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Biomedical subjects

W McCormick

Publications and source records attributed to W McCormick.

At least 19 recordsLinked to original sources
PubMed2006

Conservation of Pitx1 expression during amphibian limb morphogenesis.

In contrast to the pattern of limb emergence in mammals, chicks, and the newt N. viridescens, embryos such as Xenopus laevis and Eleutherodactylus coqui initiate pelvic limb buds before they develop pectoral ones. We studied the expression of Pitx1 in X. laevis and E. coqui to determine if this paired-like homeodomain transcription factor directs differentiation specifically of the hindlimb, or if it directs the second pair of limbs to form, namely the forelimbs. We also undertook to determine if embryonic expression patterns were recapitulated during the regeneration of an amputated limb bud. Pitx1 is expressed in hindlimbs in both X. laevis and E. coqui, and expression is similar in both developing and regenerating limb buds. Expression in hindlimbs is restricted to regions of proliferating mesenchyme.

Animals↗
PubMed2005

Serum cholesterol and risk of Alzheimer disease: a community-based cohort study.

OBJECTIVES: To examine the association of serum total cholesterol (TC) and high density lipoprotein (HDL) levels and subsequent incidence of dementia and Alzheimer disease (AD) in a population-based cohort study. METHODS: A cohort of cognitively intact persons, aged 65 and older, was randomly selected from Group Health Cooperative (GHC), a large health maintenance organization, and was assessed biennially for dementia. Premorbid levels of TC and HDL were obtained from a computerized clinical laboratory database at GHC. Cox proportional hazards regression was used to calculate hazard ratios (HR, 95% CI) for dementia and AD associated with quartiles of TC and HDL levels. RESULTS: Of the 2,356 eligible participants, 2,141 had at least one serum TC measure prior to the initial enrollment. Using the lowest TC quartiles as the reference group, the HR in the highest TC quartiles was not significantly elevated for dementia (1.16, 0.81 to 1.67) or for AD (1.00, 0.61 to 1.62) after adjusting for age, sex, education, baseline cognition, vascular comorbidities, body mass index, and lipid-lowering agent use. Serum HDL showed a similar lack of significant association with risk of dementia or AD. Models that included the presence of one or more APOE-epsilon4 alleles showed a typical association of epsilon4 with AD risk. This association was not materially modified by inclusion of TC level. CONCLUSION: The data do not support an association between serum total cholesterol or high density lipoprotein in late life and subsequent risk of dementia or Alzheimer disease (AD). The increased risk of AD with APOE-epsilon4 is probably not mediated by serum total cholesterol levels.

Age Factors↗
PubMed2004

Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study.

OBJECTIVE: To assess the association between statin therapy and risk of Alzheimer disease (AD) in a prospective cohort study with documented statin exposure and incident dementia. METHODS: This is a prospective, cohort study of statin use and incident dementia and probable AD. A cohort of 2,356 cognitively intact persons, aged 65 and older, were randomly selected from a health maintenance organization (HMO), and were assessed biennially for dementia. Statin use was identified using the HMO pharmacy database. A proportional hazards model with statin use as a time-dependent covariate was used to assess the statin-dementia/AD association. RESULTS: Among 312 participants with incident dementia, 168 had probable AD. The unadjusted hazard ratios (HRs) with statin use were 1.33 (95% CI 0.95 to 1.85) for all-cause dementia and 0.90 (CI 0.54 to 1.51) for probable AD. Adjusted corresponding HRs were 1.19 (CI 0.82 to 1.75) and 0.82 (CI 0.46 to 1.46). A subgroup analysis of participants with at least one APOE-epsilon4 allele who entered the study before age 80 produced an adjusted HR of 0.33 (CI 0.10 to 1.04). CONCLUSION: Employing time-dependent proportional hazards modeling, the authors found no significant association between statin use and incident dementia or probable AD. In contrast, when the data were analyzed, inappropriately, as a case-control study, the authors found an OR of 0.55 for probable AD, falsely indicating a protective effect of statins. Study design and analytic methods may explain the discrepancy between the current null findings and earlier findings.

Aged↗
PubMed2001

Applying scientific criteria to therapeutic interchange: a balanced analysis of low-molecular-weight heparins.

Under pressure to provide cost-effective healthcare, many healthcare systems have adopted Therapeutic Interchange (TI) programs-the interchange of therapeutically equivalent but chemically unique drugs-to reduce the total cost of therapy without compromising patient care. To be appropriate and feasible, a TI program for any class of drugs must meet certain rigorous criteria and undergo medical, financial, tactical, and legal reviews. Moreover, once a TI program is implemented, a process to monitor its success should be established. Application of the TI criteria to low-molecular-weight heparins (LMWHs) reveals that a blanket TI program for LMWHs does not appear advisable at this time.

Anticoagulants↗
PubMed1999

The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer disease in a community-based case series.

CONTEXT: A recent collaborative study found that apolipoprotein E (APOE) genotype, in conjunction with the clinical diagnosis of Alzheimer disease (AD), was useful in improving diagnostic specificity (correctly not diagnosing AD) relative to the clinical diagnosis alone. Since these samples are particularly enriched with patients with AD and the APOE epsilon4 allele, results may not be generalizable to patients seen in the general medical community. OBJECTIVE: To evaluate the diagnostic utility of the APOE genotype in diagnosing AD in a community-based case series from the largest health maintenance organization in an urban area. DESIGN: We examined the effect of including APOE genotype on the diagnosis of AD in a community-based case series of patients presenting with memory complaints. PATIENTS: Clinical and neuropathologic diagnoses and APOE genotype were obtained from 132 patients who underwent evaluation for dementia and subsequent autopsy. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values given various combinations of clinical diagnoses and the presence of an APOE epsilon4 allele. RESULTS: Of the 132 patients, 94 had neuropathologically confirmed AD, yielding a prevalence of 71%. The clinical diagnosis alone yielded a sensitivity of 84%, an estimated specificity of 50%, and positive and negative predictive values of 81% and 56%, respectively. The presence of an epsilon4 allele alone was associated with an estimated sensitivity of 59%, specificity of 71%, and positive and negative predictive values of 83% and 41%, respectively. Using the presence of clinical AD and an epsilon4 allele decreased the sensitivity to 49% and increased the specificity to 84%. The positive and negative predictive values were 88% and 40%, respectively. Alternatively, the clinical diagnosis of AD or the presence of an epsilon4 allele in individuals not meeting clinical criteria for AD increases the estimated sensitivity to 94% but decreases the specificity to 37%. The positive and negative predictive values were 79% and 70%, respectively. The changes in the sensitivity and specificity for the combined tests relative to clinical diagnosis alone offset each other. For lower prevalence communities, the positive predictive value will be much lower than those observed herein. CONCLUSIONS: Our findings do not support the use of APOE genotyping alone in the diagnosis of AD in the general medical community. Although the presence of an epsilon4 allele in older persons with clinical AD increased the probability of having AD and the absence of an epsilon4 allele in this group decreased the probability of having AD, the association is not strong enough in the differential diagnosis of non-Alzheimer dementia and AD.

Aged↗
PubMed1999

Validity and responsiveness of the Minimum Data Set.

OBJECTIVE: To determine the criterion validity and responsiveness to change over time of the Minimum Data Set (MDS). DESIGN: Cross sectional analysis comparing prospectively collected research data with MDS data reported from nursing homes on identical subjects. Longitudinal follow-up of subjects allowed for calculation of responsiveness to change over time. PARTICIPANTS: Subjects (n = 140) participating in epidemiological research on the natural history of Alzheimer's disease in the University of Washington Group Health Cooperative Alzheimer's Disease Patient Registry (ADPR) who entered nursing homes in Washington State from January 1990 through March 1996. MAIN OUTCOME MEASUREMENTS: Spearman's correlation coefficients to compare MDS cognitive performance scale scores with Mini-Mental State Examinations (MMSE), MDS behavior domain scores with ADPR Physician Behavior checklist scores, and MDS activities of daily living (ADL) functioning scores with Dementia Rating Scale scores for ADLs. Partial correlations were used to control for the number of days between MDS and ADPR assessments, age, and function in the other two MDS ratings of ADL, cognition, or behavior. We determined responsiveness by using the mean change in an effect size (ES) calculation for each domain of interest. RESULTS: MDS measures in all three domains were correlated modestly to the analogous ADPR research instruments, with correlation coefficients 0.45 for cognition, 0.50 for behavior, and 0.59 for ADL functioning. Controlling for age, time between ADPR and MDS assessments, and the MDS ratings of the other two MDS domains did not improve the correlations significantly. In a subgroup of 60 subjects followed for an average of 636 days, the Cognitive performance scale of the MDS had a slightly larger effect size (ES = 0.60) than the Folstein Mini-Mental Status Exam (ES = 0.39) used by the ADPR. However, the Dementia Rating Scale (ES = 0.77) used by the ADPR researchers reflected more change over time than the ADL domain of the MDS (ES = 0.02). The MDS behavior domain (ES = 0.058) was comparable to the research behavior checklist (ES = 0.065). CONCLUSIONS: These data demonstrate reasonable criterion validity of the MDS and the MMSE, ADL, and behavior rating scales and suggest that the MDS data is of adequate validity for research purposes in these areas. The MDS was less able to capture dementia-related change in ADLs in this population of patients with dementia even though the same nursing home staff completing the MDS often supplied the information for completing the research scales. As a result, the MDS may be limited as an outcome assessment instrument.

Activities of Daily Living↗
PubMed1999

Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series.

OBJECTIVES: Most clinico-neuropathological correlative studies of Alzheimer's Disease (AD) are based on research cohorts that are not necessarily generalizable to patients seen in the general medical community. In this study, we examine the accuracy of the criteria used in diagnosing AD in a community-based case series of patients with memory complaints. DESIGN AND PARTICIPANTS: Clinical and neuropathological diagnoses were obtained from 134 patients evaluated for dementia who subsequently underwent autopsy. SETTING: Subjects who exhibited new symptoms of dementia and were enrolled in the University of Washington/Group Health Cooperative Alzheimer's Disease Patient Registry were eligible for this study. MEASUREMENTS: Clinico-pathological correlation was performed using NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. RESULTS: Ninety-five of the 134 cases studied met CERAD neuropathological criteria for AD. The sensitivity of NINCDS-ADRDA "probable AD" was 83% (diagnosing AD correctly) and overall clinical diagnostic accuracy was 75%. However, there was a high rate of additional neuropathological findings. Only 34 of the 94 cases had pure AD on neuropathology, whereas the remainder frequently had coexisting vascular or Parkinson's disease lesions. CONCLUSIONS: This study of a large series of community-based incident dementia cases provides a way of judging the adequacy of currently available clinical diagnostic criteria. It also shows that co-existing neuropathological findings are common in community-based AD.

Aged↗
PubMed1997

Progression to dementia in patients with isolated memory loss.

BACKGROUND: The diagnosis of dementia requires both memory loss and at least one other type of cognitive impairment. The natural history of patients with severe memory loss but no other type of cognitive impairment is poorly understood. We studied progression to dementia in patients with isolated memory loss. METHODS: From a registry of 811 patients with cognitive complaints, 21 patients with severe isolated memory loss of unknown cause were identified and followed up for a mean of 48 months. A comparison group of 198 patients on the same register was identified with newly recognised cognitive complaints but without dementia or isolated memory loss (mean follow-up 31 months). We did a range of neuropsychological tests at intake. FINDINGS: During follow-up, 48% (n = 10) of patients with isolated memory loss-developed dementia compared with 18% (n = 36) of the comparison group. Life-table analysis showed the mean times to a diagnosis of dementia was 3.77 years (95% CI 2.99-4.56) and 5.96 years (5.60-6.31), respectively (p = 0.01). The neuropsychological tests did not predict which patients would progress to dementia. INTERPRETATION: Patients with severe isolated memory loss have an increased risk of developing dementia and should be closely followed-up.

Adult↗
PubMed1996

Identification and analysis of the dissimilatory nitrous oxide reduction genes, nosRZDFY, of Rhizobium meliloti.

The complete nos region essential for dissimilatory nitrous oxide reduction by the endosymbiotic diazotroph Rhizobium meliloti was identified in a cosmid (pYC7) carrying a 10.1-kb EcoRI fragment of the nod megaplasmid. This gene region was localized by Southern hybridization and Tn5 mutagenesis to within 8 kb downstream from the fixGHIS cluster. Nucleotide sequence determination of a 4.6-kb DNA segment including the structural gene nosZ and its flanking regions showed sequence homology and similarity in genetic organization with the nosRZDFY genes of Pseudomonas stutzeri Zobell. The genes were arranged in three complementation groups, comprising the nosZ structural gene, the nosR regulatory gene, and the nosDFY copper-processing genes. The derived amino acid sequence of the R. meliloti nosZ product (a multi-copper nitrous oxide reductase) was more similar to those of the analogous gene products of Paracoccus and Pseudomonas species than to that of Alcaligenes eutrophus. The nosZ gene was preceded by nosR, which encodes a regulatory protein containing C-terminal cysteine clusters similar to those present in the 4Fe-4S binding region of bacterial ferredoxins, The nosDFY genes, located downstream from nosZ, were identified as copper-processing genes encoding a periplasmic protein, an ATP/GTP-binding protein, and a membrane protein presumably forming a copper-processing system. A consensus sequence for an Anr- or Fnr-binding site similar to that in the upstream sequence of nosZ in Paracoccus denitrificans or P. stutzeri was absent in R. meliloti. No rpoN-binding site preceding the nos genes was detected, and none of the Tn5 insertions in the nos gene region affected symbiotic N2-fixing ability.

Amino Acid Sequence↗
PubMed1994

The Mini-Mental State Examination score and the clinical diagnosis of dementia.

To set a working cutoff score for the referral to diagnostic examination, we evaluated 150 consecutive patients with complaints potentially related to dementia, using the Mini-Mental State Examination (MMSE). All patients were later given a complete, standardized work-up and diagnosis as part of our Alzheimer's Disease Patient Registry protocol. Dementia diagnosis was made, consistent with accepted criteria, by consensus of the physicians and psychologist. Diagnosis was reaffirmed after 1-year follow-up exam; 133 of the 150 original patients completed follow-up (80 dementia, 53 no dementia). We evaluated the initial MMSE score compared with the follow-up diagnosis. Sensitivity, specificity, and predictive values were calculated for MMSE scores ranging from 22 through 29. The conventional cutoff score of < 24 shows a sensitivity of 0.63 and a specificity of 0.96; sensitivity increased at higher cutoff scores. Multivariate analysis showed that educational level added significant prediction only at scores of > or = 27. We conclude that an MMSE score of 26 or 27 should be used as a cutoff score in symptomatic populations with similar educational and socioeconomic backgrounds when the goal is to miss few true cases. Population surveys where the expected prevalence is low may require a different cutoff score to indicate the need for further diagnostic evaluation.

Aged↗
PubMed1994

Causes of death associated with Alzheimer disease: variation by level of cognitive impairment before death.

OBJECTIVE: To describe causes of death for patients with Alzheimer disease (AD) and other dementing illnesses enrolled in a population-based Alzheimer disease patient registry (ADPR) and to describe the variation in causes by the level of cognitive impairment before death in probable AD cases. SETTING: The ADPR enrolls and diagnoses newly recognized potential dementia cases occurring in a large, stable health maintenance organization. To date, 654 cases have been enrolled and followed annually to monitor cognitive decline and verify initial diagnosis. DESIGN: Longitudinal descriptive study. PATIENTS: ADPR enrollees who have died. MEASUREMENTS: Death certificates were obtained for all who died (total n = 104, probable AD = 55); reported causes of death were reviewed by a physician to determine the underlying cause. AD patients were categorized according to their Mini-Mental State Exam score (cognitive impairment) within 12 months of death as (a) mildly (21+), (b) moderately (15-20), or (c) severely (0-14) impaired, and underlying cause and all reported causes of death for each group were tabulated. MAIN RESULTS: Among probable AD patients, pneumonia and AD were most often recorded on death certificates when cognitive impairment within the year prior to death had reached the severe level; heart disease, stroke, and other common causes of death predominated in AD patients who were less cognitively impaired. CONCLUSIONS: When AD cases were followed from first diagnosis to death, the causes of death varied by level of cognitive impairment. Illnesses potentially amenable to treatment caused death at all levels of disease, but more so early in the course of AD. Cognitive impairment may make patients less able to recognize and report symptoms of medical problems, thereby complicating efforts to intervene.

Aged↗
PubMed1986

Hospice care in a long-term skilled-care facility.

Although the acute care hospital cannot provide care for terminally ill patients who are not receiving active therapy, a hospice unit has much to offer such patients. Since the elderly and the chronically ill also can benefit from palliative and supportive care, a long-term skilled-care facility is an ideal setting for a hospice unit. In this article, the authors discuss the various services provided by a hospice unit, where the emphasis is on care rather than cure.

Hospices↗
PubMed1984

Depo-medroxyprogesterone acetate compared with conjugated estrogens for the treatment of postmenopausal women.

Forty-three women who had undergone a natural or surgical menopause were randomized to receive either 0.625 mg of conjugated estrogens or an intramuscular injection of 150 mg of depo-medroxyprogesterone acetate (DMPA) for 25 days each month. Vasomotor symptoms were recorded before treatment for three weeks and weekly thereafter for three months. Serum estradiol (E2) and estrone (E1) were measured before and during the second month of treatment, as were urinary calcium, hydroxyproline, and creatinine levels. Vasomotor symptoms decreased significantly in both groups, and this reduction was of a similar magnitude with either treatment. Whereas 18% of patients in both groups did not have a reduction in vasomotor symptoms, of those women who did benefit, vasomotor symptoms decreased 61.5 +/- 7.5% with conjugated estrogens and 69.4 +/- 7.7% with DMPA. Eighteen percent of patients treated with conjugated estrogens reported no vasomotor symptoms whatsoever, as compared with 33% among those treated with DMPA. Serum estrone and estradiol increased in patients receiving conjugated estrogens, but were lower in women treated with depo-medroxyprogesterone acetate. Urinary calcium/creatinine and hydroxyproline/creatinine ratios were significantly lowered to the premenopausal range in women treated with conjugated estrogens and DMPA. There were no differences in these ratios when the two treatments were compared. Adverse side effects such as vulvovaginal complaints and weight gain were negligible in both groups and the complaints of dyspareunia were similar. The data from this short-term study suggest that depo-medroxyprogesterone acetate affords a suitable alternative to estrogen therapy for reducing vasomotor symptoms and may prevent bone resorption as well.

Adult↗
PubMed1980

Prolactin synthesis and release during pregnancy and puerperium.

Prolactin (PRL) synthesis and its release following thyrotropin-releasing hormone (TRH) administration during pregnancy and puerperium was studied in 45 women. Mean baseline E2 increased from 1,900 +/- 384 (SEM) pg/ml in the first trimester to 3,520 +/- 849 in the second trimester (P less than 0.05) and 43,057 +/- 5,765 pg/ml in the third trimester (P less than 0.001) of pregnancy. Mean baseline progesterone increased from 27.6 +/- 3.2 ng/ml in the first trimester to 41.9 +/- 6.6 in the second trimester (P less than 0.01) and 109.3 +/- 11.2 ng/ml in the third trimester (P less than 0.001) of pregnancy. Ten days after delivery, mean E2 dropped to 13 +/- 2.9 pg/ml and progesterone dropped to 0.56 +/- 0.07 ng/ml in the lactating women; in the nonlactating women, mean E2 level was 100 +/- 44 pg/ml and mean progesterone was 0.63 +/- 0.09 ng/ml. Baseline PRL increased from 27 +/- 15 ng/ml in the third trimester (P less than 0.002). The increased synthesis of PRL with increasing gestation was thought to be due to the stimulatory effects of E2 and progesterone, resulting in hyperplasia of the lactotrophs. In response to TRH, PRL demonstrated a significant increase from the first trimester to the second, with no further increase in the third. Therefore, it appears that the PRL reserve increases only during the first and second trimesters of pregnancy. Ten days after delivery, baseline PRL in response to TRH decreased to levels found in the first and second trimesters. However, the lactating women released less PRL than the nonlactating subjects (P less than 0.01), since PRL is released with each lactating episode which in turn probably reduces the PRL reserve.

Estradiol↗
PubMed1979

Nonpharmacy outlets providing prescription medications to ambulatory patients.

Nonpharmacy outlets providing prescription medication to ambulatory patients in Alachua County, Florida, were investigated. The sample included 16 ambulatory clinics and 44 dispensing physicians. The types of medications dispensed and dispensing procedures used by these outlets are described. The magnitude of prescription drug dispensing in ambulatory clinics and physicians' offices was far greater than was initially expected. Numerous drug-related problems were identified within these outlets, including a failure to comply with state and federal laws, inadequate drug control and storage, and inadequate patient medication records. Practicing pharmacists should consider the possibility of their patients receiving medication from similar outlets in evaluating therapies for appropriateness and interactions. In addition, such centers have apparent need for pharmacy consultation services to ensure adherence to the principles of responsible pharmaceutical services.

Adult↗