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Biomedical subjects

P Fiset

Publications and source records attributed to P Fiset.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics of rocuronium bromide in paediatric patients.

Rocuronium 0.8 mg kg-1 was given to 22 children between the ages of 3 months and 8 years during anaesthesia with N2O/O2, 60:40, and halothane. Blood samples were collected for 360 min for determination of rocuronium concentrations. The pharmacokinetics were best described by a two-compartment model. Two models were fitted, one proportional to weight and the other adjusted for age. Using the first model, volumes and clearances were all proportional to weight: in the second model, only the volume of the second compartment and clearance from the central compartment were proportional to age. The results do not support the use of body surface area, rather than weight for the calculation of paediatric doses of rocuronium. In this study, the volume of the central compartment was larger than the figure obtained in an adult population.

Androstanols↗

Pharmacodynamic behaviour of rocuronium in the elderly.

This study compared the potency and time course of action of rocuronium (ORG 9426) in elderly and young patients during nitrous oxide-opioid anaesthesia. One hundred ASA physical status I-II patients (60, aged 65-80 yr, and 40, aged 20-45 yr) were studied by measuring the force of contraction of the adductor pollicis in response to train-of-four stimulation of the ulnar nerve. After induction of anaesthesia with thiopentone and maintenance with N2O/O2 and fentanyl, rocuronium 120, 160, 200, or 240 micrograms.kg-1 was administered to determine dose-response curves. When maximum block had been obtained, further rocuronium to a total of 300 micrograms.kg-1 was given. Additional doses of 100 micrograms.kg-1 were administered when the first twitch height (T1) had recovered to 25% control. At the end of surgery neuromuscular blockade was allowed, whenever possible, to recover spontaneously until T1 was 90% of control before administration of neostigmine. There was no difference in the potency of rocuronium in the elderly and the younger patients. The ED50 was 196 +/- 8 (SEE for the mean) in elderly, vs 215 +/- 17 micrograms.kg-1 in young patients (NS). When individual cumulative dose-response curves were constructed, the ED50 was 203 +/- 7 (SEM) and 201 +/- 10 micrograms.kg-1 in the elderly and the young respectively (NS). However, the onset of maximum neuromuscular block was slower in the elderly 3.7 +/- 1.1 (SD) vs 3.1 +/- 0.9 min, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers.

BACKGROUND: Remifentanil (GI87084B) is a new short-acting opioid with a unique ester structure. Metabolism of remifentanil by ester hydrolysis results in very rapid elimination. The aim of this study was to characterize in detail the pharmacokinetic profile of remifentanil in healthy male volunteers. METHODS: Ten healthy adult male volunteers received a zero-order infusion of remifentanil at doses ranging from 1 to 8 micrograms.kg-1.min-1 for 20 min. Frequent arterial blood samples were drawn and analyzed by gas chromatographic mass spectroscopy to determine the remifentanil blood concentrations. The raw pharmacokinetic data were analyzed using three different parametric compartmental modeling methods (traditional two-stage, naive pooled data, and NONMEM). The raw pharmacokinetic data also were analyzed using numeric deconvolution and a nonparametric moment technique. A computer simulation using hte pharmacokinetic parameters of the NONMEM compartmental model was performed to provide a more intuitively meaningful and clinically relevant description of the pharmacokinetics. The simulation estimated the time necessary to achieve a 50% decrease in remifentanil concentration after a variable-length infusion. RESULTS: For each parametric method, a three-compartment mamillary model that accurately describes remifentanil's concentration decay curve was constructed. The NONMEM analysis population pharmacokinetic parameters included a central clearance of 2.8 l/min, a volume of distribution at steady state of 32.8 l, and a terminal half-life of 48 min. The mean results of the nonparametric moment analysis included a clearance of 2.9 l/min, a volume of distribution at steady state of 31.8 l, and a mean residence time of 10.9 min. The computer simulation revealed the strikingly unique pharmacokinetic profile of remifentanil compared to that of the currently available fentanyl family of opioids. CONCLUSIONS: Remifentanil is a new, short-acting opioid with promising clinical potential in anesthesiology.

Adult↗

Cell-mediated immune responses of adults to vaccination, challenge with Rickettsia rickettsii, or both.

As a part of a study to evaluate a formalin-killed Rickettsia rickettsii vaccine, lymphoproliferative (LT) and delayed-type hypersensitivity (DTH) skin test responses to killed R. rickettsii were measured as correlates of cell-mediated immunity in volunteers who were vaccinated, challenged with R. rickettsii, or both. We detected LT responses in 26 (51%) of 51 volunteers after vaccination. After challenge, six of six unvaccinated volunteers and 12 of 16 vaccinated volunteers developed Rocky Mountain spotted fever (RMSF); all 22 mounted LT responses. The vaccinated individuals developed LT responses of greater magnitude and 1-2 weeks earlier than unimmunized controls (41,049 versus 15,084 mean net counts per minute [cpm]), suggesting that vaccination primed the cellular immune system. Moreover, development of LT responses postvaccination was associated with the amelioration of RMSF, as indicated by a slightly longer mean incubation period (328 hr versus 302 hr) and a shorter illness (19 hr versus 26 hr) in LT responders than in LT nonresponders. However, the postvaccination LT response did not discriminate between vaccinated individuals who resisted challenge and those who did not. Skin tests using killed R. rickettsii as antigen, performed in volunteers 14-17 months postvaccination or 12-15 months after challenge, revealed a weak but significant reaction in 50% of those who had received vaccine only, and a moderately strong reaction in all vaccinated and unvaccinated volunteers who had been challenged with R. rickettsii. The relationships between induction of protective immunity against intracellular bacteria by killed and replicating organisms and LT and DTH responses are discussed.

Adolescent↗

Vecuronium is more potent in Montreal than in Paris.

This study was undertaken to compare the potency of vecuronium in patients anaesthetized in Montreal or Paris. Anaesthesia was induced with thiopentone and maintained with N2O, and intermittent boluses of thiopentone and fentanyl in 18 patients in Paris and 19 in Montreal. Neuromuscular blockade was measured using train-of-four stimulation of the ulnar nerve. The force of contraction of the adductor pollicis muscle was measured. Single doses of vecuronium, 20, 30, or 40 micrograms.kg-1 were given by random allocation. Dose response curves were constructed by obtaining the linear regression of the logit of the first response (T1) neuromuscular blockade versus log dose. The patients in Paris required 27% more vecuronium (95% confidence limits 5-53%; P = 0.01) for the same intensity of blockade. In Montreal, the ED50 and ED90 (+/- SEE for the mean) values were 26.0 +/- 1.4 and 44.2 +/- 2.5 micrograms.kg-1 compared with 33.0 +/- 3.3 and 71.9 +/- 7.2 micrograms.kg-1 in Paris respectively. The patients were comparable with respect to age, sex, height and weight. These results confirm, for vecuronium, the transatlantic difference in potency of neuromuscular blocking drugs which was previously observed with d-tubocurarine between London and New York.

Adult↗

Nitrous oxide potentiates vecuronium neuromuscular blockade in humans.

This study was designed to measure the potency of vecuronium with and without nitrous oxide. Anaesthesia was induced with thiopentone and fentanyl in 56 adult patients. The subjects were randomly assigned to receive nitrous oxide, 70%, or intermittent boluses of thiopentone and fentanyl for maintenance of anaesthesia. Train-of-four stimulation was applied to the ulnar nerve every 20 sec, and the force of contraction of the adductor pollicis muscle was measured. Vecuronium, 20, 30 or 40 micrograms.kg-1 was given by random allocation five minutes after induction of anaesthesia. Maximum depression of the first response (T1) in the train-of-four was measured, and dose-response curves were constructed. In the absence of nitrous oxide, the ED50 and ED95 were mean +/- standard error of the mean (SEM), 29.2 +/- 1.8 and 59.3 +/- 3.6 micrograms.kg-1, respectively. In the group receiving nitrous oxide, these values were 25.3 +/- 1.2 and 42.3 +/- 2.0 micrograms.kg-1 respectively. By analysis of covariance, the dose-response curves were shown to be shifted with respect to one another (P less than 0.05). Administration of nitrous oxide was associated with a 19.5% increase in potency (95% confidence limits: 1.7 to 40.4%). It is concluded that nitrous oxide has a slight potentiating effect on neuromuscular blockade, and that this effect occurs within five to ten minutes after the beginning of its administration.

Adult↗

[Serological approach to the occurrence of rickettsioses in the Central African Republic].

A serosurvey for evidence of human rickettsial infections was carried out in the Republic of Central Africa on 144 sera by indirect immunofluorescence (IIF) and microagglutination tests (MA). There was no serological evidence of epidemic typhus and only two sera were positive for murine typhus. Approximately 15% of the surveyed population was serologically positive by MA for R. conorii antibodies. However, 48% of this population had spotted fever group antibodies as detected by IIF but were negative in MA for R. conorii, R. rickettsii and R. akari antibodies. These sera with high titers in IIF and negative in MA lead us to believe that in Central Africa there are rickettsiae pathogenic for man that are related to the Spotted Fever group and are yet to be identified.

Agglutination Tests↗

Serodiagnosis of Rocky Mountain spotted fever: comparison of IgM and IgG enzyme-linked immunosorbent assays and indirect fluorescent antibody test.

To characterize IgM and IgG antibody responses in Rocky Mountain spotted fever (RMSF), a microtiter enzyme-linked immunosorbent assay (ELISA) using density gradient-purified Rickettsia rickettsii as antigen was developed. Sera of vaccinated individuals and patients with RMSF were tested by ELISA and by indirect fluorescent antibody (IFA) tests. Diagnostic agreement between ELISA and the IFA test was 76% and 52% for IgG and IgM antibody, respectively. Diagnostic agreement between the ELISA for IgG antibody and the IFA test for total immunoglobulins was 84%. The ELISAs for IgM and IgG antibody were as specific (100%) and as sensitive (100%) as the IFA test (83%-100%) in detecting antibody increases in paired sera from persons with RMSF and were superior to the IFA test in detecting seroconversions in vaccinees. The ELISA also detected antibodies in a single convalescent-phase serum with sensitivity and reliability. The ELISA for IgG antibody is appropriate for seroepidemiology and serodiagnosis since it permits measurement of antibody at a single dilution of serum up to a year after illness.

Adult↗

Reactogenicity, immunogenicity, and efficacy of a chick embryo cell-derived vaccine for Rocky Mountain spotted fever.

A new formalin-inactivated vaccine prepared by sucrose density gradient centrifugation of tissue culture-grown Rickettsia rickettsii was evaluated for safety and immunogenicity in a placebo-controlled, double-blind study. Most of the 52 seronegative adult vaccinees, 88% after the first and 66% after the second dose, experienced brief, mild (mostly local) reactions, but only 50% exhibited a systemic immune response to vaccination. Six unvaccinated volunteers (controls) and 16 of these vaccinees were challenged with R rickettsii one month after vaccination. Vaccine efficacy was 25%; all six controls and 12 of 16 vaccinees developed typical Rocky Mountain spotted fever. The incubation period was longer, the duration of constitutional symptoms shorter, and the height of fever lower in ill vaccinees than in controls. The vaccine provided only partial protection against Rocky Mountain spotted fever but ameliorated the illness.

Adolescent↗

Mechanisms of immunity in typhus infection: analysis of immunity to Rickettsia mooseri infection of guinea pigs.

To study the mechanisms of immunity to Rickettsia mooseri (R. typhi) infection, sera and splenic cells collected from nonimmune and immune guinea pigs were inoculated separately into syngeneic nonimmune recipients which were subsequently challenged intradermally. Protection was measured by comparing the course of the challenge infections of recipients with infections initiated with the same rickettsial inocula in nonimmune animals. Recipients of splenic cells collected 21 days after donor infection were protected from lesion development at sites of intradermal challenge and showed fewer rickettsiae in their kidneys. Cells obtained from nonimmune donors did not protect against either skin lesion development at sites of challenge or kidney infection. Antibody-containing sera collected 21 days after donor infection, but not normal sera, reduced levels of kidney infection, but immune sera did not protect against the development of lesions at sites of intradermal challenge. It was concluded that both immune sera and immune splenic cells possess capacities to effect a partial control of the systemic phase of R. mooseri infection in guinea pigs, but that immune splenic cells possess a capacity not shared by immune sera, i.e., the capacity to protect from infection at local sites of intradermal inoculation.

Animals↗

Mechanisms of immunity in typhus infection: adoptive transfer of immunity to Rickettsia mooseri.

When nonimmune guinea pigs are inoculated intradermally (i.d.) with Rickettsia mooseri (R. typhi), the rickettsiae replicate at the site of inoculation, leading to the development of a grossly observable lesion. In contrast, guinea pigs which have recovered from R. mooseri infection are resistant to challenge and prevent both rickettsial growth and the formation of lesions. To study the mechanisms of this immunity, sera or splenic cells collected from nonimmune or immune guinea pigs were inoculated separetely into nonimmune recipients. Splenic cells collected from immune donors protected R. mooseri-naive recipients from i.d. challenge as measured by control of rickettsial growth and by prevention of development of lesions at i.d. sites of inoculation. In contrast, serum from immune and nonimmune doners failed to protect nonimmune recipients by either criterion.

Animals↗

Taxonomic relationship of vole agent to Rochalimaea quintana.

We investigated the recent claim that the vole agent, a rickettsia-like microorganism isolated from wild voles by Baker in 1946, is actually a strain of Rochalimaea quintana, the etiological agent of trench fever. The two organisms were compared on the basis of percent guanine-plus-cytosine content, genome size, deoxyribonucleic acid-deoxyribonucleic acid hybridization, polypeptide composition, and serological relationships. Although the two organisms do have identical or nearly identical deoxyribonucleic acid base ratios and show some serological cross-reactions, they differ substantially by all of the other criteria employed. They are clearly different, although possibly related, organisms. It remains to be determined whether they can be regarded as two species of the same genus. On the other hand, an Old World strain and a New World strain of R. quintana were indistinguishable from one another by the same criteria.

Agglutination Tests↗

Antibody response in man following a small intradermal inoculation with Coxiella burnetii phase I vaccine.

A small inoculum (0.2 microgram) of phase I Coxiella burnetii vaccine given to individuals previously sensitized to CO burnetii elicited a positive skin reaction and a strong IgM phase I antibody response as determined by microagglutination, complement fixation and microimmunofluorescence tests. A similar inoculum administered to nonsensitized individuals did not elitic a skin reaction nor stimulate a recognizable antibody response. Serum from one of these sensitized and skin tested individuals was fractionated by gel filtration methods. The serum and serum fractions were titrated in a mouse seroprotection test using primary chicken embryo cell culture plaque technique as the assay procedure. Results of the mouse seroprotection test indicated that most of the protective activity of the serum was associated with the IgM fraction and that phase I IgM antibody suppressed the growth of C. burnetii in mouse spleen when mixed with the rickettsial suspension prior to inoculation.

Adult↗

Rocky mountain spotted fever caused by blood transfusion.

Transfusion of 500 ml of blood, contributed by a donor three days before the onset of Rocky Mountain spotted fever and refrigerated for nine days, caused this disease in the recipient. The blood donor died of Rocky Mountain spotted fever after six days; rickettsia were identified in various tissues by immunofluorescence techniques. The recipient of the blood became mildly ill and recovered fully; specific antibiotic treatment was initiated on the fourth day of illness. Diagnosis of Rocky Mountain spotted fever was confirmed in the recipient by positive serologic reactions and isolation of Rickettsia rickettsii from blood after inoculation in animals and tissue culture.

Aged↗

Legionnaires' disease: antigenic peculiarities, strain differences, and antibiotic sensitivities of the agent.

Paired sera from victims of Legionnaires' disease showed, in many cases, significant rises in immunoglobulin G antibodies to both the causative agent (LA) of Legionnaires' disease and Chlamydia psittaci, but concurrent rises in immunoglobulin M antibodies only against LA. Guinea pigs experimentally infected with LA likewise responded with antibodies to both C. psittaci and LA. Guinea pigs infected with LA also reflected significant differences in antigenic makeup and in pathogenicity among four strains of LA examined. In antibiotic studies, rifampin was 200 times more effective than erythromycin and 17,000 times more effective than tetracycline in plaque reduction tests of LA in monolayer cultures of primary chick embryo cells. An isolate of LA recovered from a healthy person was compared with three isolates from persons with fatal infections.

Animals↗