Split renal function in patients with renal masses: utility of parenchymal volume analysis vs nuclear renal scans.

OBJECTIVES: To evaluate the utility of parenchymal volume analysis (PVA) for estimation of split renal function (SRF) in patients with renal masses. SRF is important for deciding about partial vs radical nephrectomy (PN/RN) and assessing risk for developing severe chronic kidney disease after surgery. For renal donors PVA is routinely used to estimate SRF, but the utility of PVA for the more complex renal mass population remains undefined. PATIENTS AND METHODS: All patients (n = 374) with renal tumours and a normal contralateral kidney managed with PN (2010-2018), with preoperative/postoperative nuclear renal scans (NRS) and cross-sectional imaging were analysed. Parenchymal volumes were measured by free-hand scripting or software analysis. Concordance between ipsilateral estimated glomerular filtration rate (eGFR) values based on SRF from NRS vs PVA were evaluated by Pearson correlation and Bland-Altman plots. Parallel analysis of all 155 patients managed with RN at our centre (2006-2016) with preoperative NRS and imaging was also performed. RESULTS: For PN, the median age and tumour size were 62 years and 3.4 cm, respectively. The median preoperative ipsilateral parenchymal volume and eGFR were 181 cm3 and 36.9 mL/min/1.73 m2 , respectively. Parenchymal volumes estimated by free-hand scripting vs software analyses correlated strongly (r = 0.98, P < 0.001). Preoperative ipsilateral eGFR based on SRF from PVA vs NRS also correlated strongly (r = 0.94, P < 0.001). Ipsilateral eGFR saved after PN correlated strongly with parenchymal volume preserved (all r >0.60); however, the correlation was much stronger when ipsilateral eGFRs were based on SRF from PVA rather than NRS (z-statistic = 3.15, P = 0.002). For RN patients, preoperative eGFR in the contralateral kidney based on SRF from PVA vs NRS also correlated strongly (r = 0.87, P < 0.001). CONCLUSION: PVA has utility for estimation of SRF in patients with renal masses, even though this population is older and more comorbid than renal donors and the tumour can complicate the analysis. PVA can be obtained by software analysis from preoperative cross-sectional imaging and thus readily incorporated into routine clinical practice.

[OPTIMIZATION OF EARLY DIAGNOSIS OF ACUTE KIDNEY INJURY IN NEWBORNS IN CRITICAL CONDITION].

UNLABELLED: Current diagnosis of acute kidney injury (AKI) is one of the most pressing problems in the newborn in critical condition. OBJECTIVE: To determine the diagnostic value of indicators of renal blood flow as a marker of acute kidney injury in critically ill newborns. MATERIALS AND METHODS: The study included 40 infants in critical condition. A clinical assessment of severity of the condition during admission was carried out with Neonatal Multiple Organ Dysfunction Score (NEOMOD) and Neonatal Therapeutic Intervention Scoring System (NTISS). All patients underwent evaluation of clinical and instrumental parameters, including ultrasound of the renal vessels, renal vascular resistance index and speed performance. CONCLUSIONS: 1) biochemical markers used in routine clinical practice were not sufficiently informative for the diagnosis of AKI. 2) For a more accurate assessment of the risk of AKI using serum creatinine, GFR calculation and evaluation on a scale RIFLE it is should be focused on performance standards, appropriate for gestational age and birth weight. 3) Evaluation of blood flow at a particular index in the resistance of the main renal arteries had the greatest predictive value and had a relatively high sensitivity and specificity for the diagnosis of AKI.

Idiotypic repertoire of anti-hen eggwhite lysozyme antibodies probed with hybridomas. Selection after immunization of an IdX marker common to antibodies of distinct epitope specificity.

A panel of hybridoma antibodies obtained from lymphoid cells that were fused during a primary response ("early") or a secondary response ("late") gave results concordant with analysis of conventional, in vivo-produced anti-lysozyme idiotypes: early antibodies did not display the predominant anti-hen eggwhite lysozyme idiotype (IdX-HEL), whereas late antibodies all displayed IdX-HEL. Furthermore, individual late hybridomas could each remove the entire anti-IdX-HEL activity by absorption, whereas early hybridomas could not. The epitope specificities of the hybridomas in both the early and late populations were heterogenous. We conclude that epitypic specificity in the response to HEL is determined independently from idiotypic specificity and that the predominant idiotype is selected for during the maturation of the anti-lysozyme response.

Updated growth curves for Turkish children aged 15 days to 60 months.

BACKGROUND: Growth reference values are useful in paediatric health care as a health indicator. Secular changes in height for age values are also known to affect the timing of puberty and brain weight. Different populations may be at different stages of this secular trend. It is, therefore, necessary to periodically update the growth reference values for each population to identify these changes. The aim of this study was to update the growth reference values for Turkish infants and young children. METHODS: Background information and height/length, weight and head circumference measurements on a sample of 2391 boys and 2102 girls were obtained from Well Child Clinic Records. The LMS method was used for the analyses. The percentage of exclusive breastfeeding was 62% at 4 months and 26.6% at 6 months. The continuation rate of breastfeeding at 12 months was 62.5%. RESULTS: Comparison with previous Turkish data showed an increase in height of 0.9 cm for boys and 1.1 cm for girls at age 5 years. The increase in weight was 0.220 kg in girls, while a decrease of 0.160 kg was noted in boys. Comparison with the 2000 US and Swedish values indicated that population differences may exist in pre-pubertal years. CONCLUSION: This study provides an enhanced instrument to evaluate the growth of Turkish infants and young children.

The effect of economic status on height, insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in healthy Turkish children.

OBJECTIVES: The effect of economic status (ES) on growth, insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-3 in healthy children is not well characterized. We aimed to study the interrelationship between height, weight, IGF-I, IGFBP-3, mid-parental height (MPH) and ES. DESIGN/SUBJECTS: Eight hundred and fourteen healthy children (428 boys, 386 girls; age 3-18 years) were classified according to income of the families as low, middle and high. Standard deviation scores (SDSs) of height, weight, MPH, IGF-I and IGFBP-3 were compared between the groups. The combined effect of these parameters and ES on height SDS was investigated with complex statistical models. RESULTS: There was a significant trend for height and weight SDSs to increase with higher income levels in boys, but not in girls. Body mass index (BMI) SDSs were similar in three groups. There was a general trend for MPH SDS to increase with income levels in both sexes. In boys, IGF-I SDS was significantly higher in high ES group than low ES. In girls, IGFBP-3 SDSs were significantly higher in high ES group than in middle ES group. For both genders, height SDS was highly correlated with weight SDS and moderately correlated with BMI SDS, MPH SDS and IGF-1 SDS. All correlations were significant and positive. Complex models showed that MPH (19%), IGF-I (13%) and ES (3%) in boys, and MPH (16%) and IGF-I (7%) in girls have significant contribution to height SDSs. CONCLUSIONS: ES per se, independent of overt malnutrition, affects height, weight, IGF-I and IGFBP-3 with some gender differences in healthy children. Influence of income on height and weight show sexual dimorphism, a slight but significant effect is observed only in boys. MPH is the most prominent variable effecting height in healthy children. Higher height and MPH SDSs observed in higher income groups suggest that secular trend in growth still exists, at least in boys, in a country of favorable economic development.

Glyburide-stimulated glucose transport in cultured muscle cells via protein kinase C-mediated pathway requiring new protein synthesis.

To study the mechanism of action of sulfonylurea agents on peripheral tissues without the potentially confounding influences of insulin, the direct effect of glyburide (i.e., in the absence of insulin) was evaluated in the L6 cultured myogenic cell line. Glyburide approximately doubled the incorporation of [14C]-glucose into glycogen. The rate-determining enzymes of glycogen metabolism, glycogen synthase and glycogen phosphorylase, were unaffected by the drug. Glucose transport (2-deoxyglucose uptake) was also approximately doubled. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) also doubled glucose transport and showed the same lag period (4-6 h) as glyburide before an effect occurred. Blockade of protein kinase C activity by either 1-(5-isoquinolinesulfonyl)-2 methyl piperazine (H7) or chronic exposure to TPA completely abolished the stimulation by glyburide. Cycloheximide, a protein synthesis inhibitor, also completely eliminated the effect of glyburide. The presence of ATP-sensitive K+ channels was assessed by measuring 86Rb efflux in ATP-depleted L6 muscle cells and RINm5F cells (which served as a positive control). Such channels were present and responded appropriately to glyburide and diazoxide in pancreatic beta-cells but were not present in muscle cells. Glyburide stimulation of glucose transport was completely eliminated by both Quin 2, an intracellular chelator of Ca2+, and verapamil, a Ca2+ channel blocker. However, glyburide did not raise intracellular Ca2+ levels. We conclude that glyburide stimulates glucose transport in cultured L6 muscle cells by a protein kinase C-mediated pathway that requires new protein synthesis. Although intracellular Ca2+ metabolism may also be involved, the initial step in the mechanism of action is probably different between pancreatic beta-cells and muscle cells.

Regulation of rat granulosa cell differentiation by extracellular matrix produced by bovine corneal endothelial cells.

The effect of bovine corneal extracellular matrix (ECM) on gonadotropin-primed rat granulosa cells in vitro was studied by examining the following parameters: 1) rate of cell attachment to culture dishes; 2) modulation of cell morphology; 3) specific binding of [125I]human(h)CG to LH/hCG receptors; 4) cAMP response to hCG stimulation; and 5) basal and hCG stimulated progesterone production. Attachment of cells to culture dishes occurred significantly earlier on ECM, as compared with uncoated dishes (6 h vs. 24 h). Cells grown on ECM were epitheloid and organized in multilayer aggregates, closely resembling their organization in the intact wall of the ovarian follicle. In contrast, cultures on uncoated dishes grew as a monolayer of markedly flattened cells. A 2-fold increase in number of LH/hCG receptors occurred on ECM within 48 h, probably due to de novo synthesis. Scatchard analysis revealed no change in hormone affinity to the receptor during the culture period [association constant (Ka) = 2.5 X 10(10)M-1 for hCG]. Cells grown on ECM had a parallel increase in cAMP responsiveness to hCG stimulation. Cells grown in serum-free medium on ECM-coated dishes preserved only 50% of LH/hCG receptors and cAMP responsiveness after 48 h. Cells cultured on ECM showed a marked elevation in progesterone production even in the absence of gonadotropin stimulation, whereas cells grown on uncoated dishes almost completely lost their ability to produce progesterone both in the presence and absence of hCG. These results indicate that ECM plays a substantial role in the maintenance and further propagation of granulosa cell differentiation in vitro.

Synergistic effect of human chorionic gonadotropin and extracellular matrix on in vitro differentiation of human granulosa cells: progesterone production and gap junction formation.

The effects of extracellular matrix (ECM) in the form of a native basement membrane and of hCG on progesterone production, cellular morphology, and gap junction formation in cultured human granulosa cells (GCs) were examined. GCs were harvested from human preovulatory follicles in the course of oocyte retrieval for in vitro fertilization. Cells grown on ECM secreted by bovine corneal endothelial cells (BCE) produced significantly higher amounts of progesterone (up to 3-fold) than cells on uncoated dishes. Culturing of cells on BCE-ECM in the presence of hCG resulted in a further increase in progesterone production; in the first 2 days an additive effect was noted, and on days 3, 4, and 5 a synergistic effect became evident (1.2- to 1.8-fold above the sum of the individual treatments). LH/hCG receptor content on day 3 of culture was 4-fold higher in GCs grown on BCE-ECM compared to that in uncoated dishes. A similar elevation was found when cells were grown on ECM secreted by PFHR-9 mouse endodermal cells. Cells grown on both types of ECM maintained their epithelioid shape but, in addition, formed cytoplasmic processes interconnected with neighboring cells by gap junctions. Morphometric analysis revealed that the area of cell membrane occupied by gap junctions increased by 3- to 4-fold on ECM compared to that in cells grown on plastic. Enlargement of endoplasmic reticulum was evident on ECM along with clustering of numerous mitochondria, lipid droplets, and lysosomes characteristic of highly luteinized cells. Cells grown in the presence of hCG on ECM showed morphological modulation similar to that of cells cultured on ECM alone. These observations suggest that growing of human GCs on a ECM similar to a naturally produced basement membrane enhances morphological and biochemical differentiation, and that ECM and gonadotropin affect synergistically the extent of luteinization in these cells.

Spatial tuning curves along the chick basilar papilla in normal and sound-exposed ears.

Intense sound exposure destroys chick short hair cells and damages the tectorial membrane. Within a few days postexposure, signs of repair appear resulting in nearly complete structural recovery of the inner ear. Tectorial membrane repair, however, is incomplete, leaving a permanent defect on the sensory surface. The consequences of this defect on cochlear function, and particularly frequency analysis, are unclear. The present study organizes the sound-induced discharge activity of cochlear nerve units to describe the distribution of neural activity along the tonotopic axis of the basilar papilla. The distribution of this activity is compared in 12-day postexposed and age-matched control groups. Spontaneous activity, tuning curves, and rate-intensity functions were measured in each unit. Discharge activity at 60 frequency and intensity combinations was identified in the tuning curves of hundreds of units. Activity at each of these criterion frequency/intensity combinations was plotted against the unit's characteristic frequency to construct spatial tuning curves (STCs). The STCs depict tone-driven cochlear nerve activity along the length of the papilla. Tuning sharpness, low- and high- frequency slopes, and the maximum response were quantified for each STC. The sharpness of tuning increased with increasing criterion frequency. However, within a frequency, increasing sound intensity yielded more broadly tuned STCs. Also, the high-frequency slope was consistently steeper than the low-frequency slope. The STCs of exposed ears exhibited slightly less frequency selectivity than control ears across all frequencies and larger maximum responses for STCs with criterion frequencies spanning the tectorial membrane defect. When rate-intensity types were segregated, differences were observed in the STCs between saturating and sloping-up units. We propose that STC shape may be determined by global mechanical events, as well as localized tuning and nonlinear processes associated with individual hair cells. The results indicated that 12 days after intense sound exposure, global and local contributions to spatially distributed neural activity are restored.

Ultrastructural characterization of human granulosa cells in stimulated cycles: correlation with oocyte fertilizability.

The fine structure of human granulosa cells (GC) obtained in the course of an in vitro fertilization procedure was correlated with oocyte fertilizability. The investigation was performed by light-microscopic and electron-microscopic examination of ultrathin sections and replicas of freeze-fractured material. GC associated with nonfertilizable oocytes (group I) had significantly smaller cell areas, tended to be tightly packed, and exhibited abundant intercellular gap junctions and adherence junctions. Multiple structural variations of cytoplasmic organelles were observed in comparison to cells associated with fertilizable oocytes (group II). Cells in group II tended to be widely dispersed, frequently contained interiorized gap junctional elements (annular junctions), and showed morphologic correlates of high steroidogenic activity. Structural dissimilarities between groups I and II were not consistently related to follicle size, as determined by volume of aspirated follicular fluid. In view of the sequential ultrastructural changes known to occur during follicular maturation and ovulation, it is concluded that GCs related to nonfertilizable oocytes were lacking structural correlates of luteinizing hormone/human chorionic gonadotropin responsiveness.

Culture of human granulosa cells from an in vitro fertilization program: effects of extracellular matrix on morphology and cyclic adenosine 3',5' monophosphate production.

Human GCs obtained from patients undergoing an IVF procedure and treated with CC, hMG, and hCG, lack cAMP responsiveness to hCG stimulation in vitro. After 48 hours in culture, recovery of cAMP production was significantly higher in hCG-stimulated cells grown on dishes coated with ECM than in cells grown on uncoated dishes. This difference correlated with a higher degree of morphologic differentiation of cells cultured on ECM. It is concluded that ECM provides superior culture conditions for the recovery of hormone-stimulated cAMP production and the maintenance of morphologic differentiation of preovulatory GCs from stimulated cycles.

Subtle abnormalities in follicular development and hormonal profile in women with unexplained infertility.

A prospective study of six unselected couples diagnosed as having unexplained infertility was done. In three of six patients, subtle abnormalities in follicular development were detected. In the first case poor follicular growth was observed. There was a premature small rise of luteinizing hormone (LH) with subsequent low levels of estradiol (E2) in the late follicular phase and unusual wide LH peak. This was followed by low progesterone levels in the luteal phase. In the second case follicular growth was abrupted by premature LH surge. This surge was triggered by early rise of E2 level while the follicle was still small in size. In the third case luteinized unruptured follicle syndrome was diagnosed, on ultrasound examination. All of the abnormalities were repetitive.

Analysis of Brugia pahangi microfilariae surface carbohydrates: comparison of the binding of a panel of fluoresceinated lectins to mature in vivo-derived and immature in utero-derived microfilariae.

A fluoresceinated lectin binding assay was employed to detect carbohydrates on the sheath and cuticle of mature in vivo-derived, and immature in utero-derived Brugia pahangi microfilariae. The sheath of mature microfilariae bound concanavalin A and wheat germ agglutinin, indicating the presence of N-acetylglucosamine and glucose or mannose. In addition to binding concanavalin A and wheat germ agglutinin, the sheath of in utero-derived microfilariae also bound Limulus polyphemus agglutinin, peanut agglutinin, Ricinus communis agglutinin-I, and soybean agglutinin, indicating the presence of the additional sugars galactose, sialic acid, and N-acetylgalactosamine. There was no evidence of cuticle carbohydrates, as none of the tested fluoresceinated lectins bound to either mature or immature exsheathed microfilariae. The significance of these results in terms of the survival of microfilariae in the mammalian host, and development to third-stage larvae in the mosquito vector, is discussed.

Analysis of lead body burden in Turkey.

Here we report the results of pilot screening for the environmental lead contamination in Turkey. Lead blood concentrations were determined in 342 subjects from 17 cities. The mean lead blood concentration, 3.65 +/- 1.66 micrograms/dl, is much lower than the values reported previously. People smoking tobacco and driving motor vehicles had elevated concentrations of lead in blood. There was also a moderate relationship between the urban population size and the lead in blood values, but no differences were observed, that could be related to distinct geographical locations. Motor traffic was assumed to be the main source of lead pollution in the urban environment in Turkey, and the low lead blood levels were linked to the reduction of lead additives in gasoline, in 1989. Although at present, the environmental lead contamination does not pose a considerable threat to public health, in the near future, when the motorization rate and gasoline consumption will possibly double or triple, the lead content in gasoline might need to be further reduced.

Parameters influencing the susceptibility of neonate mice to infection with Brugia pahangi.

A total of 307 young mice between less than 1 day (neonate) and 4 wk after birth were inoculated either subcutaneously or intraperitoneally with infective larvae of Brugia pahangi to determine the best protocol for the establishment of patent infections. For both male and female neonates, i.p. infection produced higher adult worm burdens than did s.c. infection. Although the numbers of adult worms harbored by male and female mice were not statistically different, male mice were more prone to develop a patent infection; no neonate female mice became microfilaremic , whereas seven of 113 i.p.-infected male mice developed microfilaremia. More female adult worms were recovered, on the average, than were male worms, regardless of the age of mice used for infection. However, the younger the mice were at infection, the higher were the numbers of male worms recovered. A high number of gravid female worms were recovered from amicrofilaremic mice. Adult female and male worms harvested from amicrofilaremic mice, implanted into the peritoneal cavity of jirds (Meriones unguiculatus), did not produce microfilariae although approximately 50% of the jirds contained gravid female parasites. Jirds implanted with worms from microfilaremic mice did, however, contain peritoneal microfilariae. It appeared that amicrofilaremic mice irreversibly damaged female worms to the extent that worms could survive and appear healthy, but could not release microfilariae.

Characterization of the exposed carbohydrates on the sheath surface of in vitro-derived Brugia pahangi microfilariae by analysis of lectin binding.

Adult female Brugia pahangi were maintained metabolically active in vitro for up to 35 days in Click's medium supplemented with 10% horse serum. For the first 14 to 18 days microfilariae were released into culture. Although these in vitro-derived microfilariae were morphologically identical to in vivo-derived microfilariae, they could be differentiated by their characteristic of binding to a panel of fluorescein-conjugated lectins. The results suggest that maturation and release of microfilariae are correlated with glycosidic alterations on the sheath surface.

Evaluation of between-sample carryover on an automated coagulation instrument: recommendations for quality control procedures.

OBJECTIVE: To assess sample probe carryover levels in a modern automated coagulation analyzer. SETTING: Washoe Medical Center Clinical Laboratory, Reno, Nevada. DESIGN: Analysis of the relative degree of prolongation of coagulation assays using a sequential series of samples following a sample with inherent or added components with the potential for prolonging or accelerating coagulation when significant sample probe carryover is present. PARTICIPANTS: Not applicable. MAIN OUTCOME MEASURE: The extent of prolongation or acceleration of APTT or PT assays. RESULTS: The first sample positions assayed subsequent to specimans with potential accelerating or prolonging coagulation activity were affected by 3.9% to 17.8%. CONCLUSION: Results suggest that a potential exists in automated sampling coagulation analyzers. A mechanism for quality control analysis of carryover should be incorporated in automated probe coagulation analyzers. A suggested "1-2-1" control sequence is discussed as a possible quality assurance tool for measuring carryover within individual assay runs.

Maternal and umbilical cord blood lead levels: an Istanbul study.

Current mean lead concentrations in umbilical cords and in maternal blood in Istanbul were 1.69 +/- 0.91 (standard deviation) microg/dl and 2.37 +/- 0.89 microg/dl, respectively. These levels were much lower than values reported in previous years. Umbilical cord blood lead levels, which correlated significantly with mothers' blood lead levels, were approximately 70% of the latter. The drastic decrease in blood lead levels likely reflects the reduction in use of tetraalkyl lead in gasoline subsequent to 1989.

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Z-score reference values for height in Turkish children aged 6 to 18 years.

OBJECTIVE: Standard deviation score or Z-score reference charts are used in some countries in preference to percentile charts and are considered as better tools in assessing children with measurements outside the accepted limits of normality. Growth data for Istanbul children have previously been reported as percentiles; hence, the aim of this study is to present these data in Z-score reference tables. Data on secular trend in height in Turkish children will also be presented. METHODS: Height and weight data based on a total of 11 664 height and 11 655 weight measurements in 1100 boys and 1020 girls between 6 and 18 years of age obtained by biannual visits to schools were analyzed. All children came from well-to-do families and were all healthy. All measurements were made by two trained technicians. The LMS method was used in the analyses. The results were expressed as Z-score values for age. RESULTS: Heights of the boys and girls in all age groups were close to the updated USA growth references and showed an upward trend from previous data on Turkish children. CONCLUSIONS: Height growth in Turkish school-age children of high socioeconomic level conforms to the updated growth data for USA children and also shows a secular trend. The data also point to the importance of updating local growth data periodically.