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Biomedical subjects

D F Martin

Publications and source records attributed to D F Martin.

At least 163 records · Page 9Linked to original sources
PubMed1986

Effectiveness and biological effects of techniques used to induce hypoxia in solid tumors.

Acute hypoxia is often induced in rodent tumors during studies of the oxygenation or the therapeutic responses of the tumors, either by clamping the blood supply to the tumors or by asphyxiating the hosts with nitrogen. Analyses of data from such experiments generally assume that these processes have no effects other than the induction of hypoxia and that uniform, severe hypoxia is produced throughout the tumors. The studies described in this report test several aspects of these assumptions using BA1112 rat rhabdomyosarcomas and EMT6 mouse mammary tumors. Both clamping and asphyxiation appear to be effective in producing hypoxia in the tumors. Induction of artificial hypoxia for the times necessary for irradiation was not toxic to the tumor cells and generally did not alter the growth of unirradiated tumors. However, the techniques are not without significant effects. Prolonged clamping produced extensive cytotoxicity. Clamping BA1112 tumors for 30 min and removing the clamp just before irradiation altered the tumor cell survival curve and the TCD50. Furthermore, anesthesia and/or restraint (necessary during clamping) have significant effects on tumors and hosts. The data show that the assumptions underlying the use of clamping and N2-asphyxiation to produce hypoxia for short periods in vivo are generally reasonable for BA1112 and EMT6 tumors, but illustrate the necessity for carefully examining the effects and efficacies of the procedures in each tumor/host system.

Animals↗
PubMed1986

Contrast-enhanced computed tomography of the normal and abnormal gallbladder.

One hundred and fourteen upper abdominal computed tomography examinations performed before and after intravenous contrast were reviewed. In 48 patients who had no evidence of biliary or pancreatic disease, the mean gallbladder wall attenuation before contrast was 25 +/- 13 HU and after contrast 42 +/- 18 HU, with a wall thickness of 1.9 +/- 0.43 mm. In 14 patients with chronic pancreatitis these values were 24 +/- 10.5 HU, 44 +/- 25 HU and 2.0 +/- 0.54 mm, respectively. In a further group of 15 patients with chronic biliary disease, the values were 34 +/- 15 HU, 53 +/- 18 HU and 2.3 +/- 0.9 mm. The degree of wall enhancement was statistically significant in each group. There was no statistical difference in the attenuation characteristics or wall enhancement between normal patients and those with chronic pancreatitis. Patients with chronic biliary disease had a thicker gallbladder wall with higher attenuation before contrast but a similar degree of enhancement.

Biliary Tract Diseases↗
PubMed1985

The mechanism of Ptychodiscus brevis toxin-induced rat vas deferens contraction.

Ptychodiscus brevis, which causes Florida red tide, produces Ptychodiscus brevis toxin (PBTX) known to contain neurotoxins and to induce rhinorrhea, tearing, and cough in normal humans and wheezing in asthmatic subjects. It was previously reported (J Allergy Clin Immunol 69:418, 1982; 73:824, 1984) that PBTX causes canine tracheal smooth muscle contraction via stimulation of sodium channels in the axons of parasympathetic postganglionic nerves and the release of acetylcholine from these nerve endings. This was postulated to be an asthma-triggering mechanism. In this article the toxins were evaluated to determine if they also stimulate sodium channels on adrenergic nerve endings and release norepinephrine. Rat vas deferens was selected as the experimental tissue. Both PBTX and norepinephrine contracted rat vas deferens. Prazosin 10(-6) mol/L blocked the response to PBTX (3 micrograms/ml) (88.3% to 27.3% contraction [n = 6; p less than 0.001]) and the response to norepinephrine (EC50 was shifted from 1.67 X 10(-6) mol/L to 1.25 X 10(-4) mol/L in the presence of prazosin 10(-6) mol/L [n = 6; p less than 0.001]). Phentolamine 10(-6) mol/L also blocked both PBTX and norepinephrine. Tetrodotoxin 10(-7) mol/L, a sodium channel blocker, completely blocked the response to PBTX but not to norepinephrine. The response to PBTX was significantly reduced from 1.53 gm of tension in controls to 0.29 gm of tension (n = 6; p = 0.002) in tissues obtained from rats pretreated with reserpine (2 mg/kg per day for 2 days, injected intraperitoneally). Verapamil 10(-5) mol/L blocked the PBTX response, and PBTX caused no contraction in calcium-free media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The aetiology and significance of distal choledochoduodenal fistula.

Thirteen patients undergoing investigation for biliary or pancreatic disease were found at endoscopic retrograde cholangiopancreatography to have unsuspected choledochoduodenal fistula. In only one patient could the presenting symptoms be directly attributed to the fistula. Ten of the thirteen patients had previously undergone exploration of the common bile duct and instrumentation at surgery is postulated as being the most likely cause of these fistulae. Treatment of the uncomplicated fistula appears unnecessary.

Adult↗
PubMed1984

The site of action of Ptychodiscus brevis toxin within the parasympathetic axonal sodium channel h gate in airway smooth muscle.

The red tide toxin produced by Ptychodiscus brevis ( PBTX ) may cause cough, sneezing, and asthma. Previous in vitro studies with isolated canine tracheal smooth muscle demonstrated that PBTX stimulates sodium channels of parasympathetic nerve endings and thus causes a contractile response. The present study investigated the mechanism of the PBTX effect on canine tracheal smooth muscle. Repeated exposure of the muscle strip to PBTX (final concentration 46 micrograms/ml) followed by washout of the toxin resulted in reestablishment of baseline tension but a failure of contraction on further addition of PBTX . However, veratridine and scorpion toxin (SCT), which are voltage-sensitive sodium channel activators, still induced contraction. Furthermore, the contraction caused by veratridine was enhanced by a high dose of PBTX , whereas contraction caused by SCT was not. Responses to veratridine and SCT as well as PBTX (previously reported) were blocked by tetrodotoxin (a sodium channel blocker), while acetylcholine responsiveness remained intact. These results indicate that PBTX receptors in parasympathetic nerves influence Na+ flux at the h gate, that these receptors differ from the veratridine and SCT receptors, and that the conformational change in the receptors induced by PBTX affects the tissue response to veratridine.

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↗
PubMed1984

Tumor-to-tumor variability in the hypoxic fractions of experimental rodent tumors.

Paired determinations of the radiation responses of normally-aerated and artificially hypoxic rodent tumors, performed to measure the hypoxic fractions of the tumors, were obtained from our own laboratories and from the literature. The data were reanalyzed to assess whether the variabilities in the radiation responses of the normally-aerated and artificially hypoxic tumors were similar. If there were large differences in the hypoxic fractions of individual tumors within the experiments, the variability in the data from aerobic tumors would be expected to be greater than the variability in the data from artificially hypoxic tumors (which should all be brought to uniform hypoxia and therefore uniform radioresistance). The analyses revealed the variability to be as great or greater for hypoxic tumors as for normally-aerated tumors. This finding suggests that factors other than tumor-to-tumor differences in oxygenation produce most of the variability in the radiation responses of individual tumors from an experimental tumor line.

Animals↗
PubMed1984

Tumor cure studies on the rat sarcoma BA1112 using continuous low-dose-rate radiation.

Delivery of continuous low-dose-rate radiation at a constant rate using an after-loading plastic helmet system can achieve the local cure of the BA1112 rat sarcoma. Complete dose response curves for local tumor cure have been obtained at 170 rad (1.7 Gy) and 130 rad (1.3 Gy) per hour. The results are consistent with the known radiobiological properties of the BA1112 tumor.

Animals↗
PubMed1984

Effect of aponin, a substance from a green alga Nannochloris species, on the spore germination of two fungi.

Fungistasis which occurs in soil has also been reported to exist in seawater. Nannochloris sp. (Chlorophyta) found along the west coast of Florida, has been shown to elaborate a compound which is cytolytic towards Ptychodiscus brevis, the Florida red tide organism. Aponin, a chloroform extract containing the cytolytic compound or compounds, was tested on the spore germination of two fungi, Dendryphiella salina, a facultative marine organism and Curvularia sp. a terrestrial one. Aponin was stimulatory towards D. salina at all concentrations tested, while Curvularia sp. was stimulated at the highest concentration used but inhibited at the lower concentrations. The culture age of the two fungi did not alter the relative sensitivity of both fungi towards aponin but the germination percentage of Curvularia sp. was affected by the culture age. An aqueous extract of Nannochloris sp. was also tested on the two fungi and was shown to be inhibitory to both. The results seem to indicate that more than one compound from Nannochloris sp. is capable of affecting spore germination indicating that this alga might be playing a role in the reported fungistasis in seawater. Gulf seawater was tested and found to have little if any fungistatic activity.

Chlorophyta↗
PubMed1984

A spectroscopic technique for evaluating sterol-aponin interactions and implications for management of Ptychodiscus brevis red tides.

A double-beam quadruple-cell spectrophotometric technique is described that can be used to evaluate the interaction between sterols and HPLC fractions from Nannochloris sp. which are cytolytic (aponin) toward the red tide organism. The interaction with ergosterol but not beta-sitosterol is consistent with complex formation and also with the reduction of cytolytic activity of aponin in the presence of ergosterol, as previously noted. Implications for the mechanism of aponin cytolytic activity are considered.

Cholesterol↗
PubMed1984

Hypoxic fraction determinations with the BA1112 rat sarcoma: variation within and among assay techniques.

Measurement of the hypoxic fraction in the same tumor system by different assay techniques often gives incompatible results. The hypoxic fraction of the BA1112 sarcoma has been measured by three assay techniques: tumor control and growth delay assays in which the tumors remain in situ after irradiation, and paired survival curve assays in which the tumors are excised after irradiation. The assays were done with and without anesthesia on tumors growing in two different subcutaneous sites. Anesthesia of the hosts produced a statistically significant decrease in the calculated hypoxic fraction in a tumor control assay, but not in a paired survival assay. The excision assays gave consistently higher hypoxic fraction estimates than either the tumor control or growth delay assays. Some of the factors which could produce higher hypoxic fractions in excision assays than in in situ assays are discussed. Interpretation of the results was complicated by disagreements between the growth delay and tumor control assays, and by disparities between replicate determinations. The discrepancies among assays are caused almost entirely by variations in the response of the artificially hypoxic tumors, rather than variations in the response of aerobic tumors. These results indicate that assumptions commonly made when measuring hypoxic fractions may not be valid.

Aerobiosis↗
PubMed1983

Development of an in vitro assay for the survival of cells suspended from BA1112 rat sarcomas.

A method has been developed for the in vitro assay of the survival of BA1112 rat sarcoma cells following treatment in vivo. The BA1112 tumor was not adapted for growth in culture and was maintained by serial transplantation in vivo. The assay used a feeder layer of heavily irradiated cells to eliminate any changes in plating efficiency caused by the large number of dying cells which must be plated when assaying cell survival after intensive treatments. The plating efficiency of the tumor cells was not affected significantly by the age of the feeder layer (between 1 and 4 days), the density at which the experimental cells were plated or the interval between preparation of the cell suspension and plating (up to 4 hr). Using the in vitro assay a survival curve was determined for cells from tumors irradiated in air-breathing animals. This curve was similar to that determined previously for BA1112 tumor cells using an in vivo assay to measure cell survival.

Animals↗
PubMed1983

Venous complications of two diazepam preparations related to size of vein.

The venous complications associated with the administration of two preparations of diazepam, an aqueous (Valium) or a lipid (Diazemuls) preparation were investigated in 100 patients before upper gastrointestinal endoscopy in a double-blind randomized study. No differences in pain during injection or subsequent thrombophlebitis were found when a large vein was used for the injections. In a retrospective study of 78 patients who had received either preparation in a vein on the dorsum of the hand, the frequency of thrombophlebitis was significantly less with the lipid preparation. Both preparations provided effective sedation for endoscopy.

Arm↗
PubMed1983

The effect of subtotal resection on the dose of radiation required to cure the rat rhabdomyosarcoma BA1112.

Dose response curves were established for local control of the rat rhabdomyosarcoma BA1112 for radiation alone and for radiation following a cytoreductive operation. Removal of one-half of the tumor prior to irradiation did not significantly alter the dose of radiation necessary to cure 50 per cent of the tumors. This experimental result confirms the theoretic predictions and suggests that, to be useful in combination with radiation, surgical treatment must remove in excess of 90 per cent of the tumor.

Animals↗
PubMed1982

Effects of toxin of red tide, Ptychodiscus brevis, on canine tracheal smooth muscle: a possible new asthma-triggering mechanism.

The red tide toxin produced by Ptychodiscus brevis becomes airborne by the thrashing action of the surf and wind and induces cough, rhinorrhea, watery eyes, and sneezing in normal humans and wheezing in asthmatic patients. The mechanism of the contractile response induced by P. brevis toxin (PBTX) was investigated with isolated canine tracheal smooth muscle. Tetrodotoxin and atropine blocked the contractile effect of PBTX, and neostigmine potentiated the contraction. Mepyramine, phentolamine, methysergide, and chlorisondamine did not inhibit the effect of PBTX. This is the first description of a naturally occurring airborne substance that causes smooth muscle contraction by stimulating the axon sodium channels, resulting in the release of acetylcholine at postganglionic parasympathetic efferent nerve endings. The in vitro effect of PBTX on canine tracheal smooth muscle indicates that PBTX is capable of causing respiratory irritation and thus may precipitate an asthmatic attack. It is possible, however, that the mechanism is vivo may also include stimulation of a cough receptor reflex and/or stimulation of sodium channels of afferent vagus nerve fibers. In vitro evidence suggests that isoproterenol, atropine, and verapamil may be used to eliminate or prevent the respiratory symptoms that follow exposure to airborne red tide toxin. The use of high-pressure liquid chromatography separated fractions indicates that the neurotoxic component, not the hemolytic component, is responsible for contractions.

Acetylcholine↗
PubMed1982

Heterotopic gastric mucosa in the duodenum.

Thirteen patients are described who, on routine endoscopy of the upper gastrointestinal (GI) tract, were found to show a characteristic appearance in the proximal duodenum. This consisted of multiple small mucosal nodules, predominantly in the anterior wall. All cases were biopsied, and showed identical histological appearances of heterotopic gastric mucosa of body type. The incidence of this condition is probably much higher than reported previously, and may be present in up to 2% of the population. In all our patients a diagnosis was reached, other than heterotopic gastric mucosa, to explain the GI tract symptoms. In none was a healed or active duodenal ulcer evident and in none was there a history of a pre-existing ulcer. In our opinion these nodules are probably of little or no clinical significance.

Adult↗
PubMed1982

Likelihood of relapse of duodenal ulcer after initial treatment with cimetidine or colloidal bismuth subcitrate.

Colloidal bismuth subcitrate (CBS, DE-NOL) and cimetidine have been compared in a double-blind randomized trial in the management of 75 patients with duodenal ulcer. The drugs had similar potency with respect to ulcer healing. At one month the healing rates were 66% for CBS and 59% for cimetidine. At two months the rates were 89% and 85% respectively. When the drugs were withdrawn patients who had received CBS had significantly lower relapse rates than those who had received cimetidine. Relapse rates for CBS and cimetidine were 13% and 70% at six months and 39% and 85% at one year respectively.

Adolescent↗