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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 469 records · Page 26Linked to original sources

Working group recommendations: measuring outcomes of care in geriatric evaluation and management units.

Issues related to measuring outcomes of care in geriatric evaluation and management (GEM) units were identified by the outcomes working group of the GEM evaluation conference. GEM units have as a major goal the improvement or maintenance of both physical and psychosocial function. Suggested outcome measures for physical health included survival, restricted activity days, general health perceptions, comprehensive physical function, and miscellaneous specific types of functioning. In the area of psycho-social function, the working group suggested measuring cognitive function, affect/life satisfaction, social function, and satisfaction with care. The patient's caregiver (eg, spouse or child) is often an important target of GEM care, and the group suggested measuring caregiver burden, life satisfaction, and assessment of patient behavior problems. While the primary goal of GEM units is to improve health status, their effects on the utilization and cost of health care are important to decisions about wide-spread implementation and funding. The group therefore suggested a comprehensive assessment of these outcomes. Among the large array of recommended outcomes, the most important were thought to be mortality, function, and cost.

Activities of Daily Living↗

A new breast screening programme--an audit of the first year.

The experience of a new breast screening unit is reported. In the first 12 months there was a 72.1% response rate with 9890 women being screened. After the initial screen 598 (5.8%) were referred to the Assessment clinic. Following repeated mammography and clinical examination 166 patients were referred for a surgical opinion; 105 (1.06% of the total screened) were considered to be possibly malignant; 61 further patients with clinical and mammographically benign disease were kept under review by a single surgeon; 101 patients had excision biopsies; 28 of 32 palpable breast lumps and 36 of 69 non-palpable lesions proved to be malignant.

Biopsy↗

An insight into early reproductive processes through the in vivo model of ovum donation.

To gain insight into early reproductive processes we have prospectively designed ovum donation protocols to elucidate several phenomena relating to embryo implantation and pregnancy sustenance. Artificial endometrial cycles with variable follicular phases were induced in 60 recipients by sequential estrogen and progesterone. A total of 964 oocytes were retrieved throughout 43 ovum donation attempts, for an average of 22.4 (range, 16-41) eggs/retrieval. The overall delivery rate per egg retrieval (donors and recipients combined) was 72.1% (31 of 43). The shortest estrogen stimulation (short follicular phase) resulting in ongoing pregnancies was 5 days in duration, while the longest (long follicular phase) was 35 days in duration before progesterone initiation. Utilization of variable length follicular phases, artificially extended the stage of endometrial receptivity to over 4 weeks. To assess the window of implantation, same age embryos were transferred onto endometrium of different maturational stages. Pregnancies were documented with embryo transfers between luteal day 1 (day 15) to luteal day 6 (day 20), extending the window of implantation in the human to at least 6 consecutive days. To evaluate the relative contribution of oocyte quality and endometrial receptivity to pregnancy outcome, common source ova were transferred onto endometrium with variable hormonal exposure. Despite the drastically different follicular phase estradiol levels and periods of exposure, similar delivery rates were attained in donor cycles (29.4%) and recipient cycles during short follicular phases (29.6%). Slightly higher delivery rates (39.4%) were observed with long follicular phases. The comparable pregnancy rates in donors and recipients are attributed to the common source oocytes regardless of endometrial stimulation.

Adult↗

The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation.

The segment polarity genes of Drosophila were initially defined as genes required for pattern formation within each embryonic segment. Some of these genes also function to establish the pattern of the adult cuticle. We have examined the role of the armadillo (arm) gene in this latter process. We confirmed and extended earlier findings that arm and the segment polarity gene wingless are very similar in their effects on embryonic development. We next discuss the role of arm in pattern formation in the imaginal discs, as determined by using a pupal lethal allele, by analyzing clones of arm mutant tissue in imaginal discs, and by using a transposon carrying arm to produce adults with a reduced level of arm. Together, these experiments established that arm is required for the development of all imaginal discs. The requirement for arm varies along the dorsal-ventral and proximal-distal axes. Cells that require the highest levels of arm are those that express the wingless gene. Further, animals with reduced arm levels have phenotypes that resemble those of weak alleles of wingless. We present a description of the patterns of arm protein accumulation in imaginal discs. Finally, we discuss the implications of these results for the role of arm and wingless in pattern formation.

Animals↗

Demonstration of SLUMIS: a clinical database and management information system for a multi organ transplant program.

Because of the rapid evolution of the heart, heart/lung, liver, kidney and kidney/pancreas transplant programs at our institution, and because of a lack of an existing comprehensive database, we were required to develop a computerized management information system capable of supporting both clinical and research requirements of a multifaceted transplant program. SLUMIS (ST. LOUIS UNIVERSITY MULTI-ORGAN INFORMATION SYSTEM) was developed for the following reasons: 1) to comply with the reporting requirements of various transplant registries, 2) for reporting to an increasing number of government agencies and insurance carriers, 3) to obtain updates of our operative experience at regular intervals, 4) to integrate the Histocompatibility and Immunogenetics Laboratory (HLA) for online test result reporting, and 5) to facilitate clinical investigation.

Academic Medical Centers↗

The concept of uterine preservation with ovarian malignancies.

A 30-year-old woman with bilateral, recurrent, borderline papillary serous cystadenocarcinoma of the ovary was treated with bilateral oophorocystectomy and omentectomy with uterine preservation. Ten years later, through induction of an artificial endometrial cycle and ovum donation, she conceived twins and delivered two healthy infants. Staging exploratory laparotomy at the time of cesarean delivery was negative for malignancy. This case illustrates the value of uterine preservation for cases in which classical teaching has indicated hysterectomy with bilateral salpingoophorectomy.

Adult↗

Prevalence of psychoactive drug use among North Dakota group home residents.

To determine the prevalence of psychoactive medication usage among persons with mental retardation residing in community settings in the state of North Dakota, we sent a questionnaire to all group homes serving persons with developmental disabilities. The return rate was 97%. Psychoactive medications were used by 37% of residents represented. Results were discussed in relation to previous studies that have primarily involved institutionalized populations.

Adolescent↗

Characterization of the binding of a novel nonxanthine adenosine antagonist radioligand, [3H]CGS 15943, to multiple affinity states of the adenosine A1 receptor in the rat cortex.

The triazoloquinazoline CGS 15943 is the first reported nonxanthine adenosine antagonist that has high affinity for brain adenosine receptors. In the present study, the binding of [3H] CGS 15943 to recognition sites in rat cortical membranes was characterized. Saturation experiments revealed that [3H]CGS 15943 labeled a single class of recognition sites with high affinity (Kd = 4 nM) and limited capacity (Bmax = 1.5 pmol/mg of protein). Competition studies revealed that the binding of [3H]CGS 15943 was consistent with the labeling of brain adenosine A1 receptors. Adenosine agonists inhibited 1 nM [3H]CGS 15943 binding with the following order of activity N6-cyclopentyladenosine (IC50 = 15 nM) greater than 2-chloroadenosine greater than (R)-N6-phenylisopropyladenosine greater than 5'-N6-ethylcarboxamidoadenosine greater than (S)N6-phenylisopropyladenosine greater than CGS 21680 greater than CV 1808 (IC50 greater than 10,000 nM). The potency order for adenosine antagonists was CGS 15943 (IC50 = 5 nM) greater than 8-phenyltheophylline greater than 1,3-dipropyl-8-(4-amino-2-chloro)phenylxanthine greater than 1,3-diethyl-8-phenylxanthine greater than theophylline = caffeine (IC50 greater than 10,000 nM). Antagonist inhibition curves were steep and best described by a one-site binding model. In contrast, adenosine A1 agonist competition curves were shallow, as indicated by Hill coefficients less than unity. Computer analysis revealed that these inhibition curves were best described by a two-site binding model. Agonist competition curves generated in the presence of 1 mM GTP resulted in a rightward shift and steepening of the inhibition-concentration curves, whereas antagonist binding was not altered in the presence of GTP. The complex binding interactions found with adenosine agonists indicate that [3H]CGS 15943 labels both high and low affinity components of the adenosine A1 receptor in the rat cortex. Additionally, the present data also provide some evidence that [3H]CGS 15943 may also recognize an additional low affinity binding component, which may represent a putative low affinity A2b receptor in this tissue.

2-Chloroadenosine↗

Haloperidol induces Fos and related molecules in intrastriatal grafts derived from fetal striatal primordia.

Haloperidol induces Fos and related molecules (Fos-related antigens, FRAs) in adult striatal neurons. We tested whether a similar induction of Fos and FRAs by haloperidol injection would occur in fetal striatal neurons transplanted into adult quinolinic acid-lesioned striatum. We found that Fos and FRAs were induced in striatal neurons after haloperidol. This induction had a time course in transplanted neurons that was identical to the time course of induction in normal adult striatum. Furthermore, the relative numbers of Fos- and FRA-immunopositive neurons induced by haloperidol were identical for both transplanted and normal striatal neurons. These results provide the first demonstration that neurons in intrastriatal grafts derived from fetal striatal primordia have similar intracellular biochemical characteristics to normal adult striatal neurons.

Animals↗

Cloning and sequence analysis of the VH and VL regions of an anti-myelin/DNA antibody from a patient with peripheral neuropathy and chronic lymphocytic leukemia.

We have cloned and determined the nucleotide sequence of the Ig VH and VL region genes of an IgM kappa mAb that binds to denatured DNA and myelin from a patient (POP) with chronic lymphocytic leukemia and peripheral neuropathy. Sequence analysis indicates that the V region of the kappa L chain gene (PopVK) has 99% homology to a V kappa IIIa germ-line gene and the V region of the mu H chain gene (PopVH) has 96% homology to the VH26 germ-line gene that is a member of the VH3 gene family. It is likely the V kappa and VH genes arose from these respective germ-line genes via somatic mutation or from closely related genes. V kappa III genes have frequently been used by other IgMk mAb especially those with rheumatoid factor activity, and the VH26 gene with no somatic mutation has been used by several anti-DNA antibodies, suggesting the possibility of preferential association of these or related germ-line genes with autoantibodies. The minor differences between the sequences of POP's VH and V kappa genes and sequences used by other autoantibodies, may be responsible for this antibody's crossreactivity with myelin and, as a result, the autoimmune neuropathy.

Amino Acid Sequence↗

Relationships between central and autonomic measures of arousal at age 15 years and criminality at age 24 years.

Previous studies have indicated that criminality is in part genetically determined, but it is not clear how this predisposition manifests itself at a biological level. This prospective study tests the hypothesis that a psychophysiological predisposition to criminality partly manifests itself through autonomic and central nervous system underarousal. Psychophysiological measures, taken at the age of 15 years, were related to criminality status that was assessed at the age of 24 years. Criminals had a significantly lower resting heart rate, skin conductance activity, and more slow-frequency electroencephalographic activity than noncriminals. Differences were not mediated by social, demographic, and academic factors. These results constitute the first clear evidence that implicates underarousal in all three response systems (electrodermal, cardiovascular, and cortical) in the development of criminality. Although arousal variables correctly classified 74.7% of all subjects, psychophysiological factors alone cannot fully account for criminal behavior and do not negate the potential role of social variables in predicting criminal behavior.

Adolescent↗

Human central nervous system primitive neuroectodermal tumor expressing nerve growth factor receptors: CHP707m.

A primitive neuroectodermal tumor (PNET) presented as a cerebral hemispheric mass in a 33-year-old man. Bone marrow metastases were discovered 11 months later. A cell line (CHP707m) was derived from these metastases. In culture, the cells showed features of neuronal differentiation, forming short neurites and synthesizing low-molecular-weight neurofilament protein. Northern blotting showed the tumor cells express nerve growth factor (NGF) receptor messenger RNA, and fluorescence-activated cell-sorting demonstrated NGF receptors on the cell surface. Western blotting showed CHP707m NGF receptors are truncated. The receptors are functional; they bind iodine 125-labeled mouse NGF with an affinity of 1.6 x 10(-9) M, and short-term treatment with NGF induces expression by the tumor cells of the proto-oncogene, c-fos. Although CHP707m is the first central nervous system PNET cell line proven to express NGF receptors, immunohistological survey of tissue sections prepared from human central nervous system PNETs showed that 13 of 35 contained NGF receptor-positive tumor cells. Thus, more than one-third of such tumors might be responsive to the effects of NGF.

Adult↗

Evaluation of the penetration test for bicyclists' helmets: comparative performance of hard shell and foam helmets.

A project was undertaken to evaluate the utility of the penetration test in the Australian Standard devoted to the testing of lightweight helmets for bicycle riders. The project revealed aspects of the protective performance of conventional hard shell helmets and recently developed helmets manufactured entirely from expanded polystyrene foam. Hard shell helmets were found to provide good performance in a range of loading conditions applied to them during testing. In contrast, foam helmets provided very poor resistance to concentrated loads produced during impacts with small, sharp objects but they had greater capacity than hard helmets to withstand distributed loads produced during impacts with flatter objects. The presence of the penetration test in the Australian Standard was determined to have produced the good all round performance of hard helmets which met its requirements. Two tests were proposed as alternatives to the penetration test. They would evaluate foam and hard helmets on equal terms at the cost of abandoning the requirement of helmets to withstand concentrated loads.

Australia↗

The production and purification of PCR-derived recombinant simian immunodeficiency virus p27 gag protein; its use in detecting serological and T-cell responses in macaques.

The polymerase chain reaction (PCR) was used to amplify a region of the gag gene, encompassing the core protein p27, from genomic DNA of cells infected with SIVmac251 (32H isolate). The 767 base pair PCR product was cloned into the bacteriophage M13 and fully sequenced before sub-cloning into the expression vector pUC19. The 30 kilodalton (kDa) fusion protein of lacZ-p27 was expressed as a soluble protein in E. coli JM101 cells and purified to greater than 90% purity by affinity chromatography. The affinity purified product was used in serological and T-cell assays to assess immune function in cynomolgus macaques immunised or challenged with immunodeficiency virus derived material. This reagent and accompanying methods provide valuable assays for monitoring the efficacy of vaccines for SIV as a model for human AIDS.

Animals↗

The ventricle-brain ratio (VBR) in functional psychoses: an admixture analysis.

An admixture analysis of the ventricle-brain ratio (VBR) on the computed tomographic (CT) scans of 72 patients with functional psychosis and 50 healthy controls was made, to determine whether two distinct distributions could be demonstrated. The patients showed a more positively skewed distribution, and a significantly higher mean VBR, but there was no evidence of more than one underlying normal distribution of values. The use of VBR alone to define a biologically separate subgroup of patients is not supported.

Adolescent↗