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Biomedical subjects

J S Nelson

Publications and source records attributed to J S Nelson.

At least 145 records · Page 8Linked to original sources
PubMed1986

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery: final report of an RTOG study.

This randomized RTOG study evaluated misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. One hundred and forty-six evaluable patients were treated with conventional radiation therapy to 60.00 Gy in 6-7 weeks plus BCNU 80 mg/m2/d for 3 days every 8 weeks (XRT + BCNU). One hundred and forty-seven evaluable patients were treated with misonidazole 2.5 gm/m2 once a week for 6 weeks, radiation therapy to 60 Gy and BCNU (MISO + XRT + BCNU). Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics was comparable among the treatment groups. The median survival for XRT + BCNU was 55.0 weeks, and for MISO + XRT + BCNU 46.0 weeks (p = 0.35). With patients on a minimum dose of dexamethasone of 3 mg/d, misonidazole neurotoxicity included 8.8% peripheral neuropathy, 2.7% CNS toxicity, and a 0.68% ototoxicity. BCNU pulmonary toxicity occurred in 9.3% of patients who received 902-2062 mg/m2 of BCNU.

Adult↗
PubMed1986

Motoneuron electrophysiological and muscle contractile properties of superior oblique motor units in cat.

Intracellular techniques were used to study single motor units of the trochlear nucleus and superior oblique muscle in the cat. Motoneuron electrophysiological properties were correlated with muscle-unit contractile characteristics assessed under isometric conditions. Two distinct motor-unit types were identified and designated as twitch and nontwitch. Nontwitch units made up 5% of the total population studied. They responded only to tetanic stimulation with graded force that increased as stimulus frequency was increased up to 300-400 Hz. These units made up a homogeneous population in that they were innervated by slowly conducting axons, produced weak tetanic tensions, and were extremely fatigue resistant. Twitch units made up the majority (95%) of units studied. These units responded to single pulse stimulation with typical twitch contractions. The contraction speed and tension ranges for these units were comparable with those obtained from other extraocular muscle single units. Superior oblique twitch units, mechanically comparable with multiply innervated conducting units, identified in the cat inferior oblique muscle (31) were not observed. The twitch-unit population was heterogeneous in terms of neuromuscular fatigue resistance. Unit fatigability was inversely related to maximal tetanic tension. Motoneuron conduction velocity was related to muscle-unit contractile properties in a way similar to that seen in extremity motor units. The slowest twitch units were weak, fatigue resistant, and innervated by slow conducting axons. The fastest units were, in general, innervated by faster conducting axons, produced greater tetanic tensions, and were more susceptible to fatigue. Correlations among input resistance, rheobase, and conduction velocity were also observed. At present, subdivisions of the twitch-unit population on the basis of any one or combination of unit properties does not seem appropriate.

Animals↗
PubMed1985

Survival and prognosis of patients with astrocytoma with atypical or anaplastic features.

This study confirms the importance of histologic tumor necrosis as a major prognostic variable in malignant glioma. Necrosis is present in glioblastoma multiforme (GBM), and absent in astrocytoma with atypical or anaplastic features (AAF). This paper evaluates 94 patients with AAF and 462 patients with GBM treated with radiation therapy with or without BCNU on 3 consecutive randomized protocols of the Radiation Therapy Oncology Group (RTOG) between 1974 and 1983. Multivariate analyses of the 556 patients confirmed histology as a significant independent variable that is prognostically relatively more important than Karnofsky performance status (KPS) and extent of surgery, and somewhat less important than age. The median survival for AAF was 36.2 months and for GBM was 8.6 months. In addition, separate multivariate analyses of AAf cases determined that the extent of surgery is a significant independent variable that is relatively more important than KPS, but less important than age. The median survival of AAF patients who underwent surgical excision was 46.8 months compared with 15.2 months for those biopsied (p less than .001).

Adolescent↗
PubMed1985

Fast neutrons and misonidazole for malignant astrocytomas.

Twenty-five patients with biopsy proven malignant supratentorial astrocytomas were entered into a Phase I/II study of misonidazole combined with neutron radiation at Fermilab Neutron Therapy Facility (NTF) between August 1979 and April 1981. The main objectives were to determine tissue tolerance in terms of acute and late effects, and to estimate tumor clearance and survival rates. The total dose was 18.0 Gy given in weekly fractions of 3.0 Gy over 39 days. Four hours before each irradiation, 2.5 gm/m2 misonidazole was administered orally. Patients' ages ranged from 28-69 years. Karnofsky status for most patients was 80 or 90; the lowest grade was 60. The majority of patients had glioblastoma multiforms. Most were already on steroids prior to initiation of therapy. The median survival for the whole group was 12.0 months; 25% were alive at 18 months with some neurological compromise. The median survival remained unchanged for subgroups of patients with ages between 40-60 years and with Karnofsky performance status above 80. Among the 19 patients with glioblastoma multiforme, the median survival was 10 months. Acute toxicity was within tolerable limits. Details of toxicity and tissue analysis from post mortems and second craniotomy samples are presented.

Adult↗
PubMed1985

Comparison of fluorescence and photodynamic activities of whole hematoporphyrin derivative and its enriched active components.

The in vivo biologic activities of the hematoporphyrin derivative (Photofrin) and the enriched, so-called "active fraction" (Photofrin II) were determined by measuring the necrosis produced in implanted tumors in DBA/2Ha mice exposed to various total doses of light (20-100 J/cm2) after ip administration of 10 mg/kg standard doses of either Photofrin or Photofrin II. Total relative percentage increase in fluorescence in tumor tissue, as compared to fluorescence in control tissue, also was measured for both Photofrin and Photofrin II. In response to total light doses (630 nm) of 40-100 J/cm2, mice that received Photofrin had comparable amounts of tumor necrosis to those mice that received Photofrin II. At doses of 40-60 J/cm2, 80% tumor destruction resulted, and at 80-100 J/cm2, tumor destruction was 100%. However, at a total light dose of 20 J/cm2, the tumors that received Photofrin II exhibited 60-80% tumor necrosis, whereas those animals that received Photofrin had only small areas of patchy necrosis associated with signs of vascular thrombosis and hemorrhage into the surrounding perivascular stroma. A 25.2% total increase in maximal tissue fluorescence over that in controls was observed for animals that received Photofrin II, as compared to 13.9% for those animals that received Photofrin. It is concluded that the greater demonstrable efficacy of treatment with Photofrin II, as compared to treatment with Photofrin, is due to enrichment of those nonpolar hydrophobic components of the hematoporphyrin derivative mixture that are thought to be primarily responsible for the in vivo biologic activities.

Animals↗
PubMed1985

Histopathological comparison of the effects of hematoporphyrin derivative on two different murine tumors using computer-enhanced digital video fluorescence microscopy.

A comparison study of the effects of hematoporphyrin derivative (HPD) photoradiation therapy on two different mouse sarcoma tumor model systems (RIF-1 + EMT-6) was performed. Twenty-four h after i.v. administration of HPD, the responses to total laser light doses of 50-400 J/cm2 were evaluated by histological examination and the uptake and distribution of HPD using a computer enhanced digital video fluorescence microscopy technique. In response to total laser light dose (630 nm) of 50-400 J/cm2, 40 mice with RIF-1 tumor showed only minimal superficial tumor necrosis upon histological examination and a 9-12% increase in maximal tissue fluorescence. In contrast, 40 mice with EMT-6 tumor showed marked areas of patchy coagulation necrosis and vascular hemorrhage at doses as low as 50 J/cm2 and essentially total tumor destruction at total light doses of 150 J/cm2 or more. A 59-74% increase in maximal tissue fluorescence was observed using digital video fluorescence microscopy. It is concluded that the greater efficacy of treatment in the EMT-6 tumor as compared to the RIF-1 tumor was due to the greater localization of HPD as demonstrated by digital video fluorescence microscopy.

Animals↗
PubMed1984

Neuropathy of nitroimidazole radiosensitizers: clinical and pathological description.

The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. Subjective changes occur with or without minimal objective changes on neurologic exam. All of the neuropathies occurred within 30 days of the last drug dose and are of variable duration. Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes.

Etanidazole↗
PubMed1984

Cerebral astrocytic neoplasms in the adult: contribution of histologic examination to the assessment of prognosis.

Cerebral astrocytomas are the most common primary central nervous system (CNS) tumors in adults. As a group these tumors are characterized by histologic variability and inconstant prognosis. Nevertheless, microscopic examination of these tumors with identification of certain histologic features provides useful prognostic information. Evidence of anaplasia including necrosis, vascular endothelial proliferation, mitotic activity, cytologic pleomorphism, and foci of increased cellularity, when present in diffusely infiltrating astrocytic gliomas, is associated with aggressive behavior. In particular, the occurrence of tumor necrosis in anaplastic astrocytomas is reliably predictive of a highly unfavorable outcome. Specific histologic subtypes of cerebral astrocytoma with relatively benign course may also be identified. These include juvenile pilocytic astrocytoma, subependymal giant-cell astrocytoma, and, in some cases, pleomorphic xanthoastrocytoma. The critical influence of tumor location and the limitations imposed by potentially nonrepresentative biopsy material must be appreciated when assessing prognosis in cerebral astrocytomas. Prognostic data provided by histologic examination are useful in selecting treatment regimens and for evaluation of newly proposed therapies.

Adult↗
PubMed1983

Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study.

Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty-seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6-7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1-2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl-CCNU (125 mg/m2/day orally X 1 and repeat methyl-CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18-month survival of 64%, patients who were age 40-60 years had an 18-month survival of 20%, and patients who were older than age 60 had an 18-month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40-60-year-old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one-sided). Similarly, methyl-CCNU + DTIC was suggestively better than the control (P = 0.08, one-sided). The higher radiation dose, 7000 rad/8-9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl-CCNU + DTIC produced some toxicity. The combination of methyl-CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.

Adult↗
PubMed1983

Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas.

Surgical specimens of malignant, supratentorial, astrocytic gliomas from 503 patients randomized on an RTOG-ECOG treatment protocol were examined by central pathologic review. The diagnosis of glioblastoma multiforme (GBM) was made only when one or more foci of coagulation necrosis involving astrocytic tumor cells were identified histologically. Malignant astrocytic neoplasms without necrosis were classified as astrocytoma with atypical or anaplastic features (AAF). The median survival stratifying for treatment for patients with GBM was eight months compared to 28 months for patients with AAF. In most cases the specimens were received with a Kernohan grade. On the basis of these grades, patients with astrocytoma Grade 3 had a median survival of ten months as compared to a median survival of nine months for those with astrocytoma Grade 4. Observations demonstrate that necrosis is a reliable, decisive prognostic factor associated with malignant, supratentorial, astrocytic gliomas. The Kernohan system is of limited value in assessing prognosis for this group of tumors.

Aged↗
PubMed1983

Neuropathological studies of chronic vitamin E deficiency in mammals including humans.

Lesions in the nervous system and skeletal muscles of vitamin E-deficient rats, monkeys and humans were studied morphologically and morphometrically. The experimental animals were fed purified, vitamin E-deficient diets for periods from two months to six years. In some studies deficient animals were repleted by feeding 200 mg all-rac-alpha-tocopheryl acetate/kg diet. The humans were children with congenital biliary atresia, low serum levels of vitamin E, and a consistent, progressive neurological syndrome. These studies demonstrate that chronic vitamin E deficiency in rats, monkeys and humans is characterized by a progressive, systematic degeneration of large calibre, myelinated sensory axons in spinal cord and peripheral nerves. The axonopathy is most severe in the rostral segments of the posterior or dorsal columns. Dystrophic axons are numerous in the sensory relay nuclei of cord and medulla in rats and humans, and infrequent in monkeys. Primary, necrotizing myopathy occurs regularly in vitamin E-deficient rats and monkeys. Regenerative changes in the peripheral nerves and skeletal muscles of deficient animals are morphologically typical and develop promptly, despite the deficiency. Repletion of deficient animals with vitamin E interrupts both the axonopathy and the myopathy, indicating the direct role of vitamin E deficiency in the pathogenesis of both lesions.

Animals↗
PubMed1983

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery; preliminary results of an RTOG study.

A randomized prospective study was performed to evaluate misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. The control arm, Group A, consisted of conventional radiation therapy (6000 cGy/6-7 weeks) to the whole brain plus BCNU (80 mg/m2 on day 3, 4, 5, and then repeated q 8 weeks for 2 years). The BCNU schedule was identical in both arms. In the experimental arm, Group B, misonidazole 2.5 gm/m2 was given once a week for six weeks, to a total dose of 15 gm/m2. It was given orally four hours prior to 400 cGy on Mondays. On Tuesdays, Thursdays and Fridays, 150 cGy was delivered to a total of 5100 cGy/6 weeks. An additional 900 cGy/5F/1 week was given without misonidazole. Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics among the treatment groups was comparable. As of March 1, 1982, 245 patients were randomized with follow-up information available on 202 patients. The median follow-up is 12 months (range 3-39 months). There is no significant difference in the survival of the two groups. The median survival for Group A was 12.6, and for Group B, 10.7 months. Misonidazole toxicity included an 11% peripheral neuropathy and a 3% central nervous system toxicity. BCNU toxicity included severe hematologic toxicity in 25%, including one death, and significant pulmonary toxicity in 6 out of 55 patients who received a minimum total dose of 960 mg/m2 of BCNU.

Adolescent↗
PubMed1983

Intracerebellar hemorrhage in a premature newborn: diagnosis by real-time ultrasound and correlation with autopsy findings.

The identification of intracerebellar hemorrhage in a living premature infant by real-time ultrasound scan and confirmation of the findings at autopsy are described. This represents the first demonstration of the value of this noninvasive, convenient, and safe means of brain imaging in diagnosis of this lesion. Previous studies have described the role of the computed tomography (CT) scan in identification of intracerebellar hemorrhage in the newborn. Because infants with intracerebellar hemorrhage are usually critically ill, a means of identification of the lesion that could be utilized at the bedside rather than an approach that requires transport to a CT scanner is needed. This study indicates that portable real-time ultrasound scanning can satisfy that need.

Cerebellar Diseases↗
PubMed1981

A progressive neurologic syndrome in children with chronic liver disease.

A progressive neurologic syndrome developed in six children with longstanding cholestatic liver disease. The neurologic abnormalities included areflexia, gait disturbance, decreased proprioceptive and vibratory sensation, and paresis of gaze. Serum vitamin E concentrations were uniformly low. Neuropathological studies carried out in two of the three fatal cases revealed degeneration of the posterior column, selective loss of large-caliber, myelinated axons in peripheral nerve, and spheroids in the gracile and cuneate nuclei. These lesions are similar to those found in animals with experimentally induced vitamin E deficiency. We therefore speculate that the neurologic syndrome in these children may be the result of chronic vitamin E malabsorption.

Adolescent↗
PubMed1981

Progressive neuropathologic lesions in vitamin E-deficient rhesus monkeys.

A consistent group of progressive central and peripheral nervous system lesions developed in seven rhesus monkeys maintained on a vitamin E-deficient diet for 30 to 33 months. These lesions were absent from vitamin E-supplemented monkeys. The principal neuropathologic alteration was loss of sensory axons in the posterior columns, sensory roots, and peripheral nerves. Morphologic and morphometric studies indicated that the distal segments of the axons were affected most severely and large-caliber myelinated fibers are selectively involved. Swollen, dystrophic axons (spheroids) occurred infrequently. Degeneration and phagocytosis of small numbers of neuronal perikarya were observed in the dorsal root ganglia and the anterior horns. The number of affected neurons was not proportional to the number of affected axons. Accumulation of lipopigment was evident in neuronal perikarya and CNS endothelial cells. The nervous system lesion were usually accompanied by a chronic necrotizing myopathy. The neuropathologic lesions in vitamin E-deficient monkeys are compared with those in vitamin E-deficient rats and in humans with low serum vitamin E concentrations. A similar type of sensory axonopathy is associated with chronic deficiency of vitamin E in these three species.

Animals↗
PubMed1981

Association of cerebral infarction and chronic alcoholism: an autopsy study.

Central nervous system (CNS) infarcts were present at autopsy in 10 of 23 alcoholic patients and in 9 of 36 nonalcoholic patients. There were more males than expected in the infarct population and in the alcoholic population. Male subjects comprised the entire population of alcoholics with infarcts. In addition, a history of alcohol abuse was present in every case of cerebral infarction dying before age 75. The incidence of cardiomegaly was increased among the alcoholics. There were no differences between alcoholics and nonalcoholics in the incidence of diagnosed hypertension, moderate-to-severe coronary atherosclerosis, or adult onset diabetes. However, CNS infarction was more likely to occur at an earlier age in alcoholics than in nonalcoholics. Excessive alcohol consumption may be a risk factor in the premature development of cerebrovascular disease in males.

Adult↗
PubMed1981

Experimental diabetic autonomic neuropathy.

The regular occurrence of autonomic neuropathy, colonic dilatation, and loss of fecal consistency was investigated in streptozotocin-diabetic, age-matched control, and pancreatic-islet--transplanted rats using ultrastructural, histochemical, and biochemical methods. Degenerating unmyelinated axons were observed by electron microscopy in the colonic submucosa and muscularis, ileal mesentery, and splenic pedicle in 5--7 months diabetic animals; similar changes were not found in control rats or animals subjected to islet transplantation three weeks after induction of diabetes and sacrificed 4--6 months later (colon only). Regenerative changes, including axons with identifiable growth cones, were demonstrated in the mesenteric nerves of chronically diabetic animals. Formaldehyde-induced catecholamine fluorescence and cholinesterase histochemistry suggested deficiencies in colonic adrenergic and cholinergic innervation; histochemical findings in islet-transplanted animals were comparable to those of untreated control animals. Biochemical measurements of the adrenergic and cholinergic nervous system marker enzymes dopamine-beta-hydroxylase and choline acetyltransferase, respectively, in colon and spleen confirm a deficit in adrenergic (colon and spleen) and cholinergic (colon) innervation in chronically diabetic animals.

Animals↗