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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 253 records · Page 14Linked to original sources

Reduced MTR in the corticospinal tract and normal T2 in amyotrophic lateral sclerosis.

The objective of this study was to test the hypothesis that magnetization transfer ratios (MTR) are decreased in the corticospinal tract of patients with amyotrophic lateral sclerosis (ALS); to determine if T2 is increased in corticospinal tract or reduced in motor cortex in ALS; to determine if corticospinal tract MTR correlates with a clinical measure of motor neuron function in ALS. Ten ALS patients and 17 age-matched controls were studied. Double spin echo MRI and 3D gradient echo MRI with and without off-resonance saturation were acquired on each subject. 3D data sets were coregistered and resliced to match the spin echo data set. MTR was calculated for corticospinal and non-corticospinal tract white matter. T2 was calculated for corticospinal and non-corticospinal tract white matter, motor cortex and non-motor cortex. MTR was reduced by 2.6% (p < .02) in corticospinal, but not in non-corticospinal, tract white matter in ALS. There was no difference in T2 in any brain region. The correlation between a clinical measure of motor neuron function and corticospinal tract MTR was statistically significant. These findings are consistent with the known pathology in ALS and suggest that MTR is more sensitive than T2 for detecting involvement of the corticospinal tract. Quantitative MTR of the corticospinal tract may be a useful, objective marker of upper motor neuron pathology in ALS.

Adult↗

High-dose nitrates in the immediate management of unstable angina: optimal dosage, route of administration, and therapeutic goals.

Nitrates are commonly used for rapid relief of ischemia in the initial management of unstable angina. However, their optimal dosage, route of administration, and therapeutic goals have not been fully established. This study was conducted to determine the optimal dosage and mode of administration (intravenous bolus versus sublingual spray) of nitrates and the therapeutic goals of their use in the immediate management of unstable angina. In a single-center prospective trial, 72 consecutive patients with unstable angina accompanied by typical ST-segment depression on electrocardiogram were randomly assigned to receive isosorbide dinitrate either as repeated intravenous boluses or as sublingual sprays while being delivered to the hospital by a mobile intensive care unit. Optimal nitrate dosage was tailored to pain relief while monitoring mean blood pressure reduction to an optimal range (5% to 20%) without dosage restriction. The mean nitrate dosage needed for ischemia control during the first hour of treatment was 7.8 +/- 3.8 mg. Optimal blood pressure reduction was achieved by significantly more intravenously treated patients than sublingually treated patients (68% v 41%, P = .037). Intravenously treated patients also experienced a more pronounced therapeutic effect, as assessed by reduction in chest pain score (67% v 39%, P = .0004) and decrease in ST-segment depressions (57% v 27%, P = .004). These results show that higher doses of nitrates than previously recommended are required for ischemia control during the initial management of unstable angina. The use of repeated intravenous boluses is safe and more easily controlled and, therefore, more efficacious than sublingual sprays in inducing the maximal anti-ischemic effect while avoiding significant hypotension.

Administration, Sublingual↗

A protocol-contract for opioid use in patients with chronic pain not due to malignancy.

The legal, psychosocial, and medical factors that we believe have contributed to the success of our protocol-contract in prescribing opioids to patients with chronic pain not due to malignancy are outlined. These factors may be applicable to the treatment of a variety of chronic nonmalignant pain syndromes such as postherpetic neuralgia or human immunodeficiency virus/acquired immunodeficiency syndrome. The intended target audience of this paper is the physician (primary care, chronic pain specialist) who is involved in prescribing opioids for the treatment of chronic, nonmalignant pain.

Acquired Immunodeficiency Syndrome↗

A ligand-mediated dimerization mode for vancomycin.

BACKGROUND: Vancomycin and related glycopeptide antibiotics exert their antimicrobial effect by binding to carboxy-terminal peptide targets in the bacterial cell wall and preventing the biosynthesis of peptidoglycan. Bacteria can resist the action of these agents by replacing the peptide targets with depsipeptides. Rational efforts to design new agents effective against resistant bacteria require a thorough understanding of the structural determinants of peptide recognition by vancomycin. RESULTS: The crystal structure of vancomycin in complex with N-acetyl-D-alanine has been determined at atomic resolution. Two different oligomeric interactions are seen in the structure: back-to-back dimers, as previously described for the vancomycin-acetate complex, and novel face-to-face dimers, mediated largely by the bound ligands. Models of longer, naturally occurring peptide ligands may be built by extension of N-acetyl-D-alanine. These larger ligands can form an extensive array of polar and nonpolar interactions with two vancomycin monomers in the face-to-face configuration. CONCLUSIONS: A new dimeric form of vancomycin has been found in which two monomers are related in a face-to-face configuration, and bound ligands comprise a large portion of the dimer interface. The relative importance of face-to-face and back-to-back dimers to the antimicrobial activity of vancomycin remains to be established, but face-to-face interactions appear to explain how increased antimicrobial activity may arise in covalent vancomycin dimers.

Anti-Bacterial Agents↗

Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States)

To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer.

Adult↗

HIV follow-up care at a London teaching hospital.

Counselling around all stages of HIV infection is important for those infected and affected with HIV disease. Partner notification may promote safer sexual practices and increase HIV-related social support which might in turn prompt the psychological adjustment to a terminal illness. This paper describes the counselling service used at the Royal Free Hospital's HIV Unit and explores the notification patterns of an HIV diagnosis to family, partners and significant others. Retrospective data was abstracted from counselling notes for 100 HIV-positive patients attending the unit for the first time between November 1995 and March 1996. The majority of the sample were gay males who tested from 1995 onwards. Most patients tested at the Same Day Testing Clinic (SDTC) were gay males. In contrast, patients who tested elsewhere were more likely to be females. Rates of pre- and post-test counselling were high and the majority (85%) of the patients had notified a family member, partner or significant other. Few significant differences in demographics were found between those who had notified others and those who had not, although patients who had been diagnosed more recently were less likely to have notified other family members. The implication of the results are discussed.

Adolescent↗

Tissue-conserving surgery for prognosis, treatment, and function preservation.

OBJECTIVES: To describe an approach based on initial tissue-conserving surgery used to obtain histologically determined prognostic information that has therapeutic implications and the potential to enhance preservation of function. STUDY DESIGN: Analysis of a group of patients with head and neck cancer treated initially with tissue-conserving surgery based on Mohs' histographic sectioning and selected neck dissection to derive histologically determined prognostic information with therapeutic implications and preservation in function. METHODS: This study is primarily based on an analysis of patients from January 1, 1989, through June 4, 1996 assigned to a protocol evaluating resection of oral cavity squamous cell cancer with margin control using Mohs' histographic technique and/or a group of patients with neck assessment of NO on clinical examination who are undergoing supraomohyoid neck dissections. RESULTS: Thirty-three primary tumor resections were performed using the Mohs' technique, and 54% required two or more Mohs' sections before clear histologic margins were obtained following resection based on clinically determined negative margins. There were 44 patients who underwent unilateral or bilateral supraomohyoid neck dissections, and 33% had occult, histologically positive nodes. When compared with the disease of the neck specimens, a preoperative computed tomography scan had a sensitivity of 25%, a specificity of 77%, and an accuracy of 63%. CONCLUSIONS: This report describes the effectiveness of Mohs' histographic sectioning and selective neck dissection as a means of determining prognostic information that can be used to develop a focused and cost-effective treatment program that, along with contemporary reconstructive techniques, provides a potential enhancement of function preservation.

Adult↗

Phenytoin auto-induction.

Information regarding phenytoin auto-induction is sparse and conflicting. However, confirmation of the presence or absence of auto-induction by phenytoin could have important implications in phenytoin therapy and research. This was an open, randomized, three-way crossover study in which each of the eighteen volunteers received three different formulations of phenytoin, which was allocated in a random order. The period effect between each crossover was determined to assess the effect of the previous exposure to phenytoin on the area under the concentration-time curve (AUC). The point estimate ratio of AUC(o-t) for the third dose relative to the first dose was 81.19% with 90% t-confidence limits of 74.37% to 88.00% and p = 0.3847. The point estimate ratio of AUC(o-infinity) for the third dose relative to the first dose was 76.25% with 90% t-confidence limits of 65.3% to 87.2% and p = 0.7169. These results suggest that the AUC (o-infinity) and AUC(o-t) measured after the third dose of phenytoin was statistically significantly smaller than those measured after the first dose. This decrease in AUC after the third dose of phenytoin is probably caused by enhanced elimination of the drug as a result of enzyme induction.

Adolescent↗

Treatment of multiple trichoepithelioma with electrosurgery.

Multiple trichoepithelioma are benign skin tumors that present a significant cosmetic problem in young people. We report the successful treatment of two patients with electrosurgery. Specifically, through the use of a blended current, loop and triangular electrodes were used to remove the papules flush with the facial contour. In comparison to carbon dioxide laser, this modality yields identical cosmetic results yet is less expensive and considerably more time efficient.

Adult↗

Clinical aspects of Pneumocystis carinii pneumonia in HIV-infected patients: 1997.

In 1997 in Europe P. carinii pneumonia is largely a disease of individuals who are either unaware of their HIV serostatus or who decline prophylaxis despite knowing they are HIV positive. Although fibre optic bronchoscopy and bronchoalveolar lavage is the diagnostic 'gold standard' polymerase chain reaction (PCR) amplification applied to oropharyngeal washings appears to have a moderate to high diagnostic yield. With further development this may provide a truly non-invasive diagnostic test. There is a clear need for an inherently more effective regimen for prophylaxis both for those with adverse reactions (ADR) to co-trimoxazole and also for those with low CD4 lymphocyte counts. Ideally, new drug regimens should afford cross-prophylaxis against bacterial, mycobacterial and other fungal infections. Given the high frequency of ADR to co-trimoxazole when used as treatment for P. carinii pneumonia, there is also a need for effective, non-toxic alternative therapies.

AIDS-Related Opportunistic Infections↗

Evidence of CNS impairment in HIV infection: clinical, neuropsychological, EEG, and MRI/MRS study.

OBJECTIVES: To identify by clinical examination, EEG, MRI, and proton spectroscopy, and neuropsychological assessment the prevalence of signs of CNS involvement in patients infected with HIV, and to relate such findings to the evidence of immunosuppression. METHODS: The design was a cross sectional analysis of a cohort of male patients with infected HIV with an AIDS defining diagnosis or low CD4 count (<350), and seropositive asymptomatic subjects, both groups being followed up in a longitudinal study. Control groups consisted of seronegative subjects from the same genitourinary medicine clinics. RESULTS: This report sets out the cross sectional findings at the seventh visit in the longitudinal study. Patients with AIDS had more signs of neurological dysfunction, poorer performance on a neuropsychological test battery, were more likely to have an abnormal EEG, and to have abnormalities on MRI. They more often had cerebral atrophy, abnormal appearing white matter, and abnormal relaxometry and spectroscopy. There was little evidence of abnormality in seropositive people who had a CD4 count >350 compared with seronegative people from a similar background. CONCLUSIONS: Detailed testing failed to disclose significant CNS impairment without immunosuppression in men infected with HIV. Findings from MRI and magnetic resonance spectroscopy (MRS) correlated with those of the neurological examination and neuropsychological assessment. A combination of such assessments offers a simple surrogate for studies of CNS involvement in HIV disease.

AIDS Dementia Complex↗

Inhalation by nebulization of albuterol-ipratropium combination (Dey combination) is superior to either agent alone in the treatment of chronic obstructive pulmonary disease. Dey Combination Solution Study Group.

Combination bronchodilator therapy for chronic obstructive pulmonary disease (COPD) potentially can provide increased benefit over single-agent therapy. The objective of this double-blind, randomized, positive-control trial was to determine the effectiveness of an albuterol-ipratropium solution aerosol combination (Dey combination solution, Dey LP, Napa, Calif., USA) compared with solution aerosols of both component medications administered alone in patients with COPD. The trial consisted of a 6-week, 3-period crossover phase followed by a 6-week parallel phase during which patients self-administered study medications by inhalation from a nebulizer. A total of 863 patients were initially randomized to each of the six possible treatment sequences of the three study medications in the crossover phase and received each study medication in turn for a 2-week period. Patients continued to receive the same treatment administered during the last 2-week period of the crossover phase for an additional 6 weeks in the parallel phase. Assessment of 1-second forced expiratory volume (FEV1) curves before and after dosing on the last day of each 2-week period indicated that the combination was superior to either single agent in peak effect and area under the curve up to 8 h after dosing (FEV1-AUC0-8), in both phases of the trial. The use of Dey combination during the crossover phase resulted in 24% more improvement in peak FEV1 than was seen with albuterol alone (p < 0.001), and 37% more than was seen with ipratropium alone (p < 0.001). Similarly, when examining FEV1-AUC0-8, Dey combination resulted in 30% more improvement than was seen with albuterol alone (p < 0.001), and 32% more than was seen with ipratropium alone (p < 0.001). The combination affords a convenient dosing regimen and incorporates enhanced benefit without compromising the safety profile of either component agent.

Adult↗

The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks.

BACKGROUND AND PURPOSE: The Greater Cincinnati/Northern Kentucky Stroke Study was designed to be the first large, population-based metropolitan study of temporal trends in stroke incidence rates and outcome within a biracial population. METHODS: We are identifying all hospitalized and autopsied cases of stroke and transient ischemic attack (TIA) among the 1.3 million inhabitants of a five-county region of Greater Cincinnati/Northern Kentucky for the period 7/1/93-6/30/94. We have already prospectively monitored for out-of-hospital stroke and TIAs for this same time period at 128 screening sites, including a random sample of all primary care physicians and nursing homes in the region. We have already identified all hospitalized and autopsied cases of stroke and TIA among blacks for 1/1/93-6/30/93 and report preliminary incidence rates for this 6-month period. RESULTS: The overall incidence rate for all first-ever hospitalized or autopsied stroke (excluding TIAs) among blacks in the Greater Cincinnati region was 288 per 100000 (95% CI, 250 to 325, age- and sex-adjusted to 1990 US population). The overall incidence rate for first-ever and recurrent stroke (excluding TIAs) was 411 per 100000 (95% CI, 366 to 456). By comparison, the overall incidence rate of first-ever stroke among whites in Rochester, Minn, during the period 1985-1989 was 179 per 100000 (95% CI, 164 to 194, age- and-sex adjusted to 1990 US population). The incidence rates among blacks in Greater Cincinnati were substantially greater than the rates among whites in Rochester, Minn, for all age categories except ages 75 and older, for which the rates were similar. CONCLUSIONS: We conservatively estimate that 731100 first-ever or recurrent strokes occurred in the United States during 1996. Studies of first-ever as well as total stroke among biracial and representative populations are critical for understanding temporal trends in the incidence rate and the burden of stroke in the US population.

Adult↗

Research bronchoscopies do not adversely affect HIV-infected individuals' future health-care decisions.

STUDY OBJECTIVES: Asymptomatic HIV-infected individuals are increasingly recruited for studies involving invasive procedures such as bronchoscopy. We sought to determine the response to and outcome of a request for a research bronchoscopy in HIV-positive individuals with no respiratory disease, and whether this would adversely affect future decisions to have a medically indicated bronchoscopy. DESIGN AND SETTING: Prospective, semistructured, questionnaire-based study in a London teaching hospital HIV outpatient clinic. PARTICIPANTS: One hundred and seven consecutive HIV-infected eligible individuals. Thirty-one healthy volunteers served as a control group for the subjective response to bronchoscopy. MAIN OUTCOME MEASURES: Subjects' attitudes and responses to requests for bronchoscopy and subsequent behavior when they required medically indicated bronchoscopy. RESULTS: Seventy-five patients (70%) agreed to the procedure in principle, predominantly for altruistic reasons. Thirty-nine subjects underwent bronchoscopy. Five percent found it worse than expected; and 79% agreed to another research bronchoscopy (performed in 11 subjects approximately 2 years later). All patients said they would undergo bronchoscopy again for diagnostic purposes (required in seven during the study). When compared to a healthy volunteer population within the same study, postbronchoscopy symptoms were similar in frequency although somewhat different in nature. Subjects felt that a clear explanation of what was involved enhanced their participation in this research. CONCLUSIONS: Invasive research procedures such as bronchoscopy can be performed and are repeatable in a healthy HIV-infected population. Performance of procedures for research purposes does not appear to adversely affect future health-care decisions.

Adolescent↗

Nutritional evaluation of two agroindustrial by-products for ducks and pigs.

Forty-eight male White Pekin ducks and 24 crossbred barrows (Landrace or Yorkshire sows; PIC Line 355 boars) were used in three experiments to evaluate the nutritional value of two by-products generated from agricultural industries. In each experiment, test ingredients consisted of a dried meat solubles product (DMS) from swine processing facilities and a yeast fermentation product (YFP) from a commercial source. Soybean meal (SBM) with a CP content of 48% served as the control ingredient in the three experiments. Different batches of each by-product were evaluated in the three experiments utilizing an apparent ME (AME) assay for poultry (Exp. 1 and 2) and a digestibility assay for barrows (Exp. 3). The nitrogen-corrected AME (AMEn) for SBM, DMS, and YFP in Exp. 1 were 2.909, 2.801, and 3.292 kcal, respectively. The AMEn for SBM, DMS and YFP in Exp 2 were 2.809, 3.207, and 3.565 kcal, respectively. In Exp. 3, diets were formulated such that the test ingredients provided the sole source of amino acids in each experimental diet. The AME of SBM, DMS, and YFP in Exp. 3 were 3.844, 2.208, and 3.552 kcal, respectively. Based on the results of the ME assay for poultry, the DMS product compares well to SBM and seems to be suitable for feeding to ducks. The YFP does not seem to be suitable for feeding nonruminant species based on poor ability to support nitrogen retention in both species (-36% and -20% in Exp. 1 and 2, and 20% in Exp. 3).

Agriculture↗

Dry cow diet, management, and energy balance as risk factors for displaced abomasum in high producing dairy herds.

The objective of this study was to determine prepartum risk factors for displaced abomasum. The design was a prospective study of 1170 multiparous Holstein cows from 67 high producing dairy herds in Michigan. Each farm was visited four times within a 6-wk period. At each visit, data on nutrition and management were collected. All multiparous cows within 35 d of projected calving were assigned a body condition score, and blood was sampled to determine the concentration of nonesterified fatty acids in plasma. A multivariable linear regression model was used to determine risk factors associated with the incidence of displaced abomasum during lactation on a herd basis. A multivariable logistic regression model with random effect was used to determine risk factors for displaced abomasum on an individual cow basis. Significant risk factors for displaced abomasum included a negative energy balance prepartum (as estimated from plasma nonesterified fatty acids), a high body condition score, suboptimal feed bunk management prepartum, prepartum diets containing > 1.65 Mcal of net energy for lactation/kg of dry matter, winter and summer seasons, high genetic merit, and low parity.

Abomasum↗

Quantitation of DNA from exfoliated colonocytes isolated from human stool surface as a novel noninvasive screening test for colorectal cancer.

The only widely used screening test for early detection of colorectal cancer, the fecal occult blood test, lacks both sensitivity and specificity because it relies upon incidental bleeding rather than the neoplastic process. With the purpose of developing a new noninvasive diagnostic approach, we quantified DNA extracted from cells isolated from the surface of human stools by a novel procedure. Stools collected from 28 healthy individuals, 17 colorectal cancer patients, and 11 colorectal polyp patients were analyzed. A stool DNA index (SDNAI), expressed as DNA amount in nanograms per gram of stool, had a remarkable 4.5-fold difference in mean values between colorectal cancer patients and healthy people of comparable age. SDNAI was 2133 +/- 407 in the cancer group versus 469 +/- 65 in healthy people of the older (> 50 years) age group (P = 0.0005). The difference was independent of tumor location and size. If 700 ng of DNA/g of stool was taken as a cutoff SDNAI value in discrimination between older healthy people and cancer patients, sensitivity and specificity values reached 1.00 and 0.81, respectively. Age dependence of SDNAI was demonstrated by substantially lower SDNAI values (mean, 227 +/- 41) in younger healthy individuals. Polyp patients sometimes displayed elevated SDNAI values, but considerable variation was observed (mean, 1215 +/- 548). These preliminary findings indicate that SDNAI provides a novel, simple, and powerful noninvasive test for colorectal cancer early detection and screening. The fundamental advantage of the SDNAI is that it directly characterizes colonic epithelium involved in carcinogenesis.

Adult↗