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Biomedical subjects

J F Wilson

Publications and source records attributed to J F Wilson.

At least 199 records · Page 11Linked to original sources

The pathology of non-Hodgkin's lymphoma of childhood: II. Reproducibility and relevance of the histologic classification of "undifferentiated" lymphomas (Burkitt's versus non-Burkitt's).

The Children's Cancer Study Group conducted prospective clinical trials of 608 children with non-Hodgkin's lymphoma from 1977 to 1983. In 1980, significant differences in survival of children with disseminated disease correlated with histologic diagnosis and the randomized treatment employed. A pathology reproducibility review showed the lymphoblastic lymphoma cases to be virtually 100 per cent distinguishable histologically from the nonlymphoblastic lymphomas (Burkitt's, non-Burkitt's, and "histiocytic"). However, diagnostic reproducibility of the pathologist-of-record was 59 per cent in the Burkitt's and non-Burkitt's lymphoma group. Therefore, 159 cases, agreed on by the pathologist-of-record and the "lymphoma panel" as Burkitt's (77 cases) or non-Burkitt's lymphoma (82 cases) and designated as the "reference diagnosis," were blindly reviewed twice each by two hematopathologists to yield the "review diagnoses." Consensus agreement was achieved in 67 per cent of cases overall, 82 per cent of Burkitt's and 54 per cent of non-Burkitt's lymphoma. Using the "reference diagnoses," we found that the relative frequency of Burkitt's and non-Burkitt's lymphoma was associated with the extent of disease at diagnosis (P = 0.06) but not with other prognostic factors. Despite the difficulties in histologic classification, analyses that used either "reference diagnoses" or "consensus review diagnoses" and that were adjusted for extent of disease consistently demonstrated significantly shorter event-free survival for patients having Burkitt's lymphoma; their failure rate was four times that for patient's with non-Burkitt's lymphoma. Newer cell biologic techniques hopefully will enhance histopathologic distinctions that remain the basis for diagnosis.

Burkitt Lymphoma↗

The effects of delay in standard treatment due to induction chemotherapy in two randomized prospective studies.

It is often suggested that tumors will respond to induction chemotherapy and result in improved survival for patients with squamous cell carcinoma of the head and neck. Two regimens of induction chemotherapy were studied in separate randomized, prospective trials over the last 6 years. Eighty-three patients with advanced disease were entered into the first study (43/chemotherapy; 40/control), and 60 into the second (27/chemotherapy; 33/control). Patient randomization was stratified by stage (III/IV) and site (oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, paranasal sinuses). The first study utilized bleomycin, Cytoxan, methotrexate and 5-fluorouracil in two cycles (one cycle if no tumor response), followed by standard treatment which consisted of combined irradiation and surgery or, in some instances, primary irradiation alone. The second study utilized cisplatin and 5-fluorouracil in three cycles prior to standard treatment. An objective tumor response to chemotherapy was observed in 68% in the first study and 85% in the second. The patient survival in both studies (at 24 months in the first; at 19 in the second) was better in the control than that in the experimental groups (43% to 31%; 69% to 46%). In the second study, the average length of delay of standard treatment was longer than in the first study (95 days vs. 66 days; P less than .02). Results combining the P-values of both studies indicate that the relative risk of having persistent disease was 2.9 times greater for patients who received chemotherapy. While toxicity to chemotherapy was not a factor in survival, the number of patients who withdrew from the studies and those who did not comply with treatment were greater in the chemotherapy groups. Except for new drug regimens of exceptional promise, it is recommended that future studies be designed so that chemotherapy is given concurrent with, or following the completion of standard treatment.

Antineoplastic Combined Chemotherapy Protocols↗

An animal model of excessive eating: schedule-induced hyperphagia in food-satiated rats.

Nineteen rats were maintained throughout the experiment on ad libitum wet mash and water and were trained to press a lever on fixed-interval or fixed-ratio schedules of reinforcement with electrical brain stimulation. Fourteen rats ate at least 150% more mash during intermittent reinforcement sessions than during baseline, massed reinforcement control, and/or extinction sessions. In a 3-hr session, 11 of those 14 consumed more than 22 g of wet mash (13 g dry weight), the equivalent of nearly half an animal's daily food intake. In subsequent control sessions, the electrodes did not support stimulus-bound eating despite attempts to make stimulation parameters optimal. These results indicate that the eating was schedule induced or adjunctive, and suggest that the procedure may provide an animal model of excessive nonregulatory eating that contributes to obesity in humans.

Animals↗

Spontaneous death of Echinococcus multilocularis: cases diagnosed serologically (by Em2 ELISA) and clinical significance.

Nine cases of asymptomatic alveolar hydatid disease (AHD) of the liver were diagnosed in 1985 among Eskimos from the endemic region of western Alaska. The patients were identified by screening with the enzyme-linked immunosorbent assay, using purified Echinococcus multilocularis antigen (Em2 ELISA). Five patients, and one diagnosed earlier (1979), were found to have lesions in which the larval E. multilocularis had died spontaneously at an early stage of infection. Viability was assessed histologically; by the avidin-biotin immunohistochemical method; and in vivo through intraperitoneal inoculation of membranes of the larval cestode into red-backed voles, Clethrionomys rutilus. The results were in agreement with the clinical impression, based on findings by computerized tomography and ultrasound scanning, and on the macroscopic appearance of the lesions, that the cestode was dead. Spontaneous death of E. multilocularis in humans has not been previously reported. The findings show that the Em2 ELISA may be positive in patients having lesions of AHD in which the etiologic agent is no longer viable.

Aged↗

Albendazole therapy in alveolar hydatid disease: a report of favorable results in two patients after short-term therapy.

Albendazole was administered preoperatively to two patients with active alveolar hydatid disease for 58 and 84 days. Vesicles of larval Echinococcus multilocularis obtained from surgical tissues were inoculated into red-backed voles for in vivo testing viability. No proliferation of the larval cestode had occurred when the animals were dissected three months post-inoculation. These findings suggest that short-term therapy with albendazole was effective in killing the larval cestode in these two cases. Albendazole was found to be hepatotoxic but resulting transaminase abnormalities have been reversible. Close monitoring of liver function and hematology is essential in patients under albendazole therapy.

Adult↗

Comparison of serologic tests for the diagnosis and follow-up of alveolar hydatid disease.

Alveolar hydatid disease is a serious and often fatal condition caused by infection with the metacestode form of Echinococcus multilocularis. Sera of 21 patients with histologically confirmed disease were tested by an enzyme-linked immunosorbent assay (ELISA) using a semi-purified E. multilocularis antigen fraction (Em2) and by indirect hemagglutination (IHA) and double diffusion (DD5) tests using antigens prepared from E. granulosus cyst fluid. At diagnosis, sera from all 21 patients were positive by Em2 ELISA, 18 (86%) by IHA, and 5 (24%) by DD5. Em2 ELISA detected an antibody response earlier than IHA in 4 of 9 patients from whom sera were available before diagnosis. Following complete surgical resection, Em2 ELISA converted from positive to negative in serum of 2 of 3 patients, while IHA results did not change. Following incomplete resection, 14 of 15 patients tested remained positive by Em2 ELISA, while 12 remained positive by IHA. Of sera from 361 healthy persons from regions free of E. multilocularis, none were positive by Em2 ELISA, while 8% were positive by IHA. Of sera from 59 patients with non-echinococcal parasitic infections, none were positive by Em2 ELISA, while 31% were positive by IHA. Thus, in comparison with tests using E. granulosus antigens, Em2 ELISA appears to be more sensitive and specific for diagnosing AHD, useful on follow-up of resected patients, and positive earlier in the course of disease.

Adult↗

Prognostic significance of interval from preoperative irradiation to hysterectomy for endometrial carcinoma.

From 1965 through 1980, 193 patients with histologically proven endometrial carcinoma, FIGO-AJC Stage I-III, received preoperative radiation therapy. One hundred forty-two patients had Stage I (G1:41, G2:68, G3:33), 47 Stage II, and 4 Stage III endometrial carcinoma. All patients were treated with preoperative radiation therapy (intracavitary application, external pelvic irradiation or both) followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). They were followed from 3 to 18 years (median, 6.2 years) after the completion of the treatment and none was lost to follow-up. Overall 5-year actuarial disease-free survival was 85%. The interval between the completion of radiation therapy and TAH-BSO ranged from 3 days to 123 days (median, 40 days). Five-year and 10-year survivals were 95% among 65 patients who did not have residual cancer in the hysterectomy specimen compared to 75% and 70%, respectively, among 128 patients who had positive hysterectomy specimens (P less than 0.01). The presence or absence of residual carcinoma in the surgical specimen after preoperative irradiation was the only important prognostic variable. The most significant factors associated with residual cancer cells were the interval from the completion of radiation therapy to TAH-BSO (P less than 0.001) and the method of preoperative irradiation in patients with Stage I Grade 3 and Stage II external pelvic irradiation was less frequently associated with residual cancer than intracavitary applications (P = 0.043). With one exception, all patients who failed had residual cancer in the hysterectomy specimen. The depth of myometrial invasion of residual tumor in the hysterectomy specimen after preoperative irradiation was correlated to the frequency of failures (P = less than 0.05). Failures were distributed equally among the pelvis, para-aortic nodes, and distant sites. Complications of treatment were infrequent (7%) and were mild; no fatal complications were seen. The data suggest an optimal interval for hysterectomy is 29 to 42 days after completion of radiation therapy in unfavorable carcinomas of the endometrium. These patients also benefit from external pelvic irradiation with or without intracavitary applications as this therapy provides the highest probability there will be no residual cancer cells in the surgical specimen.

Adenocarcinoma↗

Noise-induced eating in rats facilitated by prior tail pinch experience.

In order to integrate the results of procedures that induce excessive nonregulatory eating, it is necessary to develop new procedures that elicit eating in satiated animals. To that end, the present study examined the effects of 90-dB white noise on eating in satiated rats. Twenty-four rats, including sixteen with prior tail pinch-induced eating experience, were presented with mash in baseline and noise conditions. Whereas white noise induced eating in tail pinch-experienced rats, noise did not do so in naive subjects. It was concluded that experience with eating in response to arousal increased the likelihood that an animal would respond to a different kind of arousal by eating.

Animals↗

Is adenocarcinoma/large cell carcinoma the most radiocurable type of cancer of the lung?

Radiation therapy is widely considered the primary treatment for inoperable "non-small" cell carcinoma of the lung. In clinical investigations, distinction has been infrequent among the histopathologic subtypes of non-small cell carcinoma. Studies have shown significant differences between squamous cell carcinoma and adenocarcinoma/large cell carcinoma; adenocarcinoma/large cell carcinoma has a greater propensity for extrathoracic dissemination, especially to the brain, and it is less curable by resection when regional lymph node metastases are present. No differences have been documented between adenocarcinoma and large cell carcinoma. A retrospective study was undertaken to determine the results of definitive radiation therapy by histopathologic subtype of non-small cell carcinoma of the lung. Between July 1977 and April 1983, 134 patients with non-small cell carcinoma of the lung underwent definitive radiation therapy with curative intent. All patients had performance status scores of 80 to 100 (Karnofsky), and received minimum total doses within the tumor of 60 Gy in 6 to 7 weeks, five fractions per week. The median period of observation was 63 months. Ninety patients had squamous cell carcinoma; 44 had adenocarcinoma/large cell carcinoma. The two groups of patients were comparable in respect to age and Stage; there were significantly more women with adenocarcinoma/large cell carcinoma (27%) than with squamous cell carcinoma (13%). The median survival for patients with squamous cell carcinoma was 11.5 months; the 2 and 4 year survival rates were 21 and 7%, respectively. The median survival for patients with adenocarcinoma/large cell carcinoma was 18 months; 2 and 4 year survival rates were 38 and 23%, respectively. Comparison of the overall survival experience did not show a significant difference between the two cell types (p = .12 using Gehan's generalized Wilcoxon test). However, comparison of the proportion of patients with adenocarcinoma/large cell carcinoma surviving 18 months (50%) was significantly higher (p = .02) than that with squamous cell carcinoma (30%). A small body of data from the literature also suggests a better long-term prognosis for adenocarcinoma/large cell carcinoma. This observation requires confirmation from large trials with histopathologic review. If it is confirmed, there are important implications for therapeutic strategies in future clinical investigations of inoperable carcinoma of the lung.

Adenocarcinoma↗

Consequences of continuous mebendazole therapy in alveolar hydatid disease--with a summary of a ten-year clinical trial.

The assessment of a ten-year clinical trial of continuous therapy in eight patients revealed further evidence of a significant therapeutic effect of mebendazole on alveolar hydatid disease. Life-expectancy was increased when compared to untreated historical controls, especially in the patients over 55 years of age. All symptomatic patients showed subjective improvement. In four patients, three had a 50% or greater reduction in the diameter of massive hepatic lesions, and in the fourth, progressively enlarging metastases were arrested. Fall in the IHA titre suggested that the causative organism had been destroyed in two additional patients. Of greater significance was the absence of progression of the disease process as measured by changes in the size of the hepatic lesion or lack of development of distant metastases in patients under therapy. In contrast, progressive enlargement of hepatic lesions or the appearance of distant metastases were cardinal features of untreated cases (15 of the 16 cases followed). In vivo determination of viability of tissues of the larval Echinococcus multilocularis from patients receiving long-term therapy was considered important in evaluating efficacy of the drug. Such tissues, obtained by autopsy from two patients under continuous therapy for four and ten years, failed to proliferate when inoculated into rodents (red-backed voles), whereas similar inoculations from untreated patients or those receiving 15 months' or less of therapy brought about production of vesicles in rodents in eight of 11 tests (73%). These two deaths, unrelated to therapy, resulted from late fibrotic constriction of end-stage parasitic lesions about the portal vein and major bile ducts. The clinical findings in combination with negative in vivo tests and other data indicate that the mebendazole therapy significantly alters the clinical course of alveolar hydatid disease. The evidence strongly indicates that long-term therapy may eventually have a lethal effect on the larval cestode in advanced disease.

Adult↗

Exercise-induced hand tremor: a possible test for beta 2-adrenoceptor selectivity in man?

The effects of intravenous doses of propranolol, sotalol, timolol, atenolol and placebo on exercise-induced tachycardia and exercise-induced increases in hand tremor were assessed in four healthy volunteers. All active drugs produced significant reductions in exercise-induced tachycardia. Exercise caused consistent significant increases in hand tremor which were blocked by the three non-cardioselective drugs but not by atenolol or placebo. The blockade of exercise-induced hand tremor is suggested as a possible test for the assessment of the selectivity of beta-adrenoceptor blockade in man.

Adrenergic beta-Antagonists↗

Alexander's disease.

This is the first pathologic report of an infant at 37 weeks' gestation with Alexander's disease. The findings demonstrate that the disease can arise in utero and be extensive at birth before myelination begins.

Adult↗

The guide gutter or loop techniques of interstitial implantation and the Paris system of dosimetry.

The predictive dosimetry system for implants known as the Paris system can be used with either loops or hairpins. When using the guide gutter technique, implant geometry is predetermined by the inherent spacing and parallelism of the branches of the hairpins. When using loops, their branches should not be spaced too widely apart and should be parallel over an adequate distance to obtain a fairly regular dose distribution between them. The basic principles of implantation are the same as for rectilinear sources. Branches must be rectilinear, parallel, arranged so that their centers are located in the same plane (central plane). Adjacent branches must be equidistant from each other and the reference linear kerma rate (or the linear activity) must be uniform and identical for all sources. When these conditions are met, the dimensions of the treated volume (volume encompassed by the reference isodose surface with a value equal to 85% of the basal dose rate) can be estimated at the time of the implantation procedure. In practice, only a few relationships presented in this paper, with examples of application, must be known. Although, the Paris system permits forecasting the final dosimetry, the geometry of the implant must be verified and the dose calculated according to the implantation as actually achieved. The best method of checking the exact position of radioactive sources in an implant and determining the dose rate at any desired point is a reconstruction by computer program although alternative methods are occasionally appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

Brachytherapy↗

Tremor: an alternative approach for investigating adrenergic mechanisms in thyrotoxicosis?

The effects of nadolol (or placebo) and carbimazole on thyrotoxic tremor were investigated in 18 thyrotoxic patients. Both nadolol and carbimazole produced significant reductions in tremor power although nadolol did not cause any change in serum free tri-iodothyronine and free thyroxine concentrations. The results are discussed in terms of the pathogenesis of thyrotoxic tremor and the potential usefulness of tremor in the investigation of adrenergic mechanisms in thyrotoxicosis.

Adrenergic beta-Antagonists↗