Postoperative pain is often stated to be a significant contributor to a sympathetic stress response after surgery. However, hardly any evidence has been published to support this assumption. Hence it was the aim of this trial to investigate the relationship between postoperative pain and hemodynamic, endocrine, and autonomic parameters. A total of 85 postoperative patients in the recovery room were repeatedly asked to rate their pain on a numeric rating scale (NRS). Concurrently, the parameters of heart rate variability (HRV) were analysed, and mean arterial pressure (MAP), heart rate (HR) and respiration rate (RR) were recorded. Pain was categorized into no, mild, moderate, and severe. Blood samples were taken for epinephrine (EPI) and norepinephrine (NE) plasma level assessment at the time of recovery room admission and discharge, and each time pain was found decreased in categorized severity. A total of 239 pain readings were obtained. None of the investigated parameters correlated with NRS scores. NE was higher at NRS 5 to 10 vs. NRS 0 to 4 (mean [SEM]: 1009 [73] pg/mL vs. 872 [65] pg/mL; P<0.01). This was also found for MAP, but not for EPI or the parameters of HRV, HR, and RR. In contrast to common belief, the severity of postoperative pain does not appear to be associated with the degree of sympathetic stress response after surgery, and other factors such as surgical trauma may be more important. Importantly, the absence of signs of sympathetic stimulation cannot be seen as a guarantee for the absence of significant pain.

Clarithromycin was administered to nine previously untreated lepromatous leprosy patients. Patients received two 1,500-mg doses on the first day, followed by 7 days of no treatment, in order to evaluate the potential efficacy of intermittent therapy. Patients then received 1,000 mg daily for 2 weeks followed by 500 mg daily for 9 weeks. The efficacy of therapy was monitored clinically, by changes in morphological index, mouse footpad infectivity, and radiorespirometric activity of Mycobacterium leprae obtained from serial biopsies and by serum levels of phenolic glycolipid I. Clarithromycin was well tolerated, with only minor side effects noted in two patients. Most patients showed reductions in morphological index and radiorespirometry 1 week after the first two doses. Within 3 weeks of starting treatment (total of 17 g of clarithromycin), biopsy-derived M. leprae specimens from all patients had a morphological index of zero, were noninfectious for mice, and had less than 1% of the radiorespirometric activity of pretreatment specimens. Reductions in serum phenolic glycolipid I levels were observed for most patients at 3 weeks. Significant clinical improvement was evident after 4 weeks of treatment. All analyses indicate that clarithromycin is rapidly bactericidal for M. leprae in humans.Clarithromycin is a new semi-synthetic macrolide with activity, pharmacokinetics, and gastric tolerance superior to those of erythromycin. Clarithromycin has demonstrated exceptional activity against Mycobacterium leprae both in vitro (3, 4) and in vivo (5, 7, 8, 11); its activity surpasses that of other macrolides (5,8) and approximates that of rifampin (5, 7).A recent clinical trial of 500 mg of clarithromycin daily against leprosy showed good activity as determined by loss of infectivity of biopsy-derived M. leprae for mice (10). Because of the exceptional tolerance of clarithromycin and increased half-life at increasing dosage (3) and considering the current use of intermittent rifampin therapy in leprosy, we evaluated the effect of both a single day's dose and a higher daily dose of clarithromycin for nine lepromatous leprosy patients and monitored efficacy by a number of rapid assays in addition to the mouse footpad assay. MATERUILS AND METHODSPatients and treatment. Nine male, previously untreated patients with multibacillary leprosy were recruited; all patients had at least one lesion with a bacteriologic index (BI) of >4+ and a morphologic index (MI) of >1% and of sufficient size so that five 6-mm skin punch biopsy specimens could be taken. By clinical evaluation, patients 1 to 3 were classified as borderline lepromatous and patients 4 to 9 were classified as polar lepromatous. Patients ranged from 14 to 56 (median, 31) years in age. Patients had neither a recent history nor signs or symptoms of lepra reactions upon admission. Examination procedures on admission and during the trial were as previously described (1).Patients, who were hospitalized at the Research Institute for Tropical Medicine, Manila, Philippines, for...

This study has shown that men consuming moderate-to-high alcohol as RW for 4 weeks had increased BP, 20-HETE, and oxidative stress, as well as specific SPM that resolve inflammation. These paradoxical findings require further studies to determine whether alcohol stimulates different CYP450 enzymes and whether the findings can be replicated in females.

Nine previously untreated patients with lepromatous leprosy were treated with 200 mg of sparfloxacin daily for 12 weeks to determine whether this drug is bactericidal for Mycobacterium leprae in humans. The efficacy of therapy was monitored both clinically and by measuring changes in morphological index, mouse footpad infectivity, and the radiorespirometric activity of M. leprae organisms obtained from serial biopsy specimens and also by determining titers of phenolic glycolipid-I in serum. Most patients showed clinical improvement within 2 weeks of treatment; this was accompanied by significant reductions in the morphological index, mouse footpad infectivity, and bacillary radiorespirometric activity. After 4 weeks of treatment, all patients had a morphological index of zero and specimens from most patients were noninfectious for mice, while the median decrease in radiorespirometric activity was >99%v. Overall results by the rapid radiorespirometric assay paralleled those of the mouse footpad and morphological index assays. Sparfloxacin given at 200 mg once daily appears to be rapidly bactericidal in humans, with activity similar to that observed in a previous clinical trial with 400 mg of ofloxacin.Among the fluoroquinolones, only ofloxacin and pefloxacin have been subjected to clinical trials in patients with leprosy (11), and both have displayed potent bactericidal activity. Sparfloxacin is a new fluoroquinolone with superior activity against most gram-positive bacteria (14) and Mycobacterium tuberculosis (16). The recent development of radiorespirometric assays for rapidly assessing the drug susceptibility of Mycobacterium leprae in vitro (5) made possible a comparative study of 20 fluoroquinolones (7). Sparfloxacin (AT-4140) was found to be the most active clinically relevant quinolone; its in vitro activity surpassed those of both pefloxacin and ofloxacin. Comparative studies (versus ofloxacin) in both nude mice (10, 20) and healthy immune-competent mice (6, 9) confirmed the in vitro observations. Considering its favorable plasma half-life of 17 h (13) and efficacy against other intracellular infections, sparfloxacin was chosen for a clinical trial in the treatment of patients with leprosy.A dosage of 200 mg of sparfloxacin given once daily was chosen on the basis of in vitro radiorespirometry (7), activity in the mouse footpad model (6), human pharmacokinetics (13), and the recommendation of the manufacturer.In addition to clinical response, morphological index (MI) and mouse footpad infectivity, this trial was monitored by measuring phenolic glycolipid-I (PGL-I) antigen levels in serum and radiorespirometric determination of the oxidation of palmitic acid by biopsy-derived M. leprae. Serum and biopsy specimens were collected just prior to the initiation of treatment and at 2-week intervals for 8 weeks. BI was determined from skin slit smears from at least six sites. MI (the percentage of solid-staining bacilli) was determined from slides prepared from homogenates of biopsy specimens. MATERIALS AND METHO...

Fusidic acid was assessed for antileprosy activity in nine lepromatous leprosy patients. Patients received fusidic acid at either 500 mg/day for 12 weeks or 750 mg/day for 4 weeks followed by 500 mg/day for 8 weeks. All patients showed time-dependent clinical improvement and decreases in bacillary morphological index, radiorespirometric activity and PCR signal, and in serum phenolic glycolipid I. Fusidic acid appears to be a weakly bactericidal antileprosy agent which may have a role in the multidrug treatment of leprosy pending an evaluation of lepra-reaction-suppressive activity. 64 ,ug/ml (11, 18, 23) and, when combined with ethambutol, against some Mycobacterium avium complex strains (18).Fusidic acid is active against Mycobacterium leprae both in axenic medium and in macrophage culture as determined in the BACTEC 460 system (50% inhibition at 1.25 to 2.5 ,ug/ml) (9). An earlier attempt to detect antileprosy activity of fusidic acid in the mouse footpad was unsuccessful (7), possibly because of poor absorption of this compound in mice (14).On the basis of the in vitro activity against M. leprae and human pharmacokinetic properties, a clinical trial of filmcoated sodium fusidate (Fucidin; Leo Pharmaceutical) was conducted with lepromatous leprosy patients. In addition to clinical response, morphological index (MI), and mouse footpad infectivity, patient response was also monitored by measurement of serum phenolic glycolipid I antigen as well as radiorespirometry (10) The patients were hospitalized and received either (i) 500 mg of fusidic acid daily for 8 weeks (patients 1 to 5) or (ii) 750 mg of fusidic acid daily for 4 weeks followed by 500 mg daily for 4 weeks (patients 6 to 9). For all patients, this treatment was followed by an additional 4 weeks of administration of 500 mg of fusidic acid daily as outpatients in order to evaluate the clinical response further.The degree of clinical improvement was assessed according to previously described criteria (3). Serum and 6-mm skin punch biopsy samples were collected just prior to initiation of treatment and at 2-week intervals for 8 weeks. Part of each biopsy sample was processed for mouse footpad assay, radiorespirometry, and MI. The remaining portion was processed separately for PCR. The BI was determined from skin slit smears from at least six sites.The procedure of Cho et al. (6) for measuring phenolic glycolipid I antigen levels was followed. Scoring was based on the relative intensity of color development from the reaction of peroxidase with 4-chloro-1-naphthol.The infectivity for mice of 5, 50, 500, or 5,000 acid-fast bacilli (AFB) from skin biopsy homogenates was determined as previously described (3