Factors associated with ocular surface disease and severity in adults with atopic dermatitis: a nationwide survey.

BACKGROUND: Ocular surface diseases (OSDs), including conjunctivitis and blepharitis, are common in atopic dermatitis (AD) patients, but the magnitude and patient characteristics are unclear. OBJECTIVES: To examine the prevalence of OSDs in adults with AD and identify patient characteristics and risk factors. METHODS: We designed a cross-sectional questionnaire-based survey and sent it via a secure public mail to all adult Danes with a hospital diagnosis of AD (ICD-10 code L20.x) registered in the National Patient Register (n = 16 718) between 2000 and 2019 and 7044 (42%) participated. Primary outcomes were OSDs and severity according to Ocular Surface Disease Index (OSDI). Adjusted odds ratios (aOR) were calculated with 95% confidence intervals (CIs) using logistic regression models. RESULTS: Respondents were mostly females and middle-aged (67.4%, mean [SD] age, 39.0 [15.5] years). Based on Patient-Oriented SCORing Atopic Dermatitis 49% had mild AD, 35% moderate, 10% severe and in 6% AD was inactive; 44.3% reported physician-diagnosed asthma bronchiale and 55.8% rhinitis. The lifetime prevalence of OSDs was 66.6% for conjunctivitis, 63.5% for hordeolum, 11.0% for blepharitis, 9.7% for keratitis, 2.0% for pterygium, 1.5% for symblepharon, 1.1% for keratoconus and 12.7% reported current conjunctivitis. Factors associated with lifetime occurrence of conjunctivitis included mild, moderate, and severe AD (aOR = 1.48 [95% CI, 1.02-2.14], aOR = 1.73 [95% CI, 1.19-2.53], aOR = 2.17 [95% CI, 1.42-3.21]), asthma bronchiale and rhinitis (aOR = 1.76 [95% CI, 1.49-2.07]), childhood-onset of AD (aOR = 1.34 [95% CI, 1.16-1.56]) and systemic AD treatment (aOR = 1.27 [95% CI, 1.08-1.50]). Use of soft and hard contact lenses (aOR = 2.15 [95% CI, 1.65-2.80], aOR = 3.35 [95% CI, 1.62-6.92]) were associated with lifetime occurrence of keratitis. Moderate and severe AD, asthma bronchiale and rhinitis were also associated with a higher OSDI level. CONCLUSIONS: This study identified important patient factors associated with OSDs. Clinicians should be attentive of ocular signs and symptoms in AD patients and ask about these.

Stabilized incidence of diabetic patients referred for renal replacement therapy in Denmark.

Despite an improvement in diabetes care during the last 20 years, the number of diabetic patients starting renal replacement therapy (RRT) has continued to increase in the Western world. The aim was to study the incidence of patients starting RRT in Denmark from 1990 to 2004. Data were obtained from The Danish National Registry; Report on Dialysis and Transplantation, where all patients actively treated for end-stage renal disease have been registered since 1990. The incidence of end-stage renal disease increased until 2001. Thereafter the incidence stabilized on 130 per million people (pmp). The number of diabetic patients starting RRT increased steadily from: 52 (number of patients) in 1990, 113 in 1995, 150 in 2000, 168 in 2001, and 183 in 2002. However, during the years 2003 and 2004 this number was significantly reduced by 15% to 156 and 155, respectively. This was mainly due to a 22% reduction in the number of non-insulin- treated (type II) diabetic patients (number of patients): 98, 82, and 76 in 2002, 2003, and 2004, respectively. The mean age in the background population, the mean age in diabetic patients starting RRT and the incidence of type I and type II diabetes increased during the study period. The encouraging stabilization in the incidence of diabetic patients referred for RRT observed in Denmark could be the result of implementation of a multifactorial and more intensive renoprotective intervention in patients with diabetes and chronic progressive renal disease.

TGF-beta1 gene mutations in insulin-dependent diabetes mellitus and diabetic nephropathy.

PCR assays were established for easy and fast analysis of two transforming growth factor-beta1 (TGF-beta1) gene mutations, a C to T transition at position 76 in exon 5 resulting in a change from threonine to isoleucine in position 263 (Thr263Ile) of the propeptide and a deletion of a C in the intron sequence eight bases prior to exon 5 (713-8delC). These mutations were evaluated in insulin-dependent diabetes mellitus (IDDM) patients (n = 137) and control subjects (n = 105) and in IDDM patients with (n = 170) and without (n = 99) nephropathy. After evaluating intra- and interindividual variation in TGF-beta1 expression levels, the TGF-beta1 mRNA level in phorbol 12-myristate-13-acetate-stimulated (1 ng/ml) lymphocytes from individuals with different TGF-beta1 genotypes was also studied. No association of the two TGF-beta1 sequence variations with IDDM in general was found. However, a weak but significant association of the Thr263Ile mutation with diabetic nephropathy was found (P = 0.03). No correlation between TGF-beta1 transcription level and genotype of any of the two studied polymorphisms was found. However, significant interindividual differences in TGF-beta1 mRNA levels were observed between the tested individuals (P < 0.0001) compatible with a genetic control mechanism of TGF-beta1 synthesis at the mRNA level.

Immunohistochemical quantification of heparan sulfate proteoglycan and collagen IV in skeletal muscle capillary basement membranes of patients with diabetic nephropathy.

In IDDM patients, an increased permeability of the glomerular capillaries has been associated with a general loss of negatively charged heparan sulfate proteoglycans (HSPGs) within basement membranes (BMs). In the present study, we used immunohistochemical staining to quantify heparan sulfate (HS), HSPG core protein, and collagen IV in capillary basement membranes of skeletal muscle biopsies taken from 9 healthy control subjects (C) and 20 IDDM patients: 7 with normal albumin excretion rate (<30 mg/24 h) (D0), 5 with incipient nephropathy (albumin excretion rate 30-300 mg/24 h) (D1), and 8 with clinical nephropathy (albumin excretion rate >300 mg/24 h) (D2). In the capillaries, staining was measured by a scanning and integrating microspectrophotometer. A significant difference in the absorbance of HS was found among the four subgroups (means +/- SD): 0.477 +/- 0.082 (C), 0.627 +/- 0.031 (D0), 0.542 +/- 0.098 (D1), and 0.371 +/- 0.118 (D2) (P = 0.006). Similarly, an overall significant difference in the absorbance of collagen IV was demonstrated (means +/- SD): 0.836 +/- 0.111 (C), 0.838 +/- 0.300 (D0), 0.970 +/- 0.173 (D1), and 0.512 +/- 0.248 (D2) (P = 0.02). No statistical difference in the absorbance of core protein was demonstrated among the groups. Within the diabetic groups, HS was inversely correlated to albuminuria (r = -0.76, P = 0.003) and albuminuria corrected for creatinine clearance (r = -0.69, P = 0.008). Because, in IDDM patients with albuminuria, alterations of the content of HS and collagen IV within the capillary BM have been demonstrated immunohistochemically, not only in the glomerular filtration barrier, but also in the skeletal muscle capillary BM, we suggest that these changes reflect universal quantitative or qualitative alterations within the capillary filtration barrier.

Skeletal muscle lipoprotein-lipase activity in insulin-dependent diabetic patients with and without albuminuria.

In patients with insulin-dependent diabetes mellitus (IDDM), albuminuria reflects widespread vascular dysfunction. Albuminuria has been associated to defects of heparan sulfate proteoglycan (HSPG) within the extracellular matrix. Our hypothesis is that loss of HSPG in vascular walls reduces the HSPG-bound lipoprotein-lipase activity (LPLA), thereby causing elevated levels of plasma triglyceride (TG) seen in IDDM patients with albuminuria. The aim of the present study was to evaluate whether LPLA in muscle capillaries could be related to TG in IDDM patients with and without albuminuria. This is a cross-sectional study including ten healthy control subjects (group C), nine patients with IDDM and urinary albumin excretion rate (AER) of 30 mg/24 h or less (group D0) and 20 patients with IDDM and AER greater than 30 mg/24 h (group DA). Muscle LPLA, plasma TG, total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and very-low-density lipoprotein cholesterol (VLDL) were measured. Between groups no difference in total cholesterol, TG, VLDL, and LDL was found. In patients with albuminuria, LPLA was reduced compared to controls, however, the difference between the groups was not statistically significant [median (range)] 35.9 mU/g (20.4-103) versus 44.6 mU/g (28.2-57.2) and 40.9 mU/g (21.7-53.5) in group DA, C, and D0, respectively, p = 0.76. AER was not correlated to LPLA. An overall negative correlation between TG and LPLA was found; r = -0.33, p = 0.04, supported by an overall significant positive correlation between LPLA and HDL; r = 0.32, p = 0.045. We conclude that, in insulin-dependent diabetes mellitus, skeletal muscle lipoprotein-lipase activity is associated with plasma triglyceride, while an association between lipoprotein-lipase activity and urinary albumin excretion is questionable.

Genetic variation of a collagen IV alpha 1-chain gene polymorphism in Danish insulin-dependent diabetes mellitus (IDDM) patients: lack of association to nephropathy and proliferative retinopathy.

In insulin-dependent (Type 1) diabetes mellitus (IDDM) the development of nephropathy is partly due to genetic susceptibility. Previously one study has demonstrated a relationship between a HindIII restriction polymorphism of the collagen IV alpha 1-chain gene and diabetic nephropathy. The aim of the present study was to evaluate such as association in a case-control study including 207 Danish IDDM patients: 116 with nephropathy (urinary albumin excretion rate (AER) > 300 mg 24 h-1) and 91 without nephropathy (AER < 30 mg 24 h-1). Using genomic DNA, HindIII restriction fragment length analysis revealed a bi allele polymorphism visualized by southern hybridization with a cDNA probe recognizing the collagen IV alpha 1-chain gene. No differences in genotype frequencies or allele frequencies were demonstrated comparing patients with and without nephropathy: p = 0.39 and p = 0.96, respectively. Neither were there any difference in genotype frequencies or allele frequencies when the patients were stratified according to the presence of proliferative retinopathy: p = 0.44 and p = 0.84, respectively. Pooling the diabetic groups revealed genotype frequencies and allele frequencies comparable to those found in 57 healthy unrelated Danish individuals. We conclude that in a Danish IDDM population a HindIII restriction polymorphism of the collagen IV alpha 1-chain gene is not associated with diabetic nephropathy, diabetic retinopathy or with diabetes per se.

Analysis of an interferon-gamma gene (IFNG) polymorphism in Danish and Finnish insulin-dependent diabetes mellitus (IDDM) patients and control subjects. Danish Study Group of Diabetes in Childhood.

A CA-repeat polymorphism within the first intron of the interferon (IFN)-gamma gene was analyzed. This polymorphism was recently demonstrated to be associated with insulin-dependent diabetes mellitus (IDDM) in Japanese subjects. We typed 266 IDDM patients and 195 control subjects of Danish Caucasoid origin. No significant differences in allele or genotype frequencies between patients and control were observed. In addition, we typed 168 IDDM and 110 control subjects of Finnish origin. A significant disease association of the studied IFN-gamma allelic pattern was found (p = 0.029). Analysis of data according to HLA-DQB1 susceptibility status did not reveal heterogeneity of risk at the IFN-gamma locus in either of the populations. Fifty-five Danish and 94 Finnish IDDM multiplex families with at least two affected siblings (660 individuals) were typed to test for transmission disequilibrium (TDT). No evidence for overall transmission disequilibrium using either an allele-wise (p = 0.42; combined data) or a genotype-wise analysis (p = 0.21; combined data) could be detected. Thus, the modest significance level observed in the Finnish case-control study and the failure to replicate it by the TDT provide little support for the hypothesis that the IFN-gamma gene microsatellite is associated with IDDM.

Flavor and texture characteristics of low fat ground beef patties formulated with whey protein concentrate.

Low fat ground beef patties (10-11% fat), formulated with 10% water, 0.5% salt and 1-4% whey protein concentrate (WPC), were evaluated for cooking characteristics and compared with controls of higher fat content. A reduction in the fat level from 22 to 11% improved all cooking parameters with respect to better cooking yield (p < 0.01) and fat retention (p < 0.05), increased cooked moisture content (p < 0.05) as well as reduced shrinkage (p < 0.05). Texture profile analysis (TPA) showed an increase in chewiness for low fat samples over the high fat control, while hardness and springiness remained unaffected. Adding 10% water to the low fat meat did not change the cooking characteristics, except for a further increase in cooked moisture content (p < 0.05) and an increase in the value for springiness (p < 0.05). Addition of increasing levels of WPC with 10% water to low fat meat resulted in a linear increase (p < 0.05) in cooked yield with a linear decrease (p < 0.05) in shrinkage. The 4% WPC level produced the highest cooking yield (125% of the high fat control) and the least shrinkage (49% of the high fat control). Sensory analysis showed the 4% WPC level to be preferred over lower levels with respect to juiciness and overall acceptability. Addition of 0.3% of texture-modifying additives showed that calcium chloride and hydroxypropylmethylcellulose had a detrimental effect on yield and shrinkage, whereas the effect of tripolyphosphate (TPP) was positive (p < 0.05). Perception of juiciness and overall acceptability of formulated low fat products was significantly better (p < 0.05) with the addition of TPP (0.3%) and lactose (1.2%) to the WPC formulations. Fat levels (11, 18 and 22%) and lactose levels (0.24 and 1.2%) affected volatile components of the beef patties as measured by dynamic head space analysis. Ketones, i.e. 2-butanone, 2-pentanone and 3-hydroxy-2-butanone increased with an increase in fat content from 11 to 22% fat. Addition of WPC and lactose decreased the relative concentrations of pentane, hexane and heptane. The increase of lactose level in meat was accompanied by an increase in 4,4 diethyl-2-oxetanone and 2-methyl-butanal, two compounds that may originate from non-enzymatic browning of lactose.

Diurnal variation in glomerular charge selectivity, urinary albumin excretion and blood pressure in insulin-dependent diabetic patients.

The urinary albumin excretion rate (AER) in a subgroup of patients with insulin-dependent diabetes mellitus (IDDM) steadily increases. In these patients a concomitant reduction of the glomerular charge selectivity index (SI) has been demonstrated. The aim of the present study was to evaluate whether diurnal variation in AER could be related to a diurnal variation in SI and/or a diurnal blood pressure variation. Thirty-three patients with IDDM, 27 with normal albumin excretion (AER < 20 micrograms/min; group D(o)) and six with incipient nephropathy (AER from 20 to 200 micrograms/min; group DA), were studied. AER and SI (renal clearance ratio of total-IgG/IgG4) were measured in three different urine collecting periods: period A (8:00 a.m. to 12:00 a.m.), period B (12:00 a.m. to bedtime) and period C (bedtime to 8:00 a.m.). A significant increase in SI was seen during the nighttime: period A, 1.6 (0.2 to 3.8; mean, range); period B, 1.7 (0.3 to 3.0); and period C, 2.0 (0.2 to 4.0); P = 0.01. Corresponding to this observation, an overall significant decrease in AER was found: period A, 10 (3 to 137) micrograms/min (median, range); period B, 8 (3 to 84) micrograms/min; and period C, 5 (0 to 78) micrograms/min; P < 0.001. In all three sampling periods a negative correlation was found between AER and SI. When group D(o) was analyzed alone, the results were similar. Diurnal variation in blood pressure was significantly positively correlated with AER in group DA, but was not correlated to variation in AER in D(o). We suggest that in normoalbuminuric IDDM patients diurnal variation in AER is related to diurnal variation in SI.

Characterization of polymorphisms of an interleukin 1 receptor type 1 gene (IL1RI) promotor region (P2) and their relation to insulin-dependent diabetes mellitus (IDDM). The Danish Study Group of Diabetes in Childhood.

We have identified two PstI polymorphisms of the interleukin 1 receptor type I gene (IL1RI). One of these (RFLP-A) showed significant association to IDDM (P = 0.027), whereas no difference between patients and control subjects was found for RFLP-B (p = 0.42). RFLP-A was physically mapped to the 5'UTR of the gene. We sequenced and analysed a 411 bp region of a putative promotor region (P2) around RFLP-A. RFLP-A was due to a C to T transition in exon 1B of the IL1RI gene. This single-base mutation did not affect any known transcription factor recognition sequence or the predicted secondary mRNA structure. In addition, we found two other single-base substitutions in more than one individual. Neither of these showed specific disease association or absolute linkage with the RFLP-A.

Possible effect of angiotensin-converting enzyme inhibition on glomerular charge selectivity.

Angiotensin-converting enzyme (ACE) inhibitors are known to reduce urinary albumin excretion (UAE) in diabetic patients. Animal studies have shown that, besides diminishing the glomerular capillary pressure, ACE inhibitors might reduce albuminuria by influencing glomerular charge selectivity through glomerular preservation of heparan sulphate proteoglycan. In humans, an indirect measurement of glomerular charge selectivity can be obtained by calculating the glomerular charge selectivity index (SI), a clearance ratio of IgG/IgG4, two identically sized but differently charged molecules. The aim of the present study was to evaluate the effect of ACE inhibition on charge selectivity by comparing SI in type I (insulin-dependent) diabetic patients with microalbuminuria after 6 years of treatment either with or without captopril. Thirty-five of 45 patients participating in a prospective randomized study evaluating the effect of captopril in preventing the development of diabetic nephropathy were included in the present study, 17 being treated with captopril, 18 left as untreated controls. The selectivity index was calculated after measuring s-IgG, u-IgG, s-IgG4, and u-IgG4. The results demonstrated a higher selectivity index in the captopril-treated group [1.21 (0.51-1.94) median (range)] compared to the control group [0.94 (0.31-1.87)], however, the difference was not statistically significant (p = 0.16). A negative correlation between the selectivity index and UAE was demonstrated in the captopril-treated group (r = -0.77; p = 0.0004), whereas the correlation in the control group did not reach statistical significance (r = -0.3; p = 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus.

We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU unfractionated heparin, or 2000 anti-Xa IU low-molecular-weight heparin. Unfractionated and low-molecular-weight heparin induced a significant reduction in urinary albumin excretion (p = 0.04 and p = 0.004). The mechanism and clinical relevance is unknown but deserve further attention.

[The geriatric clinical picture in a department of internal medicine]. / Det geriatriske sygdomsbillede i en intern-medicinsk afdeling.

In order to assess the proportion of geriatric patients in a medical department, all of the inpatients admitted to the Medical Department of Hørsholm Hospital during the period 19.3.1987-15.4.1987 were assessed in view of the geriatric clinical picture. The criteria for assessment as a geriatric patient were established in advance and included: Presence of several medical problems inhibition of functions and social problems and an estimated need for prolonged hospitalization to solve these problems, including rehabilitation. Out of 191 inpatients, 15 (8%) were considered to be geriatric patients. These 8% were all aged 60 years or more, were hospitalized for an average of 23 days and used 21% of the total number of bed days. The remaining patients aged more than 60 years were hospitalized for an average of nine days and comprised 47% of the total number of inpatients and used 49% of the bed days. The geriatric patients differed, in addition, from the other patients aged over 60 years in that 85% compared with 58% were readmitted within a period of two years. No difference in the mortality was observed during a period of two years. This investigation supports previous suppositions about the proportion of geriatric patients and indicates that assessment as to whether a geriatric patient is concerned or not may be made already during the first 24 hours in hospital.

[Hospital employees' knowledge about HIV disease. A study from 2 provincial hospitals]. / Hospitalsansattes viden om HIV-sygdommen. En undersøgelse fra to provinssygehuse.

The knowledge of and attitudes to HIV infection were investigated by means of questionnaires during the period 1.10.1988 to 30.4.1989 in two small Danish Hospitals. Two hundred and thirty two nurses, 147 nursing aids, 44 doctors, 25 laboratory workers and 22 midwives took part in the investigation. The overall response was 99% of the staff contacted. The questionnaires were anonymous and were completed immediately and without use of any sources of information. Poor knowledge was revealed concerning symptoms, sources of infection, precautions to avoid infection, high-risk groups and patients duty to provide information. In fact, none of the groups exceeded 66% correct answers on these subjects. A total of 70% of the whole group had been in contact with patients, whom they suspected to be HIV-positive. Every third individual had felt insecure regarding HIV at work. Incidents at work had caused 18 employees to be tested for HIV. Only about half had been instructed about HIV. A total of 73% expressed needs for further instruction about the disease. The investigation shows difference between the staff opinion of possible claims on the patients about tests and to the policy of the Danish Department of Health concerning voluntary testing.

[The palliative effect of bilateral orchiectomy in metastatic cancer of the prostate]. / Den palliative effekt af bilateral orkiektomi ved metastaserende prostatacancer.

The effect of bilateral orchidectomy in relieving pain in 70 patients with metastatic carcinoma of the prostate was investigated by review of the case reports of a patient material from a urological department. 74% of the patients stated that the intervention was effective. Relief of pain lasting for more than seven months and attributable solely to the orchidectomy occurred in 19%. It did not prove possible to differentiate by means of biochemical or clinical parameters between the patient groups with and without beneficial effects from the intervention. 30% died during the first postoperative year. The five year survival rate was calculated to be 19%.

Behavioral treatment of psychogenic polydipsia.

This report describes the behavioral treatment of psychogenic polydipsia in an autistic, severely mentally retarded woman who had a history of self-induced water intoxication. Treatment emphasized the use of edibles and reductions in activity demands to reward water refusal. Employing this procedure, paraprofessional staff normalized the client's water consumption, and thereby prevented further episodes of potentially-fatal water intoxication.

Isolation of sialic acid from casein and reclamation of residual casein.

Crystalline sialic acid was isolated in 50 to 60% yields from a commercial grade of dry isoelectric casein by Warren's hydrolysis procedure. One part of casein was heated at 80 C/60 min in ten parts of .18 N sulfuric acid (pH 1.5). A crude sialic acid preparation (7.8%) was obtained from the hydrolysate after addition of calcium hydroxide to remove protein at pH 4.6 and sulfate as calcium sulfate at pH 7.0 followed by concentration and lyophilization of the soluble material. Highly purified sialic acid (95%) was obtained by chromatography on Dowex-1 X 8 with a gradient of 0 to 2 M sodium acetate. The sialic acid positive fraction was passed through Duolite C20H followed by lyophilization. Slow evaporation of a concentrated solution of this material produced typical crystals of N-acetylneuraminic acid. The study also included an examination of the properties of the residual sialic acid-free casein. Electrophoretic patterns, solubility properties, rennet sensitivity, and viscous character revealed that the residual casein was remarkably similar to intact casein. However, the calcium sensitivity of this modified protein was increased in the presence of .1 M calcium chloride.