Expression of vitamin D-metabolizing enzymes in human adipose tissue -- the effect of obesity and diet-induced weight loss.

OBJECTIVE: Low vitamin D (VD) levels are common in obesity. We hypothesized that this may be due to metabolism of VD in adipose tissue (AT). Thus, we studied (1) whether the VD-metabolizing enzymes were expressed differently in AT of lean and obese individuals and in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and (2) whether their expression was influenced by weight loss. METHODS: Samples of SAT and VAT were analyzed for expression of the vitamin-D-25-hydroxylases CYP2R1, CYP2J2, CYP27A1 and CYP3A4, the 25-vitamin-D-1α-hydroxylase CYP27B1, the catabolic vitamin-D-24-hydroxylase CYP24A1, and the vitamin D receptor, using reverse transcriptase-PCR. Moreover, plasma 25-hydroxy-vitamin D (25OHD) level was measured and related to the expression of these enzymes. Samples of SAT and VAT from 20 lean women and 20 obese women, and samples of SAT from 17 obese subjects before and after a 10% weight loss were analyzed. RESULTS: A plasma 25OHD level <50 nmol l(-1) was highly prevalent in both lean (45%) and obese (90%) women (P<0.01). Plasma 25OHD increased by 27% after weight loss in the obese individuals (P<0.05). Expression levels of the 25-hydroxylase CYP2J2 and the 1α-hydroxylase CYP27B1 were decreased by 71% (P<0.0001) and 49% (P<0.05), respectively, in SAT of the obese. CYP24A1 did not differ between lean and obese women, but the expression was increased by 79% (P<0.05) after weight loss. CONCLUSION: Obesity is characterized by a decreased expression of the 25-hydroxylase CYP2J2 and the 1α-hydroxylase CYP27B1 in SAT, whereas the catabolic CYP24A1 does not differ between lean and obese women. However, the expression of CYP24A1 is increased after weight loss. Accordingly, AT has the capacity to metabolize VD locally, and this can be dynamically altered during obesity and weight loss.

Sustained effect of SQ-standardized grass allergy immunotherapy tablet on rhinoconjunctivitis quality of life.

BACKGROUND: The prevalence of allergic rhinoconjunctivitis has increased significantly over the past decades with grass pollen being a common trigger. The impact of allergy on patient's quality of life is substantial. AIM: To investigate the sustained effect on quality of life during the grass pollen season 1 year after 3 years of treatment with the SQ-standardized grass allergy immunotherapy tablet (AIT), Graza (Phleum pratense 75,000 SQ-T/2800 BAU; ALK, Denmark). METHODS: The trial was a randomized, parallel-group, double-blind, placebo-controlled trial in adult subjects with a history of moderate-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. Subjects received 3 years of grass AIT (n = 157) or placebo (n = 126), followed by 1 year of follow-up. Quality of life assessments were based on the standardized rhinoconjunctivitis quality of life questionnaire (RQLQ(S)); completed weekly during the entire grass pollen season. RESULTS: During follow-up, the overall RQLQ(S) score for the entire grass pollen season was significantly improved in the active group (relative difference to placebo: 23%, P = 0.004). The improvement was higher during the peak pollen season (28%, P = 0.001). The treatment effect of grass AIT during the follow-up year and the previous three treatment years was similar. Improvements were found in all seven RQLQ(S) domains. The RQLQ(S) as a function of the weekly average pollen counts showed a clear separation between the treatment groups (P < 0.001). CONCLUSION: In subjects inadequately controlled by symptomatic medications, grass AIT provided sustained and clinically relevant improvements in rhinoconjunctivitis quality of life compared to placebo. The effect increased with increasing grass pollen exposure.

Estimation of ejection fraction and stroke volume using single- and biplane magnetic resonance imaging of the left cardiac ventricle.

BACKGROUND: In cardiac magnetic resonance imaging (MRI), left ventricular stroke volume (SV) and ejection fractions (EF) are occasionally calculated using single-plane and biplane ellipsoid models. In previous studies, the calculated SV and EF using single- and biplane ellipsoid models have been compared to reference values calculated from short-axis (SA) images. In these studies, however, it has been emphasized that through-plane motion of the basal SA images represents an important source of error, which may result in incorrect reference values. PURPOSE: To compare the calculated SV and EF using single-plane and biplane ellipsoid models with SV and EF calculated from SA images in which compensation was made for through-plane motion. MATERIAL AND METHODS: A group of 20 patients who underwent MRI examination were included in the study. SV and EF were calculated using the stack of SA images (which had been compensated for through-plane motion) and compared to the SV and EF calculated according to the single- and biplane ellipsoid models. RESULTS: The mean difference between the single-plane model and the reference was -0.3+/-6.5 for EF and 7.2+/-17.1 ml for SV. Corresponding comparison between the biplane method and the reference resulted in a mean difference of 0.3+/-6.1 for EF and 11.8+/-14.9 ml for SV. CONCLUSION: The results from this study show that left ventricular EF can be adequately estimated using the single- and biplane ellipsoid models, while SV tends to be overestimated using both geometrical models.

Computer-assisted evaluation of dipyridamole thallium-201 SPECT in patients with aortic stenosis.

UNLABELLED: Dipyridamole SPECT detects significant coronary artery disease (CAD) in patients without aortic stenosis. This study was done to establish normal 201Tl distribution limits in patients with aortic stenosis and to apply these normal limits to patients with aortic stenosis and angiographically significant CAD (> or = 75% area reduction). METHODS: Fifty-two patients (mean age 68 yr; mean valve area 0.67 cm2) were examined with 201Tl SPECT after dipyridamole infusion (0.56 mg/kg during 4 min). After tomographic reconstruction, basal, mid-ventricular and apical short-axis slices were selected. The highest activity in each six-degree segment was normalized to the maximal activity of each slice. RESULTS: Significant CAD was found in 24 patients. Five patients without CAD, but with localized hypokinesia or left bundle-branch block, were excluded from the reference group which finally consisted of 16 patients. Sensitivity for CAD was 88% when the lowest relative activity in each segment was used as the lower limit of normal. With -2 s.d. and -2.5 s.d. curves the sensitivity was 83% and 75%, respectively. Gender-specific limits were not used. Nonsignificant CAD was found in seven patients (< 75% stenoses). CONCLUSIONS: This study presents the normal distribution of 201Tl uptake for patients with aortic stenosis, using dipyridamole SPECT. The range method had the highest sensitivity for detection of significant CAD.

Chondroitin sulfate proteoglycan distribution in the primate optic nerve head.

PURPOSE: To evaluate the presence and distribution of chondroitin and dermatan sulfate-containing proteoglycans in normal human and monkey optic nerve heads by light microscopic immunohistochemistry. METHODS: Monoclonal antibodies specific for glycosaminoglycan attachment sites remaining after incubation of tissues with chondroitinase ABC and ACII were used to detect proteoglycans containing unsulfated chondroitin (OS), chondroitin-4 and/or dermatan sulfate (4S), and chondroitin-6 sulfate (6S) glycosaminoglycans. RESULTS: 4S antibody labeling after chondroitinase ABC was heavily and evenly distributed within the peripapillary sclera and in the core of laminar beams and optic nerve septa. Preincubation with chondroitinase AC, which exposes only chondroitin sulfate attachment sites, diminished labeling intensity in the lamina cribrosa and sclera and almost completely eliminated it in the retrolaminar optic nerve septa. In contrast, 6S antibodies demonstrated a more intermittent linear distribution throughout the laminar beams and optic nerve septa. No qualitative differences were seen between human and monkey optic nerve heads. CONCLUSION: Chondroitin and dermatan sulfate-containing proteoglycans exist throughout the support tissues of the optic nerve head. The specific distribution patterns demonstrated by these monoclonal antibodies, and, in particular, the unique confinement of one of them to the lamina, indicate the presence of different core proteins or different functional glycosaminoglycan side chains that may influence the behavior of the lamina cribrosa.

Dental caries and salivary and microbial conditions in 50-60-year-old persons.

In a group of 124 persons, 50-60 yr old, the prevalence at baseline of mutans streptococci (MS) and lactobacilli and the salivary secretion rate and buffer capacity were examined. The mean secretion rate was 1.58 mL/min with a flow rate below 1 mL/min found in 20% of the persons. A buffer capacity below end pH 5.5 was observed in 64% of the subjects. MS was not detected in 5% of the persons whereas 17% had 10(6) or more MS per ml saliva. Lactobacilli were not found in 10% of the persons while 21% had counts in excess of 10(5) CFU mL. A new examination 5 yr later in 1986 revealed no significant changes in secretion rate and buffer capacity or in the population of lactobacilli, whereas markedly elevated levels of salivary MS were found. S. sobrinus was detected in 35-37% of the persons at the two examinations. Persons with both S. mutans and S. sobrinus had more MS than persons with only S. mutans.

Shigella in Tulsa County, 1993: epidemiology, day care center association, and control.

Tulsa County experienced an epidemic of Shigella sonnei infection and diarrheal disease during 1993. Of the 298 cases documented, 262 occurred in day care centers. There were 227 epidemiologically-linked secondary cases, primarily in parents and siblings. The mode of transmission was primarily person-to-person among family members and children in day care centers. In addition, transmission may also have occurred as the result of fomities in some day care centers. Control was achieved by antibiotic therapy, inspection, and retraining all day care centers' staffs in hand washing techniques and infection control concepts.

[Suicide and other causes of death in patients admitted for attempted suicide. 10-year follow-up]. / Selvmord og andre dødsårsager hos patienter indlagt efter selvmordsforsøg. Ti års opfølgning.

The purpose of this study has been to describe the course over ten years and prognosis for a cohort of patients who had been admitted to a psychiatric department following a suicide attempt. The cohort consisted of 207 patients who had been admitted in the period 1.10.1980-20.4.1981 to a department of psychiatry following a suicide attempt. At the index attempt 99 patients were randomly selected and interviewed. Information on the remainder was obtained from psychiatric case histories, casualty records and discharge reports. Ten years after the index attempt information concerning death, date and cause was collected. Of the 207 patients involved, 52 (25.1%) were dead. Twenty-five (12.1%) had committed suicide, the remainder had died of natural, accidental or unknown causes. Relative to the general population the death rate from suicide and other causes was extremely high. Predictors of suicidal outcome were substance abuse and dangerous index attempt. At least one of these two predictors was present for 72% of those who committed suicide and for 43% of those who did not commit suicide. Aging and previous suicide attempts were the only significant predictors of other causes of death.

[Differences between male and female alcoholics and differences in their need of treatment]. / Forskelle mellem kvindelige og mandlige alkoholmisbrugere og forskelle i deres behandlingsbehov.

The present study covers 375 consecutive patients referred to the three outpatient clinics at the Psychiatric Department of Odense University Hospital from November 1995 to February 1997. The aim of the study was to describe differences in problem profiles for men and women. All patients were assessed by means of the Addiction Severity Index at admission. All patients needed treatment for alcohol problems. Significantly more female alcoholics, however, had problems with mental health, physical health, drug use and family/social life. More men than women had legal problems. Almost half of the women had previously attempted to commit suicide, and almost one third of the women suffered from anxiety disorder at the time of admission. Significantly more women than men had partner who also had an alcohol problem.

[Factors related to suicidal behavior among alcoholics]. / Faktorer relateret til suicidal adfaerd blandt alkoholmisbrugere.

Of 181 alcoholics who consecutively sought treatment as out- or inpatients, 68 (37.6%) had attempted suicide at least once. Compared with non-attempters, the suicide attempters were significantly more likely to be female, have had a chaotic upbringing and to have known suicide attempts in the family and social circle. Significantly more attempters suffered from depressive disorder, feelings of hopelessness, anxiety attacks, agoraphobia, substance abuse or cluster B personality disorders (dissocial, impulsive, borderline, and histrionic). Also significantly more suicide attempters had committed crimes and received early pension. Assessment of coping showed that suicide attempters had a significantly lower tendency to make plans or to make the best of a stressful situation by growing from it. They were significantly more likely to show mental disengagement, to resort to denial and drink alcohol or take drugs when faced with stressful events or difficulties. When evaluated on the Addiction Severity Index Scale, the suicide attempters were found to have a significantly greater need of treatment.

[Therapy control of perphenazine in paranoid conditions. 1. Organizational aspects]. / Terapistyring af perfenazinbehandling ved paranoide tilstande. 1. Organisatoriske aspekter.

A prospective investigation was carried out in the Department of Psychiatry, Odense University Hospital, on therapy control by serum monitoring of the neuroleptic, perphenazine for a period of one year. Newly admitted patients requiring treatment for paranoid symptoms, excluding mania, were offered medication with perphenazine (fixed dosage, oral or parenteral (depot)) which would be serum-monitored. A global record was made of the therapeutic effect and the side-effects by the physicians in the department. In the investigation period, 605 admissions were registered in the department, of them 363 were prospectively registered in the investigation. In all 199 were found to satisfy the inclusion criteria. Either one or two blood tests were carried out on each of 141 patients in the treatment period, i.e. six weeks. The gap in registration is consistent with the result from other investigations. Participation in the investigation varied from ward to ward (33%-87%). The reason for the variation is mainly due to different treatment procedures and traditions. The main conclusion drawn from the investigation is that it is possible to set up a stable treatment/serum-monitored system. In the majority of cases, the team of physicians in the department succeeded in finding the dosage most appropriate on the basis of the serum concentration level. Laboratory recommendations were followed in 93% of the cases.

[Educational requirements of younger psychiatrists]. / Yngre psykiateres uddannelsesønsker.

In order to define the requirements junior medical staff in postgraduate psychiatric training would wish to make for future postgraduate training in adult psychiatry, a questionnaire with 66 questions was sent in June 1990 to postgraduate trainees at all departments of child psychiatry and adult psychiatry in the country. Response was anonymous. The article deals with the responses from 264 persons either intending to undergo specialist training in adult psychiatry or having already completed it. Sixty-four percent stated a need for better individual clinical guidance. The majority stated that eight hours every week should be earmarked for formal tuition and research (two hrs clinical tuition, two hrs theory, two hrs supervision in psychotherapy, and two hrs for research). On average, the trainees had used 4200 DKK of their own income and four free days on courses over the previous year. Twenty-four months was proposed as adequate for an introductory appointment. The majority held that appointments should be made on the basis of the traditional curriculum vitae (82%) and a personal interview (86%), while about 20% believed that written or oral references should also be a requirement. Sixty-nine percent believed that selection of applicants for teaching appointments should be made locally with central supervision. Twenty-six percent felt they had been passed over in appointment situations, and 68% claimed it was due to nepotism. Recommendations for modifications of the future postgraduate training according to the responses are proposed, and it is concluded that earmarked resources are necessary, if the intention in the educational reform now in progress is to be realized.

Left and right ventricular systolic long-axis function and diastolic function in patients with takotsubo cardiomyopathy.

AIMS: Takotsubo cardiomyopathy is characterized by apical wall motion abnormalities without coronary stenosis. Limited information is available on the genesis of the underlying reversible contractile disorder. Our objective in this prospective study was to investigate biventricular changes in systolic long-axis function and diastolic parameters in the acute phase and after recovery. METHODS AND RESULTS: Thirteen consecutive patients were examined by echocardiography and coronary angiography at admission and again by echocardiography after 3 months. Amplitudes, systolic and diastolic velocities of the mitral and tricuspid annuli and conventional diastolic parameters were measured. Systolic long-axis shortening of the left ventricle (LV) and right ventricle (RV) improved from 9.6 ± 2.2 mm to 11.2 ± 1.9 mm (P = 0.02) and from 21.3 ± 3.6 mm to 24.1 ± 2.8 mm (P = 0·02), respectively. LV systolic, early and late diastolic velocities measured by pulsed-wave tissue Doppler also improved, while additional conventional diastolic parameters of the LV and RV diastolic function were unchanged. CONCLUSIONS: Takotsubo cardiomyopathy temporarily affects systolic LV and RV function, while most diastolic parameters remain unchanged.

Heart rate variability in children with Fontan circulation.

Heart rate variability (HRV) can be used to study cardiovascular autonomic control. This study examines HRV in children with Fontan circulation and its change over time. Thirty-four children in two groups were examined. Group A consisted of 10 patients who had undergone total cavopulmonary connection. Group B consisted of 24 healthy children/adolescents matched for gender, height, and weight. To analyze HRV parameters, all examinations included echocardiography and 24-hour ambulatory electrocardiogram. Comparing all patients and controls, there were no significant differences in HRV parameters. Analyzing subgroups of patients younger than 10 years old, two of the HRV parameters were significantly different compared to controls. For the group of patients older than 10 years, eight of the HRV parameters were significantly reduced. Most significant differences were found regarding low-frequency range (p < 0.008) and high-frequency range p < 0.008. This study confirms the finding of earlier studies that patients with Fontan circulation have a reduced HRV, and our findings indicate that there is a progressive reduction of HRV over time.

Electrocardiographic ST segment depression and clinical function in children with Fontan circulation.

Previous studies noted that Fontan patients have electrocardiographic ST depressions during exercise tests and on 24-hour ambulatory electrocardiographic (ECG) monitoring. This study investigated whether the ST depressions were correlated to clinical function (NYHA Functional Classification). Forty-five children in two groups were examined--15 patients with Fontan circulation and 30 with a structurally normal heart, matched for sex, height, and weight. Clinical and echocardiographic examinations were performed. The clinical state was defined as NYHA functional classes I-IV. All 45 children underwent 24-hour ECG and an analysis of ST changes was performed, with ST segment depression > 0.20 mV at ST 60 regarded as significant. Twelve of 15 patients had significant 24-hour ECG ST depressions; in 9 of 12 patients these occurred on more than one occasion. Comparing 24-hour ECG recordings from patients in NYHA I with patients in NYHA II or III showed a significant difference in depth (p = 0.0023), duration (p = 0.0016), and number of ST depressions (p = 0.0001). None of the matched healthy children showed ST depressions. Repeated ST analysis on 24-hour ECG shows that the ST depressions seem to be correlated to functional status and this may be a useful tool in clinical praxis.

Childhood experiences and repeated suicidal behavior.

The aim of this study was to elucidate the influence of various events in childhood on suicidal behavior in adult age. For this purpose, 99 patients admitted to the Department of Psychiatry of Odense University Hospital after making a suicide attempt were followed for 5 years, to register repeated suicidal behavior. The results showed that three fourths of the patients attempted suicide more than once (62% nonfatal and 14% fatal outcome). The sex distribution was about the same among the first-evers as among the repeaters. Most repeaters were younger people in their twenties and thirties, and the first-evers on average were past the age of 40. Somewhat unexpectedly, significantly more repeaters than first-evers had grown up with both their parents. However, the results also showed that significantly more repeaters than first-evers had had an unhappy childhood. This indicates that the psychological climate of the home may be more important than the rupture of early home life. It is noteworthy that the group of repeaters, as against the first-evers, could be characterized by personality disorders and abuse, especially of alcohol: disorders known to be precipitated by a discordant childhood. It is commonly agreed that the experience in childhood of suicidal behavior among family members or other persons in the close environment is of importance in future suicidal risk. The results of this study indicate that the predictive value of this factor mainly applies to attempts with no fatal outcome: the suicidal act is perceived--and learned--as way to solve problems.

Electrocardiographic ST-segment depression in children with fontan circulation.

Despite successful operation, many patients palliated with a Fontan-type procedure continue to show effort limitation. We previously observed that these children showed electrocardiographic ST depression during exercise tests. The purpose of the study was to investigate whether electrocardiographic ST depression is a common finding in children with Fontan circulation. Forty-two children in two groups were examined: group A consisted of 14 patients who had all undergone a modified Fontan procedure, and group B consisted of 28 children with a structurally normal heart, matched for length, weight and gender to group A. Complete echocardiographic examinations were performed in all patients and controls. All 14 patients and all 28 healthy children underwent standard 24 h ambulatory electrocardiographic monitoring. All the recordings were analysed by a PC-based Holter system where an analysis of ST changes was performed. Seven patients and 14 matched healthy children were exercised on bicycle ergometers. Four patients and eight matched healthy children underwent exercise testing by walking/running a treadmill. Ten of 13 patients analysed had significant ST depressions on ambulatory electrocardiogram (>0.20 mV). Three of the 10 patients with ST depression were on digoxin. Three patients showed depressions of the ST segment in the electrocardiogram during exercise, with a maximal depression of 0.20-0.35 mV. None of the 28 matched healthy children showed electrocardiographic ST depression on the ambulatory 24 h ECG. These findings indicate that ST depression in daily activity is a common finding in children with Fontan circulation.

Zuclopenthixol and perphenazine in patients with acute psychotic states. A double-blind multicentre study.

Fifty-four patients with acute psychotic states were included in a double-blind multicentre study of zuclopenthixol and perphenazine given orally. Fourteen patients had not received test preparations for a minimum of 3 weeks as stated in the protocol, and were excluded. The remaining 40 patients received the test preparations for 3 to 12 weeks, with an average of 49 days for patients receiving zuclopenthixol and 45 days for patients receiving perphenazine. Clinical evaluations were done at baseline and at weeks 1, 2, 4, 6, 8, and 12 including the CGI, a CPRS subscale for schizophrenia, and the UKU Side Effects Rating Scale. The patients received on average 37 mg zuclopenthixol or 30 mg perphenazine daily. Statistically, significant reductions on the CGI, severity of illness, and on the CPRS (total score) were found for both drugs when comparing baseline with later scores. No significant differences between the drugs were found. It was also impossible to demonstrate a difference in clinical profile between the two drugs on the basis of the single items on the CPRS. Although small differences between the two drugs were found, as regards number and type of side effects, it is concluded that the pattern of side effects was almost identical in the two treatment groups.

Effect of preventive measures in 50-60-year-olds with a high risk of dental caries.

Salivary and microbial conditions were examined in 124 50-60-yr-old patients attending a dental clinic of the Public Dental Health Service. They were then randomly divided into a control and a test group. Patients with low salivary secretion rate and buffer capacity and high numbers of mutans streptococci and lactobacilli in the test group received special caries preventive measures during 1 yr. In the control group all patients were given prevention according to routine procedures. The incidence of dental caries between the groups was compared. The risk patients in the control group developed 1.67 new carious lesions as compared to 0.19 in the test group. The difference was statistically significant (P less than 0.05). Also the numbers of mutans streptococci and lactobacilli were significantly lower in the risk patients in the test group after 1 yr compared with baseline values. After the experimental year all patients were treated according to routine procedures. Five years after the start of the study a new examination showed increased caries activity in the risk patients in the test group and the gain which had been made during the experimental year was almost lost.