bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of TTS Fentanyl as a Single Opioid for Cancer Pain Relief: A Safety and Efficacy Clinical Trial in Patients Naive to Mild or Strong Opioids
Authors: Mystakidou Kyriaki , Befon Sofia , Tsilika Eleni , Dardoufas Kostas , Georgaki Stavroula , Vlahos Lambros 
Published: April 2003

<i>Background:</i> Up to now, a transdermal therapeutic system (TTS) of fentanyl has been applied to cancer patients on opioid analgesics previously treated with mild opioids or morphine. The aim of this study was to investigate the efficacy and safety of TTS fentanyl (patch) administration as an analgesic to patients treated with opioid analgesics for moderate-to-severe cancer pain, with immediate-release oral morphine only as rescue medication. The prior analgesic medication of the patients did not include mild or strong opioids. <i>Methods:</i> The study group consisted of 113 patients (54 men and 59 women; age range: 21–87 years, mean ± SD 61.3 ± 14.84 years) with undertreated chronic cancer pain. The study period was 42 days. The patients were hospitalized for the first 3 days of the study; thereafter they were transferred to their home for the rest of the study. Daily cards were completed, noting their pain score (0–10 VAS), nausea, vomiting, constipation, skin reactions, dizziness or any other complaints. Vital signs were also recorded. Data assessments were made at baseline, on days 1, 2 and 3 (during hospitalization) and thereafter on days 7, 14, 21, 28, 35, and 42 after hospital discharge. The initial TTS fentanyl delivery rate was chosen depending on the patient’s analgesic requirements. All patients were given an oral morphine solution (5–10 mg), every 4–6 h, for the first 12 h, as rescue medication. <i>Results:</i> Baseline pain score was between 6 and 10 (mean ± SD 7.1 ± 1.7). The initial TTS fentanyl delivery rate was between 25 and 50 µg/h (mean ± SD 36.5 ± 15.7). On day 3, 95 patients (84%) reported a pain score ≤3 (mean ± SD 0.5 ± 0.8), 14 patients (12.4%) a pain score of 4 and 4 patients (3.5%) of 5–8. No adverse effects suggesting the discontinuation of the study were reported. From day 7 until the completion of the study, the mean pain score was between 1.3 and 0.16 while the TTS fentanyl delivery rate on day 42 was between 25 and 400 µg/h (mean ± SD 122.1 ± 81.2 µg/h). <i>Conclusion:</i> Analgesic treatment with TTS fentanyl used as a single opioid is effective and safe for cancer pain relief, given that is cautiously applied, in patients requiring strong opioid analgesics even if they were naive to strong or mild opioids.
Impact of Increased Intraocular Pressure on Long-Term Corneal Endothelial Cell Density after Penetrating Keratoplasty
Authors: Nguyen N.X. , Langenbucher A. , Seitz B. , Küchle M. , Naumann G.O.H. 
Published: April 2003

<i>Purpose:</i> Besides immunological graft rejection, persistently increased intraocular pressure (IOP) is among the most important causes for graft failure after penetrating keratoplasty (PK). The purpose of this study was to assess the longitudinal development of IOP after PK and to investigate possible correlations with corneal endothelial cell density. <i>Methods:</i> This longitudinal prospective study included 209 eyes after PK with a complete follow-up at 3 months, 6 months, before first suture removal (16 ± 5 months) and after complete suture removal (21 ± 5 months). At each examination, IOP was measured by Goldmann applanation tonometry. Endothelial cell density was assessed by specular microscopy (EM 1100, Tomey). The indications for PK were 48% keratoconus, 34% Fuchs’ dystrophy, 5.4% stromal dystrophies, 8.6% secondary bullous keratopathy and 4% corneal scars. An iridotomy was performed routinely during PK. The postoperative treatment with topical steroids was standardized. <i>Results:</i> Preoperatively, the mean IOP was 13.6 ± 2.9 mm Hg with increased IOP (>21 mm Hg) in 2.0% of eyes. After 3 months, the incidence of increased IOP (24.5 ± 4.6 mm Hg) was highest (6.7%) and decreased thereafter to 3.0% after complete suture removal. No patients showed IOP higher than 30 mm Hg. A persistently increased IOP for more than 3 months was seen in 2% of patients. At 3 months postoperatively, the mean endothelial cell density was 1,977 ± 496/mm<sup>2</sup> and did not decrease significantly (p > 0.05) until 6 months (1,771 ± 507 cells/mm<sup>2</sup>). At the end of the follow-up period, the mean endothelial cell density was significantly reduced (1,347 ± 501 cells/mm<sup>2</sup>). There was no significant correlation between IOP and mean endothelial cell density at any postoperative examination stage (p > 0.24). Patients with persistently increased IOP for more than 3 months did not have significantly different endothelial cell densities in comparison with those without increased IOP. <i>Conclusion:</i> From 6 months after PK, the incidence of increased IOP was not higher than the preoperative level. Mild to moderate temporary IOP elevations after PK do not seem to affect the endothelial cell density of the graft until complete suture removal. Further long-term studies are necessary to assess the clinical relevance of these observations.
A Comparison of the Short-Term Hypotensive Effects and Side Effects of Unilateral Brimonidine and Apraclonidine in Patients with Elevated Intraocular Pressure
Authors: Yüksel Nurşen , Karabaş Levent , Altıntaş Özgül , Yildirim Yusuf , Çağlar Yusuf 
Published: April 2003

<i>Purpose:</i> To compare the short-term ocular hypotensive efficacy and side effects of 0.2% brimonidine and 0.5% apraclonidine in patients with elevated intraocular pressure (IOP). <i>Methods:</i> We performed a double-masked, placebo-controlled study to compare the efficacy of the application of 0.2% brimonidine and 0.5% apraclonidine for the effect of IOP, systemic blood pressure and heart rate in 20 newly diagnosed ocular hypertensive patients. Effects on the untreated fellow eye and ocular side effects were also determined. All measurements were performed 1, 2, 4, 6 and 8 h after the instillation of one drop. <i>Results:</i> Brimonidine and apraclonidine significantly reduced IOP from baseline at all observation times. No significant difference was observed between the treatment groups. IOP decreased significantly in the untreated fellow eye in the brimonidine group at 4-, 6- and 8-hour checks and at 6-hour checks in the apraclonidine group when compared with placebo. Blood pressure and heart rate decreased significantly in the brimonidine group compared with placebo. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. The pupil diameter and the interpalpebral fissure width significantly increased in the apraclonidine group, but not in the brimonidine group. There were no significant differences in the overall incidence of foreign body sensation, burning and stinging and dry mouth in the treatment groups. <i>Conclusions:</i> In the short-term, brimonidine was effective in reducing IOP in patients with elevated IOP and was equivalent in efficacy to apraclonidine. On the other hand, a significant change in blood pressure and heart rate was observed with brimonidine; there was no change at all in the apraclonidine group.
Effect of Sympathetic Denervation on Rabbit Choroidal Blood Flow
Authors: Chou Ping-I , Lu Da-Wen , Chen Jiann-Torng 
Published: April 2003

In this study we demonstrate the existence of sympathetic innervation and compare the effect of unilateral or bilateral superior cervical sympathectomy on albino rabbit choroidal blood flow (CBF) during changes in perfusion pressure (PP). Forty albino rabbits weighing between 2.0 and 3.0 kg were randomly divided into three groups. The bilateral sympathectomy group (group S) included 10 rabbits (20 eyes) that received bilateral sympathectomy 1 week prior to the study. The unilateral sympathectomy group (group U) included 20 rabbits (20 eyes) that received unilateral sympathectomy 1 week prior to the study. Only the eyes ipsilateral to sympathectomy were utilized. The other 10 rabbits (20 eyes) served as controls (group N), each received the same procedure as the experimental groups except that the superior cervical ganglion (SCG) was preserved. The blood cell flux (PF), velocity (V), and concentration of moving blood cells (CMBC) were recorded simultaneously by means of a laser Doppler flowmeter (Perimed PF4001), while the intraocular pressure was increased linearly with a syringe pump. When the PP decreased steadily, the PF, V, and CMBC remained constant until PP <55 mm Hg, then decreased proportionally to the PP. When the PP decreased from 75 to 0 mm Hg, the PF, V and CMBC decreased from 100 to 6.87 ± 0.97%, 8.44 ± 0.92%, and 18.67 ± 0.91% in group N, to 18.56 ± 1.62%, 19.30 ± 1.84%, and 38.02 ± 9.10% in group U, and to 18.38 ± 2.89%, 16.78 ± 1.48%, and 34.58 ± 4.42% in group S. The changes in PF, V, and CMBC were similar in groups S and U. Both group S and U had higher PF, V, and CMBC values than group N at comparable PPs below 55 mm Hg. These results indicate that the SCG plays a role in CBF regulation. Both unilateral and bilateral sympathectomy led to a higher PF in both groups S and U rabbits, indicating increased CBF while PP decreased gradually. This suggests that the rabbit choroid does not receive crossed innervation. The plateau response in each curve demonstrates the presence of autoregulation. This autoregulation was unchanged by either unilateral or bilateral sympathetic denervation.
Prevention of Neurotoxin Damage of 6-OHDA to Dopaminergic Nigral Neuron by Subthalamic Nucleus Lesions
Authors: Chen Lin , Liu Zonghui , Tian Zengmin , Wang Yaqi , Li Shiyue 
Published: April 2003

<i>Object:</i> To investigate the possibility that subthalamic nucleus (STN) ablation could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). <i>Methods:</i> Sixty rats were divided into 6 groups (n = 10). The control group received a unilateral microinjection of 6-OHDA into the right ventral tegmental area (VTA) and the right median forebrain bundle (MFB). Group 1 received an administration of kainic acid (KA) into the right STN and, 1-week later, an injection of 6-OHDA in the right VTA and MFB. Groups 2–5 received an injection of 6-OHDA in the right VTA and MFB, 1 h, 2 h, 3 days, and 7 days before KA in the right STN respectively. Four weeks later, the changes of tyrosine hydroxylase (TH)-positive (dopaminergic) neurons in the SNc were investigated with immunocytochemical and morphometrical methods. <i>Results: </i>The number of TH-positive cells in the SNc on the injected side of treated groups (groups 1–5) and control group were 71.46 ± 6.84, 57.07 ± 5.54, 51.09 ± 4.85, 12.68 ± 2.67, 4.15 ± 1.60 and 3.40 ± 1.54/slice, which decreased to 96.7, 72.9, 69.8, 17.2, 5.6 and 4.4% of the non-injected side, respectively. The number of TH-positive neurons in groups 1–4 significantly increased in comparison with the controls (p < 0.05, 0.01). In group 5, there were no remarkable differences in contrast to the number of TH-positive neurons of the controls (p > 0.05). The difference in the number of TH-positive neurons between groups 1–5 was statistically significant (p < 0.01). <i>Conclusion: </i>The results indicate that STN ablation can provide antiglutamate-based neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA toxicity.
Clinical Efficacy of Amphotericin B Colloidal Dispersion against Infections Caused by <i>Aspergillus</i> spp
Authors: Gurwith M. 
Published: April 2003

Three published clinical trials of the efficacy of amphotericin B colloidal dispersion (ABCD) against infections caused by <i>Aspergillus</i> spp were reviewed. A total of 376 patients was treated. Systemic aspergillosis was identified in 67 evaluable patients. Overall, a complete or partial response was achieved in 47.8% of the evaluable patients, although there were substantial differences in the response rates between studies. Reasons for recruitment caused a marked difference in response rates. The overall response rate for ABCD in patients in which conventional amphotericin B (CAB) was contra-indicated or had previously failed was 34.3%, whereas the response rate in bone marrow transplant (BMT) or patients with renal impairment was 57.9 and 62.5% respectively. The efficacy of ABCD at doses of 4 mg/kg/day appears to be at least as good as in studies using CAB. The levels of renal toxicity were low at a dose of 4 mg/kg/day. Dose-limiting studies indicate that dosages can be safely increased to 7.5 mg/kg/day creating opportunity for improved efficacy.
Safety and Efficacy of Amphotericin B Colloidal Dispersion
Authors: Herbrecht R. , Letscher V. , Andres E. , Cavalier A. 
Published: April 2003

The efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) have been investigated on 572 patients in five Phase I/II clinical trials. The patients were all selected to present a challenging test; having a fungal infection superimposed on severe illness. In 442 cases ABCD was used after amphotericin B, which had been withdrawn. One hundred and forty patients had pre-existing nephrotoxicity. Most patients received doses of 3–6 mg/kg/day of ABCD. Complete or partial recovery was reported in 149/260 (57.3%) patients evaluable for therapeutic response. Patients with <i>Candida</i> infection responded better than those with systemic aspergillosis showing 70.1% recovery vs. 48.8%. ABCD therapy made no difference to serum creatinine levels, even in patients with pre-existing renal failure, nor to liver function as measured by SGOT, alkaline phosphatase and total bilirubin levels in serum. Infusion-related adverse events were the most frequently reported side effects of ABCD. However these studies show clearly that ABCD can be administered safely to patients without the risks of renal toxicity, even when renal toxicity had already developed following therapy with conventional amphotericin B deoxycholate.
Association between Antibiotic Resistance and the Expression of Dr Adhesin among Uropathogenic <i>Escherichia coli</i>
Authors: Kachroo B.B. 
Published: April 2003

<i>Background:</i> Urinary tract infections (UTIs) are a significant health problem and <i>Escherichia coli</i> has been exported to be the primary pathogen in approximately 80% of cases. <i>E. coli</i> express structures called adhesins, fimbriae or pili that help them bind to specific tissue receptors. One such adhesin is Dr, which binds to the complement decay-accelerating factor (CD55) on the host cell. The purpose of the present study was to review the epidemiology and antimicrobial sensitivity spectrum of Dr adhesin-bearing <i>E. coli</i> isolates in women with UTI. <i>Methods and Results:</i> A total of 337 uropathogenic <i>E. coli</i> isolates were collected, and mannose-resistant hemagglutination was observed in 43%, while 12.4% expressed Dr adhesin. All 337 uropathogenic <i>E. coli</i> isolates were found to be resistant to penicillin, oxacillin, bactericin and cloxacillin. None of the isolates was resistant to quinolones. The resistance to sulfamethoxazole was most common (90%), followed by nalidixic acid (51%) and ampicillin (41%). Interestingly, uropathogenic <i>E. coli</i> expressing Dr adhesin had a high incidence of ampicillin resistance (83%), and only 17% of the Dr-bearing isolates were found to be resistant to an ampicillin/sulbactum combination. <i>Conclusion:</i> These results indicate that UTIs may be successfully treated with ampicillin in combination with a β-lactamase inhibitor, so that selective colonization by Dr adhesin-bearing uropathogenic <i>E. coli</i> is prevented, which is probably promoted by treating these patients with ampicillin alone.
Investigation of Oxacillin-Hydrolyzing Beta-Lactamase in Borderline Methicillin-Resistant Clinical Isolates of <i>Staphylococcus aureus</i>
Authors: Gál Zsuzsanna , Kovács Péter , Hernádi Ferenc , Barabás György , Kiss László , Iglói Attila , Szabó István 
Published: April 2003

<i>Background: </i>Mechanisms of borderline resistance of <i>Staphylococcus aureus </i>to penicillinase-resistant penicillins (PRPs) may include hyperproduction of classical penicillinase and/or production of β-lactamase hydrolyzing also PRPs. <i>Methods:</i> β-Lactamase activity of whole cells and purified enzymes was estimated spectrophotometrically and in isolated cytoplasmic membranes by bioassay with <i>Bacillus subtilis</i> as test strain. <i>Results:</i> Out of 53 clinical isolates of <i>S. aureus</i>, 18 showed oxacillin MIC values from 0.5 to 2 µg/ml, which were reduced by sulbactam and/or clavulanic acid in the case of four isolates producing large quantities of inducible, type A β-lactamase. Cytoplasmic membranes isolated from these strains showed oxacillin-hydrolyzing activity. One of these strains was grown also in the presence of globomycin, an antibiotic known to interfere with the anchorage of membrane lipoproteins; this treatment eliminated the oxacillin-hydrolyzing activity. <i>Conclusions:</i> The resistance in these strains was due to a membrane-bound lipoprotein with oxacillin-hydrolyzing activity.
Selection of <i>Klebsiella pneumoniae </i>Mutants with High-Level Cefotaxime Resistance during Growth in Serum Containing Therapeutic Concentrations of Cefotaxime
Authors: Bedenić Branka 
Published: April 2003

<i>Background:</i> In a previous investigation of the genetic characterization of extended-spectrum β-lactamases (ESBLs) in <i>Klebsiella pneumoniae </i>from Zagreb, Croatia, 20 strains were found to produce SHV-2 β-lactamase. Those strains displayed varying degrees of β-lactam resistance and a wide range of β-lactamase activity. We concluded that more resistant isolates were hyperproducers of SHV-2 β-lactamase. <i>Methods:</i> In this investigation, we tried to develop hyperproducing variants from 8 low-level SHV-2 β-lactamase-producing <i>Klebsiella</i> strains by subculturing them in serum containing therapeutic concentrations of cefotaxime (CTX). <i>Results:</i> In most cases, there was a moderate increase in CTX resistance (twofold to threefold), except in one strain which displayed a 16-fold increase in the minimum inhibitory concentration (MIC) of CTX after incubation in the serum. That strain showed a marked increase in enzyme activity as well. The strains with a moderate increase in CTX MIC did not produce more enzyme after exposure to the serum, except for one strain which had a threefold rise in β-lactamase activity after exposure to serum. <i>Conclusions:</i> In this investigation, it was established that the mutants with high-level CTX resistance developed very quickly in the biological fluids containing therapeutic concentrations of CTX. It is reasonable to expect that a similar process occurs in patients infected with an ESBL-producing <i>K. pneumoniae </i>strain during antibiotic treatment. Since most of the high-level CTX-resistant mutants did not have a marked rise in β-lactamase activity after exposure to serum, it is possible that the elevated resistance was due to some other mechanism, such as reduced penicillin-binding protein affinity, changes in outer membrane proteins or efflux by multidrug efflux pumps.
Possible Role of Nitric Oxide and Adrenomedullin in Bipolar Affective Disorder
Authors: Savaş Haluk A. , Herken Hasan , Yürekli Muhittin , Uz Efkan , Tutkun Hamdi , Zoroğlu Süleyman Salih , Özen Murat Eren , Cengiz Beyhan , Akyol Ömer 
Published: April 2003

Nitric oxide (NO) has been implicated to play a role in the pathogenesis of depressive disorders. Adrenomedullin (AM) induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of NO. AM immune reactivity is present in the brain, consistent with a role as neurotransmitter. Therefore, it is suggested that these two molecules may play a role together in the brain. We aimed to examine AM and NO in bipolar affective disorder (BPAD). Forty-four patients with BPAD and 21 healthy control subjects were included in this study. DSM-IV diagnosis of bipolar affective disorder (type I, manic episodes) was independently established by two psychiatrists and the Turkish version of the Bech-Rafaelson Mania Scale was administered. Also, a semistructured form was used to ascertain several sociodemographic and clinical variables of the patients. AM and NO were studied in plasma. The mean value of plasma NO levels in the BPAD group of 46.58 ± 13.97 µmol/l was significantly higher than that of controls (31.81 ± 8.14 µmol/l) (z = –4.15, p = 0.000). Mean plasma AM levels were found to be increased in patients with BPAD (35.13 ± 5.26 pmol/l) compared to controls (16.22 ± 3.02 pmol/l) (z = –6.16, p = 0.000). AM levels of BPAD patients were approximately 2-fold higher than controls. AM levels were positively correlated with the duration of hospitalization for the current episode and negatively correlated with the total duration of illness. Both NO and AM may have a pathophysiological role in BPAD (type I, manic episodes) and the clinical symptomatology and prognosis of BPAD.
Changes in Renal Resistive Index and Urinary Albumin Excretion in Hypertensive Patients under Long-Term Treatment with Lisinopril or Nifedipine GITS
Authors: Leoncini Giovanna , Martinoli Carlo , Viazzi Francesca , Ravera Maura , Parodi Denise , Ratto Elena , Vettoretti Simone , Tomolillo Cinzia , Derchi Lorenzo E. , Deferrari Giacomo , Pontremoli Roberto 
Published: April 2003

<i>Introduction:</i> Increased renal vascular resistance and microalbuminuria are associated with hypertensive target organ damage and may be predictors of hypertensive nephrosclerosis. <i>Aim:</i> We investigated changes in renal resistive index (RI) and urinary albumin excretion (UAE) in a group of patients with primary hypertension before and during long-term antihypertensive treatment. <i>Methods:</i> Thirty-two patients were randomized to receive antihypertensive treatment with either a calcium channel blocker (nifedipine GITS, up to 90 mg/day, n = 16) or an ACE inhibitor (lisinopril, up to 20 mg/day, n = 16), alone or in association with a diuretic (chlortalidone, 25 mg/day). Blood pressure, renal resistive index (by US Doppler) and UAE (mean of three nonconsecutive timed urinary collections, µg/min) were evaluated at baseline and over the course of 24 months of treatment. <i>Results:</i> Both regimens effectively lowered blood pressure (mean blood pressure from 123 ± 1.8 at baseline to 103 ± 1.5 mm Hg at 24 months in the lisinopril group and from 122 ± 1.9 at baseline to 104 ± 0.8 at 24 months in the nifedipine group, p < 0.001 for both groups). Overall, blood pressure decrease was associated with a reduction in UAE and no change in RI throughout the study. However, despite similar blood pressure reduction, the two regimens showed different specific effects. Lisinopril was associated with a significant decrease in both UAE (33.8 ± 16.2 at baseline and 9.1 ± 2.1 at 24 months, p < 0.01) and renal RI (0.61 ± 0.02 at baseline and 0.56 ± 0.04 at 24 months, p < 0.05) while nifedipine GITS did not significantly influence UAE (35.7 ± 12.2 at baseline and 31.2 ± 12.1 at 24 months, n.s.) or RI (0.61 ± 0.01 at baseline and 0.59 ± 0.02 at 24 months, n.s.). <i>Conclusion:</i> Effective blood pressure control over a long period of time reduces the severity of organ damage, namely UAE while maintaining renovascular resistance in patients with essential hypertension. Different classes of antihypertensive agents might convey additional specific renal protection beyond blood pressure control. These data could be useful in devising individualized therapeutic strategies in hypertensive patients at increased renal risk.