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Biomedical subjects

L A Gordon

Publications and source records attributed to L A Gordon.

46 records · Page 3Linked to original sources

An evaluation of the mouse sperm morphology test and other sperm tests in nonhuman mammals. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The literature on the mouse sperm morphology test and on other sperm tests in nonhuman mammals was reviewed (a) to evaluate the relationship of these tests to chemically induced spermatogenic dysfunction, germ-cell mutagenicity, and carcinogenicity, and (b) to make an interspecies comparison to chemicals. A total of 71 papers were reviewed. The mouse sperm morphology test was used to assess the effects of 154 of the 182 chemical agents covered. 4 other murine sperm tests were also used: the induction of acrosomal abnormalities (4 agents), reduction in sperm counts, (6 agents), motility (5 agents), and F1 sperm morphology (7 agents)). In addition, sperm tests for the spermatogenic effects of 35 agents were done in 9 nonmurine mammalian species; these included analyses for sperm count, motility, and morphology, using a large variety of study designs. For the mouse sperm morphology test, 41 agents were judged by the reviewing committee to be positive inducers of sperm-head shape abnormalities, 103 were negative, and 10 were inconclusive. To evaluate the relationship between changes in sperm morphology and germ cell mutagenicity, the effects of 41 agents on mouse sperm shape were compared to available data from 3 different mammalian germ-cell mutational tests (specific locus, heritable translocation, and dominant lethal). The mouse sperm morphology test was found to be highly sensitive to germ-cell mutagens; 100% of the known mutagens were correctly identified as positives in the sperm morphology test. Data are insufficient at present to access the rate of false positives. Although it is biologically unclear why one might expect changes in sperm morphology to be related to carcinogenesis, we found that (a) a positive response in the mouse sperm morphology test is highly specific for carcinogenic potential (100% for the agents surveyed), and (b) overall, only 50% of carcinogens were positive in the test (i.e., sensitivity approximately equal to 50%). Since many carcinogens do not produce abnormally shaped sperm even at lethal doses, negative findings with the sperm test cannot be used to classify agents as noncarcinogens. We conclude that the mouse sperm morphology test has potential use for identifying chemicals that induce spermatogenic dysfunction and perhaps heritable mutations. Insufficient numbers of chemicals agents have been studied by the other sperm tests to permit similar comparisons. A comparison of 25 chemicals tested with sperm counts, motility, and morphology in at least 2 species (including man, mouse and 9 other mammals) demonstrated good agreement in response among species. With further study, interspecies comparisons of chemically induced sperm changes may be useful for predicting and evaluating human effects.

Animals↗

An evaluation of human sperm as indicators of chemically induced alterations of spermatogenic function. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

To evaluate the utility of sperm tests as indicators of chemical effects on human spermatogenesis, the literature on 4 sperm tests used to assess chemically induced testicular dysfunction was reviewed. The tests surveyed included sperm count, motility, morphology (seminal cytology), and double Y-body (a fluorescence-based test thought to detect Y-chromosomal nondisjunction). There were 132 papers that provided sufficient data for evaluation. These reports encompassed 89 different chemical exposures: 53 were to single agents; 14 to complex mixtures; and 22 to combinations of 2 or more identified agents. Approximately 85% of the exposures were to experimental or therapeutic drugs, 10% were to occupational or environmental agents, and 5% were to drugs for personal use. The most common sperm parameter studied was sperm count (for 87 of the 89 exposures reviewed). Sperm motility was evaluated for 59 exposures, morphology for 44, and double Y-bodies for only 4. The 89 exposures reviewed were grouped into 4 classes: those which adversely effected spermatogenesis, as measured by one or more of the sperm tests (52); those suggestive of improving semen quality (11); those showing inconclusive evidence of adverse effects from exposure (14); and those showing no significant changes (12). Since the reviewed reports had a large variety of study designs, and since every attempt was made to include all reports with interpretable data, these classifications were based on reviewing committee decisions rather than on uniform statistical criteria. This review gives strong evidence that human sperm tests can be used to identify chemicals that affect sperm production, but because of our limited understanding of underlying mechanisms, the extent to which they can detect mutagens, carcinogens or agents that affect fertility remains uncertain. For the very few agents studied with both human and mouse sperm tests, similar test-responses were seen; thus sperm tests in mice and other laboratory mammals may have a potential role in hazard identification. An overall comparison of the 4 human sperm tests suggests that no one test is biologically more responsive than another; all of them may thus be needed when testing for chemically induced changes from agents of unknown activity. This review also gives evidence that sperm tests can be used to assess the extent and the potential reversibility of induced spermatogenic damage. The reviewing committee recommends further studies to determine (a) the dose-response characteristics of the human sperm tests, (b) details of the reversibility of induced changes with time after exposure, (c) the relative responses in the 4 sperm tests in exposed individuals, (d) the mechanism of action, (e) the biological and genetic implications of chemically induced effects, and (f) the comparison of responses among different species for risk assessment. The reviewing committee outlines specific considerations for planning new sperm studies on chemically exposed men.

Animals↗

Active sperm production after cancer chemotherapy with doxorubicin.

The sperm production of 14 cancer patients who received doxorubicin was examined after cessation of therapy. Doxorubicin was used in several multiple-drug protocols for the treatment of various malignancies. Seven patients also received radiotherapy to different sites. Total cumulative doses of doxorubicin ranged from 145 to 625 mg./m.2. Sperm concentration, motility, morphology and the frequency of quinacrine-stained sperm with 2 fluorescent bodies (2F sperm) were measured 7 to 79 months after discontinuation of doxorubicin. Of the patients 6 remained azoospermic, 3 were oligospermic and 5 were normospermic. Sperm motility among the 8 patients with sperm ranged from 20 to 80 per cent. Morphology and 2F sperm distributions were not significantly different from controls. We conclude that, in contrast with the mechlorethamine, vincristine, procarbazine and prednisone protocol, active sperm production within relatively short recovery times is possible after treatment with protocols that include doxorubicin.

Adult↗

Temporary effects of AMSA (4'-(9-acridinylamino) methanesulfon-m-anisidide) chemotherapy on spermatogenesis.

Spermatogenesis in a melanoma patient treated with 12 courses of acridinyl anisidide (AMSA) (20 mg/m2/course) was studied by monitoring sperm concentration, motility, and morphology at various phases of treatment. Chemotherapy was interrupted for 20 weeks between the ninth and tenth course. Sperm concentration and motility began to decline after the second course. At the third course, the percentage of morphologic abnormalities had increased to 86.5% from a pretreatment value of 57.8% (P less than 0.001). Azoospermia was observed at the sixth course and persisted until 12 weeks after the ninth course, when semen levels returned to pretreatment levels: 20 million/ml; 70% motility; 60.1% abnormal forms. Three weeks after the 12th course, the sperm count was reduced to 250,000/ml, motility to 5%, and abnormalities increased to 84.0%. The rapid recovery of normal spermatogenesis observed during the chemotherapy interruption indicates that AMSA has only a temporary, reversible effect on differentiating germinal cells with no toxicity to stem cells.

Adult↗

Microfibrillar collagen hemostatic pledgets.

The use of topical microfibrillar collagen hemostatic agents is increasing in many areas of clinical surgery. We have developed a method of preparing the hemostatic agent by which a pledget is formed in a syringe. This gives it a firm consistency and allows easier handling and application and can be done at the operating room table.

Collagen↗

Changes in testosterone levels in the rat following intraperitoneal cocaine HCl.

Independent groups of mature rats were administered IP injections of either 15 mg cocaine HCl or normal saline. Animals were lightly anesthetized after 45', 90', 120', or 180' and blood plasma assayed for testosterone by RIA. Experimental subjects showed increasing levels until the longest delay value when a substanial drop was noted. The importance of this finding is noted, both with regard to the issue of drug abuse as well as a potential confounding element in the analysis of chemical kindling experiments.

Animals↗

Simultaneous double obstruction of the proximal colon: a case report.

A rare case of simultaneous obstructions of the proximal colon secondary to an obstructing carcinoma of the transverse colon and an ascending colon volvulus at the hepatic flexure is presented. Their probable interrelationship and resulting radiographic features are discussed.

Aged↗

Problem-solving in laparoscopic surgery.

The advent of the laparoscopic revolution and the wider applicability of laparoscopic procedures has caused surgeons to re-think the dynamics of intraoperative problem-solving. Problems of body habitus, previous surgery, exposure, bleeding, and anesthesia, as well as the problem cholangiogram, require new and innovative approaches, a practical approach to each of these common laparoscopic problems is presented.

Abdomen↗

Mesenteric desmoid of the appendix--a case report.

A case of an isolated mesenteric desmoid (fibroma) is presented with two unusual characteristics. First, it arises from the mesentery of the appendix. Second, it presents as a twisted desmoid. The CT and US characteristics are presented. This patient was without risk factors for mesenteric fibrosis such as Gardner's syndrome or previous surgery.

Appendiceal Neoplasms↗