RESUMEN
Type I and type III procollagen are reduced in photodamaged human skin. This reduction could result from increased degradation by metalloproteinases and/or from reduced procollagen synthesis. In the present study, we investigated type I procollagen production in photodamaged and sun-protected human skin. Skin samples from severely sun-damaged forearm skin and matched sun-protected hip skin from the same individuals were assessed for type I procollagen gene expression by in situ hybridization and for type I procollagen protein by immunostaining. Both mRNA and protein were reduced ( approximately 65 and 57%, respectively) in photodamaged forearm skin compared to sun-protected hip skin. We next investigated whether reduced type I procollagen production was because of inherently reduced capacity of skin fibroblasts in severely photodamaged forearm skin to synthesize procollagen, or whether contextual influences within photodamaged skin act to down-regulate type I procollagen synthesis. For these studies, fibroblasts from photodamaged skin and matched sun-protected skin were established in culture. Equivalent numbers of fibroblasts were isolated from the two skin sites. Fibroblasts from the two sites had similar growth capacities and produced virtually identical amounts of type I procollagen protein. These findings indicate that the lack of type I procollagen synthesis in sun-damaged skin is not because of irreversible damage to fibroblast collagen-synthetic capacity. It follows, therefore, that factors within the severely photodamaged skin may act in some manner to inhibit procollagen production by cells that are inherently capable of doing so. Interactions between fibroblasts and the collagenous extracellular matrix regulate type I procollagen synthesis. In sun-protected skin, collagen fibrils exist as a highly organized matrix. Fibroblasts are found within the matrix, in close apposition with collagen fibers. In photodamaged skin, collagen fibrils are shortened, thinned, and disorganized. The level of partially degraded collagen is approximately 3.6-fold greater in photodamaged skin than in sun-protected skin, and some fibroblasts are surrounded by debris. To model this situation, skin fibroblasts were cultured in vitro on intact collagen or on collagen that had been partially degraded by exposure to collagenolytic enzymes. Collagen that had been partially degraded by exposure to collagenolytic enzymes from either bacteria or human skin underwent contraction in the presence of dermal fibroblasts, whereas intact collagen did not. Fibroblasts cultured on collagen that had been exposed to either source of collagenolytic enzyme demonstrated reduced proliferative capacity (22 and 17% reduction on collagen degraded by bacterial collagenase or human skin collagenase, respectively) and synthesized less type I procollagen (36 and 88% reduction, respectively, on a per cell basis). Taken together, these findings indicate that 1) fibroblasts from photoaged and sun-protected skin are similar in their capacities for growth and type I procollagen production; and 2) the accumulation of partially degraded collagen observed in photodamaged skin may inhibit, by an as yet unidentified mechanism, type I procollagen synthesis.
Asunto(s)
Colagenasas/farmacología , Fibroblastos/metabolismo , Procolágeno/biosíntesis , Envejecimiento de la Piel , Piel/metabolismo , Anciano , División Celular , Células Cultivadas , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Matriz Extracelular/fisiología , Femenino , Fibroblastos/citología , Antebrazo/fisiología , Expresión Génica/efectos de los fármacos , Cadera/fisiología , Humanos , Masculino , Persona de Mediana Edad , Piel/citología , Piel/ultraestructura , Rayos UltravioletaRESUMEN
Between August 1985 and September 1989, 62 patients with medically inoperable or surgically unresectable, non-small cell lung cancer were treated with both external beam radiotherapy and high dose rate bronchial brachytherapy. Treatment consisted of external beam radiotherapy (5000-6000 cGy in 5-6 1/2 weeks) and weekly high dose rate bronchial brachytherapy (three to five fractions, 500 cGy at 1 cm from the source) delivered either concurrently or sequentially. Median survival for all patients was 13 months (m). Stage I and Stage IIIA-B patients had median survivals of 20 m and 10 m, respectively. Patients without nodal disease (No) had a significantly longer median survival compared to patients with regional node metastases (N1-3), 17 m versus 9 m. A total of 54 patients were evaluable for local tumor control analysis. Local tumor control was achieved in six of eight patients who had a normal pre-treatment radiograph. Patients with measurable tumor on the pre-treatment radiograph and negative regional nodes had local tumor control in eight of twenty-two (36%) cases. In patients with regional lymphadenopathy, loco-regional tumor control was achieved in four of eight cases. Additionally, there were sixteen patients with non-measurable tumor due to associated effusion, atelectasis and/or infiltrate. Four of these (25%) were considered to have local tumor control. Of 60 evaluable patients, there were nine occurrences of fatal hemorrhage, one of whom was disease-free (NED) at autopsy. The remaining eight patients had either clinical or pathological evidence of recurrent or persistent tumor. Patients who had follow up bronchoscopies were found to have varying degrees of concentric narrowing in the treated areas. One such patient had total lung collapse with no evidence of tumor. While this form of treatment may yield high local control rates in earlier stages, this study suggests the potential risk of fatal complication. Additional studies are warranted to further investigate the use of this modality in the treatment of lung cancer.
Asunto(s)
Braquiterapia , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radioterapia de Alta Energía , Adenocarcinoma/epidemiología , Adenocarcinoma/mortalidad , Adenocarcinoma/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/radioterapia , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/mortalidad , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Based upon this survey, the technical cost per RVU is $16.87 in freestanding radiation oncology centers. A 47% increase in technical reimbursement is needed in order to cover technical radiation oncology costs. Because technical costs are continuing to escalate, the gap between cost and reimbursement will widen unless modifications in the system are made. The data from this survey does not justify the implementation of an energy modifier for reimbursement purposes (although there was limited data from single unit, high energy facilities). Total costs increase with increasing beam energy; however, total services or RVUs are inversely proportional to beam energy and the resultant technical cost per RVU does not increase with treatment beam energy. In this survey, 13 of 80 centers (16%) had the capability to treat with a photon beam energy greater than 11 MV.
Asunto(s)
Instituciones de Atención Ambulatoria/economía , Instituciones Oncológicas/economía , Oncología Médica/economía , Radiología/economía , Costos y Análisis de Costo/estadística & datos numéricos , Estudios de Evaluación como Asunto , Humanos , Neoplasias/radioterapia , Escalas de Valor Relativo , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Over a period of four years, 693 third-year medical students were offered the opportunity to receive half of their required internal medicine clerkship clinical experience by rotating on a well-established family medicine inpatient service in a university hospital. This learning experience was designed and evaluated by the physician and behavioral science faculty of the department of family medicine. The family medicine inpatient experience provided the student with a greater number of individual patient encounters and a greater variety of clinical problems than an internal medicine experience. Scores on an internal medicine national board test showed no statistical difference between those students who completed a traditional internal medicine clerkship and those receiving a portion of their internal medicine experience by rotating on a family medicine inpatient service. The success of this student experience was a significant factor in the eventual acquisition of curriculum time for a third-year required family medicine clerkship.
Asunto(s)
Prácticas Clínicas/métodos , Educación de Pregrado en Medicina/métodos , Medicina Familiar y Comunitaria/educación , Medicina Interna/educación , Facultades de Medicina , Enseñanza/métodos , Georgia , HumanosRESUMEN
A patient with hyperviscosity syndrome was noted to have an abnormal liver radionuclide scan. Ultrasound and normalization of the liver scan after plasmapheresis confirmed the non-neoplastic nature of the patchy labeling defects. This case suggests a new cause for labeling abnormalities on liver radionuclide scans in patients with a syndrome where liver biopsies would be unusually hazardous. Possible mechanisms for this scintigraphic pattern in the hyperviscosity syndrome are briefly discussed.
Asunto(s)
Viscosidad Sanguínea , Enfermedades Hematológicas/diagnóstico por imagen , Hígado/diagnóstico por imagen , Anciano , Humanos , Masculino , Cintigrafía , Síndrome , Macroglobulinemia de Waldenström/diagnóstico por imagenRESUMEN
The six Centers for Radiological Physics performed periodic thermoluminescent dosimetry (TLD) reviews for photon beams at 276 facilities across the country. The purpose of the reviews and the techniques in use are briefly described. Results from 2413 mailed reviews of megavoltage units indicate that, in 92% of the reviews, a specified dose was delivered within +/- 5% of the TLD-measured dose. A comparison is made to other mailed TLD review systems.