bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of [4‐O‐methyl‐11C]KW‐6002 as a potential PET ligand for mapping central adenosine A2A receptors in rats
Authors: Hirani E. , Gillies J. , Karasawa A. , Shimada J. , Kase H. , Opacka‐Juffry J. , Osman S. , Luthra S.K. , Hume S.P. , Brooks D.J.
Published: August 2002

KW‐6002, a xanthine‐based adenosine A2A antagonist, was labelled with the positron emitter carbon‐11 by O‐methylation of its precursor, KF23325, using [11C]iodomethane and was evaluated in rats as a putative in vivo radioligand for positron emission tomography (PET). Following intravenous injection of [11C]KW‐6002, radioactivity was measured in blood, plasma, peripheral tissues, and in discrete brain tissues over a 2‐h time period commensurate with PET scanning. In brain, [11C]KW‐6002 showed highest retention in striata, with evidence of saturable binding, and lowest retention in frontal cortex (a tissue low in adenosine A2A receptors). PET scanning with [11C]KW‐6002 demonstrated a specific signal in the striata which could be described using compartmental modelling. Specific binding was, however, also detected in extrastriatal regions, including brain areas reported to have low adenosine A2A receptor density. Blocking studies with the A1 selective antagonist KF15372 and the non xanthine‐type A2A antagonist ZM 241385 failed to elucidate the nature of this binding. Thus, although [11C]KW‐6002 shows some potential for development as a PET ligand for quantifying striatal adenosine A2A receptor function, its in vivo selectivity requires further investigation. Synapse 42:164–176, 2001. © 2001 Wiley‐Liss, Inc.
Changes in neuronal activation with increasing attention demand in healthy volunteers: An fMRI study
Authors: Adler Caleb M. , Sax Kenji W. , Holland Scott K. , Schmithorst Vince , Rosenberg Lee , Strakowski Stephen M.
Published: August 2002

Several lines of evidence suggest that structures involved in mediating attention differentially respond to increasing processing demand. Investigation of differences in neuronal activation, however, has been complicated by methodological inconsistencies and concomitant discrepancies in degree of difficulty and subject effort between disparate tasks. In this study, we utilized fMRI to compare neural activation patterns associated with two related attention tasks associated with different degrees of processing load while controlling for degree of performance difficulty. Healthy volunteers performed two continuous performance tasks, utilizing an identical pairs paradigm (CPT‐IP) and a matched simple number recognition paradigm with degraded stimuli (CPT‐DS) during a single fMRI scan. Degree of stimulus resolution degradation in the latter CPT was designed to equalize degree of performance difficulty between the two tasks. CPT‐IP and CPT‐DS were both associated with activation of frontal, limbic, subcortical, and sensory integratory structures. CPT‐IP administration was associated with significantly greater activation of left dorsolateral prefrontal cortex, bilateral posterior temporal cortex, bilateral putamen, and thalamus. This study demonstrates both that differing attention tasks are associated with a high degree of functional overlap and that increasing processing demand is associated with increased activation of specific portions of attentional networks. Synapse 42:266–272, 2001. © 2001 Wiley‐Liss, Inc.
Realizing the benefits of the CMMISM with the CeBASE method
Authors: Boehm Barry , Port Daniel , Basili Victor
Published: August 2002

Future systems will be increasingly software‐intensive, but the type of software development they will need is not well covered by current development and maturity models such as the waterfall model and Software Capability Maturity Model® (CMM®). Future development of software‐intensive systems will need situation‐specific balancing of discipline and flexibility to address such issues as COTS, open source, distribution, mobility rapid change, agents, collaboration support, and simultaneous achievement of rapid development and high dependability. This article shows how the CMMISM's integration of modern systems engineering, software engineering, and integrated process and product development concepts provides a framework for redressing the shortfalls of the Software CMM®, and for enabling projects and organizations to achieve the right balance of discipline and flexibility for their particular situations. But the CMMISM has shortfalls of its own. It provides little guidance on how to define and execute specific processes for a specific project or organization. The article summarizes various process model generators for software intensive systems such as the spiral, the Rational Unified Process (RUP), MBASE, and the CeBASE Method. It concludes that the CeBASE Method best covers the full range of concerns in the CMMISM, resolves its practice‐focus shortfalls, and covers additional best practices not in the CMMISM, such as business case analysis, requirements prioritization, and evolution requirements. © 2002 John Wiley & Sons, Inc. Syst Eng 5: 73–88, 2002; DOI 10.1002/sys.10016
Reproductive toxicology: The science today
Authors: Neubert Diether
Published: August 2002

Reproductive toxicology is concerned with chemical or physical agents interfering with fertility in both gender. Adverse effects may be induced directly, especially in adult males by damaging the semen producing epithelium (e.g., DBCP), or indirectly, predominantly by interfering with sex hormonal homeostasis. Many critical events must occur during well‐defined periods of prenatal and early postnatal development of the reproductive system. Most of such differentiation processes, several of which in the male critically depend on inducing influences of androgens, cannot take place at later stages, and lack of “imprinting” will result in irreversible defects or dysfunctions. These processes might be disturbed by interfering agents (e.g., by anti‐androgens: feminization), provided that the exposure is high enough. Several of the processes known to be essential for male development can also be altered in females by exposure to a large excess of androgens (masculinization). Essential processes required for normal male development include: 1) androgen‐dependent differentiation of the male phenotype during late embryonic development, 2) differentiation of the male secondary sex organs during the fetal period, 3) formation of a fixed number of Sertoli cells during the perinatal period, 4) imprinting of male sexual behavior in defined brain areas during the perinatal period, 5) imprinting of the pulsatile GnRH regulation of hypophysial hormone formation in both gender via the hypothalamico‐hypophysial axis, and 6) differentiation of the male organism during puberty. Many effects on fertility can be induced on the adult organism. Besides a direct action on the receptors, inhibition of the feed back mechanism that guarantees sex hormonal homeostasis is another mode of action. Many synthetic steroid compounds exhibit effects on more than one receptor, thus causing a complex situation. This must also be taken into account when analyzing possible effects of “ecohormones.” Adverse hormonal actions are well established from experience in clinical and experimental medicine, using either natural or synthetic sex hormones, or enzyme inhibitors. Possible effects of “environmental” agents either mimicking or inhibiting sex hormonal actions are less well studied in clinical trials. Because of considerable species differences in hormonal effects, especially in pharmacokinetics, data of animal studies are of limited predictive value for extrapolations in preventive hazard minimization (but may be useful for revealing possible mechanisms of action). Data of in‐vitro studies are even less suitable for extrapolations. It may be doubted that exposure of the general population to “ecohormones” or “xenohormones” is sufficient to induce clear‐cut clinical effects. Adverse effects induced by, e.g., greatly unbalanced diets or after accidental overdoses cannot be excluded. Teratogenesis Carcinog. Mutagen. 22:159–174, 2002. © 2002 Wiley‐Liss, Inc.
Mutation analysis of left‐right axis determining genes in NOD and ICR, strains susceptible to maternal diabetes
Authors: Maeyama Katsuhiro , Kosaki Rika , Yoshihashi Hiroshi , Casey Brett , Kosaki Kenjiro
Published: August 2002

Background

Genetic background of the fetus contributes to the pathogenesis of congenital malformation after teratogen exposure. Such contribution is illustrated in left‐right axis malformations observed in the F1 offspring of nonobese diabetic (NOD) mouse dams and sires from different strains. When sires of the NOD, ICR, or C57BL/6J were mated with NOD dams, incidence varied depending on the fetal genotype, with 65% in NOD × NOD, 24% in NOD × ICR, and 7% in NOD × C57BL/6J.

Methods

As a first step in elucidating the molecular basis of the interstrain differences in susceptibility to situs defects, we compared genomic sequences of six genes HNF3beta, Acvr2b, Nodal, ZIC3, Lefty1, and Smad2, which are involved in the normal development of left‐right axis among NOD, ICR, and C57BL/6J strains.

Results

The outbred strain ICR had 1) a 0.2‐kb insertion in the putative promoter region of the isoform E of HNF3beta together with a G to A change that could create a potential splice acceptor in the exon 3 of HNF3beta (gene frequency P = 0.36), 2) five single base substitutions within the 5′ controlling element and a proline to serine substitution (P2S) of Lefty1 (P = 0.77), and 3) a tyrosine to histidine substitution within the prodomain of Nodal (P = 0.48). The inbred strain NOD had the same G to A change as ICR and a three‐base deletion in the putative promoter of isoform E of HNF3β.

Conclusions

We suggest that sequence variations in HNF3β, Lefty1, and Nodal might account, in part, for the interstrain differences in susceptibility to situs abnormalities among the offspring of diabetic dams. Teratology 63:119–126, 2001. © 2001 Wiley‐Liss, Inc.
Morocco
Authors: Gray Kenneth R. , Amine Lyn S.
Published: August 2002

In 1999 a new king came to the throne in Morocco, Mohamed VI. This event is proving to be a watershed in the
economic and political history of Morocco as new policies, initiatives, and goals are being developed and
implemented. This article provides background information on the business environment of Morocco regarding
history, politics, culture, the economy, regulations and laws, human resource management, and marketing
practices. Detailed insights are presented to enable foreign investors and business people to understand
inportant aspects of doing business in Morocco. Finally we present our expectatons for the future of Morocco and
its trading partners. © 2002 Wiley Periodicals, Inc.
Research Note: Strategic Combinations and Their Evolution in the Global Marketplace
Authors: Powers Thomas L. , Jones Rachel Collins
Published: August 2002

The global marketplace of the twenty‐first century will contain many new competitors formed from the
mergers and alliances that are currently taking place. This article demonstrates how the globalization process
is in reality an extension of a pattern that has existed since the Industrial Revolution, that today continues
to create competitive advantage. Significant managerial implications are given based on this discussion. ©
2001 John Wiley & Sons, Inc.
Apoptotic effect of cyanobacterial extract on rat hepatocytes and human lymphocytes
Authors: Mankiewicz Joanna , Tarczynska Malgorzata , Fladmark Kari Espolin , Doskeland Stein Ove , Walter Zofia , Zalewski Maciej
Published: August 2002

Toxic cyanobacterial blooms are an increasing problem in Poland. The production of cyanobacterial toxins and their presence in drinking and recreational waters represent a growing danger to human and animal health. This is connected with the increase of cyanobacterial biomass caused by excessive eutrophication of the water ecosystem. There is evidence that cyanobacterial hepatotoxins can act as a potent promoter of primary liver cancer. The apoptotic effect of microcystins in Polish cyanobacterial bloom samples on rat hepatocytes and human lymphocytes was observed using light and fluorescence microscopy, flow cytometry, and electrophoretic analysis. The incubation time needed to observe the first morphological apoptotic changes in hepatocytes was approximately 30 min; however, the characteristic biochemical changes in DNA were not observed even after 120 min. In lymphocyte cultures the morphological changes characteristic for apoptosis were observed after 24 h of incubation and a 48‐h incubation was found to be optimal for analysis of internucleosomal DNA fragmentation, which is one of the main biochemical hallmarks of programmed cell death. These cells are an easily isolated and inexpensive material for medical diagnostics. Therefore the apoptotic changes, together with the clastogenic effect seen in lymphocyte cultures, are proposed as a future analytical method for these toxins. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 225–233, 2001
High‐level production of human type I collagen in the yeast Pichia pastoris
Authors: Nokelainen Minna , Tu Hongmin , Vuorela Annamari , Notbohm Holger , Kivirikko Kari I. , Myllyharju Johanna
Published: August 2002

Four human genes, two of them encoding the proα1 and proα2 chains of type I procollagen and two of them the two types of subunit of prolyl 4‐hydroxylase (4‐PH), were integrated into the genome of Pichia pastoris. The proα1 and proα2 chains expressed formed type I procollagen molecules with the correct 2:1 chain ratio, and the 4‐PH subunits formed an active enzyme tetramer that fully hydroxylated the proα chains. Chains lacking their N but not C propeptides formed pCcollagen molecules with the 2:1 chain ratio and, surprisingly, the expression levels of pCcollagen were 1.5–3‐fold relative to those of procollagen. Both types of molecule could be converted by pepsin treatment to collagen molecules that formed native‐type fibrils in vitro. The expression levels obtained for the pCcollagen using only single copies of each of the four genes and a 2 l fermenter ranged up to 0.5 g/l, indicating that it should be possible to optimize this system for high‐level production of recombinant human type I collagen for numerous medical applications. Copyright © 2001 John Wiley & Sons, Ltd.
The diversity of retrotransposons in the yeast Cryptococcus neoformans
Authors: Goodwin Timothy J. D. , Poulter Russell T. M.
Published: August 2002

We have undertaken an analysis of the retrotransposons in the medically important basidiomycetous fungus Cryptococcus neoformans. Using the data generated by a C. neoformans genome sequencing project at the Stanford Genome Technology Center, 15 distinct families of LTR retrotransposons and several families of non‐LTR retrotransposons were identified. Members of at least seven families have transposed recently and are probably still active. For several families, only partial elements could be identified and these are quite diverse in sequence, suggesting that they are ancient components of the C. neoformans genome. Most C. neoformans elements are not closely related to previously identified fungal retrotransposons, suggesting that the diversity of fungal retrotransposons has been only sparsely sampled to date. C. neoformans has fewer distinct retrotransposon families than Candida albicans (37 or more), in particular fewer families represented solely by ancient and inactive elements, but it has considerably more families than either Saccharomyces cerevisiae (five) or Schizosaccharomyces pombe (two). The findings suggest that elimination of retrotransposons is faster in C. neoformans than in C. albicans, but perhaps not as rapid as in S. cerevisiae or Sz. pombe. The identification of the retrotransposons of C. neoformans should assist in the molecular characterization of this important pathogen, and also further our understanding of the role played by retroelements in genome evolution. Copyright © 2001 John Wiley & Sons, Ltd.
The KlTrk1 gene encodes a low affinity transporter of the K+ uptake system in the budding yeast Kluyveromyces lactis
Authors: Miranda Manuel , Saldaña Carlos , Ramírez Jorge , Codiz Guadalupe , Brunner Aurora , Ongay‐Larios Laura , Coria Roberto , Peña Antonio
Published: August 2002

Potassium uptake in Saccharomyces cerevisiae is mediated by at least two proteins, known as Trk1p and Trk2p. Direct involvement in cation movements has been demonstrated for Trk1p, which is the high affinity transporter. S. cerevisiae cells also show low affinity potassium uptake, perhaps mediated by Trk2p. Mutants lacking Trk1p, lose high affinity system, but when grown with moderate potassium concentrations, Trk2p seems to replace it. Mutants lacking both proteins are viable but require at least 10 mM K+ in the medium to sustain growth. Here we report the cloning and characterization of a gene from Kluyveromyces lactis encoding a homologue of these two proteins. KlTrkp is a 1070 amino acid peptide that shows, overall, higher homology with Trk2p than with Trk1p, and its disruption gives rise to cells with deficient potassium transport and with an increased K+ requirement for normal growth. Determination of kinetic parameters in the K. lactis wild‐type and Kltrk1Δ strains, as well as in Sctrk1Δ Sctrk2Δ S. cerevisiae cells expressing KlTrk1, indicated that this is a low affinity component of a major potassium uptake system in K. lactis. The sequence has been deposited in GenBank under Accession No. AF136181. Copyright © 2002 John Wiley & Sons, Ltd.
Copper adaptation and methylotrophic metabolism in Candida boidinii
Authors: Santovito Gianfranco , Salvato Benedetto , Manzano Marisa , Beltramini Mariano
Published: August 2002

The importance of the antioxidant enzyme superoxide dismutase (CuZnSOD) in the metabolic switch from normotrophic to methylotrophic conditions was studied in the facultative methylotrophic yeast Candida boidinii. Copper adaptation was performed to qualify C. boidinii as a suitable cellular system to study the effect of induction of CuZnSOD, and other biochemical components along the copper detoxification system, on methanol adaptation. Copper adaptation results in the induction of CuZnSOD peroxidase activity as well as of glutathione. The effects at the metabolic level of exposure to both copper and methanol were also studied: the results suggest that the effect on antioxidant enzyme levels as a function of the change of trophic condition are predominant with respect to the effects of copper administration. Thus, the methanol‐dependent induction of such enzymes is likely to provide a sufficient protection for the cells against toxic effects depending on copper administration. Administration of copper under methylotrophic conditions decreases the growth rate in spite of the high levels of antioxidant enzymes that are elicited by copper treatment. The adaptation to methanol metabolism was studied alsoafter methanol‐independent induction of CuZnSOD, glutathione and catalase levels, obtained by exposure to high copper concentrations in glucose‐containing medium. The metabolic changes induced by copper are persistent over several re‐inoculations in normo‐cupric glucose medium, thus allowing the study of the glucose‐to‐methanol switch on cells exhibiting high levels of antioxidant enzyme activities. Under such conditions the lag time observed during the transition from normotrophic to methylotrophic conditions is strongly reduced. Copyright © 2002 John Wiley & Sons, Ltd.
Perspectives on mammalian conservation
Authors: Dinon John
Published: August 2002

A review of Priorities for the Conservation of Mammalian Diversity: Has the Panda Had Its Day? edited by Abigail Entwistle and Nigel Dunstone. Cambridge, Cambridge University Press, 2000, 455 pages, $110.00 hardbound; $34.95 paperback.
Results of End‐to‐end Cavocavostomy during Adult LiverTransplantation
Authors: Glanemann Matthias , Settmacher Utz , Langrehr Jan M. , Stange Barbara , Haase Roland , Nuessler Natascha C. , Lopez‐Hänninen Enrique , Podrabsky Petr , Bechstein Wolf‐Otto , Neuhaus Peter
Published: August 2002

The results of end‐to‐end cavocavostomyduring adult liver transplantation were analyzed with special regard tocaval complications. In a series of 1000 liver transplants, we observed17 patients who suffered from postoperative caval obstruction (6patients) or caval stenosis (11 patients), for an incidence of 1.7%.Surgical therapy was performed in 10 patients (58.8%), and 5 patientsrequired retransplantation (29.4%). Four patients died during thelater postoperative course. Two fatalities were related to cavalcomplications, resulting in a mortality rate of 11.8%. Our resultsindicate that end‐to‐end cavocavostomy is a safe technique forcavocaval anastomosis. For only a few exceptions, such as pediatrictransplantation, reduced size livers, or size mismatch between donorand recipient, should alternative techniques such as end‐to‐side orside‐to‐side cavocavostomy be performed.
Factors Affecting Management and Outcome in Blunt Renal Injury
Authors: Kuo Ramsay L. , Eachempati Soumitra R. , Makhuli Mark J. , Reed R. Lawrence
Published: August 2002

Blunt renal trauma patients often have multiple injuries. We retrospectively analyzed factors that could be predictive of outcome and the need for nephrectomy in this population.
Blunt renal injury patients admitted to a Level I trauma center from January 1989 to July 1997 were identified and their charts reviewed.
Multiple factors were examined. Using logistic regression analysis,
factors predictive of mortality and the need for nephrectomy were determined. Of 11,847 trauma patients admitted, 95 (0.80%) suffered blunt renal injury. Mean age and ISS were 31.4 and 23.7, respectively.
The number of deaths and nephrectomies was 11 and 10, respectively.
Higher renal injury grade, as well as higher ISS values and 24‐hour transfusion needs, directly correlated with the need for nephrectomy.
Greater age, higher ISS, and higher 24‐hour transfusion requirements lowered probability for survival. Patients with blunt renal injuries often sustain multiple injuries. The grade of renal injury, the overall injury severity of the patient, and the requirement of blood transfusion are the primary factors in determining the patient’s need for nephrectomy and overall outcome.
Effect of Bile Acid Replacement on Endotoxin‐induced Tumor Necrosis Factor‐a Production in Obstructive Jaundice
Authors: Sheen‐Chen Shyr‐Ming , Chen Han‐Shiang , Ho Hsin‐Tsung , Chen Wei‐Jen , Sheen Chih‐Chi , Eng Hock‐Liew
Published: August 2002

There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice due to sepsis. Tumor necrosis factor‐a (TNF‐a) is considered a crucial mediator in inducing and processing the inflammatory cascade. We hypothesize that obstructive jaundice leads to an increased endotoxin‐induced TNF‐a production and that intestinal bile acid replacement can prevent this phenomenon. Sprague‐Dawley rats were randomized to three groups of 12 animals each. Group 1 underwent common bile duct ligation (CBDL) with oral intestinal bile acid
(deoxycholic acid 5 mg/100 g body weight/3 times daily) replacement
(CBDL + bile acid); group 2 underwent common bile duct ligation with the same amount of normal saline replacement orally (CBDL +
saline); and group 3 underwent a sham operation (sham control). After 2
days, endotoxin was given to the animals, and after 90 minutes, tissues
(liver and lung) and blood were collected for checking the TNF‐a levels and biochemical analyses. Comparisons among these three groups were performed and recorded. While serum and tissue (liver and lung)
TNF‐a levels of group 2 (CBDL + saline) were significantly increased after endotoxin challenge, these elevations were reduced to control levels (sham control) following oral replacement of intestinal bile acid (CBDL + bile acid). Obstructive jaundice leads to an increased endotoxin‐induced TNF‐a production and intestinal bile acid replacement can inhibit this phenomenon.
Case Series of Acute Abdominal Surgery in Rural Sierra Leone
Authors: McConkey Samuel J.
Published: August 2002

In many poor countries of the world the need for surgical treatment of acute abdominal emergencies is largely unmet. In some cases this service is provided by physicians with little postgraduate surgical training, and there is a paucity of published data on the outcomes of this service. This series of sequential cases of acute abdominal surgical emergencies from a hospital in rural Sierra Leone illustrates the causes, outcomes, and challenges in this setting.
All patients with an acute abdomen from September 1992 until September
1994 who required surgery were identified by review of theater records,
ward books, and patients’ notes. Altogether, 173 cases were identified. Operative diagnoses included ectopic pregnancy
(n = 43), strangulated hernia (n =
45) 15 of which required bowel resection, appendicitis
(n = 15), normal appendix (n = 4),
uterine rupture (n = 9), perforated ulcer
(n = 8), tubal or pelvic abscess (n =
7), volvulus (n = 6), and others. Ninety percent survived to discharge after a median postoperative stay of 9.2 days
(range 7–127 days). Of the 18 deaths, 83% occurred during the first 3
days. Factors associated with poor outcome were ileal perforation due to typhoid fever and resection of bowel after a strangulated hernia.
These results show that acute abdominal surgery can be done at the district level in poor countries using limited facilities by staff without extensive surgical training. The outcomes are comparable to those from larger centers.
Endorectal Ultrasonography and Treatment of Early Stage Rectal Cancer
Authors: Akasu Takayuki , Kondo Hitoshi , Moriya Yoshihiro , Sugihara Kenichi , Gotoda Takuji , Fujita Shin , Muto Tetsuichiro , Kakizoe Tadao
Published: August 2002

The purpose of this study was to evaluate the accuracy of preoperative staging by endorectal ultrasonography (EUS) and its contribution to treatment of early stage rectal cancer (ESRC). The results of EUS for 154 consecutive patients with ESRC (pTis to pT2) were compared prospectively with histologic findings, assessed according to the TNM classification. Results of treatment selection and long‐term outcomes were analyzed retrospectively. There were 35 patients histologically staged as pTis, 8 as pT1‐slight (invasion confined to the superficial one‐third of the submucosa), 37 as pT1‐massive (invasion extending to the deeper submucosa), and 74 as pT2. The equipment used was an echoendoscope GF‐UM2 or GF‐UM3 (Olympus, Tokyo, Japan). Sensitivity/specificity/overall accuracy rates for detection of slight submucosal invasion, massive submucosal invasion, and muscularis propria invasion were 99%/74%/96%, 98%/88%/97%, and 97%/93%/96%, respectively. Incidences of lymph node metastasis in pTis, pTis to pT1‐slight, pT1, pT1‐massive, and pT2 cases were 0%, 0%, 18%, 22%, and 30%, respectively. Incidences of lymph node metastasis in ESRCs staged by EUS (u) as uTis, uT1‐slight, uT1‐massive, uT2, and uT3 by EUS were 0%, 0%, 26%, 36%, and 64%, respectively. Sensitivity, specificity, and overall accuracy rates for detection of positive nodes in overall ESRCs were 53%, 77%, and 72%, respectively. Of the 43 patients with pTis to pT1‐slight tumors, 22 underwent endoscopic polypectomy or local excision, 20 radical surgery, and 1 radical surgery after endoscopic polypectomy due to vascular invasion. All these patients are alive and all but one (who refused radical surgery due to vascular invasion after local excision and developed liver and lung metastases) are disease‐free. Of the 37 patients with pT1‐massive tumors, 34 underwent radical surgery and 3 transcoccygeal segmental resection. All these patients are alive disease‐free except for one who died of peritoneal carcinomatosis after radical surgery. All patients with pT2 tumors underwent radical surgery. The overall 5‐year survival rates for pTis, pT1, and pT2 cases were 100%, 98%, and 97%, respectively. EUS is an accurate method for evaluating invasion depth in ESRC. Patients with uTis or uT1‐slight tumors staged by EUS are at low risk of positive nodes and good candidates for endoscopic polypectomy or local excision. Those with uT1‐massive or uT2 lesions should be treated with a radical operation because of the high incidence of positive nodes.
Differentiated Thyroid Cancer: “Complete” Rational Approach
Authors: Kebebew Electron , Clark Orlo H.
Published: August 2002

Controversy continues regarding the optimal management of patients with differentiated thyroid cancer because no prospective randomized studies evaluating the merits of (1) extent of thyroidectomy, (2) postoperative radioactive iodine ablation, or (3) thyroid‐stimulating hormone (TSH) suppressive therapy exist. Patients with low risk differentiated thyroid cancer enjoy a relatively good prognosis with a mortality rate of about 2% to 5% and a recurrence rate of about 20%. Despite the excellent prognosis in patients considered to be at low risk, total or near‐total thyroidectomy in patients with differentiated thyroid cancer has the advantages that: (1) postoperative radioactive iodine can be used to detect and treat residual normal thyroid tissue and local or distant metastases; (2) follow‐up serum thyroglobulin levels are a more sensitive marker of persistent or recurrent disease when all thyroid tissue has been removed; and (3) total or near‐total thyroidectomy with postoperative 131I ablation and TSH suppressive therapy is associated with better survival and lower recurrence rates. Patients with occult papillary thyroid cancer and minimally invasive follicular thyroid cancer can be treated by thyroid lobectomy because they have a near‐normal life expectancy. Virtually all other patients with differentiated thyroid cancer appear to benefit from more extensive initial treatment.
Mediastinal Tumors: Diagnosis and Treatment
Authors: Wright Cameron D. , Mathisen Douglas J.
Published: August 2002

Mediastinal tumors are uncommon and often asymptomatic if benign. Tumors have a predilection for arising in one of three mediastinal compartments; anterior, middle, or posterior. If symptoms are present, they are usually compressive in origin. Computed tomography is almost always the imaging modality of choice. Benign‐appearing lesions are usually resected for cure. Malignant‐appearing lesions usually require biopsy by the least invasive route appropriate for the suspected tumor type.
Optimum Treatment Strategy for Superficial Esophageal Cancer: Endoscopic Mucosal Resection versus Radical Esophagectomy
Authors: Fujita Hiromasa , Sueyoshi Susumu , Yamana Hideaki , Shinozaki Koji , Toh Uhi , Tanaka Yuichi , Mine Takashi , Kubota Masahiro , Shirouzu Kazuo , Toyonaga Atsushi , Harada Hiroshi , Ban Sigeki , Watanabe Masahide , Toda Yukihiko , Tabuchi Emi , Hayabuchi Naofumi , Inutsuka Hiroki
Published: August 2002

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.
Effect of Pneumoperitoneum on Interatrial Pressure Gradient During Laparoscopic Cholecystectomy
Authors: Iwase Kazuhiro , Kamiike Wataru , Uchikoshi Fumihiro , Takenaka Hiroaki , Miyata Masahiko , Matsuda Hikaru
Published: August 2002

Alterations of the left atrial/right atrial pressure gradient were determined using a Swan‐Ganz thermodilution catheter in 20 patients who underwent laparoscopic cholecystectomy with 12 mmHg pneumoperitoneum (LAP) and 13 patients who underwent minilaparotomy cholecystectomy (MINI). Right and left atrial pressures were both elevated by pneumoperitoneum. A diminished or reversed left/right interatrial pressure gradient was recognized during pneumoperitoneum in 4 of the 20 patients (20%) in the LAP group, whereas it was not recognized during operation in any of the 13 patients in the MINI group. Evaluation of the elevation of intrathoracic pressure during pneumoperitoneum using peak inspiratory airway pressure or pulmonary arterial pressure could not predict the occurrence of this paradoxical interatrial pressure gradient.
Elective Surgery for Corrosive‐Induced Gastric Injury
Authors: Chaudhary Adarsh , Puri Amarinder Singh , Dhar Puneet , Reddy Pratap , Sachdev Ajay , Lahoti Deepak , Kumar Nirmal , Broor Sohan Lal
Published: August 2002

Gastric cicatrization is a well recognized late sequela of corrosive gastric injury, but the optimum timing and type of surgery for this complication are still unclear. Over a 7‐year period (1988–1994) 34 patients underwent elective surgery for gastric lesions secondary to corrosive ingestion. A total of 18 (53%) patients had an associated esophageal stricture and presented with dysphagia, 15 (44%) patients had features of gastric outlet obstruction, 6 (18%) had diffuse gastric injury, and 28 (82%) had a segmental lesion. A tube jejunostomy was done in 23 (68%) patients to improve nutrition and resulted in a significant increase in weight and in the serum protein level after 8 weeks of tube feeding. Elective surgery was performed 3 to 24 months (average 7 months) after ingestion of the corrosive substance. Gastric resection was done in 20 (59%) patients and gastrojejunostomy (without vagotomy) in 11 (32%); at follow‐up the latter group did not exhibit development of a stomal ulcer. In patients with an associated esophageal stricture, endoscopic dilatation was successful in 89% patients and simplified the surgical approach. In conclusion, the success of surgery for corrosive‐induced gastric injury depends on selecting the right procedure and intervening at the appropriate time.
Analysis of Vascular Anatomy and Lymph Node Metastases Warrants Radical Segmental Bowel Resection for Colon Cancer
Authors: Yada Hirokazu , Sawai Kiyoshi , Taniguchi Hiroki , Hoshima Masakazu , Katoh Makoto , Takahashi Toshio
Published: August 2002

To determine the indications for limited colon cancer surgery in each location, we reviewed the arterial branching patterns and lymph node metastases along the course of specific vascular trunks in 344 colon cancer patients who had undergone preoperative angiography and colectomy with lymph node dissection. Our conclusions are follows: Because the ileocecal artery always arises from the superior mesenteric artery and lymph node metastases of cecum cancer were limited to nodes along the ileocolic artery, cecum cancer can be cured by ileocecal resection. The right colic artery has various origins, and ascending colon cancer shows various patterns of lymph node metastases. Therefore a right hemicolectomy should be performed for ascending colon cancer. The middle colic artery forks into right and left branches, and each branch has different branching variations. If the right colic and middle colic arteries have a common trunk, a right hemicolectomy should be performed for transverse colon cancer on the right side. If the left branch of the middle colic artery has an independent replaced origin, lymph node dissection should be modified according to the variant origin. If the left colic artery and the first sigmoidal artery have a common trunk, the lymph nodes along the common trunk should be removed for sigmoid colon cancer and for descending colon cancer. Of the patients with sigmoid colon cancer, 6.3% also had lymph node metastases along the superior rectal artery. Given that the lymph nodes along the superior rectal artery are skeletonized, sigmoid colon cancer can be also cured by partial sigmoidectomy.
Importance of Extended Lymphadenectomy with Lateral Node Dissection for Advanced Lower Rectal Cancer
Authors: Moriya Yoshihiro , Sugihara Kenichi , Akasu Takayuki , Fujita Shin
Published: August 2002

A total of 448 patients with advanced lower rectal cancer who underwent curative wide lymphadenectomy with autonomic nerve preservation were reviewed with respect to surgical techniques, operative burdens, node status, survival rate, and mode of recurrence. Operative time and blood loss in patients who underwent lateral dissection were much greater than those encountered with conventional resection. According to the direction of lymphatic spread in patients with Dukes C disease, the incidence of upward spread was
94% and lateral spread 27%. The overall incidence of lateral metastasis was 14%. The overall 5‐year survival was 70%. According to the Dukes classification, the 5‐year survival rates were 92% for Dukes A, 79% for Dukes B, and 55% for Dukes C, whereas it was 43% in patients with lateral node metastasis. An analysis of the survival rate was carried out with regard to the number of node metastases, direction of lymphatic spread, and autonomic nerve preservation. The overall incidence of local recurrence was 9.3% and amounted to 16.0% in patients with Dukes C disease. The case of advanced lower rectal cancer was characterized by positive lymph nodes or circular lesions around the circumference (both diagnosed by endorectal ultrasonography). We recommend extended lymphadenectomy with lateral node dissection, as it preserves the autonomic nerve.
Circulatory and Anatomic Differences among Experimental Gastric Tubes as Esophageal Replacement
Authors: Schilling Martin K. , Mettler Daniel , Redaelli Claudio , Büchler Markus W.
Published: August 2002

In this experimental study we measured microcirculatory and anatomic differences among a newly developed technique of gastroplasty—fundus rotation gastroplasty (FRG)—and conventional (CG) and reversed (RG) gastric tubes as substitutes for the thoracic and cervical esophagus. After transhiatal esophageal resection, 36 large white pigs were randomly assigned to have an FRG, CG, or RG. Tube length, gastric volume, and compliance as well as blood flow in the tube and the remaining gastric reservoir (by laser Doppler flowmetry) were measured. The FRG tubes were 35.9 ± 3.1 cm long, RG 38.7 ± 3.3 cm, and CG 27.3 ± 2.1 cm (p< 0.05). Gastric compliance was 20.8 ml in the FRG and 3.2 ml and 2.9 ml in the CG and RG, respectively (p < 0.001). Blood flow was significantly higher in FRG tubes than in RG tubes or CG tubes, resulting in a lower anastomotic failure rate (2/12 FRG, 6/12 CG, 7/12 RG). Hence a rotation flap of the gastric fundus (FRG) yields a long, well perfused tube by maintaining the blood supply of the gastric lesser curvature. FRG appears to be a good alternative to CG or RG as a substitute for the thoracic and cervical esophagus.
Implantable Vascular Access Systems: Experience in 1500 Patients with Totally Implanted Central Venous Port Systems
Authors: Kock H.‐J. , Pietsch M. , Krause U. , Wilke H. , Eigler F.W.
Published: August 2002

Totally implantable venous access systems are widely used, but large‐scale studies evaluating these systems are lacking. In this study 1500 patients (719 male, 781 female) with an average age of 49 years (15–86 years) were fitted with subcutaneously implanted venous access systems, in most cases for long‐term chemotherapy. All patients were observed until removal of the system, death, or the end of treatment. A retrospective analysis showed an average catheter life of 284 patient‐days. A total of 1308 (87%) of the patients had no implant‐related complications. Catheter infections occurred in 3.2% of the patients and catheter thromboses in 2.5%. Rarer complications, such as catheter malfunction, migration of the catheter, skin necrosis, catheter fracture, catheter disconnection, and pneumothorax, occurred in another 4.3% of the patients. The complications led to explantation of 178 access systems (11.9%). There was a significant difference (p < 0.05) between the low rate of infections and other complications in the group of patients with solid tumors (2% and 4%, respectively) and the rate in patients with hematologic diseases (6% and 8%, respectively). This study confirms the safety and convenience of using totally implantable venous access systems in patients on long‐term chemotherapy.
Genetic Alterations in Thyroid Carcinoma Associated with Familial Adenomatous Polyposis: Clinical Implications and Suggestions for Early Detection
Authors: Cetta Francesco , Olschwang Sylviane , Petracci Margherita , Montalto Giulia , Baldi Claudio , Zuckermann Michele , Costantini Renato Mariani , Fusco Alfredo
Published: August 2002

Germ‐line mutations of the adenomatous polyposis (
APC) gene, responsible for familial adenomatous polyposis (FAP) were analyzed in 15 patients with FAP‐associated papillary thyroid carcinomas: 13 had the mutation between codons 778 and 1309 (exon 15), 1 at codon 593 (exon 14), and 1 at codon 140 (exon 3). Therefore APC gene mutations clustered in the genomic area associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE) (codons 463–1387). Ocular patches were documented in 12 patients. In particular, 4 of the 15 patients, all women with a mean age of 23.5 (range 20–32), were found during the study of 15 consecutive kindreds who had undergone systematic screening for extracolonic manifestations. Three of them belonged to the same kindred and were asymptomatic. These four patients were also screened for loss of heterozygosity of APC in the thyroid tumoral tissue. No biallelic inactivation of the APC gene was found. In contrast, three of these four patients had activation of theret‐PTC oncogene. In particular, there was activation of the ret‐PTC1 isoform, a chimeric gene resulting from fusion of a gene named H4 with the RET gene. On histologic examination, three of the four patients showed Hashimoto‐like lymphocytic infiltration. Present data suggest that: (1) the incidence of FAP‐associated thyroid cancer probably has been underestimated in the past; (2) intensive screening could detect a larger than expected number of thyroid carcinomas; (3) systematic screening is recommended in patients with ocular patches and genetic mutation in exon 15; (4) Hashimoto‐like findings do not exclude carcinoma but are a frequent accompanying finding; (5) despite frequent multicentricity and early lymph node involvement, FAP‐associated thyroid tumors seem to have an excellent prognosis, in particular those showing ret‐PTC activation.
Emergency Carotid Thromboendarterectomy: Safe and Effective
Authors: Schneider Christina , Johansen Kaj , Königstein Ralf , Metzner Christoph , Oettinger Wolfgang
Published: August 2002

Whether to perform emergency carotid thromboendarterectomy (CTEA) in the presence of crescendo transient ischemic attacks or stroke‐in‐evolution is controversial, with the operative mortality in some reports exceeding 20% and improvement in neurologic deficit of less than 40% in others. Our anecdotal experience with emergency CTEA for acute, persistent, or crescendo neurologic deficit had been strikingly better than published reports. Accordingly, we carried out a restrospective comparison of 43 such patients undergoing emergency CTEA with 237 patients concurrently undergoing elective CTEA for conventional indications. A standard protocol followed in emergency CTEA patients included carotid Doppler ultrasonography, computed cerebral tomography (CT), four‐vessel cerebral arteriography, and intravenous heparin. Exclusions from emergency CTEA included coma or cerebral CT scan evidence for either hemorrhagic or ischemic infarction with edema. Operative techniques included standard carotid endarterectomy with Dacron patch or direct suture, eversion endarterectomy, or shortening resection. No mortality or central neurologic complications resulted among the 43 emergency CTEA patients, in comparison to no deaths and one temporary hemiparesis (0.4% central neurologic morbidity) in the 237 elective CTEA patients. Our results suggest that in the absence of coma or cerebral CT scan evidence for an unstable blood–brain barrier, emergency carotid reconstruction can be performed safely and with excellent outcome notwithstanding the magnitude and severity of the acute preoperative neurologic deficit.
Possible interpretation problems for the current CITES listing criteria in the context of marine fish species under commercial harvest
Authors: Butterworth D. S.
Published: August 2002

The current criteria for listing species on CITES Appendices are summarized briefly. A précis is given of problems with these criteria in a marine species context, as identified by an FAO ad hoc Expert Group meeting in November 1998. Three aspects of the criteria that are of concern to the author are discussed briefly. These are the definition of a “decline,” specifications for taking account of uncertainty, and the desirability of using existing stock‐recruitment data for marine fish species to estimate the spawning biomass level at which critical depensation might occur. This last would provide guidance in specifying resource levels at which there is a threat of extinction when reformulating the CITES criteria.