bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrathin Bronchoscopy as an Adjunct to Standard Bronchoscopy in the Diagnosis of Peripheral Lung Lesions
Authors: Rooney Cyril P. , Wolf Kurt , McLennan Geoffrey
Published: April 2003

Background: The role of the standard bronchoscope as a method of diagnosis of peripheral lung lesions is limited. Objectives: To evaluate the role of the ultrathin bronchoscope as an adjunct to standard bronchoscopy in the diagnosis of peripheral lung lesions. Methods: Seventeen consecutive patients with a peripheral lung lesion on chest radiography or chest CT. All patients underwent a bronchoscopic examination with a standard size bronchoscope, and if there was no evidence of endobronchial lesion, these patients were subsequently examined with an Olympus 3C40 ultrathin bronchoscope (external diameter of 3.6 mm). Under fluoroscopic guidance, cytological brushing samples were taken with the ultrathin bronchoscope followed by a reexamination with the standard bronchoscope which followed the same ‘pathway’ to the lesion established by the 3C40 ultrathin bronchoscope. Transbronchial biopsies (TBB) and cytological samples were taken with the standard bronchoscope. Results: The size of the lesions ranged from 1.5 to 7.0 cm. A positive bronchoscopic diagnosis by TBB was obtained in 11 out of 17 patients (64.7%) and a diagnosis of atypical cells suspicious for malignancy noted in a further 3 patients. For lesions less than 3 cm in size, a positive diagnosis by TBB was achieved in 7 out of 10 of these cases. The lesion was directly visualized with the ultrathin bronchoscope in 4 cases. Conclusions: Ultrathin bronchoscopy appears to be a useful adjunct to standard bronchoscopy by providing an accurate pathway to the lesion in question. However, further studies with larger patient groups are warranted.
Effects of Almitrine on Diaphragm Contractile Properties in Young and Old Rats
Authors: McGuire M. , Cantillon D. , Bradford A.
Published: April 2003

Background: Diaphragm muscle force and fatigue are key factors in the development of respiratory failure. Almitrine is used to improve ventilatory drive and ventilation-perfusion matching in respiratory failure. Recently, it has also been shown to improve diaphragm muscle force and endurance in young rats, but it is not known if this effect persists with ageing. Objectives: To determine the effects of almitrine on diaphragm contractile properties in young and old rats. Methods: In young and old rats, isometric contractile properties were measured in strips of isolated diaphragm muscle in physiological saline solution at 30°C with or without almitrine. Results: In young animals, almitrine increased twitch tension, reduced half-relaxation time and increased endurance, but had no effect on tetanic tension, contraction time or tension-frequency relationship. Ageing had no effect on endurance, but did reduce twitch and tetanic tension and contraction and half-relaxation time. Almitrine had no effect on contractile tension and kinetics, tension-frequency relationship or on endurance in the old animals. Conclusions: Ageing negates the beneficial effects of almitrine on diaphragm muscle force and endurance.
Flow Cytometric Assessment of Clearance and Relapse Characteristics in Psoriasis vulgaris after Treatment with Weekly Clobetasol Lotion under Hydrocolloid Occlusion versus Twice-Daily Clobetasol Ointment
Authors: Glade C.P. , van der Vleuten C.J.M. , van Erp P.E.J. , van de Kerkhof P.C.M.
Published: April 2003

Clearance and relapse characteristics of clobetasol lotion under hydrocolloid occlusion once weekly versus clobetasol ointment twice daily were assessed in a comparative flow cytometric study. Quantitative analysis of markers for epidermal proliferation, differentiation and inflammation was performed on epidermal single cell suspensions prepared from 3-mm punch biopsies taken from 15 patients with psoriasis vulgaris before therapy, at clearance and 6 weeks after clearance. After treatment both therapy regimens resulted in substantial changes of all flow cytometric parameters, but clearance was induced earlier in the corticosteroid under hydrocolloid occlusion-treated group. With respect to the relapse phase no difference was observed between both treatments. Although it is remotely possible that the outcome in the treatment of more extensive psoriatic lesions might be different, the present study suggests that the robust clinical efficacy of the treatment with a topical corticosteroid under hydrocolloid occlusion is not associated with a rebound phenomenon.
Comparison of Analgesic and Anti-Inflammatory Activity of Meloxicam Gel with Diclofenac and Piroxicam Gels in Animal Models: Pharmacokinetic Parameters after Topical Application
Authors: Gupta S.K. , Bansal P. , Bhardwaj R.K. , Jaiswal J. , Velpandian T.
Published: April 2003

Meloxicam, a non-steroidal anti-inflammatory drug, is a preferential inhibitor of cyclooxygenase-2 and has demonstrated potent analgesic and anti-inflammatory activity after oral administration. The present work was carried out to elucidate the anti-inflammatory and analgesic activity of a newer topical gel formulation of meloxicam (1% w/w gel) and compare it with 0.5% w/w piroxicam and 1% w/w diclofenac gels in experimental animal models. The study was also extended to determine the pharmacokinetic profile of a newer formulation of meloxicam gel after topical application on depilated skin of rats. The anti-inflammatory activities of meloxicam, piroxicam and diclofenac gels were compared using carrageenan-induced acute paw oedema and complete Freund’s adjuvant-induced chronic paw oedema in rats. Meloxicam gel showed increased protection against inflammation as compared to piroxicam and diclofenac gels. Acetic acid-induced writhing and formalin-induced phase I and phase II pain models were used to compare their analgesic activity. Meloxicam gel showed significant protection in formalin-induced phase II pain whereas its analgesic activity was less as compared to diclofenac and piroxicam gels in writhing test and formalin-induced phase I pain. The pharmacokinetic studies showed peak plasma drug concentration (Cmax) of 48.48 ± 6.57 µg/ml at 2 h (Tmax) after topical application of 500 mg of meloxicam gel formulation. The area under the curve as calculated from 0 to 6 h was found to be 114.18 ± 4.23 and 194.13 ± 3.78 µg·h/ml for 0 to ∝. The results indicate that topical preparation of meloxicam could be an effective alternative to diclofenac and piroxicam gels in inflammatory conditions and its associated pain with the possibility of less systemic side-effects.
Anti-Inflammatory Efficacy of Topical Preparations with 10% Hamamelis Distillate in a UV Erythema Test
Authors: Hughes-Formella B.J. , Filbry A. , Gassmueller J. , Rippke F.
Published: April 2003

In 40 volunteers the efficacy of three lotions with 10% hamamelis distillates from different suppliers, two vehicles, dimethindene maleate 0.1% gel, hydrocortisone 1% cream and hydrocortisone 0.25% lotion were investigated in a modified UV erythema test with three UV dosages (1.2, 1.4 and 1.7 MED). The test preparations were applied occlusively over a 48-hour period following irradiation. Chromametric measurement of redness and visual assessment were performed 24, 48 and 72 h after induction of erythema. The hydrocortisone formulations were most effective in erythema suppression. An anti- inflammatory effect was noted for all three hamamelis lotions as well as for the vehicles. A significantly greater suppression of erythema than seen with the vehicles was noted for one of the hamamelis lotions at 1.4 MED. The efficacy of the antihistamine dimethindene maleate did not surpass the hamamelis lotions or the vehicles. Even though the differences between the hamamelis lotions were slight, it was possible to make an objective selection of the best hamamelis distillate for aftersun purposes.
Comparative Development of SIRC Rabbit Corneal Cells Grown on Polycarbonate- and Polyester-Based Filters
Authors: Hutak Christine M. , Kavanagh Marie E. , Reddy Indra K.
Published: April 2003

Statens Seruminstitut Rabbit Cornea (SIRC) cells were grown on sterile polycarbonate- and polyester-based filter inserts to evaluate the feasibility of substituting the polyester-based filter inserts for use in a previously developed permeability model. The two filter types were compared for differences in cellular growth rate and morphological changes following days 3, 7 and 10 in culture. There were no significant differences in the number of cell layers formed on any day examined. The numbers of cell layers formed with the polycarbonate-based filter inserts were 1.75 ± 0.09, 2.53 ± 0.14 and 2.93 ± 0.16, for days 3, 7 and 10, respectively. The numbers of cell layers formed with the polyester-based filter inserts were 1.79 ± 0.07, 2.23 ± 0.11 and 2.90 ± 0.13, for days 3, 7 and 10, respectively. The SIRC cells had a similar comparative morphology on each of the above days. Active cell growth was seen on each day with signs of maturation evident by day 7 in culture. The polyester-based filter inserts can be substituted in the previously established permeability assay without alteration of morphology or rate of growth, thus allowing confirmation of cell confluency prior to use in the permeability assay. It will also allow for photographic documentation of cell injury prior to recovery studies, without necessitating the preparation of extra samples for fixation at the time of initial injury. Future studies will be required to determine if there will be any alteration in the rate of permeability with a previously tested standard, before adoption of the new filter.
Effects of Pravastatin on Superoxide and Fibronectin Production of Mesangial Cells Induced by Low-Density Lipoprotein
Authors: Chen Hung-Chun , Guh Jinn-Yuh , Shin Shyi-Jang , Tomino Yasuhiko , Lai Yung-Hsiung
Published: April 2003

Pravastatin is a potent inhibitor of HMG-CoA reductase and is effective in lowering serum lipid levels. Recent studies have shown that pravastatin also reduces the oxidative modification of low-density lipoprotein (LDL). To determine whether pravastatin has a direct effect on glomerular mesangial cells, we have measured the effects of pravastatin on the production of superoxide and fibronectin of glomerular mesangial cells stimulated by LDL. Our results demonstrated that the superoxide production of mesangial cells increased after LDL stimulation (100 µg/ml for 4 h) and that the superoxide production was significantly suppressed by either superoxide dismutase (SOD; 500 U/ml for 36 h; p < 0.01) or pravastatin (80 µM for 36 h; p < 0.05). The production of fibronectin was also increased after LDL stimulation which was also significantly suppressed by either SOD (p < 0.01) or pravastatin (p < 0.01). SOD or pravastatin alone had no effect on the unstimulated cells. Our results indicate that pravastatin may have a direct effect as an antioxidant and suppresses the fibronectin synthesis of glomerular mesangial cells independent of its hypolipidemic effect.
Nephron Endowment and Renal Filtration Surface Area in Young Spontaneously Hypertensive Rats
Authors: Black M. Jane , Wang Yao , Bertram John F.
Published: April 2003

Background/Aims: A reduction in nephron endowment leading to reduced renal filtration surface area has been implicated in the development of hypertension. The aim of this study was to compare glomerular (and thereby nephron) number and renal filtration surface area in young Wistar-Kyoto rats (WKY) with young spontaneously hypertensive rats (SHR), prior to the development of hypertension in this model. Methods: Using unbiased stereological methods the number and size of glomeruli, as well as total renal filtration surface area were determined in perfusion-fixed kidneys of 4-week-old WKY and SHR. Results: At 4 weeks of age, in weight-matched animals, there was no significant difference in the number of glomeruli in the kidneys of SHR compared to WKY (28,620 ± 1,643 and 25,670 ± 1,263 glomeruli/kidney, respectively). Similarly, there was no difference in mean glomerular volume (SHR: 4.70 ± 0.31 × 10–4 mm3; WKY: 4.28 ± 0.20 × 10–4 mm3). Surprisingly, total renal filtration surface area was significantly greater in SHR than WKY (3,867 ± 116 and 3,176 ± 83 mm2, respectively). Conclusion: The renal abnormality underlying the development of hypertension in the SHR is not due to inborn deficits in nephron endowment and/or filtration surface area.
Withdrawal from Methadone Maintenance Treatment
Authors: Hiltunen Arto J. , Eklund Calle
Published: April 2003

Although factors associated with successful termination of methadone maintenance treatment (MMT) have been well studied, the question of why certain methadone patients try to taper off methadone while others do not is still unanswered. Those patients who wish to continue MMT should of course be allowed to stay in treatment. However, even if only a small portion of the MMT patients wish to quit maintenance treatment, they should be offered all possible support by the treatment staff to maximize the possibility of a successful outcome. In the present study, we compared two groups of well-functioning MMT patients with respect to background factors, methadone-related factors, drug-related factors and psychological characteristics: one group consisted of patients who were trying to terminate their MMT (group 1) and the other group consisted of patients who were not trying (group 2). Each of the groups contained 25 well-rehabilitated subjects matched by age, gender and the number of years in MMT. The results show that the patients who were not trying to terminate MMT (in comparison to group 1) were not influenced by others to try to quit methadone, had a long history of opiate use as well as mixed drug use prior to MMT, had a higher methadone dose and reported a lower degree of anticipated abstinence symptoms. According to the statements of the subjects in group 2, the most important reason for not quitting treatment was the belief that they needed the methadone. The fact that they knew others who had failed to quit MMT and low confidence in succeeding were other common answers. Further, our results suggest that patients who were satisfied with their overall drug situation were less inclined to make a withdrawal attempt.
Negative Effect of Transforming Growth Factor-Beta-1 on Intestinal Anastomotic Tissue Regeneration
Authors: Fukuda H. , Motohiro T. , Nakai K. , Yamamichi K. , Nakane Y. , Fujisawa J. , Hioki K.
Published: April 2003

To examine the involvement of transforming growth factor-β1 (TGF-β1) in intestinal anastomotic repair, we administered a TGF-β1-neutralizing antibody to rats after operation, and then examined its influence on the healing process and interaction with other peptide growth factors. Thirty male Sprague-Dawley rats were subjected to primary anastomosis after transection of the small intestine (n = 30) and treated by intraperitoneal administration of IgG (n = 15) or the TGF-β1 neutralizing antibody (n = 15). Treatment with the antibody against TGF-β1 resulted in more definite mucosal growth and increased vascularity on day 5 after surgery. Augmented mRNA expression of epidermal growth factor and vascular endothelial growth factor, and an increased number of cells that expressed these peptides in granulation tissue were demonstrated by RT-PCR and immunohistochemical staining. Taken together it was indicated that TGF-β1 has negative effects on regeneration of the bowel wall mucosa and angiogenesis in the course of intestinal anastomotic wound healing.
Management of Hydatid Disease of the Lung
Authors: Ammari F. , Heis H.
Published: April 2003

The objective of this study is to report our experience in the management of pulmonary hydatid disease. Fourteen patients, 6 females and 8 males, ranging in age from 6 to 35 years were seen over a period of 7 years at a Princess Basma Teaching Hospital. Most of them had a single and isolated primary lung cyst. All patients were treated by the open method without resection through a posterolateral thoracotomy. Follow-up was maintained for 5 years with chest X-ray and indirect haemagglutination test performed annually. In conclusion, the lung-preserving operation without resection or capitonnage is the treatment of choice for pulmonary hydatid disease.
Protein Restriction Ameliorates Renal Tubulointerstitial Nephritis and Reduces Renal Transforming Growth Factor-Beta Expression in Unilateral Ureteral Obstruction
Authors: Sawashima Ko , Mizuno Shinya , Mizuno-Horikawa Yoko , Kudo Tadaaki , Kurosawa Tsutomu
Published: April 2003

In contrast to the substantial evidence for attenuation of the glomerular lesions by a low-protein (LP) diet, it remains to be determined whether and how such a diet lessens the progression of tubulointerstitial lesions, which show the strongest correlation with renal function. Chronic unilateral ureteral obstruction (UUO) results in interstitial fibrosis of the affected kidney. We investigated the therapeutic effects of an LP diet on the progression of interstitial fibrosis in UUO mice. Sixty ICR mice underwent UUO or sham operation; half of these mice were fed a normal-protein (NP) and the other half a LP diet. They were sacrificed at 3, 7 and 14 days postoperatively. The degree of tubular lesion, the distribution of transforming growth factor-β (TGF-β), α-smooth muscle actin and fibronectin and the activated TGF-β1 level were determined. The LP diet significantly reduced the progression of tubular injury, depositions of fibronectin, tubulointerstitial myofibroblast formation, the interstitial expression of TGF-β-positive cells (at 14 days; NP = 6.91 ± 3.35 vs. LP = 1.67 ± 0.41; p < 0.005), and renal active TGF-β1 concentration (at 14 days; NP = 5.72 ± 2.03 vs. LP = 2.96 ± 0.72; p < 0.01). We conclude that protein restriction may aid the attenuation of progression of tubulointerstitial fibrosis through the reduction in tubulointerstitial expression of TGF-β.
P2X7 Receptors Are Expressed during Mouse Nephrogenesis and in Collecting Duct Cysts of the cpk/cpk Mouse
Authors: Hillman Katherine A. , Johnson Tanya M. , Winyard Paul J.D. , Burnstock Geoffrey , Unwin Robert J. , Woolf Adrian S.
Published: April 2003

Background: Purinergic receptors are cell-surface molecules that bind extracellular nucleotides, notably ATP. The P2X family includes seven nonselective ion channels with one member, P2X7, implicated in cytolytic pore formation and cell death. Materials and Methods: We sought P2X7 expression in mouse nephrogenesis and cpk/cpk renal cyst growth, conditions in which both proliferation and apoptosis are prominent. Results: P2X7 immunolocalized to condensed metanephric mesenchyme: both proliferation and apoptosis were detected in this compartment, assessed by proliferating cell nuclear antigen expression and propidium iodide-stained pyknotic nuclei respectively. Later in nephrogenesis, P2X7 was detected in collecting ducts, a pattern persisting to maturity. A mesenchymal to epithelial shift of P2X7 expression was also documented in ureter development. In cpk/cpk kidneys, P2X7-expressing collecting duct cysts dominated histology from two weeks until four weeks after birth, when animals die from uremia. In polycystic kidneys pyknotic nuclei were rarely identified in P2X7-expressing epithelia, but were detected between cysts, consistent with a non-apoptotic role for P2X7 in cyst enlargement. Conclusion: P2X7 is expressed during normal nephrogenesis and in a model of congenital polycystic kidney disease. Further experiments are necessary to define possible functions of P2X7 in these settings.
Regulation of Renal A1 Adenosine Receptors in vivo
Authors: Lee H. Thomas , Cuomo-Scholer Andrea , Belloni Francis L. , Thompson Carl I.
Published: April 2003

We have compared renal A1 adenosine receptor (AR) regulations in rats after chronic agonist and antagonist treatments. In one group, R-phenylisopropyladenosine (R-PIA), a selective A1 AR agonist, was infused subcutaneously for 7 days. Another group was fed theophylline, a non-selective AR antagonist, for 2 weeks. Renal cortex membrane A1 AR binding with 1,3-[3H]-dipropyl-8-cyclopentylxanthine demonstrated ∼40% reduction in the Bmax  for the R-PIA group without any changes in the Kd values. Neither the Bmax nor the Kd changed following chronic theophylline treatment. Renal cortex Giα-proteins from the R-PIA treated rats decreased by ∼30%. Renal Giα levels did not change in theophylline-treated rats. Consistent with the A1 AR desensitization, R-PIA-treated rats had significantly higher basal renin release and showed attenuated A1 AR-mediated inhibition of renin release. These data suggest that prolonged A1 AR stimulation results in downregulation of renal A1 ARs and Giα, accompanied by desensitization of A1 AR-mediated inhibitory effects on renin release. Unlike cardiac and brain A1 ARs, renal A1 receptors are not subject to up-regulation following chronic antagonist treatment.
Stem Cells in Renal Biology: Bone Marrow Transplantation for the Treatment of IgA Nephropathy
Authors: Imasawa Toshiyuki , Utsunomiya Yasunori
Published: April 2003

The pathogenesis of IgA nephropathy (IgAN) is still obscure. In this study, we investigated whether the fundamental pathogenesis of IgAN lies in bone marrow stem cells (BMCs) and whether bone marrow transplantation from normal C57BL/6j (B6) mice can attenuate glomerular lesions in a murine IgAN model (high serum level IgA ddY mouse; HIGA mouse). Mesangial deposits of IgA and C3 and glomerular sclerosis in HIGA recipients of BMCs from B6 mice (B6→HIGA) were decreased as compared with those in HIGA recipients of BMCs from HIGA mice (HIGA→HIGA). Furthermore, the serum levels of IgA and macromolecular IgA were notably lower in B6→HIGA mice than in HIGA→HIGA mice. Of note, bone marrow derived H-2b-positive cells from B6 donors were observed in the glomeruli of H-2b-negative HIGA recipients. Our data suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells and that bone marrow transplantation from normal mice may not only replace recipients’ immune cells with donors’ BMCs, but also regenerate glomerular cells in HIGA mice. This approach offers a promising strategy for the treatment of IgAN.
Renal Transcriptomes: Segmental Analysis of Differential Expression
Authors: Elalouf Jean-Marc , Aude Jean-Christophe , Billon Emmanuelle , Cheval Lydie , Doucet Alain , Virlon Bérangère
Published: April 2003

Background/Aims: Progress accomplished by complete genomes and cDNA-sequencing projects calls for methods that fully use these resources to study gene expression patterns in characterized cell populations. However, since the number of functional genes cannot be readily inferred from the genomic sequence, it is highly desirable to make use of methods enabling to study both known and unknown genes. Methods: The method of serial analysis of gene expression provides short diagnostic cDNA tags without bias towards known genes. In addition, the frequency of each tag in the library conveys quantitative information on gene expression. A microassay was set-up to perform serial analysis of gene expression in minute samples such as those obtained by microdissecting nephron segments. Results: Studies carried out in the thick ascending limb of Henle’s loop and the collecting duct of the mouse kidney provided expression data for several thousand genes. Known markers were found appropriately enriched, and several of the thick ascending limb or collecting duct specific transcripts had no database match. Conclusions: The microassay for serial analysis of gene expression makes possible large-scale quantitative measurements of mRNA levels in nephron segments. The comprehensive picture generated by analyzing both known and unknown transcripts in defined cell populations should help to discover genes with dedicated functions.
Applications for Microarrays in Renal Biology and Medicine
Authors: Böttinger Erwin P. , Ju Wenjun , Zavadil Jiri
Published: April 2003

Groundbreaking recent developments, such as the near completion of human and mouse genome sequencing efforts and the emergence of robust microarray (gene chip) technologies, enabling comprehensive analysis of transcriptomes, provide new opportunities of unprecedented scale for researchers of kidney biology and disease. Combined with advanced computational and mathematical approaches for microarray data analysis, microarray applications promise to revolutionize our understanding of molecular mechanisms of kidney development and renal pathogenesis. New knowledge in this field will facilitate new approaches for molecular diagnostics, drug discovery, and eventually ‘personalized’ renal medicine. In this review, we outline current and future research applications of microarray and computational approaches in renal biology and disease. We describe basic steps in microarray data analysis and introduce advanced computational approaches to optimize data mining of vast microarray datasets.
Congruence of Tail Use Behaviors between Male and Female Mantled Howling Monkeys (Alouatta palliata)
Authors: Wheeler Brandon , Ungar Peter
Published: April 2003

//8RDifferences between males and females in locomotor and positional behaviors have been documented for several primate species [1, 2]. In Alouatta palliata for example, females climb and use smaller substrates more than males [3–5]. Such sex differences are usually related to body size. Indeed, interspecific studies have repeatedly demonstrated relationships between body size and locomotor and positional behaviors. It is easier, for example, for a large primate to suspend beneath a branch than to balance on top of it [6, 7]. This is particularly true for primates that feed near the periphery of the crown, where branches tend to be smaller.
Importance of Early Postnatal Germ Cell Maturation for Fertility of Cryptorchid Males
Authors: Hadziselimovic F. , Herzog B.
Published: April 2003

Patients/Method: Twenty-seven adults who underwent an orchidopexy before 2 years of age have recently had their spermiograms analyzed. Results: Sixty-three percent of them had a normal sperm count; their germ cells had undergone the second stage of maturation and adult dark (Ad) spermatogonia were present at the time of surgery 20–25 years earlier. In contrast, 37% of them were infertile despite a seemingly successful orchidopexy; they had impaired second-step germ cell maturation and Ad spermatogonia were absent at orchidopexy. Conclusions: Transformation of gonocytes into Ad spermatogonia is crucial for fertility. This underscores the importance of a testicular biopsy at orchidopexy in order to identify those who could benefit from early LH-RH treatment after orchidopexy.
Abnormal Germ Cell Development in Cryptorchidism
Authors: Huff Dale S. , Fenig David M. , Canning Douglas A. , Carr Michael C. , Zderic Steven A. , Snyder III Howard M.
Published: April 2003

Background: Previous studies suggest that two fundamental, probably androgen-dependent, steps in maturation of germ cells normally occur in the prepubertal testis: the disappearance of gonocytes (the fetal stem cell pool) and the appearance of adult dark spermatogonia (the adult stem cell pool) at 2–3 months of age and the appearance of primary spermatocytes (the onset of meiosis) at 4–5 years. Previous studies of small series of cryptorchid boys suggest that both steps are defective in undescended testes and to a lesser degree in descended testes contralateral to unilaterally undescended testes. The purpose of this study is to confirm the previous findings of defective germ cell maturation in a large series of boys with unilateral undescended testes. Patients: Seven hundred and sixty-seven boys with unilateral cryptorchidism who had orchidopexy and bilateral testicular biopsies between birth and 9 years of age were studied. Materials and Methods: Total and differential germ cell counts were performed on semithin histologic sections of the biopsies. The results from the undescended and contralateral descended testes were compared using the Wilcoxon signed-rank test and the Wilcoxon-Whitney-Mann U test. Results: Gonocytes failed to disappear and adult dark spermatogonia failed to appear in undescended testes under 1 year of age indicating a defect in the first step in maturation at 2–3 months resulting in failure to establish an adequate adult stem cell pool. Primary spermatocytes failed to appear in undescended testes and appeared in only 19% of contralateral descended testes at 4–5 years of age indicating a defect in the onset of meiosis. Conclusion: Unilaterally undescended testes fail to establish an adequate adult stem cell pool which normally occurs at 2–3 months of age and fail to establish adequate meiosis which normally occurs at 4–5 years of age. Similar but less severe changes are seen in the contralateral descended testes. Defects in the two pubertal steps in germ cell maturation are associated with reduced total germ cell counts.
Fertility Potential: A Comparison of Intra-Abdominal and Intracanalicular Testes by Age Groups in Children
Authors: Wilkerson Myra L. , Bartone Francis F. , Fox Linette , Hadziselimovic Faruk
Published: April 2003

We compared a group of intra-abdominal (IA) with intracanalicular (IC) testes of the same age in order to see if there were differences in the fertility potential of the testes in these two locations. We also wished to determine at what age, if any, differences became apparent. Semithin (1 µm thick) sections of 54 IA and 103 IC testes between the ages of 3 months and 5 years were evaluated and the spermatic index (SI) calculated for each. The two groups were compared using mathematical models to describe the relationship between age and SI. Models of both IA and IC testes show a sharp decline in the SI during the first 1.8 years of life and remain near zero thereafter. The models are statistically indistinguishable, suggesting there is no detectable difference in the fertility potential of IA and IC testes up to 5 years. The SI appears to reach a critically low value in both groups between 8 and 9 months of age, suggesting that surgical intervention would be appropriate before this time.
Fertility after Bilateral Cryptorchidism
Authors: Lee Peter A. , Coughlin Michael T.
Published: April 2003

Purpose: Evaluation of the fertility of a cohort of formerly bilaterally cryptorchid men in comparison with a group of formerly unilaterally cryptorchid men, and a group of control men. Materials and Methods: Using a detailed questionnaire concerning paternity and factors related to paternity, a cohort of formerly bilateral cryptorchid men were studied and compared with men who had undergone orchiopexy for unilateral cryptorchidism, and a group of control men. All study subjects had had surgery at the Children’s Hospital of Pittsburgh, Pittsburgh, Pa., between 1955 and 1975. A subset of the full cohort underwent clinical evaluation that included a physical examination, serum hormonal determination and semen analyses. Results: Paternity rates are significantly lower among the formerly bilaterally cryptorchid men who have attempted to father a child (65.3%) as compared to the formerly unilaterally cryptorchid (89.7%; p < 0.001) and control men (93.2%; p < 0.001). Differences in the ability to father children are also apparent when semen and hormone levels are compared between the three groups. The bilateral group has significantly lower sperm density and inhibin B levels, and higher FSH and LH levels, than the unilateral and control groups. Conclusions: Men born with bilateral cryptorchidism have severely compromised fertility in adulthood. This reduction in fertility is clearly shown in comparisons of both paternity rates, and in semen and hormone analyses, between the formerly bilateral, formerly unilateral, and control groups.
13 Years’ Experience with the Combined Hormonal Therapy of Cryptorchidism
Authors: Giannopoulos Michael F. , Vlachakis Ioannis G. , Charissis Giorgos C.
Published: April 2003

Purpose: We analyze the results of the combined treatment with luteinizing hormone releasing hormone (LH-RH) and human chorionic gonadotropin (HCG) of a large series of patients with cryptorchidism. Materials and Methods: Between 1987 and 1999 and after strict differentiation between cryptorchid, retractile and gliding testes, 2,467 boys with 2,962 cryptorchid-gliding testes were treated with the combined hormonal therapy. LH-RH was administrated as a nasal spray at a dosage of 1.2 µg daily for a period of 4 weeks. HCG was injected intramuscularly, 5 times at 2-day intervals at a dosage adjusted according to the age. Results: In the prospective study 2,476 boys with 2,962 cryptorchid testes were hormonally treated. Of the 2,962 evaluated cases 1,200 (40.52%) have been treated surgically after the hormone therapy. In 1,762 cases, 59.48% of cryptorchid testes were in the scrotum after combined hormone treatment. Conclusions: Treatment with LH-RH and HCG induced the descent of the testes to a normal scrotal position of boys with cryptorchidism in 59.48% of the evaluated cases. The combined treatment was effective for inducing descent of cryptorchid and gliding testes. According to the evaluated intraoperative findings, the failure of the combined therapy in 40.52% of the cases is due to the fact that the free descent is limited by local factors such as anatomical alterations of the inguinal canal, epididymal abnormalities or ectopic distal attachment of the lig. testis.
Erythropoietin May Reduce the Risk of Germ Cell Loss in Boys with Cryptorchidism
Authors: Cortes Dina , Visfeldt Jakob , Thorup Jørgen M.
Published: April 2003

Purpose: In boys with cryptorchidism older than 2 years a testicular biopsy at time of orchiopexy shows lack of germ cells in 10–40% of the cases. The number of spermatogonia per tubule is prognostic for subsequent fertility potential. A biopsy without germ cells is associated with 33–100% risk of infertility. In order to increase the number of germ cells, and thereby the fertility potential, additional hormonal therapy has been attempted before surgery. In a study, small doses of the gonadotropin-releasing hormone analogue buserelin before orchiopexy caused higher values. Others have found that hormonal treatment with human chorionic gonadotropin or gonadotropin releasing hormone analogue may harm the germ cells in cryptorchidism. The aim of the study is to demonstrate that additional hormonal therapy with erythropoietin has a positive effect on the number of germ cells. Materials and Methods: Erythropoietin (Eprex) 100 IU/kg were administered subcutaneously weekly for 3 months prior to surgery in two cryptorchid boys, 6 months old and 1 year 9 months old, respectively, with renal function impairment. Results: The number of spermatogonia per tubular cross-section in testicular biopsies was unusually high in both erythropoietin- treated cryptorchid cases compared to the control material of biopsies from the undescended testes of 698 cryptorchid patients and compared to the normal values. Conclusion: There are several hypothetic mechanisms that can explain the elevated number of spermatogonia seen in our erythropoietin treated cryptorchid patients. Erythropoietin may have a positive effect on germ cell proliferation in cryptorchidism.
Insulin Resistance in Nonobese Patients with Polycystic Ovary Syndrome
Authors: Toprak Saip , Yönem Arif , Çakır Bekir , Güler Serdar , Azal Ömer , Özata Metin , Çorakçı Ahmet
Published: April 2003

Objectives: Most patients with polycystic ovary syndrome (PCOS) are obese and known to have insulin resistance. Obesity per se is a cause of insulin resistance. This study was performed to determine whether insulin resistance occurs in patients with PCOS in the absence of obesity and acanthosis nigricans. Method: For this purpose, an euglycemic hyperinsulinemic clamp study was performed in 12 nonobese patients with PCOS and in 10 healthy control subjects matched for age and weight. Results: The mean serum testosterone and luteinizing hormone (LH) levels were significantly elevated (4.09 ± 1.32 vs. 1.18 ± 0.53 pg/ml, p < 0.001, and 11.63 ± 5.37 vs. 4.98 ± 2.73 mIU/ml, p < 0.001, respectively), and the serum sex hormone binding globulin level was significantly reduced (40.96 ± 14.94 vs. 73.98 ± 30.40 nmol/l, p < 0.001) in patients with PCOS as compared with the values in control subjects. The mean serum insulin level was also elevated in patients with PCOS as compared with control subjects (32.33 ± 4.98 vs. 19.56 ± 2.21 µU/ml, p < 0.05). The insulin sensitivity was lower in patients with PCOS as compared with the control subjects (200 ± 27.8 vs. 427.8 ± 88.9 µmol kg–1min–1, p < 0.001). In patients with PCOS, the serum levels of free testosterone (r = –0.89, p < 0.001) and LH were inversely correlated with the insulin sensitivity (r = –0.63, p < 0.05). Serum follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate levels were similar in both groups. Conclusions: These results indicate that a significant degree of insulin resistance exists in nonobese patients with PCOS and that this insulin resistance is significantly related to serum LH and free testosterone levels. Thus, measures to decrease insulin resistance may have to be considered earlier to decrease the potential risks of developing diabetes mellitus and coronary artery disease at later ages of life in these patients.
No Influence of Prednisolone on IGFBP-3 Proteolysis in Healthy Young Men
Authors: Dall Rolf , Wolthers Troels , Flyvbjerg Allan , Grøfte Thorbjørn , Sandahl Christiansen Jens , Jørgensen Jens Otto
Published: April 2003

Aims: The impact of growth hormone (GH) and prednisolone on the GH/insulin-like growth factor (IGF) axis with special emphasis on IGF binding protein-3 (IGFBP-3) proteolysis was studied in 8 healthy adults in a double-blind cross-over study with four periods: (1) placebo; (2) s.c. GH 0.1 IU/kg/day; (3) oral prednisolone 50 mg/day, and (4) co-administration of GH and prednisolone. Methods: Each treatment period lasted for 4 days followed by a washout period of 10 days. We measured IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 by immunoassays, IGFBP-3 by Western ligand blotting (WLB) and finally in vitro IGFBP-3 proteolysis by a 125I-IGFBP-3 degradation assay. Results: IGF-I levels increased by 99% during GH administration and 67% during co-administration of GH and prednisolone (p < 0.0005), whereas no significant change was seen during prednisolone alone. IGFBP-1 levels decreased 55% during the prednisolone period (p < 0.002), but the between period changes were not significant (p < 0.1). IGFBP-2 decreased 33% during co-administration of GH and prednisolone (p < 0.002). IGFBP-3 increased 12% during GH and 7% during co-administration of GH and prednisolone (p < 0.003 and p < 0.03 compared to placebo, respectively), whereas prednisolone alone induced no significant changes. IGFBP-3 measured by WLB did not change significantly, neither did IGFBP-3 proteolysis. Conclusions: Prednisolone administration induces only minimal changes in circulating components of the IGF axis and is not accompanied by alterations in IGFBP-3 proteolysis. This indicates that the metabolic effects of glucocorticoids do not depend on serum IGF-I.
Clinical and Endocrine Characteristics in Atypical and Classical Growth Hormone Insensitivity Syndrome
Authors: Burren C.P. , Woods K.A. , Rose S.J. , Tauber M. , Price D.A. , Heinrich U. , Gilli G. , Razzaghy-Azar M. , Al-Ashwal A. , Crock P.A. , Rochiccioli P. , Yordam N. , Ranke M.B. , Chatelain P.G. , Preece M.A. , Rosenfeld R.G. , Savage M.O.
Published: April 2003

Objective: Classical growth hormone insensitivity syndrome (GHIS) comprises a dysmorphic phenotype, extreme short stature (height SDS < 3), normal GH and low IGF-I and IGFBP-3. Wide clinical variation is recognised with classical and atypical forms. We aimed to delineate features of the milder ‘atypical’ GHIS phenotype, and to determine whether this correlates with milder auxological and biochemical features. Methods: Fifty-nine patients from a European series of 82 patients with GHIS, with strict diagnostic criteria of GHIS, were studied and assigned to classical or atypical GHIS groups according to facial phenotype, i.e. ‘classical’ required 2 of 3 recognized GHIS features (frontal bossing, mid-facial hypoplasia and depressed nasal bridge), ‘atypical’ required 0 or 1 of these facial features. Classical and atypical GHIS groups were compared in terms of (1) phenotypic features, including high-pitched voice, sparse hair, blue sclera, hypoglycaemia, microphallus, (2) birth length, height SDS, and (3) basal IGF-I, IGF-II, IGFBP-1, IGFBP-3, GHBP and increase in IGF-I on IGF-I generation testing. Results: Fifty patients [24 males, 26 females, aged 8.6 ± 4.6 years (mean ± SD)] had ‘classical GHIS’, 9 patients (7 males, 2 females, aged 7.8 ± 4.1 years) had ‘atypical GHIS’, 7 with normal facies. Atypical GHIS patients had lesser height deficit (Ht SDS –4.0 ± 1.4) compared to classical GHIS (–6.7 ± 1.4), less reduction in IGFBP-3 SDS (atypical –5.5 ± 3.3; classical –8.6 ± 2.4), and more had normal GHBP (>10% binding). Other variables were also less frequent in atypical GHIS patients: high-pitched voice 11% (70% classical), sparse hair 11% (42% classical), blue sclera 0% (38% classical), hypoglycaemia 11% (42% classical), and microphallus 14% (1 of 7 males), compared to 79% of classical (19 of 24 males). Conclusions: Atypical GHIS patients, with relatively normal facial appearance, demonstrate less height defect and biochemical abnormalities compared to classical patients. GH insensitivity may be present in children with short stature and an otherwise normal appearance.
The Treadmill Exhausting Test Is Not Suitable for Screening of Growth Hormone Deficiency!
Authors: Donaubauer Juliane , Kratzsch Jürgen , Fritzsch Christian , Stach Barbara , Kiess Wieland , Keller Eberhard
Published: April 2003

Background/Method: We compared the growth hormone response to a modified exercise test – the treadmill exhausting test – to pharmacological stimulation tests in 77 children with short stature. Each child underwent the treadmill test to individual exhaustion and at least one pharmacological test for GH stimulation. To determine the point of individual exhaustion, the heart rate, workload and oxygen consumption were measured. Results: The mean ± SEM peak GH concentration (ng/ml) in 47 small, normally growing children (group 1) was 16.1 ± 1.3 in the pharmacological tests vs. 5.0 ± 0.6 after a treadmill exhausting test. Thirty children with GH deficiency (group 2) had mean ± SEM peak GH concentrations (ng/ml) of 5.5 ± 0.5 in the pharmacological tests and 4.1 ± 0.7 after physical exercise. The groups differed significantly in the pharmacological tests (p < 0.001) but not in the exhausting test. We found a 90% sensitivity but only a 11% specificity for the treadmill exhausting test compared to the diagnosis obtained by pharmacological testing. Conclusion: We do not recommend the treadmill exhausting test in clinical practice of pediatric endocrinology at all.
New Compound Heterozygous Mutation in the CYP17 Gene in a 46,XY Girl with 17α-Hydroxylase/17,20-Lyase Deficiency
Authors: Katsumata Noriyuki , Satoh Mari , Mikami Atsushi , Mikami Shoko , Nagashima-Miyokawa Atsuko , Sato Naoko , Yokoya Susumu , Tanaka Toshiaki
Published: April 2003

Background: 17α-Hydroxylase/17,20-lyase deficiency is caused by a defect of P450c17 which catalyzes both 17α-hydroxylase and 17,20-lyase reactions in adrenal glands and gonads. Results: In the present study, we analyzed the CYP17 gene in a Japanese patient with 17α-hydroxylase/17,20-lyase deficiency. The patient was a phenotypic girl and referred to us for right-sided inguinal hernia at the age of 4 years. Biopsy of the herniated gonad showed testicular tissue. The karyotype was 46,XY. At 6 years of age, hypertension was clearly recognized and the patient was diagnosed as having 17α-hydroxylase/17,20-lyase deficiency based on the clinical and laboratory findings. Analysis of the CYP17 gene revealed a compound heterozygous mutation. One mutation was an undescribed single nucleotide deletion at codon 247 in exon 4 (CTT to CT: 247delT) and the other was a missense mutation resulting in a substitution of His to Leu at codon 373 in exon 6 (CAC to CTC: H373L), which has been previously shown to abolish both 17α-hydroxylase and 17,20-lyase activities. The functional expression study of the 247delT mutant showed that this 247delT mutation completely eliminates both 17α-hydroxylase and 17,20-lyase activities. Conclusions: Together, these results indicate that the patient is a compound heterozygote for the mutation of the CYP17 gene (247delT and H373L) and that these mutations inactivate both 17α-hydroxylase and 17,20-lyase activities and give rise to clinically manifest 17α-hydroxylase/17,20-lyase deficiency.
Albright’s Hereditary Osteodystrophy Associated with Cerebellar Pilocytic Astrocytoma: Coincidence or Genetic Relationship?
Authors: Sobottka Stephan B. , Huebner Angela , Haase Markus , Ahrens Wiebke , Rupprecht Edgar , Schackert Hans K. , Schackert Gabriele
Published: April 2003

Albright’s hereditary osteodystrophy (AHO) is a rare inherited disease characterized by skeletal abnormalities, short stature, and, in some cases, resistance to parathyroid hormone, resulting in pseudohypoparathyroidism (PHP). Heterozygous inactivating mutations of the GNAS1 gene are responsible for reduced activity of the alpha subunit of the Gs protein (GSα), a protein that mediates hormone signal transduction across cell membranes. Gsα is also known to have oncogenic potentials, leading to the development of human pituitary tumors and Leydig cell tumors. Here, we report the 1st case, a 3.5-year-old girl, with classic AHO phenotype and PHP type 1A associated with a cerebellar pilocytic astrocytoma. Coincidence or genetic relationships of both diseases are discussed according to molecular findings and current literature.
Evaluation of Neonatal Screening for Congenital Adrenal Hyperplasia
Authors: Honour John W. , Torresani Toni
Published: April 2003

Neonatal screening for congenital hypothyroidism has been effective in early detection and treatment of the condition. The position with respect to neonatal screening for congenital adrenal hyperplasia has been debated for many years. Some countries have performed congenital adrenal hyperplasia screening for many years, others have conducted pilot studies that were then not adopted. This article endeavours to summarize the complex issues behind decisions whether to screen or not and summarizes the findings of neonatal congenital adrenal hyperplasia screening programmes.