Post-colonoscopic retrograde ileography.
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Biomedical subjects
Publications and source records attributed to D F Martin.
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Seventy-three patients with retained stones in the common duct after biliary surgery underwent attempted endoscopic removal at a mean interval of 39 days after surgery. Endoscopic extraction was successful in 63 patients (86 per cent). Complications occurred in 14 patients (19 per cent). The most frequent complication was haemorrhage which occurred in nine patients, four of whom required surgery; two other patients required surgery for complications. The complication rate of endoscopic sphincterotomy in recently operated patients may be higher than in the non-operated patient. Less invasive methods, such as dissolution therapy or T tube track extraction, may be preferable as they are associated with less risk. Endoscopic sphincterotomy should be reserved for patients in whom these alternative techniques fail or are inappropriate.
Airborne Ptychodiscus brevis toxin (PBTX), produced by Ptychodiscus brevis (Florida red tide), induces cough, rhinorrhea, watery eyes, and sneezing in normal individuals and wheezing in subjects with asthma. The mechanism of PBTX-induced contractile response has been investigated by the authors in vitro in dog and rat tissue. PBTX stimulates neuronal sodium channels, resulting in activation of autonomic cholinergic and adrenergic nerve endings in canine upper and lower airway smooth muscle and in rat vas deferens, respectively. This article concerns the investigation of the effect and mechanism of action of PBTX on human airways in order to determine the unique role of the toxin in the pathogenesis of asthma. PBTX elicited contractions of isolated human airway smooth muscle with a threshold concentration of 0.1 micrograms/ml, very similar to values obtained in canine lower airways. Pharmacologic analysis demonstrated that atropine (10(-6) mol/L) blocked the response to both PBTX and acetylcholine; tetrodotoxin (10(-7) mol/L) blocked PBTX but not acetylcholine; and verapamil (10(-5) mol/L) attenuated but neostigmine (10(-8) mol/L) potentiated the response to PBTX. Other selected blockers did not affect the PBTX response. These data indicate that PBTX produces contraction of human lower airway smooth muscle via stimulation of cholinergic nerve fiber sodium channels. The concept that PBTX triggers asthma through this mechanism is strengthened by these results.
The uncinate process of the pancreas has been assessed in 106 consecutive patients without pancreatic disease in order to establish normal features. The process measures approximately 1 X 1.3 cm in size, is frequently inseparable from the superior mesenteric vein without contrast enhancement and can adopt a number of cross-sectional configurations.
A novel approach to the management of Mirizzi's syndrome due to a mucocele of the gallbladder is reported. Endoscopic retrograde catheterisation of the gallbladder permitted decompression, and was followed by extracorporeal shockwave lithotripsy of gallbladder calculi in an 80-year-old man considered unfit for operation.
Campylobacter pylori (CP) is implicated as a probable pathogen in gastritis and peptic ulcer disease. A blinded prospective study of 112 subjects evaluated how Gram's-stained touch preparations of mucosal biopsies compared with culture, routinely processed hematoxylin and eosin (H and E) and Warthin-Starry (WS) staining in confirming the presence of CP. At endoscopic examination, two mucosal biopsies were taken from the gastric antrum and two from the fundus of each subject. One biopsy from each site was Gram's stained and cultured and the other submitted for H and E and WS. Fifty of the 112 subjects had positive results for CP by at least two of the tests (44.6%). Histologically, 48 (96%) of the CP-positive subjects showed the presence of gastritis. Of 55 subjects who had gastritis, 50 had CP (91%). If both sites in the stomach were taken into account, the sensitivity and specificity of Gram's staining in detecting CP were 92% and 100%, respectively. These results are comparable to H and E and WS and slightly better than culture. The diagnosis of CP can be made accurately, rapidly, and inexpensively by Gram's stained touch preparations of mucosal biopsies.
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We have been using the 9L rat brain tumor model to investigate the effect of the combination of a perfluorochemical emulsion, Fluosol-DA 20%, and carbogen breathing on the therapy of brain tumors. The combination of Fluosol, carbogen breathing, and carmustine (BCNU) was more effective at prolonging survival than was BCNU alone. This difference was small but significant (P less than 0.25). neither Fluosol without carbogen nor carbogen without Fluosol significantly altered the effect of BCNU. Fluosol and carbogen alone did not affect the survival of tumor-burdened rats. Fluosol and carbogen breathing did not alter the effect of single doses of radiation on these tumors. This result supports the hypothesis that 9L brain tumors contain few, if any, critical hypoxic cells. However, these tumors may contain cells which are oxygen deficient but not radiobiologically hypoxic. The Fluosol-carbogen combination may be changing the intratumor environment in such a way that the metabolism or activity of BCNU is altered.
Spirogermanium (SPG) was investigated in the 9L rat brain tumor model in vivo and in vitro. Used at a single ip dose of 50 or 60 mg/kg or at 5 daily doses of 10 mg/kg, SPG was ineffective in prolonging survival of rats burdened with the intracerebrally implanted tumor, i.e., the median survival time (MST) was the same as that for the controls. Only a schedule of 3 X 20 mg SPG/kg every other day improved the MST compared with controls. Single-dose (20-Gy) radiation therapy (RT, cesium-137 whole-head irradiation) did prolong survival. However, when single-dose SPG was combined with RT (1 hr or 1 day before, or 1 hr after RT), the survival response was worse than after RT alone. When the daily SPG was combined with daily RT (5 doses of 6 Gy), survival was no better than after daily RT alone. In vitro, SPG produces a concentration-dependent, exponential decrease in cell survival as measured by colony formation assay. When combined with radiation, there is an additive effect on cell lethality. Aside from the possibility that SPG does not penetrate the rat brain tumor itself, we have no explanation why SPG shows some activity against human brain tumors and is cytotoxic against 9L cells in vitro, yet is both ineffective by itself and fails to potentiate RT in the 9L rat brain tumor model.
Endoscopic sphincterotomy was attempted in 81 patients with gallbladders for the primary management of symptomatic common duct stones and was successful in 80. Immediate complications occurred in six (7 per cent) and one patient died (1 per cent). Clearance of the common duct was achieved in 70 (86 per cent). Eight patients required surgery for failed clearance of the duct and suffered no operative mortality. Of 70 patients with cleared ducts, 5 underwent elective cholecystectomy. Four other patients with persistent or recurrent symptoms have required cholecystectomy, also without mortality. Sixty-one patients were reviewed 12-44 months (mean 24; median 22 months) after endoscopic sphincterotomy. Eighteen have died, none from biliary disease. Forty-three patients remain alive and well, free of biliary symptoms since, endoscopic sphincterotomy. When the surgical risk of cholecystectomy and choledocholithotomy is high, endoscopic sphincterotomy is effective and safe. Routine cholecystectomy is not indicated when the common duct has been cleared.
Enteric duplication cysts (enterogenous cysts) are found most commonly in the distal ileum, the posterior mediastinum, and the third part of the duodenum. Rarely, enteric cysts can occur distant from the gut. This paper describes the clinical and radiologic features of a cystic lesion in the body of the pancreas which was shown on resection to be an enteric cyst.
Ptychodiscus brevis toxin (PBTX) is produced by the organism Ptychodiscus brevis. This toxin causes a phenomenon that has come to be known as Florida red tide. It also stimulates neuronal sodium channels, resulting in activation of the cholinergic and adrenergic nerve endings of the autonomic nervous system in upper airway smooth muscle and rat vas deferens, respectively, as previously reported. It is the cholinergic stimulating action that has been implicated as a possible "triggering" event in bronchial asthma. This article concerns the investigation of whether PBTX may also affect lower airways and by what mechanism any contractile response to PBTX in lower airways may be induced. PBTX was found to elicit contractions in isolated canine lower airway smooth muscle. The threshold concentration was 0.15 microgram/ml, the peak response occurred at 6.0 micrograms/ml, and the concentration causing half-maximal response of the group was 0.57 microgram/ml. Pharmacologic analysis demonstrated that atropine (10(-6) mol/L) blocked the response to both PBTX and acetylcholine, tetrodotoxin (10(-7) mol/L) blocked the response to PBTX but not to acetylcholine, and verapamil (10(-5) mol/L) blocked the response to PBTX and reduced the response to acetylcholine. Four consecutive contractile responses to PBTX (3 micrograms/ml) produced rapid tachyphylaxis. The fourth contraction was 60% less than the initial response. A fifth response to PBTX after exposure to indomethacin (2.8 X 10(-6) mol/L) was increased and resulted in a contraction that was only 25% less than the initial response. The exogenous addition of prostaglandins (PG), PGE1 and PGE2, to indomethacin-treated lower airway strips selectively suppressed the contractile response to PBTX. Other PGs tested (PGA2, PGB2, PGD2, PGF2 alpha and PGI2) did not affect the PBTX response. These results indicate that PBTX produces spasm in lower airway smooth muscle and that it does this by stimulation of sodium channels in the cholinergic nerve fibers. The results also demonstrate a rapid reduction in the contractile response to PBTX. The results also demonstrate that the reduction is mediated by PGs of the E series.
The presence of radioresistant hypoxic cells in tumors is believed to be one of the limiting factors in achieving local tumor control by radiotherapy. Treatment with hyperbaric oxygen during irradiation has been shown to improve the radiation response of many solid tumors in rodents and of some tumors in patients. Intravenous administration of perfluorochemical emulsions combined with oxygen breathing at atmospheric pressure has also been shown to improve the radiation response of several rodent tumors. Theoretical considerations suggest that the combination of a perfluorochemical emulsion and hyperbaric oxygen should be significantly more effective than either agent alone. This hypothesis was tested by examining the radiation response of BA1112 rhabdomyosarcomas growing in WAG/rij-Y rats. Treatment with a perfluorochemical emulsion, Fluosol-DA, plus hyperbaric oxygen (3 Atmospheres O2) significantly increased the radiation response of the malignant cells in these solid tumors. The observed changes in the tumor cell survival curve suggest that the combination of Fluosol-DA and HBO decreases the proportion of severely hypoxic cells in the tumor to less than 1.5% of the original value. The effect of the Fluosol-DA dose and the duration of pretreatment with HBO are described.
An 241Am applicator for continuous low-dose-rate irradiation of the rat sarcoma BA1112 has been developed. The irradiator consists of two disc sources, each containing 800 mCi of 241Am, an isotope which emits primarily 60 keV photons. The disc sources are held in a specially-designed light-weight helmet which surrounds the tumor on the head of the rat. Dose distributions produced by these sources have been measured using an ionization chamber, thermoluminescent dosimeters and Fricke dosimeter. A computerized treatment planning system has been modified to compute dose distributions from 241Am sources, to optimize the design of this applicator. Computed and measured dose distributions for several values of separation between the 241Am discs are presented. A survival curve for cells from tumors irradiated in vivo with this applicator has been determined by an in vitro colony formation technique. The mean lethal dose DO was found to be 720 cGy for an average tumor dose rate of 95 +/- 7 cGy/hr. The major advantages of the 241Am applicator in comparison with the 192Ir applicator used previously for continuous low-dose-rate studies are: a considerably smaller half value layer thickness and the longer half life of the radionuclide. These features make it more suitable for long-term tumor cure studies because of the lower whole body dose to the animal, the availability of relatively constant dose-rate irradiators for many years, the decreased shielding requirements for the animal care facility and the diminished exposure to laboratory personnel involved with the implants on the animals.
The superior mesenteric artery (SMA) is constant in its retroperitoneal course and easily identified on computed tomography (CT). In 225 CT examinations, anterior and lateral displacement from a defined normal position of the proximal SMA were assessed and correlated with the presence of retroperitoneal disease. Displacement beyond the left margin of the adjacent vertebral body was always due to disease, whereas an SMA situated to the right of a normal aorta was virtually always normal. Lesser degrees of displacement were not reliably associated with disease. In cases where there was minor SMA displacement but CT appeared normal, clinical follow-up revealed retroperitoneal disease in only three out of 40 patients (7.5%). Minor displacement of the SMA is not a good indicator of occult retroperitoneal disease.
The effect of treatment with a perfluorochemical emulsion (Fluosol DA, 20%), carbogen, or the combination of these two agents on the radiation response of BA1112 tumors in WAG/rij rats was examined. Fluosol and carbogen as single agents had only small effects on the tumor cell survival curve. The combination of Fluosol plus carbogen had a larger effect on tumor cell survival, reducing the hypoxic fraction of the tumor from 23 to 1.6%. The amount of sensitization was a function of the Fluosol dose, with maximal augmentation of the radiation response obtained at doses of 7.5-15 ml/kg. Carbogen pretreatments ranging from 5 to 60 min in duration all had similar effects on tumor radiosensitivity. The effect of the perfluorochemical emulsion plus carbogen on the survival of irradiated tumor cells appears to reflect changes in tumor oxygenation, rather than cytotoxic or immunological effects, since the perfluorochemical emulsion (with or without carbogen) had no effect on the viability of cells in unirradiated tumors. These experiments extend previous studies by ourselves and others using mouse tumors to show that the combination of a perfluorochemical emulsion and carbogen breathing can also increase the radiation response of a nonimmunogenic rat tumor.
There is relatively poor documentation of the effect of metoclopramide on the human esophageal body. We, therefore, studied several parameters of esophageal function in 19 normal volunteers both before and after 20 mg intravenous metoclopramide. Contraction amplitude, wave duration, velocity, and propagation time were increased after metoclopramide. These changes were more pronounced in the distal esophagus. At the most distal manometric recording level located 2 cm above the lower esophageal sphincter, contraction amplitude increased 39% (p less than 0.01) and duration increased 22.5% (p less than 0.01) after metoclopramide. We conclude that in normal subjects metoclopramide has an effect predominant in the distal body of the esophagus.
It has been postulated that tumors contain hypoxic cells of decreased radiation sensitivity, which limit curability with radiation therapy. Hyperbaric oxygen has been used in an attempt to improve tumor oxygenation. The nature of the oxygen concentration-radiation sensitivity relationship (oxygen increases the slope of the radiation cell survival curve) suggests that a small number of hypoxic cells, as few as one in one million, would limit tumor curability. Oxygen moves by diffusion from the capillary into the tumor. An increase in partial pressure in the capillary will increase the effective diffusion distance. To improve tissue oxygenation effectively the partial pressure of oxygen in blood must be significantly increased throughout the length of the capillary, in particular at the venous end. Theoretical considerations indicate that hyperbaric oxygen as presently used in radiation therapy, 3 ATA, would lead to only marginal improvement. PartO2 may be as much as 0.8 atm below that of the inspired gas; this plus the consumption of oxygen along the length of the capillary lead to predictions of values for PEnd CapO2 of less than twice normal. Such considerations explain the rather limited success of hyperbaric oxygen with radiation therapy. Thus it is unnecessary to postulate an absence of hypoxic cells to explain this clinical observation. In the presence of perfluorocarbon micelles the non-hemoglobin-bound oxygen carrying capacity of blood is significantly increased. Theoretical considerations predict that the difference between PartO2 and PO2 of the inspired gas should be decreased. Furthermore, the nonhemoglobin-bound oxygen carrying capacity should be adequate to satisfy tissue consumption requirements without unloading hemoglobin, thereby avoiding the "PO2 buffering effect of hemoglobin" and permitting a significant increase in PO2 throughout the capillary length. This effect has been demonstrated using a rodent tumor model.