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Biomedical subjects

R L Stephen

Publications and source records attributed to R L Stephen.

At least 37 records · Page 2Linked to original sources

Potential novel methods for insulin administration: I. Iontophoresis.

It is theoretically feasible to administer an ionized solute transcutaneously using an electric current. Attempts by our group to administer conventional, regular (soluble) insulin to human volunteers by iontophoretic methods failed, probably because such insulin is only weakly ionized and much of it is present in the polymeric form. Animal experiments with pigs defined patterns of portal and systemic insulin concentrations for native insulin secretion, intraperitoneal injection of insulin, and peripheral (intramuscular) injection of insulin. Using a more strongly ionized and predominantly monomeric form of insulin, transcutaneous administration of this hormone by iontophoresis was demonstrated in an experimental animal.

Animals↗

Potential novel methods for insulin administration: II. Self-regulating internal drug delivery systems.

Several glycosylated insulins were synthesized and their binding constants to a lectin, Concanavalin A (Con A), as compared to that of glucose, were assessed. When Con A-glycosylated insulins were placed in fluids containing different concentrations of glucose, competitive displacement of glycosylated insulin occurred to a degree dependent upon the ambient concentration of glucose. As these glycosylated insulins possess a biological activity (80% of that of standard soluble insulin) such results demonstrate the beginnings of a "chemical" artificial beta cell.

Animals↗

Intraperitoneal insulin regimens and diabetic nephropathy.

Five patients with severe diabetic nephropathy (SN) and six patients with moderate diabetic nephropathy (MN) have been treated with intraperitoneal (i.p.) insulin administered by multiple injections. The five SN patients progressed to end-stage kidney disease. The six MN patients (five of whom are described) show stabilisation (and in two cases possibly some improvement) of renal function over time intervals ranging from eight to 23 months.

Blood Glucose↗

Pressure control of ultrafiltration rate with high-flux dialysis membranes.

Control of ultrafiltration with high-flux dialysis membranes is normally achieved using complex, expensive, volumetric control methods. By using high-flux dialyzers with distensible membranes (parallel-plate dialyzers) in the cocurrent rather than in the countercurrent mode, ultrafiltration can be controlled simply and inexpensively by controlling the outlet pressure differential. Since this is the traditional method of ultrafiltration control, only minor, inexpensive equipment modifications are needed. As expected from transport theory, small molecule clearances are lower with cocurrent than with countercurrent flow. They are, however, adequate and superior to those achieved with post-dilutional hemofiltration (urea clearance greater than 110 ml/min with cocurrent single-pass, high-flux dialysis). Ultrafiltration control with this method is so simple and predictable that clearances at zero net ultrafiltration rates can easily be measured rather than extrapolated. Since dialysate pressure is always positive, no deaeration systems would be needed in dialysis equipment designed for use with cocurrent single-pass, high-flux dialysis.

Blood↗

The quantity and distribution of radiolabeled dexamethasone delivered to tissue by iontophoresis.

A pilot study was conducted in the first of two monkeys using either radiolabeled Dm-Na-P or radiolabeled hydrocortisone sodium succinate, together with lidocaine HCl. This study indicated an approximately tenfold increase in the quantity of Dm-Na-P delivered to the test electrodes (4 mA; 20 minutes) whereas the quantity of hydrocortisone delivered from the test electrodes was only marginally (approximately 10%) increased as compared with that from the controls. In terms of an anti-inflammatory activity, the effective dose of Dm-Na-P in all tissue layers underlying the test electrodes was at least tenfold that of the hydrocortisone. Therefore, further trials with hydrocortisone were abandoned. In the second animal, positive test electrodes (5 mA; 20 minutes, were sited over five joints on the right side of the body and matching control electrodes (0 mA; 20 minutes) were placed over corresponding joints on the left side of the body. The control and test electrodes each contained 1.0 ml tritium-labeled Dm-Na-P (approximately 4.0 mg) and 2.0 ml 4% lidocaine HCl (80 mg). Local tissue concentrations of Dm-Na-P were higher than those that would be obtained by systematic therapy and lower than would be obtained by local injection.

Animals↗

Portable system for simultaneous measurements of blood electrolytes.

Miniature, rugged Chemfet sensors have been developed by coating field-effect transistors with ion-sensitive membranes. These sensors have been combined with a flow injection analysis manifold to demonstrate feasibility of a small portable system capable of simultaneous determinations in 10 seconds of hydrogen, potassium and calcium ion activities in 20 microliters samples of whole blood, serum or dialysate.

Blood Chemical Analysis↗

Lidocaine anesthesia: comparison of iontophoresis, injection, and swabbing.

The duration and depth of anesthesia produced by lidocaine with three methods of administration were studied. To test duration of anesthesia, either lidocaine or placebo was administered by iontophoresis, subcutaneous infiltration, or swabbing to each of three sites 3 cm apart on the flexor surface of each forearm of 27 subjects. To test for feeling, the tip of a 21-gauge hypodermic needle was pressed on each application site every five minutes until feeling returned. The depth of anesthesia achieved with iontophoresis or infiltration of lidocaine was tested on the flexor surface of each forearm of 12 subjects, with a random assignment of application methods to each arm. Lidocaine iontophoresis produced local anesthesia of significantly longer duration (p less than 0.001) than topical application of lidocaine or placebo by any route of administration, but of significatnly shorter duration (p less tahn 0.001) than lidocaine infiltration. The results showed that lidocaine iontophoresis is an effective method of producing local anesthesia for about five minutes without requiring the use of a hypodermic needle and syringe.

Administration, Topical↗

On betaH-Leu5-endorphin and schizophrenia.

A previously unknown peptide, betaH-Leu5-endorphin, has been reported in the dialysates of schizophrenic patients. Accordingly, hemofiltrates from two schizophrenic and two control patients were examined for the presence of betaH-Leu5-endorphin. The opioid peptides were detected by a radioreceptor assay after separation and identification by gel filtration and high-performance liquid chromatography. With a detection limit of 30 pmole/L of hemofiltrate, no betaH-Leu5-endorphin or Met5-endorphin was found in controls or in patients. Whatever the possible involvement of endorphins in schizophrenic behavior, they are not present at detectable levels in the hemofiltrates of two well-characterized schizophrenic patients, thereby casting doubt on a general relationship of Leu-endorphin and schizophrenia.

Adult↗

Dialysis/hemofiltration in schizophrenia: a journey by night and cloud.

Hypotheses for the etiology of schizophrenia are discussed and related to possible treatments utilizing artificial kidney systems. For hemofiltration particularly, a theoretical framework is presented for treatment planning. Emphasis is placed on the necessity of using rigid diagnostic criteria for patient selection. Results are reported on two "strict" schizophrenic patients after a series of hemofiltration treatments. One patient showed no clinical improvement after seventeen treatments and died subsequently in a mountaineering accident. Though clinical improvement was noted in the second patient (22 treatments in four months), it is unjustifiable to attribute this solely to hemofiltration. Increased family and medical staff attention towards the patient is sufficient explanation for all changes noted in the patient's symptomatology. Chemical analyses so far have failed to detect any endorphins, normal or abnormal, in the hemofiltrates of either the two patients or two normal controls (sensitivity 30 pmol/L).

Blood-Brain Barrier↗

Hypogeusia and zinc depletion in chronic dialysis patients.

Dialysis patients generally have a poor appetite, do not enjoy eating, and complain of food, particularly protein, as being disagreeable. Twenty dialysis patients with the above symptoms were tested for taste acuity, serum zinc (Zn), Zn concentrations in hair samples (intracellular Zn), and daily caloric intake. A double-blind, cross-over study was instituted using a Zn supplement and a placebo. After supplementation with Zn, taste acuity markedly improved in 95% of patients and Zn concentrations in hair increased in 85% of patients. The patients' appetites were improved; the average caloric intake increased by 675 kcal/day, and intolerance to protein diminished. In addition 10 normal control subjects were studied pre- and post-Zn supplementation for fasting blood glucose, serum Zn levels, and hair Zn concentration. Side effects were noted, and these usually correlated with elevated serum Zn levels and were minimized or disappeared with decrease in dosage or cessation of therapy.

Adult↗