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Biomedical subjects

M A Williams

Publications and source records attributed to M A Williams.

At least 127 records · Page 7Linked to original sources
PubMed1999

Body mass index and risk of renal cell carcinoma.

To examine the association between body mass index and renal cell carcinoma risk, we analyzed data from a case-control study of members of a health maintenance organization in western Washington State. We identified cases diagnosed between 1980 and 1995 through a population-based cancer registry. We selected controls from membership files. We collected adult weight and height from medical records. Increased body mass index was associated with increases in risk for both men and women (for the top quartile relative to the bottom quartile of maximum body mass index: in women, OR = 3.3, 95% CI = 1.2-8.7; in men, OR = 2.3, 95% CI = 1.2-4.5).

Adult↗
PubMed1999

Tumor necrosis factor alpha regulates CXC chemokine receptor expression and function.

The alpha chemokine family is central to the participation of neutrophils in the acute inflammatory response. These substances interact with neutrophils through two cell surface receptors, CXCR-1 and CXCR-2 (formally known as IL-8R-1 and IL-8R-2). We investigated the possible regulatory effects of tumor necrosis factor alpha (TNFalpha) pretreatment on CXCR-1 and CXCR-2. To this end, we examined these receptors with flow cytometry, radioligand binding, Northern blot analyzes, calcium mobilization, and chemotaxis experiments on human neutrophils. In flow cytometry experiments, TNFalpha pretreatment substantially decreased cell surface CXCR-2 receptor levels but showed partial recovery at 120 min. On the other hand, CXCR-1 receptor levels had a sharp decline at 15 min and maintained that level to 120 min. Northern blot analyzes showed that mRNA levels of both IL-8 receptors were essentially unchanged after 45 min of TNFalpha pretreatment, but declined markedly following 2 h of pretreatment. Chemotaxis experiments on cells treated with TNFalpha for 5-120 min showed a substantial down-regulation of chemotaxis to IL-8 and GROalpha. This was noted to be much greater than the decline in cell surface receptors. Calcium mobilization experiments revealed minimal inhibition of the IL-8-induced increase in calcium after pretreatment with TNFalpha, but the response to NAP-2 was substantially inhibited. The data demonstrate differential regulation of the IL-8 receptor.

Blotting, Northern↗
PubMed1999

Length of pregnancy in African Americans: validation of a new predictive rule.

This study evaluated whether a new predictive rule is more accurate for estimating the length of pregnancy in African Americans than Nägele's rule, the accepted standard. After identifying women in early pregnancy, telephone interviews were conducted to obtain information about 16 previously established determinants of gestational length. Based on these data, a linear multivariate regression model was used to predict an estimated delivery date (EDD) for each mother. In addition, the EDD was determined using Nägele's rule. Later, the actual delivery date was compared with the EDD predicted by the new rule and with the EDD predicted by Nägele's rule. Each pregnancy was assigned to its better prediction group, either the new rule's group or the Nägele's rule group. Fifty-seven pregnancies were identified prospectively and monitored. The new rule predicted the actual delivery date more accurately in 66% (37/56) of pregnancies, Nägele's rule was a better predictor in 34% (19/56) of pregnancies, and both rules were equally accurate in predicting the delivery date for one pregnancy. The new rule was more precise than Nägele's rule (P = .022) when the binomial distribution was used. When using the linear regression model rule, a more accurate EDD can be determined for African-American women. Moreover, it is possible to predict the risk of preterm delivery (those occurring > 3 weeks earlier than the EDD).

Adult↗
PubMed1999

Severe renal hemorrhage caused by pyelonephritis in 7 horses: clinical and ultrasonographic evaluation.

Case records of 7 horses diagnosed with pyelonephritis were reviewed to determine common features that might aid in diagnosis, treatment, and prognosis of this disease. All 7 horses had been admitted for evaluation of hematuria. During cystoscopy of 5 horses, hemorrhage was observed from one or both ureters. Renal biopsy of 1 horse, laboratory analysis of ureteral discharge of 2 horses, and renal ultrasonography of all horses indicated that pyelonephritis was the cause of hemorrhage. Sonographic renal changes included decreased length, increased echogenicity, abnormal outline, loss of corticomedullary distinction, pyelectasia, and focal hypoechoic or hyperechoic cortical defects. Renal hemorrhage in all horses eventually resolved but recurred in 4 of 5 horses that were followed long-term.

Animals↗
PubMed1998

Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors.

A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized and evaluated for influenza A and B neuraminidase inhibitory activity. The size and geometry of side chains have been modified systematically in order to investigate structure-activity relationships of this class of compounds. The X-ray crystal structures of several analogues complexed with neuraminidase revealed that the lipophilic side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224, and Ile222 of the enzyme active site. The structure-activity relationship studies of this series have also demonstrated remarkably different inhibitory potency between influenza A and B neuraminidase. This indicated that the lipophilic side chains had quite different hydrophobic interactions with influenza A and B neuraminidase despite their complete homology in the active site. Influenza B neuraminidase appeared to be much more sensitive toward the increased steric bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive structure-activity relationship investigation reported in this article, GS 4071 emerged as one of the most potent influenza neuraminidase inhibitors against both influenza A and B strains.

Acetamides↗
PubMed1998

Sleepiness, driving, and motor vehicle crashes. Council on Scientific Affairs, American Medical Association.

OBJECTIVE: To assess the contribution of driver sleepiness to highway crashes and review recent recommendations to change federal hours-of-service regulations for commercial motor vehicle drivers. DATA SOURCES: Information was derived from a search of the MEDLINE, Transportation Research Information Service (TRIS), and Bibliographic Electronic Databases of Sleep (BEDS) databases from 1975 through 1997 and from manual review of the reference lists in relevant journal articles, government publications, conference proceedings, and textbooks. DATA SYNTHESIS: Driver sleepiness is a causative factor in 1% to 3% of all US motor vehicle crashes. Surveys of the prevalence of sleepy behavior in drivers suggest that sleepiness may be a more common cause of highway crashes than is reflected in these estimates. About 96% of sleep-related crashes involve passenger vehicle drivers and 3% involve drivers of large trucks. Risk factors include youth, shift work, alcohol and other drug use, over-the-counter and prescription medications, and sleep disorders. CONCLUSIONS: Increased awareness of the relationship between sleepiness and motor vehicle crashes will promote the health and safety of drivers and highway users. Physicians can contribute by encouraging good sleep habits, recognizing and treating sleep-related problems, and counseling patients about the risks of driving while sleepy. To protect public health and safety, the American Medical Association recommends continued research on devices and technologies to detect the signs of sleepiness and prevent the deterioration of driver alertness and performance. Educational programs about the risks of falling asleep while driving are needed for physicians, the public, and commercial truck drivers.

Accidents, Traffic↗
PubMed1998

Validity and reliability of subject and mother reporting of perinatal factors.

The authors used data from a population-based case-control study of breast cancer in women aged < or = 44 years (cases, n = 975; controls, n = 866) conducted between 1994 and 1996 in three counties of western Washington state to assess the validity and reliability of reported perinatal factors. For a sample of participants, exposure information from self-administered questionnaires was validated with information from birth certificates (cases, n = 378; controls, n = 283). Detailed information regarding perinatal characteristics of their daughters was also collected from subjects' mothers (case mothers, n = 510; control mothers, n = 436) to assess the reliability of subjects' reporting of these events. Although reporting of birth weight by subjects (cases, r = 0.83; controls, r = 0.80) and their mothers (case mothers, r = 0.89; control mothers, r = 0.84) was highly correlated with the birth certificates, there was differential measurement error by subjects; cases reported birth weight accurately on average, but controls tended to underestimate their birth weight. Agreement between the subject and mother report was excellent for birth weight (cases, r = 0.85; controls, r = 0.87) and good for other perinatal factors, but birth order and maternal diethylstilbestrol use were underreported among cases and reported accurately among controls. Differential measurement error of birth weight by case-control status resulted in biased odds ratios for breast cancer risk.

Birth Weight↗
PubMed1998

Visual reproduction subtest of the Wechsler Memory Scale-Revised: analysis of construct validity.

This study assessed the construct validity of Visual Reproduction (VR) Cards A (Flags) and B (Boxes) from the original Wechsler Memory Scale (WMS) compared to Flags and Boxes from the revised edition of the WMS (WMS-R). Independent raters scored Flags and Boxes using both the original and revised scoring criteria and correlations were obtained with age, education, IQ, and four separate criterion memory measures. Results show that for Flags, there is a tendency for the revised scoring criteria to produce improved construct validity. For Boxes, however, there was a trend in the opposite direction, with the revised scoring criteria demonstrating worse construct validity. Factor analysis suggests that Flags are a more distinct measure of visual memory, whereas Boxes are more complex and significantly associated with conceptual reasoning abilities. Using the revised scoring criteria, Boxes were found to be more strongly related to IQ than Flags. This difference was not found using the original scoring criteria.

Adult↗
PubMed1998

Magnetic resonance imaging, unstable intracranial pressure and clinical outcome in patients with normal pressure hydrocephalus.

To identify features on magnetic resonance imaging (MRI) scans that are associated with unstable intracranial pressure (ICP) and outcome after CSF shunting in patients with NPH, we reviewed MRI scans of 17 patients who had continuous ICP monitoring performed prior to ventriculo-peritoneal shunt insertion. We evaluated the association between periventricular/deep white matter lesion burden, focal impingement of the corpus callosum, aqueductal CSF flow void, and B-waves with outcome after shunting. The change in neurological function between pre- and post CSF shunting evaluation was scored according to a standard scale (range -3 or +3). Patients were divided into those with clinical improvement (score > 0) or without improvement (score < or = 0) after shunt surgery. Focal impingement of the corpus callosum was more frequent in patients who improved after CSF shunting compared to those without improvement (8 of 13 vs 0 of 4, p = 0.05). Patients with focal impingement of corpus callosum had more B-wave time than those without impingement (60.5% vs 24.7%, p = 0.02). Focal impingement of corpus callosum on MRI may be associated with unstable intracranial pressure in patients with NPH and may be useful in identifying patients who will benefit from CSF shunting.

Aged↗
PubMed1998

Evaluation of shunt function in patients who are never better, or better than worse after shunt surgery for NPH.

We investigated the cause of poor outcome in patients with normal pressure hydrocephalus (NPH) who did not respond as expected after shunt surgery. Two methods were used to evaluate shunts: radionuclide shunt patency study, or continuous ICP monitoring. 33/52 shunted patients (64%) from 1989 to 1995 had poor outcome, and 28/52 (54%) were investigated. Of those investigated, 9/28 (32%) were never better, and 19/28 (68%) were initially better then worse. Of 9 patients who were never better, ineffective shunt function was seen in 7; 5 had shunt revision (2 declined), and 1 improved. Of 19 patients who were initially better then worse, 15 had ineffective shunts; 15 underwent shunt revision, and 13 improved. Poor clinical outcome occurred in two-thirds of all patients after shunt surgery for NPH, but a potentially treatable cause (i.e. obstruction of the shunt or a shunt system that was patent but did not adequately correct the CSF circulatory disorder) was found in nearly 80% (22/28) of those investigated. The predominant cause of ineffective shunt function was obstruction of the peritoneal catheter. Clinical recovery occurred in 70% (14/20) of patients who had shunt revision surgery. We conclude that ineffective shunt function is a frequent cause of poor outcome after shunt surgery to treat NPH that should be sought and treated. These results have implications for longitudinal studies of the diagnosis and treatment of NPH. The effect of unrecognized shunt ineffectiveness on prior studies is unknown. Future studies should be designed to confirm that shunts are functioning before the diagnosis of NPH is considered incorrect.

Cerebrospinal Fluid Shunts↗
PubMed1998

Comparison of Pcsf monitoring and controlled CSF drainage diagnose normal pressure hydrocephalus.

We evaluated 86 patients for possible normal pressure hydrocephalus (NPH) by: 1) CSF pressure (Pcsf) monitoring and analysis for percent of time with A or B-waves, and 2) controlled CSF drainage for 3 days via a lumbar subarachnoid catheter. Clinical outcome after CSF drainage and shunt surgery was assessed as change of clinical exam, with grades of none, minor, moderate, or marked change. For outcome analysis in 47 patients after shunt surgery, NPH was defined as moderate or marked clinical improvement. We assessed the diagnostic discrimination of percent-of-time thresholds of A and B-waves for 38 patients. At 10%, sensitivity for NPH is 91%, specificity is 13%, positive predictive value (PPV) is 62%, and the false positive rate is 38%. At the 25% threshold, sensitivity is 78%, specificity is 40%, PPV is 67%, false positive rate is 33%, and the false negative rate is 22%. For CSF drainage (threshold of minor improvement or better), the sensitivity is 97%, specificity is 60%, PPV is 84%, negative predictive value (NPV) is 90%, and the false negative rate is 3%. We conclude: 1) clinical response to controlled CSF drainage accurately predicts the outcome after shunt surgery in patients suspected of having NPH, and 2) A or B-waves poorly predict which patients will respond to shunt surgery. Three days of CSF drainage seems to encompass critical thresholds of CSF volume removal or duration of Pcsf reduction necessary for neuronal function to begin returning and symptoms to begin resolving in patients with NPH.

Catheters, Indwelling↗
PubMed1998

Editing and translation of ribosomal protein S13 transcripts: unedited translation products are not detectable in maize mitochondria.

Maize mitochondrial transcripts for the ribosomal protein S13 gene (rps13) have six C- to -U editing sites, and each nucleotide conversion causes a change in the amino acid specified by the effected codons. Sequence analysis of 30 cDNA clones indicated that 73% of the cDNAS were edited at all six sites and 3% were completely unedited. Antibodies were produced against synthetic peptides that corresponded to unedited or edited translation products at editing sites V and VI (80% and 83% edited, respectively). Antibody preparations were purified that selectively recognized the edited or unedited forms of the epitope. The antibody preparations were highly sensitive to the amino-acid residue encoded at editing site VI, but relatively insensitive to the residue encoded at editing site V. Immunological analyses demonstrated that the edited translation product accumulated as a ribosomal protein, but that the unedited translation product was not detected in the mitochondrion, in the ribosomal fraction, or in a post-ribosomal supernatant. These results, taken together with other studies which demonstrated that incompletely edited transcripts are incorporated into polyribosomes, suggest that incompletely edited transcripts may be translated, but polypeptides encoded by incompletely edited RNAs may be unstable and, consequently, fail to accumulate.

Amino Acid Sequence↗
PubMed1998

Clinical research: assessing the future in a changing environment; summary report of conference sponsored by the American Medical Association Council on Scientific Affairs, Washington, DC, March 1996.

Concerns about funding of clinical research underlie all other problems identified at the Council on Scientific Affairs conference. Future National Institutes of Health (NIH) budgets are likely to be constant at best, and the general public expects cost containment to be an ongoing goal; this is exacerbated by the impending Medicare Trust Fund crisis. Meanwhile, traditional financial support of clinical research in academic medical centers (AMCs) through cross-subsidization is imperiled by competitive pressures largely caused by managed care. Although managed care organizations (MCOs) are potentially rich sources of funding and other resources, and some not-for-profit companies are conducting some research, for-profit MCOs have not demonstrated an understanding of the importance of clinical research. Young physicians are being discouraged from careers as clinical researchers and established investigators are "dropping out" because of demands for clinical productivity and competition for research grants, loss of patients/research subjects to managed care, perceived lack of status and compensation, and overall uncertainty about continued financial support. Efforts to assist current and potential clinical investigators are discussed in this report. Loss of patients, denial of reimbursement, and competition with MCOs and contract research organizations (CROs) have placed AMCs under unprecedented pressure. However, research centers located in AMCs have allowed investigators to conduct clinical research by providing a "protected environment." Furthermore, many AMCs are determined to continue conducting clinical research and are addressing related problems. Although the NIH will continue to be a major source of funding for clinical research, partnerships between various private and public entities provide important opportunities to maximize the productivity of all individuals and institutions involved. Potential partnerships include MCOs, AMCs, CROs, pharmaceutical companies and other industry, the Department of Defense, the Veterans Health Administration, practice-based physicians, and private foundations and patient support groups. "Partnerships in advocacy" for clinical research will be essential. Efforts to recruit for-profit MCOs to the clinical research endeavor identified in this report include (1) emphasizing issues of interest to them (eg, outcomes research); (2) stressing the significance of some research to the marketplace; (3) developing criteria to distinguish individual MCOs on the basis of their contribution to the public interest; (4) equating money spent on research with "R&D dollars" spent in nonmedical business enterprises; and (5) educating purchasers of health care (eg, corporate health plan directors) about clinical research. Conducting clinical research in all managed care settings requires leadership, the understanding and cooperation of physicians and support staff, wise use of limited resources (ie, funding only the best research projects), sound methodology, and above all, the perception that the research will ultimately improve patient care.

American Medical Association↗
PubMed1998

Plasma tumor necrosis factor-alpha soluble receptor p55 (sTNFp55) concentrations in eclamptic, preeclamptic and normotensive pregnant Zimbabwean women.

We sought to examine the relationship between excessive tumor necrosis factor-alpha (TNF-alpha) release (as measured by sTNFp55 plasma concentrations) and risk of eclampsia and preeclampsia, respectively, among sub-Saharan African women delivering at Harare Maternity Hospital, Zimbabwe. In total, 33 pregnant women with eclampsia, 138 women with preeclampsia and 185 normotensive women were included in a case-control study conducted during the period, June 1995 through April 1996. Postpartum plasma sTNFp55 was measured by enzyme linked immunosorbent assay. Women with eclampsia had significantly higher sTNFp55 than normotensive controls (1.87 vs 1.35 ng/ml, P<0.001). Similarly, women with preeclampsia had sTNFp55 concentrations higher than normotensive controls (1.69 vs 1.35 ng/ml, P < 0.001). The odds ratio for eclampsia was 5.00 (adjusted odds ratio (OR) 5.00, 95% confidence interval (CI) 1.20-20.92) among women in the highest quartile of the control sTNFp55 distribution compared with women in the lowest quartile. The corresponding odds ratio and 95% CI for preeclampsia was 2.37 (1.11-5.06). Postpartum plasma sTNFp55 concentrations are increased among Zimbabwean women with eclampsia and preeclampsia as compared with their normotensive counterparts. These findings are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia/eclampsia. Additional work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy; and to assess whether measurements of sTNFp55 early in pregnancy may be used to identify women likely to benefit from anti-inflammatory therapy.

Antigens, CD↗
PubMed1998

The inter-relation of maternal immune competence, HIV-1 viral load, and nutritional status in preventing vertical transmission: an alternative to chemoprophylaxis?

As the human immunodeficiency virus (HIV) global pandemic moves towards the end of its second decade, women of reproductive age throughout the world have been shown to be increasingly at risk for acquiring HIV-1 infection. Recently, the focus for preventive measures has expanded to include preventing the perinatal transmission of HIV-1 to fetuses and newborns. This manuscript reviews the available literature that examines risk factors for perinatal transmission, immunopathogenesis of HIV-1 infection, and the role that antioxidant micronutrients play in modulating immune response to HIV-1 disease progression. The available information provides a compelling case for the design of studies that evaluate the extent to which maternal HIV-1 viremia and disease progression are modulated by her nutritional status. Should results from these studies confirm that antioxidant micronutrient status is inversely related to HIV-1 RNA load, particularly in economically vulnerable populations, carefully designed and executed supplementation trials would be warranted.

Anti-HIV Agents↗
PubMed1998

The relationship between cardiac function and neuropsychological status among heart transplant candidates.

BACKGROUND: Cognitive deficits among heart transplant candidates have been well documented. This study was designed to examine the hypothesis that impaired cognitive test performance among heart transplant candidates may be attributed, in part, to decreased cerebral perfusion secondary to poor cardiac function. METHODS AND RESULTS: Sixty-two patients participated in the study who underwent heart catheterization within 1 day of completing a battery of cognitive tests. Multiple demographic and patient characteristics were examined for their potential moderating role in the relationship between measures of cardiac function and cognitive performance including age, education, race, gender, psychiatric history, medication usage, cardiac surgical history, and self-reported symptoms of depression and anxiety. Only age and education were significantly related to cognitive performance (P < .01). Thus, partial correlation analyses controlling for age and education were used to examine the relationship between cardiac function and cognitive performance. In general, increasing hemodynamic pressure variables (ie, pulmonary artery pressure and right atrial pressure), and to a lesser extent cardiac output and cardiac index, were related (r = - .32 to - .43; P < .01) to decreased performance on cognitive tasks that assessed simple attention, speed of mental processing, and mental flexibility (Digit Span-Forward, Trail Making Test-Part B, Symbol Digits Modalities Test, and Stroop Neuropsychological Screening Test). Left ventricular ejection fraction, systemic and pulmonary vascular resistance, and mean arterial pressure were largely unrelated to cognitive performance in this sample of patients with end stage cardiac disease. CONCLUSIONS: Hemodynamic pressure variables seem to be most consistently related (ie, inversely) to cognitive functioning among heart transplant candidates.

Cognition Disorders↗
PubMed1998

Problems and abnormalities found on routine clinical head and neck examination.

During the initial examination of a patient, the orthodontist may encounter various findings that will, for the most part, be normal or variants of normal. Most pathological conditions encountered will be derived from structures normally found in the anatomic locations examined. Knowledge of the anatomy and common pathological entities based on location can prove helpful when abnormalities are encountered. This article describes anatomic locations and their contents in and around the oral cavity and discusses pathological processes commonly encountered in these locations. Syndromes involved with various abnormalities also are briefly mentioned. The intent of this article is to give the clinician a working knowledge of commonly occurring pathological entities.

Diagnosis, Oral↗