bluuebunny/crossref_metadata_2025 huggingface dataset:
Further evidence for the role of free radicals in the limb teratogenicity of L‐NAME
Authors: Fantel Alan G. , Person Richard E.
Published: August 2002

Background

L‐NAME (NG‐nitro‐L‐arginine methyl ester), a nitric oxide synthase inhibitor, causes severe limb reduction malformations when gravid rats are treated intraperitoneally on gd‐17. Hemorrhages, appearing within hours of L‐NAME administration, and defects at term can be significantly reduced by co‐treatment with PBN (α‐phenyl‐N‐t‐butylnitrone), a spin trap antioxidant. We have proposed that limb defects result from ischemia‐reperfusion injury. We examine the role of xanthine oxidase and ROS formation in the limb effects of L‐NAME.

Methods

Gravidas were treated with L‐NAME (50 mg/kg) in the presence or absence of allopurinol, a xanthine oxidase inhibitor. Spatial patterns of limb hemorrhage were determined promptly and at term as was digit length at the latter interval. Xanthine oxidase activities were assayed in control and treated limbs with and without allopurinol co‐treatment.

Results

Allopurinol significantly reduced hemorrhage severity in a dose‐responsive fashion when fetuses were examined at term. Higher doses of allopurinol significantly preserved digit length. Xanthine oxidase activities in fetal limb were significantly increased by L‐NAME treatment whereas co‐treatment with allopurinol restored activities to near‐control levels.

Conclusions

These findings support the role of excess reactive oxygen species (ROS) formation in L‐NAME‐induced limb reduction. We propose that nitric oxide (NO) depletion by L‐NAME interferes with vascular integrity, and causes vasoconstriction. Resultant hypoxia stimulates superoxide formation and nitric oxide formation catalyzed by the inducible isoform of nitric oxide synthase. The reduction products of superoxide or the products of its reaction with nitric oxide oxidize or nitrate endothelial components resulting in limb reduction defects. Teratology 66:24–32, 2002. © 2002 Wiley‐Liss, Inc.
E‐business model design, classification, and measurements
Authors: Dubosson‐Torbay Magali , Osterwalder Alexander , Pigneur Yves
Published: August 2002

“Business model” is one of the latest buzzwords in the Internet and electronic business world.
This article has the ambition to give this term a more rigorous content. The objective is threefold. The first
objective is to propose a theoretical e‐business model framework for doing business in the Internet era.
The second is to propose a multidimensional classification‐scheme for e‐Business Models, as opposed
to the actual tendency in academic literature to use two‐dimensional classifications. The final objective
is to define critical success factors, based on a field study in order to find out and compare the performance
indicators used by e‐business firms that are competing with similar business models. © 2002 John
Wiley & Sons, Inc.
Toxicology of a Microcystis ichthyoblabe waterbloom from Lake Oued Mellah (Morocco)
Authors: Sabour Brahim , Loudiki Mohammed , Oudra Brahim , Vasconcelos Vitor , Martins Rosario , Oubraim Said , Fawzi Brahim
Published: August 2002

In the Lake Oued Mellah cyanobacteria waterblooms occur periodically in late spring and summer with Microcystis ichthyoblabe as the main bloom‐forming species. In 1999, a heavy waterbloom of M. ichthyoblabe occurred during May June with a maximal biomass of 298 mg/l. During this period, several bloom samples were collected. The toxicity assessment was done by mouse and brine shrimp (Artemia) bioassays. Apart from the sample collected on 15/06/1999, all the other samples were toxic by mouse bioassay. The LD50 determined by intraperitoneal injection to mice during active cyanobacterial growth and decline phases were 518 and 1924 mgDW/kg respectively. Using Artemia bioassay, the 24hLC50 varied from 6.0 to 40.6 mg/ml and the 48hLC50 ranged from 2.8 to 18.2 mg/ml. The separation and identification of microcystin variants was performed by high performance liquid chromatography–photodiode array detection. Eleven toxins were separated and preliminarily identified as microcystin variants as they exhibit a typical UV spectra like the microcystin‐LR standard. The quantification of total microcystins determined by enzyme‐linked immunosorbent assay showed that the contents were varied between 0.1 and 0.76 μg/g DW. © 2002 by Wiley Periodicals, Inc. Environ Toxicol 17: 24–31, 2002
Inhibition of sulfate‐reducing bacteria by metal sulfide formation in bioremediation of acid mine drainage
Authors: Utgikar Vivek P. , Harmon Stephen M. , Chaudhary Navendu , Tabak Henry H. , Govind Rakesh , Haines John R.
Published: August 2002

Acid mine drainage (AMD) containing high concentrations of sulfate and heavy metal ions can be treated by biological sulfate reduction. It has been reported that the effect of heavy metals on sulfate‐reducing bacteria (SRB) can be stimulatory at lower concentrations and toxic/inhibitory at higher concentrations. The quantification of the toxic/inhibitory effect of dissolved heavy metals is critical for the design and operation of an effective AMD bioremediation process. Serum bottle and batch reactor studies on metal toxicity to SRB indicate that insoluble metal sulfides can inhibit the SRB activity as well. The mechanism of inhibition is postulated to be external to the bacterial cell. The experimental data indicate that the metal sulfides formed due to the reaction between the dissolved metal and biogenic sulfide act as barriers preventing the access of the reactants (sulfate, organic matter) to the necessary enzymes. Scanning electron micrographs of the SRB cultures exposed to copper and zinc provide supporting evidence for this hypothesis. The SRB cultures retained their ability to effect sulfate reduction indicating that the metal sulfides were not lethally toxic to the SRB. This phenomenon of metal sulfide inhibition of the SRB has to be taken into account while designing a sulfate‐reducing bioreator, and subsequently an efficient biotreatment strategy for AMD. Any metal sulfide formed in the bioreactor needs to be removed immediately from the system to maintain the efficiency of the process of sulfate reduction. © 2002 by Wiley Periodicals, Inc. Environ Toxicol 17: 40–48, 2002
Theoretical study of a secondary target XRF setup at different operational tube voltages
Authors: Zarkadas Ch. , Karydas A. G. , Paradellis Th.
Published: August 2002

An algorithm was developed that allows a theoretical step‐by‐step study of secondary target XRF setups for different combinations of anode materials, secondary targets and operating tube voltages. By use of three different descriptions of x‐ray tube spectral distributions, the qualitative and quantitative characteristics of the x‐ray beam after the secondary target are examined. Calculations are presented for different combinations of anode material and secondary target such as YMo, MoMo, RhMo and WMo. Additionally, universal functional relationships of the secondary target characteristic line intensities with respect to the operational voltage are presented. These relationships can be applied to any XRF setup that includes an x‐ray diffraction tube and a secondary target. Copyright © 2001 John Wiley & Sons, Ltd.
Cdc4 is involved in the transcriptional control of OCH1, a gene encoding α‐1,6‐mannosyltransferase in Saccharomyces cerevisiae
Authors: Cui Zhifeng , Horecka Joe , Jigami Yoshifumi
Published: August 2002

The Saccharomyces cerevisiae OCH1 gene encodes an α‐1,6‐mannosyltransferase that initiates the polymannose outer chain elongation of N‐linked glycans. Transcription of OCH1 is regulated by two transcription factors, Swi4 and Skn7. To learn more about the signals that feed into the Swi4 regulation, we isolated a mutant, bon1‐1 (bypass of Skn7), that activates OCH1–HIS3 and OCH1–lacZ reporters in a strain deleted for SKN7. bon1‐1 is an allele of CDC4 (cdc4bon) and leads to the additional phenotypes of temperature sensitivity and abnormal cell morphology. The cdc4bon mutant is partially suppressed by CLB5 overexpression and accumulates Sic1 protein, indicating that OCH1 transcription is controlled by the ubiquitin‐dependent degradation pathway through the Skp1–Cdc53–F boxCdc4 protein complex. We suggest that transcriptional control of OCH1 by cdc4bon is through Swi4, because cdc4bon cannot activate the OCH1–lacZ reporter in a strain deleted for SWI4. Interestingly, cdc4bon and Δswi4 show a synthetic growth defect when combined. Copyright © 2002 John Wiley & Sons, Ltd.
Application of a noninvasive, PCR‐based test for sex identification in an endangered parrot, Amazona guildingii
Authors: Russello Michael A. , Amato George
Published: August 2002

The St. Vincent Amazon Parrot Consortium was established during the 1980s in an effort to cooperatively manage the captive population of the St. Vincent parrot (Amazona guildingii) and support conservation of the wild population. Ex situ management of A. guildingii has been hindered by the sexual monomorphism of the group, mediated in the past through the use of time‐consuming, expert‐driven, and sometimes hazardous sexing procedures. In this article, we apply a noninvasive, molecular sexing technique, using the polymerase chain reaction (PCR) and DNA from a single feather tip to the captive populations of A. guildingii residing on St. Vincent (66 individuals) and Barbados (13 individuals). This study allowed for the rapid assessment of gender, while posing no threat to individual health, and will facilitate the efforts of the consortium breeding programs in the United States, Europe and on the islands of St. Vincent and Barbados. Zoo Biol 20:41–45, 2001. © 2001 Wiley‐Liss, Inc.
A novel inserter instrument (Crossbow) for installation of self‐reinforced bioabsorbable arrows into meniscus tissue
Authors: Törmälä P. , Karhi O. , Koho P. , Tamminmäki M.
Published: August 2002

A novel inserter, Crossbow, was developed for arthroscopic installation of self‐reinforced bioabsorbable meniscus arrows into meniscus tissue. The Crossbow comprises a reservoir cartridge for up to four arrows, a triggering mechanism, and an interchangeable (curved or straight) trocar for guiding and installation of an arrow. A randomized biomechanical study was carried out by installing 13‐mm‐long meniscus arrows into fresh porcine menisci with the Crossbow and with the standard manual inserter trocar system. The mean pull‐out force for Crossbow‐installed arrows was 56.8±14.2 N, and that for arrows installed with the manual system was 43.7±13.8 N; the difference was statistically significant. While Crossbow is easy and rapid to use and gives good grip of arrows into pig meniscus, it may be an attractive alternative instrument to treat bucket‐handle lesions of the menisci arthroscopically.
Smoking Is a Risk Factor for Recurrence of Groin Hernia
Authors: Tue Sorensen Lars , Friis Esbern , Jorgensen Torben , Vennits Bo , Ristorp Andersen Betina , Iben Rasmussen Gitte , Kjaergaard Johan
Published: August 2002

Studies of connective tissue from patients with inguinal hernia have shown that smoking may be associated with hernia formation due to a defective connective tissue metabolism.
Whether smoking is a risk factor for recurrence, too, was examined in this study. From December 1990 through December 1995, 649 patients underwent hernia repair as open sutured repair (Cooper ligament or abdominal ring repair) or as open mesh repair. Five hundred forty‐four eligible patients were evaluated for recurrence 2 years postoperatively. Association between recurrence and 17 patient‐,
disease‐, and intraoperative variables were analyzed by multiple logistic regression. The results showed that smoking was significantly and independently associated with recurrence compared to nonsmoking
[odds ratio (OR = 2.22; 95% confidence interval (95% CI) =
1.19–4.15)]. Open sutured repair compared to open mesh repair was the most significant predictor for recurrence (OR = 7.23; 95% CI
= 3.01–17.37). Surprisingly, local anesthesia was associated with a higher risk of recurrence compared to general anesthesia (OR =
2.44; 95% CI = 1.19–5.09). Potential confounders and other risk factors for hernia recurrence such as age, alcohol consumption,
previous surgery, and anatomical characteristics of the hernia were adjusted for in the analysis. In conclusion, smoking is an important risk factor for recurrence of groin hernia, presumably due to an abnormal connective tissue metabolism in smokers.
Prostatitis: The Last Frontier
Authors: Nickel J. Curtis
Published: August 2002

Abstract

Prostatitis, the neglected third disease (after benign prostatic hypertrophy and prostate cancer) is the last frontier of prostate disease. Innovative new research and clinical initiatives have revived urologists' interest in this difficult and frustrating disease. New funding initiatives, industry interest and powerful patient lobby groups have put this long‐neglected syndrome back on the urologic agenda. Presented here is an inventory of what is and is not known about prostatitis. It is based on a review of the literature, undisputed facts, solid hypotheses, and common sense. Also offered is a series of personal challenges to the urologic community. As we enter the twenty‐first century we must develop a rational management strategy for patients who present with symptoms of prostatitis.
Access Routes for Nutritional Therapy
Authors: Waitzberg Dan L. , Plopper Caio , Terra Ricardo M.
Published: August 2002

Enteral nutrition (EN) and total parenteral nutrition (TPN) may provide life‐sustaining therapy for surgical patients. The duration of nutritional therapy (enteral or parenteral) implies distinct access routes. We review the main aspects related to access routes for nutrient delivery. The enteral route, whenever feasible, is preferred. For EN lasting less than 6 weeks, nasoenteric tubes are the route of choice. Conversely, enterostomy tubes should be used for longer‐term enteral feeding and can be placed surgically or with fluoroscopic and endoscopic assistance. The first choice for patients who will not be submitted to laparotomy is percutaneous endoscopic gastrostomy. Postpyloric access, although not consensual, must be considered when there is a high risk of aspiration. For intravenous delivery of nutrients lasting less than 10 days, the peripheral route can be used. However, because of frequent infusion phlebitis, its role is still in discussion. Central venous catheters (CVCs) for TPN delivery may be (1) nonimplantable, percutaneous, nontunneled—used for a few days to 3 to 4 weeks; (2) partially implantable, percutaneous, tunneled—used for longer periods and permanent access; or (3) totally implantable subcutaneous ports—also used for long‐term or permanent access. The subclavian vein is usually the insertion site of choice for central venous catheters. Implantable ports are associated with lower rates of septic complications than percutaneous CVCs. The catheter with the least number of necessary lumens should be applied. Central venous nutrient delivery can also be accomplished through peripherally inserted central catheters, which avoid insertion‐related risks.
Clinical Relevance of Vascular Endothelial Growth Factor for Thyroid Neoplasms
Authors: Huang Shih‐Ming , Lee Jeng‐Chang , Wu Ta‐Jen , Chow Nan‐Haw
Published: August 2002

Angiogenesis is of vital importance during the development and progression of solid tumors. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and could be produced by some cancer cells. To investigate the clinical relevance of VEGF in the tumorigenesis of human thyroid, an immunohistochemical study was performed on archival materials of follicular adenomas (n= 13), Hürthle cell adenomas (n= 6), papillary carcinomas (n= 76), follicular carcinomas (n= 12), Hürthle cell carcinomas (n= 2), and anaplastic carcinomas (n= 8). Patterns of VEGF expression were analyzed in relation to histologic subtypes of thyroid tumors and were correlated to biologic indicators of papillary carcinoma. All papillary carcinomas and Hürthle cell neoplasms revealed a strong, diffuse staining reaction, whereas anaplastic carcinoma usually exhibited weak and infrequent immunoreactivity. VEGF levels were usually higher in follicular adenomas than in follicular carcinomas. With regard to prognostic value, VEGF expression did not correlate with tumor size, extent of invasion, or scores on the AGES system (i.e., patient age, tumor size, histologic grade, tumor extent, distant metastasis) or the MACIS system (i.e., metastasis, age, completeness of resection, invasion, tumor size) for papillary carcinomas (p > 0.05, respectively). The results of the current study indicate that VEGF may play a role in the development of human thyroid cancer. Determination of the angiogenic phenotype may have limited prognostic value for patients with papillary carcinoma.
Use of Monoclonal Antibodies in Colorectal Cancer: A Review
Authors: Schulte William J.
Published: August 2002

This is a review article covering the development of monoclonal antibodies attached to a radioactive isotope which are used in scanning for metastatic adenocarcinoma of the colon. The most recent and complete study described 223 patients, of which 169 were evaluated. All patients required an operation. At operation, biopsies were taken of the resected tumor. Some false negative areas, such as dilated varicosities and inflammatory areas, were encountered. The latter can be seen as a chronic inflammatory process such as a leaking anastomosis with a diverticulum or old traumas in the pelvis. This technique allows a physician to follow patients, especially those who have had an abdominal perineal or exoneration of their pelvic organs, for possible recurrence in this area. There is also some discussion about possible future uses in the treatment of the metastatic disease.
Prevention and Therapy of Multiple Organ Failure
Authors: Vincent Jean‐Louis
Published: August 2002

Multiple organ failure (MOF) stems from a complex interaction between the host’s immune response and inadequate tissue perfusion. Prevention of MOF therefore addresses these two components. The risk of inflammation is reduced through treatment of any infection and early stabilization of traumatized regions. Adequate respiratory and cardiocirculatory resuscitation is achieved to restore and maintain tissue perfusion. Although a supranormal cardiac output is often indicated, it is difficult to define precise endpoints for hemodynamic stabilization. Instead of increasing the oxygen supply to supranormal values in all patients, it is probably safer and more effective to increase it only in those patients for whom persistent ischemia is suspected. Provision of adequate nutritional support is important, and whenever possible the enteral route is preferred. Once MOF has developed, treatment turns to support of individual organs. Unfortunately, there is no single treatment for MOF that seems to reverse the associated trend of high mortality. Survival is more likely when the cause of MOF can be found and eliminated.
Protection of the Gastroduodenal Mucosa from the Effects of Diclofenac Sodium: Role of Highly Selective Vagotomy and Misoprostol
Authors: Giannoukas Athanasios D. , Baltoyiannis Georgios , Milonakis Manolis , Nastos Dimitrios , Papagikos Lambros , Kappas Angelos M. , Fatouros Michalis , Papadimitriou Constantinos , Cassioumis Diamantis
Published: August 2002

The aim of this study was to determine the effectiveness of highly selective vagotomy (HSV) or misoprostol, a prostaglandin E1 (PGE1) analog, for protecting the gastroduodenal mucosa (GDM) from the effects of diclofenac sodium (DS). Fifty mongrel dogs were randomly allocated to five groups. HSV alone was performed in group I dogs (controls) to standardize the operation. DS was given intramuscularly for 12 consecutive days to the group II dogs, whereas in the group III dogs HSV was performed, followed a month later by DS administration, as in group II. DS was given in combination with misoprostol for 12 days to the group IV dogs. HSV was performed on the group V dogs, and a month later DS and misoprostol were given, as in group IV. After sacrificing the animals the GDM was examined for macroscopic and histologic lesions. Statistical analysis was made by Fisher’s exact test. HSV alone did not protect the gastric or duodenal mucosa from the effects of DS (p= 0.474 andp= 0.62, respectively). Misoprostol alone also did not offer significant protection to the gastric or the duodenal mucosa (p= 0.08 andp= 0.65, respectively). The combination of HSV plus misoprostol protected the gastric mucosa (group V,p= 0.007) but not the duodenal mucosa (group V,p= 0.08). Hence HSV or misoprostol alone offers no protection to the GDM from the effects of DS. The combination of HSV and misoprostol offers significant protection only to gastric mucosa. Enhancement of the mucosal defense mechanisms combined with strong reduction of gastric acidity may offer adequate protection to gastric mucosa from the effects of nonsteroidal antiinflammatory drugs.
Effect of Growth Factors on Growth of Bovine Parathyroid Cells in Serum‐Free Medium
Authors: Sadler Gregory P. , Jones Derek L. , Woodhead J. Stuart , Horgan Kieran , Wheeler Malcolm H.
Published: August 2002

Published work has suggested a possible role of the epidermal growth factor receptor (EGFr) in parathyroid disease. Bovine parathyroid cells (BPCs) are frequently used as a tissue model for studying parathyroid disorders. We have studied the effect of the EGFr ligands EGF and transforming growth factor α (TGFα), alone and with insulin‐like growth factors IGF‐I and IGF‐II on BPC growth. Experiments were run in triplicate and repeated three times. Cell numbers were assessed on day 5 by colorimetric MTT assay as well as by tritiated thymidine uptake. Results show that TGFα alone (p< 0.05) and IGF‐I and IGF‐II alone (p< 0.05) significantly stimulated growth over controls (t‐test). Furthermore, the combination of TGFα with IGF‐I and IGF‐II exhibited significant enhancement above that seen with IGF‐I and IGF‐II alone (p< 0.01). EGF did not stimulate growth over controls. EGFr may be expressed in BPCs, but TGFα exhibits a more potent growth stimulus than EGF. Addition of IGF‐I or IGF‐II to the growth medium further enhances this effect.
Enzymatic Properties of Transplanted Glomerulosa Cells
Authors: Scheumann Georg F.W. , Heitmann Philip , Teebken Omke E. , Mössinger Eckart , Mellon Synthia H. , Pichlmayr Rudolf
Published: August 2002

There are several theories about the physiologic regeneration of adrenals and maintenance of physiologic steroid secretion after subtotal loss of adrenal cortical cells. According to the cell migration theory, adrenocytes from the zona glomerulosa migrate centripetally toward the medulla. This theory is opposed by the zonal theory according to which each zone resplenishes its cells independently. What these theories have in common is that they are based on data from the intact adrenal gland. We transplanted purified glomerulosa cells under the kidney's capsule of Lewis rats. The tissue was removed 30, 60, 90, and 150 days after transplantation to investigate the presence of two specific enzymes that are responsible for the secretion of aldosterone and corticosterone. Cytochrome p‐450as is specific for glomerulosa cells producing aldosterone, and cytochrome p‐45011β is specific for fasciculata cells producing corticosterone. After sequencing the genetic code of these enzymes it became possible to demonstrate expression of the enzymes by in situ hybridization. The transplanted glomerulosa cells turned their enzymatic property to fasciculata cells expressing cytochrome p‐45011β. Our results suggest that glomerulosa cells are able to take over the physiologic function of a whole adrenal cortex in the absence of fasciculata cells, and that they are sufficient to maintain the function of the adrenal cortex.
Hemostatic Methods for the Management of Spleen and Liver Injuries
Authors: Uranüs Selman , Mischinger Hans‐Jörg , Pfeifer Johann , Kronberger Leo , Rabl Hans , Werkgartner Georg , Steindorfer Peter , Kraft‐Kirz Julius
Published: August 2002

The spleen and liver are the most frequently injured organs during blunt and penetrating abdominal trauma. Emergency laparotomy is crucial for early control of bleeding and to prevent “secondary” injury as a result of physiologic splanchnic vasoconstriction and free oxygen radicals. Altogether 98 patients with spleen and liver injuries were treated over an 8‐year period. Primary orthotopic spleen preservation could be achieved in 46 of 63 patients. In 58 patients with hepatic trauma, hemostatic treatment was chosen based on the severity of the injury. Nonoperative management was used for four splenic and seven hepatic trauma patients. The most commonly used techniques were fibrin sealing, suturing, and débridement for hepatic injury and mesh splenorrhaphy, fibrin glue, and partial resection with a TA stapler for splenic injury. The death of patients with complex injuries was mainly due to preclinical massive blood loss and multiple organ failure.
Increased surface expression of CD18 and CD11b in leukocytes after tourniquet ischemia during elective hand surgery
Authors: Sutter Paul M. , Spagnoli Giulio C. , Marx Axel , Gürke Lorenz , Troeger Hans , Fricker Renato , Harder Felix , Heberer Michael
Published: August 2002

The surface expression of β2‐integrins was investigated in leukocytes from patients undergoing ischemia induced by tourniquet application for elective hand surgery. Blood samples were obtained before initiation, at the end of ischemia, and after 15 minutes of reperfusion from ischemic and contralateral arms of five patients. Comparable expression of CD18, CD11a, CD11b, and CD11c could be detected by immunofluorescence in leukocytes from samples drawn from either arm before tourniquet application. In contrast, a significant increase in the expression of CD18 was detectable in monocytes, granulocytes, and lymphocytes from the ischemic arm compared with that in the nonischemic contralateral control, at the end of the ischemia time (80 ± 16 minutes). A significantly increased expression of CD11b, but not CD11a or CD11c, determinants was also observed in granulocytes and monocytes. Concomitantly, a significant reduction in the percentages of granulocytes in samples from ischemic areas was detectable. After 15 minutes of reperfusion, differences in the expression of these adhesion molecules were no longer significant. The expression of the genes encoding interleukins IL‐1α, IL‐1β, and IL‐6 and tumor necrosis factor alpha (TNFα) proinflammatory cytokines was also studied by reverse polymerase chain reaction (rPCR) in peripheral blood mononuclear cells (PBMCs) obtained from the same samples in three patients. IL‐1β or IL‐6 gene expression was never observed. Expression of IL‐1α and TNFα genes, as detected in two patients, was not related with induction of ischemia. However, in these patients expression of one or both these genes was observed in samples derived from the ischemic but not the control arm after 15 minutes of reperfusion. These data document that overexpression of adhesion molecules and sequestration of leukocytes take place following short ischemia times, as routinely applied clinically for minor surgical procedures.
Infectious Concerns of Cross‐Species Transplantation: Xenozoonoses
Authors: Michaels Marian G.
Published: August 2002

Xenotransplantation is a potential solution to the current donor shortage for allotransplantation. Likewise it is being investigated for a number of other disease states such as Parkinson's disease, diabetes, and acquired immunodeficiency disease. Infections are a concern with the use of any biologic agent and as such have proved to be a substantial cause of morbidity and mortality after allotransplantation. Similarly, infections will likely cause disease after xenotransplantation. Public debate on the ethics of whether the field of xenotransplantation should move forward has focused on the concern of novel infections, xenozoonoses. Accordingly, the role of animal microbes must be critically examined. This article reviews mechanisms for xenogeneic infections and details what is known and what still needs to be learned as the field of xenotransplantation progresses. Emphasis is placed on microbial agents of baboons and swine, as they are currently the most common species considered as donor sources for xenotransplantation.
Allogeneic Vascularized Grafting of Human Knee Joints under Postoperative Immunosuppression of the Recipient
Authors: Hofmann Gunther O. , Kirschner Martin H. , Wagner Frithjof D. , Brauns Lars , Gonschorek Oliver , Bühren Volker
Published: August 2002

Vascularized knee joint transplantations have been performed in various animal systems. Up to now no allogeneic vascularized transplantation of a fresh and perfused human knee joint has been realized. This paper reports on the first four grafted human knee joints, performed between April 1996 and July 1997 at the Trauma Center Murnau. The indication for transplantation of a human knee joint is total loss of the joint, including the extensor apparatus, following severe trauma. Management of this defect is first to effect closure of the soft tissue defect combined with external transfixation and bone cement spacers. For the second phase the external stabilization is switched to internal stabilization using femoral and tibial nails and a temporary knee joint prosthesis manufactured of polyethylene. The transplantations are performed with respect to ABO compatibility, ignoring the HLA system after a negative crossmatch. Osteosyntheses are employed by femoral and tibial nails. The vascular anastomoses are established in an end‐to‐side technique between the recipient's superficial femoral vessels and the graft vascular pedicles. Immunosuppression starts as quadruple induction therapy for 3 days. Subsequently it is reduced to a two‐drug maintenance protocol with cyclosporin A and azathioprine. We utilize radiography, digital subtraction angiography, duplex sonography, scintigraphy, and arthroscopy for graft monitoring. Six months after transplantation the osteotomies were bridged with callus, and the patients were completely mobilized. The motion in the transplanted knee joint ranges from complete extension to 110° flexion.
Present Role of Classic Open Choledochostomy in the Surgical Treatment of Patients with Common Bile Duct Stones
Authors: Csendes Attila , Burdiles Patricio , Diaz Juan Carlos
Published: August 2002

Open choledochostomy still represents an important step of biliary surgery, even during the era of laparoscopic surgery. Although its application has decreased with the widespread use of endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy, still there are some patients in whom it is necessary to perform open choledochostomy and place a T‐tube. The morbidity and mortality rates depend mainly on the presence or absence of an acute suppurative cholangitis, rather than the performance of the choledochostomy. In patients with mild cholangitis or those no cholangitis and less than 60 years of age, the mortality rate is lower than that observed after ERCP. This procedure is still an important technique for surgeons dedicated to biliary surgery, and therefore several technical aspects of common bile duct exploration are important to remember.
Significant Correlation between Serum Level of Hepatocyte Growth Factor and Progression of Gastric Carcinoma
Authors: Han Sang‐Uk , Lee Jae‐Ho , Kim Wook‐Hwan , Cho Yong‐Kwan , Kim Myung‐Wook
Published: August 2002

Hepatocyte growth factor (HGF) can promote proliferation of many types of tumor cells including gastric cancer cells. To study the role of HGF in the progression of gastric carcinoma, HGF levels were measured by an enzyme immunoassay (EIA) system in sera of gastric cancer patients and followed up the levels after the operation. The mean serum HGF level in 212 healthy control subjects, 140 patients with primary gastric cancer, and 13 patients with recurrent gastric cancer were 0.199 ± 0.073, 0.325 ± 0.209, and 0.578 ± 0.258 ng/ml, respectively. The increase of the levels was significantly correlated with the progression of tumor stage. The levels decreased to normal levels 1 month after curative resection of the tumors. However, the levels did not decrease significantly in nonresected cases. During the follow‐up of the patients for several months, the level was significantly increased in recurrent gastric cancer patients, whereas there was no increase in nonrecurrent patients. In conclusion, the serum HGF levels significantly correlated with the aggressiveness of the tumors, suggesting an important role of HGF in the progression of gastric carcinoma.
Ultrasound of Soft Tissue Masses
Authors: Gandhi Mitesh R. , Benson Mark D.
Published: August 2002

The current clinical applications of ultrasonography (US) of soft tissue masses are discussed. These include the detection of occult masses, the characterization of palpable masses, tumor surveillance, and US guided percutaneous aspirations/biopsies of soft tissue masses.
Natural Course of Adrenal Incidentalomas: Seven‐year Follow‐up Study
Authors: Sirén Jukka , Tervahartiala Pekka , Sivula Arto , Haapiainen Reijo
Published: August 2002

Most adrenal incidentalomas are nonfunctioning cortical adenomas that do not require surgery. Operative treatment is indicated if the incidentaloma has malignant features as seen during the radiologic workup, is hormonally active, or grows during follow‐up. A conservative attitude is justified in asymptomatic patients if we know that the natural course of these tumors is not disadvantageous. We followed a group of patients treated by observation to determine the natural course of adrenal incidentalomas. Altogether 30 incidentalomas in 27 patients were detected in the Helsinki University Central Hospital from June 1981 through December 1992 and were re‐examined during 1997. The patients were evaluated clinically, and hormonal testing was done by performing a 1‐mg overnight dexamethasone suppression test; the next day we measured the 24‐hour urinary excretion of vanillylmandelic acid, metanephrines and normetanephrines, and serum potassium. Magnetic resonance imaging (MRI) was used to determine the size of the tumor. If the patient had died during the follow‐up period, the causes of death from the death certificates and autopsy reports were reviewed. The mean follow‐up was 7 years. Nine patients had died, with none of deaths related to the incidentaloma. Sixteen patients were evaluated clinically and by the basic hormonal tests and MRI; none showed any signs of hormonal activity or features of malignancy. Two patients did not want to be reexamined but stated that they were asymptomatic. This follow‐up study supports the conclusion that conservative therapy is justified because the growth tendency of adrenal incidentalomas is slow and they seem to remain hormonally inactive.
One‐Lung Versus Two‐Lung Ventilation in the Closed‐Chest Anesthetized Dog: A Comparison of Cardiopulmonary Parameters
Authors: Cantwell Shauna L. , Duke Tanya , Walsh Peter J. , Remedios Audrey M. , Walker David , Ferguson James G.
Published: August 2002

Objective— To evaluate cardiopulmonary effects of one‐lung ventilation (OLV) versus two‐lung ventilation (TLV) in closed‐chest anesthetized dogs.

Study Design— Controlled, randomized experiment.

Animals— Fourteen, 2‐ to 7‐year‐old adult dogs, weighing 23 ± 6 kg.

Methods— The dogs were anesthetized with acepromazine, morphine, thiopental, and halothane in oxygen, ventilated, and paralyzed with vecuronium. Tidal volume was 10 mL/kg. Respiratory rate was set to maintain end‐tidal CO2 (ETCO2) at 40 ± 2 mm Hg before instrumentation then not changed. The left bronchus of 7 dogs was obstructed with a Univent bronchial blocker (Fuji Systems Corp, Tokyo, Japan). Blood gas analysis and hemodynamic measurements were taken at predetermined intervals for 1 hour in the TLV group and at baseline and following bronchial obstruction in the OLV group.

Results— Shunt fraction was not significantly different between groups, but in OLV shunt increased from baseline at 5 minutes. Arterial oxygen (Pao2) decreased after baseline in OLV compared with TLV. Arterial carbon dioxide (Paco2) increased with OLV and decreased with TLV. In OLV, systemic vascular resistance was variable and decreased compared with TLV. Cardiac index increased over time in both groups but was not affected by treatment. Heart rate, mean arterial pressure, and diastolic arterial pressure increased with OLV compared with TLV but did not change over time.

Conclusion— This study shows that OLV statistically decreases oxygen tension and transiently increases shunt fraction, but with 100% O2 it appears to be a feasible procedure with minimal cardiopulmonary side effects in healthy dogs.

Clinical Relevance— OLV is a feasible procedure in anesthetized dogs to better facilitate thoracic procedures such as bronchopleural fistula repair and thoracoscopy.
Aspects of the theory of environmental policy in developing countries
Authors: Batabyal Amitrajeet A. , Beladi Hamid
Published: August 2002

We study two issues relating to the conduct of environmental policy in developing countries (DCs). First, when faced with a self‐financing constraint, should an environmental authority (EA) raise/lower pollution taxes over time or should it run a deficit/surplus? Second, given recent findings about the dynamic inconsistency of optimal environmental policy, should an EA make its preferences about the relative benefits of environmental protection versus production public, or should it keep its preferences private? Our analysis reveals that when faced with a self‐financing constraint, it is optimal for the EA to run a deficit/surplus. Second, social losses are lower when this EA keeps its preferences private.
Compounds in the series from boron subphthalocyanine to boron subnaphthalocyanine
Authors: ZYSKOWSKI CHRISTOPHER D. , KENNEDY VANCE O.
Published: August 2002

The four compounds in the series from chloro[subphthalocyaninato]boron(III) to chlo-ro[subnaphthalocyaninato]boron(III) were synthesized in a one-pot reaction. To obtain a more soluble set of compounds, the mixture was then reacted with the sodium salt of trihexylsilanol. This mixture was separated by chromatography to provide trihexylsiloxy[subphthalocyaninato]boron(III), trihexylsiloxy[ Sub N 1 P 2]boron(III), trihexylsiloxy[ Sub N 2 P 1]boron(III) and trihexylsiloxy[subnaphthalocyaninato]boron(III). These compounds were characterized by 1 H NMR , EI-MS and UV-vis. They show interesting spectral features in the visible region.
Excessive anticoagulation in patients with mild renal insufficiency receiving long‐term therapeutic enoxaparin
Authors: Busby Leslie T. , Weyman Anne , Rodgers George M.
Published: August 2002

Low‐molecular‐weight heparins, such as enoxaparin, are increasingly being used for treatment of venous thromboembolism. We describe two patients who received therapeutic enoxaparin for several months. Although their serum creatinine values were normal, both had mild renal insufficiency (creatinine clearance 60–70 ml/min), and both accumulated the drug abnormally and experienced clinical bleeding. These results suggest that patients receiving enoxaparin (or other low‐molecular‐weight heparins) in therapeutic doses for periods of more than 4 weeks should be considered for laboratory monitoring to avoid bleeding. Am. J. Hematol. 67:54–56, 2001. © 2001 Wiley‐Liss, Inc.
Detection of human herpesvirus 6 and JC virus in progressive multifocal leukoencephalopathy complicating follicular lymphoma
Authors: Daibata Masanori , Hatakeyama Nobuo , Kamioka Mikio , Nemoto Yuiko , Hiroi Makoto , Miyoshi Isao , Taguchi Hirokuni
Published: August 2002

Progressive multifocal leukoencephalopathy (PML), a demyelinating infectious disease caused by JC virus (JCV), occurs almost exclusively in immunocompromised patients usually with malignant diseases. We report here a Japanese female with follicular lymphoma who subsequently developed PML. In addition to JCV, human herpesvirus 6 (HHV‐6) was detected in the affected brain lesions of the patient by polymerase chain reaction and by in situ hybridization. HHV‐6, recognized as a neurotropic virus, is known to be reactivated during immunosuppression and can cause fatal complications such as encephalitis/encephalopathy. It is likely that impaired immunity associated with lymphoma and the additional immunosuppression following cytopenia‐inducing chemotherapies predisposed the patient to reactivated HHV‐6 infection. Although it remains to be clarified whether HHV‐6 plays an important role as a co‐agent with JCV in causing demyelination of the brain, our observation alerts physicians to the possible association of HHV‐6 with the pathogenesis of PML. Am. J. Hematol. 67:200–205, 2001. © 2001 Wiley‐Liss, Inc.
Impact of open lung biopsy for undiagnosed pulmonary infiltrates in patients with hematological malignancies
Authors: Dai Ming‐Shen , Lee Shih‐Chun , Ho Ching‐Liang , Chen Yu‐Chin , Kao Wei‐You , Chao Tsu‐Yi
Published: August 2002

Pulmonary complications are frequently encountered in patients with hematological malignancy. The optimal therapeutic decision including open lung biopsy (OLB) for such patients is uncertain. We herein examine the clinical impact of OLB on these patients. Seven patients with progressively diffuse pulmonary infiltrates despite aggressive medical treatment were examined. The underlying diseases, prior treatment for presumptive pneumonia, the change in therapeutic approach after operation, and clinical outcome were reviewed retrospectively. Diffuse pulmonary infiltrates were caused by infection in two patients and by noninfectious etiology such as alveolar proteinosis, idiopathic interstitial pneumonitis, leukemic involvement, and drug‐induced alveolar damage in the others. Four patients who had serious underlying hematologic diseases such as myelodysplastic syndrome, acute and chronic myeloid leukemia, and T cell lymphoma died. Three patients with acute lymphoid leukemia survived. In two of these three, change of therapeutic strategies after OLB was created for the survival. OLB in patients with hematological malignancy may be useful in selected patients with a treatable hematologic disease who have treatable underlying causes of the pulmonary infiltrate. Am. J. Hematol. 68:87–90, 2001. © 2001 Wiley‐Liss, Inc.
Airways inflammation after exposure in a swine confinement building during cleaning procedure
Authors: Larsson Britt‐Marie , Larsson Kjell , Malmberg Per , Palmberg Lena
Published: August 2002

Background

Healthy volunteers exposed for 3 hr during weighing of pigs develop an airway inflammation characterized by a massive influx of neutrophilic granulocytes in the upper and lower airways and increased bronchial responsiveness to methacholine. The purpose of the present study was to investigate health effects from exposure during cleaning of the swine confinement building and to evaluate the effect of a respiratory protection device.

Methods

Sixteen subjects were exposed for 3 hr during cleaning of a swine confinement room with a high‐pressure cleaner. Seven out of sixteen subjects were equipped with a mask during exposure.

Results

The bronchial responsiveness increased in all subjects following exposure, significantly more in the group exposed without a mask (P < 0.05). The cell concentration (mainly neutrophilic granulocytes) in nasal lavage fluid as well as the concentration of interleukin‐8, increased significantly only in those subjects exposed without a respiratory protection device. In peripheral blood, an increase of neutrophilic granulocytes was observed in both groups, although it was significantly higher in the group without mask (P < 0.05). The inhalable dust level was 0.94 (0.74 – 1.55) mg/m3 and respirable dust 0.56 (0.51–0.63) mg/m3.

Conclusion

Exposure to dust aerosols during the cleaning of the interior of a swine confinement building induces increased bronchial responsiveness and an acute inflammatory reaction in the upper airways. The use of a mask attenuated but did not abolish the inflammatory response. This suggests that gases and/or ultrafine particles in this environment could be important factors in the development of increased bronchial responsiveness. Am. J. Ind. Med. 41:250–258, 2002. © 2002 Wiley‐Liss, Inc.
Serotonin transporter gene polymorphism and psychiatric disorders in NF1 patients
Authors: Bellivier Frank , Laplanche Jean‐Louis , Fournier Geneviève , Wolkenstein Pierre
Published: August 2002

Neurofibromatosis type 1 (NF1) is an autosomal‐dominant genetic disease characterized by a broad clinical expression. Comorbid affective disorders, anxiety disorders, and suicide are frequently observed during NF1. The promoter marker (5‐HTTLPR) of the serotonin transporter gene (5‐HTT) has been shown to be associated with major affective disorders, anxiety‐related trait, and more recently with suicidal behavior. This gene is adjacent to the NF1 gene, raising the question of the implication of the 5‐HTT gene in the psychiatric comorbidity during NF1. Eighty‐eight patients with NF1 and 184 screened controls were typed for the 5‐HTTLPR. No deviation from the Hardy‐Weinberg equilibrium in patients was observed. In addition, allele and genotype frequencies were similar in the two groups. Our data do not support the implication of the 5‐HTT gene in the psychiatric comorbidities of NF1. © 2001 Wiley‐Liss, Inc.
PRINS tandem labeling of satellite DNA in the study of chromosome damage
Authors: Russo Antonella
Published: August 2002

Tandem labeling of satellite DNA was proposed a few years ago (1) for evaluating preferential chromosome breaks in the pericentromeric regions of mammalian chromosomes, and (2) for distinguishing chromosome breaks from chromosome segregation errors in interphase cells. In the presence of primers and modified nucleotides, primed in situ labeling (PRINS) tags repetitive DNA sequences, and serves as a useful alternative to fluorescence in situ hybridization (FISH). We developed a two‐color method for PRINS tandem labeling of centromeric and pericentromeric sequences. The method, which appears to be more sensitive than FISH, was used to assay micronuclei in mouse splenocytes and early spermatids, and it provided insight into mechanisms of induction of chromosome damage in these cells. We compared the sensitivity of this method and of a different two‐color approach, based on simultaneous labeling of centromeric and telomeric sequences. © 2001 Wiley‐Liss, Inc.
Association of APOE ε2/ε3/ε4 and promoter gene variants with dementia but not cardiovascular mortality in old age
Authors: Heijmans Bastiaan T. , Slagboom P. Eline , Gussekloo Jacobijn , Droog Simone , Lagaay A. Margot , Kluft Cornelis , Knook Dick L. , Westendorp Rudi G.J.
Published: August 2002

The common apolipoprotein E (APOE) alleles ε2, ε3, and ε4 are associated with the risk of dementia and cardiovascular disease. Recently, two functional variants (− 219G/T and −491A/T) were identified in the promoter of the APOE gene that enable a further characterization of the role of the APOE locus in disease. We investigated the contribution of these APOE gene variants to dementia and cardiovascular mortality in old age using a population‐based cohort of 648 subjects aged 85 years and over (Leiden 85‐Plus Study). Genotypes containing an APOE ε4 allele were associated with a 4.1‐fold (95% CI, 2.2–7.7) increased risk of dementia as compared to the ε3/ε3 genotype in old subjects. Moreover, homozygosity for the −219T allele was found to be associated with a 2.4‐fold (95% CI, 1.0–5.8) increased risk independently of ε2 and ε4; the −491A/T variant was not associated with dementia. Over a 10‐year follow‐up period, the risk of cardiovascular mortality was not increased among ε4 carriers (RR, 0.6; 95% CI, 0.4–1.0) or −219T homozygous subjects (RR, 1.1; 95% CI, 0.7–1.7), nor did it decrease among −491T homozygous subjects (RR, 1.4; 95% CI, 0.6–3.1). In conclusion, both the APOE ε2/ε3/ε4 and the −219G/T variant were identified as risk factors for dementia but not cardiovascular mortality in old age. Our results support the hypothesis that both the isoform and the amount of APOE may influence the risk of dementia. Furthermore, they emphasize that variation at the APOE locus has a higher impact on the risk of dementia than on the risk of cardiovascular disease in old age. © 2001 Wiley‐Liss, Inc.