[Prevalence of hepatitis A, B, C and E virus markers among patients with elevated levels of Alanine aminotransferase and Aspartate aminotransferase in Phnom Penh (Cambodia) and Nha Trang (Central Vietnam)]. / Prévalence de marqueurs d'infection des hépatites virales A, B, C et E chez des patients ayant une hypertransaminasémie a Phnom Penh (Cambodge) et Nha Trang (Centre Vietnam).

In order to describe the respective part of viral hepatitis in liver diseases observed in Cambodia and Vietnam, ninety consecutive patients with Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) > or = 100 Ul/l were tested for hepatitis A, B, C and E markers in Phnom Penh and Nha Trang. The markers were IgM antibodies to hepatitis A virus (anti-HAV IgM), hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCVAb) and IgG antibodies to hepatitis E virus (anti-HEV IgG). Recruited patients were predominantly adults and male (sex ratio 76%). Among these patients, 81% were tested positive to at least one marker in Nha Trang and 79% in Phnom Penh. In Nha Trang, HBsAg was more frequent (73%) than anti-HCV Ab (9%) while in Phnom Penh both markers were closely similar (HBsAg: 41%, anti-HCV Ab: 39%). In both population samples, HBsAg was more prevalent among young people whereas anti-HCV Ab were only detected in adults. No case of acute HAV infection was diagnosed in Nha Trang while anti-HAV IgM were detected in 20% of Cambodian patients. Anti-HEV IgG were infrequent (2% in Nha Trang, 5.5% in Phnom Penh). Only one case was notified, a male Vietnamese patient probably suffering from acute hepatitis E. More studies would be useful to improve the control measures against viral hepatitis in the public health programs.

[Serological study of toxoplasmosis in Vietnam in a population of drug users (Ho Chi Minh city) and pregnant women (Nha Trang)]. / Etude sérologique de la toxoplasmose au Vietnam dans une population de toxicomanes (Ho Chi Minh ville) et de femmes enceintes (Nha Trang).

Toxoplasmosis is a neglected disease in Vietnam particularly in populations with a high risk of developing complications. The seroprevalence of Toxoplasma gondii was calculated by testing blood samples for Toxoplasma specifically immunoglobulin G and immunoglobulin M on 300 intravascular drug users and on 300 pregnant women. Among intravascular drug users, the seroprevalence of IgG and IgM was 7.7% and 0.08%, respectively. In pregnant women the prevalence of anti-toxoplasmosis IgG and IgM was respectively 11.2% and 0%. 0.28% of all estimated pregnancies in Vietnam are affected with toxoplasmosis, i.e. around 4800 pregnancies per year. In conclusion, a screening of Toxoplasma infections should be recommended in HIV/AIDS patients.

A high-performance liquid chromatography-tandem mass spectrometric method for the determination of pharmacokinetics of ganaxolone in rat, monkey, dog and human plasma.

A method for determining concentration levels of ganaxolone in rat, monkey, dog and human plasma was validated in the range of 5-1500 ng/ml using a 200-microl plasma sample volume. This validation report describes the linearity, specificity. sensitivity, reproducibility, accuracy, recovery and stability of the analytical method. The inter-day C.V. ranged from 0.5 to 9.2%, intra-day C.V. from 0.7 to 8.8% and intra-day accuracy (mean absolute percentage difference) ranged from 0.0 to 14.0% for rat, monkey, dog and human plasma. The method was used for the routine analysis of ganaxolone in rat, monkey, dog and human plasma and summary of the pharmacokinetic data are presented.

Development of a high-performance liquid chromatographic-tandem mass spectrometric method for the determination of pharmacokinetics of Co 102862 in mouse, rat, monkey and dog plasma.

A method for determining concentration levels of Co 102862 in mouse, rat, monkey and dog plasma was validated in the range of 5 to 2000 ng/ml using 200 microl plasma sample volume. This validation report describes the linearity, specificity, sensitivity, reproducibility, accuracy, recovery and stability of the analytical method. The inter-day RSD ranged from 3.5 to 10.1%, intra-day RSD from 0.6 to 5.7% and intra-day accuracy (mean absolute percent difference) ranged from 2.2 to 14.9% for rat, monkey and dog plasma. A mini-validation (5-2000 ng/ml) of Co 102862 was performed in mouse plasma using the same methods. Additionally, the assay range at the low end was successfully extended to 0.5 ng/ml for monkey plasma. The method was used for the routine analysis of Co 102862 in mouse, rat, monkey and dog plasma and summary of the pharmacokinetic data are presented.

Synthesis, corticotropin-releasing factor receptor binding affinity, and pharmacokinetic properties of triazolo-, imidazo-, and pyrrolopyrimidines and -pyridines.

The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure-activity relationships of these series and resulted in the identification of a variety of high-affinity agents (Ki's < 10 nM). On the basis of this property and lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability, high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted further PK studies in the dog following both iv and oral routes of administration. Results from this work indicated 4i,x had properties we believe necessary for a potential therapeutic agent, and 4i1 has been selected for further pharmacological studies that will be reported in due course.

Analysis of corticosterone in rat plasma by high-performance liquid chromatography.

A sensitive and specific high-performance liquid chromatographic assay for the determination of corticosterone in rat plasma using dexamethasone as the internal standard is reported. Rat plasma (0.5 ml) is extracted with methylene chloride, washed with 0.1 M sodium hydroxide and then with water. The extract is analyzed by HPLC on a C18 column with ultraviolet absorbance detection at 254 nm. Pooled rat plasma was treated with activated decolorizing carbon to remove endogenous corticosterone, and was then used to prepare standards for the assay. Using 0.5 ml plasma for extraction, the detection limit of the assay is 10 ng/ml. The standard curve is linear over the concentration range 10-500 ng/ml. The recovery of corticosterone after extraction was independent of concentration and ranged from 87 to 95%. The coefficient of variation for intra-day and inter-day precision ranged from 2.4 to 7.4% and 2.1 to 8.7%, respectively. In addition, for concentrations ranging from 10 to 500 ng/ml the accuracy is within 5% of the spiked standards. The assay was utilized to examine the circadian rhythm of plasma corticosterone, and to examine the effect of immobilization stress on corticosterone levels in rats.

An extensive experience with postoperative pain relief using postoperative fentanyl infusion.

From October 1, 1987 through December 31, 1989, 517 patients who were undergoing both thoracic and abdominal surgical procedures were treated for postoperative pain with epidural fentanyl citrate infusion under the direction of an anesthesia pain service. Infusion rates of 4 micrograms/mL of solution were essentially the same for all subjects. Sixty-five percent of patients experienced superior pain control without the use of adjunctive analgesia. Twenty-eight percent of subjects achieved satisfactory pain control but required additional low-dose analgesics. Only 7% of patients remained uncomfortable despite additional intravenous narcotic administration. There were no deaths or respiratory arrests. Six percent of patients experienced nausea, and 0.8% of the cohort required catheterization for urinary retention. This technique of postoperative pain control was safe and provided excellent results. Catheter position was a major determinant of the efficacy of the method.

Discovery of Crohn's disease at celiotomy.

Many patients with Crohn's disease have abdominal operations, but the role of surgical exploration in the recognition of this syndrome has not been assessed. We reviewed the operative records of 78 patients with a presumptive diagnosis of Crohn's disease who had a celiotomy between 1968 and 1979 at The University of Iowa Hospitals and Clinics. The patients were divided into two groups according to the likelihood of having Crohn's disease. Clinical presentation and operative indications were similar to those commonly reported for Crohn's disease. Most findings at celiotomy occurred with similar frequency in the two groups. Fat wrapping and thickening of the intestinal wall were the most common findings. These were closely followed in frequency of occurrence by the presence of adhesions, abdominal masses or serosal changes. Less common changes included strictures, intestinal dilation, skip lesions, fistulas and abscesses. Free peritoneal fluid and mesenteric lymph node enlargement were rare in 63 patients with established Crohn's disease but were comparatively more common in 15 patients deemed unlikely to have the disease. Even though the diagnosis of Crohn's disease was not firmly established preoperatively in more than one-fourth of the patients, the surgeon rarely took steps to make a specific diagnosis. Preoperatively, the diagnosis in four patients was changed from carcinoma of the cecum in two, from appendicitis in two and from ischemic colitis in one patient to a correct diagnosis of Crohn's disease, but never was a diagnosis preoperatively of Crohn's disease changed postoperatively to an alternative. We conclude that presently recognized operative findings are of limited value in the differential diagnosis of the disease because, in our experience, the preoperative diagnosis of Crohn's disease was never altered at operation. The diagnosis should be made with caution in the presence of free peritoneal fluid or mesenteric lymphadenopathy.