Search PubMed⌕ Search

Biomedical subjects

A L Finn

Publications and source records attributed to A L Finn.

At least 37 records · Page 2Linked to original sources
PubMed1985

Effects of intracellular sodium and potassium iontophoresis on membrane potentials and resistances in toad urinary bladder.

Glass microelectrodes were used to measure membrane potentials and the ratio of apical to basolateral membrane resistances before and after the passage of current from the potential-recording microelectrode to ground, in toad urinary bladder epithelium, in order to iontophorese cations into the cell. After application of the current, there was a transient change in the tip potential of the microelectrode. This artifact was measured with the microelectrode in the mucosal medium and was subtracted from the potential recorded in the cell. The serosal medium was bathed by Ringer's solution containing 51.5 mM K+ to minimize any current-induced increase of K+ in the unstirred layer. Under those conditions, both Na+ and K+ iontophoresis caused a significant hyperpolarization of basolateral membrane potential (Vcs) and a significant increase in the ratio of apical to basolateral membrane resistances (Ra/Rb). When bladders were exposed to amiloride in the mucosal solution, Na+ iontophoresis caused the basolateral membrane to hyperpolarize, but no significant changes were observed in Ra/Rb. When Na+ was injected in the presence of serosal ouabain, Vcs depolarized and Ra/Rb increased. K+ iontophoresis caused the basolateral membrane potential to hyperpolarize in the presence of ouabain but Ra/Rb did not change significantly. These results indicate that the Na+ pump in toad bladder is rheogenic, that apical Na+ conductance is sensitive to the cell levels of Na+ and K+ and that the basolateral membrane is K+ permeable.

Amiloride↗
PubMed1985

Effects of mucosal sodium removal on cell volume in Necturus gallbladder epithelium.

Necturus gallbladder epithelium transports sodium and chloride by a process that first involves the cellular entry of each ion across the apical membrane in an electrically silent process. In this paper we present results from cell volume and fluid flux measurements in the presence of different inhibitors and at normal and reduced sodium concentrations, which bear on the process by which ionic entry is effected. We find that reduction of mucosal sodium to a concentration of 10 mM has no effect on either cell volume or on the rate of transepithelial fluid transport, whereas the complete removal of sodium causes a significant decrease in cell volume in addition to its known inhibitory effect on fluid transport. Amiloride had no effect on cell volume at normal sodium concentrations but markedly reduced it when the sodium concentration was reduced to 10 mM. Amiloride, bumetanide, and dipyridamole markedly and reversibly inhibited fluid transport. Finally, the addition of ouabain to the serosal medium induced cell swelling, which was prevented by the removal of potassium from the mucosal medium. These results indicate that the process of sodium entry at the apical membrane is complicated and likely includes both cotransport (NaCl or Na-K-2Cl) and parallel exchange (Na-H and Cl-HCO3) transport mechanisms, and that the proportion of NaCl transported by the different mechanisms varies with the conditions.

Amiloride↗
PubMed1985

Cell volume regulation in frog urinary bladder.

We have studied the problem of cell volume homeostasis in toad and frog urinary bladder by using electrophysiological measurements and an optical measure of cell volume. After osmotically induced swelling, urinary bladder cells spontaneously regulate their volume through a net loss of potassium, chloride, and water. During inhibition of sodium transport by amiloride the cells swell to the same extent as controls, but the volume-regulatory process is blocked. Electrophysiological results under isosmotic conditions indicate that basolateral membrane resistance increases simultaneously with the amiloride-induced rise in apical membrane resistance during transport inhibition. These independent observations indicate that inhibition of apical membrane sodium entry results in a secondary decrease in basolateral membrane potassium permeability. When cells are exposed to calcium-free, hyposmotic Ringer's solution, cell volume regulation is blocked; subsequent addition of the calcium ionophore A23187 is ineffective in restoring the regulatory process. The ionophore does induce volume regulation, however, in amiloride-inhibited, osmotically swollen cells in the presence of external calcium. Calcium thus seems to control basolateral membrane potassium permeability and may be the intracellular mediator of apical and basolateral membrane interactions.

Amiloride↗
PubMed1985

Treatment of lower urinary tract infections with single-dose trimethoprim-sulfamethoxazole.

Two hundred three women from a primary care medical practice with symptoms of lower urinary tract infection and positive urine cultures were treated with trimethoprim-sulfamethoxazole. One hundred eleven women received a single dose and 92 were treated for ten days. Cure rates were 87 percent and 89 percent, respectively, one week after therapy. A narrow 95 percent confidence interval for the difference between the two cure rates (.02 +/- .09) suggests the treatments are equally effective. Patients were followed by chart audit and a self-reporting questionnaire. No difference in recurrence rates was found between the two groups six months after therapy. Single-dose trimethoprim-sulfamethoxazole is as effective as ten-day treatment in women with symptoms suggestive of lower urinary tract infection and has no greater relapse rate.

Adult↗
PubMed1984

Improving drug prescribing in a primary care practice.

A model for improving physician prescribing that utilizes computerized feedback was studied in a family medicine residency practice. Resident and faculty physicians were stratified by level of experience and randomized into two groups. For 9 months the experimental group received monthly printouts identifying drugs they had prescribed by brand name with estimates of cost savings that might have been realized by prescribing generic drugs. The control group received no feedback. Prescription monitoring of both groups continued for 12 months after all feedback had ceased. Median weighted rates of generic prescribing for the experimental physicians were 14% for the baseline, 67% for the feedback, and 54% for the follow-up periods. Rates for the control physicians for the three periods were 32%, 37% and 31%, respectively. The increase in generic prescribing by physicians in the experimental group was significantly greater than for control physicians (P = 0.01). The feedback model improved rates of generic prescribing but should be evaluated for broader areas of physician prescribing.

Computers↗
PubMed1983

Effects of changes in serosal chloride on electrical properties of toad urinary bladder.

Conventional microelectrode and tracer flux techniques were used to study the effects of reduction in serosal chloride concentration ([Cl]s) on the electrical properties of toad urinary bladder epithelium. Reduction in [Cl]s resulted in a transient change in transepithelial potential (Vms) (and of apical and basolateral membrane potentials) that was inversely dependent on the base-line values of those potentials. In all cases, however, there was a decrease in transepithelial resistance (Rt) that was explained by an increase in the sodium conductance of the apical membrane. In tissues in which the transepithelial potential increased, there was a rise in the active mucosal-to-serosal sodium flux. The increase in conductance was directly related to the increase in short-circuit current. The changes in Vms and Rt brought about by reduction in [Cl]s were prevented by agents known to modify sodium transport, including low mucosal sodium concentration, addition of amiloride or amphotericin B to the mucosal solution, or of ouabain to the serosal solution. The results are best explained by a primary effect of chloride reduction on sodium extrusion across the basolateral membrane, with a secondary increase in apical sodium conductance. In addition, the data provide new evidence for the existence of a basolateral chloride conductance pathway.

Animals↗
PubMed1982

Sodium transport effects on the basolateral membrane in toad urinary bladder.

In toad urinary bladder epithelium, inhibition of Na transport with amiloride causes a decrease in the apical (Vmc) and basolateral (Vcs) membrane potentials. In addition to increasing apical membrane resistance (Ra), amiloride also causes an increase in basolateral membrane resistance (Rb), with a time course such that Ra/Rb does not change for 1-2 min. At longer times after amiloride (3-4 min), Ra/Rb rises from its control values to its amiloride steady state values through a secondary decrease in Rb. Analysis of an equivalent electrical circuit of the epithelium shows that the depolarization of Vcs is due to a decrease in basolateral electromotive force (Vb). To see of the changes in Vcs and Rb are correlated with a decrease in Na transport, external current (Ie) was used to clamp Vmc to zero, and the effects of amiloride on the portion of Ie that takes the transcellular pathway were determined. In these studies, Vcs also depolarized, which suggests that the decrease in Vb was due to a decrease in the current output of a rheogenic Na pump. Thus, the basolateral membrane does not behave like an ohmic resistor. In contrast, when transport is inhibited during basolateral membrane voltage clamping, the apical membrane voltage changes are those predicted for a simple, passive (i.e., ohmic) element.

Amiloride↗
PubMed1981

Lignocaine disposition in blood in epilepsy.

1 The plasma concentration of alpha 1-acid glycoprotein (AAG) was significantly greater in 27 epileptic subjects receiving anticonvulsants compared with 27 age- and sex-matched drug-free control subjects. 2 Increased AAG concentration was associated with enhanced lignocaine binding in the plasma of epileptics. 3 Increased AAG concentration was also associated with a redistribution of lignocaine out of red cells and into plasma thus lowering the blood to plasma concentration ratio. 4 Enhanced lignocaine binding in epileptics receiving anticonvulsant therapy may result in lower free (unbound) plasma concentrations of the drug compared to normal subjects with equivalent total plasma lignocaine concentrations.

Adult↗
PubMed1981

The effects of salicylate on the pharmacokinetics of phenytoin.

The pharmacologic effect of a highly protein-bound drug is a function of the free serum concentration. In vitro studies have demonstrated that phenytoin is displaced from its protein-binding sites by acetylsalicylic acid. This resulted in increased concentrations of free serum phenytoin and raised the possibility of clinical toxicity. We have studied the effects of salicylates on six patients receiving long-term phenytoin therapy. This reduced the total serum phenytoin concentration but did not alter the free serum concentration. There was no loss of seizure control or toxicity. Total phenytoin concentrations in such patients may not accurately reflect pharmacologic activity and may be misleading.

Aspirin↗
PubMed1981

Phenytoin: pharmacokinetics and clinical therapeutics.

Phenytoin is a highly effective anticonvulsant medication that is considered to be the treatment of choice for generalized major motor and focal epileptic seizures. An understanding of the pharmacokinetic properties of phenytoin greatly facilitates the management of seizure patients. The judicious use of serum-monitoring techniques coupled with careful clinical evaluations enable one to obtain the optimal anticonvulsant effect, freedom from dose-related toxicity, and the avoidance of unnecessary polypharmacy.

Abnormalities, Drug-Induced↗
PubMed1980

Microelectrode studies in toad urinary bladder epithelium. effects of Na concentration changes in the mucosal solution on equivalent electromotive forces.

Microelectrode techniques were employed to measure membrane potentials, the electrical resistance of the cell membranes, and the shunt pathway, and to compute the equivalent electromotive forces (EMF) at both cell borders in toad urinary bladder epithelium before and after reductions in mucosal sodium concentration. Basal electrical parameters were not significantly different from those obtained with impalements from the serosal side, indicating that mucosal impalements do not produce significant leaks in the apical membrane. A decrease in mucosal Na concentration caused the cellular resistance to increase and both apical and basolateral EMF to depolarize. When Na was reduced from 112 to 2.4 mM in bladders with spontaneously different baseline values of transepithelial potential difference (Vms), a direct relationship was found between the change in Vms brought about by the Na reduction and the base-line Vms before the change. A direct relationship was also found by plotting the change in EMF at the apical or basolateral border caused by a mucosal Na reduction with the corresponding base-line EMF before the change. These results indicate that resting apical membrane EMF (and, therefore, resting apical membrane potential) is determined by the Na selectivity of the apical membrane, whereas basolateral EMF is at least in part the result of rheogenic Na transport. These results are consistent with data of others that suggested a link between the activity of the basolateral Na pump and apical Na conductance.

Animals↗
PubMed1980

Anion-sensitive sodium conductance in the apical membrane of toad urinary bladder.

Membrane potentials and the electrical resistance of the cell membranes and the shunt pathway of toad urinary bladder epithelium were measured using microelectrode techniques. These measurements were used to compute the equivalent electromotive forces (EMF) at both cell borders before and after reductions in mucosal Cl- concentration ([Cl]m). The effects of reduction in [Cl]m depended on the anionic substitute. Gluconate or sulfate substitutions increased transepithelial resistance, depolarized membrane potentials and EMF at both cell borders, and decreased cell conductance. Iodide substitutions had opposite effects. Gluconate or sulfate substitutions decreased apical Na conductance, where iodide replacements increased it. When gluconate or sulfate substitutions were brought about the presence of amiloride in the mucosal solution, apical membrane potential and EMF hyperpolarized with no significant changes in basolateral membrane potential or EMF. It is concluded that: (a) apical Na conductance depends, in part, on the anionic composition of the mucosal solution, (b) there is a Cl- conductance in the apical membrane, and (c) the electrical communication between apical and basolateral membranes previously described is mediated by changes in the size of the cell Na pool, most likely by a change in sodium activity.

Animals↗
PubMed1979

Amphotericin B and K+ transport across excised toad urinary bladder.

The transmural electric PD of bladders bathed by Na2SO4 Ringer was not affected by amphotericin (5 x 10(-6) M, mucosal) but the PD followed the direction for K+ diffusion in the presence of a transmural K+ gradient. Increases in bathing solution K+ increased conductance. Ouabain pretreatment did not affect drug-induced changes in PD or conductance. Unidirectional fluxes of radiolabeled Na+ and K+ but not SO42- across the short-circuited bladder were increased by amphotericin. Ninety percent of the rise in the serosal-to-mucosal flow of Na+ disappeared when mucosal Na+ was replaced by choline. Amphotericin induced a 20-fold increase in mucosal-to-serosal K+ flux but K+ serosal-to-mucosal flow increased 200-fold. This flux asymmetry persisted for 110 min, was abolished by pre- or posttreatment with ouabain, and was immeasurable when bathing solution K+ was increased from 2.4 to 59 meq/liter. With 2.4 meq K+/liter the ratio of active Na+ reabsorption to K+ secretion was 8 to 1, but K+ secretion was not closely linked to Na+ transport. The results suggest that amphotericin induces a paracellular K+-selective path, Na+ isotope exchange, and K+ secretion.

Amphotericin B↗
PubMed1978

The paracellular pathway in toad urinary bladder: permselectivity and kinetics of opening.

Determination of serosa-to-mucosa fluxes of Na, K, and Cl yields information about the properties of the shunt pathway in toad urinary bladder. We show that measurement of these fluxes at 30-sec intervals following an abrupt increase in mucosal osmolality yields evidence on the rate of opening of the path and of its permselectivity. The relationship between the fluxes of any pair of these ions indicates that the shunt is paracellular both before and after the increase in conductance effected by hyperosmolality and that the transepithelial PD affects the permselectivity properties (at 0 mV, PK/PNa/PCl=1:0.71:0.57; at + 25 mV, Pk/PNaPCl=1:0.71:0.99). The relationship between any of the fluxes and the total transepithelial conductance is linear and yields an estimate of cellular conductance (the intercept of this regression on the conductance axis) which is in accord with that measured electrically. These studies provide information on tight junction permeability to nonelectrolytes, as well. Finally, they provide new information about the role of the shunt path as a controlling influence on transepithelial sodium transport and raise the possibility that, in both leaky and tight epithelia, differences in transepithelial conductance from tissue to tissue, organ to organ, and species to species may be due, in the absence of edge damage, to changes in conductance of the paracellular pathway.

Animals↗