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Biomedical subjects

D Harmon

Publications and source records attributed to D Harmon.

51 records · Page 3Linked to original sources

Doxorubicin chemotherapy in the treatment of soft-tissue sarcoma. Combined results of two randomized trials.

In 1978, there were initiated two independent randomized, prospective trials of adjuvant doxorubicin hydrochloride (Adriamycin) following primary therapy for soft-tissue sarcoma. The virtual identity of these two protocols permits their combination for analysis. A total of 75 patients (42 men, 33 women) with soft-tissue sarcoma (stages IIB to IVA) were randomized, after receiving optimal regional therapy, to receive either doxorubicin hydrochloride (450 mg/m2) (37 patients) or observation (38 patients). Follow-up has ranged from 16 to 80 months (median, 49 months). Twenty-five patients (33%) died, and two patients receiving doxorubicin developed cardiotoxicity. No significant differences in local control, metastasis-free survival, disease-free survival, and overall survival were observed for the two treatment arms. Despite temporary prolongation of disease-free survival with doxorubicin in some subgroups, we conclude that there is no advantage to the use of adjuvant doxorubicin in the treatment of soft-tissue sarcoma.

Clinical Trials as Topic↗

Static magnetic field influence on rat tail nerve function.

Motor nerve conduction and excitability were measured on the tail nerve of anesthetized rats before and after the nerve was exposed perpendicularly to a static electromagnetic field of various intensities and durations. There was no significant change in either the distal latencies or the amplitudes of the compound muscle action potential (CMAP) measured from stimulating the tail nerve after it was exposed to the electromagnetic field with a density up to 1.2 Tesla (T) for a duration of 60 seconds. However, the nerve excitability expressed as changes of the amplitudes of the submaximally evoked CMAP increased significantly when the tail nerve was exposed to a magnetic field with a density higher than 0.5T for more than 30 seconds. The finding that an electromagnetic field increases motor nerve excitability suggests a possible mechanism of its therapeutic effects.

Action Potentials↗

Ruminal evacuation's effect on microbial activity and ruminal function.

The influence of evacuating, mixing and returning ruminal contents on microbial populations, volatile fatty acid (VFA) concentrations and liquid flow rate was investigated with four ruminal-cannulated Hereford steers (247 kg avg wt). Ruminoreticular contents were sampled, then completely removed, mixed for 5 min and returned to the rumen. Subsequent samples were taken immediately, 1 h and 4 h later. Non-evacuated steers were sampled at identical time intervals either 1 d before or after evacuation. Averaged over time, there was no significant difference between evacuated and non-evacuated steers in total anaerobic, cellulolytic and facultative bacteria, protozoa, oxidation-reduction potential, VFA concentrations, and liquid flow rates. There were no treatment X time interactions and, except for holotrich protozoa and VFA, no differences from time of sampling. Ruminal evacuation does not appear disruptive to anaerobiosis or detrimental to ruminal microorganisms and digestive processes.

Animals↗

Deficits in response inhibition and attention in rats rendered mentally retarded by early subcortical brain damage.

Young rats with lesions to either the globus pallidus, substantia nigra, median raphe, or pontine reticular formation have previously been reported to be deficient in learning a wide variety of laboratory tasks. In the current study, weanling rats subjected to one of these lesions were rested for three weeks, then examined for acquisition and extinction of a water-motivated straight alley task, and finally tested on luminous flux discriminations of increasing difficulty. All brain-damaged groups were slower than the controls in extinguishing the alley task and only the median raphe group failed to show an impairment on the discrimination problems. These results and others suggest that the foregoing lesions produce deficits in inhibitory and attentional processes. The possibility is discussed that young rats bearing these lesions might serve as a model for the investigation of the neurobiological and cognitive disturbances underlying certain classes of mental retardation in children.

Animals↗

Colonic absorption of 1,2-dimethyl hydrazine (DMH) in the rat.

1,2-Dimethyl hydrazine (DMH) is absorbed in the colon by passive diffusion in the 0.1-5.0 mM concentration range. Absorption of DMH is enhanced by both conjugated and unconjugated bile acids. The presence of hydroxy-fatty acids in the colon markedly increased DMH absorption while fatty acids of different chain length did not influence absorption.

1,2-Dimethylhydrazine↗

Effects of thoracic spinal cord transection on colonic motor activity in rats.

The resting colonic motor activity before and consecutively after spinal cord transection was recorded in male Sprague-Dawley rats. Recording probes were anchored surgically in the ascending and descending colon. Pressure changes were recorded on a dynograph using a low compliance perfusion system. A motility index took into account the amplitude, duration and frequency of contractions. Following a baseline recording animals were subjected either to spinal cord transection at T4 level or a sham operation. The recording sessions continued regularly on alternate days for the observation period of 3 weeks. Transection of the thoracic spinal cord markedly reduced the motility index of the distal colon on the first postoperative day. However, the motor activity gradually returned to pre-operative values after 7 days. Sham surgery did not influence the motor activity. These findings suggest that colonic motor activity is influenced by spinal shock and probably by different neural mechanisms mediating proximal and distal activities of the colon in rats.

Animals↗

Antineutrophil antibodies in infectious mononucleosis.

Antineutrophil antibodies were detected in the serum of 12 of 14 patients with acute Epstein-Barr virus-induced infectious mononucleosis. These antibodies were present in two patients with mononucleosis and severe neutropenia, and in 10 patients with mononucleosis uncomplicated by severe neutropenia. Antineutrophil antibodies were not detected in serum from five patients with cytomegalovirus-induced mononucleosis, or five renal allograft recipients with primary or reactivation Epstein-Barr virus infection. This study suggests that antineutrophil antibodies are among those produced by the polyclonal activation induced by Epstein-Barr virus during acute infectious mononucleosis.

Adult↗

Colonic absorption of acetylsalicylic acid in the rat.

Aspirin is absorbed in the colon by passive diffusion to a significant degree in spite of the alkaline pH of the colonic lumen. Aspirin absorption by the colon is enhanced by increasing the hydrogen ion concentration. Butyric acid, by markedly reducing the absorption rate of aspirin, may be partially responsible for the unpredictable absorption of rectally administered aspirin. The addition of glycerol to aspirin preparations does not hinder the absorption of aspirin by the colon.

Animals↗

Radiation therapy of retroperitoneal soft tissue sarcomas.

Between 1971 and 1982, 23 patients have been treated with radiation therapy at the Massachusetts General Hospital (MGH) for retroperitoneal soft tissue sarcomas. Seventeen patients were treated with curative intent and six with palliative intent. Of the patients treated with curative intent, the 5 year actuarial survival rate was 54% and the 5 year actuarial local control rate was also 54%. With a complete surgical resection local tumor control was obtained in 5 of 7 patients (71%), 4 of 7 (57%) with incomplete resection and 1/3 (33%) with no resection having local control. The radiation dose appeared to influence tumor control with 2 of 6 patients (33%) having local control with less than 5,000 cGy compared to 0 of 5 patients with doses of 5,000 to 6,000 cGy and 5 of 6 (83%) with doses greater than 6,000 cGy. An effect of tumor grade on either local control or on rate of metastasis formation could not be demonstrated in this series. Long-term local control and survival appears to be associated with maximal surgical resection and high dose radiation therapy.

Adult↗

Preliminary results of a randomized trial of adjuvant doxorubicin for sarcomas: lack of apparent difference between treatment groups.

Forty-two patients with localized intermediate and high-grade sarcoma were randomized after optimal primary treatment to receive five cycles of adjuvant doxorubicin 90 mg/m2 every three weeks (20 patients) or observation (22 patients). Patients were stratified for grade, size, extent of surgical margin, and soft tissue versus other sarcomas. Groups appeared balanced for histology and superficial versus deep lesions. Eight patients (19%) have died. Follow-up times range from two to 69 months (median, 16 months). Two patients receiving doxorubicin (10%) developed cardiotoxicity presenting as pulmonary edema. One patient returned to normal activity on digoxin and diuretics; the other (age, 28 years) died of intractable failure and arrhythmias after four weeks. While a nonsignificant difference in local control, metastasis-free survival, disease-free survival, and survival was observed for extremity lesions, the advantage may be outweighed by the risk of cardiotoxicity. Seventy-six percent of the control patients with extremity lesions remain disease free. Because control patients do well, a very large study is required to define the role of adjuvant doxorubicin.

Adult↗

Characterization of a distinct nuclear acidic protein antigen (MA) and clinical findings in systemic lupus erythematosus patients with MA antibodies.

Circulating antibodies against certain nuclear acidic protein antigens have been shown to have diagnostic and prognostic importance in connective tissue disease. We describe a new precipitin system found in the sera of patients with systemic lupus erythematosus. The antigen, called MA, was prepared from calf thymus nuclei, and was shown to be distinct from other nuclear acidic protein antigens by physicochemical and immunologic techniques. MA antibodies were detected in the serum of 12 of 66 lupus patients and in none of 554 sera from normal controls or patients with other rheumatic diseases. Lupus patients having MA antibodies had more severe disease than did lupus patients with Sm or native DNA antibodies, manifested by recalcitrant skin rashes and a significantly greater incidence of hypocomplementemia, serious renal disease, hypertension, hepatosplenomegaly, lymphadenopathy, and neurological disease (P values range from 0.025 to 0.005). The presence of circulating MA antigen was demonstrated in three lupus patients immediately before a flare of nephritis. These data suggest that MA is a nuclear acidic protein antigen that may identify a subset of lupus patients with very severe disease. The presence of the antigen in the circulation before clinical flares suggests a possible biologic role for the MA system in an immune complex nephritis.

Antibodies, Antinuclear↗

Hypermethylation of the Myf-3 gene in human colorectal cancer.

Abnormal methylation of DNA is one of the earliest detectable changes in human tumors. We investigated hypermethylation of the Myf-3 gene, the human homolog of the mouse myogenic gene Myo-D1, in colorectal adenomas and adenocarcinomas. Histologically normal gut mucosa from colorectal cancer patients showed moderately higher levels of methylation than in other normal tissues. Varying degrees of Myf-3 hypermethylation were found in all five adenomas and eight adenocarcinomas examined. Carcinomas arising from within adenomas generally showed a decrease in both the heterogeneity and intensity of Myf-3 methylation. Regional hypermethylation of this gene therefore appears to be an early event in human colorectal neoplasia.

Colorectal Neoplasms↗

Hypermethylation of HpaII recognition sequences within the 5' coding region of the estrogen receptor gene is not associated with estrogen receptor negativity in primary breast tumours.

Estrogen receptor negative tumours are unable to respond to antiestrogen therapy. The underlying molecular mechanisms of estrogen receptor negativity are poorly understood. Cytosine mechylation is one of the mechanisms of gene control and previous studies, particularly on breast tumour derived cell lines have suggested that hypermethylation of HpaII recognition sequences within the 5' coding region of estrogen receptor may be responsible for gene inactivity. This study has examined the methylation status of HpaII recognition sequences in estrogen receptor positive and negative breast tumours taking into account a polymorphic HpaII site in the 5' coding region of the estrogen receptor gene. It is concluded that hypermethylation of one or more of the 4 or 5 HpaII recognition sequences in the 5' coding region of estrogen receptor is not associated with ER negativity in primary breast tumours.

Adenocarcinoma↗