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Biomedical subjects

G Baker

Publications and source records attributed to G Baker.

At least 55 records · Page 3Linked to original sources
PubMed1995

The Neurotoxicity Scale: the validity of a patient-based scale, assessing neurotoxicity.

The validity of a patient-based scale, presumably measuring adverse effects of drugs on cognitive function, was examined in a normal volunteer study. Thirty subjects were randomly assigned to placebo or one of two doses of a benzodiazepine, temazepam (10 mg and 20 mg), in a double-blind placebo-controlled parallel group design. Plasma samples were taken before the scale was completed and up to 8 hours post-dose. After administration of the medication the subjects were asked to maintain their normal daily routine as much as possible (reading, studying, conversations). The inventory was administered twice, at 50 minutes and 2 hours post-dose (peak level). The overall score was different between the three groups, only for the second assessment, 2 h post-dose (ANOVA, P < 0.02). Multiple t-testing between the three groups revealed statistically significant differences between placebo and the 10 mg temazepam group (P = 0.02) and between placebo and the 20 mg temazepam group (P = 0.006). No significant difference was found between the two temazepam groups. Analysis of the separate questions showed least sensitivity for questions related to the domain of 'hyperexcitability' and most sensitivity for 'fatigue' and 'slowing.' The overall score appeared to be sensitive already for the lower toxicity range suggesting an 'all or nothing effect'. The subjective reports, collected by using this scale, may therefore be used for the detection of gross overall changes in cognitive functioning.

Adult↗
PubMed1995

High fertilization rate with intracytoplasmic sperm injection in mosaic Klinefelter's syndrome.

With the introduction of intracytoplasmic sperm injection (ICSI) as a practical successful treatment for male infertility, we are able to offer the procedure to a group of patients who probably could never father a child of their own. From a patient with mosaic Klinefelter's syndrome, sufficient motile sperm for intracytoplasmic sperm injection were obtained from a fresh ejaculate estimated to contain < 100 motile sperm. In the first IVF-ICSI attempt, out of seven oocytes that were collected from the wife, four were mature and were injected by ICSI. Fertilization occurred in all four oocytes but only one cleaved and was transferred to the uterus. Pregnancy test was negative 16 days after ET. In the second treatment cycle four out of eight oocytes were selected for ICSI. All four fertilized, three cleaved at the right time, and two were transferred into the wife's uterus. One embryo was frozen. Pregnancy test 16 days after ET was negative. The high fertilization rate achieved in this case indicates the potential of ICSI to treat extreme male infertility. Its use offers hope to those patients with conditions previously considered to be untreatable.

Adult↗
PubMed1995

Development of a scale to measure core beliefs and perceived self efficacy in adults with epilepsy.

A scale based on underlying core beliefs generated by the experience of epilepsy was developed. The scale, with measures of coping, adaptability, and knowledge, was used to examine the commonly-reported differences in emotional adjustment between patients (EP) and a non-epileptic population (NEP). The EP had significantly lower perceived self efficacy and was more depressed and anxious than the NEP controls. The NEP showed greater knowledge of medical aspects of epilepsy than the EP. Positive correlations between scale values and measures of mastery, self esteem, affect balance, felt stigma and impact of epilepsy were found. Factor analysis produced a three factor solution of emotion, knowledge and anxiety which explained 61.6% of the variance in scores. Results are discussed in terms of Bandura's theory of self efficacy as the motivating and sustaining force in the ability to change behaviour. Core beliefs are central to both the development and maintenance of anxiety and depression in epilepsy patients and need to be addressed in any attempts at remedial intervention.

Adaptation, Psychological↗
PubMed1994

Effect of 6-hydroxydopamine lesions of the amygdala on intravenous cocaine self-administration under a progressive ratio schedule of reinforcement.

Bilateral six-hydroxydopamine (6-OHDA) lesions were placed in the amygdala of rats self-administering cocaine (1.5 mg/kg per injection i.v.) under a progressive ratio schedule of reinforcement. Post-lesion access to three doses of cocaine (1.5, 0.75 and 0.37 mg/kg per injection i.v.) revealed a lesion effect only at the highest dose. At this dose, the lesion caused a significant increase in breaking point. No change in the breaking point was produced at the lower two doses. The biochemical results show a significant reduction in dopamine and DOPAC levels within the amygdala and an increase in dopamine within the NACC. In contrast, noradrenaline and serotonin (5-HT) levels were unaffected by the lesion in any of the dissected areas. These results demonstrate that no specific effect on cocaine reinforcement was produced by 6-OHDA lesions of the amygdala. The possibility that the lesion may have attenuated the anxiogenic qualities of the high dose of cocaine is discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Immunocytochemical identification of murine and human megakaryocyte colonies in soft-agar cultures.

Murine megakaryocyte (MK) colonies in soft-agar cultures were immunocytochemically stained with platelet antiserum and an immuno-alkaline phosphatase procedure. Subsequently, cytochemical staining for acetylcholinesterase was used to confirm the specificity of the immunolabelling technique. The correlation of numbers of megakaryocyte colonies enumerated by independent observers was excellent. A comparable platelet antiserum directed against human platelet epitopes was utilized to identify human MK colonies in soft-agar cultures of human bone marrow. Using this method, we determined that the frequency of detectable human MK colonies in our agar culture system was maximal between days 10 and 12. The immunocytochemical staining technique we have developed for identification of MK colonies in soft-agar cultures yielded good cellular morphology and produced an intensely specific label against a clear background; it therefore facilitated accurate enumeration of MK colonies. This non-fluorescent method avoids dependence upon a non-permanent marker, and allows the simultaneous enumeration of positive and negative colonies.

Acetylcholinesterase↗
PubMed1994

Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls.

Twenty-six patients with RDC bipolar disorder were compared with a previously reported group of 48 RDC schizophrenics and 34 healthy controls, using volumetric MRI measurements of cerebral, cortical and sulcal volumes. The bipolar group appeared no different from the controls, and both of these groups had significantly larger cerebral and cortical volumes than the schizophrenics. Our previous report of a significantly reduced cortical volume in the schizophrenic group, with a corresponding increase in the volume of sulcal fluid is, therefore, not a generalized feature of psychotic illness but may be more specific to schizophrenia.

Adult↗
PubMed1993

Engineering a novel specificity in subtilisin BPN'.

The specificity of subtilisin BPN' toward substrates with large hydrophobic P4 residues has been improved by single amino acid replacements at positions 104 and 107. Mutations were designed to (i) increase the size of the P4 binding pocket by replacing Ile107, which is at the bottom of the S4 pocket, by Val, Ala, and Gly and (ii) lose the hydrogen bond between Tyr104 and Ser130 at the entrance of the P4 binding pocket by changing Tyr104 to Phe and thus reduce interactions between small P4 side chains and residue 104. All mutant subtilisins, except for I107V, have increased specificity for residues with large side chains at P4 compared with wild type. Using the conventional definition of specificity as the competition of different substrates for the same enzyme, the I107G mutant subtilisin has one of the largest improvements in substrate specificity reported for subtilisin so far; kcat/KM is increased > 200-fold for Phe compared with Ala as the P4 residue. Further, the activity of I107G toward its specific substrate is comparable to that of the wild-type enzyme. Surprisingly, much of the increase in specificity on mutation of Ile107-->Gly appears to result from a lesion that is transmitted through the structure and effects catalysis. The value of kcat/KM for the small substrate acetyltyrosine ethyl ester, which binds to the S1 pocket, drops by 93% on mutation of Ile107-->Gly. The lesion in subtilisin I107G is complemented, however, on binding of longer substrates that have a large hydrophobic P4 amino acid side chain that can bind in the S4 pocket.

Amino Acid Sequence↗
PubMed1993

Measuring the impact of epilepsy: the development of a novel scale.

The impact of a chronic illness is experienced not only through its physical symptoms, but also as a result of its effect on psychosocial functioning. In the case of an illness such as epilepsy, where the physical manifestations are transient, the psychosocial consequences may, with time, come to be of greater concern. We have been involved in developing a quality of life model for epilepsy. As part of the refinement of the initial model, we have devised a novel scale to measure the impact of the condition on a number of different aspects of daily life. The scale was administered to 75 patients attending an epilepsy out-patient clinic. Initial analysis of its psychometric properties is encouraging, although the inclusion of an item relating to employment reduced the scale's reliability. As a result, the wording of the existing item has been amended and an additional item has been incorporated. We hope the scale will be useful in investigations of treatment for epilepsy and of its psychosocial aspects.

Adolescent↗
PubMed1993

The impact of counselling with a practical statistical model on patients' decision-making about treatment for epilepsy: findings from a pilot study.

To ascertain the impact of a computer-based predictive model on patients' decisions about continuing treatment of their epilepsy, 72 subjects were asked to complete questionnaires prior to and following counselling with the model. The subjects were attending the neurology out-patient clinic in a large UK hospital, and were identified from medical records as eligible for withdrawal of AEDs. The effect of counselling with the model was to make the majority of patients opt to continue AED therapy. Positive or negative framing of risk information appeared to influence the decisions of patients who were initially uncertain about continuing treatment, as did patients' perceptions of the clinician's views. The prognostic model appeared to allow relatively complex statistical information to be conveyed to patients in an accessible form. We suggest its use will aid clinicians in counselling patients and will help patients reach better-informed decisions about treatment.

Counseling↗
PubMed1993

Seizure severity and the quality of life.

The efficacy of an antiepileptic drug (AED) is determined at present by the drug-elicited reduction in seizure frequency. Reduction of seizure frequency as the sole measure of efficacy does not account for treatment-induced reductions in seizure severity and positive psychological effects experienced by the patient. A clinical trial was undertaken in which seizure frequency was the primary and seizure severity and psychological well-being were the secondary measures of efficacy. Psychological assessment and seizure frequency were monitored in patients whose epilepsy was treated with lamotrigine (LTG) or placebo. The results indicate that LTG is an effective AED, causing reductions in seizure frequency and severity and improvements in mood and mastery. In addition, the study demonstrated that the use of seizure severity scales, especially the ictal subscale, may enhance the sensitivity of assessment of trials of AED treatments.

Anticonvulsants↗
PubMed1993

Biological and biochemical characteristics of murine megakaryoblastic cell line L8057.

Biological and biochemical characteristics of a murine megakaryoblastic cell line (L8057), derived from an irradiated C3H/He mouse, were studied. The L8057 cells grew in liquid cultures with a doubling time of 24 to 27 hours. By light and electron microscopy, the L8057 cells were small and basophilic with a high nuclear/cytoplasmic ratio, but large cells (approximately 25 to 60 microns) were sometimes seen. Western blot analysis of cell extracts demonstrated that murine megakaryocyte and platelet antigens, glycoprotein (GP) IIb/IIIa, fibronectin, and factor VIII:RAg were expressed in L8057 cells. Acetylcholinesterase (AChE)-positive cells were rare (< 2.0%). Flow cytometric analysis demonstrated that 8.7% of the cells were spontaneously polyploid (> 4N DNA levels). In response to phorbol diester (TPA, 50 nm), L8057 cells showed a decrease in proliferation and a marked increase in cell size and amount of cytoplasm. The morphology of the cells became similar to that of megakaryocytes, with larger and lobulated nuclei and expansion of the demarcation membrane system compartment. The proportion of cells with ploidy levels greater than 4N increased to 40.8% (8N, 21.3 +/- 3.2%; 16N, 13.1 +/- 2.6%; > or = 32N, 6.4 +/- 4.9% [n = 4]). More than 90% of the cells became AChE-positive. TPA also increased the expression of GP IIb/IIIa, fibronectin and factor VIII:RAg. Thus, the L8057 cell line provides a potentially superior model with which to study the characteristics of megakaryocytic biology, differentiation and biochemistry.

Acetylcholinesterase↗
PubMed1992

Detection of calcified atherosclerotic plaque by laser-induced plasma emission.

The use of fluorescence spectroscopy to discriminate atherosclerotic from normal tissue is limited by a lower sensitivity for calcified than noncalcified atherosclerotic plaque (65% vs. 93%, respectively). To evaluate plasma emission as a means to detect calcified plaque, 325 normal and atherosclerotic cadaveric aortic sites were irradiated through a 100-micron silica fiber in blood by a pulsed holmium laser (lambda = 2.1 microns, fluence = 4 J/mm2). A photodiode positioned near the proximal end of the fiber detected plasma emission during a laser pulse. Plasma emission was detected at 0% (0/110) of normal, 0% (0/107) of noncalcified atherosclerotic tissue, and 91% (98/108) of calcified atherosclerotic sites. Spectroscopic analysis confirmed the presence of calcium lines in the plasma emission from calcified atherosclerotic plaque. Although ablative fluences (greater than 3 J/mm2) were required for plasma generation, a single laser pulse ablated only to a depth of 67 +/- 16 microns in normal tissue. In an additional 10 calcified atherosclerotic sites, laser ablation was continued as long as plasma emission was detected. In all cases, plaque ablation was terminated before arterial perforation. Furthermore, the adjunctive use of plasma detection improved the accuracy of fluorescence spectroscopic classification of normal and atherosclerotic tissue. In conclusion, plasma detection has a high sensitivity (91%) and specificity (100%) for calcified atherosclerotic plaque and may be a useful adjunct for laser angioplasty guidance. Furthermore, plasma detection can be implemented both simply and inexpensively.

Aluminum Silicates↗
PubMed1992

Prediction of silicosis and lung cancer in the Australian labor force exposed to silica.

Empirical models for risk, based on recently published epidemiologic data, and simple prediction formulas were used to predict the occurrence of silicosis and lung cancer in the Australian labor force currently exposed to crystalline silica dust. As a result of an 0.9 (range 0.4-1.9)% average lifetime risk, approximately 1010 (range 380-2410) silicosis cases were predicted for the next 40 years among the estimated 136,400 men exposed at current silica dust levels [0.01-0.8 (average 0.094) mg.m-3]. Approximately 630 extra lung cancer cases (95% confidence interval 120-1320) would appear with an average excess risk of 0.5 (interval 0.1-1.1)%, the proportion of silica-induced lung cancer cases being about 15%. Currently 77% of the at-risk labor force is exposed to silica dust levels of < or = 0.1 mg.m-3. With this level as the limit, about 440 (range 140-1210) silicosis cases and 410 (interval 90-780) extra lung cancer cases would occur in 40 years. Adopting this level as the national exposure standard would reduce the risk of silicosis cases by 52% and the excess risk of lung cancer by 36%.

Adult↗