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The epidemiology of functional gastrointestinal disorders in North America.

This article has summarized the epidemiology of several disorders commonly seen in a gastroenterologist's practice. The emphasis has been on population-based data because many people with these disorders never seek health care, and psychological features have been shown to be strongly associated with health care-seeking behavior. Each of these disorders is common in the community; in fact, the majority of the population experiences intermittent gastrointestinal symptoms. In general, the national surveys sponsored by the U.S. Public Health Service have been shown to underestimate the prevalence of these conditions. In part, this is due to the fact that subjects are asked to report diagnoses rather than symptoms, and current coding schemes do not provide specific codes for each of the functional gastrointestinal disorders. Still, these studies have demonstrated the large number of physician visits and overall costs attributable to these disorders. A number of surveys of more limited populations have been done to assess the prevalence of these disorders. Rates have varied because of the definitions used and the degree to which organic diagnoses are excluded. These studies have been helpful in demonstrating the burden of illness in the community. Age and gender differences in the community have been much less marked than those identified in clinic-based studies, thus highlighting the importance of population-based research. Future studies need to focus on the incidence and natural history of these disorders. Studies of incidence cases can best evaluate the role of etiologic factors, whereas studies of prevalent cases are best for assessing the burden of disease in the community. Understanding the natural history of these disorders is important in determining the efficacy of future therapeutic interventions. The fact that these disorders represent 50% of visits to a gastroenterologist practice highlights the importance of these disorders and the potential contribution of gastrointestinal dysmotility in clinical practice.

Colonic Diseases, Functional↗

Assessment of health and growth of ring-necked pheasants following consumption of infected insects or conidia of entomopathogenic fungi, Metarhizium anisopliae var. acridum and Beauveria bassiana, from Madagascar and North America.

Isolates of two fungi (Beauveria bassiana and Metarhizium anisopliae var. acridum) from Madagascar are being developed for control of grasshoppers and locusts, as part of a search for alternatives to environmentally detrimental chemical insecticides. The probable effects of these entomopathogens on nontarget species must be determined before operational use. Birds may become exposed to these fungi either directly, by consuming spores deposited on their food items, or secondarily, by consuming grasshoppers or locusts that have died from infection by these biocontrol agents. This article presents the results of per os challenge from fungus-infected food items. Male and female ring-necked pheasants (Phasianus colchicus) were exposed at 4 d of age and again at 9 d of age to challenge treatments, or 2 control treatments (18 male and 18 female birds per treatment group). Pheasants were weighed at 9, 17, and 25 d of age, tarsal length was measured at 25 d of age, and they were observed daily for signs of adverse effects of the experimental treatments. At the time of euthanasia (25 d of age), 2 or 3 randomly selected birds from each of the groups exposed to infected grasshoppers, plus the 2 control groups, underwent complete necropsies and histopathological examination of 16 tissues from each bird. Results show that in both sexes, weight gain at both 17 and 25 d was not significantly different between challenge groups and control groups. Tarsal length at 25 d of age, an indication of structural growth, was also not markedly different among challenged and control groups. Histopathological changes were generally undetectable, mild, or moderate, and not consistently associated with any treatment. Based on these findings, there is little indication that birds are susceptible to detrimental health effects from direct or secondary exposure to the two entomopathogenic fungi studied.

Animal Feed↗

Characterization of a unique variant of bat rabies virus responsible for newly emerging human cases in North America.

The silver-haired bat variant of rabies virus (SHBRV) has been identified as the etiological agent of a number of recent human rabies cases in the United States that are unusual in not having been associated with any known history of conventional exposure. Comparison of the different biological and biochemical properties of isolates of this virus with those of a coyote street rabies virus (COSRV) revealed that there are unique features associated with SHBRV. In vitro studies showed that, while the susceptibility of neuroblastoma cells to infection by both viruses was similar, the infectivity of SHBRV was much higher than that of COSRV in fibroblasts (BHK-21) and epithelial cells (MA-104), particularly when these cells were kept at 34 degrees C. At this temperature, low pH-dependent fusion and cell-to-cell spread of virus is seen in BHK-21 cells infected with SHBRV but not with COSRV. It appears that SHBRV may possess an unique cellular tropism and the ability to replicate at lower temperature, allowing a more effective local replication in the dermis. This hypothesis is supported by in vivo results which showed that while SHBRV is less neurovirulent than COSRV when administered via the intramuscular or intranasal routes, both viruses are equally neuroinvasive if injected intracranially or intradermally. Consistent with the above findings, the amino acid sequences of the glycoproteins of SHBRV and COSRV were found to have substantial differences, particularly in the region that contains the putative toxic loop, which are reflected in marked differences in their antigenic composition. Nevertheless, an experimental rabies vaccine based on the Pittman Moore vaccine strain protected mice equally well from lethal doses of SHBRV and COSRV, suggesting that currently used vaccines should be effective in the postexposure prophylaxis of rabies due to SHBRV.

Animals↗

Extremity lawn-mower injuries in children: report by the Research Committee of the Pediatric Orthopaedic Society of North America.

In a multicenter study of pediatric lawn-mower injuries (push or riding gas-powered machines), we reviewed 144 children at an average age of injury of 7.0 years; 77% were boys. Most injuries (92 of 104) occurred in the afternoon. The child was the machine operator in 36 cases, a bystander in 84, and a passenger in 21. The average hospital stay was 13.3 days with 2.6 surgeries per child. Amputations occurred in 67 children; 63 were unilateral and four bilateral; the most common level was the toes (63%). Blood transfusions were given to 35 children. Children injured by riding lawn mowers, when compared with those by push lawn mowers, were younger (5.4 vs. 11.0 years), less frequently the operator (15 vs. 60%), had longer hospitalizations (15.0 vs. 8.9 days), and required more surgeries (3.0 vs. 1.6) and blood transfusions (41 vs. 3%). Children with free flaps needed more transfusions (78 vs. 26%), and transfused children were younger (4.6 vs. 8.1 years), more likely to be bystanders (91 vs. 63%), required more surgeries (4.1 vs. 2.0), and were hospitalized longer (21.6 vs. 9.7 days). Soft-tissue infections occurred in eight of 118 and osteomyelitis occurred in six of 117 children. At an average follow-up of 1.9 years, there were 43 satisfactory and 84 unsatisfactory results. When excluding those children with amputations of digits, there were 42 satisfactory and 47 unsatisfactory results. If children younger than 14 years had not been permitted around lawn mowers, approximately 85% of the injuries in this report would have been prevented. Further public dissemination of the following information is needed: (a) children younger than 14 years should not operate lawn mowers, (b) children younger than 14 years should not be in the yard while the lawn is being mowed, and (c) no passengers, regardless of age, should be allowed on riding mowers.

Accidents, Home↗

Tests of pleistocene speciation in montane grasshoppers (genus Melanoplus) from the sky islands of western North America.

There has a been a resurgence of debate on whether the Pleistocene glaciations inhibited speciation. This study tests a model of Pleistocene speciation, estimating the phylogenetic relationships and divergence times of 10 species of montane grasshoppers, genus Melanoplus, using 1300 bp of the mitochondrial gene cytochrome oxidase I (COI). Based on average pairwise distances (corrected for multiple substitutions using Kimura's two-parameter model), all species appear to have originated within the Pleistocene. Sequence divergences between species are less than 4%, corresponding to divergence times less than 1.7 million years ago. Branching patterns among the species suggest that speciation was associated with more than one glacial-interglacial cycle. A likelihood-ratio test rejected a model of simultaneous species origins, the predicted branching pattern if species arose from the fragmentation of a widespread ancestor. These grasshoppers live in an area that was previously glaciated and, as inhabitants of the northern Rocky Mountain sky islands, underwent latitudinal and probably altitudinal shifts in distribution in response to climatic fluctuations. Given the repeated distributional shifts and range overlap of the taxa, there most likely has been ample opportunity for population mixing. However, despite periodic glacial cycles, with more than 10 major glaciations over the past million years and climatic fluctuations over as short a time scale as 10(3) to 10(4) years, the dynamic history of the Pleistocene did not preclude speciation. Although relationships among some taxa remain unresolved, these grasshopper species, even with their recent origins, exhibit genetic coherence and monophyletic or paraphyletic gene trees. The frequency of glacial cycles suggests that the speciation process must have been extremely rapid. These species of grasshoppers are morphologically very similar, differing primarily in the shape of the male genitalia. These characters are posited to be under sexual selection, may play an important role in reproductive isolation, and are known to diverge rapidly. This suggests the rapidity of evolution of reproductive isolation may determine whether species divergences occurred during the Pleistocene glaciations.

Animals↗

Metaviromic profiling of mosquito excreta using superhydrophobic collection devices expands the known RNA virome of North America.

Nearly 30% of emerging infectious disease events worldwide are transmitted by arthropod vectors, and this proportion continues to rise. Rapid and accurate detection is critical for directing vector control interventions, thereby reducing the likelihood of widespread transmission. Surveillance of infected mosquitoes can provide an early warning of impending human infection; however, conventional virus testing relies on processing large pools of mosquitoes and requires labor-intensive pre-processing. During rapidly developing epidemic or panzootic events, these delays may limit the effectiveness of public health responses. Mosquito excreta has recently emerged as a promising alternative substrate for pathogen detection. Sugar-fed mosquitoes regularly excrete gut contents, offering a rich source of nucleic acids. In this study, we developed and applied custom superhydrophobic excreta-collection funnels that efficiently aggregate excreta produced by field-collected Culex mosquitoes into attached microcentrifuge tubes. Shotgun metagenomic sequencing of this material revealed a diverse RNA virome, including both globally distributed viruses and those reported here for the first time from the Americas. Beyond virus detection, additional analyses enabled confirmation of host mosquito species and identification of trypanosomatid parasites, demonstrating the broader utility of mosquito excreta for integrated surveillance. We anticipate that methods and devices of this type will become valuable components of vector surveillance programs, particularly in remote or resource-limited settings where repeated collections are challenging. Overall, our findings highlight the potential of excreta-based monitoring to improve early detection of emerging or unknown pathogens of One Health importance, refine our understanding of mosquito virome biogeography, and facilitate the discovery of previously undescribed viruses.IMPORTANCEMany infectious diseases that affect people and animals are spread by mosquitoes and other biting insects, and the number of these outbreaks is increasing. Detecting pathogens in mosquito populations early can provide a critical warning before human cases begin, allowing health officials to act quickly. However, traditional surveillance requires collecting and processing large numbers of mosquitoes, which can be slow and labor-intensive during fast-moving outbreaks. Here we demonstrate a simpler approach: testing mosquito waste. When mosquitoes feed on sugar, they excrete material that contains genetic traces of viruses and other organisms. Using specially designed collection devices and modern genetic sequencing, we show that mosquito excreta can reveal a wide range of viruses and parasites while also identifying the mosquito species present. This method could make disease surveillance faster and more practical in remote or resource-limited settings, improving our ability to detect emerging pathogens that threaten human, animal, and environmental health.

Animals↗

Detection of Candida dubliniensis in oropharyngeal samples from human immunodeficiency virus-infected patients in North America by primary CHROMagar candida screening and susceptibility testing of isolates.

Candida dubliniensis has been associated with oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV). C. dubliniensis isolates may have been improperly characterized as atypical Candida albicans due to the phenotypic similarity between the two species. Prospective screening of oral rinses from 63 HIV-infected patients detected atypical dark green isolates on CHROMagar Candida compared to typical C. albicans isolates, which are light green. Forty-eight atypical isolates and three control strains were characterized by germ tube formation, differential growth at 37, 42, and 45 degreesC, identification by API 20C, fluorescence, chlamydoconidium production, and fingerprinting by Ca3 probe DNA hybridization patterns. All isolates were germ tube positive. Very poor or no growth occurred at 42 degreesC with 22 of 51 isolates. All 22 poorly growing isolates at 42 degreesC and one isolate with growth at 42 degreesC showed weak hybridization of the Ca3 probe with genomic DNA, consistent with C. dubliniensis identification. No C. dubliniensis isolate but only 18 of 28 C. albicans isolates grew at 45 degreesC. Other phenotypic or morphologic tests were less reliable in differentiating C. dubliniensis from C. albicans. Antifungal susceptibility testing showed fluconazole MICs ranging from </=0.125 to 64 microgram/ml. Two isolates were resistant to fluconazole (MIC, 64 microgram/ml) and one strain was dose dependent susceptible (MIC, 16 microgram/ml). MICs of other azoles, including voriconazole, itraconazole, and SCH 56592, for these isolates were lower. C. dubliniensis was identified in 11 of 63 (17%) serially evaluated patients. Variability in phenotypic characteristics dictates the use of molecular and biochemical techniques to identify C. dubliniensis. This study identifies C. dubliniensis in HIV-infected patients from San Antonio, Tex., and shows that C. dubliniensis is frequently detected in those patients by using a primary CHROMagar screen.

AIDS-Related Opportunistic Infections↗

Asian ethnicity and adenocarcinoma histology continues to predict response to gefitinib in patients treated for advanced non-small cell carcinoma of the lung in North America.

Institutional series suggest specific subgroups of patients with non-small cell lung cancer (NSCLC); female, Asian, non-smokers, respond preferentially to gefitinib. Vancouver, BC, has a large Asian population and therefore is an ideal location to study this differential effect in a Western setting. We performed a retrospective analysis of patients treated with single agent gefitinib to determine if our experience reflects this observation. The pathology, radiology, laboratory investigations and clinical records of 61 patients treated with gefitinib at the BCCA between April 2002 and May 2004 were reviewed. Partial radiologic response was defined as per SWOG response criteria. Symptom responses were subjectively evaluated from chart review. Baseline characteristics at diagnosis; 62% Caucasian, 38% Asian, male 47%, smokers 67%, non-smokers 33%, ECOG 0/1 59%; tumor histology: 57% adenocarcinoma, 13% bronchoalveolar variant, 7% squamous, 23% other. Median treatment duration was 2 months. On radiologic review, 14 patients had a partial response, 25 had stable disease, 21 progressed, and 1 unknown. Twenty patients reported improved symptoms after>/=1 month, 23 had no change, 17 had symptom progression and 1 unknown. Toxicity was minimal; one patient had grade 3 hepatotoxicity that resolved with treatment cessation. Of the 14 radiological responders, 10 were Asian, 10 ECOG 0/1, 10 female, 8 non-smokers, 8 adenocarcinoma and 4 bronchoalveolar variant. At the BCCA, in a select number of patients with advanced NSCLC, gefitinib demonstrated radiologic evidence of anti-tumor activity and provided clinical benefit with minimal side effects. Most of the responders were patients of Asian ethnicity who had immigrated to Canada from China, Taiwan or Hong Kong. Our results suggest that the preferential response to gefitinib seen in the Asian population is preserved in a Western setting. The molecular basis of the improved response rate observed in the subset of female, Asian, non-smokers with adenocarcinoma or bronchoalveolar variant is currently being explored by gene sequencing studies at the British Columbia Cancer Agency Genome Science Centre.

Adenocarcinoma, Bronchiolo-Alveolar↗

What remaining questions regarding Helicobacter pylori and associated diseases should be addressed by future research? View from North America.

Several areas regarding Helicobacter pylori that need improvement or clarification in the United States include treatment of dyspepsia, physician education on disease associations with H. pylori, and evidence from U.S. studies that 7-day H. pylori eradication regimens are more effective than current regimens. Dyspepsia, a ubiquitous condition in the United States, is routinely managed on the basis of a positive H. pylori serology without other investigations. This approach has been fostered by cost-effectiveness studies of various approaches to duodenal ulcer and dyspeptic patients. Serology-directed therapy was the most cost-effective option vs. endoscopy-directed management. The option of not obtaining endoscopy had broad appeal to primary care physicians. In addition, a recent survey suggests that even gastroenterologists routinely attempt H. pylori eradication in infected patients with nonulcer dyspepsia, despite a number of negative efficacy studies. Finally, the option of not eradicating a World Health Organization-defined carcinogen in the litigious United States is unappealing to clinicians. Eradication of H. pylori in patients with dyspepsia despite more negative trials is likely to continue. There is evidence that U.S. physician awareness of the H. pylori-disease associations and the best therapies are improving rapidly, but further improvement is needed. Discrepancy of awareness of H. pylori between gastroenterologists and family physicians exists. In a recent survey, 94% and 72% of gastroenterologists regarded H. pylori as a causative agent in duodenal and gastric ulcer, respectively, vs. 68% and 68% of family physicians, and only 9% of family physicians believed there was a definite relationship between H. pylori infection and gastric cancer vs. 21% of gastroenterologists. One hundred three different H. pylori regimens were being used; 31% of family physicians and 11% of gastroenterologists used ineffective regimens or regimens of unknown effectiveness. Although 1-week proton pump inhibitor triple therapy is promising, there is skepticism that U.S. studies will yield the optimistic results that have characterized the European studies. Unlike in Europe, the U.S. standard is to use double diagnostics to prove eradication rather than just the urea breath test and to use intent-to-treat rather than assessable patient analyses. Both approaches reduce apparent eradication rates.

Dyspepsia↗

The emergence of Lyme disease in a changing environment in North America and central Europe.

Lyme disease has recently begun to emerge as a significant threat to human health, both in Europe and the United States. Late sequellae, resembling those of neurosyphilis and multiple sclerosis, may occur many years after initial infection. Spontaneous abortion accompanies arthritis, carditis and neuritis as burdensome short-term sequellae. Thousands of new infections are recognized each year on each side of the Atlantic, although reporting may be incomplete. The disease was described in Europe nearly a century ago and named erythema chronicum migrans, but its etiology has only recently been defined. The name "Lyme disease" was coined to describe a particularly intense American focus of disease, but the term has gained wide acceptance on both continents. The identity of the American and European etiological agents involved has yet to be determined. In America, a deer-associated, often bird-transported tick transmits this mouse-reservoired spirochete. The European situation seems more complex because the vector tick feeds on a greater variety of vertebrates. The reservoir hosts of the spirochete have yet to be determined. The role of Ixodes ricinus and possible other vectors in perpetuating transmission of the European infection remains to be defined. Whether I. ricinus as well as I. dammini merely serve as a bridge to the human population or are important for the maintenance of the feral cycle remains to be seen. The capacity of a tick to maintain transmission of Lyme disease spirochetes depends upon a complex set of properties, including competence as a host for the spirochete, a pattern of feeding that focuses on a particular reservoir favored by a pattern of tick activity, during each transmission season, in which nymphs feed before larvae. Transmission would be favored by an environment, such as that of islands, in which the variety of potential reservoir hosts is restricted. Hosts, for example reptiles, that might fail to support growth of the spirochete would serve to dilute effective transmission in nature. Similarly, the capacity of a vertebrate to maintain the infection requires long-term support of the spirochete in a tissue site accessible to vector ticks, tolerance of repeated feeding by vector ticks and a pattern of host activity that exposes the host to numerous bites. The intensity of infection depends upon a continuous pattern of transmission in which each generation is infected anew. The rare event in which the vector inherits infection would serve mainly to transport the spirochete to a new site, most effectively by migrating birds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Morphological and histochemical observations on the duodenal glands of eight wild ungulate species native to North America.

The duodenal glands of the species examined (Alces alces, Ovis canadensis, Cervus canadensis, Oreamnos americanus, Bison bison, Antilocapra americana, Odocoileus virginianas, Odocoileus heminous) are confined primarily to the submucosa of the small intestine. In one species, the moose, a significant population of secretory tubules also is observed in the mucosa. The ducts of the duodenal glands pierce the overlying muscularis mucosae to empty most often independently into the intestinal lumen. Those of the bison, unlike the other species examined, drain into intestinal glands. The duodenal glands consist primarily of a simple columnar epithelium, the cells of which contain basally positioned round or oval nuclei. The lumina of scattered duodenal glands in the pronghorn and to some extent those of the moose, white-tailed deer, and mule deer may be extremely dilated, and the surrounding epithelium thin and attenuated. Component cells of the duodenal glands of all the species examined show remarkably similar ultrastructural features. They exhibit scattered profiles of rough endoplasmic reticulum, dilated cisternae of which contain an electron-dense, amorphous material. Numerous well-developed Golgi complexes occupy the supranuclear region together with transport vesicles and forming secretory granules. Electron-dense, membrane-bound secretory granules generally are concentrated in the apical cytoplasm immediately subjacent to the cell membrane. The apical cell membrane exhibits short, scattered microvilli; and the basal cell membrane is smooth without apparent specialization. Histochemically, the duodenal glands of most species examined in this study consist of a heterogeneous population. The majority of the glands of the moose, elk, mountain goat, bison, pronghorn, and white-tailed deer elaborate a neutral mucin, whereas scattered individual glands, tubules or cells also produce acid mucins. Cells near the terminations of the ducts of the bighorn sheep are the only elements to produce acid mucins in the duodenal glands of this species. The duodenal glands of the bison are unusual in that only the peripheral portions of individual glands produce acid mucins. The remainder of the glands elaborate neutral mucins. Morphological differences between the two regions were not observed. The duodenal glands of the mule deer secrete both acid and neutral mucins. The structural and histochemical observations appear unrelated to the diet of individual species.

Animals↗

Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America.

UNLABELLED: BACKGROUND. Ribavirin is active in vitro against hantaviruses, but the findings of an open trial of the use of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome (HCPS) were inconclusive. METHODS: Subjects with suspected HCPS in the prodrome or cardiopulmonary phase but without shock were eligible for randomization to receive either intravenous ribavirin (33 mg/kg [<or=2 g], followed by 16 mg/kg [<or=1 g] given every 6 h for 4 days and by 8 mg/kg [<or=.5 g] given every 8 h for 3 days) or placebo (administered for 7 days or until the initial Sin Nombre virus antibody test result was confirmed to be negative). The primary outcome was survival at day 28 of the study without the need for extracorporeal membrane oxygenation (ECMO). RESULTS: Thirty-six subjects were enrolled in the trial from March 1996 through July 2001, at which point the study was terminated prematurely because of both the slow rate of accrual of subjects and the findings of a futility analysis. Of the 36 subjects enrolled, 23 (all of whom were enrolled during the cardiopulmonary stage of HCPS) had HCPS confirmed by serologic testing. The severity of illness at entry into the study was similar among the 10 subjects with HCPS who received ribavirin and the 13 subjects with HCPS who received placebo. The proportion of subjects who survived and who did not require ECMO was similar among ribavirin recipients and placebo recipients (70% vs. 62%, respectively); 2 ribavirin recipients and 2 placebo recipients died, including 3 of 7 subjects treated with ECMO. The frequency of adverse events, including anemia, was similar between treatment groups. CONCLUSIONS: The rate of accrual of subjects in the present study was inadequate to clearly assess the safety or efficacy of ribavirin in the treatment of HCPS. However, ribavirin was well tolerated, and the lack of trends supporting the use of intravenous ribavirin suggests that it is probably ineffective in the treatment of HCPS in the cardiopulmonary stage.

Adult↗

Systematics of the nematodes that cause ostertagiasis in cattle, sheep and goats in North America.

The systematics of the Ostertagiinae is unsettled with no agreement on how many genera and species are present in cattle and sheep. Ten species of Ostertagiinae are commonly parasitic in cattle and sheep. The males can be identified on the basis of differences in morphology of spicules and genital cones but the females of most species cannot be identified. The species-level systematics have been complicated by the proposal that the ten species are polymorphs of only five species. The systematics at genus level has been complicated by the use of numerous genera for the ten species, at present most commonly Ostertagia, Teladorsagia and Marshallagia. This report (1) describes the current knowledge of the systematics and (2) provides diagnoses of the genera recommended for the ten species. The morphology of the ten species was studied to determine whether characteristics could be found to identify females or to further differentiate the males. Characters studied included the system of longitudinal and surface cuticular ridges (synlophe), the internal morphology of the esophagus and the orientation of rays of the copulatory bursa. The study of species morphology resulted in additional support for the polymorphism proposal. All minor species were found to be identical to their major species in characteristics of the synlophe, esophagus and rays of the copulatory bursa. Two recent classifications of the Ostertagiinae both recommended the use of the genus Teladorsagia for the species T. circumcincta and the two minor species that occur with it, T. trifurcata and T. davtiani. Teladorsagia is characterized by a copulatory bursa in which the five lateral rays are arranged 2-2-1 and a ventral swelling of the genital cone (proconus) is absent. One pair of species, Marshallagia marshalli (major species) and Ostertagia occidentalis (minor species) should be included in the genus Marshallagia. This genus has been characterized by an elongated bursa in which the posterior pair of lateral rays are much longer than the ventral pair. The remaining two pairs of species (O. ostertagi and its minor species O. lyrata, and O. leptospicularis and its minor species O. kolchida) and O. bisonis belong in the genus Ostertagia which is characterized by a 2-1-2 arrangement of the five lateral rays of the copulatory bursa and the presence of a proconus.

Animals↗

Antimicrobial usage and resistance trend relationships from the MYSTIC Programme in North America (1999-2001).

BACKGROUND: The MYSTIC Programme is a global, longitudinal antimicrobial surveillance network of hospitals that frequently utilize carbapenems. One aspect of the programme is the ability to capture antimicrobial consumption data from participating institutions. The current report evaluates these relationships for Enterobacteriaceae and Pseudomonas aeruginosa over the initial 3 year period of the programme in the USA. METHODS: Between 10 and 15 medical centres participated during 1999-2001, each submitting up to 200 isolates/year (7003 strains overall). Evaluations of the relationship between drug usage and antimicrobial resistance in P. aeruginosa and Enterobacteriaceae for the carbapenems (imipenem and meropenem), cefepime, ceftazidime, ciprofloxacin, gentamicin and piperacillin-tazobactam were determined. Data were analysed based on: (1) aggregate usage results; (2) medical centre-specific usage compared with resistance rates; and (3) medical centre-specific usage results compared with yearly changes in resistance rates (DeltaR). The parameter of drug usage was the defined daily dose (DDD)/100 patient days calculated from total grams administered, using WHO definitions. RESULTS: Resistance (1999-2001) among Enterobacteriaceae did not change significantly for beta-lactams, but tended to increase slightly for gentamicin (+1.1%) and ciprofloxacin (+3.1%). P. aeruginosa resistance rates (1999-2001) for gentamicin (+9.0%) and ciprofloxacin (+10.2%) increased, in contrast to a significantly decreased resistance rate for meropenem (-7.7%). Formulary-use changes were noted: increased meropenem and ciprofloxacin use and decreased consumption for imipenem, aminoglycosides, ceftazidime and cefepime. Aggregate ciprofloxacin DDD/100 days rates were directly related (+3.3 DDD) to Enterobacteriaceae and P. aeruginosa resistance changes, whereas among P. aeruginosa, usage and resistance were inversely correlated for gentamicin (-3.8 DDD; +9.0% resistant). Medical centre-specific antimicrobial usage calculations did not demonstrate a correlation to rates of resistance (r = -0.38 to 0.61) or yearly changes in resistance rates (r = -0.56 to 0.43). CONCLUSIONS: The availability of aggregate USA medical centre antimicrobial usage data enabled us to identify several important trends in the incidence of resistance among P. aeruginosa and Enterobacteriaceae: (1) increased use of ciprofloxacin associated with a higher resistance among Enterobacteriaceae; and (2) a correlation between ciprofloxacin categories of resistance and levels of resistance to other antimicrobial classes in P. aeruginosa. Medical centre-specific antimicrobial usage and resistance did not demonstrate direct statistical relationships, and require a continued search for other monitoring methods that can better identify antimicrobial/environmental factors that lead to resistance.

Anti-Bacterial Agents↗

Chemical contaminants in gray whales (Eschrichtius robustus) stranded along the west coast of North America.

The concentrations of selected chlorinated hydrocarbons (e.g. PCBs, DDTs, DDEs, chlordanes) and essential (e.g. zinc, selenium, copper) and toxic (e.g. mercury, lead, arsenic) elements were measured in tissues and stomach contents from 22 gray whales (Eschrichtius robustus) stranded between 1988 and 1991 at sites from the relatively pristine areas of Kodiak Island, AK, to more urbanized areas in Puget Sound, WA, and San Francisco Bay, CA. The majority of animals were stranded at sites on the Washington outer coast and in Puget Sound. The gray whale has the unique feeding strategy among Mysticeti of filtering sediments to feed on benthic (bottom dwelling) invertebrates. Thus, the wide geographical distribution of the stranded whales allowed (1) an initial assessment of whether concentrations of chemical contaminants in these whales exhibited region specific differences and (2) whether toxic chemicals that accumulate in sediments may have contributed to the mortality and stranding of gray whales near the more polluted urban areas. Analyses for chlorinated hydrocarbons in blubber from 22 animals showed no apparent significant differences among stranding sites. The concentrations of sigma PCBs and sigma DDEs in blubber, for example, ranged from 120 to 10,000 and 9 to 2100 p.p.b. (ng/g) wet weight, respectively. Additionally, analyses of chlorinated hydrocarbons and selected elements in liver (n = 10) also showed no apparent significant differences between whales stranded in Puget Sound and whales stranded at more pristine sites (Alaska, Washington outer coast and Strait of Juan de Fuca and Strait of Georgia). For example, the concentrations of sigma PCBs and sigma DDEs in liver ranged from 79 to 1600 and 7 to 280 p.p.b., respectively, and the concentrations of the toxic elements, mercury and lead ranged from 9 to 120 and 20 to 270 p.p.b., respectively. Analyses of stomach contents revealed low concentrations of chlorinated hydrocarbons, but high concentrations (wet weight) of aluminum (1,700,000 +/- 450,000 p.p.b.), iron (320,000 +/- 250,000 p.p.b.), manganese (23,000 +/- 15,000 p.p.b.), and chromium (3400 +/- 1300 p.p.b.), but no significant differences were observed between whales stranded in Puget Sound compared to whales stranded at the more pristine sites. The relative proportions of these elements in stomach contents of stranded whales were similar to the relative proportions in sediments, which is consistent with a geological source of these elements from the ingestion of sediment during feeding. Thus, overall, the concentrations of anthropogenic chemicals in stranded gray whales showed little relation to the levels of chemical contaminants at the stranding sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗

Screening for neuroblastoma in North America. Preliminary results of a pathology review from the Quebec Project.

BACKGROUND: The Quebec Neuroblastoma Screening Project was initiated to assess clinical and biologic aspects of neuroblastomas detected by screening infants born in the province of Quebec from May 1, 1989, to April 30, 1994. METHODS: Infants were screened for preclinical detection of neuroblastoma by determination of catecholamine metabolites, vanillylmandelic acid (VMA), and homovanillic acid (HVA). Patients with tumors discovered through this screening as well as patients in the same birth cohort with clinically detected tumors were referred to Quebec Oncology Centers for further investigation, diagnosis, and treatment. Pathology specimens were submitted to Childrens Hospital Los Angeles for central review. Tumors were histopathologically classified according to the Shimada system. RESULTS: As of August, 1993, 340,000 infants were screened at 3 weeks and 245,000 of them were retested at 6 months of age. Thirty-one tumors were detected through this screening and removed. Histologic material was available for 27 cases: 14 were detected at 3 weeks of age and 13 at 6 months of age. Twenty-six patients had tumors with favorable histology (FH), and one patient had a Stage I tumor with unfavorable histology (UH). At the time of this writing, all mass screening patients are alive, including one child with relapsed disease. During this period, 48 tumors were detected clinically in the same birth cohort, 40 of which were evaluated histologically. Of these 40 cases, 28 of 29 tumors diagnosed in patients up to age 12 months indicated an FH, whereas 9 of 11 tumors diagnosed in patients older than age 12 months indicated a UH. All patients with FH tumors are alive including a child with relapsed disease. The single patient with UH diagnosed before age 12 months died of disease. Of the nine patients with UH diagnosed after age 12 months, four died of disease, one relapsed, and four are alive (including one treated with bone marrow transplantation) after variable follow-up periods. CONCLUSIONS: The tumors detected by mass screening, similar to those tumors detected through clinical examination before age 12 months, were predominantly FH with good prognosis. However, those tumors that were missed by screening and were detected clinically after the patient was 12 months of age were predominantly UH, with serious clinical problems. This subgroup of patients not detectable by the current screening system presents an immediate and important clinical challenge that should be addressed in future studies.

Age Factors↗

Wegener's granulomatosis: survey of 701 patients in North America. Changes in outcome in the 1990s.

OBJECTIVE: To study the medical and socioeconomic impact of Wegener's granulomatosis (WG) in a large cohort (n = 701) of patients who are members of the international WG Support Group (WGSG). METHODS: Forty questions designed and validated by one of the authors and reviewed by the medical consultants of the WGSG International were mailed to 1690 patients with WG who are members of the WGSG; 701 (41%) patients returned the questions. Diagnosis of WG was self-reported for purpose of this questionnaire. Study domains included demographic features, education, analysis of categories of medical care providers, organ system involvement, delay in diagnosis, frequency and sites of biopsies to assist in diagnosis, treatment outcome, familial association, disability, and financial effect. We compared some of these features in patients whose diagnosis was made in the 1970s, 1980s, or 1990s. RESULTS: In our cohort WG was slightly more prevalent in women (56%), particularly if the disease started at a younger age (9-40 years). Peak age period at disease onset was 45-65 years. Ninety-eight percent of patients were Caucasian. Diagnosis of WG was usually made by a specialist, and the majority of patients received subsequent care by specialists. During the past decade only 7% of patients received a diagnosis of WG upon their first visit to a physician. A period of 3-12 months passed from onset of features of WG to achieving a diagnosis in the majority of patients. Compared to the period 1970-90, in recent years fewer patients had biopsies performed for diagnostic purposes. This observation correlated with increased use of antineutrophil cytoplasmic antibodies. In the 1990s the most common reported therapy was combination of corticosteroids and cyclophosphamide (73%). Patients also reported initial therapy with methotrexate (11%), trimethoprim-sulfamethoxa-zole (32%), and azathioprine (5%). Patients rarely reported other family members with WG. In none of 12 WG patients who had a twin did the twin have WG. The survey did not identify any specific environmental exposure, occupation, or hobby that was overrepresented among patients. One hundred seventy-nine WG patients reported that their disease had a significant financial impact on their lives. CONCLUSION: Information from this survey of 701 patients is consistent with physician reported data about organ involvement, initial manifestations and therapy, and outcomes in WG. More WG patients in the 1990s were diagnosed after first physician encounter. This survey did not reveal any predisposing or inducing environmental or familial factors, and showed fewer patients become disabled and more were able to work full time.

Adolescent↗

Six new Eimeria species from vespertilionid bats of North America.

Twenty species of bats (Molossidae, Vespertilionidae) were collected from California, New Mexico, Oregon, South Carolina, Utah, and Baja California Norte (Mexico), and 29 of 404 (7%) animals, including Antrozous pallidus, Eptesicus fuscus, Myotis auriculus, Myotis californicus, Myotis ciliolabrum, Myotis evotis, Myotis lucifugus, Myotis thysanodes, Myotis vivesi, Myotis volans, Myotis yumanensis, and Nycticeius humeralis were infected with Eimeria spp., which represent 6 new species. Sporulated oocysts of a new species from A. pallidus are subspheroidal, 24.8 x 21.6 (22-27 x 19-24) microm with a polar granule and a large globular residuum. The oocyst wall is sculptured, with 2 layers, approximately 1.5 thick. Ovoidal sporocysts are 11.5 x 7.8 (9-13 x 7-10) microm, with Stieda body and residuum of many large granules. Sporulated oocysts of a new species from M. californicus are subspheroidal, 20.7 x 18.2 (19-23 x 16-20) microm, with 1-7 tiny polar granules, but without oocyst residuum. The oocyst wall is rough, with 2 layers, approximately 1.4 thick. Ovoidal sporocysts are 11.2 x 7.3 (10-12 x 7-8) microm, with Stieda body and a globular residuum. Sporulated oocysts of a second new species from M. californicus are subspheroidal, 23.1 x 20.7 (20-26 x 19-23) microm, with residuum and 1 polar granule, but a micropyle is absent. The oocyst wall is rough with 2 layers, approximately 1.5 thick. Ovoidal sporocysts are 12.5 x 7.2 (11-14 x 7-8) microm, with a Stieda body and residuum. Sporulated oocysts of a new species from M. ciliolabrum are subspheroidal, 24.9 x 20.1 (18-27 x 17-23) microm, with 1-2 polar granules, but without micropyle and residuum. The oocyst wall is rough with 2 layers, approximately 1.5 thick. Ellipsoidal sporocysts are 12.5 x 9.0 (8-14 x 7-10) microm, with Stieda and substieda bodies and residuum. Sporulated oocysts of a new species from M. evotis are subspheroidal, 21.3 x 18.6 (20-24 x 15-20) microm, with a prominent polar granule, but without micropyle and residuum. The oocyst wall is smooth with 2 layers, approximately 1.0 thick. Ovoidal sporocysts are 12.2 x 8.0 (11-13 x 7.5-9) microm, with Stieda and substieda bodies and residuum. Sporulated oocysts of the new species from N. humeralis are subspheroidal, 22.4 x 18 (21-24 x 17-20) microm, with 1-3 polar granules, but residuum and micropyle are absent. The oocyst wall is lightly sculptured with 2 layers, approximately 1.4 thick. Ovoidal sporocysts are 10.9 x 7.7 (9-12 x 6-8) microm, with Stieda body and residuum. Sporulated oocysts of E. pilarensis Scott and Duszynski, 1997 and those of at least 12 other morphological forms were seen in the other infected bats; these latter forms were seen in too few numbers to be adequately described as new species.

Animals↗