Oral lysine feeding in gyrate atrophy with hyperornithinaemia--a pilot study.
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Administration, Oral↗
Biomedical subjects
K Pulkki
Publications and source records attributed to K Pulkki.
Serum oncostatin M in multiple myeloma: impact on disease severity and prognosis.
Since high levels of serum IL-6 predict a poor prognosis of patients with multiple myeloma (MM), we investigated if a related cytokine, oncostatin M (OSM), correlates with clinical or biochemical findings or has prognostic significance in patients with MM. Among 82 newly diagnosed MM patients, OSM was detected in the sera in 45 (55%). Serum OSM had a borderline statistical correlation with serum IL-6 (r = 0.198, p = 0.074) and C-reactive protein (r = 0.199, p = 0.074) concentrations. However, OSM did not have prognostic significance alone or in combination with other factors. The median survival of patients with detectable serum OSM concentration was 41 months (range 2-124 months) and of OSM negative patients 35 months (1-75 months). Serum OSM concentration was not associated with clinical factors or severity of bone disease at diagnosis. We conclude that serum OSM concentration is not a prognostic factor in MM patients.
Adult↗
Interferon-alpha treatment decreases serum cross-linked C-terminal telopeptide of type I collagen in haematological diseases.
Interferon-alpha (IFN-alpha) is used in the treatment of many haematological diseases and it is known that IFN-alpha may affect bone turnover. The effect of IFN-alpha on bone metabolism was studied in 10 haematological patients. The mean duration of the treatment was 4 (range: 2.8-7.2) months. Besides the usual markers of bone metabolism, levels of the cross-linked C-terminal telopeptide of type I collagen (ICTP), the N-terminal propeptide of type I procollagen (PINP) and the bone-specific alkaline phosphatase were measured. The bone mineral density was measured by computed tomography. During IFN-alpha treatment, serum ICTP decreased from a mean of 5.4 (range: 1.8-12.4) to 3.6 (range: 1.4-8.8) microg/l (P = 0.017). All other variables reflecting bone metabolism remained unaltered during IFN-alpha treatment. The bone mineral density remained unchanged. It was concluded that the observed decrease in ICTP may be an indicator of a beneficial therapeutic effect of IFN-alpha on bone turnover, resulting in decreased bone resorption. However, it is possible that elevated pretreatment ICTP values reflected disease of the bone marrow.
Adult↗
Serum soluble tumor necrosis factor-alpha receptor 2 is elevated in obesity but is not related to insulin sensitivity: a study in identical twins discordant for obesity.
Tumor necrosis factor-alpha (TNFalpha) and its soluble receptor 2 (TNFR2) are expressed in adipose tissue and are possibly involved in the pathogenesis of insulin resistance. Information about serum levels of TNFR2 in human obesity, especially the possible role of genetic factors and body fat distribution, is scanty. We measured serum TNFalpha and soluble TNFR2 concentrations in 23 identical twin pairs who had an average 18-kg intrapair difference in body weight. The mean TNFalpha concentration was 44.1 ng/L in obese and 34.2 ng/L in lean cotwins (P = 0.051). The respective values for TNFR2 were 1,989 and 1,840 ng/L (P = 0.004). The intrapair difference in TNFR2 level correlated positively (r-value always > or = 0.56; P < or = 0.01) with intrapair differences in body mass index, percent body fat, and abdominal sc fat area (assessed by magnetic resonance imaging), but not with differences in visceral fat area, glucose or insulin areas under the curve, or insulin sensitivity index in the oral glucose tolerance test. The intraclass correlation for TNFR2 was 0.67, and the genetic variation in circulating TNFR2 level was almost 6-fold higher than the variation due to obesity. We conclude that the soluble TNFR2 concentration is determined by both genetic factors and adiposity, especially sc fat. Measurement of circulating TNFR2 does not seem to be useful in identifying obese individuals who are insulin resistant.
Aged↗
Prediction of short-term outcome in patients with suspected myocardial infarction.
STUDY OBJECTIVE: Although specific cardiac injury markers have enhanced early patient classification, the ECG remains a necessary investigation in the acute phase of chest pain. Combined use of both tests could further improve the diagnostic and prognostic accuracy. METHODS: We studied 311 consecutive patients who came to the emergency department of a regional referral hospital for the differential diagnosis of acute chest discomfort. The admission ECG was classified using an automated interpretation program and tested together with elevated admission creatine kinase isoform MB (CK-MB) and cardiac troponin I (TnI) concentration for prediction of final myocardial injury (44%) and in-hospital mortality (14%). RESULTS: Combining the information from the admission ECG and cardiac markers, the sensitivity for becoming final myocardial injury (maximal CK-MB >/=11 microg/L) was 90% and specificity 61%. The proportion of false-negative results (10%) was independent of symptom duration. Age, positive ECG findings, and increased admission TnI levels were predictive for in-hospital mortality. CONCLUSION: The commonly available biochemical and ECG criteria allow risk stratification of patients with a suspected acute ischemic event. The data analysis can easily be automated and is independent of patient delay.
Adult↗
Rapid single-tube screening of the C282Y hemochromatosis mutation by real-time multiplex allele-specific PCR without fluorescent probes.
BACKGROUND: An accurate determination of the major HFE mutation (C282Y), which is associated with hereditary hemochromatosis, is important in diagnosis and risk assessment for this disease. We report a single-tube high-throughput PCR method for the detection of C282Y. METHODS: We combined three previously described principles: allele-specific PCR, mutagenically separated PCR, and amplicon identification by specific dissociation curves. PCR amplification was performed with fluorescence detection or conventional thermocycler using the same primers, reactant constituents, and cycling protocol. Primer cross-reactions were prevented by deliberate primer:primer and primer:template mismatches. RESULTS: PCR products were identified by their characteristic melting temperatures based on SYBR Green I fluorescence. For each of the 256 random and 17 known HFE C282Y samples, mutant homozygous, wild-type, and heterozygous samples were unequivocally distinguished. CONCLUSIONS: This homogeneous assay is rapid, reproducible, does not require fluorescent oligonucleotide probes, and correctly identifies HFE genotypes.
Alleles↗
Automated electrocardiographic scores to estimate myocardial injury size during the course of acute myocardial infarction.
The automated ST-elevation score at admission and maximal QRS score during hospitalization provide good estimates of biochemical injury size during the course of first myocardial infarction. Being easily computerized, such scores could be used routinely to monitor the effect of injury-limiting therapy.
Clinical Enzyme Tests↗
Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency.
Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterised by thymine-uraciluria in homozygous deficient patients and has been associated with a variable clinical phenotype. In order to understand the genetic and phenotypic basis for DPD deficiency, we have reviewed 17 families presenting 22 patients with complete deficiency of DPD. In this group of patients, 7 different mutations have been identified, including 2 deletions [295-298delTCAT, 1897delC], 1 splice-site mutation [IVS14+1G>A)] and 4 missense mutations (85T>C, 703C>T, 2658G>A, 2983G>T). Analysis of the prevalence of the various mutations among DPD patients has shown that the G-->A point mutation in the invariant splice donor site is by far the most common (52%), whereas the other six mutations are less frequently observed. A large phenotypic variability has been observed, with convulsive disorders, motor retardation and mental retardation being the most abundant manifestations. A clear correlation between the genotype and phenotype has not been established. An altered beta-alanine, uracil and thymine homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency.
Animals↗
Procalcitonin concentrations in patients with neutropenic fever.
To assess the usefulness of markers of inflammation in distinguishing bacterial infection from severe systemic nonbacterial inflammation, concentrations of procalcitonin, neopterin, endotoxin, tumor necrosis factor, and interleukin-6 were measured in 28 neutropenic patients at the onset of fever and twice thereafter at 4 h intervals. Infection was found in 11 patients, and 17 patients had fever of undetermined origin. The procalcitonin concentration increased rapidly in patients with infection: the response was detectable within 8 h of the onset of fever. Procalcitonin is a specific but not a sensitive marker of infection in patients with neutropenic fever. Its poor sensitivity was related to an absent or delayed response in patients with gram-positive infections. Considerable overlap between infected and noninfected patients was found in levels of endotoxin, tumor necrosis factor, and interleukin-6.
Adult↗
Bone mineral density after allogeneic bone marrow transplantation.
Bone turnover markers and bone mineral density (BMD) were studied in 25 adult patients (14 females, 11 males) who had undergone allogeneic bone marrow transplantation (BMT). The interval from BMT to the first examination was at least 1 year (mean 3, range 1-10). Mean age of the patients at the time of first evaluation was 42 (range 19-54) years. Blood samples and urine collections for evaluation of biochemical factors reflecting skeletal turnover were performed together with the first BMD measurement. BMD was measured from the lumbar vertebrae (L2 to L4) with computed tomography and results were expressed as Z-scores. At the time of the first measurement five patients (20%) had Z-scores <-2.5 s.d. and 12 patients (48%) between -1 and -2.5 s.d. In 12 patients BMD assessments were repeated and it seemed that reduction in BMD had mostly occurred during and shortly after BMT and remained the same during follow-up. The cross-linked carboxyterminal telopeptide of type I collagen (ICTP) correlated negatively with BMD (r = -0.45, P = 0.045) as did bone-specific alkaline phosphatase (BAP; r = -0.64, P = 0.002). No correlation between BMD and time interval from diagnosis to BMT, conditioning regimen, corticosteroid use or hospital stay during transplantation was found. In conclusion, bone disease is common after BMT. Our findings demonstrate an increased collagen and bone turnover and a high risk of osteoporosis. BMD measurements must be repeated regularly and collagen markers such as ICTP and BAP can be beneficial in estimating the activity of bone disease.
Adult↗
Is routine echocardiography useful in patients hospitalized for chest pain? Evidence of areal myocardial dysfunction detected only by echocardiography.
To assess the diagnostic value of routine two-dimensional echocardiography in the coronary care unit setting, we studied 81 unselected patients admitted for acute chest pain. Using electrocardiography (ECG), clinical history and serum markers of myocardial injury, the patients were retrospectively diagnosed as having had definite acute myocardial infarction (AMI) with (n=13) or without (n=31) previous infarction, possible AMI with (n=14) or without (n=15) previous infarction, and non-coronary cardiac or other causes of chest pain (n=8). Abnormal wall motion was observed in 75/77 patients with a cardiac origin of symptoms (sensitivity 97%), and there were no false-positive wall motion findings. In the 73 patients who were finally diagnosed with coronary artery disease (CAD), echocardiography showed wall motion abnormality in at least one additional coronary territory area in which there were no diagnostic ECG changes for 56% of patients with CAD (41/73) (P<0. 001). These areas were considered to be indicative of the presence of myocardium at risk for future cardiac events. We conclude that in addition to being a sensitive and accurate tool for detection of ischaemic wall motion abnormalities, two-dimensional echocardiography can give valuable information about the area of myocardium at risk. Therefore, therapeutic decisions can be affected by the findings of the routine echocardiographic examination, which is recommended even in unselected coronary care unit patients.
Adult↗
Muscle creatine phosphate in gyrate atrophy of the choroid and retina with hyperornithinaemia--clues to pathogenesis.
BACKGROUND: In gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), inherited deficiency of ornithine-o-aminotransferase leads to progressive fundus destruction and atrophy of type II skeletal muscle fibres. Because high ornithine concentrations inhibit creatine biosynthesis, the ensuing deficiency of high-energy creatine phosphate may mediate the pathogenesis. MATERIALS AND METHODS: Relative concentrations of inorganic phosphate (Pi), creatine phosphate (PCr) and ATP in resting calf muscle were recorded in 23 GA patients and 33 control subjects using 31P-magnetic resonance spectroscopy (MRS). Eight patients with autosomal recessive retinitis pigmentosa with matched control subjects constituted an additional reference group. RESULTS: The PCr/Pi and PCr/ATP ratios (means +/- SD) were lower for the GA patients than for healthy control subjects [4.66 +/- 0.37 vs. 9.75 +/- 2.17 (P < 0.0001) and 2.85 +/- 0.37 vs. 3.70 +/- 0.50 (P < 0.05) respectively]. In retinitis pigmentosa the respective values were 9.12 +/- 2.57 and 4.25 +/- 0.45. Age and stage of the disease had no effect. CONCLUSION: Muscle 31P-MRS spectra were markedly abnormal in all GA patients.
Adenosine Triphosphate↗
Cardiomyocyte apoptosis and progression of heart failure to transplantation.
BACKGROUND: Cardiomyocyte apoptosis has been found in congestive heart failure, but its clinical significance has been difficult to study. We compared the occurrence of cardiomyocyte apoptosis in explanted hearts with the progression of severe heart failure until the need for transplantation. DESIGN: Using the TUNEL assay, apoptotic cardiomyocytes were quantified in explanted failing hearts from patients with either idiopathic dilated cardiomyopathy (n = 21) or ischaemic heart disease (n = 14). The percentage was compared with the clinical severity and progression of endstage heart failure. Samples obtained at autopsy and during open heart surgery served as controls. RESULTS: The number of apoptotic cardiomyocytes was significantly increased in failing hearts regardless of aetiology (medians 0.075% in ischaemic heart disease and 0.119% in dilated cardiomyopathy) compared with control myocardium. In patients with dilated cardiomyopathy, apoptotic cardiomyocytes were more numerous in subjects with a rapidly deteriorating clinical course (0.192%, n = 10) than in patients with intermediate (0.093%, n = 6, P = 0.03) or slow (0.026%, n = 5, P = 0.003) progression. No such association was observed in patients with ischaemic heart disease, in whom we found significantly increased cardiomyocyte apoptosis adjacent to scars of previous infarctions (0.576%) in contrast to the diffuse distribution seen in dilated cardiomyopathy. Expression of Bcl-2, an antiapoptotic protein, was increased in all failing hearts by immunohistochemistry. CONCLUSION: Cardiomyocyte apoptosis is a consistent feature of end-stage heart failure in man and appears to be quantitatively related to the clinical severity of deterioration in dilated cardiomyopathy. Increased expression of Bcl-2 in cardiomyocytes indicates activation of an antiapoptotic response. These observations suggest that cardiomyocyte apoptosis is a clinically relevant and potentially modifiable pathophysiological phenomenon in severe heart failure.
Adult↗
Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia.
BACKGROUND: Eye fundus destruction and type II muscle fiber atrophy in gyrate atrophy of the choroid and retina with hyperornithinaemia (GA) may be mediated by elevated ornithine concentrations which strongly inhibit creatine biosynthesis. This results in deficiency of creatine phosphate (PCr), a key intracellular energy source, as we have demonstrated in skeletal muscle of the patients by 31P magnetic resonance spectroscopy (31P MRS). MATERIALS AND METHODS: Possible correction of the relative PCr deficiency by long-term daily exogenous supplementation of creatine or its precursors was investigated in four GA patients receiving creatine and in five patients treated with guanidinoacetic acid-methionine combination. The relative PCr concentration, expressed as PCr/Pi (Pi; inorganic phosphate) or as PCr/ATP ratios, was compared with the values of untreated GA patients, and matched healthy volunteers. RESULTS: Muscle PCr/Pi ratios (mean +/- SD) of the untreated and creatine supplemented GA patients and controls were 4.9 +/- 1.4, 7.9 +/- 0.4 and 8.4 +/- 1.3. Guanidinoacetate-methionine combination was similarly effective (respective PCr/Pi ratios: 4.9 +/- 0.7, 6.3 +/- 1.1 and 10.7 +/- 2.8). CONCLUSION: Supplementation with creatine or creatine precursors almost normalised low muscle PCr/Pi ratios of patients with GA.
Adolescent↗
Epidemiological classification of acute myocardial infarction: time for a change?
AIMS: The classification of an acute ischaemic cardiac event is traditionally based on cardiac enzymes, electrocardiography (ECG) and clinical symptoms. The impact of new specific cardiac markers on the diagnostic classification of suspected acute myocardial infarction remains poorly studied. We therefore set out to compare the diagnostic and prognostic information provided by the MONICA code and a patient classification based on the maximal level of creatine kinase MB isoenzyme. The significance of typical pain and various ECG algorithms were separately analysed. METHODS AND RESULTS: The study population consisted of 311 consecutive patients who were evaluated for suspected acute myocardial infarction in a regional referral hospital. Patients were retrospectively classified according to the MONICA criteria, by a simplified code combining symptoms and creatine kinase MB, and solely using the maximal creatine kinase MB concentration. Total mortality was followed for 1 and 5 years. The creatine kinase MB based classification was shown to be the strongest predictor of mortality (OR=2.8-3.7, p<0.001) for outcome both at 1 and 5 years. Typical pain and a positive Minnesota ECG had no prognostic relevance. However, an analysis algorithm of the admission ECG was predictive of 1- and 5-year survival. CONCLUSIONS: The epidemiological classification of suspected acute myocardial infarction could be based solely on a specific cardiac marker, such as creatine kinase MB mass. This approach contains prognostic information and is accurate enough for the structured diagnosis of acute myocardial infarction. Other outcome predictors could be used to identify patient subgroups and assess therapy.
Age Distribution↗
Immune response after laparoscopic and conventional Nissen fundoplication.
OBJECTIVE: To compare the changes in the immune responses of patients undergoing laparoscopic or conventional Nissen fundoplication. DESIGN: Prospective randomised clinical study. SETTING: University hospital, Finland. SUBJECTS: 20 patients undergoing Nissen fundoplication for symptomatic erosive oesophagitis. INTERVENTION: Laparoscopic Nissen fundoplication (n = 10) or conventional open Nissen fundoplication (n = 10). MAIN OUTCOME MEASURES: Leucocyte and differential counts; percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD16 and CD20 positive lymphocytes); and monocytes (CD 14); phytohemagglutinin, concanavalin A and pokeweed mitogen-induced and unstimulated proliferation of separated lymphocytes; plasma interleukin-6 (IL-6), serum C-reactive protein (CRP), albumin, and cortisol concentrations; and group II phospholipase A2 (PLA2) activity. RESULTS: Laparoscopic fundoplication was associated with less tissue damage (IL-6, and CRP concentrations) than the conventional open operation. However, although there were pronounced changes in immune responses over time, there were no differences between the groups. CONCLUSION: Laparoscopic fundoplication seemed to cause less tissue damage than the conventional open operation, but this difference was not reflected in patients' immune responses.
Esophagitis↗
Computer-assisted electrocardiography in structured diagnosis of acute myocardial infarction.
The purpose of this study was to investigate the applicability of computerized electrocardiogram interpretation in classifying patients with suspected acute myocardial infarction. Computerized acquisition and analysis of the 12-lead electrocardiogram can increase the consistency and reduce the workload of patient classification. The serial electrocardiograms of 311 consecutive patients with suspected myocardial infarction were studied and a new computerized myocardial infarction (CMI) electrocardiographic classification was developed and compared with one commercially available and two manual codes. Statistically, there was almost no correlation between the four ECG codes. Compared with the WHO enzymatic criteria, the sensitivity of the CMI code toward detecting definite and possible infarction was 69.2% and 29.8% with a specificity of 62.1% and 79.7%, respectively. In subjects without previous infarction (n = 214) the sensitivity of the CMI code for definite enzymatic infarction was 71.9% and specificity 77.6%. Substituting the CMI for the Minnesota code had no effect on patient classification by the WHO MONICA criteria in 78% of patients with first infarction. Judged by cardiac macromolecular leakage, all electrocardiographic classifications of possible infarction were poorly correlated with myocardial tissue injury. We have developed a new computerized coding system to detect electrocardiographic myocardial infarction. The structure of the code allows interactive redefinition of criteria to meet user-defined needs. However, because of the weak relationship between electrocardiographic and biochemical criteria of myocardial injury, the role of ECG in the diagnostic classification of acute ischemic syndromes should be re-evaluated.
Aged↗