bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystallization Inhibitors in the Pathophysiology and Treatment of Nephrolithiasis
Authors: Marangella Martino , Bagnis Cristiana , Bruno Michele , Vitale Corrado , Petrarulo Michele , Ramello Adriano
Published: May 2004

It is currently agreed that stone formation in the urinary tract requires supersaturation with respect to a given solid phase. However, this principle fully applies only to stones other than calcium-containing stones, in which case compounds acting as inhibitors are postulated to naturally occur in urine. Stone formation would therefore ensue from an imbalance between promoters and inhibitors. The saturation state can be estimated by means of computer model systems based on ab initio calculations, which account for the main soluble complexes formed in urine between relevant cations and anions. This estimates the overall promoting potential of urine. However, in the case of calcium nephrolithiasis, supersaturation does not make a clear-cut separation between normal subjects and patients. Several studies in the last two decades have identified many inhibitors of calcium oxalate and calcium phosphate crystallization, which are classified into the ionic and macromolecular. They have been shown to act on kinetics by interfering with nucleation, growth and aggregation of crystals. Unfortunately, except for citrate, none of the newly discovered substances has been definitely characterized in its molecular composition and structure, type and potency of inhibition, differences in concentration and structure between stone-forming and non stone-forming subjects. Citrate exhibits a dual action in urine, opposing crystal formation by both thermodynamic and kinetic mechanisms. At present it is the only natural inhibitor which can be measured in urine, quantitated as to inhibitory activity and used in medical treatment.
Genetics of Primary Hyperparathyroidism
Authors: Brandi Maria Luisa , Falchetti Alberto
Published: May 2004

Primary hyperparathyroidism, a genetically heterogeneous disease, usually occurs as a sporadic disorder due to the presence of parathyroid adenoma/s, hyperplasia or, rarely, carcinoma. In the last decades familial forms of primary hyperparathyroidism have been described. Recognizing such forms is essential for a correct clinical management of affected individual subjects and families. In fact, primary hyperparathyroidism may be the typical feature of familial syndrome or alternatively only an associated disorder within the context of a more complex syndromic picture. Several responsible genes have been so far identified, making their mutational analysis possible, which provides not only early identification of asymptomatic gene carriers, but could also add new important knowledge of the molecular mechanisms underlying parathyroid tumorigenesis. Such mechanisms could, in the near future, become an ideal target for new therapeutic strategies of primary hyperparathyroidism.
Osteoporosis and Urolithiasis
Authors: Caudarella R. , Vescini F. , Buffa A. , La Manna G. , Stefoni S.
Published: May 2004

Several studies have indicated that up to 60% of idiopathic calcium stone formers present hypercalciuria. Many authors have described reduced bone mineral density (BMD) in stoneformers with hypercalciuria, but osteopenia has also been found in normocalciuric patients. Moreover, Jaeger’s group found that bone mass was reduced in all patients with calcium stone disease, independently of hypercalciuria. Many factors may contribute to the pathogenesis of osteopenia in stone formers. A predominant role has been given to the low-calcium diet that is still prescribed in nephrolithiasis. Also slight metabolic acidosis, which is frequently present in stone formers eating a diet rich in animal protein, can contribute to bone loss. Finally, some authors described a pathogenetic role for cytokines, prostaglandins and vitamin D receptor gene polymorphisms.
Pathophysiology of Reno-Ureteral Colic
Authors: Travaglini F. , Bartoletti R. , Gacci M. , Rizzo M.
Published: May 2004

Introduction: Reno-ureteral colic presents with a complex of acute symptoms that usually indicate the presence of a stone in the collecting system, The aim of any treatment is pain relief, stone removal and preservation of kidney function. We focused our review on the pathophysiological aspects of reno-ureteral colic and, briefly, on its treatment. Materials and Methods: A complete overview of contemporary literature regarding renoureteral colic was performed by using MEDLINE and website on-line publications like EAU Guidelines. Results: Clinical presentation of renoureteral colic, of mechanisms of ureteral peristalsis and pathophysiology of renal colic is described. An overview of the available medical treatments is presented. Conclusions: An accurate comprehension of the pathophysiology of reno-ureteral colic allows the physician to tailor the best treatment for each patient.
Uric Acid, Phosphate and Oxalate Stones: Treatment and Prophylaxis
Authors: Caramia G. , Di Gregorio L. , Tarantino M.L. , Galuffo A. , Iacolino R. , Caramia M.
Published: May 2004

Medical treatment for the most commonly encountered types of renal stones is described. Nowadays treatment for uric acid stones is well-defined: alkalinizing urine is easy with drugs that are sufficiently active and well enough managed. Relapse is avoided in a high percentage of patients. Medical treatment of phosphate or calcium stones is a more open question as results are far from satisfactory compared with intra- and extra-corporeal approaches which are often minimally invasive and well accepted by both patient and urologist. Relapses are not easy to control because prophylactic measures such as changes in lifestyle and diet are never activated or because they are adopted for a brief period of time. Water therapy is examined, with the choice of water depending on the type of stone, together with drug therapy. Drugs such as citrate, with or without magnesium, and thiazides are considered excellent for curing renal stones and relapses. Although medical therapy has a limited role in many types of stones, its use is decisive in some others.
Body Weight, Diet and Water Intake in Preventing Stone Disease
Authors: Meschi Tiziana , Schianchi Tania , Ridolo Erminia , Adorni Giuditta , Allegri Franca , Guerra Angela , Novarini Almerico , Borghi Loris
Published: May 2004

Nutrition plays a major role in the pathogenesis of the most widespread forms of nephrolithiasis, i.e. calcium (calcium oxalate and phosphate) and uric acid stone disease. For this reason, dietary measures are the first level of intervention in primary prevention, as well as in secondary prevention of recurrences. An unbalanced diet or particular sensitivity to various foods in stone formers can lead to urinary alterations such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and an excessively acid urinary pH. Over the course of time, these conditions contribute to the formation or recurrence of kidney stones, due to the effect they exert on the lithogenous salt profile. The fundamental aspects of the nutritional approach to the treatment of idiopathic nephrolithiasis are body weight, diet and water intake. This paper will present data resulting from our own investigations and the most significant evidence in literature.
Pain Killers and Antibacterial Therapy for Kidney Colic and Stones
Authors: Porena Massimo , Guiggi Paolo , Balestra Antonio , Micheli Carla
Published: May 2004

In 85% of patients, renal colic is caused by renal-ureteral stones with extrinsic obstructions such as pelvic, retroperitoneal or intestinal abnormalities, and intrinsic reno-ureteral obstructions, e.g. junction pathologies and malformation, accounting for only 10 and 5%, respectively. The objectives of therapy for renal colic therapy are to eliminate pain, preserve renal function and eliminate the obstruction by the excretory pathway. Many drugs can be used to relieve pain: non-steroid anti-inflammatory agents (NSAIDs), opioid analgesics, antidiuretic hormone (ADH), loco-regional anesthesia and acupuncture. Opiates are the first-choice therapy during pregnancy as no other drug is indicated because of tetragenic potential. Paracetamol (N-acetyl-p-aminophenol) is the only NSAID that is registered for pediatric use because it has none of the adverse side effects that are associated with NSAIDs. Tamsulosin, an alpha-lithic drug, has very recently been included among the drugs that are used for stone expulsion. The rationale underlying its use is that a high concentration of α-1D adrenergic receptors has been recently detected in the terminal ureter, especially in the intramural tract. Inhibition of α-1D receptor stimulation should relax smooth muscle in the intramural ureteral tract, making stone expulsion easier.
Lithiasic Obstructive Uropathy
Authors: Magno C. , Blandino A. , Anastasi G. , Minutoli F. , Crea G. , Galì A. , Caramia M. , Melloni D.
Published: May 2004

Objectives: The purpose of this study was to evaluate the role of magnetic resonance (MR) pyelography in patients affected by hydronephrosis due to ureteric stones, in order to identify a pyonephrotic condition. Materials and Methods: In the last 3 years, 315 patients, who had originally been investigated by ultrasonography, were evaluated with MR pyelography in order to define the etiology of obstruction. In 67 patients hydronephrosis was referred as caused by lithiasis. Results: MR pyelography not only confirmed urinary tract dilatation in all patients, but also identified grade and site of obstruction, both in acute dilatation (25 patients) and in chronic obstructions (42 patients). In 7 patients, MR pyelography documented pyonephrosis that was obviously confirmed by nephrostomic drainage. Conclusion: MR pyelography, made with ultrafast breath-hold sequences, has a great value in identifying hydronephrosis in patients with ureteric stones. Furthermore, it provides the chance to identify pyonephrosis requiring an immediate drainage of the kidney before major complications develop.
ESWL: Comparing Two Analgesic Techniques
Authors: Saita A. , Bonaccorsi A. , Aquilino M. , Guzzardi F. , Lazzara A. , Motta M.
Published: May 2004

Objective: We compared the effects of intramuscular analgesia versus intramuscular analgesia associated with topical application of Luan® (gel containing lidocaine 1%) on the efficacy of extracorporeal shockwave lithotripsy (ESWL). Material and Methods: From January 2001 to November 2002, 300 patients (mean age 46) were treated for kidney or upper ureteral radiopaque stones with ESWL, using a Dornier Compact Delta magneto lithotripter. The patients were divided into two groups: group A, 180 patients, received intramuscular analgesia with Ketorolac 30 mg, Tramadolo 100 mg and, during treatment, intravenous betametasone 4 mg. Group B, 120 patients, received the same pharmacological treatment associated with topical application of Luan. Results: At 3 months, the stone-free rate in group A was 61% compared with 79% in group B. The energy of treatment was less than 13 kV in group A and less than 15 kV in group B. Conclusions: For ESWL treatment of kidney stones of 20 mm or less and ureteral stones of 15 mm or less, we suggest local analgesia with topical Luan and intramuscular analgesia. This approach increases the success rate of ESWL and reduces the discomfort associated with treatment.
Dornier Lithotripter S
Authors: Di Pietro C. , Micali S. , De Stefani S. , Celia A. , De Carne C. , Bianchi G.
Published: May 2004

Introduction: We assessed the short-term efficacy of extracorporeal shockwave lithotripsy with the Dornier Lithotripter S in the treatment of renal and ureteral stones. Materials and Methods: Between February and April 2003, 32 renal and 19 ureteral stones were treated. Patients were evaluated 1 and 3 months afterwards. Stone size and location, total number of shockwaves and the stone-free rate were taken into consideration. Results: The stone-free rate for ureteral stones was 63% at 1 month and 84.2% at 3 months. The stone-free rate for renal calculi was 75% at 1 month and 87.5% at 3 months. The overall stone-free rate was 70.6% at 1 month and 86.3% at 3 months. Analgesia was necessary in 12 patients (23.5%). No serious complications were seen, except for one steinstrasse. Conclusions: The Dornier Lithotripter S is very effective in the treatment of renal and ureteral calculi.
Comparing Two Different Ballistic Intracorporeal Lithotripters in the Management of Ureteral Stones
Authors: De Sio Marco , Autorino Riccardo , Damiano Rocco , Oliva Andrea , Perdonà Sisto , D’Armiento Massimo
Published: May 2004

Introduction: During the 1990s, two different in situ ‘ballistic’ lithotripters were introduced into clinical practice. The Swiss Lithoclast (SLC) was the first to be clinically tested. After a few years, a very similar device, the electrokinetic lithotripter (EKL), was described and has recently become available to us. In this paper we compare the clinical efficacy and features of these two ballistic lithotripters in the ureteroscopic treatment of ureteral stones. Materials and Methods: Thirty-eight patients with ureteral stones were randomized into two equal groups to undergo fragmentation using the SLC or the EKL via semirigid ureteroscope. In both groups the stones were in the mid- or lower ureter. The following parameters were evaluated: total procedure duration, complete fragmentation rate, time to complete fragmentation, proximal migration rate, complications and need for further procedures. Results: Although not statistically significant, a trend towards a higher fragmentation rate, a shorter time to fragmentation and a slightly higher proximal migration rate emerged in the SLC group. No difference was found in the stone-free rate in the two groups (94.7 vs. 89.4%). Only 2 cases of minor ureteric injury were observed in each group. Conclusions: As previously described by others, the SLC and EKL are both attractive cost-effective options in the treatment of ureteral stones. Ten years after its introduction, the SLC still remains probably the best choice for most urologists.
Expanding Applications of the Access Sheath to Ureterolithotripsy of Distal Ureteral Stones
Authors: De Sio Marco , Autorino Riccardo , Damiano Rocco , Oliva Andrea , Pane Umberto , D’Armiento Massimo
Published: May 2004

Objective: Distal ureteral stones are routinely managed with semirigid ureteroscopy without the need for ureteral dilatation, but some conditions, e.g. large stone burden or difficult catheterization of the ureteral meatus, are time-consuming and would require a tool to facilitate multiple insertions of the ureteroscope and to avoid ureteral injury. An access sheath is now available and it facilitates ureteroscopy of the upper ureter. To answer the question whether its application could be expanded to the distal ureter is the aim of our paper. Patients and Methods: 12 distal ureteral stone patients, 8 with stone size >1 cm and 4 with a large prostate, underwent ballistic ureterolithotripsy with the aid of the Access Sheath. The results of the procedure were compared to a second group of 16 patients from our archives. Results: There was no significant difference in operating time and stone-free rate. Although no complications were related to the ureteroscopy, in 42% (5 patients) of the access group the procedure could be completed only after removing the sheath. Conclusion: The Access Sheath does not improve the results of the semirigid ureteroscopy of difficult stones in the distal ureter.
Dynamism of NF-κB and AP-1 Activation in the Signal Transduction of Ischaemic Myocardial Preconditioning
Authors: Jancso G. , Lantos J. , Borsiczky B. , Szanto Z. , Rőth E.
Published: May 2004

Nuclear factor (NF)-ĸB and activation protein (AP)-1 transcription factors play an important role in the signal transduction of delayed ischaemic preconditioning (PC) leading to myocardial cytoprotection. Because the exact mechanism of the activation of these factors is still not clear, we aimed to monitor the time fluctuation of NF-ĸB and AP-1 induction in an in vivo animal model. Furthermore, we measured the induction rate of these factors using repeated cycles of PC. Following median thoracotomy, anaesthetized animals (24 New Zealand White rabbits) were subjected to ischaemic PC by occlusion of the left anterior descending coronary artery for 5 min. After 10 and 30 min, and 1, 2, 3 and 4 h of reperfusion, tissue samples were taken from the ischaemic myocardium, and the DNA binding activity of the transcription factors was measured with electrophoretic mobility shift assay. A further 12 animals were subjected to 2 ×, 3 × or 4 × 5-min ischaemic PC, and after a 30-min or 1-hour reperfusion period, we investigated the possible modulation of NF-ĸB and AP-1 induction. Our results show significant, biphasically increased NF-ĸB activity with peak levels at 30 min and 3 h of reperfusion in preconditioned myocardium. AP-1 increased monophasically, with the peak level at 1 h of reperfusion. Repeated PC stimuli enhanced the activity of both transcription factors analyzed, but there was no significant correlation between the number of cycles and the rate of activation. Our results show that the activation of NF-ĸB and AP-1 have a specific time curve, and the induction of these factors is only slightly influenced by the number of PC cycles.
Beneficial Effects of Recombinant Platelet-Activating Factor Acetylhydrolase and BN 52021 on Bacterial Translocation in Cerulein-Induced Pancreatitis
Authors: Bedirli A. , Gokahmetoglu S. , Sakrak O. , Soyuer I. , Ince O. , Sozuer E.
Published: May 2004

Background: Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after acute pancreatitis (AP). The aim of this study was to investigate the effects of the platelet-activating factor (PAF) inactivator, recombinant PAF-acetylhydrolase (rPAF-AH), and the PAF receptor antagonist, BN 52021, in AP. Methods: Forty-eight male Wistar rats were divided into 4 groups: the sham group received saline intraperitoneally every hour for 6 h; the control group received cerulein 50 g/kg i.p. every hour for 6 h; the rPAF-AH group received AP plus rPAF-AH (5 mg/kg i.v. bolus), and the BN52021 group received AP plus BN 52021 (5 mg/kg i.v. bolus). The animals were sacrificed 12 h after the first cerulein injection. Results: Supramaximal cerulein stimulation induced an increase in serum pancreatic enzymes, interleukin (IL)-6, pancreatic edema, and produced histologic evidence of AP. Compared with the control group, the addition of PAF receptor antagonists had a significant effect on serum pancreatic enzymes, pancreatic edema, and the histologic score of the pancreatitis. AP caused significant increases in BT in mesenteric lymph nodes (MLNs), pancreas, liver, spleen and blood. Compared with the control group, both rPAF-AH and BN 52021 decreased BT in the pancreas and blood. In addition, rPAF-AH decreased BT in the MLNs. We also found that PAF receptor antagonists suppressed the elevation in IL-6 levels. Conclusion: PAF antagonists attenuated the severity of experimental AP and reduced pancreatitis-induced BT to distant sites.
Local and Remote Ischemia-Reperfusion Injury Is Mitigated in Mice Overexpressing Human C1 Inhibitor
Authors: Inderbitzin D. , Beldi G. , Avital I. , Vinci G. , Candinas D.
Published: May 2004

Activation of the classical complement pathway is crucially involved in complement-mediated endothelial cell damage in ischemia-reperfusion injury. C1 inhibitor is the only known physiological inhibitor of classical complement pathway activation. Transgenic mice overexpressing human C1 inhibitor were used in a surgical lower torso and a liver ischemia-reperfusion model. Organ-specific endothelial disruption was determined by 125I-tagged albumin extravasation. In the lower torso ischemia-reperfusion model, transgenic mice overexpressing the C1 inhibitor were protected in the muscle and the lungs from endothelial cell damage. In the liver ischemia-reperfusion model, endothelial cell integrity was preserved in transgenic animals in the liver, the gut and the lungs. Our data indicate that inhibiting complement activation by a transgenic approach is effective in protection against ischemia-reperfusion injury.
In vivo and in vitro Cellular Ingrowthinto a New Generation of Artificial Ligaments
Authors: Trieb K. , Blahovec H. , Brand G. , Sabeti M. , Dominkus M. , Kotz R.
Published: May 2004

Artificial ligaments are a useful tool in ligament reconstruction. Although the new generation of artificial ligaments shows encouraging clinical results, in contrast to earlier generations studies on the biological properties are lacking. Biopsies were taken from a ligament advancement reinforcement system (LARS) 6 months after implantation and investigated by histochemistry. An in vitro study seeding human fibroblasts or osteoblast-like cells (up to 106 cells for 21 days) on ligament pieces (5 × 5 mm) was conducted and analyzed by histochemistry. The biopsies showed complete cellular and connective tissue ingrowth in the LARS ligament. In vitro fibroblasts and osteoblast-like cells encapsulated the fibers by building a cellular net around them. To our knowledge, these findings demonstrate for the first time the cellular ingrowth into the LARS ligament. This mechanism might explain the strength and the inert behavior of the ligament without the synovialitis shown in clinical studies.
Morphological Alterations in Small Intestine of Rats with Myenteric Plexus Denervation
Authors: Deniz M. , Kilinç M. , Hatipoğlu E.S.
Published: May 2004

We aimed to investigate the effect of myenteric denervation by benzalkonium chloride (BAC) on small intestine morphology in the rat, and whether segmental myenteric denervation alters morphology elsewhere in the small intestine. Forty male Sprague-Dawley rats were equally divided into 4 groups: control (0.9% NaCl); denervation (0.062% BAC); chemical inflammation (5% acetic acid), and intraluminal stasis produced by partial obstruction. 28 days after operation tissue samples were taken from the treated segment, 10 cm distal to the treated segment, and 20 cm proximal to the treated segment. Morphological changes and the number of ganglion cells were examined under the light microscope. BAC application reduced the number of myenteric neurons by 85% in the treated segment. Denervation increased villus height and crypt depth in the treated and proximal segments. But changes in muscle thickness were seen throughout the intestine. As a result, although myenteric plexus denervation caused mucosa morphology in the treated and proximal segments, it caused smooth muscle changes throughout the small intestine.
Effects of Hyperosmolar Agents – Lactulose, Lactitol, Sodium Phosphate and Polyethylene Glycol – on Cecal Coliform Bacteria during Traditional Bowel Cleansing: An Experimental Study in Rats
Authors: Demirogullari B. , Poyraz A. , Cirak M.Y. , Sonmez K. , Ozen I.O. , Kulah C. , Karabulut B. , Basaklar A.C. , Kale N.
Published: May 2004

Mechanical bowel cleansing is considered to be necessary prior to colorectal surgery, some radiological or endoscopic procedures, and for fecal disimpaction. Traditional bowel cleansing (TBC) with cathartics and enemas is a method of mechanical bowel cleansing for patients who have restrictive factors for whole-bowel irrigation (WBI), such as excessive fecal impaction, cardiac, hepatic or renal disorders. In this experimental study, TBC with hyperosmolar agents was evaluated in terms of their effects on colonic flora and bacterial translocation (BT). Sprague-Dawley rats were divided into 6 groups. The animals, except controls, were not fed for 72 h but received tap water ad libitum. During this period, lactulose, lactitol, sodium phosphate (NaP), polyethylene glycol 3350 (PEG3350) and physiological saline gavages were administered to the rats in groups 1–5, respectively, once a day. All animals except controls (group 6) received enemas with 15 ml of warm saline twice a day. The cecum, mesenteric lymph nodes (MLNs) and portal vein blood were sampled for microbiological and histopathological analysis. The highest level of coliform bacterial overgrowth and BT to MLNs were observed in the lactulose group, although the others, except the saline and control groups, also caused some degree of BT. Portal vein cultures were negative for all groups. Histopathological damage was not associated with cecal bacterial count and BT. As a result of this study, PEG3350 seems to be safer and more effective than lactulose, lactitol and NaP during TBC.
Does Botulinum Type-A Toxin Affect Motor Activity after Proctocolectomy and Ileal Pouch-Anal Anastomosis?
Authors: Willis S. , von Felbert V. , Hölzl F. , Ulmer F. , Fackeldey V. , Schumpelick V.
Published: May 2004

Aim of the Study: The use of anticholinergic drugs has provided a useful therapeutic approach to reduce stool frequency in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA). Botulinum type-A (BTA) toxin has been shown to specifically block acetylcholine release in the intestinal wall. Therefore this study investigated the effect of BTA on small intestinal and J-pouch motility after IPAA. Material and Methods: Proctocolectomy and IPAA were performed in 4 dogs. The motility of the small intestine and the ileal pouch was recorded by serosal electrodes and strain gauge transducers. The intestinal transit time was determined radiologically and pouch compliance was determined manometrically. Multiple measurements were performed before and after endoscopic injection of BTA into the pouch wall. Results: This treatment did not significantly influence stool frequency, intestinal transit time or pouch compliance. Intrinsic pouch motility was characterized by irregular contractions, the amplitudes and frequencies of which remained unchanged after BTA administration. With the exception of lower contraction amplitudes directly proximal to the pouch, there were no significant differences in the characteristics of the migrating myoelectric complex or in the fed pattern of the small intestine and ileal pouch. Conclusions: BTA does not significantly affect ileal pouch motility. The beneficial effects of anticholinergic drugs therefore seem to be due to their multifactorial mode of action and not to the inhibition of cholinergic neurons in the pouch.
Effects of Intra-Aortic Balloon Occlusion on Intestinal Perfusion, Oxygen Metabolism and Gastric Mucosal PCO2 during Experimental Hemorrhagic Shock
Authors: Cruz Jr. R.J. , Poli de Figueiredo L.F. , Bras J.L.M. , Rocha e Silva M.
Published: May 2004

Background: Aortic occlusion has been suggested for the initial treatment of severe uncontrolled hemorrhagic shock. Our objective is to determine the impact of aortic occlusion, during hemorrhagic shock, on splanchnic mucosal perfusion and to correlate these findings with other systemic and regional markers of splanchnic ischemia. Methods: Fourteen dogs (17 ± 1.7 kg) anesthetized with pentobarbital were bled to a mean arterial pressure (MAP) of 40 mm Hg. After 30 min, the animals were randomly assigned to controls (no aortic occlusion, n = 7) and transfemoral aortic occlusion (TAO) at T9 level (n = 7). Superior mesenteric artery blood flow (SMABF, ultrasonic flow probe), gastric mucosal PCO2 (gastric tonometry) and splanchnic oxygen extraction ratio (O2ERsplanc) were evaluated for 120 min. Results:Hemorrhage caused a marked reduction in SMABF and increases in PCO2-gap and O2ERsplanc in both groups. TAO significantly improved MAP and further increased the PCO2-gap and O2ERsplanc, with a decreased SMABF. After reperfusion, SMABF, MAP and O2ERsplanc returned to pre-occlusion values, although the PCO2-gap remained higher in the TAO group. Conclusion: Aortic occlusion promotes blood pressure restoration with an additional insult to mucosal perfusion, which could be adequately predicted by global and/or splanchnic oxygen-derived variables during ischemia, but not during the early reperfusion period.
Devascularization Surgical Model of Acute Liver Failure in Minipigs
Authors: Ryska M. , Kieslichová E. , Pantoflíček T. , Ryska O. , Zazula R. , Skibová J. , Hájek M.
Published: May 2004

Aim: The study was designed to develop a readily reproducible model of acute liver failure (ALF) in the minipig, to gain an 8-hour therapeutic window to mimic, as closely as possible, acute liver failure in man. Method: We used reversible devascularization model of ALF in the minipig involving hepatic artery ligation and establish an end-to-side portocaval anastomosis. Standard laboratory monitoring was complemented with intracranial pressure (ICP) measurement. Material: Twenty minipigs (weight 25–30 kg) were used for the experiment. The animals were divided into 3 groups: I: 10 animals in an experimental group with ALF; II: 5 animals in an experimental group with ALF and ICP measurement, and III: 5 animals in a control group without ALF. Results: Laboratory testing has shown the significant changes in levels of AST (33.44 ± 39.96 vs. 1.56 ± 0.50 mmol/l), lactate (2.97 ± 1.16 vs. 1.18 ± 0.61 mmol/l), and ammonia (264.3 ± 93.05 vs. 42.5 ± 12.98 mmol/l) between ALF groups and controls (p < 001) 6 h after the operative procedure, and significant changes in hypoglycemia and intracranial pressure were found 4 h after the operative procedure. The difference in Quick values (67.4 ± 17.03 vs. 75.2 ± 2.68) was not significant. We assume that the therapeutic window starts 4 h after the beginning of the experiment. Conclusion: Our devascularization model of ALF is simple and readily reproducible. The therapeutic window occurring shortly after surgery and persisting for a mean 9 h is suitable to evaluate bioartificial liver devices.
Selecting Loop Breakers in General Pedigrees
Authors: Vitezica Zulma G. , Mongeau Marcel , Manfredi Eduardo , Elsen Jean-Michel
Published: May 2004

The presence of loops in pedigrees poses severe computational problems in likelihood calculation that can be solved by creating an equivalent unlooped pedigree. We introduce a heuristic polynomial-time dynamic-programming algorithm, called SFH, that addresses the problem of selecting a minimal-cost set of loop breakers. We report computational experiments on simulated pedigrees with up to 1000 individuals and 361 loops, and multiple marriages. We compare the loop-breaker set selected by our method with that obtained using the software package FASTLINK 4.1P. Our approach outperforms FASTLINK 4.1P on the computational-time point of view, on the point of view of quality of the loop-breaker set obtained, and on the point of view of the size of the problem that can be addressed.
Examination of Potential Overlap in Autism and Language Loci on Chromosomes 2, 7, and 13 in Two Independent Samples Ascertained for Specific Language Impairment
Authors: Bartlett Christopher W. , Flax Judy F. , Logue Mark W. , Smith Brett J. , Vieland Veronica J. , Tallal Paula , Brzustowicz Linda M.
Published: May 2004

Specific language impairment is a neurodevelopmental disorder characterized by impairments essentially restricted to the domain of language and language learning skills. This contrasts with autism, which is a pervasive developmental disorder defined by multiple impairments in language, social reciprocity, narrow interests and/or repetitive behaviors. Genetic linkage studies and family data suggest that the two disorders may have genetic components in common. Two samples, from Canada and the US, selected for specific language impairment were genotyped at loci where such common genes are likely to reside. Significant evidence for linkage was previously observed at chromosome 13q21 in our Canadian sample (HLOD 3.56) and was confirmed in our US sample (HLOD 2.61). Using the posterior probability of linkage (PPL) to combine evidence for linkage across the two samples yielded a PPL over 92%. Two additional loci on chromosome 2 and 7 showed weak evidence for linkage. However, a marker in the cystic fibrosis transmembrane conductance regulator (7q31) showed evidence for association to SLI, confirming results from another group (O’Brien et al. 2003). Our results indicate that using samples selected for components of the autism phenotype may be a useful adjunct to autism genetics.
Power Loss for Linkage Analysis due to the Dichotomization of Trichotomous Phenotypes
Authors: Corbett Jonathan , Gu C. Charles , Rice John P. , Reich Theodore , Province Michael A. , Rao D.C.
Published: May 2004

Objectives: Some traits, while naturally polychotomous, are routinely dichotomized for genetic analysis. Dichotomization, intuitively, leads to a loss of power to detect linkage, as some phenotypic variability is discarded. This paper examines this power loss in the context of a trichotomous trait. Methods: To examine this power loss, we performed a simulation study where a trichotomous trait was simulated in a sample of 1,000 sib-pairs under various genetic models. The study was replicated 1,000 times. Linkage analysis using a variance components method, as implemented in Mx, was then performed on the trichotomous trait and compared with that on a dichotomized version of the trait. Results: A comparison of the power and false positive rates of the analyses shows that power to detect linkage was increased by up to 22 percentage points simply by examining the trait as a trichotomy instead of a dichotomy. Under all models examined, the trichotomous analysis outperformed the dichotomous version. Conclusions: Comparable levels of false positive rates under both methods confirm that this power gain comes solely from the information lost upon dichotomization. Thus, dichotomizing tri- or poly-chotomous traits can lead to crippling power loss, especially in the case of many loci of small effect.
Multilocus Analysis of Hypertension: A Hierarchical Approach
Authors: Williams Scott M. , Ritchie Marylyn D. , Phillips III John A. , Dawson Elliot , Prince Melissa , Dzhura Elvira , Willis Alecia , Semenya Amma , Summar Marshall , White Bill C. , Addy Jonathan H. , Kpodonu John , Wong Lee-Jun , Felder Robin A. , Jose Pedro A. , Moore Jason H.
Published: May 2004

While hypertension is a complex disease with a well-documented genetic component, genetic studies often fail to replicate findings. One possibility for such inconsistency is that the underlying genetics of hypertension is not based on single genes of major effect, but on interactions among genes. To test this hypothesis, we studied both single locus and multilocus effects, using a case-control design of subjects from Ghana. Thirteen polymorphisms in eight candidate genes were studied. Each candidate gene has been shown to play a physiological role in blood pressure regulation and affects one of four pathways that modulate blood pressure: vasoconstriction (angiotensinogen, angiotensin converting enzyme – ACE, angiotensin II receptor), nitric oxide (NO) dependent and NO independent vasodilation pathways and sodium balance (G protein-coupled receptor kinase, GRK4). We evaluated single site allelic and genotypic associations, multilocus genotype equilibrium and multilocus genotype associations, using multifactor dimensionality reduction (MDR). For MDR, we performed systematic reanalysis of the data to address the role of various physiological pathways. We found no significant single site associations, but the hypertensive class deviated significantly from genotype equilibrium in more than 25% of all multilocus comparisons (2,162 of 8,178), whereas the normotensive class rarely did (11 of 8,178). The MDR analysis identified a two-locus model including ACE and GRK4 that successfully predicted blood pressure phenotype 70.5% of the time. Thus, our data indicate epistatic interactions play a major role in hypertension susceptibility. Our data also support a model where multiple pathways need to be affected in order to predispose to hypertension.
Percentiles of the Null Distribution of 2 Maximum Lod Score Tests
Authors: Ulgen Ayse , Yoo Yun Joo , Gordon Derek , Finch Stephen J. , Mendell Nancy R.
Published: May 2004

We here consider the null distribution of the maximum lod score (LOD-M) obtained upon maximizing over transmission model parameters (penetrance values, dominance, and allele frequency) as well as the recombination fraction. Also considered is the lod score maximized over a fixed choice of genetic model parameters and recombination-fraction values set prior to the analysis (MMLS) as proposed by Hodge et al. [1]. The objective is to fit parametric distributions to MMLS and LOD-M. Our results are based on 3,600 simulations of samples of n = 100 nuclear families ascertained for having one affected member and at least one other sibling available for linkage analysis. Each null distribution is approximately a mixture p2₀ + (1 – p)2v. The values of MMLS appear to fit the mixture 0.202₀ + 0.80χ21.6. The mixture distribution 0.132₀ + 0.87χ22.8. appears to describe the null distribution of LOD-M. From these results we derive a simple method for obtaining critical values of LOD-M and MMLS.
Powerful Allele Sharing Statistics for Nonparametric Linkage Analysis
Authors: Lange Ethan M. , Lange Kenneth
Published: May 2004

Nonparametric linkage analysis is widely used to map susceptibility genes for complex diseases. This paper introduces six nonparametric statistics for measuring marker allele sharing among the affected members of a pedigree. We compare the power of these new statistics and three previous statistics to detect linkage with Mendelian diseases having recessive, additive, and dominant modes of inheritance. The nine statistics represent all possible combinations of three different IBD scoring functions and three different schemes for sampling genes among affecteds. Our results strongly suggest that the statistic Trecblocks is best for recessive traits, while the two statistics Tkinpairs and Tallkin vie for best for an additive trait. The best statistic for a dominant trait is less clear. The statistics Tkinpairs and Tallkin are equally promising for small sibships, but in extended pedigrees the statistics Tdomblocks and Tdompairs appear best. For a complex trait, we advocate computing several of these statistics.
Pulmonary Function Testing in Interstitial Lung Diseases
Authors: Chetta Alfredo , Marangio Emilio , Olivieri Dario
Published: May 2004

Interstitial lung diseases (ILDs) are functionally characterized by a restrictive ventilatory defect due to a reduced distensibility of the lung parenchyma. ILD patients also show a reduced exercise tolerance, the main factors limiting exercise capacity being ventilatory and gas exchange abnormalities. Functional abnormalities in ILDs are typical, but not specific. Despite the fact that different lung function patterns have been described among ILDs, they overlap and their practical application to differentiate ILDs is poor. Resting pulmonary function and exercise-induced hypoxemia can aid in defining the prognosis of ILDs and in referring patients for lung transplantation. Additionally, spirometry and diffusing capacity are useful to monitor the response of patients to therapy.
Metalloproteinase-9 in Induced Sputum Correlates with the Severity of the Late Allergen-Induced Asthmatic Response
Authors: Boulay Marie-Eve , Prince Philippe , Deschesnes Francine , Chakir Jamila , Boulet Louis-Philippe
Published: May 2004

Background: Asthma is characterized by airway inflammation and remodeling in which matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) play an important role. Allergen exposure activates the inflammatory/repair process in sensitized subjects. Induced-sputum analysis is a non-invasive method that allows the assessment of changes in inflammatory and remodeling mediators implicated in asthma. Objectives: To evaluate the changes in MMP-9 and its principal inhibitor (TIMP-1) in sputum and plasma of mild allergic asthmatic subjects after whole-lung allergen challenge. Methods: Induced sputum and blood samples were obtained at baseline, and 6 and 24 h after challenge. MMP-9 and TIMP-1 levels in sputum and plasma were measured by ELISA. Results: Allergen challenge increased the percentage of sputum eosinophils and MMP-9 levels 6 and 24 h after the challenge compared to baseline levels, but TIMP-1 levels did not vary significantly. A significant correlation was observed between MMP-9 levels at 6 h and the maximum percent fall in FEV1 during the late response. Throughout the study, MMP-9 levels correlated significantly with the number of neutrophils in sputum. Conclusions: This study shows that analysis of induced sputum is a useful tool to study the variations in MMP-9 and TIMP-1 levels following allergen challenge, therefore allowing to evaluate their role in allergen-induced airway damage and repair.
The Position of Pranlukast, a Cysteinyl Leukotriene Receptor Antagonist, in the Long-Term Treatment of Asthma
Authors: Obase Yasushi , Shimoda Terufumi , Matsuse Hiroto , Kondo Yuki , Machida Ikuko , Kawano Tetsuya , Saeki Sachiko , Tomari Shinya , Mitsuta-Izaki Kazuko , Matsuo Nobuko , Fukushima Chizu , Kohno Shigeru
Published: May 2004

Background: Adverse effects, tachyphylaxis, and the position of pranlukast, a cysteinyl leukotriene receptor antagonist, in asthma treatment have not been fully established. Objectives and Methods: To address these questions, adverse effects and long-term efficacy of pranlukast were evaluated in 82 patients [28 patients with moderate asthma (group I), 27 with severe persistent asthma not on oral corticosteroid (OCS; group II) and 27 with severe persistent asthma on OCS (group III)] at 4 and 16 weeks. In the following, pranlukast was either withdrawn 1 year after the start of therapy, or if that was not possible due to reappearance of symptoms, the dose of OCS or inhaled corticosteroid (ICS) was reduced. The efficacy of pranlukast was evaluated during 5 years by peak expiratory flow rate (PEFR), and symptom and treatment scores. Results: Adverse reactions appeared in 4 patients (4.9%; diarrhea, dizziness and leg edema). The mean improvement in PEFR on week 16 was 18.5 ± 2.3, 18.8 ± 3.2, and 15.2 ± 3.8% in groups I–III, respectively (p < 0.01, for all groups). However, increases in PEFR in 29 of 72 patients (40.3%) were less than 15%. Pranlukast could not be withdrawn in 28 of 42 responders (66.7%), but their dose of ICS was reduced by 363 ± 97 µg/day (group II) and that of OCS by 3.4 ± 0.7 mg/day (group III). Tachyphylaxis was not recognized during the 5-year period. Conclusion: Pranlukast is safe when taken for up to 5 years, and is effective irrespective of asthma severity. In the majority of patients with persistent asthma, pranlukast may help to control the disease in the long term.
Long-Term Deterioration of Lung Function in Asthmatic Outpatients
Authors: Kupczyk Maciej , Kupryś Izabela , Górski Paweł , Kuna Piotr
Published: May 2004

Background: Although the long-term deterioration of lung function in asthmatic patients has been described, the exact mechanism remains to be determined. Objectives: The aim of this study was to find correlations between age, sex, atopic status, duration of asthma, asthma severity and the decline in pulmonary function. Method: The medical histories of 1,006 randomly chosen asthmatic outpatients were studied and retrospective data on asthma duration, spirometry results, treatment and symptomatology were gathered. A screening spirometry was performed. Results: 598 women and 408 men (age: 44.59, range 12–95 years) participated in the study. Intermittent asthma was diagnosed in 35.4%, chronic mild asthma in 33.4%, moderate asthma in 23.8% and severe asthma in 7.45% of the patients. Statistically significant correlations between patient age, asthma duration and lung function measurements were found. Linear regression revealed the following differences in lung functions per year of asthma duration: FEV1: –0.882% of predicted; FVC: –0.509% of predicted; FEV1/FVC: –0.324% of predicted. The unadjusted annual decline was 80.1 ml/year (p = 0.00003) in FEV1 and 20.5 ml/year (p = 0.036) in FVC. A multiple regression model revealed that asthma severity appears to be the strongest factor influencing pulmonary function (β = –0.55, p < 0.001 for FEV1). Also, significant associations between pulmonary function measurements, patient age, atopic status and male sex were noted. Conclusions: The results of this large cohort study show that asthmatic patients develop a progressive decline in pulmonary function correlated with age, sex, duration of asthma and asthma severity. Early diagnosis and intervention is necessary to ameliorate any potential negative impact of asthma on lung function.
Decreased Serum Levels of P-Selectin and Eosinophil Cationic Protein in Patients with Mild Asthma after Inhaled Salbutamol
Authors: Sjöswärd Kerstin Naidu , Uppugunduri Srinivas , Schmekel Birgitta
Published: May 2004

Background: Asthma is a chronic inflammatory disease of the airways associated with selective recruitment of activated eosinophils. P-selectin, a cell adhesion molecule, may be an important controller of the inflammation by mediating selective eosinophil cell influx to the lung. Serum levels of eosinophil cationic protein (ECP) have been used as a marker of eosinophil inflammation, and indirectly as a marker of disease activity of asthma. ECP levels may not be elevated in some patients with asthma, and this fact prompted us to search for additional surrogate markers for monitoring disease activity in asthma. Objectives: To evaluate whether repeated inhalations of salbutamol, a β-2-receptor agonist used for bronchodilation, would lead to reduced serum levels of P-selectin and/or ECP. Methods: Fourteen patients with asymptomatic mild stable asthma were enrolled into a randomised crossover study. Salbutamol was inhaled three times every 3 h. Blood was sampled 4 h after the last inhalation. Nine non-treated healthy volunteers served as control subjects. Serum ECP and P-selectin levels were measured using radioimmunoassay and ELISA, respectively. Results: P-selectin and ECP levels in serum obtained from asymptomatic asthmatics were close to those of the volunteers, and inter-day variability tended to be lower for levels of P-selectin than for ECP. Significant decreases of P-selectin (p = 0.01) and ECP (p = 0.03) were recorded after salbutamol inhalation. There was no association between the changes in ECP and P-selectin levels in serum. Conclusions: We conclude that decreases in P-selectin and ECP may have different kinetics, suggesting different pathways of action of salbutamol. We judge that P-selectin may be used as a sensitive marker in mild asthma.