bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Vitamin B12 Requirement Associated with Chronic Acid Suppression Therapy
Authors: Force Rex W , Meeker Angela D , Cady Paul S , Culbertson Vaughn L , Force Wendy S , Kelley Craig M
Published: March 2003

BACKGROUND:

Assimilation of vitamin B12 from dietary sources requires gastric acid. By decreasing acid production, the proton pump inhibitors (PPIs) and histamine2 (H2)-blockers may reduce vitamin B12 absorption.

OBJECTIVE:

To determine whether chronic acid suppression therapy is associated with the initiation of vitamin B12 supplementation, we conducted a retrospective case–control study using a state-wide Medicaid population.

METHODS:

Case patients were identified as those who initiated vitamin B12 supplementation during the study period. Four control patients were age-and gender-matched to each case. Patients (n = 109 844) with a paid claim between September 27, 1995, and September 27, 1997, were eligible for inclusion. Chronic acid suppression therapy was defined as treatment with H2-blockers or PPIs for ≥10 of the 12 months prior to the first vitamin B12 injection. Comparisons were made between the case and control groups regarding exposure to chronic acid suppression therapy.

RESULTS:

One hundred twenty-five cases were matched to 500 controls. Twenty-three patients (18.4%) had been exposed to chronic acid suppression therapy compared with 55 (11.0%) of the control group (p = 0.025; OR 1.82; 95% CI 1.08 to 3.09).

CONCLUSIONS:

Initiation of vitamin B12 supplementation was associated with chronic gastric acid suppression therapy.
Usefulness of Herbal and Dietary Supplement References
Authors: Sweet Burgunda V , Gay Wendy E , Leady Michelle A , Stumpf Janice L
Published: March 2003

OBJECTIVE:

To describe the usefulness of some of the most common tertiary references that healthcare professionals employ to answer requests about herbal and dietary supplements.

METHODS:

All requests for information on herbal and dietary supplements received by the drug information service between April and September 2000 were evaluated. Each question was independently reviewed by 4 clinicians using a 4-point scale; 14 references were searched for appropriate answers. The percent of responses for each of the possible scores for each reference overall and by category of question was reported to determine the most helpful references for answering the broadest range of questions.

RESULTS:

Fifty questions regarding herbal and dietary supplements were analyzed. The electronic databases (Natural Medicine Comprehensive Database, Micromedex) and the Internet site (The Natural Pharmacist) were determined to be overall the most helpful references for providing information on herbal and dietary supplements. The Natural Therapeutics Pocket Guide was the most helpful book reference.

CONCLUSIONS:

These results will facilitate the retrieval of useful information on herbal and dietary supplements and enable healthcare professionals to determine appropriate allocation of resources as they build a drug information library for handling requests about these products.
Orlistat Enhances Warfarin Effect
Authors: MacWalter Ronald S , Fraser Hazel W , Armstrong Katherine M
Published: March 2003

OBJECTIVE:

To report a case of increased international normalized ratio (INR) associated with the addition of orlistat to the drug regimen of a patient receiving warfarin therapy.

CASE SUMMARY:

A 66-year-old white man with a history of chronic atrial fibrillation (treated with a stable dose of warfarin), hypertension, and diet-controlled type 2 diabetes mellitus was started on orlistat for weight reduction. An increased INR was reported after the introduction of orlistat; there had been no other recent changes to medication or medical conditions. Warfarin was withheld and the dose reduced to allow INR control to be reestablished. According to the Naranjo probability scale, this reaction was probable.

DISCUSSION:

Control of the INR within therapeutic limits is always a challenge. Dietary intake of vitamin K, intercurrent illness, concomitant medication, herbal remedies, and other factors can interfere with warfarin dosing. Orlistat use may be associated with patient alteration of diet to compensate for adverse effects or other mechanisms by which orlistat alters warfarin control, including direct effect on absorption of vitamin K.

CONCLUSIONS:

The introduction of chronic dosing of orlistat may reduce the absorption of fat-soluble vitamins, including vitamin K, with the result that a lower dose of warfarin may be required. This may be due in part to change to a lower fat diet with decreased amounts of vitamin K. It may also be due to an effect on vitamin K absorption. Caution should be exercised when these 2 drugs are used concurrently.
Hemostatic Effects of Atorvastatin versus Simvastatin
Authors: Kadikoylu Gurhan , Yukselen Vahit , Yavasoglu Irfan , Bolaman Zahit
Published: March 2003

OBJECTIVE:

To compare the effects of simvastatin and atorvastatin on hemostatic parameters.

METHODS:

Sixty-one patients with primary hypercholesterolemia without coronary heart disease were treated with atorvastatin 10–20 mg/d or simvastatin 10–20 mg/d. At baseline, 4, 12, and 24 weeks, lipid levels such as low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triglycerides (TGs), and hemostatic parameters such as platelet counts, partial thromboplastin time (PTT) prothrombin time (PT), and fibrinogen levels were measured.

RESULTS:

At 12 weeks, the doses of the statins were increased to 20 mg/d in 10 of 35 (28.5%) patients treated with atorvastatin and 18 of 26 (69.2%) patients treated with simvastatin when the target level of LDL-C (130 mg/dL) was not reached. Mean doses were atorvastatin 12.8 mg/d and simvastatin 16.9 mg/d. After 24 weeks, 5 patients (14.3%) in the atorvastatin group and 4 patients (15.3%) in the simvastatin group had not reached the goal. In patients with diabetes, target level (LDL-C <100 mg/dL) was not reached in 35.7% of patients in the atorvastatin group and 44.4% of patients in the simvastatin group. Both simvastatin and atorvastatin were effective in lowering TC and LDL-C levels (p < 0.001). Atorvastatin lowered TGs significantly (p < 0.01). Neither atorvastatin nor simvastatin significantly reduced VLDL-C levels. HDL-C levels increased with atorvastatin, but there was no significant difference between the 2 groups. Platelet counts decreased with both statins nonsignificantly. Moreover, fibrinogen levels decreased with simvastatin and atorvastatin, but these reductions were significant only for simvastatin (p < 0.05). We detected prolongation of the PT with both drugs (p < 0.05); however, prolongation of the PTT was significant only with simvastatin (p < 0.001). Effectiveness of both statins on lipid and hemostatic parameters was dose related. Adverse effects were seen in 5 patients (14.2%) treated with atorvastatin and 3 patients (11.5%) treated with simvastatin. Elevations in serum transaminase levels >3 times the upper limit of normal and in creatine phosphokinase >5 times the upper limit of normal were not observed in any group.

CONCLUSIONS:

Atorvastatin was more effective than simvastatin on lipid parameters, although statistically insignificantly, while simvastatin produced more significant changes than atorvastatin on hemostatic parameters. The mean dose of simvastatin was greater than that of atorvastatin. Both statins had increased effects on lipid and hemostatic parameters when doses were increased. Atorvastatin and simvastatin were well tolerated. Different effects of statins on lipid levels and on coagulation parameters should be considered in patients with hypercholesterolemia and tendency to coagulation, especially in preventing thrombotic events. Further studies in larger trials are needed to confirm these observations.
Infliximab Treatment of Sarcoidosis
Authors: Serio Ryan N
Published: March 2003

OBJECTIVE:

To determine whether there is sufficient evidence in the literature to support the use of infliximab in the treatment of sarcoidosis.

DATA SOURCES AND SELECTION:

Literature was accessed through MEDLINE (1966–August 2002), OVID (2001–January 2003), and bibliographic searches. Additional databases were also searched. Published literature relevant to the use of infliximab in the treatment of sarcoidosis was evaluated.

DATA SYNTHESIS:

In theory, tumor-necrosis factor-α blockade appears to be an optimal strategy for treating sarcoidosis. Case series reporting the use of infliximab in refractory sarcoidosis was reviewed to evaluate its potential role as a treatment option.

CONCLUSIONS:

Although there is insufficient evidence suggesting that infliximab is an appropriate alternative to conventional treatment options as first-line therapy for sarcoidosis, the preliminary outlook on its use in treatment-refractory cases is promising.
Clinical Trial Response and Dropout Rates with Olanzapine versus Risperidone
Authors: Santarlasci Benedetta , Messori Andrea
Published: March 2003

BACKGROUND:

In schizophrenia, comparing treatment dropouts between olanzapine and risperidone can be useful to better understand their relative effectiveness.

OBJECTIVE:

To analyze the differences in the rates of dropout from clinical trials and response between these 2 antipsychotics.

METHODS:

Literature search was based on MEDLINE (1966–May 2002). Analysis 1 included 4 randomized studies (838 patients), analysis 2 included 2 randomized studies (n = 716), and analysis 3 assessed 5 clinical studies for olanzapine (n = 928) and 3 for risperidone (n = 290). Odds ratios were estimated by the fixed-effect model.

RESULTS:

The risk of treatment discontinuation (analysis 1) was significantly greater for risperidone than for olanzapine (42% vs. 33%, respectively). The response rates were identical for the 2 drugs (analysis 2). A slightly better pattern of maintenance of response was found for olanzapine (analysis 3).

CONCLUSIONS:

The pattern of dropout and maintenance of remission seems to be better controlled for olanzapine than for risperidone.
Toxicity Related to Chloroquine Treatment of Resistant Vivax Malaria
Authors: Davis Timothy ME , Syed David A , Ilett Kenneth F , Barrett P Hugh R
Published: March 2003

OBJECTIVE:

To report a case of severe chloroquine toxicity in the presence of high-grade chloroquine-resistant Plasmodium vivax.

CASE SUMMARY:

A febrile 36-year-old seaman from Mumbai (Bombay) was prescribed >5 times the usual dose of chloroquine for malaria diagnosed empirically onboard ship. His fever resolved, but he developed symptoms consistent with those of chloroquine toxicity. Fever recurred 30 days after his initial presentation, and blood smear–positive vivax malaria was diagnosed. A serum chloroquine concentration at this time (91 μg/L) was above that considered effective for chloroquine-sensitive P. vivax (>15 μg/L). The patient responded to atovaquone plus proguanil followed by primaquine.

DISCUSSION:

The patient was given chloroquine by his captain in a dosage regimen appropriate for quinine (2 tablets 3 times daily for 7 d). Pharmacokinetic modeling suggested that the patient's initial over-treatment was as reported and that the predicted maximum serum concentration of chloroquine (902 μg/L) was within the range seen in fatal chloroquine overdose.

CONCLUSIONS:

Chloroquine-resistant vivax malaria is increasingly widespread, and transmission can occur within large tropical population centers. For drugs with a narrow therapeutic index such as chloroquine, recommended dosing regimens should be respected, and adequate information sources must be available where such drugs are dispensed by untrained personnel.
Rapid Imipenem/Cilastatin Desensitization for Multidrug-Resistant Acinetobacter Pneumonia
Authors: Gorman Sean K , Zed Peter J , Dhingra Vinay K , Ronco Juan J
Published: March 2003

OBJECTIVE:

To report a successful case of rapid imipenem desensitization in a critically ill patient with multidrug-resistant Acinetobacter baumannii ventilator-associated pnemonia (VAP).

CASE SUMMARY:

A 40-year-old white man who had a lengthy stay in the intensive care unit (ICU) following a motorcycle accident developed VAP caused by A. baumannii. Treatment with imipenem was necessary due to the bacteria's resistance to all other antibiotics. However, this patient was diagnosed with an allergy to imipenem following exposure earlier in his hospitalization in addition to a positive penicillin skin test. Thus, we attempted rapid desensitization to imipenem using a continuous infusion protocol. The patient was desensitized within 4 hours and was successfully treated for 21 days with a continuous infusion of imipenem combined with daily amikacin. He experienced no adverse reaction during the desensitization process or the remainder of his treatment course.

DISCUSSION:

The protocol used in this case was modified from a previously reported case, and differed in the speed of desensitization and total daily dose. We assumed that a more gradual escalation of the dose in our modified protocol would prevent the occurrence of adverse events, thereby resulting in more rapid desensitization. Rapid desensitization was necessary in this patient due to the presence of a life-threatening infection. The lower total daily dose of imipenem was in response to impaired renal function.

CONCLUSIONS:

Therapeutic options for multidrug-resistant pneumonia in the ICU are significantly limited in the presence of imipenem allergy. An option of last resort is to desensitize the patient using a rapid administration protocol. Our modified rapid imipenem desensitization protocol was successful and allowed for effective treatment of life-threatening pneumonia.
Opioid Withdrawal in Critically Ill Neonates
Authors: Dominguez Karen D , Lomako Dawn M , Katz Robert W , Kelly H William
Published: March 2003

OBJECTIVE:

To determine the occurrence of and risk factors for opioid withdrawal in critically ill neonates receiving continuous infusions of fentanyl.

DESIGN:

A prospective interventional cohort study was conducted in a university hospital neonatal intensive care unit with 19 neonates who received a minimum of 24 hours of fentanyl by continuous infusion.

MEASUREMENTS:

Fentanyl total dose, duration of infusion, and peak infusion rate were recorded. Patients were evaluated for withdrawal using the Neonatal Abstinence Scoring System of Finnegan. Patients with a score ≥8 were considered to have opioid withdrawal.

MAIN RESULTS:

Withdrawal was observed in 10 (53%) of 19 neonates. The fentanyl total dose (median 525 vs. 168 μg/kg, respectively; p = 0.03) and infusion duration (median 10 vs. 7 d, respectively; p = 0.04) were significantly greater in neonates with withdrawal compared to those without withdrawal. A fentanyl total dose ≥415 μg/kg predicted withdrawal with 70% sensitivity and 78% specificity. A fentanyl infusion duration ≥8 days predicted withdrawal with 90% sensitivity and 67% specificity. The most frequent symptoms of withdrawal were sleeping <3 hours after feeding (81%) and increased muscle tone (55%). In all neonates with withdrawal, onset occurred within 24 hours of fentanyl discontinuation.

CONCLUSIONS:

Opioid withdrawal occurs frequently in critically ill neonates who receive continuous infusions of fentanyl. Longer infusion duration and higher total dose were associated with withdrawal symptoms.
Nesiritide Treatment of Noncardiogenic Pulmonary Edema
Authors: Bobadilla Rodel V , Oppelt Thomas F , Hirshy Thadd C
Published: March 2003

OBJECTIVE:

To report the efficacy of nesiritide in treating noncardiogenic pulmonary edema.

CASE SUMMARY:

A 50-year-old African American woman with a complex medical history including morbid obesity, acute bronchitis, obstructive sleep apnea, hypertension, and numerous hospitalizations for volume overload presented to the emergency department with severe dyspnea. A portable chest X-ray displayed perihilar congestion and bilateral pulmonary edema. An echocardiogram demonstrated normal left-ventricular systolic and diastolic function. She was aggressively treated with nitrates, diuretics, bronchodilators, and oxygen. Despite these efforts, the patient's arterial blood gas (ABG) continued to show respiratory acidosis, the oxygen saturation was significantly depressed, and the dyspnea continued. Since standard therapies were failing after 12 hours, the patient was treated with intravenous nesiritide. The results were profound in terms of rapid symptomatic and prognostic improvement (i.e., ABG) beginning within 45 minutes of administration, and the patient was discharged after a 5-day hospital course.

DISCUSSION:

Nesiritide is a human B-type natriuretic peptide that has been shown to improve hemodynamic function and symptoms associated with decompensated heart failure. This is primarily due to the actions of this medication, including diuresis, decreased mean arterial pressure, and improvement of pulmonary arterial occlusion pressure as determined by published clinical trial outcomes. This case describes the use of nesiritide as an effective adjunctive therapy in treating a patient with noncardiogenic pulmonary edema.

CONCLUSIONS:

Nesiritide appears to be an efficacious treatment for acute pulmonary edema, resistant to standard-of-care therapies, in the presence of normal left-ventricular function.
Stability of Sotalol in Two Liquid Formulations at Two Temperatures
Authors: Nahata Milap C , Morosco Richard S
Published: March 2003

BACKGROUND:

Sotalol is used in certain pediatric patients to treat, suppress, or prevent the recurrence of life-threatening ventricular arrhythmias. However, it is commercially unavailable in a liquid dosage form. The use of an extemporaneously prepared liquid dosage form must be supported by the documentation of the chemical and physical stability of sotalol.

OBJECTIVE:

To determine the stability of sotalol hydrochloride extemporaneously prepared from tablets in 2 oral suspensions stored at 2 temperatures.

METHODS:

Five bottles contained Ora Plus: Ora Sweet (1:1) and the other 5 bottles had 1% methylcellulose:simple syrup NF (1:9), with a sotalol concentration of 5 mg/mL. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating HPLC analytical method (n = 15).

RESULTS:

At 4°C, the mean concentration of sotalol was at least 98.9% of the original concentration in Ora Plus: Ora Sweet suspension and 95.5% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. At 25°C, the mean concentration of sotalol was ≥95.5% of the original concentration in Ora Plus: Ora Sweet suspension and 94.4% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. The pH did not change substantially during the study period. Further, no changes in physical appearance were seen during the study.

CONCLUSIONS:

Sotalol hydrochloride can be prepared in either of 2 liquid dosage forms and stored in plastic bottles for 13 weeks at 4 or 25°C without substantial loss of potency.
Ritonavir-Enhanced Pharmacokinetics of Nelfinavir/M8 during Rifampin Use
Authors: Bergshoeff Alina S , Wolfs Tom FW , Geelen Sibyl PM , Burger David M
Published: March 2003

OBJECTIVE:

To describe a case of successful protease inhibitor–based highly active antiretroviral therapy (HAART) concomitant with rifampin.

CASE SUMMARY:

In a 7-month-old male infant with tuberculosis and HIV-1 infection, tuberculosis therapy including rifampin and HAART containing the protease inhibitor nelfinavir 40 mg/kg every 8 hours was started. Intensive steady-state pharmacokinetic sampling from baseline to 8 hours revealed very low plasma concentrations of nelfinavir: area under the plasma concentration–time curve (AUC0–24) <10% of adult population values for 750 mg every 8 hours and nonquantifiable concentrations of nelfinavir's principal metabolite (M8). Nelfinavir 40 mg/kg every 8 hours was then substituted with nelfinavir 30 mg/kg twice daily plus ritonavir 400 mg/m2 twice daily. Intensive steady-state (0–12 h) pharmacokinetic sampling was repeated. Nelfinavir concentrations had improved, but remained low when compared with adult population values of 1250 mg every 12 hours: AUC0–24 21.9 versus 47.6 mg/L•h (46%) and 12-hour trough level (C12) 0.25 versus 0.85 mg/L (29%). However, concentrations of M8 considerably exceeded population values: AUC0–24 57.5 versus 13.6 mg/L•h (443%) and C12 1.35 versus 0.28 mg/L (482%). Since M8 concentrations were highly elevated, pharmacokinetic parameters for (nelfinavir + M8) were used rather than those for nelfinavir alone. Thus, AUC0–24 (nelfinavir + M8) and C12 (nelfinavir + M8) comprised 130% and 142%, respectively of the adult population values. This, in addition to good clinical response and tolerability, favored continuation of the regimen.

CONCLUSIONS:

In an infant, nelfinavir-containing HAART was successfully used with rifampin after the addition of ritonavir. Ritonavir resolved the pharmacokinetic interaction between rifampin and nelfinavir by boosting nelfinavir and, especially, M8 concentrations. More research is needed to confirm these results.
Analgesic Efficacy of Calcitonin for Vertebral Fracture Pain
Authors: Blau Linsey A , Hoehns James D
Published: March 2003

OBJECTIVE:

To evaluate the analgesic efficacy of calcitonin for treating the pain of vertebral fractures associated with osteoporosis.

DATA SOURCES:

Searches of MEDLINE (1966–July 2002), Cochrane Library, International Pharmaceutical Abstracts (1977–July 2002), and an extensive manual review of journals were performed using the key search terms calcitonin, analgesic, osteoporosis, vertebral fracture, and pain.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified from the data sources were evaluated and all information deemed relevant was included for this review.

DATA SYNTHESIS:

Fractures, especially vertebral fractures, are a common complication of osteoporosis, leading to significant pain. Calcitonin has been studied for its analgesic properties. Fourteen double-blind, placebo-controlled trials that evaluated the analgesic efficacy of calcitonin for osteoporosis-related vertebral fracture pain were identified and reviewed. Thirteen of these studies demonstrated statistically significant improvement in pain or function in calcitonin-treated patients.

CONCLUSIONS:

Calcitonin has proven efficacy in acute pain associated with osteoporosis-related vertebral fractures. Analgesic effects are seen with intranasal, parenteral, and rectal administration. Future studies comparing calcitonin with other commonly used analgesics are needed to more clearly define its place in therapy.
Mechanisms for Linezolid-Induced Anemia and Thrombocytopenia
Authors: Bernstein Wendy B , Trotta Richard F , Rector James T , Tjaden Jeffery A , Barile Anthony J
Published: March 2003

BACKGROUND:

Linezolid has been associated with anemia and thrombocytopenia. Mechanisms for neither have been elucidated.

OBJECTIVE:

To propose mechanisms for linezolid-induced anemia and thrombocytopenia.

CASE SUMMARY:

A 78-year-old white woman with Staphylococcus epidermidis endocarditis was treated with linezolid after developing resistance to multiple antibiotic regimens. After 7 days of linezolid therapy, she developed thrombocytopenia, while an anemia present since admission remained unchanged. A bone marrow biopsy was performed, primarily looking for a mechanism for the thrombocytopenia. Histopathology revealed adequate megakaryocytes, ringed sideroblasts, and vacuolated pronormoblasts. A course of immune globulin (IVIG) was administered, with slowing in the rate of decline in platelets. She died 24 hours after her last dose of IVIG of congestive heart failure.

DISCUSSION:

The presence of ringed sideroblasts and vacuolated pronormoblasts suggests that linezolid-induced anemia is secondary to a chloramphenicol-like suppression of erythropoiesis. The presence of adequate, normal-appearing megakaryocytes suggests immune-mediated thrombocytopenia, not marrow suppression. Although the response to IVIG is difficult to interpret because of the patient's death, there was a slowing in the rate of decline of the platelet count, further supporting immune-mediated thrombocytopenia. An objective causality assessment indicated that the adverse drug event was probably due to linezolid.

CONCLUSIONS:

There appear to be 2 distinct mechanisms for linezolid-induced cytopenias. While anemia is reversible and manageable with transfusions, thrombocytopenia can be a treatment-limiting toxicity. The ability to treat through an immune-mediated cytopenia with IVIG may be beneficial for critically ill patients with few therapeutic options.
Factors Associated with Uncontrolled Hypertension in an Affluent, Elderly Population
Authors: Inciardi John F , McMahon Kay , Sauer Barbara L
Published: March 2003

OBJECTIVE:

To explore demographic, economic, and treatment-related associations with uncontrolled hypertension in a relatively affluent, community-dwelling population.

METHODS:

Two home surveys of 655 and 432 subjects with a diagnosis of hypertension were completed in 1995 and 1999, respectively. Trained surveyors recorded medication history plus demographic and socioeconomic variables, as well as several measurements of blood pressure in the home. Uncontrolled hypertension was defined according to guidelines set forth by the Sixth Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Odds ratios for observing an elevated blood pressure given the patients' medication history, income, insurance coverage, demographic variables, and concomitant disease were estimated using multivariable logistic regression.

RESULTS:

On both occasions, >60% of the study population had an average blood pressure that was above recommended levels. Diuretic therapy alone (1995 survey) or in combination with an angiotensin-converting enzyme inhibitor (1999 survey) decreased the odds ratio for uncontrolled hypertension by 39% (p = 0.027) and 62% (p = 0.005), respectively. Lack of prescription drug insurance and a history of arthritis had negative effects, increasing the odds ratio for uncontrolled hypertension by more than twofold (p < 0.05).

CONCLUSIONS:

Uncontrolled hypertension occurs commonly among elderly patients notwithstanding a relatively high standard of living. The choice of medication, presence of concomitant disease, and availability of insurance may be important factors influencing blood pressure control.
Treatment of Female Sexual Dysfunction
Authors: Ragucci Kelly R , Culhane Nicole S
Published: March 2003

OBJECTIVE:

To review the pathophysiology and psychology of female sexual dysfunction (FSD) and describe potential prevention and treatment strategies for the disorder.

DATA SOURCES:

Articles identified from a MEDLINE search (1966–June 2002) using the term female sexual dysfunction. Additional references were obtained from cross referencing retrieved articles.

STUDY SELECTION AND DATA EXTRACTION:

After evaluating various review articles, clinical trials, and investigational studies, all information that was deemed relevant by the reviewers was included.

DATA SYNTHESIS:

FSD is a multicausal and multidimensional problem combining biological, psychological, and interpersonal factors. The American Foundation for Urological Disease classifies FSD into 4 broad categories: sexual desire disorders, arousal disorder, orgasmic disorder, and sexual pain disorders. Depending on specific individual characteristics and category of disorder, a variety of potential treatments are available. Pharmacists can play a role in identifying and managing medication-related adverse effects that may be exacerbating FSD and educating women on treatment modalities.

CONCLUSIONS:

FSD is a complicated disorder that is often difficult to identify, classify, and treat appropriately. Pharmacists should have an understanding of the potential causes of FSD and the treatment options available so that they may make appropriate recommendations and counsel women effectively.
Cover Picture: Transition‐Metal‐Free Suzuki‐Type Coupling Reactions (Angew. Chem. Int. Ed. 12/2003)
Authors: Leadbeater Nicholas E. , Marco Maria
Published: March 2003

Biaryl compounds can be prepared in an aqueous Suzuki‐type coupling reaction without the need for a transition‐metal catalyst. The Suzuki coupling reaction (palladium‐catalyzed coupling of aryl halides with boronic acids) has virtually become the method of choice for the synthesis of biaryl compounds. Under the right conditions, however, it is possible to perform catalyst‐free Suzuki‐type couplings. Further details are reported in the Communication by N. E. Leadbeater and M. Marco on page 1407 ff.
Unusual Complex Chemistry of Rare‐Earth Elements: Large Ionic Radii—Small Coordination Numbers
Authors: Dehnicke Kurt , Greiner Andreas
Published: March 2003

Because of their large ionic radii and relatively low oxidation states rare‐earth elements generally form complexes which have high coordination numbers and weak metal–ligand bonds. They are often not suitable for homogeneous catalysis on account of their instability of configuration in solution. Complexes of the corresponding metal atoms with low coordination numbers may be an improvement. This type of complex can be obtained in the classical way by the introduction of bulky ligands, and recently, they were also prepared in reactions with ligand groups which offer remarkable metal–ligand bond features. This concept is demonstrated for complexes with bulky bis(trimethylsilyl)amido ligands {N(SiMe3)2}− and “slim” phosphoraneiminato ligands (NPR3−). Their suitability as catalysts for the ring‐opening polymerization of lactones is reported as well.
A Powerful Combinatorial Screen to Identify High‐Affinity Terbium(III)‐Binding Peptides
Authors: Nitz Mark , Franz Katherine J. , Maglathlin Rebecca L. , Imperiali Barbara
Published: March 2003

Lanthanide‐binding tags (LBTs) are protein fusion partners consisting of encoded amino acids that bind lanthanide ions with high affinity. Herein, we present a new screening methodology for the identification of new LBT sequences with high affinity for Tb3+ ions and intense luminescence properties. This methodology utilizes solid‐phase split‐and‐pool combinatorial peptide synthesis. Orthogonally cleavable linkers allow an efficient two‐step screening procedure. The initial screen avoids the interference caused by on‐bead screening by photochemically releasing a portion of the peptides into an agarose matrix for evaluation. The secondary screen further characterizes each winning sequence in a defined aqueous solution. Employment of this methodology on a series of focused combinatorial libraries yielded a linear peptide sequence of 17 encoded amino acids that demonstrated a 140‐fold increase in affinity (57 nM dissociation constant, KD) over previously reported lanthanide‐binding peptides. This linear sequence was macrocyclized by introducing a disulfide bond between flanking cysteine residues to produce a peptide with a 2‐nM apparent dissociation constant for Tb3+ ions.
Direct Observations of the Cleavage Reaction of an L‐DPPC Monolayer Catalyzed by Phospholipase A2 and Inhibited by an Indole Inhibitor at the Air/Water Interface
Authors: Zhai Xiuhong , Li Junbai , Brezesinski Gerald , He Qiang , Möhwald Helmuth , Lai Luhua , Liu Ying , Liu Liang , Gao Ying
Published: March 2003

The enzymatic hydrolysis of an L‐dipalmitoylphosphatidylcholine (L‐DPPC) monolayer at the air/water interface, catalyzed by phospholipase A2 (PLA2), serves as a model for biospecific interfacial reactions. The cleavage of L‐DPPC was investigated by Brewster angle microscopy. Different types of domain defects were observed to form in the coexisting liquid expanded and liquid condensed phases during the hydrolysis reaction. The adsorption of the enzyme was quantitatively recorded as the increase of the surface pressure over a fixed molecular area with time. In the case of L‐DPPC, the surface pressure first increases and then starts to decrease, which indicates that a soluble product (lysolipid) is produced during the catalytic cleavage reaction. The increase and decrease of the surface pressure, which corresponds to the change of shape and number density of domains, indicated the occurrence of the following processes: adsorption of PLA2, cleavage reaction, and rearrangement of substrate and product molecules at the interface. Addition of a PLA2 inhibitor to the lipid monolayer leads to a fast surface pressure increase after enzyme injection. The surface pressure reaches a maximum value and then does not change for a long time. During this period, no change in the domain shape and number density was observed, which indicates that the enzyme is inhibited for a certain period of time. The experimental results provide the possibility of a direct way to prove inhibitor activity.
Synthesis of Novel Acceptor Substrates for the Dolichyl Phosphate Mannose Synthase from Yeast
Authors: Sprung Ines , Carmès Laurence , Watt Gregory M. , Flitsch Sabine L.
Published: March 2003

Dolichols are polyisoprenoid lipid components of mammalian membranes consisting of an average of 20 head‐to‐tail linked isoprene units of which the first isoprene is fully saturated. The unusual size of these lipids is intriguing and poses questions about the role of dolichol structure in biological processes. In order to probe structure and function we have synthesised potential dolichyl analogues that retain only the first two isoprene units and carry a second functional group within the terminal lipid chain. Such analogues were evaluated as substrates for a key enzyme in the dolichyl‐dependent pathway of glycan biosynthesis, dolichyl phosphate mannose (Dol‐P‐Man) synthase. It was shown that some functional groups, including labels such as biotin, could be tolerated. When the synthetic analogues were attached to a solid support they were still substrates for the Dol‐P‐Man system and thus allowed the enzymatic solid‐phase synthesis of glycolipids.
Assessment of specimen adequacy reproducibility: An Italian experience
Authors: Montanari Gioia , Confortini Massimo , Bellomi Alberto , Cocchi Valeria , Dalla Palma Paolo , D'Ambrosio Enrico , Giovagnoli Maria Rosaria , Navone Roberto , Ronco Guglielmo
Published: March 2003

Interobserver disagreement on smear adequacy may influence the evaluation of the performance of samplers as well as Pap test sensitivity and follow‐up. In 1998, the Italian Group for Cervical Cancer Screening (GISCi) promoted a study on the reproducibility of adequacy criteria using a modified version of the Bethesda system. A set of 200 smears was circulated among six Italian laboratories situated in different parts of the country. For each smear, participants were requested to provide a summary judgment on its adequacy and on the cause(s) of inadequacy, if any. Agreement was measured using kappa‐type statistics. The agreement among laboratories was generally good. In comparisons, among five laboratories, kappa values ranged from 0.47 to 0.66. At the consensus meeting on 42 slides, on which at least 2 laboratories dissented from the majority, agreement was reached unanimously for 31 reviewed slides and among 5–6 centers for 11. In this article, some guidance is given in order to attribute to one of the two categories satisfactory/unsatisfactory those smears that have been traditionally considered as candidates for the category of “satisfactory but limited by …” (SBLB). New Italian guidelines on adequacy proposed the GISCi are presented and the recommendation is made to eliminate the SBLB category. Diagn. Cytopathol. 2003;28:224–226. © 2003 Wiley‐Liss, Inc.
Inflammatory fibroid polyp of the ileum causing intussusception: Report of two cases with emphasis on cytologic diagnosis
Authors: Savargaonkar Pratima , Morgenstern Nora , Bhuiya Tawfiqal
Published: March 2003

Inflammatory fibroid polyp (IFP) of the gastrointestinal tract is a type of inflammatory pseudotumor or inflammatory myofibroblastic tumor that occurs most commonly in the stomach but also in the small and large bowel. Small‐bowel IFP usually presents with intussusception. The purpose of the current study is to describe cytological features of this lesion with differential diagnoses since pathologists may be called on to render a diagnosis on fine‐needle aspiration. Two cases of IFP are described with diagnostic features on imprint smears. Both were middle‐aged obese women with a history of prior intra‐abdominal surgical procedures who presented with signs of intestinal obstruction and were found to have a tumor causing intussuscption. At intraoperative consult, scrape cytology specimens showed cellular smears with a heterogeneous population of myofibroblasts, inflammatory cells and vessels. The features together with clinical history are sufficient to suggest the diagnosis. IFP is a lesion with a characteristic morphology. The differential diagnosis includes several other lesions, hence triage of cytological specimen for culture, electron microscopy, and immunohistochemistry is important in facilitating a correct diagnosis. Although a surgical procedure may still be necessary once a diagnosis of IFP is made, treatment may be tailored for a less aggressive process. Diagn. Cytopathol. 2003;28:217–221. © 2003 Wiley‐Liss, Inc.
Clinical and diagnostic significance of blood in cervical smears
Authors: Boon Mathilde E. , Ouwerkerk‐Noordam Elisabeth , van Leeuwen Antoine W.M.F. , van Haaften‐Day Caroline
Published: March 2003

A heavy admixture of blood in cervical smears can be problematic for the screener, as the presence of blood can influence the staining quality of the cancer cell nuclei. However, it might also be a blessing in disguise. A retrospective study of 40 clinically important smears, 34 originally signed out as negative for squamous cell carcinoma of the cervix and 6 smears as unsatisfactory, was carried out in comparison with 100 smears from healthy women. Sample parameters were analyzed by macroscopy and neural network scanning. Differences between the two study groups were measured by Pearson's χ2 test. Of the 40 study cases, one case featured insufficient material, while 16 cases (40%) could confidently be classified as malignant or negative for malignancy. The most important macroscopic parameter of the smears was an admixture of blood. This background feature was also highlighted by the NNS system. Angiogenesis was visualized by the expression of CD34 in many sampled capillary fragments included in the smears. In conclusion, blood in cervical smears may have clinical and diagnostic significance. The rate of “failed smears” in routine cervical screening might thus by CD34 be considerably decreased. Diagn. Cytopathol. 2003;28:181–185. © 2003 Wiley‐Liss, Inc.
Primary diagnosis and REAL/WHO classification of non‐Hodgkin's lymphoma by fine‐needle aspiration: Cytomorphologic and immunophenotypic approach
Authors: Mourad W.A. , Tulbah A. , Shoukri M. , Al Dayel F. , Akhtar M. , Ali M.A. , Hainau B. , Martin J.
Published: March 2003

The Revised European American lymphoma (REAL) and World Health Organization (WHO) classification of non‐Hodgkin's lymphoma (NHL) relies on the constellation of cytologic, phenotypic, genotypic, and clinical characteristics of NHL. For the most part, the classification does not rely on architectural pattern for classification of neoplasms. This classification makes it possible to diagnose and classify lymphomas by fine‐needle aspiration (FNA). In this study, we attempted to evaluate the accuracy of FNA in diagnosing and classifying NHL within the context of the REAL/WHO classifications. Cases included only those in which FNA was the primary diagnosis, followed by a surgical biopsy for confirmation. Flow cytometry (FCM) for phenotyping was carried out whenever material was available. Two groups of pathologists were identified. Group A consisted of pathologists with background training in cytopathology and/or hematopathology (three pathologists). Group B consisted of experienced surgical pathologists with no training in cytopathology and/or hematopathology (four pathologists). Seventy‐four cases were included in the study. FCM phenotyping was performed in 53 cases (71%). Large cell lymphoma constituted 63% of the cases. The remaining lymphomas included Burkitt's, small lymphocytic, lymphoblastic, follicle center cell, Ki‐1, mantle cell, marginal zone, and natural killer cell lymphoma. The diagnosis of lymphoma was rendered for all cases. The correct classification was seen in 63% of the cases. Classification was more accurate in immunophenotyped than in nonimmunophenotyped cases (84% vs 33%; P = 0.00004). Group A pathologists showed higher incidence of proper classification than group B (80% vs 56%; P = 0.046). The diagnosis and classification of NHL can be achieved in a large number of cases on FNA material. This accuracy can be increased if cytomorphologic criteria are established for different entities of NHL aided by FCM for phenotyping. Diagn. Cytopathol. 2003;28:191–195. © 2003 Wiley‐Liss, Inc.
Endocrine effects of dehydroepiandrosterone and its fluorinated analog, fluasterone, in rats
Authors: Brown Alan P. , Kirchner Debra L. , Morrissey Robert L. , Das Saroj R. , Fitzgerald Robert L. , Crowell James A. , Levine Barry S.
Published: March 2003

Cancer chemoprevention is the use of pharmacologic agents to inhibit the development of cancer. The adrenal steroid dehydroepiandrosterone (DHEA) has demonstrated chemopreventive efficacy in animal models of tumorigenesis. However, due to DHEA's undesirable hormonal actions, the fluorinated analog fluasterone (fl‐DHEA), which also has chemopreventive characteristics, was synthesized as a potential alternate agent. It is not known whether fl‐DHEA has hormonal actions. The endocrinologic effects of DHEA and fl‐DHEA in adult male and female Fischer 344 rats were examined following 28 days of daily oral treatment. Initial doses tested were 30 and 300 mg/kg/day for each drug (n=12/sex/group), which are equivalent to 104 and 1,042 µmoles/kg/day DHEA, and 103 and 1,034 µmoles/kg/day fl‐DHEA. However, due to weight loss at the high dose, doses were lowered to 150 mg/kg/day for each drug (521 and 517 µmoles/kg/day DHEA and fl‐DHEA, respectively). Administration of DHEA resulted in dose‐dependent increases in plasma DHEA and DHEA‐S 1 h after dosing in week 4. DHEA produced an estrogenic effect in female rats expressed as decreased plasma FSH and LH, inhibition of ovulation, prolonged estrus, and increased uterine estrogen receptors. DHEA also increased plasma levels of androstenedione in males and females. Administration of fl‐DHEA increased the estrus cycle length due to a prolonged diestrus II phase and decreased the weights of the uterus, prostate, seminal vesicles, and testes. In addition, fl‐DHEA decreased plasma FSH, LH, and tissue estradiol, and increased plasma dihydrotestosterone levels in both sexes. These results indicate that fl‐DHEA is hormonally active and additional studies are warranted to further describe its endocrinologic effects. Drug Dev. Res. 58:169–178, 2003. © 2003 Wiley‐Liss, Inc.
Effects of antihistamines, ebastine and terfenadine, on electrocardiogram in conscious dogs and cats
Authors: Kii Yoshihide , Nakatsuji Katsuyoshi , Nose Isamu , Yabuuchi Masafumi , Matsuda Michiaki , Ito Tsugutaka
Published: March 2003

The purpose of this study was to evaluate the effects of ebastine and terfenadine on the electrocardiogram of conscious dogs and cats. In dogs, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the electrocardiographic QT interval and the corrected QT (QTc) interval on the seventh day, whereas the drug did not affect these parameters on the first day. Plasma concentrations of terfenadine and its active metabolite, fexofenadine, reached 306 and 8,541 ng/mL, respectively, on the seventh day. Ebastine at oral doses of 30 and 100 mg/kg once a day for 7 days was without effect on the QT and QTc intervals, whereas the drug slightly shortened the RR interval. On the seventh day following the dose of 100 mg/kg, plasma concentrations of ebastine and its active metabolite, carebastine, reached 36 and 1,939 ng/mL, respectively. In conscious cats, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the QT and QTc intervals, QRS duration, JT and the corrected JT intervals. Unexpectedly, terfenadine induced ventricular tachyarrhythmia and premature beats. On the other hand, ebastine at oral doses of 100 mg/kg once a day for 7 days was without effect on the electrocardiographic parameters in cats. These results suggest that the electrocardiographic changes indicative of the proarrhythmic potential of terfenadine can be evaluated in conscious dogs and especially in conscious cats by repeated oral administration, and that ebastine does not induce such changes. 58:209–217, 2003. © 2003 Wiley‐Liss, Inc.
Nonlinear analysis of the development of sitting postural control
Authors: Harbourne Regina T. , Stergiou Nicholas
Published: March 2003

The development of sitting postural control in five normal infants was examined longitudinally at three stages of sitting: Stage 1, when infants could hold up their head and upper trunk, but could not sit independently; Stage 2, when infants began to sit independently briefly; and Stage 3, when infants could sit independently. Methods from nonlinear dynamics were used to analyze center of pressure (COP) data during sitting in terms of stability of the neuromuscular system (Lyapunov Exponent), movement dimensionality (Correlation Dimension), and complexity/regularity (Approximate Entropy). Results indicated significant changes in the nonlinear measures over time, with increased stability and increased regularity revealing a more stable and periodic strategy of maintaining postural control. Dimensionality decreased from Stage 1 to 2, indicating a constraint of the degrees of freedom. Subsequently, dimensionality increased from Stage 2 to 3, indicating a release of the degrees of freedom as sitting independence emerged. Nonlinear analysis of the COP time series supports the perspective that the development of postural control is a dynamic process whereby the infant learns to control the body's degrees of freedom to achieve the sitting posture. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 42: 368–377, 2003.
A new separate‐identification method of two stator equivalent core‐loss resistances corresponding to hysteresis and eddy‐current losses for parallel‐type mathematical models of AC motors
Authors: Shinnaka Shinji
Published: March 2003

This paper proposes a new unified method for identifying equivalent stator core‐loss resistance of AC motors, which can be applied to both induction and synchronous motors. In order to realize AC motors that exhibit high performance such as precise torque generation and/or efficient energy transmission, stator core loss cannot be neglected in designing vector control systems. It is common to model stator core loss in magnetic circuits as loss caused by equivalent resistance in electrical circuit. One of the best mathematical models for controlling AC motors with core loss is a kind of parallel‐type model that succeeds in modeling both eddy‐current and hysteresis losses. The newly proposed method succeeds in identifying separately and simultaneously two kinds of equivalent core‐loss resistances on the model corresponding to eddy‐current and hysteresis losses. The practical usefulness of the method is evaluated and confirmed through experiments using two induction motors of 5.5 and 2.0 kW having relatively high core losses and a permanent magnet synchronous motor of 750 W having relatively low core losses. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 50–63, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10152