bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Pressure Is Correlated with Vitamin D3 Serum Levels in Dialysis Patients
Authors: Argilés Àngel , Lorho Ronan , Servel Marie-Françoise , Couret Isabelle , Chong Guillaume , Mourad Georges
Published: April 2003

Background/Aim: The blood pressure, the most influencing factor in cardiovascular disease in end-stage renal failure patients, follows a seasonal variation during the year. Since vitamin D3 is known to be related to sun exposure, we wanted to evaluate the putative participation of the vitamin D3 metabolism in blood pressure modifications. Methods: We studied 22 stable hemodialysis patients (11 females and 11 males, mean age ± SD 56 ± 1 year) who had been continuously treated in our dialysis unit for more than 1 year between 1994 and 1997 and did not receive pulse vitamin D3 treatment. Supine systolic and diastolic blood pressures were measured before every dialysis session (>12,000 measurements) and the intact parathormone (iPTH), 25-hydroxyvitamin D3 [25(OH)D3], and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels every 3 months (>300 determinations). The mean values of blood pressure per season and per patient were taken for analysis using a 4-year longitudinal study design. Results: The blood pressure varied during the years studied following a seasonal trend. It was highest during autumn and tended to decrease during spring and warmer months. Systolic as well as diastolic blood pressures were significantly correlated with the 25(OH)D3 levels (p = 0.0291 and p = 0.0327, respectively). No correlation was observed between blood pressure and 1,25(OH)2D3 or iPTH levels. Conclusions: There is a link between blood pressure and 25(OH)D3 level. This interrelation is not secondary to a iPTH modulation. Although it cannot be excluded that vitamin D3 and blood pressure vary following a third factor with seasonal variations, since vitamin D3 varies during the year, mainly following sun exposure, we suggest that vitamin D3 is one of the factors participating in the seasonal variation of the blood pressure. Other factors known to control the blood pressure and particularly the extracellular volume overload may also participate.
Prevention of Gastric Cancer by Helicobacter pylori Eradication?
Authors: Schandl Laslo , Malfertheiner Peter , Ebert Matthias P.A.
Published: April 2003

The incidence of gastric cancer is decreasing; however, in some parts of the world this malignancy is still the second most common cause of cancer-related deaths and recent epidemiological analysis indicates that approximately 1,000,000 individuals will die from gastric cancer every year. Therefore, finding potent mechanisms of cancer prevention is of great importance, since this disease is commonly diagnosed in advanced stages. This review will provide a short update on the mechanisms of gastric carcinogenesis and will present recent data obtained from first clinical intervention studies aimed at the prevention of gastric cancer by Helicobacter pylori eradication.
The Role of Genomic Instabilities in Affecting Treatment Responses of Colorectal Cancer
Authors: Ricciardiello Luigi , Bazzoli Franco
Published: April 2003

Colorectal cancer is one of the most common tumors worldwide. The knowledge gained on its biology and molecular changes is helping us to choose the best chemotherapeutic treatment. Two different pathways, i.e. the chromosomal and microsatellite instabilities, give the same result but with totally different biological behaviors. In fact, the response to treatment with 5-FU or platinum compounds is dramatically different in both settings. In the future, the use of these compounds should require molecular testing of the speciment prior to treatment.
Loss of Expression of Tumor Suppressor p16INK4 Protein in Human Primary Gastric Cancer Is Related to the Grade of Differentiation
Authors: Rocco Alba , Schandl Laslo , Nardone Gerardo , Tulassay Zolt , Staibano Stefania , Malfertheiner Peter , Ebert Matthias P.A.
Published: April 2003

Background: Recent research has revealed a rapid increase in the number of alterations underlying oncogenesis and the proteins which regulate the cell cycle. p16 is a cell cycle regulatory protein acting as a cyclin-dependent kinase inhibitor (CDKI). Because of its antiproliferative effect, p16 has been suggested to be a tumor suppressor gene. Deletions, mutations and functional inactivation of p16 occur with a frequency second only to p53 in most human malignancies. Aim: to evaluate the p16 protein expression in primary gastric cancer in order to understand the possible differences in relation to histotype and grade of tumors. Material and Methods: Immunohistochemical expression of p16 was investigated in matched normal and cancerous tissues from 70 patients with gastric cancer (52 intestinal and 18 diffuse type). Results: In non-cancerous gastric tissues the immunostaining of p16 was weak and limited to antral glands. In gastric cancer tissues, the enhanced immunoreactivity of p16 was not significantly different in intestinal and diffuse type of gastric cancer. However, the intensity of immunostaining was inversely related to the grade of differentiation of these tumours. Conclusions: The overexpression of p16 seems to be a common event in the development of both intestinal and diffuse type of gastric cancer and it is likely that it may be driven by features of the neoplastic state. Likewise, the absence of p16 in the lowest grade of differentiation may reflect increased selection pressure and clonal expansion of the cells with a more aggressive phenotype.
Ulcerative Colitis and Colon Cancer: Strategies for Cancer Prevention
Authors: Campbell Simon , Ghosh Subrata
Published: April 2003

The risk of development of colon cancer in patients with ulcerative colitis is an emotive issue with patients and a potential medico-legal problem for physicians caring for such patients. The exact magnitude of the risk is not clearly defined. Current surveillance programmes use dysplasia as a marker for the risk of invasive carcinoma development, but this strategy has inherent limitations. A number of new molecular markers have been investigated but none are currently considered robust enough for routine clinical use. Recommendations for patient selection and interval for colonoscopic surveillance are currently pragmatic, and not entirely evidence-based. Nevertheless, optimal medical management and adherence to a surveillance programme geared to detect dysplasia might still be the best risk reduction strategy.
Role of Vehicles in Diagnosing Contact Allergy: An Update
Authors: Lee Ernest E. , Maibach Howard I.
Published: April 2003

In suspected allergic contact dermatitis, the proper choice of vehicles for patch testing may be critical. The role of vehicles in diagnostic patch testing has been summarized, suggesting that improved delivery systems might significantly increase the reproducibility and reliability of patch tests. We review the literature subsequent to 1992 for advances in our knowledge of the optimization of vehicles for patch testing. A universal vehicle more efficient than petrolatum or water remains elusive; in vitro percutaneous penetration data provide insight that questions standard dogma.
Contact Dermatitis – Relation between Job Assignment and Work Motivation in a Young Israeli Adult Population
Authors: Moshe S. , Ingber A. , Slodovnik D. , Lerman Y.
Published: April 2003

Background: In this study, we evaluated the role of motivation and other parameters on job assignment in young Israeli soldiers who changed their occupation after the diagnosis of contact dermatitis (CD). Objective: To evaluate the influence of motivation and other parameters on job assignment in young Israeli soldiers with CD. Methods: The files of 336 soldiers who were diagnosed as having CD after their conscription to military service during the years 1986–1989 in the Israel Force were investigated. We compared the rate of occupational changes in the different commands and evaluated different discipline parameters between soldiers who did or did not change their job due to CD. Results: The percentage of job assignment (42.3%) in the study population was higher than the expected rate. A difference was detected in the rate of occupational changes following the diagnosis of CD among different military commands. The frequency of discipline parameters was higher among soldiers who changed job assignment following the diagnosis of CD (n = 142) and soldiers who did not (n = 194). Conclusion: The occupational changes in the various military commands and the differences in the discipline parameters imply that motivation is an important determinant affecting changes in job assignment following the diagnosis of CD.
Interlabial Contact Pressures Exhibited in Dysarthria following Traumatic Brain Injury during Speech and Nonspeech Tasks
Authors: Goozée Justine V. , Murdoch Bruce E. , Theodoros Deborah G.
Published: April 2003

A miniature pressure transducer was used to assess the interlabial contact pressures produced by a group of 19 adults (mean age 30.6 years) with dysarthria following severe traumatic brain injury (TBI) during a set of speech and nonspeech tasks. Ten parameters relating to lip strength, endurance, rate of movement and lip pressure accuracy and stability were measured from the nonspeech tasks. The results attained by the TBI group were compared against a group of 19 age- and sex-matched control subjects. Significant differences between the groups were found for maximum interlabial contact pressure, maximum rate of repetition of maximum pressure, and lip pressure accuracy at 50 and 10% levels of maximum pressure. In regards to speech, the interlabial contact pressures generated by the TBI group and control group did not differ significantly. When expressed as percentages of maximum pressure, however, the TBI group’s interlabial pressures appeared to have been generated with greater physiological effort.
Auftreten eines serös-papillären Adenokarzinoms mit Müllerscher Neoplasie nach prophylaktischer Ovarektomie
Authors: Kaltenegger Angela , Stieglbauer Wolfgang , Veith Christian , Hartmann Beda
Published: April 2003

Die prophylaktische Ovarektomie, d.h. die Entfernung makroskopisch unauffälliger Ovarien im Rahmen einer Laparotomie oder vaginaler Hysterektomie, schützt nicht obligatorisch vor dem Auftreten eines Ovarialkarzinoms. In dieser Kasuistik berichten wir über eine 76jährige Patientin mit einer malignen Müllerschen Neoplasie nach prophylaktischer Ovarektomie und diskutieren die relevante Literatur.
Einfluss der abdominalen Sakrokolpopexie und der vaginalen sakrospinalen Fixation (nach Amreich-Richter) auf das vordere Kompartiment
Authors: Anthuber C. , Stosius P. , Rebhan H. , Dannecker C.
Published: April 2003

Fragestellung: Welchen Einfluss üben die abdominale Sakrokolpopexie (aSKP) und die vaginale sakrospinale Fixation (vssF) auf das vordere Kompartiment aus? Patientinnen und Methodik: Es wurden retrospektiv durchschnittlich 24 Monate postoperativ 25 Patientinnen nach aSKP (Gruppe 1) und 60 Monate postoperativ 28 Patientinnen nach vssF (Gruppe 2) bezüglich folgender Parameter untersucht: Rezidivrate von Scheidenblindsackvorfall, Rate an rezidivierenden Zystozelen und Stressinkontinenz, De-novo-Stressinkontinenz, Drangsyndrom/Dranginkontinenz. Zusätzlich wurde eine Literaturübersicht der Jahre 1970–2002 durchgeführt. Ergebnisse: Beide Verfahren sind bezüglich der untersuchten Parameter vergleichbar. Es gab kein Scheidenstumpfprolapsrezidiv. Mittel- bis hochgradige Zystozelen fanden sich postoperativ bei 38% (Gruppe 1) bzw. 43% (Gruppe 2). Die Rate an objektiv nachweisbarer Stressinkontinenz betrug 24% (Gruppe 1) bzw. 25% (Gruppe 2). Drangbeschwerden blieben unverändert häufig. In der Literatur sind ähnliche Zahlen zu finden, die Rate an Zystozelen liegt allerdings niedriger (durchschnittlich bei 11,6% nach vssF und 21,6% nach aSKP). Schlussfolgerungen: Beide Operationen sind erfolgreich zur Fixierung des prolabierten Scheidenstumpfs. Es ist vermutlich nur durch die häufigere Kombination mit Zusatzeingriffen eine Steigerung der Erfolgsraten erreichbar.
Influence of Hepatitis C Virus Subtype on Hepatocellular Carcinogenesis: A Multivariate Analysis of a Retrospective Cohort of 593 Patients with Cirrhosis
Authors: Ikeda Kenji , Kobayashi Masahiro , Someya Takashi , Saitoh Satoshi , Tsubota Akihito , Akuta Norio , Suzuki Fumitaka , Suzuki Yoshiyuki , Arase Yasuji , Kumada Hiromitsu
Published: April 2003

Objective: The influence of hepatitis C virus (HCV) subtypes on hepatocellular carcinogenesis was prospectively investigated. Methods: A total of 593 patients with HCV-related cirrhosis were recruited and their HCV subtype was determined. Results: The carcinogenesis rates in the patients with HCV group 1 (genotype 1a +1b, n = 442) and group 2 (genotype 2a +2b, n = 136) were 32.0 and 26.6% at the end of the 5th year, 57.4 and 48.1% at the end of the 10th year and 71.8 and 71.0% at the end of the 15th year, respectively (p = 0.10). As to those patients without a history of regular drinking (i.e. less than 200 kg on a pure alcohol basis), the carcinogenesis rates in group 1 (n = 277) and group 2 (n = 90) were 30.8 and 16.3% at the end of the 5th year, 52.8 and 34.4% at the end of the 10th year and 70.6 and 67.1% at the end of the 15th year, respectively (p = 0.025). Although HCV subtype did not influence carcinogenesis in patients with a drinking history of 200 kg or more (p = 0.62), it significantly affected the carcinogenesis rate in patients without a history of regular drinking. Multivariate analysis showed that HCV subtype group 1 significantly increased the carcinogenesis in the group without a history of regular drinking after adjustment for age and gender (hazard ratio = 2.57, p = 0.0085). Conclusion: The interaction between HCV subtype and drinking history should be considered in the prediction of carcinogenesis using a multiplicative proportional hazard model.
Child Abuse in Kuwait: Problems in Management
Authors: Al-Ateeqi Wafa’a , Shabani Issa , Abdulmalik Aida
Published: April 2003

Objectives: To explore the extent of child abuse in Kuwait and examine the difficulties associated with its management. Subjects and Methods: A retrospective analysis of the 60,640 medical records of children admitted to Al-Amiri and Mubarak Al-Kabeer Hospitals, Kuwait, between 1991 and 1998 was done. Results: Of the 60,640 records, 16 children showed evidence of abuse. Of these, the perpetrator was a parent in 75% of the cases, which involved the following abuses: physical, 13; sexual, 2; and Munchausen syndrome by proxy in 1. Children with physical abuse had more than one type that included bruises (77%), burns (38%), intracranial haemorrhage (38%), fractures (23%) and cut wounds (15%). Seven of the children were returned to their biological parents, 7 were lost to follow-up and 2 died. Conclusion: Child abuse exists in Kuwait and is probably underreported. Management proceedings are not ideal and guidelines as well as legislation are needed.
Is the Bioreactivity of Vitamin-E-Modified Dialyzer an Expression of Increased Plasmatic Vitamin E Concentration?
Authors: Senatore M. , Nicoletti A. , Rizzuto G.
Published: April 2003

The present study was designed to test the biocompatibility of a new vitamin E-modified multilayer membrane compared with highly biocompatible polysulphone dialyzer and acrylonitrile dialyzer. Thirty patients (mean age 53.2 ± 15.3 SD years; dialytic age 36 ± 5.6 months) were selected for the study. The study was divided into three periods of 6 months (phases A, B and C). In the first phase (from Jan. 1999 to June 1999) patients undergoing maintenance bicarbonate dialysis were randomly divided into three filter groups composed, respectively, of 10 patients: acrylonitrile group, polysulphone group and vitamin E-coated dialyzer group. In the phase B (from July 1999 to Dec. 1999) and in the phase C (from Jan. 2000 to June 2000), all three groups changed their own dialysis membranes. Vitamin E-coated dialyzer causes significant decreases in β2-microglobulin, ferritin and immunoglobulin G, a normalization of complement C3 and an increase of plasmatic vitamin E compared to other filters. In the VE group homocysteine decreases but not in a significant manner. In addition, this dialyzer seems not to influence lipid pattern and protein-energy malnutrition parameters. These results clearly show a positive effect of this new filter in influencing different biochemical parameters, perhaps saving vitamin E and reducing polymorphonuclear cell activation.
Role of Ribavirin in Membranoproliferative Glomerulonephritis Associated with Hepatitis C Virus Infection Refractory to Alpha-Interferon
Authors: Pérez-Calvo Juan , Lasierra Pilar , Moros Manuel , Iñigo Pablo
Published: April 2003

Chronic hepatitis C virus (HCV) has been associated with several extrahepatic diseases, such as membranoproliferative glomerulonephritis (MPGN). α-Interferon is currently the treatment of choice for this association. When this therapy fails clinicians face a difficult challenge due to the lack of useful information in these particularly difficult patients. We report the case of a severe nephrotic syndrome due to MPGN associated HCV infection, in which a triple association – interferon plus ribavirin and cyclophosphamide – was needed to control the disease.
Lymphopenia in Wegener’s Granulomatosis
Authors: Izzedine Hassane , Cacoub Patrice , Launay-Vacher Vincent , Bagnis Corinne , Deray Gilbert
Published: April 2003

Background: Significant lymphopenia is a prominent feature in systemic erythematous lupus, but has not been described in Wegener’s granulomatosis (WG). We suggest from a retrospective analysis that lymphopenia may also be an index of WG disease activity. Methods: Medical charts form 19 patients diagnosed with systemic active WG between 1990 and 2000 were reviewed retrospectively. All patients had crescentic glomerulonephritis and alveolar hemorrhage. Clinical and biological markers were reviewed at three different time points: diagnosis, time of relapse, and during remission. Results: Average lymphocyte count was significantly lower at diagnosis and relapse than during remission times (p < 0.008 and p < 0.000002, respectively). During disease activity either at diagnosis and during relapses, ANCA titers were highly positive (≧50 IU/ml) in 27.5% of patients (8/29). The corresponding lymphocyte counts were below normal (1,500/min3) in 28 of 29 patients (96.5%). In patients with either negative or weakly positive ANCA, mean lymphocyte count was 728.5, 744.2 and 2,551/ml at diagnosis, during relapse and remission times, respectively. There was a clear negative correlation between the lymphocyte count and disease activity. Conclusion: Lymphopenia appears to be a good marker of WG activity. This index might be useful in all patients including those with negative ANCA.
Cyclosporin A Toxicity of the Renal Allograft – a Late Complication and Potentially Reversible
Authors: Sommerer Claudia , Hergesell Olaf , Nahm Anna-Maria , Schwenger Vedat , Waldherr Rüdiger , Andrassy Konrad , Zeier Martin
Published: April 2003

Cyclosporin A (CsA) has improved patient and organ graft survival, but the dichotomy of benefit and toxicity is still an issue. In a retrospective analysis of 392 renal transplant recipients we documented CsA nephrotoxicity (striped fibrosis, arteriolar wall hyalinosis) in 28 (7.1%) patients (23 male/5 female) in a follow-up of more than one year post transplantation. Median age at renal transplantation was 41 years (13–60) and the period between transplantation and graft biopsy was 42 months (12–122). Median CsA trough levels (ng/ml) at 12 months post transplantation, at time of graft biopsy and at last follow-up were: 114 (71–265), 130 (78–285), 66 (24–115). The following parameters were assessed at 12 months post transplantation, at time of biopsy and at last follow-up: s-creatinine (µmol/l), Doppler resistive index, systolic and diastolic blood pressure (mm Hg) and the number of antihypertensives. Median s-creatinine at 12 months post transplantation was 150.3 (94.6–247.5), at biopsy 225.4 (121.1–353.6) and at last follow-up 160.0 (106.1–247.5) (p < 0.001 for biopsy vs. last follow-up). Resistive index decreased from 0.70 (0.64–0.88) to 0.68 (0.51–0.84) (p < 0.005), systolic blood pressure from 137 (100–168) to 130 (105–144) (p < 0.05) and the number of patients with more than 4 antihypertensives from 10 to 6 between biopsy and last follow-up, with no acute rejection episodes after modification of immunosuppressive therapy (50% of previous CsA trough level and addition of azathioprine or mycophenolate mofetil). Conclusion: CsA nephrotoxicity occurs late after renal transplantation with increased systolic blood pressure and Doppler resistive index. Reduction of CsA improves renal function, reduces graft resistive index and systolic blood pressure.
Dynamic Extremes of Voice in the Light of Time Domain Parameters Extracted from the Amplitude Features of Glottal Flow and Its Derivative
Authors: Vilkman Erkki , Alku Paavo , Vintturi Juha
Published: April 2003

In the first part of the study, the subjects (4 females, 4 males) produced sustained breathy, normal and pressed types of phonation. The maximum AC flow (fac) and the negative peak amplitude (dmin) of the first derivative of the glottal flow were extracted from glottal volume velocity waveforms estimated by inverse filtering. The ratio between fac and dmin (amplitude quotient, AQ), which gives an estimate of the closing time of the glottal flow, and its normalised version (NAQ) were computed. The NAQ values correlated strongly with the closing quotient of glottal flow. In the second part of the study, the aim was to investigate the dynamic extremes of the human voice in terms of F₀, SPL, fac, dmin, AQ and NAQ as well as the intraoral pressure (p) used for subglottal pressure estimation. Eleven normal subjects (5 females, 6 males) participated in this experiment. The subjects started with the production of soft phonation (approximately 55 dB at 40 cm) and increased their vocal intensity at 5-dB steps up to the level of 105 dB. At the analysis stage, the voice samples were divided into three categories: soft (<70 dB), normal (70–90 dB) and loud (>90 dB). In soft and normal phonation, intensity change was correlated with changes in the shape of the glottal flow waveform, whereas the loud voice samples showed a large increase in F₀ and p values. At the loudest extreme, dmin approached its maximum and AQ its minimum values and NAQ started to rise. In terms of the NAQ values of stressed syllables, the type of phonation was breathy in the soft intensity category, whereas in the normal and loud intensity categories it was within the range of the pressed type of phonation of sustained phonation samples.
Regional Inequality in the Risk of Acute Myocardial Infarction in Finland: A Case Study of 35- to 74-Year-Old Men
Authors: Karvonen M. , Moltchanova E. , Viik-Kajander M. , Moltchanov V. , Rytkönen M. , Kousa A. , Tuomilehto J.
Published: April 2003

In this paper, the spatial distribution of the first event of acute myocardial infarction among 35- to 74-year-old men in Finland was examined for the cross-section years 1983, 1988 and 1993. The analysis was performed using a Bayesian hierarchical spatial approach to the geographically referenced data. The population data and case data received from nationwide registries were aggregated into 10 × 10 km cells. The estimated maps show that along with the overall decreasing incidence, the high-risk area withdrew deeper into the northeast, with an incidence 7–12% higher in rural than in urban areas. It could be concluded that eastern Finland is likely to remain a high-risk area in the future due to the concentration of certain risk factors.
Economical Aspects of High-Sensitivity C-Reactive Protein as Predictor of Coronary Heart Disease
Authors: Ess Silvia M. , Szucs Thomas D.
Published: April 2003

Background/Objectives: Measurement of high-sensitivity C-reactive protein (hs-CRP) in addition to lipid fraction measurements has been shown to improve the prediction of increased cardiovascular risk significantly. Moreover, baseline concentrations of hs-CRP seem to modulate the effectiveness of two preventive therapies: aspirin and statins. We evaluated the cost effectiveness (CE) of two primary prevention strategies, including hs-CRP determination versus no testing of hs-CRP, in three European countries: France, Spain and Switzerland. Methods: Using a decision analytic model, we evaluated the costs and consequences of two prevention strategies, including screening with hs-CRP in addition to standard lipid screening compared with no measurement of CRP levels. We analysed a hypothetical cohort of 100,000 apparently healthy men in three age groups (35–44, 45–54 and 55–64 years). Individuals with hs-CRP levels >3 mg/l were administered either aspirin or statin according to their lipid levels. Each cohort was followed for 5 years. The analysis was performed from the societal perspective. Extensive sensitivity analysis was performed in order to test the robustness of our conclusions. Results: Prevention strategies that include CRP determinations in addition to standard lipid screening improve outcomes with modest increments or even a reduction in the total expenditures. The results depended on: (1) whether statins were used more restrictively or extensively; (2) the age of the cohort, and (3) the local incidence of cardiovascular disease. Sensitivity analysis performed on the variables ‘test price’ and ‘cost of cardiovascular events’ resulted in minimal changes of the CE ratios. Conclusions: In the primary prevention setting, determination of CRP blood levels in addition to lipid screening can help better target individuals at higher risk, identifying those who will profit the most from existing therapies. Screening with hs-CRP can improve outcomes and result in more cost-effective prevention strategies.
Aggrenox® (Extended-Release Dipyridamole and Low-Dose Aspirin in Combination): Protecting Platelets from Excessive Activation in Patients with Vascular Events
Authors: Malinin Alex I. , Eisert Roswith M. , Atar Dan , Barkagan Zinoviy , Serebruany Victor L.
Published: April 2003

Aspirin has become an established therapy in patients for preventing recurrent stroke and the incidence of acute coronary events. Aggrenox®, a novel combination of low-dose aspirin with dipyridamole, represents a safe and promising combination alternative for mild but sustained platelet inhibition and the reduction of occurrences of both arterial and venous thrombi. In a recent, large, well-controlled trial (European Stroke Prevention Study 2; ESPS-2) evaluating antiplatelet agents for stroke prevention, Aggrenox was twice as effective as either aspirin or dipyridamole. Results of experimental studies show that dipyridamole combined with aspirin at ratios of about 10:1 or higher effectively inhibit thrombus formation, whereas a ratio of 1:1 has little effect. Indeed, one of the reasons that the ESPS-2 trial appears so convincing was the fact that a high dose of extended-release dipyridamole was combined with low-dose aspirin at a dose ratio of 8:1. Combination therapy with Aggrenox inhibits platelet aggregation much more strongly than aspirin or dipyridamole alone, and it may gain an additional clinical benefit due to synergic targeting of leukocytes, through an increase in endothelial nitric oxide production. Based on in vitro data showing that platelet adhesivity and aggregation induced by adenosine diphosphate (ADP), adrenaline and collagen is diminished, as well as through measurements of malondialdehyde production (marker of free radical production), it is known that dipyridamole and aspirin indeed exhibit a potentiated synergism as platelet inhibitors. On the other hand, clopidogrel, a novel thienopyridine and a potent ADP receptor blocker, has also been proven to yield a clinical benefit in unstable angina patients and during coronary interventions. Considering recent trends to combine clopidogrel with aspirin, it remains to be seen which combination will better serve various clinical scenarios in the near future. Further well-designed and carefully conducted clinical trials should elucidate possible benefits of Aggrenox during coronary interventions, especially in conjunction with new and aggressive reperfusion techniques. The benefits of Aggrenox in an expanding array of clinical conditions, including ischemic stroke, may be directly related to platelet inhibition. Moreover, marginal clinical benefits and recently reported severe bleeding events in some patients after oral platelet glycoprotein IIb/IIIa therapy may advance Aggrenox as a safe and efficient alternative for patients with vascular disease. This review summarizes the latest and often confusing data on the effects of aspirin, dipyridamole and Aggrenox on platelets and attempts to relate these data to bleeding complications and clinical outcomes.
Hormonal Control of Growth Hormone Secretion
Authors: Pombo M. , Pombo C.M. , Garcia A. , Caminos E. , Gualillo O. , Alvarez C.V. , Casanueva F.F. , Dieguez C.
Published: April 2003

Growth hormone secretion by the somatotroph cells depends upon the interaction between hypothalamic regulatory peptides, target gland hormones and a variety of growth factors acting in a paracrine or autocrine fashion. This review will be focused on recent data regarding the mechanism by which growth hormone-releasing hormone (GHRH) influences somatotroph cell function and the physiological role played by Ghrelin and leptin in the regulation of growth hormone (GH) secretion. It is well established that binding of GHRH to its receptor leads to activation of protein kinase A (PKA). More recently, it was found that GHRH can also activate mitogen-activated protein (MAP) kinase both in pituitary cells and in a cell line overexpressing the GHRH receptor. Whether somatotroph adenomas, either with or without a GS-alpha mutation, have alterations in some of the components of the activation of the MAP kinase pathway remains to be known. The recent isolation of Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, can be considered a landmark in the GH field, which opens up the possibility of gaining greater insight into our understanding of the mechanisms involved in the regulation of GH secretion and somatic growth. Indeed, preliminary evidences indicate that this peptide exerts a marked stimulatory effect on plasma GH levels in both rats and humans. Finally, it is well known that GH secretion is markedly influenced by nutritional status. Leptin has emerged as an important adipose tissue-generated signal that is involved in the regulation of GH secretion, thus providing an integrated regulatory system of growth and metabolism. Although the effects of leptin on GH secretion in humans remain to be clarified, indirect evidences indicate that it may play an inhibitory role.
The Potential of Prediction Models Based on Data from KIGS as Tools to Measure Responsiveness to Growth Hormone
Authors: Ranke Michael B. , Lindberg Anders , Chatelain Pierre , Wilton Patrick , Price David A. , Albertsson-Wikland Kerstin
Published: April 2003

Various prediction models have been developed, based on data documented within KIGS (Pharmacia International Growth Database), for use in the growth hormone (GH) treatment of children with short stature resulting from GH deficiency (GHD) or other causes. In addition to the practical value of such models as part of a ‘forward strategy’ guiding GH treatment, we now propose that prediction models may also be useful for the identification of individual variance in responsiveness. In a comparison involving 1,800 children with idiopathic GHD (IGHD), 151 children who acquired GHD after treatment for medulloblastoma and 192 children with GHD accompanying craniopharyngioma, it was shown that the responsiveness to GH of patients with craniopharyngioma equalled that of IGHD patients, whereas patients with medulloblastoma were less responsive. These observations and the identification of ‘good’ and ‘poor’ responders to GH have practical clinical consequences (e.g. modification of treatment), and will, in the future, lead to the identification of those factors which determine the variability of sensitivity to GH. This will improve the efficacy and safety of GH treatment as well as reducing the costs involved.
Commercial Assays Available for Insulin-Like Growth Factor I and Their Use in Diagnosing Growth Hormone Deficiency
Authors: Clemmons David R.
Published: April 2003

Radioimmunoassays of insulin-like growth factor I (IGF-I) are commonly used for screening adults and children for growth hormone (GH) deficiency or excess. There are, however, many problems with such assays. Attempts to resolve these problems have focused on methods of separating IGF-I from its binding proteins, and on reducing inter- and intra-assay variability. In particular, the collection of sufficient high-quality normative data is a major difficulty in many laboratories. Clinical evaluation of assays is also problematic. IGF-I levels vary with age after puberty, and this is complicated by the maintenance of IGF-binding protein 3 levels by IGF-II. Generally, studies have shown that IGF-I is sensitive and specific for the diagnosis of acromegaly, but screening for GH deficiency (GHD) is less precise. The most commonly used commercial assays are immunoradiometric (IRMA) sandwich assays, using antibodies specific to IGF-I. IRMA assays are quick and accurate, and the two-site antibody reactivity produces a high degree of specificity. Additional techniques such as acid-ethanol extraction or saturation with IGF-II can improve reliability. More recently, the introduction of chemiluminescence has provided enhanced speed and sensitivity. The clinical use of these assays has provided a wealth of information regarding the diagnosis of GHD, and it may be possible to reduce the number of patients who require provocative GH testing. IGF-I assays are also of great use in monitoring GH replacement therapy. Despite the problems, IGF-I measurement is currently the best indirect method available for screening and monitoring patients with GHD.
21st Century Perspective on Chronic Obstructive Pulmonary Disease
Authors: Ward Susan A. , Casaburi Richard
Published: April 2003

The prediction that chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2020 has enormous economic repercussions. Yet many issues and questions remain unresolved. For example, how can population studies of morbidity and mortality be viewed as comparable, without a worldwide consensus on the definition of COPD? How can the early diagnosis of COPD be improved? Why is it that only a minority of smokers develop COPD, despite tobacco smoking being the primary risk factor for chronic bronchitis and emphysema? How can the efficacy of smoking cessation interventions be improved? To what extent are the pathologic changes in the lungs reversible – and, if so, at what stage? And to what degree is it appropriate to emphasize the similar features of COPD and asthma? It is to be hoped that the emerging post-genomic and proteomic climate will facilitate the unlocking of the genetic substrate for COPD, and thus promote greater therapeutic specificity and efficacy.
Humoral Immune Responses in Uremia and the Role of IL-10
Authors: Girndt Matthias
Published: April 2003

Chronic renal failure severely influences the immune functions of the host. Recent work has shown that uremic intoxication as well as its treatment alters distinct aspects of immunity and that the organism has certain mechanisms to compensate, at least in part, for these influences. Failure of the humoral branch of immune function becomes apparent when vaccinations are applied to the dialysis patient. Severely impaired vaccine responses are common, particularly against hepatitis B, tetanus, or influenza. In contrast, patients with chronic renal failure may develop adequate humoral responses against vaccines such as pneumococcus. The degree of impairment of humoral responses is related to the antigen’s dependence on T-helper lymphocyte activation, which is high for hepatitis or influenza, and low for large polysaccharide antigens. T-helper cell activation on the other hand is greatly influenced by inflammatory processes, e.g. the secretion of cytokines such as interleukin (IL-)-1 or IL-6. These inflammatory processes are induced by uremic toxins and contacts between blood and extracorporeal surfaces of the dialysis equipment. They are subject to the body’s compensatory mechanisms for inflammation, which are mainly based on the anti- inflammatory cytokine IL-10. Genetically determined differences in the secretion capacity for this compensatory cytokine strongly influence humoral immunity in the patient with chronic renal failure and thus allow the definition of a high-risk group for infection and vaccine nonresponse.
Schizophrenic Patients Who Develop Postoperative Confusion Have an Increased Norepinephrine and Cortisol Response to Surgery
Authors: Kudoh Akira , Takahira Yoko , Katagai Hiroshi , Takazawa Tomoko
Published: April 2003

The purpose of this study was to investigate the relationship between postoperative confusion and the plasma norepinephrine (NE), adrenocorticotropin (ACTH) or cortisol response to surgery in schizophrenic patients. We studied 50 schizophrenic patients and 35 control patients who underwent orthopedic surgery and perioperatively measured plasma NE, ACTH and cortisol levels. Postoperative confusion during 72 h after the end of the operation occurred in 14 of 50 schizophrenic patients (28%) and in 2 of 35 control patients (6%). Plasma NE levels 15 min after skin incision, the next day, the second day and the third day after operation in schizophrenic patients with postoperative confusion (668.0 ± 59.2, 522.0 ± 96.5, 463.2 ± 71.2 and 398.9 ± 56.2 pg/ml, respectively) were significantly higher than those in schizophrenic patients without confusion (524.1 ± 62.6, 342.4 ± 38.6, 311.2 ± 58.3 and 314.1 ± 77.1 pg/ml, respectively). Plasma cortisol levels 15 min after the skin incision and the next and second days after operation in schizophrenic patients with postoperative confusion (23.6 ± 3.2, 21.1 ± 4.3 and 19.9 ± 4.4 µg/dl, respectively) were significantly higher than those in schizophrenic patients without confusion (15.2 ± 4.5, 14.3 ± 5.1 and 13.8 ± 3.8 µg/ dl, respectively). In conclusion, the occurrence of postoperative confusion in schizophrenic patients is associated with an increase in plasma norepinephrine and cortisol levels during and after surgery.
Cortisol Response to Surgery and Postoperative Confusion in Depressed Patients under General Anesthesia with Fentanyl
Authors: Kudoh Akira , Takahira Yoko , Katagai Hiroshi , Takazawa Tomoko
Published: April 2003

The purpose of this study was to investigate the relationship between postoperative confusion and plasma cortisol response to surgery in depressed patients. We studied 80 depressed patients and 40 control patients who had undergone orthopedic surgery and perioperatively measured plasma cortisol and adrenocorticotropin levels. Postoperative confusion in the first 3 postoperative days occurred in 5 (13%) depressed patients given fentanyl during anesthesia, 13 (33%) patients without fentanyl and 1 (3%) control patients. Plasma cortisol concentration (19.7 ± 6.9 and 19.2 ± 8.0 µg dl–1) 15 min after skin incision and 60 min after the end of surgery in depressed patients with fentanyl was significantly lower than that (24.2 ± 7.2 and 23.5 ± 8.1 µg dl–1) of depressed patients without fentanyl. Plasma cortisol levels during and after surgery in depressed patients with postoperative confusion were higher than those of depressed patients without postoperative confusion. We conclude that the occurrence of postoperative confusion in depressed patients is associated with an increase in plasma cortisol levels during and after surgery. The incidence of postoperative confusion in depressed patients with fentanyl was significantly lower than that of depressed patients without fentanyl.
Surfactant with SP-B and SP-C Analogues Improves Lung Function in Surfactant-Deficient Rats
Authors: Walther Frans J. , Hernández-Juviel José M. , Mercado Pamela E. , Gordon Larry M. , Waring Alan J.
Published: April 2003

The use of mammalian lung surfactant extracts has sharply reduced mortality and morbidity from respiratory distress syndrome in premature infants. Synthesis of surfactant protein B and C (SP-B and SP-C) analogues may lead the way to a synthetic surfactant preparation. Dimeric SP-B1–25 (dSP-B1–25) is based on the N-terminal domain of human SP-B and SP-Cfc is a modified human SP-C in which a single phenylalanine is substituted for a palmitoylated cysteine residue in the N-terminal segment (Phe-4 > Cys-4 variant). We tested the effects of synthetic surfactants with 1 or 2% dSP-B1–25 and 1% SP-Cfc on lung function in surfactant-deficient rats. Four experimental surfactant preparations were prepared by mixing 1% dSP-B1–25, 2% dSP-B1–25, 1% dSP-B1–25 +1% SP-Cfc, and 2% dSP-B1–25 +1% SP-Cfc with phospholipids (PL). PL and Survanta, a bovine lung extract, were controls. Groups of 8 rats were ventilated, lavaged until surfactant deficiency, and treated with 100 mg/kg surfactant. Arterial blood gas values and dynamic compliance were measured every 15 min and after 2 h of ventilation, the rats were killed and pressure-volume curves performed. Oxygenation improved quickly after instillation of surfactant with synthetic peptides and Survanta. Oxygenation and lung volumes were consistently higher in the 2% than in the 1% dSP-B1–25 groups. Addition of 1% SP-Cfc to the synthetic surfactants further improved oxygenation and lung volume, but to a lesser extent than increasing the dSP-B1–25 content from 1 to 2%. These data indicate that improvements in oxygenation and lung volume in lavaged rats are dependent on the concentration of dSP-B1–25 in the surfactant preparation and that the presence of SP-Cfc has a relative minor effect on these parameters.
Nitric Oxide Synthesis Inhibition during Cerebral Hypoxemia and Reoxygenation with 100% Oxygen in Newborn Pigs
Authors: Kutzsche Stefan , Solas Anne-Beate , Lyberg Torstein , Saugstad Ola D.
Published: April 2003

The objective of our study was to evaluate the effects of Nσ-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the nitric oxide (NO) pathway, on cerebral microcirculation during hypoxemia and reoxygenation with 100% oxygen in newborn pigs. Twenty-two pigs were randomized to hypoxemia [inspired fraction of oxygen (FIO2) 0.08; 20 min] and reoxygenation (FIO2 1.0; 60 min) or normoxia. The hypoxemic animals were further randomized to receive either an intravenous bolus injection of 5 mg/kg L-NAME (n = 8) or a corresponding volume of isotonic saline (n = 8) 30 min before the onset of hypoxemia. The normoxemic group (n = 6) received the same pretreatment with L-NAME. Cerebral hemodynamics were assessed by laser Doppler flowmetry and intracranial pressure monitoring. The cerebral NO concentration was continuously measured using an electrochemical sensor. Pretreatment with L-NAME resulted in a more severe systemic hypotension and reduced cerebral microcirculation during the period of hypoxemia compared with the saline/hypoxemia group. NO synthesis inhibition during reoxygenation with 100% oxygen, however, blunted the increase in NO concentration (p < 0.05) without reduction of cerebral blood flow and cerebral perfusion pressure. In conclusion, in this newborn pig model, pretreatment with a bolus infusion of L-NAME induced severe hypotension and reduced cerebral microcirculation during hypoxemia. However, it appears to have no significant adverse effect on cerebral hemodynamics during the period of reoxygenation with 100% oxygen. This deleterious effect during hypoxemia limits the use of L-NAME as a preventive drug but suggests beneficial effects during reoxygenation with 100% oxygen.
Smoking in Chronic Schizophrenic Inpatients in Taiwan
Authors: Liao Ding-Lieh , Yang Jen-Yi , Lee Shin-Min , Chen Hong , Tsai Shih-Jen
Published: April 2003

Objective: This study investigated the prevalence of smoking and its association with the clinical characteristics of Chinese inpatients with chronic schizophrenia. Method: Schizophrenic patients hospitalized in chronic wards were assessed using Brief Psychiatric Rating Scale (BPRS), Abnormal Involuntary Movements Scale (AIMS) and Folstein Mini-Mental Status Examination (MMSE) testing. Results: Of 257 patients, 105 smoked and 4 had ceased. Males exhibited a higher prevalence of smoking than females (p < 0.001). Smoking was not significantly associated with age at onset (AAO), chlorpromazine equivalents, MMSE, AIMS, BPRS positive symptom subscale, BPRS negative symptom subscale or total BPRS scores. Smokers had higher BPRS general subscales. Conclusion: Compared to the general population, smoking prevalence was slightly higher in schizophrenic males, double in schizophrenic females, but no difference in refractory schizophrenic clozapine users. Smoking did not affect patient AAO or daily antipsychotic dose. Patients with a higher BPRS general subscale may smoke to relieve affective symptoms.
Impact on Thai Psychiatrists of Passive Dissemination of a Clinical Practice Guideline on Prescribing Attitudes in Treatment-Resistant Schizophrenia
Authors: Udomratn Pichet , Srisurapanont Manit
Published: April 2003

This study aimed to determine the impact of a particular clinical practice guideline (CPG) following its passive dissemination on Thai psychiatrists’ prescribing attitudes towards treatment-resistant schizophrenia (TRS). Two surveys were conducted before and after the dissemination of the CPG. Ninety-four questionnaires from the first survey and 84 from the second were analysed. Over 70% of the respondents were male. The mean age and duration of practice were 42.3 and 15.3 years, respectively. The respondents’ characteristics were not significantly different in sex, age, years of practice, specialty, or clinical setting. In the first survey, the first three favoured interventions for TRS were switching to risperidone alone, switching to another conventional antipsychotic (CA), and adding carbamazepine to the on-going CA. In the second round, the first three interventions were switching to risperidone alone, switching to another CA, and switching to clozapine alone. Although there was a trend in the direction suggested by the CPG, there was no significant difference between the two surveys. The interventions chosen as first, second-, and third-line treatments were also not significantly different. Of 80 respondents who expressed their opinions on the CPG, 55, 15, and 10 stated that they knew, did not know, and were uncertain about the availability of a guideline, respectively. Of 55 respondents who knew about the availability of the guideline, 40 had read it. The mean (SDs) of the guideline acceptance and the impact of the guideline on the practice obtained from those 40 respondents were 70.9 (13.7) and 58.9 (19.6), respectively.