bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Copolymeric Gels Composed of Polydimethylsiloxane and Polyethylene Oxide Network Chains and Their Specific Characteristics
Authors: Kohjiya Shinzo , Tsubata Hideki , Urayama Kenji
Published: February 2006

Copolymeric networks composed of two chemically different network chains, polydimethylsiloxane (PDMS) and polyethylene oxide (PEO), are prepared by the two synthetic methods: (1) Vinyl-terminated PDMS and PEO are end-linked with the multi-functional silane compounds; (2) Vinyl-terminated PEO and silyl-terminated PDMS are end-linked with each other. The compositions in the resulting two-component networks are determined by two independent methods: 1H NMR analysis of the extracted unreacted materials and thermogravimetric analysis of the network samples. The appearances of the copolymeric networks are transparent. The differential scanning calorimetry and dynamic mechanical analysis show that the copolymeric networks have the microphase separated structures composed of PDMS and PEO phases. Swelling experiments in various solvents clearly indicates the amphiphilic character of the copolymeric networks. The Li-doped copolymeric networks, which are obtained by immersing the gels in LiClO4, exhibit conductivity of the order of 10−6 S cm−1 at room temperature. The temperature dependence of the conductivity obeys the William–Ferry–Landel equation based on the free volume theory.
Structure-Reactivity Relationship in Allyl and 2-Propynyl Complexes of Group 10 Metals Relevant to Homogeneous Catalysis
Authors: Kurosawa Hideo , Ogoshi Sensuke
Published: February 2006

Recent developments in the understanding of some fundamental reactions undergone by group 10 metal allyl and propargyl (2-propynyl) complexes are described. Emphasis was placed on the bonding-reactivity relationship of these complexes which are relevant as key intermediate models in transition metal catalyzed transformations of allylic and propargylic substrates as well as related transformations involving unsaturated hydrocarbons. The specific complexes surveyed include group 10 metal complexes of allyl and propargyl ligands bound to the metal both in η1- and η3-fashions. Specific reactions to be discussed include oxidative addition, nucleophilic and electrophilic attack at the allyl or propargyl ligands, and reductive elimination of the allyl ligands.
Synthesis and Properties of Photochromic Diarylethenes with Heterocyclic Aryl Groups
Authors: Irie Masahiro , Uchida Kingo
Published: February 2006

A new class of thermally irreversible and fatigue resistant photochromic molecules named diarylethenes has been developed. Theoretical consideration based on the state correlation diagrams of electrocyclic reactions revealed that the thermal irreversibility is attained by introducing aryl groups that have low aromatic stabilization energy. According to the molecular design principle thermally irreversible photochromic diarylethenes having heterocyclic five-membered rings, such as furan, thiophene (or benzothiophene), or thiazole rings, have been newly synthesized. Among them, diarylethenes having benzothiophene aryl groups showed an excellent fatigue resistant property. They underwent photochromic cycles more than 1.0 × 104 times. The absorption maxima of the closed-ring forms varied from 425 to 828 nm depending on the aryl groups, substituents of the aryl groups, and the substitution position of the aryl groups to the ethane moiety. The response times of both cyclization and ring-opening reactions were less than 10 ps in solution as well as in a crystalline phase. The chemical and thermal control of photochromic reactivity was achieved by introducing intramolecular hydrogen bonding groups or oligothiophene aryl groups to the diarylethenes. Some of the dithienylperfluorocyclopentene derivatives were found to show photochromic reactivity in the crystalline phase. The reactivity was dependent on the conformation and molecular packing in the crystals.
Electrical and Structural Properties and Phase Diagram of a Molecular Superconductor β-[(CH3)4N][Pd(dmit)2]2
Authors: Kobayashi Akiko , Miyamoto Akihito , Kato Reizo , Sato Akane , Kobayashi Hayao
Published: February 2006

β-[(CH3)4N][Pd(dmit)2]2 is isomorphic to [(CH3)4N][Ni(dmit)2]2, which is the first pure π acceptor molecular conductor exhibiting a superconducting transition. The crystal structure at low temperature, pressure dependence of the resistivity and the magnetic susceptibility of β-[(CH3)4N][Pd(dmit)2]2 were examined. The general features of the phase diagram of β-[(CH3)4N][Pd(dmit)2]2 resemble those of the organic superconductors. At ambient pressure, the resistivity increases gradually with lowering temperature. A superconducting transition was observed at 6—9 kbar. The highest Tc was 6.5 K. Between 5 and 6.3 kbar, a characteristic rapid resistivity decrease was observed at the small temperature range above the offset temperature of the superconducting transition. Although the resistivity is not zero, this temperature region can be regarded as a “pre-superconducting region.” Above 9 kbar the metallic state is stabilized down to low temperature. Above 5 kbar, most of the crystals exhibited resistivity anomalies around 60 K, which may be ascribed to the metal-insulator transition of the domains with α-type structure (α-[(CH3)4N][Pd(dmit)2]2), which became mixed in with the crystals of β-[(CH3)4N][Pd(dmit)2]2. The resistivity data of the highly conducting state were very noisy in the pressure range where the superconducting transition could be observed.
Cannabinoid Analgesia as a Potential New Therapeutic Option in the Treatment of Chronic Pain
Authors: Burns Tammy L , Ineck Joseph R
Published: February 2006

Objective:

To review the literature concerning the physiology of the endocannabinoid system, current drug development of cannabinoid agonists, and current clinical research on the use of cannabinoid agonists for analgesia.

Data Sources:

Articles were identified through a search of MEDLINE (1966–August 2005) using the key words cannabis, cannabinoid, cannabi*, cannabidiol, nabilone, THC, pain, and analgesia. No search limits were included. Additional references were located through review of the bibliographies of the articles identified.

Study Selection and Data Extraction:

Studies of cannabinoid agonists for treatment of pain were selected and were not limited by pain type or etiology. Studies or reviews using animal models of pain were also included. Articles that related to the physiology and pharmacology of the endocannabinoid system were evaluated.

Data Synthesis:

The discovery of cannabinoid receptors and endogenous ligands for these receptors has led to increased drug development of cannabinoid agonists. New cannabimimetic agents have been associated with fewer systemic adverse effects than delta-9-tetrahydrocannabinol, including recent development of cannabis medicinal extracts for sublingual use (approved in Canada), and have had promising results for analgesia in initial human trials. Several synthetic cannabinoids have also been studied in humans, including 2 cannabinoid agonists available on the international market.

Conclusions:

Cannabinoids provide a potential approach to pain management with a novel therapeutic target and mechanism. Chronic pain often requires a polypharmaceutical approach to management, and cannabinoids are a potential addition to the arsenal of treatment options.
Lanthanum Carbonate
Authors: Joy Melanie S , Kshirsagar Abhijit , Candiani Corina , Brooks Tyson , Hudson Joanna Q
Published: February 2006

Objective:

To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of lanthanum carbonate, a phosphate binder for chronic kidney disease (CKD).

Data Sources:

Information was selected from PubMed (1965–October 2005). All studies presented as scientific posters and abstracts from nephrology meetings from 1999 to 2005 were also included.

Study Selection and Data Extraction:

All published articles regarding lanthanum carbonate were included. In addition, abstracts and presentations from scientific meeting symposia were also considered for inclusion.

Data Synthesis:

Lanthanum carbonate has been recently approved as non-calcium-based therapy for phosphate reduction in patients with stage 5 CKD requiring dialysis. The recommended dose is 250–500 mg with meals, for a maximum of 1500 mg daily. Clinical studies have shown short- and long-term safety with lanthanum carbonate administration. Adverse effects were primarily gastrointestinal in nature. Clinical trials have also shown reductions in serum phosphorus to target concentrations, reductions in associated calcium-phosphorus product, and minimal effects on serum calcium and parathyroid hormone concentrations.

Conclusions:

Lanthanum carbonate is an effective phosphate-binding agent without significant risk of hypercalcemia or worsening metabolic acidosis. Lanthanum carbonate is a safe and effective drug for reduction of elevated serum phosphorus levels associated with stage 5 CKD. The role of lanthanum carbonate relative to other phosphate-binding drugs, such as calcium salts and sevelamer, remains to be determined.
Bivalirudin Use in Carotid Endarterectomy in a Patient with Heparin-Induced Thrombocytopenia
Authors: Finks Shannon W
Published: February 2006

Objective:

To describe the successful use of bivalirudin as the primary procedural anticoagulant in a patient with suspected heparin-induced thrombocytopenia (HIT) undergoing carotid endarterectomy (CEA).

Case Summary:

A 73-year-old white man presented for an elective CEA 3 weeks after emergent, on-pump coronary artery bypass grafting. Bivalirudin was used for procedural anticoagulation because of seropositivity for heparin-PF4 antibodies and a clinical history consistent with HIT. The dose was administered as a 0.75 mg/kg bolus and 1.75 mg/kg/h infusion as reported in percutaneous coronary intervention, based on review of the available bivalirudin literature. The dosage was adjusted for the patient's renal dysfunction. The outcome was successful, with the patient discharged home in 8 days without significant complications.

Discussion:

During active HIT, when thrombocytopenia and heparin-PF4 antibodies are present, heparin therapy must be avoided. In patients with subacute HIT, when platelet counts have recovered but HIT antibodies are still present, it is also prudent to avoid heparin administration. In the case of a patient in whom anticoagulation is necessary but heparin use is contraindicated, a direct thrombin inhibitor, such as bivalirudin, may offer a viable alternative. Bivalirudin is not immunogenic and does not cross-react with the heparin-PF4 antibodies associated with HIT. To our knowledge, as of January 20, 2006, this is the first report of the use of bivalirudin for procedural anticoagulation during CEA in a patient with HIT antibodies and recent exposure to heparin.

Conclusions:

Further investigation is warranted to clarify the clinical benefits of bivalirudin for patients undergoing vascular surgery of the carotids, including potential advantages for vulnerable patient populations such as those with diagnosed or suspected HIT as well as those with renal dysfunction.
Drug-Gene Interaction Between the Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Antihypertensive Therapy
Authors: Schelleman Hedi , Klungel Olaf H , van Duijn Cornelia M , Witteman Jacqueline CM , Hofman Albert , Boer Anthonius de , Stricker Bruno HCh
Published: February 2006

Background:

Despite the availability of a variety of effective drugs, inadequate control of blood pressure is common. There are some indications that the angiotensin-converting enzyme (ACE) gene modifies the response to antihypertensive drugs, but the results have been inconclusive.

Objective:

To investigate whether the insertion/deletion polymorphism of the ACE gene modifies blood pressure differences among subjects using diuretics, β-blockers, calcium-channel antagonists, or ACE inhibitors.

Methods:

Data were used from the Rotterdam Study, a population-based, prospective, cohort study in the Netherlands, which started in 1990 and included 7983 subjects aged 55 years or older. Data from 3 subsequent cross-sectional investigations were used, as well. Subjects were included if they had high blood pressure during one or more examinations and/or used monotherapy with a diuretic, β-blocker, calcium-channel antagonist, or ACE inhibitor. A marginal, generalized, linear model was used to assess the association between the mean difference in systolic/diastolic blood pressure and antihypertensive classes stratified by the 3 genotypes.

Results:

In total, 3025 hypertensive individuals were included, and 6500 measurements of blood pressure were taken. The percentages of DD, ID, and II genotypes were 28.3%, 51.4%, and 20.3%, respectively. The mean differences in systolic blood pressure between the II and DD genotypes were 0.23 mm Hg (95% Cl −5.48 to 5.94) for diuretics, −2.41 mm Hg (95% Cl −6.72 to 1.90) for β-blockers, 2.12 mm Hg (95% Cl −4.64 to 8.89) for calcium-channel antagonists, and −2.01 mm Hg (95% Cl −9.82 to 5.79) for ACE inhibitors.

Conclusions:

The adjusted mean difference in diastolic and systolic blood pressure among diuretic, β-blocker, calcium-channel antagonist, or ACE inhibitor users was not modified by the ACE insertion/deletion polymorphism.
Successful Clearance of Catheter-Related Bloodstream Infection by Antibiotic Lock Therapy Using Ampicillin
Authors: Elwood Robert L , Spencer Steven E
Published: February 2006

Objective:

To report a case in which ampicillin was used successfully as lock therapy for a central venous intravascular catheter and to discuss the implications of ampicillin used in this modality.

Case Summary:

A 14-month-old girl with a long-term central venous catheter acquired a polymicrobial (Escherichia coli and Enterococcus durans) bloodstream infection. The central venous catheter was suspected as the source for the bacteremia based on the timing and number of positive blood cultures in relation to therapy with antibiotics. Antibiotic sensitivity testing revealed ampicillin monotherapy to be an ideal choice to treat both organisms. A combination of systemic therapy via a temporary catheter and antibiotic lock therapy of the central venous catheter was then instituted using ampicillin without anticoagulants. The patient tolerated this therapy without complications, and follow-up cultures demonstrated effective clearance of the bacteria.

Discussion:

Antibiotic lock therapy has been shown to be useful in the treatment of catheter-related bloodstream infections. However, many antibiotics have yet to be tested with this modality. Ampicillin, which is frequently used in the treatment of Enterococcus and E. coli infections, has not previously been reported as a single agent for lock therapy.

Conclusions:

Ampicillin may be a useful agent with the relatively new modality of lock therapy for central venous catheters. Further studies are needed to demonstrate possible compatibility of this agent with anticoagulants, such as heparin, as well as its efficacy in treating catheter-related bloodstream infections.
Emerging Role of Epidemiologic Literacy
Authors: Draugalis JoLaine Reierson , Plaza Cecilia M
Published: February 2006

Background:

The ability to understand and apply epidemiology methods is a growing part of pharmacy practice, pharmacy accreditation standards, and evidence-based practice.

Objective:

TO examine the trends in epidemiology-related terminology used in the literature over the past 20 years.

Methods:

The frequency of the use of epidemiology-related terminology in 3 representative pharmacy Journals, 2 representative medical journals, and 1 public health journal from January through December 1984, 1994, and 2004 was recorded. The 3 pharmacy journals were the American Journal of Health-System Pharmacy (formerly American Journal of Hospital Pharmacy), The Annals of Pharmacotherapy (formerly Drug Intelligence and Clinical Pharmacy), and Pharmacotherapy. The 2 medical journals were the New England Journal of Medicine and The Journal of the American Medical Association (JAMA), and the public health journal was the American Journal of Public Health. The number of times an epidemiology-related term was used was summed for each year and each journal.

Results:

For all the journals examined in this study combined, the proportion of epidemiologic terms used in the literature has increased over the past 20 years. In 1984, of the total articles published in the 6 journals, 7.02% contained epidemiologic terms increasing to 12.27% and 15.46% in 1994 and 2004, respectively. The most dramatic differences in the 20-year comparisons were noted for Pharmacotherapy (0 to 17.75%) and JAMA (7.32 to 26.72%).

Conclusions:

The increase in the use of epidemiology-related terms has implications for both curricular planning in schools and colleges of pharmacy, as well as for continuing education programs and effective interprofessional communication.
Meropenem by Continuous Versus Intermittent Infusion in Ventilator-Associated Pneumonia due to Gram-Negative Bacilli
Authors: Lorente Leonardo , Lorenzo Lisset , Martín María M , Jiménez Alejandro , Mora María L
Published: February 2006

Background:

It is known that β-lactam antibiotics exhibit time-dependent bactericidal activity. Several studies have found continuous infusion of meropenem more effective than intermittent infusion in maintaining constant serum concentrations in excess of the minimum inhibitory concentration. However, limited data exist on the clinical efficacy of meropenem administered by continuous infusion.

Objective:

To evaluate the clinical efficacy of continuous versus intermittent infusion of meropenem for the treatment of ventilator-associated pneumonia (VAP) due to gram-negative bacilli.

Methods:

A retrospective cohort study was conducted of patients with VAP caused by gram-negative bacilli who received initial empiric antibiotic therapy with meropenem. We analyzed 2 contemporary cohorts: one group received meropenem by continuous infusion (1 g over 360 min every 6 h), the other by intermittent infusion (1 g over 30 min every 6 h). The administration method was prescribed according to the physician's discretion. Patients received meropenem plus tobramycin for 14 days.

Results:

There were no significant differences between patient groups with regard to gender, age, APACHE-II at intensive care unit admission, diagnosis, microorganism responsible for VAP, or organ dysfunction severity at the time VAP was suspected. The group receiving medication by continuous infusion showed a greater clinical cure rate than the group treated with intermittent infusion (38 of 42, 90.47%, vs 28 of 47, 59.57%, respectively, with OR 6.44 [95% Cl 1.97 to 21.05; p < 0.001]).

Conclusions:

Meropenem administered by continuous infusion may have more clinical efficacy than intermittent infusion.
Successful Recovery After an Overdose of Argatroban
Authors: Yee Andrew J , Kuter David J
Published: February 2006

Objective:

To report the case of a critically ill man with heparin-induced thrombocytopenia (HIT) who received a 125 mg overdose of the direct thrombin inhibitor argatroban.

Case Summary:

A 74-year-old man with a history of Crohn's disease underwent takedown of an ileorectal fistula. He developed HIT postoperatively and was treated with argatroban. He became critically ill and was transferred to the intensive care unit. On postoperative day 24, he accidentally received argatroban 125 mg over 1 hour (26 μg/kg/min). Treatment with fresh frozen plasma (FFP) was effective, and there were no significant complications. The partial thromboplastin time, however, continued to be prolonged 48 hours after the overdose.

Discussion:

Medication errors with direct thrombin inhibitors are common. However, there is no known reversal agent for this class of anticoagulants. This patient was treated with FFP and did well, with no bleeding complications. However, the clearance of argatroban was prolonged.

Conclusions:

This case illustrates that supratherapeutic doses of argatroban can be managed with FFP and tolerated without significant complications.
Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury
Authors: Schneider H J , Schneider M , Saller B , Petersenn S , Uhr M , Husemann B , von Rosen F , Stalla G K
Published: February 2006

Objective: Cross-sectional studies report a high prevalence of hypopituitarism after traumatic brain injury (TBI); however, no longitudinal studies on time of manifestation and reversibility exist. This study was conducted to assess hypopituitarism 3 and 12 months after TBI.

Design: This was a prospective, longitudinal, diagnostic study.

Methods: Seventy-eight patients (52 men, 26 women, mean age 36.0 years) with TBI grades I–III and 38 healthy subjects (25 men, 13 women, mean age 36.4 years) as a control group for the GHRH + arginine test were studied. The prevalence ofhypopituitarism was assessed 3 and 12 months after TBI by GHRH + arginine test, short adrenocorticotropic hormone (ACTH) test, and basal hormone measurements in patients.

Results: After 3 months, 56% of all patients had impairments of at least one pituitary axis with axes being affected as follows: gonadotropic 32%, corticotropic 19%, somatotropic 9% and thyrotropic 8%. After 12 months, fewer patients were affected, but in some cases new impairments occurred; 36% still had impairments. The axes were affected as follows after 12 months: gonadotropic 21%, somatotropic 10%, corticotropic 9% and thyrotropic 3%.

Conclusions: Hypopituitarism occurs often in the post-acute phase after TBI and may normalize later, but may also develop after the post-acute phase of TBI.
Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele-specific PCR amplification (MASA)
Authors: Sapio Maria Rosaria , Posca Daniela , Troncone Giancarlo , Pettinato Guido , Palombini Lucio , Rossi Guido , Fenzi Gianfranco , Vitale Mario
Published: February 2006

Objective: The somatic point mutation in the BRAF gene, which results in a valine-to-glutamate substitution at residue 600 (BRAFV600E), is an ideal hallmark of papillary thyroid carcinoma (PTC). However, its prevalence is varyingly reported in different studies, and its expression in the follicular variant PTC is controversial, reducing its potential usefulness as diagnostic marker.

Design and methods: We developed an assay based on mutant allele-specific PCR amplification (MASA) to detect BRAF mutation. We compared the sensitivity of MASA, single-strand conformation polymorphism (SSCP) and direct DNA sequencing of PCR products. Then, we used MASA 78 to analyze 78 archival thyroid tissues, including normal samples, follicular adenomas, follicular carcinomas and PTC.

Results: The MASA assay proved to be a more sensitive method than SSCP and DNA sequencing of PCR products. BRAF mutation was found by MASA in 19/43 (44.2%) of PTC, including 14/31 (45.2%) classic forms and 5/12 (41.7%) follicular variants. No mutations of BRAF were detected in the normal thyroid tissues, nor in follicular adenomas or follicular carcinomas. No correlation was found between BRAF mutation and clinicopathologic features nor with recurrence during a postoperative follow-up period of 4–11 years. BRAFV600E significantly correlated with absence of node metastasis.

Conclusions: BRAFV600E is present in PTC, both in the classic form and in follicular variant with similar prevalence. No correlation was found between BRAF mutation and aggressive clinical behavior. MASA-PCR proved to be a specific, sensitive and reliable method to detect BRAF T1799A in DNA extracted from different sources, including cytologic samples obtained either fresh or from archival glass slides. We propose this method as a useful tool to improve accuracy of preoperative diagnosis identifying PTC from biopsies with indeterminate cytologic findings.
The octreotide test dose is not a reliable predictor of the subsequent response to somatostatin analogue therapy in patients with acromegaly
Authors: Pokrajac Ana , Claridge Andrew G , Shakoor S K Abdul , Trainer Peter J
Published: February 2006

In many centres, a test dose (TD) of octreotide is administered before commencing somatostatin analogue therapy (SAT), although the merits of this procedure are uncertain. We have analysed the value of the GH response to a TD in predicting the efficacy of subsequent SAT in 47 patients with acromegaly (25 male, median age 51 years, range 20–82). The primary goal of SAT was a mean GH of < 5 mU/l. Median baseline GH was 19.3 mU/l (2.2–233 mU/l) and with the TD fell by 78% (35–98%) to a nadir of 4.2 mU/l (<0.3–85 mU/l). Optimal predictive power was observed when GH fell to < 5 mU/l after the TD. With this criterion, the TD had a positive predictive value (PPV) of achieving the primary goal on SAT of 82% and a negative predictive value (NPV) of 50%. However, baseline GH was also highly predictive of the likelihood of successful SAT (GH < 5 mU/l). The GH response to the TD had PPV of 83% and NPV of 61% of normalising IGF-I on SAT. In summary, baseline GH and nadir after a TD are highly predictive of a good response to SAT; however, a poor response to a TD does not exclude an optimal response to SAT. Furthermore, failure to achieve biochemical control does not equate to no benefit, as biochemical improvement was seen in every patient; therefore, no patient should be deprived of octreotide therapy because of the result of a TD. In conclusion, our data indicate that the octreotide TD has no place in selecting patients for SAT.
Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients
Authors: Oltmanns Kerstin M , Dodt Baerbel , Schultes Bernd , Raspe Hans H , Schweiger Ulrich , Born Jan , Fehm Horst L , Peters Achim
Published: February 2006

Objective: The prevalence of type 2 diabetes mellitus is increasing rapidly in industrialized countries, and adrenal glucocorticoids may intensify this disease. We sought to assess the relationship between diabetes-associated metabolic disturbances and cortisol concentrations in patients with type 2 diabetes.

Design: We investigated 190 type 2 diabetic patients who volunteered from a population study of 12 430 people in Luebeck and its suburbs. The target population comprised men and women born between 1939 and 1958 who initially received a postal questionnaire about their health status. We identified 346 subjects with confirmed diabetes mellitus and 216 patients participated in the study. Patients with type 1 diabetes were excluded.

Methods: Five salivary cortisol samples were collected before and after lunch, in the evening and then the next morning before and after standing. Clinical variables associated with diabetes were measured and correlated with cortisol concentrations.

Results: None of the cohort had salivary cortisol concentrations that exceeded the normally accepted range. Based on cortisol samples collected just prior to a standard lunch, the cohort was divided into tertiles. Cortisol was positively related to: fasting blood, urinary and postprandial glucose; glycosylated hemoglobin; and systolic and diastolic blood pressures (all P < 0.05). Cortisol concentrations also correlated with the relative abdominal mass (P < 0.05) when patients with marked glucosuria were excluded.

Conclusions: The degree of severity of several clinical measures of type 2 diabetes correlates with cortisol concentrations. Moreover, the results provide evidence for a positive relationship between metabolic disturbances and cortisol concentrations that are within the accepted normal range.
Quinagolide – a valuable treatment option for hyperprolactinaemia
Authors: Barlier Anne , Jaquet Philippe
Published: February 2006

Hyperprolactinaemia is characterised by gonadal dysfunction, including infertility and reduced libido and, if left untreated, is associated with an increased risk of long-term complications, such as osteoporosis. The first-line therapy for patients with hyperprolactinaemia is pharmacological intervention with a dopamine agonist. Currently, there are three dopamine agonists available for hyperprolactinaemia therapy: bromocriptine, quinagolide and cabergoline. Bromocriptine has a long history of use; however, a range of 5–18% of patients are reported to show bromocriptine resistance, with only partial lowering of plasma prolactin levels and an absence of tumour shrinkage. The newer dopamine agonists, quinagolide and cabergoline, offer improved efficacy over bromocriptine, with a lower incidence of adverse events. Quinagolide and cabergoline have also demonstrated efficacy in many patients intolerant or resistant to bromocriptine. Thus, the selection of dopamine agonists available provides more than one option for pharmacological intervention of hyperprolactinaemia. This review discusses the clinical use of quinagolide in comparison to other dopamine agonists for hyperprolactinaemia therapy. Quinagolide may improve patient compliance to treatment owing to its reduced side effect profile, simple and rapid titration over just 7 days, once-daily dosing regimen and easy to use starter pack (available in some countries). Quinagolide offers an additional benefit for patients wishing to become pregnant, as it can be used until the point of confirmation of pregnancy. Therefore, as a well tolerated and effective therapy, with a simple dosing regimen, quinagolide should be considered as a first-line therapy in the treatment of hyperprolactinaemia.
The role of thiocyanate in the etiology of goiter in an industrial metropolitan area
Authors: Brauer V F H , Below H , Kramer A , Führer D , Paschke R
Published: February 2006

Objective: Thiocyanate (SCN−) has concentration dependent antithyroid properties and a role in the etiology of goiter has been suggested in several studies. In 1991 an epidemiological survey conducted in the region of Halle/Leipzig (Saxony), an area with significant air pollution, suggested an inverse relationship between urinary iodine (I−)/SCN− excretion and goiter prevalence. 10 years later, we reinvestigated the same industrial area to clarify if the situation has changed after the elimination of most industrial waste products and moreover, if SCN− excretion levels alone or in combination with air pollution or smoking as a SCN− source are critical for thyroid function.

Design and methods: We investigated a cohort of 708 probands for I−, SCN− and creatinine excretion in spot urine samples and determined the prevalence of goiter and thyroid nodules by high resolution ultrasonography.

Results: Probands with goiter (n = 79, 11%) had significantly higher urinary SCN− excretions than probands without (3.9 ± 2.8 vs 3.1 ± 3.4 mg SCN−/g creatinine) and significantly lower urinary I−/SCN− ratios than patients without thyroid disorders (41 ± 38 vs 61 ± 71 μg I−/mg SCN−/l). Mean urinary I− excretions were not different between probands with or without goiter. Smokers showed significantly elevated urinary SCN−/creatinine ratios in comparison to non-smokers (4.3 ± 4.3 vs 2.4 ± 2.1 mg SCN−/g creatinine). ANOVA revealed a prediction of thyroid volume through age (P < 0.001), gender (P < 0.001), body weight (P < 0.05) and smoking (P < 0.05).

Conclusions: In our investigation, age, gender and smoking (raising SCN− levels by CN− inhalation) were predictive for thyroid volume and the urinary I−/SCN− ratios were able to detect probands with an increased risk of developing goiter in contrast to urinary I− excretion levels alone. These data suggest, that in an era and area of decreased cyanide pollution, SCN− may remain a cofactor in the multifactorial aetiology of goiter.
Decreased soluble leptin receptor levels in women with polycystic ovary syndrome
Authors: Hahn Susanne , Haselhorst Uwe , Quadbeck Beate , Tan Susanne , Kimmig Rainer , Mann Klaus , Janssen Onno E
Published: February 2006

Objective: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level.

Design: We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27 ± 5.7 years) and 81 healthy controls (aged 25 ± 4.0 years).

Methods: Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism.

Results: In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyper-androgenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7 ± 20.7 vs 45.4 ± 25.0 vs 67.7 ± 28.8 ng/ml, P < 0.0001) and sOB-R (8.0 ± 3.4 vs 6.4 ± 2.5 vs 5.7 ± 2.3 ng/ml, P < 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0 ± 3.4 vs 12.7 ± 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 ± 3.9 vs 2.8 ± 2.2, P = 0.0285).

Conclusion: Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.
Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis
Authors: Biering H , Saller B , Bauditz J , Pirlich M , Rudolph B , Johne A , Buchfelder M , Mann K , Droste M , Schreiber I , Lochs H , Strasburger C J
Published: February 2006

Objective: The new GH receptor antagonist pegvisomant is the most effective medical therapy to normalize IGF-I levels in patients with acromegaly. Based on currently available data pegvisomant is well tolerated; however, treatment-induced elevation of transaminases has been reported and led to the necessity for drug discontinuation in some patients in the pivotal studies. The aim of this study was to evaluate and characterize the prevalence of elevated transaminases and to describe in detail the findings in a single case who required drug discontinuation because of elevation of transaminases which emerged during treatment and who underwent liver biopsy.

Design and methods: Retrospective safety analyses were carried out on 142 patients with acromegaly receiving pegvisomant treatment in Germany between March 2003 and the end of 2004. Of these patients, 123 were documented in a post-marketing surveillance study, one case of elevated transaminases was reported spontaneously and the other patients were treated in a clinical study.

Results: Mean treatment duration with pegvisomant in the ongoing observational study at the end of 2004 was 28.3 ± 19.9 (S.D.) weeks. Twelve out of the 142 patients had elevated transaminases above three times the upper limit of normal, likely caused by biliary obstruction in five of the patients. All patients but one affected by elevated transaminases had been previously treated with somatostatin analogues. In six out of 142 (4%) of patients, pegvisomant was permanently withdrawn because of elevated transaminases. The same number of patients showed a transient increase of transaminases with either spontaneous remission without dose modification (n = 4) or no re-increase of transaminases after temporary discontinuation and re-exposure (n = 2). The liver biopsy of one patient who was permanently withdrawn showed a chronic mild hepatitis with a mixed portal inflammation including eosinophilic granulocytes.

Conclusions: Liver function tests should be regularly followed on pegvisomant treatment. Biliary complications, which may arise from restitution of normal gall bladder motility after cessation of somatostatin analogue treatment, need to be differentiated from pegvisomant-induced abnormalities. The histological pattern of the liver biopsy performed in one of the patients showed a mild chronic active hepatitis. The lack of dose dependency and rather low frequency of elevated transaminases in those cases where a biliary disorder was excluded render this reaction an idiosyncratic drug toxicity.
Fetal microchimerism in Hashimoto’s thyroiditis: a quantitative approach
Authors: Klintschar Michael , Immel Uta-Dorothee , Kehlen Astrid , Schwaiger Patrizia , Mustafa Tarek , Mannweiler Sebastian , Regauer Sigrid , Kleiber Manfred , Hoang-Vu Cuong
Published: February 2006

Objective: Fetal microchimerism (MCH) has been implicated in the etiology of autoimmune diseases such as autoimmune thyroiditis. The goal of the study was to reliably estimate the number of fetal engrafted cells and to further investigate factors influencing the development of MCH.

Methods: Quantitative real-time PCR amplification using Y-chromosome specific (DYS14) and autosomal (β-globin) loci was performed on thyroid gland specimens. Furthermore, we compared the distribution of ABO and rhesus systems in mothers with and without blood MCH in relation to the blood groups of the children.

Results: MCH was detected in eight of 21 Hashimoto patients in a frequency range of 15 to 4900 male cells per 100 000 total cells (median 97 cells), but in none of 17 healthy thyroid glands. In a third group, consisting of 18 nodular goiters, only one sample was positive (182 male cells/100 000 total cells). No woman who had not had a prior pregnancy with a male fetus showed MCH. Mothers both with and without MCH showed the same rate of mother/child incompatibilities for the ABO and rhesus systems.

Conclusions: The percentage of microchimeric cells varies to a great extent in Hashimoto’s thyroiditis, and this phenomenon can occur in nodular goiter in rare instances, but it appears to be absent from normal thyroid glands. Nevertheless, the biological significance of MCH remains unclear. Moreover, we have concluded that the tested blood group systems (as opposed to their role in graft vs host disease after transplantations) have no effect on fetal MCH.
Cybernetic principles in the systematic concept of hypothalamic feeding control
Authors: Fricke Oliver , Lehmkuhl Gerd , Pfaff Donald W
Published: February 2006

Research on biological mechanisms of eating behavior and related disorders, such as obesity and anorexia nervosa, has become a large field of research in the last 15 years. With the discovery of peptides related to hypothalamic control of food intake (e.g. leptin and ghrelin) the search for the biological ‘master key’ of feeding control was renewed. As a result, mid-20th century biological concepts based on systematic and cybernetic thoughts fell into oblivion. This review highlights discoveries of hypothalamic-controlled feeding and eating behavior with a cybernetic and systematic perspective. Interestingly, older ideas of hypothalamic function offer possibilities for the incorporation of new molecular discoveries into systematic concepts of feeding behavior.
Leukemia inhibitory factor reduces body fat mass in ovariectomized mice
Authors: Jansson John-Olov , Movérare-Skrtic Sofia , Berndtsson Anna , Wernstedt Ingrid , Carlsten Hans , Ohlsson Claes
Published: February 2006

Objective: Ovariectomized (OVX) mice are known to gain body fat while exposure to estrogens decreases fat mass. We have previously shown that estrogen replacement therapy enhances the expression of receptors for the cytokine, leukemia inhibitory factor (LIF). LIF and other cytokines acting via the gp130 signal transducing receptor have been reported to decrease obesity. In the present study, we investigated whether LIF treatment can reduce obesity in OVX mice.

Design: Eight-week-old female C57Bl/6 mice were OVX or sham-operated. The mice were treated with LIF, 30 μg/kg or PBS via daily i.p. injections for 15 days (n = 9–10).

Methods: Dual X-ray absorptiometry and computerized tomography.

Results: We found that LIF treatment of OVX mice caused a significant reduction in the weight of white fat depots (P = 0.017) and serum leptin levels (P = 0.011). LIF also caused a significant decrease in brown fat mass (P = 0.036). Treatment with LIF decreased thymus weight but did not affect crown-rump length, femur length, trabecular bone mineral density or the weight of several non-fat organs including the uterus.

Conclusion: The cytokine, LIF, decreases body fat mass in OVX mice, suggesting that estrogen signaling is not required for this effect.
Association between serum ferritin and the insulin resistance syndrome in a representative population
Authors: Wrede C E , Buettner R , Bollheimer L C , Schölmerich J , Palitzsch K-D , Hellerbrand C
Published: February 2006

Objective: Unexplained hepatic iron overload with increased serum ferritin (SF) values has been associated with the insulin resistance syndrome (IRS), defined by the presence of one or more of the following criteria: increased body mass index (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association between IRS and SF in a representative population has not been investigated.

Methods: The study subjects participated in a nationwide epidemiological survey on metabolic disorders in the adult German population. The 1200 probands included in this study are representative of the German population. To eliminate major causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C were excluded. For all remaining 1070 probands, complete clinical data of SF, HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and blood pressure were available.

Results: SF values were significantly increased in men and women with high BMI (> 25 kg/m2), increased cholesterol (> 200 mg/dl), and increased systolic (> 160 mmHg) blood pressure, in women with diabetes, and in men with increased diastolic (> 95 mmHg) blood pressure. Furthermore, there was a significant correlation between the number of IRS criteria and SF.

Conclusions: This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. Interestingly, the severity of the IRS seems to be associated with increased SF levels suggesting a causal connection. Further studies are required to investigate the pathophysiological mechanism and consequences of increased SF levels in patients with IRS.
Plasma adiponectin concentration and tumor necrosis factor-α system activity in lean non-diabetic offspring of type 2 diabetic subjects
Authors: Kowalska Irina , Strączkowski Marek , Nikolajuk Agnieszka , Krukowska Agnieszka , Kinalska Ida , Górska Maria
Published: February 2006

Objective: There is growing evidence that adiponectin function is related to the pathogenesis of insulin resistance. Insulin resistance might be present even in lean subjects with a strong family history of type 2 diabetes. The aim of the study was to look for adiponectin’s role in the pathogenesis of insulin resistance in offspring of type 2 diabetic patients, and its relation to the activity of the tumor necrosis factor (TNF)-α system.

Research design and methods: The study was carried out in 23 lean offspring of type 2 diabetic subjects and in 23 controls matched for age, sex and body mass index. The oral glucose tolerance test for glucose and insulin estimations and hyperinsulinemic, euglycemic clamp studies were performed in all patients. The plasma concentration of adiponectin, TNF-α, soluble TNF receptors 1 and 2 (sTNFR1, sTNFR2), HbA1c, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein-cholesterol and triglycerides were estimated.

Results: The insulin sensitivity index, normalized for fat-free mass (Mffm) and adiponectin concentrations were markedly decreased in offspring of type 2 diabetic subjects compared with the control group (P = 0.0046 and P = 0.00 058 respectively). TNF-α and sTNFR1 concentrations did not differ between the studied groups; however the concentration of sTNFR2 was markedly increased in the offspring of type 2 diabetic patients (P = 0.0002). Adiponectin concentration was positively correlated to the insulin sensitivity index (r = 0.34; P = 0.020) and to HDL-cholesterol (r = 0.29, P = 0.047) and was inversely related to sTNFR2 (r = −0.33, P = 0.027).

Conclusions: The obtained results suggest that adiponectin could play a role in the pathogenesis of insulin resistance in lean offspring of type 2 diabetic subjects.
Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor
Authors: Lefevre Hervé , Bouvattier Claire , Lahlou Najiba , Adamsbaum Catherine , Bougnères Pierre , Carel Jean-Claude
Published: February 2006

Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal-dominant disorder characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation and increased predisposition to various neoplasms. Endocrine manifestations in PJS include gynecomastia due to calcified Sertoli cell testicular tumors usually referred to as large-cell calcifying Sertoli cell tumors (LSCT).

Objective: To evaluate the value of endocrine markers and aromatase inhibitor treatment in children with PJS and LSCT.

Design and setting: Familial cases, followed in a tertiary care center.

Patients: Two male siblings aged 7 and 9 years with PJS and LSCT.

Intervention: Third generation aromatase inhibitor (anastrozole) in one of the patients.

Main outcome measures: Longitudinal measurements of sex-steroids, gonadotropins, Sertoli cell markers and auxological evaluation.

Results: The two male siblings with PJS had similar bilateral multifocal testicular calcifications and biochemical evidence of Sertoli cell dysfunction manifested by elevated plasma inhibin-α levels. Only one sibling had gynecomastia. Estradiol levels were normal in both. During treatment with anastrozole, estradiol levels, growth and skeletal maturation, as well as Sertoli cell markers (inhibin B, inhibin-α and anti-Mullerian hormone) decreased.

Conclusions: Inhibin-α may be considered as a marker for LSCT in children with PJS, pointing to a specific defect in inhibin regulation in this condition. Moreover, the decrease in Sertoli cell markers during aromatase inhibitor treatment suggests that increased estrogen production is a primary event regulating downstream production of Sertoli cell peptides. Anastrozole is efficient in controlling the clinical features of the disease and should be proposed as an alternative to bilateral orchidectomy, which is often performed in this condition.