bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostate-Specific Antigen Levels and Density in the Internal and External Glands of the Prostate in Benign Prostatic Hyperplasia Patients with Normal or Gray-Zone PSA Levels
Authors: Zuo Wei , Hiraoka Yasunori
Published: July 2003

Objective: In patients with benign prostatic hyperplasia (BPH) showing normal prostate-specific antigen (PSA) levels (normal PSA group) and those with BPH showing gray-zone PSA levels (gray-zone PSA group), we assessed PSA levels secreted from the internal and external glands. Materials and Methods: We performed transurethral enucleation of the prostate (TUE) in 102 BPH patients with normal PSA and 59 BPH patients with gray-zone PSA at our department from 1999 to 2001. Preoperatively and approximately 6 months postoperatively, we measured serum PSA levels and determined prostatic volumes via transrectal ultrasonography (TRUS) to calculate PSA levels secreted from the internal and external glands as well as various PSA density (PSAD) values. Results: The total PSA level was 1.8 and 6.1 ng/ml in the normal and gray-zone PSA groups, respectively. The PSA level of the external gland was 0.6 and 0.8 ng/ml and the PSAD of the external gland was 0.07 and 0.08 ng/ml/cm3 in the normal and gray-zone PSA groups, respectively. The internal gland PSA was 1.3 and 5.4 ng/ml and the internal gland PSAD value was 0.11 and 0.30 ng/ml/cm3 in the normal and gray-zone PSA groups, respectively. Conclusions: Our results demonstrated that increased PSA levels in BPH cases with gray-zone PSA were attributable to increased PSA secreted from the internal gland rather than from the external gland. In our opinion, the determination of PSA and PSAD of the internal and external gland may be clinically significant in the future.
Increased Prostate-Specific Antigen in Subclinical Prostatitis: The Role of Aggressiveness and Extension of Inflammation
Authors: Yaman Önder , Göğüş Çağatay , Tulunay Özden , Tokatlı Zafer , Özden Eriz
Published: July 2003

Objectives: Subclinical prostatitis is a very frequent histologic finding in pathological examinations of prostate biopsy and prostate surgery material. In this study, we tried to investigate the correlation between the morphological parameters of histological prostatitis and total serum prostate-specific antigen (PSA)-PSA density (PSAD) to determine if either the extent or aggressiveness of inflammation might affect serum PSA. Methods: 269 patients who had undergone TURP or transvesical prostatectomy with pathological diagnosis of BPH and prostatitis were included in the study. We retrospectively reviewed and scored the extent and aggressiveness of inflammation in prostate specimens of BPH, according to the scale that has been reported by Irani et al. and then correlated those scores with PSA and PSAD. Results: When the inflammation grades correlated with PSA and PSAD, the extent of the inflammation did not show a significant correlation with total PSA and PSAD (p > 0.05). However, there was a statistically significant correlation between aggressiveness grades and total PSA and PSAD (p < 0.001). Median PSA levels in grades 0, 1 and 2 of aggressiveness of inflammation were 3.2, 4.2 and 5.8 respectively. Conclusion: Aggressiveness grade of the inflammation in subclinical prostatitis is the most important morphological factor that is responsible for PSA elevation. We believe that it should be a more accurate guide for the clinician if pathologists report on the aggressiveness grades of the inflammation, especially on initial prostate biopsies, in order to help for timing of the further biopsy.
Periprostatic Nerve Blockade before Transrectal Ultrasound-Guided Prostate Biopsy: The Ankara Numune Experience
Authors: İnal Gurdal , Yazici Sertaç , Adsan Öztug , Özturk Bulent , Çetinkaya Mesut
Published: July 2003

Objectives: To assess the efficacy and morbidity of periprostatic local anesthesia before transrectal ultrasound-guided biopsy of the prostate. Methods: From August 2001 to December 2001, 58 patients underwent transrectal ultrasound-guided prostate biopsy at the 2nd Department of Urology, Ankara Numune Education and Research Hospital. Fifty patients who fulfilled the inclusion criteria were randomized into 2 groups of 25 patients each. Group 1 received periprostatic local anesthesia with 1% lidocaine while group 2 received no local anesthesia. Pain scale responses were analyzed for each aspect of the biopsy procedure with a visual analog scale. Results: There was no difference between the 2 groups in pain scores during digital rectal examination, intramuscular injection and probe insertion. The mean pain scores during needle insertion in group 1 receiving periprostatic nerve block and in group 2 receiving no local anesthesia were 3.00 ± 2.22 and 6.16 ± 2.85, respectively, and were found to be significantly different (p < 0.001), but morbidity after the biopsy was not statistically different between the 2 groups. Conclusion: Periprostatic local anesthesia before prostate biopsy is a safe and easy method to increase patient comfort during the procedure.
Patient-Controlled Epidural Analgesia after Major Urologic Surgeries
Authors: Aribogan Anis , Doruk Nurcan , Aridogan Atilla , Akin Sule , Balcioglu Okan
Published: July 2003

The efficiency and safety of patient-controlled epidural analgesia by using tramadol alone and combined with bupivacaine were investigated for postoperative pain treatment after major urological surgeries. For PCEA: in group I (n = 17) a loading dose of 20 mg tramadol with a continuous infusion of 1 mg/ml tramadol at a rate of 8 ml/h was given. In group II (n = 17), patients received an initial loading dose of 20 ml bupivacaine 0.125% and a supplemental continuous infusion of 8 ml/h. In group III (n = 17), a loading dose of 20 mg tramadol with 20 ml bupivacaine 0.125% were given and a supplemental infusion of 1 mg/ml tramadol in 20 ml bupivacaine 0.125% combination was begun with a rate of 8 ml/h. A demand epidural bolus dose of 5 ml with a lockout time of 30 min was also used in all patients. VAS for pain intensity, vital signs, sedation scale and side effects was monitored at 0, 15, 30 min and 1, 2, 3, 4, 8, 12, and 24 h of the postoperative period. Statistical significance was determined using Kruskal-Wallis, Fisher’s exact, analysis of variance for repeated measurements and Tukey tests. The hemodynamic values and sedation scales were insignificantly different (p > 0.05). The adequate analgesia was provided in all patients. However VAS values were significantly lower in group III than in groups I and II at every measurement (p < 0.05). The incidence of side effects in all three groups was low (p > 0.05). In conclusion, we suggested that a combination of tramadol with bupivacaine can provide the most effective and safe postoperative analgesia with minimal risk for side effects.
How Reliable Is Conventional Urinary Cytology in Post-Transplant Patients?
Authors: Reichelt Olaf , Wunderlich Heiko , Neiser Grit , Schubert Jörg
Published: July 2003

Introduction and Objectives: Factors like cold, flushing solutions, ischemia and reperfusion may alter the microscopic appearance of transitional cells leading to falsely positive results of urinary cytology in patients after kidney transplantation. After seeing 1 patient presenting with two consecutive highly suspicious cytology specimens 3 days after transplantation and no sign of urothelial tumor at retrograde urography, we analyzed the cytological picture of transitional cells in post-transplant patients. Material and Methods: We investigated 31 urine specimens of 11 patients undergoing kidney transplantation preoperatively (if possible) and on days 1, 3 and 9 postoperatively. Microscopic cytology was performed by using Papanicolaou’s criteria: 0 – no cytology possible (no cells), I+II – negative cytology, III – doubtful, IV – suspicious for tumor, V – tumor cells. All microscopic examinations were performed by one experienced senior pathologist. Results: Mean patient age was 55.8 (± 17.5) years, mean residual diuresis 856 (± 636) ml, mean cold ischemia time 13.6 (± 6.4) h, mean creatinine level on day 1: 582 µmol/l, day 3: 533 µmol/l and day 9: 259 µmol/l. None of the urinary cytology results were suspicious for malignant transformation (Papanicolaou I+II). No patient presented signs of urothelial malignancy after a mean follow-up of 3 months. Conclusion: Although microscopic urinary cytology may be falsely positive in 1–12% of non-transplanted patients due to urothelia atypia, inflammation or radiation/chemotherapy, the present study suggests that conventional microscopic cytology examinations in post-transplant patients are not heavily altered and do not lead to an increased false-positive rate.
Pyogenic Psoas Abscess: Difficulty in Early Diagnosis
Authors: Hamano Satoshi , Kiyoshima Keijiro , Nakatsu Hiroomi , Murakami Shino , Igarashi Tatsuo , Ito Haruo
Published: July 2003

Aim: To report on the clinical features, diagnosis, and treatment of psoas abscess (PA) with special attention to the presence of septic shock. Patients and Methods: This study included 17 patients (mean age 66.2, range 43–81 years) with PA. Treatment consisted of intravenous administration of antibiotics and abscess drainage, either surgical or percutaneous with ultrasound guidance. Results: The typical patients presented with fever >38°C (16/17, 94%), pain in back, flank, or abdomen (15/17, 88%), hip flexion contracture with pain extension (14/17, 82%), and mass felt in the flank (5/17, 29%). All 8 patients without septic shock (100%) had the clinical triad (fever, pain in back, flank, or abdomen, and hip flexion contracture) as compared with 4 of 9 patients with septic shock (44%) (p = 0.012). The duration of symptoms before hospitalization was significantly shorter in the patients with septic shock (median 2, range 1–5 days) than in those without septic shock (median 18.5, range 11–63 days; (p = 0.0005). The mortality rates were 33% (3 of 9) and 0% (0 of 8) in the patients with and without septic shock, respectively (p = 0.071). Conclusions: PA patients with septic shock had a tendency to have nonspecific symptoms and an occult clinical course as compared with those without septic shock. A delay in diagnosis and treatment can result in a worse clinical outcome (death or totally disabled state). Increased awareness of this condition should lead to earlier diagnosis and treatment with improved outcomes.
Surgical Enucleation for the Treatment of Renal Tumors
Authors: Franks Michael E. , Hrebinko Ronald L. , Konety Badrinath R.
Published: July 2003

Introduction: We analyzed our institutional experience with surgical enucleation for the primary treatment of small renal tumors. Materials and Methods: Patient demographics, histological features, effect of different types of vascular control and outcome from surgery were analyzed in 45 patients. A majority of the tumors (67%) were diagnosed incidentally. Results: All were stage T1, 77% were low grade (I–II) and 23% were high grade (III–IV). Complication occurred in 12% of patients. At a mean follow-up of 34 months (range 7–97), 28 of 33 patients (84%) with malignant tumors were alive without evidence of disease. One patient with a solitary kidney developed recurrent tumor after enucleation that required nephrectomy. Mean operative time was significantly lower with the compression technique versus direct vascular control (164 ± 12 min vs. 233 ± 15 min, p = 0.002). There were no differences in outcome between the two techniques. Conclusions: Surgical enucleation is a safe and viable procedure for the treatment of small renal tumors. Manual compression of the kidney appears to be at least as effective as clamping of the renal vessels in obtaining vascular control during the procedure and is more expeditious.
Outcome of Nephron-Sparing Surgery: Elective versus Imperative Indications
Authors: Kural Ali Rıza , Demirkesen Oktay , Onal Bulent , Öbek Can , Tunc Burcin , Onder Ali Ulvi , Yalcin Veli , Solok Vural
Published: July 2003

Introduction: The increase in the detection of renal tumors incidentally in earlier stages has enhanced the enthusiasm for nephron-sparing surgery (NSS). Patients and Methods: We performed NSS in 76 patients (53 male, 23 female) with a mean age 52.3 between December 1988 and September 2001. Patients were sub-classified into 2 groups as elective or imperative indication group. They were compared regarding surgical technique, time of surgery, pathological analysis, complications, and disease free status. Results: Elective indication group (group I) with a normal contralateral kidney consisted of 50 patients, whereas there were 26 patients in the imperative indication group (group II). Tumors were incidentally detected in 63%; 74% in group I and 42% in group II. Although the mean diameter of the tumor was slightly higher in group II (39.1 vs. 36.3 mm), this difference did not reach statistical significance (p > 0.05). The partial nephrectomy was performed more frequently compared to enucleation in group I (90 vs. 69%, p = 0.050). However, the mean operation time as well as the mean clamping time did not differ significantly between the two groups (p > 0.05). In the histological evaluation tumors were benign in 16 (21%) and malignant in 60 patients. All of the patients but one with renal cell carcinoma had stage T1-T2 disease. Major complications were observed in 14 (18%) and 12 were from group II. Complication rate was significantly higher in group II (p = 0.000). Of 60 patients with renal cell carcinoma, 2 died of unrelated causes. One patient died with multiple visceral metastases. One patient was lost to follow-up. In the remaining 56 patients with a mean follow-up of 37.1 months (1–152), local recurrence or distant metastases were not detected. Serum creatinine levels have remained almost the same compared to preoperative levels (1.2 ± 0.6 vs. 1.5 ± 0.9). Overall and cancer-specific survivals were 100 and 100% in group I, 85 and 95% in group II, and 94 and 98% for the entire patient population, respectively. Conclusion: NSS is an effective and reliable treatment in low stage renal tumors. It prevents unnecessary nephrectomy in benign lesions that could not be diagnosed preoperatively. However, the patients who underwent NSS with elective indication outcome with better results, compared to those with imperative indication.
Renal Cysts: Can Percutaneous Ethanol Injections Be Considered an Alternative to Surgery?
Authors: Gasparini Daniele , Sponza Massimo , Valotto Claudio , Marzio Andrea , Luciani Lorenzo G. , Zattoni Filiberto
Published: July 2003

Aim: To evaluate the efficacy of a new sclerotization technique with pure ethanol in the treatment of symptomatic renal cysts. Patients and Methods: Fourteen patients having renal cysts with a meant diameter of 10 (range 5–15) cm were treated. Our technique includes: ultrasound-guided percutaneous puncture with an 18-gauge needle, positioning of a 5-Fr catheter, complete cyst fluid aspiration, injection of pure alcohol equal to 15% of the initial cyst volume, and alcohol aspiration after 90 min. The procedure was repeated eight times within 5 days. The patients were followed up by ultrasound and/or CT scan for 1 year. Results: All patients became symptom free. Follow-up showed a progressive reduction of the cyst diameter in all cases. Three cysts only (in 2 patients; cyst diameter <2 cm) persisted after 12 months. No significant complications were observed. Conclusions: In our experience, injections of pure ethanol in renal cysts, repeated after some days, were effective in eliminating recurrences and related symptoms. The procedure was not associated with significant complications. Our findings suggest that it be considered the first-choice procedure in the treatment of renal cysts, due to the good results and the low cost of ethanol.
Open Pyeloplasty in Children: Experience with an Improved Stenting Technique
Authors: Reed M.J. , Williams M.P.L.
Published: July 2003

Objective: To describe the use of an alternative and improved nephrostostent in open pyeloplasty procedures. Materials and Methods: A series of 27 consecutive patients (between 4 months and 14 years of age) undergoing an open pyeloplasty procedure had their urinary system drained via a nephrostostent which passes from the ureteric anastomosis to the skin and which unlike other described nephrostostents does not cross the vesico-ureteric junction. All children received an ultrasound and MAG3 scan 3 months post-operatively and were followed up for 18–24 months. Results: The use of this stent was associated with no serious complications. There was a decreased incidence of vesico-ureteric reflux, post-operative urinary tract infection and stent displacement compared to previously described methods of drainage. Conclusion: This method of open pyeloplasty drainage, which has not been described before, could be associated with fewer complications than existing stenting techniques.
Endopyeloureterotomy Using the Holmium:YAG Laser for the Management of Adult Ureteral and Ureteropelvic Junction Obstructions
Authors: Kobayashi Takashi , Nishizawa Koji , Watanabe Jun , Ogura Keiji
Published: July 2003

Aim: To determine the efficacy of endopyeloureterotomy using a holmium:YAG laser for the management of adult benign ureteral and ureteropelvic junction obstructions. Patients and Methods: We reviewed the clinical outcomes of eight primary procedures performed in 5 patients. The causes of the strictures were idiopathic in five and stone impaction in three procedures. All strictures except one were approached in a retrograde fashion with either a rigid (8.0 Fr) or flexible (9.3 Fr) ureteroscope. The only energy source employed was the laser, and no balloon dilation was performed. In all cases, a 4.8-Fr ureteral stent was left indwelling, and retrograde ureteropyelography was performed within 6–8 weeks to remove the catheter. Results: Follow-up was performed in all patients for a mean period of 14.9 (minimum 10) months. Two strictures in 1 patient failed to be stent free, while six strictures were patent on postoperative radiographic imaging. There were no perioperative complications. Conclusions: Endopyeloureterotomy using a holmium:YAG laser is safe and effective. Its relative noninvasiveness and its retrograde approach make it a first-line alternative for the management of benign upper urinary tract strictures in adults.
Low-Dose Low-Osmolar Urography with Iohexol
Authors: Gupta Rakhee , Airon Raj Kumar
Published: July 2003

Objectives: To study the diagnostic efficacy of low-dose iohexol (90 mg iodine/kg body weight) for intravenous urography. Materials and Methods: Intravenous urography was performed using low-dose iohexol in 50 patients with various urinary complaints. Patients with elevated blood urea and serum creatinine levels were excluded. The urographic films were evaluated with regard to diagnostic information about renal parenchyma, calyces, collecting system and overall image. Patients were also observed for adverse reactions. Results: A satisfactory diagnosis could be reached in 94% of patients with low-dose iohexol. Only a minor reaction in the form of heat sensation was noted in 1 patient, which did not require any treatment. Conclusion: Iohexol is safe and very useful diagnostically in a low dose for routine intravenous urography.
Gastrocystoplasty in Pigs and Effect of Selective Antral Vagotomy on Acid Secretion of the Reconstructed Bladder
Authors: Acar O. , Demirtas M. , Kacar S. , Vural P. , Devecioglu Y. , Saroglu M. , Culha M. , Gökalp A.
Published: July 2003

Introduction: The aim of this study was to investigate the outcome of gastrocystoplasty and the effects of selective antral vagotomy (SAV) on the postprandial gastrin secretion from the antrum as well as on the acid secretion from the augmented bladder. Materials and Methods: In this study on 12 male pigs, we applied subtotal cystectomy plus gastric augmentation plus SAV to the study group and the same procedure without SAV to the control group. The animals were followed up for 3 months with respect to feeding, weight, and urine output. The urine pH levels and the gastrin levels of the pigs in the two groups were then followed up and compared. Results: The use of gastric segments in bladder reconstruction was found to be appropriate in terms of both gastric function and urinary system function. Nevertheless, regarding the effect of SAV, the differences between either the urinary pH levels or the gastrin levels of the pigs in the two groups were statistically significant. Conclusions: Although gastric segments in the bladder reconstruction were found to be appropriate in terms of both gastric function and urinary system function, SAV did not prevent postprandial gastrin secretion and the resulting increase of the urine acidity.
Seromuscular Gastrocystoplasty in Dogs
Authors: Vastyan Attila M. , Pinter Andrew B. , Farkas Andrew P. , Vajda Peter , Lantos Janos , Mehes Gabor , Roth Elizabeth
Published: July 2003

Introduction: The aim of this study was to investigate the feasibility of seromuscular gastrocystoplasty (SGCP) in an animal model and to compare it to conventional gastrocystoplasty (CGCP). Materials and Methods: CGCP and SGCP (using gastric segments without mucosa) were each performed in 6 dogs. In both procedures, two-thirds of the dome of the bladder were excised and the gastric segment anastomosed to the bladder remnant. Cystography, cystomanometry, measurements of urine pH, and gross and microscopic pathological studies were carried out preoperatively, and postoperatively, at 6 and 12 weeks. Results: All seromuscular gastric segments proved viable, and 6 weeks after the operation they were covered by a thin layer of transitional epithelium, which had gradually thickened by the end of the 12-week follow-up. There was no difference in bladder capacity and compliance between the two groups, however, fasting urinary pH values were higher (less acidic) in the SGCP group. Conclusions: Stripping off the mucosa of the gastric segment appears to stop hydrochloric acid secretion, thereby lessening the possible risk of ulceration, perforation, dysuria-haematuria, metaplasia and malignancy. The uroepithelium overgrowth of the seromuscular gastric segments might provide a more physiological neo-bladder than when using full-thickness gastrocystoplasty.
SRY-Positive 46,XX Male with Cryptorchidism as the Only Presenting Clinical Feature
Authors: Moreno-García Marta , Sánchez del Pozo Jaime , Gutierrez-Díez Pilar , Gil-Fournier Belén , Barreiro Miranda Emilia
Published: July 2003

The SRY gene, located on the short arm of the Y chromosome, is responsible for differentiation of the testis from the undifferentiated gonad. We report a 4-year-old patient with male phenotype and female karyotype (46,XX) with cryptorchidism as the only presenting clinical abnormality. Fluorescent in situ hybridization analysis, using Y- and X-specific (whole chromosome painting WCP Y WCP X) DNA and SRY probes, detected a small Y chromosome fragment, including the SRY gene, transferred to the short arm of the X chromosome.
Unexpected Presentation of Syringocele
Authors: Türker Köksal İsmail , Erdoğru Tibet , Usta Mustafa , Ateş Mutlu , Baykara Mehmet
Published: July 2003

Cowper’s syringocele is an uncommon deformity in the male urethra that is a distention of the duct of the Cowper’s gland. Symptoms attributed to Cowper’s syringocele in adults consist of lower urinary tract symptoms. To our knowledge there are no data on acontractile bladder due to Cowper’s syringocele. We describe a patient who had acontractile bladder and a Cowper’s syringocele.
Leiomyoma of the Female Urethra
Authors: Deka P.M. , Rajeev T.P.
Published: July 2003

We report a case of leiomyoma of the female urethra and a review of the literature. A mass protruding from the urethral meatus caused voiding difficulty and dysuria. Uroflowmetry showed an obstructive pattern with low maximum urine flow. Cystourethroscopy revealed a mass arising from lateral urethral wall extending from meatus up to 2 cm proximally. Histopathological studies confirmed urethral leiomyoma. Surgery completely resolved the original symptoms.
Infected Hydrocoele of the Canal of Nuck in a Neonate
Authors: Ameh Emmanuel A. , Garba Ekundayo S.
Published: July 2003

Hydrocoele of the canal of Nuck is an uncommon presentation in the neonate and complications are rare. A 6-day-old girl presented with a right groin swelling from birth. The swelling remained static until age 3 days when it increased rapidly in size. There was no fever or gastrointestinal symptoms. Physical examination showed a large nontender mass extending from the right groin into the ipsilateral labium majus with distortion of the external genitalia. Needle aspiration yielded cloudy fluid, which gave a growth of Klebsiella on culture. A hydrocoele of the canal of Nuck was confirmed at surgery and was excised. Postoperative course was uneventful and there has been no recurrence at 2 years of follow-up.
Clear Cell Adenocarcinoma of the Bladder in a Male Patient: Clinicopathologic Analysis of a Case
Authors: Signori Gianbattista , Tonini Gerolamo , Aulenti Vito , Taher Bassam , Rad Farshid-Kalantary , Tosana Michelangelo , Ungari Marco , Zorzi Fausto
Published: July 2003

Clear cell adenocarcinoma arising in the lower urinary tract is unusual. We report a case of clear cell adenocarcinoma of the bladder in a 54-year-old male. Cystoscopic examination revealed a tumour arising from the dome of the urinary bladder. Histologically, the tumour was chiefly composed of tubulocystic and papillary glands lined by glycogen-rich, cubical or hobnail cells with clear to eosinophilic cytoplasm. The tumour infiltrated into the inner muscular layer. The patient was treated by partial cystectomy.
Benign Retroperitoneal Schwannoma Presenting as a Giant Adrenal Tumor
Authors: Hettiarachchi Janaka A. , Finkelstein Michael P. , Schwartz Alec M. , Johnson G. Blake , Konno Sensuke , Choudhury Muhammad S.
Published: July 2003

We report a 51-year-old man with a primary adrenal tumor presenting as a giant juxta-adrenal benign schwannoma. The patient was initially admitted for persistent fevers and underwent a sepsis workup. Abdominal ultrasound initially revealed an incidental right suprarenal mass, which measured 10 × 10 × 11 cm, estimated by computed tomography. Following a successful laparotomy, histologic examination confirmed that this giant tumor was a benign retroperitoneal schwannoma. Postoperatively, the patient remains disease-free, undergoing rehabilitation.
A False-Negative Diuretic Radionuclide Renography in a Patient with Urinary Ascites due to Retroperitoneal Fibrosis
Authors: Arslan Deniz , Değirmenci Berna , Aslan Güven , Özdoğan Özhan , Esen Adil , Durak Hatice
Published: July 2003

In this case report we present a rare manifestation of a false-negative diuretic radionuclide renography in a patient with urinary ascites due to retroperitoneal fibrosis. Diuretic renography may lead to false-negative results and should be carefully evaluated in this group of patients.
Serum Insulin-Like Growth Factor I Reference Values for an Automated Chemiluminescence Immunoassay System: Results from a Multicenter Study
Authors: Brabant Georg , von zur Mühlen Alexander , Wüster Christian , Ranke Michael B. , Kratzsch Jürgen , Kiess Wieland , Ketelslegers Jean-Marie , Wilhelmsen Lars , Hulthén Lena , Saller Bernhard , Mattsson Anders , Wilde Jürgen , Schemer Rudolf , Kann Peter
Published: July 2003

Background: Analysis of insulin-like growth factor I in serum (S-IGF-I) is an integral component in the diagnosis of GH-related disorders and is going to be of interest in the diagnosis and follow-up of many disorders. The objective of the present study was to develop cross-sectional reference values for S-IGF-I measured by an automated chemiluminescence immunoassay (Nichols Advantage®). Methods: The study included samples from 3,961 healthy subjects (2,201 males, 1,760 females) aged 1 month to 88 years. Six laboratories were involved in this study and the samples were analyzed by one of seven automated immunoassay systems run in these laboratories. For data analysis, polynomial age and sex-specific models were fitted after transformation of S-IGF-I values. Results: The results show the well-known age dependency of S-IGF-I levels. At ages <20, higher S-IGF-I levels were seen in girls with an estimated mean peak of 410 µg/l at age 14 and an estimated mean peak of 382 µg/l at age 16 in boys. Thereafter, a rapid decrease was seen to approximately 25 years of age, followed by a slow age-dependent decrease. In adulthood, S-IGF-I in males were slightly, but significantly higher than in females. It could be shown that the mean values of some reference sample subgroups differed significantly from the total mean. However, the multicenter approach used in this study reduces the impact of systematic population, sample handling and laboratory differences on the calculated reference mean. Conclusion: The present study establishes age- and sex-specific reference values for a fully automated immunoassay system based on a large population of healthy subjects. The established reference values may be used for this immunoassay system in different laboratories provided that the systematic difference between systems is low.
Lipoprotein Lipase Activity and Common Gene Variants in Severely Hypertriglyceridemic Patients with and without Diabetes
Authors: Chadarevian Rita , Foubert Luc , Beucler Isabel , Kottler Marie-Laure , Raisonnier Alain , Ajlouni Ali , Giral Philippe , Turpin Gérard , Bruckert Eric
Published: July 2003

Objectives: In severe type IV hypertriglyceridemia (triglyceride levels >10 g/l), it is yet unknown whether lipoprotein lipase (LPL) differs according to the presence or not of diabetes. Methods: We compared LPL activity and the presence of four common variants in the LPL gene (Asp 9 Asn (exon 2), Gly 188 Glu (exon 5), Asn 291 Ser (exon 6) and Ser 447 Ter (exon 9)) in a group of 34 patients of whom 17 presented diabetes mellitus. Results: Maximum triglyceride, cholesterol levels and distribution of apolioprotein E phenotypes did not differ between the two subgroups. Mean post-heparin LPL activity was lower in non-diabetic compared to diabetic patients (9.74 vs. 12.98 µmol FFA/ml/h, p = 0.033). Four patients were carrying a mutation in exon 9 (1 non-diabetic), 6 patients in exon 2 (4 non-diabetic) and 1 patient in the non-diabetic subgroup in exon 5. All mutations were at the heterozygous state. Conclusion: We found that LPL activity was lower in type IV hyperlipidemia in the absence of diabetes. Genetic defects in the LPL gene that could lead to this lower LPL tended to be more frequently observed in patients without diabetes. These data suggest that the pathomechanisms which contribute to severe type IV hyperlipidemia are different according to the presence or not of diabetes.
Expression of Growth Hormone Receptor Isoform Exon-3-Excluding and Exon-3-Retaining Messenger RNAs in Peripheral Lymphocytes from Normal and Acromegalic Subjects
Authors: Ochoa Raquel , Zárate Arturo , Cerbón Marco A. , Salcedo Mauricio , López Ricardo , Galván Rosa E. , Hernández Marcelino
Published: July 2003

Aim: To determine the expression of two isoforms of the growth hormone (GH) receptor (GHR), which differ by the presence (GHR3+) or absence (GHR3–) of exon 3, and their correlation with circulating GH and insulin-like growth factor I (IGF-I) in normal subjects and in acromegalic patients. Methods: The expression of GHR isoforms was determined by reverse-transcriptase polymerase chain reaction in lymphocytes from 12 normal subjects and from 11 patients with acromegaly. The levels of GHR mRNA were normalized to those of β-actin, and ratios were calculated to assess the relative levels of expression. Results: All samples showed expression of both GHR isoforms, but the expression of GHR3+ and GHR3– was similar in acromegalic patients (6.0 ± 1.7 vs. 8.3 ± 2.0%, mean ± SE). In contrast, in healthy subjects, GHR3– was the predominant isoform (11.8 ± 3.0 vs. 5.1 ± 0.68%; p < 0.05), and the levels of expression of GHR3– correlated significantly with IGF-I. Conclusions: These data demonstrate coexpression of both GHR isoforms under normal and pathological conditions; however, GHR3– is the predominant form in normal subjects and shows a negative correlation with IGF-I levels.
Genital Skin Fibroblasts (GF) of Patients with Androgen Insensitivity Syndrome Express Higher Insulin-Like Growth Factor Binding Protein (IGFBP)-2, -3 and -5 than GF of Normally Virilized Males
Authors: Diesing D. , Elmlinger M.W. , Schuett B.S. , Weidemann W. , Romalo G. , Schweikert H.U. , Spindler K.-D. , Ranke M.B.
Published: July 2003

Background: We investigated the effects of androgens, estradiol (E2) and insulin-like growth factor (IGF)-I on IGF-II, insulin-like growth factor binding protein (IGFBP)-2, -3 and -5 and mRNA in genital fibroblasts (GF) from patients with complete androgen insensitivity (CAIS) and normally virilized males (C). Methods: Proteins were measured by specific RIA and Western ligand blot, and specific mRNA levels by RT-PCR normalized by GAPDH levels. Results: Secretion of IGF-II was lowered in CAIS (p < 0.001) GF and by testosterone + IGF-I in C GF. Secretion of IGFBP-2 was higher (p < 0.001) in CAIS GF and IGFBP-2 mRNA levels were increased by E2 in C GF (p < 0.05). E2 stimulated IGFBP-2, -3 and -5 expression in CAIS GF. CAIS GF also secreted more IGFBP-3 (p < 0.001) and accumulated 3–5 times more IGFBP-5 mRNA than C GF (p < 0.001). Conclusion: In contrast to C GF, the availability of IGF-II in CAIS GF is apparently decreased by two facts: by the decreased expression and by increased expression of IGFBP-2, -3 and -5. Furthermore, E2 and IGF-I modulate the expression of IGF-II and IGFBP in GF. This may play a role in the failure to develop male external genitals in CAIS patients.
Thyroid Cancer in Patients with Hyperthyroidism
Authors: Gabriele Raimondo , Letizia Claudio , Borghese Mario , De To ma Giorgio , Celi Massimiliano , Izzo Luciano , Cavallaro Antonio
Published: July 2003

Objective: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. With the aim of assessing the clinical relevance of this association, we have retrospectively analyzed the incidence of thyroid cancer in 425 hyperthyroid patients seen and treated by surgery in our institutions. Methods: Among these hyperthyroid patients, we observed 241 (56.7%) cases of multinodular toxic goiter, 120 (28.3%) of uninodular toxic goiter and 64 (15%) cases of Graves’ disease. Results: Thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients. Histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in 2 cases. Neoplasia was detected in 4 patients with nodular toxic goiter and in 3 with uninodular toxic goiter. None of the patients with Graves’ disease had thyroid cancer. During the follow-up of 74 months (range 4–154), there were no deaths or any recurrences. Conclusion: Although the occurrence of thyroid cancer in hyperthyroid patients is a rare event, the presence of a ‘cold’ nodule in a hyperfunctioning thyroid should be carefully evaluated to exclude the presence of concurrent malignancy.
Growth Analysis in Patients with 21-Hydroxylase Deficiency Influence of Glucocorticoid Dosage, Age at Diagnosis, Phenotype and Genotype on Growth and Height Outcome
Authors: Grigorescu-Sido Anca , Bettendorf Markus , Schulze Egbert , Duncea Ileana , Heinrich Udo
Published: July 2003

Objective: To evaluate the impact of hydrocortisone dosage, age at diagnosis, compliance, genotype and phenotype on growth and height outcome in 21-hydroxylase-deficient patients. Methods: We analyzed 37 patients with 21-hydroxylase deficiency (17 had completed growth, 20 still growing). Final (FH)/predicted final height (pFH) and loss of height potential related to target height (TH) were calculated and the impact of 4 hydrocortisone (HC) dosage regimens on height outcome and growth velocities was evaluated. Mean FH SDS and pFH SDS were analyzed in accordance to age at diagnosis, compliance, genotype and phenotype. Results: Mean (FH SDS, pFH SDS) was –1.8 ± 1.06 SD, with 35.1% of all 37 patients exhibiting short stature. Doses >20 mg/m2/day during the first year and >15 mg/m2/day during age 1–5 and at puberty resulted in significantly lower FH SDS, pFH SDS and greater height losses. Age at diagnosis, compliance, genotype and phenotype played only a minor role in growth development. Conclusions: Hydrocortisone substitution in 21-hydroxylase-deficient patients should be kept at the lowest efficient level, if possible <20 during the first year and <15 mg/m2/day until age 5 and during puberty. Normal growth and not complete androgen suppression should be aimed for.
Effects of Leptin to Cultured Growth Plate Chondrocytes
Authors: Nakajima Ryoichi , Inada Hiroshi , Koike Tatsuya , Yamano Tsunekazu
Published: July 2003

Objective: This study aimed to evaluate whether leptin has any effect on growth plate chondrocytes. Methods: We studied the effects of exogenous leptin on cultured rabbit growth plate chondrocytes. This involved assessing [3H]thymidine incorporation, alkaline phosphatase (ALP) activity, proteoglycan production, leptin receptor (Ob-R) activity, and detection of Ob-R using Western blot analysis. Results: The existence of Ob-R in growth plate chondrocytes was revealed by Western blot and Ob-R activity. Prior to semiconfluence, leptin increased [3H]thymidine incorporation while at the semiconfluent and early confluent stages, leptin promoted ALP activity and tended to promote proteoglycan production. Conclusion: Growth plate chondrocytes possess Ob-Rs, and leptin enhance chondrocyte proliferation and subsequent cell differentiation.
Hyperplasia of Adrenal Rest Tissue Causing a Retroperitoneal Mass in a Child with 11β-Hydroxylase Deficiency
Authors: Storr Helen L. , Barwick Tara D. , Snodgrass Graeme A.I. , Booy Robert , Morel Yves , Reznek Rodney H. , Savage Martin O.
Published: July 2003

We report the case of a child with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency, with hyperplasia of adrenal rest tissue presenting as a retroperitoneal mass. Complete resolution of the mass was noted after 18 months of hydrocortisone replacement therapy.
Diabetic Nephropathy: An Inherited Disease or Just a Diabetic Complication?
Authors: Berger Mario , Mönks Detlev , Wanner Christoph , Lindner Tom H.
Published: July 2003

Type 2 diabetic nephropathy is the most common cause of end-stage renal disease in western Europe and the United States. Although patients with overt nephropathy generally experience greater cumulative glycemic exposure, the difference in glycemic control between patients developing nephropathy and to those who did not could not be demonstrated. This observation is consistent with the finding that factors other than glycemic control are involved in the development of nephropathy. Genetic factors which specifically increase the susceptibility to nephropathy in patients with diabetes have been proposed. A range of linkage, association, and gene expression studies have been performed for revealing the genetic background of diabetic nephropathy but were not yet successful in identifying mutations which could explain the development of diabetic nephropathy in the majority of diabetic patients. Because of relatively small case numbers of all studies being performed so far, conclusions from those studies are limited. With the development of better technologies for an affordable genomewide association study using thousands of markers, it might become possible to unravel the genetic susceptibility factors for diabetic nephropathy. Comparing the expression levels of thousands of genes in patients and controls may identify key players in the pathogenesis of diabetic nephropathy and targets for pharmacologic intervention in the future.
Epidermal Growth Factor Regulates Ca2+ Uptake in Primary Cultured Renal Proximal Tubule Cells: Involvement of cAMP, PKC and cPLA2
Authors: Han Ho Jae , Park Soo Hyun , Lee Yun Jung
Published: July 2003

Epidermal growth factor (EGF) is known to play an important role in modulating renal transport functions. Thus, we investigated the effect of EGF on Ca2+ uptake and its related signals in the primary cultured rabbit renal proximal tubule cells. EGF (50 ng/ml, 1 h) stimulated Ca2+ uptake. Its effect was blocked by AG 1478 (an EGF receptor antagonist), genistein or herbimycin A (tyrosine kinase inhibitors). EGF increased intracellular cAMP level and SQ 22536 (an adenylate cyclase inhibitor), Rp-cAMP (a cAMP analogue), or PKI (a protein kinase A inhibitor) blocked the EGF-induced stimulation of Ca2+ uptake. EGF-induced stimulation of Ca2+ uptake was also blocked by neomycin or U-73122 (phospholipase C inhibitors), staurosporine, H-7, or bisindolylmaleimide I (protein kinase C inhibitors), nifedipine or methoxyverapamil (L-type Ca2+ channel blockers). It increased IPs formation by 167 ± 5% compare to control within 90 s. On the other hand, EGF increased [3H]-arachidonic acid release, which was significantly blocked by PKC inhibitors. In addition, PGE2, one of cyclooxygenase metabolites, and 5,6-EET, one of cytochrome P-450 metabolites, increased Ca2+ uptake. These results suggest that cAMP, PLC/PKC, and PLA2 are involved in EGF-induced stimulation of Ca2+ uptake.
Role of Nitric Oxide in the Renal and Systemic Vasodilatory Responses to Platelet-Activating Factor in the Rat, in vivo
Authors: Handa Rajash K. , Strandhoy Jack W. , Handa Shelly E.
Published: July 2003

Background/Aim: Chemical mediator(s) involved in the renal vasodilatory and systemic hypotensive effects of platelet-activating factor (PAF) remain unresolved. Because nitric oxide (NO) and PAF have many similar cardiovascular actions, we examined whether endogenous NO contributes to the renal and systemic actions of PAF. Methods: PAF was administered into the renal arterial or systemic venous circulation of anesthetized rats. The change in renal blood flow (RBF) and/or mean arterial blood pressure (MAP) was recorded in the absence and presence of NO synthase inhibition. Results: Transient exposure of the renal vacsular bed to intrarenal PAF boluses (1–10 ng kg–1) resulted in an immediate increase in RBF that was partially inhibited by the intrarenal administration of a NO synthase inhibitor, whereas the ensuing rapid fall in MAP was unaffected by NO synthase blockade. A sustained exposure to intrarenal PAF infusion (2.5 ng min–1 kg–1) in intrarenal NO synthase inhibitor-treated rats (hypertensive with vasoconstricted kidneys) had no effect on RBF and MAP, which was in contrast to the increase in RBF and modest fall in MAP in control intrarenal vasopressin-treated rats (hypertensive with vasoconstricted kidneys). To dissociate the influence of systemic hypotension on the RBF response, rat kidneys were denervated and MAP elevated by a pressor agent whilst maintaining renal arterial blood pressure constant. Subsequent intrarenal PAF infusion at 2.5 and 10 ng min–1 kg–1 resulted in a substantial rise in RBF and modest fall in MAP, responses that were abolished by intrarenal NO synthase inhibition at the lower intrarenal PAF infusion or abolished/attenuated at the higher intrarenal PAF infusion. Additional experiments administered drugs intravenously to exclude the possibility that the modified MAP response by NO synthase inhibition was related to the drugs being administered into the kidney. Intravenous PAF boluses (0.1–1 µg kg–1) resulted in a transient fall in MAP that was independent of the NO pathway, whereas the systemic hypotension induced by intravenous PAF infusion (10 ng min–1 kg–1) was greatly attenuated by NO synthase inhibition. Conclusion: NO has a major role in mediating the renal and peripheral vasodilatory responses induced by a sustained exposure to PAF in the rat, whereas NO’s overall contribution was less or absent during transient PAF exposure.
Four Additional CLCN5 Exons Encode a Widely Expressed Novel Long CLC-5 Isoform but Fail to Explain Dent’s Phenotype in Patients without Mutations in the Short Variant
Authors: Ludwig Michael , Waldegger Siegfried , Nuutinen Matti , Bökenkamp Arend , Reissinger Annette , Steckelbroeck Stephan , Utsch Boris
Published: July 2003

Background: Dent’s disease is caused by mutations in the CLCN5 gene coding for the chloride channel CLC-5. However, sequencing of CLCN5 exonic regions in some patients presenting with low-molecular-weight proteinuria and hypercalciuria – the hallmarks of Dent’s disease – failed to identify causative mutations. Aim: Given the observation that some species harbour a CLCN5 mRNA encoding an extended CLC-5 aminoterminus compared with the so far known human form, we worked on the presumption that an orthologous (longer) CLCN5 transcript is also present in humans and that our patients may have mutations herein. Methods: Extensive databank mining, reverse transcription polymerase chain reaction (RT-PCR) and automated sequencing were used in the search for novel CLCN5 transcripts. The human CLCN5 gene was investigated in 7 patients out of five families by direct automated sequencing of PCR-amplified DNA products. Results: Two new human CLCN5 transcripts expressed in kidney and various other tissues could be identified. These arise from a novel site of transcription initiation, alternative splicing and the use of four additional CLCN5 exons. If being translated, both these mRNAs would lead to an enlarged CLC-5 protein consisting of 816 amino acids by adding 70 aminoterminal residues to the so far known 746-amino-acid-long isoform. Sequence analysis of the henceforward 17 CLCN5 exons revealed no mutation in the patients with a phenotype resembling Dent’s disease. Conclusions: Despite the identification of further targets to explain Dent’s disease, the molecular defect in our patients remains to be elucidated. Hence, their phenotype may be explained by mutations that affect so far unknown regulating elements of the CLCN5 gene or another gene(s), probably encoding CLC-5 accessory protein(s).
Effects of LDL Apheresis and Vitamin E-Modified Membrane on Carotid Atherosclerosis in Hemodialyzed Patients with Arteriosclerosis obliterans
Authors: Nakamura Tsukasa , Kawagoe Yasuhiro , Matsuda Takaharu , Takahashi Yutaka , Sekizuka Keiko , Ebihara Isao , Koide Hikaru
Published: July 2003

Background: Hemodialysis patients manifest accelerated atherosclerosis. Hemodialysis is associated with oxidative stress, which can be partially prevented with the use of a vitamin E-coated dialyzer. Adsorption of low-density lipoprotein (LDL) has been applied in the treatment of arteriosclerosis obliterans (ASO). The aim of the present study was to determine whether the vitamin E-coated dialyzer and/or LDL apheresis affects carotid atherosclerosis in hemodialysis patients with ASO. Methods: Thirty hemodialysis patients with ASO were divided into four treatment groups: treatment with conventional cellulose or synthetic membranes (group A, n = 12), treatment with vitamin E-coated membrane (group B, n = 7), treatment with conventional membrane and LDL apheresis (group C, n = 6), and treatment with vitamin E-coated membrane and LDL apheresis (group D, n = 5). Carotid artery intima-media thickness (IMT) and arterial stiffness assessed by pulse wave velocity (PWV), plasma C-reactive protein (CRP) and interleukin (IL)-6 were measured before and 10 weeks after treatment and compared between groups. All values were referred to measurements after LDL apheresis. Results: IMT and PWV, plasma CRP and IL-6 showed little change in group A throughout the experimental period. These decreased slightly from the baseline value in group B, but the change was not significant. In group C, IMT decreased from 1.12 ± 0.24 to 1.02 ± 0.18 mm (p < 0.05), and PWV decreased from 2,266 ± 380 to 1,968 ± 342 cm/s (p < 0.05). Plasma CRP and IL-6 concentrations also decreased significantly compared with baseline (p < 0.05). In group D, IMT decreased from 1.18 ± 0.26 to 0.92 ± 0.18 mm (p < 0.01), and PWV decreased from 2,284 ± 390 to 1,786 ± 284 cm/s (p < 0.01). Plasma CRP and IL-6 levels also decreased significantly compared with baseline (p < 0.01). Conclusion: These data suggest that LDL apheresis and the vitamin E-coated membrane dialysis in combination may prevent further progression of atherosclerosis in hemodialysis patients with ASO.