Hyperbaric oxygen in treatment of neonatal arterial thromboembolism of lower extremities.

Arterial thromboembolism (TE) in the absence of current or recent history of a central catheter is a rare condition in newborn period. We report a case of severe lower extremities arterial TE of unclear etiology in a full-term neonate. By adding hyperbaric oxygenation to thrombolytic and antithrombotic therapy, we achieved improved perfusion of the upper leg tissues, preserving the knee and enabling below-the-knee amputation.

Feasibility of instructing radiology technologists in the performance of gastrointestinal fluoroscopy.

OBJECTIVE: We sought to determine if dedicated gastrointestinal technologists could be trained to properly perform esophagography and double-contrast barium enema examinations. SUBJECTS AND METHODS: Ninety-four patients undergoing double-contrast barium enema examinations and 123 patients undergoing esophagographic examinations were included in the study. The study was conducted over a 4-month period, with examinations performed by eight gastrointestinal technologists, 10 radiology residents, and four staff radiologists. Four random lists were generated for each set of examinations. Each staff gastrointestinal radiologist, who was unaware of who had performed the examination, independently scored the representative radiographs. RESULTS: For the double-contrast barium enema examinations, no statistically significant differences were found between the technologists and residents for amount of barium used, degree of distention, cecal opacification, and quality of spot radiographs. The technologist-performed examinations had a statistically significant lower mean fluoroscopy time (3.2 min, compared with 4.0 min for staff radiologists and 5.7 min for residents). For the esophagrams, no statistically significant differences between technologists and residents were found for single-contrast esophagrams; radiographs of the gastric cardia; assessment of motility, reflux, and transit of a solid bolus; and fluoroscopy time. Double-contrast esophagrams obtained by technologists received a better mean score than did those of the residents. CONCLUSION: Radiology technologists can be trained to perform high-quality esophagography and double-contrast barium enema examinations without an unacceptably high radiation dose.

Selenium-based digital radiography versus conventional film-screen radiography of the hands and feet: a subjective comparison.

OBJECTIVE: The purpose of this study was to subjectively compare the visibility of normal anatomy of the hands and feet using selenium-based digital radiography versus conventional film-screen (100-speed) radiography. SUBJECTS AND METHODS: Digital and film-screen images of the hands and feet of 24 patients were obtained without an antiscatter grid using identical X-ray exposure. Each pair of images was evaluated independently by five experienced radiologists for visibility of normal anatomy using a six-point rating scale. Soft tissues, cortical bone, and trabeculae were evaluated. For each observer, "equivalence" was defined as a mean difference in image quality of less than 1 unit on the 0-5 scale used in the study. Paired t tests were also performed to determine whether the average visibility rating of one technique was statistically superior to that of the other at a .05 level of significance for each observer and at each anatomic landmark. RESULTS: In all categories, selenium-based digital images were rated equivalent to film-screen images by the five observers. Using the sum of the nine landmarks, four of the five observers rated the quality of selenium-based digital images superior to that of film-screen images. CONCLUSION: Subjective visibility of normal anatomy of the hands and feet using selenium-based digital radiography was similar to that achieved using conventional film-screen radiography.

Interaction between DNA-dependent protein kinase and a novel protein, KIP.

DNA-dependent protein kinase (DNA-PKcs) is the only eukaryotic kinase activated by DNA ends. Mutation of DNA-PKcs results in murine severe combined immune deficiency in mice and radiation sensitivity. Both the immune and the radiation defects are due to a failure in double-strand break repair. Biochemical studies indicate that DNA-PKcs kinase activity is stimulated by the presence of the DNA end binding protein. Ku. Autophosphorylation of DNA-PKcs results in its inactivation. Based on these studies, DNA-PKcs is presumed to play a direct and important role in the repair of double-strand breaks, but the details of its role are quite unclear. We have done two-hybrid analysis of this entire protein to identify other proteins with which it interacts. Thus far, extensive analysis has only revealed one strong interaction that satisfies both high genetic and biochemical stringency. The interaction is with a novel human protein that has 26% amino acid identity with the phosphatase component, calcineurin B. We discuss the interaction of DNA-PKcs with this novel calcium-binding protein family member in the context of possible kinase-phosphatase regulation of DNA end joining.

Hyperbaric oxygen therapy for nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To evaluate the effectiveness of hyperbaric oxygen therapy in reducing optic nerve damage in acute nonarteritic anterior ischemic optic neuropathy. METHODS: Twenty-two eyes in 20 patients with acute nonarteritic anterior ischemic optic neuropathy were treated with hyperbaric oxygen (100% oxygen, 2.0 absolute atmospheres of pressure) in two 90-minute inhalation sessions per day for ten days. Changes in mean visual acuity and mean sensitivity loss were compared with those of 27 untreated control patients with acute nonarteritic anterior ischemic optic neuropathy, and proportions of patients with a change in acuity or mean sensitivity loss were compared with controls. Similar analysis was performed on subgroups based on time delay from symptom onset to therapy. RESULTS: Mean values for visual acuity were increased at final examination in both groups; although the increase was greater in controls, the difference was not statistically significant. Mean visual field sensitivity loss was minimally increased; although the increase was smaller in controls, the difference between groups was not significant. There was no significant difference between groups in proportions of patients with change in acuity score or mean sensitivity loss. Stratification by time delay to therapy did not suggest that treatment within nine days produced better visual results than that for either controls or those treated later. CONCLUSIONS: Hyperbaric oxygen therapy using 100% oxygen and 2.0 absolute atmospheres of pressure did not produce a significant improvement in visual acuity or visual field for patients with acute nonarteritic anterior ischemic optic neuropathy.

Force, development, and neoplasia: development from another perspective as illustrated through a study of in vitro plant development from neoplasm.

Differentiation from the neoplastic state can be a dynamic adaptation to the localized stress of increasing cohesive forces in tissue. Repulsive forces, occurring within and between cells, are seen as leading to de-differentiation into the neoplastic state or neoplasm. During early development, especially where and when mitosis occurs frequently, cohesive and repulsive forces may necessarily coexist in oscillating degrees. Correspondingly, cohesive-force and repulsive-force generating metabolites may co-exist in oscillating concentrations. Cancer or neoplasia occurs, according A. Szent-Gyorgyi, when cohesiveness breaks down locally, probably thru the conversion of methylglyoxal into lactic acid. Cancer may also occur due to the accumulation of such putatively, repulsion-generating factors as lactic acid. Plant tumors in vitro respond adaptively to cohesion-generating chemicals, such as ascorbic acid and methylglyoxal, by generating buds, embryos, and plantlets.

Directed intravascular precipitation of bisantrene for pelvic malignant lesions: preclinical studies.

Bisantrene, a clinically active anticancer drug with limited solubility at physiologic pH, was delivered by selective injection into the internal iliac artery of male calves. The percutaneous transfemoral angiographic techniques used in the calves were identical to those used in adult human patients. Directed intravascular precipitation of bisantrene at the maximal tolerable clinical dose for intravenous administration (260 mg/m2) caused severe tissue damage in 5 of 10 animals that received these intra-arterial injections. (One calf in this study group died of unknown causes 10 days after the drug infusion). A reduced intra-arterial dose (50 mg/m2) was used in seven calves, and no local tissue damage was evident on gross or microscopic examination. Nevertheless, resultant concentrations of bisantrene deposited in the ipsilateral bladder wall were 10- to 100-fold those concentrations found after intravenous administration of a dose 5 times higher. These animal toxicology and pharmacology data support initiation of a phase I clinical trial of directed intravascular precipitation of bisantrene in humans. This clinical trial will be developed for patients with advanced refractory cancers of the anatomic true pelvis, such as those originating in the urinary bladder, prostate, rectum, and uterine cervix.

Application of a human tumor colony-forming assay to new drug screening.

The applicability of a human tumor colony-forming assay to drug screening was investigated in terms of feasibility, validity, and potential for discovering new antitumor drugs. Feasibility was addressed in a pilot study during which basic methods, appropriate assay quality controls, and a standardized protocol for screening were developed. Considerable variability was noted in the availability and colony growth of different tumor types. The majority of the evaluable experiments utilized breast, colorectal, kidney, lung, melanoma, or ovarian tumors. For many tumor types, little evidence of growth was observed, or only rare specimens formed colonies. Colony-forming efficiencies ranged from 0.05 to 0.11% for the six most useful tumors listed above. A set of quality control measures was developed to address technical problems inherent in the assay. Testing of standard agents in the pilot study established that most of these agents could be detected as active. However, it also identified three assay limitations: compounds requiring systemic metabolic activation are inactive; medium constituents may block the activity of certain antimetabolites; and compounds without therapeutic efficacy may be positive in the assay. The assay categorized nontoxic clinically ineffective agents as true negatives with 97% accuracy. Of 79 compounds which were negative in the current National Cancer Institute prescreen (leukemia P388), 14 were active in the assay. Several demonstrated outstanding in vitro activity and are structurally unrelated to compounds already in development or in clinical trials. A subset of these active compounds were found to lack activity in a P388 in vitro colony-forming assay. This indication of differential cytotoxicity to human tumor cells makes this subset of compounds particularly interesting as antitumor drug leads. The demonstrated sensitivity to most standard agents, discrimination of nontoxic compounds, reproducibility of survival values within assays and between laboratories, and evidence of ability to identify active compounds which were negative in the in vivo prescreen suggest that the human tumor colony-forming assay may be a valuable tool for antitumor drug screening. However, because of technical limitations inherent in the current assay methodology, this must be confined to selected tumor types and limited to screening on a moderate scale.

Technical problems with soft agar colony formation assays for in vitro chemotherapy sensitivity testing of human solid tumors: Mayo Clinic experience.

If soft agar colony formation assays for primary human tumor cells are going to be performed and the results assessed by optical analysis of colony formation, then we believe it is mandatory in such assay techniques to objectively count control plates on the day of culture initiation using stained plates, use universal cytotoxic control compounds which should uniformly eliminate all viable cell proliferation, and use a vital stain such as the tetrazolium dye INT to document the presence or absence of viable cell colonies when cultures are assessed. There is no question, however, after careful observation of thousands of soft agar cultures of primary human tumor cells in my laboratory, that significant proliferation of small tumor cell aggregates often takes place in vitro and can in fact be used to assess cytotoxic drug effects in vitro. We do not believe that this is demonstrably stem cell or clonal growth. Nevertheless, it almost certainly is in vitro tumor cell proliferation. With very careful controls, we believe that optical methods can be used reliably to evaluate drug effects on this soft agar proliferative capacity of primary human tumor cells. However, it may eventually prove more useful to study human tumor cell proliferation in vitro (even soft agar colony growth) by other methods, such as incorporation of radiolabeled bases into newly synthesized DNA or other macromolecules, or by the simple use of vital dyes, as discussed elsewhere in this volume.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro chemotherapy sensitivity patterns of human colon carcinoma continuous cell lines.

The cells obtained from four established human colon carcinoma cell lines were cultured in soft agar in the presence of eight chemotherapeutic agents that have been used clinically in patients with metastatic colorectal carcinoma. 5-Fluorouracil, mitomycin C, adriamycin, and cis-platinum were highly cytotoxic in vitro at the concentrations employed. These findings were in marked contrast to in vitro chemotherapy sensitivity patterns previously reported by us for a large series of primary human colorectal carcinomas cultured in soft agar. The possible reasons behind these differences are discussed.

Human colorectal carcinoma: patterns of sensitivity to chemotherapeutic agents in the human tumor stem cell assay.

The human tumor stem cell assay (HTSCA) was applied to 103 primary and metastatic colorectal carcinomas. Thirty-four carcinomas could not be evaluated for colony formation (clonogenicity) because of microbial contamination. Of the remaining 69 carcinomas, 18 (26%) demonstrated clonal growth in vitro. Colony formation did not correlate with the clinicopathologic stage of the tumor, the histological grade of the tumor, the method used to disperse the solid tumors into single cells (mechanical or enzymatic), or cell viability (exclusion of trypan-blue) prior to plating. The in vitro chemotherapy sensitivity data of the 18 tumors which formed colonies indicated that most tumors were generally resistant to chemotherapeutic drugs and that a few tumors were sensitive to multiple agents. Use of the human tumor stem cell assay may facilitate an individualized approach to clinical chemotherapy of colorectal carcinoma for certain patients.