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Biomedical subjects

S H Roth

Publications and source records attributed to S H Roth.

At least 55 records · Page 3Linked to original sources
PubMed1994

A longterm endoscopic evaluation of patients with arthritis treated with nabumetone vs naproxen.

OBJECTIVE: To compare the gastrointestinal safety, ulcerogenic potential, and clinical efficacy over 5 years of nabumetone and naproxen therapy, in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: Fifty-two patients entered a randomized, double blind study. Patients were randomized to 3 months treatment with either nabumetone, 1000 mg nightly, or naproxen, 250 mg twice daily, followed by an endoscopist-blind 5-year followup study. After the double blind phase, 15 patients in the nabumetone group and 12 in the naproxen group continued in the longterm endoscopist-blind phase. Endoscopic evaluations for gastroduodenal damage and global assessments of arthritis activity and degree of pain for efficacy were measured. RESULTS: Over the 5-year period, endoscopically visible gastroduodenal ulceration was found in 8 of the naproxen treated patients compared with one of the nabumetone treated patients (p = 0.02). There was a significant difference in the time to develop an ulcer, with a greater risk of developing an ulcer sooner while taking naproxen (p < 0.01). Patients in both groups reported significant improvements in arthritis symptoms (p < 0.01). CONCLUSION: Nabumetone appears to have a significantly lower ulcerogenic potential than naproxen over a 5-year period, and there is a trend toward better tolerability as measured by withdrawals for adverse experiences.

Aged↗
PubMed1994

Healing of NSAID-induced gastric ulcers with a synthetic prostaglandin analog (enprostil).

OBJECTIVE: Conventional ulcer therapy has not been proven effective in healing gastric ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) if the NSAIDs are continued. Our objective in this study was to determine whether a prostaglandin analog is an effective treatment for such NSAID-induced lesions. METHODS: To make this determination, we conducted a 9-wk double-blind trial comparing placebo with enprostil 35 micrograms twice daily and three times daily. Use of antacids was not allowed. Three centers entered 145 patients with chronic inflammatory arthritis and osteoarthritis, mean age 63 yr, who required continuous fixed-dose NSAID therapy within the range of therapeutic dosage. The minimum entrance criterion was the presence of either four gastric erosions or one gastric ulcer. Two pretreatment endoscopies within a 2-wk interval were performed to establish the presence of stable baseline gastric lesions. Endoscopy was repeated at wk 6 and 9 during treatment. All groups were similar with regard to age distribution, sex, weight, height, smoking usage, and alcohol consumption. RESULTS: The ulcer healing rates were 14%, 57%, and 68% at 6 wk and 19%, 68%, and 74% at 9 wk for the groups receiving placebo, enprostil twice daily, and enprostil three times daily, respectively (p < 0.01). Complete mucosal healing of all erosions and ulcers at 9 wk occurred in 59% of enprostil-treated patients and in 10% of placebo-treated patients. Additional gastric erosions and gastric ulcers developed in 16% of placebo patients and 4% of the enprostil patients. Eighteen percent of enprostil patients withdrew early from the study due to adverse experiences, such as diarrhea and abdominal pain. CONCLUSION: We concluded that during continued NSAID therapy 1) enprostil 35 micrograms (taken either twice daily or three times daily) heals NSAID-induced gastric ulcers and erosions and protects the mucosa from further NSAID-induced gastric injury; 2) gastric ulcers and erosions rarely heal spontaneously, and 3) enprostil results in a high incidence of diarrhea.

Aged↗
PubMed1994

A double blind study comparing the efficacy and safety of enteric coated naproxen to naproxen in the management of NSAID intolerant patients with rheumatoid arthritis and osteoarthritis. Naproxen EC Study Group.

OBJECTIVE: To compare efficacy and gastrointestinal (GI) tolerability of a new enteric coated formulation of naproxen (NAP-EC) with standard immediate release naproxen (NAP-STD). METHODS: One hundred seventy-nine patients with osteoarthritis (OA) and one hundred seventy-six patients with rheumatoid arthritis (RA) at high risk for developing GI side effects to nonsteroidal antiinflammatory drug (NSAID) therapy were enrolled in a double blind, parallel, multicenter study. All patients had either discontinued as NSAID during the previous one year or required cotreatment with antiulcer drugs for control of GI complaints related to NSAID use. The treatments were evenly divided in both diagnostic cohorts. RESULTS: Except for minor differences in alcohol consumption, baseline characteristics of patients in both treatment groups were statistically similar. Both naproxen formulations were highly efficacious by all variables of disease activity when changes were measured from baseline. No statistically significant between formulation difference was found in the primary efficacy variable, overall disease activity. Overall, between formulation differences in efficacy measures were few, though most favored NAP-STD. GI complaints were reduced by 15% (51% NAP-EC vs 60% NAP-STD, p = 0.077) and GI complaints thought to be drug related were reduced by 36% (16% NAP-EC vs 25% NAP-STD, p = 0.024). Withdrawals due to GI complaints were reduced by 37% in the NAP-EC group (12% NAP-EC vs 19% NAP-STD, p = 0.054), and withdrawals due to GI complaints judged to be drug related were reduced by 55% in the NAP-EC group (6% NAP-EC vs 12% NAP-STD, p = 0.025). CONCLUSION: Enteric coated naproxen is an effective treatment for OA and RA. All observed differences in GI tolerability favor NAP-EC over NAP-STD.

Adult↗
PubMed1993

A controlled study comparing the effects of nabumetone, ibuprofen, and ibuprofen plus misoprostol on the upper gastrointestinal tract mucosa.

BACKGROUND: This study was developed to compare the incidence of endoscopically diagnosed ulcers in elderly patients taking nabumetone, ibuprofen, or concomitant ibuprofen/misoprostol. Further research is indicated to better establish the clinical relevance of these endoscopy findings. METHODS: We conducted a prospective, multicenter, randomized, endoscopist-blinded, 12-week study involving 171 patients with osteoarthritis aged 60 years and older. Patients were randomized to receive nabumetone, 1000 mg (n = 58); ibuprofen, 600 mg four times daily (n = 53); or ibuprofen, 600 mg four times daily, administered concomitantly with misoprostol, 200 micrograms four times daily (n = 60). Endoscopy was performed at baseline and at weeks 2, 6, and 12. Endoscopy results were scored on a scale of 1 to 9. Significant ulcers were defined as breaks in the mucosa greater than 5 mm with appreciable depth. RESULTS: Of the 171 randomized patients, 148 completed the study. There was no significant difference in the incidence of significant ulcers between the nabumetone group and the ibuprofen/misoprostol group (one vs zero). There were significantly fewer significant ulcers in the nabumetone and ibuprofen/misoprostol groups than in the ibuprofen monotherapy group (one and zero vs eight; P < .01). There also was a significant difference in the time to ulcer development, with a greater risk of developing an ulcer sooner with ibuprofen treatment (P < .01) than either nabumetone or ibuprofen/misoprostol treatment. The severity of osteoarthritis, based on physicians' assessments, improved in 64% of patients in the nabumetone group, 55% of those in the ibuprofen group, and 63% of those in the ibuprofen/misoprostol group. CONCLUSIONS: Nabumetone is equivalent in ulcerogenicity to concomitant ibuprofen/misoprostol and is significantly less ulcerogenic than ibuprofen alone.

Aged↗
PubMed1993

In vitro determination of human dura mater permeability to opioids and local anaesthetics.

The permeability of human thoracic and lumbar dura mater to various compounds in clinical use was determined in vitro. Sections of dura mater, 3 to 4 cm in diameter, obtained at post-mortem were placed between the ports (area = 3 cm2) of two glass chambers (A and B) which fitted tightly together to form a two-chamber apparatus for measuring permeability through the dura. Each chamber contained 5 ml of artificial cerebrospinal fluid. A sample of test drug solution was introduced into one chamber (A) and 50 microliters aliquots were withdrawn from the other chamber (B) at predetermined intervals. Permeability was determined by calculating the rate of diffusion (slope) from the plot of mean drug concentration (chamber B) versus time. Dura mater permeability was shown to be a simple diffusion process and to be independent of lipid-solubility and molecular weight. Permeability appeared to increase with age and may have a linear relationship to the initial concentration.

Adult↗
PubMed1993

Double-blind comparison of efficacy and gastroduodenal safety of diclofenac/misoprostol, piroxicam, and naproxen in the treatment of osteoarthritis.

OBJECTIVES: To compare the efficacy and gastroduodenal safety of a fixed-dose combination of diclofenac sodium 50 mg and misoprostol 200 micrograms twice daily with those of piroxicam 10 mg twice daily and naproxen 375 mg twice daily in patients with osteoarthritis. METHODS: A 4 week, randomised, double-blind, parallel-group, multicentre study was conducted in 643 patients with symptomatic osteoarthritis of the hip and/or knee, who required continuous non-steroidal anti-inflammatory drug therapy for 4 weeks and who were without significant upper gastrointestinal damage as confirmed by endoscopy. RESULTS: For patients who had pre- and post-treatment endoscopic examinations, gastroduodenal ulcers developed in 3 (1.5%) of 200 patients treated with diclofenac/misoprostol, 21 (10.3%) of 204 piroxicam-treated patients, and 17 (8.6%) of 198 patients receiving naproxen (Chi square = 13.771, p = 0.001). The improvement in the osteoarthritis severity index was greater in the diclofenac/misoprostol group than in the piroxicam group (p = 0.004). Changes in physician and patient global assessments showed no significant differences between treatment groups. The incidences of diarrhoea and abdominal pain were higher in the diclofenac/misoprostol group than in the piroxicam and naproxen groups. CONCLUSIONS: Diclofenac/misoprostol at twice daily dosing is associated with significantly fewer gastroduodenal ulcers than either piroxicam or naproxen. The efficacy of diclofenac/misoprostol in treating the signs and symptoms of osteoarthritis is at least comparable to that of piroxicam and naproxen.

Adult↗
PubMed1993

Synergistic effects of monensin in combination with permethrin or neomycin on neuronal activity.

Drug combinations have the potential to produce novel and unpredictable responses on nervous tissue. This study was designed to test the hypothesis that the effects of combinations of monensin (an ionophore antibiotic) and either neomycin (an aminoglycoside antibiotic) or permethrin (synthetic pyrethroid) are synergistic. Effects of the drug combinations upon the electrical properties and membrane activities of an in vitro sensory neuron preparation were found to be greater than expected from addition of the effects of the same drugs acting individually, indicating synergism and thus supporting the hypothesis. It was concluded that drugs acting at different neuronal membrane sites and applied in combination produce unpredictable responses. Such drug combinations behave as if they were novel drugs.

Animals↗
PubMed1992

Psychological factors in abortion. A review.

Psychological research is increasingly involved in debates regarding abortion. While recognizing the diversity of ethical and moral issues intertwined with abortion, the American Psychological Association (APA) has focused its involvement on psychological factors, most recently by appointing an expert panel to review the literature on psychological effects. This article notes the history of APA involvement and reports on the panel's conclusions. It presents evidence that abortion is not likely to be followed by severe psychological responses and that psychological aspects can best be understood within a framework of normal stress and coping rather than a model of psychopathology. Correlates of more negative responses following abortion are also discussed.

Abortion, Induced↗
PubMed1992

Low concentrations of hydrogen sulphide alter monoamine levels in the developing rat central nervous system.

The central nervous system is one of the primary target organs for hydrogen sulphide (H2S) toxicity; however, there are limited data on the neurotoxic effects of low-dose chronic exposure on the developing nervous system. Levels of serotonin and norepinephrine in the developing rat cerebellum and frontal cortex were determined following chronic exposure to 20 and 75 ppm H2S during perinatal development. Both monoamines were altered in rats exposed to 75 ppm H2S compared with controls; serotonin levels were significantly increased at days 14 and 21 postnatal in both brain regions, and norepinephrine levels were significantly increased at days 7, 14, and 21 postnatal in cerebellum and at day 21 in the frontal cortex. Exposure to 20 ppm H2S significantly increased the levels of serotonin in the frontal cortex at day 21, whereas levels of norepinephrine were significantly reduced in the frontal cortex at days 14 and 21, and at day 14 in the cerebellum.

Animals↗
PubMed1992

Toxicology of hydrogen sulfide.

Significant progress has been made in determining the action of sulfide on the primary target organs. It is reasonably clear that sulfide causes both K(+)-channel-mediated hyperpolarization of neurons and potentiation of other inhibitory mechanisms. It is not clear whether these processes are similar to those that occur in anoxia. Changes in perinatal and adult brain neurotransmitter content and release may be related to clinical impairment of cognition. H2S exposures at concentrations below the current occupational limits cause physiological changes in pulmonary function, thus suggesting that asthmatics are at risk. Studies of fetal and neonatal brain tissue have shown an abnormal development, and the long-term consequences of these neuronal changes have not yet been assessed. Finally, new approaches to therapy are required, such as the use of agents that actively remove sulfide from its sites of action. This may prove more useful in preventing some of the long-term adverse sequelae than the use of nitrites and hyperbaric O2, although the latter should be used in cases of pulmonary edema.

Animals↗
PubMed1992

Upper gastrointestinal safety with nabumetone.

Nabumetone is a nonacidic nonsteroidal antiinflammatory drug (NSAID) that is effective and appears to cause minimal NSAID gastropathy. The lack of significant untoward gastrointestinal (GI) effects has been demonstrated in large and longterm clinical experiences. The United States Food and Drug Administration reports an annual ulcer incidence of 2 to 4% with chronic NSAID use. The ulcer incidence after therapy with nabumetone, however, is far below the reported range. Only 1 (0.1%) ulcer in 930 patients was determined clinically in United States short term (6-week to 6-month) double blind studies. Additionally, in the long-term (8-year), open label study, only 16 (0.95%) ulcers occurred in 1677 patients. Endoscopically determined ulcers, on the other hand, occur in about 20% of chronic NSAID users. In our short term (3-month) and longterm (5-year) endoscopically controlled study, a 5% (1 of 19 patients) ulcer incidence was determined. Overall, these results suggest a significantly reduced rate of ulcer development.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Nabumetone: a new NSAID for rheumatoid arthritis and osteoarthritis.

Fifteen nonsteroidal anti-inflammatory drugs (NSAIDs) are available in the United States today, yet no clear distinctions among their indications, risk-benefit profiles, or cost effectiveness have been proved. Nabumetone (Relafen), a new NSAID for the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), may differ from the others. Studies have shown that, when compared with currently available NSAIDs, nabumetone may be associated with a significantly lower incidence of gastroduodenal ulcer, and that nabumetone also appears to be safer for use in elderly patients and in those with renal or hepatic impairment.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Chronic exposure to low concentrations of hydrogen sulfide produces abnormal growth in developing cerebellar Purkinje cells.

Hydrogen sulfide (H2S) may produce deleterious effects on the developing central nervous system. The dendritic fields of developing cerebellar Purkinje cells were analyzed to determine the effects of chronic exposure to low concentrations of H2S during perinatal development. Treatment with two concentrations (20 and 50 ppm) of H2S produced severe alterations in the architecture and growth characteristics of the Purkinjec cell dendritic fields. The architectural modifications included longer branches, an increase in the vertex path length and variations in the number of branches in particular areas of the dendritic field. The treated cells also exhibited a nonsymmetrical growth pattern at a time when random terminal branching is normally occurring. These findings suggest that developing neurons exposed to low concentrations of H2S are at risk of severe deficits.

Aging↗