A titrated morphine analgesic regimen comparing substance users and non-users with AIDS-related pain.

To compare morphine dosage and effectiveness in AIDS patients with/without prior substance use and pain, a prospective, open-label case series lasting 3-18 days was conducted in both outpatients and inpatients at major pain service teaching programs. Forty-four patients, 13 with prior drug use history, who had pain associated with HIV infection or its treatment were administered sustained-release morphine (SRM) every 12 hours. The dose was titrated to pain relief for a period of > or =3 consecutive days (associated with < or =2 immediate-release morphine tablets per 24 hours), or until the patient discontinued from the study or completed 18 study days. Forty-four patients were enrolled (13 with a prior drug use history). Forty were evaluable for an intent-to-treat analgesia, including 11 with a drug use history. Twenty-four (6 users) completed this study. Former users and non-users were similar in demographics, baseline pain intensities, causes of pain, discontinuation, quality of life, and acceptability of therapy. Pain intensity decreased by > or =50% in both groups (P < or = 0.0001). To identify a stable dose, the dose of SRM more than doubled in former users and rose by 31% in non-users (mean final dose 177.4 mg and 84.9 mg, respectively) (P = 0.0018). Immediate-release morphine decreased in both; former users required more (P = 0.0006). These data suggest the utility of morphine for AIDS-related pain. Patients with a prior drug use history benefited but required substantially more morphine.

Sustained-release morphine sulfate in the management of pain associated with acquired immune deficiency syndrome.

Sustained-release morphine (SRM) was studied in patients with acquired immune deficiency syndrome (AIDS)-related chronic pain. Outpatients and inpatients with AIDS-related pain were studied for 3-18 days in an open-label prospective survey. Patients were stratified according to prior opioid analgesic use for the purposes of initiating and titrating SRM, which was administered at a 12-hr interval. Immediate-release morphine (IRM) was offered every 2 hr as needed for supplemental analgesia at one-quarter to one-third of the 12-hourly SRM dose. Pain intensity (PI), quality of life (QL), acceptability of therapy (AT), side effects, safety, and morphine usage were evaluated. Of 44 patients enrolled, 40 (91%) were evaluable for intent-to-treat analysis, and 24 (55%) completed the study. PI decreased by 50% (from severe to mild-moderate) in the intent-to-treat patients and by 65% (from severe to mild) in the completed patients. QL was fair to good in 80% and poor in 20% of both groups. AT was good to excellent in 78% of the intent-to-treat and in 96% of the completed patients. Of 61 adverse events reported, 61% required intervention, and 92% were resolved. Total morphine dose remained stable while IRM dosage and frequency of use significantly decreased with escalation of the SRM dose. A significant reduction in PI was achievable with SRM in a variety of painful conditions experienced by AIDS patients, with limited or manageable side effects in most. This study supports the usefulness of opioid analgesia for severe pain in AIDS.

Efficacy and safety of pentoxifylline in geriatric patients with intermittent claudication.

The effects of pentoxifylline on intermittent claudication were evaluated at a dose of 1200 mg/day in an open-label twelve-week study on geriatric patients with chronic occlusive arterial disease (COAD). Standardized treadmill testing and clinical signs and symptoms of COAD were followed up before and during drug administration. Twenty-four subjects with a mean age of 73.5 years, capable of walking between 20 and 200 meters on the treadmill, were entered into the trial; 22 participated for eight weeks and 19 completed the study in terms of treadmill walking distance measurements at 12 weeks. The mean walking distance for all patients was increased 111% over baseline at week 12. Thirteen subjects were considered drug responders (greater than or equal to 50% increase in treadmill walking distance) and 9 were considered nonresponders (less than 50% increase). Improvements in clinical signs and symptoms of COAD were noted. Decreases in elevated systemic systolic pressures (but not diastolic) were unexpectedly observed in many drug responders. Seven of 19 males reported sexual function improvements while receiving pentoxifylline. Fourteen (58%) of the 24 subjects reported mild side effects of dyspepsia, nausea, vomiting, dizziness, headache, or insomnia; no subjects were withdrawn from the study because of side effects. In summary, pentoxifylline improved function and symptoms in 13 of 22 geriatric patients with intermittent claudication; the drug was safe and well tolerated at the usual dosage in this geriatric patient population.

Analgesic efficacy and safety of two oral controlled-release morphine preparations in orthopedic postoperative pain.

This single-dose, double-blind, randomized, parallel-group study compared the analgesic efficacy and safety of MS Contin (MSC) and Oramorph SR (OSR), two controlled-release preparations of oral morphine sulfate, in patients following orthopedic surgery. One hundred patients received MSC 30 mg, MSC 60 mg, or OSR 60 mg (two 30-mg tablets) when postoperative pain became moderate or severe. Patients self-rated pain intensity and relief on categorical (CAT) and visual analogue scales (VAS) hourly for up to 12 hours. MSC 60 mg produced the greatest peak analgesic effect and was more efficacious than OSR 60 mg through the sixth hour, with statistical significance achieved at 1, 2, and 3 hours postdosage. Compared with OSR 60 mg, both MSC dosages provided significantly more rapid times to peak effect by CAT and VAS ratings. The OSR group experienced almost twice as many adverse events as did the two MSC groups and also reported somnolence and dizziness more frequently. MSC 60 mg provided more rapid and greater peak analgesia with fewer adverse effects than did OSR 60 mg.

Stimulation of human synovial fibroblast plasminogen activator production by mononuclear cell supernatants.

Conditioned medium from concanavalin A-stimulated human peripheral blood mononuclear cells (c-MCCM) stimulates the plasminogen activator (PA) production of nonrheumatoid human synovial fibroblasts obtained from explant cultures. The effect of this synovial fibroblast-stimulating activity is observed within 2 to 4 hr and requires RNA and protein synthesis. Reversible morphological changes in the synovial cells can be observed as a result of c-MCCM action. These enzymatic and morphologic changes are similar to some of the effects of transforming viruses and tumor promoters on target cells. The possible significance of these data for an understanding of the cellular interactions involved in the formation and function of the rheumatoid "pannus" is discussed.

1-Deamino-8-D-arginine vasopressin and cryoprecipitate in variant von Willebrand disease.

The effect of infusing DDAVP and cryoprecipitate either singly or in combination was studied in a patient with variant von Willebrand disease. Both DDAVP and cryoprecipitate caused only partial correction in the hemostatic defect when used as a single agent. A combination of DDAVP and cryoprecipitate induced a complete correction of the hemostatic defect as well as factor VIII related properties.

Human synovial fibroblast plasminogen activator. Modulation of enzyme activity by antiinflammatory steroids.

Human synovial fibroblasts in culture have been shown to have low plasminogen activator (PA) activity; however, conditioned medium from concanavalin A-stimulated peripheral blood mononuclear cells (c-MCCM) stimulates the cellular levels of this protease. The present study shows that low concentrations of a series of antiinflammatory steroids inhibit the PA activities of both unstimulated and c-MCCM-stimulated fibroblasts. Dexamethasone, the corticosteroid studied in greatest detail, suppresses both the extracellular and cell-associated enzyme activities; this inhibition is rapid, reversible, and is not due to the inhibition of cellular RNA, protein, or DNA synthesis. PA has been invoked as possibly being generally important for the processes of cell migration, tissue remodeling, and inflammation. These in vitro observations suggest that physiologic and/or pharmacologic control of the PA levels in synovial fibroblasts might also be achieved in vivo by the interacting effects of mutually antagonistic agents, namely, a product from stimulated mononuclear cells and glucocorticoids.