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Biomedical subjects

M Anttila

Publications and source records attributed to M Anttila.

At least 55 records · Page 3Linked to original sources
PubMed1996

Management of stage-I borderline ovarian tumors.

OBJECTIVE: To evaluate the surgical management and outcome of stage-I borderline ovarian tumors. METHODS: A series of 95 cases of FIGO stage-I borderline ovarian tumors was retrospectively reviewed. RESULTS: The age of the patients ranged from 17.6 to 88.9 years (mean 52.7 years). Serous and mucinous tumors were equally represented (47.5% and 47.4%, respectively), endometrioid and clear cell tumors comprising the remaining three (3.2%) and two (2.1% cases. Extirpative primary surgery was performed on all patients. Three patients received postoperative chemotherapy. Nineteen of the 28 patients (67.9%) who were younger than 40 years underwent conservative surgery in which ovarian tissue and the uterus were preserved in order to maintain reproductive potential, and nine of them had successful pregnancies later. Ninety patients were followed regularly for 0.75-21.3 years (average 7.3 years). Seven patients suffered a tumor relapse (7.8%) within 0.6-4.3 years, and four (57.1%) of them (three with mucinous tumors, one with clear cell tumor) died of the disease within 1-10.8 years. The 5- and 10-year overall survival rates were 97.0% and 86.3%, respectively, and the disease-free survival rates were 90.8% in both 5- and 10-year follow-ups. CONCLUSIONS: Even though the prognosis of surgically treated stage-I borderline ovarian tumors is excellent, mucinous and clear cell subtypes are associated with potential mortality.

Adolescent↗
PubMed1995

Buccal delivery of an alpha 2-adrenergic receptor antagonist, atipamezole, in humans.

OBJECTIVE: To evaluate the pharmacokinetics, systemic effects and clinical applicability of buccally administered atipamezole in healthy volunteers. METHODS: The study was carried out in two parts. In the first part, spray preparations of atipamezole hydrochloride in water/alcohol (50/50) solution were applied on buccal mucosa of six volunteers. Single doses of 5, 10, 20, and 40 mg atipamezole hydrochloride were administered in ascending order during separate sessions. In the second part, nine subjects received single 20 mg doses as buccal spray, intravenous infusion, or oral solution in randomized order. RESULTS: Values for area under the concentration-time curve for atipamezole (mean +/- SD) ranged from 26 +/- 4 ng x hr/ml after 5 mg to 112 +/- 21 ng x hr/ml after 40 mg and peak concentrations ranged from 11 +/- 3 ng/ml after 5 mg to 38 +/- 9 ng/ml after 40 mg. Individual peak concentrations were mainly measured at 30 and 60 minutes after administration. Mean elimination half-lives were approximately 1 1/2 hours after every treatment. In part two, a mean bioavailability of 33% was calculated for buccal administration (compared with intravenous), whereas systemic availability after an oral dose was < 2%. After intravenous administration the mean total clearance, apparent volume of distribution, and elimination half-life were 1.2 L/hr/kg, 2.9 L/kg, and 1.8 hours, respectively. The intravenous administration of 20 mg atipamezole hydrochloride produced a fivefold elevation in mean plasma norepinephrine concentration, a slight and short-lasting elevation in blood pressure and, in most subjects, increased tension, alertness and restlessness, and sweating. After buccal administration, some subjects reported short-lasting restlessness or tension after the 20 and 40 mg doses. No significant changes in heart rate, blood pressure, or plasma catecholamines were observed. No effects were observed after swallowing of 20 mg atipamezole hydrochloride. The spray caused local reactions at buccal mucosa. Superficial white spots or areas were observed for several hours; these disappeared gradually. Subjects also reported transient numbness at the application site. CONCLUSION: Atipamezole hydrochloride is well absorbed systemically through oral mucosa. The oral bio-availability of atipamezole is negligible, probably because of extensive first-pass metabolism.

Administration, Buccal↗
PubMed1995

Pharmacokinetics of the novel antiestrogenic agent toremifene in subjects with altered liver and kidney function.

OBJECTIVES: The pharmacokinetics of toremifene was investigated in an open study with four parallel groups of 10 subjects each. Subjects with impaired liver function (biopsy-proven liver disease), activated liver function (drug-induced), and impaired kidney function were compared with normal subjects. METHODS: A single oral 120 mg dose of toremifene was administered after an overnight fast, and blood samples were collected over 28 days. Serum levels of toremifene and its metabolites were determined; appropriate pharmacokinetic parameters were calculated and statistically evaluated. RESULTS: In normal subjects, the average peak level of 414 ng/ml toremifene was achieved at 3 hours after dosing, the terminal half-life was 6.2 days, apparent oral clearance was 5.1 L/hr, apparent volume of distribution was 958 L, and the fraction not bound to protein was 0.3%. The peak level (130 ng/ml) of the major metabolite, N-demethyltoremifene, appeared in serum with large variation in the time to peak level (median, 3 days) and a terminal half-life of 21.0 days. Low levels of deaminohydroxytoremifene were also measured, and two other metabolites could be quantified at some time points in some patients. The elimination rate of toremifene and the main metabolite was significantly increased in patients with activated liver function, resulting in decreased terminal half-lives (3.0 days and 4.5 days, respectively), and was decreased in patients with impaired liver function (10.9 days and 29.6 days, respectively). The subjects with impaired kidney function showed normal elimination kinetics. CONCLUSION: Liver, but not kidney, function should be taken into account when toremifene is administered.

Administration, Oral↗
PubMed1995

Oral contraceptive containing natural estradiol for premenopausal women.

An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone acetate. The participants were 288 women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use the new pill as their only contraceptive method. In total, 23% of the women were smokers. The cumulative experience was 2800 treatment cycles during the first year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was almost as good as that of the modern low dose oral contraceptives. This is the first pill containing natural estradiol that has gained clinical acceptance and which can also be prescribed for smokers over 35 years old until the climacteric.

Adult↗
PubMed1995

Atipamezole increases medetomidine clearance in the dog: an agonist-antagonist interaction.

Medetomidine, an alpha 2-adrenoceptor agonist, is a potent sedative and analgesic agent in the dog. When necessary, its action can be effectively antagonized by atipamezole. The present work was designed to study the effects of these drugs on each others' pharmacokinetics when a single intramuscular dose of medetomidine (50 micrograms kg-1) was followed by a dose of atipamezole (250 micrograms kg-1). Three different treatments were used: medetomidine alone, atipamezole alone, and atipamezole after medetomidine. Drug concentrations in plasma were measured by GC-MS. Statistical analysis of the results (ANOVA) revealed significant differences between treatments in the kinetic parameters of medetomidine. Atipamezole decreased the AUC of medetomidine from 41.3 to 28.6 ng h ml-1 (P = 0.005), t1/2 from 1.44 to 0.87 h (P = 0.015), and increased Cl from 21 to 31 ml min-1 kg-1 (P = 0.017). Differences in Vz did not reach statistical significance. The only statistically significant effects of medetomidine on the pharmacokinetics of atipamezole in this study were the slight decrease of Cl and Cmax as well as the increase of AUC. It is suggested that the large dose of medetomidine used caused haemodynamic changes, resulting in decreased hepatic circulation and slower drug metabolism. Antagonism by atipamezole restored the hepatic blood flow and, consequently, increased the elimination of medetomidine by biotransformation.

Adrenergic alpha-Agonists↗
PubMed1994

The effect of a recent previous visit to a physician on outcome after childhood bacterial meningitis.

OBJECTIVE: To assess the effect of a recent previous visit to a physician on the outcome of meningitis in children. DESIGN: Evaluation of data from children examined by a physician and sent home, either the previous day or 2 to 4 days before meningitis was diagnosed, and children whose meningitis was diagnosed at once. The patients were examined daily during hospitalization, neurologic examinations were repeated at 2 weeks and 3 and 6 months after discharge, and hearing was assessed 2 or more months after discharge. SETTING: Eighteen pediatric hospitals in Finland from 1984 through 1991. POPULATION: A total of 325 children aged 3 months to 15 years with bacterial meningitis. MAIN OUTCOME MEASURES: Clinical and laboratory findings on admission, recovery during hospitalization, mortality, and neurologic abnormalities at 6 months of follow-up. RESULTS: In 74% of the patients, meningitis was diagnosed at once, 14% had visited a physician on the previous day, and 11% had seen a physician 2 to 4 days before diagnosis. The group seen 2 to 4 days earlier had a better level of consciousness, less frequent seizures, and more respiratory symptoms and otitis media than the other groups. The cerebrospinal fluid leukocyte count, white blood cell count, and erythrocyte sedimentation rate were highest and the cerebrospinal fluid glucose concentration was lowest in the children who had visited a physician 2 to 4 days earlier, although they also had lower cerebrospinal fluid protein and urine sodium and potassium levels. This group had the most rapid return to normal consciousness. There was no difference in the incidence of hearing impairment or neurologic sequelae. Even the mortality was virtually the same in the three groups: 4%, 4%, and 3% in the "same day," "previous day," and "2 to 4 days earlier" groups, respectively. CONCLUSIONS: Children who had visited a physician the previous day or 2 to 4 days before meningitis was diagnosed did not exhibit an increased frequency of hearing impairment, other neurologic abnormalities, or overall adverse outcome compared with children whose meningitis was diagnosed at once.

Adolescent↗
PubMed1994

Clinical criteria for estimating recovery from childhood bacterial meningitis.

A comparison study was conducted between 105 children (aged 3 months to 15 years) who had recovered from bacterial meningitis uneventfully and 29 children who had suffered from subsequent neurological complications or sequelae. The objective was to find a potential correlation between easily measurable clinical variables and the risk of developing neurological complications. Sixteen clinical signs and measurements routinely registered in patients with bacterial meningitis were recorded daily during the first 14 days of hospitalization. Differences found between the two groups were mean morning temperature, presence of neck rigidity and willingness to leave the supine position. The results indicate that if a child recovering from bacterial meningitis continues to be feverish, has neck rigidity, or is reluctant to leave the supine position over seven days, she/he runs a special risk of developing neurological complications or sequelae, which should be actively sought for using all available measures.

Adolescent↗
PubMed1993

Length of prediagnostic history related to the course and sequelae of childhood bacterial meningitis.

The relationship between length of prediagnostic history and course and sequelae of childhood bacterial meningitis was prospectively examined by collecting data from 286 children with bacteriologically confirmed bacterial meningitis. The cases were divided into three groups: short (< or = 24 hours, N = 141); intermediate (> 24 to 48 hours, N = 75); and long (> 48 hours, N = 70) history. The level of consciousness and serum C-reactive protein normalized sooner during hospitalization in patients with a longer history. They also showed neck stiffness more often and longer and had thrombocytosis earlier and more prominently than patients with a shorter history. The differences were not influenced by etiology, sex or age. The occurrence of neurologic abnormalities in the hospital or during the first 6 months after discharge was not affected by duration of illness before hospitalization. We conclude that our results support the view that bacterial meningitis presents in two forms. At presentation the more acute form often has a history of less than 24 hours and poses a great danger to the patient. In contrast the other form develops insidiously and is more difficult to detect but does not have a worse prognosis than the acute form.

Adolescent↗
PubMed1992

Rapid disappearance of Haemophilus influenzae type b meningitis after routine childhood immunisation with conjugate vaccines.

Mortality from meningitis caused by Haemophilus influenzae type b (Hib), a disease that affects mainly infants and young children, can reach 5% in industrialised countries and ten times that in non-industrialised countries. To determine the efficacy of vaccination against Hib, we carried out a retrospective survey of the incidence of Hib meningitis over five decades in the Greater Helsinki area of Finland, where all children with bacterial meningitis are treated in one of three centres. Except for a meningococcal epidemic in the early 1970s, Hib was the leading cause of childhood bacterial meningitis until the Hib conjugate vaccines changed the picture profoundly. In 1986-87 the polysaccharide-diphtheria toxoid conjugate (PRP-D) was given experimentally to 50% of infants. In 1988-89 all infants were vaccinated, 50% with PRP-D, 50% with another conjugate vaccine, the oligosaccharide-CRM197 protein conjugate (HbOC). Since 1990 a third conjugate vaccine, the polysaccharide-tetanus toxoid (PRP-T), has been administered routinely to all infants. The vaccines were administered at age 3-6 months, with a booster dose at 14-18 months. In the first 5 years of the Hib vaccination programme the number of cases of Hib meningitis in children aged 0-4 years fell sharply, from 30 in 1986 (the first year of the programme) to none in 1991. The decline contrasts sharply with the rising trend up to the mid 1980s. Vaccination seems to be the only explanation for the observed change in the epidemiology of Hib meningitis.

Adolescent↗
PubMed1992

Comparative bioavailability of carbamazepine from two slow-release preparations.

In order to compare the multiple-dose bioavailability of carbamazepine (CBZ) from 2 slow-release preparations, Neurotol slow and Tegretol Retard, a single-blind, randomized, cross-over study was carried out. 21 adult patients with epilepsy were enrolled in the study. At the end of both 2-week treatment periods, a blood sample series was drawn after the administration of the morning CBZ dose. The serum concentrations of CBZ, CBZ-10,11-epoxide (CBZE) and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZD) were measured using HPLC. The mean bioavailability of CBZ from Neurotol slow was 11% (P = 0.002) higher than from Tegretol Retard. Owing to the better bioavailability, the peak (Cmax), lowest (Cmin) and mean (Css) concentrations of CBZ were also significantly higher during Neurotol slow treatment. Fluctuation of serum CBZ concentrations (Cmax-Cmin/Css, ADCss/AUC0-12h) did not differ significantly between the 2 treatments; neither did tmax. Similar results were obtained with CBZE and CBZD. There were more epileptic seizures on Tegretol Retard than on Neurotol slow, but the difference was not statistically significant. We conclude that there are significant differences in the bioavailability of CBZ from these 2 slow-release preparations.

Adult↗
PubMed1992

Pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine.

The pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine--a novel alpha 2-adrenergic receptor agonist under development for preanesthetic use--were studied in healthy male volunteers. Single intramuscular doses of dexmedetomidine (0.5, 1.0, and 1.5 microgram/kg) and placebo were administered to six subjects in a single-blind, multiple crossover study. Dexmedetomidine induced dose-related impairment of vigilance assessed both objectively and subjectively. The drug also caused moderate decreases in blood pressure and heart rate. Plasma norepinephrine was dose-dependently (maximum 89%) decreased. The intramuscular doses resulted in linearly dose-related plasma concentrations of dexmedetomidine. Pharmacokinetic calculations revealed a time to maximum concentration from 1.6 to 1.7 hours, an elimination half-life of 1.6 to 2.4 hours, an apparent total plasma clearance of 0.7 to 0.9 L/hr/kg, and apparent volume of distribution of 2.1 to 2.6 L/kg. The sedative effect of dexmedetomidine dissipated during the 6-hour observation time, but all other effects were still evident 6 hours after administration of the higher doses, paralleling the plasma concentration curves. The relationship of plasma concentrations of dexmedetomidine to pharmacodynamic variables was consistent with a linear pharmacodynamic model. The pharmacodynamic-pharmacokinetic profile of intramuscular dexmedetomidine may be suited to the proposed preanesthetic clinical use of this alpha 2-agonist.

Adrenergic alpha-Agonists↗
PubMed1992

Thrombocytosis and thrombocytopenia in childhood bacterial meningitis.

To assess factors affecting the development of reactive thrombocytosis during bacterial meningitis, thrombocyte counts of 311 children with cerebrospinal fluid culture-positive bacterial meningitis were followed during hospitalization. Thrombocytosis (platelet counts greater than 500 x 10(9)/liter) was seen in 49% of the patients after the first week of treatment. Thrombocyte counts were higher in infants and in patients with long duration of illness before admission. Subdural effusion and cephalosporin therapy were associated with more pronounced thrombocytosis We found no relation between thrombocytosis and neurologic complications, but the patients who died developed thrombocytopenia instead of thrombocytosis. The difference between the thrombocyte curves of the surviving and dying patients might be utilized in predicting the final outcome in the severest cases of bacterial meningitis. We speculate that inflammatory cytokines, especially interleukin 1-beta, induce reactive thrombocytosis in bacterial meningitis.

Adolescent↗
PubMed1992

Precise quantification of fever in childhood bacterial meningitis.

Precise quantity of fever was determined in 191 cases of childhood bacterial meningitis by calculating the areas between the line indicating 37.8 degrees C or 39.5 degrees C temperature and the line connecting all individual temperature values. Temperature measurements were performed rectally one to four times a day throughout the hospitalization. The obtained areas under the curves (AUC), expressed as degree-hours, proved to be a sensitive index for delineating each individual fever pattern and reflected the magnitude of fever more precisely than the traditional fever curves. Children under five had significantly (p less than 0.05) greater AUC than those at five to 15 years; similarly, patients with Haemophilus influenzae meningitis showed greater AUC (i.e., had more fever) than those with meningococcal disease (p less than 0.05). The overall rates of secondary (14%), persistent (16%), and prolonged fever (8%) were virtually identical to previous reports; no drug fever was reported in this study. In cases with prolonged fever, a significantly higher rate (40%) of neurological complications was found compared to those who became afebrile earlier. This method is potentially utilizable in other diseases and conditions where precise measurement of fever is of clinical or scientific relevance.

Adolescent↗
PubMed1991

Severity of childhood bacterial meningitis and duration of illness before diagnosis.

Rapid diagnosis of childhood bacterial meningitis (BM) is generally believed to be essential to avoid poor outcome. To see whether duration of illness before admission to hospital was related to the severity of illness, data from children with BM diagnosed in 18 paediatric hospitals in Finland from 1984 to 1989 were collected prospectively. We divided 286 cases with culture-positive cerebrospinal fluid (CSF) into three groups: BM with a history of up to 24 h (short-history group, n = 141), of more than 24 h and up to 48 h (intermediate-history group, n = 75), and of more than 48 h (long-history group, n = 70). The longer the history, the better the clinical condition of the child. If symptoms or signs of BM lasted 48 h or less, the child did significantly worse, as judged by seven variables, than if the history was longer than 48 h (level of consciousness, p less than 0.001; seizures, p less than 0.01; CSF protein concentration, p less than 0.001; positive CSF gram-stain, p less than 0.01; positive blood culture, p less than 0.05 in Haemophilus influenzae meningitis; serum C-reactive protein, p less than 0.01 between intermediate-history and long-history groups; and urine sodium concentration, p less than 0.001). The differences were not affected by causative organism, sex, age, or preadmission oral antimicrobial agents. The findings show that if BM follows an insidious pattern of disease, diagnostic delay may be unavoidable, which may have medicolegal implications.

Adolescent↗
PubMed1991

Treatment of epilepsy in mentally retarded patients with a slow-release carbamazepine preparation.

Pharmacokinetic properties and efficacy of a conventional (C) carbamazepine (CBZ) preparation divided into three daily doses and a slow-release CBZ preparation (SR) divided into two daily doses were evaluated in a randomized, double-blind, cross-over study. The trial started with a 8-week baseline period followed by the two treatment periods each 10 weeks long. At the end of each period, a 24-h blood sample series for determination of serum CBZ and carbamazepine-10,11-epoxide (CBZE) was collected. The occurrence of seizures was monitored day and night during the whole study period by experienced nurses. The mean age of the 20 evaluable patients was 24.9 and the duration of epilepsy 19.2 and carbamazepine treatment 7.0 years. The bioavailability of CBZ from the two preparations was similar. The mean fluctuation of serum CBZ concentration (Cmax-Cmin/Css) was 16% smaller during SR. The mean serum CBZ concentration in the morning samples was significantly (P less than 0.001) higher during SR treatment. The mean total number of seizures was approximately four per week and did not differ between the two treatments, but during the last 2 weeks of the study period the occurrence of seizures was significantly smaller during SR (P = 0.02).

Adolescent↗
PubMed1991

Types of fluid disorder in children with bacterial meningitis.

As part of a prospective study of children with bacterial meningitis we analyzed in 36 patients of our hospital the fluid balance on admission and during the first three days of treatment. On admission 10 of them (28%) had inappropriate antidiuretic hormone secretion SIADH, 10 (28%) hypo-osmolal and 10 (28%) iso-osmolal contraction. Six patients (17%) had no clear fluid disorder. The patients with SIADH had significantly lower mean serum NA+ (127 vs. 132 mEq/l, p less than 0.01) and higher mean urine Na+ (111 vs. 26 mEq/l, p less than 0.01) concentration as well as higher mean urinary Na+/K+ ratio (2.23 vs. 0.365, p less than 0.005) than the patients with hypo-osmolal contraction. They also tended to be younger and have a shorter history of fever. The patients with SIADH had a less strict fluid restriction than the patients with hypo-osmolal contraction, and their fluid balance normalized more slowly. Our findings support initial water restriction for all children with bacterial meningitis.

Child↗