Cholesterol metabolism and non-cholesterol sterol distribution in lipoproteins of type 1 diabetes: the effect of improved glycemic control

In type 1 diabetes, the ratios to cholesterol of serum absorption markers, e.g., cholestanol, are elevated and those of synthesis markers, e.g., lathosterol, are reduced suggesting perturbed cholesterol metabolism. We studied 17 subjects with type 1 diabetes in poor glycemic control at baseline to assess whether improvement of glycemic control affects lathosterol and cholestanol ratios to cholesterol and their distribution in lipoproteins. Cholesterol and the non-cholesterol sterols were assayed directly from serum, and free and ester fractions after thin-layer chromatographic separation of lipoprotein sterols with gas-liquid chromatography. After the 2-6 months follow-up, the mean value of HbA1(c) decreased from 10.8% to 8.6% (p=0.001). Even though the concentrations of serum and lipoprotein cholesterol remained unchanged, the serum lathosterol to cholesterol ratio increased by 28% (p<0.05) and the lathosterol/cholestanol proportion by 23% (p<0.05). The ratios of total and esterified lathosterol to cholesterol in serum, chylomicrons and LDL, and free lathosterol to cholesterol in serum and IDL, were negatively associated with HbA1(c) at baseline and after follow-up, suggesting that the better glycemic control, the higher was cholesterol synthesis. The absorption markers were less consistently associated with HbA1(c). About half of the serum lathosterol and cholestanol was carried in LDL and one-fourth to one-fifth in HDL, but the lathosterol ratios were roughly similar in all lipoproteins. In contrast, cholestanol accumulated in chylomicrons and HDL. Glycemic control did not affect the distributions of lathosterol and cholestanol. In conclusion, improvement in glycemic control increased cholesterol synthesis, but had no effect on cholesterol absorption as measured by the serum or lipoprotein cholestanol to cholesterol ratio. From a clinical point of view, the better the glycemic control, the more antiatherogenic cholesterol metabolism may be in type 1 diabetes.     

Structure of needs among persons with schizophrenia

Abstract Background The importance of needs assessment for service development has been widely recognised. Several studies have focused on the associations between ratings of needs by patients and staff and have found clear differences, especially concerning the unmet needs. Methods The present study is part of a Nordic Multicentre study that investigates the life and care of outpatients with a schizophrenia group illness in all the Nordic countries. The aim of this paper is to study the patterns of needs as identified by patients and staff according to the Camberwell Assessment of Needs (CAN). Quality of life, level of functioning, and psychiatric symptoms were assessed. Results The sample includes 300 patients, 194 (65%) men and 106 (35%) women. The factor analysis identified five factors for patients and four factors for staff in the questionnaire on ratings of needs. In four of the five patient-related factors a meaningful interpretation was possible, and the factors were named skills, illness, coping, and substance abuse. The staff-related factors were named skills, impairment, symptom, and substance abuse. There were significant associations between the sum scores constructed from the factors and measures of functioning level and symptoms. Conclusions It seems that the sum factor reflecting secondary needs was the most important of the identified factors among both patient and staff ratings. The item-by-item comparisons in previous studies have emphasised differences between patient and staff ratings, but our analysis of the structure of needs also found similarities in the structures and in the associations between the identified sum scores and measures of symptoms, functioning level, and quality of life.     

Temporal cortex dopamine D2/3 receptor binding in major depression

The aim of this study was to assess the dopamine function of the temporal cortex in major depressive disorder using [¹²³I]epidepride to image D_2/3 receptor binding sites. Ten major depressives and 10 healthy controls were selected from a general population sample for single-photon emission computed tomography imaging. Among the major depressives there was a strong bilateral correlation between the scores on the 21-item Hamilton Depression Rating Scale and D_2/3 receptor binding. Dopaminergic abnormalities may be present in the temporal cortices of major depressives.     

N-Glucuronidation of some 4-arylalkyl-1H-imidazoles by rat, dog, and human liver microsomes.

N-Glucuronidation in vitro of six 4-arylalkyl-1H-imidazoles (both enantiomers of medetomidine, detomidine, atipamezole, and two other closely related compounds) by rat, dog, and human liver microsomes and by four expressed human UDP-glucuronosyltransferase isoenzymes was studied. Human liver microsomes formed N-glucuronides of 4-arylalkyl-1H-imidazoles with high activity, with apparent V(max) values ranging from 0.59 to 1.89 nmol/min/mg of protein. In comparison, apparent V(max) values for two model compounds forming the N-glucuronides 4-aminobiphenyl and amitriptyline were 5.07 and 0.56 nmol/min/mg of protein, respectively. Atipamezole showed an exceptionally low apparent K(m) value of 4.0 microM and a high specificity constant (V(max)/K(m)) of 256 compared with 4-aminobiphenyl (K(m), 265 microM; V(max)/K(m), 19) and amitriptyline (K(m), 728 microM; V(max)/K(m), 0.8). N-Glucuronidation of medetomidine was highly enantioselective in human liver microsomes; levomedetomidine exhibited a 60-fold V(max)/K(m) value compared with dexmedetomidine. Furthermore, two isomeric imidazole N-glucuronides were formed from dexmedetomidine, but only one was formed from levomedetomidine. Dog liver microsomes formed N-glucuronides of 4-arylalkyl-1H-imidazoles at a low rate and affinity, with apparent V(max) values ranging from 0.29 to 0.73 nmol/min/mg of protein and apparent K(m) values from 279 to 1640 microM. Rat liver microsomes glucuronidated these compounds at a barely detectable rate. Four expressed human UDP-glucuronosyltransferase isoenzymes (UGT1A3, UGT1A4, UGT1A6, and UGT1A9) were studied for 4-arylalkyl-1H-imidazole-conjugating activity. Only UGT1A4 glucuronidated these compounds at an activity of about 5% of that measured for 4-aminobiphenyl. The observed activity of UGT1A4 does not explain the high efficiency of glucuronidation of 4-arylalkyl-1H-imidazoles in human liver microsomes.     

Quality of myocardial perfusion single-photon emission tomography imaging: multicentre evaluation with a cardiac phantom

The aim of the study was to evaluate quality of myocardial perfusion single-photon emission tomography (SPET) imaging in Finnish hospitals. Nineteen nuclear medicine departments participated in the study. A myocardial phantom simulating clinical stress and rest conditions was filled with routinely used isotope solution (technetium-99m or thallium-201). The cardiac insert included three reversible defects (simulating ischaemia): 30×30×14 mm³ septal (90% recovery at rest), 30×20×14 mm³ posterobasal (full recovery) and 20×20×14 mm³ lateral (full recovery). There were two fixed defects (simulating infarct): 30×20×14 mm³ postero-apical and 10×10×6 mm³ apical. The phantom was imaged and interpreted as a myocardial perfusion patient. Reconstruction, printout and reporting were performed according to the clinical routine of each centre. Three nuclear medicine specialists anonymously evaluated the quality of the image sets. The visual scores of the experts were ranked from 1 to 5. Additionally, points from 0 to 8 were given to research reports according to how well perfusion defects were detected. Quantitative points were calculated by comparing background-subtracted and -normalized counts from 12 regions of interest between stress and rest images. Results for technetium studies (12 departments) were better than those for thallium (7 departments). The average visual scores of the experts were 3.7±0.9 for all image sets, 3.2±0.5 for thallium users and 3.9±0.6 for technetium users (P=0.003). Five laboratories received a low score which, according to the specialists, is barely sufficient for limited clinical use. Average points for the reports were 5.6±2.1, 4.9±1.5 and 6.5±1.7 (P=0.051), and for the quantitation 8.2±1.0, 7.9±0.4 and 8.4±1.1 (P=0.185), respectively. Seven out of 22 interpreters did not detect the lateral 20×20×14 mm³ defect; five of them used thallium. This study demonstrated the heterogeneity of myocardial perfusion SPET in Finland. The participating laboratories used a wide scale of methods and, sometimes, inappropriate imaging protocols. The need for quality assurance in nuclear cardiology, correct use of SPET instrumentation and objective comparison of clinical studies is evident. The method described is suitable for external quality assurance and quality improvement of myocardial SPET imaging, and is recommended for regular use in nuclear medicine. Reiceived 15 March and in revised form 9 May 1999     

A modification of the Hammett equation for predicting ionisation constants of p-vinyl phenols

Currently there are several compounds used as drugs or studied as new chemical entities, which have an electron withdrawing group connected to a vinylic double bond in a phenolic or catecholic core structure. These compounds share a common feature – current computational methods utilizing the Hammett type equation for the prediction of ionisation constants fail to give accurate prediction of pK_a's for compounds containing the vinylic moiety. The hypothesis was that the effect of electron-withdrawing substituents on the pK_a of p-vinyl phenols is due to the delocalized electronic structure of these compounds. Thus, this effect should be additive for multiple substituents attached to the vinylic double bond and quantifiable by LFER-based methods. The aim of this study was to produce an improved equation with a reduced tendency to underestimate the effect of the double bond on the ionisation of the phenolic hydroxyl. To this end a set of 19 para-substituted vinyl phenols was used. The ionisation constants were measured potentiometrically, and a training set of 10 compounds was selected to build a regression model (r² = 0.987 and S.E. = 0.09). The average error with an external test set of six compounds was 0.19 for our model and 1.27 for the ACD-labs 7.0. Thus, we have been able to significantly improve the existing model for prediction of the ionisation constants of substituted p-vinyl phenols.     

Detection of chromatic deviations from white across the human visual field

We studied how much blue, green, or red light had to be added to or subtracted from white to obtain veridical hue perception (blue, green, red, or their complementary colours) at various locations in the temporal visual field. The CIE 1931 (x, y) chromaticity coordinates corresponding to a veridical hue perception were subtracted from the chromaticity coordinates of the white (0.35, 0.35) in order to obtain the threshold differences (dx, dy) in chromaticity coordinates. When stimulus size was constant at all visual field locations, dx and dy changed with eccentricity. However, when the stimulus was M-scaled by magnifying its size with increasing eccentricity in inverse proportion to the lowest local sampling density across the human retina (cones and ganglion cells at eccentricities 0-10 and above 10 deg, respectively), dx and dy remained constant at all eccentricities.     

A 3-D model-based registration approach for the PET,MR and MCG cardiac data fusion

In this paper, a new approach is presented for the assessment of a 3-D anatomical and functional model of the heart including structural information from magnetic resonance imaging (MRI) and functional information from positron emission tomography (PET) and magnetocardiography (MCG). The method uses model-based co-registration of MR and PET images and marker-based registration for MRI and MCG. Model-based segmentation of MR anatomical images results in an individualized 3-D biventricular model of the heart including functional parameters from PET and MCG in an easily interpretable 3-D form.     

Hospitalized burns in Finland: 36 305 cases from 1980–2010

To analyse the epidemiology of burns in Finland, a comprehensive study was conducted among all hospitalized burn patients between 1980 and 2010. All patients with burn injury as the main diagnosis, 36 305 cases in total, treated in the public and private sectors, were included.Patient data were obtained from the Finnish Hospital Discharge Register (FHDR). The incidence of hospitalized injuries declined from over 30 to 17 per 100 000 persons. Men were at higher risk than women in all age groups. Children aged under ten years were overrepresented throughout the period and the highest incidence was found among one year old boys. The median total length of stay shortened from seven days in 1980–1995 to five days in 1996–2010. The annual number of hospitalized patients is recently under 1000 cases (17/100 000). The male predominance (70%) did not change but the age group with the most injuries shifted from 20–39 years to 40–59 years. Injuries were most common during the summer months.This study of all hospitalized burn injuries of one entire country shows similar tendency of diminishing numbers and rising age of burn victims as in other western countries. The FHDR is a reliable source of data in epidemiological studies but precise recording of E- and N-codes in the registry would enable the accurate analysis of types and extent of injury.