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Biomedical subjects

M Valtonen

Publications and source records attributed to M Valtonen.

At least 37 records · Page 2Linked to original sources

Diurnal rhythm of melatonin in bovine milk: pharmacokinetics of exogenous melatonin in lactating cows and goats.

We investigated whether the melatonin levels in bovine milk exhibit a similar daily rhythm as serum levels. In 4 Ayrshire cows at the beginning of the lactation period in May the nocturnal rise in milk melatonin was moderate (from 7 +/- 2 pg/ml at noon to 15 +/- 1 pg/ml at night; mean +/- SEM) and did not correlate well with the melatonin level in serum (from 7 +/- 2 pg/ml to 27 +/- 7 pg/ml, respectively). On the other hand, 6 cows in a later phase of lactation, studied in February, showed a clear long-lasting nocturnal melatonin increase both in serum (from 9 +/- 1 pg/ml at noon to 26 +/- 3 pg/ml at night) and in milk (from 12 +/- 5 pg/ml to 26 +/- 7 pg/ml, respectively). Melatonin kinetics during lactation was studied in more detail in 4 Ayrshire cows and 4 dairy goats by giving an intravenous bolus injection of melatonin. A 3-compartment model with melatonin elimination from the central compartment was used to describe the data. The values (mean +/- SD) for the cows and the goats were: elimination half-life 27 +/- 4 min and 27 +/- 1 min, mean residence time 24 +/- 4 min and 18 +/- 4 min, steady state distribution volume 1.0 +/- 0.3 l/kg and 0.6 +/- 0.1 1/kg (p < 0.05), and plasma clearance 0.044 +/- 0.004 l/kg/min and 0.035 +/- 0.011 l/kg/min, respectively. Following injection, the melatonin concentration in milk increased rapidly and exceeded the corresponding serum value 15-30 min later, remaining thereafter above the serum level. Our results suggest that milk melatonin levels reflect blood concentrations of melatonin with a short delay.

Animal Husbandry↗

Plasma interleukin-8, interleukin-10, and E-selectin levels in neutropenic and non-neutropenic bacteremic patients.

Plasma interleukin-8 (IL-8) interleukin-10 (IL-10), and E-selectin concentrations were studied in 39 neutropenic and 30 non-neutropenic bacteremic patients; 54 nonbacteremic patients were analyzed as controls. Interleukin-8 concentrations were significantly higher in neutropenic than in non-neutropenic bacteremic patients (median 475 vs. 0 pg/ml, p < 0.0001). Median IL-8 and IL-10 levels were higher in bacteremic than in non-bacteremic patients (330 vs. 0 pg/ml, p < 0.0001 and 20 vs. 0 pg/ml, p = 0.04, respectively). In contrast, concentrations of IL-10 were similar in neutropenic and non-neutropenic patients. Median levels of E-selectin were not increased in any of the patient groups. Neutropenic bacteremic patients showed significantly lower concentrations of E-selectin than did non-neutropenic bacteremic patients (p < 0.0001). In conclusion, neutropenic bacteremic patients had significantly higher concentrations of IL-8 than non-neutropenic bacteremic patients. Levels of IL-10 were higher in bacteremic than in nonbacteremic patients, but neutropenic and non-neutropenic patients had similar levels of IL-10. Increased levels of E-selectin were not found in any of the patient groups, although neutropenic patients with bacteremia had lower concentrations than did non-neutropenic patients.

Adult↗

Effect of continuous venovenous haemofiltration and haemodiafiltration on the elimination of fluconazole in patients with acute renal failure.

The elimination of fluconazole was studied in six patients with acute renal failure undergoing continuous venovenous haemofiltration (CVVH) for 24 h, continuous venovenous haemodiafiltration (CVVHD) 1 L/h for 24 h and CVVHD 2 L/h for 24 h. Fluconazole 200 mg once daily was given intravenously on three successive days and the concentrations of fluconazole in serum, ultrafiltrate/dialysate and urine were determined for 24 h after each dose. The half-life of fluconazole in patients during CVVH (83.5 +/- 30.1 h; mean +/- S.D.) was significantly (P < 0.05) longer than that during CVVHD 1 L/h (30.4 +/- 5.0 h) or CVVHD 2 L/h (21.8 +/- 3.5 h). The total fluconazole clearance was 0.57 +/- 0.16 L/h, 1.50 +/- 0.24 L/h and 1.85 +/- 0.17 L/h in CVVH, CVVHD 1 L/h and CVVHD 2 L/h, respectively, and there was a significant difference (P < 0.05) between all these treatments. Daily renal excretion of fluconazole was minimal, ranging from 0.002 mg to 11.2 mg in different patients with different treatment modes. The methods tested increased the elimination of the unchanged drug 20- to 400-fold in patients with acute renal failure. Patients undergoing CVVHD therapy with a dialysis flow rates of 1 or 2 L/h should be treated with a daily dose of at least 200 mg of fluconazole to maintain therapeutic drug concentrations. However, in patients on CVVH therapy smaller doses of fluconazole may be enough.

Acute Kidney Injury↗

Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting.

BACKGROUND: Alpha 2-adrenergic agonists decrease sympathetic tone with ensuing attenuation of neuroendocrine and hemodynamic responses to anesthesia and surgery. The effects of dexmedetomidine, a highly specific alpha 2-adrenergic agonist, on these responses have not been reported in patients undergoing coronary artery bypass grafting. METHODS: Eighty patients scheduled for elective coronary artery bypass grafting received, in a double-blind manner, either a saline placebo or a dexmedetomidine infusion, initially 50 ng.kg-1.min-1 for 30 min before induction of anesthesia with fentanyl, and then 7 ng.kg-1.min-1 unit the end of surgery. Filling pressures, blood pressure, and heart rate were controlled by intravenous fluid and by supplemental anesthetics and vasoactive drugs. RESULTS: Compared with placebo, dexmedetomidine decreased plasma norepinephrine concentrations by 90%, attenuated the increase of blood pressure during anesthesia (3 vs. 24 mmHg) and surgery (2 vs. 14 mmHg), but increased slightly the need for intravenous fluid challenge (29 vs. 20 patients) and induced more hypotension during cardiopulmonary bypass (9 vs. 0 patients). Dexmedetomidine decreased the incidence of intraoperative (2 vs. 13 patients) and postoperative (5 vs. 16 patients) tachycardia. Dexmedetomidine also decreased the need for additional doses of fentanyl (3.1 vs. 5.4), the increments of enflurane (4.4 vs. 5.6), the need for beta blockers (3 vs. 11 patients), and the incidence of fentanyl-induced muscle rigidity (15 vs. 33 patients) and postoperative shivering (13 vs. 23 patients). CONCLUSIONS: Intraoperative intravenous infusion of dexmedetomidine to patients undergoing coronary artery revascularization decreased intraoperative sympathetic tone and attenuated hyperdynamic responses to anesthesia and surgery but increased the propensity toward hypotension.

Adjuvants, Anesthesia↗

Meningoencephalitis caused by Cryptococcus macerans.

A case of meningoencephalitis caused by Cryptococcus macerans is described. The infection caused a severe form of epilepsy. Antifungal therapy based on fluconazol was successful in halting the disease process. The patient remained, however, unable to resume his job and previous activities.

Adult↗

A clinical study of beta-haemolytic groups A, B, C and G streptococcal bacteremia in adults over an 8-year period.

All of the 88 episodes of beta-haemolytic streptococcal bacteremia (2.9% of all bacteremias) in adult patients during the years 1987-94 in a university hospital were reviewed. 38 bacteremias (43%) were caused by group A, 24 (27%) by group B, 3 (4%) by group C, and 23 (26%) by group G beta-haemolytic streptococcal. There was a statistically significant increase in group A and decrease in group C and G bacteremias (p < 0.02) compared to an earlier 8-year period in the same hospital, although the total number of streptococcal bacteremias remained the same. The most common T types of group A streptococcal strains were T11 (26%), T28 (14%), T6 and T1 (11% each), and T12 (8%). Cardiovascular disease, skin lesions, malignancy, and alcohol abuse were the most common underlying conditions. The most usual types of infection were skin (47%) and respiratory tract infections (23%). The overall mortality was 16%. It was highest in group A (24%) and lowest in group C (0%), 38% of patients with pneumonia died. All streptococcal strains were sensitive to penicillin, vancomycin, and cephalosporins. 11% of group A and 12% of all the strains had decreased sensitivity to erythromycin, 14 and 38% to tetracycline, and 0 and 2% to clindamycin, respectively.

Adolescent↗

Serological findings in patients with acute syndromes fulfilling the proposed criteria of adult onset Still's disease.

In order to analyse possible triggering or contributing infections and HLA-B27 frequency in patients with acute febrile joint syndrome fulfilling the proposed criteria of adult Still's disease (AOSD), we studied prospectively the serological findings of 25 patients. They were aged 15-62 years and diagnosed between 1978-1992. We then compared results with a control group consisting of 119 healthy persons. Positive viral or bacterial serology was found in 12 patients (48%) in the AOSD group compared with 13 cases (11%) in the control group (p < 0.001). Fourfold or higher viral antibody rise was found in two patients and bacterial antibody rise in three patients. High stable viral antibody titre was observed in one patient and high stable bacterial antibody titre in six patients. HLA-B27 was not overrepresented in the study group (12%) compared with a healthy Finnish population (14%). We conclude that many different bacterial and viral infections may trigger or contribute to AOSD.

Acute Disease↗

Skeletal muscle of patients with gyrate atrophy of the choroid and retina and hyperornithinaemia in ultralow-field magnetic resonance imaging and computed tomography.

Gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), an autosomal recessive disease, affects skeletal muscle in addition to the eye. Muscle biopsy samples show prominent type 2 muscle fibre atrophy. Atrophic fibres also contain accumulations of tubular aggregates in electron microscopy. To evaluate skeletal muscle involvement in detail, the thigh muscles of 7 patients with GA were examined using semi-open conchotome muscle biopsies, computed tomography (CT) and ultralow-field magnetic resonance imaging (MRI) at 0.02 T. In MRI, the T1 and T2 proton relaxation times were measured. Type 2 muscle fibre atrophy was found in all biopsy samples (100%) and tubular aggregates in 6 of the 7 samples studied (87%). The CT density of the muscle tissue was increased in the only child of the study, decreased in 3 elderly subjects, and normal in the remaining 3 patients. Mean T1 relaxation times of the patients were decreased (135 +/- 5 ms) as compared to those of 6 healthy controls (157 +/- 12 ms) (p = 0.002). The T2 relaxation time was slightly increased (40 +/- 3 ms) as compared to the controls (35 +/- 7 ms; not significant, p = 0.3). Our findings suggest that the thigh muscles of the patients with GA universally show changes in CT and MRI studies, but relaxation time measurements gave little additional information on the muscle metabolism.

Adolescent↗

Effects of melatonin implants on winter fur growth and testicular recrudescence in adult male raccoon dogs (Nyctereutes procyonoides).

The effects of melatonin implants were investigated on winter fur growth, monitored by counting growing and mature hairs per bundle and testicular recrudescence, judged by testis width, score count of spermatogenesis, and serum testosterone in the adult male raccoon dogs. Melatonin administration in July highly elevated melatonin concentrations in serum and urine and induced an earlier decrease in prolactin secretion (August in the treated group vs September in the control group), winter fur growth (July-beginning of November in the treated group vs. August-end of November in the control group) and testicular recrudescence (October in the treated group vs. November in the control group). In the control animals, urinary excretion of melatonin between 1500-0900 hr increased during autumn followed by a rapid fall in winter. The increase from July (1.8 +/- 0.4 ng) to August (3.9 +/- 0.5 ng) and the subsequent unchanged levels until October coincided with the period of winter fur growth. The further increase in November (6.5 +/- 1.2 ng) coincided with the significant elevation in both testis width and score count of spermatogenesis. These results suggest a role of the increase in endogenous melatonin secretion during autumn in the growth of winter fur and testicular recrudescence in this species under natural conditions. Relatively high serum concentrations of prolactin were shown in two animals, one in the control group and another in the treated group. However, the parameters for testis and winter fur growth in the two cases were similar to those in the remainder of the animals. Thereby, the role of prolactin in the winter fur growth and the initiation of testicular recrudescence, if it is truly involved, is manifested through its decreasing secretion rather than the actual blood concentrations.

Animals↗

Effects of experimental fat embolism on central hemodynamics and oxygenation in pigs.

Nine anesthetized and mechanically ventilated test pigs were intracavally infused with a 10% allogeneic bone marrows suspension at a dose of 100 mg/kg over 5 min; 9 control pigs received saline. The cardiac index decreased slightly in the fat embolism animals. Left ventricular stroke work remained unchanged in both groups, whereas right ventricular stroke work rose in the fat embolism animals. Mean arterial pressure remained stationary in the test group but rose in the controls. Pulmonary capillary wedge pressure and central venous pressure rose slightly in the test group. After infusion of the bone marrow suspension, mean pulmonary arterial pressure, pulmonary vascular resistance, pulmonary shunt and alveoloarterial oxygen tension difference increased immediately and remained elevated throughout the study period. Simultaneously, arterial and mixed venous oxygen tension and hemoglobin oxygen saturation decreased. Arterial carbon dioxide tension and hematocrit remained stationary. The fat embolism animals developed gradual fever. In conclusion, increased mean pulmonary arterial pressure, pulmonary vascular resistance, pulmonary shunt and alveoloarterial oxygen tension difference proved to be useful early indicators of experimental fat embolism.

Animals↗

Oral empiric treatment of community-acquired pneumonia. A multicenter, double-blind, randomized study comparing sparfloxacin with roxithromycin. The Scandinavian Sparfloxacin Study Group.

STUDY OBJECTIVE: Comparison of efficacy and safety of sparfloxacin (Spfx) vs roxithromycin (ROXI) for treatment of community-acquired pneumonia (CAP). DESIGN: Multicenter, double-blind, randomized study. SETTING: Twenty-three university and community hospitals in Scandinavia. PATIENTS: Three hundred four adults (> or = 18 years of age) with CAP treated as outpatients (25%) or inpatients (75%). INTERVENTIONS: Randomization 1:1 to Spfx, 400 mg on day 1, then 200 mg once daily, or ROXI, 150 mg twice daily, 10 to 14 days. Safety and efficacy analyses in intention-to-treat (ITT) and evaluable populations. RESULTS: Three hundred three of 304 patients were included in the ITT and safety analyses and 260 (86%) were evaluable at the end of follow-up. Streptococcus pneumoniae was the cause of pneumonia in 62 (20%) patients (11 with bacteremia), Chlamydia pneumoniae in 40 (13%), and Mycoplasma pneumoniae in 38 (13%) patients. The success rates for Spfx and ROXI at the end of follow-up were 82% and 72%, respectively, in the ITT population, and 94% and 79%, respectively, in the evaluable population. The odds ratio Spfx/ROXI for success was 4.5 (95% confidence interval, 1.9, 10.8) for the evaluable population. Both drugs were, overall, equally safe. GI symptoms were the most common adverse experiences in both groups. Prolongation of QTc, without clinical symptoms, was seen in 3% of Spfx patients and in 1% of ROXI patients, and photosensitivity, mostly mild to moderate, was seen in 5% of the Spfx group. CONCLUSIONS: Oral treatment with Spfx was superior to ROXI for the treatment of moderately severe CAP. Spfx was effective for all isolated pathogens, including S pneumoniae, and may be an alternative for empiric treatment of CAP, especially in areas with a high incidence of beta-lactam-resistant pneumococci.

Administration, Oral↗

Decrease in melatonin precedes follicle-stimulating hormone increase during perimenopause.

Melatonin, the hormone of the pineal gland, which in animal studies has been found to inhibit aging processes, is secreted in smaller amounts towards senescence. Menopause, an aging process in women, is known to be associated with typical changes in gonadotropin and sex steroid secretion. Our main objective was to study the possible role of melatonin in the hormonal regulation of menopause. This study focused on detailed changes in melatonin and follicle-stimulating hormone (FSH) secretion cross-sectionally in pre- to postmenopausal females. Special attention was paid to females aged around 50 years, which is the mean menopausal age. Seventy-seven healthy female volunteers aged 30-75 years were the subjects of this study. Melatonin was measured radioimmunologically from nocturnal urine collected between 20.00 and 08.00 h, and FSH and melatonin from blood samples taken at 0.900 h. Nocturnal urinary excretion of melatonin was found to decline significantly from premenopause to postmenopause. The youngest premenopausal women (age group 30-39 years) excreted the highest amounts of melatonin (21.2 +/- 2.2 pmol/h, mean +/- SEM, N = 17). In the age group 40-44 years the excretion declined by 41% (p < 0.05). The second significant decline (35%, p < 0.05) took place between the age groups 50-54 years and 55-59 years. A declining trend as a function of age was also seen in morning serum melatonin. Serum FSH rose sharply to high levels before the age of 50 (p < 0.01) and remained at a high level thereafter. Urinary melatonin correlated negatively with serum FSH (r = -0.32, p < 0.05). In conclusion, the inverse changes in melatonin and FSH secretion during the perimenopausal years, with the sharpest decline in nocturnal excretion of melatonin far before menopause, suggest that melatonin may be permissively linked to the initiation of menopause.

Adult↗

Plasma endotoxin and cytokine levels in neutropenic and non-neutropenic bacteremic patients.

Plasma endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 1 receptor antagonist (IL-1ra), and interleukin 6 (IL-6) concentrations in 69 bacteremic patients were compared with those in 54 nonbacteremic patients suffering from suspected bacterial infections. Only three (11%) of the 27 patients with gram-negative bacteremia showed detectable levels of endotoxin. TNF-alpha was detected in 6% of the bacteremic patients and in none of the nonbacteremic patients. Median IL-6 levels were significantly higher in bacteremic than in nonbacteremic patients (55 vs. 0 pg/ml, p = 0.0008). IL-6 concentrations were similar in neutropenic and non-neutropenic bacteremic patients (median 55 vs. 74 pg/ml). In contrast, neutropenic bacteremic patients had significantly lower concentrations of IL-1ra than non-neutropenic bacteremic patients (250 vs. 1,950 pg/ml, p < 0.0001). Patients with fatal bacteremia had significantly higher concentrations of IL-6 and IL-1ra than the survivors (median, 450 vs. 40, p = 0.012 and 7,600 vs. 420 pg/ml, p = 0.0075, respectively). Determinations of endotoxin or TNF-alpha in patients with suspected bacteremia failed to offer clinically relevant data on the prognosis of these patients. IL-6 levels correlated with both the presence of bacteremia and the risk of death. Granulocytopenic patients with bacteremia had lower levels of circulating IL-1ra than patients with normal granulocyte counts, and these levels correlated with poor outcome.

Adult↗

Report of four cases of Yersinia pseudotuberculosis septicemia and a literature review.

Yersinia pseudotuberculosis is a rare cause of disease in humans, the most common manifestation being mesenteric lymphadenitis accompanied by abdominal pain and fever. A septicemic form of Yersinia pseudotuberculosis infection has been reported only rarely. It is usually seen in patients with underlying disorders such as diabetes, hepatic cirrhosis or iron overload. Fifty-four cases of septicemic infection were found in the literature. The earlier published cases are reviewed, and four cases occurring in Finland during the period February to June 1992 are reported.

Adolescent↗