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Biomedical subjects

C Knott

Publications and source records attributed to C Knott.

At least 19 recordsLinked to original sources
PubMed2005

Disease and injury among participants in the Agricultural Health Study.

The Agricultural Health Study (www.aghealth.org) is a cohort of 89,658 pesticide applicators and their spouses from Iowa and North Carolina assembled between 1993 and 1997 to evaluate riskfactorsfor disease in ruralfarm populations. This prospective study is just now reaching sufficient maturity for analysis of many disease endpoints. Nonetheless, several analyses have already provided interesting and important leads regarding disease patterns in agricultural populations and etiologic clues for the general population. Compared to the mortality experience of the general population in the two states (adjusted for race, gender, age and calendar time), the cohort experienced a very low mortality rate overall and for many specific causes and a low rate of overall cancer incidence. A few cancers, however, appear elevated, including multiple myeloma and cancers of the lip, gallbladder, ovary, prostate, and thyroid, but numbers are small for many cancers. A study of prostate cancer found associations with exposure to several pesticides, particularly among individuals with a family history of prostate cancer. Links to pesticides and other agricultural factors have been found for injuries, retinal degeneration, and respiratory wheeze. Methodological studies have determined that information collected by interview is unbiased and reliable. A third round of interviews scheduled to begin in 2005 will collect additional information on agricultural exposures and health outcomes. The study can provide data to address many health issues in the agricultural community. The study investigators welcome collaboration with interested scientists.

Accidents, Occupational↗
PubMed2004

Decision-making about hormone replacement therapy by women in England and Scotland.

OBJECTIVE: The aim of this study was to explore women's decision-making about the balance of risks and benefits of taking hormone replacement therapy (HRT) based on the latest evidence from the Women's Health Initiative (WHI) trial of combined HRT. METHODS: Women aged 50-69 years, who were eligible for the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) trial, were invited to participate in one of eight focus groups. Participants were asked to discuss their views about taking HRT based on the latest international evidence. RESULTS AND CONCLUSIONS: Eighty-two women participated overall. Qualitative content analysis was applied to the discussion transcripts. Women regarded the decisions they make about taking HRT as highly personal, and, for women currently taking HRT, the overwhelming reason for continuation was perceived improvement in quality of life regardless of either the risks or the benefits in the longer term.

Aged↗
PubMed2002

Elevated glial brain-derived neurotrophic factor in Parkinson's diseased nigra.

We show the cellular distribution of immunoreactivity (IR) for brain-derived-neurotrophic-factor (BDNF), neurotrophin-3 (NT-3) and tyrosine kinase receptors TRKB and TRKC in idiopathic Parkinson's disease (IPD) and controls at post-mortem. In both groups, nigral neurons, astrocytes, ramified and amoeboid microglia expressed all antigens. Caudate-putamen neurons expressed all antigens except BDNF with similar distribution between groups. In IPD nigra, increased numbers of BDNF-IR and, less frequently, NT-3-IR ramified glia surrounded fragmented neurons, accompanied by BDNF-IR in surrounding neuropil. Amoeboid microglia were abundant only in IPD nigral scars. In IPD, glia might up-regulate neurotrophins in response to signals released from failing nigral neurons.

Aged↗
PubMed2002

Sensitivity of the Procleix HIV-1/HCV assay for detection of human immunodeficiency virus type 1 and hepatitis C virus RNA in a high-risk population.

The Procleix HIV-1/HCV Assay is a high-throughput nucleic acid test for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA during blood donor screening. This study evaluated the clinical sensitivity of the Procleix assay and assessed the assay's ability to identify HIV-1- and HCV-infected individuals undetected by standard serologic tests. Plasma samples were obtained prospectively from 539 individuals at high risk for HIV-1 and HCV infection at seven clinics affiliated with Johns Hopkins University. Samples were tested in the Procleix HIV-1/HCV Assay and, if reactive, were then tested in the Procleix HIV-1 and HCV discriminatory assays to differentiate the source of viral RNA positivity. Of these 539 subjects, 287 (53.2%) tested reactive in the Procleix HIV-1/HCV Assay. In discriminatory assay testing, 12 of 287 subjects (4.2%) were reactive for HIV-1 RNA only, 260 (90.6%) were reactive for HCV RNA only, and 11 (3.8%) were coinfected with HIV-1 and HCV. The clinical sensitivity for samples tested neat was 100% for HIV-1 and 99.3% for HCV. Three subjects with Procleix HCV reactive/seronegative results seroconverted upon follow-up and were confirmed as Procleix HCV yield cases. The Procleix HIV-1/HCV Assay is a highly sensitive test that detects ongoing and early HIV-1 and HCV infection in a significant number of subjects at high risk for these diseases. Confirmation of Procleix yield cases upon follow-up demonstrated the ability of the Procleix HIV-1/HCV Assay to detect the presence of HIV-1 and HCV in blood earlier than standard serologic tests.

AIDS Serodiagnosis↗
PubMed2001

Universal newborn hearing screening coming soon: "hear's" why.

Screening the hearing of all newborns, both NICU and well nursery, is rapidly becoming the standard of care. The impetus for universal newborn hearing screening (UNHS) has come from outside the domain of nursing and the newborn nursery. Because nursing will be involved in nearly all aspects of UNHS, nurses need a thorough knowledge base about permanent childhood hearing loss (PCHL) and UNHS. Technology exisits today that can objectively and physiologically screen for this condition at a cost comparable to metabolic screening. PCHL occurs more than twice as often as all the hemoglobinopathies and inborn errors of metabolism combined. Undiagnosed hearing loss often leads to permanent developmental delays. The ultimate goal of early diagnosis and intervention for a congenital hearing loss is to enable the child to develop language and communication skills that correspond to his chronological age and innate cognitive abilities.

Developmental Disabilities↗
PubMed2000

Glial heterogeneity in expression of the inwardly rectifying K(+) channel, Kir4.1, in adult rat CNS.

Previous electrophysiological evidence has indicated that astrocytes and oligodendrocytes express inwardly rectifying K(+) channels both in vitro and in vivo. Here, for the first time, we have undertaken light microscopic immunohistochemical studies demonstrating the location of one such channel, Kir4.1, in both cell types in regions of the rat CNS. Some astrocytes such as those in the deep cerebellar nuclei, Bergmann glia, retinal Müller cells, and a subset in hippocampus express Kir4.1 immunoreactivity, but not others including those in white matter. Oligodendrocytes also express this protein, strongly in perikarya and to a lesser extent in their processes. Expression of Kir4.1 in astrocytes and oligodendrocytes would enable these cells to clear extracellular K(+) through this channel, whereas nonexpressors might use other mechanisms.

Animals↗
PubMed2000

Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2.

Degeneration of dopaminergic neurons and focal gliosis are pathological hallmarks of Parkinson's disease and although the brain is described as immune-privileged focal immune reactions surround failing nigral neurons. We examined the cellular distribution of pro- and anti-inflammatory molecules in human parkinsonian and neurologically normal substantia nigra and caudate-putamen postmortem. An up-regulation of nitric oxide synthase- and cyclo-oxygenase-1- and -2-containing amoeboid microglia was found in parkinsonian but not control nigra. Astroglia contained low levels of these molecules in both groups. Lipocortin-1-immunoreactive amoeboid microglia were present within the astrocytic envelope of neurons adjacent to or within glial scars in parkinsonian nigra only. Lipocortin-1 is known to have neuroprotective and anti-inflammatory properties. Up-regulation of nitric oxide synthase is generally associated with neurodestruction whereas prostaglandin synthesis may be either neurodestructive or protective. The balance of these molecules is likely to be decisive in determining neuronal survival or demise.

Aged↗
PubMed2000

Neurologic function among termiticide applicators exposed to chlorpyrifos.

Chlorpyrifos is a moderately toxic organophosphate pesticide. Houses and lawns in the United States receive a total of approximately 20 million annual chlorpyrifos treatments, and 82% of U.S. adults have detectable levels of a chlorpyrifos metabolite (3,5, 6-trichloro-2-pyridinol; TCP) in the urine. The U.S. Environmental Protection Agency has estimated that there are 5,000 yearly reported cases of accidental chlorpyrifos poisoning, and approximately one-fourth of these cases exhibit symptoms. Organophosphates affect the nervous system, but there are few epidemiologic data on chlorpyrifos neurotoxicity. We studied neurologic function in 191 current and former termiticide applicators who had an average of 2.4 years applying chlorpyrifos and 2.5 years applying other pesticides, and we compared them to 189 nonexposed controls. The average urinary TCP level for 65 recently exposed applicators was 629.5 microg/L, as compared to 4.5 microg/L for the general U.S. population. The exposed group did not differ significantly from the nonexposed group for any test in the clinical examination. Few significant differences were found in nerve conduction velocity, arm/hand tremor, vibrotactile sensitivity, vision, smell, visual/motor skills, or neurobehavioral skills. The exposed group did not perform as well as the nonexposed group in pegboard turning tests and some postural sway tests. The exposed subjects also reported significantly more symptoms, including memory problems, emotional states, fatigue, and loss of muscle strength; our more quantitative tests may not have been adequate to detect these symptoms. Eight men who reported past chlorpyrifos poisoning had a pattern of low performance on a number of tests, which is consistent with prior reports of chronic effects of organophosphate poisoning. Overall, the lack of exposure effects on the clinical examination was reassuring. The findings for self-reported symptoms raise some concern, as does the finding of low performance for those reporting prior poisoning. Although this was a relatively large study based on a well-defined target population, the workers we studied may not be representative of all exposed workers, and caution should be exercised in generalizing our results.

Adult↗
PubMed1999

BRCA1 partially reverses the transforming activity of the ras oncogene.

The BRCA1 gene is associated with hereditary breast and ovarian cancers. BRCA1 fits the model of a classic tumor suppressor gene, a hypothesis supported by recent work demonstrating that expression of BRCA1 inhibits growth of breast and ovarian cancer cell lines. The present study was designed to test the potential of BRCA1 to reverse the transforming activity of the ras oncogene. The v-Ha ras oncogene was cloned downstream of the retrovirus LTR and stably expressed in Rat-1 cells (Rat-1/ras). Rat-1/ras (R/R) cells were fully transformed as indicated by change in morphology, colony formation in soft-agarose and tumor induction in nude mice. BRCA1 was stably expressed in R/R cells under the CMV promoter (R/R-BRCA1). The expression of ras and BRCA1 was confirmed by Western blot using monoclonal antibodies (mAbs) specific to ras and BRCA1, respectively. R/R-BRCA1 cells grew slower than the negative control, which was R/R cells transfected with vector alone (R/R-pCEP4). R/R-BRCA1 cells generated approximately 5 to 10 times less colonies in a soft-agarose assay compared to the negative control. When injected into nude mice, R/R-BRCA1 cells exhibited a delayed onset of tumorigenesis and generated smaller tumors compared to R/R or R/R-pCEP4 cells. These data strongly suggest that BRCA1 partially reverses the transforming activity of the v-Ha ras oncogene indicating that BRCA1 can bypass the effects of the v-Ha ras oncogene on cell growth. BRCA1, therefore, may be used in therapy of tumors arising due to activation of v-Ha ras oncogene.

Animals↗
PubMed1998

Substituting home care for hospitalization: the role of a quick response service for the elderly.

The purpose of the present study was to examine the role of a rapid access home-based service as a means for the elderly to avoid admission to an acute-care hospital. The setting for the study included emergency departments in three acute care hospitals and a home care program in a mid-size Canadian city. Multiple sources of information were obtained to evaluate the service. Hospital emergency department records and home care records were reviewed. Patients who participated in the service (n = 96) and physicians and nurses (n = 119) who had involvement with the service were surveyed appraising the service in terms of relevance, access, quality and coordination. Study results revealed that elderly women with multiple health problems who lived alone were the most frequent users of the service. The majority of the patients admitted to the service presented with problems of a functional nature that were the result of a fall or mobility problems. The results indicated that the service did avert hospital admissions and facilitated a process by which patients could avoid the intermediate step of hospitalization before placed in a higher level of care or returning to previous levels of functioning. Economic analysis indicated that the value of the service stemmed from the benefits to patients and caregivers rather than from cost savings offered to acute care hospitals.

Activities of Daily Living↗
PubMed1995

Lamotrigine as an add-on drug in typical absence seizures.

INTRODUCTION: Lamotrigine is licensed in many countries for use in patients with partial seizures. Evidence suggests that it may also be effective in generalised epilepsies. MATERIAL & METHODS: We analysed retrospectively our patients with idiopathic generalised epilepsy with refractory absences. RESULTS: Fifteen patients with idiopathic generalised epilepsies were identified who had been treated with lamotrigine for 3 months or more. All patients were also treated with sodium valproate. Fourteen patients had active absences. Nine (64%) had a total or virtual cessation of absences and in a further patient they became milder and less frequent. One patient reported an increase in seizures. The effective dose of lamotrigine was 1.6-3.0 mg/kg/day in children and 25-50 mg/day in adults. Patients who responded did so after the first or second dose. Lamotrigine was well tolerated. CONCLUSION: Low-dose lamotrigine added to sodium valproate appears to be effective in typical absence seizures. A therapeutic interaction of the two drugs seems likely.

Adolescent↗
PubMed1995

Therapy of streptozotocin induced diabetes with a bifunctional antibody that delivers vinca alkaloids to IL-2 receptor positive cells.

IVA039.1 is a bifunctional antibody with specificity for the murine IL-2 receptor and vinca alkaloids. Biodistribution studies show that IVA039.1 can target and deliver vinca alkaloids to tissues that contain IL-2 receptor positive cells. Vinca alkaloids are lymphocytotoxic. Therapy of diabetic mice with IVA039.1 plus vincristine results in a significant decrease in the glucose levels of diabetic compared to untreated mice. The therapeutic effect of IVA039.1 plus vincristine therapy was additive but surprisingly not synergistic. The binding of IVA039.1 to vincristine has moderate affinity with a slow off rate. In vitro studies suggest that, when bound to IVA039.1, the vincristine is inactivated. We attribute the lack of an enhanced therapeutic response to bifunctional antibody therapy using IVA039.1 plus vincristine to the inaccessibility of the drug to the target cells.

Animals↗
PubMed1994

Will immunogenicity limit the use, efficacy, and future development of therapeutic monoclonal antibodies?

While monoclonal antibodies show promise for use in the treatment of a variety of disease states, including cancer, autoimmune disease, and allograft rejection, generation of anti-antibody responses still remains a problem. For example, 50% of the patients who receive OKT3 produce blocking antibodies that interfere with its binding to T cells, thus decreasing the therapeutic effect (51). HAMA responses have also interfered with tumor imaging (39,40) and radioimmunotherapy (56). The generation of an anti-antibody response is dependent on many factors. These include the dose of antibody, the number of injections of antibody, the immunogenicity of the antibody, the form of the antibody, and the immunocompetence of the recipient. Predictably, both the number of injections of antibody and the dosage are influential in the generation of an anti-antibody response. It is apparent that human antibodies, chimeric antibodies, and mouse Fab fragments are much less likely to induce anti-antibody responses than intact mouse monoclonal antibodies or mouse F(ab')2 fragments when one injection is administered. Injections of human or chimeric antibodies appears to reduce immunogenicity, but the probability that anti-antibody responses can still be induced on multiple injections must be considered and appropriately evaluated. Several areas demand extensive investigation to enhance the clinical utility of monoclonal antibodies. First, results of thorough clinical trials with human or chimeric antibodies need to be evaluated for the induction of anti-antibodies after multiple injections of antibodies. Second, less immunogenic forms of antibodies (Fab, Fv) need to be studied for their clinical efficacies and for their abilities to induce anti-antibody responses.

Animals↗
PubMed1993

Age-related regional sensitivity to pertussis toxin-mediated reduction in GABAB receptor binding in rat brain.

GABAB binding was performed in rat brain membranes incubated with pertussis toxin (PTX; 7-15 micrograms/mg protein) or vehicle during postnatal development. In peripubertal rats, GABAB binding was reduced by PTX in corpus striatum and hippocampus but not in cortex or cerebellum, while in sexually mature adults binding was reduced in all areas except the corpus striatum. These data may indicate regional differences in the postnatal development of GABAB receptor-G protein linkage.

Aging↗