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Biomedical subjects

M Nichols

Publications and source records attributed to M Nichols.

At least 19 recordsLinked to original sources

Using semi-automated image processing and desktop systems to incorporate actual patient volumetric data in immersive surgical planning and viewing systems for multiple patients.

This paper describes how patient specific volumetric data are managed from image acquisition through final processing for the purposes of creating a 3D VR rendering of user selected and manipulated 3D models. The system described here allows for the development of quick, inexpensive, and clinician manipulated patient-specific models. The utility of this process is demonstrated by being able to move VRML models to desktop or immersive environments for both pre-operative planning and patient-specific surgical and anatomical training.

Computer Simulation↗

Sex, drugs, and hypertension: a methodological approach for studying a sensitive subject.

Sexual dysfunction is a recognized side effect of hypertension and antihypertensive medications in men, but is not established as a side effect in women, due to the lack of established methodology. An ambulatory medical record-based, case-control study was designed to study sexual function in treated and untreated hypertensive women and healthy controls. The research was performed in a teaching hospital with satellite clinics in upstate New York. There were 3312 medical records reviewed, 640 premenopausal Caucasian women in heterosexual relationships subjects were eligible for participatic diagnosis of mild hypertension (BP > or =140/90 mmHg and < 160/100 mmHg) for cases; no other significant medical history. A total of 241 women agreed to participate, 224 (35%) completed both a self-administered questionnaire and a telephone interview (112 healthy, 112 hypertensive). There was an initial 74% response rate among those eligible to participate, with 35% completing the entire study. Age and average blood pressure were not significant between 224 participants and 416 nonparticipants by 2-tailed t-test analysis. Seven composite variables were formed from a 47-item sexual response questionnaire. Initial unadjusted chi2 results reported women with hypertension had more difficulty than did healthy controls achieving lubrication and orgasm. Seven questions, each with the highest correlation to its respective composite variable (by Spearman's correlation), formed an abbreviated questionnaire. Quality of female sexual function was quantified in an ambulatory outpatient setting. A method was described to address hypertension, pharmacotherapy, and sexual functioning by employing self-administered questionnaires and telephone interviews. Initial analysis suggested that hypertensive women may have an impaired physiological sexual response. The abbreviated questionnaire generated from questions with the highest correlation to their respective composite variables may be useful in further evaluating this issue.

Adult↗

The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer.

BACKGROUND & AIMS: Estimates of the frequency of hereditary nonpolyposis colon cancer (HNPCC) based on clinical criteria have varied widely. Recent studies of germline mismatch repair gene mutations have suggested that HNPCC accounts for close to 3% of all colon cancer, but this estimate may have been inflated by inclusion of founder effects peculiar to Finland. We therefore determined by genetic criteria the colon cancer burden associated with HNPCC in a population-based study of 1066 individuals from Utah and California. METHODS: The coding regions of mismatch repair genes hMSH2 and hMLH1 were sequenced from the germline of those individuals whose tumors exhibited microsatellite instability. RESULTS: Microsatellite instability was present in 16% (171/1066) of tumors. Pathogenic germline mismatch repair gene mutations were identified in 7 individuals, and missense amino acid changes of uncertain significance were identified in another 6 individuals. After adjusting for the availability of sufficient germline DNA for sequencing, the 7 clearly pathogenic mutations accounted for 0.86% of colon cancer at the population level. Individuals with these mutations were significantly younger, more likely to have a family history of colon and endometrial cancer, and more likely to have first-degree relatives with a young-age onset of colon cancer than individuals with unstable tumors but without germline mutations (P < 0.01). CONCLUSIONS: We conclude that genetically defined HNPCC accounts for a very small percentage of colon cancer at the population level, a percentage less than that estimated by most previous clinical studies.

Adaptor Proteins, Signal Transducing↗

Perceptions of the extent of problem gambling within new casino communities.

Several recent studies using objective measures have found that the rate of pathological gambling in the U.S. is less than 5%. To determine the general population's perception of the prevalence of pathological gambling, a survey was conducted in seven communities where casinos have recently opened. Of the 1631 respondents who provided an estimate, the mean response was that 16% of the community residents were problem gamblers, more than three times the rate found by studies using specific diagnostic criteria. A regression equation found several demographic and attitudinal items are associated with higher prevalence estimates. In addition, the data support a "close to home" hypothesis that respondents who have relatives who have experienced problems with gambling will tend to perceive higher rates of problem gambling in the community.

Journal Article↗

The roles of clinical assessment, human chorionic gonadotropin assays, and ultrasonography in medical abortion practice.

The clinical assessment of patients who request early medical abortion includes confirmation of the diagnosis of pregnancy and estimation of gestational age. Accurate gestational dating is essential, because the efficacies of medical abortion regimens decline as pregnancy advances. Whereas medical abortion researchers in the United States have relied on routine ultrasonography for gestational dating, abortion providers experienced with mifepristone and prostaglandin regimens outside the United States have reported high efficacy and safety primarily with clinical dating parameters. Diligent follow-up of patients allows clinicians to confirm that complete abortion has occurred without complications. In cases of uncertain outcome or suspected ectopic pregnancy, transvaginal ultrasonography and beta-human chorionic gonadotropin assays can assist in prompt diagnosis and management. As medical abortion with mifepristone and misoprostol becomes more prevalent in the United States, studies will be needed to further evaluate the effects of these modalities on medical abortion outcomes.

Abortifacient Agents↗

Primary nodal marginal zone B-cell lymphoma arising from more than one clonal neoplastic population.

Primary nodal marginal zone B-cell lymphoma is an uncommon monoclonal B-cell lymphoproliferative disorder. We report a case of a 79-year-old woman who presented with generalized lymphadenopathy. Histologic and immunohistochemical examinations of biopsy sections from an axillary lymph node were consistent with nodal marginal zone B-cell lymphoma. Flow cytometry analysis showed 2 distinct clonal B-cell populations expressing lambda or kappa light chain restriction. Subsequently, genomic deoxyribonucleic acid (DNA) isolated from a paraffin-embedded lymph node section was analyzed for the presence of gene rearrangements. Polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain genes revealed 3 rearranged DNA bands, confirming the presence of more than one clonal B-cell population. These immunophenotypic and genotypic findings have not been previously described in association with this type of lymphoma. To our knowledge, this represents the first reported case of biclonal nodal marginal zone B-cell lymphoma.

Aged↗

Instituting medical abortion services: changes in outcome and acceptability related to provider experience.

A prospective case series carried out at 34 Planned Parenthood sites studied the safety, efficacy, and acceptability of medical abortion with methotrexate and misoprostol in 1973 women. Women with pregnancies of 26 to 49 gestational days were given methotrexate followed by vaginal misoprostol. Eighty-one percent of women had documented complete medical abortions; abortion was not confirmed by examination in 6%, and 13% had documented suction curettage. The rate of suction curettage decreased with site experience, from 17% during the first 20 procedures to 10% at sites that had performed more than 50. Sites that had previous experience with either methotrexate or mifepristone medical abortion had a rate of 9% after they had performed at least 50 procedures. Exit interviews with 755 of the 902 women having abortions in the first year inquired about the level of comfort with the abortion and its overall acceptability. Women's satisfaction with the side effects did not directly correlate with site experience. Overall satisfaction with the abortion experience was related to whether the women had complete medical abortions or suction curettage.

Abortifacient Agents, Nonsteroidal↗

Cerebral lateralization: relationship of language and ideomotor praxis.

OBJECTIVE: To determine the relationship of language lateralization and hand preference to praxis performance following left and right hemispheric amobarbital-induced inactivations. BACKGROUND: Patients who are aphasic from left cerebral dysfunction also frequently exhibit ideomotor apraxia in which they make temporal, spatial, and postural errors of learned skilled movements. However, hemispheric lateralization of the systems mediating ideomotor praxis in patients with atypical cerebral language dominance (i.e., bilateral or right hemispheric language function) remains uncertain. METHODS: Subjects included 90 patients with intractable seizures who were undergoing the intracarotid amobarbital procedure (IAP) as part of their preoperative evaluation for epilepsy surgery. Hand preference was determined by the Benton Handedness Questionnaire. Praxis was assessed by the subject's performance when pantomiming the use of four pictured tools. RESULTS: During left IAP, patients with typical language dominance made more ideomotor apraxic errors than did patients with atypical language dominance. During right IAP, patients with atypical language dominance made more ideomotor apraxic errors than did patients with typical language dominance. Overall, patients with atypical language dominance made fewer ideomotor apraxic errors than did patients with typical language dominance. These relationships were present irrespective of hand preference. CONCLUSIONS: Language dominance is more closely associated with the laterality of temporal and spatial movement representations (i.e., ideomotor praxis dominance) than is hand preference. Patients with atypical language dominance exhibit more bilateral cerebral distribution of both language and praxis function.

Adult↗

Effect of low-dose oral contraceptives on androgenic markers and acne.

Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.

Acne Vulgaris↗

"The silent killer": chronic acetaminophen toxicity in a toddler.

We report a case fatality from chronic acetaminophen (APAP) toxicity in an 18-month-old toddler, born 14 weeks premature, who had been receiving less than the standard toxic threshold of the pediatric suspension of APAP for 4 days prior to presentation. Furthermore, he had been on prolonged total parenteral nutrition (TPN) as an infant. We hypothesize that TPN-induced hepatic changes may have diminished the patient's hepatic reserve, making him more susceptible to APAP toxicity. We propose that different "therapeutic" APAP dosing may be needed for those with underlying risk factors for hepatotoxicity.

Acetaminophen↗

Chloral hydrate: the good and the bad.

Chloral hydrate (CH) is a widely used oral sedative hypnotic drug. Our Regional Poison Control Center frequently receives calls regarding unintentional and intentional chloral hydrate overdose. The chief manifestations of toxicity are due to central nervous system depressant action and its arrhythmogenic potential. After absorption, it is immediately converted to trichloroethanol (TCE), which is the active drug. Levels of TCE at which significant toxicity occurs have been variable. Ingestions of greater than 1.5 to 2.0 g of chloral hydrate have produced symptoms in children and adults. Management includes consideration of gastrointestinal decontamination, supportive care for altered mental status and treatment of arrhythmias. For routine use of chloral hydrate as sedation for pediatric procedures, the American Academy of Pediatrics (AAP) guidelines for sedation in children should be followed to decrease the likelihood of untoward complications.

Arrhythmias, Cardiac↗

Different positioning of the ligand-binding domain helix 12 and the F domain of the estrogen receptor accounts for functional differences between agonists and antagonists.

The estrogen receptor is capable of binding a diverse set of ligands that are broadly categorized as agonists or antagonists, depending on their abilities to induce or interfere with transcriptional responsiveness. We show, using a fusion protein assay for ligand-binding which does not rely on transcriptional responsiveness, that agonists and antagonists differently position the C-terminus of the ligand-binding domain (helix 12) and the F domain. Upon antagonist binding, the F domain interferes with the fusion protein activity. Mutational disruption of helix 12 alters the position of the F domain, imposing interference after agonist or antagonist binding. Genetically selected inversion mutations where only agonists, but not antagonists, induce interference are similarly reliant on helix 12 and F domain positioning. Our results demonstrate that agonists and antagonists differently position helix 12 and implicate the F domain in mechanisms of antagonist action.

Amino Acid Sequence↗

Positive and negative discrimination of estrogen receptor agonists and antagonists using site-specific DNA recombinase fusion proteins.

Activation of the estrogen receptor (ER) by hormone involves at least two steps. First, hormone binding initially relieves repression, a property imposed on ER in cis by its ligand-binding domain (EBD). Subsequently, the derepressed ER binds specific genomic sites and regulates transcription. In addition to the natural hormone, ER binds a broad range of ligands that evoke a spectrum of responses ranging from full ER activation by agonists to partial activation and inhibition by partial or complete antagonists. How these different ligands evoke different ER responses remains unclear. To address this issue, we have developed a nontranscriptional assay for ER ligand responsiveness based on Flp recombinase/human EBD protein chimeras. These fusion proteins transduce the transient event of ligand binding into a permanent DNA change in a human cell line system. A fusion protein including ER D, E, and F domains was activated by all the ER ligands tested, demonstrating that both agonists and antagonists serve to relieve initial repression, and that differences between them lie downstream in the activation pathway. Mutant variants of the Flp-ER protein that distinguish between agonists and antagonists, and a mutant EBD that selectively lost the ability to respond to 17beta,-estradiol but not to other ligands, were also identified. Thus, agonists and antagonists can be functionally distinguished in a nontranscriptional assay.

DNA Nucleotidyltransferases↗

Impact of a Medicaid primary care provider and preventive care on pediatric hospitalization.

OBJECTIVE: This study evaluates the impact that a Medicaid managed care program had on avoidable hospitalization, a form of health care misuse that we hypothesize can be reduced by improved access to and quality of primary care in the context of a managed care program. Ambulatory care sensitive (ACS) hospitalizations, a previously defined categorization of hospitalization, as well as all pediatric hospitalizations were also studied. INTERVENTION: The Maryland Access to Care (MAC) was a fee-for-service, gatekeeper, Medicaid managed care program with assigned primary medical providers and required Early Periodic Screening, Diagnosis, and Treatment (EPSDT) examinations. Medicaid managed care elements include: 1) assignment to primary medical provider (PMP) either by voluntary choice or mandatory enrollment of eligible Aid to Families With Dependent Children (AFDC), Medical Assistance (medical needy), and Supplemental Security Income; 2) a medical home accessible 24 hours a day, 7 days a week; 2) PMP must authorize emergency department (ED), inpatient, and specialty care but there were no disincentives to PMP for referral; 3) fee-for-services reimbursement (with a physician rate increase) for primary care, authorized specialist care, and hospitalization; and 4) an on-line eligibility verification system was available to all medical providers. Pre-enrollment as well as publicity allowed MAC to be phased in rapidly, resulting in 70% to 80% enrollment by the end of the first program year. DESIGN: The design of this study is that of a pre- and postevaluation of the MAC program using Medicaid claims analysis of data 3 years pre-MAC and 2 years post-MAC. In multivariate analyses, this study also compares MAC-enrolled children to non-MAC-enrolled children (before and after MAC began) to estimate the impact of MAC enrollment while controlling for potential confounders. SETTING: State of Maryland from 1989 to 1993. PATIENTS: MAC-eligible children 18 years of age. OUTCOME MEASURES: Claims data were used to define avoidable hospitalization (based on ambulatory care received before hospitalization), to define ACS hospitalizations (based on the International Classification of Diseases-Clinical Modification, Ninth Revision [ICD-9-CM] codes), and to summarize use of ambulatory and inpatient care. ACS hospitalizations have been defined as those conditions for which timely and effective primary care can help to reduce the risk of hospitalizations. These are based solely on ICD-9-CM discharge codes that were studied by Billings and Teicholz in 1990 and used by an Institute of Medicine report in 1993. Examples include hospital discharge diagnoses of asthma (ICD-9-CM = 493), gastroenteritis (ICD-9-CM = 558.9), and dehydration (ICD-9-CM = 276.5). Usage measures, such as preventive care visits or ED visits, were created using Maryland Medicaid codes, Current Procedural Terminology codes, and ICD-9-CM codes. Linear regression was used to model trend. Logistic regression was used to model the probability of ambulatory and inpatient care given MAC enrollment and other covariates. First, logistic regression was used to predict the probability of any ambulatory care use among all MAC-eligible children during a quarter to model changes in access that may have occurred during MAC. Then, among users of ambulatory care or inpatient care, logistic regression was used to predict the probability of hospitalization. RESULTS: Most of the children studied were in the AFDC program, about half were African-American, one third resided in Baltimore City, and 9% of children had ICD-9-CMs reflecting chronic disease. The mean percentage of time children were MAC-eligible per quarter was 91%. Only 5% of children were continuously enrolled for all 20 quarters included in this study. Per-capita ambulatory care visits, especially per-capita preventive care visits, increased significantly during the study period (b = 0.003) whereas per-capita ED visits did not change. The mean n

Adolescent↗

The care and feeding of a fledgling chapter.

The success of an organization is determined by the dedication and commitment of its members. This essay aptly illustrates how members of the American Society of Ophthalmic Registered Nurses (ASORN) assisted in the formation of the 34th local chapter of ASORN and improved the strength and professionalism of registered nurses working in ophthalmology.

Humans↗

FLP recombinase/estrogen receptor fusion proteins require the receptor D domain for responsiveness to antagonists, but not agonists.

The ligand-binding domains of steroid receptors convey ligand-dependent regulation to certain proteins to which they are fused. Here we characterize fusion proteins between a site-specific recombinase, FLP, and steroid receptor ligand-binding domains. These proteins convert ligand binding into DNA recombination. Thus, ligand binding is directly coupled to an enzyme activity that is easily measured by DNA rearrangements or heritable genetic changes in marker gene expression, as opposed to the multiple events leading to transcription. Recombination by a FLP-estrogen receptor (FLP-EBD) fusion is activated by all tested estrogens, whether agonists or antagonists, indicating that all induce EBD release from the 90-kDa heat shock protein complex. Altering the distance between FLP and the EBD domain in the fusion proteins, by reducing the included length of the estrogen receptor D domain, affects ligand efficacy. A FLP-EBD with no D domain shows reduced inducibility by agonists and, unexpectedly, complete insensitivity to induction by all antagonists tested. A FLP-EBD including some D domain shows a ligand-inducible phenotype intermediate to those displayed by FLP-EBDs containing all or none of the D domain. Thus, we observed a tethered interference between FLP and the EBD domains that differs depending on the distance between the two domains, the conformations induced by agonists or antagonists, and which presents a previously undetectable distinction between estrogen agonists and antagonists in yeast.

Amino Acid Sequence↗

A novel cationic lipid greatly enhances plasmid DNA delivery and expression in mouse lung.

Effective gene therapy for lung tissue requires the use of efficient vehicles to deliver the gene of interest into lung cells. When plasmid DNA encoding chloramphenicol acetyltransferase (CAT) was administered intranasally to BALB/c mice without carrier lipids, CAT activity was detected in mouse lung extracts. Plasmid DNA delivered with optimally formulated commercially available transfection reagents expressed up to 10-fold more CAT activity in lung than observed with naked DNA alone. Liposome formulations consisting of (+/-)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis (dodecyloxy)-1-propanaminium bromide (GAP-DLRIE) plus the neutral colipid dioleoylphosphatidylethanolamine (DOPE) enhanced CAT expression by more than 100-fold relative to plasmid DNA alone. A single administration of GAP-DLRIE liposome-CAT DNA complexes to mouse lung elicited peak expression at days 1-4 posttransfection, followed by a gradual return to baseline by day 21 postadministration. Readministration of GAP-DLRIE liposome CAT complexes at day 21 led to another transient peak of reporter gene expression. Histological examination of lungs treated with GAP-DLRIE complexed beta-galactosidase DNA revealed that alveolar epithelial cells were the primary locus of expression and that up to 1% of all alveoli contained epithelial cells expressing the transgene.

Administration, Intranasal↗