Liquid chromatographic-ultraviolet methods for furegrelate in serum and urine: preliminary pharmacokinetic evaluation in the dog

Analytical methods have been developed for the quantitative determination of furegrelate (1), a thromboxane synthetase inhibitor, in dog serum and urine specimens. The methods use ion-pairing reversed-phase high-performance liquid chromatography (HPLC) with UV detection at 268 nm and have the necessary specificity, linearity, and sensitivity to quantitate 100 ng/mL of the drug in serum and 20 micrograms/mL in urine. Preliminary pharmacokinetic and bioavailability evaluations in the dog indicate that 1 was rapidly distributed and had a terminal half-life of 132 min after an intravenous dose. The primary route of elimination was renal with approximately 70% of the parent drug excreted in urine. Fasted dogs dosed orally with the drug in solution or capsule had similar absorption and elimination kinetics and agreed favorably with the intravenous results. The bioavailability of 1 dosed orally was 77-80% based on serum area under curve and greater than 90% based on urinary excretion of the parent compound. The serum kinetics, but not the urinary elimination, of 1 appeared to be altered in fed dogs given drug in capsule.     

Bromocriptine concentration in saliva and plasma after long-term treatment of patients with Parkinson's disease

Summary Salivary and plasma concentrations of bromocriptine (BCT), a dopamine agonist, were measured by gas chromatography in four patients with Parkinson's disease. All the patients had been on mono-therapy with BCT for years, and during the 3 weeks prior to the investigation they received constant but individually different dosage regimens. Paired samples of pure, parotid, serous saliva and of blood were collected hourly during one eight hour dose interval. The concentrations of BCT in saliva were very low and there was a ten-fold range in the areas under the salivary and plasma concentration/time curves. It is concluded that in clinical practice measurement of BCT in saliva is not suitable for exact estimation of the plasma concentration of BCT. Using the measured salivary pH and the plasma BCT concentration, calculations based on the Henderson-Hasselbalch equation showed that the assumption of about 99% plasma protein binding of BCT best fited the observed concentrations of BCT in saliva.     

Characteristics of a good ward atmosphere

Thirty-five short term wards were evaluated with the WAS and a good milieu index. The results indicated that psychotic and non-psychotic patients need different types of atmosphere. Psychotic patients seem to benefit primarily from a milieu with a high level of Support, Practical orientation and Order and organization, and a low level of Anger and aggression, whereas non-psychotic patients seem to benefit mostly from a milieu with a high level of all subscales except for two: the level of Staff control ought to be low and the level of Anger and aggression ought probably to be intermediate.     

HLA-B27 in juvenile chronic arthritis

The prevalence of HLA-B27 in 88 patients with juvenile chronic arthritis was 22/88 (25%) with little variation among the 3 commonly recognized onset types. This was significantly more frequent than the prevalence of 9.4% in a Danish reference population. A strong association was found between the HLA-B27 antigen and 3 subgroups of patients: (1) boys with pauciarticular and late onset disease; (2) girls with apophyseal joint fusion; (3) a group of patients in whom the clinical picture was compatible with reactive arthritis or incomplete Reiter's syndrome. When these 3 subgroups were excluded from the total patient population, only 8 of the remaining 63 patients carried the B27 antigen, i.e., 13%, which was not significantly different from the prevalence in the reference population. Thus, the 3 subgroups account completely for the increase of B27 in the entire group of patients.     

Pharmacokinetics and metabolism of trimethoprim in neonatal and young pigs

The pharmacokinetics and metabolism of trimethoprim (TMP) was studied in newborn, 1 and 8-week-old piglets after intravenous administration of 5 mg/kg. Kinetic parameters were calculated using a two-compartment open model. Steady-state volume of distribution increased from 0.78 L/kg at birth to 1.32 L/kg at 1 week, and 1.83 L/kg at 8 weeks due to changes in plasma protein binding and tissue accumulation. Elimination half-life decreased from 485 minutes at birth to 224 minutes at 1 week, and 120 minutes at 8 weeks leading to a rise in body clearance from 1.18 to 11.8 ml/min/kg during the same period. Urinary excretion data indicated that the increase in body clearance reflects maturational changes in both metabolic capacity and renal function. Metabolism was the main contributor to the elimination of TMP at all ages, although the major metabolic pathway, O-demethylation and subsequent conjugation, was only slightly developed at birth. The capacity to form conjugates with either glucuronic acid or sulphate appeared to be at least as high as the capacity for O-demethylation since more than 90% of the metabolites were excreted as conjugates in all groups.     

The bioavailability of thyroxine and 3,5,3'-triiodothyronine in normal subjects and in hyper- and hypothyroid patients

A new method for the estimation of the bioavailability of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) is described based on gel separation followed by antibody extraction of labelled T4 and T3 from serum, and using the area under the curve of disappearance of the tracer (AUC) for the calculations. The peak serum concentrations of radioactive labelled T4 and T3 were reached approximately 90 min after oral administration of both tracers. The relative difference of duplicate estimations was below 10% (n = 3). The bioavailability of T4 in 6 euthyroid controls was in median 65% (range 64-75%), and it was significantly increased both in hyperthyroidism (88% (75-99%), n = 6, P less than 0.01) and hypothyroidism (84% (67-100%), n = 6, P less than 0.02). The bioavailability of T3 in 6 euthyroid controls was in median 78% (69-99%) and significantly greater than that of T4 (P less than 0.02). The bioavailability was unaffected by hyperthyroidism (79% (61-98%), n = 9) and hypothyroidism (77% (66-97%), n = 7). No significant difference between T4 and T3 bioavailabilities was found in hyper- or hypothyroidism. The clinical implication of the present study is that the bioavailability of T4 and T3 is almost identical and approximately 80% in patients with severe hypothyroidism.     

Detection by ELISA of IgG-subclass-specific antibodies in primary respiratory syncytial (RS) virus infections

The IgG-subclass specific antibody response was investigated in primary RS-virus infections in infants and small children by using an ELISA with monoclonal antibodies against the four human IgG subclasses. When 78 serum samples obtained from 21 patients during the first 3-4 mo following the onset of illness were studied, only IgG-1 and IgG-3 antibodies could be detected. Both of these subclass specific antibodies appeared during the second week following the beginning of illness. Approximately 4 wk after the onset of illness, IgG-1 antibodies reached maximum levels, which persisted during the following months. Approximately 3 wk after the onset of illness, IgG-3 antibodies reached maximum levels, which decreased during the following months. Both IgG-1 and IgG-3 antibodies showed neutralizing capacity.     

Neurological disease among women with silicone breast implants in Denmark

OBJECTIVES: To investigate the risk of neurological disease among women with cosmetic breast implants. MATERIAL AND METHODS: We identified 1,653 women who had undergone breast implant surgery at private clinics in Denmark and a comparison cohort of 1,736 women who underwent other types of cosmetic surgery at the same clinics. Ratios of observed-to-expected numbers of hospitalizations for neurological disease in the private implant and comparison cohorts were calculated, separately and combined with data from updated public hospital cohorts. RESULTS: The occurrence of neurological disease in the private clinic implant cohort was comparable to that in the general population. A similar risk pattern was observed in the private clinic comparison cohort. When data for these private clinic cohorts were combined with updated data for public hospital cohorts, excess risks for neurological disorders were seen in both implant and comparison cohorts, reaching statistical significance only in the comparison cohort. CONCLUSION: Our findings indicate no causal association between silicone breast implants and neurological disease.     

Capsular contracture after cosmetic breast implant surgery in Denmark

The authors investigated the association between the occurrence of capsular contracture and implant and patient characteristics. All women with breast implants from 1977 to 1997 were identified from the files of two private plastic surgery clinics in Denmark. Information on implant and patient characteristics, surgical procedure, and complications was obtained through medical records and self-administered questionnaires. Of 754 women (1,572 implants), average age at implantation was 32 years. Implant types were silicone double lumen, textured, 31.2%; silicone single lumen, textured, 27.8%; silicone single lumen, smooth, 24.5%; silicone double lumen, smooth, 0.8%; and other or missing, 15.7%. Placement was submuscular for more than 90% of implants. Capsular contracture occurred in 7.9% of implanted breasts, on an average of 621 days postoperatively, with 51.6% being bilateral. Overall, 66.1% of capsular contractures were recorded within the first 12 months postoperatively, and 79.0% were recorded within 24 months. Double-lumen implants were associated with a significantly (p < 0.01) reduced occurrence of capsular contracture. In summary, capsular contracture typically occurs within the first 2 years of implantation. Host factors may be important because more than half the capsular contractures in the current study were bilateral. Occurrence of capsular contracture did not appear to be associated with implant surface or placement, occurrence of local complications, or patient characteristics, although these findings should be interpreted cautiously.