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Biomedical subjects

P D Mitchell

Publications and source records attributed to P D Mitchell.

At least 19 recordsLinked to original sources
PubMed2005

Effect of extended diapause on evolution of resistance to transgenic Bacillus thuringiensis corn by northern corn rootworm (Coleoptera: Chrysomelidae).

We develop a population genetics model for the northern corn rootworm, Diabrotica barberi Smith & Lawrence, to examine the effect of extended diapause on the evolution of resistance to transgenic Bacillus thuringiensis (Bt) corn, Zea mays L. We model conditions found in the center of the extended diapause problem along the Minnesota-South Dakota-Iowa borders. The proportion of resistance alleles in eggs oviposited after 15 simulated years is used to measure the evolution of resistance. Sensitivity analysis indicates that although population genetics parameters (fecundity, initial egg density, density-dependent larval survival, random mating, insecticide mortality, and gene expression) affect the evolution of resistance, product characteristics (e.g., Bt toxin dose) and farmer management practices (e.g., insecticide use on refuge corn and rotation pattern) generally have a larger impact on the development of resistance. Exceptions to this generalization exist: 1) if the resistance allele is dominant, resistance evolves quickly; 2) the level of random mating is an important determinant of how quickly resistance evolves for a theoretical high dose product; and 3) small differences in insecticide mortality imply large differences in resistance for medium- and low-dose products with high levels of Bt corn adoption and a predominance of 1- and 2-yr corn rotations. When extended diapause spreads into a new area, it typically reduces resistance to Bt corn, assuming Bt corn is used only on continuous corn. In the study region where extended diapause already exists, increasing extended diapause (increasing hatch rates after two or three winters while holding total hatch constant), tends to increase resistance because the resistance increasing effect of the hatch rate after two winters dominates the resistance decreasing effect of the hatch rate after three winters. However, this is not always the case, because combinations of rotation pattern, toxin dose, and soil insecticide use exist for which the net effect of extended diapause decreases resistance. Results are interpreted as a combination of two offsetting effects. First, extended diapause injects older alleles with lower resistance allele frequencies into the breeding population, which slows resistance. Second, extended diapause speeds the population's recovery from perturbations (reduces the undercompensating density dependence of population dynamics), which accelerates resistance.

Animals↗
PubMed2005

Economic analysis of dynamic management strategies utilizing. Transgenic corn for control of western corn rootworm (Coleoptera: Chrysomelidae).

We studied management strategies for western corn rootworm, Diabrotica virgifera virgifera LeConte, using transgenic corn, Zea mays L., from both a biological and an economic perspective. In areas with and without populations adapted to a 2-yr rotation of corn and soybean (rotation-resistant), the standard management strategy was to plant 80% of a cornfield (rotated and continuous) to a transgenic cultivar each year. In each area, we also studied dynamic management strategies where the proportion of transgenic corn increased over time in a region. We also analyzed management strategies for a single field that is the first to adopt transgenic corn within a larger unmanaged region. In all areas, increasing the expression of the toxin in the plant increased economic returns. In areas without rotation-resistance, planting 80% transgenic corn in the continuous cornfield each year generated the greatest returns with a medium toxin dose or greater. In areas with alleles for rotation-resistance at low initial levels, a 2-yr rotation of nontransgenic corn and soybean, Glycine max (L.) Merr., may be the most economical strategy if resistance to crop rotation is recessive. If resistance to crop rotation is additive or dominant, planting transgenic corn in the rotated cornfield was the most effective strategy. In areas where rotation-resistance is already a severe problem, planting transgenic corn in the rotated cornfield each year was always the most economical strategy. In some cases the strategies that increased the proportion of transgenic corn in the region over time increased returns compared with the standard strategies. With these strategies the evolution of resistance to crop rotation occurred more rapidly but resistance to transgenic corn was delayed compared with the standard management strategy. In areas not managed by a regional norm, increasing the proportion of transgenic corn and increasing toxin dose in the managed field generally increased returns. In a sensitivity analysis, among the parameters investigated, only density-dependent survival affected the results.

Agriculture↗
PubMed2003

Economics versus alleles: balancing integrated pest management and insect resistance management for rotation-resistant western corn rootworm (Coleoptera: Chrysomelidae).

Western corn rootworm, Diabrotica virgifera virgifera LeConte, has overcome crop rotation in several areas of the central United States. We expanded a simple model of adult behavior and population genetics to explain how rotation resistance may have developed and to study ways to manage the western corn rootworm in a landscape of corn, soybean, and winter wheat where evolution of resistance may occur. We modeled six alternative management strategies over a 15-yr time horizon, as well as a strategy involving a 2-yr rotation of corn and soybean in 85% of the landscape, to investigate their effectiveness from both a biological and economic perspective. Generally, resistance to crop rotation evolves in fewer than 15 yr, and the rate of evolution increases as the level of rotated landscape (selection pressure) increases. When resistance is recessive, all six alternative strategies were effective at preventing evolution of rotation resistance. The two most successful strategies were the use of transgenic rotated corn in a 2-yr rotation and a 3-yr rotation of corn, soybean, and wheat with unattractive wheat (for oviposition) preceding corn. Results were most sensitive to increases in the initial allele frequency and modifications of the density-dependent survival function. Economically, three alternative strategies were robust solutions to the problem, if technology fees were not too high. Repellant soybean, attractive rotated corn, and transgenic rotated corn, all in 2-yr rotations, were economically valuable approaches. However, even the currently common 2-yr rotation was economical when resistance was recessive and the actual costs of resistance would not be paid until far in the future.

Agriculture↗
PubMed2003

Sensory testing in leprosy: comparison of ballpoint pen and monofilaments.

The 10 g monofilament has been replaced by the ballpoint pen in routine sensory testing of nerves in leprosy control in Ethiopia. Results of sensory testing between the ballpoint pen and different monofilaments on hands and feet were compared. Ballpoint pen underdiagnosis of loss of sensation was defined to occur when the pen was felt and the monofilament was not. Differences were evaluated both for individual test points (test point level) and for the test points of extremities collectively (extremity level). An extremity (either a hand or a foot) was defined as having sensory nerve function impairment (SNFI) if a supplying nerve had SNFI, which was the case when sensation was absent in two or more test points in the area supplied by that nerve. At test point level, the percentages with ballpoint pen underdiagnosis relative to the 2, 10, 20 and 50 g monofilaments were 40, 21, 9 and 7%, respectively, in the hands, and 47, 30, 15 and 7% in the feet. Ballpoint pen underdiagnosis percentages of SNFI at extremity level were 32, 18, 8 and 9% in the hands, and 37, 26, 14 and 6% in the feet. The risk of ballpoint pen underdiagnosis appears to be higher in extremities without visible damage. In conclusion, substantial levels of underdiagnosis of sensory loss with the ballpoint pen were observed. However, the consequences for the prognosis of treatment with corticosteroids in patients with the more subtle sensation loss noted here need to be established. Development and testing of guidelines is a prerequisite for the use of the ballpoint pen.

Adolescent↗
PubMed2001

Population-based incidence of human granulocytic ehrlichiosis in northwestern Wisconsin, 1997-1999.

The incidence of human granulocytic ehrlichiosis (HGE) in the upper Midwest is uncertain. Active surveillance for suspected HGE was conducted from 1997 through 1999 in a 13-county region of northwestern Wisconsin. Suspected HGE cases were classified, according to the national case definition, as confirmed, probable, or not HGE. In total, 112 confirmed cases and 30 probable cases of HGE were identified. The median age of the 142 case patients was 56 years, and 92 (65%) were male; 111 (78%) were residents of the surveillance region. The mean annual incidence of confirmed and probable HGE was 9.3 cases per 100,000 residents; there was no increase from 1997 to 1999. The incidence was highest among persons > or =50 years old and residents of Washburn County. The incidence of HGE in this region exceeded prior estimates, but it was lower than the reported incidence in areas of endemicity in Connecticut.

Adolescent↗
PubMed2001

Antibody response to IR6, a conserved immunodominant region of the VlsE lipoprotein, wanes rapidly after antibiotic treatment of Borrelia burgdorferi infection in experimental animals and in humans.

Invariable region (IR)(6), an immunodominant conserved region of VlsE, the antigenic variation protein of Borrelia burgdorferi, is currently used for the serologic diagnosis of Lyme disease in humans and canines. A longitudinal assessment of anti-IR(6) antibody levels in B. burgdorferi-infected rhesus monkeys revealed that this level diminished sharply after antibiotic treatment (within 25 weeks). In contrast, antibody levels to P39 and to whole-cell antigen extracts of B. burgdorferi either remained unchanged or diminished less. A longitudinal analysis in dogs yielded similar results. In humans, the anti-IR(6) antibody titer diminished by a factor of > or =4 in successfully treated patients and by a factor of <4 in treatment-resistant patients. This result suggests that the quantification of anti-IR(6) antibody titer as a function of time should be investigated further as a test to assess response to Lyme disease therapy or to determine whether a B. burgdorferi infection has been eliminated.

Adult↗
PubMed2001

Tickborne infections as a cause of nonspecific febrile illness in Wisconsin.

Lyme disease, human granulocytic ehrlichiosis (HGE), and babesiosis are tickborne infections that are indigenous to Wisconsin. To assess their importance as a cause of nonspecific fever, we recruited patients with febrile illness at 10 clinics in northwestern Wisconsin from May through August of both 1997 and 1998. Eligible patients had a temperature >38.0 degrees C but no rash or other localizing source. Acute and convalescent serological tests were performed for Borrelia burgdorferi, Babesia microti, and Ehrlichia equi; polymerase chain reaction was performed to detect granulocytic Ehrlichia rDNA. Seventeen (27%) of 62 eligible patients had laboratory evidence of tickborne infection, including 7 (11%) with probable Lyme disease only, 8 (13%) with HGE only, and 2 (3%) with apparent coinfection. No patients with Babesia infection were identified. Patients with and without tickborne infection were similar with regard to age, sex, symptoms, history of tick bite, and outdoor exposure. The results suggest that tickborne infections are an important cause of nonspecific febrile illness during the tick season in northwestern Wisconsin.

Adolescent↗
PubMed2001

Stochastic dynamic population model for northern corn rootworm (Coleoptera: Chrysomelidae).

A stochastic dynamic population model for the complete life cycle of northern corn rootworm, Diabrotica barberi Smith & Lawrence, is described. Adult population dynamics from emergence to oviposition are based on a published single-season model for which temperature-dependent development and age-dependent advancement determine adult population dynamics and oviposition. Randomly generated daily temperatures make this model component stochastic. Stochastic hatch is 50+/-8%. A stochastic nonlinear density-dependent larval survival model is estimated using field data from artificial infestation experiments. A regional model of corn phenology is estimated to incorporate the effect of dispersal on adult mortality. Random daily weather is generated using parameters for Brookings, SD. Model performance is evaluated with deterministic simulations, which show that the population converges to zero unless adult mortality is reduced by the availability of corn pollen from the regional model of corn phenology. Stochastic model performance is evaluated with stochastic daily weather, egg hatch, and larval survival in various combinations. Sensitivity analysis is conducted to evaluate model responsiveness to each parameter. Model results are generally consistent with published data.

Animals↗
PubMed2001

The threshold for protective sensation that prevents neuropathic ulceration on the plantar aspect of the foot: a study of leprosy patients in a rural community in India.

The protective sensation threshold is an important concept in the prevention of plantar ulceration in leprosy patients. Previous studies have suggested that skin with sensory nerve damage on the plantar aspect of the foot which can still detect the 5.07 Semmes-Weinstein monofilament (approximately 10 g) is highly unlikely to develop ulceration. While the threshold is thought to be less than the 610 filament (approximately 75 g), no work just testing adjacent to current ulcers has been undertaken to assess this more accurately. This is important, as it has been shown that a significant proportion of healthy individuals who wear sandals or go barefoot in India may fail to detect this 5.07 filament in at least some areas of the sole, especially in older age groups, and in certain cases the 5.46 filament (approximately 30 g) is the lightest detected. In an attempt to address this problem, a cross-sectional study on 26 current plantar ulcers in male adults with stable neuropathy due to leprosy was carried out in the rural town of Salur, India. It was confirmed that the ability to detect the 5.07 filament (approximately 10 g) did prevent the development of ulceration while in contrast the ability to detect the 5.46 filament (approximately 30 g) did not. This suggests that the threshold for protective sensation lies between these two filaments. An approach is suggested which may help to differentiate feet genuinely at risk of ulceration from those merely unable to detect the 5.07 filament on account of thickened skin callus or advancing age.

Adult↗
PubMed2000

The age-dependent deterioration in light touch sensation on the plantar aspect of the foot in a rural community in India: implications when screening for sensory impairment.

Regular testing for impaired sensation is important in the management of diseases that can cause progressive nerve damage, such as leprosy. It has been shown that light touch sensibility decreases with age in the hands of healthy individuals, but little research has been undertaken to assess possible changes in the feet in developing countries. This information is needed to allow an appropriate level of sensation to be chosen when screening for nerve damage in the foot. To clarify this, a cross-sectional study on male adults was carried out in the rural town of Salur, Andhra Pradesh, India. A range of Semmes-Weinstein monofilaments were employed at 12 locations on the foot to determine sensation to light touch stimuli in individuals from each decade of adult life. It was found that in this population, sensibility threshold in the foot increases with age and this was noted in both soft and callous skin. This shows the increase was due to neurological factors, not merely due to an increase in callous deposition with advancing age. In the majority of individuals in their fifties and sixties, the callous skin at the forefoot and heel was unable to detect the 5.07 monofilament (equivalent to 8-12 g), previously recommended as a method to screen for plantar neuropathy. All areas of all feet were able to detect the 5.46 filament (approximately 30 g). The size of this study (54 individuals) prevents the determination of definitive normal ranges for each decade of life in this population. However, it does demonstrate the degree to which sensation deteriorates with age and could be used as an approximate guide when interpreting the results of sensory testing in similar rural areas of the developing world.

Adult↗
PubMed1999

The assessment of acute knee injuries by Senior House Officers in the Accident and Emergency department.

This study in a large inner city Accident & Emergency (A&E) department investigated the awareness of new Senior House Officers (SHO's) of the major symptoms and signs of significant trauma to the knee. They were able to identify a knee effusion clinically but were unable to differentiate a haemarthrosis from a reactive effusion. An acute haemarthrosis is suggestive of significant damage such as fracture, cruciate ligament rupture, major meniscal tear, synovial tear or patella dislocation (Maffulli N, Binfield PM, King JB, Good CJ. J Bone Joint Surg [Br] 1993;75(6):945-949 [1]; Noyes FR, Basset RW, Grood ES, Butler DL. J Bone Joint Surg [Am] 1980;62-A:687-695 [2]; Jain AS, Swanson AJG, Murdoch G. Injury 1983;15:178-181.] [3]). In many cases a haemarthrosis may be the only abnormality demonstrable in the acute setting (Dehaven KE. Am J Sports Med 1980;8:9-14 [4]; Visuri T, Koskenvuo M, Dahlstrom S. Milit Med 1993;158(6):378-381 [5]). If this diagnosis is missed then patients may be inappropriately sent home without suitable treatment and follow up. Greater emphasis should be placed on the differentiation between reactive effusion and haemarthrosis in the knee during the teaching of orthopaedics both at medical school and also on arrival at the A&E department.

Acute Disease↗
PubMed1999

Clinical and epidemiological features of early Lyme disease and human granulocytic ehrlichiosis in Wisconsin.

To compare clinical features and assess risk factors for human granulocytic ehrlichiosis (HGE) and early Lyme disease, we enrolled patients in a case-control study during the 1996 and 1997 tick seasons. Clinical and demographic characteristics were assessed for patients with laboratory-confirmed cases of HGE or Lyme disease, and risk factors were compared with those of matched control subjects. We identified 83 persons with Lyme disease, 27 with HGE, and 11 with apparent coinfection. Unsuspected Ehrlichia infection was identified in 8 (13%) of 60 patients with Lyme disease. Patients with HGE were older and more likely to have fever, chills, or dyspnea than were those with Lyme disease only. Most patients with apparent coinfection did not have hematologic abnormalities. In the risk factor analysis, tickborne illness was independently associated with rural residence and camping. The clinical spectrum of HGE overlaps that of Lyme disease, and physicians in areas of endemicity should consider both diseases in treating patients with a compatible rash or febrile illness.

Adult↗
PubMed1998

Immunoglobulin M capture assay for serologic confirmation of early Lyme disease: analysis of immune complexes with biotinylated Borrelia burgdorferi sonicate enhanced with flagellin peptide epitope.

We previously reported on the efficacy of the enzyme-linked immunoglobulin M capture immune complex (IC) biotinylated antigen assay (EMIBA) for the seroconfirmation of early Lyme disease and active infection with Borrelia burgdorferi. In earlier work we identified non-cross-reacting epitopes of a number of B. burgdorferi proteins, including flagellin. We now report on an improvement in the performance of EMIBA with the addition of a biotinylated form of a synthetic non-cross-reacting immunodominant flagellin peptide to the biotinylated B. burgdorferi B31 sonicate antigen source with the avidin-biotinylated peroxidase complex detection system used in our recently developed indirect IgM-capture immune complex-based assay (EMIBA). As in our previous studies, the enzyme-linked immunosorbent assay (ELISA) reactivities of antibodies liberated from circulating ICs (by EMIBA) were compared with those of antibodies in unprocessed serum (antibodies found free in the serum, thus as an IgM-capture ELISA, but not EMIBA, because the antibodies were not liberated from ICs), the sample usually used in standard ELISAs and Western blot assays. The addition of the flagellin epitope enhanced the ELISA signal obtained with untreated sera from many Lyme disease patients but not from healthy controls. In tests with both free antibodies and ICs, with or without the addition of the flagellin epitope to the sonicate, we found the most advantageous combination was IC as the source of antibodies and sonicate plus the flagellin epitope as the antigen. In a blinded study of sera obtained from patients with early and later-phase Lyme disease, EMIBA with the enhanced antigenic preparation compared favorably with other serologic assays, especially for the confirmation of early disease.

Antibodies, Bacterial↗
PubMed1997

Genetic heterogeneity of Borrelia burgdorferi in the United States.

To examine in detail Borrelia burgdorferi strain diversity in the United States, 186 isolates from human, tick, and rodent sources were analyzed from multiple distinct geographic regions of the United States and abroad. Strains were characterized by genomic macrorestriction analysis and ospA and 23S rDNA gene sequencing followed by phylogenetic analysis. Results indicate that spirochetal isolates from the United States fall into two major divisions and nine or more subdivisions; human isolates fell into five of these subdivisions. Greater genetic diversity was observed among B. burgdorferi isolates from moderate climatic regions, consistent with increased tick vector and reservoir diversity. All of the Borrelia isolates were reactive by ospA polymerase chain reaction except for Borrelia hermsii controls and several tick isolates from the Northeast, which were shown to lack the 49-kb plasmid encoding outer surface protein A (OspA). The data suggest that US B. burgdorferi isolates demonstrate substantial genetic heterogeneity, with regional differences in spirochete populations.

Animals↗
PubMed1997

Characterization of an immunoreactive protein from the agent of human granulocytic ehrlichiosis.

A gene that is homologous to the Ehrlichia chaffeensis groEL operon was recovered and characterized by broad-range PCR amplification of whole blood from patients with human granulocytic ehrlichiosis (HGE) and from infected HL60 cell cultures. Sequence analysis of an 820-bp DNA fragment recovered directly from human blood showed 76.5 and 76.3% identity with cognate sequences from E. chaffeensis and Cowdria ruminantium, respectively. Analysis of a 1.6-kb DNA fragment derived from an HGE agent-infected HL60 cell culture indicated a near-complete open reading frame that contained 75.6 and 75.2% sequence identity with the E. chaffeensis and C. ruminantium groEL sequences, respectively. Phylogenetic analysis of this fragment showed that the HGE agent-derived sequence was related to, but distinct from, the sequences of E. chaffeensis and C. ruminantium. Polyvalent antibody responses to a recombinant fusion protein based on the HGE agent groEL homolog were detected in three of three BALB/c mice that were infected by syringe inoculation with a Wisconsin strain of the HGE agent (WI-1) and nine of nine mice infected by Ixodes scapularis (Ixodes dammini) tick inoculation of an isolate from Nantucket Island, Mass. (NCH-1). No response was detected in mice infected with Borrelia burgdorferi or in control BALB/c mice. Further characterization of the sensitivity and specificity of immune responses to this protein will be facilitated by the use of recombinant fusion proteins or peptides based on the HGE agent-specific groEL homolog.

Amino Acid Sequence↗
PubMed1997

Prevalence of granulocytic Ehrlichia infection among white-tailed deer in Wisconsin.

Human granulocytic ehrlichiosis (HGE) is caused by an agent that is nearly indistinguishable from the veterinary pathogens Ehrlichia equi and Ehrlichia phagocytophila. The deer tick, Ixodes scapularis, is a vector of the HGE agent, and the white-tailed deer is the primary host for adult Ixodes ticks. We assessed the distribution of granulocytic Ehrlichia infection among deer living within (Wisconsin) and outside (western and southern Iowa) the geographic range of L. scapularis. Whole-blood samples were tested for HGE 16S ribosomal DNA (rDNA) by PCR, and E. equi antibody was detected by indirect immunofluorescence assay (IFA). Antibody titers of > or = 1:64 were defined as positive, and all positive samples were retested with a second lot of substrate antigen. E. equi antibody was present in 14 (8%) of 187 Wisconsin deer and 0 of 60 Iowa specimens (rate ratio undefined; P = 0.025). An additional 30 serum samples from Wisconsin deer were excluded because IFA results were discrepant between substrate lots. The reciprocal antibody titers ranged from 64 to 512 (geometric mean, 141) for positive samples. PCR results were positive for 27 (15%) of 181 Wisconsin deer. The prevalence of infection in northwestern Wisconsin deer was not significantly different from that in central Wisconsin deer, as determined by IFA and PCR. In two samples that were sequenced, the 16S rDNA was nearly identical to that of the granulocytic Ehrlichia species but distinct from that of Anaplasma marginale. The DNA sequences of the samples differed from the published sequences for E. equi, E. phagocytophila, and the HGE agent by 1 or 2 nucleotides (> or = 99.1% homology) at phylogenetically informative sites. Granulocytic Ehrlichia organisms in deer are widely distributed within the geographic range of L. scapularis in Wisconsin. Deer may serve as useful sentinels for areas where HGE transmission to humans may occur.

Animals↗
PubMed1996

Immunoserologic evidence of coinfection with Borrelia burgdorferi, Babesia microti, and human granulocytic Ehrlichia species in residents of Wisconsin and Minnesota.

In Wisconsin and Minnesota, Ixodes scapularis (Ixodes dammini) ticks are the vector of three microorganisms that may cause significant disease in humans and lower mammals. These diseases include Lyme borreliosis, which is caused by Borrelia burgdorferi, babesiosis, which is caused by Babesia microti, and human granulocytic ehrlichiosis (HGE), which is caused by an apparently new species in the genus Ehrlichia. Immunoserologic testing was performed on sera from patients with a diagnosis of one of these diseases to determine if there was evidence of coinfection with one or more of the other agents. Of 96 patients with Lyme borreliosis, 9 (9.4%) demonstrated immunoserologic evidence of coinfection: 5 (5.2%) with the agent of HGE, 2 (2.1%) with B. microti, and 2 (2.1%) with both microorganisms. Of 19 patients diagnosed with HGE, 3 (15.8%) showed immunoserologic evidence of coinfection: 1 (5.3%) with B. burgdorferi, 1 (5.3%) with B. microti, and 1 (5.3%) with both microorganisms. One patient diagnosed with babesiosis was also seropositive for ehrlichiosis. These results provide evidence for coinfection, perhaps explaining the variable manifestations and clinical responses noted in some patients with tick-transmitted diseases. In certain clinical settings, laboratory testing for coinfection is indicated to ensure that appropriate antimicrobial treatment is given.

Animals↗