A randomized placebo-controlled trial of lisofylline in HLA-identical, sibling-donor, allogeneic bone marrow transplant recipients. The Lisofylline Marrow Transplant Study Group.

The purpose of the study was to evaluate the effect of lisofylline (LSF) on engraftment, regimen-related toxicities (RRT), and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). We performed a multicenter, randomized placebo-controlled trial in 60 patients with hematologic malignancies receiving BMT from HLA-identical sibling donors. Patients were randomized to receive either placebo, 2 mg/kg LSF or 3 mg/kg LSF every 6 h, beginning before conditioning and continuing to day 21 or hospital discharge. Treatment groups were balanced with respect to conditioning regimen and disease stage. However, significantly more patients in the 2 mg/kg LSF group were at high risk for RRT due to performance status >/=1, age >/=40 years, and prior exposure to CMV. Nausea and vomiting were the only adverse events observed in a higher proportion of LSF-treated patients that led to study withdrawal in six of 42 patients (14%). The times to neutrophil recovery to >/=500/microl and platelet recovery (>20 000/microl) were not improved by LSF treatment. Nevertheless, no patient who received treatment with 3 mg/kg LSF developed a documented infection between day 0 and 35 or had a serious or fatal infection between day 0 and 100 (P = 0.003 vs placebo for both). The day-100 survival rate was also significantly improved in the 3 mg/kg LSF group (89%), compared with either the 2 mg/kg LSF (48%) or placebo (61%) groups (log-rank test, 3 mg/kg LSF vs placebo, P = 0. 026). We conclude that treatment with LSF 3 mg/kg reduced the incidence of infections and improved 100-day survival in patients receiving related-donor allogeneic bone marrow transplantation. Bone Marrow Transplantation (2000) 25, 283-291.

A comparison of remifentanil and morphine sulfate for acute postoperative analgesia after total intravenous anesthesia with remifentanil and propofol.

BACKGROUND: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized mu-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol. METHODS: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 microg x kg(-1) x min(-1) remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 microg x kg(-1) x min(-1) and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed. RESULTS: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] > or =8 breaths/min and pulse oximetry > or = 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 microg x kg(-1) x min(-1) (range, 0.05-0.23 microg x kg(-1) x min(-1)), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, > or = 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05). CONCLUSIONS: Remifentanil provided safe and effective postoperative analgesia when administered at a final rate of 0.05-0.23 microg x kg(-1) x min(-1) in the immediate postextubation period. Remifentanil provided more effective postoperative analgesia than did intraoperative treatment with morphine (0.15 mg/kg) followed by morphine boluses (< or = five 2-mg boluses). The effects of remifentanil dissipated rapidly after ending the infusion, and alternate analgesia was required. Further studies are underway to define transition regimens that will improve postoperative analgesia in patients receiving anesthesia with remifentanil.

Oral sumatriptan is effective and well tolerated for the acute treatment of migraine: results of a multicenter study.

The efficacy and tolerability of oral sumatriptan (Imitrex tablets) were assessed in 187 migraineurs enrolled in a randomized, double-blind, parallel-group, placebo-controlled study. In the clinic, patients received oral sumatriptan 25 mg, 50 mg, or 100 mg, or placebo, for the treatment of a migraine attack. The results demonstrate that by 2 hours postdose, 52 to 57% of patients treated with sumatriptan 25 mg, 50 mg, 100 mg compared with 17% of patients treated with placebo achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). By 4 hours postdose, 65 to 78% of sumatriptan-treated patients compared with 19% of placebo-treated patients achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). Oral sumatriptan also effectively relieved nausea and photophobia and improved clinical disability. No serious or unusual adverse events were reported, and the pattern and incidence of adverse events did not vary among the sumatriptan doses. Each dose--25 mg, 50 mg, or 100 mg--of sumatriptan was effective and generally well tolerated.

Genotoxic potential of acephate technical: in vitro and in vivo effects.

The genotoxic potential of acephate technical (AT) in vitro and in vivo has been studied in bioassays detecting primary DNA damage, chromosomal alterations, and gene mutation. Results from in vitro assays have ranged from negative to weakly positive; AT is apparently a direct-acting agent in these tests. However, expressed in terms of molar potency, AT has generally been at least 100-1000 times less potent than known positive mutagens tested in vitro. Following in vivo exposure at maximum tolerated doses, AT did not induce chromosomal aberrations, sister chromatid exchange, or micronuclei in mouse bone marrow cells; a dominant lethal study in mice was also negative. In a supplemental study, no induced chromosomal aberrations or sister chromatid exchange could be detected in lymphocytes from a pair of cynomolgus monkeys following exposure to AT at a low dose level for 20 days. At dose levels limited by toxicity, no positive results were observed for induction of sex-linked, recessive lethality in D. melanogaster. Acephate technical (ORTHENE) appears to present little or no genetic hazard to in vivo mammalian systems.

Bacteroides bacteremia. Analysis of 142 episodes from one metropolitan area.

Overall mortality for 142 patients with Bacteroides bacteremia encountered in the four hospitals of one metropolitan area between 1977 and 1982 was 41%. Only 43% of deaths of these patients, however, were attributed directly to Bacteroides infection according to the criteria used in this study. Deaths of patients with Bacteroides bacteremia, compared with deaths of patients with bacteremia due to aerobic gram-negative rods, were less likely to occur early after onset of bacteremia. Choice of antimicrobial therapy had no obvious relationship to eventual outcome. Nonobstetrical Bacteroides bacteremia identifies a group of patients at high risk of death during hospitalization. The diversity of both clinical and microbiologic features of these infections, however, makes specific recommendations regarding optimum therapy difficult to formulate.

Staphylococcal bacteremia: current patterns in nonuniversity hospitals.

We studied 390 consecutive episodes of Staphylococcus aureus bacteremia in the four nonuniversity hospitals of one metropolitan area between 1977 and 1981. Overall mortality was 31%, with 52% of deaths being attributed to the infection. The 4.9% incidence of recognized endocarditis was lower than that previously reported. Although 41% of deaths occurred by the end of the third day after positive blood cultures had been obtained, choice of antimicrobial therapy bore no apparent relationship to eventual clinical outcome.