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Biomedical subjects

K J Davis

Publications and source records attributed to K J Davis.

At least 19 recordsLinked to original sources
PubMed2006

Lung function decline and outcomes in an elderly population.

OBJECTIVE: To determine the risk factors for and outcomes associated with the rapid decline in lung function in a cohort of elderly US adults. METHODS: Data from 4923 adult participants aged 65 years and older at baseline in the Cardiovascular Health Study were analysed. Subjects were classified using a modification of the GOLD criteria for chronic obstructive pulmonary disease (COPD) and a "restricted" category (FEV1/FVC>or=70% and FVC<80% predicted) was added. Cox proportional hazard models were used to determine the risk of lung function decline over 4 years on subsequent mortality and COPD hospital admissions after adjusting for age, race, sex, smoking status, and other factors. RESULTS: Of the participants in the initial cohort, 3388 (68.8%) had spirometric tests at the year 4 visit. Participants with GOLD stages 3 or 4 COPD at baseline were less likely than normal subjects to have follow up spirometric tests (52.7% v 77.9%, p<0.01) and were more likely to be in the most rapidly declining quartile of FEV1 (28.2% v 21.3%, p<0.01) with an annual loss of FEV1 of at least 3.5%. Overall, being in the most rapidly declining quartile of FEV1 from baseline to year 4 was associated with an increased risk of admission to hospital for COPD (adjusted hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.3 to 2.0) and all-cause death (adjusted HR 1.5, 95% CI 1.2 to 1.7) over an additional 7 years of follow up. CONCLUSION: More rapid decline in lung function is independently associated with a modest increased risk of hospital admissions and deaths from COPD in an elderly cohort of US participants.

Aged↗
PubMed2006

Poor asthma control in children: evidence from epidemiological surveys and implications for clinical practice.

The objectives of this study is to compile current knowledge about asthma control in children in relation to goals proposed in international guidelines, to elucidate the factors associated with insufficient asthma control and to address the implications for clinical practice. Review of recent worldwide large population epidemiological surveys and clinical asthma studies of more than 20,000 children are the methods used in this study. The studies report high frequencies of sleep disturbances, emergency visits, school absence and limitations of physical activity due to asthma. Only a small percentage of children with asthma reach the goals of good asthma control set out by Global Initiative for Asthma (GINA). There is evidence of underuse of inhaled corticosteroids even in children with moderate or severe persistent asthma and over-reliance on short-acting beta(2)-agonist rescue medication. Both parents and physicians generally overestimate asthma control and have low expectations about the level of achievable control. Many children with asthma are not being managed in accordance with guideline recommendations, and asthma management practices vary widely between countries. Asthma control falls short of guideline recommendations in large proportions of children with asthma worldwide. Simple methods for assessing asthma control in clinical practice are needed. Treatment goals based on raised expectations should be established in partnership with the asthmatic child and the parents. Effective anti-inflammatory treatment should be used more frequently, and patients should be reviewed regularly.

Adolescent↗
PubMed2004

Adjuvant biofeedback following anal sphincter repair: a randomized study.

AIMS: To evaluate the impact of adjuvant biofeedback following sphincter surgery. METHODS: Thirty-eight patients were randomized into sphincter repair or sphincter repair plus biofeedback groups. Outcome measures included a symptom questionnaire, patient's rating of satisfaction with continence function and improvement, change in continence score, quality of life and anorectal physiology. Endoanal ultrasonography was also performed pre- and post-operatively. RESULTS: Immediately following surgery, there was no statistically significant difference in any of the functional or physiological variables between the groups. Continence and patient satisfaction scores improved with a mean difference of -0.48 (95% CI: -3.30-2.33, P = 0.73) and 1.03 (95% CI: -1.40-3.46, P = 0.39), respectively. Only the difference in embarrassment scores reached statistical significance (mean) 0.56 (95% CI: 0.12-0.99, P = 0.014). Resting and squeeze pressures also improved. Thirteen of 14 in the biofeedback and 11 of 17 (control) reported symptomatic improvement. In the biofeedback group, although not statistically significant continence and satisfaction scores improved and were sustained over time. In the control group, continence and satisfaction scores changed little between 3 and 12 months (P = NS). Quality of life measures improved within the biofeedback group but there was no statistical difference between the groups. CONCLUSION: Following surgery continence function improves in all patients but adjuvant biofeedback therapy improves quality of life and maintains symptomatic improvement over time.

Adult↗
PubMed2004

Systematic review: the epidemiology of ischaemic colitis.

BACKGROUND: Ischaemic colitis has been associated with co-morbid conditions, medications, vascular surgery and advanced age in case reports and case series. Few data exist on the baseline incidence in the general population or on the increased risk imposed by these risk factors. AIM: To systematically review the literature regarding the incidence, prevalence and risk factors for ischaemic colitis. METHODS: Searches of bibliographic databases were performed independently by two investigators. Studies were included if they used population-based samples, disease-specific population samples or case-control population-based samples of adults with ischaemic colitis, and reported the incidence, prevalence or risk factors for ischaemic colitis. Eligible articles were reviewed and data were abstracted in a duplicate, independent manner. RESULTS: Four studies were identified that reported the general population incidence and four that reported the disease-specific population incidence. The incidence of ischaemic colitis in general populations ranged from 4.5 to 44 cases per 100 000 person-years. The risk was increased two- to four-fold by either prevalent irritable bowel syndrome or chronic obstructive pulmonary disease. The risk was also increased in females and in subjects of 65 years and older. CONCLUSIONS: Ischaemic colitis is uncommon in the general population. The effect sizes of the most commonly reported risk factors have not been adequately quantified in population-based studies.

Adult↗
PubMed2004

Component and whole-system respiration fluxes in northern deciduous forests.

We measured component and whole-system respiration fluxes in northern hardwood (Acer saccharum Marsh., Tilia americana L., Fraxinus pennsylvanica Marsh.) and aspen (Populus tremuloides Michx.) forest stands in Price County, northern Wisconsin from 1999 through 2002. Measurements of soil, leaf and stem respiration, stem biomass, leaf area and biomass, and vertical profiles of leaf area were combined with biometric measurements to create site-specific respiration models and to estimate component and whole-system respiration fluxes. Hourly estimates of component respiration were based on site measurements of air, soil and stem temperature, leaf mass, sapwood volume and species composition. We also measured whole-system respiration from an above-canopy eddy flux tower. Measured soil respiration rates varied significantly among sites, but not consistently among dominant species (P < 0.05 and P > 0.1). Annual soil respiration ranged from 8.09 to 11.94 Mg C ha(-1) year(-1). Soil respiration varied linearly with temperature (P < 0.05), but not with soil water content (P > 0.1). Stem respiration rates per unit volume and per unit area differed significantly among species (P < 0.05). Stem respiration per unit volume of sapwood was highest in F. pennsylvanica (up to 300 micro mol m(3) s(-1)) and lowest in T. americana (22 micro mol m(3) s(-1)) when measured at peak summer temperatures (27 to 29 degrees C). In northern hardwood stands, south-side stem temperatures were higher and more variable than north-side temperatures during leaf-off periods, but were not different statistically during leaf-on periods. Cumulative annual stem respiration varied by year and species (P < 0.05) and averaged 1.59 Mg C ha(-1) year(-1). Leaf respiration rates varied significantly among species (P < 0.05). Respiration rates per unit leaf mass measured at 30 degrees C were highest for P. tremuloides (38.8 nmol g(-1) s(-1)), lowest for Ulmus rubra Muhlenb. (13.1 nmol g(-1) s(-1)) and intermediate and similar (30.2 nmol g(-1) s(-1)) for T. americana, F. pennsylvanica and Q. rubra. During the growing season, component respiration estimates were dominated by soil respiration, followed by leaf and then stem respiration. Summed component respiration averaged 11.86 Mg C ha(-1) year(-1). We found strong covariance between whole-ecosystem and summed component respiration measurements, but absolute rates and annual sums differed greatly.

Acer↗
PubMed2002

Spontaneous pancreatic islet amyloidosis in 40 baboons.

Spontaneous amyloidosis occurs in many nonhuman primate species but remains difficult to diagnose and treat. Nonhuman primates continue to offer promise as animal models in which to study amyloidosis in humans. Amyloidosis was not diagnosed clinically but was found histologically in four male and 36 female baboons. The baboons averaged 18 years of age at death (range, 7-28 years). Clinical signs, if present, were hyperglycemia and cachexia. Blood glucose values were elevated in 12 of 30 baboons with available clinical pathology data. Four baboons had been clinically diagnosed as diabetic and three were treated with insulin. Amyloid was found in the islets of Langerhans of the pancreas in 40 baboons; 35 baboons had amyloid only in the islets of Langerhans. Amyloid was found in nonislet tissue of baboons as follows: five, nonislet pancreas; four, intestine and adrenal; three, kidney; two, prostate and spleen; and one each, lymph node, liver, gall bladder, stomach, tongue, urinary bladder, and salivary gland. Sections of paraffin-embedded tissues were evaluated for amyloid with hematoxylin and eosin (HE) and congo red (CR) staining, and using immunohistochemistry for human islet amyloid polypeptide (IAPP), calcitonin gene-related peptide (CGRP), glucagon, pancreatic polypeptide (PP), somatostatin (SS), and porcine insulin. Islet amyloid was positive with HE in 40 baboons, with CR in 39 baboons, and with IAPP and CGRP in 35 baboons. IAPP and CGRP only stained islet amyloid. PP, SS, glucagon, and porcine insulin did not stain amyloid. Islet amyloidosis in the baboon appears to be difficult to diagnose clinically, age-related, and similar to islet amyloidosis in other species. The baboon may be a good model for the study of islet amyloidosis in humans.

Amyloid↗
PubMed2001

Pathogenesis of experimental Ebola Zaire virus infection in BALB/c mice.

Guinea-pigs and non-human primates have traditionally been used as animal models for studying Ebola Zaire virus (EBO-Z) infections. The virus was also recently adapted to the stage of lethal virulence in BALB/c mice. This murine model is now in use for testing antiviral medications and vaccines. However, the pathological features of EBO-Z infection in mice have not yet been fully described. To identify sites of viral replication and characterize sequential morphological changes in BALB/c mice, adult female mice were infected with mouse-adapted EBO-Z and killed in groups each day for 5 days post-infection. Tissues were examined by light microscopy, immunohistochemistry, electron microscopy and in-situ hybridization. As in guinea-pigs and non-human primates, cells of the mononuclear phagocytic system were the earliest targets of infection. Viral replication was observed by day 2 in macrophages in lymph nodes and spleen. By the time of onset of illness and weight loss (day 3), the infection had spread to hepatocytes and adrenal cortical cells, and to macrophages and fibroblast-like cells in many organs. Severe lymphocytolysis was observed in the spleen, lymph nodes and thymus. There was minimal infection of endothelial cells. All of these changes resembled those observed in EBO-Z-infected guinea-pigs and non-human primates. In contrast to the other animal models, however, there was little fibrin deposition in the late stage of disease. The availability of immunodeficient, "gene-knockout" and transgenic mice will make the mouse model particularly useful for studying the early steps of Ebola pathogenesis.

Animals↗
PubMed2000

The role of Mg2+ as an impurity in calcite growth.

Magnesium is a key determinant in CaCO3 mineralization; however, macroscopic observations have failed to provide a clear physical understanding of how magnesium modifies carbonate growth. Atomic force microscopy was used to resolve the mechanism of calcite inhibition by magnesium through molecular-scale determination of the thermodynamic and kinetic controls of magnesium on calcite formation. Comparison of directly measured step velocities to standard impurity models demonstrated that enhanced mineral solubility through magnesium incorporation inhibited calcite growth. Terrace width measurements on calcite growth spirals were consistent with a decrease in effective supersaturation due to magnesium incorporation. Ca(1-x)Mg(x)CO3 solubilities determined from microscopic observations of step dynamics can thus be linked to macroscopic measurements.

Journal Article↗
PubMed2000

Specialized dementia programs in residential care settings.

The authors conducted a telephone survey in 7 states to determine the prevalence of residential care specialized dementia programs (RC-SDPs) and to identify a sample of homes (n = 56) for more detailed study. The 56 homes were site visited, and data were gathered on facility administration, therapeutic environment, and characteristics of 259 randomly selected residents. Comparison data from 138 nursing home Special Care Units (NH-SCUs) and 1,340 of their residents were obtained from 4 studies conducted in the same 7 states. RC-SDPs were smaller, provided a more homelike environment, and had a higher proportion of residents paying privately, compared with NH-SCUs. Mean levels of cognitive and physical impairment among residents were higher in NH-SCUs; prevalences of psychotropic medication use and problem behaviors were similar. Among RC facilities, small homes were more homelike, provided fewer structured activities, and charged less than larger facilities. RC-SDPs include 5 types: small, independently operated homes; multiple small homes with joint administration; larger, all-dementia facilities; SDPs operated within larger, exclusively RC facilities; and RC-SDPs in multilevel facilities.

Aged↗
PubMed1999

Isolation and chemical analysis of a lipopolysaccharide from the outer membrane of the oral anaerobic spirochete Treponema pectinovorum.

Isolation of a putative lipopolysaccharide from the surface of the oral treponeme, Treponema pectinovorum, revealed it to contain larger amounts of 3-deoxy-D-manno-octulosonic acid compared with other oral Treponema species. This molecule was isolated from the outer membrane of T. pectinovorum and had chemical characteristics of a putative lipopolysaccharide. The yield of lipopolysaccharide was between 0.6% and to 1.1% of the bacterial dry weight. The purified molecule was resistant to the action of proteinases and consisted of both sugars and lipids. 3-Deoxy-D-manno-octulosonic acid and hexoses accounted for 6.1-8.7% and 17.6-20.2%, respectively of the dry weight. Carbohydrate compositional analysis revealed the presence of glucose, galactose, 2-acetamido-2-deoxy-glucose, rhamnose and 6-deoxy-talose in the molar ratio of 1.00:0.96:0.19:0.88:0.98, respectively. No heptose was detected. The fatty acid analysis determined the presence of straight chain, C13:00, C14:00, C15:00 and C17:00 acids, as well as branched chain, C13:00, C14:00 and two species of C15:00, acids. Electrophoretic analysis indicated that the lipopolysaccharide was present as two major species.

Cell Membrane↗
PubMed1999

Pathogenesis of experimental Ebola virus infection in guinea pigs.

The subtype Zaire of Ebola (EBO) virus (Mayinga strain) was adapted to produce lethal infections in guinea pigs. In many ways, the disease was similar to EBO infections in nonhuman primates and humans. The guinea pig model was used to investigate the pathologic events in EBO infection that lead to death. Analytical methods included immunohistochemistry, in situ hybridization, and electron microscopy. Cells of the mononuclear phagocyte system, primarily macrophages, were identified as the early and sustained targets of EBO virus. During later stages of infection, interstitial fibroblasts in various tissues were infected, and there was evidence of endothelial cell infection and fibrin deposition. The distribution of lesions, hematologic profiles, and increases in serum biochemical enzymes associated with EBO virus infection in guinea pigs was similar to reported findings in experimentally infected nonhuman primates and naturally infected humans.

Adrenal Glands↗
PubMed1998

Antibiotic treatment of experimental pneumonic plague in mice.

A mouse model was developed to evaluate the efficacy of antibiotic treatment of pneumonic plague; streptomycin was compared to antibiotics with which there is little or no clinical experience. Infection was induced by inhalation of aerosolized Yersinia pestis organisms. Antibiotics were administered by intraperitoneal injection every 6 hours for 5 days, at doses that produced levels of drug in serum comparable to those observed in humans treated for other serious infections. These studies compared in vitro to in vivo activity and evaluated the efficacy of antibiotics started at different times after exposure. Early treatment (started 24 h after challenge, when 0 of 10 mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, aztreonam, ampicillin, and rifampin (but not cefazolin, cefotetan, or ceftizoxime) demonstrated efficacy comparable to streptomycin. Late treatment (started 42 h after exposure, when five of five mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, and a high dose (20 mg/kg of body weight every 6 h) of gentamicin produced survival rates comparable to that with streptomycin, while all of the beta-lactam antibiotics (cefazolin, cefotetan, ceftriaxone, ceftazidime, aztreonam, and ampicillin) and rifampin were significantly inferior to streptomycin. In fact, all groups of mice treated late with beta-lactam antibiotics experienced accelerated mortality rates compared to normal-saline-treated control mice. These studies indicate that netilmicin, gentamicin, ciprofloxacin, and ofloxacin may be alternatives for the treatment of pneumonic plague in humans. However, the beta-lactam antibiotics are not recommended, based upon poor efficacy in this mouse model of pneumonic plague, particularly when pneumonic plague may be associated with bacteremia.

Animals↗
PubMed1998

Comparative neurovirulence and tissue tropism of wild-type and attenuated strains of Venezuelan equine encephalitis virus administered by aerosol in C3H/HeN and BALB/c mice.

To assess the potential for aerosol administration of vaccines for Venezuelan equine encephalitis virus (VEE), we compared the neurovirulence and tissue tropism of the wild-type Trinidad donkey (TrD) strain to those of the attenuated TC83 and V3526 strains of VEE in mice. Six to 8-week-old female C3H/HeN and BALB/c mice were aerosol exposed to one of the three VEE strains. Three mice of each strain were euthanatized at different times and their tissues were processed and stained using hematoxylin and eosin, immunohistochemistry, and in situ hybridization. All three viral strains infected the brains of mice and induced encephalitis. TrD spread caudally from the olfactory bulbs to all regions of the brain, caused widespread necrotizing panencephalitis by day 5, and resulted in 100% mortality (geometric mean = 7 days) in both mouse strains. By comparison, TC83 relatively spared the caudal regions of the brain but still caused 100% mortality in the C3H/HeN mice (geometric mean = 12 days), yet it did not kill any BALB/c mice. V3526 infectivity of the brain was the most limited, mainly affecting the neocortex and diencephalon. This virus was not lethal in either mouse strain. The TrD strain also infected the olfactory neuroepithelium, local lymphoid tissues, teeth, and vomeronasal organs, whereas the affinity of TC83 and V3526 outside the brain was essentially limited to the olfactory neuroepithelium. Attenuated VEE strains administered to mice by aerosol have restricted tissue tropism as compared with wild-type virus; however, even attenuated strains can infect the brain and induce encephalitis.

Animals↗
PubMed1997

Studies on the role of plasminogen activator in systemic infection by virulent Yersinia pestis strain C092.

Plasminogen activator is an outer membrane protease of Yersinia pestis encoded by the pla gene on plasmid pPst. Pla of the KIM-10 strain of Y. pestis appears to be required for the virulence from a subcutaneous (sc) but not an intraperitoneal (ip) or intravenous (iv) route of infection in mice. However, other strains of Y. pestis are highly virulent by the sc route yet lack pPst and pla. In this study, the pPst- Pestoides F strain was lethal to mice inoculated sc, with an LD50 (3 cfu), equal to that of C092, a virulent pPst+ strain. To analyse further the role of Pla in invasive infection, isogenic derivatives of C092, including one harboring pla with a frameshift mutation and another cured of pPst, were made. Although the ip LD50 of pPst- C092 and of the pla mutant were nearly identical to that of the wild type, the subcutaneous LD50 of the cured and mutant strains were 4 to 6 logs greater than that of wild type. Thus, pPst appears to be required for development of a lethal infection by some strains after sc inoculation but not after direct ip inoculation. Pla-associated virulence did not appear to be mediated by interference with the phagocyte chemoattractant C5a, as shown by the lack of correlation of C5a production with susceptibility to Y. pestis in C5a+ and C5a- congenic mice. In a footpad model of the early host response to subcutaneous infection, pPst- C092 proliferated at the subcutaneous injection site to a similar extent as did the wild type parent strain, and elicited a similarly large, local inflammatory response. However, the wild type was present at higher concentrations at more distant sites such as the popliteal lymph node and spleen.

Animals↗
PubMed1997

Experimental infection of nonhuman primates with sandfly fever virus.

Due to the lack of an animal model, previous studies of sandfly fever have relied upon human challenge trials. We examined the infectivity and potential pathogenicity of sandfly fever virus in cynomolgus monkeys (Macaca fascicularis). Three different preparations of sandfly fever virus. Sicilian strain, and a placebo were compared by different routes of administration. The most notable postchallenge clinical event was a decrease in lymphocytes in the intramuscularly challenged monkeys. Plaque-reduction neutralization responses peaked earlier in animals challenged intravenously as compared with those in animals challenged intramuscularly. There was no evidence for neurotropism or meningeal inflammation. Sandfly fever virus was infectious for cynomolgus monkeys, but produced no detectable clinical disease that might serve as a marker for animal modeling studies. On the other hand, the preclinical data provide supportive evidence for safe parenteral administration of a Sicilian strain of sandfly fever virus inoculum to humans as a challenge model for sandfly fever disease.

Animals↗
PubMed1997

Pathology of experimental Ebola virus infection in African green monkeys. Involvement of fibroblastic reticular cells.

BACKGROUND: Ebola virus has been responsible for explosive lethal outbreaks of hemorrhagic fever in both humans and nonhuman primates. Previous studies showed a predilection of Ebola virus for cells of the mononuclear phagocyte system and endothelial cells. OBJECTIVE: To examine the distribution of lesions and Ebola virus antigen in the tissues of six adult male African green monkeys (Cercopithecus aethiops) that died 6 to 7 days after intraperitoneal inoculation of Ebola-Zaire (Mayinga) virus. METHODS: Tissues were examined histologically, immunohistochemically, and ultrastructurally. RESULTS: A major novel finding of this study was that fibroblastic reticular cells were immunohistochemically and ultrastructurally identified as targets of Ebola virus infection. CONCLUSIONS: The role of Ebola virus-infected fibroblastic reticular cells in the pathogenesis of Ebola hemorrhagic fever warrants further investigation. This is especially important because of recent observations indicating that fibroblastic reticular cells, along with the reticular fibers they produce, maximize the efficiency of the immune response.

Adrenal Glands↗
PubMed1997

Bacterial filamentation of Yersinia pestis by beta-lactam antibiotics in experimentally infected mice.

OBJECTIVE: To identify alternatives to streptomycin for treating pneumonic plague, we evaluated beta-lactam antibiotics to treat experimental pneumonic plague in mice. METHODS: Mice were exposed to a lethal inhaled dose of Yersinia pestis and treated with beta-lactam antibiotics administered every 6 hours, starting 42 hours postexposure. RESULTS: The mice died or were euthanized in extremis 3 days postexposure. We observed marked bacterial filamentation of Y pestis in the tissues of mice treated with ceftazidime (10/10 mice), aztreonam (9/10 mice), or ampicillin (1/10 mice), but not in the tissues of mice treated with cefotetan, cefazolin, ceftriaxone, or saline. There was no evidence of septation of the filamentous bacteria by light or electron microscopy. The filamentous bacteria were confirmed as Y pestis based on their reactivity with rabbit anti-Y pestis F1 serum. CONCLUSIONS: Marked bacterial filamentation of Y pestis can be produced in vivo by certain beta-lactam antibiotics. This antibiotic-induced morphologic change is important because filamentous bacteria in clinical samples could possibly be confused with filamentous actinomycotic organisms.

Animals↗