Do contaminants compromise the use of recycled nutrients in organic agriculture? A review and synthesis of current knowledge on contaminant concentrations, fate in the environment and risk assessment.

Use of nutrients recycled from societal waste streams in agriculture is part of the circular economy, and in line with organic farming principles. Nevertheless, diverse contaminants in waste streams create doubts among organic farmers about potential risks for soil health. Here, we gather the current knowledge on contaminant levels in waste streams and recycled nutrient sources, and discuss associated risks. For potentially toxic elements (PTEs), the input of zinc (Zn) and copper (Cu) from mineral feed supplements remains of concern, while concentrations of PTEs in many waste streams have decreased substantially in Europe. The same applies to organic contaminants, although new chemical groups such as flame retardants are of emerging concern and globally contamination levels differ strongly. Compared to inorganic fertilizers, application of organic fertilizers derived from human or animal feces is associated with an increased risk for environmental dissemination of antibiotic resistance. The risk depends on the quality of the organic fertilizers, which varies between geographical regions, but farmland application of sewage sludge appears to be a safe practice as shown by some studies (e.g. from Sweden). Microplastic concentrations in agricultural soils show a wide spread and our understanding of its toxicity is limited, hampering a sound risk assessment. Methods for assessing public health risks for organic contaminants must include emerging contaminants and potential interactions of multiple compounds. Evidence from long-term field experiments suggests that soils may be more resilient and capable to degrade or stabilize pollutants than often assumed. In view of the need to source nutrients for expanding areas under organic farming, we discuss inputs originating from conventional farms vs. non-agricultural (i.e. societal) inputs. Closing nutrient cycles between agriculture and society is feasible in many cases, without being compromised by contaminants, and should be enhanced, aided by improved source control, waste treatment and sound risk assessments.

Hexaaminobenzene derivatives: synthesis and unusual oxidation behavior.

The syntheses and the electrochemical behavior of the monomeric peralkylated hexaamino(1,3)metacyclophane 4, the dimeric dodecaamino(1,3)cyclophane 5a, and the dodecaamino(1,3,5)cyclophane 6 are described. Electrochemical measurements show that the hexaaminobenzene units in 4 and 5a undergo an unusually slow two-electron transfer attributed to the deformation of the rings into bis-cyanine cations when oxidized to the respective dication. Further oxidations to tri-, tetra-, and hexacationic units occur at more positive potentials. In the dimeric structures, no interaction between the rings can be seen in the (1,3)cyclophane, but strong interaction for the (1,3,5)cyclophane is observed.

Novoste Beta-Cath integrity test with the active source train.

Intravascular brachytherapy (IVB) to prevent restenosis is currently being performed using several different commercial delivery devices. The Novoste Beta-Cath system uses a source train of 90Sr/90Y pure beta emitters and two gold radiopaque markers. A nonactive transfer device with dummy sources is also supplied to test the delivery catheter. We have developed an alternate procedure using an acrylic shield to test both the active transfer device and delivery catheter prior to patient treatment.

Gamma knife radiosurgery for trigeminal neuralgia: the initial experience of The Barrow Neurological Institute.

PURPOSE: To assess the efficacy and complications of Gamma Knife radiosurgery for trigeminal neuralgia. METHODS AND MATERIALS: The Barrow Neurological Institute (BNI) Gamma Knife facility has been operational since March 17, 1997. A total of 557 patients have been treated, 89 for trigeminal neuralgia (TN). This report includes the first 54 TN patients with follow-up exceeding 3 months. Patients were treated with Gamma Knife stereotactic radiosurgery (RS) in uniform fashion according to two sequential protocols. The first 41 patients received 35 Gy prescribed to the 50% isodose via a single 4-mm isocenter targeting the ipsilateral trigeminal nerve adjacent to the pons. The dose was increased to 40 Gy for the remaining 13 patients; however, the other parameters were unvaried. Outcome was evaluated by each patient using a standardized questionnaire. Pain before and after RS was scored as level I-IV per our newly-developed BNI pain intensity scoring criteria (I: no pain; II: occasional pain, not requiring medication; III: some pain, controlled with medication; IV: some pain, not controlled with medication; V: severe pain/no pain relief). Complications, limited to mild facial numbness, were similarly graded by a BNI scoring system. RESULTS: Among our 54 TN patients, 52 experienced pain relief, BNI score I in 19 (35%), II in 3 (6%), III in 26 (48%), and IV in 4 (7%). Two patients (4%) reported no relief (BNI score V). Median follow-up was 12 months (range 3-28). Median time to onset of pain relief was 15 days (range 0-192), and to maximal relief 63 days (range 0-253). Seventeen (31%) noted immediate improvement (

Brachytherapy in the treatment of thoracic tumors. Lung and esophageal.

Brachytherapy for carcinoma of the lung is most often performed using HDR remote afterloading equipment which delivers the treatment within the tracheal-bronchial tree in an outpatient setting. It provides excellent palliation, rapidly, and can also be selectively used with for curative intent. Permanent implantation using iodine seeds at the time of surgery improves the local control rate for those patients. Esophageal brachytherapy is performed as an intraluminal technique, most often using HDR equipment in an outpatient setting, and is used for palliation as a single modality and as a boost following chemo/radiation for curative patients. In this latter situation, the more aggressive therapy provides significantly better palliation than is possible with single-modality therapy.

Pulsed low dose rate brachytherapy for uterine cervix carcinoma.

PURPOSE: To analyze the outcome and complication rates for patients treated with curative-intent pulsed low dose rate (PLDR) brachytherapy and external beam radiation therapy (EBRT) for uterine cervical carcinoma. METHODS AND MATERIALS: Fifty-two patients have been treated, of whom 6 were excluded from analysis due to limited follow-up. Six patients were stage Ib, 3 were IIa, 11 IIb, 3 IIIa, 14 IIIb, 1 IVa, and 9 were treated for local recurrences following primary surgery for stage Ib disease. Thirty-six patients had squamous cell carcinoma, 8 adenocarcinoma, 1 adenosquamous, and 1 carcinosarcoma. Thirty-one had a staging laparotomy prior to radiation therapy. Brachytherapy was interstitial in 18 patients, and intracavity in 28. The median EBRT central pelvis dose was 45 Gy in 25 fractions. Median total prescribed doses (EBRT plus PLDR) were 75.8 Gy to the implant volume with interstitial, and 84.1 Gy to the A points with intracavitary, at a median dose rate of 0.55 Gy per pulse per hour. Six patients had laparotomy-documented periaortic node involvement, and received EBRT to this site, 45 Gy in 25 fractions. Thirty patients received concomitant weekly cisplatin chemotherapy (40 mg/m2). RESULTS: With a median follow-up of 25 months (range 6 to 55 months) actuarial 4-year disease-free survival (DFS) rates are 66% for the entire group: stage Ib 100%, stage II 69%, stage III/IVa 68%, and 43% in patients treated for recurrences after surgery for initial stage Ib disease. Pelvic nodes contained tumor in 13 of the 31 patients (41.9%) who underwent laparotomy, as did periaortic nodes in 6 (19.4%). Patients with negative pelvic nodes had a 4-year actuarial DFS of 75% versus 59% with positive pelvic (and negative periaortic) nodes, and 50% with positive periaortic nodes. Using the RTOG late radiation morbidity scoring criteria, there were no grade V complications. Grade IV complications occurred in 2 patients (4.3%). One was a rectovaginal fistula and the other a vesicovaginal fistula, each occurring subsequent to a biopsy revealing benign tissue. One patient (2.2%) had a grade III complication (frequent hematuria), and 5 (10.9%) had grade II complications. CONCLUSIONS: PLDR brachytherapy is a safe and effective brachytherapy method in the treatment of cervix carcinoma. It combines the physics benefits of dose optimization and the radiobiologic advantages of low dose rate brachytherapy. It eliminates radiation exposure to staff and visitors as well as the need for a source inventory. Although further follow-up will be required, it appears to provide outcome which compares favorably to other methods of brachytherapy delivery, and results in a low rate of complications.

The American Brachytherapy Society perspective on intravascular brachytherapy.

BACKGROUND: Recent clinical studies indicate that intravascular brachytherapy (IVB) can reduce the rate of restenosis substantially after angioplasty procedures. However, no clinical guidelines exist for optimal therapy. METHODS: The members of the IVB Subcommittee of the American Brachytherapy Society (ABS) identified the areas of consensus and controversies in IVB to issue the ABS perspective on IVB, based on analysis of published reports and the clinical experience of the members in brachytherapy. RESULTS: IVB is still experimental. The long-term efficacy, toxicity, the target tissue, and dose required for IVB are not established. The ABS recommends that IVB procedures must be performed, with careful attention to radiation-related issues, in the context of controlled multidisciplinary clinical trials with the approval of the institutional review board, the Nuclear Regulatory Commission, the Food and Drug Administration, and under an Investigational Device Exemption. The therapeutic radiologist, with a qualified radiation physicist, is responsible for dose prescription and delivery and needs to be present during the IVB procedure as part of this multidisciplinary team. The long-term outcome from these studies should be reviewed critically and published in peer-reviewed journals. The ABS endorsed the dosimetric guidelines of the American Association of Physicists in Medicine Task Group 60 (AAPM TG-60) report. The ABS recommends that dose specification be defined clearly; to allow comparisons between studies, the dose should be prescribed at 2 mm from the source for intracoronary brachytherapy and at an average luminal radius of +2 mm for peripheral vascular brachytherapy. The prescription doses at the above point is generally in the 12-18 Gy range. Comprehensive procedures for quality assurance, radiation protection, and emergencies should be in place before initiating an IVB program. Higher energy beta sources, lower energy gamma sources, dose-volume histograms, and correlation of three-dimensional reconstructions of delivered dose with patterns of failure are areas for further research. CONCLUSION: The ABS perspective on IVB is presented to assist the interventional team in developing protocols for the use of IVB in the prevention of restenosis. Long-term outcome data with a standardized reporting system are needed to establish the role of brachytherapy in preventing vascular restenosis. Endovascular brachytherapy is a new and evolving modality, and these recommendations are subject to modifications as new data become available.

Gamma knife radiosurgery for trigeminal neuralgia: experience at the Barrow Neurological Institute.

Forty-three patients with trigeminal neuralgia (TN) unresponsive to pharmacologic treatment and/or prior invasive procedures underwent stereotactic radiosurgery with the Gamma Knife (GK). Outcome was evaluated by a standardized questionnaire mailed to each patient. The mean follow-up was 9 months. Fifteen patients (35%) reported no trigeminal pain and were no longer taking medication. Three patients (7%) experienced occasional pain, but were no longer taking medication. In 15 patients (35%), pain improved and was adequately controlled by medication, often in lower dosages than preoperatively. Pain was reduced in 9 patients (21%), but their symptoms were still inadequately controlled by drug therapy, and 1 patient (2%) reported no pain relief after treatment. Three patients (7%) described new facial numbness, but in none was this bothersome. GK radiosurgery for TN appears to have minimal morbidity, although the success rate may be slightly lower than that of other operative procedures. More patients and longer follow-up are needed before drawing final conclusions regarding efficacy and complications.

American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA.

INTRODUCTION: There is wide variation in the indications, treatment regimens, and dosimetry for brachytherapy in the treatment of cancer of the esophagus. No guidelines for optimal therapy currently exist. METHODS AND MATERIALS: Utilizing published reports and clinical experience, representatives of the Clinical Research Committee of the American Brachytherapy Society (ABS) formulated guidelines for brachytherapy in esophageal cancer. RESULTS: Recommendations were made for brachytherapy in the definitive and palliative treatment of esophageal cancer. (A) Definitive treatment: Good candidates for brachytherapy include patients with unifocal thoracic adeno- or squamous cancers < or = 10 cm in length, with no evidence of intra-abdominal or metastatic disease. Contraindications include tracheal or bronchial involvement, cervical esophagus location, or stenosis that cannot be bypassed. The esophageal brachytherapy applicator should have an external diameter of 6-10 mm. If 5FU-based chemotherapy and 45-50-Gy external beam are used, recommended brachytherapy is either: (i) HDR 10 Gy in two weekly fractions of 5 Gy each; or (ii) LDR 20 Gy in a single course at 0.4-1 Gy/hr. All doses are specified 1 cm from the midsource or mid-dwell position. Brachytherapy should follow external beam radiation therapy and should not be given concurrently with chemotherapy. (B) Palliative treatment: Patients with adeno- or squamous cancers of the thoracic esophagus with distant metastases or unresectable local disease progression/recurrence after definitive radiation treatment should be considered for brachytherapy with palliative intent. After limited dose (30 Gy) EBRT, the recommended brachytherapy is either: (i) HDR 10-14 Gy in one or two fractions; or (ii) LDR 20-25 Gy in a single course at 0.4-1 Gy/hr. The need for external beam radiation in newly diagnosed patients with a life expectancy of less than 3 months is controversial. In these cases, HDR of 15-20 Gy in two to four fractions or LDR of 25-40 Gy at 0.4-1 Gy/hr may be of benefit. CONCLUSION: ABS guidelines for esophageal brachytherapy now exist and will be updated by the ABS in the future, as clinical data using more uniform treatment techniques becomes available.

Angiographic follow-up in 37 patients after radiosurgery for cerebral arteriovenous malformations as part of a multimodality treatment approach.

Modified Linac radiosurgery was utilized at our institution between 1990 and 1995 in 54 patients with cerebral arteriovenous malformations (AVMs) as part of a multimodality therapeutic approach. Most patients also underwent surgery and embolization of the AVMs prior to radiosurgery. The goal of the adjunctive radiosurgical treatment was the complete angiographic obliteration of the deep residual AVM after subtotal embolization and resection. Radiosurgery was used as the primary treatment of some small deep AVMs which were judged to have a high risk of morbidity if approached surgically. Of the 54 patients, 37 have had follow-up angiograms available for review. The median time interval between radiosurgery and the most recent angiogram was 22 months (range 5-66 months). This is a retrospective report on the angiographic follow-up available on this selected group of patients with difficult AVMs. All angiograms were evaluated for the presence of residual AVM. If any residual AVM was present, a decrease in size of more than 50% was noted as significant. The hospital and office charts of all patients were reviewed and the patients and families were contacted for up-to-date clinical follow-up. Prior to treatment, 11 patients had Spetzler-Martin grade 5 AVMs, 12 patients had grade 4 AVMs, and 14 patients had grade 3 AVMs. There were no grade 1 or 2 AVMs treated with radiosurgery. Of these 37 patients, 13 (35%) were completely obliterated on follow-up angiography. Three of the 11 (27%) grade 5 AVMs were completely obliterated. Seven of the 12 (58%) grade 4 AVMs were obliterated. Three of the 14 (21%) grade 3 AVMs have documented radiosurgical obliteration, however 8 others have had a significant decrease in size on the first posttreatment angiogram (median follow-up 14 months) and have further angiographic follow-up pending. There were 5 hemorrhages after radiosurgery, 1 was fatal and 1 resulted in permanent morbidity. Six patients have been reembolized since radiosurgery and 2 of those had their AVMs surgically resected thereafter. Only 1 patient of 6 (17%) in this series who was treated with radiosurgery alone has had documented AVM obliteration. None of 3 treated with embolization alone prior to radiosurgery have had complete obliteration. Three of the 5 patients (60%) who had only surgery prior to radiosurgery had their AVMs completely obliterated. Of the 23 patients who had all three treatments (embolization, surgery, and radiosurgery), 10 (43%) had complete obliteration of their AVMs. One patient (2%) developed moderate permanent neurological disability as a result of radiosurgery-induced necrosis. This patient did have complete obliteration of her AVM. These data support the use of radiosurgery for treatment of cerebral AVMs as part of a multimodality approach if the surgical risk of any residual AVM after embolization and microsurgical resection is deemed excessive. The adjunctive use of radiosurgery in this series resulted in the safe complete obliteration of many very difficult grade 4 and 5 AVMs. These data do not support the use of radiosurgery as the primary treatment of surgically resectable AVMs since there is a risk of interval hemorrhage and the obliteration rate is far inferior to that of microsurgical resection.

Endoscopic brachytherapy.

Intraluminal radiation for the local control of bronchogenic carcinoma has recently undergone rapid technological progress. Remote afterloading of high intensity radiation sources into endoscopically placed multiple small catheters with computerized optimization of dosimetry is the state-of-the-art. Fractionated high dose rate (HDR) outpatient treatment has been shown to reduce airway obstruction and improve performance status and quality of life.

Remote afterloading brachytherapy for the local control of endobronchial carcinoma.

PURPOSE: The study was designed to, (a) standardize endobronchial brachytherapy and, (b) to evaluate the relief of obstructive signs and symptoms. METHODS: Patients with endobronchial carcinoma were treated on a protocol (n = 342) with remote afterloading brachytherapy. Group 1 patients were treated with medium dose rate and received 1000 cGy at 5 mm depth for three fractions (n = 47). Group 2 were treated with high dose rate, 1000 cGy to a 10 mm depth for three fractions (n = 144) and Group 3 received 750 cGy delivered to a 10 mm depth for three fractions (n = 151). Each group was divided into curative, palliative, and recurrent categories. Neodymium yttrium aluminum garnet photoresection was used in 24% of patients prior to brachytherapy. RESULTS: Evaluation consisted of symptom index scoring with weighted responses of hemoptysis 99%, obstructive pneumonia 99%, cough 85%, and dyspnea 86%. Obstruction improvement was 80% overall, curative 87%, palliative 84%, and recurrent 70% of mean pretreatment scores. Survival 10% alive, 88% expired, and 2% lost to follow-up. Cause of death was intrathoracic carcinoma 41%, metastatic carcinoma 38%, intercurrent disease 9%, and unknown cause 13%. Survival from diagnosis and first treatment was, respectively, for curative 10.8 and 9.5 months, palliative 14 and 5.6 months, and recurrent 25.6 and 6.2 months. Significant complications were fatal hemoptysis 7%, and radiation bronchitis and stenosis 11%. CONCLUSION: Endoluminal brachytherapy provides excellent palliation of the endobronchial portion of neoplastic disease.

Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation.

PURPOSE: To describe a new clinical entity observed in follow-up bronchoscopies in patients who were treated with high dose rate and medium dose rate remote afterloading brachytherapy of the tracheobronchial tree. METHODS AND MATERIALS: Patients treated by protocol with medium dose rate, 47 patients receiving 1000 cGy at a 5 mm depth times three fractions, high dose rate 144 patients receiving 1000 cGy at a 10 mm depth for three fractions and high dose rate 151 patients receiving 750 cGy at a 10 mm depth for three fractions followed by bronchoscopy. RESULTS: Incidence of this entity was 9% for the first group, 12% for the second, and 13% for the third group. Reactions were grade 1 consisting of mild mucosal inflammatory response with a partial whitish circumferential membrane in an asymptomatic patient; grade 2, thicker complete white circumferential membrane with cough and/or obstructive problems requiring intervention; grade 3, severe inflammatory response with marked membranous exudate and mild fibrotic reaction; and grade 4 a predominant fibrotic reaction with progressive stenosis. Variables associated with a slightly increased incidence of radiation bronchitis and stenosis included: large cell carcinoma histology, curative intent, prior laser photoresection, and/or concurrent external radiation. Survival was the strongest predictor of the reaction. CONCLUSION: Radiation bronchitis and stenosis is a new clinical entity that must be identified in the bronchial brachytherapy patients and treated appropriately.

Expression of platelet-derived growth factor and its receptor in AIDS-related Kaposi sarcoma in vivo suggests paracrine and autocrine mechanisms of tumor maintenance.

As previously described, proliferation of Kaposi sarcoma (KS)-derived cells in vitro is dependent on the presence of platelet-derived growth factor (PDGF). To test the hypothesis that PDGF may also be a major growth factor for KS cells in vivo, we performed in situ hybridization and immunohistochemical staining for PDGF and PDGF receptors in tissue sections of AIDS-related KS. The data suggest that KS consists of two types of tumor cells. (i) The main population are spindle-shaped cells with elongated nuclei (KS-s cells). They reveal a strong expression of PDGF beta receptors but do not express the PDGF-A and PDGF-B isoforms. (ii) A minor population of KS cells express PDGF beta receptor as well as PDGF-A and PDGF-B (KS-p cells). These cells are often grouped in whorls and surrounding vascular slits. They reveal spherical nuclei with evenly distributed chromatin and inconspicuous nucleoli. PDGF alpha receptor is not expressed in either form of KS cells. The results suggest that the isoforms of PDGF and the PDGF beta receptor are differentially expressed in two different cell types in KS and that PDGF isoforms may contribute to the pathogenesis of KS.

Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man.

The ultrastructural quantitative composition of normal myocardial cells has been studied in 10 different species: man, dog, pig, cat, rabbit, ferret, guinea-pig, rat, mouse, and bat. Volume densities of mitochondria, myofibrils, and cytoplasm were determined using morphometry. It was found that the content of mitochondria differs in various species ranging between 22.0-37.0%. It is a very specific and constant value for any particular species, the smallest having the highest content. A close correlation exists between the mitochondrial volume density, heart rate and the rate of basal oxygen consumption in any group of animals. The myofibrillar volume density shows no species variability. It was about 60.0% in all species. It is concluded that the mitochondrial volume density is a good indicator of the oxidative capacity of cardiac muscle and that the species specific normal ultrastructural myocyte composition should be a useful baseline in pathophysiological studies of the heart in various animals.