bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment Strategies in Cardiogenic Shock Complicating Acute Myocardial Infarction
Authors: Boesgaard Søren , Gruhn Nicolai , Wanscher Michael C.J. , Sander Kaare M. , Mortensen Svend A. , Aldershvile Jan
Published: April 2003

Even though treatments of both acute myocardial infarction (MI) and congestive heart failure have improved substantially, the management of cardiogenic shock following acute MI remains a major problem. Cardiogenic shock is characterized by sustained hypotension (systolic BP <90 mm Hg), dysfunction of many organs (i.e. oliguria) and activation of the sympathetic nervous system (tachycardia, peripheral hypoperfusion). It may be seen in as many as 5–10% of patients experiencing acute MI, and in-hospital mortality often exceeds 70% despite admission to coronary centres using modern pharmacological therapy (including thrombolysis). Recent investigations suggest that early invasive revascularization, either with percutaneous transluminal coronary angioplasty or coronary bypass surgery, may substantially reduce mortality in selected groups of patients and lead to marked prognostic improvements. Consequently, the benefits of acute early invasive revascularization should be incorporated into the treatment strategy of most patients with cardiogenic shock.
Platelets and Thrombolysis: Cooperation or Contrariety?
Authors: Callahan Kevin P. , Malinin Alex I. , Gurbel Paul A. , Alexander John H. , Granger Christopher B. , Atar Dan , Serebruany Victor L.
Published: April 2003

Fibrinolytic therapy is the established treatment for the management of patients with ST elevation acute myocardial infarction (AMI). Present thrombolytic regimens have a number of limitations, including the failure to produce early and sustained reperfusion, as well as an inability to prevent reocclusion in at least some patients. Platelets play an important role in coronary thrombosis responsible for AMI. The effect of coronary thrombolysis on platelets has been extensively debated in the literature, with controversial evidence of both platelet activation and inhibition. Among fibrinolytic agents, tissue plasminogen activator (t-PA) is considered to be the cornerstone in the treatment of acute coronary occlusion. The native t-PA molecule has been modified in an attempt to achieve improved lytic characteristics with less risk of bleeding events. Extensive research has led to a group of mutant t-PA variants referred to as third-generation plasminogen activators. TNK-t-PA is one bioengineered variant of t-PA; another is reteplase (r-PA). They have been developed to establish more rapid, complete and stable coronary artery patency, thus promising reduced mortality. Both r-PA and TNK-t-PA are effective when given as bolus therapy, a feature that may facilitate earlier treatment initiation as well as lower treatment costs. New acute coronary treatment regimens include potent antiplatelet agents on top of thrombolysis that may improve sustained reperfusion. This review summarizes the latest and often contradictory data on the interaction between fibrinolytic therapy and platelets in certain in vitro, animal and clinical scenarios.
Noradrenaline-Induced Paxillin Phosphorylation, ERK Activation and MEK-Regulated Contraction in Intact Rat Mesenteric Arteries
Authors: Ward Donald T. , Alder Angela C. , Ohanian Jacqueline , Ohanian Vasken
Published: April 2003

In rat mesenteric arteries, noradrenaline (NA) induces a time-dependent increase in tyrosine phosphorylation of a number of proteins, one of which was identified as paxillin. NA-induced protein tyrosine phosphorylation was ablated by tyrosine kinase inhibition, virtually unaffected by protein kinase C (PKC) inhibition or PKC downregulation and was mimicked by KCl. NA also caused a time-dependent activation of the extracellular signal-regulated kinases (ERK)1 and ERK2. These responses were blocked by the ERK-activating kinase (MEK) inhibitor PD98059 and by tyrosine kinase inhibition but only modestly attenuated by PKC downregulation or inhibition. Pretreatment of cannulated mesenteric arteries (50 mm Hg internal pressure) with PD98059 significantly reduced the contractile responsiveness of the vessels to NA (1.56 ± 0.14 µM, EC50 control; 3.32 ± 0.49 µM, EC50 + PD98059, p < 0.01). Thus, NA induces time-dependent increases in protein-tyrosine phosphorylation and ERK activation in rat mesenteric arteries that could suggest a role for Ca2+-dependent non-receptor tyrosine kinases and ERKs in the response of small arteries to NA. In addition, the modulation of NA-induced mesenteric artery contraction by inhibition of the MEK/ERK pathway further implicates ERK in the regulation of, though perhaps not the mediation of NA-induced small artery contraction.
Inward Remodeling Follows Chronic Vasoconstriction in Isolated Resistance Arteries
Authors: Bakker Erik N.T.P. , van der Meulen Esther T. , van den Berg Bernard M. , Everts Vincent , Spaan Jos A.E. , VanBavel Ed
Published: April 2003

The hypothesis was tested that chronic vasoconstriction is followed by a structural reduction in lumen diameter, measured at full dilation. An in vitro model of pressurized rat skeletal muscle arterioles was used. During a 3-day experimental period, constriction of active vessels was achieved with fetal calf serum or endothelin-1 (ET-1). Maximal dilation revealed inward remodeling from 179 ± 6.5 µm lumen diameter on day 0 to 151 ± 6.3 µm on day 3 at 75 mm Hg in vessels incubated with serum (n = 8). Similarly, ET-1 induced inward remodeling from 182 ± 5.2 to 164 ± 3.7 µm (n = 6). When constriction during organoid culture was inhibited with papaverin or verapamil, inward remodeling was fully prevented: 184 ± 6.3 to 184 ± 5.8 µm for papaverin (n = 6) and 174 ± 5.5 to 177 ± 7.4 µm for verapamil (n = 6). A chronic reduction in diameter without tone was achieved in vessels that were kept at a low pressure (2–5 mm Hg; n = 6). Here, no remodeling was found, thereby ruling out that a chronic reduction in diameter alone is sufficient for inward remodeling. These data show that a persistent active reduction in lumen diameter is followed by inward remodeling of arterioles.
Role of Capsaicin-Sensitive Afferents in Fever and Cytokine Responses during Systemic and Local Inflammation in Rats
Authors: Gourine Alexander V. , Rudolph Karin , Korsak Alla S. , Kubatko Justin , Tesfaigzi Johannes , Kozak Wieslaw , Kluger Matthew J.
Published: April 2003

Objective: Peripheral afferents play an important role in fever. In the present study, we investigated the role of capsaicin-sensitive afferents in fever and cytokine responses during systemic (induced by intraperitoneal lipopolysaccharide, LPS) and local (induced by injection of Freund’s incomplete adjuvant, FIA, into the paw) inflammation. Methods: Fevers in rats (8–10 weeks of age) whose capsaicin-sensitive afferents were depleted by neonatal capsaicin (50 mg/kg) treatment were compared to those of rats treated as neonates with vehicle. To investigate a possible involvement of cytokines, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured during LPS- and FIA-induced fever in rats after capsaicin-induced desensitization. Body temperature was measured by biotelemetry. IL-6 and TNF bioactivities in plasma were determined using bioassays. Results: The initial but not the late phase of LPS (50 µg/kg)-induced fever was markedly higher (∼1.0°C) in rats whose capsaicin-sensitive neurons were destroyed by neonatal capsaicin treatment. Capsaicin-induced desensitization also resulted in significantly higher plasma levels of IL-6 and TNF 1 but not 4 h after LPS challenge. In contrast, the day after injection with FIA (0.1 ml), rats treated with capsaicin had significantly lower body temperatures compared with vehicle-treated animals. No differences were found in plasma levels of IL-6 and TNF between capsaicin- and vehicle-treated animals in response to FIA. Conclusions: These data indicate that the role of capsaicin-sensitive afferents in fever depends on the type of inflammatory response. During systemic inflammation, capsaicin-sensitive afferents may be involved in modulating fever by regulating the levels of pyrogenic cytokines. During local inflammation, the late phase of fever is partially mediated via capsaicin-sensitive afferents.
Evidence of Prolactin Immunoreactivity in the Bone Marrow of Untreated Multiple Myeloma Patients
Authors: Gadó Klára , Nagy György , Hasitz Ágnes , Tóth Béla E. , Rimanóczi Èva , Domján Gyula
Published: April 2003

The role of prolactin (PRL) in the physiological regulation of the immune system and in hematopoiesis is well known. There is also evidence of the significance of PRL in several pathological conditions such as autoimmune diseases and some malignancies, e.g. colon and breast carcinomas and also B cell malignancies. Multiple myeloma is known as a B cell malignancy. It is the result of malignant transformation of a single clone of neoplastic plasma cells that synthesize abnormal amounts of monoclonal immunoglobulins or immunoglobulin fragments. In our present studies, the possible expression of PRL in bone marrow cells obtained from diagnosed multiple myeloma (17 cases) or nonmyeloma (5 cases) patients was examined by the method of immunocytochemistry. Samples obtained from those multiple myeloma patients (13 cases) who had not received chemotherapy for 6 months prior to these studies showed a positive immunocytochemical reaction for PRL. Bone marrow smears of patients diagnosed with multiple myeloma who had received chemotherapy within 6 months of the study and also the smears of patients without diagnosed multiple myeloma failed to show a positive immune reaction for PRL. In the case of a patient who was examined prior to and also after a period of 3 months of chemotherapy, the PRL-immunopositive bone marrow cells had disappeared due to the treatment. According to the light microscopic analysis of the cell morphology, PRL-immunopositive cells in the bone marrow were mainly, but not exclusively, plasma cells. There was no correlation between the positive PRL staining of cells and the type of monoclonal immunoglobulin or the ratio of plasma cells detected in the bone marrow. Taken together, our results indicate a possible role of PRL in multiple myeloma. Further experiments are necessary to identify the prognostic value of PRL in multiple myeloma.
Lipopolysaccharide-Induced Tumor Necrosis Factor-Alpha Release Is Controlled by the Central Nervous System
Authors: Mastronardi Claudio A. , Yu Wen H. , McCann Samuel M.
Published: April 2003

Objective: Lipopolysaccharide (LPS) injection in mammals orchestrates the release of many proinflammatory and anti-inflammatory cytokines. Intravenous administration of 0.2 mg/kg of LPS into unanesthetized rats with indwelling jugular catheters provoked a rapid, 50-fold increase in plasma tumor necrosis factor (TNF)-α within 30 min, which declined by 60% by 120 min. To test our hypothesis that such a rapid increase of TNF-α would be either neurally or hormonally controlled, the effect on TNF-α release of anesthesia (ketamine/acepromazine/xylazine) and catecholaminergic agonists and antagonists, either alone or in the presence of LPS, was determined. Methods: Rats bearing indwelling external jugular catheters were injected with the test drug or saline after removal of 0.6 ml of blood (–10 min). At time zero, LPS or saline was administered. Thereafter, blood samples were drawn at 15, 30, 120, 240 and 360 min. TNF-α was measured by immunoassay. Results: Among all the drugs tested, only propranolol increased plasma TNF-α. Anesthesia significantly blunted the LPS-induced TNF-α peak by 50%. Isoproterenol, a β-adrenergic agonist, also blocked LPS-induced TNF-α release by 70% at 30 min and 90% at 120 min. On the contrary, propranolol, a β-receptor blocker, induced a highly significant 3-fold increase in plasma TNF-α concentrations at 30 min and augmented the response to LPS 2-fold after endotoxin injection. Phentolamine, an α-receptor blocker, decreased the LPS-induced TNF-α release by 57% at 30 min. Similarly, α-bromoergocryptine, a dopamine D2 receptor agonist, decreased the LPS-induced TNF-α peak by 70% at 30 min and 50% at 120 min. Conclusions: We conclude that TNF-α is at least in part neurally controlled since the anesthetic blocked its response to LPS. The fact that isoproterenol decreased the LPS-induced TNF-α release, whereas propranolol augmented basal and LPS-induced release suggests that the sympathetic nervous system inhibits basal and LPS-stimulated TNF-α release via β-adrenergic receptors. Since phentolamine blocked LPS-induced release, this release may be induced, in part at least, by LPS-stimulated adrenergic drive acting on α-adrenergic receptors. The suppressive action of bromoergocryptine, a dopamine D2 receptor agonist, on LPS-induced TNF-α release may be mediated in part by suppression of prolactin release, which triggers TNF-α release.
Comparable Effects of Adrenalectomy and C Fiber Depletion on Delayed-Type Hypersensitivity in Rats
Authors: Katafuchi Toshihiko , Kondo Tetsuya , Hori Tetsuro
Published: April 2003

Objective: To determine the influence of the hypothalamic-pituitary-adrenal (HPA) axis and sensory C fibers on cell-mediated immunity, the time course of allergic contact dermatitis (ACD) was examined in normal, adrenalectomized (ADX) and capsaicin (CAP)-treated rats. Methods: Five days after sensitization with 2,4-dinitro-1-fluorobenzene (DNFB) onto the back, rats were challenged with DNFB on the pinna. ADX or CAP treatment was performed a week before the sensitization. Results: Ear swelling in normal rats reached a peak 24 h after the challenge and subsided gradually to about half of this peak 72 h afterwards. Plasma ACTH levels increased about 9 times more than those of nonsensitized rats 72 h after the challenge. ADX rats, in which the plasma corticosterone level was significantly lower than that in sham-operated animals, exhibited more rapid development of ACD, which reached a peak 12 h after the challenge. However, the swelling returned to about half of the maximum within 48 h. In CAP-treated rats, ACD reached a peak 6 h after the challenge and recovered quickly as in ADX rats. Plasma ACTH levels in CAP- treated rats were significantly lower than those in vehicle-treated rats. Conclusions: The rapid development of and recovery from ACD in ADX and CAP-treated rats, both of which showed suppression of the HPA axis, indicated a biphasic action of the HPA axis on ACD, i.e. inhibitory in the early phase but augmentative in the late phase of ACD.
The Inflammatory Cascade in Acute Ischemic Renal Failure
Authors: Okusa Mark D.
Published: April 2003

The pathogenesis of human acute ischemic renal failure is complex. Studies in animals have revealed a number of factors that could contribute to the injury associated with acute ischemic renal failure. Despite these discoveries, we have yet to devise a therapeutic regimen that will ameliorate or prevent acute renal failure in humans. Nevertheless we have made great strides in understanding mechanisms that contribute to acute ischemic renal failure. An important component is the contribution of the inflammatory cascade brought about by tissue reperfusion following an ischemic period. This review summarizes recent studies that implicate the inflammatory cells in the development of renal injury associated with acute ischemic renal failure. Because of the complex overlapping pathways involved in the inflammatory cascade, blocking single molecules is unlikely to be successful in reducing renal injury. Rather broadly abrogating the inflammatory cascade is likely to yield the greatest success in the treatment and prevention of acute ischemic renal failure.
High Postdialysis Urea Rebound Can Predict Intradialytic Increase in Intraocular Pressure in Dialysis Patients with Lowered Intradialytic Hemoconcentration
Authors: Tovbin David , Belfair Nadav , Shapira Sorin , Rosenthal Gideon , Friger Michel , Feldman Leonid , Lifshitz Tova , Tessler Zvi
Published: April 2003

Background: Intradialytic (ID) decrease in intraocular pressure (IOP) parallel to ultrafiltration-induced hemoconcentration has been recently reported. However, exacerbation of glaucoma in hemodialysis (HD) patients during HD sessions is occasionally observed. Postdialysis urea rebound (PDUR) is induced by the lag in urea removal from the cells to urea removal from the extracellular fluid, which when increased can result in ID drag of water to intracellular compartment. It is our hypothesis that similar lag in urea removal from ocular compartments may also be reflected by PDUR, and may induce drag of water into ocular compartments counteracting the effect of hemoconcentration. Our assumption was, therefore, that PDUR might predict ID increase in IOP. Methods: IOP, serum urea and hematocrit levels were measured at the start, end and 1 h postdialysis, in 19 chronic HD patients with normal IOP. Results: PDUR was positively correlated with mean (both eyes) ID changes in IOP (MIDIOP) (r = 0.5, p = 0.03) and % MIDIOP (r = 0.55, p = 0.02). ID increase in IOP was observed only in the 7 patients with relatively higher PDUR (≧9 mg%), who had also a relatively lower % ID change in Hct (<8%). MIDIOP was negatively correlated with % ID changes in Hct (r = –0.65, p = 0.03) in the 12 patients with PDUR ≧9 mg, and positively correlated with PDUR (r = 0.57, p = 0.03) in the 14 patients with % ID change in Hct <8%. Conclusion: High PDUR may predict susceptibility to ID increase in IOP in patients with lowered ID hemoconcentration.
Membranous Glomerulonephritis Associated with Renal Cell Carcinoma: Failure to Detect a Nephritogenic Tumor Antigen
Authors: Togawa Akashi , Yamamoto Tatsuo , Suzuki Hiroo , Watanabe Kouhei , Matsui Katsuyuki , Nagase Mitsumasa , Hishida Akira
Published: April 2003

A 57-year-old man with renal cell carcinoma associated with membranous glomerulonephropathy (MGN) developed a transient amelioration of the nephrotic syndrome after excision of the tumor. We tried to identify a nephritogenic tumor antigen using the immunoblotting technique in this patient with MGN, since previous studies examined the interaction between tumor antigens and IgG eluted from the kidney tissue using immunofluorescence or immunodiffusion techniques, and no studies have identified the specific tumor antigen with the immunoblotting method. In the present study, no significant immunoreactivity was noted between the IgG eluted from renal cortical tissues of the patient and renal cell carcinoma proteins. Further studies are necessary to establish the pathogenic mechanism of MGN associated with malignancy.
Comorbidity and Mortality in Peritoneal Dialysis: A Comparative Study of Type 1 and 2 Diabetes versus Nondiabetic Patients
Authors: Miguel Alfonso , García-Ramón Rafael , Pérez-Contreras Javier , Gómez-Roldán Carmen , Alvariño Javier , Escobedo José , García Héctor , Lanuza Manuel , López-Menchero Ramón , Olivares Jesús , Tornero Fernando , Albero Dolores
Published: April 2003

We conducted a retrospective study with 750 peritoneal dialysis (PD) patients in a Spanish multicenter registry between 1993 and 1999 to analyze comorbidity and mortality in type 1 diabetes (T1D), type 2 diabetes (T2D) and nondiabetic (ND) patients. 163 patients (21.7%) were diabetic – 96 T1D (58.8%) and 67 T2D (42.2%) – while 587 were not (78.3%). Different comorbidity factors such as the presence of cardiovascular disease, age over 70 and dyslipidemia at the start of PD were analyzed as well as the incidence of peritonitis, the peritonitis-free interval, need for hospitalization, mortality rate, early mortality rate, survival curves (log rank) and the impact factor (Cox) on mortality for the different variables. The comorbidity index (number of comorbidity factors when starting the treatment) and the peritonitis incidence were higher for T2D. Hospitalization rates were similar, but mortality rates were higher for T2D and early mortality rates (death during the 1st year of treatment) were higher for T1D. The actuarial survival curves showed a higher mortality for T2D with no differences between ND and T1D after adjustment for age. The mortality odds ratio was 1.78 for T2D and 1.13 for T1D, differences which were not significant after adding age over 70 and cardiovascular disease to the variables analyzed. Our results show that associated comorbidity is the most important difference between ND, T1D and T2D. While cardiovascular comorbidity is responsible for the higher percentage of early mortality found in T1D when compared to ND, both age and cardiovascular disease are responsible for the higher comorbidity and mortality found in T2D.
Spontaneous Normalization of Negative T Waves in Infarct-Related Leads Reflects Improvement in Left Ventricular Wall Motion even in Patients with Persistent Abnormal Q Waves after Anterior Wall Acute Myocardial Infarction
Authors: Nagase Kimiaki , Tamura Akira , Mikuriya Yoshiaki , Nasu Masaru
Published: April 2003

This study aimed to clarify whether spontaneous T-wave normalization (TWN) in infarct-related leads reflects improvement in left ventricular (LV) wall motion even in patients with persistent abnormal Q waves after acute myocardial infarction (AMI). Eighty-five patients were classified into the following 3 groups: patients with Q-wave regression (group A, n = 21), those with persistent abnormal Q waves and TWN (group B, n = 36), and those with persistent abnormal Q waves and absence of TWN (group C, n = 28). Groups A and B had greater improvement in LV ejection fraction and regional wall motion between 1 and 6 months after AMI than group C. In conclusion, spontaneous TWN in the healing stage of anterior AMI reflects functional recovery of viable myocardium in the infarct region even in patients with persistent abnormal Q waves.
Amlodipine: Effective for Treatment of Mild to Moderate Essential Hypertension and Left Ventricular Hypertrophy
Authors: Islim Ismail F. , Watson Robert D. , Ihenacho H.N.C. , Ebanks Mike , Singh Shyam P.
Published: April 2003

This was a 20-week, open-label, uncontrolled clinical investigation of the long-acting calcium antagonist amlodipine in 33 male or female patients with essential hypertension and left ventricular hypertrophy (LVH). A once-daily dose (5–10 mg/day) of amlodipine provided a consistent antihypertensive effect, reducing the sitting diastolic (–13.8% change) and systolic (–13.0% change) blood pressures by clinically meaningful and statistically significant (p = 0.0001, n = 33) amounts. Amlodipine had no effect on heart rate. A significant regression in LVH was seen (left ventricular mass index reduced from 169.0 [SD 30.7] g/m2 to 140.6 [SD 19.6] g/m2, p < 0.01, n = 12). There was also a significant reduction in total peripheral resistance and improvement in left ventricular diastolic filling (E/A ratio increased from 0.86 pre-treatment to 1.03 post-treatment, p = 0.038, n = 12). These results are consistent with other studies in showing that a relatively short treatment regimen with amlodipine is associated with a significant reduction in left ventricular mass index.
Cerebral Ischemia: From Animal Studies to Clinical Practice. Should the Methods Be Reviewed?
Authors: de Leciñana María Alonso , Díez-Tejedor Exuperio , Carceller Fernando , Roda Jose María
Published: April 2003

The development of experimental models of focal cerebral ischemia has allowed for a better knowledge of its pathophysiology and for testing therapeutic strategies. However, most neuroprotective substances giving favorable results in these models have later not been shown to be clinically effective. This could be explained by several reasons. First, the homogeneity obtained in animal models in order to achieve results is not seen in clinical practice in humans, in whom a given pathological condition may show a high variability depending on several parameters. This makes it difficult to achieve groups of patients sufficiently large and homogeneous to obtain valid conclusions in the clinical trials. The lack of agreement between the experimental studies and the clinical practice can also be explained by other reasons, such as the methods of the experimental model itself; by the fact that the methods to assess results in these models are not comparable to those used in clinical practice; by pathophysiological differences between experimental animals and man, and even by the fact that the substances tested have different pharmacological properties in the different species. These disadvantages must not invalidate preclinical neuroprotection studies. Rather, the knowledge of the reasons for divergences with the clinical situation can help to optimize experimental models so that both become actually comparable, and the laboratory results can be confirmed by clinical studies.
Benefit of ADP Receptor Antagonists in Atherothrombotic Patients: New Evidence
Authors: Bogousslavsky Julien
Published: April 2003

In the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial, clopidogrel showed a statistically significant superiority over aspirin in the prevention of ischaemic stroke, myocardial infarction and vascular death in patients with symptomatic atherosclerosis. More recently, post-hoc analysis of the data also showed that repeat hospitalization for ischaemic or bleeding events was decreased with clopidogrel compared with aspirin. Complementary analyses show that the benefit of clopidogrel over aspirin is amplified in a large population at very high risk of further atherothrombotic events (diabetics, patients with high cholesterol, and patients with previous manifestations of atherothrombosis). A potential clinically useful advantage of clopidogrel is its low propensity for adverse interaction with angiotensin-converting enzyme (ACE) inhibitors, contrary to what may be seen with aspirin, as observed in a post-hoc CAPRIE analysis. The putative aspirin-ACE inhibitor interaction is being tested prospectively in the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial – a randomized comparison of warfarin, clopidogrel and aspirin in patients with chronic heart failure. The good gastrointestinal tolerance of clopidogrel seen in CAPRIE has been further demonstrated in a study in healthy volunteers where there was a markedly lower gastroduodenal erosion score after 8 days’ administration of clopidogrel 75 mg/day compared with aspirin 325 mg/day (p < 0.001). Following the positive findings obtained with clopidogrel plus aspirin in the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS) trial, other studies of clopidogrel plus aspirin have been initiated or are planned. These include Management of Atherothrombosis with Clopidogrel in High-risk patients (MATCH), a randomized comparison of clopidogrel plus aspirin versus clopidogrel in high-risk patients with recent stroke or transient ischaemic attack.
Gastrointestinal Cancer Refractory to Chemotherapy: A Role for Octreotide?
Authors: Cascinu Stefano , Catalano Vincenzo , Giordani Paolo , Baldelli Anna Maria , Agostinelli Romina , Catalano Giuseppina
Published: April 2003

Although octreotide has been shown to inhibit the growth of gastrointestinal (GI) tumors in vitro and in vivo, preliminary clinical trials have reported disappointing results for this somatostatin analog in patients with GI cancers. The results of these trials probably reflect the difficulty in assessing the therapeutic potential of an agent such as octreotide in GI cancers. Thus, it is possible that treatment with octreotide could be useful in the stabilization of disease if it is associated with an improvement in survival. On the basis of these considerations five randomized trials were carried out to evaluate the therapeutic potential in patients with GI cancers. Four trials (one in patients with colorectal carcinoma and three in patients with carcinoma of the pancreas) did not show any advantage of octreotide in untreated patients; in contrast, one trial reported that octreotide prolonged survival in patients with GI cancers refractory to chemotherapy. Some clinical features of the latter study (treatment with chemotherapy, different schedules) may explain these conflicting results. Although data from randomized trials suggest that octreotide is not effective in untreated asymptomatic advanced GI cancer patients, further studies are warranted to assess the efficacy of octreotide in chemotherapy refractory patients in order to clarify the impact of octreotide in terms of not only survival but also on the patients’ quality of life.
Anti-Fibrillin-1 Autoantibodies in Systemic Sclerosis Are GM and KM Allotype-Restricted
Authors: Pandey Janardan P. , Page Grier P. , Silver Richard M. , LeRoy E. Carwile , Bona Constantin A.
Published: April 2003

GM and KM allotypes – genetic markers of immunoglobulin (Ig) γ and ĸ chains, respectively – have been shown to play an important role in genetic predisposition to some autoimmune diseases. To determine their role in susceptibility to systemic sclerosis (SSc; scleroderma) and in the generation of anti-fibrillin-1 antibodies, 148 SSc patients and 191 controls were typed for several GM and KM allotypes by a standard hemagglutination inhibition method. IgG and IgM antibodies to fibrillin-1 were measured by radioimmunoassay. GM and KM phenotypes were not significantly associated with SSc. However, these determinants significantly influenced the production of anti-fibrillin-1 antibodies in SSc patients. In Caucasians, GM1,3,17 23 5,13,21 and GM3 23 5,13 phenotypes were associated with the presence and absence of IgG autoantibodies, respectively. The production of these autoantibodies was also associated with KM allotypes, KM1,3 heterozygosity being associated with response and homozygosity for the KM3 allele with nonresponse to fibrillin-1. In African-Americans, the KM1 homozygotes were associated with the absence of anti-fibrillin-1 antibodies and the KM3 homozygotes with the presence of autoantibodies. In this ethnic group, the GM1,17 5,13 phenotype was associated with the absence of IgM autoantibodies. This represents the first description of genetic control of autoimmunity to fibrillin-1 in scleroderma.
Analysis of the Sequence Polymorphism within Class II Transactivator Gene Promoters
Authors: Janitz Michal , Reiners-Schramm Luzie , Muhlethaler-Mottet Annick , Rosowski Mark , Lauster Roland
Published: April 2003

The class II transactivator is a major transcriptional factor acting on the promoters of MHC class II genes. Transcription of the CIITA gene is driven by four alternative promoters, which exhibit cell-type-specific activity. The CIITA promoter III (PIII) is constitutively active in B cells, whereas promoter IV (PIV) becomes activated upon interferon-γ activation. The aim of this study was to investigate whether these two promoters exhibit a sequence variability like the MHC class II promoters do. We isolated PIII and PIV fragments from healthy individuals and rheumatoid arthritis patients and screened them for sequence polymorphisms. Single base pair substitutions within the CIITA PIV were found in 9% of the individuals analyzed. The majority of the substitutions were located upstream of the known cis-acting elements of the promoter. PIII was non-polymorphic. To evaluate the functional relevance of the detected polymorphism we cloned variable PIV upstream of the luciferase reporter gene. Such prepared constructs were transfected into monocytes, melanoma and HeLa cells, which were subsequently stimulated with interferon-γ. The analysis of promoter activities did not reveal significant differences in all three cell types. We conclude that the level of CIITA expression does not vary within the population. Thus the differences in the level of MHC class II expression, which are observed between individuals, stem for the polymorphisms of the MHC class II promoters themselves.
Nomenclature of the Human Immunoglobulin Lambda (IGL) Genes
Authors: Lefranc Marie-Paule
Published: April 2003

‘Nomenclature of the Human Immunoglobulin Lambda (IGL) Genes’, the 18th report of the ‘IMGT Locus in Focus’ section, provides the first complete list of all the human IGL genes. The total number of human IGL genes per haploid genome is 87–96 (93–102 if the orphons are included), of which 37–43 genes are functional. IMGT/Human Genome Organization (HUGO) gene names and definitions of the human IGL genes on chromosome 22q11.2 and IGL orphons on chromosomes 8 and 22 are provided with the gene functionality and the number of alleles, according to the rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences and with the accession ID of the Genome Database GDB and NCBI LocusLink databases, in which all the IMGT human IGL genes have been entered. The tables are available at the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.
Clinical Relevance and Treatment Possibilities of Bipolar Rapid Cycling
Authors: Grunze H. , Amann B. , Dittmann S. , Walden J.
Published: April 2003

Bipolar rapid cycling (RC) is defined as 4 or more affective episodes within 1 year. It has been postulated that RC is related to a poor response to lithium, to the same extent as mixed episodes or other atypical symptoms of the illness. This article reviews the current status of alternative pharmacological or otherwise supportive therapies of RC. Biological parameters and characteristics of the illness associated with RC like gender prevalence in women, hyperthyroidism, catecholamine-O-methyltransferase allele, the influence of sleep, different subtypes of bipolar disorder and the risk of antidepressant-induced cycling will be discussed in detail.
Depressive Symptoms and Academic Self-Image in Adolescence
Authors: Masi Gabriele , Tomaiuolo Francesco , Sbrana Barbara , Poli Paola , Baracchini Graziella , Pruneti Carlo A. , Favilla Letizia , Floriani Chiara , Marcheschi Mara
Published: April 2003

The aim of this paper was to specifically analyse the relationship between the different components of academic self-image, defined as the way adolescents represent themselves as students, and self-reported depressive symptoms, assessed with the Children’s Depression Inventory (CDI), in a non-clinical sample of 298 adolescents. We considered both adolescents’ beliefs about their own cognitive functioning in academic performance and beliefs about their emotional attitude in achievement situations. Our data indicate that the pattern of correlation between emotional beliefs about schooling and learning are significantly related to CDI scores, but this correlation is not evident for the cognitive beliefs. This pattern of correlation is affected by actual school functioning, because correlation between CDI and beliefs is much more significant in subjects without school failure. Differences between gender in CDI scores, beliefs about schooling and learning, and pattern of correlation are considered. These results can enable to focus supporting psychological interventions on more specific targets.
Immediate and Delayed Memory Performance in Schizophrenia Spectrum Patients: Use of Matched Tasks
Authors: Calev Avraham
Published: April 2003

Rapid forgetting has been observed in long-term schizophrenic patients in the past. In this study, the rate of forgetting was assessed in short-term schizophrenic, schizophreniform and schizoaffective patients who had positive symptoms in the past, and in schizophreniform patients who never had positive symptoms. Four groups of patients representing these distinctions and a group of normal controls were assessed using immediate and delayed recall tasks, while controlling for effects of discriminating power of tasks, using matched-task methodology. The results showed that all schizophrenia spectrum patients with positive symptoms showed rapid forgetting as compared to schizophreniform patients with negative symptoms and normal controls. It is concluded that better immediate than delayed recall characterizes schizophrenia spectrum patients who have had positive symptoms. However, schizophrenia spectrum patients with negative symptoms may be qualitatively different from patients with positive symptoms in showing a slower rate of forgetting. The results support the hypothesis that there is at least one and possibly two brain dysfunctions affecting memory in schizophrenia.
Stability of DSM-III-R Diagnoses: Study of a Case Register
Authors: Huguelet Philippe , Schneider El Gueddari Nora , Glauser Daniel
Published: April 2003

We studied the diagnostic stability and the factors associated with it in 1,443 psychiatric patients with multiple admissions for a period of 45 months. We successively considered the whole population, the psychotic and then the schizophrenic patients. Demographic and DSM-III-R diagnostic information was collected on a computerized database. During the observation period, 1,443 patients were hospitalized twice or more. Diagnostic stability ranged from 34 to 86%. Psychotic disorder was the most stable, whereas adjustment and anxiety disorders were the least stable. Among schizophrenic patients, higher stability appeared for residual and disorganized types (83 and 71%, respectively). Statistical analysis did not show any variable associated with change, apart from the diagnoses themselves. The reasons that could explain changes are discussed, as well as the clinical consequences of these shifts.
Relationship between Subjective Cognitive Symptoms and Frontal Executive Abilities in Chronic Schizophrenic Outpatients
Authors: Zanello Adriano , Huguelet Philippe
Published: April 2003

The aim of this study was to investigate the relationship between executive abilities and subjective basic symptoms in a group of outpatients with schizophrenia. Fifty patients underwent a neuropsychological testing battery. Basic symptoms were assessed using the Frankfurt Complaint Questionnaire. Using Pearson’s product-moment correlations or partial correlations calculated by regression procedure, cognitive performance was not related to subjective experience. When patients were divided into two groups, with and without ‘hypofrontality’, as assessed by the neuropsychological testing, we did not find any significant difference in basic symptoms rating. Thus, it is likely that basic symptoms and neurocognitive functioning are unrelated in schizophrenic outpatients, probably because the expression of subjective experience and cognitive impairment is less pronounced than in inpatients. Also, subjective self-perceived basic symptoms and neurocognitive functioning may be unrelated, because these concepts are based on different theoretical backgrounds.
Charles Bonnet Syndrome with Auditory Hallucinations: A Diagnostic Dilemma
Authors: Hori Hiroko , Terao Takeshi , Nakamura Jun
Published: April 2003

Charles Bonnet syndrome (CBS) appears to be commoner in elderly people than was previously thought. Nonetheless, as yet, no firm diagnostic criteria have been established for CBS, leaving the need for well-defined diagnostic criteria describing this syndrome unfulfilled. Two recently proposed diagnostic criteria for CBS insist on an absence of hallucinations in modalities other than visual. However, we experienced 2 cases suffering from probable CBS who experienced auditory hallucinations. In this report, we recommend that even if CBS coexists with other hallucinations, we should not exclude CBS as a probable diagnosis when the patients recognize their hallucinations as unreal. We believe that this modification of CBS diagnostic criteria will contribute to psychiatric epidemiology by correcting the current underestimation of CBS prevalence.
Melancholia as a Desynchronization: Towards a Psychopathology of Interpersonal Time
Authors: Fuchs Thomas
Published: April 2003

Starting from psychopathological analyses of lived time in melancholia, the paper first examines the continuous processes of synchronization effective in biological as well as social life. These processes enable the individual to compensate for states of shortage, to adapt to changed circumstances, finish with past events and reconnect with the present. Examples of such resynchronizing processes are regeneration, sleep, dreaming, forgetting, remorse or grief. Melancholia is then interpreted as the result of a desynchronization, i.e. an uncoupling in the temporal relation of organism and environment, or of individual and society. With the processes of resynchronization failing, the person falls out of common environmental time. This conception allows a parallel to be drawn between chronobiological and psychosocial results of research. Moreover, it offers the possibility to understand not only the psychopathology, but also the triggering of melancholic episodes on the basis of a disturbance of time. Consequences for a ‘resynchronizing therapy’ are outlined.
Major Depression and Somatic Symptoms in a Mind/Body Medicine Clinic
Authors: Nakao Mutsuhiro , Yamanaka Gaku , Kuboki Tomifusa
Published: April 2003

This study examined the prevalence of somatic symptoms and psychiatric characteristics of major depression in a Japanese psychosomatic outpatient clinic. A total of 2,215 outpatients referred for mind/body complaints were assessed by DSM-III-R or DSM-IV. Somatic symptoms were rated using the Cornell Medical Index Questionnaire. Ninety-one outpatients (4.1%) were diagnosed with major depression. Prevalence of fatigue (86%), insomnia (79%), nausea/vomiting (50%), and back pain (36%) as well as degrees of psychosocial stress (DSM-III-R axis IV) were higher (all p < 0.05) and scores of global assessment of psychosocial functioning (DSM-III-R/DSM-IV axis V) were lower (p < 0.001) in the major depressive patients compared to the remaining outpatients. Among the major depressive patients, the total number of somatic symptoms was larger (p < 0.05) in patients with ‘severe’ major depressive episodes than in those with ‘mild’ depressive episodes. These findings suggest that the level of depression is closely linked to the reporting of somatic symptoms in a psychosomatic medicine population.
The Relationship between Dissociative Proneness and Alexithymia
Authors: Elzinga Bernet M. , Bermond Bob , van Dyck Richard
Published: April 2003

Background: Dissociative reactions and alexithymia are two strategies that have been put forward as coping mechanisms to alleviate painful emotions. It is the clinical impression that dissociation is related to certain alexithymia features. In line with the coping hypothesis, it was predicted that the relationship between dissociative tendencies and alexithymia would be partly mediated by current levels of stress and/or by past traumatic experiences. Furthermore, dissociation may also be related to enhanced fantasizing, although alexithymia has traditionally been associated with an incapacity to fantasize. Methods: Data were obtained from 833 nonclinical participants on dissociative tendencies, alexithymia, childhood abuse, current stress and socially desirable behavior. Correlation analyses followed by multiple regression were performed. Results: Dissociative tendencies appeared to be especially related to one alexithymic feature: a difficulty in identifying feelings. This relationship was partially mediated by levels of current stress. A history of trauma did not predict dissociation measures. Furthermore, highly dissociative participants were more fantasy prone than low-dissociative participants. Conclusions: The results of this study support the idea that in a nonclinical group dissociation may provide a way to cope with current stressful events, and that this is associated with a difficulty in identifying feelings. It is argued that two types of dissociation may exist, one trait-like type of dissociation that is associated with fantasy proneness and other related factors, and a trauma-related type of dissociation that is more apparent within the clinical range.
The Neurobiology of Tobacco Dependence: A Commentary
Authors: Balfour David J.K.
Published: April 2003

This commentary summarises the evidence that nicotine has the pharmacological properties of a psychostimulant drug of dependence. Behaviourally it serves as a reinforcer in self-administration experiments. Within the brain, acute nicotine stimulates the release of dopamine (DA) in the shell of the nucleus accumbens whereas repeated nicotine results in selective sensitization of its effects on DA overflow in the accumbal core. These effects are thought to play a central role in the acquisition of responding for nicotine and the development of associations between delivery of the drug and cues that predict its delivery. These responses, therefore, are thought to be pivotal to its ability to cause dependence. The commentary also emphasises the evidence that cigarette smoke provides a vehicle for nicotine that maximises its addictive potential since it delivers nicotine directly into the lungs and, within 10–15 s, to the brain. For habitual cigarette smokers, this process is repeated frequently and regularly and in the context of many other sensory cues within the smoke that potentially provide additional conditioned reinforcers. This, it is argued, explains the strong addiction that many smokers develop to tobacco smoke. Smoking cessation is also associated with the expression of an abstinence syndrome that can, largely, be attributed to nicotine withdrawal and is also likely to contribute to the maintenance of the habit. The commentary closes with a brief review of the pharmacological mechanisms that may contribute to the efficacy of nicotine replacement therapy and Zyban® (bupropion) as aids to smoking cessation.
Bronchiolitis obliterans in a Case of Juvenile Rheumatoid Arthritis Presented with Pneumomediastinum
Authors: Dikensoy Oner , Bayram Nazan , Bingol Ayfer , Filiz Ayten
Published: April 2003

We present a case of bronchiolitis obliterans associated with juvenile rheumatoid arthritis in whom pneumomediastinum was the presenting manifestation. Diagnosis of bronchiolitis obliterans was made on the basis of the clinical history, pulmonary function tests and high-resolution computerized tomography scan findings. Pneumomediastinum resolved in a few days following high-dose nasal oxygen. This case shows that bronchiolitis obliterans can occur in patients with juvenile rheumatoid arthritis. Complicating pneumomediastinum in such cases should be considered as an indication of underlying bronchiolitis obliterans.
Effects of Tibolone on Thromboxane B2 Levels in Postmenopausal Women
Authors: Canbaz Mukaddes , Vural Pervin , Akgül Cemil
Published: April 2003

This study was carried out in 16 premenopausal (control) and 24 postmenopausal women (study group) to investigate the effect of menopause and tibolone treatment (2.5 mg/day for 6 months) on plasma thromboxane B2 (TxB2), a well-known vasoconstrictor and stimulator of platelet aggregation. The TxB2 levels were measured using [125I] RIA kit. Statistical significance was analyzed by Student’s t test for paired and unpaired data, and Pearson’s correlation analysis. Plasma TxB2 concentrations of postmenopausal women were higher than those of premenopausal women. Tibolone treatment decreased plasma TxB2 in postmenopausal women. There was no correlation between TxB2 and blood pressure and heart rate. It was concluded that tibolone, decreasing the plasma concentrations of TxB2, might have beneficial effects on prostaglandin metabolism and thus reduce the risk of cardiovascular disease.