bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Microcirculation in Mild and Severe Experimental Pancreatitis
Authors: Kahrau S. , Schneider P. , Loddenkemper C. , Buhr H.J. , Foitzik T. 
Published: August 2003

<i>Background:</i> Research aimed at elucidating the pathogenesis of pancreatitis-associated lung injury and evaluating novel strategies for preventing respiratory complications in acute pancreatitis (AP) has not yet involved intravital microscopic (IVM) studies of pulmonary microcirculation in animals with severe disease. <i>Objective:</i> To characterize and compare pulmonary microcirculation in severe/necrotizing (NP) and mild/edematous pancreatitis (EP) in the rat. <i>Methods:</i> EP was induced by intravenous cerulein infusion (n = 10) and NP by a standardized intraductal infusion of glycodeoxycholic acid followed by intravenous cerulein (n = 10). After 24 h a left-sided thoracotomy was performed for IVM examination of pulmonary capillary blood flow, permeability, leukocyte sticking and the thickness of alveolar septi. Further measurements included monitoring of arterial blood gases and histological evaluation of lung injury. <i>Results:</i> In animals with NP, histology revealed severe pulmonary edema together with clustering of polymorphonuclear leukocytes in pulmonary microvessels and alveoli. IVM showed a greater number (n) of leukocytes sticking on the endothelium of pulmonary capillaries (9.4 ± 0.7 vs. 1.8 ± 0.2 in healthy control animals) and increased capillary permeability (260 ± 14 vs. 136 ± 6% relative fluorescein intensity) while capillary blood flow was decreased (0.41 ± 0.05 vs. 0.57 ± 0.03 mm/s). In comparison, changes in EP were significantly less pronounced (flow 0.5 ± 0.04 mm/s, permeability 156 ± 4%, leukocyte sticking n = 4.6 ± 0.7). <i>Conclusions:</i> These findings suggest that deterioration of pulmonary microcirculation in AP correlates with disease severity and that a model featuring NP may therefore be more suitable to further study pancreatitis-associated pulmonary injury.
Combination Radiation and Adenovirus-Mediated <i>p16</i><sup>INK4A</sup> Gene Therapy in a Murine Model for Head and Neck Cancer
Authors: Rhee Juong G. , Li DaQing , O’Malley Jr. Bert W. , Suntharalingam Mohan 
Published: August 2003

Since adenoviral <i>p16</i><sup>INK4A</sup> gene transfer has shown limited promise in preclinical studies, we developed a strategy combining ionizing radiation (x-rays) with Ad-<i>p16 </i>gene therapy. Both radiation (2 Gy) and Ad-<i>p16</i> alone demonstrated anti-tumor responses. The combination of radiation and Ad-<i>p16</i> in vitro showed an augmented therapeutic response. Two head and neck squamous cell carcinoma (HNSCC) cell lines treated with Ad-<i>p16</i> demonstrated positive staining to annexin V and terminal deoxynucleotidyl-transferase, suggesting apoptosis. When the HNSCC cell lines were grown in nude mice, the anti-tumor response by Ad-<i>p16</i>, radiation, and combination therapy ranged from limited benefit of the single-agent therapy to a statistically significant additive response to combination therapy. Our data suggest that Ad-<i>p16</i> gene therapy may prove effective in treating human HNSCC that is refractory to radiation therapy.
Comparison of the Protective Efficacy of Neurotrophins and Antioxidants for Vibration-Induced Trauma
Authors: Zou Jing , Bretlau Poul , Pyykkö Ilmari , Toppila Esko , Olovius N. Petri , Stephanson Niklas , Beck Olof , Miller Josef M. 
Published: August 2003

<i>Background:</i> Patients undergoing temporal bone surgery or subjects working with vibrating tools may develop vibration-induced hearing loss (VHL). The aim of this study was to characterize the effects of pretreatment with N-acetylcysteine (NAC) or the neurotrophic factors, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), on VHL in an animal model. <i>Methods:</i> Trauma to the cochlea was created with a vibrating probe placed on the bone of the external ear canal. BDNF and CNTF<sub>A×1</sub> were delivered into the cochlea with mini-osmotic pumps. NAC was delivered into the cochlea by round window membrane (RWM) injection, by RWM permeation, or by oral administration. Hearing was evaluated with electrocochleography (ECoG). <i>Results:</i> For control animals, vibration resulted in an average immediate threshold shift of 42 ± 26 dB. NAC provided no protective benefit in animals subjected to VHL, regardless of the delivery method, with average threshold shifts varying from 38 to 56 dB across groups. NAC injection through the round window membrane was toxic, causing a ECoG threshold shift of >25 dB. In BDNF+CNTF<sub>A×1</sub>-treated animals, immediate hearing loss was similar to that in control animals. There was a trend of threshold recovery by 1 day after vibration; however, the improvement was not statistically significant, nor was there a significant difference in 1-day thresholds across groups. <i>Conclusions:</i> Local infusion of BDNF and CNTF<sub>A×1</sub> may enhance the rate of recovery from VHL, compared to control animals. In contrast, NAC had no effect on VHL, and when delivered by RWM injection, was actually toxic to the inner ear.
Phase I Study of Combination Chemotherapy Using Irinotecan Hydrochloride and Nedaplatin for Advanced or Recurrent Cervical Cancer
Authors: Machida Shizuo , Ohwada Michitaka , Fujiwara Hiroyuki , Konno Ryo , Takano Masashi , Kita Tsunekazu , Kikuchi Yoshihiro , Komiyama Shinichi , Mikami Mikio , Suzuki Mitsuaki 
Published: August 2003

<i>Objective:</i> We performed a phase I clinical study to evaluate combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin (CPT-11/nedaplatin) for cervical cancer. <i>Methods:</i> This study included patients with primary or recurrent cervical cancer. The regimen for CPT-11/nedaplatin therapy consisted of CPT-11 administered 3 times over 2 weeks (days 1, 8 and 15) and nedaplatin infused intravenously as a single dose (day 1). This course was repeated at 4-week intervals. The step 1 doses of the two agents were 50 mg/m<sup>2</sup>, respectively. Dose escalation was performed in tandem. Plasma CPT-11, SN-38, total platinum, and filterable platinum levels were measured. <i>Results:</i> In step 3 (CPT-11, 60 mg/m<sup>2</sup>; nedaplatin, 60 mg/m<sup>2</sup>), dose-limiting toxicity was observed in 2 of 3 patients. The step 3 doses were regarded as the maximum tolerated doses. The incidences of grade 3/4 adverse events in the first courses (n = 12) [and all courses (n = 45)] were: leukopenia 33% (22%), neutropenia 42% (31%), anemia 17% (20%), nausea 8% (7%), and diarrhea 8% (7%). Following CPT-11 administration, the mean areas under the curve (AUC; ng·h/ml) of SN-38 were 0.11 at 50 mg/m<sup>2</sup> and 0.17 at 60 mg/m<sup>2</sup>. Following nedaplatin administration, the mean AUCs (µg·h/ml) of filterable platinum were 6.0 at 50 mg/m<sup>2</sup>, and 6.0 at 60 mg/m<sup>2</sup>. The response rate was 50% (2 complete responses and 2 partial responses). <i>Conclusion:</i> The recommended doses of CPT-11 and nedaplatin for a phase II clinical study were established as 50 and 60 mg/m<sup>2</sup>, respectively.
High Incidence of Angina pectoris in Patients Treated with 5-Fluorouracil
Authors: Wacker Annette , Lersch Christian , Scherpinski Ute , Reindl Laurence , Seyfarth Melchior 
Published: August 2003

<i>Objective: </i>Angina pectoris, arrhythmic sudden death and myocardial infarction, all these cardiac events have occasionally been reported during 5-fluorouracil (5-FU) chemotherapy. Underlying mechanisms leading to these events are unknown; damage to the myocytes or vasospasms have been discussed. <i>Methods:</i> 102 consecutive and unselected patients were monitored with 12-lead ECG, echocardiography and radionuclide ventriculography prior to the first cycle of 5-FU chemotherapy and 3 months from baseline. <i>Results: </i>19% of the patients developed reversible symptoms of angina pectoris during treatment which lasted up to 12 h after cessation of the infusion. Most of the 19 patients showed corresponding ECG changes. 6 out of the 19 patients with severe angina pectoris had subsequent coronary angiography. In none of these patients the coronary angiography showed coronary artery disease, but it showed low ventricular function (ejection fraction <50%) in 2 patients. The ejection fraction did not increase over time. Arrhythmias were screened for with Holter monitoring during 5-FU chemotherapy. The frequency of bradycardia and ventricular extrasystoles increased significantly (p < 0.05) during treatment compared to arrhythmias in Holter monitoring 3 months later. Furthermore the Qtc time in the ECG 3 months later was significantly prolonged (p < 0.05) compared to baseline values. <i>Conclusions:</i> The incidence of angina pectoris in patients during 5-FU treatment seems higher than previously suspected. As myocardial ischemia can be fatal, attentiveness to these symptoms and immediate treatment are crucial.
Interleukin-1α Enhances Integrin α<sub>6</sub>β<sub>1</sub> Expression and Metastatic Capability of Human Pancreatic Cancer
Authors: Sawai Hirozumi , Funahashi Hitoshi , Yamamoto Minoru , Okada Yuji , Hayakawa Tetsushi , Tanaka Moritsugu , Takeyama Hiromitsu , Manabe Tadao 
Published: August 2003

<i>Objective:</i> To investigate the mechanisms of metastasis formation in metastatic human pancreatic cancer, we examined the enhancement in integrin expression, and adherence to and invasiveness into extracellular matrix (ECM) proteins of human pancreatic cancer cells after exposure to interleukin (IL)-1α. <i>Methods:</i> Expression of IL-1 receptor type I (IL-1RI) and alterations in integrin subunits by IL-1α were examined by flow-cytometric analysis and by cellular enzyme-linked immunosorbent assay in four human pancreatic cancer cell lines (BxPC-3, PaCa-2, PANC-1, and SW1990), respectively. In addition, assays of cancer cell adhesion and invasion to ECM proteins were performed to investigate whether increased integrin expression affected the adhesive and invasive interaction between cancer cells and the putative integrin ECM ligands. Furthermore, immunohistochemistry was used to assess integrins and IL-1R1 expression in pancreatic tissues. <i>Results:</i> In metastatic cancer cells, expression of the α<sub>6</sub> subunit was enhanced by IL-1α treatment. While metastatic cancer cells exhibited preferential adherence to and invasion into laminin, these properties were enhanced by IL-1α. The α<sub>6</sub> subunit and IL-1RI were strongly expressed in pancreatic tissues from pancreatic cancer patients with liver metastasis. <i>Conclusions:</i> In pancreatic cancer, IL-1α enhanced α<sub>6</sub>β<sub>1</sub>-integrin expression, probably via increased IL-1RI levels. Our results indicated that α<sub>6</sub>β<sub>1</sub>-integrin and IL-1RI expression may play important roles in metastasis formation.
Effects of Some Antidepressant Drugs on Tryptaminergic Responses of the Rat Jejunum
Authors: Liu Haihuang , Coupar Ian M. , Irving Helen R. 
Published: August 2003

The rat isolated jejunum was used as a functional model to screen some antidepressant drugs at the ‘atypical’ 5-HT<sub>7</sub> receptor. Mianserin acted as a surmountable antagonist of 5-CT with a <i>p</i>A<sub>2</sub> value of 8.22 ± 0.33. The apparent <i>p</i>K<sub>B</sub> of maprotiline against 5-CT was 7.67 ± 0.24 at 100 nmol/l, but higher concentrations suppressed the maxima. An apparent <i>p</i>K<sub>B</sub> could not be obtained for amitriptyline, because 10 nmol/l reduced the E<sub>max</sub> of 5-CT without causing parallel displacement. Higher concentrations of 30 and 100 nmol/l caused further suppressions. Amoxapine, loxapine and desipramine (each at 100 nmol/l) caused similar effects, suppressing the E<sub>max</sub> values to 5-HT by approximately 50%, while lower concentrations failed to cause parallel displacements. These results further extend the activity profiles of the drugs investigated.
Antinociceptive Effects of Methysergide in Various Pain Models
Authors: Chung Ki-Myung , Choi Seong-Soo , Han Ki-Jung , Han Eun-Jung , Lee Han-Kyu , Suh Hong-Won 
Published: August 2003

Several studies have demonstrated that the nonselective opioid receptor antagonist naloxone produces a paradoxical antinociception in the formalin test. The opioid system is related to the serotonergic system for producing antinociception at the spinal level. Here we also asked whether systemic (i.p.) and intrathecal (i.t.) administrations of a nonselective serotonergic antagonist, methysergide, might produce paradoxical antinocicpetion similar to naloxone in the mouse formalin test. A diluted formalin solution was injected into the mouse plantar region of the hind paw and the duration of licking responses was measured at periods of 0–5 min (1st phase) and 20–40 min (2nd phase) after formalin injection. Methysergide administered i.p. and i.t. showed an attenuated licking duration only in the 2nd phase. The effect observed in the 2nd phase was reversed in the 5,7-dihydroxytriptamine, but not N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine pretreated group of mice, suggesting that descending serotonergic, but not noradrenergic, systems are involved in the methysergide antinociception. To further investigate the mechanism by which methysergide inhibited the nociceptive behaviors induced by formalin, the antinociceptive effect of methysergide was also tested in substance P (i.t.) and excitatory amino acids (i.t.), such as glutamate, N-methyl-<i>D-</i>aspartic acid, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and kainic acid, which are major components in the formalin-induced nociceptive transmission in the spinal cord pain models. The duration of nociceptive behaviors shown in these models was significantly shortened by i.p. and i.t. administration of methysergide. These results suggest that methysergide also produces a paradoxical antinociception in various pain models including the formalin test, similar to the results of naloxone.
Pharmacokinetics of Isoflurane: Uptake in the Brain
Authors: Lu Chih-Cherng , Ho Shung-Tai , Wang Jhi-Joung , Wong Chih-Shung , Hu Oliver Yao-Pu , Chang Sun-Yran , Lin Chung-Yuan 
Published: August 2003

We studied the effect of the inspired isoflurane concentration (C<sub>I</sub>iso) on the pharmacokinetics of isoflurane uptake in the brain by comparing the isoflurane concentration in internal jugular-bulb blood (Jiso) with that in arterial blood (Aiso), and analyzed this by gas chromatography. Sixteen patients (aged 43–76 years) undergoing colorectal surgery were enrolled, and anesthesia was maintained with a constant C<sub>I</sub>iso of either 1% (group 1, n = 8) or 2% (group 2, n = 8) during the 1st hour of isoflurane anesthesia. Under constant volume-controlled ventilation, we measured the C<sub>I</sub>iso and the end-tidal isoflurane concentration (C<sub>E</sub>iso) at the mouthpiece by infrared analysis. Our results demonstrate that it takes 40 min for the brain tissue concentration to equal Aiso for 1% C<sub>I</sub>iso, and 50 min for 2% C<sub>I</sub>iso. The Aiso (and/or Jiso) for 2% C<sub>I</sub>iso was approximately double when compared to that for 1% C<sub>I</sub>iso. Except during the initial wash-in period of the functional residual capacity in the first 3 min, the differences between C<sub>I</sub>iso and C<sub>E</sub>iso revealed that the body uptake of isoflurane for 2% C<sub>I</sub>iso was twice that for 1% C<sub>I</sub>iso. These results demonstrate that the pharmacokinetics of isoflurane uptake in the brain is time-dependent for Jiso to equal Aiso, and the midpoint between Aiso and Jiso (likely representing the isoflurane concentration in brain tissue) was dependent on C<sub>I</sub>iso.
4-Aminopyridine Transiently Increases Intraocular Pressure in Rabbits
Authors: Socci Robin R. , Chu Eugenia , Bayorh Mohamed A. , Chu Teh-Ching 
Published: August 2003

The purpose of this study is to determine the mechanisms of action involved in the ocular hypertension induced by 4-aminopyridine (4-AP), a voltage-dependent potassium (K<sup>+</sup>) channel blocker, in rabbits. Topical application of 4-AP elevated intraocular pressure (IOP). This action caused increases in the aqueous flow rate as well as aqueous levels of protein and norepinephrine. In isolated iris-ciliary body preparations, 4-AP (0.01, 0.1, 1 mmol/l) caused dose-related increases in field-stimulated norepinephrine release by 43, 222 and 243%, respectively. Taken together, the IOP-elevating effect evoked by 4-AP was associated with enhancement of aqueous norepinephrine levels and norepinephrine release from sympathetic nerves of the iris-ciliary body. These results demonstrate that the 4-AP-sensitive K<sup>+</sup> channels in sympathetic nerves and the ciliary epithelium are the potential sites of action of the 4-AP-induced ocular hypertension.
An Anthropological View of Vision
Authors: Marazzi Antonio 
Published: August 2003

The image of the cave described by Plato in Book VII of the Republic is the most frequently quoted emblematic example of the belief in the illusory nature of what sight transmits to the mind. ‘We must compare the world of the senses with the view of those who live in a prison’, says Socrates, referring to the cave in which there are men in chains who can see nothing but a wall onto which are projected shadows of objects lit by a fire behind them, and who, ignorant of the objects themselves, are inclined to give more credit to the shadows than the objects, as long as they are not free and able to rise in their souls from the visible to the intelligible world.The whole history of human thought could be rewritten in terms of the confrontation between the eye and the mind. The immediate power, poignant charm, evocative force of the messages sent from one to the other have encouraged a bewitching abandon, internal illuminations, but also moments of deliberate blindness and destructive furies. Starting from periods of vague iconophilia, a large number of societies have moved to periods of obsessive iconoclasm in public forms of representation. From sublime experiences of divine mystical visions to the most degenerate forms of violence and pornography, it is the visual image, perceptible or mental, that imposes itself.
Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia
Authors: Ooi Jun , Iseki Tohru , Takahashi Satoshi , Tomonari Akira , Takasugi Kashiya , Shimohakamada Yoko , Yamada Toshiki , Ishii Koji , Ohno Nobuhiro , Nagamura Fumitaka , Uchimaru Kaoru , Tojo Arinobu , Asano Shigetaka 
Published: August 2003

Abstract
We report the results of unrelated cord blood transplantation (CBT) for 18 adult patients with de novo acute myeloid leukemia (AML). The median age was 43 years, the median weight was 55.2 kg, and the median number of cryopreserved nucleated cells was 2.51 × 107/kg. Seventeen patients had myeloid reconstitution and the median time to more than 0.5 × 109/L absolute neutrophil count was 23 days. A self-sustained platelet count more than 50 × 109/L was achieved in 16 patients at a median time of 49 days. Acute graft-versus-host disease (GVHD) above grade II occurred in 11 of 17 evaluable patients and chronic GVHD occurred in 14 of 17 evaluable patients. Fourteen patients are alive and free of disease at between 185 and 1332 days after transplantation. The probability of disease-free survival at 2 years was 76.6%. These results suggest that adult AML patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.
Mactinin: a modulator of the monocyte response to inflammation
Authors: Luikart Sharon D , Krug Hollis E , Nelson Robert D , Hinkel Timothy , Majeski Peter , Gupta Pankaj , Mahowald Maren L , Oegema Theodore 
Published: August 2003

AbstractDuring inflammatory processes, monocytes leave the blood stream at increased rates and enter inflammation tissue, where they undergo phenotypic transformation to mature macrophages with enhanced phagocytic activity. α-Actinin, a cytoskeletal protein, is present in focal adhesion complexes and left in the microenvironment as a result of cell movement. Mactinin, a 31 kDa amino-terminal fragment of α-actinin, is generated by the degradation of extracellular α-actinin by monocyte-secreted urokinase. We have previously demonstrated that mactinin promotes monocyte/macrophage maturation. We now report that 0.5–10 nM mactinin has significant chemotactic activity for monocytes. Mactinin seems to be present in inflammatory arthritis synovial fluid, because affinity-purified antisera reacted with a protein of the expected molecular mass in various types of arthritis fluids that were immunoaffinity-purified and subjected to Western analysis. Thus, six of seven samples from patients with psoriatic arthritis, reactive arthritis, gout, or ankylosing spondylitis contained mactinin at levels that are active in vitro. Initially, mactinin was not found in affinity-purified rheumatoid arthritis samples. However, it was detectable after the dissociation of immune complexes, suggesting that it was complexed to anti-microfilament auto-antibodies. In addition, mactinin was found in the lavage fluid from the arthritic knee joints of rabbits with antigen-induced arthritis and was absent from the contralateral control knee fluids. We conclude that mactinin is present in several types of inflammatory arthritis and might modulate mononuclear phagocyte response to inflammation.
Does an early increased-intensity interdisciplinary upper limb therapy programme following acute stroke improve outcome?
Authors: Rodgers Helen , Mackintosh Joan , Price Christopher , Wood Ruth , McNamee Paul , Fearon Tracy , Marritt Anna , Curless Richard 
Published: August 2003

Objective: To determine whether an early increased-intensity upper limb therapy programme following acute stroke improves outcome. Design: A randomized controlled trial. Setting: A stroke unit which provides acute care and rehabilitation for all stroke admissions. Subjects: One hundred and twenty-three patients who had had a stroke causing upper limb impairment within the previous 10 days. Intervention: The intervention group received stroke unit care plus enhanced upper limb rehabilitation provided jointly by a physiotherapist and occupational therapist, commencing within 10 days of stroke, and available up to 30 minutes/day, five days/week for six weeks. The control group received stroke unit care. Main outcome measures: The primary outcome measure was the Action Research Arm Test (ARAT) three months after stroke. Secondary outcome measures: Motricity Index; Frenchay Arm Test; upper limb pain; Barthel ADL Index; Nottingham E-ADL Scale; and costs to health and social services at three and six months after stroke. Results: There were no differences in outcomes between the intervention and control groups three and six months after stroke. During the intervention period the intervention group received a median of 29 minutes of enhanced upper limb therapy per working day as inpatients. The total amount of inpatient physiotherapy and occupational therapy received by the intervention group was a median of 52 minutes per working day during the intervention period and 38 minutes per working day for the control group ( p = 0.001). There were no differences in service costs. Conclusions: An early increased-intensity interdisciplinary upper limb therapy programme jointly provided by a physiotherapist and occupational therapist did not improve outcome after stroke. The actual difference in the amount of therapy received by intervention and control groups was less than planned due to a competitive therapy bias.