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Biomedical subjects

R L Stephen

Publications and source records attributed to R L Stephen.

At least 19 recordsLinked to original sources

Iontophoretic delivery of morphine for postoperative analgesia.

Iontophoresis is a method of transdermal administration of ionized drugs in which electrically charged molecules are propelled through the skin by an external electrical field. This was a prospective, randomized, single-blind study to determine the effectiveness of iontophoretically delivered morphine HCl for the control of postoperative pain. Thirty-eight patients who underwent total knee or hip replacement completed this clinical trial. Informed consent was obtained before surgery and patients were instructed on the use of a patient-controlled analgesia (PCA) device. Postoperatively, pain in the recovery room was initially controlled with IV meperidine, and thereafter with PCA therapy using meperidine, 2 mg/cc, with a dose of 10 mg IV and a lock-out period of 15 min. The dose was adjusted as necessary and the lock-out period remained the same. The number of patient requests and the dose (mg) administered was recorded hourly. On the morning following surgery, iontophoresis devices were attached for 6 hr to patients who received either morphine HCl or lactated ringers solution. During this period and for 12 hr following completion of iontophoresis, PCA analgesia remained available to patients. Venous blood samples for determination of morphine levels were obtained every 30 min during iontophoresis, then every 60 min for 2 hr following iontophoresis. Of the 38 patients, 17 received iontophoresed morphine, and 21 received iontophoresed lactated ringers. The morphine group utilized the PCA device more than the control group during the baseline period. However, following the institution of iontophoresis and continuing up to 12 hr following completion of iontophoresis, the morphine group used significantly less PCA meperidine to maintain analgesia than the control group (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Iontophoretic administration of lidocaine anesthesia in office practice. An appraisal.

BACKGROUND: Obtaining anesthesia for dermatologic, office-based surgeries often involves the pain of needle stick and burning upon injection of local anesthetic agents. No truly effective method for obtaining painless anesthesia is well accepted in the United States. OBJECTIVE: A study was carried out using iontophoresis of lidocaine with epinephrine to determine the practicality of this method of delivering local anesthesia prior to invasive procedures in dermatology offices. METHODS: A two-center, open-label study was undertaken using iontophoretic administration of 4% lidocaine with epinephrine 1:50,000 before painful procedures occurring in the dermatologists' office. RESULTS: Ninety-four procedures in 64 patients were evaluated. Both patients and physicians recorded 51% of procedures as painless, 36% as minor (partial), and 14% causing moderate to severe pain. Iontophoretic local anesthesia was 80 to 100% effective for pain relief for injections, abrasions, laser surgery, and cautery; it was significantly less effective in effecting pain relief for dermal excisions. CONCLUSIONS: Iontophoretic administration of anesthesia is a useful adjunct to the armamentarium of dermatologists performing surgical procedures in their office.

Adolescent

Effect of osmotic pressure on uptake of chemotherapeutic agents by carcinoma cells.

Intraperitoneal chemotherapy has been used to treat cancers which are confined to the abdominal cavity. Several variables which affect drug delivery into tumor cells have been identified, but the effect of osmotic pressure has not been studied. Tumor cell lines were used to evaluate the effect of fluid tonicity on drug uptake. HeLa cells and a murine teratoma cell line were suspended in solutions of tonicities 154, 308, and 616 mosM, each containing the same quantity of 5-fluorouracil, and uptake of the drug was measured at different intervals over 30 min. At all time points the amount of 5-fluorouracil taken up by cells in solutions of 154 mosM was greater than that in 310 mosM solutions, which was greater than the uptake in 616 mosM solutions, each by an average of 40-50%. Incorporation of drug into tumor cells was also assayed in vivo using a teratoma cell line propagated i.p. in mice. Tumor cell uptake of doxorubicin was increased to a similar extent when this drug was administered in hypotonic solutions of 154 mosM and was decreased by administration in hypertonic solutions of 465 mosM, as compared to solutions of 310 mosM. These results demonstrate that the uptake of chemotherapeutic agents into tumor cells is increased significantly when these drugs are infused in solutions of lower osmolalities, a finding which may be exploited in clinical situations.

Animals

Painless cauterization of spider veins with the use of iontophoretic local anesthesia.

Treatment of small vascular abnormalities of the skin is painful, and injections of local anesthetic agents distort the operating field. Iontophoresis of salt-free, 4% lidocaine, with and without epinephrine, delivered to the skin from a receptacle with a semipermeable membrane, and with the use of a current-controlled electrical system, resulted in effective anesthesia of the skin for cauterization of "spider" veins. Fourteen subjects received 32 treatments. Sixteen paired areas of spider veins were anesthetized with iontophoresis of lidocaine and with lidocaine plus epinephrine 1/50,000. The duration of anesthesia with lidocaine averaged 14 minutes; relief of pain was complete in 9/16 treatments, adequate in 6/16, and inadequate in 1/16. Lidocaine plus epinephrine supplied anesthesia for 56 minutes; relief of pain was total in 14/16 treatments and adequate in the remaining two. Thus iontophoresis with the use of selected local anesthetic and iontophoretic equipment provides adequate conditions for cauterization of spider veins, a procedure poorly served by conventional local anesthesia.

Anesthesia, Local

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

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