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Biomedical subjects

G Kaya

Publications and source records attributed to G Kaya.

At least 19 recordsLinked to original sources

Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice.

We show here that the alpha, beta, and gamma isotypes of peroxisome proliferator-activated receptor (PPAR) are expressed in the mouse epidermis during fetal development and that they disappear progressively from the interfollicular epithelium after birth. Interestingly, PPARalpha and beta expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing. Using PPARalpha, beta, and gamma mutant mice, we demonstrate that PPARalpha and beta are important for the rapid epithelialization of a skin wound and that each of them plays a specific role in this process. PPARalpha is mainly involved in the early inflammation phase of the healing, whereas PPARbeta is implicated in the control of keratinocyte proliferation. In addition and very interestingly, PPARbeta mutant primary keratinocytes show impaired adhesion and migration properties. Thus, the findings presented here reveal unpredicted roles for PPARalpha and beta in adult mouse epidermal repair.

Animals↗

Expression of CD44 and its isoforms in the fetal neuroblasts.

CD44 is a polymorphic transmembrane glycoprotein that exists as multiple isoforms resulting from alternative splicing and posttranslational modifications. Enhanced expression of CD44 has been correlated to the tumorigenicity and metastatic behavior in different malignant tumors. In contrast, human neuroblastomas exhibit an inverse correlation between CD44 expression and tumor malignancy. To determine whether there is a CD44 silencing in sympatho-adrenal precursors as a possible explanation for the down-regulation of CD44 in neuroblastomas, the expression of standard CD44H and v6, v7, v7v8, or v10 isoforms was analyzed by immunohistochemistry in human adrenal glands of 14- to 20-week-old gestational age fetuses. All of the fetal neuroblasts localized in the adrenal gland parenchyma and migrating from the sympathetic nerve chain into the fetal adrenal cortex strongly expressed CD44H but none of the CD44 isoforms could be detected in these cells. In contrast, a strong expression of CD44v7 and v6 was detected in the fetal adrenal cells. These results indicate that, as for many other cell types, the CD44H expressed by fetal neuroblasts may contribute to controlling their migration into the adrenal medulla and that the down-regulation of CD44H in neuroblastoma cells should be explained by mechanisms other than the fetal suppression of CD44H expression in their normal counterparts.

Adrenal Glands↗

Chronic borreliosis presenting with morphea- and lichen sclerosus et atrophicus-like cutaneous lesions. a case report.

We report on a case of chronic cutaneous borreliosis with manifestations clinically compatible with morphea and lichen sclerosus et atrophicus. The histopathologic features of these lesions were those of acrodermatitis chronica atrophicans. Our case illustrates the concept that clinical aspects of morphea and lichen sclerosus et atrophicus pertain to the spectrum of cutaneous borreliosis.

Abdomen↗

An experimental study on the relationship of intra-abdominal pressure and renal ischemia.

This study was undertaken in order to determine whether or not the increased intra-abdominal pressure during laparoscopic procedures causes renal ischaemia and parenchymal pathology. Fifteen adult New Zealand rabbits were used in the study. Anaesthesia was maintained by 2% isoflurane, 50% O2 in air. Heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), end-tidal carbon dioxide (PETCO2), airway pressure (Paw) and blood gases were monitored. Rabbits in control group (group C, n = 7) and study group (group S, n = 8) had a Veress needle placed supraumbilically. Group S was insufflated with CO2 sequentially at 5, 10 and 15 mmHg of intra-abdominal pressures (IAP); each pressure level was maintained for 20 minutes. At the end of the study, laparotomy was performed and blood was withdrawn from renal vein for measurements of renin and angiotensin I levels, and the other kidney was removed simultaneously for pathological evaluation. Haemodynamic and respiratory measurements were stable in group C and were variable in group S. The renin level was 7.27 +/- 0.34 ng.mL-1 and angiotensin I was 5.01 +/- 0.32 ng.mL-1 in group C. In group S, levels of renin and angiotensin I were 26.2 +/- 5.9 ng.mL-1 and 39.4 +/- 12.1 ng.mL-1 respectively, being significantly higher than group C (p < 0.05). Pathological scores were 0.02 +/- 0.008 in group C and 0.82 +/- 0.124 in group S (p < 0.05). There were significant histological changes in group S compared with group C. During prolonged laparoscopic operations high intra-abdominal pressures may result in intra-abdominal organ ischaemia.

Abdomen↗

Anterior mitral leaflet prolapse as a primary cause of pure rheumatic mitral insufficiency.

BACKGROUND: This study was designed to revise the mechanisms and repair techniques of anterior mitral leaflet prolapse observed during the correction of pure rheumatic mitral regurgitation in children. METHODS: From March 1993 to May 1998, 36 children suffering from pure rheumatic mitral regurgitation due to anterior leaflet prolapse underwent mitral valve repair. The mean age was 12.5 years (range, 6 to 16 years). Anterior leaflet prolapse was due to chordal elongation in 25 patients (group A), chordal rupture in 6 patients (group B), and retraction of anterior secondary chordae tendineae, creating a V-shaped deformity in the middle of the anterior leaflet, thus moving the free edge of the anterior leaflet away from the coaptation plane, in 5 patients (group C). Chordal shortening, transposition, and resection of anterior secondary chordae tendineae were used to correct anterior leaflet prolapse according to the predominantly responsible mechanism. RESULTS: All patients were available for clinical follow-up, which ranged from 6 months to 5 years (mean follow-up, 3 years). Echocardiographic studies were obtained until the 3rd postoperative month, and all patients showed significant improvement in their left ventricular and atrial dimensions. There was one late death related to endocarditis. Two patients in group C who had mitral valve repair underwent mitral valve replacement on the 19th and 24th postoperative months, respectively, because of failure of mitral valve repair. CONCLUSIONS: Mitral valve repair for pure mitral regurgitation due to rheumatic anterior leaflet prolapse can be performed safely for all types of mechanisms. Although the techniques we used provide stable short-term results in each of these groups, midterm results are better in groups A and B, where tissue thickening is less important, recurrences of rheumatic carditis are lower, and the interval between the first rheumatic attack and the surgical procedure is shorter than in group C.

Adolescent↗

Systemic stress response during operations for acute abdominal pain performed via laparoscopy or laparotomy in children.

We compared the endocrine and metabolic changes during acute emergency abdominal surgery performed using either laparoscopy or laparotomy in children. Twenty-nine children aged 1.5-14 years were assigned to undergo laparoscopy (n = 15) or laparotomy (n = 14) with a standard anaesthesia technique. Arterial blood gases and blood prolactin, cortisol, interleukin-6, glucose, insulin, lactic acid and epinephrine levels were determined 5 min after the induction of anaesthesia, 30 min into surgery and at the end of surgery. Intra-operative heart rate and mean arterial pressure were stable in both groups. In the laparoscopy group, slight respiratory acidosis occurred during surgery (p < 0.01) but there were no changes in the laparotomy group. Insulin, cortisol, prolactin, epinephrine, lactate and blood glucose levels increased in both groups (p < 0.05) although there was no difference between the groups. The surgical stress and trauma imposed by laparoscopy seems similar to that caused by laparotomy in children undergoing emergency abdominal surgery.

Abdominal Pain↗

Lidocaine 10% in the endotracheal tube cuff: blood concentrations, haemodynamic and clinical effects.

The purpose of this study was to evaluate the effects (common haemodynamic variables, peak cuff pressures, the incidence of reaction ('bucking') during extubation and the incidence of sore throat after operation) of lidocaine 10% instilled into the endotracheal tube cuff in intubated patients. Plasma concentrations of lidocaine were assayed. Seventy ASA class I-II patients scheduled for plastic surgery were studied. Patients were randomly divided in two groups: the cuff of the endotracheal tube was inflated with either lidocaine 10% (group L) or with saline (group S) immediately after endotracheal intubation. In group L patients, the haemodynamic changes were less (P < 0.05), and the peak cuff pressure was lower (P < 0.01) than for group S. At extubation, more patients reacted ('bucked') in group S (70.5% vs. 19.4%, P < 0.01). The incidence and severity of sore throat were significantly lower in group L 1 and 24-h after extubation. Plasma lidocaine concentrations did not reach toxic values. Lidocaine 10%, compared with saline, in the endotracheal tube cuff was associated with less disturbance of haemodynamic responses and less incidence of bucking during tracheal extubation. Lidocaine was also effective in reducing of incidence and severity of sore throat after operation.

Adolescent↗

The efficacy of pre- versus postsurgical axillary block on postoperative pain in paediatric patients.

We compared the effects of pre- and postsurgical axillary block on pain after hand and forearm surgery in 55 children in a double-blind randomized study. The successful blocks are reported here (n=49). Children aged 1-11 years and ASA I or II were allocated randomly to receive axillary block with 2 mg.kg-1 of 0.25% bupivacaine, either after induction but before the surgery (presurgical group, n=25) or immediately after surgery, before the end of anaesthesia (postsurgical, n=24). In all patients, a standard general anaesthesia technique was used. The Faces Pain Scale (FPS) and analgesic requirements were recorded for 24 h at various times after operation. Eight patients (32%) in the presurgical group and 20 patients (83.33%) in the postsurgical group did not require additional analgesic within the first 24 h after operation (P< 0.05). In patients who had pain during the observation period, the pain started 13.66+/-2.61 h in the presurgical group and 13.14+/-2.34 h in the postsurgical group after performing block (P> 0.05). The FPS scores were similar in both groups during the first 8 h in the postoperative period (P> 0.05). There was a significant difference at 10 h after surgery (P< 0.05). Cumulative FPS score was higher in the presurgical group (10.50+/-1.06) than in the postsurgical group (9.45+/-1.28) (P< 0.05), but both groups had effective analgesia overall, the mean FPS score being less than 2. Additional analgesic consumption was similar in these patients in both groups. A lower isoflurane concentration was used in the presurgical group (0.68% vs 1.72%, P< 0.001). We did not demonstrate the superiority of preemptive analgesia, but our results indicate that presurgical axillary block with 0.25% bupivacaine allows the use of inhalational anaesthetics at lower concentrations while providing a reasonably painless postoperative period.

Analgesia↗

Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerosus et atrophicus.

CD44 is a polymorphic integral membrane glycoprotein that serves as the principal cell surface receptor for hyaluronate, the major component of the extracellular matrix. CD44 is abundantly found in the skin and functions as a cell adhesion molecule. In a recent study we have observed a massive dermal accumulation of hyaluronate as a result of the in vivo selective suppression of CD44 in keratinocytes in mice expressing a keratin 5 promoter-driven CD44 anti-sense transgene. As the histologic features of the dorsal skin of these transgenic mice display some similarities to those of the skin lesions of lichen sclerosus et atrophicus, we explored the nature of the material accumulated in the dermis of genital and extragenital lesions of 14 patients with lichen sclerosus et atrophicus by Alcian Blue and human CD44 receptor globulin stainings, as well as the epidermal expression of CD44 protein and mRNA by immunohistochemistry and in situ hybridization. In this study we provide evidence that hyaluronate is accumulated in the superficial dermis of lichen sclerosus et atrophicus lesions, in particular by the use of human CD44 receptor globulin staining, which binds specifically to hyaluronate. In addition we show that the protein and mRNA expression of CD44 in the epidermis of the involved lichen sclerosus et atrophicus skin from genital and extragenital areas is significantly decreased, and in some cases completely lost. In contrast, keratinocyte CD44 expression was un-altered in the skin lesions of lupus erythematosus, scleroderma and reticular erythematous mucinosis, despite the presence of a mucinous material in the dermis. These results suggest that a decrease in CD44 in the keratinocytes may be correlated with an abnormal dermal accumulation of hyaluronate in the lesions of lichen sclerosus et atrophicus, and may play a pathogenetic role in this disease. J Invest Dermatol 115:1054-1058 2000

Adolescent↗

The cardiorespiratory effects of laparoscopic procedures in infants.

We assessed the cardiorespiratory effects of laparoscopic procedures in 27 infants aged between 36 and 365 days. Infants were monitored and anaesthetised in a standardised manner. Heart rate, mean arterial pressure, end-tidal carbon dioxide and oxygen saturation were recorded, and blood gases were measured at 5 min after intubation, 15 and 30 min after carbon dioxide pneumoperitoneum, 5 min after desufflation and after extubation. The pH, PaO2, base excess, SaO2 and SpO2 decreased, and PCO2 increased by insufflation of carbon dioxide intraperitoneally, and improved following deflation. Changes in pH and PaO2 during the study were statistically significant (p < 0.0001). The increase in PaCO2 30 min after pneumoperitoneum was statistically significant when compared with initial values. Transient arrhythmias were observed in 10 infants 1 min after pneumoperitoneum. There were no statistically significant alterations in heart rate and systolic blood pressure.

Anesthesia, Inhalation↗

Renal duplex Doppler ultrasonography as a predictor of preclinical diabetic nephropathy in children.

PURPOSE: To perform Doppler US in patients with insulin-dependent diabetes mellitus (IDDM) as a predictive method in diabetic nephropathy (DN). MATERIAL AND METHODS: Twenty-five patients with type I diabetes mellitus underwent renal Doppler US examination. Children were divided into three age groups: group I, 3-7 years; group II, 8-10 years; and group III, 11-18 years. The age-matched control group consisted of 56 healthy children who underwent renal Doppler US only. RESULTS: The mean values of the resistive index (RI) were, respectively, 0.64+/-0.03, 0.59+/-0.04, 0.59+/-0.02 in age groups I, II, and III for healthy children and 0.68+/-0.03, 0.62+/-0.04, 0.59+/-0.04 in age groups I, II, and III of the diabetic patients. There were no significant differences between the diabetic and healthy subjects. The mean RI value was not different in the patients with glomerular hyperfiltration compared to patients with normal filtration rate. Additionally, there were no significant differences between the mean RI value in patients with or without microalbuminuria. CONCLUSION: Renal Doppler US is not useful for prediction or for early diagnosis of DN.

Adolescent↗

Case control study of diarrhoea and faecal soiling in two- to six-month-old lambs.

A case control study was nested within a longitudinal study of faecal soiling on eight commercial farms in the south west of England. Eighty-two incident cases of faecal soiling in lambs between two and six months of age were individually matched with a single unaffected control lamb. A range of variables was examined including sex, neonatal history, trace element concentrations in blood, wool characteristics and faecal bacteriology and parasitology. Odds ratios and their 95 per cent confidence limits were estimated by using Mantel Haenszel methods and conditional logistic regression. Faecal soiling was significantly associated with longer fleeces, lower crimp frequencies, male lambs and multiple births. Significant relationships were also found between faecal soiling and neonatal diarrhoea, blood selenium concentration and the presence of Clostridium perfringens type A in the faeces.

Animal Husbandry↗

Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation.

CD44 is a broadly distributed polymorphic glycoprotein that serves as the principal cell-surface receptor for hyaluronate. Although CD44-mediated cell interaction with hyaluronate has been implicated in a variety of physiologic events, including cell-cell and cell-substrate adhesion, cell migration, proliferation, and activation, as well as hyaluronate uptake and degradation, the biologic role of CD44 in vivo in various tissues remains to be determined. In the present work we have developed transgenic mice that express an antisense CD44 cDNA driven by the keratin-5 promoter. These mice lack detectable CD44 expression in skin keratinocytes and corneal epithelium and display abnormal hyaluronate accumulation in the superficial dermis and corneal stroma, distinct morphologic alterations of basal keratinocytes and cornea, and defective keratinocyte proliferation in response to mitogen and growth factors. These alterations are reflected by a decrease in skin elasticity, impaired local inflammatory response and tissue repair, delayed hair regrowth, and failure of the epidermis to undergo hyperplasia in response to carcinogen. Our observations indicate that two major functions of CD44 in skin are the regulation of keratinocyte proliferation in response to extracellular stimuli and the maintenance of local hyaluronate homeostasis.

9,10-Dimethyl-1,2-benzanthracene↗

Histological changes following epidural injection of midazolam in the neonatal rabbit.

Midazolam can produce antinociceptive effects when used via intrathecal or epidural routes. Neurotoxicity studies are scanty especially for neonates. The aim of this study was to carry out electron microscopic (EM) examinations in the neonatal rabbit to determine the histological effects of epidural midazolam on spinal cord. Twenty white New Zealand neonatal rabbits were randomly assigned to three groups receiving single dose of 0.9% saline (Group I; Control, n = 4), 0.9% saline titrated to pH = 3.9 by addition of hydrochloric acid (Group II; n = 6), midazolam 250 micrograms.kg-1 (Group III; n = 12) epidurally. Half of each group were sacrificed on the second day and the remainder on the seventh day and spinal cord sections were evaluated by EM. Control group displayed normal histology on grids. Group II and II showed a variable degree of neurotoxic effects such as degeneration of vacuoles, cytoplasm and neurofilaments, disruption of myelin sheaths, lysis of cell membranes, perivascular oedema, pyknosis of nuclei. The toxic effects of acidic saline and midazolam are similar, in view of these results the epidural use of acidic midazolam (commercially available preparations) in neonates should be avoided.

Anesthetics↗

The effects of intranasal midazolam on urodynamic studies in children.

OBJECTIVE: To determine the influence of midazolam on the function of the lower urinary tract when used to sedate the patient. PATIENTS AND METHODS: Urodynamic studies were performed on 20 patients (seven boys and 13 girls, mean age 4.04 years, range 1 day to 10 years) before and after the intranasal administration of 0.5 mg/kg of midazolam. The patients' heart rate, respiratory rate and oxygen saturation were monitored and the level of sedation recorded by an anaesthesiologist and a surgeon during the study. RESULTS: Heart rate and respiratory rate did not change and the percentage oxygen saturation remained stable throughout the study period. The childrens' behaviour began to change 3-5 min after the intranasal administration of midazolam. The sedation lasted 2 h and the full co-operation of the patient was assured. The difference between the initial and post-midazolam evaluation of maximal cystometric capacity, contractility, compliance, intravesical pressure, maximum flow rate, intravesical pressure at maximum flow and the amount of residual urine were statistically insignificant (P > 0.05). Electromyographic characteristics showed no significant change with the use of midazolam (P > 0.05). CONCLUSION: Despite the suggestion that benzodiazepines, especially diazepam, are useful for the relaxation of pelvic floor striated musculature in voiding dysfunctions, there was no effect on urodynamic variables when midazolam was used in a single dose intranasally. The anxiolytic and sedative effects allowed children to undergo urodynamic studies in comfort.

Administration, Intranasal↗

Diazepam serum concentration-sedative effect relationship in patients with liver disease.

Sedative effects and drug elimination characteristics after intravenous bolus administration of diazepam 0.15 mg/kg were investigated in 15 patients with liver disease (Group I), and in 15 normal patients (Group II) during diagnostic laparoscopy. Diazepam induced heavier sedation in patients with liver disease (P < 0.02). Serum concentration of diazepam 30 minutes after administration was significantly lower in Group I (group with liver disease) when compared with Group II (control group) (210.68 +/- 112.65 ng/ml vs 451.57 +/- 239.87 ng/ml, p < 0.02). The sedation scores during the laparoscopy procedures correlate negatively with serum benzodiazepine levels. The benzodiazepine concentration-time profiles of the groups vary significantly (p < 0.02). Heavier sedative effect and lower benzodiazepine concentrations in patients with liver diseases suggests that the permeability of blood brain barrier increases and that higher affinity to benzodiazepine receptors exists. Differences in concentration-time courses of diazepam in patients with liver diseases is a warning indicating the accumulation of the drug when infused or used frequently.

Adjuvants, Anesthesia↗