Minority cancer patients and their providers: pain management attitudes and practice.

BACKGROUND: The goals of the current studies were: 1) to determine the pain treatment needs of socioeconomically disadvantaged African-American and Hispanic patients with recurrent or metastatic cancer and 2) to assess the attitudes of health care professionals who treat them. METHODS: In the first study 108 African-American and Hispanic patients with metastatic or recurrent cancer and pain completed a survey about their pain intensity, pain interference, and attitudes toward analgesic medications. Physicians also rated their patients' pain and the adequacy of the patients' current analgesic prescriptions was assessed. In the second study 55 physicians and nurses who treat these patients completed a questionnaire regarding cancer pain and its management in their practice settings. RESULTS: Approximately 28% of the Hispanic and 31% of the African-American patients received analgesics of insufficient strength to manage their pain. Although the majority of patients received appropriate analgesics, 65% reported severe pain. Physicians underestimated pain severity for 64% of the Hispanic and 74% of the African-American patients. Physicians were more likely to underestimate the pain severity of female patients than male patients. Inadequate pain assessment, patient reluctance to report pain, and lack of staff time were perceived as barriers to pain management. CONCLUSIONS: Although the data suggest recent improvements in analgesic prescribing practices for African-American and Hispanic cancer patients, the majority of patients reported high levels of pain and limited pain relief from analgesic medications. Inadequate pain assessment remains a major barrier to optimal cancer pain treatment.

Effect of felbamate on plasma levels of carbamazepine and its metabolites.

Felbamate (FBM) is a novel antiepileptic drug (AED) currently undergoing clinical evaluation in the United States. During a controlled clinical trial conducted at the National Institutes of Health Clinical Center, FBM was added to constant carbamazepine (CBZ) monotherapy. CBZ total concentrations were reduced during active FBM treatment (mean reduction 25%, range 10-42%, p less than 0.001). The effect was evident after the first week of treatment and reached a plateau in 2-4 weeks. To clarify the interaction mechanism, free and total concentrations of CBZ and its plasma metabolites were determined by high-performance liquid chromatography (HPLC) and ultrafiltration in four patients. In these patients, FBM treatment reduced CBZ concentrations and increased CBZ-epoxide (CBZ-E) concentrations (p less than 0.01). Free fractions of all compounds were unmodified. FBM appears to be capable of inducing CBZ metabolism. CBZ-FBM interaction may be clinically relevant.

Angiotensin converting enzyme inhibitory activity of SCH 33844 (spirapril) in rats, dogs and monkeys.

SCH 33844 is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of the synthetic substrate hippuryl-histidyl-leucine by rabbit lung ACE in vitro with an IC50 (concentration inhibiting enzyme by 50%) of 0.81 nM. The ester was 83 times less active. Intravenous administration of SCH 33844 and its diacid inhibited pressor responses to angiotensin I (AI) in anesthetized rats with calculated ID50's of 16 and 8 micrograms/kg, respectively. Oral administration of SCH 33844 (0.03-1 mg/kg) inhibited AI pressor responses in conscious rats with a duration of 24 hr at the highest dose. The diacid was inactive. Intravenous administration of SCH 33844 (100-1000 micrograms/kg) or its diacid (30 micrograms/kg) to anesthetized dogs inhibited AI pressor activity and potentiated the depressor response to bradykinin. SCH 33844 inhibited AI responses in conscious dogs following oral administration of 0.3-3 mg/kg. Oral administration of SCH 33844 (1 mg/kg) to conscious monkeys inhibited AI pressor responses for the 4 hr duration of study. In conclusion, SCH 33844 is a potent, orally effective ACE inhibitor in rats, dogs and monkeys.

Prevention of acute aspirin-induced gastric mucosal injury by 15-R-15 methyl prostaglandin E2: an endoscopic study.

The deleterious effects of aspirin on gastric mucosa have been well documented in experimental and clinical studies. Prostaglandins offer a potential method by which this injury may be prevented. In these studies, we developed a single-dose endoscopic assay system of aspirin-induced gastric mucosal injury in normal volunteers. With this system, 27 of 30 volunteers (90%) demonstrated severe mucosal injury after ingestion of aspirin. Subsequently, we evaluated whether pretreatment with 15-R-15 methyl prostaglandin E2 prevented severe injury after ingestion of aspirin. Following an initial dose-response study, a double-blind crossover trial was performed using pretreatment with placebo or with 10-micrograms doses of 15-R-15 methyl prostaglandin E2 for 24 h before treatment with aspirin. The results of this trial indicate that prostaglandin pretreatment significantly prevented the occurrence of endoscopically visible severe gastric mucosal injury after single-dose aspirin administration.

Mechanism of the pressor response to tetradecapeptide renin substrate in the rat.

The synthetic tetradecapeptide renin substrate (TDP; Asp-arg-val-tyr-ile-his-pro-phe-his-leu-leu-val-tyr-ser) has been employed frequently to elucidate the enzymatic action of renin in vitro and, to a lesser extent, in vivo. We assessed the utility of TDP as a renin substrate in vivo using conscious spontaneously hypertensive rats. Intravenous injection of TDP (1 and 3 micrograms/kg) increased diastolic pressure by 45 +r2 and 67 +/- 2 mmHg, respectively. The pressor response to TDP was significantly inhibited by captopril (3 mg/kg, po), indicating its dependence on conversion by ACE to some active molecule. Pressor responses to TDP also were less in animals subjected to bilateral nephrectomy 18-24 hr before study. However, responses to angiotensin I and II also were reduced, implying a non-specific effect of nephrectomy. Intravenous infusion of the renin inhibitor pepstatin (200 micrograms/min) inhibited pressor responses to hog renin by approximately 60%, but did not affect those to TDP. Intravenous infusion of the water soluble renin inhibitor, pepstatinyl-arginine-o-methyl ester (500 micrograms/min), also inhibited pressor responses to renin (approx. 80%) and did not affect those of TDP. Incubation to TDP (5 microM) with rabbit lung ACE resulted in generation of AI that was blocked by captopril (1 microM). These data suggest that TDP is a substrate for ACE and that the increase in blood pressure produced by TDP is due to its sequential cleavage by ACE to AII and can be independent of renin.