bluuebunny/crossref_metadata_2025 huggingface dataset:
A LIBERAL DOSE OF FISCAL DISCIPLINE: THE 20–40 SOLUTION
Authors: Sawicky Max B.
Published: February 2005

Notwithstanding the execrable state of the federal budget, a fiscally responsible, progressive, liberal path for the future is feasible. The ingredients of such a path are twofold: returning the tax share of GDP to 20 percent, and maintaining the ratio of federal debt to GDP at 40 percent. This “20–40 solution” permits ample growth of worthwhile domestic spending programs over the next ten years. Potential savings in defense spending, which has risen significantly since 2000, strengthen the case further. In the long run, some anticipate budget problems, but these are not due to domestic spending in general. They arise from rapid growth in Medicare and Medicaid.
Dating Violence Prevention in Middle School and High School Youth
Authors: Close Sharron M.
Published: February 2005

TOPIC:  Dating violence and interpersonal abuse among middle school and high school students.

PURPOSE:  To review the current literature and evaluate the need of conducting further study in order to create early interventions for the prevention of relationship abuse.

SOURCES USED:  Case report and review of the literature.

CONCLUSIONS:  Dating violence among middle school and high school youth must be addressed by screening risk and offering anticipatory guidance during each health maintenance visit in order to prevent victimization of youth in dating and attraction relationships.
Sexual Abuse of Boys
Authors: Valente Sharon M.
Published: February 2005

TOPIC:  Sexual abuse in childhood can disable self‐esteem, self‐concept, relationships, and ability to trust. It can also leave psychological trauma that compromises a boy's confidence in adults. While some boys who willingly participate may adjust to sexual abuse, many others face complications, such as reduced quality of life, impaired social relationships, less than optimal daily functioning, and self‐destructive behavior. These problems can respond to treatment if detected.

PURPOSE:  In this paper, we examine the prevalence, characteristics, psychological consequences, treatment, and coping patterns of boys who have been sexually abused and their failure to disclose abuse unless asked during a therapeutic encounter. Nurses have a responsibility to detect the clues to sexual abuse, diagnose the psychological consequences, and advocate for protection and treatment.

SOURCES USED:  Computerized literature search of the Medline and PsychInfo literature and books on sexual abuse of boys.

CONCLUSIONS:  Psychological responses to abuse such as anxiety, denial, self‐hypnosis, dissociation, and self‐mutilation are common. Coping strategies may include being the angry avenger, the passive victim, rescuer, daredevil, or conformist. Sexual abuse may precipitate runaway behavior, chronic use of sick days, poor school or job performance, costly medical, emergency and or mental health visits. In worst cases, the boy may decide that life is not worth living and plan suicide. The nurse has a key role to play in screening, assessing, and treating sexual abuse children.
An Internet Discussion Board for Parents of Mentally Ill Young Children
Authors: Scharer Kathleen
Published: February 2005

PURPOSE: This paper reports parents’ use of electronic bulletin board for social support during a pilot study of an Internet intervention.

METHODS: Parents participated for a mean of 13.83 weeks. The convenience sample consisted of six parents. Data were from site access information and parents’ postings.

FINDINGS: Excluding one mother who checked frequently for messages, mothers have an average of 5.2 postings. Excluding this one mother, the postings/ accesses ratio was greater than 60%. Parents made postings in four categories of “child's illness” having 37 comments and 36 comments for “group maintenance”.

CONCLUSIONS: While the study findings cannot be generalized, these results suggest that parents will use electronic discussion boards.
Internet Social Support for Parents: The State of Science
Authors: Scharer Kathleen
Published: February 2005

TOPIC: Parents of emotionally disturbed young children have expressed the need for more social support but societal constraints limit their ability to obtain adequate social support.

PURPOSE: This paper discusses what is currently known about coping, social support and Internet social support. It proposes the use of electronic social support to meet the needs of parents of emotionally disturbed children.

SOURCE: Review of literature.

CONCLUSIONS: Electronic forms of social support have the potential to meet the identified needs of parents for more social support.
Multiple Metabolic Roles for the Nonphotosynthetic Plastid of the Green Alga
Prototheca wickerhamii
Authors: Borza Tudor , Popescu Cristina E. , Lee Robert W.
Published: February 2005

The presence of plastids in diverse eukaryotic lineages that have lost the capacity for photosynthesis is well documented. The metabolic functions of such organelles, however, are poorly understood except in the case of the apicoplast in the Apicomplexa, a group of intracellular parasites including
Plasmodium falciparum
, and the plastid of the green alga
Helicosporidium
sp., a parasite for which the only host-free stage identified in nature so far is represented by cysts. As a first step in the reconstruction of plastid functions in a nonphotosynthetic, predominantly free-living organism, we searched for expressed sequence tags (ESTs) that correspond to nucleus-encoded plastid-targeted polypeptides in the green alga
Prototheca wickerhamii
. From 3,856 ESTs, we found that 71 unique sequences (235 ESTs) correspond to different nucleus-encoded putatively plastid-targeted polypeptides. The identified proteins predict that carbohydrate, amino acid, lipid, tetrapyrrole, and isoprenoid metabolism as well as de novo purine biosynthesis and oxidoreductive processes take place in the plastid of
P. wickerhamii
. Mg-protoporphyrin accumulation and, therefore, plastid-to-nucleus signaling might also occur in this nonphotosynthetic organism, as we identified a transcript which encodes subunit I of Mg-chelatase, the enzyme which catalyzes the first committed step in chlorophyll synthesis. Our data indicate a far more complex metabolism in
P. wickerhamii
's plastid compared with the metabolic pathways predicted to be located in the apicoplast of
P. falciparum
and the plastid of
Helicosporidium
sp.
Functional Specialization ofChlamydomonas reinhardtiiCytosolic Thioredoxin h1 in the Response to Alkylation-Induced DNA Damage
Authors: Sarkar Nandita , Lemaire Stéphane , Wu-Scharf Danxia , Issakidis-Bourguet Emmanuelle , Cerutti Heriberto
Published: February 2005

DNA damage occurs as a by-product of intrinsic cellular processes, like DNA replication, or as a consequence of exposure to genotoxic agents. Organisms have evolved multiple mechanisms to avoid, tolerate, or repair DNA lesions. To gain insight into these processes, we have isolated mutants hypersensitive to DNA-damaging agents in the green algaChlamydomonas reinhardtii. One mutant, Ble-1, showed decreased survival when it was treated with methyl methanesulfonate (MMS), bleomycin, or hydrogen peroxide (H2O2) but behaved like the wild type when it was exposed to UVC irradiation. Ble-1 carries an extensive chromosomal deletion that includes the gene encoding cytosolic thioredoxin h1 (Trxh1). Transformation of Ble-1 with a wild-type copy ofTrxh1fully corrected the MMS hypersensitivity and partly restored the tolerance to bleomycin.Trxh1also complemented a defect in the repair of MMS-induced DNA strand breaks and alkali-labile sites. In addition, a Trxh1-β-glucuronidase fusion protein translocated to the nucleus in response to treatment with MMS. However, somewhat surprisingly,Trxh1failed to correct the Ble-1 hypersensitivity to H2O2. Moreover,Trxh1suppression by RNA interference in a wild-type strain resulted in enhanced sensitivity to MMS and DNA repair defects but no increased cytotoxicity to H2O2. Thioredoxins have been implicated in oxidative-stress responses in many organisms. Yet our results indicate a specific role ofChlamydomonasTrxh1 in the repair of MMS-induced DNA damage, whereas it is dispensable for the response to H2O2. These observations also suggest functional specialization among cytosolic thioredoxins since anotherChlamydomonasisoform (Trxh2) does not compensate for the lack of Trxh1.
Ran GTPase Regulates Mad2 Localization to the Nuclear Pore Complex
Authors: Quimby B. Booth , Arnaoutov Alexei , Dasso Mary
Published: February 2005

In yeast and mammalian cells, the spindle assembly checkpoint proteins Mad1p and Mad2p localize to the nuclear pore complex (NPC) during interphase. Deletion of
MAD1
or
MAD2
did not affect steady-state nucleocytoplasmic distribution of a classical nuclear localization signal-containing reporter, a nuclear export signal-containing reporter, or Ran localization. We utilized cells with conditional mutations in the yeast Ran GTPase pathway to examine the relationship between Ran and targeting of checkpoint regulators to the NPC. Mutations that disrupt the concentration of Ran in the nucleus displaced Mad2p but not Mad1p from the NPC. The displacement of Mad2p in M-phase cells was correlated with activation of the spindle checkpoint. Our observations demonstrate that Mad2p localization at NPCs is sensitive to nuclear levels of Ran and suggest that release of Mad2p from NPCs is closely linked with spindle assembly checkpoint activation in yeast. This is the first evidence indicating that Ran affects the localization of Mad2p to the NPC.
Coevolution of Cyclin Pcl5 and Its Substrate Gcn4
Authors: Gildor Tsvia , Shemer Revital , Atir-Lande Avigail , Kornitzer Daniel
Published: February 2005

Gcn4, a transcription factor that plays a key role in the response of
Saccharomyces cerevisiae
to amino acid starvation, is regulated at both the levels of translation and of protein stability. Regulated degradation of Gcn4 depends on its phosphorylation by the cyclin-dependent kinase Pho85, in conjunction with the cyclin Pcl5. The pathogenic yeast
Candida albicans
contains a functional homolog of Gcn4, which is involved in amino acid metabolism, as well as in the regulation of filamentous growth in response to starvation. Here, we show that
C. albicans
Gcn4 (CaGcn4) is rapidly degraded and that this degradation depends on a Pho85 cyclin homolog, CaPcl5. The regulatory loop that includes Gcn4 and Pcl5 is conserved in
C. albicans
: like in
S. cerevisiae
, CaPcl5 is transcriptionally induced by CaGcn4 and is required for CaGcn4 degradation. However, the proteins have coevolved so that there is no cross-recognition between the proteins from the two species: phosphorylation-dependent degradation of CaGcn4 occurs only in the presence of CaPcl5, and
S. cerevisiae
Gcn4 (ScGcn4) requires ScPcl5 for its degradation. Phenotypic analysis of the Ca
pcl5
mutant indicates that CaPcl5 also modulates the filamentous response of
C. albicans
in amino acid-rich media.
Amiloride Uptake and Toxicity in Fission Yeast Are Caused by the Pyridoxine Transporter Encoded by
bsu1
+
(
car1
+
)
Authors: Stolz Jürgen , Wöhrmann Heike J. P. , Vogl Christian
Published: February 2005

Amiloride, a diuretic drug that acts by inhibition of various sodium transporters, is toxic to the fission yeast
Schizosaccharomyces pombe
. Previous work has established that amiloride sensitivity is caused by expression of
car1
+
, which encodes a protein with similarity to plasma membrane drug/proton antiporters from the multidrug resistance family. Here we isolated
car1
+
by complementation of
Saccharomyces cerevisiae
mutants that are deficient in pyridoxine biosynthesis and uptake. Our data show that Car1p represents a new high-affinity, plasma membrane-localized import carrier for pyridoxine, pyridoxal, and pyridoxamine. We therefore propose the gene name
bsu1
+
(for vitamin B
6
uptake) to replace
car1
+
. Bsu1p displays an acidic pH optimum and is inhibited by various protonophores, demonstrating that the protein works as a proton symporter. The expression of
bsu1
+
is associated with amiloride sensitivity and pyridoxine uptake in both
S. cerevisiae
and
S. pombe
cells. Moreover, amiloride acts as a competitor of pyridoxine uptake, demonstrating that both compounds are substrates of Bsu1p. Taken together, our data show that
S. pombe
and
S. cerevisiae
possess unrelated plasma membrane pyridoxine transporters. The
S. pombe
protein may be structurally related to the unknown human pyridoxine transporter, which is also inhibited by amiloride.
The High-Mobility-Group Domain Transcription Factor Rop1 Is a Direct Regulator of
prf1
in
Ustilago maydis
Authors: Brefort Thomas , Müller Philip , Kahmann Regine
Published: February 2005

In the smut fungus
Ustilago maydis
, the pheromone signal is transmitted via a mitogen-activated protein kinase module to the high-mobility-group (HMG) domain transcription factor Prf1, leading to its activation. This triggers sexual and pathogenic development since Prf1 binds to the PRE boxes located in the promoters of the
a
and
b
mating type genes. Here, we present the characterization of
rop1
and
hmg3
, encoding two additional sequence-specific HMG domain proteins. While
hmg3
mutants are slightly impaired in mating and do form conjugation hyphae,
rop1
deletion strains display a severe mating and filamentation defect and do not respond to pheromone stimulation. In particular,
rop1
is essential for pheromone-induced gene expression in axenic culture. Constitutive expression of
prf1
fully complements the mating defect of
rop1
mutants, indicating that
rop1
is required for
prf1
gene expression. Indeed, we could show that Rop1 binds directly to specific elements in the
prf1
promoter. Surprisingly, on the plant surface,
rop1
deletion strains do form conjugation hyphae and express sufficient amounts of
prf1
to cause full pathogenicity. This indicates the involvement of additional components in the regulation of
prf1
gene expression during pathogenic growth.
Overlapping Roles of the Cytoplasmic and Mitochondrial Redox Regulatory Systems in the Yeast
Saccharomyces cerevisiae
Authors: Trotter Eleanor W. , Grant Chris M.
Published: February 2005

Thioredoxins are small, highly conserved oxidoreductases which are required to maintain the redox homeostasis of the cell.
Saccharomyces cerevisiae
contains a cytoplasmic thioredoxin system (
TRX1
,
TRX2
, and
TRR1
) as well as a complete mitochondrial thioredoxin system, comprising a thioredoxin (
TRX3
) and a thioredoxin reductase (
TRR2
). In the present study we have analyzed the functional overlap between the two systems. By constructing mutant strains with deletions of both the mitochondrial and cytoplasmic systems (
trr1 trr2
and
trx1 trx2 trx3
), we show that cells can survive in the absence of both systems. Analysis of the redox state of the cytoplasmic thioredoxins reveals that they are maintained independently of the mitochondrial system. Similarly, analysis of the redox state of Trx3 reveals that it is maintained in the reduced form in wild-type cells and in mutants lacking components of the cytoplasmic thioredoxin system (
trx1 trx2
or
trr1
). Surprisingly, the redox state of Trx3 is also unaffected by the loss of the mitochondrial thioredoxin reductase (
trr2
) and is largely maintained in the reduced form unless cells are exposed to an oxidative stress. Since glutathione reductase (Glr1) has been shown to colocalize to the cytoplasm and mitochondria, we examined whether loss of
GLR1
influences the redox state of Trx3. During normal growth conditions, deletion of
TRR2
and
GLR1
was found to result in partial oxidation of Trx3, indicating that both Trr2 and Glr1 are required to maintain the redox state of Trx3. The oxidation of Trx3 in this double mutant is even more pronounced during oxidative stress or respiratory growth conditions. Taken together, these data indicate that Glr1 and Trr2 have an overlapping function in the mitochondria.
Chromosomal Translocation and Segmental Duplication in
Cryptococcus neoformans
Authors: Fraser James A. , Huang Johnny C. , Pukkila-Worley Read , Alspaugh J. Andrew , Mitchell Thomas G. , Heitman Joseph
Published: February 2005

Large chromosomal events such as translocations and segmental duplications enable rapid adaptation to new environments. Here we marshal genomic, genetic, meiotic mapping, and physical evidence to demonstrate that a chromosomal translocation and segmental duplication occurred during construction of a congenic strain pair in the fungal human pathogen
Cryptococcus neoformans
. Two chromosomes underwent telomere-telomere fusion, generating a dicentric chromosome that broke to produce a chromosomal translocation, forming two novel chromosomes sharing a large segmental duplication. The duplication spans 62,872 identical nucleotides and generated a second copy of 22 predicted genes, and we hypothesize that this event may have occurred during meiosis. Gene disruption studies of one embedded gene (
SMG1
) corroborate that this region is duplicated in an otherwise haploid genome. These findings resolve a genome project assembly anomaly and illustrate an example of rapid genome evolution in a fungal genome rich in repetitive elements.
The Function of the Coding Sequences for the Putative Pheromone Precursors in
Podospora anserina
Is Restricted to Fertilization
Authors: Coppin Evelyne , de Renty Christelle , Debuchy Robert
Published: February 2005

We cloned the pheromone precursor genes of
Podospora anserina
in order to elucidate their role in the biology of this fungus. The
mfp
gene encodes a 24-amino-acid polypeptide finished by the CAAX motif, characteristic of fungal lipopeptide pheromone precursors similar to the
a
-factor precursor of
Saccharomyces cerevisiae
. The
mfm
gene encodes a 221-amino-acid polypeptide, which is related to the
S. cerevisiae
α-factor precursor and contains two 13-residue repeats assumed to correspond to the mature pheromone. We deleted the
mfp
and
mfm
coding sequence by gene replacement. The mutations specifically affect male fertility, without impairing female fertility and vegetative growth. The male defect is mating type specific: the
mat
+
Δ
mfp
and
mat
− Δ
mfm
mutants produce male cells inactive in fertilization whereas the
mat
− Δ
mfp
and
mat
+
Δ
mfm
mutants show normal male fertility. Genetic data indicate that both
mfp
and
mfm
are transcribed at a low level in
mat
+
and
mat
− vegetative hyphae. Northern-blot analysis shows that their transcription is induced by the mating types in microconidia (
mfp
by
mat
+
and
mfm
by
mat
−). We managed to cross Δ
mfp
Δ
mfm
strains of opposite mating type, by complementation and transient expression of the pheromone precursor gene to trigger fertilization. These crosses were fertile, demonstrating that once fertilization occurs, the pheromone precursor genes are unnecessary for the completion of the sexual cycle. Finally, we show that the constitutively transcribed
gpd
::
mfm
and
gpd
::
mfp
constructs are repressed at a posttranscriptional level by the noncognate mating type.
Elimination of Foreign DNA during Somatic Differentiation in
Tetrahymena thermophila
Shows Position Effect and Is Dosage Dependent
Authors: Liu Yifan , Song Xiaoyuan , Gorovsky Martin A. , Karrer Kathleen M.
Published: February 2005

In the ciliate
Tetrahymena thermophila
, approximately 15% of the germ line micronuclear DNA sequences are eliminated during formation of the somatic macronucleus. The vast majority of the internal eliminated sequences (IESs) are repeated in the micronuclear genome, and several of them resemble transposable elements. Thus, it has been suggested that DNA elimination evolved as a means for removing invading DNAs. In the present study, bacterial
neo
genes introduced into the germ line micronuclei were eliminated from the somatic genome. The efficiency of elimination from two different loci increased dramatically with the copy number of the
neo
genes in the micronuclei. The timing of
neo
elimination is similar to that of endogenous IESs, and they both produce bidirectional transcripts of the eliminated element, suggesting that the deletion of
neo
occurred by the same mechanism as elimination of endogenous IESs. These results indicate that repetition of an element in the micronucleus enhances the efficiency of its elimination from the newly formed somatic genome of
Tetrahymena thermophila
. The implications of these data in relation to the function and mechanism of IES elimination are discussed.
Receptor for Retrograde Transport in the Apicomplexan Parasite
Toxoplasma gondii
Authors: Pfluger Stacy L. , Goodson Holly V. , Moran Jennifer M. , Ruggiero Christine J. , Ye Xin , Emmons Krista M. , Hager Kristin M.
Published: February 2005

Toxoplasma gondii
and its apicomplexan relatives (such as
Plasmodium falciparum
, which causes malaria) are obligate intracellular parasites that rely on sequential protein release from specialized secretory organelles for invasion and multiplication within host cells. Because of the importance of these unusual membrane trafficking pathways for drug development and comparative cell biology, characterizing them is essential. In particular, it is unclear what role retrieval mechanisms play in parasite membrane trafficking or where they operate. Previously, we showed that
T. gondii
’s beta-COP (TgΒCOP; a subunit of coatomer protein complex I, COPI) and retrieval reporters localize exclusively to the zone between the parasite endoplasmic reticulum (ER) and Golgi apparatus. This suggested the existence of an HDEL receptor in
T. gondii
. We have now identified, cloned, and sequenced this receptor, TgERD2. TgERD2 localizes in a Golgi or ER pattern suggestive of the HDEL retrieval reporter (K. M. Hager, B. Striepen, L. G. Tilney, and D. S. Roos, J. Cell Sci.
112
:
2631-2638, 1999). A functional assay reveals that TgERD2 is able to complement the
Saccharomyces cerevisiae
ERD2 null mutant. Retrieval studies reveal that stable expression of a fluorescent exogenous retrieval ligand results in a dispersal of βCOP signal throughout the cytoplasm and, surprisingly, results in βCOP staining of the vacuolar space of the parasite. In contrast, stable expression of TgERD2GFP does not appear to disturb βCOP staining. In addition to TgERD2,
Toxoplasma
contains two more divergent ERD2 relatives. Phylogenetic analysis reveals that these proteins belong to a previously unrecognized ERD2 subfamily common to plants and alveolate organisms and as such could represent mediators of parasite-specific retrieval functions. No evidence of class 2 ERD2 proteins was found in metazoan organisms or fungi.
Radiological Studies Reveal Radial Differences in the Architecture of the Polysaccharide Capsule ofCryptococcus neoformans
Authors: Bryan R. A. , Zaragoza O. , Zhang T. , Ortiz G. , Casadevall A. , Dadachova E.
Published: February 2005

The polysaccharide capsule of the pathogenic fungusCryptococcus neoformansis an important virulence factor, but relatively little is known about its architecture. We applied a combination of radiological, chemical, and serological methods to investigate the structure of this polysaccharide capsule. Exposure ofC. neoformanscells to gamma radiation, dimethyl sulfoxide, or radiolabeled monoclonal antibody removed a significant part of the capsule. Short intervals of gamma irradiation removed the outer portion of the cryptococcal capsule without killing cells, which could subsequently repair their capsules. Survival analysis of irradiated wild-type, acapsular mutant, and complemented mutant strains demonstrated that the capsule contributed to radioprotection and had a linear attenuation coefficient higher than that of lead. The capsule portions remaining after dimethyl sulfoxide or gamma radiation treatment were comparable in size, 65 to 66 μm3, and retained immunoreactivity for a monoclonal antibody to glucuronoxylomannan. Simultaneous or sequential treatment of the cells with dimethyl sulfoxide and radiation removed the remaining capsule so that it was not visible by light microscopy. The capsule could be protected against radiation by either of the free radical scavengers ascorbic acid and sorbitol. Sugar composition analysis of polysaccharide removed from the outer and inner parts of the capsule revealed significant differences in glucuronic acid and xylose molar ratios, implying differences in the chemical structure of the constituent polysaccharides. Our results provide compelling evidence for the existence of two zones in theC. neoformanscapsule that differ in susceptibility to dimethyl sulfoxide and radiation and, possibly, in packing and composition.
Rearranged Subtelomeric rRNA Genes in
Giardia duodenalis
Authors: Upcroft Jacqueline A. , Abedinia Mahin , Upcroft Peter
Published: February 2005

Giardia duodenalis
has linear chromosomes capped with typical eukaryotic repeats [(TAGGG)

n

], subtelomeric rRNA genes, and telomere gene units. The absence of two closely associated NotI sites in the large-subunit rRNA gene was used as an indicator in hybridizations of one- and two-dimensional NotI-cleaved
Giardia
chromosome separations that some chromosomes carry only rearranged and, by deduction, nonfunctional rRNA genes.
Thioredoxin Reductase Is Essential for Viability in the Fungal Pathogen
Cryptococcus neoformans
Authors: Missall Tricia A. , Lodge Jennifer K.
Published: February 2005

Thioredoxin reductase (
TRR1
) is an important component of the thioredoxin oxidative stress resistance pathway. Here we show that it is induced during oxidative and nitrosative stress and is preferentially localized to the mitochondria in
Cryptococcus neoformans
. The
C. neoformans TRR1
gene encodes the low-molecular-weight isoform of the thioredoxin reductase enzyme, which shares little homology with that of its mammalian host. By replacing the endogenous
TRR1
promoter with an inducible copper transporter promoter, we showed that Trr1 appears to be essential for viability of this pathogenic fungus, making it a potential antifungal target.
A Silenced
Plasmodium falciparum var
Promoter Can Be Activated In Vivo through Spontaneous Deletion of a Silencing Element in the Intron
Authors: Gannoun-Zaki Laïla , Jost Amy , Mu Jianbing , Deitsch Kirk W. , Wellems Thomas E.
Published: February 2005

Introns of
Plasmodium falciparum var
genes act as transcriptional silencing elements that help control antigenic variations. In transfected episomes, intron silencing of a drug-selectable marker under
var
promoter control is reversed by the spontaneous deletion of key intron regions. The resulting promoter activation does not affect the transcription of chromosomal
var
genes.
Acute irritant reaction to an antiseptic bath emollient
Authors: Saw N K , Hindmarsh J R
Published: February 2005

Antiseptic bath emollients are commonly prescribed for treatment of eczema and are generally safe for frequent application. Although acute irritant reactions are uncommon it is nevertheless recognised and could have significant morbidity. This case describes a young male patient who developed an acute irritant reaction localised to the external genitalia, mimicking Fournier’s gangrene, after overnight application of Oilatum Plus antiseptic bath emollients.
History of the treatment of spinal injuries
Authors: Silver J R
Published: February 2005

Injury of the spinal cord has been known since antiquity. There is no cure for the injury and until modern times patients died rapidly from a combination of pressure sores and urinary tract infection. Treatment consists of preventing complications until the spine has stabilised and the patient can be rehabilitated to an independent life. This article explores how this treatment developed in the ancient world, the middle ages, in Europe, Great Britain, and latterly in the United States. It describes how these principles of treatment were recognised particularly in Germany, the United States, and Great Britain and evaluates the relative contributions made by the different pioneers.
Unoperated tetralogy of Fallot: case report of a natural survivor who died in his 73rd year; is it ever too late to operate?
Authors: Yang X , Freeman L J , Ross C
Published: February 2005

The case history is described of a man in his 73rd year who was one of the oldest surviving patients with uncorrected tetralogy of Fallot (ToF) before succumbing with renal failure. Factors contributing to his longevity included small pulmonary arteries and presumed slow development of subpulmonary obstruction together with moderate concentric left ventricular hypertrophy—features previously seen in long term survivors. Less than 3% of all patients with uncorrected ToF survive beyond their 40s but late operative repair is still a valuable option. Practicalities of renal dialysis in the presence of an intracardiac shunt are considered.
Acute endoscopic intervention in non-variceal upper gastrointestinal bleeding
Authors: Arasaradnam R P , Donnelly M T
Published: February 2005

Upper gastrointestinal bleeding is one of the commonest emergencies encountered by general physicians. Once haemodynamic stability has been achieved, therapeutic endoscopy is vital in control and arrest of bleeding. Various methods are available and the evidence is reviewed as to the most optimal approach. Clinical parameters including timing of endoscopy, risk stratification, and predictors of failure will also be discussed together with a summary of recommendations based on current available evidence.
The Advanced Trauma Life Support course: a history of its development and review of related literature
Authors: Carmont M R
Published: February 2005

The origins, development, and success of the ATLS course are described with reference to the literature.
Artemisinins
Authors: Woodrow C J , Haynes R K , Krishna S
Published: February 2005

Artemisinins were discovered to be highly effective antimalarial drugs shortly after the isolation of the parent artemisinin in 1971 in China. These compounds combine potent, rapid antimalarial activity with a wide therapeutic index and an absence of clinically important resistance. Artemisinin containing regimens meet the urgent need to find effective treatments for multidrug resistant malaria and have recently been advocated for widespread deployment. Comparative trials of artesunate and quinine for severe malaria are in progress to see if the persistently high mortality of this condition can be reduced.
Regulation of Intestinal Phosphate Transport II. Metabolic acidosis stimulates Na+-dependent phosphate absorption and expression of the Na+-Pi cotransporter NaPi-IIb in small intestine
Authors: Stauber Annina , Radanovic Tamara , Stange Gerti , Murer Heini , Wagner Carsten A. , Biber Jürg
Published: February 2005

During metabolic acidosis, Pi serves as an important buffer to remove protons from the body. Pi is released from bone together with carbonate buffering protons in blood. In addition, in the kidney, the fractional excretion of phosphate is increased allowing for the excretion of more acid equivalents in urine. The role of intestinal Pi absorption in providing Pi to buffer protons and compensating for loss from bone during metabolic acidosis has not been clarified yet. Inducing metabolic acidosis (NH4Cl in drinking water) for 2 or 7 days in mice increased urinary fractional Pi excretion twofold, whereas serum Pi levels were not altered. Na+-dependent Pi transport in the small intestine, however, was stimulated from 1.89 ± 3.22 to 40.72 ± 11.98 pmol/mg protein (2 days of NH4Cl) in brush-border membrane vesicles prepared from total small intestine. Similarly, the protein abundance of the Na+-dependent phosphate cotransporter NaPi-IIb in the brush-border membrane was increased 5.3-fold, whereas mRNA levels remained stable. According to immunohistochemistry and real-time PCR NaPi-IIb expression was found to be mainly confined to the ileum in the small intestine, and this distribution was not altered during metabolic acidosis. These results suggest that the stimulation of intestinal Pi absorption during metabolic acidosis may contribute to the buffering of acid equivalents by providing phosphate and may also help to prevent excessive liberation of phosphate from bone.
Computer Three-Dimensional Reconstruction of the Sinoatrial Node
Authors: Dobrzynski H. , Li J. , Tellez J. , Greener I.D. , Nikolski V.P. , Wright S.E. , Parson S.H. , Jones S.A. , Lancaster M.K. , Yamamoto M. , Honjo H. , Takagishi Y. , Kodama I. , Efimov I.R. , Billeter R. , Boyett M.R.
Published: February 2005

Background—

There is an effort to build an anatomically and biophysically detailed virtual heart, and, although there are models for the atria and ventricles, there is no model for the sinoatrial node (SAN). For the SAN to show pacemaking and drive atrial muscle, theoretically, there should be a gradient in electrical coupling from the center to the periphery of the SAN and an interdigitation of SAN and atrial cells at the periphery. Any model should include such features.

Methods and Results—

Staining of rabbit SAN preparations for histology, middle neurofilament, atrial natriuretic peptide, and connexin (Cx) 43 revealed multiple cell types within and around the SAN (SAN and atrial cells, fibroblasts, and adipocytes). In contrast to atrial cells, all SAN cells expressed middle neurofilament (but not atrial natriuretic peptide) mRNA and protein. However, 2 distinct SAN cell types were observed: cells in the center (leading pacemaker site) were small, were organized in a mesh, and did not express Cx43. In contrast, cells in the periphery (exit pathway from the SAN) were large, were arranged predominantly in parallel, often expressed Cx43, and were mixed with atrial cells. An ≈2.5-million-element array model of the SAN and surrounding atrium, incorporating all cell types, was constructed.

Conclusions—

For the first time, a 3D anatomically detailed mathematical model of the SAN has been constructed, and this shows the presence of a specialized interface between the SAN and atrial muscle.
Fasting Glucose Is an Important Independent Risk Factor for 30-Day Mortality in Patients With Acute Myocardial Infarction
Authors: Suleiman Mahmoud , Hammerman Haim , Boulos Monther , Kapeliovich Michael R. , Suleiman Abeer , Agmon Yoram , Markiewicz Walter , Aronson Doron
Published: February 2005

Background—

Stress hyperglycemia in patients with acute myocardial infarction has been associated with increased mortality. Most studies looked at the relationship between admission glucose (AG) and outcome; limited information is available about the clinical significance of fasting glucose (FG).

Methods and Results—

We prospectively studied the relationship between FG and 30-day mortality in 735 nondiabetic patients with acute myocardial infarction. FG (≥8-hour fast within 24 hours of admission) and AG were measured in each patient. At 30 days, 9 deaths (2%) occurred in patients with normal FG, and 11 (10%), 14 (13%), and 31 (29%) deaths occurred in the first, second, and third tertiles of elevated FG, respectively. Compared with normal FG (<110 mg/dL), the adjusted OR for 30-day mortality progressively increased with higher tertiles of elevated FG (first tertile, 4.6; 95% CI, 1.7 to 12.7;
P
=0.003; second tertile, 6.4; 95% CI, 2.5 to 16.6;
P
<0.0001; third tertile, 11.5; 95% CI, 4.7 to 20.0;
P
<0.0001). Compared with patients categorized as having normal AG (<140 mg/d), the adjusted ORs for tertiles of elevated AG were as follows: first tertile, 1.4 (95% CI, 0.5 to 3.8;
P
=0.54); second tertile, 3.0 (95% CI, 1.3 to 7.0;
P
=0.01); and third tertile, 4.4 (95% CI, 2.0 to 9.7;
P
<0.0001). Compared with patients with normal FG and AG, the adjusted ORs for 30-day mortality were 0.71 (95% CI, 0.15 to 3.4;
P
=0.67) in patients with elevated AG and normal FG, 3.4 (95% CI, 1.1 to 10.4;
P
=0.03) for patients with normal AG glucose and elevated FG, and 9.6 (95% CI, 3.5 to 26.0;
P
<0.0001) for patients with both elevated FG and AG. Comparing nested models showed that including AG failed to improve the prediction of the model based on FG (χ
2
=5.4, 3
df
,
P
=0.15). In contrast, the addition of FG classes to the model based on AG improved model prediction (χ
2
=22.4, 3
df
,
P
<0.0001).

Conclusions—

There is a graded relation between elevated FG and AG and 30-day mortality in patients with acute myocardial infarction. FG is superior to AG in the assessment of short-term risk.
Atrial Tachycardia Remodeling of Pulmonary Vein Cardiomyocytes
Authors: Cha Tae-Joon , Ehrlich Joachim R. , Zhang Liming , Chartier Denis , Leung Tack Ki , Nattel Stanley
Published: February 2005

Background—

The pulmonary veins (PVs) are important in the pathophysiology of atrial fibrillation (AF), as is atrial tachycardia (AT) remodeling. The relative importance of AT remodeling in PVs versus other atrial sites is unknown. The present study assessed AT-induced cellular changes in PVs versus left atrium (LA) and their relationship to arrhythmogenesis.

Methods and Results—

We studied ionic currents (single-cell patch clamp) and action potentials (APs; coronary-perfused multicellular preparations) in the PVs and LA free wall of dogs after 7-day AT pacing (400 bpm), as well as in nonpaced control dogs. In controls, rapid (
I
Kr
) and slow (
I
Ks
) delayed-rectifier currents were larger in PVs; transient-outward (
I
to
), inward-rectifier (
I
K1
), and L-type Ca
2+
(
I
Ca
) currents and AP duration were smaller. AT remodeling reduced
I
Ca
and
I
to
, left
I
Kr
and
I
Ks
unchanged, and increased
I
K1
in both LA and PV. AT reduced action potential duration in both LA and PV. LA–PV AP differences became smaller in AT than in control dogs. Premature extrastimuli induced atrial tachyarrhythmias at 4.5±2.8% (mean±SEM) sites in 6 control multicellular preparations compared with 64.2±7.3% sites in 9 AT-remodeled preparations (
P
<0.001). Resection of all PVs failed to alter atrial tachyarrhythmia inducibility in AT-remodeled preparations (67.5±13.1%). PV resection did not significantly change tachyarrhythmia duration (mean 3.9 seconds per heart, range 0.7 to 15.7 seconds before resection; mean 7.0 seconds per heart, range 0.9 to 36.0 seconds after resection) or cycle length (120±6 ms before resection, 115±8 ms after resection).

Conclusions—

AT produces qualitatively similar ionic remodeling in LA and PVs but reduces PV–LA AP differences. PVs are not essential for AT-induced atrial tachyarrhythmia promotion in this model, which may relate to the failure of PV isolation to prevent AF in some patient populations.
Risk of Restenosis and Health Status Outcomes for Patients Undergoing Percutaneous Coronary Intervention Versus Coronary Artery Bypass Graft Surgery
Authors: Spertus John A. , Nerella Ravi , Kettlekamp Richard , House John , Marso Steve , Borkon A. Michael , Rumsfeld John S.
Published: February 2005

Background—

Previous comparisons of percutaneous coronary interventions (PCIs) and coronary artery bypass graft (CABG) surgery have demonstrated similar survival but have also generally found better health status outcomes (symptoms, function, and quality of life) with CABG. The principal limitation of PCI has been the occurrence of restenosis. No previous studies comparing the health status outcomes of PCI and CABG have examined differences in these outcomes as a function of patients’ preprocedural risk for restenosis.

Methods and Results—

We examined the health status outcomes, using the Seattle Angina Questionnaire (SAQ), among 1459 consecutive patients (1027 treated with PCI and 432, with CABG), stratified by their risk for restenosis. In multivariable-adjusted, linear regression analyses, no differences in 1-year angina or quality of life were observed among the 37.4% of patients at low risk for restenosis. However, among the 46.7% at intermediate risk for restenosis, 1-year health status scores were moderately better after CABG surgery compared with PCI (difference in SAQ angina frequency scores favoring CABG=6.1±1.7 points,
P
=0.0003; difference in SAQ quality of life=5.8±1.6 points,
P
=0.0004). Even larger differences in 1-year outcomes favoring CABG surgery were observed in patients at high risk for restenosis (SAQ angina frequency difference=10.8±4.2,
P
=0.01; SAQ quality of life difference=10.8±3.9,
P
=0.006).

Conclusions—

The relative health status benefits of CABG surgery compared with PCI increase as the risk of restenosis increases. Although selecting CABG or PCI is complex, preprocedural restenosis risk should be considered. It should also be tested as a means for considering drug-eluting as opposed to bare metal stents in PCI.
Low Plasma Adiponectin Levels Predict Progression of Coronary Artery Calcification
Authors: Maahs David M. , Ogden Lorraine G. , Kinney Gregory L. , Wadwa Paul , Snell-Bergeon Janet K. , Dabelea Dana , Hokanson John E. , Ehrlich James , Eckel Robert H. , Rewers Marian
Published: February 2005

Background—

Circulating adiponectin levels are lower in men than in women and lower in advanced coronary artery disease, obesity, and type 2 but not type 1 diabetes. However, it is not known whether low adiponectin levels predict development of atherosclerosis independently of other cardiovascular risk factors.

Methods and Results—

Progression of coronary artery calcification (CAC) over an average of 2.6 years (range, 1.6 to 3.3) was assessed in a cohort of patients with type 1 diabetes and nondiabetic subjects 19 to 59 years of age. In this nested case-control substudy, plasma adiponectin levels were measured in 101 cases with significant CAC progression and in 205 controls. Controls were oversampled on the basis of age, gender, diabetes status, and presence of baseline CAC. In conditional logistic regression adjusted for baseline CAC volume and other significant predictors of CAC progression, adiponectin levels were inversely related to progression of CAC in diabetic (OR, 0.47; 95% CI, 0.24 to 0.94) and nondiabetic (OR, 0.15; 95% CI, 0.05 to 0.40 for a doubling in adiponectin levels) subjects. Adjustment for additional cardiovascular risk factors did not change this association. In conditional logistic regression models by quartiles of plasma adiponectin levels, the probability value for trend was statistically significant for all participants (
P
<0.001) and nondiabetic participants (
P
<0.001) and was borderline for type 1 diabetics (
P
=0.08).

Conclusions—

Low plasma adiponectin levels are associated with progression of CAC in type 1 diabetic and nondiabetic subjects independently of other cardiovascular risk factors.
Sildenafil Prevents Endothelial Dysfunction Induced by Ischemia and Reperfusion via Opening of Adenosine Triphosphate–Sensitive Potassium Channels
Authors: Gori Tommaso , Sicuro Silvia , Dragoni Saverio , Donati Giovanni , Forconi Sandro , Parker John D.
Published: February 2005

Background—

Animal studies have demonstrated that administration of sildenafil can limit myocardial damage induced by prolonged ischemia, an effect that appears to be mediated by opening of adenosine triphosphate–sensitive potassium (K
ATP
) channels. No study has investigated whether sildenafil can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans.

Methods and Results—

In a double-blind, placebo-controlled, crossover design, 10 healthy male volunteers (25 to 45 years old) were randomized to oral sildenafil (50 mg) or placebo. Two hours later, endothelium-dependent, flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). Seven days later, subjects received the other treatment (ie, placebo or sildenafil) and underwent the same protocol. Pre-IR radial artery diameter and FMD, as well as baseline radial artery diameter after IR, were similar between visits (
P
=NS). After placebo administration, IR significantly blunted FMD (before IR: 7.9±1.1%; after IR: 1.2±0.7%,
P
<0.01). Importantly, sildenafil limited this impairment in endothelium-dependent vasodilatation (before IR: 7.0±0.9%; after IR: 6.2±1.1%,
P
=NS;
P
<0.01 compared with placebo). In a separate protocol, this protective effect was completely prevented by previous administration of the sulfonylurea glibenclamide (glyburide, 5 mg), a blocker of K
ATP
channels (n=7; FMD before IR: 10.3±1.5%; after IR: 1.3±1.4%,
P
<0.05).

Conclusions—

In humans, oral sildenafil induces potent protection against IR-induced endothelial dysfunction through opening of K
ATP
channels. Further studies are needed to test the potential clinical implications of this finding.
Transhepatic Ultrasound-Guided Cardiac Catheterization in the Fetal Lamb
Authors: Jouannic Jean-Marie , Boudjemline Younes , Benifla Jean-Louis , Bonnet Damien
Published: February 2005

Background—

Percutaneous transventricular and fetoscopic umbilical catheterization have been applied to animal and human fetuses. These methods have a high rate of failure and complications. Here, we propose an alternative route for anterograde echocardiography-guided cardiac catheterization through a transhepatic approach of the intra-abdominal vessels in the fetal lamb.

Methods and Results—

After exteriorization of the uterus in 12 pregnant ewes between 118 to 122 days’ gestation, a 4F sheath mounted over a 1.2-mm needle was placed into the intra-abdominal portion of the umbilical vein (n=2) and into the subdiaphragmatic portion of the inferior vena cava via a transhepatic approach (n=10) under ultrasound guidance. In the first 2 animals using a transumbilical approach, it was impossible to reach the heart through the ductus venosus. In the next 10 animals, using a conventional technique, echocardiography-guided catheterization of the 4 chambers was performed in the all fetuses, atrial or ventricular pacing in 6 fetuses, and ballooning of the pulmonary valve in 9 of 10 fetuses. Among the 10 fetuses catheterized through the transhepatic approach, 2 were euthanized immediately after the procedure to evaluate intraperitoneal bleeding (23 and 29 mL, respectively), and 3 died after the procedure (1 of major bleeding and 2 deaths related to balloon catheter manipulation). Finally, 5 were delivered vaginally after an uneventful pregnancy, and autopsy at day 5 did not show significant liver, vascular, or cardiac injury.

Conclusions—

Echocardiography-guided fetal cardiac catheterization through a transhepatic approach is feasible and provides an interesting alternative approach for human fetal cardiac interventions.
Myosin-Binding Protein C Phosphorylation, Myofibril Structure, and Contractile Function During Low-Flow Ischemia
Authors: Decker Robert S. , Decker Marlene L. , Kulikovskaya Irina , Nakamura Sakie , Lee Daniel C. , Harris Kathleen , Klocke Francis J. , Winegrad Saul
Published: February 2005

Background—

Contractile dysfunction develops in the chronically instrumented canine myocardium after bouts of low-flow ischemia and persists after reperfusion. The objective of this study is to identify whether changes in the phosphorylation state of myosin-binding protein C (MyBP-C) are a potential cause of dysfunction.

Methods and Results—

During low-flow ischemia, MyBP-C is dephosphorylated, and the number of actomyosin cross-bridges in the central core of the sarcomere decreases as thick filaments dissemble from the periphery of the myofibril. During reperfusion, MyBP-C remains dephosphorylated, and its degradation is accelerated.

Conclusions—

Dephosphorylation of MyBP-C may initiate changes in myofibril thick filament structure that decrease the interaction of myosin heads with actin thin filaments. Limiting the formation of actomyosin cross-bridges may contribute to the contractile dysfunction that is apparent after low-flow ischemia. Breakdown of MyBP-C during reperfusion may prolong myocardial stunning.