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Biomedical subjects

J Wicks

Publications and source records attributed to J Wicks.

34 records · Page 2Linked to original sources

Doppler echocardiographic determination of aortic valve area using the continuity equation.

The noninvasive measurement of aortic valve area by use of the continuity equation has been proposed as an accurate method for determining the severity of aortic stenosis. In 32 patients (mean age 64 +/- 14 years) with proven aortic stenosis and without significant regurgitation, aortic valve areas derived by the Gorlin equation from cardiac catheterisation data were compared with valve areas calculated from the continuity equation using Doppler echocardiography. There was a close correlation between Doppler and catheter derived aortic valve areas (r = 0.87, SEE = 0.17 cm2). The interobserver error for aortic valve area measurement in 20 patients was 9.0 +/- 6.8%. The specificity of this method for critical aortic stenosis (aortic valve area less than 0.75 cm2) was 73% and the sensitivity 88%. We conclude that in an adult, predominantly elderly population with calcific aortic stenosis, this Doppler echocardiographic method is reproducible and can be used accurately to derive aortic valve area.

Adolescent↗

Ca2+ channel blockers interact with alpha 2-adrenergic receptors in rabbit ileum.

An interaction between Ca2+ channel blockers and alpha 2-adrenergic receptors has been demonstrated in rabbit ileum by studying the effect of clonidine on active electrolyte transport, under short-circuited conditions, in the presence and absence of several Ca2+ channel blocking agents. Clonidine, verapamil, diltiazem, cadmium, and nitrendipine all decrease short-circuit current and stimulate NaCl absorption to different extents with clonidine having the largest effect. Exposure to verapamil, diltiazem, and cadmium inhibited the effects of clonidine on transport, whereas nitrendipine had no such effect. Verapamil, diltiazem, and cadmium, but not nitrendipine, also decreased the specific binding of [3H]alpha 2-adrenergic agents to a preparation of ileal basolateral membranes explaining the observed decrease in the transport effects of clonidine. The effective concentrations of the Ca2+ channel blockers that inhibited the effects of clonidine on transport were fairly similar to the concentrations needed to inhibit its specific binding. The displacement of clonidine by calcium channel blockers is ascribed to a nonspecific effect of these agents, although the possibility that their effects are exerted via their binding to the calcium channels is not excluded.

Animals↗

Secretory hormones of Entamoeba histolytica.

Watery diarrhoea as distinct from dysentery is occasionally seen in intestinal amoebiasis, suggesting a component of intestinal secretion. To study the pathogenesis of this watery diarrhoea, we evaluated the effect of lysates of Entamoeba histolytica on active intestinal electrolyte transport using rabbit ileum and rat colon studied by the Ussing chamber-voltage clamp technique. Amoebic lysates added to the ileal and colonic mucosal surfaces did not alter electrolyte transport; in contrast, addition to the ideal and colonic serosal surfaces caused an increase in short-circuit current which was transient in the ileum but more prolonged in the colon. This increase in current corresponded to inhibition of active Na+ and Cl- absorption and apparent stimulation of Cl- secretion in rat colon. In rabbit ileum, the short-circuit current response was: (1) dependent on serosal Ca2+, (2) inhibited by serosally applied verapamil, (3) associated with reversible desensitization, and (4) only partially inhibited by heating. These characteristics were similar to those of a series of neurohumoral substances present in mammalian intestinal mucosa which affect active electrolyte transport by increasing the permeability of the basolateral membrane to Ca2+. Substances with these properties identified include serotonin, substance P and neurotensin. All three substances were shown to be present in amoebic lysates by radioimmunoassay. Serotonin was also present by high performance liquid chromatography (HPLC) and thin layer chromatography, and neurotensin by HPLC. Prostaglandins were not present by radioimmunoassay. Attempts were made to determine which of these neurohumoral substances contributed to the changes in intestinal transport caused by amoebic lysates. Serotonin was thought to be involved, from the inhibition of the transport effect of amoebic lysate on rat colon by anti-serotonin antibody and by bufotenine, which inhibits the effect of serotonin on ion transport. Prostaglandins also appeared to be involved, since pretreatment with PGE2 or indomethacin inhibited the effects of amoebic lysate on transport. We conclude that amoebae contain neurohumoral substances, including serotonin, neurotensin and substance P, which may be important in the intestinal secretion caused by amoebae. Serotonin appears partially responsible for the intestinal secretion. In addition, amoebae may induce prostaglandin synthesis by the intestinal mucosa which could also contribute to the secretory response. The relation between the neurohumoral substances which act by Ca2+ and the prostaglandins presumably caused to be synthesized in the intestinal mucosa is not known.

Animals↗

Studies on role of calmodulin in Ca2+ regulation of rabbit ileal Na and Cl transport.

To study the role of calmodulin in regulation of rabbit ileal active electrolyte transport by Ca2+, the effects of the Ca2+-calmodulin antagonist naphthalenesulfonamides W12 and W13 and the weak Ca2+-calmodulin antagonist promethazine, a phenothiazine, were studied on basal ileal Na and Cl transport and on secretion stimulated by Ca2+ and by cAMP. The naphthalenesulfonamides and promethazine all stimulated basal ileal Na and Cl absorption. The stimulation of Na absorption was dependent on Cl in the bathing solutions, and the stimulation of Cl absorption was Na dependent. This suggests that the transport process stimulated was the neutral, linked NaCl absorptive process. W13, which is a better Ca2+-calmodulin antagonist but has similar hydrophobic properties to W12, stimulated active ileal absorption at a lower concentration than W12, suggesting that the naphthalenesulfonamide-induced stimulation of active ileal absorption was not due to the hydrophobic properties of these drugs but could be due to their effects on the calcium-binding protein calmodulin. W12, W13, and promethazine did not alter paracellular transport, not affecting dilution potentials or structural features of the paracellular pathway. W12 and W13 did not decrease the changes in active ileal Na and Cl transport caused by increasing ileal cAMP content or intracellular Ca2+. This suggests that calmodulin is not directly involved in the active electrolyte secretion caused by increased intestinal Ca2+ or cAMP.

Animals↗

Effect of Senokot on rat intestinal electrolyte transport. Evidence of Ca++ dependence.

The mechanism of action of Senokot, a widely used laxative, has not been established. Senokot was given orally to rats 8-14 h before intestinal water and electrolyte transport were studied. Senokot significantly decreased colonic and jejunal water absorption measured in vivo by the single-pass perfusion technique. The Senokot changes were not associated with changes in jejunal or colonic histology or adenylate cyclase activity or colonic cyclic adenosine monophosphate content. Senokot also altered active electrolyte transport in rat descending colon as measured by the Ussing chamber-voltage clamp technique. These changes consisted of an increase in short-circuit current and a decrease in active Na and Cl transport that was due to a decrease in the mucosal-to-serosal fluxes. The changes in active electrolyte transport were dependent on Ca++ in the serosal but not the mucosal bathing solution. In contrast, addition of 10(-4) M verapamil to the serosal surface did not alter the Senokot effect. In spite of a dependence on serosal Ca++, Senokot did not alter 45Ca++ entry across the colonic serosal surface. The phospholipase A2 inhibitor quinacrine (10(-4) M) also did not alter the effect of Senokot on colonic Na and Cl transport. Senokot alters active colonic Na and Cl transport via a presently unknown mechanism that is dependent on serosal Ca++.

Adenylyl Cyclases↗

Entamoeba histolytica causes intestinal secretion: role of serotonin.

Lysates of the protozoan parasite Entamoeba histolytica altered active electrolyte transport when present on the serosal surface of rabbit ileum and rat colon. The lysate-induced effects on electrolyte transport were similar to those caused by serotonin, and were blocked by bufotenine, an analog known to inhibit the action of serotonin. The transport effects were partially inhibited by antibody to serotonin. The amebic lysates were shown to contain serotonin by radioimmunoassay, high-performance liquid chromatography, and thin-layer chromatography. These results suggest that the serotonin present in Entamoeba histolytica may be important in the diarrhea seen in amebiasis.

Amebiasis↗

A computerized data base system for medical diagnostic studies (Diastu).

A computerized database system (DIASTU) has been developed for the storage and selective retrieval of the results of medical diagnostic studies. The system is being used to analyze the disease process and the efficacy and yield of selected diagnostic studies. The system runs on a DEC PDP-11/60 computer. It consists of three FORTRAN IV programs linked to a general-purpose assembly language database handler. One program, DSENT, interactively modifies the information in the database. The second, DSLIST, prints all or portions of the database. The third program, DSTAT, interactively assembles the parameters for selective searches of the database and executes them. A query language is used that allows the use of time and size specifications and Boolean operators in nested loops.

Computers↗

Topical anesthesia with 50 mg of lidocaine spray facilitates upper gastrointestinal endoscopy.

To investigate the value of 50 mg of topical lidocaine spray in upper gastrointestinal endoscopy, a randomized double-blind placebo-controlled study was undertaken with 50 mg of lidocaine spray as the active treatment. All patients were sedated with diazepam after administration of the spray. Included in the study were 158 consecutive patients aged 18 years or older being treated at the endoscopy unit of Scunthorpe district general hospital. Tolerance to upper gastrointestinal endoscopy as assessed by endoscopists and patients was evaluated. Of the 158 patients, 85 received the placebo spray and 73 the lidocaine spray. Patient acceptability for upper gastrointestinal endoscopy was significantly greater in the lidocaine group than in the placebo group (p = 0.001), and tolerance to the procedure as assessed by the endoscopist was also significantly greater in the lidocaine group than in the placebo group (p = 0.008). We conclude that topical anesthesia with 50 mg of lidocaine spray facilitates upper gastrointestinal endoscopy for the endoscopist and increases patient tolerance for the procedure.

Anesthesia, Local↗

Drug therapy for diarrheal diseases: a look ahead.

The gastrointestinal tract is involved in both absorption and secretion of electrolytes and water, with absorption as the predominant process. In diarrheal diseases this balance is disturbed, and the result is net secretion. Most of the drugs used for the treatment of diarrhea at least partially act by stimulating absorption only, both stimulating absorption and inhibiting secretion, or inhibiting secretion only. The therapeutic usefulness of an antidiarrheal agent depends on how efficiently it alters secretion and/or absorption and on how few systemic adverse reactions it causes. When more information on the regulation of absorption and secretion has been accumulated, it may be possible to develop new drugs that can be aimed directly at these processes.

Anti-Inflammatory Agents↗