The Importance of Team Alignment and Retention in Vascular Center Development: A Clinician's Perspective.

The healthcare landscape is in a state of constant evolution, presenting both challenges and opportunities. Recent trends, including the departure or retirement of medical professionals, the rise in travel and per diem positions, and the expansive growth of healthcare networks, have resulted in a palpable divide within the field. This divide often manifests as a shift from prioritizing patient care and staff well-being toward financial security and operational efficiency and productivity. Amid these ongoing changes, vascular centers possess the potential for a positive distinction that extends beyond their specialization to encompass their approaches to patient care and team dynamics. This article presents a 3-phase strategy for vascular clinicians and centers to consider as they seek to attract and retain top-tier staff, provide exceptional patient care, and attain sustainable growth and financial success.

Interferon-Induced Transmembrane Protein 1 Restricts Replication of Viruses That Enter Cells via the Plasma Membrane.

The acute antiviral response is mediated by a family of interferon-stimulated genes (ISGs), providing cell-intrinsic immunity. Mutations in genes encoding these proteins are often associated with increased susceptibility to viral infections. One family of ISGs with antiviral function is the interferon-inducible transmembrane proteins (IFITMs), of which IFITM3 has been studied extensively. In contrast, IFITM1 has not been studied in detail. Since IFITM1 can localize to the plasma membrane, we investigated its function with a range of enveloped viruses thought to infect cells by fusion with the plasma membrane. Overexpression of IFITM1 prevented infection by a number of Paramyxoviridae and Pneumoviridae, including respiratory syncytial virus (RSV), mumps virus, and human metapneumovirus (HMPV). IFITM1 also restricted infection with an enveloped DNA virus that can enter via the plasma membrane, herpes simplex virus 1 (HSV-1). To test the importance of plasma membrane localization for IFITM1 function, we identified blocks of amino acids in the conserved intracellular loop (CIL) domain that altered the subcellular localization of the protein and reduced antiviral activity. By screening reported data sets, 12 rare nonsynonymous single nucleotide polymorphisms (SNPs) were identified in human IFITM1, some of which are in the CIL domain. Using an Ifitm1-/- mouse, we show that RSV infection was more severe, thereby extending the range of viruses restricted in vivo by IFITM proteins and suggesting overall that IFITM1 is broadly antiviral and that this antiviral function is associated with cell surface localization.IMPORTANCE Host susceptibility to viral infection is multifactorial, but early control of viruses not previously encountered is predominantly mediated by the interferon-stimulated gene (ISG) family. There are upwards of 300 of these genes, the majority of which do not have a clearly defined function or mechanism of action. The cellular location of these proteins may have an important effect on their function. One ISG located at the plasma membrane is interferon-inducible transmembrane protein 1 (IFITM1). Here we demonstrate that IFITM1 can inhibit infection with a range of viruses that enter via the plasma membrane. Mutant IFITM1 proteins that were unable to localize to the plasma membrane did not restrict viral infection. We also observed for the first time that IFITM1 plays a role in vivo, and Ifitm1-/- mice were more susceptible to viral lung infection. These data contribute to our understanding of how ISGs prevent viral infections.

Characterisation of flattening filter free (FFF) beam properties for initial beam set-up and routine QA, independent of flattened beams.

Flattening filter free (FFF) beams have reached widespread use for clinical treatment deliveries. The usual methods for FFF beam characterisation for their quality assurance (QA) require the use of associated conventional flattened beams (cFF). Methods for QA of FFF without the need to use associated cFF beams are presented and evaluated against current methods for both FFF and cFF beams. Inflection point normalisation is evaluated against conventional methods for the determination of field size and penumbra for field sizes from 3 cm × 3 cm to 40 cm × 40cm at depths from dmax to 20 cm in water for matched and unmatched FFF beams and for cFF beams. A method for measuring symmetry in the cross plane direction is suggested and evaluated as FFF beams are insensitive to symmetry changes in this direction. Methods for characterising beam energy are evaluated and the impact of beam energy on profile shape compared to that of cFF beams. In-plane symmetry can be measured, as can cFF beams, using observed changes in profile, whereas cross-plane symmetry can be measured by acquiring profiles at collimator angles 0 and 180. Beam energy and 'unflatness' can be measured as with cFF beams from observed shifts in profile with changing beam energy. Normalising the inflection points of FFF beams to 55% results in an equivalent penumbra and field size measurement within 0.5 mm of conventional methods with the exception of 40 cm × 40 cm fields at a depth of 20 cm. New proposed methods are presented that make it possible to independently carry out set up and QA measurements on beam energy, flatness, symmetry and field size of an FFF beam without the need to reference to an equivalent flattened beam of the same energy. The methods proposed can also be used to carry out this QA for flattened beams, resulting in universal definitions and methods for MV beams. This is presented for beams produced by an Elekta linear accelerator, but is anticipated to also apply to other manufacturers' beams.

Benchmarking of a treatment planning system for spot scanning proton therapy: comparison and analysis of robustness to setup errors of photon IMRT and proton SFUD treatment plans of base of skull meningioma.

PURPOSE: Base of skull meningioma can be treated with both intensity modulated radiation therapy (IMRT) and spot scanned proton therapy (PT). One of the main benefits of PT is better sparing of organs at risk, but due to the physical and dosimetric characteristics of protons, spot scanned PT can be more sensitive to the uncertainties encountered in the treatment process compared with photon treatment. Therefore, robustness analysis should be part of a comprehensive comparison between these two treatment methods in order to quantify and understand the sensitivity of the treatment techniques to uncertainties. The aim of this work was to benchmark a spot scanning treatment planning system for planning of base of skull meningioma and to compare the created plans and analyze their robustness to setup errors against the IMRT technique. METHODS: Plans were produced for three base of skull meningioma cases: IMRT planned with a commercial TPS [Monaco (Elekta AB, Sweden)]; single field uniform dose (SFUD) spot scanning PT produced with an in-house TPS (PSI-plan); and SFUD spot scanning PT plan created with a commercial TPS [XiO (Elekta AB, Sweden)]. A tool for evaluating robustness to random setup errors was created and, for each plan, both a dosimetric evaluation and a robustness analysis to setup errors were performed. RESULTS: It was possible to create clinically acceptable treatment plans for spot scanning proton therapy of meningioma with a commercially available TPS. However, since each treatment planning system uses different methods, this comparison showed different dosimetric results as well as different sensitivities to setup uncertainties. The results confirmed the necessity of an analysis tool for assessing plan robustness to provide a fair comparison of photon and proton plans. CONCLUSIONS: Robustness analysis is a critical part of plan evaluation when comparing IMRT plans with spot scanned proton therapy plans.

A dosimetric characterization of a novel linear accelerator collimator.

PURPOSE: The aim of this work is to characterize a new linear accelerator collimator which contains a single pair of sculpted diaphragms mounted orthogonally to a 160 leaf multileaf collimator (MLC). The diaphragms have "thick" regions providing full attenuation and "thin" regions where attenuation is provided by both the leaves and the diaphragm. The leaves are mounted on a dynamic leaf guide allowing rapid leaf motion and leaf travel over 350 mm. METHODS: Dosimetric characterization, including assessment of leaf transmission, leaf tip transmission, penumbral width, was performed in a plotting tank. Head scatter factor was measured using a mini-phantom and the effect of leaf guide position on output was assessed using a water phantom. The tongue and groove effect was assessed using multiple exposures on radiochromic film. Leaf reproducibility was assessed from portal images of multiple abutting fields. RESULTS: The maximum transmission through the multileaf collimator is 0.44% at 6 MV and 0.52% at 10 MV. This reduced to 0.22% and 0.27%, respectively, when the beam passes through the dynamic leaf guide in addition to the MLC. The maximum transmission through the thick part of the diaphragm is 0.32% and 0.36% at 6 and 10 MV. The combination of leaf and diaphragm transmission ranges from 0.08% to 0.010% at 6 MV and 0.10% to 0.14% depending on whether the shielding is through the thick or thin part of the diaphragm. The off-axis intertip transmission for a zero leaf gap is 2.2% at 6 and 10 MV. The leaf tip penumbra for a 100 × 100 mm field ranges from 5.4 to 4.3 mm at 6 and 10 MV across the full range of leaf motion when measured in the AB direction, which reduces to 4.0-3.4 mm at 6 MV and 4.5-3.8 mm at 10 MV when measured in the GT direction. For a 50 × 50 mm field, the diaphragm penumbra ranges from 4.3 to 3.7 mm at 6 MV and 4.5 to 4.1 mm at 10 MV in the AB direction and 3.7 to 3.2 mm at 6 MV and 4.2 to 3.7 mm when measured in the GT direction. The tongue and groove effect observed from exposure of a radiochromic film to two abutting fields is an underdose of 25%. The head scatter factor at both 6 and 10 MV is similar to that from the MLCi2 collimator to within 0.8%. The uncertainty in the leaf position reproducibility is 0.05 mm (2σ). CONCLUSIONS: The Agility collimator is a low leakage, high definition collimator where both the MLC and the sculpted diaphragm have been optimized for dynamic treatments.

Small field dosimetric characterization of a new 160-leaf MLC.

The goal of this work was to perform a 6 MV small field characterization of the new Agility 160-leaf multi-leaf collimator (MLC) from Elekta. This included profile measurement analysis and central axis relative output measurements using various diode detectors and an air-core fiber optic scintillation dosimeter (FOD). Data was acquired at a depth of 10.0 cm for field sizes of 1.0, 0.9, 0.8, 0.7, 0.6 and 0.5 cm. Three experimental data sets, comprised of five readings, were made for both the relative output and profile measurements. Average detector-specific output ratios (OR[overline](f(clin))(det))) were calculated with respect to a field size of 3.0 cm and small field replacement correction factors (k(f(clin),f(msr))(Q(clin),Q(msr))) derived for the diodes using the scintillation dosimeter readings as the baseline. The standard experimental uncertainty on OR[overline](f(clin))(det)) was calculated at a 90% confidence interval and the coefficient of variation (CV) used to characterize the detector-specific measurement precision. The positional accuracy of the collimation system was also investigated by analyzing the repeated profile measurements and field width constancy investigated as a function of collimator rotation. For comparison the output and profile measurements were repeated using the Elekta 80-leaf MLCi2 on a beam matched linac at 6 MV. The measured OR[overline](f(clin))(det)) varied as a function of detector and MLC design. At the smallest field size the standard experimental uncertainty on OR[overline](f(clin))(det)) was consistent across all detectors at approximately 0.5% and 1.0% for Agility and MLCi2 collimators respectively. The CV associated with the FOD measurements were greater than that of the diodes but did not translate into increased measurement uncertainty. At the smallest field size, the diode detector correction factors were approximately 2% greater for MLCi2 than that required for the Agility. Profile data revealed the Agility MLC to have a greater positional reproducibility than both the MLCi2 and the linac diaphragms (jaws), as also reflected in the experimental uncertainties on OR[overline](f(clin))(det)). The relative output, profile widths and associated uncertainties were all found to differ between the two MLC systems investigated, as were the field size specific diode detector replacement correction factors. The data also clearly showed that the Agility 160-leaf MLC performs to a tighter positional tolerance than the MLCi2.

The structure of avian polyomavirus reveals variably sized capsids, non-conserved inter-capsomere interactions, and a possible location of the minor capsid protein VP4.

Avian polyomavirus (APV) causes a fatal, multi-organ disease among several bird species. Using cryogenic electron microscopy and other biochemical techniques, we investigated the structure of APV and compared it to that of mammalian polyomaviruses, particularly JC polyomavirus and simian virus 40. The structure of the pentameric major capsid protein (VP1) is mostly conserved; however, APV VP1 has a unique, truncated C-terminus that eliminates an intercapsomere-connecting ß-hairpin observed in other polyomaviruses. We postulate that the terminal ß-hairpin locks other polyomavirus capsids in a stable conformation and that absence of the hairpin leads to the observed capsid size variation in APV. Plug-like density features were observed at the base of the VP1 pentamers, consistent with the known location of minor capsid proteins VP2 and VP3. However, the plug density is more prominent in APV and may include VP4, a minor capsid protein unique to bird polyomaviruses.

Increased vascular permeability precedes cellular inflammation as asthma control deteriorates.

BACKGROUND: Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS) dose-reduction model. OBJECTIVES: To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back-titration. METHODS: Twenty mild-to-moderate persistent symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4 weeks of high-dose fluticasone propionate (1000 microg/day) to achieve symptom control. This was followed by dose reduction to half of the pre-study doses for 4-8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods. RESULTS: Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high-dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes. CONCLUSIONS: Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.

The matching of wedge transmission factors across six multi-energy linear accelerators.

Elekta Precise linear accelerators create a wedged isodose distribution using a single, fixed, motorized wedge with a nominal wedge angle of 60 degrees. Wedge angles of less than 60 degrees can be produced by varying the proportion of open and wedge monitor units for a given exposure. The fixed wedge can be replaced with a mobile wedge, the position of which can be moved in order to adjust the wedge transmission factor (WTF). Using the original fixed wedges installed in our fleet of six Elekta accelerators, we found a range of 4% in measured wedge transmission factor for 6 MV beams. Results are presented which demonstrate that by using the mobile wedge it is possible to match the wedge transmission factors to within 1% for the six linear accelerators over three energies.

A comparison of methods for determining genotypes at the tumour necrosis factor-alpha-308, interleukin (IL)-1beta+3953, IL-6 -174 and IL-10 -1082/-819/-592 polymorphic loci.

Induced heteroduplex genotyping (IHG) is one of many methods that can be used to determine single nucleotide polymorphisms (SNPs). It is relatively new in comparison to other polymerase chain reaction (PCR)-based techniques. The aim of this study was to compare the results of genotyping using IHG with the results of genotyping using either polymerase chain reaction-sequence-specific primers (PCR-SSP) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for SNPs in the tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10 genes. Ninety patients who consented to participate in the study had their genotypes determined by IHG and either PCR-SSP (TNF-alpha-308 and IL-10 -1082/-819/-592) or PCR-RFLP (IL-1beta +3953 and IL-6 -174). Results for each locus were compared between techniques by calculating the Kappa statistic as a measure of agreement. The IHG and more traditional genotyping methods produced very similar results at all loci. The Kappa statistics for each locus were as follows: TNF-alpha -308, K = 0.727; IL-1beta +3953, K = 0.886; IL-6 -174, K = 0.909; IL-10 -1082, K = 0.876; IL-10 -592, K = 0.920. IHG is a valid method for the determination of genotypes at the loci examined in this study and produces comparable results to those of more traditional methods of genotyping.

Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis.

BACKGROUND: We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate-to-severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from children (n = 53) at baseline and at the end of an 8-week supplementation period during which they received a probiotic (Lactobacillus fermentum PCCtrade mark) (n = 26) or a placebo (n = 27). A further sample was collected at 16 weeks (8 weeks after ceasing the supplement). Cytokine (IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNF-alpha) responses to allergens (egg ovalbumin (OVA), beta lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT)), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus (HKLB)), heat-killed Staphylococcus aureus (HKSA), Staphylococcus aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared. RESULTS: The administration of probiotics was associated with a significant increase in T-helper type 1(Th1-type) cytokine IFN-gamma responses to PHA and SEB at the end of the supplementation period (week 8: P = 0.004 and 0.046) as well as 8 weeks after ceasing supplementation (week 16: P = 0.005 and 0.021) relative to baseline levels of response. No significant changes were seen in the placebo group. The increase in IFN-gamma responses to SEB was directly proportional to the decrease in the severity of AD (r = -0.445, P = 0.026) over the intervention period. At the end of the supplementation period (week 8) children receiving probiotics showed significantly higher TNF-alpha responses to HKLB (P = 0.018) and HKSA (P = 0.011) but this was no longer evident when supplementation ceased (week 16). Although IL-13 responses to OVA were significantly reduced in children receiving probiotics after 8 weeks (P = 0.008), there were no other effects on allergen-specific responses, and this effect was not sustained after ceasing supplementation (week 16). There were no effects on vaccine-specific responses, or on responses to any of the stimuli assessed. CONCLUSION: The improvement in AD severity with probiotic treatment was associated with significant increases in the capacity for Th1 IFN-gamma responses and altered responses to skin and enteric flora. This effect was still evident 2 months after the supplementation was ceased. The lack of consistent effects on allergen-specific responses suggests that the effects of probiotics may be mediated through other independent pathways, which need to be explored further.

Mutational screening of the CD40 ligand (CD40L) gene in patients with X linked hyper-IgM syndrome (XHIM) and determination of carrier status in female relatives.

AIMS: To analyse the gene encoding the CD40 ligand (CD40L) in 11 Australian patients from 10 unrelated families with the X linked hyper-IgM (XHIM) phenotype. METHODS: The CD40L gene was screened for mutations using direct sequencing of exon specific polymerase chain reaction (PCR) products. RESULTS: Ten mutations were identified. Seven of these mutations have been described previously, whereas three new nonsense mutations were identified, namely: E108X (c.322G>T), G167X (c.499G>T), and C218X (c.654C>A). Ten of 15 female family members revealed both a mutated allele and a normal allele, indicating that they were XHIM carriers. CONCLUSION: The 10 mutations (including the three new ones) identified in this study reflect the heterogeneity of the CD40L gene, and indicate the need for accurate and reliable molecular testing of those patients suspected of XHIM.

Multi-isocenter stereotactic radiotherapy: implications for target dose distributions of systematic and random localization errors.

PURPOSE: This investigation examined the effect of alignment and localization errors on dose distributions in stereotactic radiotherapy (SRT) with arced circular fields. In particular, it was desired to determine the effect of systematic and random localization errors on multi-isocenter treatments. METHODS AND MATERIALS: A research version of the FastPlan system from Surgical Navigation Technologies was used to generate a series of SRT plans of varying complexity. These plans were used to examine the influence of random setup errors by recalculating dose distributions with successive setup errors convolved into the off-axis ratio data tables used in the dose calculation. The influence of systematic errors was investigated by displacing isocenters from their planned positions. RESULTS: For single-isocenter plans, it is found that the influences of setup error are strongly dependent on the size of the target volume, with minimum doses decreasing most significantly with increasing random and systematic alignment error. For multi-isocenter plans, similar variations in target dose are encountered, with this result benefiting from the conventional method of prescribing to a lower isodose value for multi-isocenter treatments relative to single-isocenter treatments. CONCLUSIONS: It is recommended that the systematic errors associated with target localization in SRT be tracked via a thorough quality assurance program, and that random setup errors be minimized by use of a sufficiently robust relocation system. These errors should also be accounted for by incorporating corrections into the treatment planning algorithm or, alternatively, by inclusion of sufficient margins in target definition.

The application of a PCR technique for the detection of immunoglobulin heavy chain gene rearrangements in fresh or paraffin-embedded skin tissue.

Although detection of a clonal sequence of the heavy chain gene of immunoglobulin by the polymerase chain reaction (PCR) is frequently used to assess lymphoid infiltrates in skin biopsy specimens, there are no data on the sensitivity and specificity of this test in detecting clonal B cell populations. Having refined a PCR technique for the detection of immunoglobulin heavy chain (IgH) gene rearrangement in both fresh and formalin-fixed, paraffin-embedded skin samples, we undertook to define the role of this assay in the diagnostic setting. Thirty-one cases of cutaneous B cell lymphoma (CBCL), 19 cases of B cell pseudolymphoma (lymphocytoma cutis), 34 cases of benign lymphocytic infiltrates of the skin and one case of cutaneous T cell lymphoma (CTCL) were studied using the polymerase chain reaction assay. All biopsies were formalin-fixed, paraffin-embedded skin sections apart from 13 of the 31 CBCL specimens which were fresh skin specimens. DNA from the framework region 3 (FR3) sequence of the IgH genes was amplified to ascertain the presence of a clonal IgH gene rearrangement. The findings were correlated with histological and immunophenotyping results on all samples. The assay performed with 73% sensitivity and 100% specificity, comparable to results obtained examining fresh lymphoid tissue specimens from patients with B cell tumours. The results indicate that this technique is a useful tool in the work up of suspected CBCL and in differentiating between CBCL and mixed lymphocytic infiltrates, a clearly important distinction with regards to prognosis and treatment.

Isocentric treatment of inclined volumes planned using coronal sections.

The treatment parameters necessary for the isocentric treatment of an inclined volume have to be determined either analytically or through simulation. The derivation of the treatment parameters for the treatment of a transverse plane has been described previously. This work describes the derivation of the treatment parameters necessary for the isocentric treatment of an inclined volume that has been planned from an angled coronal section. Ways of implementing the system in the clinic are described.

Development and validation of a screening test for 12 common mutations of the cystic fibrosis CFTR gene.

The results obtained using deoxyribonucleic acid (DNA) amplification-based tests must be accurate and reproducible. One such test that simultaneously detects any of 12 of the most common mutations of the cystic fibrosis transmembrane conductance regulator gene is presented in this report. An investigation was conducted into how changes of primer, DNA template and Taq DNA polymerase concentrations and of polymerase chain reaction annealing temperatures affect the test. A total of 383 DNA samples obtained from different laboratories was then examined. The preliminary studies defined the conditions under which accurate results are obtained even if the test is performed under suboptimal conditions. Subsequently, 377 (98.4%) of the DNA samples analysed were in full agreement with DNA typing results derived by other methods. The remaining 1.6% of samples were not mistyped, rather they were not scored owing to failure to detect control DNA sequences. These were also archival DNA preparations rather than freshly prepared samples from venous blood. Careful primer design and optimization of reaction conditions are important in the development of multiplex deoxyribonucleic acid amplification-based diagnostic tests. Providing the recommended protocols are followed, the test described here is simple to carry out, gives accurate results and works well if performed within defined operational windows for each reaction variable.

Clinical and upper gastrointestinal motility features in systemic sclerosis and related disorders.

OBJECTIVE: The aim of this study was to characterize the clinical and motility findings in 62 patients with systemic sclerosis or related disorders referred for evaluation of upper gastrointestinal (GI) symptoms. METHODS: Methods included retrospective clinical record review and quantitation of esophageal, LES antral, and duodenal motility (3 h fasting, 2 h fed) were compared with results of 10 symptomatic patients with normal gastric emptying. RESULTS: A total of 46 patients had systemic sclerosis, eight mixed connective tissue disease, and eight polymyositis-systemic sclerosis overlap; systemic manifestations were almost invariably present. GI symptoms were: heartburn (77%), nausea/vomiting (58%), dysphagia (61%), diarrhea (53%), constipation (31%), and fecal incontinence (13%). Anatomical studies showed esophageal erosions or GERD (53%), aperistalsis (34%), stricture (29%), and Barrett's metaplasia (16%); megaduodenum, small bowel dilation, or diverticulae (42%); and pneumatosis intestinalis (8%). A total of 36 patients underwent esophageal and 26 esophagogastrointestinal manometry. Postprandial antral motility index was abnormal in 22 of 26; amplitudes and frequency in the antrum (34 +/- 3 mm Hg and 0.6 +/- 0.1/min, respectively) and duodenum (7.3 +/- 0.9 mm Hg and 1.8 +/- 0.5/min) were significantly lower than controls (p < 0.05). CONCLUSION: In patients with GI symptoms associated with systemic sclerosis and related disorders, the amplitude and frequency of intestinal contractions are typically <10 mm Hg and <2/min. Antral amplitude is low (<40 mm Hg) when antral hypomotility is observed.

Allergy to antibiotics: T-cell recognition of amoxicillin is HLA-DR restricted and does not require antigen processing.

Allergic immune responses are initiated and maintained by T cells that recognize peptidic fragments of allergens in the context of major histocompatibility complex (MHC) class II molecules. An anomaly of this model exists in the T-cell response to haptens. Haptens are nonpeptide antigens that alone are too small to provoke an immune response. Nevertheless, T-cell responses to haptenic allergens clearly occur and are critically involved in allergic immune responses to drugs such as penicillin. Although the mechanisms that generate T-cell epitopes from protein antigens are well understood, haptens create T-cell epitopes by alternative mechanisms. These may include binding of haptens directly to preformed MHC-peptide complexes on the cell surface, or indirect association with MHC molecules after conjugation with self cell surface or serum proteins that are then processed and presented as haptenated peptide antigens. Which of these unorthodox mechanisms of epitope generation is dominant in allergy to penicillin is unknown. This study aims to determine the nature of the epitopes recognized by amoxicillin-specific T cells from allergic donors, and to clarify whether T-cell responses to penicillin antibiotics are MHC-restricted and require haptenated self proteins to be processed before recognition. Human T-cell lines specific for amoxicillin were raised and used in assays with processing-disabled and MHC-class II-typed antigen-presenting cells to determine the MHC restriction and processing requirements of T cells recognizing amoxicillin. Fixation of antigen-presenting cells with paraformaldehyde, before or after pulsing with amoxicillin, established that T cells can recognize amoxicillin-containing epitopes with a similar efficiency irrespective of whether the antigenic conjugate has been internalized and processed. These results suggest that amoxicillin can bind directly to performed MHC-peptide complexes and need not necessarily involve the processing of haptenated self carrier proteins before recognition of the conjugate by amoxicillin-specific T cells.

Implementation of the Varian EDW into a commercial RTP system.

An enhanced dynamic wedge system (EDW) has been installed onto our Clinac 600C (6 MV) linear accelerator. This paper addresses and describes the measurements taken and subsequent analysis required to enable the planning of EDW using our commercial radiotherapy treatment planning (RTP) system. This implementation into a 'closed' commercial system is performed without the use of specialized measurement equipment or the necessity of introducing new calculation algorithms and is therefore independent of the RTP manufacturer. We consider that, for incorporation of techniques such as EDW into routine clinical use, a simple verifiable method of inclusion into the RTP system must be achieved. This paper also presents a methodology for quality control of dynamic fields chosen for clinical use which is quick and easy to use by virtue of its use of film dosimetry. We present the method of film calibration used in this work.