bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Trial of an Air-Abrasion/Chemomechanical Operative Procedure for the Restorative Treatment of Dental Patients
Authors: Rafique S. , Fiske J. , Banerjee A.
Published: August 2003

The aim of this study was to investigate whether caries removal with air-abrasion/Carisolv™ gel is an acceptable and viable alternative in the treatment of dental patients. Twenty-two patients were treated with conventional methods (local anaesthetic injection/drill) followed by alternative treatment (air-abrasion and Carisolv gel) in a general practice setting, by the same operator. The participants’ pre-operative anxiety levels were measured using the Modified Dental Anxiety Scale. Their postoperative levels of anxiety/dislike for aspects of both conventional and alternative treatments were assessed using a visual analogue scale. Levels of anxiety/dislike for both treatments were compared and statistically analysed. Results showed 100% of subjects were concerned about several aspects of conventional treatment including pain/discomfort on injection, taste of anaesthetic, length of time tissues remained numb, noise of the drill, its sensory vibrations and water coolant. However, 75% of the study population were happy with all aspects of the air-abrasion technique including dust, pain/discomfort and vibrations produced. Overall, the study population found Carisolv gel to be an acceptable alternative method of caries removal in terms of time taken, pain/discomfort and taste. There were statistically significant differences between patients’ perceptions of various aspects of the two treatment methods. All participants found the alternative treatment to be pain-free, quicker and overall more acceptable compared with conventional treatment. The conclusion drawn from the study was that air-abrasion/Carisolv gel treatment was a well-accepted and viable alternative to conventional local anaesthetic injection and drill for dental patients.
Forces Exerted by a Conventional Dental Explorer during Clinical Examination
Authors: Wagner J. , Thomas G. , Stanford C.
Published: August 2003

Purpose: To measure the range of forces exerted clinically in order to determine whether research in this area uses forces that are similar to those generally seen in a clinical setting. Methods: A transducer was manufactured consisting of a force measurement sleeve positioned over the handle of a conventional explorer. The sleeve housed 4 strain gauges oriented to detect forces in a vertical and lateral direction. Five experienced dentists performed a full-mouth caries exam on three fully dentate caries-free subjects with the force-detecting probe. Results: The overall average force was 340 ± 6 (SEM) g with a standard deviation of 218 g and a range of 14–1,006 g. The average number of contacts per tooth was 6.2 ± 0.2 (SEM) with a standard deviation of 2.7. Conclusions: The data from this study show that the forces used in previous studies were sometimes greater than the average force, but were still within the observed range of forces.
The Effect of a Single Application of 40% Chlorhexidine Varnish on the Numbers of Salivary Mutans Streptococci and Acidogenicity of Dental Plaque
Authors: Gerardu V.A.M. , Buijs M.J. , ten Cate J.M. , van Loveren C.
Published: August 2003

The relationship between the numbers of salivary mutans streptococci and the acid production in dental plaque after a single application of the 40% chlorhexidine varnish EC40® has been studied. Thirteen healthy subjects were treated with EC40 varnish. Saliva samples were taken before and up to 12 weeks after treatment to count mutans streptococci and lactobacilli. At the same time points plaque samples were taken before and after sucrose challenge and analyzed for protein and organic acid. Suppression of salivary mutans streptococci was observed together with a reduced production of lactic acid in sucrose-challenged dental plaque in 9 subjects while inhibition of acid production without significant suppression of mutans streptococci was observed in the other 4 participants. The duration of the effects differed among the individuals but never exceeded 6 weeks. We conclude that a prolonged suppression of mutans streptococci and acid production was not achieved by a single treatment with EC40 varnish in all subjects. Moreover, reduced acidogenicity of dental plaque after chlorhexidine treatment was not necessarily predicted by suppression of mutans streptococci in saliva.
Detection of Streptococcus mutans and Streptococcus sobrinus on the Permanent First Molars of the Mosuo People in China
Authors: Wu Hongkun , Fan Mingwen , Zhou Xuedong , Mo Anchun , Bian Zhuan , Zhang Qi , Chen Zhi
Published: August 2003

Streptococcus mutans and Streptococcus sobrinus are associated with the development of dental caries. The purpose of this study was to differentiate these bacteria by morphology, biochemical characteristics and PCR, and to compare their occurrence with the prevalence of dental caries in the Mosuo people. Plaque samples were collected from the permanent first molar in 126 Mosuo people (83 females, 43 males, aged 25–55 years, average age 36.1 ± 7.73). Dental status was recorded as DMFT by WHO caries diagnostic criteria. Males had a significantly lower prevalence of caries and DMFT than females: 11.4 vs. 86.9% and 1.65 vs. 6.95, respectively (p < 0.001). Morphological and biochemical tests gave unreliable results. The prevalence of S. mutans and S. sobrinus was 75.4 and 57.1%, respectively. 26.5% of females and 53.5% of males were positive for S. mutans alone, 18.1% of females and 16.3% of males were positive for S. sobrinus alone, while 50.6% of females and 18.6% of males were positive for both S. mutans and S. sobrinus and4.8% of females and 11.6% of maleswere negative for bothspecies. The DMFT scores of subjects positive for both S. mutans and S. sobrinus were significantly higher than of those positive for either S. mutans or S. sobrinus alone. These results indicate that subjects harboring both S. mutans and S. sobrinus have a significantly higher prevalence of dental caries than those with S. mutans or S. sobrinus alone.
Actinomyces spp. in Supragingival Plaque of Ethnic Chinese Preschool Children with and without Active Dental Caries
Authors: Tang G. , Yip H.K. , Samaranayake L.P. , Luo G. , Lo E.C.M. , Teo C.S.
Published: August 2003

Very limited molecular epidemiological data are available on the role of Actinomyces spp. in the pathogenesis of caries in the primary dentition. Therefore, we investigated their distribution in supragingival plaque of ethnic Chinese preschool children from Singapore and Hong Kong, either with or without active caries. Plaque samples were taken from intact interproximal enamel areas using dental floss. Bacterial genomic DNA of each sample was extracted and variable regions of 16S ribosomal DNA amplified and labelled with digoxigenin. Oligonucleotide probes specific for Actinomyces bovis, Actinomyces gerencseriae, Actinomyces israelii, Actinomyces meyeri, Actinomyces odontolyticus, catalase-negative Actinomyces naeslundii (genospecies 1 and 2) and catalase-positive Actinomyces naeslundii genospecies 2 (previously Actinomyces viscosus serotype II) were used to detect these species using Southern hybridization with a Minislot and Miniblotter system. A. odontolyticus, A. gerencseriae and A. meyeri were detected with similar frequency in both Singapore and Hong Kong samples or in those with and without active caries. However, the prevalence of A. naeslundii was significantly different in the two locales (p < 0.05). A. odontolyticus (88.7%), A. gerencseriae (56.6%) and A. naeslundii (50.9%) were detected in a majority of the samples and the positive hybridization signals of A. gerencseriae in the caries-active group were stronger than from the caries-free group. A. bovis and A. israelii were undetectable in any of the samples. These data imply that A. odontolyticus, A. naeslundii and A. gerencseriae may play an important role in supragingival plaque formation on primary teeth in ethnic Chinese, with others such as A. meyeri contributing.
Pulmonary Microcirculation in Mild and Severe Experimental Pancreatitis
Authors: Kahrau S. , Schneider P. , Loddenkemper C. , Buhr H.J. , Foitzik T.
Published: August 2003

Background: 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. Objective: To characterize and compare pulmonary microcirculation in severe/necrotizing (NP) and mild/edematous pancreatitis (EP) in the rat. Methods: 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. Results: 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). Conclusions: 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.
Effects of Selective Cyclooxygenase Inhibitors on Ischemia/Reperfusion-Induced Hepatic Microcirculatory Dysfunction in Mice
Authors: Ito Y. , Katagiri H. , Ishii K. , Kakita A. , Hayashi I. , Majima M.
Published: August 2003

We examined the effects of selective cyclooxygenase (COX) inhibition on hepatic warm ischemia/reperfusion (I/R) injury in mice. A selective COX-1 inhibitor, SC-560, selective COX-2 inhibitors, NS-398 and celecoxib, and indomethacin were administered 30 min before ischemia. Four hours after reperfusion, an in vivo microscopic study showed that I/R caused significant accumulation of leukocytes adhering to the hepatic microvessels and nonperfused sinusoids. Levels of plasma alanine transaminase (ALT) and tumor necrosis factor (TNF)-α also showed increases. SC-560, NS-398, celecoxib and indomethacin significantly reduced hepatic responses to I/R including microcirculatory dysfunction and release of ALT and TNF-α. Moreover, the effects of the thromboxane (TX) A2 (TXA2) synthase inhibitor OKY-046 and the TXA2 receptor antagonist S-1452 on hepatic responses to I/R exhibited results similar to those obtained with COX inhibitors. These results suggest that COX-1 and COX-2 contribute to I/R-induced hepatic microvascular and hepatocellular injury partly through TNF-α production, and that TXs derived from COX are partly responsible for I/R-induced liver injury.
Development of ‘No-Reflow’ Phenomenon in Ischemia/Reperfusion Injury: Failure of Active Vasomotility and Not Simply Passive Vasoconstriction
Authors: Nanobashvili J. , Neumayer C. , Fuegl A. , Blumer R. , Prager M. , Sporn E. , Polterauer P. , Malinski T. , Huk I.
Published: August 2003

Background/Aim: Local blood flow failure (no-reflow phenomenon) during ischemia/reperfusion (I/R) injury may be mediated by interstitial edema formation (passive vasoconstriction) and/or microvascular spasm (active vasoconstriction). The development of the no-reflow phenomenon in the rabbit hind limb I/R model and the influence of treatment with L-arginine and/or antioxidative vitamins were investigated. Methods: Untreated rabbits were compared with those treated with L-arginine (4 mg/kg/min) or antioxidative vitamins (0.4 ml/kg) alone or in combination during hind limb I/R (2.5/2 h). Interstitial edema formation and microvessel diameter alterations were measured morphometrically. Capillary blood perfusion was measured continuously with laser Doppler flowmetry. Results: I/R injury was expressed by interstitial edema formation (interstitial space increase by 80%), microvascular constriction (microvessel cross-sectional area decrease by 30%), and development of no-reflow phenomenon (blood flow reduction by 60%). Treatment with antioxidative vitamins alone or L-arginine alone reduced interstitial edema by 22 and 31%, consequently, while combined L-arginine/antioxidative vitamin treatment showed a more pronounced edema reduction by 40%. Treatment with only antioxidative vitamins failed to influence the development of no-reflow, although interstitial edema formation was reduced. L-Arginine treatment alone or in combination with antioxidative vitamins prevented microvascular constriction and preserved blood flow after reperfusion without development of no-reflow despite still apparent interstitial edema. Conclusions: Affections of active vasomotility and not merely passive changes of external pressure (i.e., interstitial edema formation) should be considered important in the development of microvascular constriction during ‘no-reflow’ phenomenon.
Absence of a Relationship between the Increased Survival of Skin Grafts Provoked by Additional Spleen Transplantation and the Detection of Donor Chimeric Cells in Rats
Authors: García-Olmo Dolores C. , García-Olmo D. , Ontañón J. , Atiénzar M. , García-Rivas María
Published: August 2003

The goal of this study was to examine the relationship between the effects of spleen transplantation on the acceptance of a skin allograft from the same donor and the detection of donor chimerism in recipient tissues. Male Sprague-Dawley rats and female Wistar rats were used as donors and recipients, respectively. Four experimental groups were established: group C: only skin grafting was performed; group S: recipients were splenectomized before skin grafting; group 1: skin grafts were performed immediately after splenectomy of recipients and spleen transplantation, and group 2: splenectomy of the recipients and spleen grafting were performed 48 h before skin grafting. All animals were sacrificed 14 weeks after surgery. The rate of acceptance of skin grafts was significantly higher in animals that received both skin and spleen transplantations than in group C (p = 0.03) or in group S (p = 0.04). Detection of donor chimeric cells was significantly more frequent in rats after spleen transplantation than in group C (p = 0.03). However, the detection of chimeric cells was not related to the acceptance of skin grafts. To conclude, the beneficial effect of spleen auxiliary transplantation on allograft survival was not related to the detection of long-term chimerism in the recipient’s tissues.
A Rat Model for Severe Limb Ischemia at Rest
Authors: Lundberg G. , Luo F. , Blegen H. , Kalin B. , Wahlberg E.
Published: August 2003

We sought an animal model able to discriminate metabolic and angiogenic processes in limb ischemia. For that we modified and evaluated a rat model of severe unilateral limb ischemia at rest. A two-stage surgical procedure entailing left femoral artery ligation preceded by interruption of collateral vessels originating from the infra-renal aorta and left iliac arteries was performed in Sprague-Dawley rats. The model was evaluated for up to 8 weeks with a transit-time flow meter, a laser Doppler perfusion imager, microspheres, arteriography and histology. It was found to be well tolerated with low mortality and perfusion in the foot skin was reduced up to 8 weeks, while collaterals were visible after 2 weeks. Histologic signs of ischemia were seen for up to 4 weeks. This rat model of severe limb ischemia at rest lasts up to 8 weeks and seems well suited for longitudinal studies of the pathophysiology of limb ischemia and healing mechanisms like angio- and arteriogenesis.
A Comparison of the Haemostatic Effect of Vivostat® Patient-Derived Fibrin Sealant with Oxidised Cellulose (Surgicel®) in Multiple Surgical Procedures
Authors: Hanks J.B. , Kjaergard H.K. , Hollingsbee D.A.
Published: August 2003

Aim: To evaluate the haemostatic properties of Vivostat® patient-derived fibrin sealant in a broad range of surgical procedures. Method: In a prospective, randomised, multicentre, clinical study, typical surgical wounds of 69 patients (cardiothoracic, general, obstetric and gynaecologic, and vascular), requiring intervention to control bleeding, were treated with either Vivostat-derived sealant (n = 35) or Surgicel® (n = 34) as required and the time taken to arrest bleeding was assessed. Results: Compared with Surgicel, the mean time to haemostasis of Vivostat-derived sealant was significantly shorter (1.6 vs. 3.3 min, p < 0.0001) and more patients were successfully treated (i.e. no additional haemostatic measures required; 94 vs. 65%, p = 0.003). Conclusion: Vivostat-derived sealant is a more reliable and rapidly effective surgical haemostat than Surgicel.
Vypro II® Mesh in Hernia Repair: Impact of Polyglactin on Long-Term Incorporation in Rats
Authors: Rosch R. , Junge K. , Quester R. , Klinge U. , Klosterhalfen B. , Schumpelick V.
Published: August 2003

Background: To the Vypro II® mesh, a large-pore-sized multifilamentous polypropylene mesh for hernia repair, supplementary polyglactin 910 multifilaments were added to improve intraoperative handling. As it has been suggested that polyglactin induces fibroplastic reactions and wound complications, this study was designed to evaluate the long-term tissue reaction to polyglactin in the Vypro II mesh. Materials and Methods: Two mesh materials, the Vypro II composite mesh (PP + PG) and the pure polypropylene variant (PP), were compared after inlay implantation in a standardized rodent animal model. After 14, 28, 42, 56, 84 and 112 days of implantation, histological analysis of the inflammatory response was performed: material absorption, inflammatory tissue reaction, fibrosis and granuloma formation were investigated. Results: Total absorption of polyglactin filaments of the Vypro II mesh occurred between 56 and 84 days of implantation. Both the inflammatory and the fibrotic reaction were initially increased in the PP + PG mesh group. These differences disappeared in the following implantation period. After 112 days, inflammation was even less pronounced in the PP + PG mesh group. Conclusion: The present data confirm a short-term polyglactin-induced increase in inflammation and fibrosis around implanted Vypro II meshes in rats. With regard to the long-term tissue response, even an anti-inflammatory property of polyglactin multifilaments in low-weight and large-pored polypropylene meshes cannot be ruled out.
Perioperative Serum Procalcitonin Concentrations in Patients with Acute Aortic Dissection
Authors: Kin H. , Kawazoe K. , Nakajima T. , Niinuma H. , Kataoka T. , Endo S. , Inada K.
Published: August 2003

We investigated the perioperative serum procalcitonin (PCT) concentrations in 5 consecutive patients who underwent surgery for acute aortic dissection (2 men, 3 women; mean age 72 ± 9 years, age range 52–81 years). Surgery used cardiopulmonary bypass with deep hypothermic circulatory arrest. Blood samples were taken prior to surgery, upon arrival in the intensive care unit, and 6, 12, 18, 24, and 48 h after intensive care unit arrival. Prior to surgery, the PCT level was 4.2 ± 3.4 (range 0.8–8.3) ng/ml. The PCT increase was greatest at 24 h (5.8 ± 4.5 ng/ml). Preoperatively, the C-reactive protein concentration was 8.0 ± 8.3 (range 0.9–23.8) mg/dl, and the white blood cell count was 8.5 ± 3.1 × 103. C-reactive protein continued to increase at 48 h, while the white blood cell count peaked at 24 h. In spite of no symptoms of infectious diseases or septicemia, all patients had a significant preoperative PCT elevation. This finding may have something to do with the specific preoperative condition of acute aortic dissection. However, more clinical investigation is needed to clarify the PCT changes during and after surgery for acute aortic dissection.
Therapeutic Efficacy of Magnesium in Acoustic Trauma in the Guinea Pig
Authors: Haupt Heidemarie , Scheibe Fred , Mazurek Birgit
Published: August 2003

Comparative functional and morphological tests were performed in two groups of impulse noise-exposed guinea pigs treated either with magnesium (Mg) or isotonic saline as a placebo to extend the knowledge on the therapeutic efficacy of Mg in acoustic trauma demonstrated recently. The permanent threshold shifts were significantly lower in the Mg than in the placebo group as measured by auditory brainstem response audiometry, distortion product otoacoustic emissions and compound action potentials (CAPs) 1 week after exposure. This also applies to the damage to hair cell stereocilia tested with scanning electron microscopy. There were frequency-related differences in the individual functional responses. The CAP threshold shifts reflected the morphological damage most obviously.
Immunohistochemical Evidence of nNOS and Changes after Intraglandular Application of Botulinum Toxin A in Cephalic Salivary Glands of Adult Rats
Authors: Ellies Maik , Laskawi Rainer , Schütz Sebastian , Quondamatteo Fabio
Published: August 2003

The purpose of our study was to investigate the possible influence of local injections of botulinum toxin A on the activity of neuronal nitric oxide synthase (nNOS) in cephalic salivary glands of adult rats. The role of nitric oxide (NO) as a possible neuromodulator of vascular regulation and in particular regulation of secretion in the upper respiratory and aerodigestive tract is discussed. We present immunohistochemical evidence of nNOS in the salivary glands of female adult Wistar rats, both in native (untreated) glands and after intraglandular injection of botulinum toxin A under general anesthesia. Other than in the untreated glands, there was a significant decrease in nNOS in the treated organs which became stronger with extended toxin exposure time. After our laboratory had already shown a decrease in acetylcholinesterase immunoreactivity after injection of botulinum toxin A into the cephalic salivary glands of the rat, the present study discusses a possible participation of NO in the regulation of secretion from these organs. As a conclusion, it might be assumed that the influence of botulinum toxin A on nNOS in the cephalic salivary glands of the rat is able to explain the sometimes longer duration of the toxin effect at the neuroglandular junction than at the motor endplate.
Combination Radiation and Adenovirus-Mediated p16INK4A 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 p16INK4A gene transfer has shown limited promise in preclinical studies, we developed a strategy combining ionizing radiation (x-rays) with Ad-p16 gene therapy. Both radiation (2 Gy) and Ad-p16 alone demonstrated anti-tumor responses. The combination of radiation and Ad-p16 in vitro showed an augmented therapeutic response. Two head and neck squamous cell carcinoma (HNSCC) cell lines treated with Ad-p16 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-p16, 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-p16 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

Background: 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. Methods: Trauma to the cochlea was created with a vibrating probe placed on the bone of the external ear canal. BDNF and CNTFA×1 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). Results: 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+CNTFA×1-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. Conclusions: Local infusion of BDNF and CNTFA×1 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.
Detection of Viral DNA in the Endolymphatic Sac in Ménière’s Disease by in situ Hybridization
Authors: Yazawa Yoshiro , Suzuki Mikio , Hanamitsu Masakazu , Kimura Hiroshi , Tooyama Ikuo
Published: August 2003

The main purpose of this study is to search for a viral etiology in Ménière’s disease by examining the presence or absence of herpes family virus DNA in the endolymphatic sac (ES) using the in situ hybridization method. This was a prospective study with the ES from 10 patients with Ménière’s disease and from 7 control cases without any pre-mortem ear diseases except a case of acoustic tumor. These 10 patients underwent the ES surgery. The presence of herpes family virus DNA, such as herpes simplex virus types 1 and 2 (HSV1&2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and human cytomegalovirus (CMV), was examined using the in situ hybridization method. Serum antibody titers against these viruses just before the ES surgery were studied in these patients. Of the 10 specimens from the patients with Ménière’s disease, 7 were positive for VZV, 4 for EBV, 1 for CMV and none for HSV1&2, although the serum antibody titers against these viruses did not show any significant elevation in these patients just before the ES surgery. This result suggests that the viral DNA in the ES is inactive and is present in a latent form. From the statistical analysis, it can be postulated that VZV infection in early childhood may reach the ES and play a role in the pathogenesis of Ménière’s disease (p = 0.0235). The double infection with both VZV and EBV tended to be another candidate for the pathogenesis of Ménière’s disease (p = 0.0557).
Fat Augmentation following Microsurgical Removal of the Vocal Nodules: Long-Term Results
Authors: Hsiung Ming-Wang , Lin Yaoh-Shiang , Su Wan-Fu , Lee Jin-Chin , Wang Hsing-Won
Published: August 2003

While the effectiveness of autogenous fat augmentation after microsurgical removal (FAMSR) of the vocal nodules (VN) has been previously shown in patient treatment programs, relatively little information is available regarding the long-term effectiveness of such a procedure. This paper examines, in retrospect, the long-term effectiveness of FAMSR in patients with VN (n = 41) using pre- and post-FAMSR perceptual acoustic and phonatory function data and videolaryngostroboscopic findings for 33 patients. The mean follow-up time was 18 months. Thirty-three (80.4%) patients displayed excellent results; 4 (9.8%) experienced improvement, and 4 (9.8%) postprocedure failure. Patient phonatory functions showed significant improvements in shimmer, harmonic-to-noise ratio, phonation time (p < 0.05), grade, roughness and breathiness (p < 0.001). The videolaryngostroboscopic rating showed significant improvements in vocal fold edge linearity, vocal fold vibration amplitude, and mucosal wave excursion (p < 0.001). Improvements observed through long-term follow-up tended to be less dramatic in patients with recurrent VN than those with nonrecurrent VN. FAMSR is an easy, safe, and fast procedure which should be considered as an option in treating VN patients who either require surgery or do not have the time or perseverance to complete a lengthy program of speech therapy.
Fat Augmentation for Nonparalytic Glottic Insufficiency
Authors: Chen Yen-Yu , Pai Lu , Lin Yaoh-Shiang , Wang Hsing-Won , Hsiung Ming-Wang
Published: August 2003

While autogenous fat augmentation for glottic insufficiency has been used before, relatively little information is currently available on the effectiveness of fat injection in patients with nonparalytic glottic insufficiency resulting from problems such as various defects of vocal atrophy or sulcus vocalis. This paper compares retrospectively the efficiency of fat injection after surgery in patients with vocal atrophy (n = 16) and sulcus vocalis (n = 8). The perceptual acoustic and phonatory functions and videolaryngostroboscopic data were evaluated before and after fat augmentation in 24 patients. The mean follow-up time was 19.5 months. Fifteen patients displayed excellent results; 1 showed some improvement; 6 experienced postprocedure failure, and 2 were not available for follow-up analysis. Perceptual rating showed significant improvement in grade, roughness and breathiness (p < 0.05). The videolaryngostroboscopic rating showed significant improvements in vocal fold edge linearity, vocal fold vibration amplitude and mucosal wave excursion (p < 0.05). More improvement in vocal atrophy was observed compared with sulcus vocalis following fat injection procedures. Our research showed that middle defects improved more compared to those in the anterior and posterior area. Fat injection is an effective autogenous implant and may be considered as an option in the treatment of patients with vocal atrophy or sulcus vocalis. Although fat reabsorption was a problem, repeating the procedure could be considered.
Changes in Vowel Quality after Cochlear Implantation
Authors: Schenk Barbara S. , Baumgartner Wolf-Dieter , Hamzavi Jafar S.
Published: August 2003

Since auditory feedback is partially restored after cochlear implantation, the aim of the present study was to investigate features of vowels, which reflect improvements in speech production. Ten postlingually deafened subjects (5 male/5 female) were recorded reading a German text before and 3 and 12 months after implantation, respectively. Selected vowels were analysed regarding the fundamental frequency (F₀), the formant frequencies (F1, F2, F3) and the vowel space (difference between F1 and F2 in hertz). The F₀ decreased only descriptively after 3 and 12 months, respectively. F1 of the vowel /e/ was significantly lower after 12 months (411 ± 20 compared to 349 ± 25 Hz, p ≤ 0.05) and for /o/ after 3 months (446 ± 29 compared to 408 ± 31 Hz, p ≤ 0.05) for the male patients: their vowel space also expanded significantly for the vowel /o/ (372 ± 37 compared to 467 ± 32 Hz, p ≤ 0.05) after 12 months. Regained auditory feedback after cochlear implantation had an effect on the improvement of the production of vowels.
Adding Further Power to the Haseman and Elston Method for Detecting Linkage in Larger Sibships: Weighting Sums and Differences
Authors: Shete Sanjay , Jacobs Kevin B. , Elston Robert C.
Published: August 2003

Haseman and Elston (H-E) proposed a robust test to detect linkage between a quantitative trait and a genetic marker. In their method the squared sib-pair trait difference is regressed on the estimated proportion of alleles at a locus shared identical by descent by sib pairs. This method has recently been improved by changing the dependent variable from the squared difference to the mean-corrected product of the sib-pair trait values, a significantly positive regression indicating linkage. Because situations arise in which the original test is more powerful, a further improvement of the H-E method occurs when the dependent variable is changed to a weighted average of the squared sib-pair trait difference and the squared sib-pair mean-corrected trait sum. Here we propose an optimal method of performing this weighting for larger sibships, allowing for the correlation between pairs within a sibship. The optimal weights are inversely proportional to the residual variances obtained from the two different regressions based on the squared sib-pair trait differences and the squared sib-pair mean-corrected trait sums, respectively, allowing for correlations among sib pairs. The proposed method is compared with the existing extension of the H-E approach for larger sibships. Control of the type I error probabilities for sibships of any size can be improved by using a generalized estimating equation approach and the robust sandwich estimate of the variance, or a Monte-Carlo permutation test.
Regression Models for Linkage: Issues of Traits, Covariates, Heterogeneity, and Interaction
Authors: Schaid Daniel J. , Olson Jane M. , Gauderman W. James , Elston Robert C.
Published: August 2003

Regression methods offer a common framework to analyze linkage for quantitative trait loci as well as linkage for affection status using affected sib-pairs. Although numerous papers on regression methods for linkage have been published, some common themes and important caveats tend to be scattered across the literature. For example, the typical approach is to regress a function of traits on identical-by-descent (IBD) information, but the reversal (regression of IBD on a function of traits) offers important insights. A second example is the use of regression equations to assess linkage heterogeneity or gene-environment interaction, and why these two different etiologies are difficult to distinguish with affected sib-pair data. A third example has to do with the differences, and similarities, between linear regression and non-linear regression methods for affected sib-pair data. The purposes of this paper are to review some recent developments in the linkage regression framework, to emphasize strengths and weaknesses of various proposed methods, and to highlight some important assumptions and caveats.
X-Linked Extension of the Revised Haseman-Elston Algorithm for Linkage Analysis in Sib Pairs
Authors: Wiener Howard , Elston Robert C. , Tiwari Hemant K.
Published: August 2003

Haseman and Elston (H-E) proposed a regression-based robust test of linkage between a marker and an autosomal quantitative trait locus, using the squared sib pair trait difference as a dependent variable and the proportion of alleles shared identical by descent by the sib pair as an independent variable. Several authors have proposed improvement of the original H-E’s seminal work by using an optimal linear combination of squared sum and squared difference as the dependent variable. In this paper, we extend Haseman and Elston’s sib pair method to an X-linked locus. We give a general formulation of the complete regression model and details of the regression coefficients in terms of variance components. Simulation results are presented to describe the power of this technique for a theoretical best case scenario.
Effect of Box-Cox Transformation on Power of Haseman-Elston and Maximum-Likelihood Variance Components Tests to Detect Quantitative Trait Loci
Authors: Etzel C.J. , Shete S. , Beasley T.M. , Fernandez J.R. , Allison D.B. , Amos C.I.
Published: August 2003

Non-normality of the phenotypic distribution can affect power to detect quantitative trait loci in sib pair studies. Previously, we observed that Winsorizing the sib pair phenotypes increased the power of quantitative trait locus (QTL) detection for both Haseman-Elston (HE) least-squares tests [Hum Hered 2002;53:59–67] and maximum likelihood-based variance components (MLVC) analysis [Behav Genet (in press)]. Winsorizing the phenotypes led to a slight increase in type 1 error in H-E tests and a slight decrease in type I error for MLVC analysis. Herein, we considered transforming the sib pair phenotypes using the Box-Cox family of transformations. Data were simulated for normal and non-normal (skewed and kurtic) distributions. Phenotypic values were replaced by Box-Cox transformed values. Twenty thousand replications were performed for three H-E tests of linkage and the likelihood ratio test (LRT), the Wald test and other robust versions based on the MLVC method. We calculated the relative nominal inflation rate as the ratio of observed empirical type 1 error divided by the set α level (5, 1 and 0.1% α levels). MLVC tests applied to non-normal data had inflated type I errors (rate ratio greater than 1.0), which were controlled best by Box-Cox transformation and to a lesser degree by Winsorizing. For example, for non-transformed, skewed phenotypes (derived from a χ2 distribution with 2 degrees of freedom), the rates of empirical type 1 error with respect to set α level = 0.01 were 0.80, 4.35 and 7.33 for the original H-E test, LRT and Wald test, respectively. For the same α level = 0.01, these rates were 1.12, 3.095 and 4.088 after Winsorizing and 0.723, 1.195 and 1.905 after Box-Cox transformation. Winsorizing reduced inflated error rates for the leptokurtic distribution (derived from a Laplace distribution with mean 0 and variance 8). Further, power (adjusted for empirical type 1 error) at the 0.01 α level ranged from 4.7 to 17.3% across all tests using the non-transformed, skewed phenotypes, from 7.5 to 20.1% after Winsorizing and from 12.6 to 33.2% after Box-Cox transformation. Likewise, power (adjusted for empirical type 1 error) using leptokurtic phenotypes at the 0.01 α level ranged from 4.4 to 12.5% across all tests with no transformation, from 7 to 19.2% after Winsorizing and from 4.5 to 13.8% after Box-Cox transformation. Thus the Box-Cox transformation apparently provided the best type 1 error control and maximal power among the procedures we considered for analyzing a non-normal, skewed distribution (χ2) while Winzorizing worked best for the non-normal, kurtic distribution (Laplace). We repeated the same simulations using a larger sample size (200 sib pairs) and found similar results.
Efficiency Robust Tests for Mapping Quantitative Trait Loci Using Extremely Discordant Sib Pairs
Authors: Freidlin Boris , Zheng Gang , Li Zhaohai , Gastwirth Joseph L.
Published: August 2003

In 1972, Haseman and Elston proposed a pioneering regression method for mapping quantitative trait loci using randomly selected sib pairs. Recently, the statistical power of their method was shown to be increased when extremely discordant sib pairs are ascertained. While the precise genetic model may not be known, prior information that constrains IBD probabilities is often available. We investigate properties of tests that are robust against model uncertainty and show that the power gain from further constraining IBD probabilities is marginal. The additional linkage information contained in the trait values can be incorporated by combining the Haseman-Elston regression method and a robust allele sharing test.
Regression-Based Sib Pair Linkage Analysis for Binary Traits
Authors: Zeegers Maurice P.A. , Rice John P. , Rijsdijk Frühling V. , Abecasis Goncalo R. , Sham Pak C.
Published: August 2003

The Haseman-Elston (HE) regression method offers a mathematically and computationally simpler alternative to variance-components (VC) models for the linkage analysis of quantitative traits. However, current versions of HE regression and VC models are not optimised for binary traits. Here, we present a modified HE regression and a liability-threshold VC model for binary-traits. The new HE method is based on the regression of a linear combination of the trait squares and the trait cross-product on the proportion of alleles identical by descent (IBD) at the putative locus, for sibling pairs. We have implemented both the new HE regression-based method and have performed analytic and simulation studies to assess its type 1 error rate and power under a range of conditions. These studies showed that the new HE method is well-behaved under the null hypothesis in large samples, is more powerful than both the original and the revisited HE methods, and is approximately equivalent in power to the liability-threshold VC model.
Information Perspectives of the Haseman-Elston Method
Authors: Wright Fred A.
Published: August 2003

The Haseman-Elston regression approach can be viewed as a special case in a larger framework in which independent sibling pairs are ascertained, perhaps based on their phenotypes. Using likelihood arguments in an idealized setting, expressions are obtained for the inherent linkage information contained in the phenotype distributions. The results provide insight and analytic results that apply to general phenotype distributions and can be used to judge the effects of various data transformations and selective sampling of extreme phenotypes.
A Simple Nonparametric Test for Linkage with Sib-Pair Censored Event Time Observations
Authors: Wei Eric , Wei L.J. , Xu Xin
Published: August 2003

Consider the case that individual phenotype and genotype observations were collected from a large or moderate number of pedigrees. Some of the pedigrees have multi-generation nuclear families. For each nuclear family, the phenotype trait value of each sibling is the time to onset for a specific event (e.g., disease). Often, this event time may be right censored, that is, an individual is event-free at the study examination time point. In this article, we propose a purely nonparametric test for testing if the distribution of a Haseman-Elston distance measure between two siblings’ event times is independent of their mean genetic sharing identical by descent at a genetic marker based on such incomplete observations from all the nuclear families. The new test can be implemented easily and is illustrated with a data set from the Genetic Analysis Workshop 12. The validity of the new test is examined via a simulation study.
A Method for Evaluating the Results of Bayesian Model Selection: Application to Linkage Analyses of Attributes Determined by Two or More Genes
Authors: Suh Young Ju , Ye Kenny Q. , Mendell Nancy R.
Published: August 2003

Objectives: We apply and evaluate the intrinsic Bayes factor (IBF) of Berger and Pericchi [J Am Stat Assoc 1996;91:109–122; Bayesian Statistics, Oxford University Press, vol 5, 1996] to linkage analyses done using the stochastic search variable selection (SSVS) method of George and McCulloch [J Am Stat Assoc 1993;88:881–889] as proposed by Suh et al. [Genet Epidemiol 2001;21(suppl 1):S706–S711]. Methods: We consider 20 simulations of linkage data obtained under two different generating models. The SSVS is applied to a multiple regression extension [Genet Epidemiol 2001;21(suppl 1): S706–S711] of the Haseman-Elston [Behav Genet 1972;2:3–19; Genet Epidemiol 2000;19:1–17] methods. Four prior distributions are considered. We apply the IBF criterion to those samples where different prior distributions result in different top models. Results: In those samples where three different models were obtained using the four priors, application of the IBFs eliminated one of the two wrong models in 4 out of 5 situations. Further elimination using the IBF criterion for situations with two different subsets did not serve as well. Conclusions: When different priors result in three or more different subsets of markers, one can use the IBF to get this number down to two for consideration. When two subsets result we recommend that both be considered.
AFP-Producing Gastric Carcinoma: Multivariate Analysis of Prognostic Factors in 270 Patients
Authors: Adachi Yosuke , Tsuchihashi Junko , Shiraishi Norio , Yasuda Kazuhiro , Etoh Tsuyoshi , Kitano Seigo
Published: August 2003

Serum α-fetoprotein (AFP) is sometimes high in patients with primary gastric carcinoma, and there is no comprehensive study on the clinicopathologic characteristics and prognostic factors of AFP-producing gastric carcinoma (AGC). To clarify the variables associated with the survival after gastrectomy for AGC, we reviewed the data of patients with AGC and examined the independent prognostic factors. We studied 270 cases of AGC reported in the Japanese literature from June 1982 to March 2001, together with 1 patient of our own experience. The clinicopathologic findings, including serum AFP level, operative curability, and stage of the disease were examined, and factors associated with survival were determined by multivariate analysis. There were 15 stage I tumors (6%), 50 stage II tumors (19%), 51 stage III tumors (20%), and 145 stage IV tumors (55%). The tumors were characterized by frequent serosal invasion (75%), lymph node metastasis (83%), liver metastasis (33%), stage III or IV disease (75%), and noncurative operation (48%). The survival was influenced by the serum AFP level, tumor size, serosal invasion, lymph node metastasis, and liver metastasis, but the independent prognostic factors were operative curability (curative vs. noncurative) and stage of the disease (I, II vs. III, IV). Although the 5-year survival rate and median survival period in all patients were 22% and 14 months, respectively, those in patients with curative gastrectomy were 42% and 29 months, respectively. The results indicate that operative curability and stage of the disease are factors associated with the survival of patients with AGC. Although tumors are often advanced and complicated with liver metastases, long-term survival can be achieved when patients with stage I or II tumor undergo curative gastrectomy.
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

Objective: We performed a phase I clinical study to evaluate combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin (CPT-11/nedaplatin) for cervical cancer. Methods: 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/m2, respectively. Dose escalation was performed in tandem. Plasma CPT-11, SN-38, total platinum, and filterable platinum levels were measured. Results: In step 3 (CPT-11, 60 mg/m2; nedaplatin, 60 mg/m2), 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/m2 and 0.17 at 60 mg/m2. Following nedaplatin administration, the mean AUCs (µg·h/ml) of filterable platinum were 6.0 at 50 mg/m2, and 6.0 at 60 mg/m2. The response rate was 50% (2 complete responses and 2 partial responses). Conclusion: The recommended doses of CPT-11 and nedaplatin for a phase II clinical study were established as 50 and 60 mg/m2, respectively.