bluuebunny/crossref_metadata_2025 huggingface dataset:
Eotaxin Level in Induced Sputum Is Increased in Patients with Bronchial Asthma and in Smokers
Authors: Yamamoto Katsumaru , Takanashi Shingo , Hasegawa Yukihiro , Kanehira Yutaka , Kaizuka Mitsuaki , Okumura Ken
Published: January 2004

Background: Airway eosinophilia is one of the hallmarks of asthma. Eotaxin may play an important role in eosinophil recruitment. Objectives: To examine the relationship between eotaxin levels in the sputum and eosinophilic inflammation. Methods: The sputum was obtained from 11 non-smokers, 14 smokers and 13 asthmatic patients using a sputum induction method. Eotaxin and interleukin (IL)-5 levels in the sputum were determined by ELISA and immunocytochemical analysis. Results: Asthmatic patients had eosinophilia and smokers showed neutrophilia in their sputum. The eotaxin level in the sputum was significantly higher in smokers (median 412.5, range 91.1–872.2 pg/ml) and asthmatic patients (351.0, 185.0–928.0 pg/ml) compared with non-smokers (123.2, 0–369.0 pg/ml; both p < 0.05). IL-5 was detected in the sputum of 1 non-smoker, none of the smokers and 4 asthmatic patients. The percentage of eotaxin-positive cells was higher in smokers and asthmatic patients than in non-smokers, but the percentage of IL-5-positive cells was significantly higher only in asthmatic patients (p < 0.05). Conclusions: These findings suggest that the elevated eotaxin level in the sputum does not always accompany the increase in eosinophils, and cooperation with another cytokine such as IL-5 may be required for the recruitment of eosinophils.
Continuous Monitoring of Oxygen Consumption in Patients Undergoing Weaning from Mechanical Ventilation
Authors: Miwa Keisuke , Mitsuoka Masahiro , Takamori Shinzo , Hayashi Akihiro , Shirouzu Kazuo
Published: January 2004

Background: The extubation or discontinuation of mechanical ventilatory support (MVS) is only the final step in the weaning process, and an improvement in the efficiency of the weaning process is required for more successful extubation or discontinuation of MVS. Objective: To evaluate whether continuous monitoring of oxygen consumption (v̇O2) using the metabolic gas monitor is a useful predictor of failure to tolerate a weaning trial of reduced MVS. Method: Twenty adult patients meeting the criteria for weaning, who required MVS ≧7 days and who were previously deemed to have failed weaning by their attending physicians. A weaning trial was defined as a 30-min period during the strengthening training of our standardized weaning protocol. The average v̇O2, respiratory rate (RR), tidal volume (TV), minute ventilation (v̇E) and energy expenditure (EE) were recorded in respiratory muscles for a stable period of 20 min at rest and for the last 5 min of the trial. Subsequently, the oxygen cost of breathing (OCOB), the ratio of respiratory frequency to tidal volume (f/VT), ΔRR, ΔTV, Δv̇E, and ΔEE were calculated. Results: Two hundred and eight weaning trials, including 145 successful trials and 63 failed trials from 20 patients were evaluated. In nonparametric analysis, a statistical difference in OCOB, ΔRR, and ΔEE was found between successful and failed weaning trials, while no statistical differences were found for the other parameters. An OCOB <30% was the most accurate predictor of outcome of a weaning trial, and an f/VT <105 was the least accurate. In a multiple logistic analysis, the OCOB revealed the highest odds ratio among all parameters. Conclusions: Measuring the OCOB was clinically beneficial in avoiding the induction of an excessive movement load on the respiratory muscles. In patients treated with MVS, continuous monitoring of v̇O2 is a useful to predict success or failure of trials attempting to reduce MVS.
Diagnostic Yield of Transbronchial Histology Needle Aspiration in Patients with Mediastinal Lymph Node Enlargement
Authors: Hermens Frank H.W. , van Engelenburg Ton C.A. , Visser Frank J. , Thunnissen Frederik B.J.M. , Termeer René , Janssen Julius P.
Published: January 2004

Background: Transbronchial needle aspiration (TBNA) is a safe, minimally invasive technique to assess the mediastinal spread of lung cancer. Excellent results have been published by experts. However, little information is available about the diagnostic yield of TBNA with the histology needle in a non-expert center. Objectives: The aim of this study is to assess the diagnostic yield of histology TBNA in the workup of suspected lung cancer. Methods: In a non-university teaching hospital, TBNA data from patients diagnosed with lung cancer between June 1998 and July 2000 were analyzed retrospectively. TBNA had been performed by six different bronchoscopists in patients eligible for surgery with accessible N2 and N3 lymph nodes on computed tomography of the chest during the workup of an undefined mass. Cytology and histology specimens were obtained with the same 19-gauge needle. TBNA results were considered to be diagnostic if cytologic or histologic examination revealed a malignant lesion or non-malignant lymphoid cells. However, TBNA outcome was called non-diagnostic if no representative cells were obtained. Results: From a group of 264 consecutive lung cancer patients, 106 (40%) patients were eligible for TBNA. In 79%, TBNA was diagnostic in cytology and/or histology specimens. Malignancy was demonstrated in 59% (63/106). In only 32/106 patients (30%), a histologic core of tissue could be sampled. In 87.5% of these patients (28/32), TBNA was diagnostic. For cytology only, this number was slightly lower (75%, 56/74). In 12 cases, diagnostic TBNA was verified by mediastinoscopy: these diagnoses were concordant. The sensitivity is 65% if all non-confirmed cases are considered false negative. Ten mediastinoscopies were avoided because TBNA demonstrated contralateral N2 (= N3) disease. The routine use of TBNA during bronchoscopy in suspected N2 disease is a cost-effective procedure, as the total additional costs of TBNA (9,540 EUR) were lower than the costs of 10 avoided mediastinoscopies (15,500 EUR). No complications were observed. Conclusion: The diagnostic yield of TBNA relied mainly on cytology specimens, despite the use of a histology needle. Representative histology specimens could only be obtained in 28/106 patients (26%). Since TBNA was performed in a general hospital by different bronchoscopists, this procedure is useful in the workup of lung cancer patients with enlarged lymph nodes.
Reduced Fatigue in Diaphragm Muscle of Merosin-Deficient dy/dy Dystrophic Mice
Authors: van Lunteren Erik , Moyer Michelle
Published: January 2004

Background: The muscular dystrophies comprise a heterogeneous group of disorders characterized by the absence of specific glycoproteins located at or near the cell membrane. The effects of dystrophin deficiency on diaphragm contractile function are well delineated, whereas the consequences of merosin (laminin α2) deficiency are not well defined. Objectives: Studies tested the hypothesis that genetic deficiency of merosin alters diaphragm fatigue resistance. Methods: Diaphragm contractile performance was tested in vitro using dy/dy dystrophic mice, which have the same biochemical defect as human classic congenital muscular dystrophies. Results: Twitch force/area was reduced by 46% in dy/dy dystrophic diaphragm, but isometric twitch kinetics were not altered. During repetitive 25-Hz stimulation, normal muscle demonstrated early force potentiation lasting 20 s. This was followed by a fast decline in force, with total force loss of ∼45% over 2 min. Force of dystrophic diaphragm also increased at the onset of stimulation, but remained elevated over baseline values for up to 70 s. Force decline thereafter was slow, amounting to ∼5% after 2 min and (in a subset of muscle samples stimulated for longer durations) ∼20% after 5 min. Relaxation rate of normal muscle slowed considerably during repetitive stimulation, whereas that of dy/dy dystrophic diaphragm remained constant. Conclusions: Merosin deficiency increases diaphragm force potentiation and reduces fatigue despite considerable muscle weakness. We speculate that the former may be important for maintaining ventilatory homeostasis in the merosin-deficient muscular dystrophies.
An Adult Case of Bochdalek Hernia Complicated with Hemothorax
Authors: Niwa Toshiaki , Nakamura Atsushi , Kato Takashi , Kutsuna Takeo , Tonegawa Ken , Kawai Atsuro , Itoh Makoto
Published: January 2004

A 53-year-old female with mild shock due to vomiting and abdominal pain visited the emergency room of our hospital. Chest X-ray on admission showed a large amount of left pleural effusion. Thoracentesis revealed hemorrhagic pleural effusion. An upper gastrointestinal series showed interruption of the upper gastric body, but the anal side was not visualized. Contrast X-ray examination of the thoracic cavity via the drainage tube demonstrated intrathoracic herniation through the diaphragm. These findings suggested gastric impaction in the foramen of Bochdalek, and thoracotomy was immediately performed. A black-colored stomach and greater omentum, suggesting necrotic changes, were observed in the thoracic cavity, and there was bleeding from the greater omentum. Resection of the necrotic organs and closure of the hernial orifice were followed by good recovery.
Coccidioidomycosis Mimicking Lung Cancer
Authors: Petrini Björn , Sköld C. Magnus , Bronner Ulf , Elmberger Göran
Published: January 2004

A 65-year-old female smoker was admitted due to haemoptysis and a pulmonary infiltrate in the right lower lung lobe. Tumour was suspected, but there was also a history of 2 years spent in Arizona, known to be endemic for the dimorphic fungus Coccidioides immitis. IgG antibodies and airway culture for C. immitis were negative, and surgery was performed for suspected lung cancer. No malignancy was detected at histopathological investigation, but typical coccidioidal spherulae were observed by silver stain. Coccidioidoma may be a differential diagnosis to malignant tumour in individuals visiting endemic areas.
Expression of Aquaporins in the Cochlea and Endolymphatic Sac of Guinea Pig
Authors: Zhong Shi-Xun , Liu Zhao-Hua
Published: January 2004

It has been shown that the aquaporin (AQP) family forms membrane pores selectively permeable for water and some small solutes such as glycerol and urea, and thus plays important roles in regulating the fluid in many organs involved in fluid transport such as kidney, lung and brain. The aims of the present study were to investigate the cellular localization and its significance of aquaporins (AQPs) in various subregions of the cochlea and endolymphatic sac of guinea pig. The expression patterns of AQP1, 2, 3 and 4 were immunolabeled with the specific polyclonal rabbit antibodies against the rat AQP1, 2, 3 and 4. Our immunohistochemical examination showed that in the cochlea, AQP1, 3 and 4 were widely distributed in various locations including stria vascularis, spiral ligament, the organ of Corti and spiral ganglion in the similar patterns except that AQP3 in the stria vascularis was lightly weaker than AQP1 and AQP4. AQP2 was labeled only in Reissner’s membrane. In the endolymphatic sac, AQP1, AQP3 and AQP4 were strongly expressed in the epithelial cells and subepithelial cells similarly with the exception that AQP3 was lightly weaker than AQP1 and AQP4. No AQP2 immunoreactivity was detected in the endolymphatic sac. Theses results suggest that different members of the AQP family in the labyrinth may work in concert to regulate endolymph and to maintain homeostasis in the inner ear.
Ancient Schwannoma of the True Vocal Cord
Authors: Tzagkaroulakis A. , Stivaktakis J. , Nikolopoulos T. , Davilis D. , Zervoudakis D.
Published: January 2004

Ancient schwannomas are benign nerve origin neoplasms that may cause difficulties in the differential diagnosis with other benign or malignant tumors. They usually occur in the head and neck region (epiglottis, arytenoepiglottic fold, false vocal cord). Involvement of the true vocal cords is extremely rare (less than 10 cases have ever been reported in the English literature – mainly in women). The present case describes a 27-year-old man who presented with a 2-year history of hoarseness. Indirect laryngoscopy showed a small polypoid mass in the middle of the left vocal cord. During microlaryngoscopy under general anesthesia, the polypoidal mass was removed and sent for histology. Immunohistochemistry and detailed histological examination revealed an ancient schwannoma. The present case in a male patient aims to increase awareness of the possibility that these tumors may also exist in the true vocal cords mimicking other more frequent lesions.
Treatment of Spinal Involvement in Neuroblastoma Patients
Authors: Sandberg David I. , Bilsky Mark H. , Kushner Brian H. , Souweidane Mark M. , Kramer Kim , Laquaglia Michael P. , Panageas Katherine S. , Cheung Nai-Kong V.
Published: January 2004

Introduction: Considerable controversy exists regarding the appropriate management of spinal involvement in neuroblastoma (NB) patients. We review a large group of such patients and offer treatment recommendations. Methods: Forty-six patients with epidural and/or neural foraminal involvement treated between 1987 and 1998 were staged according to the International NB Staging System (INSS) and classified as high-risk (INSS stage 4; n = 31) or low-risk (INSS stage <4; n = 15). Of 13 high- risk patients with normal neurologic examinations and no radiographic high-grade spinal cord compression (HGSCC), 12 were treated initially with chemotherapy, and only 1 demonstrated neurologic deterioration. HGSCC was present in 18 patients with high-risk NB; 7 of 10 (70%) treated initially with chemotherapy and 6 of 6 (100%) managed initially with operation improved or remained stable. All 9 low-risk patients with normal neurologic examinations and no HGSCC remained neurologically intact following operations (n = 7) or chemotherapy (n = 2). All 4 low-risk patients with HGSCC treated with operations improved or remained stable, and 0 of 2 (0%) low-risk patients treated initially with chemotherapy remained stable. Spinal deformities occurred in 2 of 16 patients (12.5%) treated nonoperatively and in 9 of 30 (30.0%) who underwent operations. Conclusions: High-risk NB patients with spinal involvement but normal neurologic examinations should be offered chemotherapy. High-risk patients with HGSCC may respond to chemotherapy, but a small percentage will require operations for progressive neurologic deficits. Chemotherapy may be avoided in low-risk patients who are offered potentially curative operations. Patients treated with operations for epidural disease are at high risk of subsequently developing spinal deformity.
Molecular Biology of Medulloblastoma Therapy
Authors: Pomeroy Scott L. , Sturla Lisa-Marie
Published: January 2004

Molecular biological studies have created a new understanding of medulloblastomas, revealing key cell signaling pathways that promote tumor growth. These studies have identified molecular markers that can serve as prognostic indicators and which will provide therapeutic targets in the very near future. In contrast to conventional histological techniques, molecular biological methods are designed to detect highly unstable molecules degraded by conventional tissue collection and fixation protocols. Consequently, a new approach to tissue collection is required for molecular analysis as we enter the next era of brain tumor therapy.
Spontaneous Intracerebral Hemorrhage and Multiple Infarction in Williams-Beuren Syndrome
Authors: Kalbhenn T. , Neumann L.M. , Lanksch W.R. , Haberl H.
Published: January 2004

A 7-year-old boy diagnosed with Williams-Beuren syndrome was admitted for spontaneous right hemispheric intracerebral hemorrhage. Cerebral angiography did not reveal any source of bleeding. After a short period of clinical improvement under conservative treatment, the boy deteriorated rapidly. CT showed the beginning of a complete infarction of both hemispheres. Operative evacuation of the bleeding and bilateral osteoclastic decompression had no perceptible influence on the clinical course. To the present day, the boy has remained in a vegetative state. Reports in the literature suggest that Williams syndrome with cerebral infarction is associated with a markedly poorer prognosis when there is additional intracerebral bleeding.
Vesicourethral Anastomotic Strictures after Radical Retropubic Prostatectomy: The Experience of a Single Institution
Authors: Kostakopoulos Athanasios , Argiropoulos Vassilios , Protogerou Vassilios , Tekerlekis Panagiotis , Melekos Michalis
Published: January 2004

Objective: Stricture of the vesicourethral anastomosis remains a well-documented complication after radical retropubic prostatectomy. Materials and Methods: We performed a retrospective study of 294 patients with prostate cancer who underwent radical retropubic prostatectomy. Possible correlations between anastomotic stricture formation, tumor stage, positive surgical margins, number of anastomotic sutures, bladder neck preservation, urine leakage, previous prostate surgery and/or intraoperative blood loss were examined. Results: An anastomotic stricture was found in 18 cases (6%) requiring some kind of treatment. In 10 patients (56%), the bladder neck stricture occurred within 3 months after surgery, in 5 (28%) at 4–12 months after surgery and in 3 (16%) more than 12 months after surgery. Intraoperative blood loss (>1,000 ml) was found to be significantly correlated with urinary leakage (p < 0.001) and both correlated with anastomotic stricture formation (p < 0.005). Conclusion: Excessive intraoperative blood loss (>1,000 ml) and urine leakage was found to be significantly correlated to the formation of anastomotic stricture following radical retropubic prostatectomy.
The Band Electrode: Ongoing Experience with a Novel Turp Loop to Improve Hemostasis in 265 Patients
Authors: Reich Oliver , Faul Peter
Published: January 2004

Introduction: Intraoperative bleeding, one of the major complications of conventional transurethral resection of the prostate (TURP), has led to a search for various alternative methods of tissue ablation in patients with benign prostatic hyperplasia. In 1996, we introduced the newly designed Band Electrode, which combines a high degree of resection efficiency with a better hemostasis. Material and Methods: 265 consecutive patients with prostatism underwent TURP with the Band Electrode. This modified loop electrode does not consist of a thin wire but is rather a flat metal band with a width of 1.2 mm. International prostate symptom score (IPSS), Life Quality Index (L), peak urine flow and postvoid residual urine were evaluated pre- and postoperatively. Additionally, electrical parameters have been recorded with a specially designed high-frequency generator. Results: Median IPSS decreased from 23 preoperatively to 8 and 9 at 12 (n = 194) and 24 months (n = 172), respectively (p < 0.001). Life Quality Index (L) dropped from 4 to 2 and 2, respectively (p < 0.001). Peak urine flow increased from 8.2 ml/s to 18.2 (at postoperative day 3), 17.8 and 17.4 ml/s, respectively (p < 0.001). Median postvoid residual urine decreased from 77 to 15, 22 and 21 ml, respectively (p < 0.001). Resected tissue mass averaged 25 (8–102) g, resection time was 36.5 (18–82) min. Indwelling catheters were removed 32 (24–72) h postoperatively. None of the patients required blood transfusions or showed signs of a TUR syndrome. Despite a 1.3 times higher power need, the total energy application in vivo was comparable to conventional TURP. Conclusions: This simple exchange of active electrodes leads to a superior hemostasis and thus safety in TURP. Resection speed, tissue ablation and total energy need remain identical.
Percutaneous Pneumatic and Laser Lithotripsy as a Possible Therapeutic Strategy for Bilateral Large Calculi in a Horseshoe Kidney
Authors: Seto Chikashi , Satoh Kohji , Morishita Hiroshi , Komatsu Kazuto , Namiki Mikio
Published: January 2004

This report concerns a case of bilateral large calculi in a horseshoe kidney. Three sessions of percutaneous nephrolithotripsy for the calculi successfully disintegrated and removed the fragments without any complications. For complete stone removal we used pneumatic and laser lithotriptors which were passed, respectively, through a rigid nephroscope and a flexible pyeloscope. It is emphasized that the selection of the most suitable lithotriptor by taking their various features into account is important in endoscopic surgery for calculi which are likely to recur such as stones accompanied by infection or for anatomically anomalous kidneys such as horseshoe kidneys.
Myofibroblastic Inflammatory Tumors of the Bladder
Authors: Antonelli Alessandro , Tanello Marco , Zanotelli Tiziano , Frego Ezio , Tardanico Regina , Cosciani Cunico Sergio
Published: January 2004

Bladder myofibroblastic inflammatory tumors are rare benign proliferative lesions that can simulate both urothelial and connective tissue malign neoplasms, making a preoperative diagnosis nearly impossible. Conservative treatment appears to be curative, even though local recurrences have been reported, and so malignancy should be rouled out above all by means of an accurate follow-up. Two cases are described, 1 of which with the longest follow-up period reported so far (8 years).
Primary Non-Hodgkin’s Lymphoma of Urinary Bladder
Authors: Khaitan A. , Gupta N.P. , Goel A. , Safaya R. , Kumar L.
Published: January 2004

Primary extranodal lymphoma of the urinary bladder is a rare disorder that is diagnosed on the basis of histopathology and immunostaining. We report a case of diffuse B cell primary lymphoma of the urinary bladder and review the literature.
Granulosa Cell Tumor of the Contralateral Testis in a Man with a History of Cryptorchism
Authors: Guzzo Thomas , Gerstein Matthew , Mydlo Jack H.
Published: January 2004

We report a case of adult-type testicular granulosa cell tumor in a 33-year-old man with a history of cryptorchism of the contralateral testis as well as Crohn’s disease. The tumor was identified as a 1 × 1 × 1 cm mass on baseline ultrasound evaluation. CT evaluation of the patient revealed extensive mesenteric adenopathy, most likely secondary to his history of Crohn’s disease.
Colon Perforation after Percutaneous Nephrolithotomy Revisited
Authors: Noor Buchholz Niels-Peter
Published: January 2004

Objective was to remind the reader of a rare but nevertheless serious complication of percutaneous nephrolithotomy (PCNL) which is further complicated by the lack of pre-operative and intra-operative warning signs. A patient underwent an apparently normal PCNL. Only just before removal of the nephrostomy tube, signs of colonic perforation became apparent. In spite of no clinical signs of sepsis or shock, the patient developed severe complications during and after the ensuing surgery. Every urologist, surgeon, or radiologist performing PCNL must be aware of the risk of an aberrant retrorenal colon loop, the perforation of which will most likely not be noticed during the procedure. Abdominal symptoms of a more general nature must lead to the active exclusion of this complication. If a CT scan has been performed pre-operatively for whatever reason, attention should be paid to the juxtarenal colon. Although a CT scan can exclude a retrorenal colon, such a procedure would exceed the needs and limitations of routine evaluation in all patients for PCNL.
Recent Clinical Trial Results with Antiplatelet Therapy: Implications in Stroke Prevention
Authors: Teal Philip A.
Published: January 2004

Dual antiplatelet therapy that inhibits more than one pathway of platelet activation is appealing and biologically rational. The CURE study evaluated the efficacy and safety of clopidogrel on top of acetylsalicylic acid (ASA) versus standard therapy (including ASA) in over 12,000 patients with unstable angina or non-ST-segment elevation myocardial infarction (MI). Clopidogrel in combination with ASA reduced the relative risk of the combined atherothrombotic endpoint of cardiovascular death, MI or stroke by 20% (95% CI 0.72–0.90; p < 0.001) and the absolute risk of this composite endpoint by 2.1%. While the study was not powered or designed to demonstrate a reduction in stroke, there was a 14% reduction in stroke risk (p > 0.05). Dual antiplatelet therapy was associated with an acceptable 1% increase in the incidence of major bleeding events (p = 0.001). PCI-CURE, a prespecified substudy of patients who underwent percutaneous coronary intervention (PCI) during CURE, confirmed the early and sustained benefits of clopidogrel therapy seen in the overall CURE study. CREDO was a randomized, double-blind, placebo-controlled trial in more than 2,100 patients that evaluated the continuation of clopidogrel on top of standard therapy including ASA for 12 months after PCI, and the benefit of a preprocedural clopidogrel loading dose. The long-term results at 1 year showed that there was a 27% reduction in the risk of stroke, MI or death with long-term clopidogrel therapy (p = 0.02). There was a consistent benefit of extended clopidogrel therapy for each component of the composite endpoint, with a 25.1% relative risk reduction for all-cause stroke. In patients who received clopidogrel ≧6 h before PCI, there was a 39% reduction in the risk of death, MI or urgent target-vessel revascularization at 28 days (p = 0.051). These data suggest important implications in the future for the use of an early loading dose of clopidogrel in patients undergoing carotid stenting and, if proven in current or future trials, the use of a loading dose followed by long-term continuation of clopidogrel in other high-risk atherothrombotic patients such as those with transient ischaemic attack or ischaemic stroke.
Ongoing and Planned Trials of Antiplatelet Therapy in the Acute and Long-Term Management of Patients with Ischaemic Brain Syndromes: Setting a New Standard of Care
Authors: Hankey Graeme J.
Published: January 2004

Among high vascular risk patients, acetylsalicylic acid (ASA) reduces the relative risk of serious vascular events by about one fifth. However, because ASA fails to prevent four fifths of serious vascular events, more effective, yet equally safe and affordable, antiplatelet regimens are desired. Compared with ASA, clopidogrel alone reduces the odds of serious vascular events by about 10%, and the combination of dipyridamole and ASA reduces the odds of serious vascular events by about 6%. Combining ASA with an orally administered platelet glycoprotein (GP) IIb/IIIa blocker is not effective, and indeed more hazardous than ASA alone. Among patients with non-ST-segment acute coronary syndromes (ACS), the addition of an intravenously administered GP IIb/IIIa receptor antagonist to ASA reduces the risk of vascular events by about 10% compared with ASA, and the addition of clopidogrel to ASA reduces the risk of vascular events by 20% compared with ASA alone. Among patients undergoing percutaneous coronary intervention (PCI), both the addition of an intravenously administered GP IIb/IIIa receptor antagonist to ASA, and the addition of clopidogrel to ASA reduce the risk of vascular events by 30% compared with ASA alone. The greater efficacy of the combinations of ASA with clopidogrel, and ASA with an intravenously administered GP IIb/IIIa receptor antagonist, in patients with ACS and those undergoing PCI has fostered several ongoing and planned trials of these regimens in the acute and long-term management of patients with ischaemic brain syndromes. The combination of ASA and clopidogrel is being compared with ASA alone within 12 h of onset of symptoms of TIA in two trials (FASTER, ATARI), and the use of an intravenously administered GP IIb/IIIa receptor antagonist is being compared with placebo within 6 h of onset of acute ischaemic stroke in two trials (AbESST, AbESST-2). Six trials are assessing the combination of clopidogrel and ASA in the long-term management of patients with ischaemic brain syndromes due to atherothrombosis (MATCH, CHARISMA, ARCH, CARESS, SPS3) or atrial fibrillation (ACTIVE). The MATCH trial of clopidogrel and ASA versus clopidogrel alone in patients with recent TIA or ischaemic stroke is the first which is likely to report its results – in mid 2004. The combination of dipyridamole and ASA is being compared with ASA in the ESPRIT trial and with the combination of clopidogrel and ASA in the planned PRoFESS trial. These ongoing and planned clinical trials of antiplatelet therapy promise to further define the role of combination antiplatelet therapy in the acute and long-term management of patients with ischaemic brain syndromes.
Advances in Penumbra Imaging with MR
Authors: Davis Stephen M. , Donnan Geoffrey A.
Published: January 2004

The concept of the ischaemic penumbra as critically hypoperfused and functionally impaired, but potentially viable brain, was introduced over 25 years ago. Recent studies have used a combination of perfusion-weighted magnetic resonance imaging (PWI) and diffusion-weighted imaging (DWI) to delineate the putative penumbra. PWI provides semiquantitative cerebral blood flow imaging and DWI is an index of the largely irreversible ischaemic core. PWI > DWI mismatch is an operational definition of the penumbra that was introduced in the late 1990s. This definition has been modified in recent years with the recognition that the PWI boundary includes a region of benign oligaemia and that a portion of the DWI core is potentially salvageable with rapid reperfusion. An MRI penumbral signature is present in the majority of patients within 6 h of stroke onset, often but not invariably associated with proximal arterial occlusion on magnetic resonance angiography, and is strictly time dependent. It has been postulated that penumbral imaging using MRI can provide a physiological ‘tissue clock’ and be used to predict benefit from thrombolytic therapy beyond the established 3-hour window. This has been suggested by pilot studies, but confirmation will rely on ongoing, prospective, randomized trials. The presence and extent of the penumbra may also predict the opportunity for tissue salvage with neuroprotection strategies. DWI and PWI parameters are being used in proof-of-principle stroke trials. Such trials can be performed with 100–200 patients randomized between treated and control groups and provide a biological signal of efficacy with only 10% of the sample size required for a Phase III study.
Association Study of Onset Age, Attempted Suicide, Aggressive Behavior, and Schizophrenia with a Serotonin 1B Receptor (A-161T) Genetic Polymorphism
Authors: Hong Chen-Jee , Pan Guo-Mei , Tsai Shih-Jen
Published: January 2004

Located on the presynaptic and postsynaptic terminals of serotonergic neurons, serotonin 1B receptors (5-HT1B) are involved in the modulation of serotonergic activity. The implications of 5-HT1B study of animal models of schizophrenia and antipsychotic activity involving defective sensory processes suggest that this receptor may be involved in the pathogenesis of schizophrenic disorders. In a population-based association study, we tested the hypothesis that the allelic variant, A-161T, of the 5-HT1B gene confers susceptibility to schizophrenic disorders and is associated with age of onset, aggressive behavior and attempted suicide. We genotyped the A-161T polymorphism in 110 patients with schizophrenic disorders and in 215 normal controls. No association was demonstrated between 5-HT1B genotype or allele frequencies and schizophrenic disorders, except for a trend for later age at disease onset in A/A homozygote schizophrenics in comparison with A/T heterozygote patients (p = 0.071). No significant difference in genotype distribution was determined comparing patients with and without aggressive behavior, and those with and without a history of suicide attempt. These findings suggest that the investigated 5-HT1B genetic polymorphism does not play a major role in the pathogenesis of schizophrenic disorders.
The Influence of Parturition on the Level and Synthesis of Sulfated and Free Neurosteroids in Rats
Authors: Maayan Rachel , Abou-Kaud Machmud , Strous Rael D. , Kaplan Boris , Fisch Benjamin , Shinnar Nili , Weizman Abraham
Published: January 2004

Alterations in neurosteroid levels may play a role in affective disorders including those related to changes in the levels of ovarian steroids. The effects of pregnancy and delivery on circulatory and brain levels of dehydroepiandrosterone (DHEA), pregnenolone (PN), their sulfate esters and the enzymatic activities of sulfatase and sulfotransferase were examined in rats. Our findings indicate an increase, not reflected in the brain cortex, in serum DHEA levels, at the end of pregnancy with a partial decrease following delivery. DHEA sulfate levels in the cortex and PN levels in both serum and cortex decreased following delivery with no changes in its sulfated form. Sulfatase levels were high both before and after delivery with no changes noted in sulfotransferase levels, compared to controls. We speculate that changes in the level or ratio of sulfated and free neurosteroids may play a role in postpartum behavioral disorders due to their antagonistic GABAA modulatory effect.
Self-Organizing Neural Network Analyses of Cardiac Data in Depression
Authors: Gaetz Michael , Iverson Grant L. , Rzempoluck Edward J. , Remick Ronald , McLean Peter , Linden Wolfgang
Published: January 2004

Objective: To determine if an unsupervised self-organizing neural network could create a clinically meaningful distinction of ‘depression’ versus ‘no depression’ based on cardiac time-series data. Design: A self-organizing map (SOM) was used to separate the time-series of 84 subjects into groups based on characteristics of the data alone. Materials and Methods: Analyses included natural log transformations and two types of filtering to enhance characteristics of the data as well as classifications of unprocessed data. A Pearson χ2 analysis was performed to determine if the SOM groups bore any relation to the binary clinical groups. Results: Overall correct SOM classifications ranged from 54 to 70.2% with two classifications being clinically meaningful. Conclusions: SOM classifications of cardiac time-series data with enhanced ultradian variations and cardiac data recorded around the interval when a person was in bed were useful in differentiating clinically meaningful subgroups with and without depression.
Association between Major Depressive Disorder and the –1438A/G Polymorphism of the Serotonin 2A Receptor Gene
Authors: Choi Myoung-Jin , Lee Heon-Jeong , Lee Hye-Jin , Ham Byung-Joo , Cha Ji-Hyun , Ryu Seung-Ho , Lee Min-Soo
Published: January 2004

This study investigated the possible effect of the –1438A/G single-nucleotide polymorphism in the promoter region of the serotonin 2A receptor (5-HTR2A) gene on major depressive disorder (MDD) in a Korean population. This polymorphism was analyzed in 189 patients with MDD and in 148 unrelated healthy controls using a case-control design, which revealed a significant difference in the genotype distributions (χ2 = 10.78, d.f. = 2, p = 0.005). The frequency of the –1438G allele was also much higher in MDD patients than in normal controls (χ2 = 7.20, p = 0.007; OR = 1.52, 95% CI 1.12–2.06). We also found significantly more carriers of the G allele (GG+AG genotypes) in MDD patients than in normal controls (χ2 = 10.18, p = 0.001; OR = 2.46, 95% CI 1.40–4.32). Our results support the hypothesis that the –1438A/G polymorphism of the promoter region of the 5-HTR2A gene is associated with MDD patients in a Korean population.
Neurobiological and Psychological Correlates of Suicidal Attempts and Thoughts of Death in Patients with Major Depression
Authors: Fountoulakis Konstantinos N. , Iacovides Apostolos , Fotiou Fotis , Nimatoudis John , Bascialla Fransesca , Ioannidou Christina , Kaprinis George , Bech Per
Published: January 2004

Suicide is a major problem for psychiatry. Depression is the most common mental disorder related to suicidal behavior. The present study aimed at investigating the relationship between the symptomatology related to death, dying, and suicide and neurobiological factors in depressed patients. Fifty patients aged 21–60 years suffering from major depression were investigated. Schedules for Clinical Assessment in Neuropsychiatry version 2.0 and the International Personality Disorder Examination were used to assist the clinical diagnosis. The psychometric assessment included the Hamilton Depression Rating Scale, the Hamilton Anxiety Scale, the 1965 and 1971 Newcastle Depression Diagnostic Scales, the Diagnostic Melancholia Scale, the General Assessment of Functioning Scale, and the Personality Deviance Scale. Psychophysiological methods included electro-oculogram, flash electroretinogram under photopic and scotopic conditions, and pattern-reversal visual evoked potentials. Biological markers included the 1-mg dexamethasone suppression test, the 30-mg dexfenfluramine challenge test, and brain 99mTc-HMPAO SPECT. Statistical analysis included one-, two-, and three-way Manova and Mancova and the Scheffé test as post hoc test. Patients without thoughts of death had higher self-confidence levels and less overdependency on others and intropunitiveness. The suicidal patients had a significantly prolonged pattern-reversal visual evoked potential latency in comparison with the other patients. The findings of this were related to the status of the patient at the time of the interview but not to his/her history. They also provide neurobiological data to support the need for a combined presence of self-directed aggression and a higher arousal level or disinhibition of self-directed aggressive thoughts in order for a patient to become suicidal. Further study is needed to test whether psychophysiological methods, which are noninvasive and easy to perform, are of value in the therapeutic planning and monitoring of responses.
Transoral Carotid Ultrasonography as a Diagnostic Aid in Patients with Severe Carotid Stenosis
Authors: Kishikawa Kazuhiro , Kamouchi Masahiro , Okada Yasushi , Inoue Tooru , Ibayashi Setsuro , Iida Mitsuo
Published: January 2004

Evaluation of the distal portion of the extracranial internal carotid artery (ICA) is indispensable for the judgment of whether surgical treatment for high-grade carotid stenosis is preferable or not. When the ICA is occluded or severely stenosed by an organic lesion along the long segment, carotid endarterectomy (CEA) is abandoned. On the other hand, CEA may be beneficial in patients with severe carotid stenosis which is situated only in the restricted lesion of the proximal portion of the ICA. Conventional carotid ultrasonography sometimes cannot provide sufficient information due to calcified plaque and/or high position of bifurcation. Newly developed transoral carotid ultrasonography (TOCU) enables us to observe the distal extracranial ICA and distinguish the differential diagnosis. We herein report 3 cases of severe carotid stenosis in which TOCU provided the necessary information obtained neither by conventional carotid ultrasonography nor by angiogram. We concluded that TOCU provides prerequisite information in certain cases in which CEA is considered.
How a Sequential Design Would Have Affected the GAIN International Study of Gavestinel in Stroke
Authors: Bolland Kim , Weeks Amanda , Whitehead John , Lees Kennedy R.
Published: January 2004

While planning the GAIN International Study of gavestinel in acute stroke, a sequential triangular test was proposed but not implemented. Before the trial commenced it was agreed to evaluate the sequential design retrospectively to evaluate the differences in the resulting analyses, trial durations and sample sizes in order to assess the potential of sequential procedures for future stroke trials. This paper presents four sequential reconstructions of the GAIN study made under various scenarios. For the data as observed, the sequential design would have reduced the trial sample size by 234 patients and shortened its duration by 3 or 4 months. Had the study not achieved a recruitment rate that far exceeded expectation, the advantages of the sequential design would have been much greater. Sequential designs appear to be an attractive option for trials in stroke.
Acetylsalicylic Acid and Acetaminophen to Combat Elevated Body Temperature in Acute Ischemic Stroke
Authors: Sulter Geert , Elting Jan Willem , Maurits Natasha , Luyckx Gert Jan , De Keyser Jacques
Published: January 2004

Background: Because elevated body temperature (BT) in acute ischemic stroke is associated with poor outcome, it is currently recommended to maintain normothermia with antipyretics. Whether this can be achieved by the administration of acetylsalicylic acid (ASA) or acetaminophen is uncertain. Methods: Over a period of 9 months, patients admitted with acute hemiparetic ischemic stroke were monitored for BT in the first 48 h. When BT rose >37.5°C, patients were treated with either ASA 500 mg intravenously or acetaminophen suppository 1,000 mg. When 6 h later the BT was still or again >37.5°C, patients were further treated with acetaminophen suppository 1,000 mg up to 4 times a day. Primary outcome measure was normothermia (BT ≤37.5°C) within respectively 1 and 3 h after intervention. Secondary outcome parameters were any decrease in BT and the mean decrease in BT. Results: Of a total of 132 patients, 63 (48%) developed a BT >37.5°C. The effects of 43 injections of ASA and 89 administrations of acetaminophen were studied. After 1 h, treatment with acetaminophen produced both significantly more reductions in BT and normothermia (respectively in 60 and 20%) than treatment with ASA (respectively in 37 and 5%). At 3 h, both interventions had a similar effect, with normothermia being achieved in only 37–38%. Fever (>38.0°C) and evidence of an infection were related to unresponsiveness to treatment. Conclusions: In the majority of patients with acute ischemic stroke, ASA and acetaminophen are insufficient for reducing an elevated BT to a state of normothermia.
Development and Validation of NEWSQOL®, the Newcastle Stroke-Specific Quality of Life Measure
Authors: Buck Deborah , Jacoby Ann , Massey Anna , Steen Nick , Sharma Anil , Ford Gary A.
Published: January 2004

Background: A review of stroke-specific quality of life (QOL) measures indicated little evidence of their validity/reliability. Purpose: To describe the development/validation of a new measure – the Newcastle Stroke-Specific Quality of Life Measure (NEWSQOL). Methods: Phase I: qualitative interviews (28 stroke patients) determined QOL issues for inclusion in the measure. Initial items/response categories were pre-tested (30 patients). Administration of the NEWSQOL in the item reduction stage (100 patients) identified poorly performing items and factor analysis showed likely domains. Internal consistency was examined. Phase II: NEWSQOL and comparator measures were administered (106 patients) to examine validity/test-retest reliability. Results: Phase I: 140 items were identified for initial inclusion. Qualitative pre-testing led to an extensive revision. Item reduction resulted in a final measure of 56 items in 11 domains (feelings, activities of daily living/self-care, cognition, mobility, emotion, sleep, interpersonal relationships, communication, pain/sensation, vision, fatigue; Cronbach’s α = 0.71–0.90). Phase II: NEWSQOL domain scores, except cognition, were moderately/highly correlated (0.45–0.76) with relevant comparator measures. NEWSQOL domains feelings, communication and cognition low/moderately correlated with Barthel Index scores (–0.49 to –0.28), as predicted. Test-retest reliability was high (intraclass correlation coefficient range 0.78–0.92). Conclusions: NEWSQOL is an acceptable, patient-derived, interviewer-administered, stroke-specific QOL measure with evidence of reliability and validity, making it a promising instrument for assessing QOL after stroke. Involvement of relevant patients in determining the content and format considerably enhances confidence in its validity.
Efficacy and Tolerability of Pantoprazole Compared with Misoprostol for the Prevention of NSAID-Related Gastrointestinal Lesions and Symptoms in Rheumatic Patients
Authors: Stupnicki T. , Dietrich K. , González-Carro P. , Straszak A. , Terjung A. , Thomas K.B. , Lühmann R. , Fischer R.
Published: January 2004

Aim: To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 µg twice daily (b.i.d.), administered for 6 months to rheumatic patients who required long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing gastrointestinal lesions. Methods: This randomized, double-blind, multicenter, parallel group comparison study was performed with rheumatic patients (n = 515) who were likely to take NSAIDs continuously for at least 6 months. Patients were 55 years or older, at risk to develop gastrointestinal lesions, had less than five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not available at the time). Patients were randomized to take either pantoprazole 20 mg o.d. (n = 257) or misoprostol 200 µg b.i.d. (n = 258) for 6 months while continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months. Results: Pantoprazole was superior to misoprostol (p < 0.001) with regard to ‘therapeutic failure’ (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe gastrointestinal symptoms, and/or ‘likely’ or ‘definitely’ related adverse event leading to study termination). Estimated remission rates at 3 and 6 months (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole) and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p = 0.005) with regard to ‘endoscopic failure’ (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6 months. Estimated remission rates at 3 and 6 months were, respectively, 98 and 95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study early due to adverse events ‘likely’ or ‘definitely’ related to the study drug accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol treatment groups. Conclusion: Pantoprazole 20 mg o.d. is superior to misoprostol 200 µg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and symptoms in patients on continuous long-term treatment with NSAIDs due to rheumatic diseases and at risk to develop such lesions or symptoms.