bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Drug Interactions with the Percent Carbohydrate‐Deficient Transferrin (%CDT) Test, a New Alcohol Biomarker
Authors: Mundt Marlon P. , Kraus Connie K. , Fleming Michael F.
Published: July 2004

Study Objective.To determine the effects of drugs on levels of carbohydrate‐deficient transferrin (CDT), using the %CDT test, a new alcohol biomarker, in patients receiving drug therapy for chronic medical conditions such as diabetes mellitus, hypertension, and lipid disorders.

Design.Regression analysis of transformed data.

Setting.Eight primary care clinics in central Wisconsin.

Patients.Seven hundred ninety‐nine primary care patients who were prescribed drug therapy for a variety of chronic illnesses such as diabetes, hypertension, and lipid disorders.

Measurements and Main Results.The %CDT level, 30‐day history of alcohol consumption, symptoms of alcohol abuse or dependence, health status, and prescribed drugs were determined for each patient. All prescribed drugs that were taken by the patients in the last month were determined by self‐report, medical records, or pharmacy records. Of the 799 patients, 89 were receiving drug therapy for diabetes, 299 for hypertension, 209 for both diabetes and hypertension, and 202 for medical conditions other than diabetes or hypertension. A regression analysis was performed after the data were transformed. Alcohol consumption, sex, age, tobacco use, and 20 drug classes were entered into the model. Factors associated with increased %CDT levels were alcohol consumption, female sex, and bupropion use. Two additional drug classes, the angiotensin II receptor blockers and the tricyclic antidepressants, were associated with lower %CDT levels. The effects of bupropion and tricyclic antidepressants on %CDT levels, however, appear to be confounded by alcohol intake.

Conclusion.This study suggests that only one of 20 drug classes—the angiotensin II receptor blockers—affected %CDT levels in our primary care sample. Additional research with larger samples is needed to focus on the effects of individual drugs used in general clinical settings on %CDT levels.
Potentially Inappropriate Drug Prescribing Among First‐Visit Elderly Outpatients in Taiwan
Authors: Chang Chia‐Ming , Liu Pheng‐Ying Yeh , Yang Yea‐Huei Kao , Yang Yi‐Ching , Wu Chun‐Feng , Lu Feng‐Hwa
Published: July 2004

Study Objective. To determine the prevalence and risk factors of potentially inappropriate drug prescribing among first‐visit elderly outpatients.

Design. Cross‐sectional survey.

Setting. An urban tertiary care and academic medical center in southern Taiwan.

Patients. Eight hundred eighty‐two patients aged 65 years or older who were prescribed drugs at their first visit to either the medical center's outpatient internal medicine clinic or family medicine clinic between March 1, 2001, and July 31, 2001.

Measurements and Main Results. Potentially inappropriate drug prescribing was assessed according to updated Beers criteria. Ninety‐seven potentially inappropriate drugs were identified in 93 (10.5%) patients. The most common classes were sedative‐hypnotics (18.6%) and muscle relaxants (17.5%). Twenty (20.6%) of these inappropriate drugs had a high severity potential according to the Beers criteria. Patients prescribed potentially inappropriate drugs were more likely to be prescribed several drugs versus those who were not prescribed potentially inappropriate drugs (4.0 ± 1.9 vs 2.8 ± 1.4, p<0.001). Multiple logistic regression analysis revealed an interaction between age and the number of prescribed drugs on the risk of having potentially inappropriate drugs prescribed. In patients who were prescribed four agents or less, the risk was not associated with increasing age; in those who were prescribed five drugs or more, the risk was positively associated with increasing age.

Conclusion. Potentially inappropriate drug prescribing among first‐visit elderly outpatients was relatively low. Increasing patient age combined with increased number of drugs prescribed was associated with increased risk of having potentially inappropriate drugs prescribed.
Severe and Resistant Hypoglycemia Associated with Concomitant Gatifloxacin and Glyburide Therapy
Authors: LeBlanc Michel , Bélanger Chantal , Cossette Pierre
Published: July 2004

Severe and resistant hypoglycemia occurred in two patients with diabetes mellitus who were receiving concomitant gatifloxacin and glyburide. An 84‐year‐old woman treated with glyburide for type 2 diabetes mellitus experienced, for the first time, a severe episode of hypoglycemia after 2 days of gatifloxacin 400 mg/day for nonproductive cough. Her blood glucose level on hospital admission was 28 mg/dl. Gatifloxacin and glyburide were discontinued, and the patient was treated with intravenous dextrose infused over 36 hours. Glyburide was restarted before her discharge, with no recurrence of hypoglycemia. A 79‐year‐old man with type 2 diabetes mellitus treated with glyburide was prescribed gatifloxacin 400 mg/day for pneumonia. After 1 day of therapy, the patient was admitted to the emergency department in a coma. His blood glucose level was 18 mg/dl. Despite discontinuation of gatifloxacin and oral hypoglycemic therapy, hypoglycemia was reversed only after administration of multiple boluses of intravenous dextrose, followed by intravenous dextrose infused over 48 hours. On hospital day 7, gliclazide and levofloxacin were started; the patient experienced no recurrence of hypoglycemia and was discharged on day 10. Several cases of severe and resistant hypoglycemia associated with gatifloxacin therapy have been reported in the recent literature. Although the exact mechanism is not fully understood, it may be linked to a gatifloxacin‐induced closing of the adenosine 5′‐triphosphate—sensitive potassium channels in the pancreatic β cells, leading to insulin secretion. The onset of hypoglycemia in relation to the start of gatifloxacin suggests that the drug precipitated this adverse event. Patients receiving oral hypoglycemic agents are at greater risk of experiencing gatifloxacin‐induced hypoglycemia than patients not receiving these agents. Clinicians should be aware of this potentially life‐threatening adverse event and monitor blood glucose levels in all patients receiving concomitant oral hypoglycemic agents and gatifloxacin.
ICF syndrome in a girl with DNA hypomethylation but without detectable DNMT3B mutation
Authors: Kubota Takeo , Furuumi Hiroyasu , Kamoda Tomohiro , Iwasaki Nobuaki , Tobita Naomi , Fujiwara Nobuko , Goto Yu‐ichi , Matsui Akira , Sasaki Hiroyuki , Kajii Tadashi
Published: July 2004

A 3‐year‐old girl with phenotypic and cytogenetic manifestations of the ICF syndrome and DNA hypomethylation but without DNMT3B gene mutation is described. At age 3 months, she had an apneic spell that left her with spastic paraplegia and severe mental retardation. At age 8 months, she suffered meningococcal meningitis and sepsis. When seen by us at age 3 years with virilization, she had a cleft plate, macroglossia, and an atrial septal defect. An adenoma was surgically removed from the right adrenal cortex. Her serum immunoglobulin levels were normal except IgA at the low normal border. Her lymphocytes showed paracentromeric stretching of chromosomes 1 and 16 in 7% of metaphases, and multiradial figures involving these chromosomes in 1% of cells. Hypomethylation of classical satellite 2 DNA was observed with BstBI digestion, but in a lesser degree than those in the individuals with proven DNMT3B mutations. No mutation was found in the coding and promoter regions of the gene. Several alternative interpretations were considered to explain the low frequencies of chromosomal instabilities and the lower degree of DNA hypomethylation, and undetected DNA3B mutations. A mutation may be present in the gene but undetected, present in other DNA methyltransferases (DNMT) genes or in a DNMT‐associated protein gene. © 2004 Wiley‐Liss, Inc.
Marked phenotypic variability in progressive diaphyseal dysplasia (Camurati–Engelmann disease): Report of a four‐generation pedigree, identification of a mutation in TGFB1, and review
Authors: Wallace Stephanie E. , Lachman Ralph S. , Mekikian Pertchoui B. , Bui Kathy K. , Wilcox William R.
Published: July 2004

Progressive diaphyseal dysplasia (PDD) (Camurati–Engelmann disease) is an autosomal dominant craniotubular dysplasia characterized by hyperostosis and sclerosis of the diaphyses of the long bones and the skull. Mutations in transforming growth factor β‐1 (TGFB1) were recently found in patients with PDD. We report on a four‐generation pedigree with seven individuals affected by PDD, linkage and mutational analysis results, and review the literature. This pedigree demonstrates the autosomal dominant inheritance pattern, remarkable variation in expressivity, and reduced penetrance. The most severely affected individual had progression of mild skull hyperostosis to severe skull thickening and cranial nerve compression over 30 years. His carrier father remained asymptomatic into his ninth decade and had no radiographic hyperostosis or sclerosis of the bones. Symptomatic relatives presented with lower limb pain and weakness. They were initially diagnosed with a variety of other conditions. Two of the symptomatic individuals were treated successfully with prednisone. We genotyped 7 markers from chromosome region 19q13.1‐13.3 in 15 relatives and confirmed linkage to this region in this family. We screened the TGFB1 gene for mutations and identified a missense mutation resulting in an R218H substitution in the affected individuals, the asymptomatic obligate carrier, and another unaffected relative. We genotyped the family for seven known TGFB1 polymorphisms and a novel TAAA tetranucleotide repeat in intron 1. These polymorphisms did not appear to account for the variability in disease severity in this family. Our review illustrates how the disorder can significantly compromise health. Cranial involvement, which occurs in 61% of patients, can be severe, entrapping cranial nerves or causing increased intracranial pressure. Therapy with corticosteroids should be attempted in all symptomatic patients. © 2004 Wiley‐Liss, Inc.
A patient with a de novo 15q24q26.1 interstitial deletion, developmental delay, mild dysmorphism, and very blue irises
Authors: Spruijt L. , Engelen J.J.M. , Bruinen‐Smeijsters I.P. , Albrechts J.C.M. , Schrander J. , Schrander‐Stumpel C.T.R.M.
Published: July 2004

We report on a patient with a de novo 15q24q26.1 interstitial deletion. She presented with developmental delay, behavioral characteristics, and mild dysmorphism with very blue irises. We review the limited literature of interstitial 15q deletions. There was no distinct phenotypic overlap between these two cases in literature and the present patient. Additional reports are necessary in order to establish a possible recognizable deletion 15q24q26.1 phenotype. © 2004 Wiley‐Liss, Inc.
Five years of molecular diagnosis of Fragile X syndrome (1997–2001): A collaborative study reporting 95% of the activity in France
Authors: Biancalana Valérie , Beldjord Chérif , Taillandier Agnès , Szpiro‐Tapia Sylvie , Cusin Véronica , Gerson Fabienne , Philippe Christophe , Mandel Jean‐Louis ,   The French National Working Group on Fragile X Syndrome
Published: July 2004

The Fragile X syndrome is the most common cause of inherited mental retardation. Clinical features are neither specific nor constant and molecular diagnosis is thus widely used since the characterization of the causal mutation in 1991. The aim of this project was to study the evolution of Fragile X diagnosis in France. A preliminary study of the efficiency of screening for the Fragile X mutation in mentally retarded probands with no previous familial diagnosis was done in the Strasbourg's laboratory with a comparison between data from 1991–1994 and 1997–2000 (Biancalana et al. [2002: 1ières Assises de Génétique Humaine et Médicale: 95p]). This study showed an improvement in the use of the Fragile X testing regarding the probands' age at diagnosis and the recruitment of sporadic and female cases. To avoid possible bias in clinical referrals and to evaluate the situation nation wide, this study was enlarged to 28 of the 30 laboratories involved in the Fragile X diagnosis in France from 1997 to 2001 (20,816 probands tested, data representative of 95% of the national screening activity). Median age at diagnosis decreased from 9.2 to 5.8 (average 16–11.6y) between the 1991–1994 and the 1997–2001 studies. Over this period, 477 new families were diagnosed with Fragile X, representing 2.8% of tested male probands (417/14,867) and 1.0% of tested female probands (60/5,949). Forty one percent of positive cases corresponded to probands with a familial history of mental retardation, compared to 66% in the initial (1991–1994) study. We also discuss issues concerning premutations discovered in affected individuals and in females with premature ovarian failure (POF). © 2004 Wiley‐Liss, Inc.
Titelbild: Efficiency and Fidelity in a Click‐Chemistry Route to Triazole Dendrimers by the Copper(I)‐Catalyzed Ligation of Azides and Alkynes (Angew. Chem. 30/2004)
Authors: Wu Peng , Feldman Alina K. , Nugent Anne K. , Hawker Craig J. , Scheel Arnulf , Voit Brigitte , Pyun Jeffrey , Fréchet Jean M. J. , Sharpless K. Barry , Fokin Valery V.
Published: July 2004

Strukturelle Diversität ist bei Dendrimersynthesen möglich, die auf dem hoch effizienten Aufbau von Triazolen aus funktionalisierten Aziden und Alkinen beruhen. In ihrer Zuschrift auf S. 4018 ff. beschreiben V. V. Fokin et al. die Anwendung dieser CuI‐katalysierten Umwandlung, die bis zur dritten und vierten Dendrimergeneration nahezu quantitativ verläuft.
Cover Picture: Efficiency and Fidelity in a Click‐Chemistry Route to Triazole Dendrimers by the Copper(I)‐Catalyzed Ligation of Azides and Alkynes (Angew. Chem. Int. Ed. 30/2004)
Authors: Wu Peng , Feldman Alina K. , Nugent Anne K. , Hawker Craig J. , Scheel Arnulf , Voit Brigitte , Pyun Jeffrey , Fréchet Jean M. J. , Sharpless K. Barry , Fokin Valery V.
Published: July 2004

Structural diversity is possible in dendrimer syntheses based on the highly efficient construction of triazoles from functionalized azides and alkynes. In their Communication on page 3928 ff., V. V. Fokin et al. describe the application of this CuI‐catalyzed transformation, which proceeds in near‐quantitative yields even to the third and fourth generation.
Interactive web‐based programs to teach functional anatomy: The pterygopalatine fossa
Authors: Sinav Ahmet , Ambron Richard
Published: July 2004

Certain areas of the body contain structures that are difficult to envision in their proper spatial orientations and whose functions are complex and difficult to grasp. This is especially true in the head, where many structures are relatively small and inaccessible. To address this problem, we are designing Web‐based programs that consist of high‐resolution interactive bitmap illustrations, prepared using Adobe Photoshop, and vector‐based animations, prepared via Macromedia Flash. Flash action script language is used for the animations. We have used this approach to prepare a program on the pterygopalatine fossa, an important neurovascular junction in the deep face that is especially difficult to approach by dissection and to depict in static images in an atlas. The program can be viewed online at http://cds.osr.columbia.edu/anatomy/ppfossa/. A table of contents simplifies navigation through the program and a menu enables the user to identify each of the vascular and neuronal components and either to insert or to remove each from its position in the fossa. The functional anatomy of the nerves in the fossa is animated. For example, users can activate and subsequently follow action potentials as they course along axons to their targets. This high degree of interactivity helps promote learning. Anat Rec (Part B: New Anat) 279B:4–8, 2004. © 2004 Wiley‐Liss, Inc.
Making tracks: The forensic analysis of footprints and footwear impressions
Authors: Naples Virginia L. , Miller Jon S.
Published: July 2004

Analysis of footwear characteristics, impressions, and track ways can provide important evidence in a crime scene investigation. In this article, we present examples of how students can be involved in hands‐on laboratory‐based activities as a means of introducing the forensic sciences. The teaching methodology employs active learning strategies that allow students to discover scientific principles for themselves, develop techniques of critical thinking and problem solving, and gain appreciation for how knowledge arises. By including forensic sciences in the science curriculum, students develop an appreciation for the interrelatedness of all the sciences. From this series of activities, i.e., examining analyses of footprint and footwear impressions, students working as teams will gather information, analyze data, and draw conclusions. Moreover, students will be able to assess the significance of the quality and variability in the data collection process as well as learn the value of controls and experimental design through comparison of results with other groups. Anat Rec (Part B: New Anat) 279B:9–15, 2004. © 2004 Wiley‐Liss, Inc.
Effects of protein deficient diets on the developmental toxicity of inorganic arsenic in mice
Authors: Lammon Carol A. , Hood Ronald D.
Published: July 2004

BACKGROUND: Inorganic arsenic, when given by injection to pregnant laboratory animals (mice, rats, hamsters), has been shown to induce malformations. Arsenic methylation may be a detoxification step, and diets deficient in protein are a poor source of methyl donors and may possibly result in impaired arsenic methylation. Human health effects from chronic arsenic exposure have been reported mainly in populations with low socioeconomic status. Individuals in such populations are likely to suffer from malnutrition, which can compromise embryonic/fetal development and diminish arsenic methylating capacity. We sought to determine if dietary protein deficiency affects the developmental toxicity of inorganic arsenic. METHODS: Mated females were randomly assigned to one of 12 treatment groups. Experimental groups received either AsIII or AsV i.p. on Gestation Day 8 (GD 8, plug=GD 0) and were maintained on a 5%, 10%, or 20% protein custom mixed diet from GD 1 until sacrifice. Controls received the custom diets alone, were given AsIII or AsV i.p. on GD 8 with Teklad LM‐485 rodent diet, or were fed the LM‐485 diet alone. Test females were sacrificed on GD 17, and their litters were examined for mortality and developmental defects. RESULTS: Arsenic plus dietary protein deficiency decreased maternal weight gain and increased the incidences of exencephaly, ablepharia, and skeletal defects, such as malformed vertebral centra, fused ribs, and abnormal sternebrae (bipartite, rudimentary, or unossified). CONCLUSIONS: These results demonstrate that dietary protein deficiency enhances the developmental toxicity of inorganic arsenic, possibly by impairment of arsenic methylation. Birth Defects Res B 71:124–134, 2004. © 2004 Wiley‐Liss, Inc.
Long‐term alcohol exposure prior to conception results in lower fetal body weights
Authors: Livy Daniel J. , Maier Susan E. , West James R.
Published: July 2004

BACKGROUND: It is well known that alcohol consumption during pregnancy can result in lower birth weight babies but many women stop consuming alcohol prior to conception as a part of pregnancy planning. The purpose of this study was to determine whether alcohol consumption prior to conception may also have an effect on fetal development. METHODS: Male and female C57BL/6J mice at 4, 6, or 8 weeks of age received either a single administration of alcohol (3.0 g/kg) via intragastric gavage (IG) each day for at least 60 days, or an isovolumetric IG administration of sterile water. After 60 treatment days, males and females within each age and treatment group were mated overnight. Females continued to receive daily alcohol treatments until conception. Males continued to receive treatments until all females were successfully mated. At conception, females were isolated and left undisturbed. On embryonic day 14, fetus number, size, and weight was determined. RESULTS: Maternal food consumption, body weight at conception, and delay to conception onset did not differ between the two treatment groups or among the three age groups. Fetal body weights did not differ among the three age groups. Fetuses from females treated with alcohol had lower body weights compared to those treated with water. Male treatments did not seem to affect fetal body weight. CONCLUSIONS: Fetal growth and development can be affected by alcohol consumption prior to the time of conception. Alcohol consumption prior to conception is a potential risk factor to fetal outcome and an important consideration for those females planning to have children. Birth Defects Res B 71:135–141, 2004. © 2004 Wiley‐Liss, Inc.
Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in female rats
Authors: Terry K.K. , Cappon G.D. , Hurtt M.E. , Tassinari M.S. , Gupta U.
Published: July 2004

BACKGROUND: Lasofoxifene is a nonsteroidal selective estrogen receptor modulator (SERM). With high affinity to the α and β human estrogen receptors and greater potency than other SERMs, lasofoxifene is potentially a superior treatment for postmenopausal osteoporosis. In light of the known effects of estrogen‐modulating compounds on female reproductive indices, two studies were conducted to evaluate the effects of lasofoxifene on female rat cyclicity, reproduction, and parturition. METHODS: One study evaluated effects of lasofoxifene on estrous cyclicity, and the second study assessed effects on implantation and parturition. In the cyclicity study, lasofoxifene was administered to female rats at doses of 0.1, 0.3, and 1.0 mg/kg/day for 14 consecutive days. After treatment, there was a 3‐week reversibility phase followed by a mating phase. In the implantation study, lasofoxifene was administered to pregnant female rats at doses of 0.01, 0.03, and 0.1 mg/kg/day for 7 consecutive days (gestation day [GD] 0–6). Some animals were euthanized on GD 21, and the remainder of the group was allowed to deliver the F1 generation. Several developmental indices were evaluated in the F1 pups through post‐natal day (PND) 21. RESULTS: In the cyclicity study, all lasofoxifene‐treated females were anestrous by Study Day 7 (1.0 mg/kg) or 9 (0.3 and 0.1 mg/kg). The reversibility phase resulted in restoration of normal estrous cycles by the end of 1 (0.1 mg/kg) or 2 weeks (0.3 and 1.0 mg/kg). During the mating phase, no adverse effects occurred in pregnancy success or reproductive parameters. In the implantation study, all doses of lasofoxifene increased pre‐ and post‐implantation losses, increased gestation length, and reduced litter size. None of the developmental parameters measured on the F1 generation was adversely affected. CONCLUSION: Lasofoxifene reversibly altered the estrous cycle and inhibited implantation, consistent with what would be expected from a member of the SERM class. Birth Defects Res B 71:150–160, 2004. © 2004 Wiley‐Liss, Inc.
Embryo/fetal toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in rats and rabbits
Authors: Ozolinš T.R.S. , Gupta U.
Published: July 2004

BACKGROUND: The purpose of this study was to evaluate the effects of lasofoxifene, a selective estrogen receptor modulator (SERM), on rat and rabbit fetal development. METHODS: Lasofoxifene was administered orally to rats (1, 10, 100 mg/kg) between gestation days (GD) 6–17, and in rabbits (0.1, 1, 3 mg/kg) between GD 6–18. Maternal body weight and food consumption were monitored throughout pregnancy. Fetuses were delivered by Cesarean section on GD 21 in rats, and GD 28 in rabbits, to evaluate fetal viability, weight, and morphology. Drug concentrations in maternal plasma were measured in a separate cohort of animals at several time points commencing on GD 17 (rats) and 18 (rabbits). On GD 18 (rat) and GD 19 (rabbit) drug concentrations were measured in maternal plasma and in fetal tissue 2 hr post dosing to determine the fetal to maternal drug ratio. RESULTS: In rats, there were dose‐related declines in maternal weight gain and food consumption. Post implantation loss was significantly increased at dosages of 10 and 100 mg/kg, and the number of viable fetuses was decreased at 100 mg/kg. The placental weights increased, whereas fetal weights decreased in a dose‐dependent manner. Lasofoxifene‐related teratologic findings were noted at 10 and 100 mg/kg and included imperforate anus with hypoplastic tails, dilatation of the ureters and renal pelvis, misaligned sternebrae, hypoflexion of hindpaw, wavy ribs, and absent ossification of sternebrae. In rabbits, neither maternal weight gain nor food consumption were affected during treatment. Between GD 26–28, there was a dose‐dependent increased incidence of red discharge beneath the cages. At 1 and 3 mg/kg, resorptions and post‐implantation loss increased. There were no significant external or visceral effects, but 3 mg/kg there was an increased incidence of supernumerary ribs. Although the maternal plasma Cmax and AUC(0–24) were dose‐dependent, the exposures in the rat were many orders of magnitude greater than in the rabbit even for the same 1 mg/kg dose. The single time point fetal/maternal drug ratio was higher in the rat (1.3–0.78) than in the rabbit (0.21–0.16). CONCLUSION: In general, both maternal and fetal effects of lasofoxifene were similar to those reported with other SERMs. Although the incidence or severity of these effects was, in some instances, greater in the rat than in the rabbit, the doses and the resultant maternal and fetal exposures were many orders of magnitude higher in the rat, suggesting the rabbit to be more sensitive to the toxicological effects of lasofoxifene. Birth Defects Res B 71:161–170, 2004. © 2004 Wiley‐Liss, Inc.
Postnatal closure of membranous ventricular septal defects in Sprague‐Dawley rat pups after maternal exposure with trimethadione
Authors: Fleeman Tammye L. , Cappon Gregg D. , Hurtt Mark E.
Published: July 2004

BACKGROUND: Congenital membranous ventricular septal defects (VSD) have been shown to close during postnatal development in rats [Solomon et al., Teratology 55:185–194, 1997]. Although they may differ in size, spontaneous and treatment‐related VSD are histologically similar; however, the postnatal fate of treatment‐induced VSD is not known. The objective of this study was to determine if treatment‐induced VSD persist throughout postnatal development. METHODS: Groups of 40 female rats were given oral doses of trimethadione (TMD) at 400 mg/kg/day (200 b.i.d.) or 600 mg/kg/day (300 b.i.d.) on Gestation Days (GD) 9 and 10. Twenty dams in each group were designated for Cesarean section and 20 were allowed to deliver and rear their offspring to Postnatal Day (PND) 21. The integrity of the ventricular septum was evaluated in fetuses (GD 21) and pups (PND 21). RESULTS: The incidence of membranous VSD was 0.6, 7.6, and 49.8% per litter in the Control, 400, and 600 mg/kg groups, respectively, on GD 21. Both the incidence and severity of VSD increased with dose. The VSD at 400 mg/kg were small in size and initially detected by the presence of blood flowing through the defect from the closed right ventricle. In the 600 mg/kg dose group, the VSD, although still membranous, were larger and more readily detected without the need to examine the blood flow. At 600 mg/kg, not only were the VSD larger than those in the Control or the 400 mg/kg group, 10.1% per litter of the affected fetuses had other vessel anomalies associated with the VSD, which were incompatible with pup survival. On PND 21, VSD was noted in 0.3, 0, and 6.4% per litter evaluated in the Control, 400, and 600 mg/kg groups, respectively. This demonstrates that the small, isolated treatment‐related VSD can resolve postnatally; however, the closure of the larger or more severe VSD may be prolonged or may not occur at all. Although TMD exposure reduced group mean fetal weights at both dose levels, there was no difference between the mean weight of fetuses with VSD and those fetuses without VSD in the same group. CONCLUSION: Treatment‐induced VSD close postnatally, and appears to be a delay in cardiac development not associated with fetal weight. The timing of closure and survivability during closure is dependent on the severity of the VSD. Further characterization of the two sizes of VSD may provide diagnostic clarity; however, the current data support the smaller VSD as a variation with no significant impact on viability and growth, and the more severe VSD to be a malformation. Birth Defects Res B 71:185–190, 2004. © 2004 Wiley‐Liss, Inc.
Impact of engineering flow conditions on plasmid DNA yield and purity in chemical cell lysis operations
Authors: Meacle F.J. , Lander R. , Ayazi Shamlou P. , Titchener‐Hooker N.J.
Published: July 2004

Chemical lysis of bacterial cells using an alkaline solution containing a detergent may provide an efficient scalable means for selectively removing covalently closed circular plasmid DNA from high‐molecular‐weight contaminating cellular components including chromosomal DNA. In this article we assess the chemical lysis of E. coli cells by SDS in a NaOH solution and determine the impact of pH environment and shear on the supercoiled plasmid and chromosomal DNA obtained. Experiments using a range of plasmids from 6 kb to 113 kb determined that in an unfavorable alkaline environment, where the NaOH concentration during lysis is greater than 0.15 ± 0.03 M (pH 12.9 ± 0.2), irreversible denaturation of the supercoiled plasmid DNA occurs. The extent of denaturation is shown to increase with time of exposure and NaOH concentration. Experiments using stirred vessels show that, depending on NaOH concentration, moderate to high mixing rates are necessary to maximize plasmid yield. While NaOH concentration does not significantly affect chromosomal DNA contamination, a high NaOH concentration is necessary to ensure complete conversion of chromosomal DNA to single‐stranded form. In a mechanically agitated lysis reactor the correct mixing strategy must balance the need for sufficient mixing to eliminate potential regions of high NaOH concentrations and the need to avoid excessive breakage of the shear sensitive chromosomal DNA. The effect of shear on chromosomal DNA is examined over a wide range of shear rates (101−105 s−1) demonstrating that, while increasing shear leads to fragmentation of chromosomal DNA to smaller sizes, it does not lead to significantly increased chromosomal DNA contamination except at very high shear rates (about 104−105 s−1). The consequences of these effects on the choice of lysis reactor and scale‐up are discussed. © 2004 Wiley Periodicals, Inc.
Correlation of diafiltration sieving behavior of lysozyme‐BSA mixtures with osmotic second virial cross‐coefficients
Authors: Tessier Peter M. , Verruto Vincent J. , Sandler Stanley I. , Lenhoff Abraham M.
Published: July 2004

The role of protein–protein interactions in membrane separations of protein mixtures remains incompletely understood, largely due to the difficulty of characterizing protein self‐ and, especially, cross‐association. Recently, a novel technique, cross‐interaction chromatography, has been developed to measure weak protein cross‐association in terms of the osmotic second virial cross‐coefficient. In this work the relationship between protein cross‐association and the sieving behavior of lysozyme in the presence of BSA has been investigated. Sieving coefficients were measured using a stirred diafiltration cell over a range of pH and ionic strength, and a striking correlation between the lysozyme sieving and second virial cross‐coefficients for BSA/lysozyme mixtures has been found: when the protein cross‐interactions are most attractive (negative second virial cross‐coefficient), the lysozyme sieving coefficients are lowest, and vice versa. The correlation between the sieving and second virial cross‐coefficients may be due to the physically similar environments in the chromatography and filtration experiments since one protein is passed through a concentrated region of the second protein either immobilized on the column or accumulated at the membrane surface, and the migration rate of the mobile protein in both cases is influenced by protein cross‐association. This study represents the first time that molecular interactions in binary mixtures have been related directly to filtration behavior, and may provide a useful approach to optimize the separation of other binary protein mixtures. © 2004 Wiley Periodicals, Inc.
Quaternary Cesium Copper(I) Lanthanoid(III) Selenides of the Type CsCu3Ln2Se5 (Ln: Sm, Gd—Lu).
Authors: Strobel Sabine , Schleid Thomas
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
The New Cesium Praseodymium Thiophosphate Cs3Pr5[PS4]6.
Authors: Komm Theresa , Schleid Thomas
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
Structural and Magnetic Properties of Gd1‐xPrxMn2Si2 Silicides.
Authors: Kilic A. , Kervan S. , Gencer A.
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
Structural Study of the Pseudobinary CeCu5—CeZn5 System.
Authors: Pavlyuk V. , Rozycka‐Sokolowska E. , Marciniak B. , Prochwicz W. , Solokha P. , Dzierzanowski P.
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
Er—Fe—Sb System at 1170 K.
Authors: Morozkin A. V.
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
Growth and Characterization of BPO4 Single Crystals.
Authors: Schmidt M. , Ewald B. , Prots Yu. , Cardoso‐Gil R. , Armbruester M. , Loa I. , Zhang L. , Huang Ya‐Xi , Schwarz U. , Kniep R.
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
Naked Deltahedral Silicon Clusters in Solution: Synthesis and Characterization of Si3‐9 and Si2‐5.
Authors: Goicoechea Jose M. , Sevov Slavi C.
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis, Crystal Structure and Physical Properties of FeSr2 (Ce3/2Ln1/2)Cu2O10‐δ (Ln: Eu, Gd, and Tb).
Authors: Yang L. T. , Liang J. K. , Liu Q. L. , Liu F. S. , Luo J. , Rao G. H.
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
Polymer Bound Pd(0) Phosphine Catalyst for Homogeneous Catalysis.
Authors: Koshti Nirmal , Naik Shubhangi , Parab Bharat
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
P‐Chirogenic Diaminophosphine Oxide: A New Class of Chiral Phosphorus Ligands for Asymmetric Catalysis.
Authors: Nemoto Tetsuhiro , Matsumoto Takayoshi , Masuda Takamasa , Hitomi Tsukasa , Hatano Keiichiro , Hamada Yasumasa
Published: July 2004

For Abstract see ChemInform Abstract in Full Text.
Direct and Enantioselective Organocatalytic α‐Chlorination of Aldehydes.
Authors: Brochu Michael P. , Brown Sean P. , MacMillan David W. C.
Published: July 2004

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Reagent‐Controlled Asymmetric Iodolactonization Using Cinchona Alkaloids as Chiral Sources.
Authors: Wang Mang , Gao Lian Xun , Yue Wei , Mai Wen Peng
Published: July 2004

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Copper(I)‐Catalyzed Asymmetric Hydrosilylations of Imines at Ambient Temperatures.
Authors: Lipshutz Bruce H. , Shimizu Hideo
Published: July 2004

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The Direct Catalytic Asymmetric Cross‐Mannich Reaction: A Highly Enantioselective Route to 3‐Amino Alcohols and α‐Amino Acid Derivatives.
Authors: Cordova Armando
Published: July 2004

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Michael Additions of Aldehydes and Ketones to β‐Nitrostyrenes in an Ionic Liquid.
Authors: Kotrusz Peter , Toma Stefan , Schmalz Hans‐Guenther , Adler Andreas
Published: July 2004

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Mixed Organofluorine‐Organosilicon Chemistry. Part 13. Synthesis of Polyfluorinated Nitrogen‐Containing Heterocycles from Hemifluorinated Enones or Organofluorosilicon Building Blocks as Synthetic Equivalents.
Authors: Chanteau Frederic , Didier Benoit , Dondy Boniface , Doussot Pascale , Plantier‐Royon Richard , Portella Charles
Published: July 2004

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Pd(OAc)2‐Catalyzed Isomerization of Acetates of the Baylis—Hillman Adducts.
Authors: Park Jeong Beom , Ko Seung Ho , Kim Bong Gyu , Hong Wan Pyo , Lee Kee‐Jung
Published: July 2004

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Transition‐Metal‐Free: A Highly Efficient Catalytic Aerobic Alcohol Oxidation Process.
Authors: Liu Renhua , Liang Xinmiao , Dong Chunyan , Hu Xinquan
Published: July 2004

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Magnesium/Methanol: An Effective Reducing Agent for Peroxides.
Authors: Dai Peng , Dussault Patrick H. , Trullinger Tony K.
Published: July 2004

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Bismuth‐Mediated Reductive Dehalogenation of α‐Halocarbonyl Compounds.
Authors: Lee Yoon Joo , Chan Tak Hang
Published: July 2004

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Amidopalladation of Alkoxyallenes Applied in the Synthesis of an Enantiopure 1‐Ethylquinolizidine Frog Alkaloid.
Authors: Kinderman Sape S. , de Gelder Rene , van Maarseveen Jan H. , Schoemaker Hans E. , Hiemstra Henk , Rutjes Floris P. J. T.
Published: July 2004

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Platinum‐Catalyzed Intermolecular Hydroamination of Unactivated Olefins with Carboxamides.
Authors: Wang Xiang , Widenhoefer Ross A.
Published: July 2004

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Iron‐Catalyzed Cross‐Coupling of Primary and Secondary Alkyl Halides with Aryl Grignard Reagents.
Authors: Nakamura Masaharu , Matsuo Keiko , Ito Shingo , Nakamura Eiichi
Published: July 2004

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Mukaiyama Aldol Reactions of Silyl Enolates Catalyzed by Iodine.
Authors: Phukan Prodeep
Published: July 2004

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Tandem Enyne Metathesis‐Diels—Alder Reaction for Construction of Natural Product Frameworks.
Authors: Rosillo Marta , Dominguez Gema , Casarrubios Luis , Amador Ulises , Perez‐Castells Javier
Published: July 2004

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Platinum‐Catalyzed Selective Hydration of Hindered Nitriles and Nitriles with Acid‐ or Base‐Sensitive Groups.
Authors: Jiang Xiao‐bin , Minnaard Adriaan J. , Feringa Ben L. , de Vries Johannes G.
Published: July 2004

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[Bis(2‐methoxyethyl)amino]sulfur Trifluoride, the Deoxo‐Fluor Reagent: Application Toward One‐Flask Transformations of Carboxylic Acids to Amides.
Authors: White Jonathan M. , Tunoori Ashok Rao , Turunen Brandon J. , Georg Gunda I.
Published: July 2004

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Cascade Carbonylation Methods Leading to β‐Diketones and β‐Functionalized δ‐Diketones.
Authors: Miura Katsukiyo , Tojino Mami , Fujisawa Naoki , Hosomi Akira , Ryu Ilhyong
Published: July 2004

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The Synthesis and Photo‐Induced Deprotection Reaction of Calix[4]resorcinarene Derivatives Containing t‐Butyl Ester Moieties.
Authors: Kudo Hiroto , Mitani Kouji , Nishikubo Tadatomi , Mitsuishi Masaya , Miyashita Tokuji
Published: July 2004

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Synthesis of All Stereoisomers of the Norchrysanthemic Acid Methyl Ester.
Authors: Ujihara Kazuya , Matsuo Noritada , Kitahara Takeshi
Published: July 2004

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Indium(III) Chloride Promoted Intramolecular Addition of Allylstannanes to Alkynes.
Authors: Miura Katsukiyo , Fujisawa Naoki , Hosomi Akira
Published: July 2004

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Rate Acceleration and Diastereoselectivity in Chelation‐Controlled Indium‐Promoted Barbier Allylation of Pyridine‐2‐ and Quinoline‐2‐imines in Aqueous Solvents.
Authors: Kumar Subodh , Kaur Pervinder
Published: July 2004

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The Reaction of Hydrazine with α‐Cyanocinnamate Esters: A Caveat.
Authors: Erdman Paul J. , Gosse Jimmy L. , Jacobson Jamey A. , Lewis David E.
Published: July 2004

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Imino 1,2‐Wittig Rearrangement of Hydroximates and Its Application to Synthesis of Cytoxazone.
Authors: Miyata Okiko , Koizumi Tomoko , Asai Hiroshi , Iba Ryuichi , Naito Takeaki
Published: July 2004

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Lithium Perchlorate Mediated Three‐Component Preparation of α‐Aminonitriles under Solvent‐Free Conditions.
Authors: Azizi Najmedin , Saidi Mohammad R.
Published: July 2004

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Acyl C→N Migration in the Thioureidomethylation of 2‐(4‐Methylbenzoyl)cyclohexanone.
Authors: Shutalev Anatoly D. , Zhukhlistova Nadezhda E. , Gurskaya Galina V.
Published: July 2004

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Non‐Thiol Farnesyltransferase Inhibitors: Utilization of the Near Aryl Binding Site by 5‐Arylacetylaminobenzophenones
Authors: Mitsch Andreas , Boehm Markus , Sattler Isabel , Schlitzer Martin
Published: July 2004

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Hydrogen‐Mediated C—C Bond Formation: Catalytic Regio‐ and Stereoselective Reductive Condensation of α‐Keto Aldehydes and 1,3‐Enynes.
Authors: Jang Hye‐Young , Huddleston Ryan R. , Krische Michael J.
Published: July 2004

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Superacid‐Catalyzed Reactions of Cinnamic Acids and the Role of Superelectrophiles.
Authors: Rendy Rendy , Zhang Yun , McElrea Aaron , Gomez Alma , Klumpp Douglas A.
Published: July 2004

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α‐Oxoketene Dithioacetal Mediated Aromatic Annulation: Highly Efficient and Concise Synthetic Routes to Potentially Carcinogenic Polycyclic Aromatic Hydrocarbons.
Authors: Nandi Sukumar , Panda Kausik , Suresh J. R. , Ila Hiriyakkanavar , Junjappa Hiriyakkanavar
Published: July 2004

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A Domino Ring‐Opening/Epoxidation of 1,2‐Dioxines.
Authors: Greatrex Ben W. , Taylor Dennis K. , Tiekink Edward R. T.
Published: July 2004

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Synthesis of 2‐Cyanomethyl‐3‐hydroxy‐5‐iodomethyltetrahydrofuran from Various Isoxazolines: Effects of 3‐Substituents in the Diastereoselective Iodoetheration Reactions of Isoxazolines.
Authors: Kim Hyoung Cheul , Seo Min Jung , Kim Jung Ki , Lee Jae‐Don , No Zaesung , Kim Hyoung Rae
Published: July 2004

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Triphenylphosphine‐Induced Ring Contraction of 1,2‐Dioxines.
Authors: Greatrex Ben W. , Taylor Dennis K.
Published: July 2004

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Efficient Synthesis of 4‐(3′‐Furanyl)butenolide Derivatives via PdII‐Catalyzed Oxidative Heterodimeric Cyclization Reaction of 2,3‐Allenoic Acids and 1,2‐Allenyl Ketones.
Authors: Ma Shengming , Yu Zhanqian
Published: July 2004

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A Facile Synthesis of 3‐Substituted Phthalides.
Authors: Li Guo , Yin Dali , Liang Xiao‐Tian
Published: July 2004

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Synthesis of 2‐Aryl‐4,6‐dinitrobenzo[b]thiophenes from 2,4,6‐Trinitrotoluene.
Authors: Sapozhnikov Oleg Yu. , Mezhnev Vasily V. , Dutov Mikhail D. , Kachala Vadim V. , Shevelev Svyatoslav A.
Published: July 2004

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Introduction of Heterocycles at the 2‐Position of Indoline as Ester Bioisosteres.
Authors: Lee Sunkyung , Yi Kyu Yang , Yoo Sung‐eun
Published: July 2004

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Platinum‐Catalyzed Intramolecular Alkylation of Indoles with Unactivated Olefins.
Authors: Liu Cong , Han Xiaoqing , Wang Xiang , Widenhoefer Ross A.
Published: July 2004

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Synthesis of 1‐Azaazulenes from Cycloheptatrienylmethyl Ketone O‐Pentafluorobenzoyloximes by Palladium‐Catalyzed Cyclization and Oxidation.
Authors: Chiba Shunsuke , Kitamura Mitsuru , Saku Osamu , Narasaka Koichi
Published: July 2004

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1,3‐Dipolar Cycloaddition Route to Novel Isoxazole‐Type Derivatives Related to Combretastatin A‐4.
Authors: Kaffy Julia , Monneret Claude , Mailliet Patrick , Commercon Alain , Pontikis Renee
Published: July 2004

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Use of Thiazoles in the Halogen Dance Reaction: Application to the Total Synthesis of WS75624 B.
Authors: Stangeland Eric L. , Sammakia Tarek
Published: July 2004

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Spiro‐bithiazole Derivatives of Amidinothiocarbamides: Novel Utilization of the Synthon 2‐Arylimino‐5‐carbethoxy‐thiazolidin‐4‐one.
Authors: Chande Madhukar S. , Carvalho Peter V. R.
Published: July 2004

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Novel Conversion of 6H‐1,3,5‐Oxathiazine S‐Oxides into 5‐Membered Heterocyclic Compounds.
Authors: Rafiqul Islam Md. , Shimada Kazuaki , Aoyagi Shigenobu , Takikawa Yuji , Kabuto Chizuko
Published: July 2004

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TBAF‐Catalyzed Synthesis of 5‐Substituted 1H‐Tetrazoles under Solventless Conditions.
Authors: Amantini David , Beleggia Romina , Fringuelli Francesco , Pizzo Ferdinando , Vaccaro Luigi
Published: July 2004

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Novel Synthesis of Dihydropyrans and 2,8‐Dioxabicyclo[3.3.0]oct‐3‐enes Using Mn(III)‐Based Oxidative Cyclization.
Authors: Nguyen Van‐Ha , Nishino Hiroshi
Published: July 2004

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Mono‐nitration of Coumarins by Nitric Oxide.
Authors: Lei Liandi , Yang Desuo , Liu Zhongquan , Wu Longmin
Published: July 2004

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Synthesis of New ortho Fused Tetracyclic‐2‐substituted‐4H‐thiazolo[5,4‐c]naphtho[1,2‐e]pyran and Its Derivatives.
Authors: Kulkarni A. M. , Malviya N. J. , Karnik A. V.
Published: July 2004

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Aromatization of Hantzsch 1,4‐Dihydropyridines with a Polymer‐Supported Hypervalent Iodine Reagent.
Authors: Lee Jin‐Won , Ko Kwang‐Youn
Published: July 2004

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Synthesis of C2‐Symmetric 2,2′‐Bipyridines Derived from 4‐Substituted 1,10,10‐Trimethyl‐3‐oxa‐5‐aza‐tricyclo[5.2.1.02,6]decane.
Authors: Davies Stephen R. , Cain Christopher P. , Glossop Matthew T. , Mengent Marie‐Laure , Kee Terence P.
Published: July 2004

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Lithiation of Functionalized Fluoroquinolines: Synthesis of Dihalo‐2‐phenylquinoline‐4‐carboxamides and in vitro Evaluation as NK‐3 Receptor Ligands for Medical Imaging Studies.
Authors: Bennacef Idriss , Tymciu Sylvie , Dhilly Martine , Mongin Florence , Queguiner Guy , Lasne Marie‐Claire , Barre Louisa , Perrio Cecile
Published: July 2004

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A Novel Reaction of Aldeoxime with Dimedone under Microwave Irradiation.
Authors: Tu Shujang , Gao Yuan , Miao Chunbao , Li Tianjie , Zhang Xiaojing , Zhu Songlei , Fang Fang , Shi Daqing
Published: July 2004

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A Three‐Component, One‐Pot Synthesis of Indolizidines and Related Heterocycles via the [3 + 2] Cycloaddition of Nonstabilized Azomethine Ylides.
Authors: Pearson William H. , Stoy Patrick , Mi Yuan
Published: July 2004

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FeCl3—NaI Mediated Reactions of Aryl Azides with 3,4‐Dihydro‐2H‐pyran: A Convenient Synthesis of Pyranoquinolines.
Authors: Kamal Ahmed , Prasad B. Rajendra , Ramana A. Venkata , Babu A. Hari , Reddy K. Srinivasa
Published: July 2004

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Triphenyl Phosphonium Perchlorate Catalyzed Imino Diels—Alder Reactions: Diastereoselective Synthesis of Indolylquinolines.
Authors: Zulykama Yusuf , Nagarajan Rajagopal , Perumal Paramasivan T.
Published: July 2004

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Expeditive Synthesis of Homochiral Fused Tri‐ and Tetrazoles—Piperazines from β‐Amino Alcohols.
Authors: Couty Francois , Durrat Francois , Prim Damien
Published: July 2004

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