Search PubMed⌕ Search

Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 703 records · Page 39Linked to original sources
PubMed1984

Pharmacokinetics and bioavailability of ranitidine in humans.

Ranitidine produces a blood concentration curve with a pronounced secondary peak when administered orally and parenterally. A pharmacokinetic model is proposed to describe this reabsorption phenomenon. The choice of a discontinuous cyclic transfer was justified on the basis of physiological considerations and the good agreement with data from oral and intravenous administration. It is proposed that ranitidine accumulates mainly from the systemic circulation into a depot from which drug and bioreversible drug are spontaneously released in response to food intake. The evaluation of the extent of the first-pass effect and the evaluation of bioequivalency are complicated by the model-independent AUC approach because the area under the concentration versus time curve (AUC) is dependent on the extent of recycling and thus does not properly reflect the extent of primary absorption. By using intravenous administration as a reference dosage form and the integrated form of the regression equations to calculate the AUC values, the bioavailability of the oral dose was found to be 0.56, which corresponds well with the value of 0.58 obtained by linear-log-linear integration. The least-squares parameter estimate of the primary absorption is 0.43.

Administration, Oral↗
PubMed1984

An evaluation of two doses of isocarboxazid in depression.

Two fixed doses of isocarboxazid were studied over a 4-week period in depressed in-patients. Thirty-five patients completed treatment, 20 of whom received 30 mg isocarboxazid per day, and 15 of whom received 50 mg isocarboxazid per day. No overall difference between the two doses was observed. When patients were subdivided into melancholia/endogenous depression or non-melancholia/non-endogenous depression, the higher dose exerted significantly greater antidepressant effects in the latter groups. Diagnostic type is considered to be an important variable in studies of dose-effect relationships with antidepressant drugs. The side effects of isocarboxazid at the two doses studied did not differ materially, although there was a suggestion of greater anticholinergic effect at 50 mg.

Adult↗
PubMed1984

131-iodine conjugated antibody cell kill enhanced by bromodeoxyuridine.

131I-conjugated monoclonal and polyclonal antibodies are being administered in vivo to kill human tumor cells. Although these conjugates deliver relatively large doses of radiation to tumors (10 to 50 Gy), the rate of dose delivery is low (0.05 to 0.2 Gy/hour). Radiation delivered at low dose rates kills fewer cells that exhibit large shoulders on radiation survival curves than radiation delivered at high dose rates. To determine whether the cell kill produced by low dose rate radiation is enhanced by a radiation sensitizer (bromodeoxyuridine, BUdR) we studied the cell kill produced by an 131I-conjugated polyclonal antibody against Chinese hamster V79 cells. V79 cells were labeled with 131I-conjugated antibody (10-20 microCi/micrograms) and unconjugated antibody, and frozen for up to 30 days in liquid nitrogen. The surviving fraction of cells was measured at intervals of 5 to 10 days. Cells not containing BUdR were also studied. The 131I-conjugated antibody produced up to 40% cell kill and BUdR increased the fraction of cells killed to 75%. Our studies demonstrate that cells frozen at -196 degrees C are useful for the investigation of the cell kill produced by isotopes that deliver radiation at low dose rates and that the cell kill caused by 131I-conjugated antibodies can be enhanced by BUdR.

Animals↗
PubMed1984

Localized amyloidosis of the ureter.

We report a case of localized ureteral amyloidosis. This condition usually presents as hematuria and a ureteral stricture, and is clinically indistinguishable from a neoplasm. Treatment should consist of local resection if possible.

Adult↗
PubMed1984

Major psychosis and dopamine: controversial features and some suggestions.

Three problems with the dopamine hypothesis of major psychosis are pointed out: the long time-course of neuroleptic therapy; the absence of tolerance to the antipsychotic effects of neuroleptic drugs, or of a supersensitivity psychosis on drug withdrawal; and the absence of potent psychotogenic properties in the direct dopamine agonists. A resolution of these paradoxes is suggested relying on a role for dopamine in learning processes at a relatively high (cognitive) functional level. The hypothesis proposed is also used to explain the origin of some of the more distinctive psychotic symptoms.

Antipsychotic Agents↗
PubMed1984

A logical approach to renal stone removal.

On the basis of experience with over 350 percutaneous stone extractions, a logical approach assuring a high success rate and minimizing complications is described. The importance of the position of the kidney in the body, the caliceal anatomy, the renal arterial anatomy, and the instrumentation used on puncture site selection are discussed. Strategies for removal of caliceal, pelvic, ureteral, and staghorn calculi, rationale, and treatment of complications are also described.

Humans↗
PubMed1984

Exercise induced ventricular ectopics in patients with isolated congenital complete heart block and their association with inadequate chronotropy.

Treadmill exercise tests preformed on 13 patients with isolated congenital complete heart block are described. Premature ventricular contractions appeared with exercise in 5/13 patients. The 5 patients who developed ventricular ectopics with exercise had lesser increments in their junctional rates with exercise as compared to the remaining patients (P less than .025). Two of these 5 patients subsequently experienced syncope and required pacemaker insertion. The two groups of patients were indistinguishable in terms of age, sex, resting heart rates, presence or absence of cardiomegaly. The site of AV block appeared to be above the bundle of His in all instances (proven in 9/13). It is suggested that the association between ventricular ectopic activity and inadequate chronotropy with exercise could have a pathophysiological link and might indicate an unfavorable prognosis.

Adolescent↗
PubMed1984

MAO inhibitor therapy in trichotillomania associated with depression: case report.

Trichotillomania may sometimes be an atypical variant of depressive illness. A case is reported in which the MAO inhibitor isocarboxazid was successfully used to treat both depression and associated trichotillomania. The symptoms recurred upon discontinuation of the drug and were ameliorated by reintroduction of isocarboxazid .

Adult↗
PubMed1983

The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration: a comparison of responders and non-responders.

The pharmacokinetics of orally administered ranitidine were studied in 17 male patients with chronic duodenal ulceration. The patients were divided into 2 groups, 10 responders and 7 nonresponders, on the basis of their endoscopic response to ranitidine treatment. The 10 responders were studied both after a single 150 mg dose (SD) and after multiple dosing (MD) with ranitidine 150 mg twice daily for 4 weeks. The area under the curve (AUC) and maximum concentration (Cmax) were significantly higher (p less than 0.01 and p less than 0.05, respectively) after MD than after SD, but the half-life (t1/2) and minimum concentration (Cmin) 12 h postdosing did not differ. The non-responders were studied after MD only and their pharmacokinetic characteristics were compared with those of responders. No differences between the 2 groups were found. However, 2 non-responders had particularly low plasma ranitidine levels and high acid output. Such patients may need larger doses of ranitidine for adequate suppression of gastric acid. Five patients (4 responders and 1 non-responder) received ranitidine 20 mg i.v. The drug followed a two-compartment model, with mean values for t1/2 beta, volume of distribution steady-state and total plasma clearance of 80 min, 701 and 680 ml/min, respectively. The oral bioavailability of ranitidine in these 5 patients showed wide variation (27-76%; mean 51%).

Administration, Oral↗
PubMed1983

Pharmacokinetics of ranitidine in patients with chronic renal failure.

The pharmacokinetic behaviour of a single oral 150 mg ranitidine dose was studied in six patients with severe chronic renal failure (CRF) (creatinine clearance 2-18 ml/min) and compared to that in ten patients with duodenal ulceration but normal renal function (N) (creatinine clearance 69-125 ml/min). Although the maximum concentrations (Cmax) were significantly higher in CRF group when compared to N group (p less than 0.025) there was no difference in the time taken to reach Cmax (tmax). The area under the curve (AUC) was also significantly larger in the CRF group (p less than 0.001) than in the N group. Within the CRF group there was a large variation in Cmax (CV = 38%) and AUC (46%) which may reflect variable bioavailability of ranitidine. The terminal elimination rate constant (beta) was significantly smaller (p less than 0.001) in CRF group when compared with N group resulting in a median t1/2 for the CRF group of 7.3 h, 2.4 times that of N group. The recovery of unchanged ranitidine in the urine was significantly less in CRF group (p less than 0.001) despite a great interindividual variation in both groups. A significant linear relationship between beta and creatinine clearance was shown (r = 0.81 p less than 0.001). The results indicate that ranitidine elimination is appreciably reduced in renal failure. It is tentatively suggested that the standard 150 mg dose should be halved while keeping the dose interval unchanged at twelve hours in patients with severe renal failure (creatinine clearance less than 30 ml/min).

Adult↗
PubMed1983

Substance P and enkephalin in transected axons of medulla and spinal cord.

The accumulation of transported materials in cut axons is demonstrated by the light and electron microscopic immunocytochemical localization of substance P and enkephalin in the caudal medulla and cervical spinal cord of adult rat. Two days following unilateral knife-cuts in the caudal medulla or spinal (C2-C3) levels, substance P and enkephalin-like immunoreactivity (SPLI and ELI) are detected in lesioned axons located rostral and caudal to the transection. Rostrally, SPLI and ELI are detected in the lateral reticular region and ventrolateral fasciculus corresponding to the location of previously identified bulbospinal pathways. Caudally, previously unidentified, propriospinal pathways showing SPLI are detected in the dorsal columns and in the dorsolateral fasciculus. In contrast, ELI is found caudal to the transection only in the reticular region of the medulla. For both peptides, immunoreactivity is present throughout axons containing numerous large, dense core, and small clear vesicles. These results support the concept of both particulate and soluble modes of transport for substance P and enkephalin within axons of the central nervous system.

Animals↗