Biomedical subjects
Publications and source records attributed to D L Morris.
Both benzimidazole carbamates and isoquinoline compounds have activity against protoscoleces of Echinococcus granulosus in culture in vitro; combinations of albendazole sulphoxide and praziquantel are more effective than either agent alone.
The metacestode stage of Echinococcus multilocularis was cultured in vitro. Sensitivity of protoscoleces to the presence of albendazole sulphoxide, praziquantel and methanol was assessed. 10 micrograms/litre of praziquantel or 500 micrograms/litre of albendazole sulphoxide significantly reduced protoscolex viability. The presence of methanol (at 0.25%) had no significant effect. In vitro culture of E. multilocularis can be used to assess possible chemotherapeutic agents.
The effects of albendazole and praziquantel on the growth of Echinococcus multilocularis were studied in cotton rats. Albendazole (20 and 50 mg/kg) reduced parasite weight and increased the length of survival of infected animals but viable infection was present after treatment. In an in vitro system albendazole sulphoxide entered cysts of E. multilocularis passively. Praziquantel 100 mg/kg was ineffective but 500 mg/kg significantly inhibited growth. A combination of albendazole and praziquantel was no more effective than either agent alone.
Gastric juice was studied in five patients after Billroth II partial gastrectomy, in six patients after Roux-Y reconstruction, and in eight healthy control subjects. Juice was obtained over a 24 hour period by hourly nasogastric aspiration prior to measurement of pH, total and stable N nitrosocompounds, nitrites, bile acids (total and free), and bacterial count. Large variations in almost all compounds were seen during the 24 hour period in individual patients, and in addition, there were large variations between patients within the clinical groups. The gastric juice pH concentration was higher in the Billroth II group, as was the bacterial flora count (median 3 X 10(6) organisms/ml). Although Roux-Y bile diversion reduced the exposure to bile acids, it did not prevent it, and bacterial proliferation was increased (1 X 10(7) organisms/ml). No significant differences or sizeable trends were seen in N nitrosocompounds or nitrite concentrations.
It is remarkable that the pathogenesis of a condition with as long a history and as much morbidity as hemorrhoids is incompletely understood, but various theories still contend for acceptance. The classification, presentation, symptoms, and complications of hemorrhoids are discussed, and various treatment options--injection sclerotherapy, rubber band ligation, manual anal dilatation, sphincterotomy, cryotherapy, infrared photocoagulation, bipolar diathermy, and the galvanic generator and probe--are reviewed.
Ovine and equine protoscoleces of Echinococcus granulosus were cultured for 26 days with our without praziquantel and viability assessed, by eosin exclusion, for cultures in various drug concentrations (50, 250 and 500 micrograms/l) and periods of exposure (1, 3 or 7 days (d] before removing/'rescuing' to drug-free medium. Drug efficacy was proportional to drug concentration and to length of exposure. At higher drug concentrations shorter exposures were required to produce the effect of continuous drug treatment, 1d therapy at 500 micrograms/l killing 96% ovine protoscoleces by day 14 whereas 7d therapy at 50 micrograms/l was required to produce a similar effect. Equine protoscoleces appeared marginally less susceptible than those of ovine origin. The relevance of the results in the need for peri-operative prophylaxis against spilled protoscoleces in man is discussed.
Praziquantel (500 mg/kg) administered orally to BALB/c mice with secondary equine E. granulosus daily for 21, 30 or 30 + 30 days without the drug resulted in the majority of cysts, using bench criteria of turgidity and eosin exclusion, being assessed as 'alive'. Ultrastructural examination of 54 of these 'alive' cysts did not support this conclusion. They all showed increased vesiculation of the germinal layer leading, in many, to the loss of its integrity. Increased mitochondrial numbers occurred frequently. The longer drug treatments appeared to have greater effects on the germinal layer of 'alive' cysts and there was no detectable reestablishment of structural organization within 30 days after drug withdrawal. Subjectively, there was no substantial difference between cysts from 4-month and 9-month infections or between affected peritoneal and hepatic cysts. Tissue from collapsed cysts was necrotic. Peak serum levels of praziquantel (6430-6136 micrograms/l) occurred 5-10 min after drug administration (500 mg/kg) and dropped rapidly to less than 10 micrograms/l at 3 h. In an in vitro study at praziquantel concentrations of 1000 and 5000 micrograms/l over a 10-day period, most cysts were judged 'alive' by bench criteria but showed ultrastructurally a time- and concentration-dependent loss of integrity identical to that seen in vivo. Turgidity and eosin exclusion therefore underestimate the effect of praziquantel and the results indicate that in vitro experiments can fulfil a legitimate preliminary role in a hydatid chemotherapy programme.
Recurrence is an important problem following operations for hydatid disease in man. Significant protection against an intraperitoneal injection of 5000 protoscoleces was achieved in gerbils by a one-month course of albendazole (10 mg kg-1 day-1). However, when prophylaxis was delayed for 15 days after peritoneal inoculation albendazole had no protective effect. Whilst higher serum concentrations probably allow treatment of older infections, these data suggest that protoscoleces are most easily killed by therapy immediately following spillage.
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Stress ulcer is a dangerous complication for the critically ill patient. Prophylaxis with antacids can undoubtedly reduce this risk, if gastric pH is maintained above 3.5. Histamine receptor antagonists may achieve this more conveniently. We have studied the effects of ranitidine, given either as 50-mg boluses every 6 h or as one of two infusion regimes (125 or 250 micrograms/kg.h), in controlling pH in critically ill patients on a ventilator. The percentage of samples with a pH less than 4 fell in all groups during therapy; while there was no significant difference between groups, pH control was achieved more rapidly in the bolus group. Infusion therapy with ranitidine is an attractive concept but a loading dose must be used. The presence of occult blood in the gastric juice did not correlate with pH and was not affected by ranitidine therapy.
To evaluate the relationship between heightened sympathetic tone and maximal metabolic vasodilation, peak forearm blood flow (ml.min-1.100 ml-1) was measured plethysmographically in 18 volunteers after the release of 10 min of arterial occlusion (the peak reactive hyperemic blood flow response, RHBF) both before and after a stimulus to induce heightened sympathetic tone. The stimulus was the application of ice to the forehead for 90 s just before and during RHBF measurements. Mean arterial cuff blood pressure (MAP; mmHg) was calculated, and corresponding resistance (R; mmHg.ml-1.min.100 ml) was derived from blood pressure divided by RHBF. During ice application, blood pressure rose (pre 92 vs. post 115 ml/mmHg; P less than 0.05), peak RHBF was unchanged (pre 38.8 vs. post 36.4 ml.min-1.100 ml-1; not significant), but R during the maximal metabolic stimulus rose (pre 2.5 vs. post 3.2 mmHg.ml-1.min.100 ml; P less than 0.05). To examine the effects of heightened sympathetic tone on conduit vessels, simultaneous measurements of maximal metabolic blood flow (RHBF) and brachial artery Doppler velocity (V, cm/s) were conducted (n = 5) with and without ice applied to the forehead. Velocity rose by 70% as flow remained constant. Thus brachial artery area (area = flow/velocity) and diameter decreased substantially (20% decrease in diameter). The increase in R noted with ice was due to an alpha-mediated response, since the increase in R was blocked by oral prazosin (n = 6) and was unaffected by maneuvers to alter myogenic tone (n = 5). We conclude that maximal metabolic vasodilation can be counteracted to some extent by the effects of heightened sympathetic tone. Moreover, some of the interaction between these two opposing influences takes place at the arterial level.
A new technique induces localized myocardial infarction in closed-chest dogs by placing discrete plugs in coronary arteries without using cumbersome coaxial catheters or guide wires. Flexible plugs, essential to this method, are formed by extruding a dental impression polymer, rendered radiopaque with sodium iodide, into spaghetti-like strands. Segments of these strands can be injected through a catheter into a selected coronary artery. Contact with blood or saline causes plugs to swell. The mean increase in plug diameter due to swelling was 27 +/- 20%. Eight anesthetized dogs were embolized via carotid approach [6 left anterior descending (LAD), 1 left circumflex (LCX), and 1 LAD and LCX]. Plug positions were monitored fluoroscopically. One animal died at 2 days postembolization. The remaining seven dogs were killed after 14-37 days. Autopsies showed complete vessel occlusion and localized infarction. Infarcts resulting from coronary artery occlusion with one, two, or three plugs involved 2-26% of the left ventricular mass.
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Arterial hypoxemia may contribute to morbidity during cardiac catheterization. Therefore, we measured arterial hemoglobin oxygen saturation (SaO2) continuously using pulse oximetry in 29 patients (age range, 21 to 83 years) undergoing cardiac catheterization. Baseline SaO2 was 96 +/- 0.4 percent. All patients had a decrease in SaO2 at some time during the procedure. Eleven patients (38 percent) had episodes of arterial hypoxemia, defined as a decrease in SaO2 below 90 percent. In these 11 patients, the mean number of episodes of hypoxemia was 16 +/- 7, and the mean duration of each episode was 53 +/- 25 seconds. Multiple stepwise regression analysis showed that the minimum SaO2 during catheterization for any patient was significantly associated with the baseline SaO2, duration of the procedure, and end-diastolic volume (EDV) as described by the following regression equation: minimum SaO2 = 46.8 - 0.0580 (duration of procedure in minutes) + 0.5362 (baseline SaO2) - 0.0159 (EDV). Based on our finding of arterial hypoxemia in greater than one third of our patients, we would consider continuous SaO2 monitoring or supplemental oxygen during cardiac catheterization, especially for those patients with poor ventricular function or low resting SaO2 or those expected to have long procedures.
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Protoscoleces of Echinococcus granulosus were subjected to high concentrations of praziquantel (10-1000 micrograms/ml medium or cyst fluid) for a short, 10 min duration in vitro or in situ within cysts. Drug efficacy was then monitored either by in vitro culture in drug-free medium and/or by passage into rodents. The in vitro test of effectiveness suggested that ovine-derived protoscoleces were more sensitive than those of equine origin, and that the in vitro method of treatment was more successful than that performed in situ. However, the subsequent passage of treated protoscoleces, whether immediately after in situ or in vitro exposure or after culture in drug-free medium, indicated that the in situ administration was as effective as the in vitro treatment. Both methods reduced cyst burdens in rodents to 9-15% of control infections.
Cardiopulmonary effects were assessed in 12 yearling steers anesthetized with guaifenesin and thiamylal sodium, intubated, and allowed to breathe isoflurane or halothane in oxygen spontaneously. Light surgical anesthesia, determined using eye position as a clinical indication of anesthetic depth, was maintained during surgical placement of a rumen cannula. Heart rate and respiratory rate were measured while the steers were standing quietly (baseline). Atropine (0.06 mg/kg of body weight, IM) was given after baseline measurements were taken. Heart rate, respiratory rate, arterial blood pressures, pHa, PaCO2, PaO2, arterial [HCO3-], esophageal temperature, and end-tidal anesthetic concentration were measured every 15 minutes for 90 minutes after induction of anesthesia. Mean heart rate increased significantly (P less than 0.05) above baseline in the isoflurane group at 15 and 30 minutes. Mean respiratory rate increased significantly (P less than 0.05) above baseline in the halothane group at 45 minutes. At 45 minutes, mean respiratory rate was lower (P less than 0.05) in the isoflurane group, compared with that in the halothane group. Mean values for arterial blood pressures and arterial gases were similar for both agents at comparable times. Mean end-tidal isoflurane concentrations were less than mean end-tidal halothane concentrations at each comparable time during maintenance of similar anesthetic depth. Maintenance of anesthesia with isoflurane resulted in higher heart rates and lower respiratory rates, compared with maintenance of anesthesia with halothane in these steers.