bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Molecular-Weight Heparin versus Unfractionated Heparin in the Treatment of Patients with Acute Pulmonary Thromboembolism
Authors: Findik Serhat , Erkan M. Levent , Selçuk M. Bekir , Albayrak Selahattin , Atici Atilla G. , Doru Fatma
Published: April 2003

Background: Low-molecular-weight heparin (LMWH) appears to be as effective as unfractionated heparin (UFH) for both treatment and prophylaxis of deep vein thrombosis (DVT), but limited data are available for its use in acute pulmonary thromboembolism (PTE). Objective: To determine whether enoxaparin, a LMWH, was clinically as efficient and safe as UFH in patients with a diagnosis of acute PTE. Material and Methods: After exclusion of those with massive forms, 59 patients with acute PTE were randomly assigned to either subcutaneous enoxaparin given twice daily (1 mg/kg/dose) or adjusted dose intravenous UFH. Oral anticoagulant treatment was begun on the second day and was given for at least 6 months. We compared the treatment regimens at day 8 and day 90 with respect to a combined end point of major bleeding, recurrent venous thromboembolism (VTE), and death. Results: In the first 8 days of treatment, 1 of 30 patients assigned to receive UFH (3.3%) reached one of the end points (recurrence), as compared with none of 29 patients assigned to enoxaparin. Statistically this difference was not significant (p = 0.508). By day 90, 3 patients assigned to UFH (10%) had symptomatic recurrent VTE, as compared with 1 patient assigned to enoxaparin (3.4%). There was neither major bleeding nor death in the study groups. There was an absolute difference of 6.4 percentage points between the two treatment groups, but the difference was statistically not significant (p = 0.318). Conclusion: Initial subcutaneous treatment with enoxaparin appeared to be as effective and safe as UFH in acute PTE.
A comparative map of bovine chromosome 25 with human chromosomes 7 and 16
Authors: Antoniou E. , Gallagher Jr D. , Taylor J. , Davis S. , Womack J. , Grosz M.
Published: April 2003

A comparative genome map is necessary for the implementation of comparative positional candidate gene cloning in cattle. We have developed a medium density comparative gene map of bovine chromosome 25 (BTA25). A radiation hybrid (RH) panel was used to map nine microsatellites and nine genes. Eight of the nine comparative loci were also mapped by FISH. These results were combined with data from published articles to create a comprehensive comparative map of BTA25 with human chromosomes 7 (HSA7) and 16 (HSA16). This map should facilitate the cloning of genes of interest on bovine chromosome 25.
Isolation and characterization of a human novel RAB (RAB39B) gene
Authors: Cheng H. , Ma Y. , Ni X. , Jiang M. , Guo L. , Ying K. , Xie Y. , Mao Y.
Published: April 2003

Rab proteins are small-molecular-weight GTPases that control vesicular trafficking in eukaryotic cells. During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a cDNA clone encoding a novel Rab protein, which showed 74.2% identity with previously isolated Rab39A at the amino acid level. RAB39B was expressed in a variety of human tissues and located in human chromosome Xq28. It consisted of two exons spanning 3764 bp of human genomic DNA.
B7-1 (CD80) and B7-2 (CD 86) Expression in Human Tubular Epithelial Cells in vivo and in vitro1
Authors: Niemann-Masanek Ulrike , Mueller Alexander , Yard Benito A. , Waldherr Ruediger , van der Woude Fokko J.
Published: April 2003

Background: Tubulointerstitial inflammation with infiltration of mononuclear cells plays an important role in acute allograft rejection and in the progression of renal diseases. We therefore investigated in vivo the expression of the costimulatory molecules B7-1 and B7-2 on proximal tubular epithelial cells (PTEC) under normal and pathologic conditions and analyzed the regulation and functional role of these molecules after cytokine and CD40 activation in vitro. Methods: Immunohistological staining for B7-1 and B7-2 on cryostat sections of core needle biopsies from patients with different renal diseases was examined. Patients were divided into three groups: group A: diffuse interstitial inflammation; group B: minor interstitial inflammation; group C: no interstitial inflammation. In addition, the expression of B7-1 and B7-2 protein and mRNA of cultured PTEC that had been stimulated with cytokine-combinations in absence or presence of a stimulatory anti-CD40 antibody was investigated by means of FACS analysis and RT-PCR. The functional role was analyzed in MKLCs with cytokine and anti-CD40 prestimulated PTEC by measuring IFN-γ and IL-2 expression in absence or presence of CTLA4-Ig by ELISA. Results: Group A patients showed intense tubular staining for B7-1 and B7-2, group B patients showed mild staining, whereas in group C patients B7-1 and B7-2 staining was negative or only weakly positive. In vitro, the presence of B7-1 and B7-2 on PTEC was increased after stimulation with combinations of IL-1α, IL-4, IFN-γ or IL-13 instead of IL-4 and CD40 activation. B7-1 and B7-2 mRNA could be detected in PTEC as well. In MKLCs only cytokine and anti-CD40 prestimulated PTEC were able to stimulate IFN-γ and IL-2 production by purified T cells, which could be blocked dose-dependently by CTLA4-Ig. Conclusion: This study clearly shows that B7-1 and B7-2 can be induced on PTEC in vivo and in vitro. After B7-1 and B7-2 induction, PTEC costimulate CD28 on T lymphocytes resulting in cytokine production. This might be of relevance in allograft rejection and in various kidney diseases.
Endotoxin-Free Dialysate Improves Response to Erythropoietin in Hemodialysis Patients
Authors: Matsuhashi Naoki , Yoshioka Tetsushiro
Published: April 2003

Background/Aims: Inflammatory process induced by endotoxin is one of the causes of resistance to recombinant human erythropoietin (rHuEPO) in hemodialysis patients. Thus dialysate contaminated with endotoxin may diminish response to rHuEPO. We investigated whether dose of rHuEPO could be reduced with endotoxin-free ultrafiltered dialysate. Methods: Twenty-seven chronic hemodialysis patients receiving rHuEPO were studied. The patients did not have known causes of anemia other than chronic renal failure. An endotoxin-cut polyethylene ultrafilter was installed into the dialysate fluid circuit. Hematocrit and dose of rHuEPO were monitored before and after installation. Dose of rHuEPO was adjusted to keep hematocrit at about 30%. Endotoxin concentration of dialysate was measured by commercial limulus test (Endospecy®). Results: After installation of ultrafilter, dialysate endotoxin concentration decreased from >100 to <1.0 endotoxin units/liter (EU/l). Dose of rHuEPO decreased from 90.0 U/kg/week (median) to 57.3 U/kg/week (p < 0.05) and hematocrit increased from 30.3% (median) to 32.2% (p = 0.03) after 5 months of installation of ultrafilter. The running cost of the ultrafilter corresponded to only 4% of the cost of spared rHuEPO. Conclusions: Ultrafiltered endotoxin-free dialysate caused significant reduction in dose of rHuEPO to keep target hematocrit level. Endotoxin-cut ultrafilter was beneficial to hemodialysis patients in medical and in economical aspects.
Significant Elevations in Serum Mannose-Binding Lectin Levels in Patients with Chronic Renal Failure
Authors: Satomura Atsushi , Endo Morito , Ohi Hiroyuki , Sudo Sukemasa , Ohsawa Isao , Fujita Takayuki , Matsushita Misao , Fujita Teizo
Published: April 2003

Background/Aims: Mannose-binding lectin (MBL), a liver-derived C-type serum lectin, activates the complement cascade through the lectin pathway. Since the complement system contributes to the host defense against infections and mediates inflammatory processes including atherosclerosis, and since chronic renal failure (CRF) patients are prone to the development of infectious complications and cardiovascular disease, we focused on serum MBL levels in CRF patients who were either uremic, or who were receiving hemodialysis treatment. Methods: MBL levels were measured in the sera of subjects with CRF before they began dialysis treatment (pre-HD patients; n = 23) and in the sera of subjects who were receiving maintenance hemodialysis (HD patients; n = 178), by ELISA using polyclonal anti-rabbit IgG and a monoclonal antibody directed against MBL (3E7). Results: Mean levels (± SD) of serum MBL were significantly higher in pre-HD subjects (4.343 ± 2.533 µg/ml, p < 0.05) and in HD subjects (8.897 ± 4.920 µg/ml, p < 0.05), than in healthy controls (1.452 ± 0.692 µg/ml). Levels were also significantly higher in HD subjects than in pre-HD subjects (p < 0.05). Conclusions: Elevated serum MBL levels in patients with CRF might have significantly influence pathologic conditions such as alterations of the immune system and acceleration of atherogenesis.
Alzheimer’s Disease: Genes, Pathogenesis and Risk Prediction
Authors: Sleegers K. , van Duijn C.M.
Published: April 2003

With the aging of western society the contribution to morbidity of diseases of the elderly, such as dementia, will increase exponentially. Thorough preventative and curative strategies are needed to constrain the increasing prevalence of these disabling diseases. Better understanding of the pathogenesis of disease will enable development of therapy, prevention and the identification of high-risk groups in the population. Here, we review the genetic epidemiology of Alzheimer’s disease, the most common cause of dementia in the western world. The search for genetic risk factors, though far from completed, has been of major importance for understanding the pathogenesis of Alzheimer’s disease. Although effective therapy is still awaited, these findings have led to new avenues for the development of drugs.
Laparoscopic Wedge Resection of Gastric Submucosal Tumors
Authors: Shimizu S. , Noshiro H. , Nagai E. , Uchiyama A. , Mizumoto K. , Tanaka M.
Published: April 2003

Background/Aims: The purpose of this study was to evaluate the clinical utility of laparoscopic surgery for gastric submucosal tumor. Methods: The records of 11 patients who underwent laparoscopic wedge resection (LR group) for gastric submucosal tumors were reviewed and compared with those of 8 patients who underwent open surgery (OS group). Results: Mean operation time was 145 ± 43 min in the LR group and 127 ± 33 min in the OS group (p = 0.301). Mean blood loss was 97 ± 107 and 107 ± 47 g, respectively (p = 0.387). Patients in the LR group began walking 1.4 ± 0.7 days after surgery, which was significantly earlier than those in the OS group (2.7 ± 1.3 days, p = 0.021). The first flatus (1.5 ± 0.5 vs. 3.1 ± 0.6 days, respectively, p = 0.0004) and resumption of oral food intake (3.0 ± 1.7 vs. 4.3 ± 0.9 days, respectively, p = 0.020) were also earlier in the LR group. White blood cell count on the first postoperative day was lower (7,000 ± 2,100 vs. 11,900 ± 3,580/mm3, respectively, p = 0.004) in the LR group than in the OS group, and the duration of fever (>38.0°C; 0.1 ± 0.3 vs. 0.9 ± 0.8 days, respectively, p = 0.014) and the period of postoperative hospitalization (13.2 ± 3.7 vs. 20.8 ± 6.1 days, respectively, p = 0.014) were significantly shorter in the LR group than in the OS group. No complications occurred in either group. Conclusion: Laparoscopic surgery was superior to open surgery in terms of postoperative recovery time with comparable operation time and blood loss. Laparoscopic wedge resection is a promising surgical alternative for the treatment of gastric submucosal tumors.
Systemic Interleukin-6 Response to Colorectal Surgery Originates from the Bowel
Authors: Syk I. , Mangell P. , Bjartell A. , Jeppsson B.
Published: April 2003

Background: Surgical trauma evokes a systemic cytokine response which is enhanced in patients with colorectal cancer. The aim of this study was to locate the origin of the systemic cytokine response to colorectal surgery. Methods: The concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were analysed in systemic and mesenteric venous blood in 12 patients operated on with colorectal resections due to cancer or benign lesions. Immunohistochemical staining and analysis of tissue concentrations of IL-6 and TNF-α in homogenates from tumours and benign specimens were performed. Results: Mesenteric venous blood contained higher concentrations of IL-6 compared to systemic venous blood after resection, but not before. Tissue concentration of IL-6 was higher in the tumours compared to the benign specimens and immunohistochemistry revealed an abundance of IL-6 and TNF-α in malignant epithelium compared to benign mucosa. Conclusion: The higher concentration of IL-6 in venous blood from the mesenterium of the resected colonic segment compared to systemic levels, indicates that the bowel is the source of the IL-6 response to surgical trauma in colorectal surgery.
Genetic Engineering of Allergens: Future Therapeutic Products
Authors: Ferreira Fátima , Wallner Michael , Breiteneder Heimo , Hartl Arnulf , Thalhamer Josef , Ebner Christof
Published: April 2003

Genetic engineering of allergens for specific immunotherapy should aim at the production of modified molecules with reduced IgE-binding epitopes (hypoallergens), while preserving structural motifs necessary for T cell recognition (T cell epitopes) and for induction of IgG antibodies reactive with the natural allergen (blocking antibodies). Common approaches for engineering of hypoallergens usually require knowledge of T and B cell epitopes and involve changing specific base pairs (mutated gene), introduction of a new piece of DNA into the existing DNA molecule (chimeric or hybrid gene), and deletions (truncated gene or fragments). DNA family shuffling has the advantage that it does not require a priori knowledge of structural and functional properties for efficient generation of hypoallergens. The combination of the hypoallergen concept with the Th1-inducing genetic immunization approach might be an attractive alternative for protein-based immunotherapy.
Identification and Characterization of Major Allergens in Excretory/Secretory Products of the Worm Paragonimus ohirai
Authors: Ikeda Teruaki
Published: April 2003

Allergens present in the excretory/secretory (ES) products of adult Paragonimus ohirai were biochemically identified. Immunoblot analysis using sera from P. ohirai-infected rats revealed only two allergens to be major proteins in the ES products, with apparent molecular masses (Mr) of 27 and 29 kD. As the ES products contained a high proportion of acidic and neutral cysteine proteinases, we examined whether or not the allergens and the cysteine proteinases were identical. The acidic and neutral cysteine proteinases were biochemically purified from the ES products and showed Mr of 27 and 29 kD, respectively. The two cysteine proteinases had almost identical N-terminal amino acid sequences and were reactive with specific IgE in sera from the infected rats. The allergenicity of the cysteine proteinases was confirmed by 48-hour homologous passive cutaneous anaphylaxis. Immunoblot and immunocapture assays using anti-human IgE monoclonal antibody showed that the proteinase allergens were reactive with specific IgE of patients with paragonimiasis westermani. Also, the cysteine proteinases were reactive with specific IgG of both the infected rats and the patients. Therefore the acidic and neutral cysteine proteinases prepared from the ES products of P. ohirai will be useful allergens and antigens for the immunodiagnosis of paragonimiasis.
Prostacyclin Enhances the Expression of LPS/INF-γ-Induced Nitric Oxide Synthase in Human Monocytes
Authors: Plum Jörg , Huang Chunmei , Grabensee Bernd , Schrör Karsten , Meyer-Kirchrath Jutta
Published: April 2003

Background: Nitric oxide (NO) is an important mediator of inflammatory processes, including macrophage-mediated cellular host defense, and is found to be increased in peritonitis. The ability of human mononuclear cells to contribute to the NO production by expression of active inducible NO synthase (iNOS) is still discussed controversely. Aims: This study was designed to investigate the influence of prostacyclin receptor (IP receptor) activation on iNOS expression and NO formation in human peripheral blood monocytes. Method and Results: Using reverse transcriptase-polymerase chain reaction, we demonstrated that human monocytes express high levels of IP receptor mRNA. Stimulation of monocytes with the IP receptor selective agonist cicaprost (100 nM) significantly induced cellular cyclic adenosine monophosphate formation, indicating functional coupling of the receptor to Gs. Treatment of cells with lipopolysaccharide (LPS)/interferon gamma (IFN-γ) further enhanced the IP receptor mRNA expression 2.7 ± 0.1-fold above basal levels (n = 6). Analysis of iNOS expression revealed barely detectable mRNA levels in unstimulated monocytes which were increased 3.75 ± 0.3-fold (n = 5) after costimulation with 1 µg/ml LPS and 250 U/ml INF-γ for 16 h. Further increases of iNOS mRNA expression (9.4 ± 0.9-fold above basal, n = 5) were obtained, if the monocytes were costimulated with 1 µg/ml LPS, 250 U/ml INF-γ, and 100 nM cicaprost for 16 h. Measurement of the NO generation correlated with the polymerase chain reaction data: treatment of cells with 1 µg/ml LPS plus 250 U/ml INF-γ increased the NO2 production to 2.6 µM, being above the basal level of 2.0 µM, as determined in the cell culture medium. Additional treatment with 100 nM cicaprost further significantly increased the NO2 production to 3.43 µM. Conclusions: An IP receptor mediated increase in cyclic adenosine monophosphate formation plays an important role in enhancing LPS/IFN-γ-induced iNOS expression in human monocytes/macrophages and may, therefore, contribute to the increased production of NO during peritonitis.
Erythrocyte Ferritin in Patients with Chronic Renal Failure and Heterozygous Beta-Thalassemia
Authors: Christopoulou V. , Varsou A. , Travlou A. , Drivas G.
Published: April 2003

Aim: The aim of this research is to study the variance of erythrocyte ferritin (EF) in patients with chronic renal failure (CRF) and heterozygous β-thalassemia (β-TA), as well as the use of EF as a more reliable index for assessing the body iron status. Methods: We studied 63 subjects with CRF, 40 subjects with heterozygous β-TA, 53 subjects with CRF and heterozygous β-TA and 24 normal subjects. In 11 patients with CRF and heterozygous β-TA, sternal bone marrow aspiration was performed to evaluate iron stores in the bone marrow. EF was determined in the hemolysate of washed erythrocytes by a radioimmunoassay. Results: EF showed the strongest correlation with bone marrow iron (p < 0.001) in comparison with the remaining hematological parameters that were examined. Patients with CRF without heterozygous β-TA showed an increase in serum ferritin (SF), even in cases of iron deficiency. In the group of heterozygous β-TA without renal failure, 22.5% of patients showed an increased EF content up to 150 ag/cell and a tendency for iron overload. Patients with CRF and heterozygous β-TA showed a high value of EF, up to 200 ag/cell, and iron overload in 22.6%, almost the same proportion as in the previous group. It was also observed that a high value of SF does not indicate iron overload for these patients. In the group of hemodialysis, patients without heterozygous β-TA who were under erythropoietin (EPO) treatment presented iron deficiency. Many patients with CRF and heterozygous β-TA who were taking EPO presented iron overload, while very few of them presented iron deficiency. Conclusion: These findings suggest that EF is a reliable index for assessing the iron status in patients with CRF and heterozygous β-TA.
Resolution of Nodular Glomerular Lesions in a Patient with Light-Chain Nephropathy
Authors: Hotta Osamu , Taguma Yoshio
Published: April 2003

A 37-year-old man developed nephrotic syndrome and renal insufficiency in 1986. He had ĸ-light-chain protein both in serum and urine. A renal biopsy showed nodular glomerulosclerosis with deposition of ĸ-light-chains in the mesangial area, compatible with light-chain nephropathy. Thereafter, he was treated with steroids and melphalane and the light-chain protein disappeared from both the urine and serum. Although his moderately impaired renal function maintained stable levels for over 10 years, he was diagnosed as having renal cell carcinoma in 1998, and a right nephrectomy was performed. Histopathological examination of a portion of the removed kidney, unaffected by carcinoma, showed mild mesangial proliferation, and both the nodular lesions and light-chain deposits were no longer observed. These observations suggest that an established nodular glomerular lesion may be reversible.
Pathogenic Importance of Intestinal Hypermotility in NSAID-Induced Small Intestinal Damage in Rats
Authors: Takeuchi Koji , Miyazawa Tohu , Tanaka Akiko , Kato Shinichi , Kunikata Tomonori
Published: April 2003

Background/Aim: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin produce damage in the small intestine as a major adverse reaction. We examined the effect of various NSAIDs on intestinal motility and investigated the pathogenic importance of motility changes in the intestinal ulcerogenic response to indomethacin in rats. Methods: Animals without fasting were given various NSAIDs (indomethacin 10 mg/kg, diclofenac 40 mg/kg, flurbiprofen 20 mg/kg, naproxen 40 mg/kg) s.c., and in the case of indomethacin, the following parameters were examined in the small intestine 24 h later; the lesion score, the number of enterobacteria and myeloperoxidase (MPO) as well as inducible nitric oxide (iNOS) activity. Intestinal motility was monitored as intraluminal pressure recordings using a balloon under anesthesia. Results: All NSAIDs tested decreased mucosal PGE2 levels and produced hemorrhagic lesions in the small intestine, accompanied by intestinal hypermotility. As representative of NSAIDs, indomethacin also increased the extent of enterobacterial invasion and MPO as well as iNOS activity before the occurrence of intestinal damage, and the hypermotility response was observed earlier than the onset of any other event caused by this agent. The intestinal lesions induced by indomethacin were prevented by either supplementation with dmPGE2, inhibition of bacterial invasion with ampicillin or inhibition of iNOS activity with aminoguanidine, while the hypermotility response was prevented by dmPGE2 only. In addition, the observed effects of dmPGE2 were all mimicked by atropine when the intestinal hypermotility was suppressed by this agent. Conclusion: These results suggest the pathogenic importance of intestinal hypermotility in the intestinal ulcerogenic response to NSAIDs in rats and show that this event is critical for the occurrence of enterobacterial invasion under PG deficiency, followed by various inflammatory changes and damage in the mucosa. This study also suggests that the antispasmodic drug is protective against NSAID-induced intestinal lesions.
Acute Focal Bacterial Nephritis: Report of Four Cases
Authors: Montejo Miguel , Santiago Martin Jose , Aguirrebengoa Koldo , Garcia Blanca , Goicoetxea Josune , Martin Alex
Published: April 2003

Focal acute bacterial nephritis is a localized bacterial infection of the kidney presenting as an inflammatory mass not containing drainable pus. The further distinction between acute focal bacterial nephritis and other renal masses is aided by the appropriate use of renal sonography and computed tomography. We report 4 cases with this entity.
Antepartum Assessment of Fetal Cystic Lymphangioma by Magnetic Resonance Imaging
Authors: Ogura Tsuyoshi , Hamada Hiromi , Obata-Yasuoka Mana , Watanabe Hideki , Okuno Suzuka , Fujiki Yutaka , Yamada Naoki , Sohda Satoshi , Yoshikawa Hiroyuki
Published: April 2003

Few reports of fetal cystic lymphangioma have described assessment in utero by magnetic resonance imaging (MRI). We evaluated a fetus with cystic lymphangioma by this method. Complementing the characteristic features of cystic lymphangioma in ultrasonographic images, prenatal MRI provided a detailed view of anatomic relationships of cysts to surrounding tissues in this case. This anatomic evaluation facilitated planning of perinatal management and choice of manner of delivery. We found MRI very helpful in antepartum assessment of fetal cystic lymphangioma.
Thrombomodulin Ala455Val Dimorphism Is Not Associated with Pre-Eclampsia in Australian and New Zealand Women
Authors: Borg Anthony J. , Higgins John R. , Brennecke Shaun P. , Moses Eric K.
Published: April 2003

Thrombomodulin plays an important role in thromboresistance. A common mutation of the gene at amino acid 455 producing valine instead of alanine has been implicated as being a risk factor in myocardial infarction and chronic heart disease. However, its link with pre-eclampsia remains controversial. This report explores the Ala455Val point mutation in 280 women as a predictor of pre-eclampsia with the conclusion that in this regard, the dimorphism is essentially neutral.
Pheochromocytoma of the Urinary Bladder Presenting Only with Macroscopic Hematuria
Authors: Gyftopoulos K. , Perimenis P. , Ravazoula P. , Athanassopoulos A. , Barbalias G.A.
Published: April 2003

Pheochromocytoma of the bladder is an unusual tumor that typically presents with hypertensive crises related to micturition. We describe a case of bladder pheochromocytoma in a 42-year-old female in which macroscopic hematuria was the only alarming symptom. The diagnostic and operative issues of this type of tumor are discussed, along with the challenging treatment option of transurethral resection. Diagnosis, treatment and follow-up trends of this rare tumor are reviewed.
Economic Analysis of Galantamine, a Cholinesterase Inhibitor, in the Treatment of Patients with Mild to Moderate Alzheimer’s Disease in The Netherlands
Authors: Caro J. Jaime , Salas Maribel , Ward Alexandra , Getsios Denis , Mehnert Angelika
Published: April 2003

Background: The economic impact of dementia on the Dutch health and social services is substantial. Objective: To predict the long-term economic impact of galantamine, a cholinesterase inhibitor, in the treatment of Dutch patients with mild to moderate Alzheimer’s disease. Method: A pharmacoeconomic model was used to predict long-term outcomes. It has two components: an initial module based on clinical trials of galantamine and a subsequent module that predicts when a patient will deteriorate to a level where full time care (FTC) is needed. The analyses take a broad perspective that includes all formal (paid) care, not just those covered by the Dutch health care system. Direct cost estimates were based on resource use profiles of patients with Alzheimer’s disease in the Netherlands. Key inputs were tested in sensitivity analyses. Results: After 10.5 years all patients are predicted to require FTC. For every hundred patients starting treatment on galantamine at the mild to moderate stage, it is predicted that 18 person-years of FTC will be avoided (14.4 discounted) and about 5 quality-adjusted years of life will be gained (3.9 discounted). Net savings for those starting treatment with galantamine are estimated at NLG 3,050 (1,676 UDS). The cost of galantamine accounts for only about 5.0% of the total cost of care for treated Alzheimer’s patients. The direction of these results remained unchanged when input values and assumptions were tested in sensitivity analyses. Conclusions: The cholinesterase inhibitor galantamine is expected to bring savings in the direct cost of caring for patients with Alzheimer’s disease in the Netherlands.
Association between Gastric Acid and Mucin Secretion in Dyspeptic Patients
Authors: Niv Yaron , Hardy Britta , Koren Rivka , Rodiomov Galina , Fraser Gerald M.
Published: April 2003

Background and Aims: The maintenance of an intact gastric mucosa implies a balance between aggressive, such as acid, and protective factors such as mucin. We examined gastric aspirates to determine a possible correlation between gastric acid and mucin contents. Methods: Gastric contents were aspirated at gastroscopy in 14 patients. Acid content was evaluated by titration, and mucin content by gel filtration. In 4 other patients these measurements were also performed for 1-hour basal gastric secretion, and after pentagastrin stimulation. Western blot and dot blot for mucin protein were performed with polyclonal antibodies to the protein of MUC 5AC and MUC 6. Results: A positive correlation was demonstrated between acid and mucin content in 14 patients, r = 0.77. In 4 other patients mucin secretion, after pentagastrin injection, increased by 3–46 fold in comparison with basal secretion. A positive correlation was demonstrated between basal acid and mucin secretion, and stimulated acid and mucin secretion. In dot blot experiments, MUC 5AC had a significant higher dot blot intensity than MUC 6. Conclusions: There is a correlation between acid and mucin secretion rates. Secretagogue that causes acid secretion may also cause secretion of protective mucin.
Cigarette Smoking, Alcohol Use, and Gallstone Risk in Japanese Men
Authors: Kono Suminori , Eguchi Hiroyuki , Honjo Satoshi , Todoroki Isao , Oda Takashi , Shinchi Koichi , Ogawa Shinsaku , Nakagawa Katsuya
Published: April 2003

Background/Aim: Results of epidemiological studies concerning the association between smoking and alcohol use and gallstone risk are inconsistent. We examined the relation of smoking and alcohol use to gallstone disease in Japanese men. Methods: We investigated 174 cases having gallstones as determined by ultrasonography, 104 cases of postcholecystectomy state, and 6,906 controls having a normal gallbladder in the consecutive series of 7,637 men aged 48–59 years receiving a retirement health examination at four hospitals of the Self-Defense Forces from 1986 to 1994. Fifty men had been aware of having gallstones. Known gallstones and postcholecystectomy state were combined as known gallstone disease. Smoking and drinking habits were ascertained by a self-administered questionnaire. Statistical adjustment was made for body mass index, glucose tolerance status, Self-Defense Forces rank, hospital, and either cigarette smoking or alcohol use. Results: Cigarette smoking was not measurably associated with either prevalent gallstones or postcholecystectomy state, nor with either newly diagnosed gallstones or known gallstone disease. Alcohol use was related to a significant decrease in the prevalence odds of both gallstones and postcholecystectomy state, and the decrease was slightly more profound for known gallstone disease. Conclusions: Cigarette smoking is probably unrelated to the gallstone risk, and alcohol consumption seems to confer protection against gallstone formation.
Parkinsonism after Carbon Monoxide Poisoning
Authors: Choi Il Saing
Published: April 2003

Of 242 patients with carbon monoxide (CO) poisoning examined between 1986 and 1996, parkinsonism was diagnosed in 23 (9.5%). There were 11 men and 12 women. The age at onset ranged from 16 to 69 (mean 45.8) years, with the peak incidence during the 6th decade. The latency before the appearance of parkinsonism varied from 2 to 26 (median 4) weeks, but parkinsonism developed within 1 month after an acute insult in the majority of the patients. All showed encephalopathy with mildly to severely impaired cognitive functions during or immediately after delayed CO sequelae. The common symptoms were gait disturbance, impaired mentality, urinary incontinence, and mutism. The most frequent signs were short-step gait, hypokinesia, masked face, increased muscle tone (rigidity), glabella sign, grasp reflex, and retropulsion. Intentional tremor was occasionally found, but resting tremor could not be seen. There was no correlation between the neuroimaging findings and the development of parkinsonism. Levodopa and anticholinergic drugs were not effective. Of 16 patients followed up for 1 year, 13 (81.3%) recovered spontaneously within 6 months. In conclusion, parkinsonism after CO poisoning is not rare and usually appears as a part of delayed CO encephalopathy. Any drug is not effective, but the prognosis is good.
Effect of Mode of Inheritance when Calculating the Power of a Transmission/Disequilibrium Test Study
Authors: Iles Mark M.
Published: April 2003

In assessing the power of an association study one needs to consider a variety of genetic models and to have some knowledge of the values of the relevant population parameters in those models. One’s comparison of different models should be made such that these parameters are equal under each model. In practice one is most likely to have available estimates of the allele frequency (p) and of the relative risk to siblings of affected individuals (λs). In presenting power calculations for the transmission/disequilibrium test, previous authors have made comparisons of models which, while having the same gene frequency lead to completely different population outcomes, e.g. different values of λs. Indeed, despite having the same values for their underlying parameters, these models do not necessarily provide the most useful comparison.
Finding Ways to Study Culture in Context
Authors: Paradise Ruth
Published: April 2003

In research on cultural aspects of human development, the challenge is to find ways to study differences that (1) do not reify culture as specific behavioral or attitudinal characteristics; (2) do not isolate cultural particularities from the economic, social, political, and historical contexts in which they appear and function, buth rather take these contexts into account, and (3) recognize cultural adaptation and improvisation. This paper discusses the study of attention management stragegies as culturally informed learning behavior, and argues that this cultural aspect of learning can be researched and understood with various methodological ‘tools’ if the above challenges are appropriately taken into account.
Evolving Questions and Comparative Perspectives in Cultural/Historical Research
Authors: Edwards Carolyn Pope
Published: April 2003

In studying human development in cultural-historical context, we must integrate multiple levels of analysis and strive to identify culture’s imprint inside the contexts of socialization. Issues of methodology are complex. This paper argues that both comparative and historical-interpretive studies are valuable and indeed generative for each other, using as an example an international, collaborative research project focused on East African women and changing childrearing values. The site was Ngecha, a Gikuyu-speaking community in the Central Province of Kenya, during a period of rapid social change from an agrarian to a wage earning economy shortly after national independence (1968–1973). The experiences of Ngecha women highlighted their significant role as agents of social change in the village and stimulated the team to transform an ahistorical comparative investigation into a multifaceted case study with a strong historical component.
1α,25-Dihydroxyvitamin D3 – Not Just a Calciotropic Hormone
Authors: Kumar Rajiv
Published: April 2003

1α,25-Dihydroxyvitamin D3, the hormonal form of vitamin D3, is widely appreciated to play a central role in calcium and phosphorous homeostasis. It is becoming increasingly clear, however, that the sterol also plays an important role in the regulation of cellular growth, central nervous system function, and immune responsiveness. In this review, I will highlight some of the mechanisms by which 1α,25-dihydroxyvitamin D3 regulates cellular growth, alters central nervous system function, and immune function.
Cytokine mRNA Profile in Lipoid Nephrosis: Evidence for Increased IL-8 mRNA Stability
Authors: Laflam Paul F. , Haraguchi Soichi , Garin Eduardo H.
Published: April 2003

Background/Aims: Proteinuria in idiopathic minimal lesion nephrotic syndrome (IMLNS) is presumed to be due to the effect of circulating factors on glomerular permeability to plasma proteins. This study examines the expression of messenger ribonucleic acid (mRNA) for cytokines thought to mediate glomerular inflammation during different stages of the nephrotic syndrome. Methods: Messenger RNA expression and stability from peripheral blood mononuclear cells of IMLNS patients in relapse and in remission, and age matched normal controls were measured using a ribonuclease protection assay (RPA). The spontaneous and Interleukin 2 (IL-2) stimulated mRNA expression were studied. Results: Spontaneous mRNA expression for Interleukin 8 (IL-8) from IMLNS patients in relapse was significantly increased when compared to IMLNS patients in remission and normal controls (p < 0.05). After 14 h of IL-2 stimulation, mRNA IL-8 levels expressed by IMLNS PBMC patients in remission were not different from those observed in normal controls. However, after 5 days of PBMC incubation, a significant increase in mRNA for IL-8 in IMLNS patients compared to controls was found (p < 0.01). Stability assay demonstrated that IL-8 mRNA transcript from the nephrotic patients remained higher than those from controls and showed a significantly prolonged life t1/2 (p = 0.02). Conclusions: IL-8 mRNA expression is increased in IMLNS patients in relapse. Moreover, stability studies show that IL-8 mRNA life t1/2 is prolonged due to altered post-transcriptional regulation. This finding may explain the elevated serum IL-8 levels observed in these patients during relapse and may have pathogenic significance since IL-8 has been shown to induce proteinuria in the experimental animal.
Plasma Exchange and Interferon-Alpha Pharmacokinetics in Patients with Hepatitis C Virus-Associated Systemic Vasculitis
Authors: Hausfater P. , Cacoub P. , Assogba U. , Lebon P. , Piette J.C.
Published: April 2003

Different types of vasculitis have been reported in association with hepatitis C virus (HCV) infection, i.e. type II mixed cryoglobulinemia and polyarteritis nodosa (PAN). Therapeutic approach of such severely symptomatic patients include interferon-alpha (IFN) plus plasma exchange (PE). There are no data on IFN pharmacokinetic changes related to PE. Patients and Methods: We studied 7 HCV-infected patients (mean age: 57 years) presenting with symptomatic type II mixed cryoglobulinemia (n = 5) or biopsy-proven PAN (n = 2). All patients underwent subcutaneous IFN therapy with concomitant PE. Serum IFN concentration was measured in serial samples on days with and without PE. Results: Without PE, IFN Cmax (range: 100–750 IU/ml) was obtained 3–6 h after subcutaneous injection, followed by a 3- to 9-hour plateau. IFN concentration declined subsequently reaching a residual concentration 24 h after injection, ranging from 20 to 40 IU/ml. PE performed 6 h after IFN administration resulted in increased IFN clearance in that the concentration-time IFN-α area under the curve decreased from 3,005 IU·h/ml (1,563–4,614) on days without PE to 2,142 IU·h/ml (973–4,123) on day with PE. Conclusions: In patients with HCV-associated vasculitis, PE increase IFN clearance. Combined IFN-α and PE therapy schedule have to be further studied to optimize its biological activity.
In vivo Release of Vascular Endothelial Growth Factor from Colorectal Carcinomas
Authors: Gunsilius Eberhard , Tschmelitsch Jörg , Eberwein Martin , Schwelberger Hubert , Spizzo Gilbert , Kähler Christian M. , Stockhammer Günther , Lang Alois , Petzer Andreas L. , Gastl Günther
Published: April 2003

The formation of new blood vessels is essential for the growth of malignant tumors and their hematogenic spread. Tumor-induced neoangiogenesis occurs through sprouting of preexisting vessels. An alternative mechanism might be the recruitment of bone marrow-derived endothelial cells, or their precursors, to the tumor site by the release of vascular endothelial growth factor (VEGF) from cancer cells, i.e., tumor-induced postnatal vasculogenesis. To investigate if a significant amount of VEGF is released from malignant tumors in vivo, thus potentially mobilizing endothelial precursor cells (EPC) from the bone marrow, we measured plasma levels of soluble VEGF obtained from tumor-draining mesenteric veins (VEGF-M) during surgery and, simultaneously, in venous blood obtained distant from the tumor (VEGF-P). This analysis was performed in 29 patients with colorectal carcinoma. VEGF-M levels were substantially higher in patients with distant metastases (208 ± 61 pg/ml) compared to patients with nonmetastatic disease (99 ± 72 pg/ml, p = 0.003). Also, in patients with aggressive disease, i.e., histologically undifferentiated (G3) tumors, higher levels of VEGF-M were measured than in patients with tumors of lower histologic grading (196 ± 46 vs. 107 ± 80 pg/ml, p = 0.01). In conclusion, the release of significant amounts of soluble VEGF in vivo from clinically and/or histologically aggressive tumors might reflect their high angiogenic or vasculogenic potential, probably leading to the recruitment of EPC from the bone marrow.
Recovery of Language after Left Hemispherectomy in a Sixteen-Year-Old Girl with Late-Onset Seizures
Authors: Telfeian Albert E. , Berqvist Christina , Danielak Craig , Simon Scott L. , Duhaime Ann-Christine
Published: April 2003

Hemispherectomy is a very effective surgical treatment for intractable seizures that occur in the setting of Rasmussen’s syndrome. The decision of when to perform a dominant hemispherectomy depends greatly on how late the surgeon believes some shift in language to the nondominant hemisphere can occur. We report a right-handed patient with Rasmussen’s syndrome who underwent a left hemispherectomy at the age of 16 and has had excellent control of her seizures and remarkable language recovery. Our results indicate that dominant hemispherectomy in adolescence in the setting of late-onset seizures and Rasmussen’s syndrome in the profoundly aphasic patient does not commit the patient to the prognosis of a fixed language deficit.
Classification in Primary Care: Experience with Current Diagnostic Systems
Authors: Jenkins Rachel , Goldberg David , Kiima David , Mayeya John , Mayeya Petronella , Mbatia Joseph , Mussa Mahmoud , Njenga Frank , Okonji Max , Paton Jo
Published: April 2003

Mental disorders tend to be seen first in primary care settings around the world. To be helpful, classifications of mental disorders for primary care need to be simple. In response to these basic observations and requirements, a primary care version of the mental disorder section of ICD-10 has been developed by the WHO (ICD-10-PHC). This classification version has been used quite extensively internationally. The results of field trials with ICD-10-PHC are summarised here along with recommendations to make classifications and information systems more helpful to upgrade primary care of mental disorders around the world.
Neuroscience, Genetics, and the Future of Psychiatric Diagnosis
Authors: Hyman Steven E.
Published: April 2003

Nearly three decades after Robins and Guze’s seminal delineation of the steps required to validate a psychiatric diagnosis, a pathophysiologically based classification of psychiatric disorders remains elusive. Contrary to optimistic expectations, approaches to diagnostic validity based on clinical description, laboratory studies, natural history of illness, and familial aggregation have not converged to yield a nosology based on valid disease entities. Defining a rational nosology for disorders of the brain, the body’s most complex organ, is clearly one of the great challenges for modern medical science. Nonetheless, fundamental advances in our understanding of the genetic and environmental determinants of disease risk, and of the neural circuitry supporting normal and pathological mental processes promises to form the basis of improved classification in the coming decades.
Genetics in Primary Care: A USA Faculty Development Initiative
Authors: Burke Wylie , Acheson Louise , Botkin Jeffery , Bridges Kenneth , Davis Ardis , Evans James , Frias Jaime , Hanson James , Kahn Norman , Kahn Ruth , Lanier David , Pinsky Linda E. , Press Nancy , Lloyd-Puryear Michele A. , Rich Eugene , Stevens Nancy , Thomson Elizabeth , Wartman Steven , Wilson Modena
Published: April 2003

The Genetics in Primary Care (GPC) project is a USA national faculty development initiative with the goal of enhancing the training of medical students and primary care residents by developing primary care faculty expertise in genetics. Educational strategies were developed for the project by an executive committee with input from an advisory committee, comprising individuals with primary care, medical education and genetics expertise. These committees identified the key issues in genetics education for primary care as (1) considering inherited disease in the differential diagnosis of common disorders; (2) using appropriate counseling strategies for genetic testing and diagnosis, and (3)  understanding the implications of a genetic diagnosis for family members. The group emphasized the importance of a primary care perspective, which suggests that the clinical utility of genetic information is greatest when it has the potential to improve health outcomes. The group also noted that clinical practice already incorporates the use of family history information, providing a basis for discussing the application of genetic concepts in primary care. Genetics and primary care experts agreed that educational efforts will be most successful if they are integrated into existing primary care teaching programs, and use a case-based teaching format that incorporates both clinical and social dimensions of genetic disorders. Three core clinical skills were identified: (1) interpreting family history; (2) recognizing the variable clinical utility of genetic information, and (3) acquiring cultural competency. Three areas of potential controversy were identified as well: (1) the role of nondirective counseling versus shared decision-making in discussions of genetic testing; (2) the intrinsic value of genetic information when it does not influence health outcomes, and (3) indications for a genetics referral. The project provides an opportunity for ongoing discussion about these important issues.
From Erythropoietin to Oxygen: Hypoxia-Inducible Factor Hydroxylases and the Hypoxia Signal Pathway
Authors: Ratcliffe Peter J.
Published: April 2003

The regulation of blood red cell production by the hormone erythropoietin (Epo) provides a paradigm for control of gene expression by oxygen. Analysis of this pathway has revealed a widespread system of gene regulation based on a transcriptional complex termed hypoxia-inducible factor (HIF). Hydroxylation of specific prolyl and asparinyl residues in the α subunit of HIF by a series of non-haem iron-dependent dioxygenases has been defined as a novel mechanism of protein modification that transduces the oxygen-sensitive signal.
Involvement of Interleukin-18 in Patients on Maintenance Haemodialysis
Authors: Gangemi S. , Mallamace A. , Minciullo P.L. , Santoro D. , Merendino R.A. , Savica V. , Bellinghieri G.
Published: April 2003

Maintenance dialysis induces a clinical state of immunodeficiency. The pathway of circulating T cells from haemodialyzed patients is changed and characterized by an increase of Th1 cells. The unbalanced T helper differentiation derives from an altered regulation of interleukin-12 (IL-12), which represents an important inducer of Th1. IL-18 is a pro-inflammatory cytokine expressed by a variety of cell types that is structurally related to the Th1 family and shares biological properties with IL-12 as the promotion of Th1 responses. To explain the involvement of IL-18 in the typical disorders of dialysis, we analyzed IL-18 serum levels in a group of haemodialyzed patients. We enrolled 16 patients on chronic haemodialysis (HD) treatment for end-stage renal failure and 16 healthy volunteers as the control group. IL-18 levels were assessed by immunoenzymatic methods (detection limit was <12.5 pg/ml). HD patients strongly showed higher IL-18 serum levels compared to healthy donors (508.47 ± 314.39 vs. 193.44 ± 56.33 pg/ml, p < 0.005). Moreover, IL-18 levels in HD directly correlated to dialytic age (Rho = 0.544, p = 0.0419) and indirectly to Kt/V (Rho = 0.703, p = 0.0086). Our data represent the first evidence of the relation between IL-18 serum levels and HD. In the light of our results, we think that the unbalanced T helper differentiation may depend, at least in part, on an abnormality in the IL-18 production.