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R Larsen

Publications and source records attributed to R Larsen.

At least 19 recordsLinked to original sources
PubMed1998

Psychophysiologic responsivity in posttraumatic stress disorder: generalized hyperresponsiveness versus trauma specificity.

BACKGROUND: Clinically, subjects with posttraumatic stress disorder (PTSD) are viewed as hyperresponsive to a variety of stimuli. Psychophysiologic studies, however, have demonstrated hyperresponsiveness only to stimuli that are closely related to the original trauma. METHODS: This set of experiments uses a variety of stimuli that vary in trauma-relatedness, arousal level, sensory modality stimulated, and degree of cognitive processing demanded to assess the extent of generalization of physiologic responses. Heart rate (HR), frontal electromyogram (EMG), and skin conductance (EDG) responses were measured during presentation of each stimulus. RESULTS: PTSD subjects (n = 15) had an elevated baseline EDG and increased HR and EMG responses to the trauma-related stimulus (combat sounds) compared to normal control subjects (n = 11) and combat control subjects (n = 10). No significant differences were noted between PTSD and control groups in response to non-trauma-related arousing stimuli. CONCLUSIONS: These results suggest that the physiologic hyperresponsivity of PTSD subjects is limited to stimuli closely associated with the inciting trauma.

Acoustic Stimulation↗
PubMed1998

A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process.

The aim of this study was to identify the molecular mechanisms involved in neutrophil adhesion to immobilized platelets with particular focus on the possible existence of a juxtacrine system for neutrophil-platelet interactions. Platelets were immobilized onto collagen (type I)-coated coverslips that were placed in a flow chamber and neutrophils were perfused across these confluent monolayers at a shear stress of 1 to 4 dynes/cm2. Neutrophils rolled, and a significant proportion (25% to 50%) adhered to platelet monolayers. P-selectin was expressed in very large quantities on the surface of platelets and mediated all of the rolling, whereas the beta2-integrin mediated firm adhesion. An activation mechanism for adhesion was necessary inasmuch as fixed neutrophils continued to roll on immobilized platelets, but did not adhere. Platelets adherent to collagen produced significant levels of platelet-activating factor (PAF). Accordingly, the firm adhesion of neutrophils to platelets was significantly inhibited by a PAF receptor antagonist (WEB 2086). Treatment of only the platelets with acetylhydrolase, which converts membrane-associated PAF to lyso-PAF, prevented 60% of the adhesion. These data suggest that PAF, on the surface of platelets, mediated a significant portion of the adhesive interaction. Addition of some selectin-binding carbohydrates (fucoidan or soluble SLEx analogs but not dextran sulfate) to the platelets caused rolling neutrophils to immediately adhere, an event that was not observed on histamine or thrombin-treated endothelium or P-selectin transfectants. These data support the view that a juxtacrine activation process exists on immobilized platelets for neutrophils. This process can be greatly enhanced on platelets and may involve a signaling mechanism through P-selectin.

Anticoagulants↗
PubMed1998

[Remifentanil-propofol anesthesia in vertebral disc operations: a comparison with desflurane-N2O inhalation anesthesia. Effect on hemodynamics and recovery].

OBJECTIVE: To ascertain whether there is a difference between total intravenous anaesthesia with propofol (P) and remifentanil (R) and inhalational anaesthesia with desflurane (D) and nitrous oxide (N) with regard to haemodynamic reactions, recovery profile and postoperative analgesic demand in patients scheduled for elective microsurgical vertebral disc resection. METHODS: 50 patients (ASA I-II, 18-65 years) were randomly assigned to receive total intravenous anaesthesia with propofol and remifentanil or inhalational anaesthesia with desflurane and nitrous oxide. After standardised induction of anaesthesia in both groups (1 microgram.kg-1 remifentanil, 1.5 mg.kg-1 propofol 0.1 mg.kg-1 cisatracurium), anaesthesia was maintained in the D/N group with desflurane in 50% N2O. The patients of the P/R group received a constant infusion of 2 mg.kg-1.h-1 propofol and a constant infusion of 0.5 microgram.kg-1.min-1 remifentanil, which was reduced after 15 min by 50%. The administration of desflurane and the infusion of the anaesthetics were adjusted to maintain a surgical depth of anaesthesia. At the end of surgery the anaesthetics were discontinued and early emergence from anaesthesia was assessed by measuring time to spontaneous ventilation (VT > 4 ml/kg), tracheal extubation, opening of the eyes and stating correct name and data of birth. The frequency of analgesics and total demand for analgesics were determined using patient-controlled analgesia and recorded for 2 h postoperatively. In addition the pain level of the patients was measured on a visual analogue scale and the incidence of postoperative shivering, nausea and vomiting was noted. RESULTS: Patients anaesthetised with desflurane responded to tracheal intubation and skin incision with increasing blood pressure and showed higher heart rates than patients anaesthetised with propofol and remifentanil, but there were no other haemodynamic differences between the groups in response to surgical stimuli. There were significantly shorter times to spontaneous ventilation (3.2 vs. 6.3 min), extubation (3.8 vs. 9.5 min), eye opening (3.0 vs. 11.5 min) and giving name and date of birth (4.8 vs. 14.3 min) in patients anaesthetised with remifentanil and propofol than in those receiving desflurane and nitrous oxide. In addition, patients anaesthetised with remifentanil and propofol had a greater incidence of postoperative shivering. There were no significant differences between the two groups in the patients' pain scores, analgesic demand and incidence of nausea and vomiting. CONCLUSION: Patients anaesthetised with propofol and remifentanil have significantly shorter emergence times than patients anaesthetised with desflurane and nitrous oxide. The low incidence of postoperative pain after microsurgical vertebral disc resections requires no large-scale analgesic therapy, even after total intravenous anaesthesia including remifentanil.

Adult↗
PubMed1998

[Ondansetron. Prophylaxis and therapy of nausea and vomiting following major gynecologic procedures. Results of a national multicenter study].

UNLABELLED: This investigation was conducted as a national multicenter study to evaluate effectiveness and safety of prophylactic and therapeutic ondansetron for postoperative nausea and vomiting (PONV) in major gynaecological surgery. METHODS: 387 patients were randomised to receive either ondansetron 8 mg or placebo i.v. prior to anaesthesia induction. Anaesthesia was performed with a volatile anaesthetic, nitrous oxide and opioids. Established PONV was treated with ondansetron 4 mg i.v. Postoperative evaluation included time, duration and severeness of nausea and vomiting in the first 24 h after the operation. RESULTS: In the study period the incidence of emesis was 35% after prophylactic ondansetron and 58% after placebo (p < 0.01). Nausea occurred in 49% and 64% respectively (p < 0.01). 28% after prophylactic ondansetron and 48% after placebo required ondansetron therapy (p < 0.01). The number of adverse events was small in total and comparable for both groups. CONCLUSION: Our investigation proves the efficiency of ondansetron 8 mg prior to induction of anaesthesia in preventing PONV. Furthermore, our results demonstrate the safety of the drug for prophylaxis and therapy.

Antiemetics↗
PubMed1998

[The effect of gamma-hydroxybutyrate (GHB) on proinflammatory cytokine gene expression in coronary surgical procedures].

OBJECTIVE: To determine the influence of gamma-hydroxy-butyrate (GHB) on spontaneous and lipopolysaccharide (LPS)-stimulated release of tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interleukin-10 (IL-10) in whole blood from patients undergoing coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC). In addition, the pharmacological modulation on lipopolysaccharide (LPS)-stimulated cytokine release by GHB (GHB-Na and GHB-ethanolamide) was characterized in a separate in vitro-assay. METHODS: In a prospective, randomized, double-blinded study, 12 patients undergoing elective CABG were assigned to receive either saline (control) or GHB-Na (25 mg/kg as loading dose followed by 25 mg/kg/h) intraoperatively. Blood samples were obtained (A) preoperatively, (B) 20 min after ECC and (C) 24 h after ECC. Plasma levels (spontaneous release) as well as LPS-stimulated cytokine secretion were measured in a whole blood culture system ex vivo and correlated with mRNA-expression in peripheral blood mononuclear cells (PBMC). In addition, the dose-response characteristics of modulation of the cytokine response by GHB was studied in vitro in the same assay. RESULTS: Plasma IL-6 and IL-10 levels were significantly elevated after CABG, while TNF and IL-1 beta were detectable only occasionally in both groups. Expression of all cytokines studied was significantly reduced upon ex vivo LPS-stimulation at time point B. Despite maintained expression of TNF and IL-1 beta mRNA-transcripts upon ex vivo LPS-stimulation in patients treated with GHB, release of the cytokines in the supernatant was decreased to a similar degree as in the control group. Cytokine response upon LPS-stimulation was restored 24 h after CABG for the group mean, however, with substantial individual heterogeneity. In vitro, pharmacological doses of GHB-Na (2 mg/ml) attenuated LPS-induced IL-1 beta release. However, application of the GHB-receptor antagonist NCS-382 caused a nearly complete cessation of IL-1 beta release in vitro (to 2.5% of control). GHB-ethanolamide (LK 544) did not influence the LPS-stimulated release of the cytokines studied. CONCLUSION: The results suggest a biphasic response of stimulated PBMC cytokine gene expression during CABG with an initial tolerance to LPS-stimulation shortly after termination of ECC. However, whether or not PBMC express functional GHB receptors remains unclear in light of contradictory effects of the different ligands. In spite of the ex vivo and in vitro results, application of GHB-Na in doses which are primarily based on its use as an anesthetic agent do not seem to modulate the release of the cytokines studied.

Adult↗
PubMed1998

Desflurane or isoflurane for paediatric ENT anaesthesia. A comparison of intubating conditions and recovery profile.

BACKGROUND: The inhaled anaesthetic desflurane is characterized by a rapid wash-in and wash-out and may be useful for short paediatric ENT procedures. Therefore, this study was designed to compare the effects of desflurane or isoflurane on intubating conditions and recovery characteristics in paediatric ENT patients. METHODS: In this prospective, randomised investigation, we studied 44 children scheduled for ENT surgery, aged 4-12 yr and classified ASA I-II. After thiopentone induction (5-8 mg/kg) the lungs were ventilated by face mask and the vaporizer was dialed to 1 MAC (age-adapted) of desflurane of isoflurane. A reduced dose of vecuronium (0.05 mg/kg) was administered, and intubating conditions were rated 3 min later. Following tracheal intubation, 50% nitrous oxide were added, and the concentration of desflurane or isoflurane was adjusted according to clinical needs. At the end of surgery all anaesthetics were discontinued simultaneously and recovery times were recorded. RESULTS: Intubating conditions were rated significantly better for desflurane (excellent or good 20 of 22) than for isoflurane (12 of 22). Recovery times were significantly shorter for desflurane than for isoflurane (mean +/- SE): spontaneous ventilation 4.0 +/- 0.5 min vs. 6.0 +/- 0.7 min, extubation 8.4 +/- 0.7 vs. 11.4 +/- 1.1 min and arrival at PACU 11.5 +/- 0.8 vs. 16.6 +/- 1.5 min. No airway complications (coughing, laryngospasm, or desaturation < 97%) were noted for either anaesthetic. CONCLUSIONS: Following an intravenous induction improved intubating conditions, shorter recovery times and the lack of airway complications make desflurane a suitable alternative to isoflurane for paediatric ENT anaesthesia.

Anesthesia Recovery Period↗
PubMed1998

Total intravenous anaesthesia with gamma-hydroxybutyrate (GHB) and sufentanil in patients undergoing coronary artery bypass graft surgery: a comparison in patients with unimpaired and impaired left ventricular function.

The haemodynamic effects of anaesthesia with gamma-hydroxybutyrate (GHB)/sufentanil for elective coronary artery bypass grafting (CABG) were investigated and compared in patients with unimpaired left ventricular function (ejection fraction > or = 45%, left ventricular end diastolic pressure < or = 16 mmHg) and patients with impaired left ventricular function. In 38 consecutive patients scheduled for CABG (21 with unimpaired and 17 with impaired left ventricular function), anaesthesia was induced with etomidate, sufentanil and pancuronium. After tracheal intubation, the lungs were normoventilated (end tidal Pco2 4.9-5.6 kPa) with an oxygen-air mixture (Fio2 0.5). Total intravenous anaesthesia was maintained with GHB (20 mg kg-1 h-1 after a 'priming dose' of 40 mg kg-1) and sufentanil (2 micrograms kg-1 h-1). Haemodynamic measurements were made after induction of anaesthesia and at various times in the prebypass period. Patients in both groups showed similar haemodynamic trends. Mean arterial pressure showed a maximum reduction of 10%, whereas heart rate and right- and left-sided filling pressures remained unchanged within the groups after the induction of anaesthesia. Cardiac index remained unchanged in both groups, although values differed between the groups. A total of 14 out of 21 patients (67%) with unimpaired and 10 out of 17 patients (59%) with impaired ventricular function required supplementary administration of opioids to control temporary hypertension after sternotomy. No episodes of myocardial ischaemia were detected during the study period using ST segment analysis (leads II and V5). The results of this study suggest that GHB provides adequate haemodynamic conditions in the prebypass period and may be a suitable agent for TIVA also in patients with impaired left ventricular function undergoing CABG.

Aged↗
PubMed1998

[Remifentanil in gynecologic laparoscopy. A comparison of consciousness and circulatory effects of a combination with desflurane and propofol].

OBJECTIVES: Rapid post-anaesthetic awakening and low hypnotic potency are two characteristic properties of the new opioid remifentanil. For clinical use remifentanil must be combined with another anaesthetic agent. Propofol is well-established for ambulatory anaesthesia, however, the properties of desflurane (low blood-gas solubility, rapid elimination) suggest this volatile anaesthetic to be a comparable alternative, particularly if rapid awakening is desired. The present study was designed to compare emergence times and haemodynamics for a combination of remifentanil wich hypnotic concentrations of either propofol or desflurane. METHODS: Gynaecological patients, scheduled for elective laparoscopy, were studied at random. After oral premedication with diazepam 0.08-0.12 mg/kg, anaesthesia was induced identically in both groups: remifentanil bolus (1 microgram/kg), start of remifentanil infusion (0.5 microgram/kg/min), followed by propofol (approx. 2 mg/kg) and cisatracurium (0.1 mg/kg). For maintenance of anaesthesia remifentanil (0.25 microgram/kg/min) was combined with either desflurane (0.5 MAC = 3.0 vol%) or propofol (6 mg/kg/h). With termination of surgery anaesthetic delivery was discontinued simultaneously and recovery times were recorded. Heart rate and non-invasive blood pressure were recorded at defined points of interest. RESULTS: In total, 40 patients (desflurane n = 20, propofol n = 20) were studied in comparable groups. For both regimens, emergence after remifentanil-based anaesthesia was remarkably rapid between unconsciousness and complete recovery: In mean only 60 s elapsed from the onset of spontaneous breathing to the moment when patients could clearly state their name. In comparison, recovery times were significantly shorter after remifentanil-desflurane than after remifentanil-propofol: time to spontaneous ventilation 6.4 +/- 2.8 vs. 9.6 +/- 3.9 min (mean +/- SD, p = 0.01); extubation 6.7 +/- 2.8 vs. 9.8 +/- 4.0 min (p = 0.02) and arrival at PACU 11.1 +/- 3.4 vs. 14.7 +/- 4.2 min (p = 0.005). The courses of heart rate (HR) and mean arterial pressure (MAP) were mostly similar in both groups with only minimal or moderate cardiocirculatory reactions during intubation or start of surgery. CONCLUSIONS: Remifentanil in combination with either desflurane or propofol, used for general anaesthesia during gynaecological laparoscopy, will facilitate a smooth haemodynamic course as well as a rapid emergence thereafter. Recovery times after remifentanil-based anaesthesia are significantly shorter with 3.0 vol% of desflurane than with 6 mg/kg/h propofol. Thus, desflurane appears to be a well-suited adjunct to remifentanil and an ideal alternative to propofol, if rapid recovery is required. Differences are best explained by the pharmacological properties of both coanaesthetics and their applied dosages.

Adult↗
PubMed1998

Novel monoclonal antibodies to putative selectin carbohydrate ligands that inhibit selectin binding to myeloid cells.

Four newly developed monoclonal antibodies (MAbs) are characterized using flowcytometry, enzyme-linked immunoadsorbent assay (ELISA), immunoprecipitation and Western blots, carbohydrate epitope mapping, glycosidase cleavage, and competition binding assays. Their effects on selectin binding to myeloid cells was tested. These MAbs react only with myeloid cells. MAbs CI-1, BU60, and HIM95 recognize epitopes expressed by CD11/CD18 (beta2) integrins, while HI247 and CSLEX1 do not. The epitopes require Lewis x [Galbeta1-4 (Fucalpha1-3)GlcNAc] based on reactivity with oligosaccharide-polyacrylamide-biotin or oligosaccharide-BSA conjugates. MAb HI247 recognizes a related structure, sialyl-Lewis x, NeuAcalpha2-3GaLbeta1-4(Fucalpha1-3)GlcNAc. The three MAbs against Lewis x show some minor differences in their reactivity such as recognizing their antigens on CD11/CD18 integrins after endo-beta-galactosidase treatment and recognizing free Lewis x. The hydroxyl group on C-3 of the terminal galactose is important for recognition by MAb CI-1, BU60, and HIM95 as its substitution with sulfo group of sialic acid abolishes the binding of these MAbs. The C-3 sialic acid is crucial for the binding of MAb HI247. Its replacement by sulphate or its cleavage by sialidase eliminates recognition by this MAb. MAbs HI247 and CSLEX-1 did not react in ELISA with immobilized CD11/CD18, suggesting that the majority of sialyl Lewis x on CD11/CD18 molecules may have sialic acid 6-linked rather than 3-linked to galactose. Unexpectedly, MAb BU60 inhibited binding of P-selectin mu chain chimera to HL-60 or U937 cells, while CI-1, HIM95 and three other defined anti-Lewis x MAbs (6C7, M6-1 and LeuM1) did not. MAb HI247 inhibited binding of both E- and P-selectin chimeras to these cell lines more effectively than several characterized MAbs (CSLEX-1, FH6, HECA-452) to sialyl Lewis x and related oligosaccharides. Certain combinations of these anticarbohydrate MAbs had additive inhibitory effects on selectin binding, suggesting a potential application of these new MAbs in cell adhesion/migration and tumor metastasis studies.

Animals↗
PubMed1998

Pentoxifylline prevention of altered hepatocyte calcium regulation during hemorrhagic shock/resuscitation.

OBJECTIVE: To evaluate the effect of pentoxifylline on altered hepatocyte calcium regulation and hepatocyte oxidant injury after hemorrhagic shock. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized, male Sprague-Dawley rats, weighing 220 to 300 g. INTERVENTIONS: Hemorrhagic shock was induced by bleeding rats to a mean arterial blood pressure of 40 mm Hg for 60 min. Rats were then resuscitated with 60% of shed blood and three-fold the bleed out volume of lactated Ringer's solution without and with pentoxifylline (50 mg/kg body weight). After hepatocyte isolation by portal collagenase perfusion, the rate of hepatocyte calcium influx (Ca2+in) in the absence and presence of epinephrine (100 nM), both cellular Ca2+ uptake (Ca2+up) and membrane Ca2+ flux (Ca2+flux) were determined, using 45Ca2+ incubation techniques. Hepatocyte lipid peroxidation was fluorometrically determined by thiobarbituric acid-reactive substances. MEASUREMENTS AND MAIN RESULTS: Pentoxifylline inhibited the significant increase of hepatocyte Ca2+in, Ca2+up, and Ca2+flux observed in untreated rats subjected to hemorrhage/resuscitation. In shocked rats, pentoxifylline restored the impaired epinephrine-induced Ca2+ influx response and prevented increased hepatocyte lipid peroxidation. CONCLUSIONS: The protective effects of pentoxifylline could be attributed to its known anti-inflammatory properties reducing excessive in vivo stimulation of hepatocytes by Ca2+ agonistic mediators and attenuating oxygen radical-related disturbances of transmembrane Ca2+ transport mechanisms. Since altered cellular Ca2+ regulation is a key event of cellular dysfunction, resuscitation with pentoxifylline after hemorrhagic shock/resuscitation may provide an adjuvant therapeutic tool to prevent postischemic hepatic failure.

Animals↗
PubMed1998

Postural post-dural puncture headache after spinal and epidural anaesthesia. A randomised, double-blind study.

BACKGROUND: This study was conducted in order to investigate the effect of patient expectation in the development of postural post-dural puncture headache (PPDPH). METHODS: 224 patients less than 55 years scheduled for minor non-obstetric surgery were randomised to receive single-injection spinal (SA) or epidural (EA) anaesthesia. A 27-g Quinke needle was used for SA and a 18-g Tuohy needle for EA. Patients, operating team and postoperative ward personnel were all blinded to the anaesthetic given and so was an independent observer responsible for follow-up after 5-7 days. The occurrence of headache, backache and other complaints was recorded. Headache was classified as PPDPH or non-PPDPH, and duration and intensity of the headache was registered. The quality of anaesthesia was directly evaluated by the surgeon using a VAS scale from 1 (excellent) to 10 (very poor) and indirectly by the supplemental use of opioid analgesia and general anaesthesia in the two groups. RESULTS: 212 patients, 103 SA and 109 EA, with a mean age of 36.7 years, could be fully evaluated. The groups were comparable with regards to age, sex and surgical procedure performed. Headache occurred in 44 patients postoperatively. PPDPH was diagnosed in 16 patients (15.5%) in the SA group and 2 (1.8%) in the EA group (P = 0.0014). Non-PPDPH occurred in 13 patients in each group. PPDPH had significantly greater mean intensity and duration than non-PPHPH. More patients in the EA group had postoperative backache (31.2%) than in the SA group (22.3%), but this difference was not statistically significant. More patients in the EA received general anaesthesia and opioid analgesia than in the SA group, and the surgeon's rating was on average 1.3 in the SA group compared to 2.5 in the EA group (P = 0.0003). CONCLUSIONS: SA gave more headache but superior quality of surgical anaesthesia compared with EA. Dural puncture, and not expectation, is the major cause of PPDPH.

Adult↗
PubMed1998

Total intravenous anaesthesia with propofol and remifentanil in paediatric patients: a comparison with a desflurane-nitrous oxide inhalation anaesthesia.

BACKGROUND: Remifentanil is a new rapid-acting and ultra-short acting mu-opioid receptor agonist with few reports from use in children. Therefore, we compared a propofol-remifentanil-anaesthesia (TIVA) with a desflurane-N2O-anaesthesia (DN) with particular regard to the recovery of characteristics in children. METHODS: 50 children (4-11 yr) scheduled for ENT surgery were randomly assigned to receive TIVA (n = 25) or DN (N = 25). After standardised i.v. induction of anaesthesia in both groups with remifentanil, propofol and cisatracurium, TIVA was maintained with infusion of propofol and remifentanil. Ventilation was with oxygen in air. DN was maintained with desflurane in 50% N20. The administration of volatile and intravenous anaesthetics was adjusted to maintain a surgical plane of anaesthesia. At the end of surgery all anaesthetics were terminated without tapering and early emergence and recovery were assessed. In addition, side effects were noted. RESULTS: Both anaesthesia methods resulted in stable haemodynamics but significantly higher heart rate with desflurane. Recovery did not differ between the groups except for delayed spontaneous respiration after TIVA. Spontaneous ventilation occurred after 11 +/- 03.7 min versus 7.2 +/- 2.8 min (mean +/- SD, TIVA versus DN), extubation after 11 +/- 3.7 min versus 9.4 +/- 2.9 min, eye opening after 11 +/- 3.9 min versus 14 +/- 7.6 min and Aldrete score > or = 9 after 17 +/- 6.8 min versus 17 +/- 7.5 min. Postoperatively, there was a significant higher incidence of agitation in the DN group (80% vs. 44%) but a low incidence (< 10%) of nausea and vomiting in both groups. CONCLUSION: In children, TIVA with remifentanil and propofol is a well-tolerated anaesthesia method, with a lower peroperative heart rate and less postoperative agitation compared with a desflurane-N2O based anaesthesia.

Adenoidectomy↗
PubMed1998

E-mail influence messages of type-A scoring managers.

In a study of 158 managers' e-mail influence messages to subordinates, managers' self-reported Type-A scores were positively associated with personal responsibility, legitimate supervisors' authority, and pressure tactics, and negatively correlated with reward from supervisor tactics.

Administrative Personnel↗
PubMed1997

Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial.

PURPOSE: To study the efficacy and safety of maintenance treatment with itraconazole for disseminated histoplasmosis in patients with AIDS. PATIENTS AND METHODS: This was a prospective, multicenter, open-label study conducted at university-based hospitals participating in the AIDS Clinical Trial Group (ACTG). Forty-six AIDS patients with mild to moderate disseminated histoplasmosis who had successfully completed 12 weeks of induction treatment with itraconazole were treated with itraconazole, 200 mg once daily (42 patients) or 400 mg once daily (4 patients). Patients were followed at monthly intervals with clinical and laboratory assessment for relapse or toxicity. Primary outcome measures were relapse of histoplasmosis and survival. Secondary outcome measures included drug-limiting toxicity and changes in serum and urine Histoplasma polysaccharide antigen (HPA) levels. RESULTS: Two patients relapsed during a median follow-up period of 87 weeks. The 1-year relapse-free rate was estimated to be 95.3% (95% CI, 85.3%-99.7%). One relapse may have been related to poor adherence to treatment and the second to concurrent administration of rifampin. From the start of maintenance treatment, the estimated 1-year survival rate was 73.0% (95% CI, 67.5%-77.9%). Five patients discontinued treatment because of suspected drug toxicity, three of whom had possible or probable hepatotoxicity. Median serum and urine HPA levels declined significantly during treatment. The only patient in whom antigen levels rose >2 U developed clinical relapse 1 week later; antigen levels were unavailable in the other relapsing patient. CONCLUSIONS: Itraconazole, 200 mg daily, is effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. It is generally well tolerated, but clinicians should be alert for drug interactions and possible hepatotoxicity.

AIDS-Related Opportunistic Infections↗
PubMed1997

High-performance liquid chromatographic analysis of Peptide T in rabbit plasma with on-line column enrichment.

The present paper describes the development of a simple and sensitive analytical method for quantification of Peptide T (PT) in rabbit plasma, using standard analytical equipment and on-line column enrichment, without prior extraction, clean-up or derivatization. The analytical procedure was found to be accurate, precise and linear. The accuracy was 100% (range 97-103%) and the mean precision was 8% (range 3-14%) for all (n=6) concentrations (0, 15, 50, 100 and 200 ng/ml). The total recovery was found to be approximately 80%, and it was found to be dependent upon the injection rate onto the extraction column. The correlation between added and found concentrations was 0.9982, and the limit of detection was estimated to be around 5 ng/ml. The method is therefore found to be suitable for bioavailability studies, involving Peptide T, in rabbits.

Administration, Intranasal↗
PubMed1997

Role of platelet-activating factor in hepatocellular Ca2+ alterations during hemorrhagic shock.

A role of the potent proinflammatory Ca2+ agonist platelet-activating factor (PAF) on hepatocellular Ca2+ homeostasis and oxidant injury was investigated, since Ca2+ dysregulation has been demonstrated as a pivotal pathomechanism causing hepatic dysfunction during hemorrhagic or septic shock. In anesthetized male Sprague-Dawley rats, blood was withdrawn to a mean arterial blood pressure of 40 mm Hg for 60 min. Rats were resuscitated with 60% of shed blood and threefold the shed blood volume of lactated Ringers' (shock group). After 60 min of resuscitation, hepatocytes were isolated by portal collagenase perfusion. Hepatocellular Ca2+ uptake (Caup2+), initial rate of Ca2+ influx (Cain2+), and membrane Ca2+ flux (Caflux2+) were determined using 45Ca2+ incubation techniques. Hepatocyte oxidant injury was fluorometrically determined by thiobarbituric acid reactive substances. Caup2+ (3.37 +/- 0.15 vs. 2. 53 +/- 0.08 nmole Ca2+/mg protein), Cain2+ (0.42 +/- 0.1 vs. 0.27 +/- 0.02 nmole Ca2+/mg protein/min), and Caflux2+ (31.3 +/- 4.3 vs. 16.9 +/- 2.4 pmole Ca2+/mg/min) significantly increased in the untreated shock group compared to untreated sham-operated rats (P < 0.05). The specific PAF receptor antagonist BN52021 given 5 min before (5 mg/kg b.w.) and continuously during resuscitation (5 mg/kg/hr) significantly reduced Caup2+ in the shock group (2.73 +/- 0.2; P < 0.01) and prevented hepatocyte lipid peroxidation (shock: 91.9 +/- 1; shockBN52021: 66.7 +/- 2 nmole/mg wet weight; P < 0.01). These data suggest that platelet-activating factor plays a pivotal role in promoting hepatocyte Ca2+ overload during hemorrhagic shock by releasing Ca2+ agonistic mediators and inducing oxidative membrane alterations both of which are capable of enhancing cellular Ca2+ influx.

Animals↗
PubMed1997

[Deferoxamine-conjugated hydroxyethyl starch reduces reperfusion injury to the liver following hemorrhagic shock].

UNLABELLED: Deferoxamine is known to reduce the iron-dependent generation of toxic oxygen-derived radicals during reperfusion of ischaemic tissue. The present study investigates the antioxidative properties of a deferoxamine-conjugated hydroxyethyl starch solution and its effects on the hepatic microcirculation in a haemorrhagic-shock rat model. METHODS: Anaesthetized Sprague-Dawley rats were tracheotomized, prepared for invasive haemodynamic monitoring, and subject to haemorrhagic shock (MAP = 40 mmHg during 60 min). The animals were resuscitated blood-free with lactated Ringer's (RILA, n = 10), gelatin (GELA, n = 10), hydroxyethyl starch (HES, n = 10), or deferoxamine-conjugated HES (DFO, n = 8) solution (MAP > or = 70 mmHg). After 1 h of resuscitation the hepatic microcirculation was investigated by intravital microscopy, the glutathione concentration was measured in liver homogenate, and the thiobarbituric acid reactive substances (TBARS) were determined as markers of lipid peroxidation. RESULTS: Resuscitation resulted in restoration of MAP to > or = 70 mmHg within a short time. The volume required to stabilise the arterial pressure during 1 h of resuscitation was significantly less in the DFO group compared with HES, GELA, and RILA. Significantly higher glutathione levels in liver homogenate as well as decreased TBARS levels were observed in the DFO group. The shock-induced increase of leukocyte adhesion in liver sinusoids was significantly attenuated by DFO. CONCLUSION: DFO significantly attenuates shock-induced oxidative stress, thereby reducing the early inflammatory reaction and improving the hepatic microcirculation.

Animals↗