RESUMEN
PURPOSE: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (l)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. METHODS: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. RESULTS: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. CONCLUSIONS: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.
Asunto(s)
Terapia por Captura de Neutrón de Boro/métodos , Neoplasias Pulmonares/radioterapia , Animales , Argentina , Boro/farmacocinética , Boro/uso terapéutico , Compuestos de Boro/farmacocinética , Terapia por Captura de Neutrón de Boro/instrumentación , Estudios de Factibilidad , Fructosa/análogos & derivados , Fructosa/farmacocinética , Humanos , Pulmón/metabolismo , Pulmón/efectos de la radiación , Neoplasias Pulmonares/metabolismo , Modelos Animales , Modelos Biológicos , Fotones , Radiometría/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Ovinos , Factores de Tiempo , Distribución TisularRESUMEN
OBJECTIVE: This study evaluated the incidence, epidemiology, aetiology and outcome of chronic renal failure (CRF) in Jamaican children < 12 years old between 2001 and 2006. METHODS: The required data on all children who fulfilled inclusion criteria were obtained from their medical records at the University Hospital of the West Indies, Bustamante Hospital for Children and from practitioners in hospitals serving children islandwide. RESULTS: Eighteen new children (72.2% male) presented with CRF. The cumulative annual incidence was 4.61/million child population under age 12 years or 1.14/million total population. Congenital urological disease (44.5%) was the commonest cause of CRF, followed by glomerulonephritis (33.3%). Half of the cases of glomerulonephritis were secondary to HIV-associated nephropathy. Although all children with posterior urethral valves were diagnosed before age 6 months and promptly treated, renal failure present at birth proved irreversible. The mean age at diagnosis of CRF was 6.72 years. Ten children (55.6%) were already in CRF at first presentation with renal disease. Of these, the five with non-urological disease were already in End Stage Renal Disease (ESRD). Mortality was 44.4%. Five children died in ESRD without the benefit of dialysis. CONCLUSION: The incidence of CRF has increased from the 1985-2000 local study and is mainly due to urological pathology which progresses despite early diagnosis and treatment. Non-urological renal disease is presenting too late for therapeutic intervention. Greater public awareness of symptoms of renal disease is needed. Children's access to dialysis is unpredictable. A paediatric dialysis and transplantation programme is needed.
Asunto(s)
Nefropatía Asociada a SIDA/epidemiología , Glomerulonefritis/epidemiología , Fallo Renal Crónico/epidemiología , Nefropatía Asociada a SIDA/complicaciones , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Glomerulonefritis/complicaciones , Glomerulonefritis/terapia , Humanos , Incidencia , Lactante , Jamaica/epidemiología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Masculino , Pronóstico , Diálisis Renal/estadística & datos numéricos , Factores de Riesgo , Resultado del TratamientoRESUMEN
A novel system to determine thermal neutron flux in real time during NCT treatments was developed in the National Atomic Energy Commission of Argentina. The system is based on a special self-powered detector that can be implanted in patients owing to its small size and biocompatibility. High voltage is not required to operate this kind of detectors, which is a considerable advantage in terms of medical uses. By choosing the appropriate materials, it was possible to obtain a prototype with thermal neutron sensitivity providing for an adequate signal level in typical NCT thermal fluxes. It was also possible to minimize gamma response in order to neglect its contribution.
Asunto(s)
Terapia por Captura de Neutrón , Monitoreo de Radiación/instrumentación , Argentina , Diseño de Equipo , Neutrones Rápidos/uso terapéutico , Humanos , Prótesis e Implantes , Monitoreo de Radiación/estadística & datos numéricos , Rodio , Sensibilidad y Especificidad , CirconioRESUMEN
In order to document the incidence, aetiology and outcome of chronic renal failure in Jamaican children, paediatric surgeons and hospital based paediatricians island-wide were contacted, and the nephrology records at the island's paediatric nephrology centres searched for data on children < 12-year-old with chronic renal failure diagnosed for the first time between January 1985 and December 2000. Thirty-four children were identified, 21 were male. The cumulative annual incidence of chronic renal failure was 3.2 per million children aged < 12 years. The incidence is likely underestimated, as some children may have been undiagnosed and/or not referred. Glomerulonephritis was the commonest cause of chronic renal failure (50) followed by obstructive uropathy, reflux nephropathy, renal dysplasia and chronic pyelonephritis (41.2). Five children (14.7) had reflux nephropathy (post obstructive in four). Half the children were already in chronic renal failure at time of presentation. Mortality was 65. In Jamaica, childhood chronic renal failure is due mainly to potentially treatable diseases. Local physicians should be more aware of potentially progressive renal diseases and their prevention. Earlier referral of difficult cases for nephrological consultation is recommended. A paediatric dialysis/transplant programme is needed
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Insuficiencia Renal Crónica , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Jamaica/epidemiologíaRESUMEN
Between December 1984 and November 1996, 171 children under 12 years old presented to the University Hospital of the West Indies with nephrotic syndrome. Hepatitis B surface antigen (HBsAg) was found in ten (6%) of these children, eight of whom had membranous nephropathy (MN), and one each had mesangial proliferative glomerulonephritis (MesN) and minimal change nephrotic syndrome (MCNS). Only those children with MesN and MCNS were steroid-sensitive. The HBsAg-positive status was identified incidentally on screening. At a mean follow-up of 34 months, seven of ten children had experienced complete or partial remission and three had persistent nephrotic syndrome, although none was in renal failure. Six of the ten had biochemical hepatitis. All the children were still HBsAg-positive. Hepatitis B virus (HBV) is a factor contributory to nephrotic syndrome in Jamaican children. As diagnostic clinical markers for HBV-associated nephropathy are usually absent, all children presenting with nephrotic syndrome should be screened for HBsAg. A policy should be implemented in Jamaica for screening pregnant women and at-risk groups for HBsAg, as well as for immunising susceptible neonates, in order to reduce the incidence of HBV-associated pathology.
Asunto(s)
Hepatitis B/complicaciones , Síndrome Nefrótico/virología , Niño , Preescolar , Estudios de Seguimiento , Glomerulonefritis Membranoproliferativa/virología , Glomerulonefritis Membranosa/virología , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Nefrosis Lipoidea/virologíaRESUMEN
In order to document the incidence, aetiology and outcome of chronic renal failure in Jamaican children, paediatric surgeons and hospital based paediatricians island-wide were contacted, and the nephrology records at the island's paediatric nephrology centres searched for data on children < 12-year-old with chronic renal failure diagnosed for the first time between January 1985 and December 2000. Thirty-four children were identified, 21 were male. The cumulative annual incidence of chronic renal failure was 3.2 per million children aged < 12 years. The incidence is likely underestimated, as some children may have been undiagnosed and/or not referred. Glomerulonephritis was the commonest cause of chronic renal failure (50%) followed by obstructive uropathy, reflux nephropathy, renal dysplasia and chronic pyelonephritis (41.2%). Five children (14.7%) had reflux nephropathy (post obstructive in four). Half the children were already in chronic renal failure at time of presentation. Mortality was 65%. In Jamaica, childhood chronic renal failure is due mainly to potentially treatable diseases. Local physicians should be more aware of potentially progressive renal diseases and their prevention. Earlier referral of difficult cases for nephrological consultation is recommended. A paediatric dialysis/transplant programme is needed.
Asunto(s)
Fallo Renal Crónico , Niño , Preescolar , Femenino , Humanos , Jamaica/epidemiología , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , MasculinoRESUMEN
This report documents the clinicopathological features in two Jamaican children who presented with infective dermatitis, glomerulonephritis, renal failure and human T-cell lymphotropic virus (HTLV-1) seropositivity. Severe hypertension with hypertensive encephalopathy was the most impressive clinical feature. Histological findings from renal biopsy specimens in both cases revealed significant glomerulosclerosis with fibrosis, chronic inflammatory cell infiltrates in the interstitium, and arteriolar hypertensive changes. Membranoproliferative glomerulonephritis (MPGN) was demonstrable in case 1 and marked focal glomerulosclerosis in case 2. Case 1 developed end stage renal failure and died within 3 years of diagnosis. Case 2 remains hypertensive and in chronic renal failure. Although a causal relationship between HTLV-1 infection and renal disease cannot be proven by these two cases, it appears that renal involvement in children with HTLV-1 infection is severe, with the potential for chronic renal failure and malignant hypertension. HTLV-1 nephropathy should be suspected in children with infective dermatitis and renal disease.
Asunto(s)
Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/virología , Glomeruloesclerosis Focal y Segmentaria/virología , Infecciones por HTLV-I/complicaciones , Fallo Renal Crónico/virología , Niño , Dermatitis/patología , Dermatitis/virología , Resultado Fatal , Femenino , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Jamaica , Fallo Renal Crónico/patología , MasculinoRESUMEN
In 1998 to 1999, geminivirus-like symptoms were observed in whitefly-infested pumpkin, honeydew melon, and muskmelon in Arizona and Texas and in Coahuilla, Mexico (MX), respectively. Plants exhibited leaf curl and/or mottling, reminiscent of symptoms caused by Squash leaf curl virus (SLCV-WAZ) described from Arizona in 1981 (2). The isolate from Arizona pumpkin fields was experimentally transmitted to pumpkin seedlings by the "B type" of Bemisia tabaci (Genn.), and symptoms were indistinguishable from those observed in infected fields. Samples from AZ, MX, and TX were assessed for begomovirus presence by polymerase chain reaction (PCR) using degenerate primers that amplify a contiguous fragment containing the viral coat protein (Cp) gene and common region (CR) of the A component (CR-A) (~2,100 bp) and a fragment containing the CR of the B component (CR-B) (~1,100 bp). One to four isolates from each location were examined by PCR using both primer pairs, and at least three amplicons per isolate were cloned and their sequences determined. Alignment of viral Cp nucleotide (nt) sequences revealed that AZ [AF256199], MX, and TX field isolates shared 98.7 to 100% sequence identity, but were only 84.5 to 85.6% identical to the Cp gene of SLCV-extended (SLCV-E) [M38183] and SLCV-restricted (SLCV-R) (S. G. Lazarowitz, unpublished), respectively, suggesting a new, previously undescribed begomoviral species (3). Further, the Cp nt sequence of the three field isolates was 6 nt shorter than SLCV-E, SLCV-WAZ [AF256203], and SLCV-R Cp sequences. The CR-A [AF256200] and CR-B [AF256201] sequences (179 nt, each) of field isolates, including the theoretical Rep binding element, GGTGT, were 100% identical. Although the Rep binding site is identical among field isolates, SLCV-E, SLCV-R, and SLCV-WAZ, the field isolate CR sequence shared only 64.2, 67.5, and 66.9% overall identity with CR-A SLCV-E, SLCV-R [M63155], and SLCV-WAZ [AF256202], respectively. Prior to 1998 to 1999, SLCV-WAZ was the only New World begomovirus of cucurbits known to infect both melon (Cucumis) and pumpkin (Cucurbita) (1). Therefore, SLCV was initially suspected as the causal agent. However, here we provide evidence for a new, previously undescribed bipartite begomovirus of cucurbits in AZ, MX, and TX that is herein provisionally designated Cucurbit leaf curl virus (CuLCV). Prediction of its closest begomovirus relatives by Cp nt sequence and Rep binding site comparisons suggest that CuLCV is a new member of the SLCV lineage, also containing Bean calico mosaic virus, Cabbage leaf curl virus, SLCV-E, and Texas pepper virus-TAM. References: (1) J. K. Brown and M. R. Nelson. Phytopathology 74:1136, 1984. (2) J. K. Brown and M. R. Nelson. Ann. Appl. Biol. 115:243, 1986. (3) M. A. Mayo and C. R. Pringle. J. Gen. Virol. 97:649, 1998.
RESUMEN
Central American countries have become major production areas of melons (Cucumis melo L.) destined for export to Europe and the United States during the winter months. Double cropping in the same fields year after year has created serious vine decline diseases in melons grown in the Capco area of Guatemala. Vines typically appear healthy until the fruit are approaching maturity, when the crown leaves begin to turn yellow and collapse and the decline gradually radiates outward. There was evidence of slightly water-soaked lesions in the crown of some plants; however, the symptoms were not similar to charcoal rot or gummy stem blight. The roots exhibited some decay, lesions, and discoloration, but were not macerated and rotten. A minimum of 10 affected plants were collected from each of nine fields in the Capco area of Guatemala. Isolations were made from the crown area, primary root, and secondary roots of selected plants by excising 3- to 5-mm pieces and surface sterilizing them for 30 to 60 s with 0.5% sodium hypochlorite. The isolations were made on 2% water agar plus 0.1 g of streptomycin sulfate per liter. Plates were examined for fungal growth daily for 5 days with hyphal tips from all colonies transferred to potato dextrose agar and Synthetischer nährstoffärmer agar (2) and allowed to sporulate. Isolations revealed the presence of several fungi capable of causing vine decline or suspected of being involved in the vine decline complex. Rhizoctonia solani Kühn and Fusarium semitectum Berk. & Ravenel were isolated from more than 50% of plants in some fields. F. semitectum, R. solani, and a Stagonospora-like fungus were isolated from 38, 18, and 17% of the total plants, respectively. R. solani was isolated from the crown more often than from the roots, but its role is not understood. With one exception, F. semitectum was always isolated from the crown area, which may suggest a more significant role in the vine decline complex than suspected previously. The Stagonospora-like fungus, isolated from 30% of the plants from one field, has been reported as a pathogen of cantaloupe that may contribute to the vine decline complex (1). Monosporascus cannonballus Pollack & Uecker and Fusarium oxysporum Schlechtend.:Fr. emend. W. C. Snyder & H. N. Hans. were isolated from 60% of the plants from one field. It was the only field in which M. cannonballus was isolated. Plectosporium tabacinum (van Beyma) M. E. Palm, W. Gams et Nirenberg, a cucurbit pathogen, was isolated infrequently. This is the first report of M. cannonballus, P. tabacinum, and the Stagonospora-like fungus in Guatemala. References: (1) M. E. Miller et al. Phytopathology 86:S3, 1996. (2) H. I. Nirenberg. Mitt. Biol. Bundesanst. Land Forstwirtsch. Berlin-Dahlem. 169:1, 1976.
RESUMEN
A survey of vine decline diseases of melons (Cucumis melo L.) was conducted on three geographically separate farms (12 fields) in the area of San Lorenzo, Honduras, during the spring of 1996. Symptoms were typical of the vine declines in that the leaves began yellowing and collapsing in the crown just prior to harvest and the decline radiated outward. Crown lesions, typical of many of the vine declines, were observed infrequently. Most plants exhibited no crown lesion. Roots exhibited brown lesions and root corking, and were generally lacking root hairs, although the roots were not macerated. Fruit were small sized, low in sugars, and sunburned. Isolations were made from the crown area, primary root, and secondary roots of affected plants by excising 3- to 5-mm pieces and surface sterilizing for 30 to 60 s with 0.5% sodium hypochlorite. Four tissue pieces from each plant part were placed on 2.0% water agar plus 0.1 g of streptomycin sulfate per liter and their identity maintained. Plates were examined for fungal growth daily for 5 days and hyphal tips from all colonies were transferred to potato dextrose agar and Synthetischer nährstoffärmer agar (2) to allow for sporulation. Rhizoctonia solani Kühn was the predominant fungus isolated from affected plants in several fields, with an incidence as high as 75%. A Pythium sp. was isolated from primary and secondary roots of 50% of the plants on the Santa Rosa farm. Vines exhibiting tan to light brown crown lesions either on one side of the vine or encompassing the crown, but without gumming, always produced colonies of Fusarium semitectum Berk. & Ravenel. Fusarium solani (Mart.) Appel & Wollenweb. emend. W. C. Snyder & H. N. Hans. was isolated from roots of more than 30% of the plants, although this is not unusually high. Crown lesions typical of charcoal rot were observed in some fields, with Macrophomina phaseolina (Tassi) Goidanich being isolated from 65% of the plants in one field. Charcoal rot was a minor problem in all fields but one. Didymella bryoniae (Auersw.) Rehm was not isolated from any of the plants. A Stagonospora-like fungus, which has been demonstrated recently as a potential contributor to vine decline (1), was isolated on 17% of the plants from five fields on the Embarcadero Farm. Monosporascus cannonballus Pollack & Uecker was isolated infrequently in one field on the Santa Rosa Farm. This is the first report of M. cannonballus and a Stagonospora-like fungus in Honduras. References: (1) M. E. Miller et al. Phytopathology 86:S3, 1996. (2) H. I. Nirenberg. Mitt. Biol. Bundesanst. Land Forstwirtsch. Berlin-Dahlem. 169:1, 1976.
RESUMEN
We hypothesized that plasma arginine vasopressin (AVP) concentrations in children with meningitis are appropriate for the children's degree of hypovolemia, even though the concentrations were higher than expected for the serum osmolality. A randomized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours. Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours. Nineteen children, 2 months to 17 years of age, were studied; 13 had bacterial meningitis (12 with Haemophilus influenzae type b). Ten children (seven with bacterial meningitis) received a mean of 1.42 times the calculated maintenance fluid requirements, and nine (six with bacterial meningitis) were restricted to a mean of 0.65 times maintenance. Children in the maintenance group also received significantly more sodium (mean = 6.3 mEq/kg/24 hr) than children in the fluid-restricted group (mean = 2.0 mEq/kg/24 hr). The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun. The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction (p = 0.005), and the change in AVP concentration correlated with the amount of sodium given (p less than 0.02). This study supports the hypothesis that serum AVP concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney. Patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone.
Asunto(s)
Arginina Vasopresina/sangre , Fluidoterapia/métodos , Meningitis/sangre , Adolescente , Niño , Preescolar , Espacio Extracelular/metabolismo , Humanos , Síndrome de Secreción Inadecuada de ADH/prevención & control , Lactante , Meningitis/complicaciones , Meningitis/terapia , Meningitis por Haemophilus/sangre , Meningitis por Haemophilus/terapia , Choque/etiología , Choque/terapiaAsunto(s)
Humanos , Femenino , Líquido Amniótico , Ácidos Cólicos , Embarazo , Surfactantes PulmonaresAsunto(s)
Cordón Umbilical/fisiología , Animales , Femenino , Enfermedades Fetales/complicaciones , Feto/fisiología , Crecimiento , Humanos , Movimiento , Embarazo , Ratas , Cordón Umbilical/patologíaAsunto(s)
Embarazo , Recién Nacido , Humanos , Femenino , Amniocentesis , Líquido Amniótico , Rotura Prematura de Membranas Fetales , Pulmón , Recien Nacido PrematuroRESUMEN
The features of 27 cases of limb/body wall deficiency (formerly termed cyllosomus and pleurosomus) were evaluated and the anomalies were interpreted as being band-related defects and/or compression-related defects. The latter included limb deficiency, body wall deficiency, neural tube defects, scoliosis, postural deformations, growth deficiency, and short umbilical cord. It is hypothesized that the single event of early amnion rupture can explain both the band-related defects and the compression-related defects. Experimental animal studies are in accord with this hypothesis; amnion puncture of rat fetuses during early gestation produces a comparable array of defects. The term amnion rupture sequence is suggested to describe the overall pattern of malformation that results from amnion rupture whether these defects are band related, compression related, or a combination of the two. There is considerable variation in the phenotype of amnion rupture sequence, with limb/body wall deficiency representing the more severe end of the spectrum. It is important to recognize and correctly diagnose amnion rupture sequence because it is usually a sporadic event.