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Biomedical subjects

Z Tochner

Publications and source records attributed to Z Tochner.

36 records · Page 2Linked to original sources
PubMed1990

The persistence of neutralizing antibodies after revaccination against smallpox.

Persistence of neutralizing antibodies after revaccination against smallpox was studied. Single serum samples from 140 revaccinated donors were tested for neutralizing antibodies using the plaque reduction assay. The donors, aged 21-49 years at sampling, had been vaccinated in infancy and revaccinated at 8 and 18 years; they formed seven groups of 20 men each, revaccinated about 3, 5, 10, 15, 20, 25, and 30 years before sampling. The differences in mean titer among groups were insignificant (P greater than .01). The titer significantly decreased during the first 3 years after the revaccination but remained stable for at least 30 years thereafter (geometric mean titer, 10.5; 95% confidence interval, 6.8-16.4). The results suggest that there is probably no need for routine revaccinations beyond the primary and two revaccinations; nevertheless, persons at high risk should be revaccinated regardless of their vaccination status.

Adult↗
PubMed1990

Protection by indomethacin against acute radiation esophagitis.

The mechanism of radiation induced damage to the mucosal lining of the gastrointestinal tract, as well as mucositis, is not fully characterized. Prostaglandins may partially mediate the inflammatory response to radiation damage. The effect of the prostaglandin synthetase inhibitor indomethacin on radiation induced esophagitis, pneumonitis, and tumor response was evaluated in the C3H mouse. The effects of indomethacin on radiation induced damage to the esophagus was determined by evaluation of weigh lost, survival, and histologic findings at doses of 28-34 Gy. Although there is a clear difference that supports the use of indomethacin for the prevention of esophagitis, the radiation dose response for esophagitis is steep and likewise, the therapeutic index for the indomethacin amelioration of radiation esophagitis is narrow. Since the tumor response to radiation is unchanged and since indomethacin clearly lessens radiation induced esophagitis in the mouse, this study suggests that indomethacin should be studied in humans for lessening radiation mucositis without jeopardizing the therapy of tumors.

Acute Disease↗
PubMed1990

The effect of repeated doses of 30 mg pyridostigmine bromide on pilot performance in an A-4 flight simulator.

The effect of repeated doses of 30 mg pyridostigmine bromide every 8 h on flight skills in an A-4 simulator was tested in this crossover double-blind placebo-controlled study on 10 pilots experienced in actual and simulated A-4 flights. The pilots flew two test simulator flights 2 h after the fourth dose of pyridostigmine or placebo. The flight profile included navigation, rapid ascent, 360 degrees turns, and instrument landing. Each flight lasted approximately 20 min. Flight parameters measured included indicated air speed, true heading, barometric altitude, vertical velocity, and bank. The mean whole blood cholinesterase inhibition level was 29%. There was no decrement in performance under treatment with pyridostigmine in the percent of deviation time from the prescribed limits or in the average duration or magnitude of the deviation in each of the flight parameters. We conclude that pyridostigmine bromide in repeated doses of 30 mg every 8 h does not appear to influence pilot performance during short A-4 missions.

Adult↗
PubMed1988

Tolerance of the canine bladder to intraoperative radiation therapy: an experimental study.

An experimental study of bladder tolerance to intraoperative radiotherapy (IORT) was designed using a large animal model (adult American Foxhounds, weight 25-30 kg) to access acute and late radiation effects. Dogs were subjected to laparotomy where the bladder was mobilized and IORT was delivered using a 5 cm circular cone through a cystotomy incision with 12 MeV electrons. The bladder trigone including both ureteral orifices and the proximal urethra was irradiated in groups of 3 dogs with doses of 0, 20, 25, 30, 35, and 40 Gy. Dogs were followed clinically with repeat urinalysis, intravenous pyelogram (IVP), and cystometrogram at 1 month and then Q6 months for up to 4 years. One dog from each dose group was sacrificed electively at 1 and 2 years, whereas the other dog is being followed clinically for a minimum of 4 years. Complete autopsies were performed with particular attention to genitourinary and pelvic structures. No clinically detectable acute toxicity resulted from IORT to the bladder. Three of 15 IORT dogs (1 each at 25, 35, and 40 Gy) showed obstruction of a ureteral orifice with 2 dogs dying of renal failure secondary to bilateral hydronephrosis within 1-2 years of treatment. The remaining 12 IORT dogs and 3 control dogs have normal repeat IVP's and renal function with up to 4 years of follow-up. Serial cystometry demonstrates no major loss of bladder contractility or volume. At autopsy, histological changes of mucosal thinning and telangiectasia with submucosal fibrosis were confined to the IORT field and appeared dose-related. However, the bladder epithelium remained intact at all doses. The ureterovesical junction in animals receiving 20 Gy showed mild fibrosis of the lamina propria and moderate chronic inflammation. Above 20 Gy, these histological changes at the U-V junction were more pronounced with gross stenosis in 3 animals as predicted by the IVP. We conclude that the bladder trigone will tolerate IORT to 20 Gy without major clinical sequellae. Above 20 Gy, progressive inflammation and fibrosis of the U-V junction resulted in obstructive hydronephrosis in three animals within 1-2 years of IORT. The bladder mucosa remained intact with doses to 40 Gy, although submucosal fibrosis and chronic inflammation were evident and appeared dose-related. However, bladder function as measured by cystometry showed essentially no change with follow-up to 4 years. From this large animal study, IORT for early-stage bladder carcinoma is technically feasible and deserves a careful clinical study.

Animals↗
PubMed1988

Response of canine esophagus to intraoperative electron beam radiotherapy.

Tolerance of esophagus to intraoperative radiotherapy (IORT) was investigated in dogs. Thirteen adult foxhounds were subjected to right thoractomy, mobilization of the intrathoracic esophagus, and IORT to a 6 cm full-thickness esophageal segment using 9 MeV electrons at doses of 0, 2,000, or 3,000 cGy. Dogs were followed clinically and were evaluated at regular intervals after treatment with fiberoptic esophagoscopy, barium swallows, and postmortem histologic evaluations. One sham-irradiated control dog showed no abnormalities during follow-up of 24 months. Seven dogs receiving 2,000 cGy IORT showed transient mild dysphagia and mild esophagitis, but no clinically or pathologically significant complications. Five dogs receiving 3,000 cGy demonstrated severe ulcerative esophagitis within 6 weeks of treatment which progressed to chronic ulcerative esophagitis with stricture formation by 9 months following IORT. One 3,000 cGy dog died at 13 months from an esophageal perforation. On the basis of a pilot experience using 13 experimental animals, it was concluded that intact canine esophagus tolerates IORT well to doses of 2,000 cGy, but doses of 3,000 cGy pose serious and potentially lethal risks. The clinical application of IORT to the treatment of human intrathoracic neoplasms requiring esophageal irradiation should be approached with caution, particularly at doses exceeding 2,000 cGy.

Animals↗
PubMed1987

Response of the mediastinal and thoracic viscera of the dog to intraoperative radiation therapy (IORT).

IORT may be a potentially useful adjunctive treatment combined with surgery and/or external beam irradiation in treating locally advanced lung and esophageal tumors. To begin investigation of this modality, the tolerance of intact mediastinal structures to IORT was studied using adult American Foxhounds (wt. 25-30 kg). Groups of six animals received IORT to doses of 20, 30, or 40 Gy to two separate intrathoracic ports, using 9 MeV electrons to treat a portion of the collapsed right upper lobe, and 12 MeV electrons to treat the mediastinal structures. A group of three dogs received thoracotomy with sham irradiation. Two dogs from each treatment dose group, as well as one sham-irradiated control, were sacrificed electively at 1, 3, and 12 months following IORT. There were no acute nor late IORT related mortalities. Post-operative weight loss was minimal (average 4.5% of pre-operative weight) for all dogs. Serial esophagrams showed no inflammation or ulceration. No cardiac nor pulmonary changes were noted clinically. At autopsy, the irradiated lung showed evidence of acute pneumonitis at 1 month with progressive fibrosis at 3 months and 1 year. Esophageal reactions were minimal, with only two dogs (one 30 Gy and one 40 Gy) demonstrating histologically confirmed esophagitis at 1 month. Tracheal changes were minimal. Cardiac damage was evident in the right atrial tissues. In several dogs, this cardiac damage ranged from myocardial vascular changes to frank ischemic necrosis noted at 1 and 3 months, and dense fibrosis at 1 year. The phrenic nerves showed normal function, but had evidence of perineural fibrosis. The large vessels demonstrated only mild histologic evidence of irradiation. The results of this large animal study suggest that intact mediastinal structures will tolerate small volume IORT to doses of 20 Gy without significant clinical sequellae. Although the histologic changes in the right atrium and contralateral lung are worrisome, no cardiac nor pulmonary problems arose over the 1 year follow-up. Irradiation of the contralateral lung and other sensitive structures can be reduced by careful selection of electron beam energy and use of custom lead shielding.

Animals↗
PubMed1987

Delivery of intraoperative radiation therapy after pneumonectomy: experimental observations and early clinical results.

Intraoperative radiation therapy (IORT) is capable of delivering high doses of radiation to mediastinal structures while sparing lung parenchyma, heart, and other locoregional tissues. A canine model of pulmonary resection and IORT was investigated by performing a pneumonectomy in 15 adult foxhounds followed by 0 cGy, 2,000 cGy, 3,000 cGy, 4,000 cGy. No clinical complications developed in 4 animals in the 2,000-cGy group. However, 2 of the 8 animals given a high dose died of esophageal hemorrhage or carinal necrosis. Esophagitis occurred in 10 of 12 animals, and none of the animals experienced bronchial stump dehiscence. In a limited Phase I protocol, 4 patients with non-small cell lung cancer were treated with resection and 2,500 cGy of IORT to two separate ports encompassing the superior and inferior mediastinum. Two patients experienced life-threatening bronchopleural fistulas, and 2 patients died as a consequence of esophageal problems. One patients had recurrence with brain metastases, and the 1 long-term survivor is free from disease. As opposed to the animal model of thoracic IORT, the clinical study demonstrated major toxicity with respiratory and esophageal morbidity. The therapeutic usefulness of thoracic IORT in the management of lung cancer must be questioned in view of this small but consistent series of patients. Further carefully designed clinical studies using lower doses of IORT are needed.

Adult↗
PubMed1986

The roles of intracellular glutathione in antineoplastic chemotherapy.

Glutathione is a sulfhydryl containing tripeptide that participates in detoxification of xenobiotic compounds, including the alkylating agents melphalan, cyclophosphamide, and BCNU. The role of glutathione in the detoxification of these compounds, both in terms of initial tumor response, and drug-induced resistance to these alkylating agents is examined. Since glutathione disulfide and glutathione are a pivotal redox pair, the modulation of intracellular glutathione levels is shown to change the cytotoxicity of drugs dependent on the redox cycle, such as adriamycin and bleomycin, as well as the oxygen dependent drug neocarzinostatin. Areas of further research are discussed.

Animals↗
PubMed1986

In vivo modulation of glutathione by buthionine sulfoximine: effect on marrow response to melphalan.

The effect of giving buthionine sulfoximine (BSO), 0.0265 g/mouse (6 mM), at 12 and 6 hr before treatment with melphalan--0.0 mg, 3 mg, 6 mg, and 9 mg/kg, was studied in C3H mice, and was compared with control groups that received normal saline 12 and 6 hr before identical melphalan treatment. BSO treatment resulted in depletion of GSH levels in bone marrow, liver, and muscle to 65, 13, and 41% of control levels, respectively. Hematological toxicity was assessed by measurement of CFU-S survival and peripheral white cell counts. CFU-S survival decreased with increasing doses of melphalan, but no difference was observed with BSO pre-treatment. Likewise, WBC counts following melphalan 9 mg/kg, were similar irrespective of BSO pre-treatment. These data suggest that the marrow toxicity seen with melphalan is not worsened by pre-treatment with BSO and that if tumors can be pre-sensitized with BSO, there may be a clinical role for melphalan/BSO drug combination.

Animals↗
PubMed1986

Inhibition of the protective effect of cyclophosphamide by pre-treatment with buthionine sulfoximine.

Low dose cyclophosphamide (CTX) is protective against a subsequent challenge with a lethal dose of the same drug administered 5 days later. At the time of maximal protection, elevation of glutathione (GSH) and glutathione transferase (GST) levels are detectable in the bone marrow of pre-treated animals. Elevation of GSH levels in the bone marrow was inhibited with the use of D,L-buthionine-S,R-sulfoximine (BSO), and this resulted in loss of the protective effect of CTX pre-treatment. In contrast, the overshoot in GST levels observed in these animals was not affected by BSO therapy. Bone marrow GSH levels in animals treated with BSO alone were minimally depleted (68% of control); whereas, animals pre-treated with CTX followed by BSO exhibited a greater reduction in GSH levels (47% of control). These results suggest that GSH is important in the protective effect afforded by low dose CTX pre-treatment and that the elevation of GSH levels observed is the result of a rebound synthetic process. In CTX pre-treated animals, BSO treatment resulted in greater than predicted depletion in GSH levels, and, therefore, caution is recommended with the potential use of combinations of BSO and cytotoxic drugs in the presence of a regenerating bone marrow.

Animals↗
PubMed1986

Photodynamic therapy of ascites tumours within the peritoneal cavity.

A murine ascites tumour was treated with intraperitoneal haematoporphyrin derivative (HPD) and laser light (10mW, 514nm, Argon laser). HPD was given intraperitoneally 2 hours before 16 minute laser treatment. Uptake studies 2 hours after HPD injection showed 5-12 fold greater concentration of HPD in tumour cells than in 4 different normal tissues. A total of four HPD/laser treatments, given at 2 day intervals, resulted in 100% complete response; the cure rate was 85%. This study illustrates the effective use of intraperitoneal photodynamic therapy and opens the possibility of exploring different sensitizers, excitation wavelengths, and delivery systems in the treatment of human ascites tumours.

Animals↗
PubMed1985

Treatment of murine intraperitoneal ovarian ascitic tumor with hematoporphyrin derivative and laser light.

An ascitic murine tumor, ovarian embryonal carcinoma, was used as a model of human ovarian carcinoma restricted to the peritoneum. The tumor was treated with a combination of hematoporphyrin derivative (HPD) and i.p. 514-nm laser light. Mice were given injections of 2 X 10(5) tumor cells, and by 9 days, there were 2 to 4 g of ascitic tumor/mouse. On Day 9, mice (68) were treated as follows: (12) no treatment; (12) only HPD (50 mg/kg i.p.); (12) laser only (9.6 J for 16 min); and (32) HPD (50 mg/kg i.p.) and 2 h later, laser treatment. On Day 15, a second treatment with HPD and laser was given to 15 mice. All mice not receiving HPD-laser treatment died between Days 20 and 23. The response rate as determined by decrease in weight and abdominal size for HPD-laser-treated mice was 90%, but the response was short, and all but one animal died by Day 34. However, 6 of 15 of the twice-treated group are alive at 90 days and considered cured. Photoradiotherapy with HPD for i.p. ascitic tumors appears to have promise as a treatment modality.

Animals↗
PubMed1975

Observations on the in vivo aging of red cells in the rat.

Aging of rat erythrocytes was studied in vivo by two experimental models. In the first, a single cohort of erythrocytes labelled with radioiron was followed; in the second, sequential hypertransfusions were employed to obtain a defined red cell population, which was continuously transferred from host to host. The results are compatible with a normal red cell life span of about 60 days and with sequestration of senescent erythrocytes in the spleen and in the liver. Red cell aging was associated with a decline in cell volume, haemoglobin, G6PD and ATP content. There were no measureable changes in osmotic fragility. Thus, changes in osmotic resistance do not appear to be critical factors limiting the life span of circulating erythrocytes in the rat.

Adenosine Triphosphate↗
PubMedDate not supplied

Functional and morphological alterations following isolated rat stomach irradiation. A model for estimation of radiation injury.

Exposure of the stomach to tumoricidal doses of radiation is associated with functional and morphological changes. The experimental data have been mainly obtained from studies of whole body irradiation of the stomach. We investigated the separate effect of irradiation on the surgically exposed stomach with doses of between 3 and 30 Gy. A dose-dependent decrease in free and total acidity was observed with relatively low doses (5-9 Gy). Serum pepsinogen and serum gastrin levels increased following irradiation with doses ranging from 5 to 15 Gy. Two phases of increased regenerative activity were documented (between the 1st and 3rd weeks and between the 4th and 8th weeks). No radioprotective effect was observed when sucralfate or misoprostol were utilized. Further investigations are mandatory in order to find an effective radioprotector for the irradiated stomach.

Animals↗