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Biomedical subjects

J M Williams

Publications and source records attributed to J M Williams.

At least 127 records · Page 7Linked to original sources

Search for the optimal fetal cell antibody: results of immunophenotyping studies using flow cytometry.

Fetal nucleated cells circulating in maternal peripheral blood are a noninvasive source of fetal DNA for prenatal genetic diagnoses. The successful isolation of fetal cells from maternal blood depends upon identification of differences between fetal and maternal cell surface antigen expression. To our best knowledge, a monoclonal antibody that binds only fetal blood cells has not yet been identified. We studied antigens recognized by six different monoclonal antibodies for their biologic expression on fetal blood cells as a function of gestational age, and compared their ability to bind fetal but not maternal cells. The results suggest a relationship between gestational age and nucleated cell surface antigen expression. The monoclonal antibodies FB3-2, H3-3, CD71 and 2-6B/6 are suitable reagents for first or early second trimester fetal cell isolation, although FB3-2 and H3-3 are more specific for fetal cells due to significantly lower expression of these antigens on maternal mononuclear cells. The observation that samples from fetuses with chromosome abnormalities or multiple structural anomalies express higher levels of these antigens indicates that these reagents will potentiate the detection of abnormal fetal cells in maternal blood samples.

Abnormalities, Multiple↗

Retreatment of decentered excimer photorefractive keratectomy ablations.

PURPOSE: To present two cases of excimer photorefractive keratectomy decentration associated with visual distortion secondary to irregular astigmatism. METHOD: Patients were retreated with a repeat photorefractive keratectomy using a technique whereby the circle of adherent epithelium overlying the decentered ablation served as a mask. RESULTS: After retreatment, there was significant improvement in the patients' visual symptoms, decreased astigmatism on refraction, and better centration on corneal topography. CONCLUSION: This method appears to offer an effective means to treat photorefractive keratectomy ablation zone decentration by improving the abnormalities introduced by the initial decentration.

Adult↗

Sequence-independent effects of phosphorothiolated oligonucleotides on synaptic transmission and excitability in the hippocampus in vivo.

Antisense oligodeoxynucleotides (ODNs) have the potential to be a powerful tool for regulating gene expression and mRNA translation in spatially and temporally restricted domains. Prior to investigating the effects of antisense ODNs on hippocampal long-term potentiation, we investigated whether there are any non-specific effects of ODNs on perforant path synaptic transmission in the dentate gyrus of both pentobarbital-anaesthetized and awake, freely moving rats. Single injections of phosphorothioated antisense ODNs (4 nmol) to the immediate early gene zif/268 caused a rapid (within minutes) and long-lasting (>24 hr) profound depression of the perforant path evoked field potentials. This depressive effect was due to the phosphorothioate modification since a depression was not seen with unmodified antisense ODNs, relative to saline controls. Furthermore, the effect was not sequence-specific since modified sense ODNs caused the same degree of depression. The depression caused by the modified antisense ODNs was dose-dependent and specific to synaptic transmission, since antidromic population spikes elicited by mossy fibre stimulation were relatively unaffected compared to the orthodromic responses. A second unexpected side-effect of the modified ODNs was cellular hyperexcitability, such that bursts of epileptiform spikes in the EEG occurred both spontaneously and as a result of synaptic stimulation. While the mechanism of the synaptic depression remains unknown, these results indicate that phosphorothioate-modified ODNs exert profound non-specific effects on synaptic transmission in the hippocampus, that have the potential to seriously compromise any corresponding behavioural or electrophysiological studies.

Animals↗

Short-term memory for food reward magnitude: the role of the prefrontal cortex.

Memory for magnitude of reinforcement was assessed in rats using a go/no-go short-term memory paradigm. During the task's study phase rats were given a piece of cereal comprised of either 25 or 50% sugar. For all trials, one of the cereal types was designated positive, the other negative. On the ensuing test phase the rat was presented with an object which covered a food well. If a positive food reward was given during the study phase, a second food reward was placed beneath the object. No food reward was placed under the object if the study phase consisted of a negative food reward. Latency to object displacement was used as the measure of performance. Following the establishment of a significant difference between latency to approach the object with reward compared to latency to approach the object without reward, rats were given either agranular insular cortex, anterior cingulate cortex, pre- and infralimbic cortex or control lesions. Agranular insular cortex lesioned animals demonstrated a mild post-surgery impairment. Trials consisting of 10 and 20 s delays between the study and test phases were then introduced. Delays exacerbated the previous deficit of the agranular insular cortex lesion group, but had little effect on the other lesion groups. All animals transferred to a new set of cereals containing 25 and 50% sugar and exhibited taste preferences to sugar solutions of different concentrations. These results indicate that the agranular insular cortex may play an important role in the processing of affect-laden information within a prefrontal cortex short-term or working memory system.

Animals↗

Injury recidivism in a rural ED.

STUDY OBJECTIVE: To determine the degree of injury recidivism in our ED population and to identify indicators of injury recidivism. METHODS: We conducted a retrospective review in a university-affiliated department of emergency medicine. The study participants were patients who presented for treatment of an injury. An injury recidivist was defined as a patient who presented for treatment of two or more unique injuries during the 1-year study period. The injured population was divided into three categories: (1) those with a single injury visit, (2) those with two to three injury visits, and (3) those with four or more injury visits. Demographics, mechanism of injury, and outcome data were collected and comparative analyses performed. RESULTS: Of the 37,360 ED patient visits, 12,075 were injury related. Of the injury visit load, 2,838 of the 12,075 (24%) were injury recidivists. Of injured patients, 1,239 of 10,476 (12%) were recidivists. The sex distribution was similar among the groups, but the mean age decreased as the degree of recidivism increased. The degree of recidivism was higher for patients with Medicaid and for those who were uninsured. Lower mean medical charges per visit were found with increasing degree of recidivism, but the average total charges per patient increased with increasing degree of recidivism. Increasing degree of recidivism was associated with decreasing incidence of transportation-related injury but increased incidence of overexertion or intentional injuries. CONCLUSION: A small group of patients account for a significant proportion of ED injury visits. In comparison with injury patients seen once during the year, recidivists represent a younger population of lower socioeconomic status, and they are at increased risk of intentional injury.

Adult↗

Socioeconomic status and adolescent injuries.

Injuries are the major cause of morbidity among children and adolescents in developed countries, but there is a lack of consensus on the relationship between socioeconomic status and risk of injuries. A self-complete questionnaire survey, to gather information on non-fatal injuries and sociodemographic details, was administered in schools during April-June 1994 to a national sample of 4710 Scottish adolescents aged 11, 13 and 15 years. Although there was no evidence of a socioeconomic gradient in the total incidence of medically attended injuries among adolescents, based on the Registrar General's classifications of paternal occupation and a composite measure of family affluence, marked socioeconomic variation in the circumstances in which injuries occurred was observed. There were also socioeconomic differences in the extent and type of risk behaviours reported by adolescents, indicating differential rates of risk exposure. The finding that socioeconomic status affects the kinds of injury events adolescents experience and levels of risk behaviour has implications for the design of injury prevention strategies.

Adolescent↗

Hyaluronic acid suppresses fibronectin fragment mediated cartilage chondrolysis: II. In vivo.

Intra-articular sodium hyaluronic acid (HA) has been used as a treatment intervention in the management of osteoarthritis. It has been observed that HA can coat the articular surface, and thus, has been suggested to provide a possible prophylactic barrier for the articular cartilage. In an accompanying manuscript (Homandberg et al.), we report that a commercially available high-molecular-weight HA (approximately 800-kDa, ARTZ, Seikagaku Corp.) can partially block fibronectin fragment (Fn-f)-mediated cartilage injury in vitro. Herein we report a study of the effects of intra-articular HA on an in vivo animal model of Fn-f-mediated cartilage injury. Rabbit knees were injected with Fn-f, and after 1 week, the cartilage proteoglycan (PG) content had decreased to 59 +/- 8% of control. In sharp contrast, PG content in knees receiving pre-treatment with HA followed by Fn-f injection had only decreased to 85 +/- 27% of control (P < 0.01). Similarly, the PG content in knees receiving an injection of Fn-f, followed by an injection of HA were significantly higher (74 +/- 18% of control) than Fn-f injured knees with no treatment (P < 0.02). Intra-articular HA alone had no effect on cartilage PG content. The results in this study suggest that HA is effective in partially preventing Fn-f mediated cartilage injury, most likely by coating the articular surface. Further, HA treatment after Fn-f injury may facilitate restoration of matrix components.

Animals↗

Hyaluronic acid suppresses fibronectin fragment mediated cartilage chondrolysis: I. In vitro.

A commercial preparation of 800-kDa hyaluronic acid (HA), (ARTZ from Seikagaku, Inc.), has been used as a therapeutic intervention in the treatment of osteoarthritis (OA). We tested the effect of this HA form, HA/800, in an in vitro cartilage chondrolytic system in which a specific amino-terminal 29-kDa fragment of fibronectin (Fn-f) penetrates cartilage tissue to activate chondrocytes to amplify two major chondrolytic activities: suppression of proteoglycan (PG) synthesis and induction of matrix metalloproteinases. We report that HA/800 did not block damage by Fn-f in serum free cartilage cultures. However, HA/800 was effective in blocking the ability of 100 nM Fn-f to cause the degradation and release of half of the total cartilage PG from cartilage in 10% serum/DMEM cultures. While the Fn-f caused a half-time for PG release of 3 days, continuous exposure to 0.1 or 1 mg/ml HA/800 slowed the half-time to 12 days. Further, a single 1 day pre-incubation with 0.1 or 1 mg/ml HA/800 was sufficient to decrease the half-time of 100 nM Fn-f mediated PG depletion to 7 and 12 days, respectively. HA/800 completely blocked the effect of 10 nM Fn-f. Blocking of Fn-f-mediated cartilage PG depletion was associated with a decreased concentration of Fn-f on the superficial cartilage surface and decreased penetration into the cultured cartilage tissue. Further, the two major chondrolytic activities of the Fn-f, suppression of synthesis of PG and enhanced release of stromelysin-1, were suppressed by HA/800. HA/800 also partially restored PG in cartilage first damaged with the Fn-F. We conclude that HA/800 slows Fn-f-mediated cartilage chondrolysis in vitro and has some reparative potential. The damage blocking activity appears to be associated with the ability of HA/800 to block penetration of the Fn-f, rather than with direct effects on cartilage tissue.

Animals↗

Psychosocial influences on central and peripheral vision and reaction time during demanding tasks.

We examined perceptual deficits hypothesized in a model of stress and injury relationships. An ophthalmologic perimeter was used to measure peripheral and central vision during baseline and demanding task situations for 201 intercollegiate athletes from 10 sports. We conducted analyses of covariance with the stress measures as dependent variables and their appropriate baseline measures as covariates. Performance under demanding tasks deteriorated significantly on all the perceptual variables. Individuals with high negative life events scores experienced greater peripheral narrowing and slower central vision reaction time during stress than did those with life events scores that were low. Men with low social support had more failures to detect cues, and men with high negative life events, low social support, and low coping skills had the lowest perceptual sensitivity. Women with high negative life events and low coping skills had more failures to detect cues. We discuss the findings in terms of how stress responsivity may influence injury risk through changes in perception and attention.

Adaptation, Psychological↗

PCR quantitation of fetal cells in maternal blood in normal and aneuploid pregnancies.

Fetal cells in maternal blood are a noninvasive source of fetal genetic material for prenatal diagnosis. We determined the number of fetal-cell DNA equivalents present in maternal whole-blood samples to deduce whether this number is affected by fetal karyotype. Peripheral blood samples were obtained from 199 women carrying chromosomally normal fetuses and from 31 women with male aneuploid fetuses. Male fetal-cell DNA-equivalent quantitation was determined by PCR amplification of a Y chromosome-specific sequence and was compared with PCR product amplified from known concentrations of male DNA run simultaneously. The mean number of male fetal-cell DNA equivalents detected in 16-ml blood samples from 90 women bearing a 46,XY fetus was 19 (range 0-91). The mean number of male fetal-cell DNA equivalents detected in 109 women bearing a 46,XX fetus was 2 (range 0-24). The mean number of male fetal-cell DNA equivalents detected when the fetus was male compared with when the fetus was female was highly significant (P = .0001). More fetal cells were detected in maternal blood when the fetus was aneuploid. The mean number of male fetal-cell DNA equivalents detected when the fetal karyotype was 47,XY,+21 was 110 (range 0.1-650), which was significantly higher than the number of male fetal-cell DNA equivalents detected in 46,XY fetuses (P = .0001). Feto-maternal transfusion of nucleated cells appears to be influenced by fetal karyotype. The sixfold elevation of fetal cells observed in maternal blood when the fetus had trisomy 21 indicates that noninvasive cytogenetic diagnosis of trisomy 21 should be feasible.

Aneuploidy↗

Work-related injuries in a rural emergency department population.

OBJECTIVE: To describe the spectrum of work-related injury evaluated in a rural ED population. METHODS: An ED-based injury surveillance system (EDBISS) was used to collect injury data for all ED patients seen over a 1-year period. A patient was classified as injured if his or her record contained an ED log injury code, an ICD-9 N-code between 800 and 995 in any diagnostic field, an E-code, or an entry in the trauma registry. An injury was considered work-related if the patient reported that the injury had occurred while at work. RESULTS: Work-related injuries accounted for 1,539/12,321 (12.5%) of all injuries. The mean age of patients injured on the job was 33.8 years (range, 16-77 years), compared with a mean age of 27.7 years for all the injured patients. Males accounted for 1,026/1,537 (67%) of the work-related injury visits, compared with 57% of all the injury visits. The most common mechanisms of work-related injuries were: overexertion (313; 20%); cut or pierced by sharp implements (248; 16%); falls (250; 16%); struck by object (202; 13%); and transportation-related injuries (71; 5%). Sprains and strains were the most common type of injury sustained (415; 27%), followed by wounds to upper limbs (283; 18%), contusions (182; 12%), and fractures (151; 10%). Of the 1,539 patients presenting with occupational injuries, 178 (12%) presented to the ED via ambulance. Most (1,401; 91%) were treated and released from the ED, with the remainder (136; 9%) hospitalized. The mechanisms of injury that most commonly resulted in hospitalization included struck by an object (28; 21%), transportation (26; 19%), falls (27; 20%), crushing mechanism (13; 10%), and machinery (20; 15%). Of those requiring hospitalization, 132/136 (97)% were male, and the average length of stay was 4.4 days. Four of the hospitalized persons died of their work-related injuries. Known medical charges incurred by patients injured at work were as high as $62,622. The average charge for those treated and released was $273; the average charge for those who required hospitalization was $10,910. CONCLUSIONS: Occupational injuries contribute significantly to the overall incidence of injuries seen in this ED and are responsible for significant medical charges each year.

Accidents, Occupational↗

Calcium, magnesium, and phosphorus: emergency department testing yield.

OBJECTIVES: To investigate how often the ED ordering of stat serum calcium (Ca+2), magnesium (Mg+2), and phosphorus (PO4(-3)) levels affected clinical treatment; to define the diagnoses of patients for whom Ca+2, Mg+2, and PO4(-3) measurements did affect clinical therapy; and to suggest guidelines for more appropriate ordering of these laboratory tests. METHODS: A retrospective chart review was performed in an academic teaching hospital. All adult ED patients who had Ca+2, Mg+2, or PO4(-3) laboratory testing during the 9-month study period were included and evaluated for potential clinical impact of an abnormal Ca+2, Mg+2, or PO4(-3) laboratory test. RESULTS: 1.477 patients had Ca+2, Mg+2, or PO4(-3) measured while in the ED during the study period. Of these, 260 patients (17.6%) had a total of 312 abnormal Ca+2, Mg+2, or PO4(-3) values as defined by results exceeding +/- 15% of normal reference values. Of these, only 5 patients (0.3%) received treatment for abnormal values in the ED, while 75 patients (5.1%) were treated once admitted to the hospital. In this study, the only diagnostic groups to whom significant treatment was administered were diabetic patients (Ca+2 and PO4(-3); alcoholic patients (Mg+2); and renal failure patients (Ca+2, Mg+2, and PO4(-3). CONCLUSION: These results suggest that stat Ca+2, Mg+2, and PO4(-3) levels seldom affect clinical treatment in the ED. The frequency of ordering these tests may be reduced by obtaining Ca+2, Mg+2, or PO4(-3) measurements only for patients known to be at risk for such abnormalities, based on their existing or suspected diagnoses. The authors suggest obtaining these tests, when indicated, on a "non-stat" basis, with the subsequent laboratory results becoming available in-hospital, where treatment is more likely to occur.

Adult↗

Zygomatic salivary cyst with mucocele formation in a cat.

An eight-year-old neutered male domestic shorthair cat had a zygomatic salivary cyst with associated mucocele formation. A fluctuating swelling developed ventral to the right eye, causing bulging of the lower eyeild, and a corresponding swelling was present in the caudal vestibule of the oral cavity. Cytological examination of the fluid obtained from aspiration of the swelling was consistent with the appearance of saliva. A tentative diagnosis of zygomatic salivary mucocele was made. Surgical exploration and resection of the swelling demonstrated the presence of a multilobular cystic zygomatic salivary gland. The histopathological appearance of the resected tissue was interpreted as an inflammatory reaction to mucus derived from a multilocular salivary cyst.

Animals↗

Cognitive impairment, depression and the specificity of autobiographical memory in the elderly.

Previous research has shown that both depressed (Williams & Scott, 1988) and elderly (Winthorpe & Rabbitt, 1988) people have difficulties in being specific in autobiographical memory. However, no study has examined the joint impact of cognitive impairment and affective disturbance. In this preliminary study, 22 elderly people with memory complaints were tested with the Autobiographical Memory Test, the Brief Assessment Schedule Depression Cards, Geriatric Depression Scale and the Mini-Mental State Examination. Results showed that autobiographical specificity decreased with increasing levels of cognitive impairment. Participants were more likely to produce overgeneral memories (omissions or generic memories) than extended or specific memories. There was little relation between severity of depression and specificity in autobiographical memory, consistent with previous suggestions that overgenerality in depression is a long-term cognitive style unaffected by state depression (Brittlebank, Scott, Williams & Ferrier, 1993).

Aged↗

Selective processing of shape-related words in women with eating disorders, and those who have recovered.

OBJECTIVES: This study sought to investigate whether women with anorexia or bulimia nervosa and women who had recovered showed cognitive bias towards shape, food and adolescent issues. DESIGN: A five-group analysis of variance design was used, in which the different client groups were the independent variables. The dependent variable was performance on an emotional Stroop task. METHODS: Current anorexia sufferers (N = 31), current bulimia sufferers (N = 24), recovered anorexics (N = 23), recovered bulimics (N = 11) and women who had never suffered from eating disorders (N = 33) were recruited through health-care professionals, support groups and newspapers. Colour-naming times for target and comparison Stroop cards were measured. RESULTS: Women currently suffering from bulimia, and women who had recovered from anorexia, were found to be more distracted by shape concerns than women who had never suffered eating disorders and women who had recovered from bulimia. CONCLUSIONS: The results suggest that there may be an enduring cognitive bias among women who have recovered from anorexia. This is the first study in which impairment on an emotional Stroop task has been found to persist after recovery from a clinical condition.

Adult↗

Amygdala but not hippocampal lesions impair olfactory memory for mate in prairie voles (Microtus ochrogaster).

Exposure to an unfamiliar male conspecific results in pregnancy interruption (i.e., the Bruce effect) in rodents. Unlike most laboratory rodents, female prairie voles (Microtus ochrogaster) are induced into estrus by chemosensory stimuli contained in the urine of male conspecifics while grooming the anogenital (A-G) region of unfamiliar males. Female prairie voles maintain a brief "memory" for the stud male for 8-10 days after mating. Subsequent exposure to the same mate within this 8- to 10-day window does not elicit A-G investigation by the female and pregnancy block does not result. However, exposure to the original male after 10 days evokes A-G investigation and pregnancy block. To determine the neuroanatomic area(s) involved in olfactory memory for mate, female voles received bilateral electrolytic lesions of either the amygdala or hippocampus. Females were subsequently exposed to males for 48 h, separated for 3 days, then reintroduced to their original mate for 24 h. Although pregnancy rate did not differ among the experimental groups, a greater proportion of amygdala-lesioned females displayed pregnancy block when reexposed to their previous mates compared with hippocampal- or sham-lesioned voles. Amygdala-lesioned voles also displayed a greater number of A-G investigations compared with the other groups. Performance on olfactory tests was not impaired. Taken together, these results suggest that the amygdala plays an important role in olfactory memory for mate in prairie voles.

Amygdala↗

The prediction of premorbid memory ability.

An estimation of premorbid memory ability is necessary for clinical judgments of memory status following brain injury or illness. This paper describes the nature of clinical reasoning about memory ability and intelligence. The analysis of these reasoning problems has progressed from the simple contrast of clinical versus actuarial models to a theory that integrates all such models as applications of reasoning under uncertainty. This is followed by the first empirical study of the estimation of premorbid memory ability from demographic variables. The results of this analysis clearly suggest that demographic variables predict memory scores at a low level (R =.45); this result stands in contrast to the higher predictive power of demographics when IQ is the criterion. Practical suggestions are then proposed for establishing an empirical basis for clinical judgments of premorbid memory ability.

Journal Article↗