphoton intrapulse interference phase scan (MIIPS).

The multiphoton intrapulse interference phase scan (MIIPS) technique is modified to optimize the compressor settings of a chirped pulse amplification (CPA) laser system. Here, we use the compressor itself to perform the phase scan inherent in MIIPS measurement . A frequency-resolved optical gating measurement shows that the pulse duration of the compressor optimized using the modified MIIPS technique is 33.8 fs with a 2.24 rad temporal phase variation above 2% intensity. The measured time-bandwidth product is 0.60, which is close to that of transform-limited Gaussian pulse (0.44).

Transfixation cast technique for arthrodesis of the distal interphalangeal joint of horses.

Surgical arthrodesis of the distal interphalangeal (DIP) joint by transfixation casting was used to salvage a three-year-old filly and a yearling filly that were chronically lame because of infection of the DIP joint for breeding. Unlike previously described techniques for arthrodesis of the DIP joint, the technique used did not require insertion of implants across the joint, which may have contributed to the successful outcome.

The chromosome partitioning protein, ParB, is required for cytokinesis in Caulobacter crescentus.

In Caulobacter crescentus, the genes encoding the chromosome partitioning proteins, ParA and ParB, are essential. Depletion of ParB resulted in smooth filamentous cells in which DNA replication continued. Immunofluorescence microscopy revealed that the formation of FtsZ rings at the mid-cell, the earliest molecular event in the initiation of bacterial cell division, was blocked in cells lacking ParB. ParB binds sequences near the C. crescentus origin of replication. Cell cycle experiments show that the formation of bipolarly localized ParB foci, and presumably localization of the origin of replication to the cell poles, preceded the formation of FtsZ rings at the mid-cell by 20 min. These results suggest that one major function of ParA and ParB may be to regulate the initiation of cytokinesis in C. crescentus.

In vitro evaluation of a novel prosthesis for laryngoplasty of horses with recurrent laryngeal neuropathy.

A prosthesis, composed of a steel cable and stress-reducing washers, was developed to prevent failure of laryngoplasty, a common treatment for horses affected by recurrent laryngeal neuropathy. Laryngoplasties were performed on 15 cadaveric larynges using a polyester suture on one side and the cable prosthesis on the other. Each prosthesis was distracted at a displacement rate of 20 mm/s using a servohydraulic materials testing machine until laryngoplasty failed. Distraction force and actuator displacement were recorded and analysed. All 15 laryngoplasties performed with a suture failed at the muscular process at a mean +/- s.d. force of 55.8 +/- 13.1 N. Six laryngoplasties performed with the cable prosthesis failed at the muscular process at mean force 219.6 +/- 125.0 N. In the other 9, the arytenoid cartilage was avulsed from the larynx at mean force 206.4 +/- 75.3 N, and the cable then tore through the muscular process at mean force 357.0 +/- 32.0 N. The difference in force required to cause failure of laryngoplasty was significant (P<0.0001). Although the prosthesis resisted substantially higher forces than did the suture, the effects of the prosthesis in vivo must be evaluated.

Evaluation of postoperative peritoneal lavage in standing horses for prevention of experimentally induced abdominal adhesions.

OBJECTIVE: To evaluate the postoperative use of peritoneal lavage for prevention of experimentally induced intraabdominal adhesions in horses. STUDY DESIGN: Areas of serosal abrasion were created on the jejunum of 12 horses. Postoperatively, six horses had peritoneal lavage, and six horses did not (controls). The number of adhesions was determined at necropsy 2 weeks after surgery. ANIMALS OR SAMPLE POPULATION: 12 horses. METHODS: Five sites of jejunal serosal abrasion were created in each horse. A 32 French thoracic catheter was placed into the right ventral aspect of the abdomen before closure of the abdominal incision. Treated horses had abdominal lavage with 10 L of lactated Ringer's solution on four occasions, then catheters were removed from all horses 34 hours after celiotomy. Horses were necropsied at 2 weeks to quantify the number of intraabdominal adhesions. RESULTS: All control horses and one treated horse developed intraabdominal adhesions. The number of adhesions was significantly less (P < .0293) in treated horses. No adverse inflammatory reactions appeared to be associated with repeated peritoneal lavage using lactated Ringer's solution or use of an abdominal drain. CONCLUSIONS: Peritoneal lavage reduced the frequency of intraabdominal adhesions. CLINICAL RELEVANCE: When postoperative adhesions are likely to develop, postoperative peritoneal lavage may decrease the frequency of adhesion formation.

Effects of postoperative peritoneal lavage on pharmacokinetics of gentamicin in horses after celiotomy.

OBJECTIVE: To evaluate the effect of peritoneal lavage on pharmacokinetics of gentamicin sulfate in healthy horses after experimental celiotomy. ANIMALS: 13 clinically normal horses. PROCEDURE: Horses were randomly assigned to control or experimental groups. All horses received gentamicin (6.6 mg/kg of body weight, IV, q 24 h) before surgery, underwent experimental abdominal surgery, and had abdominal drains placed percutaneously. Horses of the experimental group received postoperative peritoneal lavage; horses of the control group did not receive peritoneal lavage. The day after surgery, 24 hours after the preoperative dose of gentamicin, a second dose of gentamicin was administered. Three and 15 hours after this second dose of gentamicin, horses of the experimental group received peritoneal lavage. Venous blood was obtained, for determination of concentration of gentamicin, immediately before and at specified intervals during the 24-hour period after the second dose of gentamicin. RESULTS: There were no differences in any of the pharmacokinetic values of gentamicin between horses of the control and experimental groups. CONCLUSIONS: Peritoneal lavage had no effect on pharmacokinetics of gentamicin in healthy horses after abdominal surgery, in which localized nonseptic peritonitis was induced. CLINICAL RELEVANCE: Peritoneal lavage in horses with localized nonseptic peritonitis or for the prevention of intra-abdominal adhesions should not necessitate alteration of the dosage of gentamicin to maintain predictable serum concentrations.

Degradation of nonionic surfactants and polychlorinated biphenyls by recombinant field application vectors.

Degradation of polychlorinated biphenyls (PCBs) in the environment is limited by their aqueous solubility and the degradative competence of indigenous populations. Field application vectors (FAVs) have been developed in which surfactants are used to both increase the solubility of the PCBs and support the growth of surfactant-degrading strains engineered for PCB degradation. Surfactant and PCB degradation by two recombinant strains were investigated. Pseudomonas putida IPL5 utilizes both alkylethoxylate [polyoxyethylene 10 lauryl ether (POL)] and alkylphenolethoxylate [Igepal CO-720 (IGP)] surfactants as growth substrates, but only degrades the ethoxylate moiety. The resulting degradation products from the alkyl- and alkylphenolethoxylate surfactants were 2-(dodecyloxy)ethanol and nonylphenoldiethoxylates, respectively. Ralstonia eutropha B30P4 grows on alkylethoxylate surfactants without the appearance of solvent-extractable degradation products. It also degrades the 2-(dodecyloxy)ethanol produced by strain IPL5 from the alkylethoxylate surfactants. The extent of degradation of the alkylethoxylate surfactant (POL) was greater for strain IPL5 (90%) than for B30P4 (60%) as determined by the cobaltothiocyanate active substances method (CTAS). The recombinant strain B30P4::TnPCB grew on biphenyl. In contrast, the recombinant strain IPL5::TnPCB could not grow on biphenyl, and PCB degradation was inhibited in the presence of biphenyl. The most extensive surfactant and PCB degradation was achieved by the use of both recombinant strains together in the absence of biphenyl. PCB (Aroclor 1242) and surfactant (POL) concentrations were reduced from 25 ppm and 2000 ppm, respectively, to 6.5 ppm and 225 ppm, without the accumulation of surfactant degradation products. Given the inherent complexity of commercial surfactant preparations, the use of recombinant consortia to achieve extensive surfactant and PCB degradation appears to be an environmentally acceptable and effective PCB remediation option.

Facility planning for small and rural hospitals.

As changes in health care delivery move faster than ever, small or rural hospitals are struggling in a catch-up mode. In order to reverse this trend, these facilities need to reassess their position in the marketplace and develop a flexible plan for responding to the needs. This document provides a model to help achieve the vision of the physical plant in its supporting role to the strategic vision for the hospital, as well as options in the business of caring in a variety of alternative caregiving and treatment environments.

Molecular diagnostics and chemical analysis for assessing biodegradation of polychlorinated biphenyls in contaminated soils.

The microbial populations in PCB-contaminated electric power substation capacitor bank soil (TVA soil) and from another PCB-contaminated site (New England soil) were compared to determine their potential to degrade PCB. Known biphenyl operon genes were used as gene probes in colony hybridizations and in dot blots of DNA extracted from the soil to monitor the presence of PCB-degrading organisms in the soils. The microbial populations in the two soils differed in that the population in New England soil was enriched by the addition of 1000 p.p.m. 2-chlorobiphenyl (2-CB) whereas the population in the TVA capacitor bank soil was not affected. PCB degradative activity in the New England soil was indicated by a 50% PCB disappearance (gas chromatography), accumulation of chlorobenzoates (HPLC), and 14CO2 evolution from 14C-2CB. The PCB-degrading bacteria in the New England soil could be identified by their positive hybridization to the bph gene probes, their ability to produce the yellow meta-cleavage product from 2,3-dihydroxybiphenyl (2,3-DHB), and the degradation of specific PCB congeners by individual isolates in resting cell assays. Although the TVA capacitor bank soil lacked effective PCB-degrading populations, addition of a PCB-degrading organism and 10,000 p.p.m. biphenyl resulted in a > 50% reduction of PCB levels. Molecular characterization of soil microbial populations in laboratory scale treatments is expected to be valuable in the design of process monitoring and performance verification approaches for full scale bioremediation.

Molecular diagnostics for polychlorinated biphenyl degradation in contaminated soils.

Molecular diagnostic methods using DNA hybridization with specific gene probes are being developed for the monitoring of microbial populations capable of polychlorinated biphenyl (PCB) degradation in contaminated soils. Evaluation of composite samples from contaminated electrical substation soil by gas chromatography (GC) indicated that the PCBs present in the soil (approximately 200 ppm) resulted from contamination with Aroclor 1248. The PCBs have been weathered or degraded so that the lower molecular weight PCB congeners are no longer present. Microbiological and molecular site characterizations are in progress to determine the abundance of PCB degradative organisms and catabolic genes present. Cloned DNA fragments for the bphC gene (2,3-dihydroxybiphenyl dioxygenase) from the biphenyl/chlorobiphenyl degradative pathways of different organisms were used as gene probes to identify indigenous microorganisms with bphC gene sequences. In colony hybridization experiments, positive signals with the pDA251 gene probe were detected in cultures from both contaminated and uncontaminated soils. The degradative abilities of indigenous microorganisms and an added PCB-degradative bacterial strain were also monitored with [14C]4-chlorobiphenyl mineralization assays and gas chromatography of PCB residues extracted from the soils. Enrichment of the contaminated soil with biphenyl and chlorobiphenyls did not stimulate the indigenous microorganisms to degrade the soil PCB. Nevertheless, enrichment of the contaminated soil with biphenyl and chlorobiphenyl and addition of the PCB-degrading strain Alcaligenes eutrophus GG4202 did result in additional degradation of the soil PCB. The results obtained from these experiments should assist in developing and monitoring a remediation plan for these PCB-contaminated soils.

Failure of Klebsiella pneumoniae antibodies to cross-react with peripheral blood mononuclear cells from patients with ankylosing spondylitis.

Cross-reactivity between antibodies to 2 strains of Klebsiella pneumoniae (K43 and F77) and the peripheral blood lymphocytes of patients with ankylosing spondylitis (AS) was examined in 3 separate antibody binding and cytotoxicity assays. Using K pneumoniae antisera in a chromium release cytotoxicity assay, we found no difference in the reactions of cells from AS patients and those from control subjects. This result contrasts with the results of previous studies. Similarly, using an enzyme-linked immunosorbent assay, we detected no significant increase in antibody binding to peripheral blood mononuclear cells (PBMC) in HLA-B27 positive patients with AS. Low levels of antibody binding were detected by a fluoresceinated antibody binding assay; however, normal rabbit serum, which was used as a control, was shown to have a binding affinity for PBMC that was significantly greater than that of specific K pneumoniae antisera. The results of our present study do not support the concept of a specific cross-reactivity between antibodies to K pneumoniae and the PBMC of patients with AS who are HLA-B27 positive.

Immunological abnormalities in patients with untreated retinal vasculitis.

Peripheral blood immunological features were assessed in 21 patients with clinical and angiographic evidence of retinal vasculitis (RV). Abnormalities of humoral and cellular immunity were frequent in this group of patients. Lymphopenia was the most common immunological abnormality, being present in 76% of patients at presentation (p less than 0.05). Peripheral blood T and B cells were decreased with a normal helper (OKT4) to suppressor (OKT8) T cell ratio in 11 patients tested (five with Behçet's syndrome and six with idiopathic RV). Significantly increased concentrations of serum immune complexes were present in 55% of patients (p less than 0.05). Results of the present study indicate the frequent association of peripheral blood immunological abnormalities in patients with active RV and indicate the possible role of immunological mechanisms in its pathogenesis.

Chlamydial antibody crossreactivity with peripheral blood mononuclear cells of patients with ankylosing spondylitis: the role of HLA B27.

We have previously reported the association of Chlamydia trachomatis with HLA B27+ related diseases. To investigate the possibility that chlamydial antibodies serve to localize the immune response in such diseases, we examined the crossreactivity of chlamydial antibodies (rabbit anti-D and anti-L2 serotypes) with peripheral blood mononuclear cells of patients with ankylosing spondylitis (AS) and anterior uveitis (AU) and with human and bovine ocular tissue and cells in culture. Our results indicate a significantly increased percentage binding of chlamydial antibody (D serotype) to the mononuclear cells of HLA B27+ patients with AS when compared with HLA B27- patients with AS (12.9% +/- 2.2 versus 5.4% +/- 2.2), B27+ controls (5.5% +/- 1.5) and B27- controls (6.1% +/- 1.0). There was no significant difference between controls and HLA B27+ patients with AU (6.6% +/- 1.9) and B27- patients with AU (8.7% +/- 1.1). This crossreactivity could not be blocked by monoclonal HLA B27 antibody. Chlamydial antibodies (D and L2) crossreact with human and bovine conjunctiva but not uvea, tissue culture derived iris fibroblasts or smooth muscle cells. Our results provide additional support for the concept of crossreactivity between antibodies to microbial agents and peripheral blood mononuclear cells of patients with HLA B27+ AS.

Decreased chemiluminescent associated phagocytic response of peripheral blood mononuclear cells to Chlamydia trachomatis in patients with HLA-B27+ anterior uveitis.

The chemiluminescent (CL) associated phagocytic response of peripheral blood monocytes to two serovars of Chlamydia trachomatis, Shigella flexneri and zymosan was assessed in a group of 26 patients with anterior uveitis (AU). HLA-B27+ patients with AU, when compared to HLA-B27- patients with AU and appropriate controls, had a significantly decreased CL response to C. trachomatis but no difference between groups in the response to S. flexneri and zymosan. The decreased chemiluminescent (phagocytic) response of mononuclear phagocytes to Chlamydiae may indicate an important abnormality in the pathogenesis of HLA-B27+ AU.

Alpha 1 antitrypsin serum levels and phenotypes in patients with retinal vasculitis.

alpha 1 antitrypsin is an important immunoregulatory protein, the serum level of which is genetically determined. Deficient phenotypes of this ubiquitous protease inhibitor are associated with a variety of inflammatory diseases including anterior uveitis. In order to investigate the role of this protease inhibitor in the pathogenesis of retinal vasculitis (RV) 25 patients were investigated. Diseases associated with RV included Behcet's syndrome (8), SLE (2), and sarcoidosis (1). Deficient phenotypes of alpha 1 antitrypsin were not associated with RV. However, the serum alpha 1 antitrypsin level was significantly increased in patients with active RV and paralleled disease activity in patients studied prospectively.

The chemiluminescence response of normal human leukocytes to chlamydia trachomatis.

The aim of the present study was to investigate the phagocytic response of normal human polymorphonuclear leukocytes (PMN) and monocytes (MN) to eight serotypes of C trachomatis (B,C,D,E,F,I,J, and L2) using a chemiluminescence (CL) assay, with luminal and lucigenin as amplifiers. The magnitude of the phagocytic cell CL response was proportional to the phagocyte-to-chlamydiae ratio, with a poor CL response detected at a ratio of 1:125 and progressively larger CL responses up to ratios of 1:50,000. The durations of the CL responses to all chlamydiae serotypes tested were considerably longer than that for zymosan. The PMN demonstrated a relatively greater CL response to all chlamydiae serotypes tested when compared with MN. The PMN and MN CL responses to "genital serotypes" (D,E,F,I, and J) (as well as lymphogranuloma venereum serotype L2) were greater than that for "ocular" serotypes (B and C). Inactivation of serum complement and specific chlamydial antibody absorption reduced the CL responses of both PMN and MN. This is the first study to characterize the CL responses of normal human PMN and MN cells to C trachomatis, and it indicates the important role of oxygen dependent antimicrobial systems in the phagocytosis of this common human pathogen.