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Biomedical subjects

M D Young

Publications and source records attributed to M D Young.

At least 37 records · Page 2Linked to original sources
PubMed1989

Determining the optimal dosage regimen for H2-receptor antagonist therapy--a dose validation approach.

A large number of clinical studies have been performed to establish the safety and efficacy of H2-receptor antagonist therapy. Few if any of these studies have attempted to address the rationale for the dosage and/or dosage regimens being studied. This study is the first large-scale clinical trial, the purpose of which is to validate the chosen regimen and to address the issue of an optimal therapy for a specific patient population. A regimen of a single nightly dosage is generally acknowledged to offer the potential for improved patient compliance. Furthermore, recent research had suggested that suppression of nocturnal acid secretion is all that is required to heal duodenal ulcers. Hence such a regimen offered the potential for an effective lowered dosage of cimetidine with minimal interference with gastric physiology, increased safety and substantial efficacy. This multicentre, double-blind, placebo-controlled trial therefore evaluated a 4-week course of single night-time dosage of cimetidine. After 4 weeks of treatment the cumulative, endoscopically proven, ulcer healing rate with an 800 mg regimen was 73%, which was statistically higher and significantly superior to the 41% healing seen with placebo (P less than 0.001). The 400 mg nocte dosage regimen of cimetidine normally used as maintenance therapy was significantly inferior to the 800 mg nocte regimen (P = 0.01), and increasing the dosage to 1600 mg nocte for 4 weeks failed to provide a significant improvement in healing over the 800 mg nocte regimen. This 800 mg nocte regimen provided rapid pain relief, with 75% of the patients being free of night-time pain and 65% free of day-time pain, by the end of the first week. The 400 mg 'maintenance dosage' was unable to provide this degree of rapid, complete and early relief to patients with a duodenal ulcer. Furthermore, increasing the dosage to 1600 mg nocte failed to increase the level of early pain relief significantly, perhaps because the extensive response of duodenal ulcer patients to the 800 mg nocte regimen leaves little room for improvement. Based both on the early symptom relief and the ulcer healing rate during 4 weeks of treatment, it is concluded that an 800 mg night-time dosage of cimetidine may be an optimal regimen for many duodenal ulcer patients, particularly those who in the physician's opinion will benefit from a once-daily regimen.

Adolescent↗
PubMed1989

Acute treatment of benign gastric ulcer with once-daily bedtime dosing of cimetidine compared with placebo.

This multicentre, double-blind study evaluated the efficacy of cimetidine 800 mg nocte compared to placebo for ulcer healing and pain relief in patients with endoscopically confirmed, benign gastric ulcers treated for up to 8 weeks. Cimetidine accelerated ulcer healing throughout the study. More cimetidine-treated patients (35 of 82, 43%) than placebo-treated patients (26 of 79, 33%) had healed ulcers after 4 weeks of therapy. Similarly, after 6 and 8 weeks of treatment, cimetidine continued to have superior healing rates, 76% (59 of 78, P = 0.02) and 91% (69 of 76, P = 0.02) heal rates for cimetidine recipients compared with 58% (42 of 73) and 74% (52 of 70) for placebo. For every week of the study except the second, a greater proportion of cimetidine-treated patients were free of daytime and night-time pain than placebo-treated patients; the differences were statistically significant for night-time pain. Adverse reaction profiles were similar for the cimetidine and placebo groups. In conclusion, cimetidine 800 mg nocte was comparably safe and significantly more effective than placebo in accelerating healing and relieving pain in the treatment of acute, benign gastric ulcer.

Adult↗
PubMed1989

Antihypertensive effectiveness of very low doses of hydrochlorothiazide: results of the PHICOG Trial.

A large, multicenter, randomized, placebo-controlled, double-blind trial was carried out to determine the effects of the lowest dose of commercially available hydrochlorothiazide. Thus, Dyazide (which contains 25 mg of hydrochlorothiazide and 50 mg of triamterene in an approximately 50% bioavailable form), one capsule, was given daily to patients with either mild or moderate hypertension (supine diastolic blood pressure of 95 to 115 mmHg) for eight weeks. At the end of this eight-week period, supine diastolic blood pressure (SDBP) fell by 11.3 +/- 6.7 mmHg (mean +/- SD) in the Dyazide-treated compared to 4.6 +/- 6.9 mmHg in the placebo-treated group (P less than 0.001). In two thirds of the patients receiving active treatment the fall in SDBP was more than 10 mmHg, and in over half SDBP was completely normalized (ie, SDBP less than 90 mmHg). Supine systolic blood pressure fell by 14.7 +/- 12.3 mmHg in the Dyazide-treated group compared to 5.3 +/- 11.6 mmHg in the placebo-treated group (P less than 0.001). Approximately 80% of the antihypertensive effect occurred within two weeks and after four weeks there was no further significant reduction. Mildly (SDBP = 95 to 104 mmHg) and moderately (SDBP = 105 to 115 mmHg) hypertensive patients responded similarly to treatment. All studied subpopulations responded to treatment with a reduction of SDBP of at least an average of 10 mmHg; the best responders were blacks, women, the elderly (greater than 65 years old), and patients weighing less than 170 lbs. Side effects were mild and infrequent. In conclusion, by examining the effects of Dyazide (one capsule/day), this investigation demonstrated the effectiveness of low-dose hydrochlorothiazide in antihypertensive therapy and quantified it both in the general population and in clinically relevant subpopulations.

Adolescent↗
PubMed1989

Reduction of indomethacin induced gastroduodenal mucosal injury and gastrointestinal symptoms with cimetidine in normal subjects.

A study was performed in 57 healthy volunteers to determine the effectiveness of cimetidine on reducing gastrointestinal (GI) mucosal lesions and symptoms induced by indomethacin. Endoscopic evidence of gastroduodenal injury and various GI symptoms appeared within 4 days after initiation of indomethacin therapy (50 mg TID) alone. Concomitant therapy with cimetidine, either 200 mg QID or 400 mg BID reduced the incidence of gastric erosions by up to 25% and duodenal erosions by up to 44% (gastric erosions from 81 to 61 and 78%, and duodenal erosions from 90 to 50 and 61%). The incidence of gastric ulcers was reduced from 24 to 0 and 6%, and of duodenal ulcers from 14 to 0 and 11%). The occurrence of moderate or severe pain was also significantly less with coadministration of cimetidine. Results from our study suggest that cimetidine may provide an effective prophylactic therapy against both NSAID related symptoms and gastroduodenal mucosal lesions.

Adolescent↗
PubMed1988

An evaluation of cimetidine and ranitidine in the pain relief and acute healing of duodenal ulcer disease.

In a multicenter, single-blind, randomized trial, the effectiveness in pain relief and healing of three regimens of H2-receptor antagonists was compared in 338 patients with endoscopically confirmed active duodenal ulcers, 112 receiving cimetidine 300 mg four times daily (QID), 110 receiving cimetidine 800 mg at bedtime (HS), and 116 receiving ranitidine 300 mg HS. Evaluation of the immediate symptomatic response during the first 24 hours of therapy showed that a greater proportion of patients with nighttime pain were improved on HS regimen and a greater portion of patients with daytime pain were improved on QID regimen. With continued treatment the differences between a once-daily and a four-times-daily regimen disappeared and the HS regimen provided as much daytime pain relief as the QID regimen. For the two once-daily regimens where ranitidine and cimetidine were directly compared, a greater proportion of patients on cimetidine 800 mg HS had an immediate symptomatic improvement than on ranitidine 300 mg HS. When those who smoked were evaluated separately this difference was also evident. During the first 24 hours, a total of 68% of the smokers in the cimetidine HS treatment groups had improvement in daytime pain versus 44% of patients in the ranitidine group at day one. Nighttime pain relief in smokers on day one was apparent in 78% of the patients receiving the cimetidine HS regimen, in contrast to 67% of ranitidine-HS-treated patients. At the completion of a four-week course of treatment, both physicians' and patients' global assessments of the reduction in the severity and frequency of ulcer-related symptoms significantly favored cimetidine HS over ranitidine HS. These results after four weeks of treatment were corroborated by the endoscopy data, which showed 71% of patients in the cimetidine HS group were healed, compared with 63% in the ranitidine HS group. The 300 mg QID cimetidine regimen produced a 69% healing rate. For those patients whose ulcers were unhealed by the end of four weeks of treatment, a further course of treatment produced almost 9C% healing in all treatment groups and symptomatic relief in virtually all patients. None of the regimens was associated with unexpected adverse effects and all patients tolerated the treatments well. The results of this study confirm the efficacy and safety of single bedtime doses of cimetidine or ranitidine, as well as the four-times-daily cimetidine regimen, in the acute treatment of duodenal ulcers.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1986

The effect of age on theophylline clearance in normal subjects.

Dose-interval AUC and clearance of theophylline at steady-state were determined in healthy male subjects in each of three age groups (18-35, 36-54 and 55-70 years old). Mean AUC in the oldest group was significantly higher than in the youngest and clearance in both the middle and oldest groups was significantly lower than in the youngest. Though clearance was significantly correlated with age, age alone accounted for only 31% of the variability in clearance.

Adult↗
PubMed1985

Effect of ivermectin on murine mites.

Two SC injections of ivermectin (200 micrograms/kg of body weight), given one week apart, safely and effectively eliminated mite infestations (Myocoptes musculinus and Myobia musculi) from laboratory mice. When one 200 micrograms/kg or one 100 micrograms/kg injection of ivermectin was given to the mice, mite infestations were reduced temporarily.

Animals↗
PubMed1985

Comparative susceptibilities of Anopheles quadrimaculatus mutants to Plasmodium yoelii.

Four homozygous mutant stocks and a wild-type stock (ORLANDO) of Anopheles quadrimaculatus were compared for susceptibility to Plasmodium yoelii. The mutant stocks, rose eye (ro) and red stripe (strd), had the same level of susceptibility as the control stock (ORLANDO), but Q2 (homozygous for brown body and nonstripe) and rose eye Q2 (roQ2), were significantly less susceptible. Body size of the adult mosquitoes had no effect on susceptibility.

Animals↗
PubMed1982

Experimental Naegleria fowleri meningoencephalitis in sheep: light and electron microscopic studies.

A sheep infected intranasally with Naegleria fowleri of human origin died 7 days after inoculation. The olfactory lobes were distinctly soft and friable. Histologic findings indicated suppurative leptomeningitis and hemorrhagic necrosis in the olfactory lobes. Protozoa were disseminated in the necrotic areas, particularly in perivascular locations; vasculitis was also observed. Meningitis and perivascular cuffing with lymphocytes were evident in the cerebrum, cerebellum, pons, medulla, and cervical spinal cord. Electron microscopy disclosed trophozoites only in the olfactory lobes. The amebae contained a central nucleus with a distinct, electron-dense nucleolus. The cytoplasm contained myelinated figures, lipid-like vacuoles, open vesicles, electron-dense granules, mitochondria, numerous free ribosomes, scant rough endoplasmic reticulum, and occasionally a phagocytized erythrocyte. Trophozoites were grouped close to arterioles, except when phagocytized by a neutrophil or endothelial cell.

Amebiasis↗
PubMed1982

Experimental transmission by mosquitoes of Plasmodium hermani between domestic turkeys and pen-reared bobwhites.

Plasmodium hermani was experimentally transmitted from domestic turkey poults (Meleagris gallopavo) to pen-reared bobwhites (Colinus virginianus) and then from these bobwhites back to domestic turkey poults. Transmission was achieved by Culex nigripalpus both by bites of the mosquito and by intraperitoneal injection of sporozoites. All of the 23 bobwhites and the 13 turkeys exposed to sporozoites became infected. These results indicate that the bobwhite might be a reservoir host for this malaria of wild turkeys in nature.

Animals↗
PubMed1980

Safety evaluation of tocainide in the American Emergency Use Program.

This is a report of the safety evaluation of tocainide in the first 369 patients entered into the American Tocainide Emergency Use Program. This humanitarian protocol has made tocainide available for emergency use in the treatment of life-threatening, intractable ventricular arrhythmias in patients who were unresponsive to or unable to take the approved antiarrhythmic drugs. TAhe most frequent adverse experiences reported were neurologic and gastrointestinal in nature and included dizziness, lightheadedness, tremors, nausea, vomiting, and anorexia. Adverse experiences resulted in the discontinuation of tocainide in 16% of these patients and were transient and reversible with no conclusive evidence of permanent organ injury. Adverse experiences having special relevance to the safety assessment of new antiarrhythmic agents are discussed, including congestive heart failure, arrhythmias and conduction disturbances, convulsions, lupus erythematosus-like illness, and deaths while on therapy. No significant abnormal trends were observed in routine hematologic and biochemical laboratory screening tests or in ophthalmologic or chest x-ray examinations. An evaluation of the effects of chronic tocainide administration of ECG intervals showed no significant change in P-R or QRS intervals but demonstrated a statistically significant decrease in Q-T duration. It is concluded that in patients with life-threatening ventricular arrhythmias, tocainide is a safe agent with a favorable risk-benefit ratio.

Anilides↗
PubMed1980

Treatment of ventricular arrhythmias with oral tocainide.

This is a report of a multicenter open study of the use of tocainide, a new lidocaine-like antiarrhythmic with a high oral bioavailability, in the treatment of life-threatening ventricular arrhythmias refractory to other therapy. The majority of patients have received 1,200 to 2,400 mg daily in divided doses and have been treated for over 6 months and some for longer than 3 years. Overall, 61% of the patients responded successfully to tocainide therapy. In the 252 patients with documented, severe, symptomatic arrhythmias, 71% responded, and the majority (87%) showed a total abolition of symptomatic events. Gastrointestinal and central nervous system events were the most common adverse experiences, and 11% had to discontinue therapy; however, the remaining 89% tolerated tocainide satisfactorily.

Adolescent↗
PubMed1980

Experimental infection of sheep with Naegleria fowleri of human origin.

A strain of Naegleria fowleri, isolated from a child who died of primary amebic meningoencephalitis in Florida, was instilled in the nostrils of a sheep to determine whether livestock are susceptible to infection with free-living amebae. The animal died 7 days later from amebic infection of the central nervous system. N. fowleri were recovered from the brain and spinal cord of the animal. A control, saline-instilled sheep that had been pair-caged with the infected animal remained healthy.

Amebiasis↗