bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematologic and Chemical Changes Observed during and after Cardiac Arrest in a Canine Model—A Pilot Study
Authors: Bleske Barry E. , Song Jessica , Chow Moses S. S. , Kluger Jeffrey , White C. Michael
Published: June 2004

Study Objective. To evaluate the effect of cardiac arrest and cardiopulmonary resuscitation (CPR) on blood chemistry in a canine model.

Design. Evaluative canine animal study.

Setting. Animal laboratory accredited by the Association for Assessment and Accreditation of Laboratory Animals.

Subjects. Twenty‐six adult mongrel dogs.

Intervention. The dogs underwent an episode of induced fibrillatory cardiac arrest for 3 minutes followed by 10 minutes of standard CPR. Blood samples were taken at baseline (before cardiac arrest), after 10 minutes of ventricular fibrillation, and 10 minutes after successful resuscitation for determination of blood chemistries and hematologic parameters.

Measurements and Main Results. Glucose, blood urea nitrogen, serum creatinine, sodium, potassium, chloride, calcium, phosphorus, uric acid, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, protein, albumin, cholesterol, triglycerides, iron, white blood cell count, red blood cell count, and hematocrit were measured. Significant changes (p<0.05) in values obtained during CPR versus baseline values were noted for all laboratory parameters except blood urea nitrogen, chloride, and alkaline phosphatase. Eighteen dogs achieved return of spontaneous circulation (ROSC); their laboratory values were obtained after CPR. Significant changes (p<0.05) after ROSC compared with baseline were noted for all laboratory values except chloride, blood urea nitrogen, uric acid, alkaline phosphatase, glucose, potassium, calcium, triglycerides, iron, red blood cell count, and hematocrit.

Conclusion. Results indicate that significant changes in blood chemistries and hematologic parameters occur during and after CPR. Clinicians should note these normal laboratory parameter changes when interpreting laboratory data in patients who experience cardiac arrest.
Effects of Metronidazole on Hepatic CYP3A4 Activity
Authors: Haas Curtis E. , Kaufman David C. , DiCenzo Robert C.
Published: June 2004

Study Objective. To evaluate the effect of a short course of oral metronidazole, commonly used for bowel‐preparation regimens, on hepatic cytochrome P450 (CYP) 3A4 activity, as measured by the [14C N‐methyl]‐erythromycin breath test (ERMBT) in healthy volunteers.

Design. Prospective, nonrandomized, interventional study.

Setting. University‐affiliated, community, teaching hospital.

Subjects. Five healthy male volunteers.

Intervention. Subjects underwent a baseline ERMBT in the morning before receiving three oral doses of metronidazole 500 mg administered at 3 p.m., 7 p.m., and 11 p.m. Repeat ERMBTs were performed at 24, 72, and 96 hours after the initial ERMBT. Changes in ERMBT values were compared with baseline results using Freidman's repeated‐measures analysis of variance on ranks.

Measurements and Main Results. The ERMBT values did not change significantly compared with baseline (p=0.82). Median (range) ERMBT values expressed as a percentage of baseline at 24, 72, and 96 hours were 110.3 (96.2–136.9), 101.3 (99.3–115.0), and 101.8 (95.5–116.3), respectively.

Conclusion. A short course of oral metronidazole does not result in a significant change in hepatic CYP3A4 activity as measured by the ERMBT.
Assessment of a Community Pharmacy‐Based Program for Patients with Asthma
Authors: Cordina Maria , McElnay James C.
Published: June 2004

Study Objective. To implement and assess a community‐based pharmaceutical care program for patients with asthma.

Design. Prospective, randomized, controlled trial.

Setting. Community pharmacies (11 control, 11 intervention) in Malta.

Patients. Community‐dwelling patients with asthma.

Interventions. A comprehensive asthma education and monitoring program was implemented. Intervention patients received verbal counseling, an educational video, an information leaflet, and subsequent monitoring with reinforcement; control patients received routine dispensing services.

Measurements and Main Results. Parameters assessed at baseline and at 4, 8, and 12 months were health‐related quality of life, peak expiratory flow (PEF), inhaler technique, compliance with therapy, hospitalization rates, days lost from work, asthma symptoms, and patient satisfaction. Health‐related quality of life of the intervention patients improved at 12 months (p=0.044). In the same time period, PEF significantly decreased in control patients compared with intervention patients (p=0.009) whereas inhaler technique improved in the intervention group (p=0.021). There were significantly fewer self‐reported hospitalizations in intervention patients.

Conclusions. A community‐based pharmaceutical care program was appreciated by the participants and had a positive impact on the vitality of patients with asthma, inhaler technique, and PEF.
Telithromycin: An Oral Ketolide for Respiratory Infections
Authors: Bearden David T. , Neuhauser Melinda M. , Garey Kevin W.
Published: June 2004

The ketolides represent a new subclass of antibiotics among the macrolide‐lincosamide‐streptogramin group. Telithromycin, the first ketolide to be awarded approvable status for clinical use, demonstrates in vitro activity against community‐acquired respiratory pathogens including penicillin‐ and erythromycin‐resistant Streptococcus pneumoniae. An extended half‐life permits once‐daily oral administration. Telithromycin is a substrate for cytochrome P450 (CYP) 3A4 and also inhibits drugs metabolized by CYP3A4. A relatively high frequency of mild‐to‐moderate gastrointestinal adverse effects has been reported. Similar clinical and microbiologic efficacy has been demonstrated with oral dosing in comparative clinical trials for community‐acquired pneumonia, acute sinusitis, acute exacerbations of chronic bronchitis, and pharyngitis. Although limited data on penicillin‐resistant S. pneumoniae and erythromycin‐resistant Streptococcus pyogenes are available from clinical trials, this drug appears promising for respiratory infections caused by these pathogens.
Clinical Implications of Drug Interactions with Coxibs
Authors: Garnett William R.
Published: June 2004

Nonsteroidal antiinflammatory drugs (NSAIDs) often are prescribed to patients who are taking concomitant drugs. Cyclooxygenase (COX)‐2 inhibitors (coxibs) rofecoxib and celecoxib are highly selective inhibitors of COX‐2, differentiating them from nonselective NSAIDs, which substantially inhibit both COX‐1 and COX‐2. Like nonselective NSAIDs, coxibs are hepatically metabolized: rofecoxib primarily by reduction by cytosolic enzymes and celecoxib by the cytochrome P450 (CYP) enzyme system. Because rofecoxib is not significantly metabolized by CYP, it has fewer confirmed or potential drug interactions than celecoxib. However, potent inducers of CYP, such as rifampin, may decrease rofecoxib concentrations because of induction of general hepatic metabolic activity. Celecoxib is metabolized by CYP2C9 and may be increased or decreased by CYP2C9 modifiers. It also inhibits CYP2D6 and may affect concentrations of CYP2D6 substrates. Similar to NSAIDs, many pharmacodynamic interactions involving coxibs are related to inhibition of production of renal prostaglandins. However, coxibs have no antiplatelet activity and may be preferred to NSAIDs in patients receiving antithrombotic therapy. Nonetheless, when a potential for an interaction exists, standard monitoring is recommended when starting or discontinuing a coxib. Due to lack of data to support these interactions, which are primarily theoretical, additional studies are necessary to establish the drug interaction profiles of coxibs.
Biopsy‐Proved Acute Tubulointerstitial Nephritis and Toxic Epidermal Necrolysis Associated with Vancomycin
Authors: Hsu Stephen I‐Hong
Published: June 2004

A 70‐year‐old man receiving vancomycin for a methicillin‐resistant Staphylococcus aureus (MRSA) abscess developed a drug‐induced hypersensitivity reaction with rash, eosinophilia, and acute renal failure requiring dialysis. Renal biopsy revealed diffuse and marked interstitial and tubular infiltration by mononuclear cells and eosinophils; acute tubulointerstitial nephritis (TIN) was diagnosed. The rash progressed to erythema multiforme major after rechallenge with vancomycin in the setting of MRSA peritoneal catheter‐related peritonitis and then to fatal toxic epidermal necrolysis in the setting of steroid taper and persistent serum vancomycin levels. This case further implicates vancomycin as a drug that infrequently can cause severe acute TIN and exfoliative dermatitis. When a renally excreted drug such as vancomycin is administered, serum drug levels should be serially monitored and high‐dosage steroids be maintained or tapered slowly until serum drug levels become undetectable.
Difficulties in Anticoagulation Management during Coadministration of Warfarin and Rifampin
Authors: Lee Craig R. , Thrasher Kimberly A.
Published: June 2004

The clinical significance of rifampin's induction of warfarin metabolism is well documented, but no published studies or case reports have quantified this interaction with respect to the international normalized ratio (INR). A patient receiving concomitant rifampin and warfarin to treat a mycobacterial infection and intraventricular thrombus, respectively, underwent routine INR testing at a pharmacist‐managed anticoagulation clinic to assess his anticoagulation regimen. A 233% increase in warfarin dosage over 4 months proved insufficient to attain a therapeutic INR during long‐term rifampin therapy. More aggressive titration of the warfarin dosage was needed. In addition, a gradual 70% reduction in warfarin dosage over 4–5 weeks was necessary to maintain a therapeutic INR after rifampin discontinuation, demonstrating the clinically significant offset of this drug interaction. Extensive changes in warfarin dosage are required to attain and maintain a therapeutic INR during the initiation, maintenance, and discontinuation of rifampin.
Quantifying the Interaction between Angiotensin‐Converting Enzyme Inhibitors and Aspirin: Are We Using the Right Method?
Authors: Etminan Mahyar
Published: June 2004

Angiotensin‐converting enzyme (ACE) inhibitors reduce mortality in patients with heart failure and coronary artery disease. Recently, there has been growing concern about the possible interaction between ACE inhibitors and aspirin. Numerous investigators have addressed this issue; however, results are equivocal. Most researchers used a statistical test of interaction, but the use of this method has been criticized. To assess the interaction between ACE inhibitors and aspirin properly, an additive model—more specifically, the Rothman Synergy Index—should be used. Further investigation with this model, however, is needed.
Fluoroquinolone Adverse Effects and Drug Interactions
Authors: Fish Douglas N.
Published: June 2004

Extensive pharmacologic and clinical development of quinolone antimicrobial agents has resulted in improved antimicrobial activity, pharmacokinetic features, toxicity, and drug‐drug interaction profiles. Nalidixic acid and other early quinolones had limited use due to poor pharmacokinetics, relatively narrow antimicrobial spectrum of activity, and frequent adverse effects. Beginning with the development of fluoroquinolones, such as norfloxacin and ciprofloxacin, in the 1980s, the agents assumed a greatly expanded clinical role because of their broad antimicrobial spectrum of action, improved pharmacokinetic properties, and more acceptable safety profile. Although the pharmacokinetics and efficacy of the drugs have improved significantly, a major area of continued emphasis is to further reduce the frequency and severity of adverse events and drug‐drug interactions. Older agents such as ciprofloxacin and ofloxacin are still extensively prescribed, but the focus of this article is on the newer fluoroquinolones (levofloxacin and other drugs that have been approved or have been under investigation since approximately 1997).
Integrating Fluoroquinolones into the Hospital Formulary
Authors: Bertino Joseph S.
Published: June 2004

With the increasing availability of new agents, selection of fluoroquinolones for formulary inclusion can be difficult. Appropriate evaluation of the important characteristics (pharmacokinetic and pharmacodynamic properties, antimicrobial activity, efficacy, tolerability, cost) of these agents should allow selection of the most cost‐effective ones. Evidence from in vitro studies and clinical trials indicates differences exist among fluoroquinolones, especially in terms of activity against gram‐positive, aerobic organisms. For selected clinical situations, it may be important to choose an agent that is available in both intravenous and oral formulations. Comparative drug costs, as well as costs associated with potential clinical failure and adverse events, should be evaluated carefully. Dosage regimens should be considered, as shorter durations of therapy and less frequent dose administration may lead to reduced labor costs and increased patient compliance, thereby improving effectiveness and economic efficiency.
What In Vitro Models of Infection Can and Cannot Do
Authors: White Roger L.
Published: June 2004

The science of pharmacodynamics analyzes the relationship between an antimicrobial's bactericidal effects and its pharmacokinetics. Ideally, randomized and well‐controlled clinical trials are the best way to determine pharmacodynamic properties. However, in vitro models that recapitulate in vivo drug clearance profiles represent an increasingly important technology for carrying out pharmacodynamic studies in a more cost‐effective, timely, and easily controlled fashion. Although in vitro pharmacodynamic models cannot incorporate all variables seen in vivo, they do provide valuable information for the drug development process and the determination of optimal dosing regimens.
Pharmacodynamics of Antiinfective Therapy: Taking What We Know to the Patient's Bedside
Authors: Rodvold Keith A.
Published: June 2004

Applied pharmacokinetics has long been a lifeline of clinical pharmacy services. National surveys during the past decade documented clinical pharmacy services and demonstrated that a substantial rate of growth occurred in clinical pharmacokinetic consultations and management of drug therapy protocols. Pharmacodynamic principles of antiinfective agents are rapidly becoming a new paradigm of clinical pharmacy services. β‐Lactams, aminoglycosides, and fluoroquinolones represent the three classes of antiinfective agents that have made the most progress toward the clinical applications of pharmacodynamics. Pharmacodynamic parameters are being used to select and compare agents within an antiinfective class (e.g., fluoroquinolones), make modifications in the dosage (e.g., extended‐interval dosing of aminoglycosides) and/or mode of administration (e.g., continuous infusion of β‐lactams), develop in vivo breakpoint determinations, and assess the development of bacterial resistance. In addition, pharmacodynamic parameters have influenced the clinical drug development of new (e.g., linezolid) and older (amoxicillin‐clavulanate, fluoroquinolones) antiinfective agents. Further investigations are needed to explore the clinician's use of validated prediction methods and patient‐specific pharmacodynamic parameters at the bedside. By linking pharmacokinetic services with pharmacodynamic principles, the opportunity for continued progress toward our assessment and decisions for successful clinical outcomes is possible with old and new antiinfective agents.
In Vitro Pharmacodynamic Analysis of Single Daily Dosing versus Conventional Dosing of Gentamicin Administered with Penicillin Against Enterococcus faecalis
Authors: Ross Gigi H. , Hovde Laurie Baeker , Ibrahim Yasir H. , Rotschafer John C.
Published: June 2004

Study Objective. To compare the effectiveness of single daily dosing (SDD) versus conventional dosing of gentamicin when administered with penicillin to treat enterococcal infections.

Design. In vitro pharmacodynamic model.

Setting. Hospital laboratory.

Measurements and Main Results. A 24‐hour in vitro pharmacodynamic model was employed to simulate SDD and 3 times/day dosing of gentamicin, in conjunction with continuously infused penicillin, against Enterococcus faecalis. Duplicate 24‐hour kill curves were generated with varying concentrations of penicillin and gentamicin alone and in combination. No difference in the rate of kill was seen between any combination of penicillin and gentamicin. Regrowth occurred only with drug combinations in which penicillin was administered continuously at the minimum inhibitory concentration. Variations in the gentamicin dosing regimen did not affect regrowth.

Conclusion. In the treatment of enterococcal infections, an SDD regimen for gentamicin shows no efficacy benefit compared with conventional dosing.
Effectiveness and Infant Acceptance of the Rx Medibottle versus the Oral Syringe
Authors: Kraus Donna M. , Stohlmeyer Leslie A. , Hannon Patricia R. , Freels Sally A.
Published: June 2004

Study Objective. To compare the effectiveness and infant acceptance of drug delivery of the Rx medibottle with the standard oral syringe.

Design. Prospective open‐label, randomized, crossover clinical study.

Setting. General pediatric outpatient clinic at an urban university.

Subjects. Thirty healthy, bottle‐fed infants, aged 2–14 months, receiving routine vaccinations.

Intervention. Each infant received a single dose of acetaminophen (Tempra syrup), with one‐half delivered by the Rx medibottle and one‐half delivered with an oral syringe.

Measurements and Main Results. Three raters independently evaluated effectiveness and infant acceptance of each drug‐delivery device. Effectiveness was based on the percentage of infants receiving 100% of the intended dose. Infant acceptance was scored using a validated infant medication acceptance scale (MAS, 10 = highest level). Significantly more infants received 100% of the intended dose with the Rx medibottle (93.3%) than with the oral syringe (56.7%, p=0.0074). Infants had a significantly higher mean MAS score when using the Rx medibottle (8.3 ± 1.8 vs 7.3 ± 1.7, p=0.002). In addition, a significantly higher percentage had ideal MAS scores of 9 or above with the Rx medibottle (73%) compared with the oral syringe (17%, p=0.0001).

Conclusion. The Rx medibottle was more effective and had a higher level of infant acceptance than the oral syringe. Although further studies are necessary, this suggests that the Rx medibottle may be a better method of delivering liquid drug and may increase infant adherence.
Evaluation of Electrocardiographic and Hemodynamic Effects of Caffeine with Acute Dosing in Healthy Volunteers
Authors: Ammar Rabab , Song Jessica C. , Kluger Jeffrey , White C. Michael
Published: June 2004

Study Objective. To evaluate the effects of moderate, single‐dose caffeine consumption on electrocardiographic variables: PR, QRS, QT, QTc, and RR intervals, and QT and QTc interval dispersion. Effects of caffeine on blood pressure and heart rate also were evaluated.

Design. Randomized, double‐blind, placebo‐controlled, crossover study.

Setting. University school of pharmacy.

Patients. Ten healthy volunteers aged 17 years or older.

Intervention. Participants abstained from caffeinated products for at least 2 days before the study began and were randomly designated to receive placebo or caffeine 400 mg on various days. For each of the study phases, a baseline 12‐lead electrocardiogram (ECG) was performed and a subsequent 12‐lead ECG performed 3 hours after ingesting the study drug. Blood pressure readings were taken with each ECG.

Measurements and Main Results. No significant changes in any intragroup or intergroup electrocardiographic variables occurred. Caffeine increased blood pressure (systolic blood pressure [SBP]/diastolic blood pressure [DBP]) from 118 ± 5/75 ± 6 mm Hg to 128 ± 8/77 ± 7 mm Hg versus baseline (p=0.0022 and p=0.0368 for SBP and DBP, respectively). After drug dosing, SBP in the caffeine group was significantly higher than in the placebo group (128 ± 8 mm Hg versus 119 ± 7 mm Hg, p=0.0174).

Conclusion. Moderate caffeine consumption by healthy young adults does not acutely affect PR, QRS, QT, QTc, and RR intervals, or QT and QTc interval dispersion. Caffeine‐naïve subjects experienced persistent elevations in SBP and DBP 3 hours after caffeine ingestion, indicating that longer caffeine abstinence than that which is recommended is necessary for blood pressure determination in the clinical setting.
Potential Interaction between Warfarin and Boldo‐Fenugreek
Authors: Lambert Jean‐Philippe , Cormier Julie
Published: June 2004

A patient was treated with warfarin for atrial fibrillation. During treatment, an increase in international normalized ratio (INR) and her admission that she was taking a variety of natural products, to include boldo and fenugreek, led us to suspect that some of these natural products could alter the effect of warfarin. When she stopped the culpable products, the INR returned to normal after 1 week. The herb‐drug interaction was observed a second time after both products were reintroduced a few days later. The imputability of this interaction to both natural products, as determined by the Naranjo algorithm, suggests a probable association between boldo‐fenugreek and increased bleeding time in patients treated with warfarin. No undesirable reaction was reported during telephone discussions with the patient. Nevertheless, we recommend that clinicians treating patients with anticoagulant therapy be vigilant when patients also take herbal agents.
Therapeutic Challenges Associated with Extended‐Spectrum, β‐Lactamase‐Producing Escherichia coli and Klebsiella pneumoniae
Authors: Wong‐Beringer Annie
Published: June 2004

The emergence of extended‐spectrum β‐lactamase (ESBL)‐producing Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae, presents significant diagnostic and therapeutic challenges to the management of infections due to these organisms. Detection of resistant isolates is difficult based on routine susceptibility testing performed by a clinical microbiology laboratory. In addition, the utility of penicillins, cephalosporins, and aztreonam in treating serious infections due to these organisms is uncertain due to reports of treatment failure despite apparent in vitro susceptibility. A critical evaluation of the English literature was performed on treatment outcomes associated with ESBL‐producing Enterobacteriaceae. Imipenem and extended‐spectrum cephalosporins were commonly administered. Discordant outcomes in relation to in vitro susceptibility of the agent did not occur exclusively with cephalosporins but with all drugs including imipenem. Until more outcome data are available, drug selection must take into consideration whether or not an outbreak is occurring and whether therapy is empirical or definitive.
Low‐Molecular‐Weight Heparins Are Essentially the Same for Treatment and Prevention of Venous Thromboembolism
Authors: Lopez Larry M.
Published: June 2004

The pharmacodynamic properties of low‐molecular‐weight heparins differ. Data from randomized clinical trials show that despite these differences, the agents have similar efficacy and safety profiles in preventing and treating new and recurrent venous thromboembolism in patients who underwent general surgery or total hip or knee replacement. Dalteparin, enoxaparin, or tinzaparin, when administered at the dosages used in the reviewed clinical trials, are essentially indistinguishable.
Differentiation of the Low‐Molecular‐Weight Heparins
Authors: Racine Eric
Published: June 2004

The three low‐molecular‐weight heparins (LMWHs) available in the United States have been extensively evaluated for a wide array of indications. Properties associated with one LMWH cannot be assumed to be the same as those associated with another LMWH, as they are different pharmacologic entities. Therefore, therapeutic interchange of these agents is inappropriate. The pharmacokinetic and pharmacodynamic differences among LMWHs can be explained by comparing methods of preparation, molecular structures, half‐lives, antithrombin‐ and non‐antithrombin‐mediated actions, effect on thrombus, and dosing interval. The Food and Drug Administration‐approved indications and their respective levels of clinical evidence further differentiate these agents. A dichotomy in the results of clinical trials has been observed with the LMWHs. As the LMWHs are distinct compounds that each possess unique pharmacokinetic and pharmacodynamic profiles, treatment decisions should be based on the available safety and efficacy data for each LMWH. Agents should be prescribed only for those indications for which they have been shown to be effective and only at dosages that have been studied.
Lipodystrophy Syndrome in Children Infected with Human Immunodeficiency Virus
Authors: Wedekind Cynthia A. , Pugatch David
Published: June 2004

Lipodystrophy syndrome (LDS), a fat‐wasting condition commonly reported in adults infected with human immunodeficiency virus (HIV), has been linked to the use of antiretroviral agents. Recently, LDS was observed in children infected with HIV. Little is known about the pathophysiology of this condition, although it is believed that LDS has many causes and modes of presentation. Even less is known about what long‐term effects LDS will have on HIV‐infected patients. Three patients who developed LDS were observed in a pediatric HIV clinic. Due to the lack of knowledge about the condition's natural course and the benefits versus risks of treatment, they were not treated specifically for LDS. Their lipid profiles, however, continue to be monitored closely twice/year.
Levofloxacin and Warfarin Interaction
Authors: Ravnan Susan L. , Locke Christy
Published: June 2004

Numerous case reports have documented an enhanced hypoprothrombinemic effect caused by an interaction between fluoroquinolones (most notably, ciprofloxacin) and warfarin sodium. Conflicting data exist regarding the clinical significance of this interaction. Two patients who had elevated international normalized ratios after receiving concurrent levofloxacin and warfarin sodium are described.
The Rationale for Aerosolized Antibiotics
Authors: Flume Patrick , Klepser Michael E.
Published: June 2004

In order for an antimicrobial agent to be effective, it must fulfill two requirements. First, the agent must reach the site of infection and remain in the vicinity for an adequate length of time. Second, it must bind to a target site and remain bound for a length of time sufficient to disrupt the life cycle of the cell. Once these requirements are met, the drug is able to exert its antimicrobial activity against the cell. In an effort to better understand and predict the killing activity of antibiotics, we have attempted to develop parameters that describe the accumulation and diffusion of drug to and from body sites (pharmacokinetics) and quantify how much of a compound is needed at the site of infection to yield the desired effect (minimum inhibitory concentration). Furthermore, integration of these parameters allows us to evaluate host, drug, and microbial factors and formulate criteria to assess and predict drug activity in patients (pharmacodynamics). Knowledge and application of pharmacodynamic principles can assist clinicians in optimizing antimicrobial therapy by allowing them to maximize the antimicrobial activity of an agent while minimizing patient exposure and thus reducing the likelihood of toxicity.
Nasopharyngoscopy in Robin Sequence: Clinical and Predictive Value
Authors: de Sousa Telma Vidotto , Marques Ilza Lazarini , Carneiro Araken Fernando , Bettiol Heloisa , de Souza Freitas JoséAlberto
Published: June 2004

Objective

To correlate nasopharyngoscopic findings with clinical manifestations during the first month of life and study the course of respiratory obstruction during the first year in infants with Robin sequence (RS).

Design

A longitudinal prospective study of children with RS.

Setting

Hospital de Reabilitação de Anomalias Craniofaciais, University of São Paulo, Bauru-SP, Brazil, 1998 to 2000.

Patients

Fifty-six children were studied from the age of 1 month to 12 months.

Interventions

The type of respiratory obstruction was defined by nasopharyngoscopy. Patients for whom glossoptosis was the only mechanism of respiratory obstruction were classified as having mild, moderate, or severe glossoptosis by nasopharyngoscopy and as mild, moderate, or severe cases with respect to the clinical manifestations.

Results

Forty-two (75%) patients showed respiratory obstruction caused by glossoptosis; seven (43.7%) of these infants with mild clinical manifestations showed moderate glossoptosis during the first month of life and five (31.3%) presented severe glossoptosis; 10 (45.5%) of the infants with severe clinical manifestations showed moderate and 11 (50.0%) severe glossoptosis. At 12 months of age, glossoptosis was mild or absent in 83.3% of the patients, moderate in 14.3% and severe in 2.4%.

Conclusions

A poor correlation between the severity of glossoptosis and the severity of clinical manifestations was observed for patients with respiratory obstruction caused by glossoptosis during the first month of life, but the correlation between glossoptosis and respiratory distress according to age was statistically significant. Nasopharyngoscopy is not a good method for predicting the severity of the clinical course of respiratory obstruction caused by glossoptosis.
Management of Craniofacial Development in the Parry-Romberg Syndrome: Report of Two Patients
Authors: Grippaudo Cristina , Deli Roberto , Grippaudo Francesca Romana , Di Cuia Tiziana , Paradisi Mauro
Published: June 2004

Objective

The aim of this article is to describe the orthodontic therapy for Parry-Romberg syndrome. The therapeutic goal is to minimize the wasting effects of progressive atrophy on facial development of a part of the face.

Design

To correct problems affecting craniofacial development of these patients, occurring during puberty, an orthodontic appliance was employed, which helps maintain parallelism of the facial planes, in particular the mandibular plane.

Setting

Orthodontic care was carried out in the Dental Clinic of the Catholic University of the Sacred Heart of Rome.

Intervention

Two patients underwent orthodontic therapy for 6 years. Appliances were checked every month and modified periodically so as to adapt to facial bone growth.

Results

At the end of craniofacial growth, the mandible was almost symmetric and the problem relating to atrophy remained confined to the initial area. Cephalometric analyses demonstrated that the occlusal plane and the mandibular plane maintained a straight orientation in relation to the bizygomatic plane. The ratio between the left and right side of the ramus and condyle, in the mandible, improved.

Conclusions

The use of orthodontic therapy allows patients affected by hemifacial progressive atrophy to present a more harmonic face at the end of puberty when final reconstruction can be planned. These results provide for a limitation of surgical intervention to the sclerodermic area alone.
Nasalance Scores for Normal-Speaking Irish Children
Authors: Sweeney Triona , Sell Debbie , O'Regan Myra
Published: June 2004

Objective

To obtain normal nasalance values during the production of a standardized speech sample for Irish children and determine whether significantly different scores exist for different speech stimuli for female and male speakers.

Design

Mean nasalance scores were obtained for normal-speaking children during the repetition of 16 test sentences that were categorized according to consonant type within the sentences (high-pressure consonants, low-pressure consonants, nasal consonants).

Participants

Seventy children (36 girls and 34 boys, aged 4 years 11 months to 13 years) with normal articulation, resonance, and voice were included.

Procedures

Children repeated each of the 16 test sentences individually. The sentences were presented in groups according to consonant type, referred to as sentence categories. Data were collected and analyzed using the Kay nasometer (model 6200.3). Nasalance scores were obtained for the total speech sample and each sentence category. Data were statistically analyzed to investigate the effects of gender, sentence category, and gender by sentence category.

Results

Normative nasalance scores were obtained for the total speech sample (26%), high-pressure consonant sentences (14%), low-pressure consonant sentences (16%), and a nasal consonant sentence (51%). There was no significant difference in nasalance scores between male and female speakers. Significant differences were found between each sentence category (p ≤ .001), except between the high-pressure and low-pressure consonant sentence categories (p = .09).

Conclusion

The present study provides normative nasalance data for English-speaking Irish children. There was a significant difference between nasalance scores for different speech stimuli.
Treatment of an Infant with a Rare Cleft Resolved with Use of an Orthopedic Appliance
Authors: Romero Martín , Latham Ralph , Romance Ana , Salvan Rafael
Published: June 2004

Objective

Cases of bilateral complete clefts of the primary palate and unaffected secondary palate are very rare. One of these cases as well as a new method of presurgical orthopedics to solve the protruding premaxilla protrusion is presented.
Evaluation of Temporomandibular Joint in Patients with Hemifacial Microsomia
Authors: Kitai Noriyuki , Murakami Shumei , Takashima Mariko , Furukawa Souhei , Kreiborg Sven , Takada Kenji
Published: June 2004

Objective

The purpose of this study was to elucidate positional relationships between temporomandibular joint (TMJ) components, including the articular discs, using magnetic resonance imaging (MRI) in patients with hemifacial microsomia (HFM).

Subjects and Methods

Twenty TMJs in 10 patients with HFM were examined at closed- and open-mouth positions using an MRI scanner. The condyle-fossa and disc-condyle relationships, disc configuration at the closed-mouth position, and the reduction of the disc at the open-mouth position were evaluated.

Results

On the unaffected side, the condyle-fossa and disc-condyle relationships appeared fairly normal at the closed mouth position. The disc-condyle relationship at the open-mouth position was also normal. The TMJ disc showed normal biconcave configurations at both closed- and open-mouth positions. On the affected side, there was considerable variation in the state of the TMJ. At the closed-mouth position, 5 of the 10 patients revealed fairly normal disc-condyle relationships, one patient showed anterior displacement of the disc, and four patients had no disc. Two patients appeared biconcave, three patients appeared biplanar, and one patient was hemiconvex. At the open-mouth position, the condyle and disc moved in harmony in five patients with normal disc-condyle relationships, but the disc was reduced in a patients with anterior disc displacement. The degree of the TMJ disc dysplasia did not necessarily correspond with the degree of mandibular dysplasia.

Conclusion

The present study contributes to an improved understanding of TMJ pathology in patients with HFM. The results suggest that, in HFM patients, the examination of the TMJ using MRI is helpful for determining treatment procedures in mandibular distraction osteogenesis.
Facial Characterization of Infants with Cleft Lip and Palate Using a Three-Dimensional Capture Technique
Authors: Hood C. A. , Hosey M. T. , Bock M. , White J. , Ray A. , Ayoub A. F.
Published: June 2004

Objective

To characterize the soft tissue features of infants with unilateral cleft lip (UCL) and unilateral complete cleft lip and palate (UCLP) prior to primary surgery and compare with noncleft controls.

Design

Prospective controlled capture of the facial morphology of infants using a noninvasive three-dimensional stereophotogrammetry method.

Participants

23 children with presurgical cleft: 11 UCL (M = 6, F = 5); 12 UCLP (M = 9, F = 3), and 21 noncleft controls (M = 7, F = 14) were imaged at approximately 3 months of age (range 10 to 16 weeks).

Main Outcome Measure

Accurate, repeatable quantification of facial soft tissues in infants with clefts prior to surgery.

Results

Significant differences (p < .05) were found between the UCLP group and UCL and control groups in anatomical and soft nose width, cleft-side alar wing length, and nasal tip horizontal displacement. Both cleft groups were significantly different from controls and from each other in cleft-side nostril dimensions, alar wing angulation, columella angle, and alar base to corner of mouth dimension; alar base width; and soft tissue defect in nose and the lip and philtrum length bordering the cleft. Significant differences between clefts and controls were identified in the nostril and philtrum on the noncleft side.

Conclusions

The use of children with UCL as controls for UCLP studies is inappropriate. This technique overcame the limitations of direct measurement of infant faces to aid the surgeon in the planning and subsequent re-evaluation of surgical rationale.
A Comparison of Craniofacial Form in Northern Irish Children with Unilateral Cleft Lip and Palate Treated with Different Primary Surgical Techniques
Authors: Johnston Chris D. , Leonard Alan G. , Burden Donald J. , McSherry Patrick F.
Published: June 2004

Objective

The quality of outcomes in patients with unilateral cleft lip and palate (UCLP) was compared between two senior plastic surgeons. One surgeon carried out a one-stage Wardill-Kilner palate repair. The other surgeon employed a vomer flap hard palate repair followed by a von Langenbeck soft palate closure (Oslo protocol).

Design

Retrospective analysis.

Patients

Thirty-four children (mean age 9.7 years) born with complete skeletal UCLP in Northern Ireland from 1983 to 1991 who received primary repair surgery from one of the two surgeons.

Main Outcome Measures

Cephalometric analysis was used to determine the craniofacial form and soft tissue profile. The quality of the dental arch relationships was independently assessed using the Goslon ranking system.

Results

Twenty-nine of the 34 subjects had good or satisfactory arch relationships. Comparison between the surgeons revealed that the Wardill-Kilner group had a greater proportion of Goslon grades of greater than 3, indicating poor arch relationships. However, this difference failed to reach statistical significance. There were no significant cephalometric differences between patients treated by the two surgeons.

Conclusions

Although the difference was not statistically significant, the highest proportion of patients likely to require orthognathic surgery was found in those treated using the Wardill-Kilner technique.
Mathematical modeling and kinetic parameter estimation in batch crystallization
Authors: Quintana‐Hernández P. , Bolaños‐Reynoso E. , Miranda‐Castro B. , Salcedo‐Estrada L.
Published: June 2004

A dynamic model of a batch crystallizer was used to estimate the kinetic parameters in a sugar cane crystallization process. The mathematical model included mass, energy, and population balance differential equations, and empirical relationships (power‐law–type) for nucleation, growth, and production–reduction rates. Experimental data were obtained from runs carried out at different agitation and cooling profiles. A nonlinear optimization process was used to fit 11 kinetic parameters to experimental data. The overall experimental error was estimated in 7.71% and the average asymptotic error of all kinetic parameters was less than 2%. The nucleation rate was favored by high agitation speed and natural cooling profiles. The maximum growth rate was reached when supersaturation was at a maximum. There was a no clear effect of agitation profiles on growth. The overall effect of the term production–reduction was in all cases positive, with the largest values found for natural cooling profiles. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1407–1417, 2004
Does bilirubin protect against hemochromatosis gene (HFE) related mortality?
Authors: Alizadeh Behrooz Z. , Njajou Omer T. , Houwing‐Duistermaat Jeanine J. , Jong Gerard de , Vergeer Jeannette M. , Hofman Albert , Pols Huibert A.P. , Duijn Cornelia M. van
Published: June 2004

Serum bilirubin is an important antioxidant that is found at increased levels in hereditary hemochromatosis patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by iron overload in carriers of mutations in the hereditary hemochromatosis gene (HFE). We studied the relation between serum total bilirubin, serum iron levels, the HFE C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population‐based follow‐up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), transferrin saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the HFE mutations had higher levels of bilirubin compared to wild‐type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9–8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0–4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by iron overload. This may explain in part the reduced penetrance of the HFE mutations. © 2004 Wiley‐Liss, Inc.
Circulating COMP is decreased in pseudoachondroplasia and multiple epiphyseal dysplasia patients carrying COMP mutations
Authors: Mabuchi Akihiko , Momohara Shigeki , Ohashi Hirofumi , Takatori Yoshio , Haga Nobuhiko , Nishimura Gen , Ikegawa Shiro
Published: June 2004

Mutations in the gene encoding cartilage oligomeric matrix protein (COMP) cause two common skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). At present, diagnosis of these diseases is based primarily on clinical and radiographic findings and is sometimes erroneous, particularly in adult patients. However, genetic diagnosis is difficult, because COMP mutations are scattered throughout the gene and five additional disease genes for MED exist. There is evidence that circulating COMP may serve as a molecular indicator of a variety of diseases affecting cartilage. Therefore, we investigated plasma COMP concentrations in 21 patients with PSACH or MED. Of these, six PSACH and seven MED patients carried COMP mutations, and the remaining eight MED patients lacked mutations in COMP. We observed significantly decreased plasma COMP levels in patients with COMP mutations compared with controls (P < 0.0001). In addition, plasma COMP levels were significantly decreased in MED patients carrying mutations in COMP relative to those who lacked COMP mutations (P = 0.001). Our results indicate that circulating COMP levels reflect genetic abnormalities in COMP, providing an easier, more rapid and cost‐efficient method for diagnosing PSACH and particularly for MED. © 2004 Wiley‐Liss, Inc.
Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity
Authors: Thompson Miles D. , Comings David E. , Abu‐Ghazalah Rashid , Jereseh Yousef , Lin Leo , Wade Judy , Sakurai Takeshi , Tokita Shigeru , Yoshida Tetsuo , Tanaka Hirokazu , Yanagisawa Masashi , Burnham W. McIntyre , Moldofsky Harvey
Published: June 2004

The orexin‐2/hypocretin‐2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro‐orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein‐coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro‐orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non‐disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild‐type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (ηM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. © 2004 Wiley‐Liss, Inc.
Genomic screen for loci associated with alcohol dependence in Mission Indians
Authors: Ehlers Cindy L. , Gilder David A. , Wall Tamara L. , Phillips Evelyn , Feiler Heidi , Wilhelmsen Kirk C.
Published: June 2004

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain illusive. This study's aims were to map susceptibility loci for DSM‐III‐R alcohol dependence and two narrower alcohol‐related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM‐III‐R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians. © 2004 Wiley‐Liss, Inc.
Using nonword repetition to distinguish genetic and environmental influences on early literacy development: A study of 6‐year‐old twins
Authors: Bishop Dorothy V. M. , Adams Caroline V. , Norbury Courtenay Frazier
Published: June 2004

This study considered whether cognitive profile could distinguish groups of children where genes or environment played a major role in influencing reading level. Same‐sex twin pairs from an epidemiological study were categorized according to parental report at 4 years of age into those with low language skills and a typically developing group. A total of 132 same‐sex twin pairs from the low language group and 66 from the control group were assessed at 6 years of age, to investigate heritability of reading ability adjusted for nonverbal IQ. For pairs where both twins had normal scores on a nonword repetition test, heritability was zero, with environmental influences explaining all the variance. For pairs where one or both twins had low nonword repetition, the heritability estimate was 0.79 and the variance due to shared environment was zero. Future studies of genetics of reading development should treat those with poor nonword repetition skills as a separate subgroup. © 2004 Wiley‐Liss, Inc.