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Biomedical subjects

R L Herting

Publications and source records attributed to R L Herting.

13 recordsLinked to original sources
PubMed1992

The effects of milacemide on item and source memory.

Prior research has shown that memory for facts and items (item memory) and memory for where one has learned these items (source memory) can be dissociated under certain conditions. In this study, we examined the effects of milacemide, a derivative of glycine, on memory for item and source information in healthy young and older adults. These results pointed to a dissociation between source memory and item memory: Milacemide administration seemed to facilitate memory for source information but did not affect recognition memory.

Acetamides↗
PubMed1992

Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type.

OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients.

Acetamides↗
PubMed1991

Milacemide enhances memory storage and alleviates spontaneous forgetting in mice.

The objective of this study was to evaluate the effectiveness of milacemide as a memory-enhancing drug in mice. Experiment 1 showed that forgetting of active avoidance learning produced by a 14-day training to test delay could be alleviated by milacemide (10 mg/kg) administered before the retention test. Experiment 2 demonstrated that the same dose of milacemide could also attenuate spontaneous forgetting of passive avoidance learning, thereby ruling out nonspecific effects as an explanation for the enhancement of performance following pretesting drug administration. A third experiment showed that the facilitation of retrieval induced by milacemide could be blocked by the NMDA receptor antagonist AP-7, suggesting that the effects of milacemide on memory may be mediated by NMDA receptor activation. A final experiment demonstrated that retention was improved when milacemide was administered immediately following active avoidance training, indicating that the drug can also facilitate remembering by its actions on consolidation and storage processes.

2-Amino-5-phosphonovalerate↗
PubMed1991

Milacemide and other drugs active at glutamate NMDA receptors as potential treatment for dementia.

Interest in the NMDA receptor as a key mechanism in long-term potentiation and possibly improved learning and memory has led to the development of milacemide as a prodrug for glycine, a modulator of the NMDA receptor. Trials of milacemide in doses ranging from 400-1,200 mg once daily in Alzheimer's disease (AD) for 4 weeks have been disappointing, but milacemide has increased the accuracy and speed of word retrieval in human volunteers. The failure of milacemide in AD has led to an interest in partial agonists of the glycine-B site in the hope of obtaining a better clinical response.

Acetamides↗
PubMed1991

Glycine prodrug facilitates memory retrieval in humans.

Modulation of glycine concentrations in the brain influences learning and memory functions in experimental animals. We administered milacemide, a glycine prodrug, or placebo to young and older healthy adults, who performed a word-retrieval task. Milacemide administration increased the number of words retrieved and decreased the latency with which these words were retrieved for both young and older adults.

Acetamides↗
PubMed1986

Overview of misoprostol clinical experience.

Misoprostol is an E1 prostaglandin analog. Most of the other synthetic prostaglandins that are being studied in advanced clinical trials for gastrointestinal diseases are E2 derivatives. Misoprostol has shown a dose-related antisecretory effect that lasted 3-5.5 hr. In addition, animal studies have shown cytoprotective properties that are being confirmed in clinical studies. Ulcer-healing trials using four times daily dosing appear to parallel the antisecretory dose-response curve up to a dose of 200 micrograms qid. Evidence presented in this supplement suggests a further increase in healing-rate response at 300 micrograms misoprostol qid. The misoprostol healing rates obtained in duodenal ulcer and gastric ulcer therapy at 200 micrograms qid are not significantly different from those seen in the same studies with cimetidine at a dose of 300 mg qid. No significant rebound in recurrence has been observed during follow-up for 12 months after short-term 100- and 200-micrograms qid misoprostol treatment. The most frequent adverse effects are dose-related diarrhea and abdominal cramping, which are transient in most patients and have not caused a significant problem in clinical use. There is also a tropic effect on the pregnant uterus, which was observed in a special pharmacologic clinical study. No significant abnormalities have been detected in clinical laboratory tests or gastric biopsies. There have also been no adverse effects noted on blood pressure, pulse, platelets, the immune system, pulmonary function, gastrointestinal hormones, or the endocrine system. These previously discussed characteristics of misoprostol, and current data, suggest that this prostaglandin E1 derivative may be an important addition to the treatment of peptic ulcer disease.

Alprostadil↗
PubMed1985

Overview of clinical safety with misoprostol.

The number of subjects who had participated in completed clinical trials of misoprostol as of 1 May 1984 was 2272. Of this number 1549 subjects were exposed to misoprostol doses as high as 400 micrograms q.i.d. and for periods up to eight weeks. In ongoing trials subjects are receiving as much as 300 micrograms q.i.d. for up to 12 weeks, or 400 micrograms daily for up to one year. Five large controlled multicenter multicountry clinical trials have been conducted with misoprostol, including double-blind placebo-controlled comparisons of misoprostol in two duodenal ulcer studies and one gastric ulcer study, and double-blind comparisons of two doses of misoprostol and cimetidine in duodenal ulcer and gastric ulcer studies. In the placebo-controlled trials the only complaint clearly associated with misoprostol therapy in a meaningful number of patients was diarrhea, defined as any change in bowel habits whether or not this included true watery diarrhea. The incidence of diarrhea was higher with misoprostol 200 micrograms (13.1% of 107 subjects) and misoprostol 100 micrograms (9.5% of 199 subjects) than with placebo (3.8% of 314 subjects). This relatively high incidence of diarrhea is offset by the fact that only four subjects had withdrawn from studies worldwide because of diarrhea. It appears that compliance was excellent. In the cimetidine-controlled studies, diarrhea and related complaints were greater with misoprostol 200 micrograms (5.6% of 337 subjects) than with misoprostol 50 micrograms (3.0% of 328 subjects) or with cimetidine 300 micrograms q.i.d. (1.8% of 327 subjects).(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1981

Multicenter comparative evaluation of netilmicin and gentamicin in adult patients. Efficacy and safety.

Netilmicin and gentamicin were compared in a multicenter clinical trial in 12 study locations. The two aminoglycosides were randomly assigned to hospitalized adult patients with systemic infections, and were administered by i.m. injection or slow i.v. infusion in divided doses generally calculated to deliver either 4-6.5 mg/kg per day of netilmicin, or 3-5 mg/kg per day of gentamicin. Lower dosages were given to patients with impaired renal function. Data from 210 patients receiving netilmicin and 212 receiving gentamicin were analyzed for efficacy. Favorable bacteriologic responses occurred in 95.5% (255/267) of the netilmicin-treated sites and in 90.1% (247/274) of the gentamicin-treated sites (p = 0.05). Netilmicin eliminated or reduced 95.6% (283/296) of all pathogens isolated from all infection sites compared with 89.5% (289/323) for gentamicin (p = 0.012). Favorable clinical responses were observed in 94.2% (275/292) of the netilmicin-treated patients and 89.5% (289/323) of the gentamicin-treated patients. Data from 377 netilmicin-treated patients and 378 gentamicin-treated patients were analyzed for safety. Evidence of nephrotoxicity probably related to treatment was observed in 8 of the netilmicin-treated patients and 14 of the gentamicin-treated patients. Audiometrically documented hearing loss probably related to treatment was observed in one gentamicin-treated patient. In one netilmicin-treated patient there were transient auditory and vestibular effects. Local tolerance to parenteral administration of the two drugs was excellent.

Adolescent↗
PubMed1980

Netilmicin: chemical development and overview of clinical research.

Netilmicin is a new semisynthetic aminoglycoside which was developed by Schering Corporation, USA, for the treatment of serious gram-negative and staphylococcal infections. Nephrotoxicity and ototoxicity in animal studies have indicated that netilmicin is both quantitatively and qualitatively safer than other aminoglycosides. Also, netilmicin has a broader spectrum of activity than either gentamicin or tobramycin. 37 clinical studies were conducted by 29 investigators in 10 countries. 840 courses of treatment in 960 infection sites were analyzed for effectiveness. Of the 724 courses in which a clinical determination could be made, 91% had either complete resolution or improvement. Bacteriologic responses were available for 782 infecting organisms and showed an 82% elimination rate. The pharmacokinetic profile of netilmicin permits twice daily administration in most patients with systemic infections and in all patients with urinary tract infections. The clinical safety of netilmicin was measured in 890 evaluable treatment courses, and only 0.4% auditory reactions, 0.6% vestibular reactions, and 0.9% renal reactions were considered to be probably netilmicin related, when netilmicin was given as recommended.

Adolescent↗