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Biomedical subjects

S Jacobsen

Publications and source records attributed to S Jacobsen.

At least 145 records · Page 8Linked to original sources

Absorption of quinidine from an enteric-coated preparation.

The absorption of quinidine from single and multiple doses of an enteric-coated preparation (Systodin) was studied in seven healthy subjects, and was compared with the pharmacokinetics of intravenously administered quinidine and the results of in vitro dissolution tests of the tablets. Absorption of quinidine began after a variable delay, 2-8 h (mean 4.8) after fasting and 3-10 h (mean 6.1) after food. The rate of absorption varied both in and between individuals. It appeared to be lower when the drug was administered after food. Multiple doses after food gave a pattern of plasma concentration-time curves similar to that found on administration of single doses after food. The delay prior to absorption was prolonged at night. The ratio between the maximum and minimum concentration of quinidine during a dose interval varied from 1.3 to 3.2 (mean 2.0). Bioavailability of quinidine in fasting subjects ranged from 69 to 95% (mean 83); variation was greater when doses were administered after food. The release of quinidine from the enteric-coated preparation was pH dependent and was sustained at low pHs as may be found in the intestines. The results indicate that the absorption of quinidine from the enteric-coated formulation was dependent on the highly variable rate of gastric emptying and the pH of intestinal fluid, and it varied greatly both within and between individuals.

Adult↗

Distribution of elimination of hydroflumethiazide in man.

The pharmacokinetics of hydroflumethiazide (HFT) were investigated after intravenous and oral administration to healthy subjects. After intravenous infusion, HFT behaved according to a three-compartment model. Two distribution phases were observed, with mean half-lives of 0.26 and 0.85 h, reflecting distribution to red blood cells and tissues. Mean biological half-life (t 1/2 beta) after infusion was 5.2 h. Renal blood and plasma clearance of HFT, as well as the ratio renal blood clearance/renal plasma clearance of HFT, were lower after infusion than during the infusion, due to the distribution characteristics of HFT. After a single oral dose of 2 micronmol/kg, t 1/2 beta was significantly shorter in all subjects than after a single oral dose of 6 micronmol/kg, with mean t 1/2 beta of 8.7 and 17.9 h, respectively. Due to lack of a sufficiently sensitive method for determination of HFT in plasma, it could not be established whether the observed dose-dependent difference in biological half-life of HFT was caused by variation in renal clearance and/or the volume of distribution.

Administration, Oral↗

Absolute bioavailability of quinidine in two sustained release preparations.

The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median values 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.

Administration, Oral↗

Extreme duct papillomatosis of the juvenile breast.

Three cases of peculiar and very severe ductal papillomatosis of the breast are reported. This ductal papillomatosis was unusual, both in its histological architecture and in occurring in juveniles, viz. girls aged 11, 14, and 17 years. In two of the patients breast cancer was diagnosed 27 and 11 years later. In one of them the ductal papillomatosis must be presumed to have been precancerosis, while in the other patient there was possibly from the outset an unusually papilliferous, intraductal carcinoma of low malignancy.

Adolescent↗

Oral candidosis--frequency, treatment and relapse tendency in a group of psychiatric inpatients.

Candida fungi are frequent in the oral cavity, especially in denture wearers. The infection can cause serious complications in elderly or debilitated subject. The present experimental group consisted of 81 female psychiatric patients (35--91 years of age). In addition to a clinical examination, smears from the palate, tongue and dentures (when present) were cultured on Nickerson's medium. Patients with a positive clinical and/or microbiological diagnosis were treated for 35 days with one of two gels containing 1% chlorhexidine. Following the treatment period patients with full or partial dentures took part in a maintenance program, in which the dentures were either soaked in a 0.2% chlorhexidine solution or mechanically cleaned every day for a period of 35 days. Two thirds of the patients showed clinical signs of oral candidosis or had positive cultures preexperimentally. The treatment with chlorhexidine gels resulted in negative cultures in 71% and negative clinical diagnosis gels resulted in negative cultures in 71% and negative clinical diagnosis in 96% of the patients. Mucosal soreness occurred during the treatment period in 8 out of 28 patients wearing full dentures. Xerostomia was not influenced by the chlorhexidine treatment. The relapse tendency was low during the post-treatment period. No clearcut differences between the two maintenance methods could be detected.

Adult↗

[Disease and dental health. Opinions of institutional dental care in a group of health personnel].

It is reasonable to expect that dental care for institutionalized persons in Norway will be considerably improved in the near future. Opinions and attitudes towards dentistry of the health personel working in the institutions, will, therefore, be of great interest. The present study which was performed by self-administered questionnaires, showed that most of the health personel at Lier sykehus, a mental hospital near Oslo, were willing to and interested in doing active preventive work. There was, however, lack of knowledge about how to perform preventive dentistry. In the future, information and instruction concerning how to prevent oral disease, will be a meaningful task for the dental health team.

Attitude of Health Personnel↗

Intellectual development and brain size in 13 shunted hydrocephalic children.

A group of 13 successfully treated hydrocephalic children living a normal social life according to their ages has been examined to evaluate the possible correlation between their brain size, intellectual development and physical disability. The brain size was assesed by ventriculography prior to initial surgery and by computer tomography (CT-scanning) at the time of investigation 6--11 years after operation. The intellectural development was evaluated by psychological investigation of the children and by evaluation of their social adaptation. The physical disability was investigated by neurological examination. Significant improvement in ventricular size was demonstrated from pneumoencephalographic examinations prior to surgery and to the CT investigations. No prediction of the intellectual development could be based on the ventriculographies prior to initial surgery. In spite of positive trends, correlation trends, correlation between the ventricular size as determined by CT-scans and the IQ was not significant, possibly due to the small number of cases available for study.

Cerebral Ventriculography↗

Distribution of methotrexate between plasma and peripheral lymph in man.

The distribution of methotrexate (MTX) to interstitial fluid has been studied by determination of MTX in peripheral lymph from the leg and in plasma after parenteral administration to 6 patients. Peak concentrations of MTX in lymph appear 0.5 to 3.25 h after peak concentrations in plasma. Maximal concentrations in lymph are 16 to 48% lower than in plasma. MTX concentration ratios lymph/plasma were higher than 1.0 (1.0-2.8) in 4 patients, and lower than 1.0 (0.2-0.8) in 2 patients. 12 to 34% of MTX was protein bound in lymph, but the variation in the ratio of bound to free MTX per g lymph protein was only 0.13 to 0.18. The patients with a lymph/plasma MTX ratio above 1.0 will have high and favourable MTX concentrations for distribution to tumours in peripheral tissue, while in the patients with a low ratio conditions for distribution are less favourable. The results indicate that pharmacokinetics of MTX are in accordance with a two or multicompartment model with varying distribution characteristics. The present observations indicate that distribution of MTX is blood flow limited, but the influence of permeability cannot be excluded.

Adult↗

Fluorometric determination of hydroflumethiazide in human plasma and urine after its oral administration.

A spectrofluorometric method for determination of hydroflumethiazide in human plasma and urine has been developed. The limit of detection was 10 ng/ml plasma and 100 ng/ml urine. The plasma concentration of hydroflumethiazide was determined for 9-11 hours and excretion in urine for 24-37 hrs after oral administration of about 1 mg/kg body weight to 7 subjects. Plasma half life in healthy subjects was 1.9-2.1 h, and 2.7-8.6 h in patients during the period 4-9 hrs after dosing. Cumulative excretion in urine was 67-79% of the dose during 31-37 hrs in 6 subjects; one patient with renal disease was found to excrete only 25.8% of dose during 24 hours. Renal clearance of hydroflumethiazide was higher in the healthy subjects (0.29-0.44 1 h-1 kg-1) than in the patients (0.040-0.15 1 h-1 kg-1). Plasma half life of hydroflumethiazide was not closely correlated with renal clearance of the drug, which suggests that other factors may play a role in determining plasma half life.

Administration, Oral↗

Influence of serum protein binding on the pharmacokinetics of quinidine in normal and anuric rats.

The pharmacokinetics of quinidine were investigated in normal and anuric rats after intravenous injection (25 mg per kg b.wt.). In normal rats only 2.6% of the injected dose was excreted as unchanged quinidine in the urine. Quinidine concentrations were determined in the blood and in different tissues after injection, and the serum protein binding was measured. Results were applied to a one compartment model. In normal rats a total body clearance of 18.5 ml/min. and a renal clearance of 0.5 ml/min. was found. The residual non-renal clearance (18.0 ml/min.), presumably taking place in the liver, exceeds the estimated liver blood flow (16.8 ml/min.), indicating efficient extraction of quinidine from plasma and blood cells (non-restrictive elimination). The apparent volume of distribution was greatly reduced, biological half-life slightly longer and the body clearance greatly reduced in anuric as compared to normal rats. The fraction of unbound quinidine in serum was 30.6 +/- 0.6 (n = 23) and 16.7 +/- 0.5) (n = 23) percent in normal and anuric rats. The reduction in the apparent volume of distribution is mainly explained by increased serum binding. The decline of body clearance of quinidine is most likely caused by a decreased liver blood flow in this complex state of renal insufficiency.

Animals↗

[Health personnel and dental health. Visits to the dentist and attitudes to dental care in a group of health personnel].

Studies among Norwegian institutionalized persons have shown an extensive unmet need for dental treatment and a potential demand for preventive dentistry among young and middle-aged institutionalized personnel. The purpose of the present study was to gain information concerning the dental habits of the health personnel working in an institution, since there is reason to believe that the attitudes and dental habits of the employees will be of importance by the introduction of preventive dental health programs. A questionnaire was sent to 454 employees at Lier Sykehus, a mental hospital near Oslo. 385 persons answered the questionnaire (response rate 85). 82% of the respondents visited a dentist regularly, most of them twice a year. Many showed interest in getting treatment at the hospital's dental clinic. It is reasonable to suggest that the dental service at hospitals also should include the health personnel. In that case, the employees should pay the usual fees of the Norwegian Public Dental Health System. In conclusion, good dental care habits of the hospital employees will presumably affect dental health behavior of the handicapped, and thus make our goal--a better dental health for institutionalized persons--easier to achieve.

Adult↗