Leisure-time physical activity and artery lumen diameters: a monozygotic co-twin control study.

Exercise is thought to increase the diameter of the conduit arteries supplying the muscles involved. We studied the effects of a physically active vs inactive lifestyle on artery diameters in monozygotic (MZ) twin pairs discordant over 30 years for leisure-time physical activity habits. In a population-based co-twin control study design, six middle-aged (50-65 years) same-sex MZ twin pairs with long-term discordance for physical activity were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in 1975 and the same co-twin remained significantly more active during the 32-year follow-up. The main outcomes were arterial lumen diameters measured from maximal intensity projections of contrast-enhanced MR angiography images. Paired differences between active and inactive co-twins were studied. Compared with inactive members, active members of MZ twin pairs had larger diameters for the distal aorta and iliac and femoral arteries (P<0.05 for all comparisons). The mean intrapair differences in the diameters of the arteries in these locations were 19% or larger. No significant differences between active and inactive co-twins (P>0.2 for all comparisons) were found in the dimensions of the carotid arteries. Our genetically controlled study confirms that habitual physical activity during adulthood enlarges arteries in a site-specific manner.

Leisure-time physical activity and high-risk fat: a longitudinal population-based twin study.

BACKGROUND AND OBJECTIVE: Exercise is thought to reduce high-risk body fat, but intervention studies are frequently limited by short follow-ups and observational studies by genetic selection. Therefore, we studied the effects of a physically inactive vs active lifestyle on high-risk (visceral, liver and intramuscular) fat in twin pairs discordant for leisure-time physical activity habits for over 30 years. DESIGN: A longitudinal population-based twin study. SUBJECTS: Sixteen middle-aged (50-74 years) same-sex twin pairs (seven monozygotic (MZ), nine dizygotic (DZ)) with long-term discordance for physical activity habits were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in 1975 and the same co-twin remained significantly more active during the 32-year-long follow-up. MAIN OUTCOME MEASURES: Magnetic resonance imaging-assessed visceral, liver and intramuscular fat. RESULTS: In within-pair analyses carried out after the adult life-long discordance in physical activity habits, the physically inactive co-twins had 50% greater visceral fat area compared with the active co-twins (mean difference 55.5 cm2, 95% confidence interval (CI) 7.0-104.1, P=0.010). The liver fat score was 170% higher (13.2, 95% CI 3.5-22.8, P=0.030) and the intramuscular fat area 54% higher (4.9 cm2, 95% CI 1.9-7.9, P=0.002) among the inactive co-twins. All the trends were similar for MZ and DZ pairs. Peak oxygen uptake was inversely associated with visceral (r=-0.46, P=0.012) and intramuscular fat area (r=-0.48, P=0.028), with similar trends in intrapair difference correlations (r=-0.57, P=0.021 and r=-0.50, P=0.056, respectively). The intrapair difference correlation between visceral and intramuscular fat was also high (r=0.65, P=0.009). CONCLUSION: Regular physical activity seems to be an important factor in preventing the accumulation of high-risk fat over time, even after controlling for genetic liability and childhood environment. Therefore, the prevention and treatment of obesity should emphasize the role of regular leisure-time physical activity.

Automated quantification of human brain metabolites by artificial neural network analysis from in vivo single-voxel 1H NMR spectra.

A real-time automated way of quantifying metabolites from in vivo NMR spectra using an artificial neural network (ANN) analysis is presented. The spectral training and test sets for ANN containing peaks at the chemical shift ranges resembling long echo time proton NMR spectra from human brain were simulated. The performance of the ANN constructed was compared with an established lineshape fitting (LF) analysis using both simulated and experimental spectral data as inputs. The correspondence between the ANN and LF analyses showed correlation coefficients of order of 0.915-0.997 for spectra with large variations in both signal-to-noise and peak areas. Water suppressed 1H NMR spectra from 24 healthy subjects were collected and choline-containing compounds (Cho), total creatine (Cr), and N-acetyl aspartate (NAA) were quantified with both methods. The ANN quantified these spectra with an accuracy similar to LF analysis (correlation coefficients of 0.915-0.951). These results show that LF and ANN are equally good quantifiers; however, the ANN analyses are more easily automated than LF analyses.

Automated classification of human brain tumours by neural network analysis using in vivo 1H magnetic resonance spectroscopic metabolite phenotypes.

We present a novel method to integrate in vivo nuclear magnetic resonance spectroscopy (MRS) information into the clinical diagnosis of brain tumours. Water-suppressed 1H MRS data were collected from 33 patients with brain tumours and 28 healthy controls in vivo. The data were treated in the time domain for removal of residual water and a region from the frequency domain (from 3.4 to 0.3 p.p.m.) together with the unsuppressed water signal were used as inputs for artificial neural network (ANN) analysis. The ANN distinguished tumour and normal tissue in each case and was able to classify benign and malignant gliomas as well as other brain tumours to match histology in a clinically useful manner with an accuracy of 82%. Thus the present data indicate existence of tumour tissue-specific metabolite phenotypes that can be detected by in vivo 1H MRS. We believe that a user-independent ANN analysis may provide an alternative method for tumour classification in clinical practice.

Left ventricular failure and pulmonary edema in acute multiple sclerosis.

We describe a young woman who developed left ventricular failure and pulmonary edema during fulminant onset of multiple sclerosis. One of the numerous plaques was located in the left inferior cerebellar peduncle near the dorsal motor vagal and solitary tract nuclei. Within two days pulmonary edema had cleared, and within three days left ventricular function was normal. To our knowledge, left ventricular failure has not earlier been verified in acute multiple sclerosis.

Radiation-induced changes in human brain metabolites as studied by 1H nuclear magnetic resonance spectroscopy in vivo.

PURPOSE: External radiation therapy for brain tumors exposes healthy areas of brain to considerable doses of radiation. This may cause cognitive and psychological impairment, which indicate neuronal dysfunction. 1H-magnetic resonance spectroscopy (MRS) was used to study brain metabolites in the adjacent regions 0.5-13 years after exposure to therapeutic irradiation. METHODS AND MATERIALS: Eight patients with irradiated brain tumors were examined by means of in vivo 1H-MRS using a point-resolved spectroscopy (PRESS) sequence with echo times of 60 or 270 ms. The metabolites were quantified by using brain water concentration as internal reference. The volume of interest (VOI) was positioned in irradiated brain areas excluding, however, scar and recurrent tumor. The respective radiation doses were measured based on radiation therapy plans, simulator films, and localization MR images. RESULTS: The concentration of the neuron-specific metabolite N-acetyl-L-aspartate (NAA) was 13.2 +/- 1.4 mmol/l in controls, whereas it was reduced in the brains of treated patients to 8.6 +/- 0.9 mmol/l (total radiation dose 59-62 Gy). Concentrations of creatine and choline-containing compounds were unchanged. The T2 of water was longer in irradiated than in unexposed brain areas. CONCLUSION: Therapeutic brain irradiation causes neuronal damage, which is reflected by reduction of N-acetyl-L-aspartate (NAA) concentrations. 1H-MRS could serve clinically as a means of evaluating adverse effects in the central nervous system, enabling intervention and rehabilitation.

Quantification of metabolites from single-voxel in vivo 1H NMR data of normal human brain by means of time-domain data analysis.

We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.

Low molecular weight heparin (enoxaparin) compared with unfractionated heparin in prophylaxis of deep venous thrombosis and pulmonary embolism in patients undergoing hip replacement.

Prophylactic efficacy and safety of a low molecular weight heparin (LMWH) and those of conventional unfractionated heparin (UH) were investigated in a randomized study. Totally, 167 consecutive patients undergoing total hip replacement were allocated to two groups. Patients in the LMWH-group (n = 83) received a fixed dose of enoxaparin 40 mg once daily, starting 12 hours preoperatively and continuing for 10 days. Patients in the UH-group (n = 84) received UH 5000 IU twice a day subcutaneously (sc), starting two hours before operation and continuing for 10 days. Deep venous thrombosis (DVT) was diagnosed by bilateral ultrasonography and confirmed by venography. Proximal DVTs were observed in four patients of UH-group (4.8%) and in one of LMWH-group (1.2%, P > 0.05). There was only one pulmonary embolism (PE) in a patient belonging to UH-group (1.2%). Low rates of thromboembolic events could be explained, in addition to heparin prophylaxis, also by early mobilization and regional anaesthesia. Local tolerance (size of haematoma), blood loss and transfusion requirements during the operation and the postoperative period did not show differences between the two study groups. The results of our study indicate that enoxaparin once daily is an effective and safe form of DVT prophylaxis in patients undergoing elective hip replacement.

Choline-containing compounds in human astrocytomas studied by 1H NMR spectroscopy in vivo and in vitro.

We have studied 14 patients with different grades of astrocytomas using 1H NMR spectroscopy in vivo. Typically, astrocytomas exhibited a low N-acetylaspartate peak, a prominent signal from choline group-containing compounds, and lactate in the 1H NMR spectra in vivo. The uncorrected choline/creatine + phosphocreatine peak area ratios were higher in tumors than in normal brain tissue. Absolute concentration of choline-containing compounds (1.74 +/- 0.09 mmol/L) in the normal brain tissue was not different in any grade of astrocytoma, but total creatine concentration in healthy brain (7.49 +/- 0.30 mmol/L) was higher than that in grade IV astrocytomas (4.84 +/- 0.89 mmol/L). Relaxation constants of choline-containing compounds did not differ in tumors from those determined in normal brain. Perchloric acid extracts of biopsy samples from 35 astrocytomas and 13 samples of normal temporal white matter were analyzed with 1H NMR. Total concentration of choline-containing compounds did not differ between controls and any grade of astrocytoma when the quantification was done in vitro. It is interesting that phosphorylcholine concentration was about twofold greater in grade IV astrocytomas than in controls or other grades of astrocytomas. We conclude that high phosphorylcholine in grade IV astrocytomas may be an indicator of degree of malignancy. The proportional changes within the group of choline-containing compounds observed in vitro were not reflected in the NMR properties of choline signal in vivo.

Reduced N-acetylaspartate concentration in temporal lobe epilepsy by quantitative 1H MRS in vivo.

We used proton magnetic resonance spectroscopy (1H MRS) to determine concentrations of N-acetylaspartate (NAA), creatine and choline in vivo (63 MHz) and in vitro (400 MHz) in seven patients undergoing surgical treatment of intractable temporal lobe epilepsy (TLE). Nine healthy volunteers were used as controls for in vivo MRS. NAA concentrations in vivo on the ipsilateral and contralateral sides were 6.5 +/- 1.3 (s.d.) and 7.9 (+/- 2.1) mmol l-1, respectively and 8.6 (+/- 0.8) mmol l-1 in the volunteers. NAA concentration in vitro was 3.2 (+/- 0.9) mumol g-1 wet weight (ww) and the corresponding concentration from the macroscopically intact brain tissue was 4.7 (+/- 1.0) mumol g-1 ww. Thus, in vivo quantitative 1H MRS identified the size of seizure focus in patients with temporal lobe epilepsy.

Quantitative metabolite patterns of human brain tumors: detection by 1H NMR spectroscopy in vivo and in vitro.

OBJECTIVE: The aim of the present study was to investigate quantitative metabolite patterns in human brain tumors by 1H nuclear MR spectroscopy (1H MRS). MATERIALS AND METHODS: Single voxel 1H MRS was used in studying metabolites in 23 primary brain tumors in vivo. The T2 relaxation times and saturation factors were determined for N-acetylaspartate (NAA), total creatine (Cr), choline-containing compounds (Cho), and water, which was used as an internal standard in computations of metabolite concentrations in vivo. Metabolites in biopsy specimens from 75 tumors were quantified by means of 1H MRS in vitro. RESULTS: The NAA concentrations were lower in brain tumors than in normal tissue in vitro and in vivo, irrespective of the histological type. The NAA was some threefold higher in vivo than in vitro, which could be due to partial volume effect and/or contributions from other metabolites to the peak at 2.02 ppm in vivo. Ratios of Cho to Cr concentrations were elevated in tumors relative to normal brain in vivo. Absolute Cho was some 50% higher in both benign astrocytomas and oligodendrogliomas in vivo than in normal brain. However, Cho concentration in vitro was significantly higher only in pituitary adenomas than in healthy white matter. Total creatine was approximately 50% lower in malignant astrocytomas and meningiomas than in normal brain. CONCLUSION: It is concluded that absolute concentrations of metabolites in vivo yield a different picture of tumor metabolites than that derived from uncorrected metabolite ratios.

Iliac crest versus artificial bone grafts in 250 cervical fusions.

Autologous (149 patients) and heterologous (101 patients) bone grafts were used for fusion in 250 patients with anterior cervical surgery. A stable fusion was achieved in 98% of patients in both groups and there was no significant difference in the clinical outcome. Donor site complications (severe pain, haematoma) were seen in one sixth of the patients with autologous bone grafts. If a fusion for anterior cervical surgery is necessary, the use of a heterologous bone graft should be preferred.

Are smokers a risk group for delayed healing of tibial shaft fractures?

A total of 135 patients with a fresh tibial shaft fracture and with no other significant injuries underwent primary conservative treatment. Data on their smoking habits were obtained from hospital records and by questionnaire. Although the smokers had better prospects for healing of the fracture at the outset than non-smokers (lower mean age and less fractures caused by high-energy injuries), the smokers were found to have a significantly longer mean time to clinical union and a higher incidence of delayed union. According to a crude calculation, smokers had a 4.1-fold risk of tibial shaft fracture caused by low-energy injury, compared with non-smokers. An accelerated failure time model showed that the more comminuted or open the fracture, the higher the number of cigarettes smoked and the older the patient, the longer was the time to clinical union of the tibial shaft fracture. Female sex appeared to be a further risk factor for delayed healing. A logit model indicated that comminution of the fracture, smoking and female sex were associated with delayed union and non-union. If a patient has a markedly raised probability of delayed union of tibial shaft fracture because of many risk factors as reported in the previous literature or in this study, operative treatment should be considered as the primary alternative instead of conservative treatment. Stopping smoking during healing of tibial shaft fracture could also promote the union of the fracture.

Adenine phosphoribosyltransferase deficiency: 2,8-dihydroxyadenine urolithiasis in a 48-year-old woman.

We report the first patient in Finland and Scandinavia with a deficiency of adenine phosphoribosyltransferase (APRT). About 30 clinically affected patients have been reported in the literature. APRT deficiency is an enzyme disorder which is inherited autosomally in a recessive manner. The use of adenine in purine metabolism is disturbed and it accumulates in the body, where it is oxidised to poorly insoluble 2,8-dihydroxyadenine by xanthine oxidase. The dihydroxyadenine forms stones which can be mistaken for uric acid stones. Our patient had had frequent episodes of urolithiasis and the diagnosis was finally made after pyelolithotomy and stone analysis. The total APRT deficiency was detected in the haemolysate of erythrocytes. Partial deficiency of APRT in the patient's relatives showed heterozygosity of the enzyme defect. The only clinical manifestation of the defect is the formation of urinary stones. This can be prevented by diet and allopurinol.