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Biomedical subjects

E H Larsen

Publications and source records attributed to E H Larsen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Cation transport by sweat ducts in primary culture. Ionic mechanism of cholinergically evoked current oscillations.

1. The coiled reabsorptive segment of human sweat ducts was cultured in vitro. Cells were then harvested and plated onto a dialysis membrane which was glued over a hole in a small disc. Cultures were maintained in a low serum, hormone-supplemented medium that allowed the cells to grow to confluency. The disc was then placed as a partition between two compartments of a miniature Ussing chamber. The chamber was mounted on the stage of an inverted microscope and intracellular potentials were recorded under transepithelial open-circuit or voltage clamp conditions. All values are given as means +/- S.E.M. and n refers to the number of preparations or duct cells. 2. Under control conditions, the cultured epithelia developed mucosa-negative transepithelial potentials (Vt) ranging from -2.5 to -38 mV (-13.5 +/- 1.5 mV, n = 36). The basolateral membrane potential (Vb) was -39.4 +/- 0.7 mV (n = 50 cells), and the apical membrane potential (Va) was linearly correlated with Vt:Va = 1.0 Vt -39.3 mV (r = -0.78, n = 50). 3. The epithelium generated inwardly directed short-circuit currents (Isc) of 12-95 microA cm-2 (45 +/- 4 microA cm-2, n = 36) with a steady-state intracellular potential. Vc = -31.1 +/- 0.6 mV and a fractional resistance of the apical membrane, fR = 0.59 +/- 0.01 (n = 115 cells). 4. The Na+ channel blocker amiloride (mucosal bath, 10 microM) abolished Isc -0.8 +/- 0.6 microA cm-2), the cells hyperpolarized to -61.0 +/- 1.2 mV, and fR increased to 0.85 +/- 0.01 (n = 44). These effects were fully reversible. 5. During initial stimulation with the cholinergic agonist, methacholine (serosa, 5 or 10 microM), the short-circuit current increased to 80 +/- 10 microA cm-2, the cells hyperpolarized to -55.8 +/- 1.2 mV, and fR increased to 0.82 +/- 0.01 (n = 35). 6. In short-circuited preparations stimulated with methacholine an increase in mucosal potassium concentration ([K+]m) from 5 to 25 mM had no significant effect, while a similar increase in the serosal K+ concentration ([K+]s) produced a change in Vc of 44 +/- 3 mV per log10[K+]s (n = 9). In non-stimulated preparations this change was only 16 +/- 2 mV per log10[K+]s (n = 13). After blocking the apical Na+ channels with amiloride the slope was 24 +/- 5 mV per log10[K+]s in unstimulated preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗
PubMed1988

Sulfate transport in toad skin: evidence for mitochondria-rich cell pathways in common with halide ions.

1. In short-circuited toad skin preparations exposed bilaterally to NaCl-Ringer's containing 1 mM SO2(-4), influx of sulfate was larger than efflux showing that the skin is capable of transporting sulfate actively in an inward direction. 2. This active transport was not abolished by substituting apical Na+ for K+. 3. Following voltage activation of the passive Cl- permeability of the mitochondria-rich (m.r.) cells sulfate flux-ratio increased to a value predicted from the Ussing flux-ratio equation for a monovalent anion. 4. In such skins, which were shown to exhibit vanishingly small leakage conductances, the variation of the rate coefficient for sulfate influx (y) was positively correlated with the rate coefficient for Cl- influx (x), y = 0.035 x - 0.0077 cm/sec (r = 0.9935, n = 15). 5. Addition of the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine to the serosal bath of short-circuited preparations resulted in a significant stimulation of the passive Cl- and SO2(-4) permeabilities. 6. It is suggested that SO2(-4) and Cl- ions are transported along the same pathway of the m.r. cells. Depending on the transport mode of the apical Cl- transport system, electro-diffusion, active transport (sulfate:bicarbonate exchange) and self-exchange diffusion take place. Irrespective of the mechanism of transport, sulfate is probably transported as a monovalent anion species.

Animals↗
PubMed1988

Comparison of ion transport by cultured secretory and absorptive canine airway epithelia.

The use of primary cell culture techniques to predict the function of native respiratory epithelia was tested in studies of dog airway epithelia. Epithelial cells from Cl- secretory (tracheal) and Na+ absorptive (bronchial) airway regions were isolated by enzymatic digestion, plated on collagen matrices, and maintained in serum-free, hormone-supplemented media. Transepithelial and intracellular studies showed that both the tracheal and bronchial culture preparations exhibited bioelectric parameters quantitatively similar to those of intact tissues. Similar to the native tissue, the tracheal preparation exhibited an equivalent short-circuit circuit (Ieq) that was sensitive to inhibitors of Cl- transport (bumetanide, diphenylamine carboxylic acid) but was insensitive to an inhibitor of Na+ transport, amiloride. In contrast, the bronchial preparation, like the native tissue, exhibited an Ieq sensitive to amiloride but insensitive to bumetanide. As compared with the trachea, the bronchial (absorptive) epithelium is characterized by 1) a large amiloride-sensitive cellular conductance and 2) a relatively depolarized basolateral membrane. We conclude that this primary cell culture technique provides epithelial preparations comparable to the native tissue and suitable for quantitative studies of regional differences in ion transport function.

Amiloride↗
PubMed1987

Ion transport by mitochondria-rich cells in toad skin.

The optical sectioning video imaging technique was used for measurements of the volume of mitochondria-rich (m.r.) cells of the isolated epithelium of toad skin. Under short-circuit conditions, cell volume decreased by about 14% in response to bilateral exposure to Cl-free (gluconate substitution) solutions, apical exposure to a sodium-free solution, or to amiloride. Serosal exposure to ouabain resulted in a large increase in volume, which could be prevented either by the simultaneous application of amiloride in the apical solution or by the exposure of the epithelium to bilateral Cl-free solutions. Unilateral exposure to a Cl-free solution did not prevent ouabain-induced cell swelling. It is concluded that m.r. cells have an amiloride-blockable Na conductance in the apical membrane, a ouabain-sensitive Na pump in the basolateral membrane, and a passive Cl permeability in both membranes. From the initial rate of ouabain-induced cell volume increase the active Na current carried by a single m.r. cell was estimated to be 9.9 +/- 1.3 pA. Voltage clamping of the preparation in the physiological range of potentials (0 to -100 mV, serosa grounded) resulted in a cell volume increase with a time course similar to that of the stimulation of the voltage-dependent Cl conductance. Volume increase and conductance activation were prevented by exposure of the tissue to a Cl-free apical solution. The steady-state volume of the m.r. cells increased with the clamping voltage, and at -100 mV the volume was about 1.15 times that under short-circuit conditions. The rate of volume increase during current passage was significantly decreased by lowering the serosal K concentration (Ki) to 0.5 mM, but was independent of whether Ki was 2.4, 5, or 10 mM. This indicates that the K conductance of the serosal membrane becomes rate limiting for the uptake of KCl when Ki is significantly lower than its physiological value. It is concluded that the voltage-activated Cl currents flow through the m.r. cells and that swelling is caused by an uptake of Cl ions from the apical bath and K ions from the serosal bath. Bilateral exposure of the tissue to hypo- or hypertonic bathing solutions changed cell volume without detectable changes in the Cl conductance. The volume response to external osmotic perturbations followed that of an osmometer with an osmotically inactive volume of 21%.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗
PubMed1987

Amoxicillin/clavulanate in urinary tract infection.

A new beta-lactamase-stable oral antibiotic (Augmentin) has been found to be effective in the treatment of urinary tract infections (uncomplicated and complicated, recurrent, and nosocomial) and bacteriuria. The literature is reviewed.

Amoxicillin↗
PubMed1987

Penile prosthesis reimplantation.

Occasionally, penile prostheses are removed following erosion, infection or malfunction and they are not replaced immediately. Patients may present later for reimplantation of a penile prosthesis after an interval free of a device. However, no information is available as to the outcome and difficulties of such a procedure. We reviewed the charts of all 305 patients undergoing implantation of a penile prosthesis at our institution and contacted all 8 who had undergone reimplantation. Bilateral prostheses were placed in 4 patients. Unilateral prostheses only could not be implanted in either side because of extensive fibrosis. Of the 8 patients 4 are able to have intercourse (1 with difficulty) and reimplantation of the prosthesis often was difficult or impossible. We conclude that reimplantation of a penile prosthesis is beneficial for some patients but they should be informed of the possibility of unsatisfactory results.

Adult↗
PubMed1987

Intracavernous self-injection with phentolamine and papaverine for the treatment of impotence.

To evaluate the efficacy and safety of intracavernous self-injection of phentolamine and papaverine for the treatment of impotence, 30 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled cross-over study of papaverine and phentolamine versus normal saline. A total of 29 patients completed the study. The phentolamine plus papaverine combination resulted in erection in 24 patients (82.8 per cent) and no erection occurred after injection of saline. Of the patients 12 (41.4 per cent) experienced technical difficulties with the injection. Ecchymosis of the penis at the site of injection was common and 1 patient experienced priapism that resolved spontaneously. No other side effects occurred. Intracavernous self-injection with phentolamine and papaverine appears to be a safe and effective treatment of impotence but long-term effects must be determined.

Aged↗
PubMed1987

Transurethral incision versus transurethral resection of the prostate for the treatment of benign prostatic hypertrophy. A preliminary report.

Thirty-seven patients with prostatism and an estimated prostatic weight of less than or equal to 20 g were randomly allocated to transurethral incision or resection of the prostate. Both procedures had an 85% success rate as judged by patients' personal evaluation. At 3 and 12 months follow-up a significant and identical improvement was noted in symptom score and uroflowmetry in the two groups. Postoperative catheterization time and hospital stay was only half as long in the incision group as in the resection group. No patients became impotent as a consequence of the procedures. Frequency of retrograde ejaculation was 28% in the incision group versus 100% in resected patients. Incision of the prostate is easy to perform and seems to be followed by less severe complications. It has a high patient acceptability and may cut the cost of transurethral surgery.

Aged↗
PubMed1987

Transurethral incisions of the prostate under local anaesthesia in high-risk patients: a pilot study.

Transurethral incision of the prostate under local anaesthesia was performed in 27 patients with symptoms of infravesical obstruction and an estimated prostatic weight of 20 g or less. Local anaesthesia (lidocaine 1%) was infiltrated transurethrally under the urethral prostatic mucosa using a special needle adaptable to the resectoscope. Pain control, assessed with a scoring system, was judged as good or very good by the majority of patients (25) and fair by the remaining 2 patients. No patient required conversion to another type of anaesthesia. The results of surgery as estimated by symptom score, uroflowmetry, and patients' personal evaluation were good. Transurethral incision of the prostate can be satisfactorily performed under local anaesthesia; this may be especially applicable to high-risk surgical patients. Incision of the prostate in the treatment of benign prostatic hyperplasia may be performed as an outpatient procedure in selected cases.

Aged↗
PubMed1987

Quinolone penetration into canine vaginal and urethral secretions.

Four newer quinolones (amifloxacin, ciprofloxacin, enoxacin, norfloxacin) were administered to female dogs by intravenous infusion. Drug concentrations in plasma, urine, and vaginal and urethral secretion were determined by bioassay. All four quinolones penetrated into vaginal and urethral secretion in concentrations several times higher than the MIC against common urinary pathogens, ciprofloxacin and norfloxacin reaching concentrations exceeding the simultaneous plasma concentrations. Because of their favorable antibacterial spectra, new quinolones should be investigated clinically for the treatment of recurrent urinary tract infection and bacterial vaginitis.

Animals↗
PubMed1986

Membrane potentials and intracellular Cl- activity of toad skin epithelium in relation to activation and deactivation of the transepithelial Cl- conductance.

The potential dependence of unidirectional 36Cl fluxes through toad skin revealed activation of a conductive pathway in the physiological region of transepithelial potentials. Activation of the conductance was dependent on the presence of Cl or Br in the external bathing solution, but was independent of whether the external bath was NaCl-Ringer's, NaCl-Ringer's with amiloride, KCl-Ringer's or choline Cl-Ringer's. To partition the routes of the conductive Cl- ion flow, we measured in the isolated epithelium with double-barrelled microelectrodes apical membrane potential. Va, and intracellular Cl- activity, acCl, of the principal cells identified by differential interference contrast microscopy. Under short-circuit conditions, Isc = 27.0 +/- 2.0 microA/cm2, with NaCl-Ringer's bathing both surfaces, Va was -67.9 +/- 3.8 mV (mean +/- SE, n = 24, six preparations) and acCl was 18.0 +/- 0.9 mM in skins from animals adapted to distilled water. Both Va and acCl were found to be positively correlated with Isc (r = 0.66 and r = 0.70, respectively). In eight epithelia from animals adapted to dry milieu/tap water Va and acCl were measured with KCl Ringer's on the outside during activation and deactivation of the transepithelial Cl- conductance (GCl) by voltage clamping the transepithelial potential (V) at 40 mV (mucosa positive) and -100 mV. At V = 40 mV; i.e. when GCl was deactivated, Va was -70.1 +/- 5.0 mV (n = 15, eight preparations) and acCl was 40.0 +/- 3.8 mM. The fractional apical membrane resistance (fRa) was 0.69 +/- 0.03. Clamping to V = -100 mV led to an instantaneous change of Va to 31.3 +/- 5.6 mV (cell interior positive with respect to the mucosal bath), whereas neither acCl nor fRa changed significantly within a 2 to 5-min period during which GCl increased by 1.19 +/- 0.10 mS/cm2. When V was stepped back to 40 mV, Va instantaneously shifted to -67.8 +/- 3.9 mV while acCl and fRa remained constant during deactivation of GCl. Similar results were obtained in epithelia impaled from the serosal side. In 12 skins from animals adapted to either tap water or distilled water the density of mitochondria-rich (DMRC) cells was estimated and correlated with the Cl current (ICl through the fully activated (V = -100 mV) Cl conductance). A highly significant correlation ws revealed (r = -0.96) with a slope of -2.6 nA/m.r. (mitochondria-rich cell and an I-axis intercept not significantly different from zero.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗
PubMed1986

3-year followup of urinary symptoms after transurethral resection of the prostate.

A total of 84 patients underwent detailed symptom analysis and urodynamic study preoperatively, and 3 and 12 months after transurethral resection of the prostate. In addition, 69 patients were contacted 3 years postoperatively for a detailed symptom analysis. These 3-year data then were compared to earlier evaluations. At 3 years 75 per cent of the patients claimed to have improvement, while 13 per cent stated that they were the same symptomatically. At the 1-year evaluation 84 per cent of the patients believed that they were improved and 10 per cent stated that they were unchanged. At 3 years 18 per cent of the patients had urge incontinence (an increase from 6 per cent at 1 year), while none complained of marked nocturia or frequency. Mean total irritative and obstructive symptoms were minimal and unchanged from the 1-year evaluation. Of the patients 33 per cent noticed decreased or absent erections and most blamed the surgery. One patient required another prostatic resection, while stricture developed in 3 and bladder neck contracture occurred in 6. We conclude that prostatic resection results in reasonable 3-year symptomatic improvement but it is hampered by other complications, including bladder neck contracture and, possibly, impotence.

Aged↗
PubMed1986

Indacrinone (MK-196)--a specific inhibitor of the voltage-dependent Cl- permeability in toad skin.

The effect of indacrinone (MK-196) on Cl- transport through toad (Bufo bufo) skin epithelium was studied by the voltage clamping technique. At the transepithelial potential, V = 50 mV (serosal bath grounded) the unidirectional fluxes, governed by a Cl- self-exchange diffusion pathway, were not affected by 1 mM racemic MK-196 in the outer bath. Likewise at V = o mV, the unidirectional fluxes as well as the active (net) inward flux of Cl- were unaffected by MK-196. Voltage clamping the epithelium in the physiological range of potentials activated a Cl- specific passive conductance that saturated for V less than or equal to -90 mV. The influx and efflux of Cl- through this pathway were inhibited by MK-196, and the (passive) Cl- current was inhibited in a dose-dependent way for [MK-196] greater than or equal to 50 microM with about 70% inhibition for [MK-196] = 1 mM. The maximum Cl- conductance was decreased without shifting the position along the V-axis of the inverted S-shaped conductance-voltage relationship. The time constants for the voltage-stimulated Cl- conductance activation were not affected by MK-196 (50 microM less than or equals [MK-196] less than or equals 1 mM). The (+) and (-) isomers and racemic MK-196 affected the voltage-dependent Cl- conductance in similar ways. It is concluded that MK-196 has the properties of a Cl- channel blocker which is specific for the voltage-dependent Cl- permeability of the epithelium. The time course for development of inhibition exhibited a fast (min) and a slow (h) component.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Concentration dependence of halide fluxes and selectivity of the anion pathway in toad skin.

The isolated toad (Bufo bufo) skin was mounted under voltage-clamp conditions in a chamber shown to cause no significant edge damage. The serosal side of the skin was bathed with NaCl-Ringer's, and the passive voltage-sensitive anion conductance studied in its fully voltage activated state, V = -80 mV (apical bath negative). The active sodium currents were eliminated by replacing external Na+ with K+. With [Cl-]o varying between 1.45 mM and 110 mM (gluconate substitution) and [I-]o = 3 mM, the total clamping current (y) and the sum of halide currents (x), estimated from flux measurements, were related by y = 1.0x-3.7 microA cm-2 (r2 = 0.98, n = 50 preparations). The increase in [Cl-]o produced a sigmoidal increase in Cl- influx and clamping current, with the rate coefficient for the influx increasing with [Cl-]o for 1.45 less than [Cl-]o less than 60 mM, but decreasing slightly again as [Cl-]o was further raised to 110 mM. A similar relationship was obtained between the rate coefficient for the Br- influx and [Br-]o, and the I- influx and [Cl-]o, indicating that these three ions are transported by a pathway that is activated by Cl-o and Br-o. The rate coefficients for the influxes ranked as follows, I-:Cl-:Br- = 0.7:1:1.3. The I-/Cl- selectivity was shown to be independent of the degree of Cl-o activation of the anion pathway, and identical with the I-/Cl- selectivity of a furosemide-sensitive, conductive pathway. With [Cl-]o, [Br-]o, or [I-]o = 110 mM, the currents ranked as follows, Cl-:Br-:I- = 1:0.68:0.06, indicating that Cl-, to a lesser extent Br-, and I-, poorly activate the conductive anion pathway. External I- was a potent inhibitor of the Cl-o activation of the Cl- conductance. The unidirectional I- fluxes ([I-]o = [I-]i = 3 mM, [Cl-]o = [Cl-]i = 110 mM) revealed passive transport for V less than -50 mV, active transport for V = o mV, and exchange diffusion for V = 50 mV, confirming our previous finding that depending on the transepithelial potential, the toad skin exhibits three modes of anion transport. A model that shares some properties with that of the anion transport system of the red cell membrane accounts for our findings, and for an inwardly directed active Cl- flux in terms of Cl-/HCO3- exchange.

Animals↗
PubMed1986

Antimicrobial prophylaxis in urologic surgery.

Nosocomial urinary tract infections represent approximately 40 per cent of all nosocomial infections, thereby contributing considerably to secondary bacteremia and sepsis and possibly increased mortality. Urethral catheterization is the single most important predisposing factor in the development of urinary tract infection. Patients at increased risk of nosocomial infectious complications are the elderly, malnourished and debilitated, those with diabetes or prosthetic devices, and those on immunosuppressive therapy. About 75 per cent of nosocomial urinary tract infections are attributable to gram-negative bacteria, a disproportionate number of which when compared with community-acquired infections are caused by Proteus, Klebsiella, and Pseudomonas. There is enough evidence in the literature to support the use of prophylaxis in urologic surgery. Antimicrobial prophylaxis reduces the incidence of postoperative urinary tract infection. It does not seem to reduce the incidence of transient perioperative bacteremia but probably prevents the development of sepsis, thereby reducing the number of serious infective complications, the average hospital stay, and the associated total cost of treatment. To achieve adequate urine, blood, and tissue levels of the antimicrobial agent at the time of surgery, the drug should be given preoperatively. A short perioperative course represents sufficient prophylaxis. Regimens with combinations of beta-lactam and aminoglycoside antibiotics or single use of an extended spectrum beta-lactam antibiotic are acceptable for this purpose.

Anti-Bacterial Agents↗
PubMed1985

A mathematical model of amphibian skin epithelium with two types of transporting cellular units.

A computer model of ion transport across amphibian skin epithelium containing two types of cellular units, their relative number and sizes, and a paracellular pathway has been developed. The two cellular units are, a large Na+ transporting compartment representing the major epithelium from stratum granulosum to str. germinativum, and a small, Cl- transporting compartment representing the mitochondria rich cell. The cellular units both contain dissipative and active pathways according to the two-membrane model. The Na+ transporting unit includes a (Na+, K+, 2 Cl-) co-transport system in the inward facing membrane. The outward facing membrane of the Cl- transporting units contains a potential gated Cl- permeability. Effects of ion distributions and changes in gating variables on the time course of transepithelial voltage clamp currents and their steady states are analyzed. The model predicts communication between the two cellular units under open circuit conditions.

Amphibians↗
PubMed1985

The role of antibacterial prophylaxis in urologic surgery.

The possible origins of post-TUR bacteriuria (urethral flora, prostate, bladder tumors, or contaminated irrigating fluids or instruments) are discussed. A review of the literature on antibacterial prophylaxis during TUR led to a positive assessment of its value. Preferred agents for prophylaxis of urinary tract infections include cephalosporins, extended-spectrum penicillins, ampicillin, and aminoglycosides. The value of antibacterial prophylaxis in open urologic surgery, such as prostatectomy, has not yet been clearly established, but studies have demonstrated significant benefit in patients undergoing transrectal needle biopsy of the prostate. New techniques of stone removal have not yet been thoroughly evaluated with respect to their potential for causing urinary tract infection and bacteremia. Since as many as 77 per cent of stones harbor bacteria, however, antibiotic prophylaxis is recommended. Nonurologic indications for antibacterial prophylaxis are outlined.

Anti-Bacterial Agents↗