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Biomedical subjects

N Nathan

Publications and source records attributed to N Nathan.

At least 73 records · Page 4Linked to original sources
PubMed1993

Pharmacokinetics of propofol and its conjugates after continuous infusion in normal and in renal failure patients: a preliminary study.

The pharmacokinetics of propofol, 2,6 diisopropylphenol, were compared in 6 end-stage renal failure patients aged 66.3 +/- 12.1 years and in 5 normal patients aged 45.5 +/- 13.5 years. Anesthesia was induced with propofol (2 and 2.5 mg.kg-1 respectively) and fentanyl (0.1 mg). Anesthesia was maintained with propofol (9 and 10 mg.kg-1 x h-1 respectively). Patients breathed spontaneously a 50 per cent oxygen in nitrous oxide mixture. Two ml blood samples were taken during anesthesia and at regular intervals until up to 24 hours after infusion. Plasma levels of propofol were determined by HPLC with electrochemical detection. Propofol conjugates were determined after hydrolysis with beta glucuronidase or HCl. Results were expressed as median [lower-upper percentiles]. Propofol clearance (1.53 [1.02-2.10] L.min-1 x kg-1 versus 1.65 [1.39-1.78] L.min-1 x kg-1 in normal patients), and half-lives elimination were not modified by renal failure. Renal failure patients exhibited a higher volume of distribution at steady state as compared to normal patients (19.28 [11.71-76.81] L.kg-1 versus 8.60 [6.58-9.81] L.kg-1, p < 0.05). Renal failure did not affect the production of conjugates but they accumulated in blood of renal failure patients. Despite this, no difference in time to eyes opening and propofol concentration were observed, confirming the absence of clinical effect of these metabolites.

Adult↗
PubMed1993

Comparison of omeprazole with cimetidine for prophylaxis of acid aspiration in elective surgery.

Gastric pH and volume were measured in four groups of 15 patients scheduled for elective surgery. The patients were randomly allocated to receive either no antacid, oral omeprazole 40 mg the evening before surgery, oral omeprazole 40 mg 2 h before surgery, or effervescent cimetidine 800 mg, 2 h before surgery. Anaesthesia was induced with thiopentone (4-6 mg kg-1), fentanyl (0.03 mg kg-1) and vecuronium (0.1 mg kg-1) and maintained with nitrous oxide in oxygen (50/50) and isoflurane. After induction of anaesthesia and on completion of surgery, gastric pH (mean +/- SEM) and volume were measured using a glass electrode and a phenol red dilution technique. Gastric pH were significantly higher in the three treated groups than in control (P < 0.01). Omeprazole and cimetidine were equally effective in reducing volume and pH of the gastric juice at the beginning and at the end of anaesthesia. Nevertheless 14.2 and 28.5% of patients who received omeprazole respectively the day before or the morning of surgery remained at risk of aspiration pneumonitis (gastric pH < 2.5 and gastric volume > 25 ml).

Administration, Oral↗
PubMed1992

PAF-acether and acetylhydrolase in stool of patients with Crohn's disease.

PAF-acether (PAF) is a phospholipid mediator with potent biological effects on the digestive tract. We report the presence of PAF in stool of patients with active Crohn's disease (39.1 +/- 13.5 ng/g of stool, mean +/- SEM, N = 19) and its absence in patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. Fecal PAF acetylhydrolase activity was higher (P less than 0.04) in patients with Crohn's disease as compared to patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. We also report a solid-phase extraction of fecal PAF using silica minicolumns, which yielded results highly correlated with those obtained with a high-performance liquid chromatography method (r = 0.86, P less than 0.001, N = 16). These findings may allow us to implicate PAF in the onset and perpetuation of digestive tract inflammatory symptoms observed during Crohn's disease. They would warrant to investigate the influence of various therapeutic agents, including PAF antagonists, on fecal PAF levels during inflammatory digestive ailments.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1992

Variations of blood PAF-acether levels during coronary artery surgery.

Extracorporeal circulation (ECC) is associated with thrombocytopenia and transient leukopenia. After ECC and coronary artery bypass graft (CABG) surgery, some patients can develop pulmonary and cardiac dysfunction, which might be related to the release of various mediators such as thromboxane A2, C5a, and C3a anaphylatoxins. The involvement of PAF-acether (PAF), a potent vasoactive thrombocytopenic and leukoneutropenic agent, has not been determined. Therefore, 10 patients were studied during and after CABG. The release of PAF, lipo PAF (PAF bound to blood lipoproteins), and lyso PAF (PAF precursor and metabolite) was measured in blood from the left atrium, radial artery, and pulmonary artery before and after CABG. PAF, lipo PAF, and lyso PAF were also determined during ECC at the entry and exit points of the oxygenator. Hemodynamic parameters, platelet, and leukocyte counts in the pulmonary artery were measured simultaneously. PAF did not increase significantly during ECC; it showed a transitory six-fold increase immediately after CABG in the radial artery (0.18 +/- 0.13 v 1.09 +/- 0.36 ng/mL, P < 0.05), but not in the pulmonary artery (0.10 +/- 0.03 v 0.56 +/- 0.21 ng/mL, P > 0.05). Blood PAF amounts in the radial artery were significantly higher than in the left atrium following ECC (1.09 +/- 0.36 v 0.06 +/- 0.04, P < 0.05), probably indicating PAF production in the heart. No variation of blood lipo PAF and lyso PAF was observed. No correlation was seen between PAF amounts and blood cell count.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

[Prevention of postoperative nausea and vomiting by ondansetron].

This study was carried out to assess the efficacy of oral ondansetron, a new 5HT3 receptor antagonist, in patients undergoing thyroid surgery. It included 60 patients, randomly assigned to two groups, and receiving orally, 1 h before induction of anaesthesia, either 8 mg of ondansetron (n = 29) or a placebo (n = 30). One patient was excluded. The same anaesthetic protocol, consisting of 3 to 5 micrograms.kg-1 of fentanyl, 4 to 6 mg.kg-1 of thiopentone, and 0.5 mg.kg-1 of atracurium, was used in all. Anaesthesia was maintained with 50% nitrous oxide in oxygen with 0.8 to 1% endtidal concentration of isoflurane and additional boluses of 0.1 mg of fentanyl as required. The incidence and intensity of nausea, graded mild, moderate or severe, and the incidence of vomiting were recorded postoperatively. During the first twelve hours after surgery, 40% of patients in the placebo group had nausea (16.7% mild, 20% moderate and 6.7% severe), and 50% vomited. In the ondansetron group, nausea and vomiting occurred in 13.8% and 20.4% of patients respectively. The 4 patients in the latter group complained of major nausea. The differences between the groups were statistically significant: p = 0.025 for nausea and p = 0.042 for vomiting. It is concluded that oral ondansetron, 8 mg taken orally 1 h before surgery, significantly reduces the incidence of nausea and vomiting during the first twelve postoperative hours. As it is easy to use and has no side-effects, it might be of interest in day-case surgery patients, despite its high cost.

Administration, Oral↗
PubMed1992

Variations in blood platelet-activating-factor levels after protamine reversal of heparin in humans.

The potent inflammatory mediator PAF-acether (PAF = platelet-activating factor) can produce the same hemodynamic and hematological effects as protamine infusion. In 10 patients, blood PAF and precursor levels were measured in the left atrium, the pulmonary and the radial artery before and after protamine reversal of heparin during coronary artery bypass graft. Blood PAF level in the left atrium increased 6-fold (17 +/- 12 pg.ml-1 vs 98 +/- 46 pg.ml-1, P = 0.03) after protamine infusion. By contrast, a 4-fold decrease was observed in the pulmonary artery blood (130 +/- 48 pg.ml-1 vs 31 +/- 23 pg.ml-1, P = 0.03) and a 9-fold decrease was noted in the radial artery blood (285 +/- 104 pg.ml-1 vs 31 +/- 15 pg.ml-1, P = 0.01). No cardiovascular impairment was observed but all patients exhibited thrombocytopenia. After protamine, PAF in the left atrium reached lower levels than those observed in the pulmonary and radial artery before protamine infusion. Moreover, no significant correlation was observed between platelet counts and PAF levels. Thus PAF seems not to mediate the platelet drop induced by heparin-protamine complexes. A positive correlation was obtained between leukocyte counts in the pulmonary artery and PAF levels in the left atrium (r = 0.78, P = 0.02). Protamine infusion may stimulate PAF biosynthesis by leukocytes in the lung, on the one hand, and accelerate the disappearance of PAF in the arterial bed, on the other hand.

Coronary Artery Bypass↗
PubMed1992

Role of paf-acether in protamine-induced thrombocytopenia in rabbits.

The effects of protamine (6 mg kg-1) injected after heparin (5 mg kg-1) have been studied in five groups of five New Zealand white rabbits. Group I was treated with the sequence heparin-protamine and group II with protamine alone. The animals of groups III and IV received respectively intravenous indomethacin (3 mg kg-1) and BN 52021 (3 mg kg-1), a paf receptor antagonist before the sequence heparin-protamine. Group V was pre-treated with indomethacin and BN 52021 before heparin reversal with protamine. In group I, immediate thrombocytopenia (44.1 +/- 4.6% of baseline level, P less than 0.05) and leucopenia (55.5 +/- 2.3% of baseline level, P less than 0.05) were observed 30 s after protamine reversal of heparin, paralleled with an increase in blood paf levels (27.6 +/- 27.6 vs. 148.2 +/- 48.9 pg ml-1, P less than 0.05). In group II, protamine alone induced no change in platelet count nor in blood paf levels (55 +/- 10 vs. 52.5 +/- 20 pg ml-1, P greater than 0.05). Pre-treatment with indomethacin alone (group III) did not protect the animals against the haematological changes induced by the heparin-protamine complexes. Pre-treatment with the paf receptor antagonist, alone or in association with indomethacin, delayed the occurrence of thrombocytopenia 3 min after protamine administration but the leucopenia was the same as in group I. This study demonstrated that paf is implicated in the immediate thrombocytopenia occurring after protamine reversal of heparin in rabbit.

Animals↗
PubMed1991

[Role of vitamin C on adrenocortical effects of etomidate].

This study was carried out to assess whether the adrenal inhibition induced by etomidate could be prevented by associating ascorbic acid with etomidate, as a protective effect of ascorbic acid administered three hours after etomidate has been described. Sixteen ASA 1 or 2 patients, less than 65 years old, free of endocrine disease, were included. At induction of anaesthesia, eight of them (group B) were given an infusion of ascorbic acid 1 g, in 500 ml of 5% glucose. Group A patients (n = 8) were given 500 ml of 5% glucose. Anaesthesia was induced with etomidate 0.3 mg.kg-1, fentanyl 0.005 mg.kg-1 and vecuronium 0.1 mg.kg-1. Maintenance was carried out using a continuous infusion of etomidate (0.1 mg.kg-1.h-1 for 10 min, followed by 0.01 to 0.02 mg.kg-1.h-1). Additional boluses of fentanyl or diazepam (10 mg) were administered when arterial blood pressure or heart rate were 20% greater than preanaesthetic values. The number of injections required was the same in both groups. Plasma cortisol concentrations were measured by radioimmunoassay (RIA) before anaesthesia (T0), 4 h (T4) and 24 h (T24) after the end of surgery. Blood ACTH levels were also assessed by RIA at T0 and T4. The adrenal insufficiency at T4 had completely ended at T24. In fact, the relative decrease in cortisol levels was greater in patients treated with ascorbic acid (T4/T0: 47.6 +/- 9% in group A vs 76.5 +/- 33% in group B, p less than 0.05); this was suggestive of a higher degree of adrenal inhibition in patients receiving ascorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1988

Transjugular liver biopsy--an Australian experience.

During the four year period 1983-87 transjugular liver biopsy was performed on 67 patients (M43, F24) aged 17-79 yr (mean 45.6 yr). Standard percutaneous biopsy was contraindicated by coagulation disorders (95%) often with ascites (17%). Biopsies were taken using a specially modified Ross trans-septal needle passed into hepatic veins under fluoroscopic guidance. Hepatic tissue samples were obtained from the initial biopsy in 62 (93%) patients. In 30 consecutive transjugular biopsies a mean area of 38.2 mm2 per section (0.9-100 mm2) was available for histology compared with an area of 15.9 mm2 (9.3-48.8 mm2) in 50 consecutive percutaneous biopsies. Improved techniques of sample washing, sieving and fixation optimised separation of hepatic tissue from blood clot and fibrin. Four patients experienced significant complications but no deaths occurred. Individual diagnoses were changed in 17 patients as a result of biopsy findings. This study confirms the efficacy and relative safety of the transjugular approach in obtaining liver biopsies from patients with contraindications to standard percutaneous techniques.

Adolescent↗
PubMed1987

Semimembranosus tenosynovitis: operative results.

Semimembranosus tenosynovitis is a common knee problem in the over-50 age-group, occurring mainly in women. It affects the reflected portion of the tendon of the semimembranosus muscle as well as the bursa below it. The tendon becomes inflamed as a result of friction at the entrance to the bony canal (semimembranosus groove), especially if osteophytes are present on the edges of the groove. Conservative treatment includes anti-inflammatory drugs, ultrasound, and friction massage. If necessary, nonresponders may be given local injection of 40-80 mg methylprednisolone acetate with 1% Xylocaine. Between 1979 and 1983 we operated on 16 patients who had not obtained relief even after three or four injections. The approach in each case was through a posterior medial oblique incision. The semimembranosus osteofibrotic tunnel was revealed and the fibrous sheath surrounding the tendon was excised. Good results were obtained in eight patients in whom the inflammatory process had been localized to only the semimembranosus insertion area: eight patients in whom the knee joint or the pes anserinus insertion was also involved achieved fair or poor results. The operation is not advised for young athletes because of the important function of the reflected head of the semimembranosus muscle.

Diagnosis, Differential↗
PubMedDate not supplied

Shortage of vaccines during a yellow fever outbreak in Guinea.

A yellow fever epidemic erupted in Guinea in September, 2000. From Sept 4, 2000, to Jan 7, 2001, 688 instances of the disease and 225 deaths were reported. The diagnosis was laboratory confirmed by IgM detection in more than 40 patients. A mass vaccination campaign was limited by insufficient international stocks. After the epidemic in Guinea, the International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control decided that 2 million doses of 17D yellow fever vaccine, being stored as part of a UNICEF stockpile, should be used only in response to outbreaks.

Disease Outbreaks↗
PubMedDate not supplied

Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study.

BACKGROUND: In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis. METHODS: In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses. FINDINGS: Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported. INTERPRETATION: Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.

Adolescent↗
PubMedDate not supplied

[Detection of meningococcal meningitis epidemics in Africa: a new recommendation].

In sub-Saharan Africa, the control of meningococcal meningitis epidemics relies on early epidemic detection and mass vaccination. However, experience shows that interventions are often initiated too late to have a significant impact on the epidemic. A new recommendation drafted by participants of a consensus meeting proposes an alert threshold and an epidemic threshold based on the weekly number or incidence of meningitis cases, according to the population size and the epidemic risk, resulting in indicators with high sensitivity and specificity for the detection of an emerging epidemic. Meningitis outbreak investigations must include an assessment of the quality of epidemiologic surveillance. The new recommendation is published in English and French in the Weekly Epidemiologic Record [12]. The success of this consensus meeting shows the value of integrating results from surveillance, field experience and operational research for designing new health strategies.

Africa↗