bluuebunny/crossref_metadata_2025 huggingface dataset:
Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis
Authors: Moreau Richard , Barrière Eric , Tazi Khalid A. , Lardeux Bernard , Dargère Delphine , Urbanowicz Waldemar , Poirel Odile , Chauvelot-Moachon Laurence , Guimont Marie-Christine , Bernuau Dominique , Lebrec Didier
Published: March 2003

In cirrhosis, lipopolysaccharide (LPS, a product of Gram-negative bacteria) in the blood may cause septic shock. LPS-elicited induction of arterial inducible nitric oxide synthase (iNOS) results in nitric oxide (NO)-induced vasodilation, which causes arterial hypotension and hyporeactivity to α1-adrenergic constrictors. In vitro studies have suggested that vasopressin inhibits iNOS expression in cultured vascular smooth muscle cells exposed to LPS. Thus, the aim of this study was to investigate the effects of terlipressin administration (a vasopressin analog) on in vivo LPS-induced aortic iNOS in rats with cirrhosis. LPS (1 mg/kg, intravenously) was administered followed by the intravenous administration of terlipressin (0.05 mg/kg, intravenously) or placebo 1 hour later. Arterial pressure was measured, and contractions to phenylephrine (an α1-adrenoceptor agonist), iNOS activity, and iNOS expressions (mRNA and protein) were investigated in isolated aortas. LPS-induced arterial hypotension and aortic hyporeactivity to phenylephrine were abolished in rats that received terlipressin. LPS-induced aortic iNOS activity and expression were suppressed in terlipressin-treated rats. In conclusion, in LPS-challenged rats with cirrhosis, terlipressin administration inhibits in vivo LPS-induced aortic iNOS expression. Terlipressin administration may be a novel approach for the treatment of arterial hypotension and hyporeactivity to α1-adrenergic constrictors in patients with cirrhosis and septic shock.
Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C
Authors: Soza Alejandro , Everhart James E. , Ghany Marc G. , Doo Edward , Heller Theo , Promrat Kittichai , Park Yoon , Liang Jake T. , Hoofnagle Jay H.
Published: March 2003

Interferon therapy of hepatitis C causes a decrease in neutrophil counts, and neutropenia is a common reason for dose adjustment or early discontinuation. However, it is unclear whether neutropenia caused by interferon is associated with an increased rate of infection. In this study, we assessed factors associated and clinical consequences of neutropenia before and during interferon therapy of chronic hepatitis C. A total of 119 patients with chronic hepatitis C treated with the combination of interferon alfa and ribavirin were analyzed. In these studies, neutropenia was not used as an exclusion or dose modification criterion. In multivariate analysis, only black race was associated with baseline neutropenia. During treatment, neutrophil counts decreased by an average of 34%. Among 3 blacks with baseline neutropenia without cirrhosis or splenomegaly, there was little or no decrease in neutrophil counts (despite typical decreases in platelet and lymphocyte counts). Documented or suspected bacterial infections developed in 22 patients (18%), but in no patient with neutropenia. United States population estimates suggest that 76,000 blacks with hepatitis C have neutrophil counts below 1,500 cells/μL and might be denied therapy if this exclusion criterion was generally applied. In conclusion, neutropenia is frequent during treatment of hepatitis C with interferon and ribavirin, but it is not usually associated with infection. Constitutional neutropenia, which is common among blacks, should not exclude patients from therapy with interferon as these patients usually have minimal further decreases in neutrophil counts on therapy and are not excessively prone to bacterial infections.
HBV superinfection in hepatitis C virus chronic carriers, viral interaction, and clinical course
Authors: Sagnelli Evangelista , Coppola Nicola , Messina Vincenzo , di Caprio Domenico , Marrocco Cecilia , Marotta Anna , Onofrio Mirella , Scolastico Carlo , Filippini Pietro
Published: March 2003

We enrolled 44 patients with hepatitis B virus (HBV) acute infection, 21 anti-hepatitis C virus (HCV)-positive for at least 1 year (case BC group), 20 anti-HCV-negative (control B group), and 3 with HBV/HCV acute concurrent infection. For each case BC, a subject with chronic HCV infection alone was selected (control C group). At the first observation, 85.7% of patients in case BC group and 85% of those in control B group were HBV-DNA-positive (polymerase chain reaction [PCR]), with a similar trend towards a decrease and negativization in about 20 days; in the case BC group, seroconversion to antibody to hepatitis B e antigen (anti-HBe) was more rapid. HCV-RNA (PCR) was undetectable in all case BC patients but 1, who shortly became negative, whereas 85.7% of subjects in control C group were positive (P < .001). Severe acute hepatitis was more frequent in the case BC group than in the control B group (28.6% vs. 0%, P < .05). Of the 14 patients in the case BC group and of the 16 in the control B group followed up for more than 6 months, 1 in the first and 1 in the second group became hepatitis B surface angiten (HBsAg) chronic carriers. Of the 13 patients in case BC group who recovered, 1 cleared both anti-HCV and HCV-RNA, 6 became HCV-RNA-positive, and 6 remained HCV-RNA-negative. In patients with HBV/HCV acute concurrent infection, HBV-DNA became undetectable in 15 days, and HCV-RNA and anti-HCV became positive at days 30 and 45, respectively; these patients developed HCV-RNA-positive chronic hepatitis. In conclusion, HBV superinfection in chronic HCV carriers has a severe clinical course and strongly and persistently depresses HCV.
Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus
Authors: Hassan Manal M. , Hwang Lu-Yu , Hatten Chiq J. , Swaim Mark , Li Donghui , Abbruzzese James L. , Beasley Palmer , Patt Yehuda Z.
Published: March 2003

Risk factors associated with hepatocellular carcinoma (HCC) are well documented, but the synergisms between these risk factors are not well examined. We conducted a hospital-based, case-control study among 115 HCC patients and 230 non-liver cancer controls. Cases and controls were pathologically diagnosed at The University of Texas M. D. Anderson Cancer Center and were matched by 5-year age groups, sex, and year of diagnosis. Information on risk factors was collected by personal interview and medical records review. Blood samples were tested for the presence of antibodies to hepatitis C virus antigen (anti-HCV), hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (anti-HBc). Conditional logistic regression was used to determine odds ratios (ORs) by the maximum likelihood method. Multivariate ORs and 95% confidence intervals (CIs) were 15.3 (4.3-54.4), 12.6 (2.5-63.1), 4.5 (1.4-14.8), and 4.3 (1.9-9.9) for anti-HCV, HBsAg, heavy alcohol consumption (≥80 mL ethanol/d), and diabetes mellitus, respectively. Synergistic interactions on the additive model were observed between heavy alcohol consumption and chronic hepatitis virus infection (OR, 53.9; 95% CI, 7.0-415.7) and diabetes mellitus (OR, 9.9; 95% CI, 2.5-39.3). Independent of the effect of HCV, HBV, and diabetes mellitus, heavy alcohol consumption contributes to the majority of HCC cases (32%), whereas 22%, 16%, and 20% were explained by HCV, HBV, and diabetes mellitus, respectively. In conclusion, the significant synergy between heavy alcohol consumption, hepatitis virus infection, and diabetes mellitus may suggest a common pathway for hepatocarcinogenesis. Exploring the underlying mechanisms for such synergisms may indicate new HCC prevention strategies in high-risk individuals.
High-dose tamoxifen in the treatment of inoperable hepatocellular carcinoma: A multicenter randomized controlled trial
Authors: Chow Pierce K. H. , Tai Bee-Choo , Tan Chee-Kiat , Machin David , Win Khin Maung , Johnson Phillip J. , Soo Khee-Chee
Published: March 2003

In the Asia-Pacific region and elsewhere, almost 85% of patients with hepatocellular carcinoma (HCC) are inoperable at diagnosis and have a dismal prognosis. Tamoxifen (TMX) is believed to inhibit HCC positive for estrogen receptor (ER), but most HCCs are ER negative. Results of previous phase 3 trials in inoperable HCC have been conflicting and inconclusive. At higher doses, however, TMX inhibits HCC through ER-independent mechanisms. A multicenter randomized controlled trial was performed to assess the role of high-dose TMX versus placebo (P) in the treatment of patients with inoperable HCC with respect to survival and quality of life (QoL). A total of 329 patients from 10 centers in 9 countries in the Asia-Pacific region enrolled in a double-blind randomized controlled trial of TMX 120 mg/d (TMX120) against P as a control arm with an intermediate dosage of TMX 60 mg/d (TMX60) to assess possible dose response. An independent data monitoring committee reviewed all aspects of the trial. QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. Three-month survival rates for the P, TMX60, and TMX120 groups were 44%, 41%, and 35%, respectively, with a statistically significant trend difference in survival across the 3 treatment regimens (P = .011). There was a significantly higher risk of death in the TMX120 group compared with the P group (hazard ratio, 1.39; 95% confidence interval, 1.07-1.81). Adverse drug reactions were reported in 3% (9 patients), and 8 patients were lost to follow-up. In conclusion, TMX does not prolong survival in patients with inoperable HCC and has an increasingly negative impact with increasing dose. No appreciable advantage to QoL with TMX was observed.
Clopidogrel but not aspirin reduces P‐selectin expression and formation of platelet‐leukocyte aggregates in patients with atherosclerotic vascular disease*
Authors: Klinkhardt Ute , Bauersachs Rupert , Adams Jan , Graff Jochen , Lindhoff‐Last Edeltraud , Harder Sebastian
Published: March 2003

Formation of platelet‐leukocyte aggregates via the CD62 ligand represents an important mechanism by which leukocytes contribute to thrombotic events. In a cross‐sectional study, we investigated platelet‐leukocyte aggregate formation and markers indicative for platelet, leukocyte, and endothelial activation (CD62, activated fibrinogin receptor glycoprotein IIb/IIIA [PAC‐1], CD11b/CD18 [MAC‐1], and soluble intercellular adhesion molecule 1) in 44 patients with atherosclerotic vascular disease and peripheral occlusions receiving clopidogrel (n = 12), aspirin (n = 17), their combination (n = 8), or no treatment (n = 7), as well as in a group of healthy subjects (n = 9). Whole‐blood flow cytometry was performed before (baseline) and after stimulation with thrombin receptor‐activating peptide or adenosine diphosphate. Both at baseline and after stimulation, untreated patients and those receiving aspirin monotherapy exhibited significantly higher levels of platelet CD62 expression (baseline CD62: untreated, 22% [median]; with aspirin, 16%) and had higher rates of platelet‐leukocyte aggregate formation (monocyte‐platelet‐leukocyte aggregates at baseline: untreated, 27%; with aspirin, 16%) when compared with patients receiving clopidogrel alone (baseline CD62: 10% [P < .05]; monocyte‐platelet‐leukocyte aggregates: 13% [P < .05]) or combined with aspirin (baseline CD62: 5% [P < .05]; monocyte‐platelet‐leukocyte aggregates: 7% [P < .05]). Up‐regulation of MAC‐1 on monocytes after stimulation with thrombin receptor‐activating peptide and adenosine diphosphate was significantly lower in patients treated with clopidogrel and aspirin. Plasma levels of soluble intercellular adhesion molecule 1 were significantly lower in the group of healthy subjects (median, 186 ng/mL) when compared with those in untreated patients (median, 352 ng/mL) (P < .05), whereas intercellular adhesion molecule 1 levels in treated patients were similar for any antiplatelet regimen (aspirin, 262 ng/mL; clopidogrel, 274 ng/mL; combination therapy, 273 ng/mL) but significantly lower than those in untreated patients. This is the first report showing that platelet‐leukocyte aggregate formation is enhanced in atherosclerotic vascular disease but was found to be reduced in patients receiving clopidogrel.

Clinical Pharmacology & Therapeutics (2003) 73, 232–241; doi: 10.1067/mcp.2003.13
Use of healthy children as volunteers in drug studies: The ethical debate
Authors: Koren Gideon , Kearns Gregory L. , Reed Michael , Pons Gerrard
Published: March 2003

Clinical Pharmacology & Therapeutics (2003) 73, 147–152; doi: 10.1067/mcp.2003.16
An evaluation of the suitability of intravenous midazolam as an in vivo marker for hepatic cytochrome P4503A activity
Authors: Rogers Janyce F. , Rocci Mario L. , Haughey David B. , Bertino Joseph S.
Published: March 2003

Clinical Pharmacology & Therapeutics (2003) 73, 153–158; doi: 10.1067/mcp.2003.23
Population differences in S‐warfarin metabolism between CYP2C9 genotype‐matched Caucasian and Japanese patients
Authors: Takahashi Harumi , Wilkinson Grant R. , Caraco Yoseph , Muszkat Mordechai , Kim Richard B. , Kashima Toshitaka , Kimura Sosuke , Echizen Hirotoshi
Published: March 2003

Objective

Our objective was to investigate population differences in the metabolic activity of cytochrome P450 (CYP) 2C9 between genotypically matched Caucasian and Japanese patients by using the unbound oral clearance of S‐warfarin as an in vivo phenotypic trait measure.

Methods

Ninety Japanese and 47 Caucasian patients receiving maintenance warfarin therapy were studied. Steady‐state plasma unbound concentrations of S‐warfarin were measured by a chiral HPLC method coupled with an ultrafiltration technique, and unbound oral clearance for S‐warfarin was estimated. By combining plasma unbound concentrations of S‐warfarin with the urinary excretion rates of S‐7‐hydroxywarfarin, the formation clearance of S‐7‐hydroxywarfarin was also determined. Genotyping of CYP2C9 was performed for 6 distinct alleles (CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*4, CYP2C9*5, and a T/C transition in intron 2).

Results

The frequency distribution of unbound oral clearance for S‐warfarin obtained from Japanese patients was shifted toward higher values as compared with that in Caucasian patients. Japanese patients had lower allelic frequencies for the 5 variants than Caucasian patients. When interpopulation comparisons of CYP2C9 activity were made for genotype‐matched subjects, Japanese patients with the homozygous CYP2C9*1 (wild‐type) genotype (n = 85) had significantly (P < .01) greater median values for unbound oral clearance and formation clearance than Caucasian patients with the corresponding genotype (n = 26), 10.4 mL × min−1 × kg−1 versus 4.25 mL × min−1 × kg−1 and 0.015 mL × min−1 × kg−1 versus 0.010 mL × min−1 × kg−1, respectively. In addition, Japanese patients heterozygous for the CYP2C9*3 genotype (n = 4) showed a significantly (P < .05) reduced unbound oral clearance for S‐warfarin, by 63%, as compared with Japanese patients possessing the homozygous CYP2C9*1 genotype. By contrast, in Caucasian patients, no significant differences were observed in this parameter between CYP2C9*1 homozygous subjects and those with heterozygous CYP2C9*2 or CYP2C9*3 genotypes.

Conclusions

These findings indicate that population differences in the frequencies of known variant CYP2C9 alleles account only in part for the variability observed in in vivo CYP2C9 activity in different populations. In addition, a gene‐dose effect of defective CYP2C9 alleles on the in vivo CYP2C9 activity is evident in Japanese patients but not in Caucasian patients. Further studies are required to identify currently unknown factor(s) (eg, transcriptional regulation) responsible for the large intrapopulation and interpopulation variability in CYP2C9 activity.

Clinical Pharmacology & Therapeutics (2003) 73, 253–263; doi: 10.1067/mcp.2003.26
Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers
Authors: Skinner Michael H. , Kuan Han‐Yi , Pan Alan , Sathirakul Korbtham , Knadler Mary Pat , Gonzales Celedon R. , Yeo Kwee Poo , Reddy Shobha , Lim Maggie , Ayan‐Oshodi Mosun , Wise Stephen D.
Published: March 2003

Background and Objectives

Duloxetine, a potent dual reuptake inhibitor of serotonin and norepinephrine currently undergoing clinical investigation for treatment of depression and stress urinary incontinence, has the potential to act as both a substrate and an inhibitor of cytochrome P4502D6 (CYP2D6). Our objectives were to determine the effect of duloxetine on the pharmacokinetics of desipramine, a tricyclic antidepressant metabolized by CYP2D6 (study 1), and the effect of paroxetine, a potent CYP2D6 inhibitor, on duloxetine pharmacokinetics (study 2).

Methods

Subjects were healthy men and women between 21 and 63 years old. All subjects were genotypically CYP2D6 extensive metabolizers. In study 1, 50 mg of desipramine was administered as a single dose alone and in the presence of steady‐state duloxetine 60 mg twice daily. In study 2, steady‐state pharmacokinetics of duloxetine 40 mg once daily were determined in the presence and absence of steady‐state paroxetine 20 mg once daily.

Results

Duloxetine increased the maximum plasma concentration of desipramine 1.7‐fold and the area under the concentration‐time curve 2.9‐fold. Paroxetine increased the maximum plasma concentration of duloxetine and the area under the concentration‐time curve at steady state 1.6‐fold. Reports of adverse events were similar whether duloxetine was administered alone or in combination with desipramine or paroxetine.

Conclusion

Duloxetine 60 mg twice daily is a moderately potent CYP2D6 inhibitor, intermediate between paroxetine and sertraline. The potent CYP2D6 inhibitor paroxetine has a moderate effect on duloxetine concentrations. The results of these 2 studies suggest that caution should be used when CYP2D6 substrates and inhibitors are coadministered with duloxetine.

Clinical Pharmacology & Therapeutics (2003) 73, 170–177; doi: 10.1067/mcp.2003.28
Dizziness: Relating the Severity of Vertigo to the Degree of Handicap by Measuring Vestibular Impairment
Authors: Pérez Nicolás , Martin Eduardo , Garcia‐Tapia Rafael
Published: March 2003

OBJECTIVE

We sought to correlate the severity of vertigo and handicap in patients with vestibular pathology according to measures of impairment.

STUDY DESIGN AND SETTING

We conducted a prospective assessment of patients with dizziness by means of caloric, rotatory test, and computerized dynamic posturography to estimate impairment. Handicap and severity of vertigo were determined with specific questionnaires (Dizziness Handicap Inventory and UCLA‐DQ).

RESULTS

A fair relationship were found between severity of dizziness and vestibular handicap. When impairment was taken into consideration, values were still fair and only moderate for a group of patients with an abnormal caloric test as the only pathologic finding. The composite score from the sensory organization test portion of the computerized dynamic posturography is fairly correlated to severity of vertigo and handicap in the whole population of patients, but no correlation was found when they were assigned to groups of vestibular impairment.

CONCLUSION

To assess vestibular impairment, the results from several tests must be taken into account. However, vestibular handicap is not solely explained with measurements of impairment and/or severity.
Jugular Bulb Diverticula: Clinical and Radiologic Aspects
Authors: Bilgen Cem , Kirazli Tayfun , Ogut Fatih , Totan Secil
Published: March 2003

OBJECTIVE

This study was performed to determine the clinical presentation of jugular diverticulum and its relevance with the extension of the lesion.

STUDY DESIGN

The records and high‐resolution CT scans of 1474 patients, with otologic symptoms or related clinical findings, were evaluated retrospectively. In 17 cases in which CT scans revealed the presence of jugular diverticulum, sensorineural symptoms were evaluated with respect to a reference line, perpendicular to the basal turn of the cochlea and tangent to the vestibule in axial CT scan images.

RESULTS

When the extension of jugular diverticulum was posterior to the reference line, sensorineural symptoms with vertigo were dominant in most patients (72.7%) in this group. On the other hand, for the patients with anterior‐extending jugular diverticulum, sensorineural symptoms without vertigo were detected in 50% of patients, whereas 33.3% had sensorineural symptoms with vertigo.

CONCLUSION

This study revealed a relationship between the extension of jugular diverticulum and clinical symptoms. However, this relationship lacks statistical evidence because of the limited number of patients.
Functional Comparison after Reconstruction with a Radial Forearm Free Flap or a Pectoralis Major Flap for Cancer of the Tongue
Authors: Su Wan‐Fu , Hsia Yi‐Jan , Chang Yen‐Chine , Chen Shyi‐Gen , Sheng Hwa
Published: March 2003

OBJECTIVE

Numerous patients in Taiwan with tongue carcinoma require tongue reconstruction. We compared the abilities of 2 methods of tongue reconstruction to reserve tongue function.

STUDY DESIGN AND SETTING

Sixty patients underwent resection of the tumors and reconstruction with a pectoralis major flap or a radial forearm flap. The Chinese articulation test was used to evaluate the place and manner of error production, and a questionnaire on dietary habits was used to evaluate deglutition 6 months to 10 years after reconstruction.

RESULTS

Patients with the free flap had more intelligible speech. The questionnaire study showed no significant difference between the 2 groups in swallowing rating. Motility caused by flap pliability increased speech intelligibility more than it did on swallowing function.

CONCLUSION

Our experience in a few selected patients shows that the functional outcome of tongue surgery is related to the reconstruction methods used (for speech) and to the extent of tongue resection (for swallowing).
Evaluation of Sleep‐Disordered Breathing in Children
Authors: Sohn Han , Rosenfeld Richard M.
Published: March 2003

OBJECTIVE

We evaluated changes in disease‐specific quality of life (QOL) for children with sleep‐disordered breathing (SDB).

PATIENTS, DESIGN, AND SETTING

We conducted a cohort study in 69 children (age range, 6 months to 13 years; median age, 6.1 years) from a hospital‐based pediatric otolaryngology practice in a metropolitan area. We used the OSA‐18, an 18‐item QOL survey with known test‐retest reliability, internal consistency, and construct validity. Survey domains included sleep disturbance, physical suffering, emotional distress, daytime problems, and caregiver concerns.

INTERVENTION

Tonsillectomy or adenoidectomy was performed as part of routine clinical care. The OSA‐18 was completed at entry by the child's caregiver and again at least 4 weeks after surgery.

MAIN OUTCOME MEASURES

The validity of the OSA‐18 change score was assessed by comparison with multiple external constructs, including a validated measure of longitudinal change (OSD‐6 survey). Responsiveness was assessed by the standardized response mean (SRM).

RESULTS

The mean baseline OSA‐18 survey score was 3.1 (SD, 0.9) of a maximum 7.0, with higher values indicating poorer QOL. Change scores were available for all children, with a mean interval between preoperative and postoperative surveys of 61 days (range, 42 to 92 days). The mean OSA‐18 change score of 1.14 (SD, 0.71) showed significant correlation with tonsil size (r = 0.40), adenoid size (r = 0.31), OSD‐6 change scores (r = 0.71), and the direct caregiver estimates of change (r = 0.34). OSA‐18 change scores showed large responsiveness to change (SRM 1.44; 95% confidence interval, 1.16 to 69), with the most responsive domains being sleep disturbance, physical suffering, and care‐giver concerns. Significant responsiveness was also demonstrated for the domains of daytime problems and emotional distress.

CONCLUSIONS

The OSA‐18 is a valid, reliable, and responsive QOL measure that combines the advantages of a discriminative and evaluative survey in a single instrument. The OSA‐18 is a useful measure of patient‐based outcomes for clinical trials, health services research, and routine clinical care.
Revisiting Outpatient Tonsillectomy in Young Children
Authors: Ross Adam T. , Kazahaya Ken , Tom Lawrence W. C.
Published: March 2003

OBJECTIVE

Postoperative same‐day discharge is safe for most children undergoing tonsillectomy. However, young children with upper airway obstruction have a higher risk of postoperative complications. We review our tonsillectomy experience in children under 36 months to evaluate the safety of outpatient tonsillectomy in this population.

STUDY DESIGN AND SETTING

We conducted a retrospective study of all children under 36 months who underwent tonsillectomy during a recent 2‐year period at The Children's Hospital of Philadelphia.

RESULTS

The indication for tonsillectomy in 96% of 421 children was upper airway obstruction. Eighteen percent required postoperative treatment to prevent respiratory compromise; 56% of these patients had no associated medical comorbidity. Patients younger than 24 months and those with medical comorbidities were more likely to require intervention.

CONCLUSION AND SIGNIFICANCE

It is not possible to preoperatively anticipate which children will have postsurgical complications. We recommend planning an overnight admission for children younger than 36 months undergoing tonsillectomy.
Percutaneous Dilation Tracheotomy Versus Surgical Tracheotomy: Our Experience
Authors: Goldenberg David , Golz Avishay , Huri Antoinette , Netzer Aviram , Joachims Henry Zvi , Bar‐Lavie Yaron
Published: March 2003

BACKGROUND

Percutaneous dilation tracheotomy (PDT) is becoming a popular alternative to surgical tracheotomy. In our department, we recently adopted the use of the PDT in intensive care unit patients. Here, we compare the results of the use of these 2 techniques on 150 patients, all performed by the same surgeon. We discuss the pros and cons of PDT and present our experience with the technique compared with surgical tracheotomy (ST).

MATERIALS AND METHODS

A prospective study of 75 PDTs and a retrospective study of 75 surgical tracheotomies (ST) were performed at the Department of Otolaryngology‐Head and Neck Surgery, Rambam Medical Center, Haifa, Israel. Age, sex, duration of intubation before surgery, time interval between the decision to perform and the performance of tracheotomy, and cost were compared.

RESULTS

One hundred fifty tracheotomies were reviewed. The indication for tracheotomy in both groups was prolonged mechanical ventilation. Seven patients were found unsuitable for PDT and underwent ST. Complications included 3 cases of mild postoperative hemorrhage in the ST group, and 1 case of subcutaneous emphysema, 1 case of stomal cellulitis and 2 cases of mild postoperative hemorrhage in the PDT group. The average waiting interval was between 2 to 5 days for ST and 1 to 24 hours for PDT. The intraoperative time for ST was 20 minutes; for PDT, 5 minutes. The cost was $565 for ST and $274 for PDT.

CONCLUSIONS

PTD provides an easy, less expensive, and convenient alternative to ST and should be added to the otolaryngologists' armamentarium of surgical airway procedures. The procedure is advantageous for the patient. Complication rates of both techniques are similar and low; however, PDT is a blind technique of obtaining a surgical airway and therefore holds more potential for serious complications. It is our conclusion that this technique is suitable for many, but not all, critical care patients and that the procedure should be performed only by surgeons who are capable of urgently obtaining a surgical airway or exploring the neck should the PDT fail.
An Evidence‐Based Review of the Treatment of Peritonsillar Abscess
Authors: Johnson Romaine F. , Stewart Michael G. , Wright Crystal C.
Published: March 2003

OBJECTIVE

Peritonsillar abscess (PTA) is commonly seen but still controversial. We performed an evidence‐based review to answer 3 questions: Are steroids beneficial? Which is the best technique for acute surgical management? When is tonsillectomy indicated?

STUDY DESIGN

We performed a MEDLINE search of the published literature using appropriate search terms to identify pertinent articles, which were reviewed and graded according to the evidence quality.

RESULTS

Forty‐two articles were analyzed. There are no published studies on steroids in PTA. There were 5 level I clinical studies on surgical technique, which indicated that needle aspiration, incision and drainage, and quinsy tonsillectomy are all effective for initial management. The overall PTA recurrence rate is 10% to 15%.

CONCLUSIONS

Overall, grade C evidence indicates that several methods of initial surgical drainage are equally effective, and the recurrence rate is low. The literature does not specifically address different treatments for children and adults.
Multiple Primary Tumors in Patients Diagnosed with Hypopharyngeal Cancer
Authors: Raghavan Ullas , Quraishi Shahed , Bradley Patrick James
Published: March 2003

OBJECTIVE

There have been few series to report on the incidence of multiple primary tumors associated with hypopharyngeal cancer. A unique consecutive patient group in a closed community who were treated by a single surgeon was available. The incidence and effect of multiple primary tumors were unknown.

STUDY DESIGN

We sought to assess (1) the incidence of multiple primary tumors among patients with hypopharyngeal cancer who were treated at a tertiary center, (2) the incidence of synchronous and metachronous tumors, and (3) the location of these multiple primary tumors and their effect on patient survival.

METHODS

We conducted a retrospective study of case notes of 150 consecutive patients with hypopharyngeal malignancy treated by a single surgeon between 1983 and 1998. Information was compiled from the patients' medical records and death data from the Family Health Services Authority.

RESULTS

Thirty‐four patients had multiple primary tumors (22.6%). There were 22 men and 12 women; piriform fossa tumor was seen in 21 men and 6 women, and postcricoid space tumor was seen in 6 women and 1 man. Second primary tumors were synchronous in 7 patients, subsequent to hypopharyngeal tumor in 5 patients, and antecedent to hypopharyngeal tumor in 14 patients. Eight patients had 2 primary tumors, of which 4 were synchronous, 4 were subsequent, and 8 were antecedent to hypopharyngeal malignancy. On the last review (2001), 3 patients were alive, and 31 had died: 17 had died from primary malignancy, 11 from another malignancy, and 3 from unrelated causes.

CONCLUSION

The presence of second primary tumors in hypopharyngeal cancer is higher than previously reported, and their presence had a significant effect on the patients' survival.
Gene Discovery Using a Human Vestibular Schwannoma cDNA Library Constructed from a Patient with Neurofibromatosis Type 2 (NF2)
Authors: Halum Stacey L. , Erbe Christy B. , Friedland David R. , Wackym Phillip A.
Published: March 2003

BACKGROUND

Despite a strong association of schwannomin/merlin gene mutations with vestibular schwannoma formation, the regulatory mechanisms and biologic pathways involved are still largely unknown. The hypothesis of this study is that the genesis and growth characteristics of neurofibromatosis type 2 (NF2)‐associated vestibular schwannomas are determined by genetic alterations that vary in gene transcript expression; this transcript expression includes oncogenic gene products that may be identified by construction and sequencing of a cDNA library from NF2‐associated vestibular schwannoma.

METHODS

Approximately 3 mL of fresh tumor was obtained during resection of a 4‐cm vestibular schwannoma from a patient with NF2. Poly(A)+ mRNA was isolated, synthesized into double‐stranded cDNA, and unidirectionally inserted into Uni‐Zap XR (Stratagene, La Jolla, CA) bacteriophage vectors. Bacteriophage vectors containing cDNA inserts were processed into phagemids according to Uni‐Zap XR protocol, and inserted vectors were sequenced and analyzed using BLAST software (National Institutes of Health, Bethesda, MD) with GenBank, EMBL, DDBJ, and PBD databases.

RESULTS

The cDNA library contained 2.4 million primary plaques. Inserts averaged 1.8 kilobases (kb) in length, with a range of 0.8 to 3.0 kb. BLAST multi‐database comparison of the sequence data obtained from 50 randomly selected clones yielded identification of 13 sequences representing known human genes and 17 sequences representing cloned sequences with unknown function. Three clones represented sequences not previously described in vestibular schwannomas but strongly implicated in oncogenesis within other tissues.

CONCLUSIONS

These data have implications for understanding the molecular mechanisms of vestibular schwannoma tumor biology. Identified genes may provide future diagnostic/prognostic markers and therapeutic targets.
Parkinson’s Disease and Electroconvulsive Therapy: A Nursing Perspective
Authors: Gaylord Kathryn M.
Published: March 2003

This article provides a nursing perspective of the use of electroconvulsive therapy (ECT) as a treatment modality for Parkinson’s disease (PD). Although improved in technique and safety, ECT continues to have the stigma of the past associated with it. A critical evaluation of the contribution that ECT can make to quality of life of patients with PD is warranted. Pathophysiology, symptomology, and the range of current treatment options for PD are reviewed and summarized. A case report and a comprehensive nursing plan of care provide direction for nurses using ECT as a treatment for patients with PD.
Ethics and Human Rights Issues Experienced by Psychiatric-Mental Health and Substance Abuse Registered Nurses
Authors: Grace Pamela J. , Fry Sara T. , Schultz Gary S.
Published: March 2003

BACKGROUND: The ethics and human rights issues experienced by psychiatric-mental health and substance-abuse registered nurses (P-MH and SA RNs) and how disturbed they are by the issues are not known.

OBJECTIVE: The purpose of this study was to identify the frequency of ethics and human rights issues experienced by P-MH and SA RNs and how disturbing the issues are to them.

STUDY DESIGN: Using Dillman’s (1978) Total Design Method, a survey of more than 8,000 RNs in six New England states was conducted. From the final sample size of 2,090 New England RN participants, responses from 162 participants who identified themselves as P-MH(n = 145) or SA (n = 17) RNs were further analyzed using descriptive statistics.

RESULTS: Protecting patients’ rights and human dignity and providing nursing care with possible health risks to the RN were identified as the most frequently experienced ethics and human rights issues. Staffing patterns that limit patient access to nursing care and implementing managed care policies that threaten the quality of patient care were identified as the most disturbing issues. Forty-one percent of the RNs reported experiencing ethics and human rights issues daily or one to four times per week in their clinical practices.

CONCLUSIONS: P-MH and SA RNs in New England encounter ethics and human rights issues in practice more frequently than all other RNs practicing in New England.
Real estate and stock returns: a multivariate VAREC model
Authors: Ullah Aman , Zhou Zhong‐guo
Published: March 2003

In this paper, we examine dynamic relationships among three housing market variables and a stock market index in a multivariate vector autoregressive error correction (VAREC) model. It is first found that, in the USA, sales and the median sales price of the existing single‐family homes and the 30‐year mortgage rate have unit roots, while the New York Stock Exchange (NYSE) value‐weighted portfolio returns appear random. Moreover, it is found that not only are three real estate variables cointegrated with one another but that they are also cointegrated with the stock index returns. After controlling for the unit root problem and cointegration, a multivariate VAREC model is further developed to examine dynamic relationships among the four variables using Johansen’s approach. It is found that the price, mortgage rate, and stock returns affect sales. It is found that the mortgage rate and stock returns affect the price. The 30‐year mortgage rate is affected by sales and the stock returns. Except for the mortgage rate which is negatively correlated with the stock returns, significant evidence is not found that sales and the median sales price affect the stock returns directly.
International unsecuritized real estate
Authors: Seiler Michael J. , Tat Lee Soon , Seiler Vicky L.
Published: March 2003

Given the paucity of good international unsecuritized real estate data and the growing interest in diversifying real estate only and mixed‐asset portfolios beyond national borders, this study introduces an unsecuritized Japanese total return index for office real estate dating back to 1970. Moreover, this study analyses risk and return characteristics and compares them with the risk and return characteristics of US domestic unsecuritized office real estate. The results indicate that first, National Council of Real Estate Investment Fiduciaries (NCREIF) and the Mitsubishi Trust and Banking Corporation and IKOMA Data Service System Co. Ltd (MTB‐IKOMA) geographic region returns are generally from a normal distribution, although neither is without exception; second, all ten sub‐indices suffer from autocorrelation at two or three lags even after lower‐order effects have been removed; third, returns in Japan are historically higher, although so too are the risks; and most importantly fourth, while returns within Japan and the USA, separately, are highly correlated, correlation between Japan and the USA is quite low. In sum, given the results of this study, it is likely that Japanese unsecuritized real estate could be used to diversify international real estate only, and mixed‐asset portfolios.
Hermite curves in the modification of integral equations for potential boundary‐value problems
Authors: Zieniuk Eugeniusz
Published: March 2003

This paper presents a modification of the classical boundary integral equation method (BIEM) for two‐dimensional potential boundary‐value problem. The proposed modification consists in describing the boundary geometry by means of Hermite curves. As a result of this analytical modification of the boundary integral equation (BIE), a new parametric integral equation system (PIES) is obtained. The kernels of these equations include the geometry of the boundary. This new PIES is no longer defined on the boundary, as in the case of the BIE, but on the straight line for any given domain. The solution of the new PIES does not require boundary discretization as it can be reduced merely to an approximation of boundary functions. To solve this PIES a pseudospectral method has been proposed and the results obtained compared with exact solutions.
Mixed convection in rectangular enclosures with adiabatic fins attached on the heated wall
Authors: Kasbioui S. , Lakhal E.K. , Hasnaoui M.
Published: March 2003

The investigation of heat transfer and fluid flow by mixed convection in a vertical rectangular cavity containing adiabatic partitions attached to the heated wall is numerically studied. The parameters governing this problem are the Rayleigh number (103≤Ra≤4×105), the Reynolds number (5≤Re≤100), the aspect ratio of the cavity (2.5≤A≤15), the partitions length (0.1≤B≤0.95), the aspect ratio of the micro cavities (0.33≤C≤0.66) and the Prandtl number (Pr=0.72). The results obtained indicate that the heat exchange between the system and the external medium, through the cold wall and the upper vent, are considerably affected by the presence of the partitions and for all the values of A and Ra considered. However, the quantity of heat released by the higher opening remains insensitive to the presence of the partitions; it depends only on the intensity of the forced flow. Moreover, it is shown that for critical values of Re and Ra, these rates of heat transfer pass by maxima of which the value is independent of A when this parameter is equal to or higher than 10. For high Reynolds numbers, the flow is dominated by forced convection for low values of Ra and high values of B. Finally, the competition between natural and forced convection occurs when Ra≥104. The heat transfer is correlated with the main parameters and presented for an eventual utilization in design.
Fully coupled thermo‐hydro‐mechanical analysis by an algebraic multigrid method
Authors: Xicheng Wang , Schrefler B.A.
Published: March 2003

In this paper, an algebraic multigrid method is suggested for the fully coupled thermo‐hydro‐mechanical analysis in deforming porous media. The mathematical model consists of balance equations of mass, linear momentum and energy and of the appropriate constitutive equations. The chosen macroscopic field variables are temperature, capillary pressure, gas pressure and displacement. The gas phase is considered to be an ideal gas composed of dry air and vapour, which are regarded as two miscible species. Phase change as well as heat transfer through conduction and convection and latent heat transfer (evaporation‐condensation) are taken into account. The problem hence presents an interaction problem between several fields with very different response characteristics. Further, the matrices are non‐symmetric and not diagonally dominated. Numerical examples are given to demonstrate the efficiency of this method.
Industrial practice in designing for quality
Authors: Booker Julian D.
Published: March 2003

The improvement of the quality of design and the reduction of failure related cost is seen as a crucial competitive requirement for UK manufacturing industry. To achieve these goals, industry must adopt current methods in support of design for quality (DFQ) for analysing potential problems and predicting quality, and integrate these effectively with the appropriate stages of their new product development process. The utilisation and success rate of these techniques in UK companies is, however, relatively low compared to those in countries such as the USA and Japan. In this paper, the fundamental concepts and key areas of opportunity in design improvement using the main DFQ support techniques are reviewed and a framework for their application and integration is presented to support concurrent product development. The typical experiences and problems concerning the application and implementation of techniques are discussed and areas where new research should be directed are touched on so that DFQ techniques may better enhance industrial practice in the achievement of high quality products.
Franchise management: a model of service‐quality interactions
Authors: Mukherjee Avinandan
Published: March 2003

The main research question addressed in this paper is how two independent retail outlets in a franchise chain would react to each other on the quality of services. To better explain the interaction, the franchise as an organizational form and its peculiar characteristics compared to the integrated firm on the one hand and market transactions on the other hand are initially discussed. The paper then proposes a theoretical model of the “free‐riding phenomenon” related to the quality of services in the franchise chain, and interactions on the quality of services between the independent outlets in different environments. As spill‐over exists, two franchisees start to react to each other's quality of services and they increase the quality as the positive spill‐over effect becomes significant. The equilibrium with spill‐over gets close to that without spill‐over, as the spill‐over effect approaches zero.
Technology‐mediated leadership development networks
Authors: Webber Charles F.
Published: March 2003

This report describes the evolution of a technology‐mediated leadership development network from its origin as a local e‐mail discussion group to a loosely‐coupled international leadership web. The report includes a description of the components of the network, which include face‐to‐face and online cross‐role discussion groups, annual seminar series, graduate degree programming, an online refereed journal, summer institutes, university partnerships, and cross‐cultural research. In addition, an explanation is offered of the challenges that the network poses for understandings of what counts as professional development, university regulations for planning and delivering instruction, communication of research, and teacher‐student roles. Then the paper offers a profile of the leadership development network in terms of its professional, role, environmental, and emotional dimensions. Finally, a set of questions is offered for readers interested in planning leadership development networks.
New technologies and educative leadership
Authors: Webber Charles F.
Published: March 2003

This overview describes the linkages between new technologies and educative leadership, the theme of this special issue. It discusses the tension between the pervasiveness of technology in society and educators’ apparent uncertainty about how to best use information and communication technology. Also, the foci of the following articles that are written from a variety of international perspectives are summarized, and a set of critical questions about how new technologies are reshaping our understandings of leadership are offered. In addition, some of the educational challenges and opportunities associated with technology are described, and a rubric that can be used to consider the capacity to link new technologies and educative leadership is proposed.
Chronic obstructive pulmonary disease due to occupational exposure to silica dust: a review of epidemiological and pathological evidence
Authors: Hnizdo E , Vallyathan V
Published: March 2003

Occupational exposure is an important risk factor for chronic obstructive pulmonary disease (COPD), and silica dust is one of the most important occupational respiratory toxins. Epidemiological and pathological studies suggest that silica dust exposure can lead to COPD, even in the absence of radiological signs of silicosis, and that the association between cumulative silica dust exposure and airflow obstruction is independent of silicosis. Recent clinicopathological and experimental studies have contributed further towards explaining the potential mechanism through which silica can cause pathological changes that may lead to the development of COPD. In this paper we review the epidemiological and pathological evidence relevant to the development of COPD in silica dust exposed workers within the context of recent findings. The evidence surveyed suggests that chronic levels of silica dust that do not cause disabling silicosis may cause the development of chronic bronchitis, emphysema, and/or small airways disease that can lead to airflow obstruction, even in the absence of radiological silicosis.