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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 613 records · Page 34Linked to original sources

Thiophene analogues of the carcinogens benzidine and 4-aminobiphenyl: evaluation in vitro.

A biologically active molecule with one or more aromatic rings often retains its activity when one of these rings is replaced by an isosteric and/or isoelectronic aromatic ring. Consideration has been given to whether this effect can be expected to apply to aromatic organic carcinogens. The literature relevant to this topic has been reviewed and the thiophene analogues of the carcinogens benzidine and 4-aminobiphenyl have been synthesized and evaluated for potential carcinogenicity. The compounds prepared were 5-p-acetamidophenyl-2-thiophenamine hydrochloride (XIII), 5-phenyl-2-thiophenamine hydrochloride (XIV), N-(5-p-acetamido-phenylthiophen-2-yl)acetamide (XV) and N-(5-phenylthiophen-2-yl)-acetamide (XVI) (see Chart for structures). Each compound was evaluated in the Salmonella reverse-mutation assay of Ames and the cell-transformation assay of Styles. The activity profiles observed for these compounds in vitro were consistent with their known chemistry, and indicate potential carcinogenicity. However, their overall chemical and biological behaviour casts doubt upon whether they would be capable of eliciting tumours in vivo. Because it is important to establish the degree of reliance which can be placed upon in vitro predictions of potential carcinogenicity generated for structurally new compounds, one of the thiophene derivatives, N-(5-phenylthiophen-2-yl)acetamide ((XVI), is currently being evaluated for carcinogenicity in mice.

Aminobiphenyl Compounds↗

Myocardial perfusion and function during acute right ventricular systolic hypertension.

Hemodynamics, myocardial function, and regional myocardial blood flow (MBF) were measured in 6 closed-chest ponies anesthetized with ketamine hydrochloride before (control) and after creation of acute right ventricular systolic hypertension (RVSH) during normoxia and isocapnic hypoxia. The right ventricular (RV) systolic pressure during each RVSH approached 90 mmHg. There were significant alterations in the pattern of total ventricular MBG distribution in favor of the RV. Because RV myocardium received proportionate increments to its endocardium as well as epicardium, it is concluded that autoregulation in the RV coronary vascular bed had not been abolished even during hypoxia + RVSH. Marked increase in MBF to the right side of the septum during each RVSH with little change in perfusion to other regions suggests that RV contraction is supported by the right side of the septum. Because these increments occurred with decreased RV coronary driving pressure they were the consequence of compensatory coronary vasodilatation. The slow heart rate of the pony in the presence of a large coronary vasodilatory reserve may have been the major factor in allowing large increments in MBF to the stressed regions despite decreased coronary driving pressure.

Acid-Base Equilibrium↗

Information variables in voluntary control and classical conditioning of heart rate: field dependence and heart-rate perception.

Two experiments focused on two information variables relevant to changes in heart rate, field dependence and the ability to perceive one's own heart rate. In Exp. I, 14 field-independent and 17 field-dependent subjects completed a heart-rate perception and a voluntary heart-rate control task. The anticipated superiority in heart-rate control by field-independent subjects was detected although no evidence was found for a relationship between the amount of biofeedback available in the situation and voluntary control of the cardiovascular system. Exp. II involved 9 field-independent and 8 field-dependent subjects in a classical conditioning paradigm involving shock sensitivity. In contrast with Exp. I, in this phase of the study heart-rate increases were correlated with the ability of the subject to discriminate heart beats, especially for the field-independent group. It was concluded that field dependence and heart-rate perception are related to classically conditioned heart-rate increase for some subjects and further that field dependence may be a potent variable operating in those situations involving the voluntary control of heart rate without exteroceptive feedback.

Biofeedback, Psychology↗

Iris nevus syndrome.

We present a case of iris-nevus or Cogan-Reese syndrome with its characteristic pathological findings. Although a rare entity, it should be considered in the differential diagnosis of heterochromia associated with elevated intra-ocular pressure. To avoid unnecessary enucleation, it should not be confused with diffuse iris melanoma.

Descemet Membrane↗

Intra- and extracellular measurements of frog neuromuscular transmission upon stretch of the muscle at different stimulus frequencies.

Flexible intracellular micro-electrodes were used to study the effect of changes in muscle length on the end-plate potential in the isolated m. cutaneus pectoris for different frequencies of stimulation (1/60-5Hz). A 20% step-wise increase in muscle length within the physiological range increases the end-plate potential immediately by about 50% (range 0-120%) at all frequencies tested. At stimulus frequencies lower than 1/5 Hz this increase is sustained during a period of 15 min stretch. At 1 Hz, however, the initial increase in the end-plate potential amplitude on the average declines within a few minutes to a steady-state value about 35% higher than the steady-state end-plate potential before stretch. At 5 Hz, the initial amplitude increase is followed by a decline of about 15 min duration and the final amplitude is not increased in comparison with the pre-stretch amplitude. The amplitude of the compound muscle action potential of the gastrocnemius muscle with intact circulation shows a similar time dependent increase upon stretch at different stimulus frequencies. It is concluded that stretch of a frog muscle gives both an immediate and a sustained increase in transmitter release from the nerve terminals during prolonged stimulation at frequencies up to about 5 Hz. This effect of stretch on transmitter release can improve in vivo neuromuscular impulse transmission.

Action Potentials↗

An interactive program on the PDP-11 for computing organ blood flow from data obtained using the radioactive microsphere technique.

An interactive, BASIC-PLUS language program is described for computation of various parameters of blood flow in research animals from data obtained using the radioactive microsphere technique. This program used in conjunction with the PDP-11 computer gives the following output for a variable number of organs studied simultaneously: (1) descriptive statistics on counts per minute; (2) total blood flow to an organ; (3) blood flow to an organ per unit weight; (4) resistance to flow in that organ; (5) total systemic arterial resistance; (6) cardiac output; and (7) percent of cardiac output distributed to each organ. Further, separate outputs can be generated when a series of different isotopes are used in the same animal to study different experimental conditions.

Animals↗

Selection of an in vitro carcinogenicity test for derivatives of the carcinogen hexamethylphosphoramide.

The demonstration that hexamethylphosphoramide (HMPA) possesses potent carcinogenic properties has raised doubts about the safety of exposure to other phosphoric amides. In order to define a suitable short-term test with which to evaluate such analogues, the response of the Salmonella typhimurium mutation assay of Ames and cell transformation assay of Styles to HMPA and 3 selected analogues has been studied. These analogues were the related leukaemogen phosphoramide, the putative non-carcinogen, phosphoric trianilide and N.N'N''-trimethylphosphorothioic triamide, a compound of unknown and hitherto unpredictable properties. While both tests found the trianilide negative, the Ames test failed to detect phosphoramide as positive and gave an erratic and predominantly negative response to HMPA. In contrast, the transformation assay found both phosphoramide and HMPA positive. This test response profile indicates that the transformation assay is the preferred test with which to evaluate analogues of HMPA for potential carcinogenicity. Some structural requirements for potential carcinogenicity within this class of compounds are tentatively deduced.

Anilides↗

Dominant lethal studies with the halogenated olefins vinyl chloride and vinylidene dichloride in male CD-1 mice.

The mutagenic activity of vinyl chloride (VC) and vinylidene dichloride (VDC) at three exposure levels was assessed in fertile male CD-1 mice with the dominant lethal test. Each compound was assessed in a separate study. Male mice were exposed by inhalation to VC at 3000, 10,000, and 30,000 ppm and to VDC at 10, 30, and 50 ppm for 6 hr/day for 5 days. By comparison with control males exposed to air, no mutagenic effects on any maturation stage of spermatogenesis in treated males were detected. There was no significant increase in the number of postimplantational early fetal deaths as shown by the number of females with one or more early deaths or the number of early deaths/pregnancy or the number of early deaths/total implants/pregnancy. There was no evidence of pre-implantational egg losses as indicated by the total implants/pregnant female. There was also no reduction in fertility. (The reduction in fertility at 50 ppm VDC was unproven). The lack of effect was not due to the insensitivity of the system used, since both the VC and VDC study a mutagenic effect was clearly demonstrated in male mice dosed IP with the positive control compounds cyclophosphamide (CTX) and/or ethylmethane sulfonate (EMS). During dosing these animals were housed under similar exposure conditions to those animals exposed to the test substances but with a flow of air through the exposure chambers.Thus, neither VC nor VDC is mutagenic in the mouse at the stated exposure levels as measured by the dominant lethal test.

Animals↗

Trimethoprim-sulfamethoxazole compared to ampicillin in the treatment of shigellosis.

Twenty hospitalized children between 1 and 11 years of age were enrolled in a comparative randomized evaluation of trimethoprim-sulfamethoxazole (TM-SM) and ampicillin for the treatment of shigellosis. Each drug was provided for five days. The group treated with ampicillin had significantly more stools per day (mean 21.25) compared to the TM-SM group (8.64). Treatment with TM-SM appeared to be associated with a more rapid reversion of stool cultures to normal, but these differences compared to ampicillin were not statistically significant. Review of all isolates of Shigella from our hospital revealed a marked decrease in sensitivity to ampicillin over the last six years. This pattern has been observed in other centers. TM-SM may be the best drug for the treatment of shigellosis in areas where multiple antibiotic-resistant organisms are common.

Ampicillin↗

Evaluation of six short term tests for detecting organic chemical carcinogens and recommendations for their use.

Six short term tests for detecting carcinogenicity have been evaluated using 120 compounds, of which half were carcinogens and the rest non-carcinogens. The results obtained indicate that the Ames test and a "cell transformation" assay are both sufficiently sensitive to carcinogenicity, or the lack of it, in the compounds studied to enable them to be employed for detecting potential carcinogens. The consequences of using short term tests under various screening conditions have been explored. In order to have confidence in the results obtained for new or previously untested compounds it is important to use such tests in a carefully controlled manner.

Alkylating Agents↗