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Biomedical subjects

E Held

Publications and source records attributed to E Held.

At least 37 records · Page 2Linked to original sources

Effect of long-term use of moisturizer on skin hydration, barrier function and susceptibility to irritants.

Moisturizers are often used in the prevention and treatment of irritant contact dermatitis. The present study was to determine whether long-term daily use of a moisturizer on normal skin would affect skin barrier function, hydration state, or susceptibility to sodium lauryl sulphate. Healthy volunteers used a moisturizer on one forearm 3 times daily for 4 weeks. The other forearm served as a control. Afterwards both forearms were challenged with a patch-test of sodium lauryl sulphate. Skin barrier function was evaluated by measuring trans-epidermal water loss and skin hydration by measuring electrical capacitance. Electrical capacitance was significantly increased on the treated arm during the treatment period. After challenge with sodium lauryl sulphate, transepidermal water loss was significantly higher on the arm treated with moisturizer than on the control arm. The results suggest that long-term treatment with moisturizers on normal skin may increase skin susceptibility to irritants.

Adult↗

Comparison between 2 test models in evaluating the effect of a moisturizer on irritated human skin.

The purpose of the present study was to compare 2 experimental models of moisturizer efficacy on the recovery of irritated skin on the hands and the volar forearms. 12 healthy volunteers had their hands immersed in sodium lauryl sulfate (SLS) 10 min 2x daily for 2 days, and at the same time the volunteers had patch tests with SLS (0.125%, 0.25% and 0.5%) applied on their forearms for 24 h. After irritation of the skin, the volunteers had a moisturizer applied on one arm/hand 3x daily for the following 9 days. The other arm/hand served as untreated control. Evaluation was done on days (D) 1, 3, 5, 8 and 12 by transepidermal water loss, electrical capacitance, laser Doppler flowmetry and DermaSpectrometry. Both models were found useful, and the moisturizer was found to accelerate regeneration of the skin barrier function in both the hands (D8, p<0.05) and the volar forearms (0.5% SLS, D5 and D8, p<0.01). When the forearm model is used in the present set-up, a relatively high concentration of SLS (>0.25%) should be used and evaluation measurements are best performed on D5-D8. The forearm model proved reliable and easy to handle and we suggest that this model is used in future studies on moisturizer evaluation.

Adult↗

Contact allergy to cosmetics: testing with patients' own products.

In a 2-year period, 1527 patients with contact dermatitis were investigated in the patch-test clinic. In 531 patients, allergy to cosmetics was suspected from the history and they were tested with their own cosmetic products. 40 (7.5%) (of the 531 patients) had 1 or more positive reactions, 82 (15.4%) had doubtfully positive reaction(s) and 31 (5.8%) had irritant reaction(s). Skin-care products were tested most frequently and were also found to cause most positive, doubtfully positive and irritant reactions, 80% of the patients with positive reactions to their own products had no history of contact dermatitis prior to the presenting attack, and in 92.5% of the cases, the positive reaction was considered relevant or partly relevant. In patients with a positive reaction, ingredients that could be responsible were found in 60% of the cases by testing with the European standard series and a series of common cosmetic ingredients. Fragrance mix and formaldehyde were found to be the ingredients most often responsible and were significantly more frequent in patients with positive reactions to their own products, compared to a control group of eczema patients also seen in the patch-test clinic.

Adult↗

[Fibrillary glomerulonephritis. Case report for differential nephrotic syndrome diagnosis].

A 67-year-old male patient presented with a nephrotic syndrome. Biopsy of the kidney revealed the characteristic of fibrillary glomerulopathy on light and electron microscopy. Other non-nephritic causes of a nephrotic syndrome (e.g. amyloidosis, immunotactoid glomerulopathy, light-chain glomerulopathy, cryoglobulinaemia, collagen-III glomerulopathy, fibronectin glomerulopathy) could be excluded. Besides the case report, differential diagnosis of fibrillary glomerulopathies is presented.

Actin Cytoskeleton↗

High glucose increases prostaglandin E2 synthesis in human peritoneal mesothelial cells: role of hyperosmolarity.

Peritoneal mesothelial cells are considered the predominant source of peritoneal prostanoid formation because they represent the largest resident cell population in the peritoneal cavity. The present study was designed to evaluate the effect of D-glucose, which is widely used in commercially available peritoneal dialysis fluids as an osmotic compound, on the synthesis of prostaglandins in cultured human mesothelial cells (HMC). Analysis of eicosanoid synthesis in HMC by reversed-phase HPLC revealed that 6-keto-PGF1alpha, the spontaneous hydrolysis product of prostacyclin (PGI2), and prostaglandin E2 (PGE2) were the main eicosanoids produced. Addition of D-glucose resulted in a time- and concentration-dependent (30 to 120 mM) increase in PGE2 production in HMC (24 h, 90 mM: 3.9+/-0.5 ng/10(5) cells versus 2.3+/-0.3 in untreated cells; P < 0.05). Mannitol (90 mM) or L-glucose (90 mM). nonmetabolizable osmotic compounds, also led to a significant (P < 0.05) but less intense increase in PGE2 synthesis (3.3+/-0.4 and 3.2+/-0.5 ng/10(5) cells, respectively). Increased PGE2 synthesis was completely blunted by coincubation with the specific protein kinase C (PKC) inhibitor Ro 31-8220 or downregulation of PKC activity by preincubation with phorbol myristate acetate for 16 h. Furthermore, coincubation with PD 98059, an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway, also inhibited increased PGE2 synthesis by D-glucose or mannitol. In contrast, the iso-osmolar glucose polymer icodextrin, which is used as an alternative to D-glucose in peritoneal dialysis solutions, had no effect on PGE2 synthesis. These data indicate that D-glucose and metabolically inert sugars increase PGE2 synthesis in HMC at least in part by hyperosmolarity and that this effect requires activation of PKC and the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway of intracellular signaling.

Arachidonic Acid↗

[Perioral dermatitis in children under steroid inhalation therapy].

Topically applied corticosteroid is a known provoking factor in perioral dermatitis. In recent years inhaled corticosteroids have become first line therapy for asthma in children. We present two characteristic cases of perioral dermatitis that developed during asthma treatment with budesonide using either a nebulizer or a spacer connected with a mask. In severe cases treatment with oral erythromycin or topical metronidazole gel may be considered. The eruption should not be confused with atopic eczema.

Administration, Inhalation↗

[Mycoplasma hominis. A rare causative agent of acute pyelonephritis].

HISTORY AND CLINICAL FINDINGS: A 23-year-old woman was admitted with typical signs of an acute urinary tract infection: fever, pain on tapping over both renal areas and in both flanks, urgency and dysuria. She had a history of renal colic with spontaneous passage of a renal stone. INVESTIGATIONS: There was marked leukocytosis and raised C-reactive protein, leukocyturia and haematuria, but no nitrites or protein in the urine. All blood and urine cultures were sterile and renal ultrasound was unremarkable. DIAGNOSIS, TREATMENT AND COURSE: As signs and laboratory data indicated acute pyelonephritis (PN) she was treated with gyrase inhibiting antibiotics. But while symptoms improved, fever, leukocyturia and haematuria continued; no micro-organism could be demonstrated. Mycoplasma was therefore considered as a rare cause of PN. Special urine cultures then grew M. hominis, > 10(5) organisms/ml. On the basis of sensitivity tests doxycycline was administered. All symptoms quickly improved and all inflammation parameters and urine sediments became normal. CONCLUSION: In rare instances M. hominis may be isolated as the causative organism of PN. If, in cases with appropriate symptoms, routine tests fail to demonstrate the causative agent, M. hominis should be included in the differential diagnosis.

Acute Disease↗

[Porphyria cutanea tarda and hepatitis C virus infection].

Porphyria cutanea tarda (PCT) is a rare metabolic disorder characterized by an abnormal porphyrin metabolism and typical cutaneous lesions. Recently a strong association between PCT and hepatitis C virus (HCV) has been proposed. Studies in the south of Europe have shown high prevalences (53 to 91%) of HCV markers in patients with sporadic PCT. Six characteristic case stories are presented. We suggest routine hepatitis C serological testing in all patients with PCT, as HCV infection is a major predisposing factor for the disease.

Adult↗

[Patient survival, a change in methods, and hospitalization in CAPD abd hemodialysis].

UNLABELLED: BACKGROUND AND OBJECTIVE OF STUDY: Continuous ambulatory peritoneal dialysis (CAPD) still plays a minor role in Germany compared with haemodialysis (HD) in the management of terminal renal failure. An investigation was undertaken to compare mortality rate, change of dialysing method as well as number and duration of hospital stays of patient undergoing CAPD or HD at a nephrological centre. PATIENTS AND METHODS: All 166 patients in terminal renal failure (except those with a malignancy) admitted between January 1987 and December 1992 were included (63 women and 103 men, aged 19-84 years). The choice between the two dialysis methods was made by the patients after detailed information had been given. Taking into account basic disease and any secondary illness as well as age and sex, survival time, any change of dialysing method and hospitalisation details were prospectively analysed for the two dialysing methods. RESULTS: After 4 years there were no significant differences in mortality rate between the two methods (HD 37%, CAPD 29%). The Cox model revealed no influence of various parameters on the mortality rate of the two methods. However, cumulative patients survival was significantly decreased by arterio-sclerotic disease (P < 0.05; probability of survival after 4 years was 53% and 73%, respectively, for HD and 57% and 77% for CAPD). Similarly, age > or = 60 years at onset of dialysis significantly lowered probability of survival (after 4 years of dialysis, 53% vs 70% for HD, 45% vs 80% for CAPD: P < 0.05). But there were no significant differences between the two methods with respect to these two factors. After 4 years, "method survival" was more common with HD (94%) than CAPD (64%), P < 0.05). In particular diabetics had a significantly lower "method survival" after 4 years than non-diabetics (29% vs 74%). There was no significant difference between the two methods regarding number and duration of hospital stays. CONCLUSIONS: These data show that, in a nephrological centre with long experience in both methods of dialysis, CAPD is an equal alternative to HD.

Adult↗

Modulation of procoagulant and fibrinolytic system components of mesothelial cells by inflammatory mediators.

Human peritoneal mesothelial cells (HMC) play a critical role in maintaining the intraperitoneal balance between fibrinolysis and coagulation by expressing the fibrinolytic enzyme tissue-type plasminogen activator (t-PA) as well as a specific plasminogen activator inhibitor, PAI-1, and the procoagulant protein tissue factor (TF). Of three compounds known to stimulate t-PA synthesis in cultured human endothelial cells, i.e., retinoic acid, the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate (PMA), and sodium butyrate, only butyrate (1 mM) caused about a threefold increase in t-PA synthesis and mRNA expression in HMC after 24 h of incubation, without markedly affecting PAI-1 synthesis. PMA (10 nM) induced a threefold increase in urokinase-type plasminogen activator (u-PA) mRNA, but u-PA antigen levels in the HMC conditioned media remained below the detection level (0.5 ng/ml), possibly as a result of rapid uptake and degradation by the u-PA receptor. The u-PA receptor mRNA levels were about fivefold enhanced above control levels after PMA treatment of the cells. An increase in intracellular adenosine 3',5'-cyclic monophosphate levels by forskolin (10 microM) diminished t-PA and PAI-1 levels 43 and 17%, respectively. Among the inflammatory mediators tested [tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha, and bacterial lipopolysaccharide], TNF-alpha (10-1,000 U/ml) showed the strongest procoagulant effects. We found that the isoflavone compound genistein (25 micrograms/ml) prevented the TNF-alpha-induced expression of PAI-1 and TF while also slightly counteracting the decrease in t-PA synthesis. The protein kinase C inhibitor R0-318220 (3 microM) only moderately opposed the TNF-alpha-induced changes in t-PA and PAI-1 synthesis but completely prevented the induction of TF mRNA. In summary, our results demonstrate that t-PA synthesis in HMC is relatively insensitive to pharmacological stimulation. To restore the balance between fibrinolysis and coagulation under inflammatory conditions, attempts to interfere with the TNF-alpha-signaling pathway were more successful.

Blood Coagulation↗

High-flux hemodialysis postpones clinical manifestation of dialysis-related amyloidosis.

Amyloidosis due to the retention of beta 2-microglobulin (beta 2-MG) is a frequent complication of hemodialysis (HD). Significant amounts of beta 2-MG can be removed from the body by highly permeable HD membranes, whereas conventional low-flux membranes are impermeable for the molecule. In a prospective and controlled study we investigated whether high-flux HD could delay the onset of dialysis-related amyloidosis (DRA). Twenty patients treated with cuprophane low-flux HD membranes were matched for age and previous time on HD either to continue their HD regimen or to receive HD treatment with high-flux polysulfone membranes. For 6 years each patient was examined for manifestations of DRA once a year or upon individual needs, additionally, serum beta 2-MG levels were monitored. After 6 years of follow-up no clinical signs of DRA were found in any of the patients dialyzed with high-flux polysulfone membranes, whereas 8/10 of the conventionally dialyzed patients had CTS and/or osteoarticular lesions. Serum levels of beta 2-MG were significantly reduced in patients treated with high-flux polysulfone membranes.

Adult↗

Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients.

Calcitriol is increasingly used for therapy of secondary hyperparathyroidism in patients with end-stage renal disease. Its therapeutic efficacy, however, often has been limited by the associated increase in intestinal calcium and phosphorus absorption. Previous studies reported that these side effects could be avoided by intermittent administration of calcitriol in high doses, subsequently referred to as pulse therapy. The present study was designed to investigate pulse oral calcitriol therapy in a patient subgroup especially susceptible to the development of hypercalcemia and hyperphosphatemia under standard continuous calcitriol treatment. We examined 15 peritoneal dialysis patients with moderate degrees of hyperparathyroidism (intact parathyroid hormone [iPTH] levels, 150 to 903 pg/mL) ingesting between 1.5 and 6 g of calcium salts as the sole phosphate binders. Treatment consisted of 0.5 microgram calcitriol twice weekly. Eight of these patients had been previously converted to low calcium dialysate to tolerate the necessary doses of phosphate-binding calcium salts. During the study period, comprising 8 pretreatment weeks and 8 weeks of therapy, dialysates and doses of calcium salts were not changed, so that only calcitriol influenced the determined parameters. As expected, iPTH levels decreased rapidly in all patients (P < 0.0001). However, within 4 weeks of treatment a marked increase in calcium phosphorus products was observed (P < 0.0001). Overt hypercalcemia developed in five patients. We concluded that pulse oral calcitriol has to be carefully monitored in peritoneal dialysis patients receiving high doses of calcium salts because of the increased risk for hypercalcemia and hyperphosphatemia.

Administration, Oral↗

Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells.

We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Biocompatible membranes in acute renal failure: prospective case-controlled study.

The mortality of critically ill patients with acute renal failure has been halved through intervention by haemodialysis. However, several reports suggest that the course of the disorder may be prolonged by this procedure. Our prospective randomised study was done to see whether the generation of inflammatory mediators by bio-compatible membranes has an adverse effect on the outcome of acute renal failure. 52 patients, similar in age, severity of acute renal failure, general disease status (APACHE II), and management of acute renal failure or its related conditions, were divided into two groups. Haemodialysis was done with cuprophane or polyacrylonitrile membranes. Cuprophane membranes induced intense activation of the complement system (as judged by measurement of C3a) and lipooxygenase pathway (leukotriene B4) resulting in alterations of neutrophil kinetics and function. The cuprophane group had a lower survival rate (38 vs 65%), a higher proportion of patients dying from sepsis (71 vs 40%), required more haemodialysis sessions (12 vs 9), and demonstrated delayed resolution and recovery from acute renal failure than the polyacrylonitrile group. The difference in mortality regarding lethal sepsis as cause of death was statistically significant. Our observations indicate that the outcome of critically ill patients with acute renal failure may be influenced by bio-incompatibility reactions to the dialysis membrane. These results have direct implications for such patients on haemodialysis.

Acrylic Resins↗

Assessment of acute parathyroid responsiveness to high calcium dialysate in uremic patients.

The response of the parathyroid glands to dialysis-induced changes in calcium has been studied in 83 normocalcemic patients receiving maintenance hemodialysis. Predialysis concentrations of intact parathyroid hormone (iPTH) were normal in 13 patients; 70 patients had increased iPTH levels of different degrees. All patients had analytically significant changes in total serum calcium (2.3 +/- 0.2 vs 2.8 +/- 0.2 mmol/l) without additional parenteral calcium loading during a standard dialysis session with a dialysis solution of 1.75 mmol calcium chloride. During hemodialysis the concentration of iPTH fell in 77 patients and was normalized in 48 of these patients. The remaining 6 patients showed no or an inadequate response (less than 30% suppression of predialysis iPTH) to the increase in Ca. Parathyroidectomy was performed in patients with refractory iPTH secretion. Histological evidence of marked parathyroid hyperplasia was obtained in all these patients. All patients with normal or partial responsiveness of the parathyroids tolerated at least small doses of 1.25 (OH)2-vitamin D3. Quantification of predialysis and postdialysis iPTH concentrations is a useful and simple method for identifying those uremic patients with true autonomy of the parathyroid glands at an early stage.

Adolescent↗