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Biomedical subjects

P Halonen

Publications and source records attributed to P Halonen.

At least 19 recordsLinked to original sources

Spacer prostheses in two-stage revision of infected knee arthroplasty.

At present, no consensus exists on the best spacer alternative for the management of two-stage exchange arthroplasty of infected knee arthroplasties. In this retrospective study, patient records of 24 patients, who had undergone two-stage revisions in which resterilised prosthetic components were used as spacers, were reviewed. The outcome was compared to that of operations performed during the same period (1993-2003) using cement spacers (n=10). With an average follow-up of 32 months, control of infection was achieved in 26 cases (76%), with good or excellent clinical outcome in 19 cases (56%). Treatment failed and resulted in amputation at the level of the thigh before reimplantation in one case. Three patients did not undergo reimplantation. In four cases (12%) infection relapsed. The reinfection rate did not differ between the two spacer groups. Patients treated with resterilised components had a superior range of motion during the period between the two stages. Operative time was shorter and there was less blood loss in the reimplantation arthroplasty when a prosthetic spacer was used. We consider resterilised prosthetic components a safe and effective alternative to cement spacers in the management of infected knee arthroplasties.

Adult↗

Role of cage material, working style and hearing sensitivity in perception of animal care noise.

During daily care, laboratory animals are exposed to a variety of sounds which may have effects on welfare and also cause physiological and behavioural changes. So far, almost no attention has been paid to individual sounds or the sound level caused by animal care or the sound level inside the animal cage. In this study, sounds from selected rat care procedures were recorded: pulling cage out of the rack, placing it onto a table and replacing the cage back into the rack; with measurements made inside the rat cage and in the adjacent cage. Diet was poured into the food hopper and sounds were recorded inside the cage and also the adjacent cage. The work was repeated in a calm and also in a hurried style, using stainless steel and polycarbonate cages. Finally, the sounds produced by running tap water were recorded. Differences between rat and human hearing were compared using novel species-specific sound level weightings: R-weighting for rats dB(R) and H-weighting for human dB(H). Hurried work with steel caused sound exposure levels exceeding 90 dB(R) when the cages were placed into the rack and about 80 dB(R) when pulling them out of the rack or placing onto a table. With polycarbonate, the levels were 10-15 dB(R) lower. Unhurried calm working produced lower sound exposure levels than hurried working in many procedures. When the procedures were repeated with measurements in the adjacent cage, the sound exposure levels were lower, but the results were similar. Pouring food pellets into a hopper above the rat's head caused 15 dB(R) higher sound exposure levels than pouring food to an adjacent cage. In general, humans hear these sounds about 10-15 dB louder than rats. In conclusion, cage material, working style and hearing sensitivity all have an impact on the sound exposure level in the rodent cage. With correct working methods, high sound levels can be efficiently avoided in most cases.

Animal Welfare↗

The C/C-13910 genotype of adult-type hypolactasia is associated with an increased risk of colorectal cancer in the Finnish population.

BACKGROUND AND AIMS: The role of nutrition in the pathogenesis of colorectal cancer is not fully understood. Milk products are an essential part of human nutrition in Western countries. Absorption of lactose, the main sugar of milk, is regulated by the activity of the lactase enzyme in the gut wall. The activity of lactase is genetically determined and is associated with a C/T single nucleotide polymorphism residing 13910 bp upstream of the lactase coding sequence. Here we have studied the relationship between the C/T(-13910) polymorphism and colorectal cancer in Finnish, British, and Spanish populations. PATIENTS AND METHODS: A total of 2766 subjects, including 963 Finnish, 283 British, and 163 Spanish subjects with colorectal cancer, and 773 Finnish, 363 British, and 221 Spanish control subjects, were genotyped for the C/T(-13910) variant by polymerase chain reaction minisequencing. RESULTS: The C/C(-13910) genotype, which is a robust molecular marker of low lactase activity (lactase non-persistence), was found to significantly associate with the risk of colorectal cancer (p = 0.015) in the Finnish subjects, with an odds ratio of 1.40 (95% confidence interval 1.07-1.85). No association was found with site, histology, or stage of the tumour. No significant risk was detected in the British or Spanish populations. CONCLUSION: Low lactase enzyme activity, defined by genotyping of the C/T(-13910) variant, may increase the risk of colorectal cancer. Further studies are warranted to investigate the role of milk and other dairy products in the pathogenesis of colon cancer in different populations.

Adult↗

Revision total knee arthroplasty with the Total Condylar III system in inflammatory arthritis.

We report a consecutive series of 16 revision total knee arthroplasties using the Total Condylar III system in 14 patients with inflammatory arthritis which were performed between 1994 and 2000. There were 11 women and three men with a mean age of 59 years (36 to 78). The patients were followed up for 74 months (44 to 122). The mean pre-operative Knee Society score of 37 points (0 to 77) improved to 88 (61 to 100) at follow-up (t-test, p < 0.001) indicating very good overall results. The mean range of flexion improved from 62 degrees (0 degrees to 120 degrees) to 98 degrees (0 degrees to 145 degrees) (t-test, p < 0.05) allowing the patients to stand from a sitting position. The mean Knee Society pain score improved from 22 (10 to 45) to 44 (20 to 50) (t-test, p < 0.05). No knee had definite loosening, although five showed asymptomatic radiolucent lines. Complications were seen in three cases, comprising patellar pain, patellar fracture and infection. These results suggest that the Total Condylar III system can be used successfully in revision total knee arthroplasty in inflammatory arthritis.

Adult↗

Prediction of mobilisation failure in patients with non-Hodgkin's lymphoma.

Factors affecting progenitor cell mobilisation in patients with non-Hodgkin's lymphoma (NHL) are incompletely understood. We have analysed factors predicting mobilisation failure in 97 consecutive patients with NHL (59 males, 38 females; median age 49 years) who received mobilisation with intermediate-dose CY (4 g/m(2)) followed by G-CSF. The histology included large cell B (N=50), mantle cell (N=16), follicular (N=16) and other NHL (N=15). The disease status was 1CR/PR/primary refractory in 66 patients and >1 CR/PR in 31 patients. The minimum criterion for successful mobilisation was the collection of >or=1.5 x 10(6)/kg CD34(+) cells. In all, 18 patients (19%) failed to reach this threshold. In univariate analysis, premobilisation factors associated with mobilisation failure included BM involvement at the time of diagnosis (P=0.001) or prior to mobilisation (P=0.001) and low platelet count just prior to mobilisation (P=0.001). In multivariate analysis, only BM involvement at diagnosis (P=0.004) and platelet count just prior to mobilisation (P=0.01) were associated with mobilisation failure. A mathematical model based on these two factors and presented in the form of a receiver operating characteristics curve showed a sensitivity of 0.71 and a specificity of 0.77 in the prediction of mobilisation failure. Patients at a high risk of mobilisation failure may benefit from novel approaches.

Adolescent↗

Patient-controlled epidural technique improves analgesia for labor but increases cesarean delivery rate compared with the intermittent bolus technique.

BACKGROUND: We tested the hypothesis that patient-controlled epidural analgesia for labor (PCEA) provides better analgesia and satisfaction than the intermittent bolus technique (bolus) without affecting the mode of delivery. METHODS: We randomized 187 parturients to receive labor analgesia using either the PCEA or bolus technique. The PCEA group received a starting bolus of 14 mg of bupivacaine and 60 micro g of fentanyl in a 15-ml volume, followed by a background infusion (bupivacaine 0.08% and fentanyl 2 microg ml(-1)) 5 ml h(-1) with a 5-ml bolus and 15-min lock-out interval. The bolus group received boluses of 20 mg of bupivacaine and 75 micro g of fentanyl in a 15-ml volume. RESULTS: Parturients in the PCEA group had significantly (P < 0.05-0.01) less pain during the first and second stages of labor. There was no difference in the spontaneous delivery rate between the groups, but the cesarean delivery rate was significantly (P < 0.05) higher (16.3% vs. 6.7%) in the PCEA group than in the bolus group. Bupivacaine consumption was significantly (P < 0.01) higher (11.2 mg h(-1) vs. 9.6 mg h(-1)) and the second stage of labor was significantly (P < 0.01) longer (70 min vs. 54 min) in the PCEA group than in the bolus group. Patient satisfaction was equally good in both groups. CONCLUSION: The PCEA technique provided better pain relief. This was associated with higher bupivacaine consumption, prolongation of the second stage of labor, and an increased rate of cesarean section.

Adolescent↗

Investigation of the mechanisms of therapy-related hypoglycaemia in children with acute lymphoblastic leukaemia.

AIM: To determine the mechanisms of fasting hypoglycaemia occurring during maintenance therapy (MT) for childhood acute lymphoblastic leukaemia (ALL). METHODS: Thirty-five children and adolescents with ALL, aged 2.4-17.4 y, were fasted for up to 16 h during MT. Nineteen of the children developed hypoglycaemia after 11 to 16 h of fasting. Blood samples for determination of metabolic changes were taken on completion of fasting. Nineteen patients underwent a glucagon stimulation test after 4 to 16 h of fasting during MT. Erythrocyte concentrations of the metabolites of methotrexate (E-MTX) and 6-mercaptopurine (E-TGN) were measured at the time of fasting. Fifteen out of 19 patients who became hypoglycaemic were re-studied 3 to 4 mo after cessation of therapy. RESULTS: In the hypoglycaemia group, plasma levels of gluconeogenic amino acids alanine and glutamine were lower (medians 117 vs 190 micromol L(-1), p = 0.009, and medians 396 vs 448 micromol L(-1), p = 0.031, respectively) than in the normoglycaemia group. Serum levels of free carnitine were lower (medians 20.3 vs 29.8 micromol L(-1), p = 0.027), free fatty acids higher (medians 3.09 vs 1.23 mmol L(-1), p < 0.001) and marked dicarboxylic aciduria was more common in the patients with hypoglycaemia (in 14/16 vs in 2/14, p < 0.001). Impaired responses to glucagon stimulation occurred in 36% (4/11) in the hypoglycaemia group and in 12.5% (1/8) in the normoglycaemia group (p = 0.243). No significant differences were detected in E-MTX and E-TGN between the groups. Most of the metabolic abnormalities returned to normal after cessation of chemotherapy. CONCLUSIONS: Low levels of gluconeogenic amino acids, especially of alanine, are associated with hypoglycaemia. Reduced hepatic glycogen stores may also be involved in the aetiology.

Adolescent↗

Effects of gestational age and prenatal and perinatal events on the coagulation status in premature infants.

OBJECTIVE: To study prospectively the effects of prematurity and perinatal events on the coagulation status of premature infants. PATIENTS AND MAIN OUTCOME MEASURES: Blood samples from premature infants born before 37 gestational weeks were taken for analysis of coagulation factors II, V, VII, and X and platelet count. RESULTS: A total of 125 premature infants, 71 boys, were studied at the median postnatal age of 40 minutes (range 12-100). The lowest median activities of coagulation factors II, V, VII, and X and the platelet count were observed, as expected, in infants (n = 21) born at 24-27 weeks gestation. Twin B (n = 14) had lower median activities of coagulation factors II, V, VII, and X than twin A. Infants with evidence of mild asphyxia (Apgar score at 5 minutes < 7 or cord pH < 7.26) had significantly (p < 0.05) lower levels of coagulation factors II, V, VII, and X and platelet counts than infants without asphyxia. Infants who were small for gestational age (SGA) had significantly (p < 0.05) lower levels of coagulation factors V and VII and platelet counts than infants of appropriate size for gestational age. Other prenatal and perinatal variables examined (sex, maternal hypertension and/or pre-eclampsia, antenatal steroid use, mode of delivery, Apgar scores) did not show any significant associations with coagulation status, which may be explained by the small number of infants studied. CONCLUSIONS: The data strongly suggest that there are distinct differences in specific coagulation tests in different patient populations, which could assist in the identification of extremely preterm, SGA, or asphyxiated preterm infants who may be susceptible to haemorrhagic problems perinatally.

Asphyxia Neonatorum↗

Factors related to non-compliance with antihypertensive drug therapy.

The objectives were to study the associations of perceived health care-related and patient-related factors with self-reported noncompliance with antihypertensive treatment. General practitioners identified all of their hypertensive patients in 26 health centres during 1 week in 1996 (n = 2219). A total of 1782 (80%) patients participated in the study, of whom 1561 were on antihypertensive medication. Based on 82 opinion statements in two questionnaires, 14 problem indices were formed by using factor analysis. Out of these, summary variables concerning problems related to the health care system and the patients were formed. Logistic regression models, including interaction analyses, were used to study the associations with non-compliance. The results were that the majority of patients had at least one perceived health care system-related (88%) and patient-related problem (92%). A high number of both perceived health care system-related problems (adjusted OR 4.77; 95% CI 2.76, 8.26) and patient-related problems (adjusted OR 3.23; 95% CI 1.79, 5.81) were associated with self-reported non-compliance. The experience of adverse drug effects was also associated with non-compliance (adjusted OR 1.41; 95% CI 1.03, 1.94). In conclusion self-reported non-compliance was associated with multiple risks of both perceived health care system-related and patient-related problems.

Aged↗

Emotional reactions and life changes of caregivers of demented patients when home caregiving ends.

Many studies indicate that the cessation of caregiving of demented patients has positive effects on caregivers' lives but contradictory findings have also been reported. The aim of this study was to investigate how the caregivers of demented patients experienced the cessation of caregiving, how caregivers' lives changed after this event, and which factors predicted emotional reactions and life changes. Data were collected from 64 caregivers of demented patients, recruited from a previous controlled intervention study. The semi-structured telephone interviews sought (1) sociodemographic data, (2) emotional reactions the caregivers recalled from the point of cessation of caregiving, and (3) life changes experienced after that time point. At the point of cessation of caregiving, spouse caregivers had higher risk for loneliness, depressive feelings and sorrow than non-spouse caregivers. Feelings of relief were associated with non-spouses. Community care support obtained during the previous intervention study had protected the caregivers from loneliness, depressive feelings and sorrow. After the end of caregiving, spouse caregivers tended to experience more negative life changes. The increased number of leisure activities was associated with the support during community care.

Aged↗

A double-blinded, randomized comparison of intrathecal and epidural morphine for elective cesarean delivery.

UNLABELLED: We randomized 150 parturients into a double-blinded trial to receive intrathecal (IT) 100 microg (IT 100 group) or 200 microg (IT 200 group) or epidural 3 mg (Epidural group) of morphine for elective cesarean delivery with a combined spinal/epidural technique. The patients additionally received ketoprofen 300 mg/d. Postoperative pain relief and side effects were registered every 3 h up to 24 h, and all patients were interviewed on the first postoperative day. Pain control was equally good, but the parturients in the IT 100 group requested rescue analgesics more often compared with the other groups (P < 0.05). Itching was a common complaint and was reported by 74% of the parturients in the Epidural group and 65% and 91% in the IT 100 and IT 200 groups, respectively (P < 0.01). Medication for itching was requested by 44%, 24%, and 45% of the patients, respectively (P < 0.05). There was no difference in postoperative nausea or vomiting. The pain relief was perceived as good by >90% of the patients in all groups. In conclusion, because of the decreased incidence of and lesser requirements of medication for itching, IT morphine 100 microg with ketoprofen is recommended in cesarean deliveries. Rescue analgesics nevertheless need to be prescribed. IMPLICATIONS: Spinal morphine is an effective analgesic after cesarean delivery, but it has several side effects. The purpose of this study was to compare the prevalence of side effects and the level of analgesia of epidural morphine with two different doses of spinal morphine after elective cesarean delivery. Although rescue analgesics may be required, intrathecal morphine 100 microg is suggested for postoperative analgesia after cesarean delivery.

Adult↗

Apolipoprotein E gene promoter (-219G/T) polymorphism is associated with premature coronary heart disease.

The relationship of two apolipoprotein (apo) E gene polymorphisms and coronary heart disease (CHD) was investigated in 118 Finnish families with premature CHD and in 110 healthy control subjects. Affected siblings and probands with premature CHD had higher frequencies of the T allele of the -219G/T promoter polymorphism and the epsilon 4 allele (genotypes epsilon 4/3 or epsilon 4/4) of the apo epsilon 2/epsilon 3/ epsilon 4 polymorphism than those of healthy control subjects. Additionally, when the two apo E gene polymorphisms were combined, affected siblings and probands had a higher frequency of the -219T allele and the epsilon 4 allele combinations than did healthy controls. The -219T and the epsilon 4 alleles both separately and together were associated with higher levels of 2-h glucose in an oral glucose tolerance test. These results indicate that the two polymorphisms of the apo E gene have similar effects on the risk of coronary atherosclerosis in families with premature CHD. This risk was not explained by the effect of apo E gene polymorphisms on cholesterol metabolism, but their effect on cardiovascular risk factor clustering with insulin resistance may be of importance. We conclude that in addition to the epsilon 4 allele, also the -219G/T promoter polymorphism of the apo E gene is associated with early onset CHD.

Age of Onset↗

Quaternary structure and metal ion requirement of family II pyrophosphatases from Bacillus subtilis, Streptococcus gordonii, and Streptococcus mutans.

Pyrophosphatase (PPase) from Bacillus subtilis has recently been found to be the first example of a family II soluble PPase with a unique requirement for Mn2+. In the present work, we cloned and overexpressed in Escherichia coli putative genes for two more family II PPases (from Streptococcus mutans and Streptococcus gordonii), isolated the recombinant proteins, and showed them to be highly specific and active PPases (catalytic constants of 1700-3300 s(-)1 at 25 degrees C in comparison with 200-400 s(-)1 for family I). All three family II PPases were found to be dimeric manganese metalloenzymes, dissociating into much less active monomers upon removal of Mn2+. The dimers were found to have one high affinity manganese-specific site (K(d) of 0.2-3 nm for Mn2+ and 10-80 microm for Mg2+) and two or three moderate affinity sites (K(d) approximately 1 mm for both cations) per subunit. Mn2+ binding to the high affinity site, which occurs with a half-time of less than 10 s at 1.5 mm Mn2+, dramatically shifts the monomer <--> dimer equilibrium in the direction of the dimer, further activates the dimer, and allows substantial activity (60-180 s(-)1) against calcium pyrophosphate, a potent inhibitor of family I PPases.

Bacillus subtilis↗

Ligand binding sites in Escherichia coli inorganic pyrophosphatase: effects of active site mutations.

Type I soluble inorganic pyrophosphatases (PPases) are well characterized both structurally and mechanistically. Earlier we measured the effects of active site substitutions on pH--rate profiles for the type I PPases from both Escherichia coli (E-PPase) and Saccharomyces cerevisae (Y-PPase). Here we extend these studies by measuring the effects of such substitutions on the more discrete steps of ligand binding to E-PPase, including (a) Mg(2+) and Mn(2+) binding in the absence of added ligand; (b) Mg(2+) binding in the presence of either P(i) or hydroxymethylbisphosphonate (HMBP), a competitive inhibitor of E-PPase; and (c) P(i) binding in the presence of Mn(2+). The active site of a type I PPase has well-defined subsites for the binding of four divalent metal ions (M1--M4) and two phosphates (P1, P2). Our results, considered in light of pertinent results from crystallographic studies on both E-PPase and Y-PPase and parallel functional studies on Y-PPase, allow us to conclude the following: (a) residues E20, D65, D70, and K142 play key roles in the functional organization of the active site; (b) the major structural differences between the product and substrate complexes of E-PPase are concentrated in the lower half of the active site; (c) the M1 subsite is functionally isolated from the rest of the active site; and (d) the M4 subsite is an especially unconstrained part of the active site.

Amino Acid Substitution↗

Delirium in the non-demented oldest old in the general population: risk factors and prognosis.

BACKGROUND: The oldest old are prone to develop delirium. Studies into risk factors for delirium have been carried out predominantly in younger age groups. The aim of this population-based follow-up study was to investigate the risk factors for delirium requiring medical attention and subsequent prognosis in the non-demented general population aged > or = 85 years. METHOD: The study included the non-demented subjects in the population-based Vantaa 85+ study. After the 3-year observation period, 199 subjects (91% of those surviving) were re-examined and their medical records were evaluated for episodes of delirium. The subjects were followed up with respect to mortality for another 2 years. RESULTS: During the 3-year observational period, 20 subjects (10%) had been diagnosed as having had an episode of delirium. A Mini-Mental State Examination score of < 24 (odds ratio (OR) 3.44, confidence interval (CI = 95%) 1.27-9.32) and high systolic blood pressure (OR 3.08, CI 1.08-8.79) were identified as independent risk factors for delirium. The association between the delirium episode and a new diagnosis of dementia was significant ( p = 0.001). The mortality rate was greater among those subjects who experienced delirium than among subjects without this syndrome ( p = 0.008). CONCLUSIONS: Mild cognitive impairment and high systolic blood pressure were found to be risk factors for delirium requiring medical attention in the general non-demented population aged > or = 85 years. The study also highlights the significant association between delirium and a new dementia diagnosis in this age group.

Aged↗

Free L-tryptophan plasma levels in antisocial violent offenders.

RATIONALE: Several studies have shown that impulsive violent behavior is associated with reduced serotonin metabolism in the brain, but no data exist on possible alterations of the serotonin precursor (free L-tryptophan) levels among violent offenders. OBJECTIVES: To study free L-tryptophan and kynurenine plasma levels among antisocial violent offenders. METHODS: Free L-tryptophan and competing amino acid (CAA) plasma levels were measured among 19 male impulsive antisocial violent offenders and 19 age-matched healthy male controls. RESULTS: Mean free L-tryptophan/(CAA) plasma levels were 160% (95% CI 116%-204%) higher among offenders than controls (P=0.000). Seventeen of the 19 offenders (89.5%) had values of more than 2 SD above the mean value of controls. The levels of kynurenine, the major metabolite of tryptophan, were slightly increased in offenders. CONCLUSION: Free plasma L-tryptophan/CAA levels were markedly increased among antisocial violent offenders indicating a disturbed tryptophan metabolism.

Adult↗

Association of angiotensin converting enzyme and plasminogen activator inhibitor-1 promoter gene polymorphisms with features of the insulin resistance syndrome in patients with premature coronary heart disease.

Polymorphisms of the angiotensin-converting enzyme (ACE) (insertion/deletion (I/D) in intron 16) and of the plasminogen activator inhibitor-1 (PAI-1) (promoter 4G/5G) genes have been linked with coronary heart disease (CHD) and/or myocardial infarction (MI). We studied the association of polymorphisms in these genes with CHD with linkage and association analyses in 118 families with premature and severe CHD and in 110 healthy controls. In linkage analysis there was no evidence for a linkage of the ACE or PAI-1 loci with CHD. However, in quantitative linkage analysis the ACE locus was linked with fasting glucose (P=0. 047) and fasting free fatty acid levels (P=0.029). In association analysis the ACE genotype frequencies of probands with CHD did not differ from those of healthy controls. Normoglycemic probands with MI and with the ACE polymorphism DD genotype had characteristics of the insulin resistance syndrome. They had higher levels of 1-h glucose (P=0.008) and 2-h free fatty acids (P=0.011) in an oral glucose tolerance test and higher levels of total (P=0.005) and very-low-density lipoprotein triglycerides (P=0.006) than probands with the ID or the II genotypes. The PAI-1 gene polymorphism was not associated with any of the variables of glucose or lipid metabolism. In conclusion, the ACE and PAI-1 gene polymorphisms are not linked with early-onset CHD. However, the ACE gene polymorphism is associated with features of the insulin resistance syndrome.

Aged↗