bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancy Outcome and Prognosisin Fetuses with Increased First-TrimesterNuchal Translucency
Authors: Mangione Raphaële , Guyon Frédéric , Taine Laurence , Wen Zong Qi , Roux Denis , Vergnaud Armand , Maugey-Laulom Brigitte , Horovitz Jacques , Saura Robert
Published: April 2003

Objective: One of the concerns of prenatal diagnosis is to find sensitive markers to screen for chromosome abnormalities, such as serum assays or nuchal translucency (NT). This study reports our experience with NT measurement during the first trimester of pregnancy. Materials: The study was performed prospectively on 252 fetuses with either NT ≧3 mm or cystic hygroma. Results: We observed 50 abnormal karyotypes, i.e. 19.8%. The incidence of chromosome abnormalities increased with increasing maternal age and increasing NT thickness. For the 202 fetuses with normal karyotypes, outcome was unfavourable in 32 cases: 23 elective terminations of pregnancy, 8 spontaneous abortions and 1 neonatal death. Outcome was favourable in 141 cases. Twenty-nine pregnancies were lost to follow-up. Conclusion: Measurement of NT at 12 weeks’ gestation seems to be a good marker for chromosome abnormalities. When the karyotype is normal, the pregnancy outcome remains correlated with the degree of NT thickness. The finding of NT >3 mm between 10 and 14 weeks’ gestation dictates rigorous ultrasound monitoring and caution when predicting pregnancy outcome.
The Role of Integrins in Human Embryo Implantation
Authors: Merviel Philippe , Challier Jean-Claude , Carbillon Lionel , Foidart Jean-Michel , Uzan Serge
Published: April 2003

Integrins are adhesion molecules present in endometrial, decidual, and extravillous cytotrophoblast (EVCT) cells. They participate in cell-cell adhesion as well as in adhesion between cells and components of the extracellular matrix, and they play an important role in the endometrial phenotype change that occurs during the secretory phase, the first stage of implantation. At the beginning of pregnancy, the change in integrin expression is synchronized with the trophoblast attachment (embryo-endometrium interactions with integrins αvβ3, α4β1, α6β1, and α7β1) and the embryo’s invasion of the decidua (integrins α6β4→α5β1→α1β1→α4β1 switch from proliferative to endovascular EVCT). Several diseases, including preeclampsia, intrauterine growth retardation caused by vascular problems and defective luteal phases, may be explained by anomalies in integrin patterns.
Is Routine Amniocentesis for Advanced Maternal Age Still Indicated?
Authors: Dommergues Marc , Audibert François , Benattar Clarisse , Champagne Catherine , Gomel Victor , Frydman René
Published: April 2003

Objective: To evaluate a policy of selective rather than routine use of amniocentesis for advanced maternal age. Method: A consecutive series of 359 pregnant women aged 38–47 underwent nuchal translucency measurement (NTM) at 10–14 weeks, maternal serum screening (MSS) by α-fetoprotein (AFP) and human chorionic gonadotropin (hCG) at 15–17 weeks, and second trimester ultrasound at 21–23 weeks. Women with NTM <3 mm, MSS-derived risk <1/250, and a normal second trimester sonography were considered at low risk and were suggested not to have an amniocentesis. Results: Either the NTM or MSS test was positive in 130 women; 105 (81%) of them elected to have an amniocentesis, versus 122 (53%) of 229 in whom both tests were negative (p < 0.001). Nineteen (5%) of 359 patients had NTM ≧3 mm; all 7 cases of Down’s syndrome were in this group; 122 (34%) of 359 patients had a MSS-derived risk ≧1/250; 6 of the 7 cases of Down’s syndrome were in this group: Ten patients had an abnormal second trimester ultrasound, 1 of which had trisomy 18. Of the 219 patients with MSS-derived risk <1/250, a NTM <3 mm, and a normal second trimester ultrasound, none had a baby with a chromosomal abnormality (95% confidence interval: 0–1.4%). Conclusion: Amniocentesis may be offered on a selective rather than routine basis in women over 38, based upon the results of noninvasive screening tests.
In utero Evaluation and the Long-Term Prognosis of Living Infants with Cystic Hygroma
Authors: Fujita Yasuyuki , Satoh Shoji , Nakayama Hideki , Taguchi Tomoaki , Suita Sachiyo , Nakano Hitoo
Published: April 2003

Objective: The aim is to evaluate the natural course and the long-term prognosis of cystic hygroma following live birth. Methods: Of 39 cases, 12 were excluded because of either artificial termination or intrauterine treatment. 27 cases were retrospectively classified into 2 groups based on the outcome, and the clinical profiles were compared. The long-term prognosis was analyzed for live births. Results: 5 (18.5%) and 22 (81.5%) cases resulted in live birth and fetal demise, respectively. Both the frequency of hydrops fetalis and the maximum size of the cyst were more significantly associated with a poor prognosis (p < 0.01). Of 5 live births, 3 cases with chromosomal or structural abnormalities were handicapped. Conclusions: Hydrops fetalis and cyst size are poor prognostic factors, and fetal chromosome and structural malformations should be taken into account when predicting the long-term prognosis.
Effects of Intrapartum Zidovudine Therapy on Fetal Heart Rate Parameters in Women with Human Immunodeficiency Virus Infection
Authors: Blackwell Sean C. , Sahai Anjali , Hassan Sonia S. , Treadwell Marjorie C. , Tomlinson Mark W. , Jones Theodore B. , Sorokin Yoram
Published: April 2003

Objective: To determine the effects of intrapartum maternal administration of zidovudine on fetal heart rate (FHR) parameters in women infected with the human immunodeficiency virus (HIV). Methods: Term HIV-infected women who delivered at our institution (1995–1998) were identified by medical records coding. Sixty minutes of FHR tracing prior to zidovudine administration and 60 min of FHR tracing 2 h after initiation of therapy were reviewed by 3 perinatologists blinded to patient status. Data were compared with paired t tests; p < 0.05 was considered significant. Inter- and intra-observer FHR interpretation variation were calculated. Results: Ten patients met study criteria. Their demographic data included: Maternal age 26.5 ± 6.5 years, gestational age 38.9 ± 1.3 weeks, median parity 2 (range 0–3). Eighty percent were African American. There were no significant differences in FHR parameters after intravenous zidovudine therapy (pretreatment versus 2 h after treatment) with respect to FHR baseline (p = 0.2), FHR variability (p = 0.3), or the number of accelerations (p = 0.1). There was also no difference in the number of variable (moderate or severe), early, or prolonged decelerations following zidovudine infusion. Conclusion: Two hours of continuous intrapartum intravenous infusion of zidovudine does not alter any parameter of the FHR in the laboring HIV-infected gravida.
Effect of Diclofenac Sodium Administration during Pregnancy in the Postnatal Period
Authors: Gökçimen Alpaslan , Aydin Gülsen , Karaöz Erdal , Malas M. Ali , Öncü Meral
Published: April 2003

Objective: The present study aimed to investigate the possible postnatal effects on the liver, kidney and testicular tissues of the offspring of rats given diclofenac sodium (DS) during pregnancy. Methods: At the beginning of the experiment, 80 rats (20 males and 60 females) were raised together for mating purposes. At the end, 50 pregnant rats were obtained and used as the experimental subjects. All pregnant rats were divided into 2 groups, each with 25 rats. The rats of the control group received physiological serum, 1 cm3/kg live weight per day, and the rats of the treatment group were injected with DS, 1 mg/kg live weight per day from the 5th to the 20th day of pregnancy. Four weeks after birth, tissue samples were obtained under anesthesia by perfusion fixation from a total of 40 offspring, 20 (10 males, 10 females) from the control group and 20 (10 males 10 females) from the DS group. Paraffin sections were dyed with hematoxylin eosin and examined under light microscopy. Results: The gestation period was significantly prolonged with DS-treated rats (p < 0.001). A moderate significant enlargement in the periportal area (p < 0.05), sinusoidal dilatation (p < 0.001), bile duct proliferation (p < 0.001), pyknosis in the nucleus of hepatocytes, and vacuolar degeneration in parenchymal cells (p < 0.001) were observed in DS-treated rats. Morphological changes in the liver were found to be similar both in female and male rats. Under light microscopy a similar morphological structure was observed in the kidney and testicular tissues of both the DS-treated and control rats. Conclusion: Significant morphological changes were observed in the livers of the offspring whose parents had been treated with DS. No significant differences were observed in liver morphology between the female and male offspring. There were no significant effects of DS on the morphology of the kidney and testis in all offspring.
Reported Exposure to Chickenpox: A Predictor of Positive Anti-Varicella-Zoster Antibodies in Parturient Women
Authors: Linder Nehama , Ferber Asaf , Kopilov Uri , Smetana Zehava , Barzilai Asher , Mendelson Ella , Sirota Lea
Published: April 2003

Objective: To determine the positive and negative predictive values of recalled exposure to chickenpox for identifying anti-varicella-zoster virus (VZV) seropositive parturient women. Methods: Blood samples were taken from laboring women during February 1998: All women completed questionnaires concerning a history of chickenpox in themselves and their children. Anti-VZV antibodies were determined by the immunofluorescent antibodies to membrane antigen (IFAMA) technique. Results: Three hundred and twenty-seven women formed the study population; 239 women (73.1%) recalled chickenpox in themselves or their children, of which 229 (95.8%) were seropositive for anti-VZV antibodies. Of the 88 women who gave a negative/uncertain history of chickenpox 82 (93.2%) were seropositive and 6 (6.8%) were seronegative. All 87 mothers who were certain their children had had chickenpox were seropositive, including all 16 mothers who had a negative personal history. Thus, a woman with a history of chickenpox had a positive predictive value of 95.8%, and a woman with a lack of history had a negative predictive value of 6.8% (sensitivity 73.6%, specificity 37.5%), while a positive history of chickenpox in a child had a positive predictive value of 100%. Conclusions: Most women with no known history of VZV infection have evidence of prior exposure by serologic testing. Moreover, 100% of women with a negative history who were exposed to VZV in their children were protected from the disease. Therefore, mothers exposed to VZV during pregnancy can be reassured that most likely they are protected. However, the practice of testing all pregnant women exposed to the disease should be continued.
A Case of Fetal Parvovirus B19 Myocarditis, Terminal Cardiac Heart Failure, and Perinatal Heart Transplantation
Authors: von Kaisenberg C.S. , Bender G. , Scheewe J. , Hirt S.W. , Lange M. , Stieh J. , Kramer H.H. , Jonat W.
Published: April 2003

We report a case of fetal cardiomegaly secondary to myocarditis as a result of intrauterine parvovirus B19 infection. The fetus was delivered through caesarean section because of increasing deterioration of cardiac function at 33 + 3 weeks with reverse flow in the ductus venosus. Four weeks later, a cardiac transplantation was carried out because of therapy-resistant dilative cardiomyopathy. This case shows that fetal parvovirus B19 infection may occur without anemia and myocarditis and does not always result in spontaneous reformation of a dilated heart and normal recovery. It may become the determining prognostic factor for the child.
Improving DNA Vaccines Targeting Viral Infection
Authors: Sin Jeong-Im , Weiner David B.
Published: April 2003

DNA vaccination techniques have been recently under intensive investigation both preclinically and in human studies aimed at impacting viral infection. Collectively, DNA vaccines expressing viral antigens induce both antigen-specific humoral and cellular immune responses which in model systems are capable of impacting viral infection. However, in clinical settings the potency of this approach is still under investigation. Efficacy is improved in specific circumstances through the addition of immunomodulatory molecules including cytokines as plasmid cassettes or through modification of the numbers of specific CpG sequences present in the backbone. Furthermore, combined vaccination schemes have been an important research focus for generating enhanced immunogenicity against viral infections. The ultimate utility of these approaches to prevent viral infection will require more work. However, improvements in the potency and focus of DNA vaccines present us with new opportunities for both basic research into protective immunity as well as novel strategies for immune therapy and prophylaxis.
Venous Thrombosis: Prevalence and Interaction of Risk Factors
Authors: Rosendaal F.R.
Published: April 2003

The key to understanding why certain individuals develop deep vein thrombosis at varying times, despite similar risk factors being present, is the realization of the importance of gene–gene and gene–environment interactions between risk factors. The discovery of factor V Leiden and several other coagulation abnormalities, which are now known to be common in the general population, has revolutionized the way in which the aetiology of venous thrombosis is viewed. On the basis of current knowledge, time-dependent models taking account of various forms of interaction have been developed.
Low-Molecular-Weight Heparins in Coronary Thrombosis: Today and Tomorrow
Authors: Wallentin L.
Published: April 2003

Data from several large-scale studies have suggested that low-molecular-weight heparin (LMWH) may be superior to standard heparin therapy in the setting of unstable coronary syndromes. Studies looking at the optimal duration of treatment have produced conflicting results; however, data from a recent large trial suggest that prolongation of treatment is associated with a significant benefit. The recommended initial treatment for patients with unstable coronary syndromes is a combination of LMWH and aspirin. Stablilized patients at moderate or high risk – such as those with ST-segment depression or increased troponin levels – should continue with this treatment until they have undergone coronary angiography and, if appropriate, an invasive procedure. In a recent small study among patients with acute myocardial infarction, the use of LMWH as an adjunct to streptokinase produced significant therapeutic benefits. Other potential uses for LMWH include a role in angioplasty.
Is there a Role for Antithrombotic Therapy in the Prevention of Pregnancy Loss?
Authors: Wechsler Bertrand , Huong Du Lê Thi , Piette Jean Charles
Published: April 2003

The antiphospholipid syndrome (APS) is now emerging as an important cause of recurrent pregnancy loss. A variety of treatments, including steroids, aspirin, heparin and immunoglobulin, alone or in combination, have been assessed in experimental studies and in clinical trials. Steroids are no longer recommended as first-line therapy for patients with APS without overt lupus, because they are associated with significant foetal and maternal morbidity. Based on data from recent trials, heparin plus low-dose aspirin appears to be the regimen of choice for patients with APS who have a history of thrombosis or pregnancy losses with aspirin alone. Aspirin is safe in pregnancy. Subcutaneous heparin does not cross the placenta and therefore has no adverse effects on the foetus. For the mother, however, potential side effects of heparin treatment include bleeding, thrombocytopenia and osteoporosis. Warfarin must be avoided during the first trimester but may have a role to play subsequently in certain subsets of patients. Some studies have demonstrated that combined therapy with prednisone and aspirin, or with heparin and aspirin, may improve the outcome in women with autoimmune disorders who are undergoing in-vitro fertilization.
Thrombolysis and Adjunctive Therapies in Acute Myocardial Infarction
Authors: Helft Gérard , Worthley Stephen G. , Zaman Azfar G. , Samama Michel M. , Badimon Juan J.
Published: April 2003

Thrombolysis and percutaneous transluminal angioplasty represent the cornerstone of the pharmacologic treatment of and the interventional approach to patients with myocardial infarction (MI). They are very effective. However, they are hampered by some critical limitations. Therefore, alternatives to standard thrombolytic therapy have been developed. Platelet glycoprotein (GP) IIb/IIIa blockade is under investigation and seems very attractive. This review will focus on the use of GP IIb/IIIa antagonists and thrombin inhibitors as adjunctive therapies to the thrombolytic treatment of patients with acute MI.
Anticoagulant Therapy Modifies Fibrinolytic Dysfunction in Chronic Atrial Fibrillation
Authors: Roldán Vanessa , Marín Francisco , Marco Pascual , Climent Vicente , Martínez Juan Gabriel , Monmeneu José V. , Bodí Vicente , Garri Francisco Sogorb
Published: April 2003

Objective: We evaluated the changes in fibrinolytic activation markers before starting anticoagulation, at 1 and 6 months following the introduction of anticoagulant therapy. Design and Methods: Tissue plasminogen activator (t-PA), its endothelial inhibitor (PAI-1), plasmin:antiplasmin complexes (PAPc), modified antithrombin III (ATM), D dimer (D-D) and fibrinogen (FIB) were measured in 36 patients with chronic atrial fibrillation. Fifteen of them had rheumatic mitral stenosis and 21 had nonrheumatic atrial fibrillation. Basal levels were compared with a sex- and age-matched healthy control group. Results: At baseline, patients with atrial fibrillation showed significantly higher plasma levels of PAI-1, ATM, D-D and FIB levels (p < 0.05) than controls, and no differences in t-PA and PAPc concentrations. Levels of t-PA, PAI-1, ATM and D-D decreased significantly under anticoagulant therapy, whereas FIB levels were not significantly modified. PAPc levels were significantly increased at 6 months in the rheumatic group but did not differ significantly in the nonrheumatic group. Conclusions: Patients with chronic atrial fibrillation show a hypercoagulant state and a relatively low fibrinolytic function. After 6 months of anticoagulant therapy, an improvement in fibrinolytic function markers was detected.
Comparison of Different Assays for von Willebrand Factor in Hemodialysis Patients
Authors: Borawski Jacek , Pawlak Krystyna , Myśliwiec Michał
Published: April 2003

Von Willebrand factor (vWF) abnormalities are involved in the hemostatic disturbances of uremia. Studies of vWF in both anemic and recombinant erythropoietin (EPO)-treated maintenance hemodialysis (HD) patients have given inconsistent results that could be partially dependent on the methodology. Therefore, the reciprocal relationships between four different vWF assays were studied in HD patients in relation to EPO therapy. Plasma vWF activity measured by ELISA using monoclonal antibodies against platelet glycoprotein (GP) Ibα (vWF:Act), plasma vWF antigen concentration by ELISA employing polyclonal antihuman vWF antibodies (vWF:Ag), and functional vWF activity by ristocetin-induced platelet aggregation (RIPA) in both platelet-rich plasma (PRP) and whole blood were studied in 70 HD patients. In the whole group, no correlations between these assays were found. In the non-EPO patients (n = 32), vWF:Act was correlated with vWF:Ag (r = 0.504, p = 0.003) but not with vWF activity by RIPA in PRP. In the EPO-treated patients (n = 38), vWF:Act was higher than in the untreated ones (p = 0.001), and vWF:Ag was related to the whole-blood RIPA (r = 0.386, p = 0.016). In conclusion, the platelet GP Ibα-binding epitope of the vWF molecule assessed by vWF:Act ELISA is intact in HD patients. However, this assay does not reflect the functional vWF activity as measured by RIPA in PRP. In EPO-treated patients, the GP Ibα-binding domains of vWF are more available but the plasmatic vWF monomers are neither more numerous by vWF:Ag ELISA nor more hemostatically active by RIPA PRP. The whole blood RIPA test has some potential for the quantification of vWF monomers in EPO-treated HD patients.
Preventing Venous Thromboembolism in General Medical Inpatients and after an Ischaemic Stroke
Authors: Gallus Alexander A.S.
Published: April 2003

Clinical trials and meta-analyses have shown that low-molecular-weight heparin and unfractionated heparin are effective in preventing deep vein thrombosis (DVT) in acutely ill medical inpatients who are at risk as they are likely to be bedridden for 6 days or more. It is not known, however, if such prophylaxis can also reduce the likelihood of fatal pulmonary embolism or decrease all-causes mortality in this patient population. No recommendations can be made regarding thromboprophylaxis in those at a lower risk of venous thromboembolism or in short-stay inpatients, as these have not yet undergone clinical trial. Current evidence suggests that high doses of heparin should be avoided after an acute ischaemic stroke, as the results of recent large trials suggest any potential treatment benefit in preventing DVT is cancelled by the increased intracranial bleeding risk caused from the underlying disease.
Extended Thromboprophylaxis following Lower Limb Arthroplasty: What Do the Clinical Trials Mean?
Authors: Cohen Alexander T. , Khushal A.
Published: April 2003

Patients undergoing major orthopaedic surgery are at high risk of thromboembolic complications. Of the available options for pharmacologic prophylaxis, the low-molecular-weight heparins (LMWHs) have been shown to be most effective in reducing the incidence of venous thromboembolic complications and are well tolerated. However, as the risk of venous thromboembolism persists for several weeks post-discharge, there is controversy regarding the ideal duration of prophylaxis. Six recent studies have examined the efficacy and safety of prolonged prophylaxis in this setting. Five of these studies have demonstrated that prolonged LMWH prophylaxis (either enoxaparin or dalteparin) for 4–5 weeks is beneficial and significantly superior to conventional prophylaxis for 7–15 days. The other study, using ardeparin, examined clinical endpoints and showed a minor trend but no significant reduction in these events. Furthermore, two of the studies – one with enoxaparin and one with dalteparin – also demonstrated a significant reduction in the incidence of proximal deep vein thrombosis. Analysis of all clinical events from the five studies that have published that information shows a halving or 51% reduction in favour of prolonged prophylaxis. On the basis of current evidence, prolonged thromboprophylaxis with LMWH for up to 35 days after major orthopaedic surgery is recommended.
Low-Molecular-Weight Heparin and Other Antithrombotic Agents in the Setting of a Fast-Track Revascularization in Unstable Coronary Artery Disease
Authors: Bassand Jean-Pierre
Published: April 2003

Revascularization procedures and particulary percutaneous transluminal coronary angioplasty are being performed more and more often in patients with unstable coronary artery disease, despite the fact that these procedures are known to carry a higher risk in such patients than in those with stable disease. This article reviews studies that have investigated the potential of modern antithrombotic therapy – low-molecular-weight heparin, anti-Xa agents, direct antithrombin inhibitors and glycoprotein IIb/IIIa inhibitors – to reduce the post-procedural event rate in such patients. The results are promising.
Low-Molecular-Weight Heparin and Other Antithrombotic Agents in the Setting of a Primarily Medical Treatment of Unstable Coronary Artery Disease
Authors: Verheugt Freek W.A.
Published: April 2003

Antithrombotic treatment of acute coronary syndromes (ACS) comprises aspirin and (low-molecular-weight) heparin. Adjunctive treatment with intravenous glycoprotein IIb/IIIa receptor antagonists may be used in high-risk individuals, especially when they undergo percutaneous coronary interventions. Results from large-scale trials studying the efficacy and safety of oral glycoprotein IIb/IIIa blockers in patients with ACS have been disappointing. Thrombolytic therapy is not indicated in ACS.
Does Low-Molecular-Weight Heparin Reduce the Costs of Venous Thromboembolism Treatment?
Authors: Bossuyt Patrick P.M.M. , Prins Martin M.H.
Published: April 2003

The development of low-molecular-weight heparins (LMWHs) has revolutionized the dominant treatment strategy of established deep vein thrombosis and pulmonary embolism. In a further attempt to simplify treatment, outpatient management using LMWH has been proposed for these patients. This management strategy has now been shown to be as safe and effective as hospital treatment in a number of large clinical trials. The question remains whether such an out-of-hospital treatment strategy actually reduces costs. This paper summarizes the economic evaluations reported in the literature. Two large economic evaluations, based on prospectively collected data on resource use, have been reported. Both pointed to a large reduction in costs of 60% or more. The size of the cost reduction depends on the proportion of patients managed at home. Several studies show that approximately 80% qualify for out-of-hospital treatment. Local facilities for organizing home care may put an upper limit on this proportion. From a societal perspective, the economic evidence in favour of outpatient treatment with LMWH presents a rare case of dominance: a situation of reduced costs with no concessions in clinical outcomes. Nevertheless, attention should be paid to the parties that will bear the healthcare costs generated by the replacement of inpatient care by outpatient care.
Secondary Prevention Measures after Acute Myocardial Infarction: Comparison between Diabetics and Non-Diabetics at a Saudi Teaching Hospital
Authors: Akbar Daad H.
Published: April 2003

Objective: To compare between the use of secondary prevention measures after acute myocardial infarction in diabetic and non-diabetic patients who were admitted to the King Abdulaziz University Hospital. Method: All patients admitted with a definitive diagnosis of acute myocardial infarction between January 1995 and December 1999 were studied. Patients’ age, sex, body mass index, development of heart failure, peak serum creatinine phosphokinase, duration of hospital stay, use of aspirin, beta-blockers or angiotensin-converting enzyme (ACE) inhibitors on discharge and outcome were reported. Results: A total of 184 patients were studied, 53% were diabetics and 47% non-diabetics. The mean age for diabetics was 56 years with a male:female ratio of 3.9:1, while for non-diabetics it was 53 years with a male:female ratio of 7.7:1 (p = 0.05, p = 0.09, respectively). Diabetic patients had a higher incidence of heart failure compared to non-diabetics, 57 versus 43% (p = 0.05), and had a longer hospital stay, 12 versus 10 days (p = 0.03). Aspirin was used by 97% of the diabetics and 94% of the non-diabetics (p = 0.4), while beta-blockers were used by 43 and 44% (p = 0.9) and ACE inhibitors by 67 and 51% (p = 0.03), respectively. Conclusion: There is no difference in the use of aspirin and beta-blockers between diabetic and non-diabetic patients. ACE inhibitors were used more by diabetics. There is underutilization of beta-blockers by diabetics and non-diabetics. Physicians should be encouraged to use beta-blockers as secondary prevention measures after acute myocardial infarction as they have substantial benefits and are of generally low treatment cost.
Surface Microbial Contamination in Some Commonly Available Tablet Dosage Forms
Authors: Obuekwe C.O. , Obuekwe I.F. , Rafiq M.
Published: April 2003

Objective: Nonprescription drugs are subject to unrestricted handling and are, therefore, potentially susceptible to postproduction contamination by microorganisms from both the handlers and the environment. The aim of this work is to investigate the occurrence of contamination of certain tablet surfaces by microorganisms. Methods: Twenty-two samples of commercially available analgesic and vitamin preparations in tablet form were obtained as sold or dispensed from retail pharmacies and clinical pharmacies in Nigeria and Kuwait. Sample surfaces of tablets were investigated by scanning electron microscopy and augmented by streaking and superficial implantation on agar media for culture development. Results: Of 22 samples tested, 14 (64%) were visually found to have surface microbial contamination. However, only 4 samples (18%) of the total samples investigated yielded positive microbial cultures on growth media. The most commonly observed surface contaminants were yeast cells. The microorganisms isolated included Saccharomyces sp., Rhodotorula rubra, coagulase-negative staphylococci and Penicillium sp. Conclusion:  Commonly available nonprescription drugs in tablet dosage form have been shown to be frequently contaminated by microorganisms. However, cases of microscopic visualization of microbial contamination of drugs do not often result in recoverable cultures on growth media.
Neurotrophic Action of Interleukin 3 and Granulocyte-Macrophage Colony-Stimulating Factor on Murine Sympathetic Neurons
Authors: Kannan Yukiko , Moriyama Mitsuaki , Sugano Tsukasa , Yamate Jyoji , Kuwamura Mitsuru , Kagaya Ariyuki , Kiso Yasuo
Published: April 2003

We investigated neurotrophic effects of interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on cultured sympathetic neurons obtained from mouse superior cervical ganglia. After 1 day of culture with physiological concentrations of mouse recombinant IL-3 and GM-CSF, the numbers of process-bearing neurons were increased. Maximum responses were elicited by 10 U/ml IL-3 and 1 U/ml GM-CSF, which were equivalent to the action of a submaximal dose (5 ng/ml) of nerve growth factor (NGF). The effects of IL-3 and GM-CSF were completely blocked by their corresponding antibodies, but not by anti-NGF, indicting their action is specific and completely independent of NGF. IL-3 and, to a lesser extent, GM-CSF were also able to protect NGF-differentiated neurons from apoptotic cell death caused by NGF withdrawal. The mitogen-activated protein (MAP) kinase signal transduction pathway is known to be involved in action of IL-3 and GM-CSF on hemopoietic cells, and thus we examined the participation of this pathway in the neurotrophic activities of IL-3 and GM-CSF. IL-3 and GM-CSF stimulation of the differentiated neurons was found to result in a rapid elevation of MAP kinase activity, and PD98059, an inhibitor of MAP kinase kinase activity, blocked both the neuritogenic and neuroprotective effects of IL-3 and GM-CSF. Immunocytochemical studies showed that IL-3 and GM-CSF receptors were present on the differentiated neurons. Thus, IL-3 and GM-CSF appear to be able to stimulate sympathetic nerve growth, via specific cytokine receptors on neurons, which lead to activation of the MAP kinase pathway that then mediates the observed neurotrophic effects.
Development and Sequels of Intestinal Inflammation in Nematode-Infected Rats: Role of Mast Cells and Capsaicin-Sensitive Afferents
Authors: Gay Jerome , Fioramonti Jean , Garcia-Villar Rafael , Bueno Lionel
Published: April 2003

Objectives: To determine whether intestinal mast cells and capsaicin-sensitive afferent nerves are involved in the development and sequels of Nippostrongylus brasiliensis-induced intestinal inflammation in rats. Methods: Two series of experiments were performed. In the first series, six groups of 8 rats were used to study the effects of mast cell stabilization by ketotifen. In the second series, six groups of 6 rats were used to study the effects of gut extrinsic sensory neuron depletion by capsaicin. For each series, four groups of rats were infected with N. brasiliensis and two groups were not infected. Results: Infection with N. brasiliensis resulted in an increase of myeloperoxidase (MPO) activity and mast cell numbers at day 12 postinfection; MPO returned to preinfection levels by day 35 while mast cell numbers remained elevated at that time. In ketotifen-treated infected rats, the increase of MPO at day 12 was less pronounced, but MPO activity remained elevated and mast cell numbers were increased at day 35. In capsaicin-treated infected rats, the MPO increase at day 12 was augmented, and MPO was still not returned to preinfection values by day 35; in contrast, the increase of mast cell numbers at days 12 and 35 was not modified by afferent nerve depletion. Conclusion: Mast cell stabilization decreased jejunal inflammation during the acute stage (day 12), but prolonged the inflammatory process until at least day 35 postinfection. The data also confirmed the protective role of gut extrinsic sensory neurons against intestinal inflammation in a model of nematode infection and revealed that these afferent nerves do not seem crucial for the development of nematode-induced hypermastocytosis.
Neuroimmune Interactions in Experimental Colitis
Authors: Fehér Erzsébet , Altdorfer Károly , Bagaméri Gábor , Fehér János
Published: April 2003

With its abundance of neurons and immunocytes, the gut is a potentially important site for the study of the interaction between the nervous and immune systems. In this electron microscopic study we have investigated the distribution of substance P (SP)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (IR) nerve terminals and the immunocytes during experimental colitis in the rat. A mild colitis was induced by a luminal enema containing trinitrobenzene sulfonic acid. The most severe inflammation was detected after 2 days and the density and the distribution of the SP- and VIP-IR nerve terminals as well as the immunocompetent cells were studied at that time. Many SP- and VIP-IR nerve terminals were observed in a very close situation to the inflammatory cells. The number of VIP-IR nerve terminals slightly increased in the inflamed area. The gap between the axolemma of the nerve terminals and immunocytes was 20–200 nm. Some lymphocytes and plasma cells were also IR for SP in the inflamed area, whereas no IR immunocytes were observed in the control and in noninflamed area from the same animal. The very close apposition of the SP- and VIP-IR nerve terminals to the inflammatory cells as well as the presence of SP-IR immunocytes in inflamed area support the suggestion that bidirectional neuroimmunomodulation exists in the colon.
Growth Hormone, Fatigue, Poor Sleep, and Disability in HIV Infection
Authors: Darko Denis F. , Mitler Merrill M. , Miller James C.
Published: April 2003

Poor sleep, daytime fatigue, and loss of cognitive ability exist during all stages of HIV infection, worsening with disease progression. These symptoms contribute to disability and poor quality of life. Data from several research groups support a role of somnogenic inflammatory process peptides elevated in HIV infection, e.g. TNFα. Though the literature is in conflict regarding an effect of HIV infection on growth hormone (GH) secretion, GH axis dysregulation and treatment with GH may be important in HIV infection, e.g. in the wasting syndrome. It has long been known that GH varies with changes in sleep. The hypothesis tested in the current study was that the relationship between delta frequency (0.5–4.0 Hz) sleep EEG amplitude (square root of power from frequency analysis) and GH secretion would differ between HIV positive (HIV+) and HIV negative (HIV–) subjects. In 14 subjects (6 HIV+ and 8 HIV–, none with current or past AIDS-defining illness) a linear relationship change across the night’s sleep was found in the coupling between delta frequency sleep EEG amplitude and GH secretion. The phase coupling change was in opposite directions in HIV+ versus HIV– subjects. This difference supports the hypothesis that the brain-based coordination of sleep and sleep-related physiology deteriorates early in HIV infection, and that GH dysregulation may contribute to this sleep pathology.
Differential Sensitivity to ACTH, but Not Stress, in Two Sources of Outbred Sprague-Dawley Rats
Authors: Matthys Laura , Castello Rosa , Zilz Alexandra , Widmaier Eric P.
Published: April 2003

Adrenocorticotropic hormone (ACTH) is the major regulator of adrenocortical steroidogenesis in mammals. By comparing the sensitivity to ACTH of isolated adrenocortical cells from two sources of the same strain (Sprague-Dawley, SD) of outbred rats, we have identified a source of rat with low sensitivity to ACTH in vitro. Cells isolated from Holtzman SD rats had a high sensitivity to ACTH (minimal effective concentration 50 pg/ml), whereas Taconic SD rats had a low sensitivity (minimal effective concentration 250 pg/ml; maximal steroidogenesis <50% of Holtzman cells). The responsiveness to analogues of cyclic adenosine monophosphate and cholesterol was also significantly lower in Taconic SD rats. Taconic adrenals were smaller, had significantly more mitochondria per cell, but approximately 20% less total lipid droplet volume per cell. There was no difference in latency to ACTH in vitro; however, steroidogenesis plateaued in Taconic cells after 25 min, while Holtzman cells secreted corticosterone almost linearly for at least 120 min. By contrast, the cyclic adenosine monophosphate secretion increased at the same rate for at least 120 min in cells from both sources. There were no differences between cells from the two sources in immunoreactive steroidogenic enzyme content. In vivo, the magnitude of the ACTH and corticosterone responses to two types of stress were similar in both sources. The thymus glands of Holtzman rats were significantly larger than those of Taconic rats. It is concluded that: (1) reduced sensitivity to ACTH in vitro in Taconic SD rats results from differences in the later stages of the steroidogenic pathway; (2)  factors in addition to ACTH are required for maximal steroidogenesis in Taconic SD rats; (3) a comparison of the steroidogenic pathways in adrenal cells from these two sources of outbred rats should be useful in further delineating the relative importance of putative intracellular signalling mechanisms involved in initiation and maintenance of steroidogenesis, and (4) these data suggest that different sources of the same strain of rats sufficiently diverge over time to become separate strains (‘substrains’). Overreliance on a single source of laboratory rodent may obscure natural variability in endocrine responses to stress and provide a misleading indication of homogeneity of responses.
Unexpected Activation of Pituitary-Adrenal Axis in Healthy Young and Elderly Subjects during Somatostatin Infusion
Authors: Ambrosio Maria R. , Campo Michela , Zatelli Maria C. , Cella Silvano G. , Trasforini Giorgio , Margutti Angelo , Rigamonti Antonello E. , Müller Eugenio E. , degli Uberti Ettore C.
Published: April 2003

In this study we explored, in man, the effect of acute attenuation of growth hormone (GH) release induced by somatostatin (SRIH) on ACTH and cortisol plasma levels. Sixteen young (8 women, aged 23–32 years, and 8 men, aged 18–27 years) and 14 elderly (8 women, aged 65–82 years, and 6 men, aged 65–70 years) healthy subjects volunteered to participate in this investigation. Each subject was tested on two separate occasions by: (1) a 90-min i.v. infusion of SRIH given in 50 ml 0.9% saline delivered at a rate of 9 µg/kg/h, and (2) a 90-min i.v. infusion of isovolumetric amounts of 0.9% saline. Plasma GH, ACTH, cortisol and glucose concentrations were determined prior and up to 180 min after SRIH or saline infusion. SRIH induced a significant (p < 0.05) decrease in plasma GH levels from basal values of 0.6 ± 0.15 and 0.5 ± 0.15 µg/l to nadir values 0.25 ± 0.1 and 0.2 ± 0.1 µg/l in young and elderly subjects, respectively. The administration of SRIH was associated with a clear-cut increase in plasma ACTH levels both in young (peak, 10.6 ± 1.6 pmol/l; AUC, 558.6 ± 147.5 pmol/l/h) and in elderly (peak, 21.3 ± 5.6 pmol/l; AUC, 841.9 ± 153.8 pmol/l/h) subjects with a significant (p < 0.01) difference as compared to saline infusion. Consistent with these results, SRIH infusion resulted in an unequivocal rise in plasma cortisol levels both in young (peak, 394.8 ± 36.4 nmol/l; AUC, 18,591.62 ± 1,372.45 nmol/l/h) and in elderly (peak, 585.6 ± 51.5 nmol/l; AUC, 24,871.05 ± 1,837.03 nmol/l/h) subjects. The ACTH and cortisol responses to SRIH were significantly (p < 0.05 and p < 0.01) higher in elderly than in young subjects. No sex-related differences occurred in the SRIH-induced activation of hypothalamic-pituitary-adrenocortical (HPA) axis. We conclude that (1) infusion of SRIH, at a dose that inhibited basal GH secretion, was associated with an activation of HPA axis, and (2) this response was higher in elderly individuals compared with younger adults. The reason for this novel and unexpected SRIH effect is presently unclear; however, the latter may be mediated, at least in part, by some central nervous system ACTH-releasing mechanisms activated by SRIH-induced decrease in GH secretion.
Acetyl Salmon Endorphin-Like and Interrenal Stress Response in Male Gilthead Sea Bream, Sparus aurata
Authors: Mosconi Gilberto , Gallinelli Andrea , Polzonetti-Magni Alberta Maria , Facchinetti Fabio
Published: April 2003

The present study investigates the role of melanotrope proopiomelanocortin-derived peptide in the interrenal stress response to different stressors in male gilthead sea bream, Sparus aurata. Plasma cortisol and acetyl salmon endorphin (acetyl s-EP), as well as pituitary acetyl s-EP contents, were measured during two stress paradigms: (a) long-term (1-month) confinement and crowding, and (b) short-term (60-min) confinement, crowding, and manipulation. In addition, naltrexone, a highly specific opioid receptor antagonist, was employed in some experimental groups to evaluate the adaptability of the opioid response to interrenal stress. In the long-term (1-month) confinement and crowding, higher plasma cortisol levels and acetyl s-EP concentrations than in the control group were found. However, although plasma cortisol levels significantly increased in both types of stress paradigm, a significant rise in plasma acetyl s-EP was observed only in the case of confinement plus crowding. These data seem to suggest a direct correlation of acetyl s-EP plasma levels exclusively in cases of specific stress, and support previous observations about the different nature of the pituitary-interrenal stress response in salmonids and in mammals. The results obtained in the short-term (60-min) experiments demonstrate the double activation of both the opioid and corticotrope systems when manipulation plus crowding was applied.
D2 Dopamine-Receptor-Mediated Inhibition of Proliferation of Rat Lactotropes in Culture Is Accompanied by Changes in Cell Shape
Authors: Arita Jun , Hashi Akihiko , Hoshi Kazuhiko , Mazawa Sachiko , Suzuki Shinichi
Published: April 2003

Dopaminergic agonists are effective in vivo in inhibiting lactotrope proliferation and prolactin (PRL)-secreting pituitary tumors. The purpose of the present study was to demonstrate in vitro actions of dopaminergic agents on proliferation and cell shape of rat lactotropes. Anterior pituitary cells cultured with serum-free, chemically defined medium were treated with dopaminergic agents and were labeled with 5-bromo-2′-deoxyuridine (BrdU) for 3 h before the end of culture. BrdU-labeling indices indicative of the proliferation rate of lactotropes were determined by double immunofluorescence staining for BrdU and PRL. Treatment with dopamine for 21 h decreased BrdU-labeling indices of lactotropes in a dose-dependent manner with a nadir at 3 × 10–7 M. The inhibitory action of 10–5 M dopamine appeared 15 h after the initiation of treatment and became pronounced with time up to 33 h. The dopamine action was mimicked by treatment with the D2 receptor agonist bromocriptine at concentrations over 10–9 M. Phase-contrast microscopy revealed that the flat polygonal cell shape of cultured lactotropes had changed to a round refractive cell shape after treatment with dopamine or bromocriptine, and that these changes in cell shape exactly paralleled those in the BrdU-labeling index. The changes in cell shape of lactotropes were accompanied by changes in subcellular distribution of actin filaments. Pretreatment with 10–7 M eticlopride, a D2 receptor antagonist, blocked the dopamine- or bromocriptine-induced changes in both BrdU-labeling index and cell shape. These results suggest that (1) the in vitro experimental system established in the present study is a good model for studying the mechanism of the antiproliferative action of dopamine and (2) D2-receptor-mediated inhibition of proliferation of lactotropes in serum-free culture is closely related to changes in actin organization and cell shape.
Seizure Activity Is Increased in Endocrine States Characterized by Decline in Endogenous Levels of the Neurosteroid 3α,5α-THP
Authors: Frye Cheryl A. , Bayon Laura E.
Published: April 2003

To examine the role of progesterone (P) and its 5α-reduced metabolite, the neurosteroid 5α-pregnan-3α-ol-20-one (3α,5α-THP), in endogenous variations in ictal activity rats were tested for kainic acid-induced seizures in different hormonal milieu. Corresponding plasma and central P and 3α,5α-THP levels were measured. Cycling Long-Evans rats in estrus and proestrus had seizures of significantly shorter duration and more central and plasma 3α,5α-THP and P than animals in metestrus or diestrus. Females with luteal functioning had seizures of significantly shorter duration and increased central and plasma 3α,5α-THP and P compared to animals that recently had luteal functioning discontinued. Pregnant rats had significantly shorter seizures and greater central and plasma 3α,5α-THP and central P than animals tested 1–2 days postparturition. In all test paradigms, seizure activity was increased in animals that had decreased 3α,5α-THP or P; overall, central 3α,5α-THP was more inversely related to ictal activity than central P or plasma P and 3α,5α-THP. To investigate a causal relationship between 3α,5α-THP and seizures, a 5α-reductase inhibitor, finasteride, or vehicle was administered to pregnant rats. Finasteride administration significantly decreased central and plasma 3α,5α-THP, but had no significant effect on plasma or central P of pregnant rats. Finasteride, but not vehicle administration, to pregnant rats significantly increased seizure duration. These findings support the hypothesis that variations in seizure threshold over endogenous hormonal milieu may be related to endogenous 3α,5α-THP. Of all of the endocrine conditions, seizure durations were greatest in diestrus animals; this group did not experience the lowest or the greatest decrease in 3α,5α-THP concentrations; however, of all of the endocrine conditions, cycling rats experienced the most rapid cycles of 3α,5α-THP variation. This suggests that cycles of endogenous variations in 3α,5α-THP may influence seizure threshold.