bluuebunny/crossref_metadata_2025 huggingface dataset:
Solutions for Difficult Diagnostic Cases of Community-Acquired Pneumonia
Authors: Fine Michael J.
Published: April 2003

Community-acquired pneumonia (CAP) is a common illness that creates significant burdens upon the healthcare system. Improving the quality of medical care for patients with this illness requires an evidence-based and cost-efficient treatment approach. The first step in this approach is to make an accurate diagnosis, while considering the full differential diagnosis of the illness. This requires an understanding of the sensitivity and specificity of the history and physical examination to establish the diagnosis of CAP. The second step is to quantify severity of illness, which can help physicians determine the appropriate initial site of treatment, intensity of the diagnostic evaluation, and choice of initial antibiotic therapy. Case histories are presented to outline the clinical application of an approach that uses the Pneumonia Patient Outcomes Research Team (PORT) prediction rule for prognosis to quantify the severity of illness, and recent guidelines for the management of CAP are highlighted.
Substance P and Affective Disorders: New Treatment Opportunities by Neurokinin 1 Receptor Antagonists?
Authors: Lieb Klaus , Treffurth Yvonne , Berger Mathias , Fiebich Bernd L.
Published: April 2003

Substance P (SP) is a neuropeptide which is abundant in the periphery and the central nervous system, where it is colocalized with other neurotransmitters such as serotonin or dopamine. SP has been proposed to play a role in the regulation of pain including migraine and fibromyalgia, asthma, inflammatory bowel disease, emesis, psoriasis as well as in central nervous system disorders. This review summarizes our current knowledge of the role of SP in the pathogenesis of neuropsychiatric disorders with special emphasis on affective disorders including bipolar disorders. It also reviews current treatment approaches with neurokinin 1 receptor antagonists which appear to be promising drugs for the future treatment of affective disorders.
Cardiovascular Effects of Beta-Blockers with and without Intrinsic Sympathomimetic Activity
Authors: Heusser K. , Schobel H.P. , Adamidis A. , Fischer T. , Frank H.
Published: April 2003

Background: Celiprolol, a newer beta-blocking agent, has been reported to have vasodilatory capacity which may be due to partial beta-2-receptor agonistic activity or to alpha-receptor antagonistic or central sympathoinhibitory effects. Methods: To more critically assess the physiologic effects of celiprolol, we measured sympathetic nerve activity to muscle (MSNA), forearm blood flow (FBF), blood pressure (BP), central venous pressure, and heart rate (HR) in 10 normal volunteers at rest, during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP), and during a cold pressor test (CPT). Responses were compared with those seen with metoprolol and with placebo, i.e. each subject was studied three times. Results: Celiprolol did not alter resting levels of hemodynamics, FBF, and MSNA nor did it alter responses to LBNP or the CPT. In contrast, metoprolol produced significant decreases of FBF and HR, and increases of forearm vascular resistance and BP, but had also no effect on responses to the applied stress tests. Conclusions: The lack of peripheral vasoconstriction seen after acute administration of celiprolol is most likely due to its partial beta-2-receptor agonistic effect and does not seem to be due to a central or reflex action or to an alpha-blocking effect. Both beta-blockers do not impair fundamental neural mechanisms involved in circulatory homeostasis.
DNA Arrays in Allergy and Immunology
Authors: Schmidt-Weber Carsten B. , Wohlfahrt Jan G. , Blaser Kurt
Published: April 2003

The DNA array technique allows the simultaneous analysis of multiple genes. This makes it an interesting tool for studies of gene expression in various diseases that are caused by or depend on multiple genes. DNA arrays are particularly applied to define certain immunological conditions such as allergic diseases. We summarize strategies on gene expression profiling of inflammatory disease and immunologically relevant cells using DNA array technology. Using DNA arrays, gene expression analysis of CD4+ T cells of allergy patients revealed interesting differences compared to healthy individuals, but also between different allergic conditions. This comparison demonstrated that T cells differed in their capacity to regulate peripheral tolerance, neuronal innervation, chemotaxis, neovascularization and epidermal growth. On the basis of these findings the DNA array technique appears to be especially interesting for the development of powerful diagnostic tools allowing fine specification and subtyping of allergic conditions, monitoring of therapy and of tailored therapy concepts.
A Hypoallergenic Derivative of the Major Allergen of the Dust Mite Lepidoglyphus destructor, Lep d 2.6Cys, Induces Less IgE Reactivity and Cellular Response in the Skin than Recombinant Lep d 2
Authors: Kronqvist Marianne , Johansson Eva , Whitley Paul , Olsson Susanna , Gafvelin Guro , Scheynius Annika , van Hage-Hamsten Marianne
Published: April 2003

Background: The major allergen of the dust mite Lepidoglyphus destructor, Lep d 2, has been produced as a recombinant allergen (rLep d 2) with IgE reactivity both in vivo and in vitro. A modified form of rLep d 2 (rLep d 2.6Cys) obtained by site-directed mutagenesis has been shown to have a reduced IgE reactivity in vitro. In this study we have compared the ability of rLep d 2 and rLep d 2.6Cys to elicit positive skin prick tests and cellular responses among L. destructor-sensitized subjects. Methods: Seventeen subjects were skin prick-tested with rLep d 2, rLep d 2.6Cys, histamine and negative controls and 17–20 h later skin biopsy specimens were taken from the skin prick-tested sites. The biopsy specimens were stained immunohistochemically for EG2+, CD3+, CD1a+, mast cell tryptase+, and IgE+ cells. Dermal cell infiltrates were judged in hematoxylin and eosin staining. Total IgE and allergen-specific IgE were determined by CAP-RAST. Results: Compared to rLep d 2, rLep d 2.6Cys induced significantly smaller and fewer skin prick test reactions (p < 0.001) and dermal cell infiltrates (p < 0.05). Further, rLep d 2.6Cys induced fewer EG2+ cells (p < 0.001) but more tryptase+ cells (p < 0.05) than rLep d 2. A positive RAST to rLep d 2 was obtained for 88.2% of the subjects, while only 35.2% displayed a positive RAST to rLep d 2.6Cys. Conclusion: This study demonstrates that rLep d 2.6Cys is less able to evoke IgE-mediated reactions and cellular responses, as measured both in skin and in serum, than rLep d 2. In the future this hypoallergenic derivative may be a promising candidate molecule for immunotherapy of L. destructor-allergic patients.
Interleukin 13: A Growth Factor in Hodgkin Lymphoma
Authors: Skinnider Brian F. , Kapp Ursula , Mak Tak W.
Published: April 2003

Classical Hodgkin lymphoma (cHL) is a malignant disorder of lymph nodes with distinctive clinical and pathologic features. These features are thought to be primarily due to the abnormal production of multiple cytokines by the malignant cell population of HL, the Reed-Sternberg (RS) cells. We have previously demonstrated that interleukin (IL)-13 expression is a common feature of HL and have studied its role as an autocrine growth factor for RS cells. IL-13 and IL-13Rα1, the IL-13-specific receptor chain, are frequently expressed by HL-derived cell lines and by RS cells from biopsy material of tissues involved by HL. Neutralization of IL-13 in cultures of the HL-derived cell lines HDLM-2 and L-1236 leads to a dose-dependent inhibition of proliferation, and is associated with increased apoptosis in L-1236 cells. Signal transducer and activator of transcription (STAT) 6 is an important mediator of IL-13 signaling. STAT6 is constitutively activated in HL cell lines due to autocrine secretion of IL-13. STAT6 is also phosphorylated (P-STAT6) in RS cells from many primary HL samples, supporting the hypothesis that IL-13 signaling occurs in these malignant cells in vivo. Coexpression of IL-13, IL-13Rα1 and P-STAT6 is uncommon in non-Hodgkin lymphomas. Following a description of the clinical and pathologic features of HL, this review will discuss the function of IL-13 as an autocrine growth factor for RS cells in HL and its potential role in mediating other features of this disease.
Evaluation of Pulmonary Edema: Stereological versus Gravimetrical Analysis
Authors: Fehrenbach Antonia , Fehrenbach H. , Wittwer T. , Ochs M. , Wahlers T. , Richter J.
Published: April 2003

Assessment of lung edema by gravimetrical analysis is a standard method to evaluate the severity of experimentally induced ischemia/reperfusion (IR) injury. The aim of this study was to compare gravimetrical assessment of pulmonary edema with a stereological approach which allows for qualitative and quantitative distinction between intravascular and edematous fluids by light microscopy. Eight experimental groups which differed in mode of preservation, ischemic storage and pharmacological treatments were studied in an extracorporeal rat lung model. Analysis of the pooled data showed that the wet/dry ratio values mainly reflected the amount of intra-alveolar edema (rs = 0.442; p = 0.0057) but only stereological assessment of edema formation revealed differences depending on the treatment used. Only stereological data correlated significantly with oxygen tension measured at the end of reperfusion (rs = –0.530; p = 0.0009). We conclude that gravimetry is of minor functional importance compared to assessment by stereological methods which prove to be a reliable and efficient tool for the evaluation of IR injury in the different experimental settings.
Subcutaneous Low-Dose Epoetin Beta for the Avoidance of Transfusion in Patients Scheduled for Elective Surgery Not Eligible for Autologous Blood Donation
Authors: Wurnig C. , Schatz K. , Noske H. , Hemon Y. , Dahlberg G. , Josefsson G. , Milbrink J. , Hamard Christiane
Published: April 2003

This randomized, multicentre, parallel-group study assessed the efficacy of epoetin beta in reducing the transfusion frequency in patients ineligible for autologous blood donation prior to surgery. The patients (n = 194) received either epoetin beta (125 or 250 IU/kg, once weekly) or no therapy for 3–4 weeks before surgery. The pre-operation haemoglobin levels were markedly increased in the epoetin beta groups (125 IU/kg: +1.1 g/dl; 250 IU/kg: +1.6 g/dl), but not in the control group. The transfusion frequency was significantly reduced in both epoetin groups as compared with the control group (p = 0.046). Epoetin beta was well tolerated, and no serious adverse events were observed. Low-dose administration of epoetin beta before elective surgery reduces the transfusion frequencies in patients not eligible for autologous blood donation.
Role of the Fas System in Liver Regeneration after a Partial Hepatectomy in Rats
Authors: Taira K. , Hiroyasu S. , Shiraishi M. , Muto Y. , Koji T.
Published: April 2003

Apoptosis is involved in the homeostatic control of organs. The aim of this study was to define the in vivo role of apoptosis-related proteins including the Fas system and Bcl-2 in liver regeneration following a partial hepatectomy (PH). We used 70% hepatectomized rats which were serially sacrificed from 12 h to 28 days. The expressions of Fas, Fas ligand, and Bcl-2 were examined by semiquantitative RT-PCR and immunohistochemistry. Liver regeneration, as examined by PCNA staining, peaked from 24 h to day 3, and declined from day 5. On the other hand, hepatocyte apoptosis, as examined by TUNEL staining, was seldom observed until 24 h, but increased from 1 week after PH. In the RT-PCR study, Fas showed an early decline by 24 h, followed by a later peak from days 3 to 5, and then a constant expression thereafter. Meanwhile, the Fas ligand was also low until day 3, but showed a remarkable increase from days 5 to 7, followed by a gradual decrease. On the other hand, Bcl-2 showed an early peak until 24 h, followed by a decline from day 5. In an immunohistochemical study, the time courses of these protein expressions were almost synchronous with their mRNAs in the RT-PCR study. We thus conclude that the coordinated interplay between these apoptosis-related proteins and hepatocyte apoptosis suggests the possible involvement of these proteins in the course of liver regeneration.
Isolated Liver Perfusion Permits Administration of High Doses of Chemotherapeutic Agents
Authors: Thorlacius H. , Larmark M. , Randell M. , Hultberg B. , Jeppsson B.
Published: April 2003

Tumor cells are dependent on glutamine metabolism and acivicin, which is a selective glutamine antagonist, has been shown to effectively retard tumor growth in several malignancies. However, systemic treatment with acivicin is associated with significant side effects. The purpose of the present study was to examine whether use of an in vivo isolated liver perfusion model may allow administration of lethal doses of acivicin and compare it to regional infusion of acivicin in the hepatic artery. Five days after tumor inoculation, acivicin was administered by an isolated liver perfusion model or by regional infusion via the hepatic artery. It was found that regional infusion of acivicin (5 and 10 mg/kg) via the hepatic artery caused systemic illness and diarrhea, and all animals in this group died within 3 days. In contrast, we observed no signs of systemic illness, diarrhea or hepatocellular injury in rats receiving isolated liver perfusion with or without acivicin (10 mg/kg) administration. Noteworthy, we found that isolated perfusion with acivicin reduced the glutamine content in liver tumors by 39% compared to perfusion with control medium. In line with this, it was found that isolated perfusion with acivicin (10 mg/kg) inhibited tumor growth in the liver. Taken together, this study suggests that application of the isolated liver perfusion model avoids the toxic and lethal effects of high doses of chemotherapy, herein acivicin, and may provide a useful approach to treat liver tumors in vivo.
Simple Tool Use by a Red-Tailed Monkey (Cercopithecus ascanius) in Kibale Forest, Uganda
Authors: Worch Eric A.
Published: April 2003

//8RAlthough rarely observed in the wild, tool use in varying contexts has been reported for numerous non-hominoid primates [1]. Guenons have been reported to drop branches at human pursuers [2] but have not previously been reported to use tools in contexts requiring more dexterous manipulations, such as feeding and grooming. This is somewhat surprising because captive Cercopithecus species manipulate objects with their fingers as frequently as Macaca, Papio and Cercocebus [3], all of which have been observed using tools as feeding or grooming aids [4–6]. The purpose in this report is to describe the use of an unmodified leaf by an adult female red-tailed monkey (Cercopithecus ascanius) to wipe a sticky substance from her fingers.
Detection of Serum and Intrahepatic Human Hepatocyte Growth Factor in Patients with Type C Liver Diseases
Authors: Yamagami Hiroaki , Moriyama Mitsuhiko , Tanaka Naohide , Arakawa Yasuyuki
Published: April 2003

We determined hepatocyte growth factor (HGF) levels in the serum and liver of patients with hepatitis C and assessed the relationship to histological findings of the liver and hepatitis C virus-related markers in the serum in patients with type C liver diseases. The subjects were 108 patients with chronic hepatitis C (CH), 70 patients with liver cirrhosis C (LC), 38 patients with hepatocellular carcinoma (HCC) and 20 patients with acute hepatitis (AH). As normal controls 20 subjects were studied. The serum HGF levels were measured using an enzyme-linked immunosorbent assay kit. Intrahepatic HGF was investigated by immunoperoxidase staining using monoclonal HGF antibody. The serum HGF level was highest in patients with AH. The serum HGF levels tended to be higher in patients with LC and HCC than those with CH. Further, the serum HGF level was related to the degree of intrahepatic inflammatory cell infiltration and fibrosis, and intrahepatic HGF was noted primarily in the cell membrane of mesenchymal cells in focal necrosis. The degree of intrahepatic HGF expression tended to be higher in patients with high serum HGF levels. In patients with HCC, however, HGF showed little localization in cancer cells, but was noted in infiltrating mesenchymal cells in both cancerous and noncancerous regions. In conclusion, the measurement of serum HGF levels may be useful for estimating the degree of intrahepatic inflammatory reaction and fibrosis. Although further study is necessary, the high serum level of HGF revealed high carcinogenic states in chronic hepatitis and liver cirrhosis type C.
DNA Vaccines for Prophylactic or Therapeutic Immunization against Hepatitis B
Authors: Michel Marie-Louise , Loirat Delphine
Published: April 2003

DNA-based or genetic vaccination is an efficient new technique to stimulate specific immune responses after in vivo delivery of bacterial plasmids encoding antigens. In mice and in various other animal models for hepadnavirus infection, DNA vaccines specific for hepatitis B virus (HBV) antigens induce a strong humoral and cell-mediated immunity that confers protection in some models. Although there are effective prophylactic vaccines already available for HBV, there is currently no effective treatment for chronic HBV infection. Patients with HBV-associated liver disease are at increased risk of developing hepatocellular carcinoma and would greatly benefit from the availability of a therapeutic vaccine against HBV. By inducing immune responses closely related to those involved in clearing virus from the host, DNA vaccines may represent an alternative therapeutic approach for chronic HBV infection.
A Novel, Recombinant Triple Antigen Hepatitis B Vaccine (Hepacare®)
Authors: Page M. , Jones C.D. , Bailey C.
Published: April 2003

Infection with hepatitis B virus (HBV) continues to be a major problem in the human population. There remains a specific requirement for HBV vaccines capable of circumventing the non-responder/inadequate responder status of some vaccinees. Hepacare has been primarily developed to (1) improve anti-SHBs antibody titres in low responders, to conventional SHBsAg vaccinees, (2) overcome difficulties of non-compliance seen with existing SHBsAg vaccine regimens. Hepacare is a novel recombinant particle produced in eukaryotic cells, consisting of pre-S1, pre-S2 and S proteins of HBV and is adjuvanted with alhydrogel. It has been demonstrated to be highly immunogenic for both B and T cells in mice, chimpanzees and humans and induces higher anti-S ‘a’ determinant antibody titres than SHBsAg vaccines in mice and humans. Hepacare has proven to be at least as efficacious as current SHBsAg vaccines in chimpanzees. Clinical trials in both Europe and the USA have clearly demonstrated its superior ability to induce anti-SHBs antibody seroconversion in low-responder groups, compared with SHBsAg vaccines.
Perspectives of Vaccination against Hepatitis E
Authors: Safary Assad
Published: April 2003

Hepatitis E, an important cause of morbidity and mortality in humans, accounts for more than 50% of acute viral hepatitis in young adults in developing countries with a 20–30% mortality rate among infected pregnant women primarily those in their third trimester. The development of inactivated or live attenuated virus vaccine has been hampered because this virus does not replicate efficiently in cell culture. A vaccine has been developed by an alternative approach through recombinant technology. Preliminary results of the first administration in man conducted in the US at Walter Reed Army Institute of Research indicate the vaccine to be safe and immunogenic and have led to the decision to further evaluate the vaccine in an endemic setting.
Significance of Serum Matrix Metalloproteinases and Their Inhibitors on the Antifibrogenetic Effect of Interferon-Alfa in Chronic Hepatitis C Patients
Authors: Ninomiya Toshiaki , Yoon Seitetsu , Nagano Hidenobu , Kumon Yoshiko , Seo Yasushi , Kasuga Masato , Yano Yoshihiko , Nakaji Miyuki , Hayashi Yoshitake
Published: April 2003

Objective and Methods: The imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an important determination of deposition and breakdown of the extracellular matrix. To investigate the antifibrogenetic effect of interferon-α (IFN-α) treatment on factors regulating hepatic fibrosis, serum MMP-1, MMP-2, TIMP-1 and TIMP-2 levels were measured by the one-step sandwich enzyme immunoassay in 27 patients with chronic hepatitis C and compared with the histological status of the patients before and at the end of treatment. Results: After 6 months of IFN-α treatment, the histological status of liver fibrosis showed improvement in 9 patients (IF group) and no change or a worsening in 18 patients (NIF group). Compared with pretreatment levels, in the IF group, IFN treatment caused a significant increase in the MMP-1/TIMP-1 ratio. In the NIF group, however, the MMP-1/TIMP-1 ratio tended towards a decrease; moreover, there was not only a significant increase in TIMP-2 levels but also a tendency towards an increase in TIMP-1 levels. Conclusion: These results suggested that an elevated MMP-1/TIMP-1 ratio may ameliorate liver fibrosis by interferon in cases of chronic hepatitis C, whereas elevated levels of TIMP-1 and TIMP-2 might impede improvement.
Characterization of Permanent Cell Lines That Contain the AAV2 rep-cap Genes on an Epstein-Barr-Virus-Based Episomal Plasmid
Authors: Neyns Bart , Vermeij Joanna , Teugels Eric , De Rijcke Martine , Hermonat Paul , De Grève Jacques
Published: April 2003

Recombinant adeno-associated virus (rAAV) has emerged as a promising gene therapy vector. Its development, however, has been hampered by the lack of a readily available efficient production method. We investigated the possibility of establishing permanent cell lines for the production of rAAV with a new Epstein-Barr-virus (EBV)-based episomal AAV rep-cap plasmid (pCEP-rep/cap). HeLa and 293 cells were stably transfected with plasmids that carry the AAV2 rep/cap genes under transcriptional control of their endogenous promoters (p5, p19 and p40) either on the pCEP-rep/cap or an integrated (pIM45) plasmid. For the ease of monitoring transgene expression in live cells, a rAAV vector expressing gfp (the green fluorescent protein gene, rAAV-gfp/neo) was used. Establishment of stable transfected cell lines with these plasmids proved feasible but their usefulness was limited because of their instability. Within 8–12 weeks after their establishment, stably transfected rep-cap cell lines invariably lost their function. In addition, the rAAV-gfp/neo vector we used was susceptible to mutation in stably transfected HeLa cells. Our observations demonstrate specific problems both at the level of rep/cap gene function and the rAAV genome that can occur with the establishment of rAAV production cell lines. These experiments should aid the further development of efficient rAAV production protocols.
Epstein-Barr Virus Nuclear Antigen-1-Dependent and -Independent oriP-Binding Cellular Proteins
Authors: Kusano Shuichi , Tamada Keiko , Senpuku Hidenobu , Harada Shizuko , Ito Sayuri , Yanagi Kazuo
Published: April 2003

Objective: Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and the replication origin, oriP, are essential for the replication and maintenance of latent EBV DNA in cells, but no enzymatic activity has been associated with EBNA-1 protein alone. In this study, we have searched for host cellular proteins that interact with EBNA-1 protein in various B cell lines latently infected with EBV, including a recently EBV growth-transformed cell line. Methods: By using gel shift analysis, we investigated the interactions of an oligonucleotide containing a single EBNA-1 recognition site, derived from the family of repeats (FR) element of oriP, with protein from cell extracts. Results: The FR oligonucleotide bound a (72-kD) cellular protein in the absence of EBNA-1 and without induction of the previously reported ‘anti-EBNA-1 proteins’. The FR oligonucleotide formed complexes with additional proteins from EBNA-1-synthesizing cell lines; these complexes were abolished or supershifted by anti-EBNA-1 monoclonal antibodies. SDS-PAGE analyses of 35S-Met-labeled proteins that bound to a biotin- conjugated FR oligonucleotide, fractionated by a glycerol gradient centrifugation and affinity-purified with streptavidin, showed three major bands, a 72-kD protein, the FR binding of which seemed to be independent of EBNA-1, a 64-kD protein in both EBNA-1-transfected and latently EBV-infected cell lines, and a 45-kD protein in EBV-infected cell lines, which was most prominent in a recently EBV growth-transformed cell line. Conclusions: The FR element forms complexes with cellular proteins in the absence and presence of EBNA-1. These 72-, 64- and 45-kD cellular proteins might be involved in the function of the oriP and EBNA-1 system.
Expression of AAV Rep Proteins in SV40-Transformed and Untransformed Cells: Reciprocal Interaction with Host DNA Synthesis
Authors: Batchu Ramesh B. , Shammas Masood A. , Wang Jing Yi , Shmookler Reis Robert J. , Munshi Nikhil C.
Published: April 2003

Adeno-associated virus (AAV) inhibits the induction of host DNA synthesis by simian virus 40 (SV40) large-tumour (T) antigen, mediated through AAV-encoded ‘Rep’ regulatory proteins. Rep proteins are normally synthesized by AAV-infected cells only in the presence of adenovirus. However, we observed a low level of Rep protein expression in SV40 transformed cells even in the absence of helper virus. In an effort to understand the functional interaction between SV40 T antigen and regulators of AAV rep expression, we evaluated Rep protein production by cell lines transformed with various T antigen mutants known to vary in their induction of host DNA synthesis. We observed Rep protein expression proportional to SV40-induced host DNA synthesis, as measured previously for these T antigen mutants in the absence of AAV, suggesting that rep gene expression – although it opposes the oncogenic stimulation of cell cycling by SV40 – may itself be elicited by host DNA synthesis. To test this, we employed two inhibitors of DNA synthesis: hydroxyurea, which acts by depleting deoxyribose nucleotide triphosphate pools, and aphidicolin, a specific inhibitor of DNA polymerases α and δ. Each inhibitor markedly and significantly reduced Rep protein levels, both in immortal cells transformed by wild-type T antigen and in normal human fibroblasts, confirming the dependence of Rep protein expression on host DNA synthesis.
A Modified Technique of the Beger and Frey Procedure in Patients with Chronic Pancreatitis
Authors: Gloor B. , Friess H. , Uhl W. , Büchler M.W.
Published: April 2003

Background: Resection of the pancreas requires control of tributaries of the superior mesenteric vein (SMV) inferior to the head of the pancreas as well as separation of the posterior surface of the pancreas from the SMV and from eventually existing collateral veins. This usually is the most tedious part when performing a resection of the pancreatic head, in particular if there are signs of portal hypertension. Portal vein pathology contributes to intra- and postoperative morbidity in pancreatic surgery. Operative Technique: Instead of dissecting the pancreas along the anterior surface of the SMV our proposed technique allows resection of the head of the pancreas without division of the gland. This approach combines elements of Beger’s duodenum-preserving pancreatic head resection and of Frey’s limited local pancreatic head excision combined with a longitudinal pancreaticojejunostomy. This modified technique avoids the risk of a bleeding complication which is increased in the presence of portal hypertension and dilation. Summary: The advantages of this modified technique over standard Beger and Frey procedures are: (1) the minimized risk of a bleeding complication in case of portal hypertension because pancreatic transsection does not need to be done, and (2) the considerably more radical excision as compared to local excision. Also, it represents the most minimal surgical trauma for resecting the head of the pancreas as compared to other commonly used techniques.
Virologic and Biochemical Changes and Prognosis after Liver Resection for Hepatitis B Virus-Related Hepatocellular Carcinoma
Authors: Kubo Shoji , Hirohashi Kazuhiro , Tanaka Hiromu , Tsukamoto Tadashi , Shuto Taichi , Higaki Ikko , Takemura Shigekazu , Yamamoto Takatsugu , Nishiguchi Shuhei , Kinoshita Hiroaki
Published: April 2003

Background/Aims: During the natural course of hepatitis B virus (HBV) infection, clearance of HB e antigen (HBeAg) and HB surface antigen (HBsAg) occurs with remission of liver disease. We investigated the effects of postoperative changes in virologic and biochemical parameters on the prognosis after liver resection for HBV-related hepatocellular carcinoma (HCC). Methods: We investigated the relationship between postoperative changes in virologic and biochemical parameters and the incidence of intrahepatic recurrence and the outcome during a 3-year period following surgery in 30 HCC patients with HBsAg. Results: The incidence of intrahepatic recurrence of HCC was significantly higher in patients with acute postoperative exacerbation of hepatitis (p = 0.0084), a sustained high serum concentration of HBV DNA (≧5.0 mEq/ml, p = 0.001), and sustained expression of HBsAg after surgery (p = 0.0421). A high serum concentration of HBV DNA was significantly associated with a shorter survival time (p = 0.0447) and the cause of death was recurrence of HCC. Conclusion: Patients with acute postoperative exacerbation of hepatitis, sustained HBsAg expression, and sustained high serum concentrations of HBV DNA after surgery may require more intensive postoperative monitoring for HCC recurrence.
In vitro Function of Islets of Langerhans Encapsulated with a Membrane of Porcine Chondrocytes for Immunoisolation
Authors: Pollok Jörg-Matthias , Lorenzen Margret , Kölln Philipp Alexander , Török Éva , Kaufmann Peter Matthias , Kluth Dietrich , Bohuslavizki Karl Heinz , Gundlach Matthias , Rogiers Xavier
Published: April 2003

Background/Aims: Widespread clinical application of islet transplantation remains restricted, because of insufficient methods to prevent rejection and autoimmune destruction of islet grafts. In this study we demonstrate long-term function of islets of Langerhans within a capsule of porcine chondrocytes which may serve as an immunoisolation barrier utilizing the immunoprivileged properties of the chondrocyte matrix. Methods: Islets of Langerhans were isolated from Lewis rats, seeded on biodegradable polyglycolic acid polymer, and encapsulated with a monolayer of porcine chondrocytes. The encapsulated constructs and controls were kept in culture for 5 weeks. One group was exposed to a glucose challenge every 5th day. The insulin concentration of the culture medium was measured. Histological and insulin-immunohistochemical studies were performed. Results: Hematoxylin and eosin histology demonstrated viability of the islets of Langerhans. The intact morphology was demonstrated by Heidenhain staining. Toluidine blue showed viability of surrounding chondrocyte layers. Immunohistochemistry was positive for insulin within the beta cells of the islets. Both encapsulated constructs and nonencapsulated controls showed increasing insulin levels after glucose challenge. Conclusions: We can tissue engineer a chondrocyte encapsulation membrane which permits diffusion of glucose and insulin. Islets of Langerhans survive within the chondrocyte capsule, and the glucose/insulin feedback mechanism remains intact.
Locally Recurrent Rectal Cancer
Authors: Radice E. , Dozois R.R.
Published: April 2003

Local recurrence (LR) varies from less than 4% to greater than 50%; several tumor factors and operative techniques may influence rate of LR. Of greatest interest has been the considerable inter-surgeon variation, even within the same institution. An LR rate of less than 10% has been consistently reported by those who use total mesorectal excision even without any form of adjuvant therapy, either preoperatively or postoperatively. These findings raise important questions about surgical technique, subspecialty teaching, place of adjuvant therapy and quality assurance. The management of LR by a multispecialty team and multimodality treatment including preoperative chemoradiation, surgical resection and intraoperative radiotherapy provides encouraging results in terms of better local control and prolonged survivorship in carefully selected patients. These uncontrolled results justify further evaluation of these salvage operations in a more controlled manner that should include repercussions on the quality of life of the patients.
Frequency of CCR5 Promoter Polymorphism Affecting the Rate of Progression to AIDS (59029-G/A) in Kuwaitis
Authors: Al-Turab Mariam , Voevodin Alexander
Published: April 2003

Objective: To estimate the frequencies of 59029-G and 59029-A alleles associated with slow and rapid progression to AIDS in Kuwaitis. Methods: The DNA was extracted from 109 blood samples of healthy unrelated Kuwaitis. The 59029-G/A polymorphism was detected by the polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) test. The amplification of a 268-bp fragment of the CCR5 gene encompassing the site of the polymorphism was followed by digestion with restriction endonuclease Bsp 1286I and sizing the DNA fragments by agarose gel electrophoresis. Results: Among 109 individuals genotyped, 10, 44 and 55 were 59029-A/A homozygous, 59029-G/G homozygous and 59029-G/A heterozygous, respectively. The frequency of the G allele was 0.66 (95% CI: 0.59–0.72) while the frequency of the A allele was 0.34 (95% CI: 0.28–0.41). Conclusions: The frequency of the AIDS-‘protective’ 59029-G allele in Kuwaitis is significantly higher than the frequency of the ‘rapid-progression’ 59029-A allele. Moreover, the frequency of the 59029-G allele in Kuwaitis is among the highest reported. However, the difference from the 59029-G allele frequencies of other ethnic groups in some cases is not statistically significant.
Diagnostic Accuracy in Appendicitis: A Histopathological Study
Authors: Sathar Sitara A. , Junaid T.A.
Published: April 2003

Objective: Although appendicectomy accounts for the highest number of unnecessary surgical procedures, there is little information on the accuracy of the procedure in Kuwait. Therefore, the objective of this study was to determine the accuracy of pre-operative diagnosis of acute appendicitis and the influence of age, gender and surgical personnel on the rate of normal appendicectomy. Materials and Methods: A retrospective histopathological review of specimens involving ‘acute appendicitis’ in the surgical pathology files of the Mubarak Al-Kabeer Hospital, Kuwait in 1982–1986 and 1992–1996 was carried out. The diagnostic accuracy (DA) was defined as the proportion of specimens in which an inflamed appendix was confirmed microscopically and the negative appendicectomy rate (NAR) was the proportion of appendices that were microscopically normal. Results: The DA was 80 and 84% for 1982–1986 and 1992–1996, respectively. There was a marked decline in the number of females in the second period from 42 to 30%. Females, who accounted for 36% of all cases, comprised 61% of normal appendicectomies with the highest NAR in the 20- to 29-year age group (23.7%). The NAR decreased in the second period from 18.4 to 12.4%. Conclusion: The results show that the clinical diagnostic accuracy of appendicitis in Mubarak Al-Kabeer Hospital is consistent with reports from several centres. However, auditing with routine histopathological examination is still necessary to improve clinical evaluation, particularly in females, many of whom are still subjected to the risks of unnecessary laparotomy.
An Evaluation of the Therapeutic Programme Conducted by the Southern Regional Alcohol-Abuse Treatment Centre: Study on the Programme’s Results One Year after Discharge from Inpatient Care
Authors: Neto Domingos , Xavier Miguel , Lucena Paula , Vieira da Silva Ana
Published: April 2003

Given the clinical and social problems caused by the consumption of alcohol in most industrialised countries, there is a strong need to develop and evaluate the effectiveness of integrated care programmes. In this study, the authors describe the results observed in 124 sequentially admitted subjects at various points throughout the course of the first year after their discharge from the Southern Regional Alcohol-Abuse Treatment Centre (CRAS) in Lisbon, Portugal. An inpatient stay at this unit of CRAS lasts for between 5 and 7 weeks and implies that the patient must submit him/herself to a therapeutic model which has been adapted from the Minnesota model. At the end of the year under study 44.3% of the patients were still abstinent, 40.3% were consuming alcohol and 15.4% did not reply. 51 patients (41.1% of the initial sample) were still in regular contact with CRAS for further treatment at that point. The variable that was found to possess the most significant association with a favourable outcome was adherence to the therapeutic programme over the course of that year.
Switch-Over from Tolcapone to Entacapone in Severe Parkinson’s Disease Patients
Authors: Onofrj M. , Thomas A. , Iacono D. , Di Iorio A. , Bonanni L.
Published: April 2003

Forty patients affected by severe Parkinson’s disease (PD) were treated with tolcapone as an adjunctive therapy to L-DOPA, for 3–7 months, until this drug was discontinued because of side-effects (2 diarrhoea, one of them with orthostatic hypotension, 2 increments of liver enzymes) or because of mandatory indications of the European drugs authority. All patients, after 3–6 months of L-DOPA therapy adjustments, received entacapone for 3 months again followed by withdrawal. L-DOPA daily dosage was significantly reduced by tolcapone and entacapone (p = 0.01 and 0.05). ‘On’ time was increased by 15% during tolcapone treatment (p < 0.05), and by 8% during entacapone treatment. ‘Off’ time was decreased by 16% during tolcapone and by 7% during entacapone treatment. Entacapone was withdrawn in the same patient who experienced diarrhoea and orthostatic hypotension during tolcapone because of recurrence of side-effects, in 6 patients because of increment of dyskinesias (with hallucinations) and in 1 patients because of rhythmic, jerking myoclonus.
Relationship between Leuko-Araiosis and Blood Pressure Variability in the Elderly
Authors: Puisieux François , Monaca Pascal , Deplanque Dominique , Delmaire Christine , di Pompeo Christophe , Monaca Christelle , Leys Didier , Pruvo Jean-Pierre , Dewailly Philippe
Published: April 2003

Although leuko-araiosis is a common finding on computed tomographic (CT) scans of the brain, its pathogenesis remains uncertain. To investigate the association between blood pressure (BP) disturbances and leuko-araiosis, we retrospectively reviewed CT scans and 24-hour ambulatory blood pressure monitorings of 79 elderly patients (57 women and 22 men; mean age: 83.3 ± 6.4 years). Of the 79 patients, 50 were demented (30 had Alzheimer’s disease and 18 vascular dementia) and 29 were not demented. The leuko-araiosis score (LA score) was determined by using Rezek’s scale. To evaluate short-term variation of BP, we determined (1) the variability of systolic and diastolic BPs (SBP, DBP; within-subject standard deviation of all readings over a 24-hour period), (2) the coefficient of variability (variability of BP/mean BP) and (3) the maximal variation of BP (difference between the maximum and minimum 24-hour BPs). Higher LA scores were associated with higher SBPs in 24-hour, diurnal and nocturnal periods, higher maximal variation of SBP, greater variability of SBP during 24-hour, diurnal and nocturnal periods and greater coefficient of variability of SBP during sleep. Our study suggests that elevations and short-term variations of SBP may contribute to the pathogenesis of white matter lesions in elderly persons.
Planum Temporale: Where Spoken and Written Language Meet
Authors: Nakada Tsutomu , Fujii Yukihiko , Yoneoka Yuichiro , Kwee Ingrid L.
Published: April 2003

Functional magnetic resonance imaging studies on spoken versus written language processing were performed in 20 right-handed normal volunteers on a high-field (3.0-tesla) system. The areas activated in common by both auditory (listening) and visual (reading) language comprehension paradigms were mapped onto the planum temporale (20/20), primary auditory region (2/20), superior temporal sulcus area (2/20) and planum parietale (3/20). The study indicates that the planum temporale represents a common traffic area for cortical processing which needs to access the system of language comprehension. The destruction of this area can result in comprehension deficits in both spoken and written language, i.e. a classical case of Wernicke’s aphasia.
Diagnosis of Abdominal Bilateral Cryptorchidism: HCG Stimulation Test
Authors: Tzvetkova P. , Tzvetkov D.
Published: April 2003

A diagnostic stimulation test with hCG (Pregnyl) was performed in clinically healthy boys and was used to diagnose cases of bilateral abdominal cryptorchidism. In clinical andrology, this test may be applied as a noninvasive and highly sensitive method.
Ultrastructure of the Trigone and Its Functional Implications
Authors: John Hubert , Hauri Dieter , Bangerter Urs , Elbadawi Ahmad
Published: April 2003

Objective: To investigate the ultrastructure of the trigonal muscle (= superficial trigone), relate it to normal function, and identify any changes it may undergo in voiding dysfunction. Materials and Methods: 20 men (median age 67 years) with low-stage prostatic carcinoma, 10 with and 10 without bladder outlet obstruction, were selected by urodynamic evaluation. Trigonal biopsy was performed at radical prostatectomy, and processed for electron-microscopic study by standard procedures. Biopsies were evaluated independently by 2 examiners without prior knowledge of urodynamic data. Results: Three obstructed and 1 unobstructed bladder had impaired detrusor contractility, and 1 obstructed bladder had detrusor overactivity. Compared to the previously investigated detrusor, the trigonal muscle had smaller compact bundles and fascicles with less collagen and more elastic tissue. Muscle cells had no or rare intermediate junctions that mediate mechanical coupling in normal detrusor, but predominant close cell appositions that mediate electrical coupling. Smooth muscle in most biopsies had widespread or focal features characteristic of the aged detrusor. None, however, had the features previously associated with obstructed detrusor, or detrusor with impaired contractility. Conclusions: The trigonal muscle does not undergo structural changes as previously described in the detrusor in association with voiding dysfunction. Its contraction depends on electrical coupling of its muscle cells, and has a supportive role in normal micturition, mooring the terminal ureters to the bladder base, to allow efflux and guard against reflux of urine. Activation of volume and tension sensory neuroterminals may contribute to some storage and voiding micturition reflexes, and may be related to normal and abnormal perception of urge.
Economic and Organizational Issues in Prenatal Screening and Diagnosis of Down Syndrome
Authors: Framarin Alicia
Published: April 2003

Objective: To evaluate the economic and organizational issues in the introduction of maternal serum screening (MSS) for Down syndrome (DS) in Quebec. Methods: A literature review and an economic analysis were performed. Relevant ethical and organizational questions were examined. Results: MSS could double the number of detected cases, reduce the number of amniocenteses per detected case and the number of procedure-related miscarriage per detected case. Even though MSS is cost-effective, prenatal screening and diagnosis would detect only 50% or less of expected DS cases. Conclusion: Effectiveness and cost-effectiveness of prenatal diagnosis of DS are improved using MSS. In spite of this performance, prenatal screening and diagnosis bring about unaffected fetal losses. Voluntary participation to MSS based on a good understanding of risks and advantages of prenatal screening appears essential for ethical reasons. Organizational issues influencing the quality of care have to be taken into account in the policy-making process along with the results of the economic analysis.
Opportunities for Public Health Genetics Trainees: Results of an Employer/Workplace Survey
Authors: Austin Melissa A. , Arnett Donna , Beaty Terri , Durfy Sharon , Fineman Robert , Gettig Elizabeth , Lochner Doyle Debra , Peyser Patricia , Sorenson James , Thompson John D. , Watts Carolyn
Published: April 2003

Objective: To conduct the first employer/workplace survey identifying employment opportunities for graduates of programs with training in public health genetics in the USA, and to determine whether employment opportunities will increase in coming years. Methods: Six public health genetics training competencies were developed. A survey about workplace and employment opportunities was then conducted with mailings to (1) departments in schools of public health and departments of preventive medicine, (2) local and regional public health officials, (3) insurance companies and health management organizations (HMOs), and (4) biotechnology and pharmaceutical companies. Results: A total of 196 surveys were returned among 1,464 that were mailed. Response rates varied from 5.8 to 46.5% among the target groups. The percent of responding organizations currently employing individuals with skills in genetics ranged from 20 to 62%. The percent currently employing individuals with skills in public health ranged from 39 to 96%. Training opportunities such as internships or practicum experiences are reported for one-third of respondents. For all of the competencies, approximately half of survey respondents who rated the competency important or very important already employ individuals with public health genetics skills. Similarly, at least a quarter of survey respondents who rated the competency important or very important plan to hire individuals with that skill in the next 5 years. Overall, approximately 40% of those surveyed are planning to hire individuals with competencies in public health genetics in the next 5 years. Conclusion: Employment opportunities already exist and new positions are becoming available in schools of public health and departments of preventive medicine, departments of public health, insurance companies and HMOs for professionals with public health genetics training. Based on our survey findings, skills and training in public health genetics are important in the workplace.