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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 325 records · Page 18Linked to original sources
PubMed1994

Synthesis of substituted 3-carbamoylecgonine methyl ester analogues: irreversible and photoaffinity ligands for the cocaine receptor/dopamine transporter.

Photoaffinity ligands are useful tools for the isolation, purification, and characterization of proteins. As a step toward the goal of producing a photoaffinity probe for the dopamine transporter, isocyanato and azido derivatives of 3-[(phenylcarbamoyl)oxy]ecgonine methyl ester were synthesized and tested for their ability to interact with the cocaine receptor of mammalian brain via two different assays. The ability of two isothiocyanato (N=C=S) (para and meta) and two azido (N3) (para and meta) derivatives, as well as (-)-cocaine, to inhibit [3H]cocaine binding and [3H]dopamine uptake and to covalently interact with the cocaine-binding site was tested. The p-N=C=S was the most potent, with IC50 values of 0.23 and 0.49 microM for [3H]cocaine binding and [3H]dopamine uptake. The m-N3 and p-N3 inhibited [3H]cocaine binding with IC50 values of 0.63 and 1.00 microM and inhibited [3H]dopamine uptake with IC50 values of 5.08 and 1.32 microM, respectively. Preincubation of synaptosomal membranes with the m- or p-N=C=S isomer either in reduced lighting or under ultraviolet light followed by two washes resulted in inhibition of 70% and 85% of [3H]cocaine binding, respectively, indicating the highly reactive properties of these compounds. After preincubation in reduced lighting, m-N3 and p-N3 inhibited 0% and 13% of [3H]cocaine binding, while following preincubation under ultraviolet light, the inhibition increased to 61% and 68%, respectively. Thus, the isothiocyanato derivatives appear to bind irreversibly to the cocaine receptor in the presence or absence of ultraviolet light, whereas the azido derivatives are photoreactive compounds which may prove useful in the purification of the receptor.

Affinity Labels↗
PubMed1994

Treatment of subdiaphragmatic Hodgkin's disease: is radiotherapy alone appropriate only for inguino-femoral presentations?

PURPOSE: Evaluate the role of staging laparotomy, and the impact of disease subsites on treatment outcome, for sub-diaphragmatic Hodgkin's Disease. METHODS AND MATERIALS: Between 1966 and 1989, 23 patients with Hodgkin's disease limited to sites below the diaphragm were treated at the Royal Adelaide Hospital. The high male:female ratio (2:8), low proportion of nodular sclerosis subtype (26%), and older age (mean = 40) relative to supra-diaphragmatic Hodgkin's disease is consistent with most other series. Thirteen patients underwent staging laparotomy. Initial treatment consisted of radiation therapy alone in 11, chemotherapy alone in 7, and combined modality therapy in 4 patients. This data was then combined with other published series over the last decade, to analyse relapse patterns and treatment results in relation to initial site(s) of disease. RESULTS: The overall, disease specific, and progression free 5 (and 10) year survival rates were 69%, 81%, and 58% respectively. There was no statistically significant effect of staging laparotomy on any of these parameters. Combining these results with those in the literature revealed an unacceptable relapse rate for patients with disease outside of the inguino-femoral region treated with inverted-Y radiation therapy alone. CONCLUSIONS: For the majority of patients with sub-diaphragmatic Hodgkin's disease, staging laparotomy can be avoided. Inverted-Y radiation therapy should only be used for inguino-femoral presentations.

Adolescent↗
PubMed1994

Family stressors in traumatic brain injury: a two-year follow-up.

A review of the literature suggests that psychosocial disability in traumatic brain-injured (TBI) individuals and distress in families continues long after the initial injury. In this study the relationship of family stress to a number of factors was studied longitudinally. Caregivers of 51 TBI inpatients were interviewed at rehabilitation admission and by phone at 6, 12, and 24 months postinjury. Caregivers' most common complaints about their relatives were a lack of involvement in leisure activities, fatigue, slowness, and forgetfulness. Increasingly severe temper outbursts, anxiety, and self-centeredness were reported over time. Aggressiveness was reported by caregivers as moderate or severe in 31% of cases by 2 years postinjury. Of all complaints, only reports of inappropriate social behavior decreased over time. Despite caregivers' increasing complaints about their relatives, there were no trends toward greater self-reported stress over time. At the 2-year assessment, stress was significantly higher for caregivers of those with an at risk psychosocial history, and for those without sufficient funds for services. Caregivers reporting financial strain increased 22% from rehabilitation admission. Forty-seven percent of caregivers had altered or given up their jobs at 1 year postinjury, and 33% at 2 years postinjury. Although self-perceived measurements of stress did not increase over time, caregivers reported notable increases in medication use and substance use, and decreases in employment and financial status over the 2-year time period. When spouse and parent caregiver responses were compared, spouses reported a consistently greater number of behavioral problems, which increased in severity over time. Those behaviors associated with mood disturbances predominated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Patient preference for high or low dose rate brachytherapy in carcinoma of the cervix.

High and low dose rate are two competing methods of brachytherapy. Existing data do not support choosing one method over the other for treating carcinoma of the uterine cervix. Arguments include clinical efficacy, monetary cost, radiation safety, and patient preference. There are no published data on patient preference. We developed a questionnaire to elicit patient preference and to measure its strength. Subjects received descriptions of both treatment options and their probable outcomes. We elicited preference for one low or three high dose rate fractions, and for two low or five high dose rate fractions, assuming both methods to be isoeffective. Strength of initial preference was measured by asking subjects how much of a change, in either the changes for cure or the chances for toxicity, would make them change preference. The questionnaire was completed by female staff at our centre (n = 90), by a group of previously treated patients (n = 18), and by a group of newly diagnosed patients (n = 20). When both methods were assumed to be isoeffective, only 34% of the 38 patients preferred three fractions of high dose rate to one fraction of low dose rate. However, when high dose rate was assumed to be 2% more curative, or 6% less toxic, a simple majority of 50% then said they would prefer high dose rate. Both preference and strength of preference for low dose rate were significantly associated with a greater travelling distance for treatments. Age, marital status, family structure, education, employment, and family income were not associated. In summary, a majority of our patients preferred low dose rate brachytherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Conservation of the tandem arrangement of alpha 1-microglobulin/bikunin mRNA: cloning of a cDNA from plaice (Pleuronectes platessa).

alpha 1-Microglobulin and bikunin are both plasma proteins which are synthesized in mammalian liver from a common mRNA with tandemly arranged coding sequences. Here, we report a piscine homologue of mammalian alpha 1-microglobulin/bikunin mRNA which was serendipitously isolated from a plaice (Pleuronectes platessa) liver cDNA library. The piscine cDNA recognized an approximately 1300 nucleotide mRNA on Northern blots of plaice liver RNA and, to a lesser extent, on blots of kidney and whole blood RNA. The deduced amino acid sequence displayed very similar tandemly arranged and homologous sequences for alpha 1-microglobulin and bikunin to those found in the corresponding mammalian cDNAs (35-38% amino acid identity for alpha 1-microglobulin and 45-50% for bikunin). Southern blots of plaice genomic DNA demonstrate that there are probably no closely related genes in addition to the gene for this cDNA. Taken together, these results suggest that the structure of the alpha 1-microglobulin/bikunin mRNA and gene is conserved in fish and mammals, implying an important common function for the tandem expression of these proteins.

Alpha-Globulins↗
PubMed1994

Age-specific antibody prevalence to hepatitis A in England: implications for disease control.

Sera from an age-stratified sample of 7196 individuals, submitted for diagnostic purposes to four public health laboratories in England in 1986/7, were tested for hepatitis A antibody. The serological profiles, which showed marked regional differences, were consistent with declining incidence in the past. The decline in the incidence of hepatitis A has resulted in an increase in susceptibility in adults. This has three main consequences: an increase in the average age of infection may be leading to an increase in morbidity; normal immunoglobulin may become less protective against hepatitis A; the risk of transmission through blood products contaminated by viraemic blood donors may rise. Current average annual incidence in 5-14-year olds was estimated to vary between regions from 0.5-1.9%. This supports the view that, in the absence of a vaccination programme, hepatitis A will remain endemic unless there are further improvements in living conditions and standards of hygiene. A vaccine giving long-lasting protection could eliminate hepatitis A transmission with modest coverage at a young age. Targeting childhood vaccination on economically deprived areas or using vaccine to control outbreaks might be more effective policies.

Adolescent↗
PubMed1994

Substance use among the mentally ill: prevalence, reasons for use, and effects on illness.

Substance use among a random sample of mentally ill, community-based patients was examined. Current use was found to have declined substantially from a high lifetime prevalence, and a family history of substance abuse was associated with moderate to heavy use. No association was found between heavy substance use and elevated psychopathology, hospitalization, or medication noncompliance. Hospital admissions and some symptoms were less prevalent among users preferring marijuana.

Adolescent↗
PubMed1994

The role of intervening patterns in the storage of the movement aftereffect.

Wohlgemuth, having measured the duration of the motion aftereffect (MAE), instructed subjects to close their eyes immediately after adaptation for a period of time longer than the MAE. Upon opening their eyes the subjects reported a residual effect, albeit somewhat shorter than the original effect. Thus the decay of the aftereffect appeared to have been retarded by the period of darkness. This effect is known as 'storage' and poses a problem for any model of the MAE based on the fatiguing of direction-selective units in the visual pathway. A reexamination is made of storage of the MAE, again concentrating on the intervening stimulation between movement adaptation and aftereffect test. The results suggest that the nature of the intervening pattern between adaptation and test conditions is remarkably unimportant. A total of 11 different storage patterns were examined after adaptation to high-contrast drifting horizontal sinewave gratings. For 10 of these patterns large and robust storage effects were found. The exception occurred when the spatial pattern of the storage stimulus was identical to the adaptation and test stimuli. It is proposed that storage cannot be understood in terms of a simple fatigue model of the MAE and that one component of the effect may share similarities with contingent aftereffects.

Contrast Sensitivity↗
PubMed1994

The effect of triacylglycerol fatty acid positional distribution on postprandial plasma metabolite and hormone responses in normal adult men.

The present study has examined the possibility that the positional distribution of fatty acids on dietary triacyglycerol (TAG) influences the postprandial response to a liquid meal in adult subjects. Postprandial TAG, non-esterified fatty acids (NEFA), ketones, glucose, insulin and gastric inhibitory polypeptide (GIP) responses were monitored in sixteen normal adult male subjects over 6 h following consumption of test meals containing dietary TAG in which palmitic acid was predominantly on the sn-1 (Control) or sn-2 positions (Betapol). Plasma total TAG, chylomicron-rich TAG and chylomicron-poor TAG concentrations were identical in response to the two test meals. The peak increase (mean (SD)) in chylomicron TAG was 0.85 (0.46) mmol/l after the Control meal and 0.85 (0.42) mmol/l after the Betapol meal. Plasma glucose, insulin, GIP, NEFA and ketone concentrations were also very similar following the two meals. It is concluded that dietary TAG containing saturated fatty acids on the sn-2 position appear in plasma at a similar level and over a similar timescale to TAG in which saturated fatty acids are predominantly located on sn-1 or sn-3 positions. The results reported in the present study demonstrate that the positional distribution of fatty acids on dietary TAG is not an important determinant of postprandial lipaemia in adult male subjects, but do not exclude the possibility that different responses may occur when these dietary TAG are given long term.

Adult↗
PubMed1994

Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure.

OBJECTIVE: Volume-controlled ventilation is frequently chosen as the initial mode of ventilatory support in patients with hypoxic respiratory failure. Recent data, however, suggest that pressure-limited ventilation, using a rapidly decelerating flow delivery pattern, may produce a more desirable clinical effect through reduced peak airway pressures and increased static compliance, tissue oxygen delivery, and consumption. This study was performed to assess the feasibility and utility of early and sustained use of pressure-limited ventilation in patients with this clinical syndrome. DESIGN: Randomized, prospective trial. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: The study encompassed all patients (n = 27) receiving care in a medical ICU for acute, severe hypoxic respiratory failure (PaO2/FIO2 ratio of < 150) during a 6-month period. INTERVENTIONS: Ventilatory support via either pressure-limited or volume-controlled ventilation, initiated within 24 hrs of endotracheal intubation. MEASUREMENTS: On-line monitoring of the following ten ventilatory variables at 1-min intervals for 72 hrs or until extubation or death (maximum of 43,200 data points per patient): peak airway pressure, mean airway pressure, end-tidal CO2 concentration, CO2 minute excretion, inspiratory tidal volume, expiratory tidal volume, pause pressure, end-expiratory pressure, static thoracic compliance, and inspiratory resistance. Additionally, PaO2/FIO2 values and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded on a daily basis, as were significant clinical events and changes in ventilator settings. RESULTS: Although the severity of illness at study entry as determined by APACHE II score and PaO2/FIO2 was similar in patients treated with pressure-limited or volume-controlled ventilation, peak airway pressure was consistently lower in patients randomized to pressure-limited ventilation (p = .05 at 12 hrs postintubation). The use of pressure-limited ventilation also was associated with a more rapid increase in static compliance (p = .05) than that found with volume-controlled ventilation. There was a trend toward more rapid normalization of CO2 minute excretion in patients treated with pressure-limited ventilation. Pressure-limited treated patients who survived their illness and were extubated, required fewer days of mechanical ventilation than did patients randomized to volume-controlled treated ventilation (p = .05). No pneumothoraces occurred in any study patients. One volume-controlled patient developed subcutaneous emphysema. Pressure-limited ventilation was well tolerated, and sedation requirements were equivalent in the two groups. CONCLUSIONS: Pressure-limited ventilation can be used safely and is well tolerated as an initial mode of ventilatory support in patients with acute hypoxic respiratory failure. Because the early initiation of pressure-limited ventilation is associated with lower peak airway pressure and more rapid improvement in static thoracic compliance than volume-controlled ventilation, pressure-limited ventilation may have a beneficial role when used as the primary ventilatory modality in patients with this clinical condition.

Adult↗
PubMed1994

Possible involvement of NMDA receptor-mediated transmission in barbiturate physical dependence.

1. The competitive antagonists at the N-methyl-D-aspartate (NMDA) receptor, CGP39551 and CGP37849, protected against the barbiturate withdrawal syndrome in mice, as measured by ratings of convulsive behaviour on handling. 2. The effective doses of these compounds were lower than those required to prevent seizures due to NMDA in naive animals; these were in turn lower than those needed to prevent the convulsive effects of the alpha-aminobutyric acid (GABA) antagonist, bicuculline. 3. The NMDA-receptor antagonists did not alter the increase in the incidence of convulsions due to the GABAA antagonist, bicuculline, that is seen during barbiturate withdrawal, although the latencies to these convulsions during barbital withdrawal were significantly increased after CGP39551. 4. Barbiturate withdrawal did not affect the convulsive actions of NMDA, whether measured by the incidence of convulsions or by intravenous infusion. 5. The Bmax for [3H]-dizocilpine ([3H]-MK801) binding was significantly increased by chronic barbital treatment in cerebrocortical but not in hippocampal tissues, while the Kd remained unaltered in either case. 6. At 1 h and 24 h after administration of a single dose of barbitone, the Bmax for [3H]-dizocilpine binding was unaltered in cerebrocortical tissue. Acute addition of barbitone in vitro did not alter [3H]-dizocilpine binding or the displacement of binding of thienylcyclohexylpyridine.

2-Amino-5-phosphonovalerate↗
PubMed1994

Bacterial meningitis in Swaziland: an 18 month prospective study of its impact.

STUDY OBJECTIVE: To describe the epidemiology, clinical features, and outcome of bacterial meningitis in Swaziland. DESIGN: Prospective study of patients diagnosed as having meningitis of nonviral aetiology during an 18 month period from February 1991 to July 1992. SETTING: Four regional hospitals covering the population of the four districts in Swaziland. SUBJECTS: All patients with non-viral meningitis admitted to hospital within the study period. MAIN RESULTS: Altogether 85 patients were reported to have bacterial meningitis: 48.3% were aged under 1 year. Causative organisms were identified in 60% of cases, and Streptococcus pneumoniae was found to be the commonest (49% of cases). Overall, case fatality was 38.8% for all age groups, and 62.5% (15 of 25) for adults. Neurological sequelae occurred in 22.4%. Three of the adult cases were HIV seropositive. Seizures, but not duration of symptoms before admission, were associated with a poor prognosis. There was a significant rise in incidence related to a period of drought. Fifteen patients were reported with tuberculous meningitis, of whom five were known to be HIV seropositive; the case fatality was 73.3%. CONCLUSIONS: The aetiology and age distribution of cases of meningitis differs greatly from that in developed countries. Rising HIV infection may have an important impact on the future incidence of meningitis. The high case mortality found should encourage efforts towards earlier diagnosis and treatment, and strengthens the need to develop appropriate vaccines.

Adolescent↗
PubMed1994

EFFECTS OF AMMONIA LOADING ON PORCELLIO SCABER: GLUTAMINE AND GLUTAMATE SYNTHESIS, AMMONIA EXCRETION AND TOXICITY

The effects of ammonia loading in the terrestrial isopod Porcellio scaber were studied by exposing animals to atmospheres of high PNH3. Isopods show a remarkable tolerance of elevated ambient PNH3, with an LD50 of 89 Pa for a 7-day exposure. However, haemolymph total ammonia concentrations generally remained below 5 mmol l-1 (PNH3=0.37 Pa) over the range of ambient ammonia levels used (6.6&shy;165 Pa). Following a 7-day loading period, whole-animal glutamine (Gln) and glutamate (Glu) levels increased in direct proportion to ambient PNH3, reaching values of 35 &micro;mol g-1 fresh mass for glutamine and 12 &micro;mol g-1 fresh mass for glutamate in 99 Pa PNH3; these correspond to control levels of 7.5 &micro;mol g-1 fresh mass and 5.9 &micro;mol g-1 fresh mass, respectively. Following transfer to ammonia-free chambers, NH3 excretion rates were augmented five- to sixfold relative to non-loaded controls. Ammonia volatilization subsequently declined, approaching control levels after 8&shy;9 days. Levels of Gln and Glu showed a concomitant decline to 13.7 &micro;mol g-1 fresh mass and 9.2 &micro;mol g-1 fresh mass, respectively. The results suggest that these amino acids function in ammonia sequestration and, hence, detoxification. Calculations indicate that mobilization of amino groups by deamination of accumulated Gln and Glu could explain 35 % of the increased ammonia production. Implications of NH3 volatilization for acid&shy;base balance are discussed.

Journal Article↗