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Biomedical subjects

A Farkas

Publications and source records attributed to A Farkas.

At least 37 records · Page 2Linked to original sources

Low-dose dithranol treatment and tape stripping induce tolerance to dithranol in a mouse ear oedema model.

BACKGROUND: It is well known from clinical practice that repeated treatment with dithranol leads to the development of tolerance. OBJECTIVES: To investigate the characteristics and mechanism of such dithranol tolerance. METHODS: The mouse ear was pretreated with a low dose of dithranol or croton oil or, in previously sensitized animals, with dinitrofluorobenzene (DNFB). Twenty-four hours later irritant dermatitis was elicited by painting the mouse ear with a high dose of dithranol, croton oil or DNFB, and the dermatitis was characterized by measurement of ear thickness. RESULTS: Low-dose dithranol significantly suppressed dithranol-induced oedema, whereas it had no effect on croton oil- or DNFB-induced dermatitis, suggesting that dithranol-induced tolerance is specific. Tolerance to dithranol could not be induced by pretreatment of the mouse ear with a low dose of croton oil or DNFB. Mild tape stripping of the mouse ear also inhibited the inflammatory effect of dithranol applied 24 h later. Superoxide dismutase treatment abolished the tolerance-inducing effect of low-dose dithranol or stripping. CONCLUSIONS: These results suggest that superoxide anion radicals are involved not only in the inflammatory effect of dithranol, but also in the induction of tolerance.

Administration, Topical↗

CD3+CD56+ NK T cells are significantly decreased in the peripheral blood of patients with psoriasis.

Psoriasis is a chronic, inflammatory, hyperproliferative skin disease, in which autoimmunity plays a great role. Natural killer T cells (NK T cells), are suggested to be involved in the pathogenesis of different autoimmune diseases. To examine the involvement of CD3+CD56+ NK T cells in the pathogenesis of psoriasis, we investigated the lymphocyte subpopulations obtained from blood samples of psoriatic patients before and after treatment, and of healthy controls, using two-colour flow cytometry. We found no significant differences between total T cells, total B cells, T helper cells, T cytotoxic cells and NK cells in patients with psoriasis before and after treatment and in controls. Increased percentage of memory T cells and decreased percentage of naive T cells was detected in psoriatic patients compared to controls, but these changes were not statistically significant. The CD3+CD56+ cells of psoriatic patients were significantly decreased relative to controls. The percentage of CD3+CD56+ cells increased after different antipsoriatic therapies, but remained significantly lower than those found in controls. CD3+CD56+ cells of healthy controls were capable of rapid activation, while in psoriatic patients activated NK T cells were almost absent. The decrease in the number of CD3+CD56+ cells may represent an intrinsic characteristic feature of patients with psoriasis, which is supported by the fact that after treatment NK T cells do not reach the values found in controls. In conclusion our results suggest that CD3+CD56+ NK T cells could be actively involved in the development of Th1 mediated autoimmune diseases.

Adult↗

Does delaying pyeloplasty affect renal function in children with a prenatal diagnosis of pelvi-ureteric junction obstruction?

OBJECTIVE: To evaluate retrospectively children with an antenatal diagnosis of pelvi-ureteric junction (PUJ) obstruction who required pyeloplasty for deteriorating renal function during the follow-up, specifically assessing the recovery of function after surgery. PATIENTS AND METHODS: Between 1988 and 2000, 44 consecutive patients with a prenatal diagnosis of PUJ obstruction who were initially treated by observation underwent pyeloplasty because their renal function deteriorated during the follow-up. Patients with bilateral disease, a single kidney or vesico-ureteric reflux were excluded from the study. The mean (sd) age of the patients was 13.3 (4.5) months and their mean (range) initial renal function 39.7 (30.4-45)%. In all patients the diagnostic criteria and indications for surgery were identical. The main indication for surgery was deteriorating renal function of >5%, confirmed by renal scintigraphy. Of 44 patients, 35 (77%) had severe dilatation of the renal pelvis by >3 cm. The mean (sd) deterioration in renal function during the follow-up, just before surgery, was 8.2 (2.4)%, and the mean time between the last acceptable renogram and the study showing deterioration was 8.3 (1.3) months; the mean follow-up was 5.1 (1.6) years. The results were assessed statistically using the unpaired nonparametric Mann-Whitney U-test. RESULTS: An improvement in hydronephrosis was confirmed in all patients, with renal function returning to the initial levels in 36 of 44 (81%) patients 6-12 months after surgery, although in two patients renal function did not improve after surgery. There was no significant difference between the preoperative characteristics and the degree of hydronephrosis, renal function or patient age with the level of renal functional improvement after surgery. CONCLUSION: In patients with an antenatal diagnosis of PUJ obstruction, expectant management is recommended and spares the children unnecessary surgery. Even if renal function deteriorates, delayed pyeloplasty recovers the initial functional level.

Decision Making↗

Modelling carcinogenic effects of low doses of inhaled radon progenies.

In this study, cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitive epithelial cell nuclei were simulated at low exposure levels to obtain useful data for the rejection or in support of the linear no-threshold dose-effect hypothesis. In this work, local distributions of deposited inhaled radon progenies in airway bifurcation models were computed at exposure conditions which are characteristic of homes and uranium mines. Then, maximum local deposition enhancement factors, that is, local per average deposition densities, were simulated, and the effects of the inhomogeneity of deposition on hit probabilities were characterised. Our results suggest that in the vicinity of the carinal regions of the central airways the probability of multiple hits can be quite high even at low doses.

Administration, Inhalation↗

Local deposition distributions of inhaled radionuclides in the human tracheobronchial tree.

There is experimental evidence that bronchogenic carcinomas originate mainly at the carinal ridges of the large central airways, where primary hot spots of deposition have been found. However, current lung dosimetry models do not take into consideration the inhomogeneity of deposition within the airways. In this study, computed local distributions of deposited inhaled radionuclides such as radon progenies in morphologically realistic human airway bifurcation models are analysed for different flow rates and particle sizes. Then, local deposition enhancement factors, defined as the ratio of local to average deposition densities, are computed by scanning along the surface of the bifurcation with pre-specified surface area elements. Computed enhancement factors indicate that cells located at carinal ridges or at the inner sides of the progeny branches may receive localised doses which are two orders of magnitude higher than the average values.

Administration, Inhalation↗

Histological findings after colocystoplasty and gastrocystoplasty.

PURPOSE: We conducted a prospective, long-term assessment of the histological changes that can occur following bladder augmentation with colon or stomach. MATERIALS AND METHODS: Histological evaluations of biopsies from 44 consecutive patients undergoing augmentation (colocystoplasty in 26, gastrocystoplasty in 18) were performed. Patients underwent endoscopic assessment and tissue sampling at 2 or 4-year intervals following the initial augmentation procedure. Patients with less than 2 years of followup were excluded from the analysis. Specimens were taken from the native bladder, the augment segment (large bowel or stomach) and the anastomotic line. Sections (4 mu.) were examined using standard histological staining methods (hematoxylin and eosin and periodic acid-Schiff) and immunohistochemistry was performed for different markers of neoplasia, cellular proliferation and blood group antigens. Histological findings were correlated with the incidence of stone formation and urinary tract infection. RESULTS: Group 1 consisted of 20 patients undergoing colocystoplasty who met the criteria for study inclusion. Of the patients 10 (50%) had stones, 19 (95%) had a positive urine culture and 6 had no histological changes. While no cases of malignancy were identified, other forms of pathological change were noted in 14 of the 20 patients (70%). Group 2 included 15 patients undergoing gastrocystoplasty who met the criteria for study inclusion. No stones or malignancy were identified in this group. Positive urine cultures were recorded in 2 patients (13%), no histological changes were found in 6 and 9 (60%) had pathological changes. CONCLUSIONS: Periodic prospective biopsy evaluation of children who have undergone either colocystoplasty or gastrocystoplasty failed to reveal any histological evidence of malignancy after 10-year followup. However, histological evidence of a premalignant lesion 13 years after followup suggests that screening for premalignant lesions should be initiated no later than 6 to 10 years following enterocystoplasty.

Adolescent↗

[Intermediate results of surgical bladder augmentation in children].

The most common origin of the urinary incontinence are the myelodysplasia and congenital urogenital malformations in childhood. Surgical augmentation of the urinary bladder with or without continent diversion, may be indicated in case of unsatisfactory result of all other conservative treatments. Between 1987-2000 bladder augmentation or substitution was carried out with large bowel or gastric segment in 37 patients. The age at surgery was between 6-21 yrs, (mean 12.3 yrs). The authors discuss the results of the 30 patients in whom follow up was at least 1 yr (12-113 months, mean 43 months). The urinary incontinence could be solved in 24/30 of the children, 6/30 remained in the same condition without worsening any of them. In 11/30 patients complication was not observed at all, but in 19/30 further surgeries were necessary in 30 times, mainly due to stone formation. The authors state that the augmentation cystoplasty is a useful method for the creation of a low pressure urinary reservoire which with or without a continent diversion may solve the urinary incontinence, however the patients need a lifelong follow-up due to the possible long-term risks.

Adolescent↗

Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell line HaCaT.

OBJECTIVE: Dithranol is highly effective in the treatment of psoriasis, however its mode of action is still not well known. Since interleukin-8 and interleukin-10 are involved in the pathogenesis of psoriasis, the aim of our study was to investigate the effect of dithranol on interleukin-8, interleukin-10 mRNA production and interleukin-10 receptor expression of the HaCaT keratinocyte cell line which is commonly used in experiments examining the effects of therapeutic drugs on keratinocytes. MATERIALS AND METHODS: Cultured HaCaT cells were treated with 0.1-0.5 microg/ml dithranol for 30 minutes. After 2 and 4 h total cellular RNA isolated from HaCaT cells was reverse transcribed (RT) to cDNA which was subjected to polymerase chain reaction (PCR) with specific primer pairs for interleukin-8, interleukin-10 and interleukin-10 receptor. For immunohistochemistry cultured HaCaT cells were stained with a monoclonal antibody against the human interleukin-10 receptor. RESULTS: Our results showed that dithranol treatment did not change the highly elevated level of interleukin-8 mRNA of HaCaT cells. Interleukin-10 mRNA signal with RT-PCR could not be detected in HaCaT cells. Depending on the concentration dithranol increased the mRNA production of interleukin-10 receptors in HaCaT cells. This dithranol induced dose dependent upregulation of IL-10 receptors in HaCaT cells was also observed on the protein level using immunohistochemistry. CONCLUSIONS: Since the interleukin-10 receptor expression of keratinocytes in psoriatic lesional skin is downregulated, the dithranol induced upregulation of the receptor in our model system might help to reveal the therapeutic action of the drug.

Actins↗

Familial inheritance of crossed fused renal ectopia.

A family with dominant inheritance of a rare renal malformation is reported. The father and one son had left crossed fused ectopic and dysplastic kidneys and another son had a horseshoe kidney and vesicoureteral reflux. We discuss various potential pathogenetic mechanisms and propose that a defect in the timing of the proper reciprocal induction of the ureteric bud and the metanephric blastema is involved.

Adult↗

1-Stage feminizing genitoplasty: 8 years of experience with 49 cases.

PURPOSE: We retrospectively evaluated the results of a modified technique for 1-stage feminizing genitoplasty in children with congenital adrenal hyperplasia (CAH) and other rare intersex conditions. MATERIALS AND METHODS: Between 1991 and 1998, 47 infants and 2 adolescents underwent 1-stage feminizing genitoplasty at our hospital. Of the patients 44 had CAH, 2 had the partial androgen insensitivity syndrome and 3 were true hermaphrodites. In 3 patients we used the Passerini-Glazel technique, while in 46 our technique of feminizing genitoplasty was used, which consists of maximal mobilization of the urogenital sinus en bloc including the vagina and urethra via the perineal approach. Two lateral plates built from dorsal split phallic and preputial skin together with the dorsal split urogenital sinus are used to construct the vaginal introitus and labia minora, and the scrotal folds are used to construct the labia majora. Reduction clitoroplasty is done according to the technique of Kogan et al. Mean age plus or minus standard deviation was 0.9 +/- 0.3 years of the patients with CAH and 13 +/- 2.3 of the remainder. Preoperative information, including status of the internal genitalia, anatomical length of the vagina site of communication between the vagina and urogenital sinus, in relation to the pelvic floor, was obtained by transabdominal pelvic ultrasound. RESULTS: Operating time ranged between 120 and 180 minutes, average hospitalization period was 4 to 5 days and mean followup was 4.7 +/- 2.6 years. Preoperative ultrasound provided the correct data regarding the vaginal and internal genitalia anatomy in all cases, and the exact communication site between the vagina and urogenital sinus was demonstrated in 93%. Complications consisted of intraoperative rectal injury in 1 case and mild wound infection of the buttocks area in 3. In 1 case total clitoris loss was observed. All patients who underwent modified genitoplasty have had successful cosmetic and early functional results. Two patients presented with repeat clitoromegalia due to inadequate adrenal suppression. CONCLUSIONS: Our adapted technique of 1-stage feminizing genitoplasty provides good cosmetic and functional results. The functional results of this operation should be reevaluated after puberty and in adulthood.

Adolescent↗

Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin.

OBJECTIVES: To evaluate the effectiveness of a hydrogel implant containing the gonadotropin-releasing hormone (GnRH) agonist histrelin in suppressing testosterone production in men with prostate cancer and to determine the effective dose (one, two, or four implants). METHODS: Forty-two men with prostate cancer and indications for androgen ablation were treated with one, two, or four implants. In two of the clinics, comprising 27 subjects, the treatment period was 12 months, with replacement with the same number of implants at 12-month intervals. In a third clinic, which treated 15 subjects, the implants were left in place for up to 30 months. The total experience was 605 treatment months. RESULTS: The histrelin levels were detected in serum proportional to the number of implants placed. The response, however, was similar among all three dose levels, with testosterone and luteinizing hormone essentially completely suppressed. Serum testosterone levels decreased from 21.9 +/- 17.6 nmol/L to 0.93 +/- 1.57 nmol/L within 1 month and were maintained at 0.55 +/- 0.24 nmol/L at 6 months and 0.60 +/- 0.28 nmol/L after 12 months of treatment. Of the 38 assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks of the initial implant placement. All patients followed for up for 12 months after placement of the initial set of implants maintained suppression of testosterone production while the implant was in place. CONCLUSIONS: The histrelin hydrogel implant provided adequate and reliable delivery of the potent GnRH agonist histrelin during at least 1 year using a single implant in men with prostate cancer. No apparent advantages were found in using more than one implant, and the question of the possible effectiveness of even lower doses remains open. This treatment modality appears to be both safe and effective.

Aged↗

A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure.

BACKGROUND: Acute renal failure (ARF) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50 to 80%. The worldwide standard for renal replacement therapy is intermittent hemodialysis (IHD). Continuous hemodialysis and hemofiltration techniques have recently emerged as alternative modalities. These two therapies have not been directly compared. METHODS: A multicenter, randomized, controlled trial was conducted comparing two dialysis modalities (IHD vs. continuous hemodiafiltration) for the treatment of ARF in the intensive care unit (ICU). One hundred sixty-six patients were randomized. Principal outcome measures were ICU and hospital mortality, length of stay, and recovery of renal function. RESULTS: Using intention-to-treat analysis, the overall ICU and in-hospital mortalities were 50.6 and 56.6%, respectively. Continuous therapy was associated with an increase in ICU (59.5 vs. 41.5%, P < 0.02) and in-hospital (65.5 vs. 47.6%, P < 0.02) mortality relative to intermittent dialysis. Median ICU length of stay from the time of nephrology consultation was 16.5 days, and complete recovery of renal function was observed in 34.9% of patients, with no significant group differences. Despite randomization, there were significant differences between the groups in several covariates independently associated with mortality, including gender, hepatic failure, APACHE II and III scores, and the number of failed organ systems, in each instance biased in favor of the intermittent dialysis group. Using logistic regression to adjust for the imbalances in group assignment, the odds of death associated with continuous therapy was 1.3 (95% CI, 0.6 to 2.7, P = NS). A detailed investigation of the randomization process failed to explain the marked differences in patient assignment. CONCLUSIONS: A randomized controlled trial of alternative dialysis modalities in ARF is feasible. Despite the potential advantages of continuous techniques, this study provides no evidence of a survival benefit of continuous hemodiafiltration compared with IHD. This study did not control for other major clinical decisions or other supportive management strategies that are widely variable (for example, nutrition support, hemodynamic support, timing of initiation, and dose of dialysis) and might materially influence outcomes in ARF. Standardization of several aspects of care or extremely large sample sizes will be required to answer optimally the questions originally posed by this investigation.

Acute Kidney Injury↗

Changes in DNA loop domain structure during spermatogenesis and embryogenesis in the Syrian golden hamster.

The DNA in eukaryotic cells is organized into loop domains that are 25 to 100 kilobases long and attached at their bases to the nuclear matrix. This organization plays major roles in DNA replication and transcription. We examined changes in DNA loop structure of the 5S rDNA gene cluster in the Syrian golden hamster as a function of cellular differentiation by direct visualization with fluorescent in situ hybridization. The 5S rDNA cluster is large enough to encompass more than one loop domain but small enough that individual loop domains can still be resolved. We found that the sizes of the 5S rDNA loops are much smaller, and that the numbers of loops per locus are larger, in all pluripotent cell types than they are in adult somatic tissue. Within the pluripotent spermatogenic cell lineage, the loop domain organization was cell specific. The loop size decreased during the early stages of spermatogenesis but did not change during spermiogenesis, suggesting that DNA loop structure is independent of the chromatin condensation that occurs when protamines replace histones. In early embryonic cells, the loop structure remained small, but in differentiated somatic cells, it became much larger. We suggest that these changes in the 5S rDNA loop domain structure may be related to the maintenance or loss of developmental potential.

Animals↗

Endoscopic puncture of ureterocele as a minimally invasive and effective long-term procedure in children.

OBJECTIVES: Over the past years the surgical approach to ureterocele has evolved from complicated major surgery to minimally invasive endoscopic treatment. Because of the high rate of secondary surgery in some recently reported series, an upper pole partial nephrectomy is again recommended as the procedure of choice. We have retrospectively evaluated the long-term results of endoscopic puncture of a ureterocele and its long-term effectiveness and applicability in children. METHODS: Over the past 8 years, 34 patients (20 female, 14 male) were treated in our service with primary endoscopic puncture of a ureterocele. The mean age of the patients was 1.1 +/- 4.3 (mean +/- SD) years. Mean follow-up was 6.1 +/- 2.4 years. Antenatally ultrasound detected the ureterocele in 5 (14%) patients, fetal hydronephrosis leading to the postnatal diagnosis in 13 (38%), and 16 (48%) children presented with symptoms of urinary tract infection (UTI). The ureteroceles presented as part of renal duplication in 31 patients (91%), 3 (9%) in a single system and 1 child had bilateral ureteroceles of a duplex system. Twenty (58%) children had intravesical ureteroceles and the remaining 14 (42%) ectopic ureteroceles. Very poorly functioning upper pole moiety presented in 26 (75%) of the cases and nonfunctioning upper poles in 5 (14%). Twenty of 34 children (58%) had initial vesicoureteral reflux (VUR) to the lower moiety, either to the ipsi (60%) or contralateral kidney (40%). A cold knife incision was carried out in 4 (11.7%), puncture by a 3-french Bugbee electrode in 20 (58%), and the stylet of a 3-french ureteral catheter was utilized to puncture the ureterocele in the remaining 10 patients (30.3%). RESULTS: Complete decompression of the ureterocele was observed in 32 of 34 children (94%). Two patients required secondary puncture 2 years following the primary procedure and are doing well. Upper pole moiety function improved postoperatively in 2 infants and remained stable in all 32 patients, no patient presented with deterioration of the renal function. Six of 20 (30%) patients who had initial VUR to the lower pole, accompanied with recurrent UTI, required surgery. Three underwent ureteric reimplantation and another 3 submucosal polytetrafluoroethylene paste (Teflon) injection. Eight (40%) patients presented with spontaneous resolution of VUR to the lower moiety following puncture of the ureterocele. An additional 6 (17.6%) patients developed VUR to the upper moiety following the puncture of the ureterocele, 3 after cold knife incision and 3 after simple puncture. In 2, submucosal Teflon injection solved the VUR and the remaining 4 patients were maintained on prophylactic antibiotics. In 1 child the reflux resolved spontaneously, and none of them presented with UTI. In 2 cases with nonfunctional upper poles, partial nephrectomy was performed due to symptomatic UTI in spite of complete collapse of the ureterocele 1 and 2 years, respectively, following the initial puncture. No difference was observed in the re-operation rate between the patients with ectopic versus intravesical ureterocele (p<0.05). CONCLUSION: We found that endoscopic puncture of a ureterocele presents an easily performed procedure which allows the release of obstructive ureters and avoids major surgery in the majority of the cases even after a long follow-up.

Adolescent↗

Ultrasound vs CT for the detection of ureteric stones in patients with renal colic.

The aim of our study was to compare the accuracy of non-contrast spiral CT with ultrasound (US) for the diagnosis of ureteral calculi in the evaluation of patients with acute flank pain. 62 consecutive patients with flank pain were examined with both CT and US over a period of 9 months. All patients were prospectively defined as either positive or negative for ureterolithiasis, based on follow-up evaluation. 43 of the 62 patients were confirmed as having ureteral calculi based on stone recovery or urological interventions. US showed 93% sensitivity and 95% specificity in the diagnosis of ureterolithiasis; CT showed 91% and 95%, respectively. Pathology unrelated to urinary stone disease was demonstrated in six patients. Although both modalities were excellent for detecting ureteral stones, consideration of cost and radiation lead us to suggest that US be employed first and CT be reserved for when US is unavailable or non-diagnostic.

Adult↗

Vaginal hysterectomy.

Vaginal hysterectomy represents the ultimate minimal access hysterectomy. The indications for the procedure extend well beyond those of prolapse. Good training and advances in surgical technique allow the removal of enlarged fibroid uteri as well as vaginal oophorectomy. This article also considers the complications which may follow.

Female↗

Patterns of protein kinase C isoenzyme expression in transitional cell carcinoma of bladder. Relation to degree of malignancy.

We determined the pattern of protein kinase C (PKC) isoform expression in human cell lines by Western blotting and immunofluorescent staining techniques. In addition, we examined PKC isoform expression in tissue samples of transitional cell carcinoma (TCC) of the bladder. PKC delta, PKC beta II, and PKC eta were found primarily in the RT4 cell line (low-grade tumor), and PKC zeta was expressed most strongly in the SUP cell line (invasive tumor). In tissue samples of urinary bladder cancer, PKC isoenzymes were expressed differentially as a function of tumor stage and grade; expression of PKC beta II and PKC delta was high in normal tissue and in low-grade tumors and decreased with increasing stage and grade of TCC. The opposite pattern was seen with PKC zeta. The differences in expression of specific isoenzymes as related to levels of malignancy of the cell lines and tissue samples suggest that the PKC family has an important role in normal and neoplastic urothelium.

Blotting, Western↗