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M Williams

Publications and source records attributed to M Williams.

At least 307 records · Page 17Linked to original sources
PubMed1997

The serological profile and molecular basis of a new partial D phenotype, DHR.

BACKGROUND AND OBJECTIVES: The Rh D antigen comprises a mosaic of at least 30 epitopes expressed on a 30-kD non-glycosylated Rh D polypeptide. The equivalent Rh CeEe polypeptide expressing the Rh C/c and E/e antigens differs in only 36 of the 417 amino acid residues. Partial D individuals have been described who fail to express a number of D epitopes. MATERIALS AND METHODS: Serologic methods were applied with monoclonal anti-D to map epitopes on the red cells of a proposita aberrant D typing. Polymerase chain reaction (PCR) and DNA sequencing were also done. RESULTS: DNA sequence analysis derived by RT-PCR using total RNA isolated from peripheral blood of this person suggests two mechanisms for the genetic basis of this variants: one here gene conversion events result in the replacement of RHD gene exons with the equivalent RHCE exons; the second where point mutation in the RHD gene generates an amino acid substitution in the Rh D protein. CONCLUSIONS: We report here a new partial D, DHR, where a single point mutation (G to A at nucleotide 686) in exon 5 of the RHD gene results in a conservative amino acid substitution (Arg229Lys), in the predicted Rh D protein. This residue is localised on the fourth predicted exofacial loop of the Rh D polypeptide as determined by hydropathy analysis. This substitution results in the lack of epD 1, 2, 12 and 20 (30 epitope model) and indicates the involvement of loop 4, and in particular the requirement of Arg229, in the expression of these epitopes.

Amino Acid Substitution↗
PubMed1997

Hemodynamic effects of aortic occlusion during hemorrhagic shock and cardiac arrest.

OBJECTIVE: To determine the hemodynamic consequences of aortic occlusion during controlled hemorrhagic arrest. METHODS: Ten anesthetized, hemodynamically monitored swine were subjected to a 40 mL/kg hemorrhage over 10 minutes, followed by a 5-minute period of apnea. At this time (T15), they were randomized into an UP group (n = 5) in which the thoracic aorta was occluded or a DOWN group (n = 5) in which the aorta was not occluded. Simultaneously, volume resuscitation with shed blood plus 20 mL/kg of normal saline was performed over a 10-minute period. Cardiac massage was performed until return of spontaneous circulation (ROSC), which was defined as a sustained systolic blood pressure > 60 mm Hg. After 30 minutes of occlusion (T45), the aortic occlusion was released. Parameters measured include mixed venous and arterial blood gases, serum lactic acid levels, cardiac index, mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), coronary perfusion pressure (CoPP), and left ventricular stroke work index (LVSWI). Oxygen delivery index (DO2I) was measured using a pulmonary artery catheter, and oxygen consumption index (VO2I) was measured by direct calorimetry (Delta Trac metabolic monitor). RESULTS: Four animals in each group achieved ROSC after 3.0 +/- 1.8 and 2.2 +/- 1.8 minutes in the occluded and nonoccluded groups, respectively. During cardiac compressions and volume resuscitation, the CoPP, MAP, and MPAP were greater in the UP group, although the differences did not achieve statistical significance. After volume resuscitation was complete and during the period of aortic occlusion (T25-T45), the UP group had significantly greater MAP (mm Hg), with a difference of 42.5 +/- 20.75 mm Hg at T25 and 44.7 +/- 19 mm Hg at T35 (p < 0.03). Despite no difference in DO2I, VO2I (mL/min/kg) was significantly lower in the UP group than in the DOWN group, 4.28 +/- 0.48 versus 8.33 +/- 0.85 at T25 (p = 0.0002) and 4.62 +/- 0.9 versus 7.09 +/- 0.72 at T35 (p = 0.0005). After release of aortic occlusion at T45, the UP group had significantly lower CoPP (mm Hg) than the DOWN group (20.5 +/- 17.3 versus 66.5 +/- 28.2 at T45, p = 0.03). LVSWI (g/kg) was also lower in the UP than in the DOWN group (18.6 +/- 8.28 versus 36.5 +/- 10.2 at T60 [p = 0.031 and 23.6 +/- 6.48 versus 48.8 +/- 15.3 at T240 [p = 0.021). After release of the occlusion, there were trends toward increased acidosis and lactic acid levels in the UP group. CONCLUSIONS: Aortic occlusion in this controlled hemorrhagic arrest model does not result in improved salvage but is associated with impaired left ventricular function, systemic oxygen utilization, and coronary perfusion pressure in the postresuscitation period.

Animals↗
PubMed1997

Peer discussion on training physicians to be competent communicators: support for a multiple discourse approach.

To consider medical educators' views about training physicians to be competent communicators, a focus group was conducted at a large southeastern medical college with faculty responsible for training interns and residents to be competent communicators. The medical school was undergoing a curriculum review and instructional development process, including an examination of the methods being used to teach communication. A discussion of a teaching faculty committee revealed several themes, including the foundational assumption that communication is a natural ability that some have and others do not. Other notions likely to affect the educators' beliefs about the importance and effectiveness of communication education include the ideas that courtesy is synonymous with good communication and that although a few fundamentals might be transmitted, experience is the best teacher. Participants identified several audiences, in addition to patients, with whom they communicate as part of their profession, including other physicians, other health care providers (e.g., nurses and lab technicians), and hospital administrators, health care insurers, and others responsible for evaluating physicians' performance. The implications of this project for the development of medical communication courses within a multiple discourse approach are discussed.

Communication↗
PubMed1997

Prevalence of psychotropic and anticonvulsant drug use among North Dakota group home residents.

In a previous study, the present authors reported on the prevalence of psychoactive (psychotropic and anticonvulsant) medication use among people with intellectual disability residing in community settings in the state of North Dakota, USA. The present study replicates the earlier survey. A questionnaire was sent to all group homes serving people with developmental disabilities. Questionnaires were obtained for 100% of North Dakota group home residents. Psychoactive medications (anticonvulsants included) were used by 38% of the 1384 residents represented. The results are discussed in relation to the previous study from North Dakota.

Adolescent↗
PubMed1997

Carrier screening for cystic fibrosis in primary care: evaluation of a project in South Wales. The South Wales Cystic Fibrosis Carrier Screening Research Team.

Population carrier screening for cystic fibrosis (CF) was offered to all patients aged 16-45 in one general practice in South Wales, excluding those in couples with a current pregnancy. Out of 1553 patients in this group, 481 subjects were tested, giving an overall uptake rate of more than 30%. The rate of uptake varied with the mode of invitation. Twenty-six carriers were identified, giving a prevalence of identified carriers of 5.4% (1 in 18.5) for those with no family history of CF. A further 18 carriers were identified by cascade testing of these 26. We describe the practical difficulties encountered in setting up this programme in primary care in South Wales. Questionnaires were administered or distributed to all subjects before and after testing. The response rate for the pre-test questionnaire was 95%, and 40-50% for the post-test questionnaires. These showed that, at 3 months post-test, 1 in 4 screen-negative subjects did not appreciate that they had a residual risk of being a carrier. At the same time, 15% of this group thought that there was a 1 in 4 chance of a child being affected if one parent was screen-positive (carried an identified mutation) and the other was screen-negative, and 40% thought there was no risk. Anxiety in relation to testing did not appear to be a major problem, although individual patterns of response to carrier status varied widely and more sensitive indicators of psychosocial impact of genetic tests are required. A pilot study of couple screening showed that this approach is unlikely to be useful in primary care, although we did not assess couple testing during pregnancy. For any programme of CF carrier screening to be established in primary care, it will be necessary to involve the primary care team from the earliest planning stage, so that the opportunity costs, training needs and other costs of the programme can be fully resourced.

Adolescent↗
PubMed1997

Possible discrimination in recruitment of psychiatry residents?

OBJECTIVE: The authors sought to determine whether there is a selection bias against international medical graduate applicants for U.S. residency training positions in psychiatry. METHOD: Identical requests for a program application were sent by two resident applicants--one international medical graduate and one graduate of a U.S. medical school--to 193 residency training programs, and the rate and character of responses were compared. RESULTS: The response rate to requests for an application form was significantly higher for the U.S. medical school graduate (159 responses) than the international medical graduate (87 responses). The quality of responses was also different in some cases. CONCLUSIONS: Some residency programs in psychiatry are attempting to limit the influx of international medical graduate applicants at the very first level: the request for an application form. The reasons for this practice are not known, but discrimination could be a possible explanation.

Educational Measurement↗
PubMed1997

Alzheimer's disease and related dementias: prospects for treatment.

Alzheimer's disease (AD) represents a major challenge to healthcare costs and to academic and pharmaceutical research efforts. The approval in 1996 of the first of the second generation acetylcholinesterase inhibitors, donepexil (Aricept, Eisai/Pfizer), has offered new hope, albeit palliative, to AD sufferers and care givers. Research has continued on the genetics of AD with the identification of the autosomal dominant inheritance of genetic defects in one of three distinct genes coding for the presensilins 1 and 2 and amyloid precursor protein (APP). While driving an ever increasing research effort related to the production, deposition and clearance of Abeta peptides, these mutations account for less than 10% of the AD cases reported, indicating that other causative factors, both genetic and environmental, may contribute to the pathophysiology of AD unrelated to familial cohorts. A newly developed transgenic mouse model and a broader appreciation of the multifactorial nature of this complex, chronic disease state may help provide a more objective approach to understanding the disease per se as opposed to amyloid neurotoxicity specifically which may or may not be causative.

Journal Article↗
PubMed1997

Cloning and characterization of a human leptin receptor using a biologically active leptin immunoadhesin.

Leptin, the product of the ob gene, is a hormone secreted by fat cells which is primarily involved in the regulation of body weight. We have generated a leptin immunoadhesin (leptin-IgG) which was more potent than leptin alone at reducing body weight and food intake when injected into ob/ob mice. This molecule was used to identify high affinity binding sites on human embryonic 293 kidney cells and subsequently to isolate a cDNA encoding the leptin receptor from this cell line by expression cloning. This receptor corresponds to the short form of the recently isolated leptin receptor. Analysis of the expression pattern of the two forms of receptor by Northern blot, in situ hybridization and quantitative PCR showed that the receptor is expressed in most tissues but that the long form is prevalent in the hypothalamus.

Animals↗
PubMed1997

Quantitating fetomaternal hemorrhages of D+ red cells using an FITC-conjugated IgG monoclonal anti-D by flow cytometry: a case report.

Several methods for quantitating fetomaternal hemorrhages (FMHs) have been described; these include the Kleihauer-Betke and red cell rosetting tests, and flow cytometry that uses an indirect antiglobulin technique, employing either FITC-conjugated IgG/unlabeled anti-D or streptavidin conjugates with biotinylated anti-D to enumerate D+ red cells in maternal blood. We have used a recently described directly conjugated FITC anti-D for direct flow cytometric (direct FC) quantitation of FMH in a patient who presented with a large fetal bleed (approx. 80 mL) as determined using the Kleihauer method. We compared the efficacy of the direct FC technique to the rosetting and Kleihauer tests in estimating the quantity of Rh immunoglobulin (RhIg) to be administered to the mother to suppress Rh alloimmunization. Both the Kleihauer and the direct FC gave precise estimates of 80 mL for the size of bleed, whereas the rosetting test failed to be as precise. The former tests predicted that a 10,000 iu dose (2,000 microg) of RhIg would be adequate; the lack of alloanti-D in a maternal follow-up sample obtained 9 months after delivery supported this prediction and underlined the reliability of the direct FC method as an alternative to the Kleihauer method for quantitating large FMHs.

Journal Article↗
PubMed1997

Abdominal compartment syndrome: case reports and implications for management in critically ill patients.

Five cases are reviewed in which intra-abdominal pressures were used to decide whether critically ill patients would undergo exploratory laparotomy. This is a retrospective case series of a convenience sample of five critically ill, postoperative patients with a variety of underlying illnesses admitted to a surgical intensive care unit in a university hospital. Intra-abdominal compartment pressures were measured using the indirect method of urinary bladder pressure. In patients with signs of abdominal compartment syndrome, intra-abdominal pressures were measured. The pressures were measured every 6 hours until the signs had resolved or the patient was taken for exploratory laparotomy. All patients had Foley catheters. The drainage tubing to the catheters was clamped after the infusion of 200 cc of sterile water. An 18-gauge needle was inserted into the sampling port of the drainage tubing proximal to the clamp, and the needle was connected to a pressure transducer. An elevated abdominal compartment pressure was considered at greater than 25 mm Hg. The case series were reviewed to determine in critically ill patients whether intra-abdominal pressures could assist in deciding which patients required emergent exploratory laparotomy. The patients underwent frequent venous and arterial blood gas and hemodynamic measurements. If the clinical course of the patients worsened as indicated by requiring additional pressors, ventilator support and/or oliguria intra-abdominal pressures were measured every 6 hours. The five patients whose intra-abdominal pressures were elevated were taken for exploratory laparotomy. Four patients were found to have urgent surgical conditions. Intra-abdominal pressures can be used to help decide which patients can be aggressively supported and observed and which patients need re-exploration. At exploration the patient may be found to have necrotic large or small intestines instead of the classical abdominal compartment syndrome findings of ascites, hematoma, and bowel wall edema. In symptomatic patients with abdominal compartment pressures greater than 30 mm Hg, the patient should be taken for exploration. It is not necessary to perform any further diagnostic tests before exploring the patient.

Abdomen↗
PubMed1997

[The nasopharynx and deep spaces of the face: anatomy and applications to pathology].

Deep facial spaces are anatomically delineated by the layers of deep cervical fascia. They are located between the skull base and the hyoid bone. Each space contains specific anatomic structures, which can be responsible for specific pathologic processes. Deep facial spaces can be divided in two medial odd spaces (pharyngeal mucosal and retropharyngeal spaces), and in three lateral even spaces (retrostylian, prestylian, and masticator spaces). The dividing of these core tissues are useful for the analysis of the lesions found in this area. CT scan and MRI (with axial and coronal views) provide precise analysis. The main lesions are: -medially, adenoidal hyperplasias and squamous cell carcinomas (pharyngeal mucosal space), adenopathies and abscess (retropharyngeal space). -laterally, salivary tumors (prestylian space), adenopathies, schwannomas and paragangliomas (retrostylian space). Masticator space (and especially pterygopalatine fossa) is an important way of communication and is often involved by the extension of locoregional pathologic processes.

Adenoids↗
PubMed1997

ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties.

Accumulating preclinical and clinical evidence data suggests that compounds that selectively activate neuronal nicotinic acetylcholine receptor (nAChR) subtypes may have therapeutic utility for the treatment of several neurological disorders. In the present study, the in vitro pharmacological properties of the novel cholinergic channel modulator ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine], are described. In radioligand binding studies, ABT-089 was shown to display selectivity toward the high-affinity (-)-cytisine binding site present on the alpha4beta2 nAChR subtype (Ki = 16 nM) relative to the [125I]alpha-bungarotoxin binding site present on the alpha7 (Ki > or = 10,000 nM) and alpha1beta1deltagamma (Ki > 1000 nM) nAChR subtypes. In cation flux and channel current studies, ABT-089 displayed a more complex profile than (-)-nicotine having agonist, partial agonist and inhibitory activities depending on the nAChR subtype with which it interacts. ABT-089 differentially stimulated neurotransmitter release. The compound displayed a similar potency and efficacy to (-)-nicotine to facilitate ACh release (ABT-089, EC50 = 3 microM; (-)-nicotine, EC50 = 1 microM), but was markedly less potent and less efficacious than (-)-nicotine to stimulate dopamine release (ABT-089, EC50 = 1.1 microM; (-)-nicotine, EC50 = 0.04 microM). Additionally, ABT-089 was neuroprotective against the excitotoxic insults elicited by exposure to glutamate in both rat cortical cell cultures (EC50 = 10 +/- 3 microM) and differentiated human IMR32 cells (EC50 = 3 +/- 2 microM). The differential full agonist/partial agonist profile of ABT-089, as compared with (-)-nicotine and ABT-418, illustrates the complexity of nAChR activation and the potential to target responses at subclasses of the neuronal and peripheral receptors.

Acetylcholine↗
PubMed1997

Dural sinus thrombosis: CT and MR imaging of different stages.

Cerebral dural sinus thrombosis remains an uneasy clinical diagnosis because it may present with a spectrum of nonspecific manifestations. CT and MR findings have been described to help recognize this entity. We report here a case with different stages of thrombosed superior sagittal and right transverse dural sinuses demonstrated by CT and MR imaging.

Adult↗