bluuebunny/crossref_metadata_2025 huggingface dataset:
Can fault‐exposure‐potential estimates improve the fault detection abilities of test suites?
Authors: Chen Wei , Untch Roland H. , Rothermel Gregg , Elbaum Sebastian , von Ronne Jeffery
Published: December 2002

Code‐coverage‐based test data adequacy criteria typically treat all coverable code elements (such as statements, basic blocks or outcomes of decisions) as equal. In practice, however, the probability that a test case can expose a fault in a code element varies: some faults are more easily revealed than others. Thus, several researchers have suggested that if one could estimate the probability that a fault in a code element will cause a failure, one could use this estimate to determine the number of executions of a code element that are required to achieve a certain level of confidence in that element's correctness. This estimate, in turn, could be used to improve the fault‐detection effectiveness of test suites and help testers distribute testing resources more effectively. This conjecture is intriguing; however, like many such conjectures it has never been directly examined empirically. If empirical evidence were to support this conjecture, it would motivate further research into methodologies for obtaining fault‐exposure‐potential estimates and incorporating them into test data adequacy criteria. This paper reports the results of experiments conducted to investigate the effects of incorporating an estimate of fault‐exposure probability into the statement coverage test data adequacy criterion. The results of these experiments, however, ran contrary to the conjectures of previous researchers. Although incorporation of the estimates did produce statistically significant increases in the fault‐detection effectiveness of test suites, these increases were quite small, suggesting that the approach might not be able to produce the gains hoped for and might not be worth the cost of its employment. Copyright © 2002 John Wiley & Sons, Ltd.
Model checking fault tolerant systems
Authors: Bernardeschi Cinzia , Fantechi Alessandro , Gnesi Stefania
Published: December 2002

This paper proposes a modelling approach suitable for formalizing fault tolerant systems, taking into account different fault scenarios. Verification of the properties of such systems is then performed using model checking. A general framework for the formal specification and verification of fault tolerant systems is defined starting from these principles, and experience with its application to two case studies is then presented. Copyright © 2002 John Wiley & Sons, Ltd.
Organic synthesis in a changing world
Authors: Ley Steven V. , Baxendale Ian R.
Published: December 2002

This article is based on a lecture presented to the Chemical Society of Japan at Wasada University on March 27, 2002, by Professor Steven V. Ley.
The lecture, “Organic Synthesis in a Changing World,” was a comprehensive account of the ongoing research efforts of professor Ley's
group in the development and application of solid‐supported reagents and scavengers for use in organic synthesis. © 2002 The Japan
Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 2: 377–388, 2002: Published online in Wiley InterScience
(www.interscience.wiley.com) DOI 10.1002/tcr.10033
L‐histidine decarboxylase as a probe in studies on histamine
Authors: Watanabe Takehiko , Ohtsu Hiroshi
Published: December 2002

Because the Falck‐Hillarp formaldehyde fluorescence method, which was superbly applied to identify catecholaminergic and serotonergic
neurons, is not applicable to histamine, the first author (T.W.) developed an antibody to L‐histidine decarboxylase (HDC)
for identification of the histaminergic neuron system in the brain. The anti‐HDC antibody was of great use for mapping the location and
distribution of this histaminergic neuron system. (S)‐α‐fluoromethylhistidine, a specific and potent irreversible inhibitor
of HDC, was also very useful in studies on functions of the neuron system. The activity of HDC is increased by various agents, treatments, and
physiological conditions. We found new compounds that increased HDC activity (i.e., tetradecanoylphobol acetate (TPA), other tumor
promoters, and staphylococcal enterotoxin A); and using mast cell‐deficient mutant (W/Wv) mice, we obtained
evidence that this increase occurred in macrophages. To further characterize the mechanism of increases in HDC activity, the second author
(H.O.) cloned human HDC cDNA and a human HDC gene. In studies on the regulation mechanism of the HDC gene, which is expressed only in limited
types of cells such as mast cells, enterochromaffin‐like cells in the stomach, cells in the tuberomammillary nucleus of the brain, and
macrophages, CpG islands in the promoter region of the HDC gene were found to be demethylated in cells expressing the gene, whereas they are methylated
in other cells that do not express the HDC gene. In collaboration with many other researchers, we developed HDC knockout mice. The resulting research
is producing a lot of interesting findings in our laboratory as well as in others. In summary, HDC has been and will be useful in studies on functions
of histamine. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 2: 369–376, 2002: Published online in Wiley
InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10036
A case study in conformation design: Learning by doing
Authors: Knust Henner , Hoffmann Reinhard W.
Published: December 2002

Efforts are described to design simple, fully flexible but conformationally preorganised ω‐hydroxy‐nonanoic acids that could
serve as the conformation controlling unit in analogues of the potent protein‐kinase C activator aplysiatoxin. Such analogues are
macrodilactones incorporating the designed ω‐hydroxy‐nonanoic acid and 3,4‐dihydroxy‐pentanoic acid, which contains
the pharmacophoric groups. The design process (replacement of CH2 groups by an oxygen atom, annelation of a six‐membered ring
and placement of alkyl substituents) of the ω‐hydroxy‐nonanoic acids was monitored by force‐field calculations. In
the end of this process simple analogues of aplysiatoxin are proposed in which the proper disposition of the pharmacophoric groups is secured by a
conformationally flexible but preorganised template structure as part of the macrodilactone ring. © 2002 The Japan Chemical Journal Forum and
Wiley Periodicals, Inc. Chem Rec 2: 405–418, 2002: Published online in Wiley InterScience (www.interscience.wiley.com) DOI
10.1002/tcr.10038
Selective transformations of organic compounds by imidozirconocene complexes
Authors: Duncan Andrew P. , Bergman Robert G.
Published: December 2002

Imidozirconocene complexes (Cp2ZrNR(THF)) possess a rich reaction chemistry, in contrast to many
imido complexes of later transition metals. The synthesis and structural characteristics of these compounds are briefly described, along with
a qualitative molecular orbital description of the metallocene‐imido interaction. Imidozirconocene complexes react at the ZrN linkage
with a variety of XH bonds, and undergo overall [2 + 2] cycloaddition reactions with a wide range of unsaturated organic
and organometallic compounds. Results of studies detailing the scope and mechanism of these reactions are presented herein, along with applications
to catalytic hydroamination, imine metathesis, and asymmetric transformations. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals,
Inc. Chem Rec 2: 431–445, 2002: Published online in Wiley Interscience(www.interscience.wiley.com)
Specific GABAA agonists and partial agonists
Authors: Krogsgaard‐Larsen Povl , Frølund Bente , Liljefors Tommy
Published: December 2002

The GABAA receptor system is implicated in a number of neurological and psychiatric diseases, making GABAA receptor ligands
interesting as potential therapeutic agents. Only a few different classes of structures are currently known as ligands for the GABA recognition site on
the hetero‐pentameric GABAA receptor complex, reflecting the very strict structural requirements for GABAA receptor recognition
and activation. Within the series of compounds showing agonist activity at the GABAA receptor site that have been developed, most of the ligands
are structurally derived from the GABAA agonists muscimol, THIP, or isoguvacine, which we developed in the initial stages of the project. Using
recombinant GABAA receptors, functional selectivity was demonstrated for a number of compounds, including THIP, showing highly
subunit‐dependent potency and maximal response. In light of the interest in partial GABAA receptor agonists as potential therapeutics,
structure–activity studies of a number of analogs of 4‐PIOL, a low‐efficacy partial GABAA agonist derived from THIP, have been
performed. In this connection, a series of GABAA ligands has been developed that exhibit pharmacological profiles from moderately potent
low‐efficacy partial GABAA agonist activity to potent and selective antagonist effects. Very little information is available on
direct‐acting GABAA receptor agonists in clinical studies. However, the results of clinical studies on the effect of the partial
GABAA agonist THIP on human sleep patterns show that the functional consequences of a direct‐acting agonist are different from those
seen after the administration of GABAA receptor modulators, such as benzodiazepines and barbiturates. © 2002 The Japan Chemical Journal
Forum and Wiley Periodicals, Inc., Chem Rec 2: 419–430; 2002: Published online in Wiley Interscience (www.interscience.wiley.com) DOI
10.1002/tcr.10040
High‐sensitivity analyses of metabolites in biological samples by capillary electrophoresis using dynamic pH junction‐sweeping
Authors: Britz‐McKibbin Philip , Terabe Shigeru
Published: December 2002

Emerging fields of biochemical research, such as metabolomics, present challenges to current separation technologies because of the large
number of metabolites present in a cell and their often low (submicromolar) concentration. Although capillary electrophoresis
(CE) holds great promise as the method of choice for high‐resolution separations of biological samples, it suffers from poor
concentration sensitivity, especially with the use of UV detection. In CE, sweeping and dynamic pH junction represent two complementary on‐line
focusing techniques that have been used for sensitivity enhancement of hydrophobic and weakly acidic analytes, respectively. However, the application
of either the sweeping or dynamic pH junction technique alone might, in some cases, be less effective for the analysis of certain sample mixtures.
Recent work in the development of a hyphenated dynamic pH junction‐sweeping technique is presented as an effective on‐line method of
preconcentration suitable for both hydrophilic (anionic) and hydrophobic (neutral) analytes. Sensitive analyses of flavin
metabolites by CE with laser‐induced fluorescence (LIF) detection is demonstrated in various biological matrixes, including cell
extracts of Bacillus subtilis, pooled human plasma, as well as heat‐deproteinized flavoenzymes. Enhanced analyte band narrowing and
improved sensitivity is achieved for flavins using dynamic pH junction‐sweeping compared to either sweeping or dynamic pH junction alone.
This results in over a 1200‐fold improvement in sensitivity relative to conventional injection methods, giving a limit of detection (LOD,
defined as S/N = 3) of about 4.0 × 10−12 M. Strategies for sensitive and
more comprehensive analyses of other cell metabolites, including nucleotides, coenzymes, and steroids, are also discussed when using on‐line
focusing techniques in conjunction with multiplexed CE and UV detection. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals, Inc.,
Chem Rec 2: 397–404; 2002: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10041
Macrotetrolide biosynthesis: A novel type II polyketide synthase
Authors: Shen Ben , Kwon Hyung‐Jin
Published: December 2002

Polyketide biosynthesis is catalyzed by polyketide synthase (PKS) and three types of bacterial PKS are known to date. Feeding experiments with
isotope‐labeled precursors established the polyketide origin of the macrotetrolides, but the labeling pattern cannot be rationalized according to the
established PKS paradigm. Genetic analysis of the macrotetrolide biosynthesis unveiled an unprecedented organization for a polyketide gene cluster that
features five genes encoding discrete ketoacyl synthase (KS) and four genes encoding discrete ketoreductase (KR) but lacking an acyl
carrier protein (ACP). Macrotetrolide biosynthesis is proposed to involve a novel type II PKS that acts directly on acyl CoA substrates, functions
noniteratively, and catalyzes both CC and CO bond formation. These findings demonstrate once again Nature's versatility in making complex
molecules and suggests new strategies for PKS engineering to further expand the scope and diversity of polyketide library. They also should serve as an
inspiration in searching for PKS with novel chemistry for combinatorial biosynthesis. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals,
Inc., Chem Rec 2: 389–396; 2002: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10042
In situ scanning tunneling microscopy of oxide‐supported metal clusters: Nucleation, growth, and thermal evolution of individual particles
Authors: Kolmakov Andrei , Goodman D. W.
Published: December 2002

An experimental approach was developed for imaging the nucleation and growth of individual oxide‐supported nanoparticles and their subsequent
in situ chemical and thermal treatments by scanning tunneling microscopy (STM). The potential of the method is demonstrated for Au nanoparticles
supported on a reduced TiO2 substrate where a cluster‐by‐cluster comparison is made of the morphological evolution and stability
of nanoparticles during their nucleation and thermal annealing. Using this methodology the details of the nucleation and growth kinetics can be directly
observed. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals, Inc., Chem Rec 2: 446–457; 2002: Published online in Wiley
InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10045
Site‐specific Design Optimization of Wind Turbines
Authors: Fuglsang P. , Bak C. , Schepers J. G. , Bulder B. , Cockerill T. T. , Claiden P. , Olesen A. , van Rossen R.
Published: December 2002

This article reports results from a European project, where site characteristics were incorporated into the design process of wind turbines, to enable site‐specific design. Two wind turbines of different concept were investigated at six different sites comprising normal flat terrain, offshore and complex terrain wind farms. Design tools based on numerical optimization and aeroelastic calculations were combined with a cost model to allow optimization for minimum cost of energy. Different scenarios were optimized ranging from modifications of selected individual components to the complete design of a new wind turbine. Both annual energy yield and design‐determining loads depended on site characteristics, and this represented a potential for site‐specific design. The maximum variation in annual energy yield was 37% and the maximum variation in blade root fatigue loads was 62%. Optimized site‐specific designs showed reductions in cost of energy by up to 15% achieved from an increase in annual energy yield and a reduction in manufacturing costs. The greatest benefits were found at sites with low mean wind speed and low turbulence. Site‐specific design was not able to offset the intrinsic economic advantage of high‐wind‐speed sites. It was not possible to design a single wind turbine for all wind climates investigated, since the differences in the design loads were too large. Multiple‐site wind turbines should be designed for generic wind conditions, which cover wind parameters encountered at flat terrain sites with a high mean wind speed. Site‐specific wind turbines should be designed for low‐mean‐wind‐speed sites and complex terrain. Copyright © 2002 John Wiley & Sons, Ltd.
Multi‐flexible‐body Dynamic Analysis of Horizontal Axis Wind Turbines
Authors: Lee Donghoon , Hodges Dewey H. , Patil Mayuresh J.
Published: December 2002

This article presents a structural dynamic analysis of horizontal axis wind turbines (HAWTs) using a new methodology. The methodology is based on representing a HAWT as a multi‐flexible‐body system with both rigid‐ and flexible‐body subsystems. The rigid‐body subsystems (nacelle, hub) are modelled as interconnected sets of rigid bodies using Kane's method. Kane's method leads to compact equations of motion for rigid‐body mechanisms. The flexible‐body subsystems (blades, tower) are modelled using geometrically exact, non‐linear beam finite elements derived from a mixed variational formulation for the dynamics of moving beams. The use of the mixed formulation allows for the direct determination of constraint forces and moments within the beam finite element and at the boundaries, thus allowing simple connectivity between the finite elements and rigid bodies. The equations for the rigid and flexible subsystems are coupled to obtain a unified framework that models the dynamic behaviour of the complete system. Linearization of the dynamic equations about the steady state solution yields system equations with periodic coefficients that must be solved by Floquet theory to extract the dynamic characteristics. Numerical studies are presented to investigate the natural frequencies and mode shapes for a HAWT with flexible blades and tower. Copyright © 2002 John Wiley & Sons, Ltd.
Sampling Statistics of Atmospheric Observations
Authors: Kristensen L. , Kirkegaard P. , Mann J.
Published: December 2002

After having specified the basic vocabulary for simple statistics, which is recapitulated for N independent observations in section two, and which leads to the concept degrees of freedom equal to N, we proceed to the statistics of consecutive events that are correlated over finite times, i.e. having a ‘memory’ measured in terms of the integral time scale 𝒯. In section three we determine what we call the effective degrees of freedom 𝒩 for the case where there are many observations over a period of duration 𝒯. In this case, 𝒩 is smaller than N. The analysis is generalized in section four to include a simple equation for the ratio 𝒩/N irrespective of the sampling rate. Finally, in section five we present, as our major contribution, a theoretical model for 𝒩/N when we have intermittent sampling of an otherwise continuous signal. The model is applied to a time series of wind speed in specified wind direction sectors. The time series is intermittently and randomly interrupted when the wind direction gets out of the specified sector. Copyright © 2002 John Wiley & Sons, Ltd.
PHARMACOLOGICAL CHARACTERISTICS OF NOVEL PUTATIVE PURINOCEPTORS IN VASCULAR ENDOTHELIUM
Authors: Liu Shu‐Hong , Shan Li‐Mei , Wang Hai
Published: December 2002

Using an isolated rat aorta with intact endothelium, a functional bioassay system was created as follows: pre‐contract the isolated rat aorta with intact endothelium in the presence of 0.62μmol/l of norepinephrine, and then add acetylcholine to obtain maximal endothelium‐dependent relaxation. In the addition of low concentration of adenosine, a P1 agonist or ATP, a P2 agonist to this system, the rat aorta smooth muscle contraction was observed. This observation could not be explained in terms of the classic P1 and P2 receptor properties, suggesting that there may be a novel subtype of purinoceptors in the endothelium of the rat aorta. The P1 and P2 agonists‐induced rat aorta smooth muscle contraction could be blocked by the pretreatments of the bioassay system with a G protein (Gi/o) inhibitor, PTX, and EDNO synthesis inhibitor, L‐NAME and cyclooxygenase inhibitor, indomethacine. The data strongly support that this novel purinoceptor may couple with PTX‐sensitive G protein, Gi or Go, and the novel purinoceptor‐mediated rat aorta smooth muscle contraction is dependent on the endogenous nitric oxide and prostaglandin synthesis. In an additional observation, pathophysiological conditions, such as hypertension, altered the characteristics of the novel receptor. Hypertension caused the novel receptor insensitive to adensone and uncoupling to PTX‐sensitive G‐proteins and lost of ability to initiate the receptor‐mediated prostaglandin synthesis. All together, the novel putative endothelial purinoceptor may play an important role in the control of vascular tone in physiological or pathophysiological statues.
BAK FOONG PILLS STIMULATE ANION SECRETION ACROSS NORMAL AND CYSTIC FIBROSIS PANCREATIC DUCT EPITHELIA
Authors: Zhu Jin Xia , Lo Pui Shan , Zhao Wen Chao , Tang Ning Chao , Zhou Qing , Rowlands Dewi K. , Gou Yu Lin , Chung Yiu Wa , Chan Hsiao Chang
Published: December 2002

The present study examined the effect of Bak Foong Pills (BFP), an over‐the‐counter traditional Chinese medicine (China registration no. Z980035), on anion secretion and the underlying signaling pathways in normal and cystic fibrosis pancreatic duct cell lines, CAPAN‐1 and CFPAC‐1, respectively, using the short‐circuit current technique. Apical addition of BFP ethanol extract (600μg/ml) induced a fast transient ISC peak that was followed by a slower but more sustained increase in ISC in CAPAN‐1 cells. However, the response to BFP in CFPAC‐1 was predominantly the first transient peak. Apical addition of DIDS (200μM) inhibited the first peak by more than 60% in both cell lines without significantly affecting the second ISC rise. More than 85% of the BFP‐induced first transient in both cell lines was inhibited when extra and intracellular Ca2+ was chelated or emptied by pre‐treatment with BAPTA (100μM) and thapsigargin (10μM), respectively. Acute addition of PMA (1μM), a PKC activator, blocked more than 95% of the BFP‐induced first peak in both cell lines, consistent with previously reported PKC modulation of Ca2+‐dependent pancreatic anion secretion. The BFP‐induced second ISC rise in CAPAN‐1 could be inhibited by 73.6% and 71.13% by pretreatment of the cells with MDL‐12330A (20μM), an adenylate cyclase inhibitor and Rp‐cAMP (200μM), a cyclic AMP antagonist, respectively. However, less than 25% of the ISC was inhibited by combined treatment with BAPTA and thapsigargin. The second rise was also completely blocked by DPC (2mM) or Glibenclamide (1mM). The results indicate that BFP ethanol extract stimulates pancreatic duct anion secretion in normal and CF cells via different signaling pathways involving both Ca2+ and cAMP.
How to pass on expertise: Pancreatoduodenectomy at a teaching hospital
Authors: Wamser Peter , Stift Anton , Passler Christian , Goetzinger Peter , Sautner Thomas , Jakesz Raimund , Fuegger Reinhold
Published: December 2002

Pancreatoduodenectomy (PD) has become a routine procedure. Recent series report perioperative mortality rates of 5% or less, moderate morbidity, and even improved long‐term survival. Nevertheless, being one of the most complex abdominal operations, a certain number of surgical procedures (i.e., personal caseload) seems essential for acceptable results. The objectives of this retrospective study were to evaluate whether PD can be safely performed as a teaching operation, and if the personal caseload of the senior surgeon affects morbidity and mortality. A series of 128 consecutive PDs carried out at a large academic teaching hospital were analyzed. The 49 operations performed by 11 residents of the surgical department as teaching operations under supervision of an experienced (senior) surgeon (ES) were compared with operations performed by an ES (group 2, n=79). Three patients died from non‐procedure‐related causes (two in group 1). Eleven patients of group 2 had to be reoperated, in contrast to three in group 1 (NS). The total number of complications and number of pancreatic fistulas were comparable in the two groups. Surgeons performing less than one PD per year had significantly more complications. Under direct supervision of an experienced surgeon PD can be performed safely as a teaching operation. A caseload of at least one resection per year seems necessary for consistently good results.
Pattern and incidence of first site recurrences following sentinel node procedure in melanoma patients
Authors: Muller Markwin G. Statius , van Leeuwen Paul A. M. , van Diest Paul J. , Pijpers Rik , Nijveldt Robert J. , Vuylsteke Ronald J. C. L. M. , Meijer Sybren
Published: December 2002

Studies of large series of melanoma patients indicated that the average incidence of developing a recurrence during follow‐up was 40%. The most frequent first sites of these recurrences were the regional lymph nodes. We hypothesized that the sentinel node (SN) procedure may change the pattern of recurrence by reducing the number of first recurrences in the regional lymph node basin during follow‐up to a negligible number, and that locoregional cutaneous and distance metastases are the major future sites of recurrence. We further studied the influence of SN status together with different influential factors on prognosis. An SN procedure with a triple technique was performed in 250 consecutive patients with proven AJCC stages I and II cutaneous melanoma. The median follow‐up was 38 months. So far, 44 patients (18%) have developed a recurrence of the disease. The distribution of localization of the first metastases was as follows: 23 patients (52%) with a locoregional cutaneous recurrence; 4 (9%) with recurrence in the regional lymph node basin; 2 (5%) with recurrence in an interval node; and 15 (34%) with distant recurrence. The relative risk of developing recurrence for SN‐positive patients is 4.2; for Breslow thickness of 1.51 to 4.00 mm it is 5.5, and thicker than 4.0 mm it is 6.2; for lymphatic invasion 7.6; and for ulceration 3.8. We conclude that the SN procedure changes the pattern of recurrences during follow‐up by reducing the number of first recurrences within the regional lymph node basin to a negligible number. High Breslow thickness, lymphatic invasion, and ulceration of the primary melanoma are strong risk factors for recurrence.
Are postoperative complaints and complications influenced by different techniques in fashioning and fixing the mesh in transperitoneal laparoscopic hernioplasty? Results of a prospective randomized trial
Authors: Leibl Bernhard J. , Kraft Barbara , Redecke Jens Daniel , Schmedt Claus Georg , Ulrich Martin , Kraft Klaus , Bittner Reinhard
Published: December 2002

It is unknown at present what the best method is among mesh implantation, central incision, reconstructing the deep inguinal ring, or a non‐incised mesh implant in laparoscopic hernia surgery. Further, it is unproven to what extent a circular enclosure of the cremasteric structures by an incised mesh implant could cause postoperative complications and complaints. To evaluate the possible effects of different configurations and fixation techniques of mesh implants in transperitoneal repair of inguinal hernias, a randomized trial (phase IlIa study) was conducted to compare incised versus non‐incised mesh and clip fixation versus suturing the mesh. A total of 360 male patients with unilateral primary hernias were randomized to 3 groups. Postoperative complaints were documented by means of a visual analog scale. These values showed no significant differences between study arms. At the first postoperative control, on day 3, patients after repair of Nyhus type II hernias had significantly fewer complaints than those after Nyhus type IlIa and IlIb repair. To gain additional facts, a duplex flow examination of testicular vessels was performed pre‐ and postoperatively. Testicular perfusion was not influenced by mesh configurations in the trial. There were no statistical differences in postoperative complications and recurrence rates between groups. In conclusion no influence on postoperative complaints and complications could be demonstrated by different mesh fashioning and fixation alternatives studied in this trial.
Intraperitoneal pethidine versus Intramuscular pethidine for the relief of pain after laparoscopic cholecystectomy: Randomized trial
Authors: O’Hanlon Deirdre M. , Colbert Sallyann , Ragheb Jackie , McEntee Gerry P. , Chambers Frank , Moriarty D. C.
Published: December 2002

Laparoscopic cholecystectomy is widely used and may be performed as an ambulatory procedure. We undertook a randomized comparison of the benefits of intraperitoneal pethidine compared with intramuscular pethidine for postoperative analgesia following laparoscopic cholecystectomy. A series of 100 consecutive American Society of Anesthesiologists (ASA) I or II patients were randomly assigned to intramuscular pethidine (54 patients) or intraperitoneal pethidine (46 patients). Each was combined with intraperitoneal bupivacaine. The primary end‐points were the pain and nausea scores at intervals after operation. All recruited patients completed the study. Pain scores at rest and upon movement were significantly lower in the group receiving the intraperitoneal pethidine at each of the time periods examined (pain at rest at 4 hours: 1.6±0.8 vs. 2.4±0.9 cm; p<0.001; pain upon movement at 4 hours: 2.1±0.9 vs. 3.1±1.2 cm; p<0.001). The total dose of pethidine administered via patient‐controlled analgesia (PCA) during the first 24 hours after surgery was also significantly lower in this group (total dose 50.9±3.9 vs. 55.9±4.4 mg; p<0.001). There were no significant differences in the respiratory rate at any of the time periods. Intraperitoneal pethidine analgesia was superior to an equivalent dose of intramuscular pethidine for the relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. This was achieved at the expense of increased nausea but no significant increase in vomiting. The accessibility of this route of analgesia administration has implications for patients undergoing laparoscopic procedures, particularly with the recent trend toward increased use of ambulatory techniques.
Is minisite cholecystectomy less traumatic? Prospective randomized study comparing minisite and conventional laparoscopic cholecystectomies
Authors: Alponat Ahmet , Çubukçu Anil , Gönüllü Nuri , Cantürk Zafer , Öbay Oğuz
Published: December 2002

The main objectives of minisite cholecystectomy (MC) are to have smaller incisions, better cosmetic results, less trauma, and a lower morbidity rate. This prospective randomized study compares MC with conventional laparoscopic cholecystectomy (CLC) in terms of surgical trauma and cosmetic results in 44 patients. Conversion from MC to CLC was required in five patients. No conversion to open surgery was needed in the CLC group. The average operating time was slightly longer in the MC group, but the difference was not statistically significant (81 minutes versus 72 minutes, p=0.22). The population characteristics, postoperative respiratory function measurements, pain scores, and analgesic requirements were similar in the two groups. The average score for scar tissue was significantly lower in the MC group (0.73 versus 1.93, p=0.0045). Only the cosmetic results of MC were superior to CLC. This technique could be a feasible alternative procedure in patients seeking better cosmetic results. However, further studies with larger sample sizes are needed to evaluate the postoperative morbidity of MC.
Reconstructive procedure after distal gastrectomy for gastric cancer that best prevents duodenogastroesophageal reflux
Authors: Fukuhara Kenichiro , Osugi Harushi , Takada Nobuyasu , Takemura Masashi , Higashino Masayuki , Kinoshita Hiroaki
Published: December 2002

Billroth I and II reconstructions are commonly performed after distal gastrectomy. Both may cause duodenogastric and duodenogastro‐esophageal reflux, conditions reported to have carcinogenetic potential. The aim of this study was to investigate which reconstructive procedure would most effectively prevent bile reflux into the gastric remnant and esophagus after distal gastrectomy. A group of 92 patients who underwent curative distal gastrectomy for gastric cancer were subjected and classified into three groups retrospectively by the reconstructive procedure undertaken: group A, Roux‐en‐Y (Roux‐Y) reconstruction (n=29); group B, Billroth I reconstruction (n=41); group C, Billroth II reconstruction (n=22). The bile reflux periods (percent time) for the gastric remnant and esophagus were measured with the Bilitec 2000 under standardized conditions. The percent time for the gastric remnant was significantly less in group A than in group B or C. In 61% of all patients, bile reflux into the esophagus was found to be more than 5.0% of the time; it was less in group A than in group B or C (p=0.057). A questionnaire revealed a good correlation between the incidence of reflux symptoms and the percent time for the gastric remnant and esophagus. Roux‐Y reconstruction is superior to either Billroth I or II reconstruction for preventing bile reflux into the gastric remnant and esophagus after distal gastrectomy.
Long‐term results of vein sparing varicose vein surgery
Authors: Raivio Peter , Perhoniemi Vesa , Lehtola Aarno
Published: December 2002

The aim of this study was to assess the long‐term functional outcome of vein sparing varicose vein surgery using handheld Doppler ultrasound (HHD). The series consisted of 171 consecutive day‐case surgery patients operated on for uncomplicated lower limb varicose veins. Venous segments considered competent were spared based on clinical examination and HHD, which was performed preoperatively only when deemed necessary by the surgeon. After a mean follow‐up of 8 years all patients were examined, a systematic HHD evaluation was performed, and the findings were classified according to the CEAP (Clinical, Etiological, Anatomical, Pathophysiological) classification, and disability scoring was performed. During the follow‐up period 17% of the legs were reoperated or scheduled for reoperation. At follow‐up 79% of all patients were asymptomatic without reoperation. In 24%, recurrent varicosities were present and venous reflux was demonstrated by HHD. Recurrence was two times more common when the saphenofemoral junction had originally been left intact. Of all recurrent cases, reflux was demonstrated in the long saphenous vein (LSV) above the knee in 62%, in the LSV below the knee in 7%, in the short saphenous vein (SSV) in 16%, in the posterior arch vein in 38%, and in a thigh perforator in 8%. Of the legs reoperated during the follow‐up period 41% presented with venous reflux at the follow‐up visit. We conclude that HHD efficiently reveals sites of reflux that have been missed during previous surgery and that a thorough preoperative HHD examination and marking of reflux routes is required.
Role of nitric oxide in the internal anal sphincter of hirschsprung’s disease
Authors: Tomita Ryouichi , Fujisaki Shigeru , Tanjoh Katsuhisa , Fukuzawa Masahiro
Published: December 2002

It is not clear what contribution the internal anal sphincter (IAS) makes to the impaired motility observed in patients with Hirsch‐sprung’s disease (HD). Nitric oxide (NO) has recently been shown to be a neurotransmitter in the nonadrenergic noncholinergic (NANC) inhibitory nerves in the human gut. To clarify the physiologic significance of NO in the IAS of HD (aganglionosis), we investigated the enteric nerve responses on lesional (aganglionic) and normal IAS muscle Strips above the dentate line. Lesional and normal LAS muscle strips above the dentate line were derived from patients with HD (10 cases) and patients who underwent rectal amputation for low rectal Cancer (12 cases). A mech‐anographic technique was used to evaluate in vitro muscle responses to electrical field Stimulation (EFS) before and after treatment with various autonomic nerve blockers, NG‐L‐nitroarginine, and L‐arginine. The following results were obtained: (1) Cholinergic nerves are mainly involved in the regulation of enteric nerve responses to EFS in the normal LAS. (2) The aganglionic LAS of patients with HD was more strongly innervated by cholinergic nerves than the normal IAS (p<0.05). (3) NANC inhibitory nerves were found to act on the normal IAS but had no effect on the enteric nerves in patients with aganglionosis. (4) NO was found to act on normal LAS, but no effect was observed in the aganglionic IAS. These findings suggest that innervation of the cholinergic nerves and a loss of NO mediation of NANC inhibitory nerves play an important role in the impaired motility observed in the IAS with HD.
Systemic immune response after laparoscopic and open cholecystectomy
Authors: Sheen‐Chen Shyr‐Ming , Chen Han‐Shiang , Eng Hock‐Liew , Chen Wei‐Jen , Jawan Bruno
Published: December 2002

The laparoscopic approach is thought to reduce the postoperative immunologic and metabolic effects of an open operation. This study was designed with the aim of comparing the systemic immune response after laparoscopic and open cholecystectomy. Seventeen patients with gallbladder stones were assigned to undergo either a laparoscopic (n=9) or open (n=8) approach. The postoperative immune response was assessed by measuring the serum levels of soluble Fas (sFas), soluble L‐selectin (sL‐selectin), and transforming growth factor‐β1 (TGFβ1) preoperatively and 2 hours, 1 day, and 2 days postoperatively. Both approaches resulted in a significant decrease in sFas levels 1 and 2 days postoperatively. The open approach evoked a transient increase in sL‐selectin levels 2 hours postoperatively. Moreover, the open approach resulted in a persistent, significant increase in TGFβ1 levels postoperatively. Comparison of open versus laparoscopic cholecystectomy has shown no significant difference in sFas level and a statistically significant increase of sL‐selectin (within 2 hours) and TGFβ levels after open surgery. Although both laparoscopic and open cholecystectomy evoked an alteration of the systemic immune response, our data showed that such immune response may be less after the laparoscopic approach.
Effects of prolonged pneumoperitoneum on hemodynamics and acid‐base balance during totally endoscopic robot‐assisted radical prostatectomies
Authors: Meininger Dirk , Byhahn Christian , Bueck Matthias , Binder Jochen , Kramer Wolfgang , Kessler Paul , Westphal Klaus
Published: December 2002

Laparoscopic techniques have become a standard approach for diagnostic and therapeutic procedures in many surgical disciplines. Recent progress in endoscopic surgery is based on the integration of computer‐enhanced telemanipulation systems. Because robot‐assisted radical prostatectomies take up to 10 hours, the present study was performed to evaluate the effects of prolonged intraperitoneal CO2 insufflation on hemodynamics and gas exchange in 15 patients with prostate cancer. When CO2 insufflation was initiated, peak inspiratory pressure increased and reached significant values after a 1.5‐hour period of intraperitoneal CO2 insufflation. With the release of CO2, peak inspiratory pressure decreased close to baseline values. A significant increase in heart rate was observed after a 4‐hour period of increased intraabdominal pressure. Mean arterial blood pressure and central venous pressure remained stable during CO2 insufflation. Minute ventilation was adjusted according to repeated blood gas analyses to maintain pH, base excess (BE), bicarbonate (HCO3−), and PaCO2 within physiologic ranges. The present data show, that prolonged CO2 insufflation during totally endoscopic robot‐assisted radical prostatectomy results in only minor changes in hemodynamics and acid‐base status. Because of the limited experience with long‐term pneumoperitoneum, we consider invasive haemodynamic monitoring and repeat blood gas analysis essential for such operations.
Clinical examination is an inaccurate predictor of intraabdominal pressure
Authors: Sugrue Michael , Bauman Adrian , Jones Felicity , Bishop Gillian , Flabouris Arthas , Parr Michael , Stewart Anthony , Hillman Ken , Deane Stephen A.
Published: December 2002

This study was designed to establish if clinical examination can accurately predict intraabdominal pressure (IAP). Between August 1998 and March 2000 a prospective blinded observational study of postoperative intensive care unit patients was undertaken at a major trauma center. IAP was measured using an intravesicular technique and compared with clinical evaluation. An IAP of at least 18 mmHg was considered elevated. The sensitivity, specificity, positive predicative value (npv), negative predictive value (npv), kappa score, and reliability analysis were calculated. A total of 110 patients provided 150 estimates of IAP, which was elevated in 21%. The kappa score was 0.37; sensitivity, 60.9%; specificity, 80.5%; ppv, 45.2%; npv, 88.6%. The mean difference in IAP values between intravesicular readings and clinical estimates was −1.0±4.1. Prediction of IAP using clinical examination is not accurate enough to replace intravesicular IAP measurements.
Outcome of histologically node‐negative esophageal squamous cell carcinoma
Authors: Tabira Yoichi , Yasunaga Masahiro , Sakaguchi Tomonori , Yamaguchi Yuji , Okuma Toshiyuki , Kawasuji Michio
Published: December 2002

The outcome of node‐negative esophageal carcinoma and the prognostic significance of lymph node micrometastasis remain unknown. The aim of this retrospective study was to clarify these two points. A series of 98 patients who underwent curative operation for histologically node‐negative (pNO in TNM classification) esophageal carcinoma were enrolled in the study. We reviewed the cause of death of these patients. The survival curves were calculated and compared after stratifications according to clinicopathologic parameters. Lymph node micrometastasis in the patients with recurrences was examined using immunohistochemical staining of cytokeratin. Their ages ranged from 45 to 83 years (mean 64.3 years). There were 83 men and 15 women. Altogether, 54 patients were still alive, and 44 had died. A total of 9 patients died from recurrence of their esophageal carcinoma, 33 died from other causes (pneumonia 11, extraesophageal carcinoma 7, and so on), and 2 died from unknown causes. Eight patients had locoregionai recurrences, and two patients had distant recurrences. The overall survival rate for the 98 patients was 58.2%. The survival for patients with pT2 or pT3 tumors was significantly worse than for those with pTis or pTl tumors (p=0.02, log‐rank test). Other clinicopathologic factors did not affect the prognosis. Immunohistochemical study found no lymph node micrometastasis in 365 lymph nodes resected from the patients with recurrences. Only the depth of tumor invasion affected the outcome of patients with node‐negative esophageal carcinoma. Altogether, 75% of patients died of other causes without recurrence, with the two main causes of death being pulmonary complications and extraesophageal carcinoma in these patients. Lymph node micrometastasis was not associated with recurrence in this series.
Total thyroidectomy for management of benign thyroid disease: Review of 526 cases
Authors: Bellantone Rocco , Lombardi Celestino Pio , Bossola Maurizio , Boscherini Mauro , De Crea Carmela , Alesina Pierfrancesco , Traini Emanuela , Princi Pietro , Raffaelli Marco
Published: December 2002

Total thyroidectomy is not frequently performed in cases of benign disease because of the associated risk of postoperative hypoparathyroidism and recurrent laryngeal nerve (RLN) damage. We chose a series of patients who had undergone total thyroidectomy (TT) for benign thyroid tumors to evaluate the safety of this approach and its role in the treatment of nonmalignant lesions of the thyroid. We considered only patients with a minimum follow‐up of 24 months. Records of 526 patients who underwent TT were carefully reviewed, assessing for perioperative complications and late sequelae. The mean age was 44 ± 15.7 years; 109 patients (20.7%) were male and 417 (79.3%) were female. Altogether, 65 patients (12.3%) were operated on for toxic goiter, 429 (81.6%) for bilateral nodular goiter, and 32 (6.1%) for thyroiditis. Postoperative hemorrhage requiring reoperation occurred in 8 cases (1.5%). The incidences of permanent RLN palsy (considered as a percentage of the nerves at risk) and permanent hypocalcemia were 0.4% and 3.4%, respectively. A trend toward a decrease in the complication rate was observed during the last 5 years. There were no disease recurrences during a mean follow‐up of 44 months. The results of our series show that TT can be performed safely in patients, with a low incidence of lifetime disabilities. TT has the advantage of reducing/avoiding the risk of disease recurrence and reoperation and should therefore be considered a valuable option for treating benign thyroid diseases.
Multifactorial risk profile for bone fractures in primary hyperparathyroidism
Authors: Nordenström Erik , Westerdahl Johan , Lindergård Birger , Lindblom Pia , Bergenfelz Anders
Published: December 2002

Primary hyperparathyroidism (pHPT) is associated with an increased fracture risk, and decreased bone density thus has been considered an indication for surgery. However, many pHPT patients have a multifactorial risk profile for osteoporosis and bone fractures. The aim of the present study was to evaluate variables associated with fracture risk within the group of pHPT patients. A series of 203 consecutive patients operated for pHPT were investigated with bone mineral content and biochemical and clinical risk factors for bone fracture. Seventeen patients (8%) had a history of at least one bone fracture up to 5 years before pHPT surgery. Twenty‐six patients (13%) had a history of at least one fracture during the 10‐year period prior to surgery. In the univariate analyses corticosteroid treatment, serum levels of alkaline phosphatase, 25‐hydroxyvitamin D3, type I collagen telopeptide, and bone mineral content were found to be associated with a history of bone fractures up to 10 years before surgery. Additionally, age and menopausal status were of importance for fractures during the 10‐year‐period, whereas a history of cardiovascular disease was important for fractures during the 5‐year‐period prior to surgery. Multivariate analyses showed that serum level of PTH was independently associated with bone fractures during the 5‐year period prior to pHPT surgery and further that serum level of 25‐hydroxyvitamin D3 was associated with fractures up to 10 years before surgery. In conclusion, serum levels of 25‐hydroxyvitamin D3 and PTH were independently associated with a history of bone fractures in pHPT. These variables should be considered when evaluating patients for parathyroid surgery.
Retrospective evaluation of carcinoid tumors of the appendix in children
Authors: Prommegger Rupert , Obrist Peter , Ensinger Christian , Profanter Christoph , Mittermair Reinhard , Hager Josef
Published: December 2002

Carcinoids of the appendix are rare in children and are usually diagnosed incidentally on histologic investigation following appendectomy for appendicitis. To investigate the significance of the diagnosis of appendiceal carcinoid in children, we conducted a retrospective study of the treatment and follow‐up of 36 children with histologically confirmed carcinoid tumors of the appendix. Between 1970 and 2000 a total of 36 patients (25 girls, 11 boys) were diagnosed with appendiceal carcinoid. The median age of the patients at diagnosis was 12.3 years (range 6–16 years). The indication for appendectomy was acute lower right quadrant pain in 27 cases and chronic right lower quadrant pain in 9 patients. In 27 specimens the tumor was localized at the apex, in 7 at the midportion, and in 2 at the base of the appendix. The median tumor diameter was 6 mm (range 3–17 mm). Concomitant severe appendicitis was diagnosed in 14 patients 2 with a perforated appendicitis. In only one tumor were mucin‐producing cells detectable. After a median follow‐up of 10 years (range 2 months to 30 years) all patients were tumor‐free. None of the patients had a synchronous or metachronous noncarcinoid malignant tumor. Appendiceal carcinoids are usually asymptomatic, and the indication for surgical Intervention is acute or chronic abdominal pains in the right lower quadrant. For most patients the prognosis is excellent after appendectomy. As in adults, appendectomy is the appropriate treatment.