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Biomedical subjects

T Heikkinen

Publications and source records attributed to T Heikkinen.

At least 55 records · Page 3Linked to original sources

Increasing importance of viruses in acute otitis media.

Acute otitis media is generally considered a simple bacterial infection that can be effectively treated with antibiotics. However, despite the extensive use of broad-spectrum antibiotics, poor clinical response to treatment of acute otitis media is common in children. Numerous studies ranging from animal experiments to extensive clinical studies have clearly demonstrated that respiratory viruses play a crucial role in the aetiology and pathogenesis of acute otitis media. Viral infection of the upper respiratory tract initiates the whole cascade of events that finally leads to the development of acute otitis media as a complication. Respiratory viruses induce a release of inflammatory mediators in the nasopharynx, increase bacterial colonization and adherence, and have a suppressive effect on the host's immune defense. Recent data indicate that at least some types of viruses actively invade the middle ear. Viruses also seem to enhance the inflammatory process in the middle ear and impair the outcome of the disease. Vaccines against the major viruses predisposing to acute otitis media hold a great promise for the prevention of this disease. Major advances in the management of acute otitis media will require further research into the mechanisms of viral infection, viral-bacterial interaction and the host inflammatory response during viral infection.

Acute Disease↗

Estrogen and NMDA receptor antagonism: effects upon reference and working memory.

Since both estrogen and NMDA receptor antagonists act on the hippocampus CA1 region and behaviorally affect hippocampal memory tasks, we examined how estrogen depletion (ovariectomy) and NMDA receptor antagonism interact upon spatial memory of the mouse. After ovariectomy or sham operation, mice were given a 2-week recovery before behavioral tests began under the influence of vehicle or (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP 2, 5 and 10 mg/kg) intraperitoneal injections. CPP is a competitive, full NMDA receptor antagonist. Spatial reference memory was tested by the water maze, spatial working memory was tested by the radial arm maze, while overall locomotive activity was monitored by the Y-maze. Results from the water maze and the Y-maze did not show any spatial reference memory or activity differences between sham-operated and ovariectomized mice. The radial arm maze, however, highlighted some working memory differences between intact and ovariectomized mice. CPP treatment impaired dose dependently--the performance of ovariectomy and sham-operated mice equally on both water maze and radial arm maze, while the drug had no effect on Y-maze performance. These results suggest that short term estrogen deprivation has no effect upon spatial-reference memory, while it impairs spatial working memory. This effect is probably not mediated by NMDA receptors.

Animals↗

Prevalence of various respiratory viruses in the middle ear during acute otitis media.

BACKGROUND: Vaccines against respiratory viruses may be able to reduce the frequency of acute otitis media. Although the role of respiratory viruses in the pathogenesis of acute otitis media is well established, the relative importance of various viruses is unknown. METHODS: We determined the prevalence of various respiratory viruses in the middle-ear fluid in 456 children (age, two months to seven years) with acute otitis media. At enrollment and after two to five days of antibiotic therapy, specimens of middle-ear fluid and nasal-wash specimens were obtained for viral and bacterial cultures and the detection of viral antigens. The viral cause of the infections was also assessed by serologic studies of serum samples obtained during the acute illness and convalescence. RESULTS: A specific viral cause of the respiratory tract infections was identified in 186 of the 456 children (41 percent). Respiratory syncytial virus was the most common virus identified in middle-ear fluid: it was detected in the middle-ear fluid of 48 of the 65 children (74 percent) infected by this virus (P< or =0.04 for the comparison with any other virus). Parainfluenza viruses (15 of 29 children [52 percent]) and influenzaviruses (10 of 24 children [42 percent]) were detected in the middle-ear fluid significantly more often than enteroviruses (3 of 27 children [11 percent]) or adenoviruses (1 of 23 children [4 percent]) (P< or =0.01 for all comparisons). CONCLUSION: Respiratory syncytial virus is the principal virus invading the middle ear during acute otitis media. An effective vaccine against upper respiratory tract infections caused by respiratory syncytial virus may reduce the incidence of acute otitis media in children.

Acute Disease↗

Oral prednisolone is an effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes.

OBJECTIVE: To determine the efficacy of a short course of oral prednisolone as an adjuvant therapy for acute otitis media draining through tympanostomy tubes. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, children with acute discharge (<48 hours) through tympanostomy tubes received either prednisolone (2 mg/kg/d; n = 23) or placebo (n = 27) for 3 days. All children received amoxicillin/clavulanate (40/10 mg/kg/d) for 7 days. The children were examined daily at the study clinic until the drainage ceased. RESULTS: The median duration of otorrhea in the prednisolone group was 1.0 days (25% to 75% range, 1.0 to 2.0 days), compared with 3.0 days (25% to 75% range, 2.0 to 4.0 days) in the children receiving placebo (P <.001). The duration of otorrhea was </=2 days in 21 (91%) children in the prednisolone group, compared with 8 (30%) children in the placebo group (P <.001). CONCLUSIONS: Oral prednisolone appears to be modestly effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes in children. Further studies seem warranted to determine whether short-term use of steroids early during the course of acute otitis media would also reduce the duration of middle ear effusion in children with intact tympanic membranes.

Acute Disease↗

Free secretory component as a standardization protein for nasopharyngeal specimens from children with upper respiratory tract infection.

Free secretory component (FSC) has been recommended as a reliable protein for correction of the unknown dilution in tracheal aspirate samples from preterm infants. To investigate whether FSC would also provide a valid standardization protein for samples of nasopharyngeal secretions, this study determined the intersubject variation and the alteration over time in the concentrations of FSC in nasal secretions from 35 children (median age 14 months) who participated in an antibiotic efficacy trial. Nasopharyngeal aspirates were obtained at enrolment and after 2-3 d. FSC in the specimens was quantified by a direct enzyme immunoassay. The concentrations of FSC in the nasal secretions ranged from 0.08 to 189.6 microg ml(-1) (median 12.3 microg ml(-1); the ratio of the highest to the lowest concentrations was 2370, the difference between the 90th and 10th percentile concentrations was 189-fold and the difference between the 75th and 25th percentile values was 26. FSC concentrations were significantly lower in children aged < or =12 months (median 2.2 microg ml(-1) than in the older children (median 21.5 microg ml(-1); p = 0.035). Between the first and the follow-up specimens, 65% of the children had > or =2-fold difference in the levels of FSC in the secretions. Because an optimal standardization protein should show minimal variation between individuals and over time, FSC may not be a suitable protein for correction of the unknown dilution of nasopharyngeal specimens from children with upper respiratory tract infection.

Child, Preschool↗

Quantification of cytokines and inflammatory mediators in samples of nasopharyngeal secretions with unknown dilution.

In the study of inflammatory mechanisms in the upper respiratory tract, the unknown dilution of collected samples of nasal secretions poses a serious problem for interpretation of the measured concentrations of various substances in the specimens. We investigated the magnitude of the dilution problem in a true clinical research situation and determined the validity of using the levels of total protein, albumin, and secretory IgA in nasal secretions to correct for the unknown dilution. The study samples consisted of simultaneously obtained nasopharyngeal aspirates and nasal lavage specimens from 52 children with upper respiratory tract infection. The dilution factors of the nasal lavage specimens varied widely between 1.8 and 432 (median, 11.2). Of the three proteins studied, total protein had the narrowest inter-subject variation in the nasal secretions of the children and thus seemed to provide the best standardization method for comparing levels of substances between individuals. Concentrations of IL-6 standardized with total protein correlated significantly better with the true IL-6 concentrations in the nasal secretions than did IL-6 levels measured in the nasal lavage specimens without standardization (p = 0.049). These findings suggest that the most common current practice of measuring substances in nasopharyngeal specimens, i.e. measuring without correction for the dilution, may produce "false-negative" results. Potentially important information on inflammatory mechanisms may be undetected if false-negative results mask real differences between groups. The use of exogenous markers of dilution might improve the accuracy of quantifying substances in nasal secretions.

Acute Disease↗

Intranasally administered immunoglobulin for the prevention of rhinitis in children.

OBJECTIVE: To determine the efficacy of intranasally administered immunoglobulin in preventing symptoms of rhinitis in children. METHODS: Forty children ages 1 to 4 years who attended day-care centers in Turku, Finland, were enrolled in the double blind, placebo-controlled study. The children were randomly assigned to receive treatment with immunoglobulin, composed mainly of immunoglobulin A, or placebo, both administered as nasal sprays twice daily for 8 weeks. During this medication period and an additional 8-week follow-up period, the parents recorded the symptoms of the children daily in the diaries provided. One child who met an exclusion criterion was withdrawn from the study after a few days of medication. RESULTS: During the 8-week medication period the 19 children in the immunoglobulin group had 42% fewer days with rhinitis than the 20 children receiving placebo (mean, 10.8 vs. 18.7 days; P=0.004). The total numbers of episodes of rhinitis in the immunoglobulin and placebo groups were 33 and 51, respectively. No significant differences were observed between the groups during the postmedication follow-up period. CONCLUSIONS: Intranasal administration of immunoglobulin appears to be an effective method to prevent symptoms of rhinitis in children, and further studies of this approach are needed.

Administration, Intranasal↗

Otitis media.

Despite extensive research on various aspects of otitis media, this disease remains an important health care problem of childhood. The rapid increase in resistance to penicillin and several other drugs among strains of Streptococcus pneumoniae will most likely have a great impact on the antibiotic treatment of acute otitis media. The increasing antimicrobial resistance has once again brought up the question of whether antibiotics are really needed in the treatment of acute otitis media. Further, the resistance problem underscores the great need for effective methods to prevent otitis media. In the current situation, the common practice of using antimicrobial prophylaxis for prevention of otitis media should be seriously reconsidered.

Acute Disease↗

Serum interleukin-6 in bacterial and nonbacterial acute otitis media.

BACKGROUND: Increasing prevalence of antibiotic-resistant bacteria is a serious clinical problem that calls for reduction of unnecessary use of antibiotics. Acute otitis media (AOM) is the most common reason for antibiotic therapy in the United States. Approximately 30% of AOM cases do not have a bacterial etiology. Rapid identification of these cases could help withhold unnecessary antibiotic treatment. OBJECTIVE: To determine the usefulness of serum levels of interleukin-6 (IL-6), an acute phase cytokine shown to be a reliable marker of neonatal bacterial infection, in differentiation between bacterial and nonbacterial AOM in children. STUDY DESIGN: IL-6 was measured in stored serum samples from 184 children (mean age, 22 months) with AOM who were enrolled in antibiotic efficacy trials at our department. The samples were obtained at enrollment and at 9 to 12 days after initiation of antibiotic therapy. Sera from 21 uninfected children (mean age, 23 months) were used as controls. The etiology of AOM was determined by bacterial and viral cultures as well as respiratory syncytial virus antigen detection in the middle ear fluids obtained by tympanocentesis. RESULTS: Bacterial etiology of AOM was confirmed in 125 children (68%), whereas in 59 children (32%) no bacterial pathogen could be detected in the middle ear fluid. Children with bacterial AOM had significantly higher IL-6 levels than those with nonbacterial AOM (median, 11.5 vs 3.7 pg/mL). However, this difference was almost entirely attributable to pneumococcal AOM specifically. IL-6 levels in children with AOM caused by Streptococcus pneumoniae were significantly higher (median, 40.1 pg/mL) than in AOM caused by Haemophilus influenzae (7.3 pg/mL) or Moraxella catarrhalis (6.8 pg/mL). At the cutoff value of 30 pg/mL, the specificity of IL-6 for detection of pneumococcal AOM was 91% with a sensitivity of 61%, but its sensitivity for detection of bacterial AOM in general was only 27%. CONCLUSIONS: Low levels of IL-6 do not rule out bacterial etiology of AOM in general; therefore, IL-6 is not sensitive enough as a marker of bacterial AOM. Surprisingly, serum IL-6 levels in pneumococcal AOM were significantly higher than the levels associated with other bacterial AOM, and serum IL-6 levels of >30 pg/mL were highly specific for pneumococcal AOM. These findings suggest a distinctive role for S pneumoniae in the pathogenesis of AOM.

Acute Disease↗

Role of viruses in middle-ear disease.

Taken together, there is ample evidence suggesting a role for viruses in the pathogenesis of OM. This evidence comes from numerous studies performed in animals and in vitro cell cultures, as well as in adults and children with URI and OM. Viruses induce host immune and inflammatory responses that result in pathology of the ET and the middle ear, and predispose the host in various ways to secondary bacterial infection. A suggested mechanism for the pathogenesis of OM following respiratory viral infection is presented in Figure 1.

Acute Disease↗

Maternal smoking and tooth formation in the foetus. III. Thin mandibular incisors and delayed motor development at 1 year of age.

Dental casts from 2159 black and white Americans with detailed neurological data available from the Collaborative Perinatal Study were examined to investigate the relationship of maternal smoking during pregnancy and delayed motor development at 1 year of age to morphological traits in the dentition. Earlier results have indicated that maternal smoking during pregnancy may cause selected tooth size metric reductions in the deciduous dentition and at least in some of the permanent teeth with prenatal crown formation, these features being influenced by sex and race differences. The present results suggest that a thinning of the incisal parts of the permanent mandibular incisors is associated with heavy maternal smoking during pregnancy, and those white girls, in whom this dental variant is found, have probably experienced more severe central damage during the smoking sensitive gestational months, as is also seen in a delayed motor development at the age of 1 year.

Black People↗

Total costs of laparoscopic and lichtenstein inguinal hernia repairs: a randomized prospective study.

In a prospective, randomized study, laparoscopic (n = 20) and Lichtenstein (n = 18) inguinal hernia repairs were compared in relation to operative time, operative costs, hospital stay, postoperative pain, return to work, patient satisfaction, complications, and total costs. All the operations were performed with the patient under general anesthesia. The median operative times in the laparoscopic and Lichtenstein groups were 71.5 (range, 43-140) and 45 (16-83) min, respectively (p < 0.001). Postoperative pain and use of analgesics was less in the laparoscopic group. The median time to return to work was 14 (8-26) days in the laparoscopic group and 19 (5-40) days in the Lichtenstein group. More complications occurred in the Lichtenstein group. The median of the operative costs, in U.S. dollars, was $1,395 and $878, respectively, and the median total costs (including community expenses resulting from lost workdays) were $4,796 in the laparoscopic and $5,320 in the Lichtenstein groups.

Adult↗

New prospects in the prevention of otitis media.

Otitis media is the most common bacterial infection in children, accounting for a substantial economic burden to the health care system. Together with concern for long-term developmental sequelae, prevention of otitis media has become a high priority area of research. A wide range of factors has been associated with an increased risk of acute otitis media. Most of these factors, however, predispose to upper respiratory tract infection which, in turn, can be considered the most important risk factor for acute otitis media. Conventionally, antimicrobial prophylaxis, tympanostomy tubes and adenoidectomy have been used for prevention of otitis media. At present, the vaccine approach seems to hold the greatest promise for ultimate prevention of otitis media. In addition to the bacterial vaccines, vaccines against the most common viruses predisposing to acute otitis media may also prove valuable in the prevention of otitis media.

Adenoidectomy↗