A changing landscape: Temporal trends in incidence and characteristics of patients hospitalized with venous thromboembolism 2006-2015.

BACKGROUND: Venous thromboembolism (VTE) has major clinical and public health impact. However, only sparse data on calendar time trends in incidence from unselected populations reflecting current clinical practice are available. OBJECTIVES: To examine temporal trends in the incidence and characteristics of patients hospitalized with first-time VTE in Denmark between 2006 and 2015. PATIENTS/METHODS: Using nationwide health care registries, we calculated yearly hospitalization rates for first-time VTE from 2006 to 2015. The rates were standardized to the age and sex distribution in 2006. Based on the hospitalization and prescription history of each patient, we assessed the risk profile and evaluated changes over time. RESULTS: We identified 67,426 patients with a first-time VTE hospitalization. The age- and sex-standardized incidence rate increased from 12.6 (95% CI: 12.3-12.9) per 10,000 person years at risk in 2006 to 15.1 (95% CI: 14.7-15.4) in 2015, corresponding to an increase of 19.8%. The increase was due to a 73.9% increase in the standardized incidence rate of pulmonary embolism (PE), whereas no increase was observed for deep vein thrombosis. The risk profile changed with an increasing proportion of elderly patients and patients with comorbidity (proportion of patients with a Charlson's Comorbidity Index score of ≥1). CONCLUSIONS: The hospitalization rate of first-time VTE, and particularly PE, has increased substantially within the last decade in Denmark. In addition, the risk profile of the VTE population has changed with more elderly and more patients with comorbidity being diagnosed. Further efforts are warranted to explore the changes in VTE epidemiology and the clinical implications.

ACS NSQIP Surgical Risk Calculator: Pilot Analysis on Feasibility in an Academic Safety Net Hospital.

BACKGROUND: Hospitals are looking for effective methods to track outcomes that are risk-adjusted for patient population characteristics. This is especially relevant for safety net hospitals (SNHs) servicing high-risk populations and in an era of quality-based reimbursement incentives. One such program with these goals is the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). This is an institution-based quality audit whereby we determined the presence and consistency of charted data required to compute perioperative risk in the ACS NSQIP risk calculator. MATERIALS AND METHODS: A retrospective chart review of 28 elective colorectal procedures was performed at an urban, academic SNH over a 1-y period. For each case, it was determined whether the required NSQIP variables were readily presented via preoperative documentation. Univariate and bivariate statistics were employed to compare data field completion rates. RESULTS: Of the 28 reviewed patient charts, none (n = 0) had all preoperative risk documentation required to complete an ACS NSQIP risk analysis. 89.3% of charts (n = 25) had ≤ 55% of required data to complete a risk assessment. However on bivariate analysis, demographic variables were more likely to have been recorded (P < 0.001) than other risk factors. CONCLUSIONS: Preoperative risk assessment and corresponding charting practices at the SNH reviewed was fragmented and incomplete. There was lack of definitive documentation of risk factors and preoperative interventions used to modulate risk. Under current reimbursement models such as the MACRA Quality Payment Program, these findings are crucial for like-institutions to consider to critically evaluate their own documentation practices.

A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury.

Men with spinal cord injury are at an increased risk for secondary medical conditions, including metabolic disorders, accelerated musculoskeletal atrophy, and, for some, hypogonadism, a deficiency, which may further adversely affect metabolism and body composition. A prospective, open label, controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled. Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12 months. Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months. The testosterone replacement therapy group increased lean tissue mass for total body (49.6 ± 7.6 vs. 53.1 ± 6.9 kg; p < 0.0005), trunk (24.1 ± 4.1 vs. 25.8 ± 3.8 kg; p < 0.005), leg (14.5 ± 2.7 vs. 15.8 ±2.6 kg; p = 0.005), and arm (7.6 ± 2.3 vs. 8.0 ± 2.2 kg; p < 0.005) from baseline to month 12. After testosterone replacement therapy, resting energy expenditure (1328 ± 262 vs. 1440 ± 262 kcal/d; p < 0.01) and percent predicted basal energy expenditure (73 ± 9 vs. 79 ± 10%; p < 0.05) were significantly increased. In conclusion, testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury, findings that would be expected to influence the practice of clinical care, if confirmed. Larger, randomized, controlled clinical trials should be performed to confirm and extend our preliminary findings.

[Exposure to smoke and its effects on pulmonary diseases]. / Effekte von Rauchexposition auf Lungenerkrankungen.

For many diseases, tobacco smoke is the most important risk factor. To understand the different risks concerning both quality and severity of the possible diseases, the differentiation between mainstream smoke, sidestream smoke and environmental tobacco smoke (ETS) is indispensable, since the different types of smoke are associated with different diseases. Before anything else, tobacco smoke is the main risk factor for the development of lung cancer and with restrictions for laryngeal and pharyngeal carcinomas as well. Moreover, the inhalation of tobacco smoke is of great importance in the genesis of chronic obstructive lung diseases (COPD). During recent years it has generally been acknowledged that ETS, besides a general activity in cancerogenesis also, seems to induce other morbidities. Nevertheless, when looking at the risks of smoking it has to be mentioned that the difficulty of gaining reliable information concerning quality and quantity of the smoking and the exposure to ETS is significant. That is why in many cases the relation between the dose of tobacco smoke and its effect is hard to make out. Not to be denied is the fact that both active and passive smoking has a great impact on the respiratory tract, which should be considered carefully when it comes to children being exposed to ETS. The age of children when exposed to regular ETS for the first time plays a key role concerning their disposition to later developing a COPD or a bronchial asthma. This subject of ETS is especially of great interest in the work of company doctors because there are many people exposed to ETS for many hours every day in their work environment. This problem is most obvious in the gastronomic work sector.

Cisplatin decreases renal cyclooxygenase-2 expression and activity in rats.

AIM: Cisplatin (CP) induced acute renal failure (ARF) has previously been associated with decreased urinary prostaglandin E2 (PGE2) excretion and reduced aquaporin 2 (AQP2) expression in kidney collecting duct. In this study we examined the expression of cyclooxygenase (COX)-1 and -2 as well as AQP2 and the Na-K-2Cl cotransporter in kidneys from rats with CP induced ARF. METHODS: Rats were treated with either CP or saline and followed for 5 days. Kidneys were dissected into three zones and prepared for immunoblotting, quantitative polymerase chain reaction (QPCR) and immunohistochemistry. Renal content and urinary PGE2 excretion was measured. RESULTS: Cisplatin treatment was associated with polyuria and a significant decreased creatinine clearance. Inner medullary PGE2 content and urinary PGE2 excretion was decreased in CP-treated rats. QPCR and semiquatitative immunoblotting demonstrated that CP treatment reduced COX-2, AQP2 and Na-K-2Cl cotransporter abundance in the different kidney zones, whereas no change in COX-1 was observed. Results were confirmed by immunohistochemistry. CONCLUSION: Cyclooxygenase-2 expression is decreased in inner medulla and cortex. Consistent with this urinary PGE2 levels were reduced. These data suggest that downregulation of COX-2 is responsible for impaired de novo generation of vasodilatory prostaglandins which may play an important role for the CP induced renal vasoconstriction and development of nephropathy.

[Pulmonary hypertension--clinical aspects, pathophysiology, diagnostic and therapy]. / Pulmonale Hypertonie--Klinik, Patho- physiologie, Diagnostik und Therapie.

Pulmonary hypertension (PH) is a disease which is characterised by an increase in the mean pulmonary arterial pressure (mPAP) in the lung circulation of over 25 mmHg in rest and over 30 mmHg in movement. Due to the chronic overload of the right ventricle, the heart is always affected by a PH and often develops a so-called cor pulmonale chronicum which can lead to right-heart failure. There are five groups in the clinical WHO Venice classification which are arranged according to pathogenetical, clinical and therapeutical criteria. In addition, an adjusted NYHA classification helps to grade the significance of the disease stages. Principally, one classifies a mostly isolated form of the pulmonary arterial hypertension (PAH) and other secondary forms of the PH which develop on the grounds of existing problems such as left-heart diseases, hypoxic lung diseases, pulmonary embolism and infections. The pathophysiological reasons for a PH are just as various as the different manifestations. Yet there are generally four main alterations in the walls of the pulmonary vessels. This includes vasoconstriction, rarefaction of vessels, vascular remodelling and the occlusion of vascular lumen by a thrombus with subsequent structural remodelling of the vascular and mounted extracellular matrix. The diagnostic procedure should be algorithm-oriented and includes anamnesis, physical examination, electrocardiogram (ECG), thoracic x-ray and echocardiography. To confirm the diagnosis and for a better measuring of the prognosis, an examination with a right-heart flow-directed balloon-tipped catheter is favourable. Because of the change in the pathophysiological concepts of the PH from a vasoconstrictive to a vasoproliterative genesis, additional pharmacological targets are developed for therapeutic treatment. Today the former regime of therapy with high-dosed calcium-channel blockers such as vasodilatators only finds application after pharmacological testing at so-called responders. The current scheme of therapy is focused on the synergic effects of different drugs, such as prostacyclines, endothelial-receptor blockers and phosphodiesterase-5 inhibitors. After the failure of pharmacological treatments, the endarteriectomy remains as the last therapy option, although it is accompanied by poor survival rates.

[MRSA--current aspects of resistance, pathology, epidemiology and therapy]. / MRSA--aktuelle Aspekte der Resistenzentwicklung, Pathomechanismen, Epidemiologie und Therapie.

The Methicillin-resistant Staphylococcus aureus (MRSA) is a Staphylococcus aureus (S. aureus) resistant against all kinds of beta-lactam antibiotics. Moreover, resistances against other antibiotics have gradually started to develop. In the last decades, MRSA started as a serious problem only in hospitals, but in recent years it also rose as an alarming community pathogen. In addition to the resistances against Penicillin which emerged in the 1940s. with the use of beta-lactamase proof antibiotics in the 1960s, the resistance of S. aureus against Methicillin started to develop. According to the kind of resistance, the genotype, the time of infection and the origin of the infection, MRSA infections are classified as hospital-associated (HA-MRSA) and community-associated (cMRSA). On the one hand, this differentiation results in distinct strategies of calculated therapy against each class of MRSA. On the other hand, it is important in order to identify relevant judicious aspects of transmission.

Contribution of highly industrially processed foods to the nutrient intakes and patterns of middle-aged populations in the European Prospective Investigation into Cancer and Nutrition study.

OBJECTIVES: To describe the contribution of highly processed foods to total diet, nutrient intakes and patterns among 27 redefined centres in the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Single 24-hour dietary recalls were collected from 36,034 individuals (aged 35-74 years) using a standardized computerized interview programme (EPIC-SOFT). Centre-specific mean food intakes (g/day) were computed according to their degree of food processing (that is, highly, moderately and non-processed foods) using a specifically designed classification system. The contribution (%) of highly processed foods to the centre mean intakes of diet and 26 nutrients (including energy) was estimated using a standardized nutrient database (ENDB). The effect of different possible confounders was also investigated. RESULTS: Highly processed foods were an important source of the nutrients considered, contributing between 61% (Spain) and 78-79% (the Netherlands and Germany) of mean energy intakes. Only two nutrients, beta-carotene (34-46%) and vitamin C (28-36%), had a contribution from highly processed foods below 50% in Nordic countries, in Germany, the Netherlands and the United Kingdom, whereas for the other nutrients, the contribution varied from 50 to 91% (excluding alcohol). In southern countries (Greece, Spain, Italy and France), the overall contribution of highly processed foods to nutrient intakes was lower and consisted largely of staple or basic foods (for example, bread, pasta/rice, milk, vegetable oils), whereas highly processed foods such as crisp bread, breakfast cereals, margarine and other commercial foods contributed more in Nordic and central European centres. CONCLUSIONS: Highly industrially processed foods dominate diets and nutrient patterns in Nordic and central European countries. The greater variations observed within southern countries may reflect both a larger contribution of non/moderately processed staple foods along with a move from traditional to more industrialized dietary patterns.

Eating out of home: energy, macro- and micronutrient intakes in 10 European countries. The European Prospective Investigation into Cancer and Nutrition.

OBJECTIVES: To assess the contribution of out-of-home (OH) energy and nutrient intake to total dietary intake, and to compare out- versus in-home nutrient patterns among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Between 1995 and 2000, 36,034 participants aged between 35-74 years completed a standardized 24-h dietary recall using a software programme (EPIC-Soft) that recorded the place of food/drink consumption. Eating OH was defined as the consumption of foods and beverages anywhere other than in household premises, irrespective of the place of purchase/preparation. Nutrient intakes were estimated using a standardized nutrient database. Mean intakes were adjusted for age and weighted by season and day of recall. RESULTS: Among women, OH eating contributed more to total fat intake than to intakes of protein and carbohydrates. Among both genders, and particularly in southern Europe, OH eating contributed more to sugar and starch intakes and less to total fibre intake. The contribution of OH eating was also lower for calcium and vitamin C intakes. The composition of diet at home was different from that consumed out of home in southern countries, but was relatively similar in the north. CONCLUSIONS: In northern Europe, OH and in-home eating are homogeneous, whereas southern Europeans consider OH eating as a distinctive occasion. In most centres, women selected more fat-rich items when eating out.

mosaic eyes: a zebrafish gene required in pigmented epithelium for apical localization of retinal cell division and lamination.

For proper function of the retina, the correct proportions of retinal cell types must be generated, they must be organized into cell-specific laminae, and appropriate synaptic connections must be made. To understand the genetic regulation of retinal development, we have analyzed mutations in the mosaic eyes gene that disrupt retinal lamination, the localization of retinal cell divisions to the retinal pigmented epithelial surface and retinal pigmented epithelial development. Although retinal organization is severely disrupted in mosaic eyes mutants, surprisingly, retinal cell differentiation occurs. The positions of dividing cells and neurons in the brain appear normal in mosaic eyes mutants, suggesting that wild-type mosaic eyes function is specifically required for normal retinal development. We demonstrate that mosaic eyes function is required within the retinal pigmented epithelium, rather than in dividing retinal cells. This analysis reveals an interaction between the retinal pigmented epithelium and the retina that is required for retinal patterning. We suggest that wild-type mosaic eyes function is required for the retinal pigmented epithelium to signal properly to the retina.

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2.

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.

Associations of Neospora caninum seropositivity with gestation number and pregnancy outcome in Danish dairy herds.

The prevalence and distribution of seropositivity towards the protozoan parasite Neospora caninum were studied in single blood samples from 1561 cows from 31 Danish dairy herds. Blood samples were analysed by an indirect enzyme-linked immunoassay and an indirect fluorescent-antibody test. Seroprevalence in 15 herds with previous abortions assigned to neosporosis ranged from 1% to 58%, with a mean frequency of 22%. In eight out of 16 herds without a history of N.caninum related abortions, no seroreactors were found. In the remaining eight herds, the seroprevalence ranged from 6% to 59%. The prevalence and distribution of seropositivity, gestation number prior to sampling, and breed were related to abortions and perinatal deaths using a random-effects logistic-regression model. Abortion risk was significantly increased in seropositive animals (OR = 3) and in > or = 2nd-gestation cows (OR = 3). Perinatal death was significantly influenced by gestation number and breed, but not by serostatus. Reproductive performance and culling risk of cows were not affected by serostatus. Seropositivity increased with "age" (i.e. gestation number) (P = 0.02). In open cows, seropositivity tended to decrease with distance from calving (P = 0.05). The proportion of seropositive pregnant cows increased with trimester (P = 0.02).

Clinical study of a digital vs an analogue hearing aid.

Digital signal processing in hearing instruments has brought new perspectives to the compensation of hearing impairment and may result in alleviation of the adverse effects of hearing problems. This study compares a commercially available digital signal processing hearing aid (HA) (Senso) with a modern analogue HA with programmable fitting (Logo). The HAs tested are identical in appearance and, in spite of a different mode of operation, the study design ensured blinding of the test subjects. Outcome parameters were: improvements in speech recognition score in noise (deltaSRSN) with the HAs; overall preference for HA; overall satisfaction; and various measures of HA performance evaluated by a self-assessment questionnaire. A total of 28 experienced HA users with sensorineural hearing impairment were included and 25 completed the trial. No significant differences were found in deltaSRSN between the two HAs. Eleven subjects indicated an overall preference for the digital HA, 10 preferred the analogue HA and 4 had no preference. Concerning overall satisfaction, 8 subjects rated the digital HA superior to the analogue one, whereas 7 indicated a superior rating for the analogue HA and 10 rated the HAs equal. Acceptability of noise from traffic was the only outcome parameter which gave a significant difference between the HAs in favour of the digital HA. It is concluded that there are no significant differences in outcome between the digital and analogue signal processing HAs tested by these experienced HA-users.

[Von Hippel-Lindau disease and molecular genetic diagnosis]. / Von Hippel-Lindaus sygdom og molekylaergenetisk diagnostik.

Von Hippel-Lindau disease (VHL) is an autosomal dominant inherited disorder, characterized by cysts and neoplastic formations mainly in the cerebellum, retina, pancreas, kidneys and adrenal glands. The disease is subdivided into two groups depending on absence or presence of phaeochromocytomas. VHL is caused by changes in a tumour suppressor gene, which was cloned in 1993 after having been mapped to chromosome 3p25-26 in 1988. We present two cases with VHL type 1. The first patient belonged to a family with 24 verified affected members, the second was the descendent of a patient carrying a presumed de novo mutation. By direct sequencing of the VHL gene, the mutation was identified in both families, thus enabling preclinical diagnosis of persons at risk in the families.

IBMX, taurine and 9-cis retinoic acid all act to accelerate rhodopsin expression in postmitotic cells.

Birth dating studies in the rodent retina have shown that rod photoreceptors are generated throughout most of retinal development, yet the majority do not begin to express rhodopsin until the first postnatal week. We show that treatment with 3-isobutyl-1-methylxanthine (IBMX) enhances rod development in reaggregate, explant, and monolayer cultures of embryonic and newborn rat neural retina and is more potent than another rod-promoting factor, taurine, but less potent than 9-cis retinoic acid (RA). The effect of IBMX on rod development is not associated with an increase in precursor cell proliferation, rod survival, or a reduction in the development of other retinal cell types. We provide evidence that IBMX, as well as the rod promoting molecules taurine and RA, all act on postmitotic rhodopsin(-)cells to accelerate their differentiation into rhodopsin(+)cells.

Epidemiology of respiratory syncytial virus infection requiring hospitalization in East Denmark.

BACKGROUND: Prophylaxis against infection caused by respiratory syncytial virus (RSV) with high titered RSV immunoglobulin or humanized antibody may soon be available in Europe. OBJECTIVE: To study the epidemiology of RSV infections requiring hospitalization in infants <6 months in East Denmark to provide a rational basis for decisions concerning prophylaxis against RSV. METHOD: Populat ion-based retrospective review of case records of infants <6 months admitted to pediatric departments with RSV infection in East Denmark from November 1, 1995, to April 30, 1996. RESULTS: Data were obtained from 459 infants. Seventy-three had predisposing conditions: prematurity, 49; pulmonary disease, 2; congenital heart disease, 7; neurologic disease, 6; others, 9. One preterm infant had bronchopulmonary dysplasia. The incidence of RSV infection requiring hospitalization in East Denmark among infants <6 months was estimated to be 34/1000/season. It was 32/1000/season among term infants and 66/ 1000/season among preterm infants (P<0.001). Infants with predisposing conditions and/or nosocomial infection (n = 24) had significantly more severe courses than otherwise healthy infants (P<0.01). One-hundred thirty infants received respiratory support by nasal continuous positive airway pressure, but only six required mechanical ventilation. No infants died. CONCLUSION: The course of RSV disease in East Denmark was milder than reported elsewhere, possibly as a result of the low prevalence of bronchopulmonary dysplasia in Denmark. However, RSV constitutes a considerable burden to the Danish pediatric health care system, and therefore prophylaxis against RSV is desirable.

Central precocious puberty in girls: internal genitalia before, during, and after treatment with long-acting gonadotropin-releasing hormone analogues.

Pelvic ultrasonography was systematically performed on 33 girls with idiopathic central precocious puberty to investigate the impact of treatment with gonadotropin-releasing hormone analogues on female internal genitalia. All girls were treated with a long-acting gonadotropin-releasing hormone analogue (Decapeptyl Depot; Ferring Co., Copenhagen, Denmark) 75 micrograms/kg every 4 weeks. Before, during, and after treatment, pelvic ultrasonography was performed and ovarian and uterine volumes were calculated. The size of follicles > 5 mm were accurately measured. The results were related to a normative study of healthy Danish schoolgirls. Our data demonstrated that ovaries and uterus are enlarged in a significant number of girls (50%) with the diagnosis of central precocious puberty at the time of diagnosis. Median ovarian volume at time of diagnosis was 1.1 standard deviation scores (range -0.6 to 3.2 SD), median uterine volume was 1.8 standard deviation scores (range 0.0 to 3.5 SD). Within 3 months of treatment, both ovarian and uterine volumes decreased significantly (p < 0.01) to normal values appropriate for age. Median ovarian volume after 3 months of treatment was 0.0 SD (range -2.4 to 1.5 SD); median uterine volume was 0.7 SD (range -0.6 to 4.1 SD). Ovarian and uterine volume remained within normal range (< 2 standard deviation scores) after discontinuation of treatment. Follicles and macrocysts regressed during treatment. None of the girls' ovaries had a polycystic appearance during or after treatment with the gonadotropin-releasing hormone analogue. Our results confirmed pelvic ultrasonography as a reliable tool for investigation of internal genitalia in girls with precocious puberty and as a valid method for evaluation of the efficacy of treatment with gonadotropin-releasing hormone analogues. We suggest that repeated investigations be performed when evaluating treatment because the morphologic changes, including follicular maturation or regression, reflect ovarian stimulation or suppression. We found no evidence that girls with precocious puberty treated with long-acting gonadotropin-releasing hormone analogues have enlarged polycystic ovaries develop.

Calcipotriol inhibits the proliferation of hyperproliferative CD29 positive keratinocytes in psoriatic epidermis in the absence of an effect on the function and number of antigen-presenting cells.

The aim of this study was to elucidate some of the possible mechanisms of action of the vitamin D analogue calcipotriol in vivo. Calcipotriol is finding increasing use in the treatment of psoriasis, but the primary target cell in vivo has not yet been identified. We treated psoriatic patients and healthy volunteers with calcipotriol and placebo ointment for 4 and 7 days, and obtained epidermal cell suspensions from treated areas. Epidermal cells were cocultured with autologous T cells, isolated from peripheral blood, in the absence or the presence of a classical antigen or a superantigen. In both psoriatic and normal skin, calcipotriol treatment did not alter the capacity of epidermal antigen-presenting cells to stimulate the proliferation of autologous T cells, either in the absence or in the presence of exogenous antigen. Epidermal cell suspensions were analysed further by staining for infiltrating leucocytes (CD45+) and Langerhans cells (CD1a+). Flow cytometric analysis showed that calcipotriol did not alter the number of CD45+ cells or Langerhans cells in psoriatic skin. These results indicate that calcipotriol does not alter either the number of the function of epidermal antigen-presenting cells in psoriatic epidermis. In contrast, we found that calcipotriol significantly inhibited the proliferation of epidermal cells isolated from psoriatic skin after in vivo treatment, as determined by propidium iodide staining and flow cytometry. More specifically, we stained for CD29+ keratinocytes and found an even more significant reduction in proliferative capacity. This cell type contains the population of hyperproliferative keratinocytes in psoriatic epidermis. In conclusion, calcipotriol seems to act via an inhibitory effect on hyperproliferative basal keratinocytes of psoriatic epidermis, rather than via an effect on infiltrating leucocytes, including antigen-presenting cells.