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Biomedical subjects

H Saxén

Publications and source records attributed to H Saxén.

At least 37 records · Page 2Linked to original sources

Oral poliovirus vaccination and pregnancy complications.

BACKGROUND: To determine whether the effect of live attenuated oral polio virus vaccine given to pregnant women increases pregnancy complications. METHODS: A study of women who had been vaccinated against poliovirus during a national vaccination campaign and who had delivered by cesarean section in three obstetrical hospitals in southern Finland. One thousand seven hundred and forty-seven vaccinated women (in three study cohorts), and their 2293 nonvaccinated controls (in two reference cohorts) were analyzed. Subjects are out of 22,000 deliveries evaluated earlier. RESULTS: Vaccinated sectioned women did not show an excess of pregnancy complications. The mean rate of cesarean sections was 18.4% in the study cohorts and 18.9% in the reference cohorts counted from the 22,000 deliveries. CONCLUSIONS: Oral live attenuated polio virus vaccine does not increase pregnancy complications and is considered a safe alternative for vaccinating pregnant women.

Adult↗

Using feed-forward neural networks for estimation of microbial concentration in a simulated biochemical process.

This work investigated the feasibility of using feed-forward neural networks for estimation of a state variable in a process with highly non-linear characteristics. A biochemical process was considered where the microorganism Saccharomyces cerevisiae, a yeast, grows in a chemostat on a glucose substrate and produces ethanol as a product of primary energy metabolism. Three state variables for the process are the microbial concentration, substrate concentration and product concentration. The Levenberg-Marquardt Method was used to train the neural networks by minimising the sum of squares of the residuals. The inputs to the networks were the measured variable (product concentration) and the control variable (dilution rate). The output of the network was an estimate for the microbial concentration. Earlier work had shown that system identification of this biochemical process could be performed quite well using feed-forward neural networks. This work demonstrated that state estimation can also be performed successfully using feed-forward neural networks. Knowledge of the process model is not required. The method is simple, reliable and accurate enough for engineering purposes. It can save a lot of expense on sensors, their installation and maintenance.

Neural Networks, Computer↗

Oral polio vaccination during pregnancy: lack of impact on fetal development and perinatal outcome.

Prompted by a nascent epidemic of poliomyelitis in Finland, a mass vaccination program with live oral poliovirus vaccine (OPV) was implemented in February and March 1985. The final rate of coverage was approximately 94%. Pregnant women were included, and a cohort study was launched to evaluate any harmful effects of OPV on the developing embryo. All records of births to mothers who were pregnant during the period of vaccination and whose infants were delivered at the three major hospitals in the Helsinki area were reviewed. Within the study cohort, mothers were grouped into three categories according to their trimester of pregnancy during the program. In addition, two reference cohorts were evaluated; these cohorts consisted of infants delivered at the same hospitals during the second half of 1984 and of 1986, respectively. Each of the three categories in the study cohort included approximately 3,000 children, while each reference cohort included approximately 6,000 children. Data were analyzed on the rate of intrauterine growth and the prevalences of stillbirth, neonatal death, congenital malformation, premature birth, perinatal infection, and neurological aberration. No differences were documented among the study and reference cohorts or among the three categories within the study cohort. Thus, under the conditions described here, the inclusion of pregnant women in programs of mass vaccination with OPV appears to be safe.

Cohort Studies↗

Oral polio vaccination during pregnancy: no increase in the occurrence of congenital malformations.

To examine the possible association between maternal vaccination with oral polio-virus and congenital malformations of the child, use was made of a nationwide mass vaccination in Finland. During a restricted period in 1985, a vaccination with trivalent oral poliovirus was implemented with coverage of 94% of the population. The study population was chosen from three major hospitals in the Greater Helsinki Region in Finland which deliver over 95% of the children of their catchment area. One study and two reference cohorts were delineated; the former consisted of pregnancies that were in their first trimester during the vaccination period. The two reference cohorts included mothers from the same hospitals whose pregnancies were likewise in the first trimester during the corresponding time period in 1984 and 1986, i.e., 12 months before and after the study period. Each cohort consisted of approximately 3,000 mothers/children whose delivery and hospital records were manually perused by trained nurses. All the structural malformations reflecting an impaired organogenesis during the sensitive first trimester were monitored. A total of 209 (2.3%) such malformations were recorded and characterized. There were no differences between the study and reference cohorts (risk ratio = 0.7, 95% confidence interval 0.5-1.0). According to the authors' power estimate, an additional prevalence greater than 0.5% would have been detected. The authors conclude that administration of oral poliovirus vaccine during early pregnancy was not associated with an elevated risk of congenital malformations.

Cohort Studies↗

Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life.

OBJECTIVE: To find a dose of fluconazole for very low birth weight infants during an outbreak of Candida parapsilosis. METHODS: Twelve premature infants (mean gestational age, 27.4 weeks; mean birth weight, 912 gm) receiving fluconazole prophylactically from the first day of life were enrolled in an open phase I-II pharmacokinetics, safety, and tolerance trial. Up to 5 doses of 6 mg/kg were administered intravenously every 72 hours during the first 2 weeks of life. Pharmacokinetic characteristics of fluconazole were determined after the first, third, and fifth doses. RESULTS: The mean peak and trough concentrations after the 3 doses were 5.5 and 2.6 micrograms/ml, 12.8 and 4.3 micrograms/ml, and 10.0 and 2.9 micrograms/ml (p = 0.0002 and p = 0.07), respectively. The mean fluconazole half-lives were 88.6 hours (n = 7), 67.5 hours (n = 9), and 55.2 hours (n = 4; p = 0.3). The mean total clearance corrected for weight (CL/kg) was 0.18 ml/min/kg (n = 7), 0.33 ml/min/kg (n = 7), and 0.52 ml/min/kg (n = 4; p = 0.02), and the mean volume of distribution 1.18 L/kg (n = 7), 1.84 L/kg (n = 7), and 2.25 L/kg (n = 4; p = 0.05). Weight-corrected clearance increased with postnatal age (r = 0.61; p = 0.007). CONCLUSIONS: With the used fluconazole dose (6 mg/kg every 3 days), the mean serum peak and trough concentrations increased during the first week but decreased during the second week. After the first week we suggest a dose of 6 mg/kg every 2 days, or even daily.

Candidiasis↗

Regional blood flow and oxygen transport in septic shock.

OBJECTIVE: To measure the blood flow distribution and regional oxygen transport in hyperdynamic septic shock during hypotension and after correction by vasopressor doses of dopamine or norepinephrine. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary care center. PATIENTS: Ten patients with hyperdynamic septic shock (ages ranging from 45.1 +/- 16.6 yrs) and a control group of 11 postoperative cardiac surgery patients (ages ranging from 54.8 +/- 7.9 yrs). INTERVENTIONS: Systemic and regional hemodynamics and oxygen transport were measured in ten patients with hyperdynamic septic shock during hypotension and after vasopressor therapy (norepinephrine or dopamine). Oxygen consumption (VO2) was measured by indirect calorimetry and splanchnic and leg blood flow with indocyanine green infusion. MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow and VO2 (p < .05) were increased in septic shock during hypotension and during vasopressor therapy. Both dopamine and norepinephrine increased systemic blood flow and VO2 independently of the arterial lactate level. Despite the relatively small changes in systemic oxygen transport, major regional changes occurred in oxygen delivery and VO2, and these changes were unpredictable from systemic changes. CONCLUSIONS: Regional changes in oxygen transport in septic shock cannot be predicted from the changes in the whole body. The increased oxygen demand in the splanchnic region is the main risk factor for splanchnic tissue hypoxia in septic shock.

Adolescent↗

Chronic lung disease of preterm infants in Finland is not associated with Ureaplasma urealyticum colonization.

The occurrence of Ureaplasma urealyticum and Mycoplasma hominis in the airways and the association of these microorganisms with chronic lung disease was studied in preterm infants with a gestational age less than 30 weeks. Tracheal aspirates from 49 preterm infants were cultured; 14 (29%) infants were positive for U. urealyticum, and 1 (2%) was positive for M. hominis. Of the 16 patients who developed lung disease, 6 (38%) were positive for U. urealyticum, while the expected number of Ureaplasma-positive patients in this group, based on the overall incidence of Ureaplasma, was 4.6. On the other hand, 8 patients were positive for U. urealyticum but did not develop chronic lung disease, nor did samples taken from 10 patients with chronic lung disease show any Ureaplasma growth. From these data we conclude that colonization of the airways with U. urealyticum has no significant role in the development of chronic lung disease in preterm infants in the Finnish (Caucasian) population.

Chronic Disease↗

Effect of polyinosinic-polycytidylic acid (pl:C) on experimental mouse salmonellosis.

The effect of the non-specific immunomodulator polyinosinic-polycytidylic acid (pl:C) on the resistance to experimental salmonellosis was studied in the mouse. The polynucleotide was unexpectedly found to decrease the innate relative resistance of the mouse to this intracellular infection. pl:C (100 micrograms/mouse) injected 24 h before either intravenous (i.v.) or intraperitoneal (i.p.) challenge resulted in an increased intracellular rate of growth of the Salmonella in the liver, but did not affect the initial extracellular survival of the bacteria in the peritoneal cavity. By contrast, pl:C did not affect the course of mouse peritonitis caused by E. coli O18:K1, which multiplies extracellularly or that of Listeria monocytogenes, which, like Salmonella, grows intracellularly in the liver. The effect of pl:C on salmonellosis could not be explained by production of alpha or beta interferon (IFN) since it could not be demonstrated by injecting purified IFN nor could it be abolished by injecting neutralizing anti-IFN antibodies. Thus, pl:C seems to have a specific effect on salmonellosis by impairing the growth restriction of these bacteria in the liver macrophages.

Animals↗

Salmonella, complement and mouse macrophages.

The structure of the polysaccharide chains that constitute the O antigen on the surface of Salmonella bacteria determines the rate of complement activation and C3b deposition on the bacteria. A fast-activating O antigen causes rapid C3-dependent opsonization of the bacteria injected intraperitoneally; as a consequence, the bacteria are taken up and killed by the resident peritoneal macrophages, and their virulence is low. A slow-activating O antigen protects the bacteria from opsonization in the peritoneal cavity, and is associated with higher virulence. However, if injected intravenously bacteria with either O-antigenic type are equally virulent; in the high complement concentration of the blood they become opsonized and taken up by macrophages in the liver and spleen, which are unable to kill them but instead provide a protected site for multiplication.

Animals↗

Protective capacity of antibodies to outer-membrane components of Escherichia coli in a systemic mouse peritonitis model.

Antibody-mediated protection was studied in an experimental murine model of peritonitis-septicaemia with Escherichia coli O18:K1. Protection from lethal intraperitoneal challenge was achieved by passive immunisation with horse anti-K1 capsular antiserum (H46) or rabbit antiserum to the homologous O18 antigen. The maximum increase in LD50 achieved with anti-K1 and anti-O18 antibodies was 10- and 5-fold, respectively. The protective capacity of the anti-O serum was found to be in the IgG fraction. Rabbits were also immunised with various semi-purified or purified outer-membrane-protein preparations (porins and OmpA protein) from rough E. coli or Salmonella strains or with whole E. coli J5 bacteria. Although this immunisation resulted in high antibody titres to homologous and, to a lesser extent, also to heterologous antigens, none of the antisera protected against challenge with the capsulate E. coli O18:K1 bacteria.

Animals↗

Alternative complement pathway activation by Salmonella O polysaccharide as a virulence determinant in the mouse.

The quality of Salmonella O polysaccharide (the O antigen) is a virulence factor in mouse salmonellosis. It affects the rate by which these bacteria are phagocytosed and by which they activate the alternative complement pathway in a manner inversely proportional to their virulence, suggesting that the rate of complement activation is crucial for the fate of the bacteria in the mouse. The effector mechanism has, however, remained open since Salmonellae survive and multiply in the macrophages of the mouse. We show in this study that although the least virulent O-6,7 Salmonellae multiply in the liver macrophages they are rapidly killed in the peritoneal cavity by the local resident macrophages. Electron microscopy showed a striking morphological feature--a 35 nm thick homogenous electron-dense deposit--on all the bacteria found in association with the macrophages but absent from all non-cell-associated bacteria. A similar precipitate was formed by incubating the bacteria in fresh mouse serum and was dependent on heat-labile serum components and bound anti-C3. The least virulent O-6,7 bacteria acquired this deposit more rapidly and in a lower concentration of serum than the more virulent O-4,12 bacteria consistent with the previously demonstrated difference between these bacteria in their rate of complement activation via the alternative pathway. Preincubation of the O-4,12 bacteria in fresh mouse serum leading to complement deposition on 80% of the bacteria effectively opsonized them for rapid killing in the peritoneal cavity. These data for the first time demonstrate how the rate of complement activation determines the virulence of Salmonellae.

Animals↗

Expression of P, type-1, and type-1C fimbriae of Escherichia coli in the urine of patients with acute urinary tract infection.

In vivo expression, in human urine, of P, type-1, and type-1C fimbriae by Escherichia coli was analyzed by indirect immunofluorescence. Urine samples from 20 patients with acute urinary tract infection, as well as cultures of the corresponding E. coli isolates, were immunostained with three polyclonal antisera to P fimbriae, antiserum to type-1 fimbriae, monoclonal antibody specific for type-1C fimbriae, and fluorochrome-conjugated second antibodies. P fimbriae were found in 17 urine samples and in 18 of the isolated strains. Type-1-fimbriate bacteria were detected in only nine urine samples, although 18 of the isolated strains expressed type-1 fimbriae after growth in vitro. Four strains possessed type-1C fimbriae; only two expressed type-1C fimbriae in urine. The bacterial populations in urine were heterogeneous, and in each positive staining, only a fraction of the bacterial cells were reactive. The results show that E. coli P fimbriae are expressed and are subject to phase variation in vivo during acute urinary tract infection.

Acute Disease↗

Bacterial induction of human activated lymphocyte killing and its inhibition by lipopolysaccharide (LPS).

Peripheral blood lymphocytes were incubated with glutaraldehyde-fixed Salmonella bacteria. This resulted in rapid activation of nonspecific cytotoxic potential of the lymphocytes. Both originally noncytotoxic, high-density Percoll-fractionated cells, and cytotoxic natural killer (NK) cell-enriched low-density cells were activated. The induction of originally noncytotoxic cells into activated killer (AK) cells was apparently independent of interferon (IFN), whereas the activation of the NK cell-enriched fractions also involved IFN production. Neither the AK nor NK activity were associated with significant bactericidal activity. The IFN-independent induction of AK activity was not dependent on the O-antigenic polysaccharide part of the lipopolysaccharide (LPS) on the bacterial cell surface, because both smooth (S) strains with differing O-antigenic structures (S-4,12 and S-6,7) and a rough (Re) strain without O-antigen were effective inducers. Isolated LPS, and especially alkali-hydrolyzed (O-deacylated, detoxified) LPS (ALPS) interfered with the induction of cytotoxicity. At concentrations of 10 to 30 micrograms/ml, ALPS totally inhibited the induction of AK activity without affecting the endogenous NK activity. Thus contact with bacteria can lead to the emergence of AK cells, and a bacterial product can effectively block this activation. These phenomena stress the complexity of interactions with host defenses that can take place during bacterial infection.

Antigens, Bacterial↗

Evidence for the importance of O antigen specific antibodies in mouse-protective Salmonella outer membrane protein (porin) antisera.

The antibodies responsible for the protective effect of sera obtained by immunizing rabbits with the major outer membrane protein porin of Salmonella typhimurium complexed with LPS (Kuusi et al., Infect. Immun., 1981; 34:328-332) were found to be directed to the O antigen. They were effective in very small concentration which probably accounted for our failure to identify them before or now by in vitro methods. Although both the porin and the LPS in the complexes used for immunization were isolated from rough (R) form organisms devoid of O antigen by all usually applied criteria, the antigen contained a small amount of smooth form LPS, most probably derived from a slight leakiness of the rfa mutation responsible for the R character. The small amount of contaminating O antigen was apparently rendered highly immunogenic by complexation with the outer membrane protein.

Animals↗