bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Suture Material and Technique on End-to-End Reconstruction in Tracheal Surgery: An Experimental Study in Sheep
Authors: Behrend M. , Klempnauer J.
Published: April 2003

Resection and end-to-end anastomosis of the trachea represent the preferred treatment for various benign and malignant diseases involving the trachea. Various studies have reported conflicting results with alternative techniques and suture materials for tracheal anastomosis. Our objective was to evaluate three frequently used techniques concerning stenosis rate and histological reaction in a large-animal species. Tracheal resection of 3 cm and end-to-end anastomosis were performed in 15 sheep with the use of three different techniques. In the first group, an interrupted suture with polyglactin, in the second group an interrupted suture with polydioxanone, and in the last group a continuous suture with polypropylene were used. The animals were killed 1, 2, 4, 8, and 24 weeks postoperatively. The luminal stenosis was determined by means of computerized planimetry. All three techniques appeared to be appropriate for tracheal anastomosis. The luminal stenosis developed within the first 8 weeks after surgery. A cross-sectional area of approximately 40–70% was finally achieved. Differences dependent on the suture material are less important than the technical details of the operation.
Generation of Kidney Transcriptomes Using Serial Analysis of Gene Expression
Authors: Schelling Jeffrey R. , El-Meanawy M. Ashraf , Barathan Shrinath , Dodig Tatiana , Iyengar Sudha K. , Sedor John R.
Published: April 2003

Chronic renal disease initiation and progression remain incompletely understood. Genomewide expression monitoring should clarify the mechanisms which cause progressive renal disease by determining how clusters of genes coordinately change their activity. Serial analysis of gene expression (SAGE) is a technique of expression profiling which permits simultaneous and quantitative analysis of 9- to 13-bp sequence tags that correspond to unique mRNAs. Key principles of the technique are use of PCR in a manner to minimize distortion and serial concatenation of tags which facilitates sequencing and permits identification of many expressed genes in a single cDNA molecule. Tags are extracted from many concatenated sequences, counted using software, and identified by comparison with existing gene databases. In aggregate, gene expression profiles generated from a tag library comprise a transcriptome which represents a comprehensive and quantitative profile of genes expressed at the time of analysis. These global snapshots of gene expression patterns can better define basic cell biology and provide insights into disease pathogenesis by simultaneously determining the net consequences of gene-gene and gene-environment interactions on expression of thousands of genes. Rather than applying a priori assumptions (i.e., hypothesis testing), transcriptome analysis is hypothesis generating and requires no prior knowledge of gene expression. SAGE kidney transcriptomes, from normal animals and animals with progressive kidney disease, are being produced and can be analyzed for novel pathogenetic mechanisms. The use of SAGE and other genomic and proteomic tools should result in a better understanding of kidney disease pathogenesis and in identification of new therapeutic targets.
Genes and Proteins in Renal Development
Authors: Davies Jamie A. , Fisher Carolyn E.
Published: April 2003

Metanephric kidney development begins with the formation of the metanephrogenic mesenchyme; this event depends on the prior action in the intermediate mesoderm of transcription factors such as Lim-1, Pax-2, Eya-1, and Foxc-1. Once it has formed, the mesenchyme secretes GDNF; this induces the nearby wolffian duct to produce a ureteric bud which invades the metanephrogenic mesenchyme and begins to arborize. Ureteric bud development and branching depends on the transcription factor Emx-2, the GDNF-cRet and probably the HGF/cMet, signalling systems, and the intracellular regulatory molecules formin IV and timeless. Proteins of the BMP family modulate ureteric bud branching and keep bud development in step with that of other tissue types. Proteins and glycosaminoglycans of the matrix, and their receptors, and also required. The metanephrogenic mesenchyme has a default fate of apoptosis and is dissuaded from suicide by factors secreted from the bud such as TGF-α, TIMP-2, EGF, and FGF-2. Other factors such as LIF and TGFβ2 cooperate with these to induce clumps of mesenchyme cells to differentiate into nephrons, while BMP-7 appears to lead them instead to form stroma. As nephrons form, they express critical transcription factors such as WT-1, Pax-2, and Hoxa11 and d11, condense, and secrete Wnt-4. Wnt-4 acts in an autocrine loop to stimulate its own synthesis and is required for cells to differentiate into epithelia; its action is antagonized by sFRP-1, secreted by stroma, but this antagonism is itself inhibited by sFRP-2 made by the developing nephron. This system probably acts both to limit the spread of Wnt-4’s influence and also to commit responding cells to their epithelial fate. As nephrons mature, regions of them differentiate to perform specific physiological functions, a process that requires the proteins WT-1, Lmx-1b, Notch-2, Jagged-1, and Hnf-1.
Gene Responses to Hyperglycaemia
Authors: Lappin David W.P. , Doran Peter , Godson Catherine , Brady Hugh R.
Published: April 2003

The rising tide of diabetic nephropathy (DN) is arguably the most challenging clinical problem confronting nephrologists at the beginning of the new century. Central to the development of novel diagnostic and therapeutic strategies will be the elucidation of the molecular events that drive this complex disease. In this review, we briefly discuss the major growth factors and cytokines identified as mediators of tissue injury in DN in the ‘pre-gene subtraction’ era. We then highlight the remarkable array of new molecular players already identified with the introduction of gene subtraction techniques, such as differential-display PCR, suppression-subtractive hybridization, and nucleotide micro-arrays, and discuss the likely impact of these technologies going forward. Finally, we summarize the current knowledge on the cell signalling events triggered by high glucose levels that influence gene expression in DN and that represent additional therapeutic targets in this setting.
Endothelial Gene Responses to Homocysteine: Relation to Atherosclerosis
Authors: Li Hong , Goligorsky Michael S.
Published: April 2003

Chronic renal failure is associated with a 20-fold increased risk of cardiovascular mortality, in part due to accelerated atherosclerosis. Hyperhomocysteinemia (HHCy) is common in patients with chronic renal failure. It has been established that HHCy is an independent and graded risk factor for atherosclerosis, though the mechanisms responsible for it remain obscure. Using the cardiovascular cDNA microarray approach, we screened the expression of 600 cardiovascular relevant genes in human umbilical endothelial cells and identified a number of homocysteine-modulated genes. These differentially displayed genes were classified according to the functional outcome of their encoded proteins: endothelial motility cluster, signaling cluster, and lipid metabolism cluster. The results may be relevant to understanding the mechanisms underlying the pathophysiological effects of HHCy, particularly those leading to endothelial dysfunction and the pathogenesis of atherosclerosis.
Using Proximity Measures to Describe Mother-Infant Relationships
Authors: Brown Gillian R.
Published: April 2003

What are the relative roles of mothers and infants in maintaining proximity with one another? How do the relative roles of the mother and infant change over time? What do proximity measures tell us about the mother-infant relationship? Questions such as these have been addressed using proximity indices devised by Hinde and coworkers in the 1960s. In this paper, I review how these indices are derived and discuss what they do, and do not, infer about the nature of the mother-infant relationship. An additional index is proposed which indicates whether the mother or the infant is responsible for the majority of changes in proximity.
The Relative Importance of Size of Food and Interfood Distance in Eliciting Aggression in Captive Rhesus Macaques (Macaca mulatta)
Authors: Mathy Jeffrey W. , Isbell Lynne A.
Published: April 2003

We conducted an experiment on a group of captive rhesus macaques (Macaca mulatta) in which we manipulated both food size and interfood distance independently to examine which factor was more important in causing aggressive competition. For each of 254 trials, the monkeys were offered simultaneously two apple pieces ranging in size from 1 to 40 g at interfood distances ranging from 1 to 5 m. In contrast to other studies, food size and interfood distance were not conflated in this study. Multiple regression analyses revealed that food size was a better predictor of aggression whereas interfood distance was a better predictor of the ability to monopolize foods. Growing evidence suggests that factors such as food size, quality and depletion time are more important than interfood distance in influencing aggression within groups.
Cryptorchidism: Aspects of Fertility and Neoplasms
Authors: Cortes Dina , Thorup Jørgen M. , Visfeldt Jakob
Published: April 2003

Purpose: An attempt to make a rational strategy for treatment of cryptorchidism. Materials and Methods: 1,335 cryptorchid boys with biopsy at surgery (1,638 specimens). We studied: frequency of no germ cells in biopsies from 698 patients <12 years at surgery; fertility potential of 140 patients who were now adults, and apperance of testicular neoplasia in all biopsies. Results: Lack of germ cells appeared from 18 months. The frequency increased with increasing age. It appeared in 30% (61/202) bilateral, and 18% (88/496) unilateral cases. In men who had undergone bilateral or unilateral orchiopexy, respectively, there was normal sperm count in 19% (14/75) and 83% (54/65), and infertility was suspected in 56% (42/75) and 8% (5/65) (FE, p < 0.00005, p < 0.00005), respectively. The lowest, the mean, and the highest age-matched spermatogonia count per tubule at orchiopexy was associated with sperm count (Spearman test, p < 0.0001, p < 0.005, p < 0.05). Isolated, this was demonstrated for the 75 formerly bilateral (Spearman, p < 0.0001, p < 0.0001, p < 0.0001), but not the 65 formerly unilateral cases (Spearman, p = 1.0). No germ cells at orchiopexy was associated with suspected infertility. Risk was 78–100% in bilateral (dependent on one or both testes affected), and 33% in unilateral cryptorchidism. There was one invasive germ cell tumor, six cases of carcinoma in situ testis, and one Sertoli cell tumor. Three neoplasms were diagnosed in intra-abdominal testes, four in boys with abnormal external genitalia, and two in boys with known abnormal karyotype. Risk of neoplasia was 5% (7/150) in patients with intra-abdominal testis, abnormal external genitalia or diagnosed abnormal karyotype, versus 0% (0/1,185) in patients without these characteristics (FE, p < 0.00005). Conclusion: We recommend surgery for cryptorchidism before 15–18 months of age because: (a) lack of germ cells is very rare before, and (b) lack of germ cells is associated with subsequent risk of infertility. At primary surgery for cryptorchidism, we recommend examination for testicular neoplasia in cases of intra-abdominal testis, abnormal external genitalia or known abnormal karyotype.
The Serum Concentration of Tumor Necrosis Factor Alpha Is Not an Index of Growth-Hormone- or Obesity-Induced Insulin Resistance
Authors: Pincelli A.I. , Brunani A. , Scacchi M. , Dubini A. , Borsotti R. , Tibaldi A. , Pasqualinotto L. , Maestri E. , Cavagnini F.
Published: April 2003

Backgound: The tumor necrosis factor alpha (TNF-α) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-α levels and insulin sensitivity in GHDA. Methods: We compared the serum TNF-α levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. Results: The serum TNF-α levels were not significantly different in OB patients (42.2 ± 12.81 pg/ml), in GHDA patients at baseline (71.3 ± 23.97 pg/ml), and in controls (55.3 ± 14.28 pg/ml). A slight decrease of TNF-α values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 ± 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 ± 0.30 mg/kg/min) as compared with control subjects (7.5 ± 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 ± 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 ± 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-α and M values (see text) in all patient groups. Conclusions: These data indicate that circulating concentrations of TNF-α do not reflect the degree of insulin resistance in obesity and GHDA. They, however, do not exclude that TNF-α may induce insulin resistance at tissue level.
Decreased Levels of Ionized Calcium One Year after Hemithyroidectomy: Importance of Reduced Thyroid Hormones
Authors: Lindblom Pia , Valdemarsson Stig , Lindergård Birger , Westerdahl Johan , Bergenfelz Anders
Published: April 2003

Background: Previously we have found reduced levels of total serum calcium and 1,25(OH)2D3 despite an unaltered stimulated parathyroid hormone (PTH) secretion 1 year after hemithyroidectomy. The present study was undertaken to elucidate the possible relationship between calcium homeostasis, thyroid hormones and bone resorption in a group of 45 consecutive patients subjected to hemithyroidectomy because of a solitary nodule. All patients had free T4 and T3 levels within normal range preoperatively. Methods: Thyroid hormones, bone mineral and biochemical variables known to reflect calcium homeostasis were studied. Patients were divided into three separate groups depending on their pre- and postoperative thyroid hormone status. Results: One year postoperatively, serum levels of free T4 were decreased and that of thyrotropin (TSH) increased in the entire group of patients. The concentration of ionized calcium was reduced from 1.25 ± 0.05 to 1.22 ± 0.04 (p < 0.001) despite an unaltered PTH value (2.8 ± 1.0 vs. 3.1 ± 1.5, p = 0.50). A significant reduction in C-terminal telopeptide type 1 collagen (1CTP) indicated decreased bone resorption 1 year after surgery (p < 0.05). Subgroup analysis showed that a reduction in ionized calcium was seen only among patients with a postoperative decrease in free T4. Patients with subclinical hyperthyroidism preoperatively presented the lowest postoperative levels of ionized calcium, significantly reduced levels of 1CTP and increased levels of phosphate and creatinine. Multiple linear regression analysis showed that age (p < 0.05) and postoperatively changed serum levels of TSH (p < 0.05), creatinine (p < 0.05), phosphate (p < 0.001) and FT4 (p < 0.01) were independently associated with altered levels of ionized calcium. Conclusion: We conclude that the reduction in ionized calcium 1 year after hemithyroidectomy was not due to PTH deficiency. Instead our results suggest that the reduced effects of thyroid hormones on bone and kidney function is essential.
Final Height in Children with Idiopathic Growth Hormone Deficiency Treated with Recombinant Human Growth Hormone: The Belgian Experience
Authors: Thomas M. , Massa G. , Bourguignon J.-P. , Craen M. , de Schepper J. , de Zegher F. , Dooms L. , Du Caju M. , François I. , Heinrichs C. , Malvaux P. , Rooman R. , Thiry-Counson G. , Vandeweghe M. , Maes M.
Published: April 2003

Background: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. Patients/Methods: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5–0.7 IU/kg/week (0.17–0.23 mg/kg/week) from the mean ± SD age of 11.9 ± 3.1 years during 5.1 ± 2.1 years. Results: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was –0.7 ± 1.1 SDS, being 170.4 ± 7.2 cm in boys and 158.0 ± 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 ± 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 ± 7.0 cm vs. 27.5 ± 6.6 cm (p < 0.005); girls: 9.6 ± 7.4 cm vs. 22.2 ± 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. Conclusions: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5–0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.
Discordant Growth Pattern and Ovarian Function in Monozygotic Twins with 45,X/46,XX Mosaicism
Authors: Lebl J. , Zahradníková M. , Vlasak I. , Neuhuber F.
Published: April 2003

Background: We report on phenotypically discordant female monozygotic twins with 45X/46,XX mosaicism in both lymphocytes and fibroblasts. Results: At 11.5 years, twin A was prepubertal, her height was 126.8 cm (–3.15 SD), bone age (BA) 9.7 years (TW2), FSH 47 IU/l and IGF-I 280 ng/ml (–0.89 SD), but twin B was pubertal (P2, B3), her height was 143.4 cm (–0.92 SD), BA 13.6 years (TW2), FSH 3.4 IU/l and IGF-I 380 ng/ml (–0.21 SD). One year later, twin A had grown 11.1 cm due to growth hormone therapy and had IGF-I 1,400 ng/ml (+5.91 SD), whereas the growth velocity of twin B (no therapy) was 5.9 cm, IGF-I 540 ng/ml (+0.57 SD) and she started regular menstruation at 12.1 years. Conclusion: To our knowledge, this is the first report on monozygotic twins with Turner mosaicism in both lymphocytes and fibroblasts who developed a discordant phenotype probably due to an unequal distribution of the two cell lines in distinct tissues.
Relevance of IGF-I, IGFBP-3, and IGFBP-2 Measurements during GH Treatment of GH-Deficient and Non-GH-Deficient Children and Adolescents
Authors: Ranke M.B. , Schweizer R. , Elmlinger M.W. , Weber K. , Binder G. , Schwarze C.P. , Wollmann H.A.
Published: April 2003

Background: Little information is available on the relevance of parameters representing the insulin-like growth factor (IGF) system with regard to growth hormone (GH) treatment during childhood. In adults, high IGF-I levels were found to be associated with side effects and long-term risks. Aim/Method: Our aim was to monitor the serum levels of IGF-I, IGF-binding protein (IGFBP) 3, and IGFBP-2 during long-term GH treatment of 156 patients with GH deficiency (GHD) and of 153 non-GHD patients. We determined the extent to which the IGF parameters exceed the normal ranges and identified those parameters which are predictive of 1st-year growth. Results: In prepubertal GHD children, the levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 exceeded the 95th centile of the reference values for this age group in 2.3, 0.3, and 7.9% of the cases, respectively, whereas in prepubertal non-GHD children, the same parameters exceeded the 95th reference centile in 20.1, 3.5, and 32.2%, respectively. In pubertal GHD children IGF-I, IGFBP-3, and IGF-I/IGFBP-3 levels exceeded the 95th reference centile in 11.1, 1.5, and 15.4%, respectively. In pubertal non-GHD children, these levels also exceeded the 95th centile in 26.7, 7.0, and 41.4%, respectively. In both GHD and non-GHD groups, however, some patients had IGF parameters which were below the reference values. Our analysis showed that, in both groups, in addition to maximum GH, all IGF parameters (IGF-I, IGFBP-3, IGF-I/IGFBP-3 ratio, IGFBP-2 or derivatives) significantly extend the scope of a calculated model for predicting 1st-year height velocity. Conclusion: For reasons of safety and optimization of GH therapy, it is essential to follow up IGF-I, IGFBP-3, and IGFBP-2 levels regularly during childhood.
Plasma Levels of Insulin-Like Binding Protein-2 in Prepubertal Short Children and Its Diagnostic Value in the Evaluation of Growth Hormone Deficiency
Authors: van Doorn J. , Ringeling A.M. , Rikken B. , van Buul-Offers S.C.
Published: April 2003

Aim: This study was designed to investigate whether determination of plasma insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) levels could be of benefit in the evaluation of childhood growth hormone (GH) deficiency (GHD). Method: A retrospective analysis was performed on 91 prepubertal children referred for investigation of short stature. Maximal GH levels in plasma after provocative stimuli were between 1.0 and 93.0 mU/l, 6 subjects exhibiting peak values of <5 mU/l. Initially a GH peak of 20 mU/l was used as a cutoff limit to define GHD and idiopathic short stature (ISS) patients. The results of GH provocative tests were compared to age- and gender-based standard deviation scores (SDS) of plasma IGFBP-2, IGF-I, IGFBP-3 and the molar ratios of the latter two to IGFBP-2. The respective normative range values for these parameters were determined in plasma samples from 353 healthy children (i.e. 171 girls, 182 boys). Results: Circulating IGFBP-2 levels did not correlate with height SDS, height velocity SDS or the peak GH levels after provocative stimuli. A weak negative relationship was found between IGFBP-2 and IGF-I. Plasma levels of IGFBP-2 in GHD patients were higher than those of ISS children, who had normal levels. Although at the optimal cutoff point of –0.71 SDS 91.5% of the GHD patients were identified correctly, a substantial proportion (71.9%) of the ISS subjects also had IGFBP-2 levels above this limit. The use of various combinations of IGFBP-2, IGF-I, IGFBP-3 and the derived ratios only slightly improved the diagnostic efficiency as compared to the results of the individual tests. Neither IGFBP-2 nor the IGFBP-3/IGFBP-2 and IGF-I/IGFBP-2 ratios were found to be related to the short- (1 year) or long-term (3 years) growth response to GH therapy. Conclusion: It is concluded that none of the tests investigated, either alone or in various combinations, are reliable in either predicting the peak GH level after provocative stimuli in prepubertal short children or in predicting their growth response to GH.
Plasma Oxytocin during Intense Exercise in Professional Cyclists
Authors: Chicharro José L. , Hoyos Jesús , Bandrés Fernando , Gómez Gallego Felix , Pérez Margarita , Lucía Alejandro
Published: April 2003

Aims: This study was designed to explore the plasma oxytocin (OT) response to exercise until exhaustion in trained male cyclists. Methods: Twelve professional cyclists (EXP group; age: 26 ± 2 years; VO2max: 4,804 ± 549 ml) and 10 sedentary young men (CONT group; age: 23 ± 2 years; VO2max: 3,146 ± 602 ml) performed a maximal incremental exercise test on a cycle ergometer. Evaluation was made of the oxygen uptake (VO2) and concentrations of blood lactate and plasma OT immediately before, during and immediately after the tests, respectively. Results: Significant increases (p < 0.01) related to exercise were recorded in VO2 and lactate concentration within each group, while no such changes were observed in OT levels. OT values, on the other hand, were significantly lower (p < 0.01) in EXP than in CONT throughout the tests. Conclusion: It was concluded that plasma OT shows no response to graded exercise until exhaustion in professional cyclists.
Leptin Concentrations Are Elevated in Newborn Infants of Diabetic Mothers
Authors: Tapanainen Päivi , Leinonen Erja , Ruokonen Aimo , Knip Mikael
Published: April 2003

Background: Infants of diabetic mothers have been characterized by macrosomia due to hyperinsulinism. A relation has been observed between circulating levels of leptin and the intrauterine growth pattern. Methods: We studied the leptin and insulin concentrations in the cord blood of 29 newborn infants of mothers with type 1 diabetes (iT1DM), 70 newborn infants of mothers with gestational diabetes and 105 newborn infants of nondiabetic mothers. Results: There were significant differences (p < 0.001) between the 3 groups with the highest leptin levels 24.9 µg/l (range 1.7–94.1) in infants of mothers with iT1DM and the second-highest levels 14.0 µg/l (range 2.6–74.9) in infants of mothers with gestational diabetes (iGDM), whereas the control infants had the lowest leptin levels 10.0 µg/l (range 0.10–45.9). Girls had higher leptin concentrations than boys among the iT1DM and control infants. The insulin concentrations were 18.1 mU/l (range 1.9–123.3), 6.1 mU/l (range 1.1–51.4) and 3.6 mU/l (range 0.5–21.5) in the 3 groups (p < 0.001), respectively. A significant correlation was observed between leptin and insulin concentrations in iGDM and control infants (r = 0.51; p < 0.001 and r = 0.25; p < 0.05). Both absolute and relative birth weights correlated with leptin levels in all 3 groups (r = 0.60, p = 0.01 and r = 0.51, p = 0.05 in iT1DM; r = 0.51 and 0.56, p < 0.001 in iGDM and r = 0.42 and 0.59, p < 0.001 in control infants). Conclusion: Our results confirm the relation between leptin concentrations and birth weight. They also suggest that leptin may be involved in the increased accumulation of adipose tissue characteristic of infants of diabetic mothers.
The Autosomal Dominant Trait of Obesity, Acanthosis nigricans, Hypertension, Ischemic Heart Disease and Diabetes Type 2
Authors: Kerem Nogah , Guttmann Hadassah , Hochberg Ze’ev
Published: April 2003

Objective: Among obese subjects, acanthosis nigricans in both males and females is not as uncommon as previously thought. Whereas this finding was extensively evaluated in females, mostly in the context of polycystic ovaries syndrome, little attention has been paid to obese males with acanthosis nigricans. As acanthosis seems to be a marker for insulin resistance, the present study was designed to evaluate the hypothesis that the clinical syndrome of obesity and acanthosis would take a different clinical course than that of simple obesity. Methods: To characterize the course of acanthosis nigricans and obesity in males, we examined 22 children and adolescents with this complex, together with their parents and grandparents and found them to follow a detrimental sequence of the metabolic syndrome. We compared the findings to 13 age-matched males with obesity but no clinical apparent acanthosis nigricans. We analyzed the clinical course, fat distribution, glucose, insulin and C-peptide and lipoproteins. Results: Onset of obesity in the metabolic syndrome group was at a mean age of 6.4 years, as compared to 2.3 years in the controls. The metabolic syndrome patients had a truncal (android) distribution of fat and their fasting blood glucose was significantly higher. HDL/total cholesterol was lower. Examination of the pedigrees suggested autosomal dominant inheritance of the obesity and acanthosis nigricans complex, extending to hypertension and ischemic heart disease in the parents’ generation, and further extending to include diabetes type 2 in the grandparents’ generation. Conclusions: This metabolic syndrome is inherited as an autosomal dominant trait, with onset of truncal obesity at age 6–7 years, acanthosis nigricans during childhood or adolescence, extending to hypertension and ischemic heart disease during young adulthood, and further extending to include diabetes type 2 in late adulthood. It is recommended that such children should be followed up as an ‘at-risk’ group, and would probably benefit from intensive weight reduction, which may prevent the later manifestations of the syndrome.
Loss of Renal Phosphate Wasting in a Child with Autosomal Dominant Hypophosphatemic Rickets Caused by a FGF23 Mutation
Authors: Kruse Klaus , Woelfel Dieter , Strom Tim M.
Published: April 2003

A girl with autosomal dominant hypophosphatemic rickets, presented with clinical, radiological and laboratory signs of rickets at the age of 11 months. She showed a good response to the treatment with low doses of oral phosphate and calcitriol. Surprisingly, she lost her renal phosphate wasting at the age of 8 years, indicating that the disturbed phosphate metabolism can be compensated by hormonal or other factors.
Detection of HGV RNA in Digestive Organs
Authors: Shimizu Toshihiro , Moriyama Mitsuhiko , Arakawa Yasuyuki
Published: April 2003

The organ where the GB virus (GBV)-C/hepatitis G virus (HGV) localizes and proliferates is not known. We examined the digestive organs for HGV RNA to determine the localization of the HGV. Two cases of patients with serum-positive HGV RNA were investigated. We embedded surgically excised materials and digestive secretion materials from cases 1 and 2 in paraffin blocks. The tissue specimens investigated included lymph nodes No. 201 and 202, ascending colon (nontumor and tumor area), ileocecum, appendix, liver (nontumor and tumor area) and gall bladder. We made cDNA after extraction of total RNA from thin tissue sections and detected HGV RNA with a reverse transcription polymerase chain reaction method. No HGV RNA was detected in liver, colon and gall bladder tissues. HGV RNA was only detected in the appendix tissue. Comparison of nucleotide sequences of PCR products from serum and appendix was almost the same. Homology between US type (PNF2161) and the serum and appendix PCR products was 92.6 and 93.6%, respectively. These results suggest that HGV proliferates in the appendix and is carried by the portal blood flow to the liver, and may cause a hepatitis reaction in the liver.
Studies of Hepatitis C Virus in Chimpanzees and Their Importance for Vaccine Development
Authors: Bukh Jens , Forns Xavier , Emerson Suzanne U. , Purcell Robert H.
Published: April 2003

Persistent infection with hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. Therefore, the development of vaccines to prevent HCV infection, or at least to prevent progression to chronicity, is a major goal. Potential HCV vaccine candidates include recombinant proteins, recombinant viruses, DNA constructs, synthetic peptides and virus-like particles. Various vaccine candidates have been shown to generate humoral and cellular immune responses in animals, primarily in mice. However, the efficacy of most vaccine candidates in protecting against HCV has not been tested because the chimpanzee, the only animal other than humans that is susceptible to HCV, is not readily available, requires special facilities, and is very expensive. The course of infection in chimpanzees is similar in its diversity to that in humans and detailed studies in this model are beginning to define the immune responses that can terminate HCV infection. Of relevance for vaccine evaluation was the titration in chimpanzees of different HCV variants to provide well-characterized challenge pools. In addition, monoclonal virus pools generated from chimpanzees infected with cloned viruses make it possible now to examine immunity to HCV without the confounding factor of antigenic diversity of the challenge virus (quasispecies). The vaccine trials performed in chimpanzees to date all have tested the efficacy of immunizations with various forms of the envelope proteins of HCV.
Dendritic Cells and Chronic Hepatitis Virus Carriers
Authors: Akbar Sk. Md. Fazle , Horiike Norio , Onji Morikazu , Hino Okio
Published: April 2003

Many individuals infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) are unable to clear these viruses following an acute infection and become chronically infected. There are more than 400 million HBV and HCV carriers in the world and a considerable number of these patients would eventually develop more severe complications like liver cirrhosis and hepatocellular carcinoma. It is not clearly known how an individual develops a chronic hepatitis virus carrier state; however, a defective immune response of the host is thought to play a critical role in the underlying pathogenetic mechanism. On the other hand, dendritic cells (DCs), the most potent antigen-presenting cells, are widely distributed in both lymphoid and nonlymphoid tissues. Recognition of the microbes or microbial antigens by DCs is one of critical events for the initiation of an immune response. DCs also play a cardinal role during the progression and termination of an immune response. The aim of this overview is to provide information regarding the role of DCs in the pathogenesis of chronic hepatitis due to HBV and HCV in humans and in animal models of HBV and HCV carrier states. First, we summarize our current understanding of the pathogenesis of hepatitis virus carrier states and also of general properties of DCs. Next, we discuss the data on the phenotypes and functions of DCs in both human and murine HBV and HCV carriers. We also discuss vaccine therapy in murine HBV carriers because activation of DCs due to vaccination-initiated HBsAg-specific immune responses in HBV transgenic mice (HBV-Tg), which in turn resulted in complete clearance of hepatitis B surface antigen and hepatitis B e antigen and decreased levels of HBV DNA in some HBV-Tg. Finally, we discuss the extracted questions and future research directions.
Effects of Cyclosporin A on Cell Fusion in a Monkey Kidney Cell Line Persistently Infected with Measles Virus
Authors: Watari E. , Shinya E. , Kurane S. , Takahashi H.
Published: April 2003

The authors studied the effects of immunosuppressive peptide cyclosporin A (CsA) on cell fusion efficiency in cells persistently infected with measles virus (448-PI-Vero cells). Treatment of 448-PI-Vero cells with 5 µM CsA enhanced the infusion. In addition, the expression of measles virus antigen on cell surface was increased by treatment with CsA. The addition of phenothiazine, an anti-calmodulin drug, enhanced the fusion of 448-PI-Vero cells in the presence of CsA, although treatment with phenothiazine alone did not affect polykaryocyte formation. The enhancement of fusion efficiency in 448-PI-Vero cells by CsA was suppressed by oligopeptide Z-D-Phe-Phe-Gly, a synthetic oligopeptide that inhibits fusion induced by measles virus. Since the cell content of major virus-specific polypeptides, such as hemagglutinin, nucleoprotein or matrix protein is the same as in untreated controls, this fusion enhancement may be related to transport and accumulation of measles virus glycoproteins.
Hepatitis C Virus and GBV-C/Hepatitis G Virus in Argentine Patients with Porphyria Cutanea Tarda
Authors: Oubiña José Raúl , Quarleri Jorge Fabián , Sawicki Mirna Alicia , Mathet Verónica Lidia , Ruiz Vanesa , Schroder Teresa , Méndez Manuel , Parera Victoria , Muramatsu Héctor , Battle Alcira , González Cappa Stella Maris , Fainboim Hugo Alberto
Published: April 2003

To investigate hepatitis C virus (HCV) and GBV-C/hepatitis G virus (HGV) genotype prevalence among HCV-infected porphyria cutanea tarda (PCT) patients, 19 HCV-infected patients with associated PCT were studied. A control group of 53 age-matched HCV-infected patients without associated PCT was selected. Eighteen of the 19 serologically positive HCV-PCT patients showed HCV RNA in serum. Genotype 1b was the most prevalent among both HCV-PCT patients (72.2%; 13/18) and age-matched HCV controls (50.9%; 27/53). Such different genotypic prevalence failed to reach statistical significance (χ2 with Yates’ correction, p = 0.19). The single HCV-PCT patient without detectable HCV RNA was also infected with genogroup 3 GBV-C/HGV. This GBV-C/HGV RNA prevalence (5.3%) among HCV-PCT patients is not statistically different from that observed among Argentine blood donors (5.5%; 11/200). To our knowledge, these results show for the first time the molecular epidemiology of both HCV and GBV-C/HGV associated to PCT in America.
Roles of TT Virus Infection in Various Types of Chronic Hepatitis
Authors: Ikeuchi Tetsu , Yokosuka Osamu , Kanda Tatsuo , Imazeki Fumio , Seta Toshikatsu , Saisho Hiromitsu
Published: April 2003

An unenveloped single-stranded virus, which might be a causative agent for posttransfusion non-A–G hepatitis, was recently found and named ‘TT virus’ (TTV). There is still controversy over the role of TTV in chronic hepatitis. Therefore, we have examined the prevalence of TTV in various types of chronic hepatitis in Japan. TTV DNA was detected in 11 of 40 patients (27.5%) with non-B, non-C chronic hepatitis, 13 of 46 patients (28.3%) with type B chronic hepatitis, 21 of 55 patients (38.2%) with type C chronic hepatitis, and 41 of 131 subjects (31.3%) with normal liver function tests. The positivity rate for TTV DNA tended to increase with age. The detection rate did not differ statistically between non-B, non-C chronic hepatitis and type B or type C chronic hepatitis, or normal subjects. The distribution of TTV genotypes was not significantly different among them. Clinical characteristics of the chronic illness were similar for patients with or without TTV in all hepatitis groups. The etiologic role of TTV in chronic hepatitis is not confirmed from the statistical and clinical standpoint.
Role of Interleukin-18 in Peripheral Blood Mononuclear Cells Infected with Human Herpes Virus Type 6
Authors: Arena A. , Iannello D. , Gazzara D. , Speranza A. , Bonina L. , Mastroeni P.
Published: April 2003

Objective: Interleukin 18 (IL-18) production represents a critical step in the polarization of the Th1 immune response. Human herpes virus type 6 (HHV-6) possesses a peculiar tropism for immunocompetent cells. To understand the relationships among immunocompetent cells, HHV-6 and cytokines, the role of IL-18 during infection of peripheral blood mononuclear cells (PBMC) with HHV-6 was evaluated. Methods: PBMC were obtained from healthy HHV-6-seronegative donors, after centrifugation of heparinized venous blood over a Ficoll-Hypaque gradient. Supernatants from PBMC were analyzed for the presence of cytokines. To study the effects of exogenous recombinant human (rh) IL-18 on HHV-6 replication, the number of cells expressing viral antigens and the amount of extracellular virus were analysed. Results: No basal production of IL-18 was found in supernatants of unstimulated PBMC. Appreciable amounts of the cytokine were produced by lipopolysaccharide (LPS)-stimulated PBMC. HHV-6 infection of LPS-treated PBMC downregulated IL-18 production. It was found that the addition of rhIL-18 to HHV-6-infected PBMC downregulated the percentage of antigen-positive cells and the release of extracellular virus. Conclusion: Impairment of IL-18 release, which is involved in the induction of antiviral cytokines, such as interferon-γ, could represent a strategy of the virus to evade the immune response of the host.
Risk Factors and Seroprevalence of Hepatitis B Virus, Hepatitis C Virus, and Human Immunodeficiency Virus Infection in Uzbekistan
Authors: Ruzibakiev Ruslan , Kato Hideaki , Ueda Ryuzo , Yuldasheva Nodira , Hegay Tatyana , Avazova Dildora , Kurbanov Fuat , Zalalieva Mariam , Tuichiev Lazis , Achundjanov Bakhodir , Mizokami Masashi
Published: April 2003

Objectives: The aim of this study was to elucidate the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection in Uzbekistan and to explore whether there is a correlation between those blood-borne agents and socioeconomic risk factors. Methods: One thousand nine hundred and eighteen subjects were studied. The subjects were divided into a low-risk group, a high-risk group and a patient group. Sera were tested for HBV surface antigen (HBsAg), anti-HCV, and anti-HIV. Results: The seroprevalence of HBsAg, anti-HCV, and anti-HIV in the general population was 13.3, 13.1 and 0%, respectively. The anti-HCV infection rate was significantly higher in intravenous drug users (62.7%) than in prostitutes (9.2%), homosexuals (11.1%), and medical laboratory employees (12.5%) (p < 0.01). In the low-risk group, positivity for anti-HCV increased with age from 2.2% in the 15- to 20-year-olds up to the highest rate of 17.6% in the 31- to 40-year-olds; the positivity then decreased to 0% in the group over 60 years of age. In the high-risk group, the positivity for anti-HCV in the age groups under 40 years was approximately 30% and significantly higher than in the low-risk group (p < 0.01). Risk factors for transmission of HCV were medical treatment in the low-risk group, drug abuse in the high-risk group, and both in the patient group. Conclusions: This study demonstrates that the seroprevalence of HBV and HCV infection is high, whereas HIV infection is yet uncommon in Uzbekistan.
Prevalence and Genetic Heterogeneity of the Reverse Transcriptase T69S-S-X Insertion in Pretreated HIV-Infected Patients
Authors: Briones Carlos , Mas Antonio , Pérez-Olmeda Mayte , Altisent Carmen , Domingo Esteban , Soriano Vincent
Published: April 2003

The emergence of resistance to antiretroviral drugs represents one of the main reasons for treatment failure in HIV-infected persons. Resistance to multiple nucleoside analogues may result from rearrangements in the HIV pol gene, in particular one insertion of two amino acids at position 69. Herein, we examined the prevalence of this resistant genotype and its genetic heterogeneity in a group of 475 healthy pretreated HIV-positive subjects in Spain. Only 4 (0.8%) carried the codon 69 insertion. It was always found coupled to the T69S mutation. The extra amino acids were S-S in 2 subjects and S-G in the other 2. The presence of the insert was seen only in subjects previously exposed to AZT monotherapy for at least 6 months.
Characteristics and Evolution of Extraintestinal Manifestations Associated with Ulcerative Colitis after Proctocolectomy
Authors: Goudet P. , Dozois R.R. , Kelly K.A. , Ilstrup D.M. , Phillips S.F.
Published: April 2003

Aims: Describe the characteristics of extraintestinal manifestations complicating ulcerative colitis present preoperatively and determine their evolution after surgery. Methods: Between 1976 and 1986, 281 patients with ulcerative colitis exhibiting one or more extraintestinal manifestations (EIM) before either IPAA (n = 147), Brooke ileostomy (n = 71), Kock pouch (n = 48) or ileorectostomy (n = 15) were assessed retrospectively. The clinical evolution of each manifestation was classified as having disappeared, improved, remained unchanged or aggravated postoperatively. An efficacy index was designed to assess the ratio of the number of cases cured or improved over the number of cases unchanged or aggravated. The relationship between EIM and gender, age, duration of disease and the type of surgery was also ascertained. Results: 433 EIM were observed in 281 patients. The most common were arthralgias of the large joints (n = 146), of the sacroiliac joint (n = 59) and the small joints (n = 51). In comparison to patients without EIM having received the same operation during the same period of time, EIM were seen more often in women, younger patients, than those with longer duration of disease and the ileoanal anastomosis group. 60% had only one EIM at a time. Based on the efficacy index, thromboembolic accidents and erythema nodosum were the most commonly cured or improved. Ocular manifestations and primary sclerosing cholangitis were unaffected. The other EIM responded favorably but variably with improvement in two thirds of patients. The presence of a rectal remnant (IRA) or ileal reservoir did not affect the evolution of the EIM. Conclusions: Thromboembolic complications which are life-threatening, erythema nodosum and arthralgia of the small and large joints which impair quality of life, benefited the most from proctocolectomy. Those conditions may be considered preoperatively when making the decision for surgery.
Stability in Incidence of Acute Appendicitis
Authors: Körner Hartwig , Söreide Jon Arne , Pedersen Erik J. , Bru Tore , Söndenaa Karl , Vatten Lars
Published: April 2003

Background/Aim of the Study: During the past 50 years, a decrease in incidence of appendicitis has been reported. The various studies were retrospective and based on different data sources. In the present study, we analyze prospectively the incidence of acute appendicitis during a 10-year period in a well defined population of 265,000. Methods: Prospective registration of all operations performed in patients with suspected acute appendicitis in the catchment area of a single institution. The diagnosis of acute appendicitis was based on histology in all cases. The annual incidence of acute appendicitis was calculated with regard to nonperforated and perforated acute appendicitis. Main Results: Between 1989 and 1998, 2,861 patients underwent surgery for suspected acute appendicitis. In 2,232 (78%) patients, acute appendicitis was confirmed histologically. Mean annual incidence was 84/100,000 (95% confidence interval 80 to 88/100,000). Crude incidence remained stable during the study period, with the exception of a significant increase in 1991 followed by a significant decrease the next year. Nonperforated acute appendicitis showed a different incidence pattern as compared to perforated acute appendicitis. Conclusion: In our prospective study, the incidence of acute appendicitis remained stable in our well-defined study population during the study period of 10 years. This is in contrast to the majority of studies during the last decades.
A Simple Technique for Laparoscopic Vertical Banded Gastroplasty – The JOVO Procedure
Authors: Joffe Jacobo , Voitk Andrus
Published: April 2003

A simple technique for laparoscopic vertical banded gastroplasty is described. With the surgeon to the patient’s left, four trochars are placed as cephalad as possible. Short gastric vessels are divided and the posterior wall of the stomach mobilized. The ETS-Flex with Articulating Head (Ethicon Endosurgery Inc.) is used to divide the stomach close to a 42-french bougie against the lesser curvature. An additional stapler bite abuts directly against a 28-french bougie to obtain correct stoma size. A ribbon of Prolene mesh is pulled through a tunnel behind the stomach at the apex of the divided gastroplasty and sutured around the distal end of the gastroplasty. To date we have used this method successfully in 5 patients with 1–11 months of follow-up. Although we lack a sufficient number of patients or follow-up for definitive conclusions, we believe this technique will produce good results, as it reproduces exactly that used successfully in open surgery and our early results parallel those following open surgery.