Identification of a mutation in the ovine uroporphyrinogen decarboxylase (UROD) gene associated with a type of porphyria

Porphyria is a group of at least eight diseases caused by abnormalities in the chemical steps that lead to haeme production. The different types of porphyria show different signs and symptoms and can be strongly influenced by environmental factors. Mutations of the uroporphyrinogen decarboxylase (UROD) gene have been shown to be causative for porphyria cutanea tarda (PCT) in humans. Porphyria is a rare disorder in livestock. Although disorders of haeme biosynthesis have been described in cattle, pigs, sheep and cats, PCT has only been reported in pigs. We observed typical signs of porphyria (photosensitivity and porphyrinuria) in a flock of German Blackface sheep and postulated that the porphyria could be caused by a mutation in the UROD gene. To investigate this, we cloned and sequenced the ovine UROD gene. We identified a single point mutation (C --> T) in UROD which leads to an amino acid substitution at Leu 131 Pro, which is located within the active cleft site of the UROD protein.     

Precipitating/aggravating factors of porphyria cutanea tarda in Spanish patients.

Erythrocyte uroporphyrinogen decarboxylase (UROD) activity was measured to classify 118 Spanish patients with porphyria cutanea tarda (PCT) into three subtypes: sporadic-, familial- and type III-PCT. Seventy-four patients (63%) had eythrocyte UROD activity within the normal range (74% to 126% of the mean activity of 43 healthy controls) and were classified as sporadic-PCT (47%) or as type III-PCT (16%) whenever a family history of PCT was documented. Forty-four patients (37%) had decreased UROD activity and were classified as familial-PCT. The frequency of both familial-PCT and type III-PCT was higher than reported in other countries. The clinical expression of PCT was associated with the coexistence of two or more risk factors in 80% of the sporadic-PCT patients and in 89% of the familial-PCT patients. Hepatitis C virus and alcohol abuse were risk factors frequently found in these patients, being unrelated to age of onset of skin lesions. A heavy alcohol intake was the main risk factor for type III-PCT. Estrogens appeared as a precipitating factor for women with familial-PCT. The H63D mutation in the hemochromatosis type 1 gene was more frequently found than the C282Y mutation. Both mutations appeared to play a role as precipitating factors in sporadic-PCT when associated with hepatitis C virus infection and alcohol abuse.     

Levels of uroporphyrinogen decarboxylase (URO-D) in erythrocytes of Italian porphyria cutanea tarda patients.

Porphyria cutanea tarda (PCT) is a human metabolic disorder due to the acquired or genetic impairment of uroporphyrinogen decarboxylase (URO-D) activity, the fifth enzyme of the heme biosynthetic pathway. A classification of inherited and non-inherited forms is based on the enzyme activity levels in red blood cells (RBC). Clinical manifestations of PCT are often precipitated by triggering factors such as alcohol, drug abuse, estrogens, virus infections, hepatotoxic chemicals and hepatic siderosis. We measured URO-D activity in RBC from a large sample of Italian PCT patients in order to define the enzyme activity distribution and to attempt a correlation among activity, risk factors and clinical outcome. Three classes of patients with low, normal and over-normal URO-D activity were defined according to control values. Low URO-D levels were present in 25.8% of patients, suggesting the familial form of PCT (type II). In this group, the outcome of PCT seems to be less influenced by risk factors. Patients with over-normal URO-D activity in RBC deserve further investigation.     

CYP1A2*1F and GSTM1 alleles are associated with susceptibility to porphyria cutanea tarda

Porphyria cutanea tarda (PCT) is a cutaneous porphyria with sporadic (type 1) and familial (type 2) subtypes, both resulting from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. Environmental and genetic factors are involved in the development of PCT, and genetic variants in the cytochrome P450 (CYP ) genes, CYP1A1 and CYP1A2, have been implicated. We investigated the association between PCT and variants in CYP1A1, CYP1A2 and CYP2E1, and the glutathione-S-transferase (GST ) genes, GSTM1 and GSTT1. PCT diagnosis was based on urinary or plasma porphyrin profiles. Patients were classified as type 1 or 2 PCT based on UROD mutation analysis. The CYP1A2*1F promoter A allele frequency was significantly higher (P < 0.022) and the A/A genotype frequency marginally higher in PCT patients overall (P < 0.057), with the A/A genotype significantly more common in type 1 PCT (P < 0.043). The presence of the wild-type GSTM1 allele also was associated significantly with PCT (P < 0.019). Neither hemochromatosis (HFE) mutations, tobacco smoking, hepatitis C and HIV infection, ethanol consumption, nor estrogen use were associated with these allelic variants. Age at onset was significantly lower in type 2 PCT patients (P < 0.001), as observed previously. Thus, positive associations between PCT and the CYP1A2*1F promoter A allele and A/A genotype and the wild-type GSTM1 allele indicates that these functional hepatic biotransformation enzymes are risk factors for the development of this disease.     

Porphyria cutanea tarda: clinical and laboratory features.

Eleven patients with porphyria cutanea tarda were studied. Biochemical confirmation of the clinical diagnosis required only determination of the total urine porphyrin concentration in a sample of urine voided on rising in the morning. The patients were divided for convenience of discussion into four groups differing in age, sex and etiologic factors. Of the six patients in whom a liver biopsy was done one was shown to have micronodular cirrhosis. Except for a modest elevation in the serum glutamic oxaloacetic transaminase values when the patients were first seen, no evidence was found for liver disease apart from the presence of porphyria cutanea tarda. One patient recovered solely by abstaining from alcohol consumption. Five patients underwent phlebotomy; their iron stores had been found to be between 2 and 3 g. Decreasing urine porphyrin values correlated well with decreasing serum ferritin values during the course of phlebotomy. Porphyria cutanea tarda, which is due to a deficiency of uroporphyrinogen decarboxylase, is manifested in association with alcohol abuse, estrogen therapy, exposure to chlorinated hydrocarbons or increased tissue iron stores, or a combination of these factors. Although relatively uncommon, this condition raises important and unresolved issues regarding the hepatotoxicity of alcohol, estrogens, chlorinated hydrocarbons and iron.     

Porphyria cutanea tarda: the etiological importance of mutations in the HFE gene and viral infection is population-dependent.

A number of factors, including increased iron stores and alcohol consumption, are known to be associated with the development of porphyria cutanea tarda (PCT) in susceptible individuals. Recent reports have described a significant association between inheritance of the C282Y and H63D mutations in the HFE gene, associated with genetic hemochromatosis (GH) and PCT. A strong association between hepatitis C virus infection and PCT has also been demonstrated, while case reports record a link between human immunodeficiency virus (HIV) and PCT. We have investigated the frequency of these factors in a racially-mixed population of patients with PCT in Cape Town, South Africa. 57 patients with PCT drawn from three ethnic groups were screened for the presence of the C282Y and H63D mutations linked to GH, and the prevalences were compared with corresponding healthy control populations. The seroprevalence of markers for HCV, hepatitis B (HBV) and HIV infection were examined in 28 of these. In the control populations, we found that both the C282Y and H63D mutations are highly prevalent in South Africans of European origin. In a population of mixed or Asian origin, the C282Y mutation is very rare whereas the H63D mutation is common. Neither mutation was encountered in any African subject. Both mutations are associated with PCT, but the association is dependent on the ethnic origins of the population to which the patient belongs. In contrast to other studies, HCV infection is numerically unimportant in PCT in our patients. HIV infection is increasingly encountered in our patients with PCT, but the strength of the association cannot be determined in view of the high background prevalence of HIV infection in some sectors of the South African population. The contribution of specific risk factors may be heavily dependent on the population from which patients are drawn, and care should be taken in extrapolating from observations in one racial or geographic population to any other.     

Alcohol and blood pressure: the INTERSALT study.

OBJECTIVES--To assess the relation between alcohol intake and blood pressure in men and women and in men at younger and older ages; to examine the influence of amount and pattern of alcohol consumption, as well as of acute effects, taking into account body mass index, smoking, and urinary sodium and potassium excretion. DESIGN--Subjects reported alcohol consumption for each of seven days before standardised blood pressure measurement, and whether they had consumed any alcohol in the 24 hours before measurement. SETTING--50 centres worldwide. SUBJECTS--4844 men and 4837 women aged 20-59. MAIN OUTCOME MEASURES--Effect of alcohol on blood pressure estimated by taking a weighted average of regression coefficients from centres. Acute effect assessed by examining mean differences in blood pressure of non-drinkers and of heavy drinkers who had and had not consumed alcohol in the 24 hours before measurement. Effect of pattern of consumption assessed by examining mean differences in blood pressure of non-drinkers compared with drinkers (i) whose intake was concentrated in fewer days or who were drinking more frequently, and (ii) whose alcohol intake varied little over the seven days or varied more substantially, as indicated by the standard deviation of daily consumption. RESULTS--Of the 48 centres in which some people reported consuming at least 300 ml/week of alcohol, 35 had positive regression coefficients linking heavy alcohol consumption to blood pressure. Overall, alcohol consumption was associated with blood pressure, significantly at the highest intake. After account was taken of key confounders, men who drank 300-499 ml alcohol/week had systolic/diastolic blood pressure on average 2.7/1.6 mmHg higher than non-drinkers, and men who drank > or = 500 ml alcohol/week had pressures of 4.6/3.0 mmHg higher. For women, heavy drinkers (> or = 300 ml/week) had blood pressures higher by 3.9/3.1 mmHg than non-drinkers. Heavy drinking and blood pressure were strongly associated in both sexes, and in men at both younger (20-39 years) and older (40-59 years) ages. In men who were heavy drinkers, episodic drinkers (those with great variation in daily alcohol consumption) had greater differences in blood pressure compared with non-drinkers than did regular drinkers of relatively constant amounts. CONCLUSION--The significant relation of heavy drinking (3-4 or more drinks/day) to blood pressure, observed in both men and women, and in younger and older men, was independent of and added to the effect on blood pressure of body mass index and urinary excretion of sodium and potassium. The findings indicate the usefulness of targeting those at high risk as well as the general population to reduce the adverse effects of alcohol on blood pressure.     

Volatile anaesthetics induce biochemical alterations in the heme pathway in a B-lymphocyte cell line established from hepatoerythropoietic porphyria patients (LBHEP) and in mice inoculated with LBHEP cells

Hepatoerythropoietic porphyria (HEP) is the homozygous form of Porphyria Cutanea Tarda (PCT), characterized by an accumulation of porphyrins due to uroporphyrinogen decarboxylase deficiency.Fluorinated volatile anaesthetics are often used to produce general anaesthesia. Anaesthesia has certainly been implicated in the triggering of acute porphyria crisis.The effects of volatile anaesthetics in a B-lymphocyte cell line established from HEP patients (LBHEP) on heme metabolism have been investigated.LBHEP cells were exposed to sodium phosphate buffer containing dissolved Enflurane, Isoflurane or Sevoflurane (10mM) during 20min.Aminolevulinate synthase (ALA-S) activity, the regulatory enzyme of heme synthesis, was 300% induced by the anaesthetics. A 25-30% diminution of porphobilinogenase (PBG-ase) activity was found when Isoflurane or Sevoflurane were added to the cells, while no significant changes were detected after Enflurane treatment.Although some oxidative stress has been induced by the anaesthetics, reflected by the 35% diminution of glutathione (GSH), no alteration in heme oxygenase (HO) activity, the enzyme involved in heme breakdown and frequently induced as a response to stress stimuli, was observed.Studies using animals inoculated with LBHEP cells were also performed. Findings here described mimic biochemical alterations in the heme pathway, which are characteristic of another hepatic porphyria, similar to those previously reported when these anaesthetics were administered to animals, and they also advertise about the possible unsafe use of these drugs in the case of hepatic non-acute porphyrias.     

Alcoholgebruik onder 55-plussers in Nederland

In The Netherlands no detailed information about alcohol consumption among older persons (55 years and older) is available. Therefore we investigated the prevalence and determinants of alcohol consumption with data from the Longitudinal Aging Study Amsterdam. The results show that 13.4% of persons of 55 years and older are heavy drinkers (male >3 glasses per day, female >2 glasses per day). Most heavy drinkers are younger than 75 years of age, and in this age group more female (22.2%) than male (14.8%) are heavy drinkers. 13% of all participants frequently drinks 6 or more glasses in a short period of time (binge drinking). In the age group of 55-65 years alcohol consumption has considerably increased over a period of ten years. This increase is stronger among females than among males. When people grow older alcohol consumption decreases, which seems associated with a decline in physical or psychological health and/or cognitive decline. Heavy and binge drinking is associated with younger age, higher education and income, and may be strongly related to their social lifes.     

Moderate alcohol consumption and loss of cerebellar Purkinje cells.

OBJECTIVE--To examine the dose-response effect of alcohol consumption on the number of cerebellar Purkinje cells. DESIGN--A prospective necropsy study combined with detailed reports on use of alcohol from a relative or friend. The number of Purkinje cells was counted in the anterior midsagittal section of the cerebellar vermis, the area of which was measured by computer assisted morphometry. SETTING--Department of forensic medicine, University of Helsinki. SUBJECTS--66 men, aged 35 to 69 years, subjected to medicolegal necropsy because of sudden or violent death. The average all year daily alcohol consumption over the year was 0 to 10 g in 17 men, 11 to 80 g in 24 men, and more than 80 g in 25 men. MAIN OUTCOME MEASURES--Number of Purkinje cells, alcohol consumption. RESULTS--The numbers and density of Purkinje cells in the cross section of vermis showed a consistent but weak decrease with increasing daily alcohol intake but not with age. A wide variation in the cell counts was observed, especially in men drinking more than 80 g, suggesting differences in the susceptibility to effects of alcohol. Compared with men drinking 40 g or less, a long term moderate consumption of an average of 41 to 80 g daily was associated with a significant average loss of 242 (95% confidence interval 45 to 439) Purkinje cells (15.2%) from a mean of 1583 to 1341 cells. In those drinking 81 to 180 g the average loss was 535 (259 to 811) cells (33.4%) to a mean of 1048 cells. The density of cells in the cross section of vermis also fell significantly by 0.9 cell/mm (0.1 to 1.7) when the daily consumption exceeded 40 g and by 1.4 cell/mm (0.3 to 2.5) when the intake was 81 to 180 g. Only three cases (4.5%) in the series showed macroscopical cerebellar atrophy. CONCLUSION--Long term intake of moderate doses of alcohol daily for 20-30 years may damage the cerebellum before the onset of macroscopical atrophy. Despite distinct individual differences an all year average daily alcohol intake of 41-80 g results in a risk of significant loss of Purkinje cells.     

The effect of alcoholization on the behavioral reactions of rats in an 8-arm radial maze

The influence of 20% alcohol consumption on training of low-active rats in 8-arm radial maze was studied. One group of animals was trained before and the other group after the alcoholization. All the animals acquired the conditioned reaction in the radial maze. However, the behavioral difference between the groups consisted in spatially-motor asymmetry. The rats trained before the alcohol consumption had less stereotyped behavior and more distinctly preferred to enter the maze arms at the angle of 45 degrees than the animals trained after the alcohol consumption. After the alcohol consumption, rats more frequently refused from behavioral task performance in comparison with the animals trained after the alcoholization. The influence of alcohol consumption of learning and memory in low-active rats is discussed.     

Hemochromatosis (HFE) and transferrin receptor-1 (TFRC1) genes in sporadic porphyria cutanea tarda (sPCT).

Porphyria cutanea tarda (PCT), a disorder characterized by a photosensitive dermatosis and hepatic siderosis, is caused by a decreased activity of the hepatic enzyme uroporphyrinogen decarboxylase (UROD). Two forms of PCT have been described: a familial one (fPCT) with an inherited decrease of UROD activity in all tissues and a sporadic one (sPCT) with a decreased UROD activity restricted to the liver. Iron overload and acquired factors including hepatic viral infections, alcohol, drugs contribute to the expression of PCT. In 65 French sPCT patients and 108 controls we have evaluated the respective role of iron and HCV status, the hemochromatosis (HFE) gene mutations frequencies (H63D. S65C, C282Y), and in a case control study we searched for an association between sPCT and the human transferrin receptor-1 (TFRC1) gene whose product is thought to be in functional association with the HFE protein: three single nucleotide polymorphisms (SNPs) previously characterized and 2 novel ones were studied. The iron-related parameters and transaminases were higher in sPCT patients than those of non-porphyric controls. Of the sPCT patients studied, 28% were HCV positive. In the HFE gene, 17% of sPCT patients carried C282Y mutation compared to 4% in controls, no significant differences were found with H63D and S65C variants. Compound heterozygous genotypes, C282Y/H63D or C282Y/S65C, were not significantly different in sPCT and control groups. Independently from HFE gene mutations, an association was found between the IVS4+198 T allele in the TFRC1 gene and sPCT patients. Analysis of HFE genotypes indicated that C282Y (but not H63D nor S65C) is a susceptibility factor for the development of sPCT in West European continental patients. However, analysis of TFRC1 genotypes suggest that sPCT should be considered as a multifactorial disorder in which other intracellular iron metabolism genes could be involved.     

Trends in tobacco consumption and incidences of associated neoplasms in Papua New Guinea.

From 1960 to 1979 total annual consumption of tobacco in Papua New Guinea increased from 573 to 1800 metric tonnes. The annual consumption of tobacco per head increased from 2.78 to 6.14 kg, and the proportion of commercial cigarettes smoked is estimated to have increased from 20% to 71% of the total tobacco consumption. Between 1965 and 1979 the average annual age standardised incidence of reported cases of carcinoma of the oral cavity increased significantly in women (p less than 0.01) but not in men (p greater than 0.05). This rise might have been related to increasing consumption of tobacco or alcohol, or both, in individuals who habitually chewed betel nut. There was no significant change in the reported incidences of carcinoma of the larynx, lung, oesophagus, pancreas, kidney, or bladder. At present there are no constraints on the marketing of tobacco in Papua New Guinea.     

Health promotion in the general practice consultation: a minute makes a difference.

OBJECTIVE--To see whether extending appointment length from seven and a half minutes or less to 10 minutes per patient would increase health promotion in general practice consultations. DESIGN--Controlled trial of 10 minute appointments. Consultations were compared with control surgeries in which the same doctors booked patients at their normal rate (median six minutes per patient). SETTING--10 general practices in Nottinghamshire. SUBJECTS--16 general practitioners were recruited. Entry criteria were a booking rate of eight or more patients an hour, a wish for longer consultations, and plans to increase appointment length. MAIN OUTCOME MEASURES--Duration of consultations; recording of blood pressure, weight, and cervical cytology in the medical record; recording of advice about smoking, alcohol, diet, exercise, and immunisation in the medical record; reporting of the above activities by patients. RESULTS--Mean consultation times were 8.25 minutes in the experimental sessions and 7.04 and 7.16 minutes in the control sessions. Recording of blood pressure, smoking, alcohol consumption, and advice about immunisation was significantly more frequent in the experimental sessions, and the proportion of consultations in which one or more items of health education were recorded in the medical notes increased by an average of over 6% in these sessions. Patients more often reported discussion of smoking and alcohol consumption and coverage of previous health problems in the experimental sessions. There was little change in discussion of exercise, diet, and weight or cervical cytology activity. CONCLUSIONS--Shortage of time is a major factor in general practitioners'' failure to realise their potential in health promotion. General practice should be organised so that doctors can run 10 minute appointment sessions.     

Provider Decisions to Treat Respiratory Illnesses with Antibiotics: Insights from a Randomized Controlled Trial

RationaleLower respiratory tract illness (LRTI) frequently causes adult hospitalization and antibiotic overuse. Procalcitonin (PCT) treatment algorithms have been used successfully in Europe to safely reduce antibiotic use for LRTI but have not been adopted in the United States. We recently performed a feasibility study for a randomized clinical trial (RCT) of PCT and viral testing to guide therapy for non-pneumonic LRTI.ObjectiveThe primary objective of the current study was to understand factors influencing PCT algorithm adherence during the RCT and evaluate factors influencing provider antibiotic prescribing practices for LRTI.ResultsDiagnosis of pneumonia on admission was the only variable significantly associated with non-adherence [7% (adherence) vs. 26% (nonadherence), p = 0.01]. Surveys confirmed possible infiltrate on chest radiograph as important for provider decisions, as were severity of illness, positive sputum culture, abnormal CBC and fever. However, age, patient expectations and medical-legal concerns were also at least somewhat important to prescribing practices. Physician agreement with the importance of viral and PCT testing increased from 42% to 64% (p = 0.007) and 49% to 74% (p = 0.001), respectively, after the study.ConclusionsOptimal algorithm adherence will be important for definitive PCT intervention trials in the US to determine if PCT guided algorithms result in better outcomes than reliance on traditional clinical variables. Factors influencing treatment decisions such as patient age, presence of fever, patient expectations and medical legal concerns may be amenable to education to improve PCT algorithm compliance for LRTI.     

Vascular effects of maternal alcohol consumption

Maternal alcohol consumption during pregnancy is a significant field of scientific exploration primarily because of its negative effects on the developing fetus, which is specifically defined as fetal alcohol spectrum disorders. Though the effects on the mother are less explored compared with those on the fetus, alcohol produces multiple effects on the maternal vascular system. Alcohol has major effects on systemic hemodynamic variables, endocrine axes, and paracrine factors regulating vascular resistance, as well as vascular reactivity. Alcohol is also reported to have significant effects on the reproductive vasculature including alterations in blood flow, vessel remodeling, and angiogenesis. Data presented in this review will illustrate the importance of the maternal vasculature in the pathogenesis of fetal alcohol spectrum disorders and that more studies are warranted in this field.     

Estimating joint kinematics from skin motion observation: modelling and validation

Modelling of soft tissue motion is required in many areas, such as computer animation, surgical simulation, 3D motion analysis and gait analysis. In this paper, we will focus on the use of modelling of skin deformation during 3D motion analysis. The most frequently used method in 3D human motion analysis involves placing markers on the skin of the analysed segment which is composed of the rigid bone and the surrounding soft tissues. Skin and soft tissue deformations introduce a significant artefact which strongly influences the resulting bone position, orientation and joint kinematics. For this study, we used a statistical solid dynamics approach which is a combination of several previously reported tools: the point cluster technique (PCT) and a Kalman filter which was added to the PCT. The methods were tested and evaluated on controlled human-arm motions, using an optical motion capture system (Vicon^TM).

The addition of a Kalman filter to the PCT for rigid body motion estimation results in a smoother signal that better represents the joint motion. Calculations indicate less signal distortion than when using a digital low-pass filter. Furthermore, adding a Kalman filter to the PCT substantially reduces the dispersion of the maximal and minimal instantaneous frequencies. For controlled human movements, the result indicated that adding a Kalman filter to the PCT produced a more accurate signal. However, it could not be concluded that the proposed Kalman filter is better than a low-pass filter for estimation of the motion. We suggest that implementation of a Kalman filter with a better biomechanical motion model will be more likely to improve the results.     

Estimating joint kinematics from skin motion observation: modelling and validation

Modelling of soft tissue motion is required in many areas, such as computer animation, surgical simulation, 3D motion analysis and gait analysis. In this paper, we will focus on the use of modelling of skin deformation during 3D motion analysis. The most frequently used method in 3D human motion analysis involves placing markers on the skin of the analysed segment which is composed of the rigid bone and the surrounding soft tissues. Skin and soft tissue deformations introduce a significant artefact which strongly influences the resulting bone position, orientation and joint kinematics. For this study, we used a statistical solid dynamics approach which is a combination of several previously reported tools: the point cluster technique (PCT) and a Kalman filter which was added to the PCT. The methods were tested and evaluated on controlled human-arm motions, using an optical motion capture system (Vicon(TM)). The addition of a Kalman filter to the PCT for rigid body motion estimation results in a smoother signal that better represents the joint motion. Calculations indicate less signal distortion than when using a digital low-pass filter. Furthermore, adding a Kalman filter to the PCT substantially reduces the dispersion of the maximal and minimal instantaneous frequencies. For controlled human movements, the result indicated that adding a Kalman filter to the PCT produced a more accurate signal. However, it could not be concluded that the proposed Kalman filter is better than a low-pass filter for estimation of the motion. We suggest that implementation of a Kalman filter with a better biomechanical motion model will be more likely to improve the results.     

Young inhabitants of the North with late chronotype and social jetlag consume more high-calorie foods and alcohol

Previous research has shown a high prevalence of late chronotype and social jetlag (SJL) among young northerners. These traits are also associated with unhealthy food preferences and greater alcohol consumption. The aim of this study was to analyze the relationships among characteristics of the sleep–wake rhythm and dietary preferences of young residents of the North. The study involved 282 participants from the Komi Republic (53.2% female) aged 18.9 ± 2.8 years old. Participants were asked to provide personal data and to complete two questionnaires: the Munich Chronotype Questionnaire and the Food Frequency Questionnaire. Females reported consuming 1.3 times more oils and fats than boys. Rural residents reported consuming 1.7 times more alcohol than urban residents. University students reported consuming 5.4 times more alcohol than secondary school students, but secondary school students consumed 1.6 and 1.5 times more meat and fruits, respectively. Participants with late chronotype reported consuming more alcohol, and those with a shorter duration of sleep reported consuming more tea and coffee. Respondents with SJL consumed more fats, oils, meat, and alcohol. The results indicate that unhealthy dietary habits of young northerners are more closely associated with SJL than with chronotype or the duration of sleep.     

Developing ways of reducing allograft immunogenicity.

Heavy alcohol consumption by the mother during pregnancy has long been suspected of being a risk factor for abnormalities in the fetus or infant. Only during the last decade have these assumptions been supported by scientific studies. A clustering of fetal defects observed in some cases has been labelled the fetal alcohol syndrome. The syndrome involves prenatal and postnatal growth retardation, central nervous system involvement and craniofacial abnormalities, some of which are characteristic of the syndrome. Fetal alcohol syndrome is relatively rare, affecting from 1 in 300 to 1 in 2000 infants; approximately 450 cases have been reported since the syndrome was identified. Despite this rarity, however, heavy alcohol consumption is an important risk factor during pregnancy. A review of the current literature indicates that in animals alcohol in high doses is embryotoxic and teratogenic, the heavy drinking is not uncommon before and during pregnancy and that the fetal alcohol syndrome and other effects on the fetus associated with alcohol abuse appear with significant frequency among mothers who drink heavily. Heavy alcohol consumption is a perinatal risk factor that not only can be detected by the physician, but also can be reduced in concerned, cooperative patients. Thus, awareness of this problem gives health care personnel an opportunity to help in the prevention of abnormal outcomes of pregnancy.