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Biomedical subjects

J S Nelson

Publications and source records attributed to J S Nelson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Does extent of surgery influence outcome for astrocytoma with atypical or anaplastic foci (AAF)? A report from three Radiation Therapy Oncology Group (RTOG) trials.

103 patients with the diagnosis of AAF were identified from the RT/BCNU arms of 3 RTOG malignant glioma trials. Pre-treatment tumor size was less than 5 cm for 48% and greater than or equal to 5 cm for 52%, and tumor sites were frontal lobe in 55%, temporal in 25%, and parietal in 16%. Surgery consisted of biopsy for 30%, partial resection for 56%, and total resection for 14%. Extent of surgery correlated with age, with 81% of patients less than 40 undergoing partial/total resection vs. 60% of those over 40 (P = 0.019). The median survival time (MST) of patients undergoing partial/total resection was 49 mo., vs. 18 mo. for those biopsied only (P = 0.002). Patients with frontal location had longer MST than those with non-frontal lesions (MST: 49 vs. 25 mo., P = 0.047), while no survival difference was apparent by univariate analysis of tumor size. Multivariate analysis demonstrated that only younger age, frontal location, and smaller tumor size correlated significantly with extended survival. Extent of surgery was not predictive. The close correlation between young age and extensive surgery obscures the survival advantage for greater surgery seen with univariate analysis. Smaller tumor size and frontal location favorably influence outcome even when adjusted by age.

Adult↗
PubMed1992

Non-Hodgkin's lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315.

Between 1983 and 1987 the Radiation Therapy Oncology Group conducted a prospective phase II study to evaluate survival in primary non-Hodgkin's lymphoma of the brain treated with whole brain irradiation to 40 Gy and a 20 Gy boost to tumor plus a 2 cm margin. Forty-one patients are reported. Full follow-up is available on 35/41 who have died. Six are alive at 8.8-67.2 months from start of radiation therapy with a median followup of 53.9 months. Overall median survival was 11.6 months from start of radiation therapy and 12.2 months from diagnosis, with 48% surviving 1 year and 28% surviving 2 years. Karnofsky Performance Status and age were significant prognostic factors. Patients with a Karnofsky Performance Status of 70-100 had a median survival of 21.1 months compared to 5.6 months for patients with a status of 40-60 (p less than .001). Fourteen patients less than 60 years of age had a median survival of 23.1 months, while 27 patients greater than or equal to 60 years of age had a median survival of 7.6 months (log-rank p = .001). Disease recurred in the brain in 25/41 (61%) of the patients, (21/41 in the brain only and 4/41 in the brain plus distant metastases). Despite high dose and large volume irradiation, primary Central Nervous System lymphoma still exhibits excessive mortality, especially in older patients. This paradox of the relative radioresistance of primary Central Nervous System lymphoma remains unresolved.

Adult↗
PubMed1992

Treatment of superficial cutaneous pigmented lesions by melanin-specific selective photothermolysis using the Q-switched ruby laser.

The Q-switched ruby laser at 694 nm, a wavelength well absorbed by melanin relative to other optically absorbing structures in skin, causes highly selective destruction of pigment-laden cells. In addition, the 20-nsec pulse duration produced by this laser approximates the thermal relaxation time for melanosomes, thereby confining the energy to the target. This new laser system produces clinically significant fading of superficial cutaneous pigmented lesions in patients, without complications such as hypertrophic scarring or changes in the normal skin pigmentation, often seen with conventional laser systems or other therapeutic methods. In ongoing clinical trials at our facility, excellent results have been obtained for lentigines, café-au-lait macules, nevus spilus, Becker's nevi, and ephelides (freckles), without skin scarring or textural or permanent pigment changes. The purpose of this report is to (1) describe the theoretical considerations that can be understood and used by a nonlaser-oriented practitioner involved in achieving selective removal of superficial cutaneous pigmented lesions, and (2) describe the practical application of the device to the clinical management of patients.

Female↗
PubMed1991

Mixed glioblastoma multiforme and sarcoma. A clinicopathologic study of 26 radiation therapy oncology group cases.

Twenty-six cases are reported of gliosarcoma (GS) retrieved from a series of 1479 glioblastomas (GBM) that were part of five consecutive, randomized Phase II or III malignant glioma protocols initiated by the Radiation Therapy Oncology Group between 1974 and 1983. The clinicopathologic features of these 26 cases, including actuarial survival times, were compared with the remaining 1453 GBM. The minimal qualitative and quantitative histologic criteria required to diagnose GS are presented. In most cases the sarcomatous component was a malignant fibrous histiocytoma; a minority were fibrosarcoma. No significant differences between GS and GBM were found with regard to age, sex, pretreatment Karnofsky performance status, tumor location, size, median survival (8.3 and 9.6 months, respectively), and actuarial survival. None of the treatment regimens, which included various combinations of radiation therapy and chemotherapy, improved the survival of GS over GBM. Selective involvement of the temporal lobe by GS was not found, and the frequency of GS was determined to be only 1.8% of all GBM.

Adult↗
PubMed1991

Differential effect of chronic vitamin E deficiency on the development of neuroaxonal dystrophy in rat gracile/cuneate nuclei and prevertebral sympathetic ganglia.

Chronic vitamin E deficiency results in the premature and exaggerated development of neuroaxonal dystrophy (NAD) in primary sensory axon terminals in rat medullary gracile/cuneate nuclei, sites in which NAD develops normally with age. In the current study we determined if chronic Vitamin E deprivation had a similar effect on the development of NAD in the celiac/superior mesenteric sympathetic ganglia (C/SMG), another site with age-dependent NAD. The frequency of NAD failed to increase in the SMG of the same vitamin-E deficient animals in which a marked increase in severity of NAD was found in the gracile nucleus. These findings indicate that different populations of neurons are selectively involved in vitamin E deficiency and that the distribution of axonopathy in the E-deficient C/SMG does not duplicate the pattern of experimental diabetes and aging.

Animals↗
PubMed1991

Long-term survival in treated anaplastic astrocytomas. A report of combined RTOG/ECOG studies.

This report evaluates the long-term survival of patients with histologically confirmed anaplastic astrocytoma on several combined RTOG (Radiation Therapy Oncology Group) studies. Included in this analysis are the following studies: RTOG/ECOG (Eastern Cooperative Oncology Group) 74-01, RTOG 76-11, and RTOG 79-18, with the various treatment arms separated into radiation therapy (RT) only (47 patients) radiation therapy and chemotherapy (Chemo) (78 patients) and radiation therapy, chemotherapy, and misonidazole (Mizo) (24 patients). Pretreatment characteristics of age, prior surgery, performance status, and neurological function classification are identified. Median survival for patients treated with RT only is 3.0 years. Median survival for patients treated with RT + Chemo is 2.3 years, and for patients treated with RT + Chemo/Miso is 1.2 years. Five-year survival rates are 35% for patients treated with RT only, 29% for patients treated with RT + Chemo, and 24% for patients treated with RT + Chemo/Miso. Age and performance status have been identified in previous studies as important prognostic variables and are confirmed in this analysis. Patients treated with misonidazole had a significantly worse prognosis after adjustment for differences in prognostic factors. Addition of chemotherapy did not improve survival except in less favorable prognostic categories. In general, more aggressive treatment regimens are associated with decreased survival compared to conventional postoperative irradiation.

Adolescent↗
PubMed1991

Selective photothermolysis and removal of cutaneous vasculopathies and tattoos by pulsed laser.

The evolution of the laser as a medical device has been a process of continued improvement. Research into increasing our understanding of the optical characteristics of skin has made it possible to concentrate not on the effects of any particular laser system, but on basic biologic and physical principles of laser-tissue interaction. The lasers available in the 1960s and 1970s offered few possibilities for modification. However, modern technology allows us to manipulate the physical characteristics of lasers and design them for specific therapeutic purposes. Selective photothermolysis relies on chromophore-specific absorption of a brief pulse of light to generate and confine heat to certain targets within the skin without nonspecific thermal damage to adjacent structures. Thermally mediated target alterations can be confined from the level of large multicellular tissue structures (e.g., blood vessels) to individual microscopic pigmented structures (e.g., tattoo pigment granules). The purpose of this report is to describe the current progress being made and to summarize the present theories for achieving increasing selective removal, without scarring or other skin textural changes, of cutaneous vasculopathies and tattoo pigment by pulsed laser.

Adult↗
PubMed1991

Mid-infrared laser ablation of stratum corneum enhances in vitro percutaneous transport of drugs.

The precise removal of stratum corneum from cadaveric swine skin by a mid-infrared erbium:yttrium scandium gallium garnet laser (lambda = 2.79 microns; 250 microseconds pulse width) was assessed by electrical resistance measurements and documented by histology. The effects of stratum corneum removal by laser ablation and by adhesive tape-stripping on the in vitro penetration of 3H-hydrocortisone and 125I-gamma-interferon were determined. Excised swine skin was irradiated with laser (1 J/cm2; 31 mJ/pulse; 1 Hz; 2 mm spot diameter). For skin penetration studies, laser pulses were delivered to discrete 2-mm areas to ablate up to 12.6% of the total 3-cm2 stratum corneum diffusional area. Franz in vitro skin penetration chambers were used to measure the cumulative 48-h penetration of 3H-hydrocortisone and 125I-gamma-interferon in laser-treated and tape-stripped skin. Electrical resistance measurements and histologic studies demonstrated that 10-14 laser pulses at the above energy density were required to abolish skin resistance and selectively ablate stratum corneum without damage to adjacent dermal structures. Laser ablation of 12.6% of the surface area of stratum corneum produced a 2.8 and 2.1-times increase in permeability constant (kp) for 3H-hydrocortisone and 125I-gamma-interferon, respectively. These studies demonstrate that a pulsed mid-infrared laser can reliably and precisely remove the stratum corneum, facilitating penetration of large molecules such as 125I-gamma-interferon that cannot penetrate intact skin. This new technique may be useful for basic and clinical investigation of skin barrier properties.

Administration, Cutaneous↗
PubMed1990

Use of multiple photosensitizers and wavelengths during photodynamic therapy: a new approach to enhance tumor eradication.

Several studies have examined the synergism of hyperthermia or chemotherapy agents in combination with photodynamic therapy (PDT) to enhance tumor eradication. In our unique approach to treatment, multiple photosensitizers and wavelengths were used: two photosensitizers, Photofrin II and meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4), irradiated at the appropriate therapeutic wavelength for each photosensitizer. EMT-6 mammary tumors were induced in the flanks of BALB/c mice. The mice were assigned to a control group (50 mice) or treatment group (150 mice). All treatment animals and some control animals received photosensitizing drug (5 mg/kg of TPPS4, 5 mg/kg of Photofrin II, or 2.5 mg/kg of both TPPS4 and Photofrin II). All treatment animals and some control animals also received light treatment (630 nm for TPPS4 and/or 658 nm for Photofrin II). The results show that the approach using both drugs and the corresponding therapeutic wavelengths enhanced the effectiveness of PDT. This approach achieved a cure rate of up to 100%, which was, depending on the light intensity used, as much as 40% greater than the rate achieved by the approach using one drug and one wavelength. The results also show that lesser amounts of drug and/or light may be required if both drugs and wavelengths are used, thus lowering the chances of side effects common to PDT. Furthermore, the results indicate that the increased tumor kill is due to a synergistic effect of the two photosensitizers that was tested on the tumor microvasculature in the first few hours after PDT.

Animals↗
PubMed1990

Long-term survival of a lung cancer patient treated with photodynamic therapy.

A 63-year-old male, status post-right pneumonectomy, presented with hemoptysis. Although chest X-ray and CAT scan film findings were negative, bronchoscopy with biopsy from the left mainstem bronchus demonstrated squamous cell carcinoma. Because of the inoperable location of the lesion, the patient was treated with photodynamic therapy (PDT) in February 1984. At present, the patient is cancer free more then 6 years after PDT.

Carcinoma, Squamous Cell↗
PubMed1990

Photochemotherapy of hypervascular dermal lesions: a possible alternative to photothermal therapy?

Continued improvement in the results of laser treatment of port wine stain, with reduction in scarring, will depend on the ability to use lasers to induce selective injury of only the abnormal blood vessels in the dermis while sparing the normal overlying epidermis. Photodynamic therapy, using an exogenous photosensitizing drug specifically activated by certain wavelengths of light, may be used to destroy selectively certain targets in biological systems. The current study demonstrates, in the chicken comb model, that photochemotherapy can be used to treat hypervascular dermal lesions while leaving the normal overlying epidermis completely intact.

Animals↗
PubMed1990

Laser assisted fixation of ear prostheses after stapedectomy.

Three different lasers (erbium:YAG, holmium:YAG, alexandrite) were used to drill a hole at the end of the long process of the incus in order to fix an ear prosthesis after stapedectomy or small fenestra stapedectomy. The energy was coupled into a 250-microns core diameter zirconium-fluoride fiber. The operations were carried out on human temporal bone models from cadavers. The fiber was guided to the incus under the stereoscopic surgical microscope. The tissue response was examined under the scanning electron microscope, and after decalcification, histologically. These studies suggest the feasibility of using the erbium:YAG laser to improve the anchorage of the prosthesis on the incus and to increase the stability in ossicular chain reconstruction.

Cochlear Implants↗
PubMed1990

The perihypoglossal projection to the superior colliculus in the rhesus monkey.

The projection of the perihypoglossal (PH) complex to the superior colliculus (SC) in the rhesus monkey was investigated using the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Following physiological identification by electrical stimulation and multiunit recording, small injections of the tracer were placed within the SC of three monkeys. The largest numbers of retrogradely labeled neurons within the PH complex were found in the contralateral nucleus prepositus hypoglossi (NPH), in the laterally adjacent medial vestibular nucleus, and in the ventrally adjacent reticular formation (the nucleus reticularis supragigantocellularis). These labeled neurons are strikingly heterogeneous in size and morphology. The nuclei supragenualis and intercalatus also contain numerous labeled neurons in the 2 cases in which the injections involve the caudal SC. Large numbers of retrogradely labeled neurons as well as anterogradely transported WGA-HRP are observed also throughout the pontine and medullary reticular formation, including the midline raphe. The PH complex, particularly the NPH, is known to be involved in the coding of eye position and has been hypothesized to be a critical component of the "neural integrator." Our data demonstrate the existence of a robust projection from the PH complex to the contralateral SC in the rhesus monkey. This projection may serve as the anatomical substrate by which a corollary of eye position could reach the SC. Such a signal is a prerequisite for the computation, at the collicular level, of saccadic motor error signals observed in the SC of rhesus monkeys.

Animals↗
PubMed1990

In vivo tumor oxygen tension measurements for the evaluation of the efficiency of photodynamic therapy.

Among the sequence of events which occur during photodynamic therapy (PDT) are depletion of oxygen and disruption of tumor blood flow. In order to more clearly understand these phenomena we have utilized transcutaneous oxygen electrodes to monitor tissue oxygen disappearance. These results provide, for the first time, non-invasive real-time information regarding the influence of light dose on tissue oxygenation during irradiation. Measurements were conducted on transplanted VX-2 skin carcinomas grown in the ears of New Zealand white rabbits. Rabbits were treated with Photofrin II and tumors were irradiated with up to 200 kJ/m2 (500 W/m2) of 630-nm light. Substantial reductions in tumor oxygen tension were observed upon administration of as little as 20 kJ/m2. For a series of brief irradiations, oxygen tension was modulated by the appearance of laser light. Tissue oxygen reversibility appeared to be dependent upon PDT dose. Long-term, irreversible tissue hypoxia was recorded in tumors for large (200 kJ/m2) fluences. These results suggest that transcutaneous oxygen tension may be useful as a general indicator of the effectiveness of PDT and as an in situ predictor of the energy required to elicit tumor damage.

Animals↗
PubMed1990

Clinical management of port-wine stain in infants and young children using the flashlamp-pulsed dye laser.

The flashlamp-pulsed dye laser (FLPDL) at 585 nm, a wavelength well absorbed by oxyhemoglobin, causes highly selective vascular injury. In addition, the 450 microsecond pulse duration produced by this laser approximates the thermal relaxation time for dermal blood vessels thereby confining the energy to the target. This new laser effects excellent lightening of port-wine stain (PWS) in infants and young children without the adverse complications of hypertrophic scarring, permanent pigmentation abnormality, or textural changes, complications often seen with conventional laser systems. The FLPDL now permits treatment of this patient population expected to gain the most benefit from early laser therapy in a much safer manner, before the psychological complications of being a "marked" person develop. The purpose of this report is to: (1) describe the theoretical considerations behind achieving selective removal of PWS that can be understood and used by a nonsurgically-oriented practitioner; and (2) describe the practical application of the device used in the clinical management of infants and young children.

Child, Preschool↗
PubMed1990

Gliosarcoma: a histologic and immunohistochemical reaffirmation.

Seven cases of mixed glioblastoma multiforme (GBM) and sarcoma, or gliosarcoma (GS) and six cases of GBM with a prominent pilocytic or spindle cell component were studied with a panel of ten antibodies using the ABC method. All 13 cases were originally diagnosed as GS based on hematoxylin and eosin- (H&E) and reticulin-stained sections. In all GS, the glial component stained strongly for glial fibrillary acidic protein (GFAP), and most stained for S-100 protein, while the sarcomatous areas of GS did not stain for either of these antigens. This resulted in a characteristic, bimorphic marmorate staining pattern. In contrast, spindled GBM stained diffusely for GFAP and S-100 protein. Vimentin was detected in neoplastic glia of both GBM and GS and in the sarcomatous foci of GS. A spectrum of cytokeratins, Factor VIII, desmin and neurofilament were not detected in either GS or GBM. Actin, Leu 7 and alpha-1-antichymotrypsin were focally and inconsistently found in both GS and GBM. Perithelial spindle cell proliferations and intramural spindle cells within thick-walled vessels stained for GFAP, S-100 protein and/or vimentin. These studies confirm that GS is a true biphasic neoplasm that frequently cannot be distinguished from pilocytic or spindled GBM on routine histologic examination. Invasion of the dura, leptomeninges, and hyperplastic or hypertrophied blood vessels by malignant glial cells particularly confounds interpretation of H&E and reticulin stains. Immunohistochemical staining for GFAP complements the reticulin stain in confirming the presence of two cell populations in GS.

Adult↗
PubMed1989

Ablation of bone and polymethylmethacrylate by an XeCl (308 nm) excimer laser.

One of the main problems in orthopaedics is the surgical removal of hard substances, such as bone and polymethylmethacrylate (PMMA). Such materials are often very difficult to remove without mechanical trauma to the remaining tissue. This study investigated the feasibility of the ultraviolet 308 nm excimer laser in the ablation of these materials. The beam was delivered through a 1 mm-diameter fiber optic at 40 Hz with energy densities at the target surface of 20-80 J/cm2 per pulse. The goal of the study was to establish the ideal dosimetry for removing bone and PMMA with minimum trauma to the adjacent tissue. Histology revealed that the 308 nm laser effectively removed bone leaving a thermal damage zone of only 2-3 microns in the remaining tissue. Increasing the energy per pulse gave correspondingly larger and deeper cuts with increasing zones of thermal damage. The excimer laser was also effective in the ablation of PMMA, creating craters in the substrate with a thermal damage zone of 10-40 microns. The debris from both substrates was evaluated.

Animals↗