bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in lymphocyte glucocorticoid andβ‐adrenergic receptors in veal calves treated with clenbuterol and steroid hormones for growth‐promoting purposes*
Authors: ODORE R. , BADINO P. , PAGLIASSO S. , NEBBIA C. , CUNIBERTI B. , BARBERO R. , RE G.
Published: March 2006

In order to identify possible peripheral markers of illegal treatments with growth‐promoting agents in veal calves,β‐adrenergic receptor (β‐AR) and glucocorticoid receptor (GR) concentrations were measured in lymphocytes of 12 male Friesian crossbred calves (six controls and six treated). The animals received a cocktail of anabolic and re‐partitioning agents [17β‐oestradiol: 3 × 10 mg intramuscular (i.m.) doses at 17‐day intervals; dexamethasone sodium phosphate: 4 mg/day for 6 days and 5 mg/day for six further days dissolved in milk; and clenbuterol: 20 μg/kg/day dissolved in milk for the last 40 days before slaughter]. Blood samples were collected by venipuncture at different time points and lymphocytes were isolated by density gradient centrifugation. Lymphocyteβ‐AR and GR levels were measured by binding assays. Treatment with re‐partitioning agents caused a significant down‐regulation of lymphocyteβ‐ARs 19 days after the beginning of clenbuterol administration and at day 55 (after dexamethasone withdrawal, just before slaughter). This phenomenon was partially reversed at day 50, after dexamethasone administration, at which time a significant decrease in GR concentrations also occurred. For both types of receptors, no significant changes in the dissociation constant values were observed at any time point. Lymphocytes express measurable concentrations ofβ‐ARs and GRs and the measurement of receptor levels highlights the fluctuation of receptor expression due to the dynamic interaction of the drugs used in combination. Lymphocyte receptor determination could therefore be included in a battery of biological assays to detect illegal treatments with anabolic agents in veal calves in the light of a multivariate approach.
The interaction between moxidectin and MDR transporters in primary cultures of rat hepatocytes
Authors: DUPUY J. , LESPINE A. , SUTRA J. F. , ALVINERIE M.
Published: March 2006

The interaction of moxidectin (a macrocyclic lactone, ML) with P‐glycoprotein (P‐gp), multidrug resistance associated proteins (MRPs) and breast cancer resistance protein (BCRP) was studied in primary cultures of rat hepatocytes by measuring the intracellular accumulation of [14C]‐moxidectin over 72 h in the presence of specific inhibitors: for P‐gp, verapamil (10 μM); for MRPs, MK571 (100 μM), indomethacin (10 μM) and probenecid (3.8 mM); and for BCRP, fumitremorgin C (5 μM). The P‐gp and MRP inhibitors increased significantly (P < 0.01) by 48.7%, 49.8%, 49.9% and 57.2% the area under the time‐intracellular concentration curve (AUC) of moxidectin in rat hepatocytes, while the BCRP inhibitor, fumitremorgin C, had no effect on the AUC compared with the control. In addition, the mRNAs of all the drug transporters studied were detected in rat hepatocytes from 0 to 72 h. Using this cellular model it has been shown that MRP inhibitors increase moxidectin intracellular concentrations to a similar extent as the P‐gp inhibitor. The identification of all the transporters that interact with MLs remains a challenge, which currently concerns several important therapeutic fields.
Clinical evaluation of clonidine added to lidocaine solution for subarachnoid analgesia in sheep
Authors: DEROSSI R. , RIGHETTO F. R. , ALMEIDA R. G. , MEDEIROS U. , FRAZÍLIO F. O.
Published: March 2006

Clonidine (CL) is aα2‐adrenergic agonist that produces analgesia in animals and humans by a non‐opiateα2‐adrenergic action in the spinal cord dorsal horn. The objective of this prospective randomized study was to investigate the clinical effects of CL/lidocaine (LD) combination administered by the subarachnoid route in sheep. Each sheep received each of three treatments, at no shorter than weekly intervals. Treatments consisted of 0.003 mg/kg CL, 1.2 mg/kg LD and a combination of CL (0.003 mg/kg) and LD (1.2 mg/kg) (CLLD). Subarachnoid injections were given in all animals between the last lumbar and first sacral vertebra. Heart rate (HR), arterial pressures, respiratory rate, rectal temperature, analgesia, sedation, and motor blockade were determined before drug administration (basal) and 5, 10, 15 and 30 min after drug administration, and at 30‐min intervals until loss of analgesia occurred. The duration of analgesia after subarachnoid CLLD administration was 187 ± 24 min (mean ± SD), i.e. more than twice of that obtained with CL (99 ± 19 min) or LD (55 ± 4.4 min) alone. In all sheep, CL, administered either alone or with LD, induced moderate sedation. After subarachnoid administration of three treatments, all sheep had ataxia and subsequent sternal recumbency. The CL treatment causes decreases in blood pressure (diastolic arterial pressure and mean arterial pressure) and HR. Data suggest that the CLLD combination could be used subarachnoidally in sheep requiring prolonged surgery.
Fexofenadine in horses: pharmacokinetics, pharmacodynamics and effect of ivermectin pretreatment
Authors: OLSÉN L. , INGVAST‐LARSSON C. , LARSSON P. , BROSTRÖM H. , BONDESSON U. , SUNDQVIST M. , TJÄLVE H.
Published: March 2006

The pharmacokinetics and the effects on inhibition of histamine‐induced cutaneous wheal formation of the histamine H1‐antagonist fexofenadine were studied in horse. The effect of ivermectin pretreatment on the pharmacokinetics of fexofenadine was also examined. After intravenous infusion of fexofenadine at 0.7 mg/kg bw the mean terminal half‐life was 2.4 h (range: 2.0–2.7 h), the apparent volume of distribution 0.8 L/kg (0.5–0.9 L/kg), and the total body clearance 0.8 L/h/kg (0.6–1.2 L/h/kg). After oral administration of fexofenadine at 10 mg/kg bw bioavailability was 2.6% (1.9–2.9%). Ivermectin pretreatment (0.2 mg/kg, p.o.) 12 h before oral fexofenadine decreased the bioavailability to 1.5% (1.4–2.1%). In addition, the area under the plasma concentration–time curve decreased 27%. Ivermectin did not affect the pharmacokinetics of i.v. administered fexofenadine. Ivermectin may influence fexofenadine absorption by interfering in intestinal efflux and influx pumps, such as P‐glycoprotein and the organic anion transport polypeptide family. Oral and i.v. fexofenadine significantly decreased histamine‐induced wheal formation, with a maximal duration of 6 h. A pharmacokinetic/pharmacodynamic link model indicated that fexofenadine in horse has antihistaminic effects at low plasma concentrations (EC50 = 16 ng/mL). However, oral treatments of horses with fexofenadine may not be suitable due to the low bioavailability.
Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous bolus dosing and its in vitro pharmacodynamics
Authors: FREISE K. J. , MARTÍN‐JIMÉNEZ T.
Published: March 2006

Gemcitabine is a chemotherapeutic agent used to treat a variety of cancers in humans and dogs. In this study, the plasma pharmacokinetics of gemcitabine and its inactive metabolite, 2′,2′‐difluorodeoxyuridine (dFdU), were investigated in dogs after intravenous bolus gemcitabine doses of 3, 10, and 30 mg/kg. Furthermore, the intracellular accumulation of the active metabolite gemcitabine triphosphate, as a surrogate pharmacodynamic endpoint, was also determined in vitro in canine melanoma cells. Gemcitabine was characterized by linear kinetics, while dFdU dose proportionality remains unknown. The average gemcitabine clearance was 0.560 L/h·kg and volume of distribution at steady‐state of 1.27 L/kg. The average terminal elimination half‐life, depending on dose, ranged from 1.75 to 3.23 h. Plasma concentrations of dFdU peaked at approximately 2 h post‐dosing. In vitro intracellular gemcitabine triphosphate accumulation was saturated with increasing extracellular gemcitabine concentrations. These data can be used to rationally design gemcitabine dosage regimes for canine oncology patients and as a basis for future investigations on the in vivo intracellular accumulation of gemcitabine triphosphate in dogs.
Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous infusion
Authors: FREISE K. J. , MARTÍN‐JIMÉNEZ T.
Published: March 2006

Gemcitabine is a relatively new chemotherapeutic compound used to treat a variety of cancers in dogs. Previous work presented in a companion paper explored the plasma kinetics of gemcitabine and its inactive metabolite, 2′,2′‐difluorodeoxyuridine (dFdU), in dogs after an intravenous bolus gemcitabine dose and demonstrated the saturation of intracellular dFdCTP (2′,2′‐difluorodeoxycytidine 5′‐triphosphate) occurs in vitro with increasing extracellular gemcitabine exposure in canine melanoma cells. In this study, the plasma pharmacokinetics (PKs) of gemcitabine and dFdU are further explored after gemcitabine doses of 10, 30, and 60 mg/kg administered by intravenous infusion with a loading dose. Gemcitabine displayed linear PKs, while the kinetics of dFdU were not dose proportional. The overall clearance, volume of distribution at steady‐state, and terminal elimination half‐life (t1/2) for gemcitabine were 0.421 L/h·kg, 0.822 L/kg, and 1.49 h, respectively. Plasma concentrations of dFdU peaked at approximately 2 h postdosing and had a t1/2 of 14.9 h.
Direct Exposure to Corticosterone During Embryonic Development Influences Behaviour in an Ovoviviparous Lizard
Authors: Uller Tobias , Olsson Mats
Published: March 2006

It is becoming increasingly clear that conditions experienced during embryonic development can be of major importance for traits subsequent to parturition or hatching. For example, in mammals, offspring from stressed mothers show a variety of changes in behavioural, morphological, and life‐history traits. The effects of maternal stress on trait development are believed to be mediated via transfer of glucocorticoids, the main hormones released during the stress response, from mother to offspring. However, also other physiological maternal responses during stress could be responsible for changes in offspring phenotype. We investigated the direct effects of corticosterone on offspring development, without other confounding factors related to increased maternal stress, by injection of corticosterone in eggs of the ovoviviparous lizardLacerta vivipara. Corticosterone‐manipulated offspring did not show impaired development, reduced body size or body condition at parturition. However, corticosterone‐treated offspring showed altered anti‐predator behaviour, as measured by the time required to emerge from shelter after a simulated predator attack. Differential steroid exposure during development, possibly mediated by maternal stress response, may explain some of the variation in behaviour among individuals in natural populations.
Thrombotic microangiopathy associated with α‐interferon therapy for chronic myeloid leukaemia (Case Report)
Authors: GALESIC KRESIMIR , BOZIC BORKA , RACIC IVANA , SCUKANEC‐SPOLJAR MIRA
Published: March 2006

SUMMARY:  The association of interferon (IFN) therapy with haemolytic uraemic syndrome in patients with chronic myeloid leukaemia (CML) has been reported infrequently. The pathogenesis of the renal lesion in such cases remains unclear. We report the case of a patient with chronic myeloid leukaemia who developed nephrotic syndrome and renal failure while being treated with hydroxyurea and IFN‐α. Renal biopsy showed features of chronic thrombotic microangiopathy. The discontinuation of IFN‐α, and a prompt institution of plasmapheresis and steroids resulted in improvement of the nephrotic syndrome and renal function. These findings suggest that long‐term IFN‐α therapy can induce thrombotic microangiopathy and haemolytic uraemic syndrome in patients with chronic myeloid leukaemia.
Inhibition of TGF‐β1 expression in human peritoneal mesothelial cells by pcDU6 vector‐mediated TGF‐β1 shRNA
Authors: LIU FUYOU , LIU HONG , PENG YOUMING , LIU YINGHONG , LI JUN , CHEN XING
Published: March 2006

Background and Aim:  Transforming growth factor‐β1 (TGF‐β1) is an important mediator of the fibrosis process. High expression of TGF‐β1 is closely related to peritoneal fibrosis. RNA interference using short hairpin RNA (shRNA) can mediate sequence‐specific inhibition of gene expression in mammalian cells. The aim of this study was to assess the effect of shRNA targeting TGF‐β1 on the expression of TGF‐β1 in human peritoneal mesothelial cells (HPMC).

Methods:  TGF‐β1 specific shRNA expression vectors were constructed and introduced to HPMC stimulated with 4.25% D‐glucose (Gs) and 10 µg/mL of lipopolysaccharide (LPS). Expression of TGF‐β1 mRNA was assessed by semiquantification reverse transcription polymerase chain reaction (RT–PCR). The TGF‐β1 protein level in the culture supernatant was determined by sandwich enzyme‐linked immunosorbent assay.

Results:  The expression of TGF‐β1 was upregulated significantly in HPMC stimulated with 4.25% D‐Gs and 10 µg/mL LPS P < 0.01. TGF‐β1 expression in pcDU6 plasmid vector‐mediated TGF‐β1 shRNA groups were obviously downregulated when compared to the 4.25% D‐Gs and 10 µg/mL LPS group (P < 0.01) and the pcDU6 void vector group (P < 0.05), with no significant difference among pcDU6 plasmid vector ‐mediated TGF‐β1 shRNA groups (P > 0.05). No significant difference was found between teh pcDNA3.1(–) vector plasmid‐mediated TGF‐β1 antisense RNA group and pcDU6 void vector group (P > 0.05). The expression of TGF‐β1 in pcDU6 plasmid vector‐mediated TGF‐β1 shRNA groups were obviously downregulated when compared to the pcDNA3.1(–) plasmid vector‐mediated TGF‐β1 antisense RNA group (P < 0.05).

Conclusion:  TGF‐β1‐specific shRNA can significantly inhibit the expression of TGF‐β1 in HPMC stimulated with 4.25% D‐Gs and 10 µg/mL LPS in HPMC. These results suggest the possible application of TGF‐β1‐specific shRNA in preventing peritoneal fibrosis in patients receiving peritoneal dialysis.
Reverse correlation between ankle‐brachial index and left ventricular hypertrophy in patients on maintenance haemodialysis
Authors: FU WENCHENG , YE CHAOYANG , MEI CHANGLIN , RONG SHU , WANG WENJING
Published: March 2006

Background:  Left ventricular hypertrophy (LVH) and peripheral vascular disease (PVD) are highly prevalent among patients undergoing maintenance haemodialysis (MHD) and contribute to most cardiovascular mortalities in this population. Ankle‐brachial index (ABI) has been recently demonstrated to be a predictor for all‐cause and cardiovascular mortality in MHD Patients. The main objective of the present study is to see whether ABI is correlated with LVH in MHD patients.

Methods:  One hundred and sixteen MHD patients selected from our dialysis unit were enrolled in this study. Colour Doppler ultrasonic examinations were performed at their hearts, both lower extremities and non‐fistula upper extremities to determine the morphological and haemodynamic changes of their hearts and the systolic pressures of both their posterior tibial arteries, dorsalis pedis arteries and non‐fistula brachial arteries. ABI was calculated on the basis of systolic pressures of the lower extremities and non‐fistula upper extremities, and the correlation between ABI and LVH was analysed.

Results:  Seventy‐four (63.8%) MHD patients presented with LVH and related haemodynamic changes of varying degrees. There was a significant difference in ABI between the LVH group and the non‐LVH group (0.96 ± 0.15 vs 1.25 ± 0.12, P < 0.001). Bivariate analysis showed that left ventricular mass index (LVMI) was negatively correlated with ABI, serum Alb and Hb (r = −0.482, −0.329, −0.247, P < 0.01), positively correlated with hypertension, serum calcium, serum phosphorus and calcium‐phosphorus product. (r = 0.235, 0.168, 0.231,0.282, P < 0.05), and ABI was reversely correlated with hypertension, serum calcium, serum phosphorus and calcium‐phosphorus product. (r = −0.195, −0.405, −0.271, −0.384, −0.461, P < 0.05), positively correlated with serum albumin (r = 0.338, P < 0.001). Multiple linear regression demonstrated ABI was independently associated with LVMI in MHD patients (β = −103.522, P = 0.000).

Conclusion:  There is high incidence of LVH and decreased ABI in MHD patients. A decrease in ABI to some extent reflects the degree of LVH in this population.
Role of PAX2 gene polymorphisms in Henoch–Schonlein purpura nephritis
Authors: YI ZHU‐WEN , FANG XIANG‐LING , WU XIAO‐CHUAN , HE XIAO‐JIE , HE QING‐NAN , DANG XI‐QIANG , ZHU CUI‐PING , MO SHUANG‐HONG
Published: March 2006

Objective:  To investigate the distribution of polymorphisms in the PAX2 gene in children with Henoch–Schonlein purpura with and without nephritis (HSPN and HSP, respectively), with particular attention to the relationship between PAX2 gene polymorphisms and the development of kidney pathology.

Methods:  Genomic DNA was extracted from the peripheral leukocytes of 39 HSPN patients, 23 HSP patients without nephritis and 100 normal children, and three known single nucleotide polymorphisms (SNP), including 1410C>T, 1521A>C and 1544C>T in exon 8 and exon 9 of the PAX2 gene were studied as the candidate polymorphisms. The above two exons were amplified, the polymerase chain reaction (PCR) products were detected by denatured high‐pressure liquid chromatography and direct DNA sequencing was performed for sequences with abnormal elution peaks.

Results:  In all samples confirmed by direct sequencing, we identified two SNP, which present as complete linkage haplotype 1410C>T + 1521A>C, in exon 8. We did not identify any SNP in exon 9. The frequency of the PAX2 heterozygous genotype 1410CT/1521AC in the HSPN group (28.20%) was significantly higher than in the HSP without HSPN group (4.35%) or in the control group (12.00%) (P < 0.05). The odds ratio (OR) values for HSPN and HSP were 6.05 and 2.62, respectively, and the 95% confidence intervals (CI) were 1.23–29.78 and 1.09–6.30, respectively. However, no differences in the frequency distribution was found between the HSP without nephritis and normal groups. Furthermore, there was no significant correlation between the polymorphism and clinical manifestation or kidney pathology in the HSPN group (P > 0.05).

Conclusion:  The 1410CT/1521AC PAX2 genotype does not increase susceptibility for HSP, but is likely to increase the susceptibility of kidney involvement, resulting in a HSPN diagnosis.
Inflammation in end‐stage renal disease: The hidden enemy (Review Article)
Authors: STENVINKEL PETER
Published: March 2006

SUMMARY:  Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end‐stage renal disease (ESRD) patients. As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this high‐risk population, inflammation (interrelated to insulin resistance, oxidative stress, wasting and endothelial dysfunction) has been suggested to be a significant contributor. Indeed, several different inflammatory biomarkers, such as high sensitivity C‐reactive protein (hs‐CRP), have been shown to independently predict mortality in ESRD patients. As CRP is so strongly associated with vascular disease it has been suggested that this hepatic‐derived protein is not only a marker, but also a mediator, of vascular disease. Although in vitro data from studies on endothelial cells, monocytes‐macrophages and smooth muscle cells support a direct role for CRP in atherogenesis, data from studies performed in vivo have been controversial. The causes of the highly prevalent state of inflammation in ESRD are multiple, including inflammatory signals associated with the dialysis procedure, decreased renal function, volume overload, comorbidity and intercurrent clinical events. As the prevalence of inflammation varies considerably between continents and races, dietary and/or genetic factors may have an impact on inflammation in ESRD. Elevated CRP in dialysis patients could be evaluated at three different levels: (i) national/regional level; (ii) dialysis unit level; and (iii) individual patient level.
Regulation of testicular function by cell‐to‐cell interaction
Authors: FUJISAWA MASATO
Published: March 2006

Cell‐to‐cell interactions in the testis play important roles in regulating testicular function. Investigating the mechanism of such interactions is essential to elucidate the cause of spermatogenic dysfunction and to create a new treatment. (Reprod Med Biol 2006; 5: 9–17)
Community‐based disaster preparedness and climate adaptation: local capacity‐building in the Philippines
Authors: Allen Katrina M.
Published: March 2006

Community‐based disaster preparedness (CBDP) approaches are increasingly important elements of vulnerability reduction and disaster management strategies. They are associated with a policy trend that values the knowledge and capacities of local people and builds on local resources, including social capital. CBDP may be instrumental not only in formulating local coping and adaptation strategies, but also in situating them within wider development planning and debates. In theory, local people can be mobilised to resist unsustainable (vulnerability increasing) forms of development or livelihood practices and to raise local concerns more effectively with political representatives. This paper focuses on the potential of CBDP initiatives to alleviate vulnerability in the context of climate change, and their limitations. It presents evidence from the Philippines that, in the limited forms in which they are currently employed, CBDP initiatives have the potential both to empower and disempower, and warns against treating CBDP as a panacea to disaster management problems.
El Niño platforms: participatory disaster response in Peru
Authors: Warner Jeroen , Oré Maria Teresa
Published: March 2006

Climate change is expected to lead to greater extremes (droughts and floods) in river regimes around the world. While the number of major calamities is predicted to rise, the efforts of the public sector, experts and local stakeholders are badly coordinated. Consequently, aid does not reach target groups, resulting in unnecessary losses. Hence, there is a need for more participatory and integrative approaches. To ensure a more concerted response to climate‐induced disasters, stakeholders could coordinate and negotiate within Multi‐Stakeholder Platforms. Such roundtables are increasingly being established for vision‐building and integrated water resource management, but could be employed in disaster management as well. After discussing the advantages and disadvantages of participation, this article trace the rise of and the problems facing two ‘El Niño’ platforms: one in Ica, a city on the Peruvian coast that flooded unexpectedly in January 1998, and one in Ayacucho, which saw a climate change‐induced drought around the same time. The issue of internal and external legitimacy receives particular emphasis.
Uptake and translocation of manganese in seedlings of two varieties of Douglas fir (Pseudotsuga menziesiivar.viridisandglauca)
Authors: Duc̆ić Tanja , Leinemann Ludger , Finkeldey Reiner , Polle Andrea
Published: March 2006

Douglas fir (Pseudotsuga menziesii) varietyglauca(DFG) but not the varietyviridis(DFV) showed symptoms of manganese (Mn) toxicity in some field sites. We hypothesized that these two varieties differed in Mn metabolism.

To test this hypothesis, biomass partitioning, Mn concentrations, subcellular localization and54Mn‐transport were investigated.

Total Mn uptake was three‐times higher in DFG than in DFV. DFV retained > 90% of54Mn in roots, whereas > 60% was transported to the shoot in DFG. The epidermis was probably the most efficient Mn barrier since DFV contained lower Mn concentrations in cortical cells and vacuoles of roots than DFG. In both varieties, xylem loading was restricted and phloem transport was low. However, sieve cells still contained high Mn concentrations.

DFV displayed higher biomass production and higher shoot : root ratios than DFG. Our results clearly show that both varieties of Douglas fir differ significantly in Mn‐uptake and allocation patterns rendering DFG more vulnerable to Mn toxicity.
End‐to‐end electronic control of the hospital transfusion process to increase the safety of blood transfusion: strengths and weaknesses
Authors: Davies Amanda , Staves Julie , Kay Jonathan , Casbard Angela , Murphy Michael F.
Published: March 2006

BACKGROUND:  Incorrect blood component transfused is a frequent serious incident associated with transfusion and often involves misidentification of the patient and/or the unit of blood.

STUDY DESIGN AND METHODS:  This study extended the evaluation of an electronic system involving bar code technology and handheld computers. Electronic control of collection of blood from blood refrigerators was incorporated into a previously described process for blood sample collection and blood administration. Practice was evaluated before and after its introduction in cardiac surgery.

RESULTS:  The baseline audits revealed poor practice. Significant improvements were found following the introduction of the electronic system, including from 8 percent to 100 percent in checking that the blood group and unit number on the blood pack matched the compatibility label and the pack was in date (p ≤ 0.0001). Similar significant improvements were found in blood sample collection, the collection of blood from blood refrigerators, and the documentation of transfusion. Staff found the system easy to operate and preferred it to standard procedures.

CONCLUSIONS:  A bar code patient identification system improved transfusion practice, although areas for improvement were identified. These results provide support for further work on the development of such systems for both transfusion and other procedures requiring patient identification.
Hemolytic disease of the newborn due to anti‐Dib: a case study and review of the literature
Authors: Mochizuki Kazuhiro , Ohto Hitoshi , Hirai Shigeru , Ujiie Niro , Amanuma Fumitaka , Kikuta Atsushi , Miura Saori , Yasuda Hiroyasu , Ishijima Ayako , Suzuki Hitoshi
Published: March 2006

BACKGROUND:  The severity of hemolytic disease of the newborn (HDN) due to Diegob (Dib) mismatch ranges from no symptoms to severe jaundice that requires exchange transfusion (ET). The clinical significance of anti‐Dib is incompletely recognized.

CASE REPORT:  A male newborn, referred with jaundice, was revealed to have HDN due to Dib mismatch and was treated successfully with phototherapy and high‐dose intravenous gamma globulin (IVGG).

STUDY DESIGN AND METHODS:  The literature of HDN caused by Dib mismatch was reviewed. The cases were classified into three groups according to their severity: the mildest needed no therapy (NO), the moderate group received phototherapy alone (PHOTO), and the most severe was treated with ET and/or high‐dose IVGG therapy plus phototherapy (ET/IVGG).

RESULTS:  Among 27 cases of HDN due to Dib reported to date, 10, 6, and 11 cases required NO, PHOTO, and ET/IVGG, respectively. A significant correlation (p < 0.01) was found between the maternal anti‐Dib titer and the severity of the disease when the ET/IVGG group was compared with the NO group. All mothers of the group that needed ET/IVGG had an anti‐Dib titer of 64 or greater.

CONCLUSION:  A maternal high titer (≥64) of anti‐Dib is associated with a higher risk of severe hyperbilirubinemia for mismatched newborns.
Capturing the Degree of Modularity Embedded in Product Architectures*
Authors: Mikkola Juliana H.
Published: March 2006

This article focuses on integrating various perspectives on product architecture modularity into a general framework and proposes a way to measure the degree of modularization embedded in product architectures. The article addresses trade‐offs between modular and integral product architectures and how components and interfaces influence the degree of modularization. The article identifies the following key elements of product architecture modularity: components (standard and new‐to‐the‐firm), interfaces (standardization and specification), degree of coupling, and substitutability. A mathematical model, termed the modularization function, is applied to measure the key elements and their combined effect on the degree of modularization embedded in product architectures. The application of the modularization function is illustrated by two distinct sets of product architectures: Chrysler Jeep's windshield wipers controllers and Schindler's hydraulic and traction‐pull transmission elevators. The analysis of the Chrysler case shows that the silent‐relay architecture produces more opportunities for modularization than the solid‐state architecture due to the higher substitutability factor and lower new‐to‐the‐firm component composition. The Schindler case captures the dynamics of modularity created by three types of components (standard, customizable, and new to the firm) and two types of interfaces (fundamental and optional). Based on the case studies, the article outlines testable propositions and discusses the managerial and theoretical implications for the modularization function.
Book Reviews
Authors: Smith Preston G.
Published: March 2006

These reviews remind us that although they are aimed at helping you reach a purchase decision on the book, perhaps more importantly, they are intended to enlighten you in emerging areas of product and service development. New books are perfect for learning about new trends or extensions of the knowledge base, and they allow you to delve into allied areas that are likely to affect your career in product innovation.

Thus, Ruediger Klein reviews our first non‐English book, which will expose non‐German readers to a German view of software management and product management. Carla Kuesten gives us an in‐depth view of a single industry—the food industry—with lessons that readers can probably translate to their field. For future issues, we have a lawyer reviewing books on intellectual property protection, and another review will cover current topics in China regarding product development.

Please let us know of other tangents we should be covering.

Books reviewed in this issue:

The PDMA ToolBook 2 for New Product Development

Democratizing Innovation

The Business of Software

Software‐Produkt‐Management

New Food Product Development: From Concept to Marketplace
Large Radiofrequency Ablation Lesions Can Be Created with a Retractable Infusion‐Needle Catheter
Authors: SAPP JOHN L. , COOPER JOSHUA M. , ZEI PAUL , STEVENSON WILLIAM G.
Published: March 2006

Background: Radiofrequency (RF) catheter ablation of ventricular tachycardia is sometimes limited by inadequate lesion depth. We report the use of a novel retractable needle‐tipped electrode catheter with intramyocardial (IM) saline infusion and IM RF energy delivery to create large myocardial ablation lesions.

Methods: The left ventricle was entered via the femoral artery in 6 and 11 anesthetized goats and swine (32–90 kg) with an 8‐F electrode catheter with an extendable 27‐gauge needle at the tip (modified for RF ablation by making the needle electrically active). The needle was advanced 5–7 mm intramyocardially and 0.9% saline was infused 1 mL/min × 60 seconds prior to, and throughout a 120‐second application of RF via the active needle, with power titrated to 12 W for 9 lesions, and 30–40 W for 37 lesions, followed by a 120‐second RF application using the 4‐mm‐tip electrode, with power titrated to achieve a 10‐Ω decrease in impedance. Needle/saline lesions were compared to 18 standard 4‐mm‐tip control lesions (power titrated to ≤50 W, to achieve a 10‐Ω impedance decrease or limited to 60°C) and to 17 irrigated 3.5‐mm‐tip lesions (power titrated to ≤50 W, temperature limited to 50°C, 30 mL/min infusion rate). Lesions were identified in the excised heart, fixed, serially sectioned from the endocardium, and digitally analyzed to calculate volume.

Results: Lesions were homogeneous and had distinct borders. Compared to 4‐mm‐tip and irrigated‐tip lesions, high‐power needle/saline lesions were significantly deeper (13 ± 2 vs 5 ± 1 and 8 ± 3 mm, P < 0.001), had significantly larger volumes (1,700 ± 750 vs 240 ± 170 and 750 ± 650 mm3, P < 0.001), and had larger cross‐sectional area at each millimeter depth beyond the 1 mm (P < 0.01).

Conclusions: IM saline infusion and IM RF energy delivery markedly increase RF lesion size as compared to standard RF ablation and is feasible with a percutaneous catheter. This method warrants further investigation because of its potential clinical utility.
Results of the Multicenter RENEWAL® 3 AVT Clinical Study of Cardiac Resynchronization Defibrillator Therapy in Patients with Paroxysmal Atrial Fibrillation
Authors: SAXON LESLIE A. , GREENFIELD RUTH ANN , CRANDALL BRIAN G. , NYDEGGER CHARLES C. , ORLOV MICHAEL , VAN GENDEREN RHONDA
Published: March 2006

Introduction: Atrial fibrillation impacts the clinical course of up to 50% of patients with advanced heart failure (HF) who are eligible for cardiac resynchronization therapy with a defibrillator (CRT‐D). While RV‐based defibrillators are available with advanced atrial diagnostics and therapies that provide rapid diagnosis and treatment of spontaneously occurring atrial tachycardia/fibrillation (AT/AF) episodes, there is no CRT‐D device that combines atrial/ventricular and CRT therapies.

Purpose: The purpose of the prospective multicenter RENEWAL® 3 AVT study is to assess the performance of atrial diagnostics and therapies used in combination with a CRT‐D device.

Methods: Enrolled patients were required to have indications for a CRT‐D device and a documented episode of AT/AF within 12 months of enrollment. A total of 170 patients were enrolled over 9 months (85% male; mean age 72 ± 10 years; NYHA classification: 88% III, 12% IV; left ventricular ejection fraction [LVEF] mean 23 ± 6%; mean QRS duration 150 ± 25 msec; 78% ischemic etiology). The documented atrial arrhythmia was AF in 77% of patients. A total of 60% of patients had the CRT‐D device placed for primary prevention of sudden death and 40% of patients had a history of ventricular arrhythmia in addition to HF. The device operates in the biventricular (BiV) triggered mode for sensed ventricular events associated with AF.

Results: A total of 159 patients (95%) had a successful CRT‐D implant. Over a mean follow‐up of 5.7 ± 2.3 months, there were a total of 152 atrial shocks delivered in 108 patients for induced (93%) or spontaneous (7%) occurring episodes of AF. Spontaneously occurring AF was observed in 40 patients (25%). The rate of first shock conversion was 118/152 (78%, mean energy 11.6 ± 5.9 J). Overall shock therapy conversion rate was 138/152 (91%). The number of shock conversions resulting in sinus rhythm maintained for at least 2 minutes postshock was 87% for induced episodes. Therapy was delivered for spontaneous ventricular tachycardia/fibrillation in nine patients (6%). There was no instance of ventricular proarrhythmia associated with atrial shock therapies, undersensing of ventricular arrhythmias, or interruption of CRT therapy associated with the combined device.

Conclusions: In CRT‐D candidates with a history of AF, 25% experience recurrent AF within 6 months of implant. Atrial detection and ventricular detection, shock, and resynchronization therapies are not compromised by the addition of atrial therapies to a CRT‐D device.
Characterizing Dual Atrioventricular Nodal Physiology in Pediatric Patients with Atrioventricular Nodal Reentrant Tachycardia
Authors: BLURTON DOMINIC J. , DUBIN ANNE M. , CHIESA NANCY A. , VAN HARE GEORGE F. , COLLINS KATHRYN K.
Published: March 2006

Introduction: Dual atrioventricular (AV) nodal physiology, defined as an AH jump ≥50 msec with a 10 msec decrease in A1A2, is the substrate for atrioventricular nodal reentrant tachycardia (AVNRT) and yet it is present in a minority of pediatric patients with AVNRT. Our objective was to characterize dual AV nodal physiology as it pertains to a pediatric population.

Methods/Results: We retrospectively reviewed invasive electrophysiology studies in 92 patients with AVNRT (age12.1 ± 3.7 yrs) and in 46 controls without AVNRT (age 13.3 ± 3.7 yrs). Diagnoses in controls: syncope (N = 31), palpitations (N = 6), atrial flutter (N = 3), history of atrial tachycardia with no inducible arrhythmia (N = 3), and ventricular tachycardia (N = 3). General anesthesia was used in 49% of AVNRT and 52% of controls, P = 0.86. There were no differences in PR, AH, HV, or AV block cycle length. With A1A2 atrial stimulation, AVNRT patients had a significantly longer maximum AH achieved (324 ± 104 msec vs 255 ± 67 msec, P = 0.001), and a shorter AVNERP (276 ± 49 msec vs 313 ± 68 msec P = 0.0005). An AH jump ≥50 msec was found in 42% of AVNRT versus 30% of controls (P = 0.2). Using a ROC graph we found that an AH jump of any size is a poor predictor of AVNRT. With atrial overdrive pacing, PR ≥ RR was seen more commonly in AVNRT versus controls, (55/91(60%) vs 6/46 (13%) P = 0.000).

Conclusions: Neither the common definition of dual AV nodes or redefining an AH jump as some value <50 msec are reliable methods to define dual AV nodes or to predict AVNRT in pediatric patients. PR ≥ RR is a relatively good predictor of AVNRT.
Saliva of patients with Type 1 diabetes: effect of smoking on activity of lysosomal exoglycosidases
Authors: Knas M , Karaszewska K , Szajda SD , Zarzycki W , Dudzik D , Zwierz K
Published: March 2006

Objective:  The aim of our study was to evaluate the influence of smoking on the activity of N‐acetyl‐β‐hexosaminidase (HEX), its isoenzymes A (HEX‐A) and B (HEX‐B) and β‐galactosidase (GAL), in the saliva of patients with Type 1 diabetes.

Methods:  In the supernatant HEX and its isoenzymes A and B, and β‐galactosidase were determined by the method of Chatteriee et al in modification of Zwierz et al (mKat kg−1 of protein). Protein was determined by the Lowry et al method (mg ml−1).

Results:  The results presented here suggest that diabetes and smoking modify activity of HEX and its isoenzymes, but only combination of diabetes and smoking give a significant increase in the specific activity of HEX and its isoenzymes.

Conclusions:  Type 1 diabetes slightly changes the composition of saliva. Smoking cigarettes significantly modifies the composition and properties of saliva in healthy individuals and patients with Type 1 diabetes.
Serum IgE levels in neurofibromatosis 1
Authors: Geller M. , Ribeiro M. G. , de Q.C. Araújo A. P. , de Oliveira L. J. B. , Nunes F. P.
Published: March 2006

A descriptive case study was performed on 75 patients with NF1 (neurofibromatosis type 1) from the CNNF (Brazil) database. Serum IgE levels were determined using the IgE radioimmunosorbent test, with the reference values of 75–502 IU mL−1. The patients were divided into groups, with 25 patients presenting plexiform neurofibromas, 25 presenting neurofibromas and 25 presenting no neurofibromas. The purposes of this study were to determine the serum IgE levels of patients with NF1 presenting plexiform neurofibromas, neurofibromas and no neurofibromas, as well as to determine possible correlations between serum IgE levels and the size of the plexiform neurofibromas and neurofibromas presented by these patients. Elevated serum IgE levels were observed in all the patient groups. We did not observe a correlation between IgE levels and age in these patients; however, we did observe correlations between IgE levels and neurofibroma and plexiform neurofibroma size. We suggest further studies to confirm these results and to investigate in greater depth the possible role of IgE in the development and growth of neurofibromas and plexiform neurofibromas in NF1.
A91V perforin variation in healthy subjects and FHLH patients
Authors: Busiello R. , Fimiani G. , Miano M. G. , Aricò M. , Santoro A. , Ursini M. V. , Pignata C.
Published: March 2006

Familial haemophagocytic lymphohistiocytosis (FHLH) is a heterogeneous autosomal recessive disorder characterized by hyperactivation of monocytes/macrophages. Perforin (PRF1) gene alterations have been documented in 40% of patients with FHLH. Although several mutations have been identified, a clear correlation between the individual molecular alteration and the phenotypic expression of the disease is still unclear. In particular, the role that the A91V substitution plays in the pathogenesis of the disease is still controversial. In the effort to make a conclusive remark to this issue, we here report on the frequency of the A91V mutation in a group of unrelated healthy families obtained from the ‘Centre d’Etude du Polymorphisme Humain’ (CEPH), which are considered representative of the worldwide population. This frequency was compared to that observed in FHLH patients recruited through the Italian National Registry. The frequency in CEPH healthy subjects is 3.7%, thus indicating that the alteration represents a polymorphism. However, the frequency of this alteration in FHLH patients associated with PRF1 mutation is much higher than that observed in controls (26.2%, P = 0.0002), suggesting that the alteration is an important genetic susceptibility factor.
HSP70‐hom gene single nucleotide (+2763 G/A and +2437 C/T) polymorphisms in sarcoidosis
Authors: Bogunia‐Kubik K. , Koscinska K. , Suchnicki K. , Lange A.
Published: March 2006

In the present study, two coding polymorphisms within the heat shock protein 70‐hom gene (HSP70‐hom) were analysed. One hundred and thirty‐eight individuals were studied, including 42 Polish patients with sarcoidosis, 13 of which presented with Löfgren's syndrome (LS), and 94 control subjects. Dimorphisms at positions +2763 (A/G) and +2437 (C/T) of the HSP70‐hom gene were typed using amplification refractory mutation system and polymerase chain reaction–restriction fragment length polymorphism technique, respectively.

A significant prevalence of the HSP(+2437)‐C allele and the HSP(+2437)‐CC homozygous genotype was observed in patients with sarcoidosis and in those presenting with LS as compared to controls (P < 0.001 in all comparisons made). A majority of HLA‐DRB1*03‐positive patients with LS were carrying both HSP(+2437)‐C and (+2763)‐G alleles, and the concomitant presence of these three genetic factors was more frequent among patients with LS as compared to patients without LS (0.54 vs. 0.17, P < 0.05) and controls (0.54 vs. 0.01, P < 0.001). The association of the HSP(+2437)‐C allele with sarcoidosis and LS appeared to be independent of the presence of DRB1*03, although this HLA specificity was associated with LS manifestation. The HSP(+2763)‐G allele was independently associated with neither sarcoidosis nor LS. However, this HSP(+2763)‐G allele was present with either DRB1*03 or HSP(+2437)‐C within the same haplotypes in the patients and this might explain the observed prevalence of DRB1*03, HSP(+2437)‐C and (+2763)‐G in patients with LS.

In conclusion, HSP(+2437)‐C allele was found as a factor associating with susceptibility to sarcoidosis and LS.
Diagnosis of pharyngeal disorders in dogs: a retrospective study of 67 cases
Authors: Billen F. , Day M. J. , Clercx C.
Published: March 2006

Objectives:To assess the frequency distribution of pharyngeal disorders and to compare clinical signs in diseases of the different pharyngeal areas. To review the investigation methods.

Methods:Medical records of 67 dogs presenting with abnormalities of the pharyngeal area were retrospectively reviewed and classified according to the anatomic area involved, i.e. the nasopharyngeal, oropharyngeal and laryngopharyngeal areas. Clinical signs, endoscopic findings and results of additional sampling were reviewed.

Results:Nasopharyngeal disorders were most frequently encountered (49 per cent), with choanal masses being the most frequent diagnosis (24 of 33), followed by laryngopharyngeal disorders (37·5 per cent) and oropharyngeal disorders (10·5 per cent). A rare condition, stenosis of the intrapharyngeal opening, was classified separately (3 per cent). An overall good correlation between matched cytology and histopathology samples was found. In all categories of diseases, clinical signs related to both the upper respiratory and digestive tracts were reported.

ClinicalSignificance:Pharyngeal disorders are more frequently localised in the nasopharyngeal area and include essentially choanal masses. The use of a flexible endoscope for retrograde rhinoscopy is essential for adequate investigation of the proximal nasopharyngeal area. Clinical signs do not allow differentiation of the pharyngeal disorder within the different pharyngeal areas.
Long‐term results of upper respiratory syndrome surgery and gastrointestinal tract medical treatment in 51 brachycephalic dogs
Authors: Poncet C. M. , Dupre G. P. , Freiche V. G. , Bouvy B. M.
Published: March 2006

Objectives: After a first clinical study showing a high prevalence of gastrointestinal tract diseases in brachycephalic dogs presented for upper respiratory syndrome, a prospective study was performed to determine the influence of medical treatment for gastrointestinal tract disorders associated with upper respiratory syndrome surgery.

Methods: The gastrointestinal tract and respiratory disorders of 61 brachycephalic dogs presented for upper respiratory syndrome were evaluated. Together with surgery of the upper respiratory tract, a specific gastrointestinal medical treatment was administered. A minimal follow‐up of six months was required for inclusion.

Results: Palatoplasty with rhinoplasty was the most common surgical correction (88·5 per cent). The mortality rate in the perioperative period was 3·3 per cent. Minor complications accounted for 26·2 per cent of cases. No aspiration pneumonia was encountered. A sufficient follow‐up was obtained in 51 dogs. The improvement was judged by the owners as excellent or good in 88·3 per cent of the respiratory disorders and in 91·4 per cent of the gastrointestinal disorders. Clinically, a statistically significant improvement was obtained for both respiratory and gastrointestinal disorders.

Clinical Significance: In comparison with other studies, digestive tract medical treatment combined with upper respiratory surgery seems to decrease the complication rate and improve the prognosis of dogs presented for upper respiratory syndrome.
A study of the vibro-acoustic modulation technique for the detection of cracks in metals
Authors: Duffour Philippe , Morbidini Marco , Cawley Peter
Published: March 2006

One implementation of the vibro-modulation technique involves monitoring the amplitude modulation of an ultrasonic vibration field transmitted through a cracked specimen undergoing an additional low frequency structural vibration. If the specimen is undamaged and appropriately supported, the two vibration fields do not interact. This phenomenon could be used as the basis for a nondestructive testing technique. In this paper, the sensitivity of the technique is investigated systematically on a set of mild steel beams with cracks of different sizes and shapes. A damage index was measured for each crack. The correlation obtained between the crack size and the strength of the modulation is fairly poor. The technique proved extremely sensitive to the initial state of opening and closing of the crack and to the setup due to the modulating effects of contacts between the specimens and the supports. A simple model is proposed which explains the main features observed and approximately predicts the level of sideband obtained experimentally.