Biomedical subjects

P Halonen

Publications and source records attributed to P Halonen.

At least 55 records · Page 3Linked to original sources

PubMed1998

Coinfection is common in measles-associated pneumonia.

BACKGROUND: Measles continues to be a significant health problem in developing countries. OBJECTIVES: To describe the clinical features of measles-associated pneumonia (MAP) and to identify other pathogens involved. METHODS: Measles diagnosis was ascertained either by the typical symptom complex or by a sensitive enzyme immunoassay for antibody among children < 5 years of age admitted to the hospital with pneumonia. Other pathogens were identified by blood culture, virus isolation or antigen detection from nasopharyngeal aspirate and antibody determination from serum. RESULTS: Of 182 MAP cases 162 (89%) had clinically typical measles. Twenty patients had a diagnostic antibody finding with an atypical clinical presentation. Thirteen percent were younger than 9 months of age. The case fatality rate was 17%, with a significantly increased odds ratio (OR) for those with cyanosis [OR 4.6, 95% confidence interval (CI) 1.7 to 13], respiratory rate > or = 60/min (OR 3, 95% CI 1.3 to 7) or fulfilling criteria for very severe pneumonia (OR 5.3, 95% CI 2.3 to 12). Mixed infection was found in 53% of patients. Blood culture was positive in 10 patients, Streptococcus pneumoniae (N = 5) being the most common finding. Adenovirus (19%) and parainfluenza (25%) viruses were the most frequent other viruses. A dense infiltrate was seen significantly more often among measles patients with bacterial coinfection (87.5%) than those with other viruses (36%, P = 0.007) or no evidence of other infection (33%, P = 0.004). CONCLUSION: In MAP, coinfection with other microbes is common. Cyanosis and a respiratory rate of > or = 60/min predict a greater risk of dying.

Child, Preschool↗

PubMed1997

Structural and functional consequences of substitutions at the tyrosine 55-lysine 104 hydrogen bond in Escherichia coli inorganic pyrophosphatase.

Tyrosine 55 and lysine 104 are evolutionarily conserved residues that form a hydrogen bond in the active site of Escherichia coli inorganic pyrophosphatase (E-PPase). Here we used site-directed mutagenesis to examine their roles in structure stabilization and catalysis. Though these residues are not part of the subunit interface, Y55F and K104R (but not K104I) substitutions markedly destabilize the hexameric structure, allowing dissociation into active trimers on dilution. A K104I variant is nearly inactive while Y55F and K104R variants exhibit appreciable activity and require greater concentrations of Mg2+ and higher pH for maximal activity. The effects on activity are explained by (a) increased pK(a)s for the catalytically essential base and acid at the active site, (b) decreases in the rate constant for substrate (dimagnesium pyrophosphate) binding to enzyme-Mg2 complex vs enzyme-Mg3 complex, and (c) parallel decreases in the catalytic constant for the resulting enzyme-Mg2-substrate and enzyme-Mg3-substrate complexes. The results are consistent with the major structural roles of Tyr55 and Lys104 in the active site. The microscopic rate constant for PPi hydrolysis on either the Y55F or K104R variants increases, by a factor of 3-4 in the pH range 7.2-8.0, supporting the hypothesis that this reaction step depends on an essential base within the enzyme active site.

Biopolymers↗

PubMed1997

Comparison of PCR primer pairs in the detection of human rhinoviruses in nasopharyngeal aspirates.

The development of a rapid and highly sensitive PCR assay for the detection of human rhinoviruses (HRVs) in nasopharyngeal aspirates is described. Two simple and fast commercial RNA extraction methods and four primer pairs were compared. The most sensitive RNA extraction method (Ultraspec) and primer pair (A) were applied to detection of HRV RNA in 49 nasopharyngeal aspirates, of which 31 had previously been found culture-positive for HRVs. All culture-positive specimens were found positive by PCR. In addition, four of the 18 culture-negative samples were positive by PCR. Primer pair A, however, is not specific for rhinoviruses; it also amplifies enteroviruses, and thus an additional hybridization step with an HRV-specific probe is needed for group-specific diagnosis. The assay was able to detect an amount of HRV-1B RNA corresponding to 0.01 infected cells. In addition, about 50 ag (about 10 genomes) of purified HRV-1B and CBV-3 RNA still gave a signal with this primer pair.

Capsid↗

PubMed1997

Depression measured by the Zung Depression Status Inventory is very rare in a Finnish population aged 85 years and over.

The purpose of this study was to obtain information about the prevalence of depressive symptoms in a representative sample of elderly subjects aged 85 years and over. The study was carried out as a population-based interview study in the City of Vantaa in Finland. The Zung Depression Status Inventory (DSI) was used to evaluate various depressive symptoms in this study population. The DSI scores range from 20 to 80; the higher the score, the more severe the disturbance. In subjects interviewed (n = 467, 362 women, 105 men), the prevalence estimates of depression with cutoff scores used in earlier studies (40 and 48) were very low: 5.2% and 1.1%. Also, the mean DSI score (SD) was very low, 27.9 (6.4). The scores tended to decrease with age, although the differences were not statistically significant. The DSI means were 28.0 (6.1) for women and 27.3 (7.2) for men (p = .0349). Women had a greater risk of being classified as depressed on the DSI (odds ratio: 1.60, 95% confidence interval: 1.00-2.57, p = .049). Feelings of emptiness, personal devaluation, and depressive mood were the most common depressive symptoms. In conclusion, the present population-based study shows that subjective experience of depression is very rare in Finnish people aged 85+. Our results suggest that optimistic mood might give some protection against death.

Aged↗

PubMed1997

Reversal of neuromuscular blockade with neostigmine has no effect on the incidence or severity of postoperative nausea and vomiting.

UNLABELLED: We performed this randomized, double-blind, placebo-controlled study to determine whether reversal of neuromuscular block with neostigmine increases the incidence and severity of postoperative nausea and vomiting (PONV). We studied 162 women undergoing abdominal hysterectomy and randomly allocated them into two groups. In Group A, neuromuscular block produced with mivacurium was antagonized with neostigmine 2.0 mg and glycopyrrolate 0.4 mg intravenously, whereas Group B received no drugs to facilitate antagonism of blockade. The incidence and severity of PONV was assessed up to 27 h after the operation. There was no difference in PONV between the groups (in Group A 35% had nausea and 33% vomited; in Group B 28% nauseated and 40% vomited) or in the amount of antiemetics given. We had a 75% chance to find a 30% difference in PONV. We conclude that the administration of neostigmine and glycopyrrolate at the end of anesthesia to reverse neuromuscular block does not increase the incidence or severity of PONV. IMPLICATIONS: Neostigmine may increase postoperative nausea and vomiting. In this study, omission of reversal of neuromuscular block with neostigmine failed to decrease the incidence or severity of postoperative nausea and vomiting.

Adult↗

PubMed1997

p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic significance of p53 expression and proliferation markers in primary laryngeal squamous cell carcinoma. PATIENTS AND METHODS: Primary tumors for analyses were obtained from 103 patients, with complete follow-up data. All patients were treated between the years 1975 and 1990. The expression of p53 was analyzed with monoclonal D07 antibody and proliferative activity with Ki-67 (MIB-1) and PCNA (monoclonal 19A2) antibodies. Volume corrected mitotic (M/V) index and histological grade were determined in hematoxylin and cosin-stained slides. RESULTS: Sixty-eight percent of the tumors overexpressed p53. During a median follow-up of 62 months, 41 (40%) of patients relapsed. In univariate analysis site of the primary tumor, stage, p53 expression, histologic grade, and M/V index were significant predictors of disease-free survival. In multivariate analysis, only M/V index was a statistically significant predictor of disease-free survival. Overall survival was significantly better for those overexpressing p53 (10-year cumulative survival rate 68% v 44%, P = .004). In multivariate analysis, M/ V index (P = .02), p53 (P = .02), and stage (P = .007) were statistically significant predictors of overall survival. When this analysis includes stratification according to the type of treatment received, M/V index (P = .007), stage (P = .0002), and p53 (P = .006) were even more significant predictors of overall survival. No association between p53 status and proliferative activity was found. CONCLUSION: Overexpression of p53 is associated with favorable disease-free and overall survival in laryngeal squamous cell carcinoma. It may also have an independent prognostic value in laryngeal cancer. M/V index, p53 overexpression, and stage predict with significant accuracy the 10-year overall survival.

Adult↗

PubMed1997

Training a large number of laboratory mice using running wheels and analyzing running behavior by use of a computer-assisted system.

A great many studies in the literature describe the variety of ways to provide physical training to small laboratory animals. Forced running on a treadmill or swimming training require considerable effort from the researcher, but permit the investigator to control the amount of exercise. Another option is to provide animals with access to running wheels, which they can voluntarily operate. Wheels can be used to investigate the running behavior of the animals. Wheel motion usually has been detected with magnets and microswitches and has been recorded using strip chart recorders or electromechanical counters. Computers also have been used in recording, but the measured parameters usually have been able to define only the total distance run in a fixed period. We designed a system, using running wheels, that can be used for long periods, up to years, for training a large number of laboratory mice simultaneously (maximal n = 96). The running parameters estimated by our system include running distance, speed, and time. Cumulative estimates of the running parameters can be produced for any period, as short as 1 sec. It is also easy to perform statistical analyses on the data. Using the system, we investigated the running behavior of 21 young C57BL/6 male mice. After the fast growth period, until 8 weeks of age, the mice ran 4 to 5 km/day at an average speed of 23 m/min, and spent 3 h running each day. This took place during the hours of darkness.

Animals↗

PubMed1997

Small, dense LDL particle concentration correlates with plasminogen activator inhibitor type-1 (PAI-1) activity.

The relation between LDL subfractions and fibrinolytic activity was studied in 150 men aged 53 to 63 years. Apolipoprotein B (apoB) concentration in the most dense LDL-5 (r = 0.39, p <0.001) and LDL-6 (r = 0.43, p <0.001) subfractions associated with plasminogen activator inhibitor type-1 (PAI-1) activity. Subjects in the highest LDL-6 apoB tertile had higher PAI-1 (24.7 vs. 13.1 AU/ml, p <0.001) and lower t-PA (0.26 vs. 0.54 IU/ml, p <0.001) activities than men in the lowest tertile. The difference in PAI-1 remained after adjusting for either triglycerides (p = 0.039) or insulin (p = 0.015) with cardiorespiratory fitness as an additional covariate, and history of cardiovascular disease and smoking as factors. In a regression analysis, plasma insulin and LDL-6 apoB, but not plasma triglycerides and body mass index, entered the model, and explained 30.6 and 3.9% of the variance in PAI-1 activity, respectively. The novel finding of the present study was the independent association between small, dense LDL particles and PAI-1 activity in middle-aged men.

Analysis of Variance↗

PubMed1996

Advances in the diagnosis of respiratory virus infections.

BACKGROUND: Advances have been made in selecting sensitive cell lines for isolation, in early detection of respiratory virus growth in cells by rapid culture assays, in production of monoclonal antibodies to improve many tests such as immunofluorescence detection of virus antigens in nasopharyngeal aspirates, in highly sensitive antigen detections by time-resolved fluoroimmunoassays (TR-FIAs) and biotin-enzyme immunoassays (BIOTH-E), and, finally, in the polymerase chain reaction (PCR) detection of respiratory virus DNA or RNA in clinical specimens. All of these advances have contributed to new or improved possibilities for the diagnosis of respiratory virus infections. OBJECTIVES AND STUDY DESIGN: This review summarizes our experiences during the last 15 years in the development of diagnostic tests for respiratory virus infections, and in use of these tests in daily diagnostic work and in epidemiological studies. RESULTS: Immunofluorescence tests based on monoclonal antibodies, all-monoclonal TR-FIAs, and biotin-enzyme immunoassays (EIAs) have about the same sensitivities and specificities. They compare well with the sensitivity of virus culture. PCR followed by liquid-phase hybridization is a sensitive method for detecting adenovirus DNA and enterovirus and rhinovirus RNA in clinical specimens. IgG EIA on paired acute and convalescent phase sera is the most sensitive serological test for respiratory virus infections and is a valuable reference method when evaluating the sensitivity of new diagnostic tests. The IgG avidity test can distinguish primary infections from re-infections at least in respiratory syncytial virus (RSV) infections. IgM antibody assays, on the other hand, had low sensitivities in our studies. CONCLUSIONS: The choice of diagnostic methods for respiratory virus infections depends on the type and location of the laboratory, the number of specimens tested, and the previous experience of the laboratory. Virus culture, whenever possible, should be the basic diagnostic method; the results, including identification of the virus, should be available no more than 24 h later than the results of rapid diagnostic tests. In small laboratories, especially in hospitals where specimen transportation is well organized, immunofluorescence may be the best choice for antigen detection with the provision that an experienced microscopist and a good UV microscope are available. If the laboratory receives a large number of specimens and has previous experience with EIAs, then biotin-EIAs or TR-FIAs may be the most practical techniques. Their advantages include the stability of the antigens in clinical samples since intact, exfoliated epithelial cells are not required, treatment of specimens is practical, testing of large numbers of specimens is possible, and reading the printed test result is less subjective than reading fluorescence microscopy. The larger role of PCR in the diagnosis of respiratory virus infections depends on future developments such as practical methods to extract DNA or RNA and to purify the extracts from nonspecific inhibitors, plus further improvements to minimize cross-contamination. Group-specific detection of enteroviruses and rhinoviruses is an example of the potential for PCR technology. In experienced laboratories. EIA IgG antibody tests should be available. Recombinant antigens may be a useful part of such assays.

Journal Article↗

PubMed1996

Five-year survival after intensive care--comparison of 12,180 patients with the general population. Finnish ICU Study Group.

OBJECTIVES: A) To examine the long-term survival of critically ill patients compared with the general population in a nationwide sample of patients requiring intensive care; and b) to analyze long-term survival stratified by specific diagnostic subgroups. DESIGN: Prospective, inception cohort study. SETTING: Twenty-five Finnish Intensive care units (ICUs) at 17 hospitals, including 13 ICUs in five tertiary care centers. PATIENTS: A consecutive sample of 12,180 adult patients who were admitted to ICUs in 1987. The sample was further divided into seven diagnostic subgroups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Vital status at 5 yrs after admission to an ICU was examined and compared to the age- and gender-adjusted survival of Finland's general population. Among ICU patients, the 5-yr mortality rate was 3.3 times that of Finland's general population (95% confidence interval 3.0 to 3.4). At 2 yrs, the survival rate paralleled that of the general population. At 5 yrs, the relative survival rate of the ICU patients was 66.7%. Cancer was a strong determinant of a poor outcome in multivariate analysis (relative risk 3.17; 95% confidence interval 2.86 to 3.51). The 5-yr mortality rate of the ICU patients compared with the general population was highest among patients admitted to the ICU after intoxication. Trauma victims and patients admitted to the ICU with a cardiovascular diagnosis reached the risk of death of the general population in the shortest time. CONCLUSIONS: ICU patients reached a life expectancy similar to the general population, on average, 2 yrs after admission. The time after which the survival parallels that of the general population depends, however, on the diagnostic category.

APACHE↗

PubMed1996

Identification of enteroviruses in clinical specimens by competitive PCR followed by genetic typing using sequence analysis.

A sensitive method based on competitive PCR was developed to detect and quantitate enteroviral RNA in clinical specimens, with special emphasis on controlling contamination and the presence of potential inhibitory factors in the specimens. Oligonucleotide primers from the conserved parts of the 5' untranslated and VP2 capsid protein-coding regions were selected to differentiate between enteroviruses and rhinoviruses on the basis of the length of the cDNA amplicons. RNA transcribed from a truncated cDNA copy of the echovirus 11 genome was used as an internal control for the reverse transcription reaction and PCR. This allowed simple differentiation of the control and viral PCR products from each other by agarose gel electrophoresis and nonradioactive quantitation of the viral RNA in the clinical specimens. By direct sequencing of the PCR products and subsequent computer analysis of the data, potential laboratory contaminations could be monitored and enteroviruses from clinical samples could be grouped into four distinct clusters, thus enabling genetic typing of the viruses. The described method can be applied to the diagnosis and epidemiology of enteroviral infections.

Base Sequence↗

PubMed1995

Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein.

BACKGROUND: The epsilon 4 allele of apolipoprotein E has been associated with an increased risk of late-onset Alzheimer's disease. In a cohort of elderly subjects we prospectively investigated the relation between the apolipoprotein E genotype, dementia, and the accumulation of beta-amyloid protein in the cerebral cortex. METHODS: Autopsy involving neuropathological analysis and DNA analysis of frozen blood samples were performed in 92 of 271 persons who were at least 85 years of age, who had been living in Vantaa, Finland, on April 1, 1991, and who had died between that time and the end of 1993. All subjects had been tested for dementia. Apolipoprotein E genotyping was done with a solid-phase minisequencing technique. The percentage of the cortex occupied by methenamine silver-stained plaques was used as an estimate of the extent of beta-amyloid protein deposition. RESULTS: The frequency of the epsilon 4 allele was significantly higher in the subjects with Alzheimer's disease than in the subjects without dementia (30 percent vs. 8 percent, P < 0.001). There was a greater accumulation of beta-amyloid protein in the brain and more neurofibrillary tangles in the subjects with the epsilon 4 allele than in those without it (P < 0.001). The deposition of beta-amyloid protein varied according to the genotype in both the subjects with dementia and those without dementia: it was lowest in those with the epsilon 2/epsilon 3 genotype, intermediate in those with the epsilon 3/epsilon 3 genotype, and highest in those with the epsilon 3/epsilon 4 genotype. A single subject had the epsilon 4/epsilon 4 genotype and had dementia. CONCLUSIONS: The epsilon 4 allele of apolipoprotein E is significantly associated with Alzheimer's disease. Even in elderly subjects without dementia, the apolipoprotein E genotype is related to the degree of deposition of beta-amyloid protein in the cerebral cortex.

Aged↗

PubMed1995

Lifelong moderate running training increases the incidence and severity of osteoarthritis in the knee joint of C57BL mice.

BACKGROUND: Inbred C57BL male mice express a high incidence of spontaneous osteoarthritis of the knee joint at the age of 18 months. We used this strain of mice to find out the effects of life-long, moderate running exercise on the health of articular cartilage and the incidence of osteoarthritis. METHODS: Male mice (294) were divided into controls and runners. The runners were trained daily between 2 and 18 months of age. The speed was 13.3 m/min and the distance on a flatbelt treadmill was 1,000 m/day. The mice were sacrificed at the ages of 2, 6, 10, 14, and 18 months. The knee joints were sectioned in frontal direction and the osteoarthritic changes were graded using a conventional light microscope. The reproducibility of the grading method was tested by calculating the extended kappa-coefficient for the results of six researchers. RESULTS: The incidence of osteoarthritis at the age of 18 months increased from 72% in controls to 88% in runners in the medial tibial condyles (P < 0.05), and from 80 to 96% in the lateral tibial condyles (P < 0.001). The incidence of the most severe osteoarthritic changes rose from 16% in controls to 36% in runners in the medial tibial condyles, and from 4 to 36% in the lateral tibial condyles. CONCLUSION: According to our results, the moderate, long-lasting running exercise accelerates the development of osteoarthritis in the knee joints of C57BL mice.

Animals↗

PubMed1995

The patients' opinions about curative factors in involuntary treatment.

The patients' opinions about their treatment are seldom solicited in psychiatry. We studied the opinions of 225 patients about curative factors in their treatment in a maximum security hospital: 90% answered the questions, which evaluated 38 forms of treatment. The patients received help from free walking in the hospital area in 98% of the patients, holidays in 93%, a personal psychiatric nurse in 91%, trips in 91%, communication in 88%, personnel's support in 87% and a psychiatrist in 86%. Medication was considered helpful in 77% and even restriction or isolation in 36% of the patients. If the patient experienced help from the psychiatrist, the cross-tabulation revealed that she or he also received help from many other treatment forms, even from the isolation. Help from the personal psychiatric nurse and medication depended on many other treatment forms. The most helpful treatment factors experienced were liberties and interactive treatment forms.

Attitude to Health↗

PubMed1995

Detection of enteroviruses and rhinoviruses in clinical specimens by PCR and liquid-phase hybridization.

A sensitive method based on PCR followed by liquid-phase hybridization for detection of enterovirus and rhinovirus RNAs in clinical specimens and cell culture supernatants is described. RNA was extracted from stool samples, throat swabs, nasopharyngeal aspirates, cerebrospinal fluid, urine, and plasma with a commercial phenol-guanidinium-chloroform reagent and purified on a polysulfone membrane, on which the reverse transcriptase reaction was also done. Two sets of oligonucleotide primers from the 5' noncoding region of picornaviruses were selected for DNA amplification of 153-bp (enterovirus) and 120-bp (rhinovirus) regions. Double-stranded amplicons were digested into single strands with T7 gene 6 exonuclease and quantitated by an assay using a europium-labeled probe, streptavidin- and biotinylated probe-coated microtitration wells, and time-resolved fluorometry. The sensitivity of the assay was about one template molecule when purified coxsackievirus A9 RNA was used. All enterovirus prototype strains, except echoviruses 22 and 23, and clinical isolates grown in cell culture or suckling mice were strongly positive by the enterovirus PCR-hybridization, as were selected prototype strains and untyped isolates of rhinoviruses by the rhinovirus PCR-hybridization. In a series of 100 clinical specimens tested, the results for 92 agreed with virus culture results. The detection method described will be useful in etiopathogenic studies on enteroviruses and rhinoviruses.

Animals↗

PubMed1995

Validity assessment of a social support index.

The purpose of this study was to reevaluate the psychometric properties of the social support sumindex used earlier in a Swedish longitudinal study. The results based on the data of a cross-sectional survey in 1992. A randomly selected cohort consisted of 212 men, aged 50 to 60 years. The population sample (n = 4853) was resident in Kuopio Province, Eastern Finland. The 34-item-index was stable. Item-total and item-item coefficients showed low internal consistency of the overall index and of most of the subindices. The index had good content validity. Limited evidence of construct validity was noticed. Index assessed well person's social network and support level, and association between the blood pressure and some of the subindices was noticed. The eight underlying subindices did not emerge in factor analysis. Before further using this index we propose its shortening with six items and re-grouping items into subindices.

Arteriosclerosis↗

PubMed1994

Lyme borreliosis associated with complete flaccid paraplegia.

We report the case of a patient with concomitant Lyme borreliosis and acute paraplegia. The paraplegia was complete, flaccid and of upper motor neurone type. The diagnosis of borreliosis was based on the detection of large amounts of IgM and IgG borrelia antibodies in the acute phase serum and on the complete disappearance of IgM antibody during the review period. IgG borrelia antibodies were also detected in the CSF, but leakage of antibodies from the blood to the intrathecal space could not be ruled out. Lymphocytosis and increased total protein concentration in the CSF were signs compatible with neuroborreliosis. Ceftriaxone therapy effected dramatic recovery of the patient. This case suggests that borreliosis should be considered a possible cause of acute flaccid paraplegia.

Acute Disease↗

PubMed1994

DNA analysis in Finnish patients with hereditary neuropathy with liability to pressure palsies (HNPP).

Hereditary neuropathy with liability to pressure palsies (HNPP) is a dominantly inherited disorder that presents as recurrent mononeuropathies precipitated by apparently trivial traumas. The presence of a deletion in 17p11.2 was analysed in 13 Finnish families with HNPP. The deletion was found in all patients who were neurologically and neurophysiologically confirmed to have HNPP. In the problematic cases the detection of the gene defect is the method of choice in the diagnosis of HNPP. Analysis of DNA can also be used to detect clinically unaffected family members.

Chromosome Deletion↗