bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Osteodystrophy in Predialysis and Hemodialysis Patients: Comparison of Histologic Patterns and Diagnostic Predictivity of Intact PTH
Authors: Coen Giorgio , Ballanti Paola , Bonucci Ermanno , Calabria Santo , Costantini Sergio , Ferrannini Michele , Giustini Marco , Giordano Rosa , Nicolai Giulia , Manni Micaela , Sardella Daniela , Taggi Franco
Published: April 2003

Background: Comparison of renal osteodystrophy in predialysis and hemodialysis has been rarely reported. Distinct patterns of renal osteodystrophy could be found in these conditions. In addition the use of parathyroid hormone (PTH) and other markers for noninvasive diagnosis may result in different predictive values in predialysis and hemodialysis patients. Methods: 79 consecutive patients with conservative chronic renal failure and 107 patients on hemodialysis were studied. All patients were subjected to bone biopsy for histological and histomorphometric evaluation. The patients had no exposure to aluminium before dialysis and relatively low exposure while on hemodialysis. Results: In the predialysis patients, bone biopsies showed 9 cases of adynamic bone disease (ABD) and 8 cases of osteomalacia (OM), 50 patients with mixed osteodystrophy and 2 cases of hyperparathyroidism. Among the hemodialysis patients 12 cases had ABD, 3 cases OM, 30 mixed osteodystrophy, and 61 patients hyperparathyroidism. In the predialysis patients with chronic renal failure, bone aluminium was on average 4.5 mg/kg dry weight, while in dialysis patients the average value was 35.4 mg/kg dry weight. Discriminant analysis of low turnover osteodystrophy (ABD and OM) by intact PTH showed higher accuracy in dialysis than in predialysis patients. Correlation studies of intact PTH versus bone formation rate, osteoblast surface/bone surface and osteoclast surface/bone surface showed significantly steeper slopes in dialysis than in predialysis patients, which indicates that bone resistance to PTH is more marked in predialysis patients. Conclusions: The prevalence of ABD and OM in the geographic area investigated is lower than in other reports. Aluminium exposure does not seem to be the cause of low turnover osteodystrophy in the present population. The predictive value of intact PTH in the noninvasive diagnosis of renal bone disease is higher in hemodialysis patients than in predialysis patients. Predialysis chronic renal failure, when compared to the dialysis stage, seems to be characterized by resistance of bone tissue to PTH.
Effect of Intraperitoneal Administration of Low-Molecular-Weight Heparin on Plasma Tissue Factor Pathway Inhibitor Levels in CAPD Patients
Authors: Demirkan Fatih , Akarsu Mesut , Sifil Aykut , Tutucu Kutlay Naci
Published: April 2003

We investigated the systemic effect of intraperitoneal low-molecular-weight heparin (LMWH) in continuous ambulatory peritoneal dialysis (CAPD) patients by measuring plasma total tissue factor pathway inhibitor (TFPI) levels, regarding the fact that the levels of plasma TFPI increases 2- to 4-fold after subcutaneous and intravenous administration of unfractioned heparin or LMWH. Eleven men and 6 women who had been on CAPD for 32 ± 26 months and 15 healthy controls were included in the study. After administration of intraperitoneal enoksiparin in dialysate, plasma samples were obtained 4 h later. TFPI levels were significantly higher in CAPD patients (207.8 ± 55 ng/ml) compared to the healthy subjects (72.5 ± 29 ng/ml) (p < 0.0001). Both TFPI levels (225.9 ± 47 vs. 207.8 ± 55 ng/ml) (p < 0.54) and plasma factor Xa (anti-FXa assay) (0.097 ± 0.14 vs. 0.093 ± 0.16 U/ml) (p < 0.54) levels did not show any statistical difference before and after intraperitoneal administration of LMWH. By these findings we might suggest that intraperitoneal LMWH does not have any systemic effect.
Carboplatin Induces Less Apoptosis in the Cochlea of Guinea Pigs than Cisplatin
Authors: Watanabe Ken-ichi , Jinnouchi Ken , Hess Alexander , Michel Olaf , Baba Shunkichi , Yagi Toshiaki
Published: April 2003

Background: Cisplatin (CDDP) is known to cause inner ear damage while carboplatin (CBDCA) induces less ototoxicity than CDDP. We examined apoptotic changes in the cochlea of guinea pigs after injection of CDDP or CBDCA using immunohistochemical and electrophysiological techniques. Methods: Three days after the injection of each solution, the cochleas were immunohistochemically examined for the presence of fragments of single-stranded DNA (ssDNA). The auditory brain stem response was recorded before and three days after the injection. Results: We detected fragments of ssDNA in the stria vascularis and the spiral ligament of the CDDP-treated cochlea. In this group, the threshold of the auditory brainstem response was significantly elevated, however, in the CBDCA group, no apparent change of the threshold was detected. In the CBDCA group, fragments of ssDNA were detected in the stria vascularis and the spiral ligament. The number of cells that stained positive for ssDNA, was less than that in the CDDP group. Conclusions: Our findings indicate that CBDCA induces less apoptosis than CDDP and that this phenomenon contributes to the ototoxicity of CDDP.
Irinotecan (CPT-11) in Patients with Advanced Colon Carcinoma Relapsing after 5-Fluorouracil-Leucovorin Combination
Authors: Tsavaris N.B. , Polyzos A. , Gennatas K. , Kosmas Ch. , Vadiaka M. , Dimitrakopoulos A. , Macheras A. , Papastratis G. , Tsipras H. , Margaris H. , Papalambros E. , Giannopoulos A. , Koufos Ch.
Published: April 2003

The purpose of the present study was to investigate the association between performance status (PS) and mean dose of irinotecan (CPT-11) in patients with recurrent advanced colorectal cancer relapsing after 5-fluorouracil and leucovorin chemotherapy. Patients who had completed their last chemotherapy course with 5-fluorouracil and leucovorin for at least 6 weeks and progressed were included. Based on PS, we administered a starting dose of 250 mg/m2 in patients with a PS 70–80 (group A), and 350 mg/m2 for those with a PS > 80 (group B). Of a total of 90 treated patients, all were evaluable, 18 had a partial response (PR) (20%), 39 stable disease (43%), and 15 progressed (37%). No significant difference was noticed between patients with PS ≧ 90 or ≤ 80 (p = 0.925), or between those who received a mean dose of CPT-11 ≧300 or ≤300 (p = 0.602), for response, survival and time to progression. Toxicity was increased in group B as expected, with significant differences for acute cholinergic syndrome (p = 0.02), diarrhea after the first 24 h (p = 0.03) and severe diarrhea (p = 0.03). According to these results, we conclude that response to CPT-11 is independent of its dose, and that a dose of 250 mg/m2 every 3 weeks might be a cost-effective and less toxic alternative in this setting. However, further adequately powered phase II or III randomized studies might be required in order to confirm this observation.
Efficacy and Tolerability of Once-Daily Therapy with Telithromycin for 5 or 10 Days for the Treatment of Acute Maxillary Sinusitis
Authors: Roos K. , Brunswig-Pitschner C. , Kostrica R. , Pietola M. , Leroy B. , Rangaraju M. , Boutalbi Y.
Published: April 2003

Background: The efficacy and tolerability of oral telithromycin 800 mg once daily for 5 vs. 10 days were assessed in patients with acute maxillary sinusitis (AMS). Methods: Adults (n = 341) with confirmed AMS diagnosed on clinical signs and symptoms and sinus X-ray showing total opacity or air-fluid level were randomized to receive oral telithromycin for 5 days (followed by placebo for 5 days; n = 170) or 10 days (n = 171). Causative pathogens were isolated by pretreatment sinus puncture (day 1). Clinical and bacteriologic outcomes, and safety and tolerability endpoints were assessed. Results: Clinical cure rates post-therapy (per-protocol; days 17–21) were comparable (91.1% in the 5-day group, n = 123; 91.0% in the 10-day group, n = 133). Bacteriologic eradication rates (per-protocol) were also similar (90.7 vs. 91.3%). Both regimens were well tolerated. Conclusions: A 5-day course of telithromycin 800 mg once daily is an effective, well-tolerated treatment for adults with AMS, comparable to a 10-day regimen.
New Advances in Lipid-Modifying Therapies for Reducing Cardiovascular Risk
Authors: Bruckert Eric
Published: April 2003

Over the last 30 years, several epidemiological and prospective studies have identified a number of risk factors for the development of cardiovascular disease. Lipid abnormalities are central among these risk factors, and their correction has been a major target for the medical community. The 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors (statins) are the most widely prescribed and best tolerated of the currently available lipid-modifying therapies. Newer agents in this class (e.g. rosuvastatin) have been developed that have proven to be more effective at lowering levels of low-density lipoprotein cholesterol (LDL-C). New formulations of drugs such as nicotinic acid can improve treatment regimens and reduce unpleasant side-effects, thereby improving patient compliance with this therapy. In terms of developing novel drugs, the introduction of cholesterol absorption inhibitors (e.g. ezetimibe) and ACAT inhibitors (e.g. avasimibe) will provide clinicians with therapies that exploit different therapeutic pathways to those currently being utilised. Combining these agents with statins could produce greater improvements in lipid profile than those seen to date. In addition, advances in our understanding of the pathophysiology of dyslipidaemia have led to the identification of other novel therapeutic targets, including cholesteryl ester transfer protein. Studies with experimental drugs have already demonstrated the potential of these approaches.
Hematopoietic Stem Cells: Self-Renewing or Aging?
Authors: de Haan Gerald
Published: April 2003

Stem cells are defined by their extensive self-renewal properties, and yet there is abundant evidence of erosion of stem cell functioning during aging. Whereas intracellular repair and protection mechanisms determine the lifespan of an individual cell, here an argument is made that somatic stem cells determine the lifespan of an entire tissue, and thus play a key role in the organismal aging process. Recently it has been shown that the developmental potential of somatic stem cells may be far greater than previously anticipated. Although the mechanisms regulating stem cell plasticity are far from clear, it is challenging to discuss the potential relevance of these findings in the aging process.
Human Mesenchymal Stem Cells: Insights from a Surrogate in vivo Assay System
Authors: MacKenzie Tippi C. , Flake Alan W.
Published: April 2003

Mesenchymal stem cells (MSC) are multipotent cells that have been isolated from the bone marrow of multiple species that can be induced to differentiate into at least bone, cartilage, and adipose tissue in vitro. Using a model of in utero cellular transplantation in which human MSC are transplanted into fetal lambs, we have shown that MSC can engraft in multiple tissues and persist for over one year. Furthermore, these cells can differentiate into cardiac and skeletal myocytes, bone marrow stromal cells, adipocytes, thymic epithelial cells, and chondrocytes. These observations lend support to the potential utility of MSC for cellular and/or gene therapy in the treatment of a variety of congenital or acquired diseases such as osteogenesis imperfecta, muscular dystrophy, lysosomal storage diseases, and for enhancement of bone marrow transplantation.
Effects of Stimulus Predictability and Interstimulus Gap on Saccades in Alzheimer’s Disease
Authors: Abel Larry A. , Unverzagt Fred , Yee Robert D.
Published: April 2003

Objectives: Studies of saccadic eye movement impairment in Alzheimer’s disease (AD) have largely focused on simple reflexive eye movements and the antisaccade task. The effects of manipulating stimulus timing have been little studied. Methods: Fourteen patients with mild to severe AD and 11 age-matched controls were studied on the antisaccade task, while latencies on simultaneous, gap and predictable tasks were recorded from 11 patients and 11 controls. Dementia severity was assessed with the Mini-Mental State Examination. Results: As a group, patients’ latencies were significantly higher and more variable on the simultaneous and gap tasks. Predictable task performance was similar in mean but significantly more variable. Grossly anticipatory responses by patients were common on the predictable, simultaneous and gap tasks. Exclusion of these from subject means revealed that AD patients, when making target-driven saccades, demonstrated a gap effect of similar magnitude to normal subjects. Patients made significantly fewer correct antisaccades and significantly more reflexive errors not followed by a corrective antisaccade than did controls. Conclusions: The frequent presence of grossly anticipatory saccades may reflect dysfunction of fixation mechanisms possibly involving projections from frontal lobe to superior colliculus. The less frequently seen, marked prolongation of latency may reflect changes in posterior parietal mechanisms mediating reflexive saccade generation. The presence of the gap effect demonstrates a continued ability to benefit from externally controlled stimulus disengagement. Patients’ ability to make appropriately timed saccades to targets of known locations was particularly impaired, but the target sequence itself was at least grossly correctly learned. Larger studies may be able to identify clinically distinct populations of AD patients.
Evaluation of the Disinfective Efficacy of Povidone-Iodine with the Use of the Transparent Film Dressing OpSite Wound
Authors: Takahashi Koichi , Muratani Tetsuro , Saito Masami , Ohno Natsumi , Matsumoto Tetsuro
Published: April 2003

To determine the duration of efficacy of disinfection with povidone-iodine (PVP-I) conducted before application of OpSite Wound (Smith and Nephew, UK), bacteriological evaluation was carried out. In 9 healthy adults, 3 sites on the forearms or other parts were chosen for application of OpSite Wound after adequate disinfection with PVP-I. As compared to the bacterial count score of 1.67–2.00 before disinfection, a significant reduction of the score was observed on removal of OpSite Wound on days 1, 2 and 3. The score of 0.5–0.67 immediately after disinfection did not change or deteriorate until removal of OpSite Wound. This finding supports the fact that unnecessary dressing changes could be avoided postoperatively for at least 3 days by disinfection with PVP-I and application of OpSite Wound particularly for operations categorized as ‘clean surgery’.
Thyroid Function in Nurses: The Influence of Povidone-Iodine Hand Washing and Gargling
Authors: Nobukuni Keigo , Kawahara Shin
Published: April 2003

The effect of povidone-iodine (PVP-I) hand washing and gargling on thyroid function was assessed. In 16 nurses using PVP-I products and 16 control subjects, serum inorganic iodine levels and thyroid functions were investigated. The status of PVP-I use was also surveyed in the nurses. Clinical symptoms considered to be attributable to thyroid dysfunctions were seen in none of the subjects, nor was a goiter observed in any of the subjects. In nurses, serum inorganic iodine levels were slightly increased as compared to those in the control subjects, although the difference was not significant. The iodine incorporated during working hours of nurses appears to be attributable to gargling rather than to hand washing. The long-term use of PVP-I for gargling should be avoided by (1) people with a high risk of developing thyroid dysfunction due to the excessive intake of iodine, (2) pregnant women and (3) breast-feeding mothers.
Investigation of Irritant Skin Reaction by 10% Povidone-Iodine Solution after Surgery
Authors: Iijima Shigeruko , Kuramochi Miyako
Published: April 2003

We report 19 patients who developed extensive patchy or linear erythema on both sides of the buttocks, the back and the posterior areas of the thighs within a few days following operations or cardioangiography. The erythema was sometimes deeply infiltrative and was also accompanied by bullae and erosion. Patch tests of the patients were strongly positive for 10% povidone-iodine (PVP-I, Isodine®) solution; however, they were negative for 10% PVP-I solution with the same amount of 8% sodium thiosulfate and for 5% potassium iodide in petrolatum. In all control individuals, the only positive result was that of a patch test with 10% PVP-I solution within 8 h after application. We diagnosed our patients as having irritant contact dermatitis caused by 10% PVP-I solution during the procedure, which might have drained along the skin to the side of the buttocks or the back. We here indicate that prolonged contact with a large quantity of 10% PVP-I solution should be avoided to prevent this problem.
cGMP-Dependent Protein Kinase Expression Restores Contractile Function in Cultured Vascular Smooth Muscle Cells
Authors: Brophy Colleen M. , Woodrum David A. , Pollock Jennifer , Dickinson Mary , Komalavilas Padmini , Cornwell Trudy L. , Lincoln Thomas M.
Published: April 2003

Vascular diseases, such as atherosclerosis and restenosis following angioplasty or transplantation, are due to abnormal vascular smooth muscle growth and gene expression. The smooth muscle cells (SMC) in response to injury lose their contractile function, become highly proliferative and synthesize and secrete extracellular matrix proteins. Similar changes in the phenotypic properties of vascular SMC occur during in vitro culture. In this report, we examined whether restoration of the expression of the major receptor protein for nitric oxide (NO) signaling in smooth muscle, the guanosine 3′:5′ cyclic monophosphate (cGMP)-dependent protein kinase (PKG), reestablished contractile function to cultured rat aortic SMC. Contractile function was monitored using the silicone polymer wrinkle assay used previously to determine contractility in cultured mesangial cells. Noncontractile rat aortic smooth muscle cells transfected with the cDNA encoding the type I isoform of PKG, but not those transfected with empty vector, formed discreet wrinkles on the substratum in response to serum indicative of contraction. Treatment of the PKG-expressing SMC with sodium nitroprusside (SNP), an NO donor, and with cGMP analogs, or with the adenylyl cyclase activator, forskolin, and with adenosine 3′:5′ cyclic monophosphate (cAMP) analogs reduced wrinkling. The expression of a major PKG substrate protein involved in smooth muscle relaxation, heat shock-related protein-20 (HSP20), was also reestablished in PKG-expressing SMC. Treatment of the PKG-expressing SMC with nitroprusside resulted in phosphorylation of HSP20. Collectively, these results indicate that PKG expression is important to establish contractility to SMC in culture.
Gene Expression and Morphological Changes in Surgically Injured Carotids of Spontaneously Hypertensive Rats
Authors: Forte A. , Di Micco G. , Galderisi U. , de Feo M. , Esposito F. , Esposito S. , Renzulli A. , Berrino L. , Cipollaro M. , Agozzino L. , Cotrufo M. , Rossi F. , Cascino A.
Published: April 2003

The expression profiles of genes involved in cell proliferation, differentiation and programmed death were investigated in carotids of spontaneously hypertensive rats (SHR) treated with a model of surgical injury that mimics events occurring during arterial grafts, endarterectomy and organ transplantation. The mRNA level of the c-myc, angiotensin II receptor 1 (AT1), Rb/p105, Rb2/p130, Bcl-2 and Bax-α genes was assessed by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique at different times up to 48 h after injury, while the morphological changes were evaluated 30 days after injury. The proliferation marker c-myc increases almost immediately, peaks after 4 h and returns to basal levels after 24 h; the AT1 receptor mRNA reaches its maximal level 48 h after injury. The level of cell cycle exit markers Rb/p105 and Rb2/p130 gradually decreases after injury. The apoptosis marker Bcl-2/Bax-α ratio shows a significant reduction only 4 h after injury, resuming the initial value after 24 and 48 h. Morphological analysis reveals that surgical injury in SHR induces adventitial and medial constrictive remodeling changes rather than intima proliferation as in balloon angioplasty. Both molecular and histological data show substantial differences with respect to normotensive rats.
The Role of Minimal Intervention in Orthodontics
Authors: Årtun Jon
Published: April 2003

Less than 15% of the population develops a normal occlusion as defined by Angle in the permanent dentition. The term ‘ideal’ may therefore be a more appropriate description, and deviations from this esthetic and functional optimum should not be considered abnormalities in the true sense of the word. Current research indicates that few malocclusions compromise dental, periodontal or temporomandibular health. To determine whether or not protruded, irregular or maloccluded teeth merit orthodontic intervention is therefore a major challenge. Another challenge is to determine to what extent a limited treatment strategy may be successful in correcting the occlusal problems according to the perceived needs of the patients. I discuss these issues in my present communication and conclude that the major reasons for recommending orthodontic treatment are psychosocial in nature. I also conclude that the majority of the orthodontic cases require comprehensive treatment to achieve successful results. Orthodontic patients are typically satisfied with the outcome of the orthodontic intervention, reporting that the esthetic improvements and the increased functional comfort of the dentition have made significant contributions to their quality of life. Technological advances have made orthodontic treatment simpler and safer over the years. Considering the potential for long-lasting results and the low risk of iatrogenic effects if the patients comply with appropriate oral hygiene measures during active appliance therapy, I conclude that treatment of minor occlusal deviations may also be justified in subjects expressing a clearly defined subjective need for treatment.
Chronic Silent Otitis media
Authors: Paparella Michael M. , Schachern Patricia A. , Cureoglu Sebahattin
Published: April 2003

Otitis media occurs along a continuum. For example, otitis media with effusion characterized by fluid pathology can lead to chronic otitis media plus chronic mastoiditis, characterized by the presence of intractable tissue pathology such as cholesteatoma, cholesterol granuloma or granulation tissue. The literature defines chronic otitis media as having a tympanic membrane perforation and otorrhea. Amongst many other sequelae, which can result from the continuum, an important common one is chronic silent otitis media. This overlooked entity which includes pathology beneath an intact tympanic membrane is commonly seen in our human temporal bone laboratory and in patients. The clinical pathological correlates of this important disease are discussed herein.
Etiopathogenesis of Otosclerosis
Authors: Niedermeyer Hans P. , Arnold Wolfgang
Published: April 2003

Otosclerosis is a frequent cause of nonsyndromic hearing loss which affects exclusively the human temporal bone. Various etiopathogenetic hypotheses have been proposed. The major hypotheses considered are genetic factors, immunologic factors and viral infection. Since the familial incidence of otosclerosis is known a recent genetic analysis has given evidence of three otosclerosis genes (OTSC1–3). Mutations in the collagen gene COL1A1 have been found in one large family with several cases of otosclerosis. Concerning an immunologic etiopathogenetic process, the presence of serum antibodies against collagen II and IX in patients with otosclerosis confirms the hypothesis of a collagen autoimmune mechanism. Finally as a possible cause of this chronic inflammatory disease morphologic and biochemical investigations have revealed a measles virus association. In conclusion, various etiopathogenetic factors may contribute to the genesis of otosclerosis.
Growth of Postoperative Remnants of Unilateral Vestibular Nerve Schwannoma: Role of the Vestibular Ganglion
Authors: Linthicum Jr. Fred H. , Saleh Emam S. , Hitselberger William E. , Brackmann Derald E. , Hung Gene
Published: April 2003

Histopathological examination of seven temporal bones from patients who underwent a removal of vestibular nerve schwannomas by the translabyrithine or middle fossa approaches has demonstrated small tumor remnants that failed to grow as long as 25 years after surgery. In spite of the high incidence of residual tumors, the clinical recurrence rate of tumors operated at our institution by the translabyrinthine or middle fossa approaches is low (0.3%). Immunohistochemical labeling of dividing cells demonstrated that segments of tumor adjacent to the vestibular nerve and ganglion contained more dividing cells than were present in areas of the tumor at a distance from them.
Simultaneous Detection of Both Nitric Oxide and Reactive Oxygen Species in Guinea Pig Vestibular Sensory Cells
Authors: Takumida Masaya , Anniko Matti
Published: April 2003

Gentamicin-induced production of reactive oxygen species (ROS) and of nitric oxide (NO) in the vestibular end organs of the guinea pig was investigated by applying two new fluorescence indicators, 4,5-diaminofluorescein diacetate for direct detection of NO and dihydrotetramethylrosamine for ROS. The vestibular sensory cells produced both NO and ROS after exposure to gentamicin. A nonspecific inhibitor of NO synthase, L-NAME, inhibited the production of NO but did not appear to affect the production of ROS following exposure to gentamicin. In contrast, a radical scavenger, D-methionine, or the neurotrophin BDNF suppressed the production of ROS, in turn stimulating NO production. These findings could indicate that both NO and ROS play an important role in aminoglycoside ototoxicity.
History of Quinolones and Their Side Effects
Authors: Rubinstein Ethan
Published: April 2003

Fluoroquinolone development from 1985 to the present was reviewed. Severe drug adverse events were noted for enoxacin, pefloxacin and fleroxacin, which were phototoxic. Temafloxacin was associated with severe hemolytic–uremic syndrome, lomefloxacin caused phototoxicity and central nervous system (CNS) effects, and sparfloxacin was associated with phototoxicity and QTc prolongation. Tosufloxacin caused severe thrombocytopenia and nephritis, and hepatotoxicity was reported for trovafloxacin. Grepafloxacin was withdrawn due to cardiovascular effects, and clinafloxacin was associated with phototoxicity and hypoglycaemia. The structure of the quinolones directly relates to both their activity and side-effect profiles. The relationship among specific substituents attached to the quinolone nucleus are clarified. The incidence of specific adverse events associated with individual fluoroquinolones was reviewed in a five-year post-marketing surveillance (PMS) study in Japan, in which a total adverse drug reaction (ADR) rate of 1.3% was found for levofloxacin, compared to total ADR rates of 3.3% for pazufloxacin, 3.6% for tosufloxacin, 4.5% for gatifloxacin and 5.4% for balofloxacin. Gastrointestinal effects were the most common adverse events for all fluoroquinolones. Levofloxacin had the lowest rate of CNS effects and skin adverse events among the agents listed.
Early Detection of Cerebral Arterial Occlusion on Magnetic Resonance Angiography: Predictive Value of the Baseline NIHSS Score and Impact on Neurological Outcome
Authors: Derex L. , Nighoghossian N. , Hermier M. , Adeleine P. , Froment J.C. , Trouillas P.
Published: April 2003

The presence of a thrombus on initial arteriography is directly related to the baseline NIHSS score. Magnetic resonance angiography (MRA) offers a noninvasive and rapid assessment of large cerebral vessel patency. We aimed at evaluating (1) the baseline NIHSS score as a tool for predicting the likelihood of an occluded artery on MRA and (2) the course of stroke within the first week according to the presence of a cerebral arterial occlusion. Patients were enrolled in this prospective study according to the following criteria: (1) acute cerebral ischemia with a neurological deficit lasting >1 h, and (2) brain MRI performed within 24 h of stroke onset. The NIHSS score assessment was performed on admission and at day 1 and day 7. The MRI protocol included: (1) T2-weighted Turbo spin echo, (2) echo-planar imaging isotropic diffusion, (3) T2*-gradient echo sequence, and (4) time of flight MRA (3D TOF Turbo MRA). The presence of a symptomatic cerebral arterial occlusion on MRA was systematically screened. Fifty-four patients were studied. Median age was 60 years. Mean time from stroke onset to NIHSS assessment was 170 ± 95 min. The mean baseline NIHSS score was 13.5 ± 7.3. The mean time from stroke onset to MRI was 384 ± 171 min. MRA was readable in 50 cases. An arterial occlusion was detected in 23 patients (46%). The median baseline NIHSS score was significantly higher in the group of patients with occlusion than in the group of patients without occlusion (18 vs. 7, p = 0.01). The predictive probability to demonstrate an arterial occlusion was related to the baseline NIHSS score. None of the patients with an NIHSS score of 1–6 (11 patients) had visible occlusion, whereas 9 (43%) out of 21 patients with an NIHSS score of 7–15 and 14 (78% ) out of 18 patients with an NIHSS score above 16 had an arterial occlusion. For an increase by one point in the NIHSS score, the odds ratio for the presence of occlusion was 1.28 (95% CI: 1.11–1.46). The course of the stroke as assessed by follow-up NIHSS score was significantly more severe if an occlusion was detected. Median day 0, day 1 and day 7 NIHSS score were, respectively, 18, 16 and 13 in patients who had an occlusion versus 7, 4 and 0 in patients who had no visible occlusion (p < 0.01). A direct relation between the baseline NIHSS score and the likelihood of the presence of an occlusion on initial MRA is demonstrated. The presence of a cerebral arterial occlusion on MRA is significantly linked to a poor neurological outcome.
In situ Evaluation of Sodium Hexametaphosphate-Containing Dentifrices
Authors: Wefel J.S. , Stanford C.M. , Ament D.K. , Hogan M.M. , Harless J.D. , Pfarrer A.M. , Ramsey L.L. , Leusch M.S. , Biesbrock A.R.
Published: April 2003

The purpose of this investigator-blinded, five-treatment, crossover human intraoral study was to evaluate the effects of two experimental dentifrice formulations containing either stannous fluoride (SnF2) or sodium fluoride (NaF) packaged with sodium hexametaphosphate in a dual-phase delivery system on demineralization-remineralization using an in situ model system. The experimental dentifrice formulations’ ability to alter demineralization-remineralization was compared to a series of three controls: SnF2-positive control, NaF-positive control and no-fluoride placebo-negative control. The single-section crown model, developed at the University of Iowa, was used to assess the fluoride efficacy of two experimental products versus the placebo containing no fluoride and positive controls. The results of the current in situ study suggest a clinical level of anticaries activity for the experimental SnF2 and NaF dentifrice formulations that was as good as either of the positive controls, when evaluated using polarized light microscopy. This supports the conclusion that the use of the sodium hexametaphosphate ingredient does not interfere with the normal fluoride activity of these toothpastes. In addition, the experimental SnF2 product was numerically better than both the NaF and placebo controls at preventing demineralization of sound root surfaces.
Videocapillaroscopic Findings in the Microcirculation of the Psoriatic Plaque
Authors: De Angelis Rossella , Bugatti Leonardo , Del Medico Patrizia , Nicolini Massimiliano , Filosa Giorgio
Published: April 2003

Background: Videocapillaroscopy (VCP) is a method to study the morphology and dynamics of microcirculation, but information about capillaroscopic features of the psoriatic plaque is limited. Objective: To investigate the distribution, morphology and density of capillaries in lesional and perilesional skin of the psoriatic plaque. Methods: VCP of a well-delimited plaque of the trunk, arms or legs in 15 consecutive patients with untreated, chronic plaque psoriasis was performed. Results: In the lesional skin, capillaries were tortuous and dilated, homogeneously appearing as ‘bushy’. In the perilesional skin, capillary loops seemed to be on a parallel course with respect to the skin surface, with their apex directed towards the marginal zone. The number of capillary loops per area unit was statistically increased in perilesional compared to lesional skin. Conclusion: According to the morphology, distribution and density of capillary loops, two different angiogenetic patterns were found in lesional and perilesional skin.
Palmar Digital Vein Thromboses: Their Different Expressions
Authors: Hofer Thomas
Published: April 2003

There have only been a few reports about thrombotic events in the volar digital veins. The observation of 2 such cases gives reason to discuss this rare symptomatology. Thrombosis of the digital veins can be categorised into three subtypes: the first shows clinical similarity to thrombotic events in veins or varicose veins of the limbs and may be related to a hypercoagulable state; the second group develops in a pre-existing normal vein or an acquired venous cavernoma and does not show clinical or histological signs of inflammation; the third category resembles Mondor’s disease and may be named Mondor’s phlebitis of the finger; histopathological examination has yet to be done. In any case of thrombosis of the volar digital veins, an inherited or acquired hypercoagulable state must be ruled out.
Hypoglossal Nerve Palsy as Complication of Oral Intubation, Bronchoscopy and Use of the Laryngeal Mask Airway
Authors: Dziewas Rainer , Lüdemann Peter
Published: April 2003

Hypoglossal nerve injury is a recognized but rare complication of oropharyngeal manipulation during intubation, bronchoscopy and use of a laryngeal mask airway. We present 2 new cases of temporary hypoglossal nerve palsy after orotracheal intubation for general anesthesia. The relevant literature is reviewed and different hypotheses concerning the pathophysiological mechanisms of nerve damage are discussed.
Cultural Narratives: Bridging the Gap
Authors: Penn Claire
Published: April 2003

Preparation of the clinician to work in multicultural contexts involves the identification of a range of skills, knowledge and values. The field of narrative medicine as well as an increased understanding of the dynamics of interpreting are areas which can add considerably to clinical effectiveness. The paper outlines some cornerstones of narrative medicine and their potential application to the field of speech-language pathology and audiology.
Improving the Power of Sib Pair Quantitative Trait Loci Detection by Phenotype Winsorization
Authors: Fernàndez José R. , Etzel Carol , Beasley T. Mark , Shete Sanjay , Amos Christopher I. , Allison David B.
Published: April 2003

Objectives: In sib pair studies, quantitative trait loci (QTL) identification may be adversely affected by non-normality in the phenotypic distribution, particularly when subjects falling in the tails of the distribution bias the trait mean or variance. We evaluated the robustness and power of reducing the influence of subjects with extreme phenotypic values by Winsorizing non-normal distributions in three versions of Haseman-Elston regression-based methods of QTL linkage analysis. Methods: Data were simulated for normal and non-normal distributions. Phenotypic values that correspond to cutoff points at the ω and 1 – ω percentiles of the distribution were identified, and phenotypic values falling outside the boundaries of the ω and 1 – ω cutoff points were replaced by the ω and 1 – ω values, respectively. One million replications were performed for the three tests of linkage for Winsorized and non-Winsorized data. Results: Winsorization reduced conservatism in the tails of the empirical type I error rate for the vast majority of the tests of linkage, increased the power of QTL detection in non-normal data and created a slight negative bias in symmetrical phenotypic distributions. Conclusions: Winsorizing can improve the power of QTL detection with certain non-normal distributions but can also introduce bias into the estimate of the QTL effect.
Expression and Immunohistochemical Localization of Adrenomedullin in the Mouse Cochlea
Authors: Tono Tetsuya , Shimozono Masami , Kawano Hirokazu , Asada Yujiro , Kitamura Kazuo , Komune Shizuo
Published: April 2003

Adrenomedullin (AM) is a novel hypotensive and vasodilator peptide. It has been shown that AM is biosynthesized in various organs and cells and is suggested to play multiple roles including electrolyte homeostasis and body fluid control. The present study describes for the first time the presence of mRNA for AM and AM-like immunoreactivity in the cochlea. A reverse transcription-polymerase chain reaction (RT-PCR) performed with gene-specific AM primer on total RNA extracted from mouse cochlea revealed a PCR product of the expected size. Immunohistochemical examination showed positive immunostaining in vascular smooth muscle cells of the modiolar arterioles and in the stria vascularis of the cochlea. These results suggest that AM may play a role in the regulation not only of cochlear hemodynamics but also of cochlear fluid dynamics.
Neuronal Nitric Oxide Synthase Immunoreactivity in the Nasal Mucosa of Patients with Idiopathic and Allergic Rhinitis
Authors: Olthoff Arno , Rohrbach Saskia , Faber Melanie , Götz Werner , Laskawi Rainer
Published: April 2003

The localization of neuronal nitric oxide synthase (nNOS) in the mucosa of the inferior and middle turbinates of 30 patients with and without allergic rhinitis was examined by immunohistochemical methods. Staining of paraffin sections from allergic and nonallergic patients revealed nNOS immunoreactivity (nNOS-IR) in the muscular layer of vessels, in the basal portion of submucosal glands and in the periost and the osteocytes of the turbinate bones. In contrast to earlier investigations, nNOS-IR was also seen in the nasal respiratory epithelium of allergic and nonallergic patients. The immunostaining of sections of submucosal glands from allergic patients was stronger than that of sections from patients with idiopathic rhinitis or patients with no nasal obstruction. The present result – nNOS-IR around glands is elevated in patients with allergic rhinitis – could indicate that this enzyme is involved in the pathogenesis and symptomatology of allergic rhinitis.
Aminoglycoside-Induced Hearing Loss in a Patient with the 961 Mutation in Mitochondrial DNA
Authors: Yoshida Mizuki , Shintani Tomoko , Hirao Motoyasu , Himi Tetsuo , Yamaguchi Akihiro , Kikuchi Kokichi
Published: April 2003

The A1555G mutation in the mitochondrial 12S ribosomal RNA gene is often found in patients with hearing loss after aminoglycoside exposure. A second pathogenic mutation in this gene, deletion of thymidine at position 961 with varying numbers of cytosines inserted (delT961Cn), has recently been found to predispose patients to aminoglycoside-induced deafness. We report on a Japanese patient bearing the delT961Cn who had streptomycin-induced deafness. Our report suggests that the delT961Cn plays an important secondary role in the pathogenesis of deafness caused by aminoglycosides. The combination of taking family histories and molecular screening at the 1555 and 961 positions is thought to reduce the frequency of tragic irreversible deafness due to aminoglycosides.
Angiotensin Actions on the Isolated Rat Uterus during the Estrous Cycle: Influence of Resting Membrane Potential and Uterine Morphology
Authors: Accorsi-Mendonça D. , Corrêa F.M.A. , Anselmo-Franci J.A. , Paiva T.B. , de Oliveira A.M.
Published: April 2003

The involvement of AT1 and AT2 receptor subtypes in the response of the isolated rat uterus to angiotensin II (AngII) was studied throughout the estrous cycle. The AngII potency varied during the different estrous cycle phases, as indicated by significantly different pD2 values. No significant differences were observed in AngII metabolism among different estrous phases. Morphological analysis indicated that external and internal myometrium layers were thicker during estrus. In addition, the highest resting membrane potential was also observed during this phase, when compared with the proestrus and diestrus phases. The AngII-induced uterine contractions were blocked by losartan. Different losartan pD2 values were observed. PD123319 had no effect on the contractile response to AngII. The results also indicate that estrous cycle-dependent changes in AngII potency are correlated with uterine morphological and/or membrane potential changes.
Actigraph Analysis of Diurnal Motor Fluctuations during Dopamine Agonist Therapy
Authors: Katayama Soichi
Published: April 2003

Background: Generally, clinicians use rating scales or descriptive writing to characterize diurnal changes in motor signs and symptoms in Parkinson’s disease (PD); however, these ratings are subjective and are not easily reproducible. Objective: To examine the usefulness of actigraphy as an objective indicator of akinesia by long-term, continuous measurement of limb motor activity (MA), visualize 24-hour circadian profiles of akinesia, and quantitatively detect cabergoline (CBG) efficacy in both hospitalized patients and outpatients with Parkinson’s disease. Methods: MA was continuously recorded with a wrist-worn activity monitor (actigraph) in 29 hospitalized PD patients without tremor or abnormal involuntary movements. In another series consisting of 8 outpatients, the response duration of CBG was measured by using averaged actigraphy. Results: By averaging data gathered every 24 h over several days, it was possible to quantify the circadian patterns of akinesia. These cumulative evaluations of the patients’ motor status determined 4 types of akinesia: (1) a wearing-off pattern seen in advanced efficacy stages, (2) stable response, (3) afternoon akinesia, and (4) morning akinesia. Following CBG therapy, the MA increased significantly throughout the daytime, i.e.: by 40% in the morning (8:00 a.m. to 12:00 noon), by 60% in the afternoon (12:00 noon to 6:00 p.m.), and by 60% in the next early morning (from time to get up until 8:00 a.m.). Conclusion: In averaged motor activity, the charting of cumulative evaluations of motor status revealed the long-acting efficacy of CBG in ameliorating existing motor fluctuations throughout the daytime and even promoting sleep benefit in the next morning. Averaged actigraphy is considered to be useful in the quantitative detection of drug responses to parkinsonian akinesia and its circadian variations. This enables titration of the lowest dose of drugs needed to alleviate akinesia.
Viral-Mediated Gene Transfer to Study the Molecular Physiology of the Mammalian Inner Ear
Authors: Holt Jeffrey R.
Published: April 2003

Several classes of viral vectors including adenovirus, adeno-associated virus, herpes simplex virus, lentivirus and vaccinia virus have been reported to infect cells of the inner ears of mammals and may be useful for protein manipulation and therapeutic purposes. We have screened a few of these for use as vectors to mediate gene transfer into the sensory hair cells of organotypic cultures from the neonatal mouse cochlea and utricle. Recombinant, replication-deficient adenovirus has emerged as a useful vector for several reasons: ease of vector generation at high titer; efficient hair cell specific infection; robust expression of reporter genes and minimal toxicity. Previously, we characterized adenovirus infected hair cells using a vector that carried the gene for green fluorescent protein (GFP). We screened GFP-positive cells electrophysiologically and found that although hair cells survive adenoviral vector infection, their mechanosensitivity was compromised. Until recently this has limited the scope of adenovirus application to the problems of inner ear physiology and pathophysiology. However, a modified adenoviral vector, now available, has been reported to have reduced ototoxicity in vivo. The modifications include the deletion of the adenoviral genes E1, E3, the viral polymerase, and the preterminal protein. We are currently working to characterize viral-mediated gene transfer into hair cells of the cultured mouse utricle using this new modified adenoviral vector. We have found that hair cells infected with the modified vector have intact hair bundles and robust mechanotransduction.
Bacteria in Blood Smears: Overwhelming Sepsis or Trivial Contamination
Authors: van der Meer W. , Verwiel J.M.M. , Gidding C.E.M. , de Metz M. , de Keijzer M.H.
Published: April 2003

It is unusual to find microorganisms in peripheral blood smears, and their presence is frequently associated with overwhelming sepsis and consequently a poor prognosis. In this report, we demonstrate 4 cases with bacteria in blood smears. Two of them had a fatal outcome, but the other 2 were caused by a contamination either via the central venous catheter or in vitro, both without dramatic outcome. The finding of bacteria in blood smears has to be interpreted carefully, and thorough examination of peripheral blood smears may be of great importance in the early diagnosis of bacteremia; however, in vitro contamination must be excluded.
Familial Frontotemporal Dementia Associated with a Novel Presenilin-1 Mutation
Authors: Tang-Wai D. , Lewis P. , Boeve B. , Hutton M. , Golde T. , Baker M. , Hardy J. , Michels V. , Ivnik R. , Jack C. , Petersen R.
Published: April 2003

We report a kindred with three cases of dementia. The proband presented with forgetfulness and personality changes at age 56, followed shortly thereafter by behavioral dyscontrol, hyperphagia, hypersexuality, delusions, illusions, disinhibition and double incontinence. Neuroimaging studies were consistent with frontotemporal dementia (FTD). In one allele, an arginine insertion at codon 352 in the presenilin 1 (PSEN1) gene was identified; no mutation was identified in the amyloid precursor protein or tau genes. We conclude that the clinical features of the Kluver-Bucy syndrome and FTD can be associated with PSEN1 mutations. Furthermore, presenilin analyses may be helpful to characterize kindreds with familial dementing illnesses regardless of the phenotype, particularly if no tau mutation is present.
Neuropsychological Deficit in Early Subcortical Vascular Dementia: Comparison to Alzheimer’s Disease
Authors: Traykov Latchezar , Baudic Sophie , Thibaudet Marie-Claude , Rigaud Anne-Sophie , Smagghe Alain , Boller François
Published: April 2003

To further clarify the cognitive syndrome in subcortical vascular dementia (VaD), we investigated 20 patients with early-stage VaD as compared with 30 patients with Alzheimer’s disease (AD) and 22 normal controls using episodic memory, attention/executive function and language tests. The patient groups were closely matched in terms of age, education and severity of dementia. The VaD patients had a significantly better free recall, cued recall and recognition memory than AD patients, the recognition being within normal limits in VaD. In addition, VaD patients had a greater number of perseverative errors during the Modified Card Sorting test, while AD patients exhibited more perseverations of semantic fluency. The results of retrieval deficit syndrome and increased number of perseverations during tasks sensitive to frontal lobe function are in agreement with the studies emphasizing the importance of frontal dysfunction in subcortical VaD. These findings are relevant for the early diagnosis of VaD and might be useful in the differential diagnosis with AD.