bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Systematics ofAnopheles: From Subgenera to Subpopulations
Authors: Krzywinski Jaroslaw , Besansky Nora J.
Published: December 2002

The century-old discovery of the role of Anopheles in human malaria transmission precipitated intense study of this genus at the alpha taxonomy level, but until recently little attention was focused on the systematics of this group. The application of molecular approaches to systematic problems ranging from subgeneric relationships to relationships at and below the species level is helping to address questions such as anopheline phylogenetics and biogeography, the nature of species boundaries, and the forces that have structured genetic variation within species. Current knowledge in these areas is reviewed, with an emphasis on the Anopheles gambiae model. The recent publication of the genome of this anopheline mosquito will have a profound impact on inquiries at all taxonomic levels, supplying better tools for estimating phylogeny and population structure in the short term, and ultimately allowing the identification of genes and/or regulatory networks underlying ecological differentiation, speciation, and vectorial capacity.
THEEVOLUTION OFALTERNATIVEGENETICSYSTEMS ININSECTS
Authors: Normark Benjamin B.
Published: December 2002

▪ Abstract  There are three major classes of insect genetic systems: those with diploid males (diplodiploidy), those with effectively haploid males (haplodiploidy), and those without males (thelytoky). Mixed systems, involving cyclic or facultative switching between thelytoky and either of the other systems, also occur. I present a classification of the genetic systems of insects and estimate the number of evolutionary transitions between them that have occurred. Obligate thelytoky has arisen from each of the other systems, and there is evidence that over 900 such origins have occurred. The number of origins of facultative thelytoky and the number of reversions from obligate thelytoky to facultative and cyclic thelytoky are difficult to estimate. The other transitions are few in number: five origins of cyclic thelytoky, eight origins of obligate haplodiploidy (including paternal genome elimination), the strange case of Micromalthus, and the two reversions from haplodiploidy to diplodiploidy in scale insects. Available evidence tends to support W.D. Hamilton's hypothesis that maternally transmitted endosymbionts have been involved in the origins of haplodiploidy. Bizarre systems of extrazygotic inheritance in Sternorrhyncha are not easily accommodated into any existing classification of genetic systems.
Manipulation of Medically Important Insect Vectors by Their Parasites
Authors: Hurd Hilary
Published: December 2002

Many of the most harmful parasitic diseases are transmitted by blood-feeding insect vectors. During this stage of their life cycles, selection pressures favor parasites that can manipulate their vectors to enhance transmission. Strategies may include increasing the amount of contact between vector and host, reducing vector reproductive output and consequently altering vector resource management to increase available nutrient reserves, and increasing vector longevity. Manipulation of these life-history traits may be more beneficial at some phase of the parasite's developmental process than at others. This review examines empirical, experimental, and field-based evidence to evaluate examples of changes in vector behavior and physiology that might be construed to be manipulative. Examples are mainly drawn from malaria-infected mosquitoes, Leishmania-infected sandflies, and Trypanosoma-infected tsetse flies.
Feather Mites (Acari: Astigmata): Ecology, Behavior, and Evolution
Authors: Proctor Heather C.
Published: December 2002

Birds host many lineages of symbiotic mites, but the greatest diversity is shown by the three superfamilies of astigmatan feather mites: Analgoidea, Pterolichoidea, and Freyanoidea. Members of this diphyletic grouping have colonized all parts of the avian integument from their ancestral nidicolous habitat. Whereas some clearly feed on feather pith or skin, acting as parasites, other feather mites are paraphages and consume feather oils without causing structural damage. Sexual dimorphism in feather mites is often extreme, and little is known of the function of many elaborate male structures. Abundance and location of vane-dwelling mites is affected by season, temperature, light, humidity, and host body condition. Because transmission between hosts usually depends on host body contact, it is unsurprising that feather mite phylogeny often parallels host phylogeny; however, recent cladistic analyses have also found evidence of host-jumping and “missing the boat” in several mite lineages.
THEASCENDANCY OFAMBLYOMMA AMERICANUMAS AVECTOR OFPATHOGENSAFFECTINGHUMANS INTHEUNITEDSTATES
Authors: Childs James E. , Paddock Christopher D.
Published: December 2002

▪ Abstract  Until the 1990s, Amblyomma americanum was regarded primarily as a nuisance species, but a tick of minor importance as a vector of zoonotic pathogens affecting humans. With the recent discoveries of Ehrlichia chaffeensis, Ehrlichia ewingii, and “Borrelia lonestari,” the public health relevance of lone star ticks is no longer in question. During the next 25 years, the number of cases of human disease caused by A. americanum-associated pathogens will probably increase. Based on current trajectories and historic precedents, the increase will be primarily driven by biological and environmental factors that alter the geographic distribution and intensity of transmission of zoonotic pathogens. Sociologic and demographic changes that influence the likelihood of highly susceptible humans coming into contact with infected lone star ticks, in addition to advances in diagnostic capabilities and national surveillance efforts, will also contribute to the anticipated increase in the number of recognized cases of disease.
Tomato, Pests, Parasitoids, and Predators: Tritrophic Interactions Involving the GenusLycopersicon
Authors: Kennedy George G.
Published: December 2002

Insect-plant interactions involving the cultivated tomato and its relatives in the genus Lycopersicon have been intensively studied for several decades, resulting in one of the best documented and in-depth examples of the mechanistic complexities of insect-plant interactions, which encompass both herbivores and their natural enemies. Trichome-mediated defenses are particularly significant in L. hirsutum f. glabratum and have been extensively implicated in negative tritrophic effects mediated by direct contact of parasitoids and predators with trichomes, as well as indirect effects mediated through their hosts or prey. Both constitutive and inducible defense traits of L. esculentum exert effects on selected parasitoids and predators. The effects of any particular plant defense trait on parasitoids and predators depend on the specific attributes of the plant trait and the details of the physical, biochemical, and behavioral interaction between the natural enemy, its host (prey), and the plant.
The Genome Sequence and Evolution of Baculoviruses
Authors: Herniou Elisabeth A. , Olszewski Julie A. , Cory Jennifer S. , O'Reilly David R.
Published: December 2002

Comparative analysis of the complete genome sequences of 13 baculoviruses revealed a core set of 30 genes, 20 of which have known functions. Phylogenetic analyses of these 30 genes yielded a tree with 4 major groups: the genus Granulovirus (GVs), the group I and II lepidopteran nucleopolyhedroviruses (NPVs), and the dipteran NPV, CuniNPV. These major divisions within the family Baculoviridae were also supported by phylogenies based on gene content and gene order. Gene content mapping has revealed the patterns of gene acquisitions and losses that have taken place during baculovirus evolution, and it has highlighted the fluid nature of baculovirus genomes. The identification of shared protein phylogenetic profiles provided evidence for two putative DNA repair systems and for viral proteins specific for infection of lymantrid hosts. Examination of gene order conservation revealed a core gene cluster of four genes, helicase, lef-5, ac96, and 38K(ac98), whose relative positions are conserved in all baculovirus genomes.
Erythropoietin Is a Novel Vascular Protectant Through Activation of Akt1 and Mitochondrial Modulation of Cysteine Proteases
Authors: Chong Zhao Zhong , Kang Jing-Qiong , Maiese Kenneth
Published: December 2002

Background—

Erythropoietin (EPO) is a critical regulator for the proliferation of immature erythroid precursors, but its role as a potential cytoprotectant in the cerebrovasculature system has not been defined.

Methods and Results—

We examined the ability of EPO to regulate a cascade of apoptotic death-related cellular pathways during anoxia-induced vascular injury in endothelial cells (ECs). EC injury was evaluated by trypan blue, DNA fragmentation, membrane phosphatidylserine (PS) exposure, protein kinase B activity, mitochondrial membrane potential, and cysteine protease induction. Exposure to anoxia alone rapidly increased genomic DNA fragmentation from 2±1% to 40±5% and membrane PS exposure from 3±2% to 56±5% over 24 hours. Administration of a cytoprotective concentration of EPO (10 ng/mL) prevented DNA destruction and PS exposure. Cytoprotection by EPO was completely abolished by cotreatment with anti-EPO neutralizing antibody, which suggests that EPO was necessary and sufficient for the prevention of apoptosis. Protection by EPO was intimately dependent on the activation of protein kinase B (Akt1) and the maintenance of mitochondrial membrane potential. Subsequently, EPO inhibited caspase 8-, caspase 1-, and caspase 3-like activities that were linked to mitochondrial cytochrome
c
release.

Conclusions—

The present work serves to illustrate that EPO can offer novel cytoprotection during ischemic vascular injury through direct modulation of Akt1 phosphorylation, mitochondrial membrane potential, and cysteine protease activity.
Effects of Long-Term Monotherapy With Eplerenone, a Novel Aldosterone Blocker, on Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure
Authors: Suzuki George , Morita Hideaki , Mishima Takayuki , Sharov Victor G. , Todor Anastassia , Tanhehco Elaine J. , Rudolph Amy E. , McMahon Ellen G. , Goldstein Sidney , Sabbah Hani N.
Published: December 2002

Background—

In heart failure (HF), aldosterone has been implicated in the formation of reactive interstitial fibrosis, a maladaptation that contributes to left ventricular (LV) remodeling. Eplerenone is a novel selective aldosterone blocker. The present study examined the effects of long-term monotherapy with eplerenone on the progression of LV dysfunction and remodeling in dogs with chronic HF.

Methods and Results—

HF was produced in 14 dogs by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with eplerenone (10 mg/kg twice daily, n=7) or no therapy at all (control, n=7). Hemodynamic measurements were made just before randomization and were repeated at the end of 3 months of therapy. In control dogs, LV end-diastolic and end-systolic volume increased significantly (62±4 versus 68±4 mL,
P
<0.001, and 38±3 versus 47±3 mL,
P
<0.001, respectively), and EF decreased significantly (38±1% versus 31±2%,
P
<0.001). In contrast, end-diastolic volume, end-systolic volume, and EF remained unchanged during the 3 months of treatment in eplerenone-treated dogs. LV end-diastolic wall stress increased significantly in control dogs but decreased significantly in eplerenone-treated dogs. Compared with control, eplerenone was associated with a 28% reduction in cardiomyocyte cross-sectional area, a 37% reduction of volume fraction of reactive interstitial fibrosis, and a 34% reduction of volume fraction of replacement fibrosis.

Conclusions—

Our results indicate that long-term therapy with eplerenone prevents progressive LV dysfunction and attenuates LV remodeling in dogs with chronic HF.
Influence of Tamoxifen on Carotid Intima-Media Thickness in Postmenopausal Women
Authors: Simon T. , Boutouyrie P. , Simon J.M. , Laloux B. , Tournigand C. , Tropeano A.I. , Laurent S. , Jaillon P.
Published: December 2002

Background—

Intima-media thickness of the common carotid artery (IMT-CCA) is an early marker of atherosclerosis. Tamoxifen is a selective estrogen-receptor modulator with estrogen-like effects on cardiovascular risk factors but as-yet unexplored effects on carotid artery structure. The goal of this study was to determine the influence of tamoxifen on IMT-CCA in menopausal women.

Methods and Results—

With a predefined calculation of the sample size, 67 menopausal women with cancer who were treated with tamoxifen for ≥1 year and 37 menopausal women with cancer who were never treated with tamoxifen were enrolled. IMT-CCA, internal diameter, and pulse pressure were determined with a high-definition echotracking device and applanation tonometry in a central core laboratory that was blinded to treatment. Both groups were similar for clinical characteristics, including cardiovascular risk factors. IMT and internal diameter were significantly lower in the tamoxifen group (mean duration of treatment, 2.4±0.9 years) than in the control group (609±117 μm versus 662±147 μm,
P
=0.04, and 4.89±0.60 mm versus 5.12±0.58 mm,
P
=0.03, respectively). Pulse pressure was not influenced by the use of tamoxifen. After adjustment for age, cardiovascular risk factors, carotid pulse pressure, duration of menopause, and previous use of hormone replacement therapy, IMT remained significantly lower among tamoxifen users (
P
<0.00001), with an impact on IMT (−70 μm) equivalent to spontaneous evolution with 12 years of aging (5 μm/y).

Conclusion—

The use of tamoxifen was associated with a significantly lower carotid IMT in menopausal women with cancer. Randomized trials are needed to confirm the cardioprotective effect of selective estrogen-receptor modulators in terms of prevention of atherosclerosis.
Differentiation Between Obesity and Insulin Resistance in the Association With C-Reactive Protein
Authors: McLaughlin Tracey , Abbasi Fahim , Lamendola Cindy , Liang Lynn , Reaven Gerald , Schaaf Patricia , Reaven Peter
Published: December 2002

Background—

Plasma C-reactive protein (CRP) concentrations are increased in obese and/or hyperinsulinemic individuals. The goal of this study was to determine if the relation between insulin resistance and CRP was independent of obesity.

Methods and Results—

Plasma CRP concentrations were measured before and after 3 months of calorie restriction in 38 healthy, obese women. Steady-state plasma glucose (SSPG) concentration during a 180-minute infusion of octreotide, glucose, and insulin was used to stratify participants into insulin-resistant (IR, n=20) or insulin-sensitive (n=18) groups, similar in terms of mean age (46±2 versus 44±2 years), body mass index (32.0±0.4 versus 31.4±0.3 kg/m
2
), and waist circumference (96±2 versus 95±2 cm). Mean CRP (0.39±0.08 versus 0.12±0.03 mg/dL,
P
=0.003) concentrations were higher in the IR group, as were day-long plasma glucose and insulin responses (
P
<0.001). There was a significant correlation at baseline between CRP and day-long plasma integrated insulin response (
r
=0.47,
P
=0.001) but not between CRP and body mass index (
r
=0.14) or waist circumference (
r
=0.10). Weight loss was similar in the two groups
(
8.7±0.9 versus 8.4±0.8 kg) but was associated with significant (
P
<0.001) decreases in SSPG and CRP concentrations in the IR group only. Regression analysis showed that SSPG and day-long plasma insulin response were the only significant predictors of CRP concentration.

Conclusions—

CRP concentrations are elevated predominantly in obese individuals who are also insulin resistant and fall in parallel with weight loss–associated improvements in insulin resistance. The relation between CRP concentrations and insulin resistance is independent of obesity.
Lipid Lowering by Simvastatin Induces Regression of Human Atherosclerotic Lesions
Authors: Corti Roberto , Fuster Valentin , Fayad Zahi A. , Worthley Stephen G. , Helft Gerard , Smith Donald , Weinberger Jesse , Wentzel Jolanda , Mizsei Gabor , Mercuri Michele , Badimon Juan J.
Published: December 2002

Background—

Statins are widely used to treat hypercholesterolemia and atherosclerotic disease. Noninvasive MRI allows serial monitoring of atherosclerotic plaque size changes. Our aim was to investigate the effects of lipid lowering with simvastatin on atherosclerotic lesions.

Methods and Results—

A total of 44 aortic and 32 carotid artery plaques were detected in 21 asymptomatic hypercholesterolemic patients at baseline. The effects of statin on these atherosclerotic lesions were evaluated as changes versus baseline in lumen area (LA), vessel wall thickness (VWT), and vessel wall area (VWA) by MRI. Maximal reduction of plasma total and LDL cholesterol by simvastatin (23% and 38% respectively;
P
<0.01 versus baseline) was achieved after ≈6 weeks of therapy and maintained thereafter throughout the study. Significant (
P
<0.01) reductions in maximal VWT and VWA at 12 months (10% and 11% for aortic and 8% and 11% for carotid plaques, respectively), without changes in LA, have been reported. Further decreases in VWT and VWA ranging from 12% to 20% were observed at 18 and 24 months. A slight but significant increase (ranging from 4% to 6%) in LA was seen in both carotid and aortic lesions at these later time points.

Conclusion—

The present study demonstrates that maintained lipid-lowering therapy with simvastatin is associated with significant regression of established atherosclerotic lesions in humans. Our observations indicate that lipid-lowering therapy is associated with sustained vascular remodeling and emphasize the need for longer-term treatment.
Transient Limb Ischemia Induces Remote Ischemic Preconditioning In Vivo
Authors: Kharbanda R.K. , Mortensen U.M. , White P.A. , Kristiansen S.B. , Schmidt M.R. , Hoschtitzky J.A. , Vogel M. , Sorensen K. , Redington A.N. , MacAllister R.
Published: December 2002

Background—

Ischemic preconditioning reduces local tissue injury caused by subsequent ischemia-reperfusion (IR), but may also have a salutary effect on IR injury of tissues remote from those undergoing preconditioning. We tested the hypothesis that limb ischemia induces remote preconditioning, reduces endothelial IR injury in humans, and reduces experimental myocardial infarct size.

Methods and Results—

Endothelial IR injury of the human forearm was induced by 20 minutes of upper limb ischemia (inflation of a blood pressure cuff to 200 mm Hg) followed by reperfusion. Remote preconditioning was induced by three 5-minute cycles of ischemia of the contralateral limb. Venous occlusion plethysmography was used to assess forearm blood flow in response to acetylcholine at baseline and 15 minutes after reperfusion. Experimental myocardial infarction was achieved by 40 minutes of balloon occlusion of the left anterior descending artery in 15-kg pigs. Remote preconditioning was induced by four 5-minute cycles of lower limb ischemia. Triphenyltetrazolium staining was used to assess the extent of myocardial infarction. In the human study, the response to acetylcholine was significantly attenuated in the control group after 15 minutes’ reperfusion, but remote preconditioning prevented this reduction. Limb ischemia caused a significant reduction in the extent of myocardial infarction relative to the area at risk compared with control (26±9% versus 53±8%,
P
<0.05).

Conclusion—

Remote ischemic preconditioning prevents IR-induced endothelial dysfunction in humans and reduces the extent of myocardial infarction in experimental animals. Transient limb ischemia is a simple preconditioning stimulus with important potential clinical applications.
Diphenhydramine as a Protective Agent in a Rat Model of Acute, Lethal Organophosphate Poisoning
Authors: Bird Steven B. , Gaspari Romolo J. , Lee Won Jae , Dickson Eric W.
Published: December 2002

Objective: To evaluate the effects of diphenhydramine chloride (DPH) on mortality in a rat model of acute, severe organophosphate poisoning (OP).Methods: Wistar rats (n = 40) were randomized to pretreatment with either normal saline (controls), 5 mg/kg atropine, 3 mg/kg DPH, 15 mg/kg DPH, or 30 mg/kg DPH given as a single intramuscular injection 5 minutes prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). The primary endpoint was 10‐minute survival. Survival at 24 hours was a secondary endpoint. Comparison of survival rates between groups was carried out by ANOVA and the Student‐Newman‐Keuls test. Results: Dichlorvos exposure resulted in profound fasciculations within 2 minutes of injection in all cohorts. In controls, fasciculations were followed by respiratory arrest within 10 minutes (0% survival). The rats receiving atropine pre‐treatment exhibited similar fasciculations (nicotinic effects) without subsequent respiratory arrest, resulting in a significant improvement in survival (88%, p < 0.001). The DPH‐treated rats exhibited a significant dose‐dependent reduction in mortality, with the 3 mg/kg, 15 mg/kg, and 30 mg/kg groups demonstrating 0%, 25%, and 100% survival, respectively. There was no additional mortality between 10 minutes and 24 hours in any group. There was no significant difference in survival between the high‐dose DPH and the atropine groups. Conclusions: Diphenhydramine chloride significantly reduced mortality in rats with acute, severe dichlorvos exposure.
End‐tidal Carbon Dioxide Predicts the Presence and Severity of Acidosis in Children with Diabetes
Authors: Fearon Deirdre M. , Steele Dale W.
Published: December 2002

Background: Patients with diabetic ketoacidosis (DKA) hyperventilate, lowering their alveolar (PACO2) and arterial carbon dioxide (PaCO2). This ventilatory response lessens the severity of their acidemia in a predictable way. Because end‐tidal CO2 (ETCO2) closely approximates PaCO2, measured ETCO2 levels should allow for predictions about the presence and severity of acidosis in diabetic patients. Objectives: 1) To evaluate the relationship between measured serum bicarbonate (HCO3) and ETCO2 measured via nasal capnography in children with suspected DKA; and 2) to assess the ability of capnography to predict DKA. Methods: Children being evaluated in a pediatric emergency department for suspected DKA (known or suspected diabetes presenting with hyperglycemia with or without ketonuria) were enrolled in a cross‐sectional, prospective, observational study. Prior to the availability of venous HCO3 results, ETCO2 values were measured using a Nellcor NPB‐70 Handheld Capnograph. Results: Forty‐two patients were enrolled. Linear regression analysis revealed a significant relationship between HCO3 and ETCO2 (R2= 0.80, p < 0.0001). Mean ETCO2 was 37 torr (95% CI = 35.5 to 37.9 torr) in the children without DKA and 22 torr (95% CI = 17.4 to 26.9 torr) in the children with DKA (p < 0.0001). An ETCO2 cut‐point of <29 torr correctly classified the most patients (95%), with a sensitivity of 0.83 (95% CI = 0.52 to 0.98) and a specificity of 1.0 (95% CI = 0.88 to 1.0). No patient with an ETCO2 of ≥36 torr had DKA, for a sensitivity of 1.0 (95% CI = 0.74 to 1.0). Conclusions: End‐tidal CO2 is linearly related to HCO3 and is significantly lower in children with DKA. If confirmed by larger trials, cut‐points of 29 torr and 36 torr, in conjunction with clinical assessment, may help discriminate between patients with and without DKA, respectively.
Performance of Multiple Cardiac Biomarkers Measured in the Emergency Department in Patients with Chronic Kidney Disease and Chest Pain
Authors: McCullough Peter A. , Nowak Richard M. , Foreback Craig , Tokarski Glenn , Tomlanovich Michael C. , Khoury Nabil E. , Weaver W. Douglas , Sandberg Keisha R. , McCord James
Published: December 2002

Objective: To evaluate the individual components of a cardiac multimarker panel in the detection of acute myocardial infarction (AMI) in patients with chest pain across a spectrum of renal dysfunction. Methods: A total of 817 consecutive patients evaluated for a possible AMI in the emergency department (ED) enrolled in a prospective study of cardiac biomarkers assessed using a point‐of‐care device with myoglobin (MYO), cardiac troponin I (cTnI), and creatine kinase myocardial band (CK‐MB), recorded at 0, 1.5, 3, and 9 hours. This study did not exclude patients on the basis of renal dysfunction. Baseline renal function was available in 808 patients. Patients were stratified by corrected creatinine clearance (CorrCrCl) into quartiles, and those on dialysis (n = 51) were considered as a fifth comparison group. Those patients with advanced renal dysfunction (CorrCrCl < 47/mL/min/72 kg) or on dialysis had higher rates of diabetes, hypertension, and prior coronary disease. Agreement for the diagnosis of AMI was required of two independent cardiologists using criteria based on history, electrocardiogram, and central laboratory assessment of serial cardiac markers. Results: More than 99% of all patients were admitted to a chest pain observation unit or the hospital. Mean MYO levels were elevated in the presence of renal dysfunction in those with and without myocardial infarction. Both MYO and CK‐MB were correlated with CorrCrCl, (r = ‐0.36, p < 0.01, and r = ‐0.10, p = 0.01, respectively), while cTnI was not (r = ‐0.10, p = 0.12). Using multiple receiver operating characteristic curve testing, cTnI was found to be the most consistent marker across all strata of renal dysfunction, including end‐stage renal disease on dialysis. The authors did not find a trend for false‐positive cTnI and renal dysfunction. Conclusions: A point‐of‐care, rapid cardiac biomarker strategy utilizing cTnI is applicable and superior to MYO or CK‐MB in the evaluation of chest pain in patients with renal dysfunction.
Renal Artery Stenosis Presenting with Status Epilepticus: A Report of One Case
Authors: Chen Tsung‐Yi , Huang Li‐Tung , Liang Chi‐Di , Ko Sheung‐Fat , Fang Chih‐Yuan
Published: December 2002

In children, renal artery stenosis is an uncommon but important cause of secondary hypertension. In this report, the authors describe a 5‐year‐old boy with no history of seizures who experienced status epilepticus. Postictal blood pressure, relative hypotension, was misinterpreted as normal on the day of admission. Two days later, his blood pressure rose gradually and peripheral plasma renin activity showed more than 1,700 μU/mL. Magnetic resonance angiography suggested renal artery stenosis. After successful percutaneous transluminal angioplasty, the patient was seizure‐free and had well‐controlled blood pressure. This case describes renal artery stenosis present with status epilepticus, and emphasizes the importance of serial measurements of blood pressure in children.
Ultrasonographic Screening of Clinically‐suspected Necrotizing Fasciitis
Authors: Yen Zui‐Shen , Wang Hsiu‐Po , Ma Huei‐Ming , Chen Shyr‐Chyr , Chen Wen‐Jone
Published: December 2002

Objective: To determine the accuracy of ultrasonography for the diagnosis of necrotizing fasciitis. Methods: This study was a prospective observational review of patients with clinically‐suspected necrotizing fasciitis presenting to the emergency department of an urban (Taipei) medical center between October 1996 and May 1998. All patients underwent ultrasonographic examination, with the ultrasonographic diagnosis of necrotizing fasciitis based on the criterion of a diffuse thickening of the subcutaneous tissue accompanied by a layer of fluid accumulation more than 4 millimeters in depth along the deep fascial layer, when compared with the contralateral position on the corresponding normal limb. The final diagnosis of necrotizing fasciitis was determined by pathological findings for patients who underwent fasciotomy or biopsy results for patients managed nonoperatively. Results: Data were collected for 62 patients, of whom 17 (27.4%) were considered to suffer from necrotizing fasciitis. Ultrasonography revealed a sensitivity of 88.2%, a specificity of 93.3%, a positive predictive value of 83.3%, a negative predictive value of 95.4%, and an accuracy of 91.9% as regards the diagnosis of necrotizing fasciitis. Conclusions: Ultrasonography can provide accurate information for emergency physicians for the diagnosis of necrotizing fasciitis.
Impact of Emergency Medicine Faculty and an Airway Protocol on Airway Management
Authors: Jones James H. , Weaver Christopher S. , Rusyniak Daniel E. , Brizendine Edward J. , McGrath Roland B.
Published: December 2002

Objective: To determine the impact of emergency medicine (EM) faculty presence and an airway management protocol on success rates of tracheal intubation in the emergency department (ED). Methods: A retrospective observational study of prospectively collected data on rates of successful intubations between June 1997 and December 2001 in the ED of a large urban teaching hospital. The authors compared success rates of the first attempt at intubation and times to intubation prior to and after EM faculty presence and the institution of an airway management protocol. Results: Prior to EM faculty presence and the airway management protocol, tracheal intubation was achieved on the first attempt 46% of the time; more than six attempts were required 2.9% of the time. The mean time to intubation was 9.2 minutes (±13.2 SD). Following EM faculty presence and the airway protocol, the success rate on the first attempt was 62%, more than six attempts were required 1.1% of the time, and the mean time to intubation was 4.6 minutes (±6.2 SD). Conclusions: First‐attempt intubation success rates and decreased mean time to successful intubation improved following EM faculty presence and the introduction of an airway management protocol.
Careers of Graduates of Combined Emergency Medicine/Internal Medicine Programs
Authors: Katz Eric D. , Katz Joel T.
Published: December 2002

In 1991, the American Boards of Internal Medicine and Emergency Medicine changed their credentialing requirements to recognize training common to both disciplines. This allowed the formation of a five‐year track for dual board eligibility. From 1995 to 1998, 28 physicians graduated from eight emergency medicine/internal medicine (EM/IM) programs. This study was an analysis of career outcomes of these graduates. Objectives: To document career outcomes of EM/IM program graduates, establish a baseline for future studies of EM/IM graduates, and elucidate the role of EM/IM graduates in medicine. Methods: The 28 EM/IM graduates were mailed a written questionnaire. Endpoints assessed included practice fields, practice environments, ongoing research, publications, academic appointments, board examination scores, career satisfaction, and career goals. Results: Surveys were obtained from 23 of 28 (82.1%) graduates. Seven (30.4%) practice EM and IM, 15 (65.2%) practice EM exclusively, and one (4.3%) practices IM exclusively. Twelve (52.2%) are involved in research. The graduates authored a total of 30 papers or chapters. Ten (43.5%) currently work in administrative positions, but many more aspire to. The most common reasons for having chosen an EM/IM program are to be a better physician (22/23, 95.7%), to practice in both fields (15/23, 65.2%), and to become better prepared for an academic career (15/23, 65.2%). The EM/IM graduates reported high career satisfaction. Conclusions: Although the majority of EM/IM graduates do not practice both IM and EM, many would prefer to. The graduates are highly satisfied with their choice of residency and career. Early in career development, the graduates appear to gravitate toward academic and leadership positions.
Apparently unrelated cytogenetic abnormalities among 462 probands referred for the detection of del(22q) by FISH
Authors: Smith Arabella , St. Heaps Luke , Robson Lisa
Published: December 2002

Laboratory‐based reports of the cytogenetic abnormalities detected during the course of testing for deletion del(22q) are scant. We report our findings from the testing with FISH of 462 patients suspected to have del(22q) between 1994 and 2000. Of these, 447 had a normal karyotype. An apparently unrelated cytogenetic abnormality was detected in 15 (3.2%). Two of these abnormalities involved reciprocal translocation with chromosome 22q and one of these showed del(22q) with FISH. The other abnormalities included sex chromosome aneuploidies and unbalanced rearrangements of various chromosomal segments. There was no commonality among these abnormalities and no correlation with other reported cases. Among those with a normal karyotype, an unexpected deletion of the control arylsulphatase A (ARSA) probe was found, providing a definite frequency of 1/262 for ARSA deletions among patients suspected to have del(22q). Of the 462 referrals, 48 (10%) had one or more additional diagnoses, and in this group, 4 (8%) had del(22q) and 2 (4%) had an apparently unrelated cytogenetic abnormality. The data highlight the importance of initial cytogenetic analysis in patients suspected of del(22q) and negates the use of interphase FISH screening by itself for del(22q). The finding of 3.2% unrelated cytogenetic abnormalities is noteworthy. FISH should be used in any structural rearrangement to ascertain if the relevant locus is deleted or not. The continued reporting of patients diagnosed with del(22q) found to have an unrelated cytogenetic abnormality will expand the phenotypic spectrum and possible gene mapping may refine phenotypic specificity. © 2002 Wiley‐Liss, Inc.
Multiple exostoses, mental retardation, hypertrichosis, and brain abnormalities in a boy with a de novo 8q24 submicroscopic interstitial deletion
Authors: Wuyts Wim , Roland Dominique , Lüdecke Hermann‐Josef , Wauters Jan , Foulon Martine , Van Hul Wim , Maldergem Lionel Van
Published: December 2002

Multiple exostoses represent a genetically heterogeneous disorder that may occur isolated or as part of a complex contiguous gene syndrome such as Langer‐Giedion syndrome on chromosome 8 and the proximal 11p deletion syndrome on chromosome 11. Here we describe a boy with multiple exostoses, hypertrichosis, mental retardation, and epilepsy due to a de novo deletion on chromosome 8q24. Molecular analysis revealed that the deletion interval overlaps with the Langer‐Giedion syndrome and involves the EXT1 gene and additional genes located distal to EXT1, but probably not encompassing the TRPS1 gene located proximal to EXT1. © 2002 Wiley‐Liss, Inc.
Perinatal risk factors for schizophrenia: Diagnostic specificity and relationships with maternal psychopathology
Authors: Verdoux Hélène , Sutter Anne‐Laure
Published: December 2002

Although a growing body of evidence supports the hypothesis that exposure to obstetric complications (OCs) increases the vulnerability for schizophrenia, some questions remain unanswered regarding the diagnostic specificity and the etiological significance of this association. Associations with a history of OCs have been reported for other severe psychiatric disorders, such as autism, anorexia nervosa, or psychotic affective disorder. Thus, OCs may increase in a relatively non‐specific way the vulnerability for a range of severe mental disorders, the expression of this vulnerability depending on the interaction between OCs and other risk factors, such as the genetic liability for specific psychiatric disorder, or exposure to later environmental risk factors. The causal pathway between OCs, maternal psychopathology, and psychotic outcome in the offspring is not fully elucidated. The directions of the associations are often bi‐directional, and the mediating variables, if any, are not clearly identified. OCs may have a direct negative impact on fetal brain development, may be on the causal pathway between prepartum maternal depression/exposure to stress and increased risk of schizophrenia, or may indirectly increase the risk of child's later psychiatric disorder by acting as risk factors for maternal postpartum depression. The links and possible interactions between somatic perinatal risk factors and maternal psychopathology in the association with offspring's increased vulnerability for psychosis have to be further explored. © 2002 Wiley‐Liss, Inc.
The New York high risk project to the Hillside recognition and prevention (RAP) program
Authors: Cornblatt Barbara A.
Published: December 2002

The sudden interest in initiating treatment before the onset of psychosis (i.e., during the prodromal stage of schizophrenia) has failed to integrate the earlier work on prediction generated by more traditional high‐risk studies. Genetic high‐risk research has most typically focused on the long‐term, prospective study of children of parents with schizophrenia. In this paper, it will be argued that high‐risk research can make at least two major contributions to prevention programs. First, previous findings can guide identification of risk factors and provide clues about causality, thus highlighting which pre‐morbid deficits should be treatment targets. For example, as discussed here, data from the New York High Risk Project points to impaired attention as a highly promising candidate risk factor, with a possible causal association with later‐emerging social deficits. Second, the high‐risk approach can provide a framework for establishing the predictive validity of prodromal clinical indicators and for understanding the nature of the schizophrenia prodrome. Preliminary findings from the Hillside Recognition and Prevention (RAP) program, integrating high‐risk methodology with an early intervention strategy, indicate that the prodrome is a developmentally complex phase of schizophrenia. In particular, a cluster of early features—including cognitive, academic, and social impairments, along with odd/disorganized behaviors—appear to anticipate positive symptoms and may constitute a core risk profile. Preliminary RAP treatment findings also suggest that medications other than anti‐psychotics may be effective for treating early prodromal symptoms, challenging the widely held hypothesis that anti‐psychotics should always be the first line preventive treatment. © 2002 Wiley‐Liss, Inc.
Molecular characterization of partial trisomy 16q24.1‐qter: Clinical report and review of the literature
Authors: Brisset S. , Joly G. , Ozilou C. , Lapierre J.‐M. , Gosset Ph. , LeLorc'h M. , Raoul O. , Turleau C. , Vekemans M. , Romana S.P.
Published: December 2002

We describe a 3½‐year‐old girl with psychomotor and mental retardation; dysmorphic features, including a high forehead with bitemporal narrowing; a broad nasal bridge and a broadened nose; downslanting palpebral fissures; abnormal ears; vertebral abnormalities; cardiac defect; genital hypoplasia; and anal abnormalities. The karyotype of our patient (550 bands) was normal. Molecular cytogenetic techniques, including comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), revealed that this girl was a carrier of a de novo derivative chromosome 7 arising from a cryptic t(7;16)(p22.3;q24.1) translocation generating a trisomy 16q24.1‐qter and a 7p22.3‐pter deletion. FISH with a series of specific chromosome 7p and 16q probes allowed us to delineate the chromosome 7 breakpoint between YAC660G6 (WD7S517) and YAC848A12 (D7S521, D7S31, and WI‐4829) and the chromosome 16 breakpoint between BAC457K7 (D42053) and BAC44201 (SGC30711). The comparison of the clinical features of our patient with those of 2 cases of pure terminal 7p deletion and 28 cases of trisomy 16q reported in the literature allowed us to establish the following phenotype‐genotype correlation for trisomy of the long arm of chromosome 16: distinctive facies (high/prominent forehead, bitemporal narrowing, periorbital edema in the neonatal period); severe mental retardation; vertebral, genital, and anal abnormalities to 16q24; distal joint contractures and camptodactyly to 16q23; cleft palate and renal anomalies to 16q22; beaked nose and gall bladder agenesis to 16q21; gut malrotation; lung and liver anomalies to 16q13; and behavior abnormalities to band 16q11‐q13. © 2002 Wiley‐Liss, Inc.
Reply to letter to the editor by Ewald and Als—“chance findings and chance replication in a study of recurrent depression?”
Authors: Zubenko George S.
Published: December 2002

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Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: Evidence from brain and lymphocytes using quantitative RT‐PCR
Authors: Mill Jonathan , Asherson Philip , Browes Clare , D'Souza Ursula , Craig Ian
Published: December 2002

Genetic association studies provide considerable evidence that the 10‐repeat allele of a variable number tandem repeat (VNTR) in the 3′‐untranslated region (3′‐UTR) of the dopamine transporter gene (DAT1) is associated with a range of psychiatric phenotypes, most notably, attention deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study, we measured DAT1 messenger RNA levels in cerebellum, temporal lobe, and lymphocytes using quantitative real‐time reverse‐transcription polymerase chain reaction. Relative to a set of four control housekeeping genes (β‐actin, GAPD, ribosomal 18S, and β2‐microglobulin) we observed that increased levels of DAT1 expression were associated with the number of 10‐repeat alleles. These data provide direct evidence that the VNTR, or another polymorphism in linkage disequilibrium with the VNTR, is involved in regulating expression of this gene. © 2002 Wiley‐Liss, Inc.
Pan‐African Sanctuary Alliance: Status and range of activities for great ape conservation
Authors: Farmer Kay H.
Published: December 2002

While wild populations continue to decrease, the number of orphaned primates, sanctuaries, and attempts to reintroduce primates back to the natural environment are increasing. An umbrella organization called the Pan‐African Sanctuary Alliance (PASA) was formed in 2000 and recently the IUCN Reintroduction Specialist Group developed a set of specific policy guidelines for primates (2002). Data presented in this report are based upon questionnaire responses by managers from 17 African facilities that have become members of PASA (membership in PASA is defined by attendance at an annual PASA workshop). These PASA facilities house over 500 great apes. (There may be other facilities not represented here simply because their managers did not attend a PASA workshop.) The majority of the apes arrived at the sanctuaries when they were less than 4 years old and half were confiscated. Over 40% were found awaiting sale, and 30% had been previously kept as pets. Common ailments upon arrival included internal parasites, behavioral abnormalities, and malnutrition; 20% of the total sanctuary population died prematurely. Most sanctuaries use a combination of enclosures surrounded by electric fencing and cages to accommodate the apes. Sanctuaries actively participate in conservation education, habitat protection, tourism, scientific data collection, local development, and reintroduction. The median total facility operating cost was US$65,000 per annum. The median facility cost per ape was US$2,222 per annum. Most funding comes from overseas nongovernmental agencies. Discussion focuses on evaluating the present status of sanctuaries, the problems facing them, and their potential role in African conservation issues. Am. J. Primatol. 58:117–132, 2002. © 2002 Wiley‐Liss, Inc.
Accumulation of 14‐3‐3 proteins in glial cytoplasmic inclusions in multiple system atrophy
Authors: Kawamoto Yasuhiro , Akiguchi Ichiro , Nakamura Shinichi , Budka Herbert
Published: December 2002

Glial cytoplasmic inclusions are the pathological hallmark of multiple system atrophy. However, the molecular mechanisms underlying the formation of glial cytoplasmic inclusions remain unclear. α‐Synuclein, a major component of glial cytoplasmic inclusions, has the ability to interact with 14‐3‐3 proteins, which mediate several types of signal transduction pathways. To elucidate the role of these 14‐3‐3 proteins in patients with multiple system atrophy, we performed immunohistochemical studies on 14‐3‐3 in brain tissue specimens from 7 control subjects and from 15 patients with multiple system atrophy. In both control and multiple system atrophy cases, 14‐3‐3 immunoreactivity was observed mainly in the neuronal somata and proximal processes, as well as the nerve fibers. Even in the severely affected regions of patients with multiple system atrophy, 14‐3‐3 immunoreactivity generally was spared in the surviving neurons, some of which were strongly immunolabeled. In addition, numerous glial cytoplasmic inclusions were intensely immunostained, and neuronal cytoplasmic inclusions and dystrophic neurites were also immunoreactive for 14‐3‐3. Our results suggest that an aberrant accumulation of 14‐3‐3 proteins may occur in brains affected by multiple system atrophy, and that 14‐3‐3 proteins may be associated with the pathogenesis of multiple system atrophy. Ann Neurol 2002;52:000–000
Changes of sodium channel expression in experimental painful diabetic neuropathy
Authors: Craner Matthew J. , Klein Joshua P. , Renganathan Muthukrishnan , Black Joel A. , Waxman Stephen G.
Published: December 2002

Although pain is experienced by many patients with diabetic neuropathy, the pathophysiology of painful diabetic neuropathy is not understood. Substantial evidence indicates that dysregulated sodium channel gene transcription contributes to hyperexcitability of dorsal root ganglion neurons, which may produce neuropathic pain after axonal transection. In this study, we examined sodium channel mRNA and protein expression in dorsal root ganglion neurons in rats with streptozotocin‐induced diabetes and tactile allodynia, using in situ hybridization and immunocytochemistry for sodium channels Nav1.1, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9. Our results show that, in rats with experimental diabetes, there is a significant upregulation of mRNA for the Nav1.3, Nav1.6, and Nav1.9 sodium channels and a downregulation of Nav1.8 mRNA 1 and 8 weeks after onset of allodynia. Channel protein levels display parallel changes. Our results demonstrate dysregulated expression of the genes for sodium channels Nav1.3, Nav1.6, Nav1.8, and Nav1.9 in dorsal root ganglion neurons in experimental diabetes and suggest that misexpression of sodium channels contributes to neuropathic pain associated with diabetic neuropathy.
Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS
Authors: Drachman Daniel B. , Frank Krystl , Dykes‐Hoberg Margaret , Teismann Peter , Almer Gabrielle , Przedborski Serge , Rothstein Jeffrey D.
Published: December 2002

The pathogenesis of cell death in amyotrophic lateral sclerosis (ALS) may involve glutamate‐mediated excitotoxicity, oxidative damage, and apoptosis. We used a transgenic mouse model of ALS to determine the effect of inhibition of cyclooxygenase‐2 in treating the disease. Cyclooxygenase‐2, present in spinal neurons and astrocytes, catalyzes the synthesis of prostaglandin E2. Prostaglandin E2 stimulates glutamate release from astrocytes, whereas cyclooxygenase‐2 also plays a key role in the production of proinflammatory cytokines, reactive oxygen species, and free radicals. Treatment with a selective cyclooxygenase‐2 inhibitor, celecoxib, markedly inhibited production of prostaglandin E2 in the spinal cords of ALS mice. Celecoxib treatment significantly delayed the onset of weakness and weight loss and prolonged survival by 25%. Spinal cords of treated ALS mice showed significant preservation of spinal neurons and diminished astrogliosis and microglial activation. Our results suggest that cyclooxygenase‐2 inhibition may benefit ALS patients. Ann Neurol 2002