Bioavailability and hypoglycemic activity of the semisynthetic bile acid salt, sodium 3alpha,7alpha-dihydroxy-12-oxo-5beta-cholanate, in healthy and diabetic rats.

Previous studies in our laboratory have shown that the semisynthetic bile acid derivative, sodium 3alpha,7alpha-dihydroxy-12-oxo-5beta-cholanate (MKC), has hypoglycemic activity. The aim of this study was to investigate the relationship between the pharmacokinetics and hypoglycemic activity of MKC in healthy and diabetic rats. Groups of healthy and alloxan-induced diabetic rats were dosed intravenously (i.v.) and orally with MKC (4 mg/kg). Blood samples were taken before administration of the dose and at 20, 40, 60, 80, 120, 150, 180, 210 and 240 minutes post-dose. MKC serum concentration was measured by HPLC, and pharmacokinetic parameters determined using the WinNonlin program. The absolute bioavailability of MKC was found to be low in healthy and diabetic rats (29 and 23% respectively) and was not significantly different between the two groups. Mean residence time (MRT), volume of distribution (Vd) and half-life (t1/2) of MKC after oral administration were significantly lower in diabetic than in healthy rats (21, 31 and 29% respectively). After the i.v. dose, the change in blood glucose concentration was not significant in either healthy or diabetic rats. After the oral dose, the decrease in blood glucose concentration was significant, reaching a maximum decrease from baseline of 24% in healthy rats and 15% in diabetic rats. The results suggest that a first-pass effect is crucial for the hypoglycemic activity of MKC, indicating that a metabolite of MKC and/or interference with metabolism and glucose transport is responsible.

Anoxic-ischemic alpha coma: prognostic significance of the incomplete variant.

The prognostic significance of post-anoxic-ischemic alpha coma (AC) is controversial. We recorded somatosensory evoked potentials (SEPs) and performed serial electroencephalography (EEG) in a 60-year-old woman in coma after cardiac arrest. The first EEG was recorded after 48 hours (GCS=5; E1-V1-M3); brain-stem reflexes were preserved. The EEG pattern showed monotonous alpha frequencies (10-11 Hz) with posterior predominance; acoustic and noxious stimuli evoked EEG reactivity. Early cortical SEPs (72 h) were normal. On the fifth day (GCS=8; E4-V1-M3), the EEG alpha pattern was replaced by a diffuse delta activity; rhythmic theta changes appeared spontaneously or in response to stimuli. The patient regained consciousness on the tenth day and EEG showed posterior theta activity (6-7 c/s) partially reactive to stimuli. At the 6-month follow-up, cognitive evaluation showed mild dementia. Recent studies identified two forms of AC. Patients with complete AC have an outcome that is almost invariably poor. Conversely, incomplete AC (posteriorly accentuated alpha frequency, reactive and with SEPs mostly normal) reflects a less severe degree of anoxic-ischemic encephalopathy. The case we report should be classified, according to the SEPs and EEG features, as incomplete AC. The fact that the patient has regained consciousness, even if with residual cognitive impairment, confirms the need to distinguish this variant from complete AC.

[Thoracic spinal stenosis. Clinical and surgical management. Study of 5 cases observed in the Abidjan department of Neurosurgery]. / Les myélopathies dorsarthrosiques. Etude clinique et thérapeutique à propos de 5 cas traités au service de Neurochirurgie d'Abidjan.

BACKGROUND: Spinal cord compression resulting from thoracic spinal stenosis is relatively frequent in Japan but rare in Europe and little know in Africa. OBJECTIVE: We report five cases of thoracic myelopathy caused by thoracic stenosis diagnosed in black African people. METHODS: This was a retrospective observational study of patients treated in the Abidjan department of Neurosurgery from 01.01.1996 to 31.12.1998. The spinal cord compression resulting from thoracic spinal stenosis was confirmed by myelography or myeloscan. The Japanese orthopaedic association (JOA) score was used to evaluate patient outcome. RESULTS: All of these patients were black Africans. The four men and one woman were aged 55, 47, 53, 52, and 60 years. The clinical presentation of thoracic spinal cord compression was confirmed by myelography in five patients and by myeloscan in four. These investigations were useful for guiding surgical treatment. Outcome was favorable in all cases. CONCLUSION: Signs of thoracic spinal cord compression in adults should suggest the diagnosis of thoracic spinal stenosis.

[Therapeutic efficacy of chloroquine in the uncomplicated malaria due to Plasmodium falciparum in hospital patients in central Ivory Coast (1997-2000)]. / Efficacité thérapeutique de la chloroquine dans le traitement du paludisme simple dû à Plasmodium falciparum des consultants hospitaliers dans le centre de la Côte d'Ivoire (1997-2000).

A study in vivo of Plasmodium falciparum sensitivity to chloroquine was carried out from April 1997 to February 2000 at Yamoussoukro, Kossou and Bouaké in the central region of Côte d'Ivoire. This study was included in the national Plasmodium falciparum-sensitivity program. One hundred and sixteen subjects consulting for suspected malaria were included according to the WHO's standard of 14 days. Chloroquine was administered on a dosage of 25 mg/kg, spread over three days. Among 108 subjects who finished the treatment, 26.9% (29/108) had therapeutic failure to chloroquine (23 precocious therapeutic failure and 6 late therapeutic failure). Chloroquine was more efficacious in Yamoussoukro (87.5% of clinical appropriate response) and Bouaké (82.5%) than in Kossou (61.7%). Parasitic reduction on subjects with therapeutic failure was higher than 85%. The risk of therapeutic failure is not linked to age of patient. Before a revaluation of this situation, chloroquine should always be recommended as a first-line treatment for uncomplicated malaria for the local populations.

[Medullary compression by Burkitt lymphoma. Analysis of 7 cases]. / Compression médullaire par lymphome de Burkitt. Analyse de 7 observations.

OBJECTIVES: Burkitt's lymphoma is one of the possible cause of spinal cord compression. We defined the surgical approach in this rare localization of Burkitt's lymphoma. PATIENTS AND METHODS: We report 7 cases of spinal cord compression secondary to Burkitt's lymphoma treated at the Yopougon University Hospital from October 1990 to October 1994. RESULTS: Mean age of the patients was 15.4 years, range 8 to 28 years. Five of the 7 patients were children. Surgery was both a diagnostic and therapeutic emergency in this rare but serious localization of Burkitt's disease, which remains highly chemosensitive. CONCLUSION: Surgical management is warranted if Burkitt's lymphoma is revealed by spinal cord compression or if there is a primary spinal epidural localization.

Comparative disposition of tripelennamine in horses and camels after intravenous administration.

The pharmacokinetics of tripelennamine (T) was compared in horses (n = 6) and camels (n = 5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection time was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal elimination half-lives were 2.39 (1.91-6.54) and 2.08 (1.31-5.65) h, total body clearances were 0.97 (0.82-1.42) and 0.84 (0.64-1.17)L/h/kg. The volumes of distribution at steady state were 2.87 (1.59-6.67) and 1.69 (1.18-3.50) L/kg, the volumes of the central compartment of the two compartment pharmacokinetic model were 1.75 (0.68-2.27) and 1.06 (0.91-2.20) L/kg. There was no significant difference (Mann-Whitney) in any parameter between camels and horses. The extent of protein binding (mean +/- SEM) 73.6 + 8.5 and 83.4 +/- 3.6% for horses and camels, respectively, was not significantly statistically different (t-test). Three metabolites of T were identified in urine samples of camels. The first one resulted from N-depyridination of T, with a molecular ion of m/z 178, and was exclusively eliminated in conjugate form. This metabolite was not detected after 6 h of T administration. The second metabolite, resulted from pyridine ring hydroxylation, had a molecular ion of m/z 271, and was also exclusively eliminated in conjugate form. This metabolite could be detected in urine sample for up to 12 h after T administration. The third metabolite has a suspected molecular ion of m/z 285, was eliminated exclusively in conjugate form and could be detected for up to 24 h following T administration. T itself could be detected for up to 27 h after i.v. administration, with about 90% of eliminated T being in the conjugated form.

The pharmacokinetics, metabolism and urinary detection time of caffeine in camels.

The pharmacokinetics of caffeine were determined in 10 camels after an intravenous dose of 2.35 mg kg(-1). The data obtained (median and range) were as follows. The elimination half-life (t(1/2)) was 31.4 (21.2 to 58.9) hours, the steady state volume of distribution (V(SS)) was 0.62 (0.51 to 0.74) litre kg(-1)and the total body clearance (Cl(T)) was 14.7 (8.70 to 19.7) ml kg(-1)per hour. Renal clearance estimated in two camels was 0.62 and 0.34 ml kg(-1)per hour. In vitro plasma protein binding (mean +/-SEM, n = 10) to a concentration of 2 and 8 microg ml(-1)was 36.0 +/- 0.24 and 39.2 +/- 0.36 per cent respectively. Theophylline and theobromine were identified as caffeine metabolites in serum and urine. The terminal elimination half-life of the former, estimated in two camels, was 70. 4 and 124.4 hours. Caffeine could be detected in the urine for 14 days.

[Exophthalmic pneumosinus dilatans: a case report]. / Le pneumosinus dilatans exophtalmique. A propos d'une observation.

Pneumosinus dilatans is a rare disease characterized by progressive development of high pressure in the facial sinuses. The etiology remains unknown. We report a case which developed in the anterior ethmoidal cell and was expressed by exophtalmia.

[Dural metastasis of prostatic adenocarcinoma presenting as acute intracranial subdural hematoma: a case report]. / Métastase durale d'un adénocarcinome de la prostate simulant un hématome sous-dural aigu intracrânien. A propas d'une observation.

Intracranial malignant metastatic dissemination usually is seen as a unique nodular formation enhanced after intravenous injection of contrast medium. Forms mimicking meningioma or subdural hematoma have been described. We report a case of dural metastasis from an adenocarcinoma of the prostate in a 60-year-old man. The CT image suggested acute subdural hematoma.

[Neurosurgical complications of purulent meningitis in the tropical zone]. / Complications neurochirurgicales des méningites purulentes en zone tropicale.

Our retrospective study concerned 35 cases of surgical complications related to bacterial meningitis in 16 adults and 19 children. The mean age was 28 years for adults (15-56 years), and 6 months for children (1-12 months). Portal of entry for meningitis was found in 12 cases (35%): 8 sinusitis and 4 otitis. Delay to appearance of complications was 4.5 days, and to diagnosis confirmation 9 days with CT scan (17 cases), and transfontanellar ultrasonography (19 cases). The complications were: hydrocephalus, 19 cases (54%), brain empyemas, 7 cases (20%), abscesses, 10 cases (28.5%), ventriculitis, 2 cases (6%). Twenty-two bacteria were isolated from the CSF: Streptococcus pneumoniae (15 cases), Haemophilus influenzae (5 cases), Neisseria meningitidis (1 case), and Escherichia coli (1 case). Fourteen patients underwent neurosurgical treatment based on aspiration in case of suppuration and external drainage in case of hydrocephalus. The associated medical treatment was antibiotics combining third-generation cephalosporins, fluoroquinolone, and metronidazol, with a mean duration of 12 days. Recovery rate was 89%, letality 11%, and after effect rate were 33%. Our results confirm the low frequency of neurosurgical complications related to bacterial meningitis, but it emphasizes the role of an early CT-scan for diagnosis and prognosis.

The disposition of theophylline in camels after intravenous administration.

The pharmacokinetics of theophylline were determined after an intravenous (i.v.) dose of 2.36 mg/kg in six camels and 4.72 mg/kg body weight in three camels. The data obtained (median and range) for the low and high dose, respectively, were as follows: the distribution half-lives (t1/2 alpha) were 1.37 (0.64-3.25) and 2.66 (0.83-3.5) h, the elimination half-lives (t1/2 beta) were 11.8 (8.25-14.9) and 10.4 (10.0-13.5) h, the steady state volumes of distribution (Vss) were 0.88 (0.62-1.54) and 0.76 (0.63-0.76) L/kg, volumes of the central compartment (Vc) were 0.41 (0.35-0.63) and 0.51 (0.36-0.52) L/kg, total body clearances (Clt) were 62.3 (39.4-97.0) and 50.2 (47.7-67.4) mL/h.kg body weight and renal clearance (Vr) for the low dose was 0.6 (0.42-0.96) mL/h.kg body weight. There was no significant difference in the pharmacokinetic parameters between the two doses. Theophylline protein binding at a concentration of 5 micrograms/mL was 32.2 +/- 3.3%. Caffeine was identified as a theophylline metabolite but its concentration in serum and urine was small. Based on the pharmacokinetic values obtained in this study, a dosage of 7.5 mg/kg body weight administered by i.v. injection at 12 h intervals can be recommended. This dosing regimen should achieve an average steady state serum concentration of 10 micrograms/mL with peak serum concentration not exceeding 15 micrograms/mL.

The pharmacokinetics of promethazine after intravenous administration in camels.

The pharmacokinetics of promethazine were determined in seven camels (Camelus dromedarius) after an intravenous dose of 0.5 mg kg body weight.-1 The data obtained (median and range) were as follows: the elimination half-life (t1/2 beta) was 5.62 (2.84-6.51) h; the steady state volume of distribution (Vdss) was 8.90 (7.10-12.00) L kg-1, total body clearance (CT) was 24.5 (17.22-33.65) ml kg-1 min-1 and renal clearance (Clr) was 4.81 (1.97-5.48) ml kg-1 min-1.

[Epilepsy disclosing cancer of the kidney]. / Epilepsie révélatrice d'un cancer du rein.

Cerebral metastases of renal cell carcinoma are not rare, but metastasis which reveal the primary tumor are uncommon. The authors report a case of a 53-year-old woman who presented with renal cell carcinoma revealed by epileptic fit.

Pharmacokinetics of tolfenamic acid and its detection time in urine after intravenous administration of the drug in camels (Camelus dromedarius).

OBJECTIVE: To document tolfenamic acid disposition variables, identify its major phase-1 metabolite and fragmentation pattern, and establish detection time in urine after single IV bolus administration to make recommendations on avoiding violative residues in racing camels. ANIMALS: 7 healthy camels (6 males, 1 female), 8 to 11 years old and weighing from 300 to 480 kg. PROCEDURE: Blood samples were collected at 0, 5, 10, 15, 30, 45, and 60 minutes and at 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 13, 14, 15, and 16 hours after IV administration of tolfenamic acid (2.0 mg/kg of body weight). Urine samples were collected daily for 14 days after drug administration. Serum tolfenamic acid concentration was measured; limit of quantification was 50 ng/ml. A metabolite of tolfenamic acid in urine was isolated and identified, and its major fragmentation pattern was verified. Screening for tolfenamic acid and its metabolite in urine was performed. RESULTS: Mean +/- SEM tolfenamic acid elimination half-life was 5.76+/-0.26 hours. Total body clearance was 0.109+/-0.011 L/kg/h, and steady-state volume of distribution was 0.68+/-0.06 L/kg. Detection time for tolfenamic acid and its hydroxylated metabolite in urine after IV administration of a dose of 2.0 mg/kg was 5 and 7 days, respectively. CONCLUSIONS: Camels eliminate tolfenamic acid mainly via metabolism more slowly than do cattle. The extrapolated dose regimen from cattle to camels appears inappropriate. Veterinarians are advised not to use tolfenamic acid in camels for at least 8 days prior to racing.

Identification of a flunixin metabolite in camel by gas chromatography-mass spectrometry.

A flunixin metabolite, a hydroxylated product, has been identified in camel urine and plasma samples using gas chromatography-mass spectrometry (GC-MS) and GC-MS-MS in the electron impact and chemical ionization modes. Its major fragmentation pattern has been verified by GC-MS-MS in daughter ion and parent ion scan modes. The method could detect flunixin and its metabolite in camel urine after a single intravenous dose of 2.2 mg of flunixin/kg body weight for 96 and 48 h, respectively, which increases the reliability of antidoping control analysis.

The activity of mixed function oxidases, estimated by in vivo antipyrine clearance, is similar in horses and camels.

The activity of hepatic mixed function oxidases was compared in horses and camels (Camelus dromedarius) by studying the pharmacokinetics of antipyrine in seven camels and five horses following intravenous administration of a single dose of antipyrine (25 mg/kg). The data obtained (mean +/- SEM and median in brackets) in camels and horses, respectively, were as follows: the elimination half-lives were 3.25 +/- 0.23 (3.19) and 3.09 +/- 0.25 (2.90) hr; the apparent volumes of distribution (area method) were 0.691 +/- 0.045 (0.648) and 0.642 +/- 0.034 (0.676) l/kg; the volumes of distribution at steady state were 0.659 +/- 0.040 (0.607) and 0.620 +/- 0.030 (0.653) l/kg; the volume of the central compartment of the two-compartment pharmacokinetic model were 0.386 +/- 0.0523 (0.349) and 0.298 +/- 0.05 (0.308) l/kg; total body clearances were 0.148 +/- 0.008 (0.158) and 0.145 +/- 0.007 (0.147) l/kg/hr; the areas under the curves to infinity were 171.0 +/- 9 (165) and 175 +/- 8.0 (170) micrograms.ml.hr. There was no statistical significance in any parameter between camels and horses which suggests that the activity of hepatic mixed function oxidases is similar in horses and camels.

Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels.

The pharmacokinetics of flunixin were determined after an intravenous dose of 1.1 mg/kg body weight in six camels and 2.2 mg/kg body weight in four camels. The data obtained (mean +/- SEM) for the low and high dose, respectively, were as follows: The elimination half-lives (t1/2 beta) were 3.76 +/- 0.24 and 4.08 +/- 0.49 h, the steady state volumes of distribution (Vdss) were 320.61 +/- 38.53 and 348.84 +/- 35.36 mL/kg body weight, total body clearances (ClT) were 88.96 +/- 6.63 and 84.86 +/- 4.95 mL/h/kg body weight and renal clearances (Clr) were 0.52 +/- 0.09 and 0.62 +/- 0.18 mL/h/kg body weight. A hydroxylated metabolite of flunixin was identified by gas chromatography/mass spectrometry (GC/MS) under electron and chemical ionization and its major fragmentation pattern was verified by tandem mass spectrometry (GC/MS/MS) using neutral loss, daughter and parent scan modes. The detection times for flunixin and its hydroxylated metabolite in urine after an intravenous (i.v.) dose of 2.2 mg/kg body weight were 96 and 48 h, respectively.