Abstract Purpose Intraoperative radiation therapy (IORT) as a form of accelerated partial breast irradiation (APBI) is controversial given the limited evidence to support its efficacy. However, it ...remains an attractive option for low-risk patients with ductal carcinoma in situ (DCIS), who derive a small absolute benefit in local control with standard whole breast irradiation (WBI). We examine how the American Society for Therapeutic Radiation Oncology (ASTRO) APBI consensus guidelines (CG) may be applied to the preoperative selection of patients with DCIS for IORT and determine treatment outcomes by CG group. Methods and Materials We identified patients with biopsy-proven pure DCIS enrolled in an institutional prospective registry IORT database using the Zeiss Intrabeam® device between September 2013 and February 2017. Based on available preoperative clinicopathologic information, patients were deemed suitable, cautionary, or unsuitable for IORT according to the ASTRO CG. Change in CG group based on final pathologic diagnosis was determined, and additional therapy was recommended for unsuitable patients. Outcome in terms of ipsilateral breast tumor recurrence was determined. Results A total of 61 DCIS lesions in 60 patients were treated with IORT. Preoperatively, 21 patients (35%) were suitable and 36 (59%) were cautionary. Four (6%) were unsuitable because of lesion size but declined WBI. Final pathologic diagnosis changed the CG grouping of 10 patients (16%) because of either occult high-grade disease in 2 (3%) or close/positive margins in 8 (13%). Ultimately 12 patients total were considered unsuitable, of whom 8 (66%) accepted additional WBI after IORT. At a median follow-up of 2.2 years, ipsilateral breast tumor recurrence was identified among 2 suitable, 1 cautionary, and no unsuitable patients. Conclusion Further investigation is necessary to refine selection of patients with DCIS who may be optimally treated with IORT alone. High acceptance of additional therapy among unsuitable patients resulted in excellent outcomes. The use of biomarkers in addition to traditional clinical and pathologic factors may help to better select patients for IORT.
Surgical pulmonary valve replacement (PVR) in previously repaired tetralogy of Fallot (TOF) is frequently required. There are few data in large series of patients with long-term follow-up. Our aim ...was to review our 40-year experience with PVR after TOF repair and to evaluate prognostic factors for reintervention and death. Between 1973 and 2012, 278 patients with repaired TOF (53% men; 31.4 ± 16.4 years) underwent first PVR 24 ± 13 years after TOF repair. Three or more previous operations were performed in 17% of the patients, and 42% were in New York Heart Association (NYHA) class III/IV. PVR types included porcine (n = 211), pericardial (n = 37), homograft (n = 27), and mechanical (n = 3). Early mortality was 1.4%. Mean follow-up was 7.3 ± 6.8 years (maximum, 34 years). Overall survival at 5, 10, and 15 years was 93%, 83%, and 80% compared with 99%, 97%, and 95% in a gender- and age-matched US population, p <0.001. Independent risk factors for death were older age at complete repair (hazards ratio HR 1.2, p = 0.012), ≥3 previous cardiac operations (HR 1.9, p = 0.019), NYHA class III/IV at PVR (HR 2.7, p = 0.019), and large body surface area at PVR (HR 1.9, p <0.001). Reintervention after initial PVR occurred in 25 patients. Overall 5, 10, and 15 years freedom from pulmonary valve reintervention was 97%, 85%, and 75%, respectively. Multivariate analysis demonstrated older age at PVR to be protective from reintervention (HR 0.7, p <0.001). In conclusion, PVR is a safe operation with a low rate of reintervention in repaired TOF. The total number of cardiac operations, surgical timing, and the NYHA classification before PVR are important prognostic factors.
• MSDD is novel disinfestation technique utilizing pressure change, modification of atmosphere and ethanol. • 90
min MSDD treatments with 371
mg
L
−1 ethanol control all lifestages of longtailed ...mealybug. • 90
min MSDD treatments with 371
mg
L
−1 did not significantly reduce fruit quality.
Metabolic stress disinfection and disinfestation (MSDD) is a potential quarantine treatment in which a combination of cycles of rapid decompression and compression are followed by exposure to ethanol vapour under decompression. The response of ‘Hass’ avocado (
Persea americana Mill., cv. Hass) to MSDD treatment for control of longtailed mealybug (
Pseudococcus longispinus) was investigated. The best treatment for the most resistant life stage (2nd/3rd instars) was 90-min MSDD treatment with 371
mg
L
−1 ethanol. Early and late season ‘Hass’ avocados were subjected to MSDD treatments (with 371
mg
L
−1 ethanol), or in air (control). Following the treatments, early season fruit were ripened at 20
°C and 25
°C. Half of the late season fruit were ripened at either 20
°C or 25
°C, and the remainder were stored at 5.5
°C for 6 weeks, then ripened at 20
°C. There were no significant difference in quality and rot incidence between non-treated controls and MSDD-treated fruit. The main disorders found were stem-end and body rots, vascular browning and flesh greying for the stored fruit. There were also no significant differences in fruit respiration rate or ethylene production. Thus, MSDD was shown to be a potentially ‘soft’ disinfestation treatment for surface pests of avocado.
Summary
Background Scleroderma, or systemic sclerosis, is characterized by aberrations of extracellular matrix deposition. These changes parallel early stages of wound healing when increased ...deposition of hyaluronan (HA) and collagen occur. Both processes result ultimately in the formation of fibrotic scar tissue. Activities of HA synthase and hyaluronidase, the enzymes that synthesize and degrade HA, are critical in HA turnover. Both become elevated whenever increased matrix deposition occurs. HA deposition occurs early in wound healing, and increases are documented in the circulation of scleroderma patients. We postulated that elevated HA and hyaluronidase may both be indicators of early‐stage disease in scleroderma, in parallel with early changes observed in wound healing. In an attempt to reduce HA accumulation and the associated fibrosis in scleroderma tissues, topical and intravenous hyaluronidase administrations have been used in the past as treatment modalities, with occasional success. This also suggested that hyaluronidase enzyme activity is involved in the disease process. It is now recognized that the hyaluronidases constitute an enzyme family. The somatic hyaluronidase Hyal‐1 is the only activity present in human serum.
Objectives To determine levels of HA and Hyal‐1 in the sera of scleroderma patients at various stages of their disease.
Methods Levels of HA and Hyal‐1 activity were determined in 25 scleroderma patients. Subjects were separated into two groups, those in the early stage with duration of disease of 2 years or less, and late‐stage patients with disease duration of more than 2 years.
Results In early‐stage scleroderma, levels of HA were elevated significantly, as predicted, in comparison with late‐stage patients and controls. Late‐stage levels of HA were comparable with those found in control sera. By contrast, levels of Hyal‐1 activity were normal in early‐stage patients, similar to those in controls, but were decreased in late‐stage patients, falling even below those of controls.
Conclusions We have confirmed that circulating levels of HA are elevated in scleroderma, but show for the first time that such elevations occur predominantly in early‐stage disease. Patients with late‐stage disease have decreased serum Hyal‐1 activity, perhaps reflecting decreased levels of HA turnover. This study also represents the first time that hyaluronidase activity levels have been determined in scleroderma patients.
Oligonucleotides labeled with hexachlorofluorescein (hex) have enabled the interaction of the restriction endonuclease EcoRV with DNA to be evaluated using fluorescence anisotropy. The sensitivity of ...hex allowed measurements at oligonucleotide concentrations as low as 1 nM, enabling K D values in the low nanomolar range to be measured. Both direct titration, i.e., addition of increasing amounts of the endonuclease to hex-labeled oligonucleotides, and displacement titration, i.e., addition of unlabeled oligonucleotide to preformed hex-oligonucleotide/EcoRV endonuclease complexes, have been used for K D determination. Displacement titration is the method of choice; artifacts due to any direct interaction of the enzyme with the dye are eliminated, and higher fluorescent-labeled oligonucleotide concentrations may be used, improving signal-to-noise ratio. Using this approach (with three different oligonucleotides) we found that the EcoRV restriction endonuclease showed a preference of between 1.5 and 6.5 for its GATATC target sequence at pH 7.5 and 100 mM NaCl, when the divalent cation Ca2+ is absent. As expected, both the presence of Ca2+ and a decrease in pH value stimulated the binding of specific sequences but had much less effect on nonspecific ones.
Tumour necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory agent produced primarily by activated monocytes and macrophages. TNF-alpha is synthesized as a precursor protein of M(r) 26,000 ...(26K) which is processed to a secreted 17K mature form by cleavage of an Ala-Val bond between residues 76-77. The enzyme(s) responsible for processing pro-TNF-alpha has yet to be identified. Here, we describe the capacity of a metalloproteinase inhibitor, GI 129471, to block TNF-alpha secretion both in vitro and in vivo. The inhibition is specific to TNF-alpha; the production of other secreted cytokines, such as the interleukins IL-1 beta, IL-2, or IL-6, is not inhibited. The mechanism of inhibition occurs at a post-translational step in TNF-alpha production. Our data suggest that TNF-alpha processing is mediated by a unique Zn2+ endopeptidase which is inhibited by GI 129471 and would represent a novel target for therapeutic intervention in TNF-alpha associated pathologies.
To describe changes in aged care residents' dependency over a 20-year period.
All residents in 1988, 1993, 1998, and 2008 were assessed using the same 23-item functional ability survey.
Residential ...aged care facilities in Auckland, New Zealand.
In 1988 there were 7516 participants (99% response rate), 6972 in 1993 (85% response rate), 5056 in 1998 (65% response rate), and 6828 in 2008 (89% response rate). Data were weighted to accommodate variation in response.
A composite dependency score with 5 ordinal levels was derived from a census-type survey reporting mobility, activities of daily living ability, continence, and cognitive function.
The proportion of "apparently independent" residents decreased from 18% in 1988 to 9% in 1993, 5% in 1998, and 4% in 2008, whereas those "highly dependent" increased from 16% in 1988, to 18% in 1993, 19% in 1998, to 21% in 2008. All functional indicators demonstrated increased dependency over the 20-year period (P < .0001). However, between 1998 and 2008 there were significant increases in dependency for continence, mobility, self-care, and orientation, but no significant changes in memory and behavior.
The increased dependency over 20 years directly affects care requirements for this population.
Connectivity is an important consideration in conservation, but is rarely quantified when assessing marine reserve performance. Mangrove–reef connectivity is known to enhance reserve effectiveness ...when habitats are close together (<250 m apart). Coral reefs are, however, often farther from mangroves, making it difficult to integrate mangrove–reef connectivity into conservation more widely. To determine if connectivity affects reserve performance beyond 250 m, we examined effects on reef fish in Hervey Bay, Queensland, Australia. Reserves affected fish assemblages and enhanced the abundances of harvested species and key functional groups on reefs within 500 m of mangroves (about 10 times greater inside reserves), but not on isolated reefs. Connectivity can affect reserve performance over broader distances than previously shown. We suggest that connectivity effects on inshore reef fish may simply be amplified on reefs located closest to adjacent mangroves, provided those reefs are within the migratory capabilities of fish. Mangrove–reef connectivity should be viewed as an important conservation target and may be broadly incorporated into reserve design by prioritizing the protection of seascapes where mangroves and reefs are closest.
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