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Biomedical subjects

J J Fischer

Publications and source records attributed to J J Fischer.

At least 37 records · Page 2Linked to original sources
PubMed1989

Randomized clinical trial of mitomycin C as an adjunct to radiotherapy in head and neck cancer.

A randomized prospective clinical trial was carried out to assess the usefulness of the addition of mitomycin C to radiation therapy used alone or in combination with surgery for the treatment of squamous cell carcinoma of the head and neck region. One hundred and twenty patients with biopsy proven tumor of the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx were randomly assigned to receive or not receive mitomycin C; all other aspects were similar in the two treatment groups. One hundred and seventeen patients were evaluable with a median follow-up time of greater than 5 years. Acute and chronic normal tissue radiation reactions were equivalent in the two treatment groups. Hematologic and pulmonary toxicity were observed in the drug treated patients. Actuarial disease-free survival at 5 years was 49% in the radiation therapy group and 75% in the radiation therapy plus mitomycin C group, p less than 0.07. Local recurrence-free survival was 66% in the radiation therapy group and 87% in the radiation therapy plus mitomycin C group, p less than 0.02. The findings demonstrate that mitomycin C can be administered safely as an adjunct to radiation therapy in the treatment of head and neck cancer. The drug improves local tumor control without enhancing normal tissue radiation reactions.

Adult↗
PubMed1989

Pulmonary function and symptoms after inhalation of endotoxin.

In previous experiments, a good relationship was demonstrated between the amount of airborne bacterial endotoxin and acute reactions after exposure to organic dusts. In the present study, 77 naive subjects were exposed to isolated endotoxin (IE) or endotoxin attached to bacterial cells (CE). Both preparations were obtained from Enterobacter agglomerans, which is a major bacterial species in many organic dusts. The major physiologic effect caused was a dose-related decrease in transfer factor, as measured by carbon monoxide diffusion. Half of the subjects reported fever and about one-third a subjective feeling of chest tightness. The exposure also caused a dose-related but small decrease in FEV1. A slightly increased bronchial reactivity was demonstrated at 4 h after endotoxin exposure. The minute volume after CO2 exposure was marginally affected. The results further support the conclusions from epidemiologic and experimental studies that the bacterial endotoxin is responsible for the acute reactions seen after exposure to many organic dusts, including that derived from cotton.

Aerosols↗
PubMed1988

Changes in the levels of bioactive components of cotton bracts accompanying senescence.

A series of bracts from Deltapine 41 variety cotton were harvested weekly from October 16 through November 25, 1982, and examined for changes in biologically active components accompanying senescence. Aqueous extracts of cotton bracts (CBE) were tested for their ability to cause 5-hydroxytryptamine (5-HT) release from human platelets and contraction of isolated canine tracheal smooth muscle (TSM). In addition, the amounts of soluble tannins (the platelet-activating factor found in CBE) and endotoxin were determined for each CBE. The amount of CBE decreased significantly from October 16 through November 25, whereas endotoxin levels rose dramatically from October 23 to November 6 and declined thereafter. The amount of soluble tannin and platelet 5-HT release both decreased from highs on October 23 to unmeasurable levels on November 25. Smooth muscle contraction was attributed to two primary factors contained in CBE. The major constrictor was a 5-HT receptor agonist and its levels remained stable from October 16 through October 30, but then decreased to unmeasurable levels by November 13. In contrast, CBE also contained lesser amounts of an acetylcholine receptor agonist whose levels paralleled the changes in endotoxin levels. We conclude that several important biochemical changes occur in cotton bracts during senescence and that these changes profoundly influence their biological activity in various assays.

Animals↗
PubMed1988

Development of an 241Am applicator for intracavitary irradiation of gynecologic cancers.

Sealed sources of 241Am that emit primarily 60 keV photons produce relative dose distributions in water comparable to those from 137Cs or 226Ra sources and can produce dose rates of up to 100 cGy/hr at 1 cm in water. Also, 241Am gamma rays can be effectively shielded by thin layers of high atomic number materials (HVL is 1/8th mm of lead) placed on the applicator or inside some body cavities (for example, hypaque in bladder, barium sulphate in rectum). These properties of 241Am sources open a new approach to optimizing intracavitary irradiation of various cancers by allowing a reduction in dose and volume of irradiated critical organs or by increasing tumor doses. The relative ease with which highly effective shielding is achievable with 241Am sources would allow the design and fabrication of partially shielded applicators which can produce asymmetric dose distributions to allow unidirectional irradiation of localized lesions. Design and dosimetry characteristics of a gynecological applicator containing 241Am sources are presented. The applicator consists of a 2, 3, or 4 segment vaginal plaque (loaded with 2 and 5 Ci 241Am sources) and a tandem made up of a single 8 Ci 241Am source. Dose rates at 2 cm from the plaques are 42.0, 47.4, 58.3 and 56.7 cGy/hr for 5-5, 5-4-5, 5-5-5, and 5-4-4-5 Ci plaques, respectively. The 5-4-5 Ci plaque in combination with the 8 Ci tandem produces dose rates of 60.0 and 22.8 cGy/hr to points A and B, respectively. Surface dose rates on the plaque applicators are 143, 124, 142 and 132 cGy/hr for 5-5, 5-4-5, 5-5-5 and 5-4-4-5 Ci applicators, respectively. The shielding effect of a 0.5 mm thick lead foil on one side of the 5-4-5 Ci applicator is found to be a factor of 16.8; for example, the dose rate at 2 cm from the unshielded side is 42.0 cGy/hr compared to a dose rate of 2.5 cGy/hr at 2 cm from the shielded side. Initial clinical experience with this applicator in the treatment of recurrent gynecological lesions is also presented.

Americium↗
PubMed1988

Olfactory neuroblastoma. Observations on seven patients treated with radiation therapy and review of the literature.

Seven patients with olfactory neuroblastoma were treated, using the staging classification proposed by Kadish (stage A two patients, stage B one, stage C three, and local recurrence one patient). Treatment was not uniform. Radiation therapy was employed initially as the only treatment modality in three patients who had stage A, B, and C, respectively. In one instance, it was used to treat a local recurrence after surgical treatment. Surgery and radiation therapy was employed in three patients: one with stage A and two with stage C. Chemotherapy was used as an adjuvant to radiation and surgery in one patient with stage C, and in three individuals, it was used for advanced disease. Four of the seven patients are alive without evidence of disease from 23 months to 16 years 8 months after treatment. A review of 11 series from the recent medical literature is presented. It is essential to follow these patients for long periods of time because of the slow growth and the propensity of local recurrence that some of these tumors have. The actual tendency in the management of this neoplasm seems to be combined therapy with surgery and radiation. The role of adjuvant chemotherapy is not well established, but has been recommended for locally advanced disease.

Adolescent↗
PubMed1988

Magnetic resonance, pathology and physiology of the BA1112 rhabdomyosarcoma in vivo.

We studied histology, findings on H-1 magnetic resonance (MR) imaging, and correlations of P-31 MR spectroscopy with microelectrode pH and pO2 measurements in the BA1112 rhabdomyosarcoma in WAG/Rij/Y rats. Intratumoral hemorrhage was a prominent feature on MR images and pathologic specimens. Eosinophilic necrosis could be seen microscopically but was not discernible on images. The peaks seen on P-31 MR spectra were similar to those reported in other tumors. The intratumoral pH was neutral despite low pO2 values and P-31 MR evidence for impaired metabolic status.

Animals↗
PubMed1988

Combined modality therapy for advanced Hodgkin's disease: 15-year follow-up data.

From 1969 through 1982, 184 patients with advanced Hodgkin's disease (HD) were treated with combined modality therapy (CMT) at Yale University. The data were reanalyzed in November 1986, with a mean follow-up of 10 years. The patient population consisted of 102 newly diagnosed stages IIIB and IV patients, and 82 patients who had relapsed after initial radical radiotherapy. From 1969 through 1978, the treatment program was induction chemotherapy with nitrogen mustard, vincristine, vinblastine, procarbazine, and prednisone (MVVPP) for three cycles (6 months) followed by low-dose radiation (1,500 to 2,500 cGy) for patients who had achieved complete remission (CR), to all disease sites present before the onset of chemotherapy. From 1978 to 1982, selected "poor-risk" advanced-stage patients received nitrogen mustard, vincristine, procarbazine, prednisone plus Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (MOPP-ABVD) induction chemotherapy, while the remaining patients were randomized between MVVPP and MOPP. One hundred fifty-one patients have achieved CR (82%); 23 (15%) of these 151 have relapsed, with the remaining 128 patients in continuous CR. A total of 62 patients have died, 45 due to HD, and 17 due to other causes. Twelve of these 17 patients died of second malignancies. The 15-year actuarial survival of all patients is 54%. It is 71% if deaths due only to HD are considered. Within the overall group of advanced HD patients, age and multiple extranodal sites of involvement continue to constitute adverse risk factors. The three drug programs used were all equivalent. No improvement resulted from the use of MOPP-ABVD in the poor-risk patients. These results compare favorably with those recently published by the National Cancer Institute (NCI). CMT resulted in an approximate 20% improvement in survival with no increase in second malignancies when compared with chemotherapy alone.

Adult↗
PubMed1987

Enhancement of tumor radiation response by the combination of a perfluorochemical emulsion and hyperbaric oxygen.

The presence of radioresistant hypoxic cells in tumors is believed to be one of the limiting factors in achieving local tumor control by radiotherapy. Treatment with hyperbaric oxygen during irradiation has been shown to improve the radiation response of many solid tumors in rodents and of some tumors in patients. Intravenous administration of perfluorochemical emulsions combined with oxygen breathing at atmospheric pressure has also been shown to improve the radiation response of several rodent tumors. Theoretical considerations suggest that the combination of a perfluorochemical emulsion and hyperbaric oxygen should be significantly more effective than either agent alone. This hypothesis was tested by examining the radiation response of BA1112 rhabdomyosarcomas growing in WAG/rij-Y rats. Treatment with a perfluorochemical emulsion, Fluosol-DA, plus hyperbaric oxygen (3 Atmospheres O2) significantly increased the radiation response of the malignant cells in these solid tumors. The observed changes in the tumor cell survival curve suggest that the combination of Fluosol-DA and HBO decreases the proportion of severely hypoxic cells in the tumor to less than 1.5% of the original value. The effect of the Fluosol-DA dose and the duration of pretreatment with HBO are described.

Animals↗
PubMed1987

Development of an 241Am applicator for continuous low-dose-rate irradiation of the rat sarcoma BA1112.

An 241Am applicator for continuous low-dose-rate irradiation of the rat sarcoma BA1112 has been developed. The irradiator consists of two disc sources, each containing 800 mCi of 241Am, an isotope which emits primarily 60 keV photons. The disc sources are held in a specially-designed light-weight helmet which surrounds the tumor on the head of the rat. Dose distributions produced by these sources have been measured using an ionization chamber, thermoluminescent dosimeters and Fricke dosimeter. A computerized treatment planning system has been modified to compute dose distributions from 241Am sources, to optimize the design of this applicator. Computed and measured dose distributions for several values of separation between the 241Am discs are presented. A survival curve for cells from tumors irradiated in vivo with this applicator has been determined by an in vitro colony formation technique. The mean lethal dose DO was found to be 720 cGy for an average tumor dose rate of 95 +/- 7 cGy/hr. The major advantages of the 241Am applicator in comparison with the 192Ir applicator used previously for continuous low-dose-rate studies are: a considerably smaller half value layer thickness and the longer half life of the radionuclide. These features make it more suitable for long-term tumor cure studies because of the lower whole body dose to the animal, the availability of relatively constant dose-rate irradiators for many years, the decreased shielding requirements for the animal care facility and the diminished exposure to laboratory personnel involved with the implants on the animals.

Americium↗
PubMed1987

Effect of a perfluorochemical emulsion on the radiation response of BA1112 rhabdomyosarcomas.

The effect of treatment with a perfluorochemical emulsion (Fluosol DA, 20%), carbogen, or the combination of these two agents on the radiation response of BA1112 tumors in WAG/rij rats was examined. Fluosol and carbogen as single agents had only small effects on the tumor cell survival curve. The combination of Fluosol plus carbogen had a larger effect on tumor cell survival, reducing the hypoxic fraction of the tumor from 23 to 1.6%. The amount of sensitization was a function of the Fluosol dose, with maximal augmentation of the radiation response obtained at doses of 7.5-15 ml/kg. Carbogen pretreatments ranging from 5 to 60 min in duration all had similar effects on tumor radiosensitivity. The effect of the perfluorochemical emulsion plus carbogen on the survival of irradiated tumor cells appears to reflect changes in tumor oxygenation, rather than cytotoxic or immunological effects, since the perfluorochemical emulsion (with or without carbogen) had no effect on the viability of cells in unirradiated tumors. These experiments extend previous studies by ourselves and others using mouse tumors to show that the combination of a perfluorochemical emulsion and carbogen breathing can also increase the radiation response of a nonimmunogenic rat tumor.

Administration, Inhalation↗
PubMed1986

Retroperitoneal sarcomas: the Yale experience and a review of the literature.

Between 1964 and 1978, 23 patients were referred for radiation therapy for retroperitoneal sarcoma. Three patients had complete excision and negative resection margins and all survived for 5 years without recurrent disease. One patient had complete resection but positive margins, but had a local recurrence 3 1/2 years after radiation. One patient had partial excision with gross residual, and this patient survived only 17 months after an incomplete radiation treatment schedule. Ten cases had biopsy only and were then referred. We found that there were only four cases that survived longer than 1 year, and their average dose of radiation was 4,400 rads, as compared to only 2,691 rads for the remaining six. We conclude that for incompletely resected or only biopsied retroperitoneal sarcoma, doses of 4,000-5,000 rads should be given and then a reevaluation for complete resection should be done with CT scan and reexploration. For completely resected cases, we feel that postoperative radiation adds to the local control. We have reviewed the literature and presented the data in support of our conclusions.

Combined Modality Therapy↗
PubMed1986

Perfluorochemicals and hyperbaric oxygen in radiation therapy.

It has been postulated that tumors contain hypoxic cells of decreased radiation sensitivity, which limit curability with radiation therapy. Hyperbaric oxygen has been used in an attempt to improve tumor oxygenation. The nature of the oxygen concentration-radiation sensitivity relationship (oxygen increases the slope of the radiation cell survival curve) suggests that a small number of hypoxic cells, as few as one in one million, would limit tumor curability. Oxygen moves by diffusion from the capillary into the tumor. An increase in partial pressure in the capillary will increase the effective diffusion distance. To improve tissue oxygenation effectively the partial pressure of oxygen in blood must be significantly increased throughout the length of the capillary, in particular at the venous end. Theoretical considerations indicate that hyperbaric oxygen as presently used in radiation therapy, 3 ATA, would lead to only marginal improvement. PartO2 may be as much as 0.8 atm below that of the inspired gas; this plus the consumption of oxygen along the length of the capillary lead to predictions of values for PEnd CapO2 of less than twice normal. Such considerations explain the rather limited success of hyperbaric oxygen with radiation therapy. Thus it is unnecessary to postulate an absence of hypoxic cells to explain this clinical observation. In the presence of perfluorocarbon micelles the non-hemoglobin-bound oxygen carrying capacity of blood is significantly increased. Theoretical considerations predict that the difference between PartO2 and PO2 of the inspired gas should be decreased. Furthermore, the nonhemoglobin-bound oxygen carrying capacity should be adequate to satisfy tissue consumption requirements without unloading hemoglobin, thereby avoiding the "PO2 buffering effect of hemoglobin" and permitting a significant increase in PO2 throughout the capillary length. This effect has been demonstrated using a rodent tumor model.

Animals↗
PubMed1986

The distribution of gram negative bacteria and endotoxin on raw cotton components.

The botanical composition of representative raw cottons from seven different growing regions was determined by manual removal and identification of all trash components greater than 50 micron in size. The number of gram negative bacteria (GNB) and the amount of endotoxin present in each of the separated raw cotton components were quantified. Low middling cotton contained significantly more bract-leaf trash than that found in higher quality cottons such as those in the middling grade division. Significantly more GNB and endotoxin were found in botanical trash components as well as lint of raw cotton derived from the southwest and southeast growing regions as compared to similar botanical components from far west cottons. For representative raw cottons from the 1980 USA crop we determined that 67% of the GNB and 89% of the endotoxin resided on white lint itself, from which all particulate larger than 50 micron in size had been removed manually.

Animals↗
PubMed1984

Differential effect of cycloheximide on normal tissue tolerance and tumor control in irradiated rats.

The effect of the protein synthesis inhibitor cycloheximide (CHM) on normal tissue tolerance and tumor control in the rat following single doses of radiation has been studied. We have previously shown that the drug protects against skin damage when administered prior to irradiation of the hind limbs. It does not protect against six-month lethality when given prior to irradiation of the kidneys. In the present studies protection of rat bone marrow as evidenced by 30-day lethality was observed when CHM was given prior to whole-body irradiation. When CHM was given to rats bearing the BA1112 tumor, it had no protective effect on radiocurability. Therapeutically favorable differential protection of rapidly proliferating normal tissue over tumor can be achieved when CHM is administered prior to single radiation doses in the rat. This effect is most likely due to inhibition of protein synthesis and resultant interruption of the cell cycle in proliferating normal tissue. Further studies are required to determine the clinical applicability of CHM.

Animals↗
PubMed1984

Radiation sensitivity of cultured rabbit aortic endothelial cells.

The radiation response of cultured rabbit aortic endothelial cells was measured using colony formation to determine survival. The dose survival curve was qualitatively similar to those reported for other cell types. At doses of 400 rad and greater, the curve was an exponential function of dose with a D0 of 120 rad and an n of 7. Exponentially growing endothelial cell cultures recovered from sublethal damage between two doses of radiation. Plateau phase cultures recovered from potentially lethal damage when incubated for 6 hr between irradiation and assay.

Animals↗