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Biomedical subjects

J Morrow

Publications and source records attributed to J Morrow.

At least 55 records · Page 3Linked to original sources

An audit of therapeutic drug monitoring of anticonvulsants.

An audit of therapeutic drug monitoring (TDM) of anticonvulsants was performed to assess both its use and misuse in the management of patients with epilepsy. Over a four week period all samples received for phenytoin, carbamazepine, sodium valproate and phenobarbitone assays were included in the audit. The aims were to establish the source of the specimens, the reasons for the requests and to ascertain what action, if any, would be taken when the result of the assay was provided. A total of 163 separate assays were performed over the four week period (43 phenytoin, 74 carbamazepine, 41 valproate, 5 phenobarbitone). Only 18.7% of all requests originated from the adult neurology department. The vast majority of tests had been ordered by junior medical staff (only 10% by consultants) and approximately 50% were 'routine' with no satisfactory clinical reason for the request offered. There was a tendency to manipulate prescribed doses on the basis of drug levels alone without taking the clinical picture into consideration. These results demonstrate a general ignorance, especially amongst junior medical staff, of the value of TDM of anticonvulsants, and reinforce the need for both an educative and interpretive service to be provided by the Chemical Pathology Department.

Adult↗

Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester.

Growth factors and tumor promoters have been shown to play a role in intestinal epithelial growth regulation and transformation. In this study, transforming growth factor-alpha (TGF alpha) and the tumor promoter, tetradecanoyl phorbol acetate (TPA), are shown to stimulate the production of eicosanoids by rat intestinal epithelial (RIE-1) cells in culture. A 4.5-kb mRNA, which hybridizes to the mouse cyclooxygenase-2 cDNA probe, is elevated 18-fold within 30 min after TGF alpha or TPA treatment. Stimulation of RIE-1 cells with TGF alpha leads to the increase of a protein (M(r) approximately 69,000), which binds a monospecific antibody to the mouse cyclooxygenase-2 protein. Dexamethasone markedly inhibits the increase of the 4.5-kb mRNA. Pretreatment of TGF alpha or TPA-stimulated RIE-1 cells with dexamethasone or cyclooxygenase inhibitors prevents the increase in eicosanoid production by these cells. Treatment of quiescent RIE-1 cells with TGF alpha stimulates mitogenesis. This mitogenic activity is blocked by pretreating the cells with dexamethasone or cyclooxygenase inhibitors. A mitogen-inducible cyclooxygenase gene is thus shown to be regulated by TGF alpha and TPA in rat intestinal epithelial cells. We suggest that products of an intestinal growth factor-inducible cyclooxygenase may play a role in the regulation of mitogenesis.

Animals↗

Characterization of humoral immunity after DNA injection.

Antibodies to the influenza virus nucleoprotein are produced after injection of a plasmid DNA expression vector containing the nucleoprotein gene. A single injection of 10 to 100 micrograms of DNA produces IgG antibodies which first appear four to six weeks post injection. Antibody titres peak at six to eight weeks and then remain stable in most animals for many months. The antibody response at early times is dose-dependent, with higher amounts of DNA producing a faster immune response as well as higher antibody titres. Titres observed many months after injection are less dependent on DNA dose.

Animals↗

Response styles and the duration of episodes of depressed mood.

We examined the relationship between ruminative and distracting styles of responding to depressed mood and the duration of mood. Seventy-nine subjects kept accounts of their moods and responses to their moods for 30 consecutive days. The majority of subjects (83%) showed consistent styles of responding to depressed mood. Regression analyses suggested that the more ruminative responses subjects engaged in, the longer their periods of depressed mood, even after taking into account the initial severity of the mood. In addition, women were more likely than men to have a ruminative response style and on some measures to have more severe and long-lasting periods of depression.

Adaptation, Psychological↗

The gene for an inherited form of deafness maps to chromosome 5q31.

Primary--i.e., nonsyndromal-postlingual deafness is inherited as an autosomal dominant phenotype in a large kindred in Costa Rica. Genetically susceptible individuals begin to lose hearing at low frequencies at about age 10 years, after language and speaking are learned. Deafness inevitably progresses by age 30 years to bilateral hearing loss of all frequencies. Intelligence, fertility, and life expectancy are normal. The family traces its ancestry to an affected founder born in Costa Rica in 1754. We have mapped the gene for deafness in this kindred to chromosome 5q31, between the markers IL9 and GRL, by linkage analysis involving 99 informative relatives.

Base Sequence↗

Toe walking and language development.

Neurodevelopmental markers that are present early in childhood may identify children at risk for later developmental disabilities. This paper attempts to clarify the relationship between one such proposed marker, toe walking, and language development in a general pediatric population. One hundred sixty-three children being seen for well-child visits were included in the study. Information from each child's caretaker was obtained for language development and a history of toe walking; observation of toe walking during the visit was also included. The frequency of toe walking was 24%. Language quotients were calculated and compared for toe walkers (n = 39) and non-toe walkers (n = 127). The mean language quotient for toe walkers tended to be consistently lower than that for non-toe walkers. The specificity of toe walking for low language scores was 85% but had a sensitivity of only 32%. Although an association between toe walking and language delay is supported by the present data, the association does not appear to be clinically significant.

Age Factors↗

Minor malformations, hyperactivity, and learning disabilities.

Standardized minor malformation scores have been reported to predict and identify children with attentional problems and hyperactivity. The reason why this marker works for only a subset of children with attention deficit hyperactivity disorder remains unclear. The dysmorphology scores on all children presenting for a multidisciplinary team evaluation of developmental disorders were examined for diagnostic correlations after children with chromosomal disorders and recognized dysmorphic syndromes were excluded. For 1233 subjects, the mean minor malformation score was 2.94 (SD = 2.05). A significant association between minor malformation scores and IQ (mean = 80.95, SD = 23.67) was accounted for by the group with IQs greater than 100 exhibiting the higher dysmorphology scores. An analysis of variance revealed no significant association between minor malformation scores and hyperactivity or attention deficit disorder. Indeed, the presence of an attention deficit disorder yielded lower mean dysmorphology scores. When the minor malformation scores were compared for those subgroups of children with and without specific learning disabilities, the learning-disabled subjects had significantly higher dysmorphology scores. Minor dysmorphic features do not relate to the presence or absence of attentional problems or hyperactivity in referred children. Rather they appear to characterize that subpopulation of children with attention deficit disorder and learning disabilities as well as a group of learning-disabled children without attentional disorders.

Adolescent↗

Neuropeptide Y, a putative cotransmitter in noradrenergic neurons, induces mast cell degranulation but not prostaglandin D2 release.

Recent evidence suggests that neural transmitters, including neuropeptides, may modulate the release of mast cell mediators. Because neuropeptide Y (NPY) has recently been recognized as a putative cotransmitter in noradrenergic neurons, we studied the effect of NPY on purified rat peritoneal mast cells. NPY induced mast cell degranulation, as assessed by a dose-dependent increase in net release of beta-hexosaminidase. The concentration that produced 50% of the maximal effect, approximately 10 mumol/L, evoked a 40% +/- 3% release. As previously reported for other neuropeptides, release was fast with maximal release already achieved at 60 seconds. Release was at 4 degrees C. In contrast to its effects on mast cell degranulation, NPY had no effect on the generation of prostaglandin D2, the major mast cell cyclooxygenase product. By comparison, the calcium ionophore A23187, at doses (4 mumol/L) that evoked comparable release of beta-hexosaminidase, stimulated a net release of 37 +/- 9 ng of PGD2 per 10(6) mast cells. These results raise the possibility that NPY may act as a modulator between the autonomic nervous system and mast cells. The results also imply that with neuropeptide stimulation, the release of preformed and newly formed mast cell mediators are mediated through independent pathways.

Animals↗

The development of a seizure severity scale as an outcome measure in epilepsy.

In controlled trials of antiepileptic drugs (AEDs) seizure frequency is often the only variable considered. With little prospect of improving assessment of AEDs, using seizure counts as the only end-point, there is a need for the development of new outcome measures. Clinical experience indicates that seizure severity is equally important to the patient and, by preventing seizure spread, AEDs can influence seizure severity without necessarily reducing seizure frequency. A scale capable of measuring seizure severity and change of severity attributable to treatment could be a useful additional outcome measure. Such a scale should exhibit the basic properties of validity and reliability. An easily administrable 16-point scale, containing 2 subscales--perception of control and ictal/post-ictal effects--has been developed. This scale has been tested on a patient population (n = 159) representative of that seen in trials of novel AEDs. Using standardised statistical methods, the scale has been shown to be both reliable and valid.

Adolescent↗

A prospective study of depression and posttraumatic stress symptoms after a natural disaster: the 1989 Loma Prieta Earthquake.

Measures of emotional health and styles of responding to negative moods were obtained for 137 students 14 days before the Loma Prieta earthquake. A follow-up was done 10 days again 7 weeks after the earthquake to test predictions about which of the students would show the most enduring symptoms of depression and posttraumatic stress. Regression analysis showed that students who, before the earthquake, already had elevated levels of depression and stress symptoms and a ruminative style of responding to their symptoms had more depression and stress symptoms for both follow-ups. Students who were exposed to more dangerous or difficult circumstances because of the earthquake also had elevated symptom levels 10 days after the earthquake. Similarly, students who, during the 10 days after the earthquake, had more ruminations about the earthquake were still more likely to have high levels of depressive and stress symptoms 7 weeks after the earthquake.

Adaptation, Psychological↗

Accuracy of pulse oximeters in estimating heart rate at rest and during exercise.

Pulse oximeters are being widely used for non-invasive, simultaneous assessment of haemoglobin oxygen saturation. They are reliable, accurate, relatively inexpensive and portable. Pulse oximeters are often used for estimating heart rate at rest and during exercise. However, at present the data available to validate their use as heart rate monitors are not sufficient. We evaluated the accuracy of two oximeters (Radiometer, ear and finger probe; Ohmeda 3700, ear probe) in monitoring heart rate during incremental exercise by comparing the pulse oximeters with simultaneous ECG readings. Data were collected on eight men (713 heart rate readings) during graded cycle ergometer and treadmill exercise to volitional fatigue. Analysis by linear regression revealed that general oximeter readings significantly correlated with those of ECG (r = 0.91, P less than 0.0001). However, comparison of heart rate at each level of work showed that oximeter readings significantly (P less than 0.05) under-estimated rates above 155 beats/min. These results indicate that the use of pulse oximeters as heart rate monitors during strenuous exercise is questionable. This inaccuracy may well originate from the instability of the probes, sweating, other artefacts during exercise, and measurement of different components in the cardiovascular cycle.

Adult↗

Rare HRAS alleles and susceptibility to human breast cancer.

The suggestion that inherited rare alleles at the HRAS oncogene locus might be associated with susceptibility to breast cancer led us to test linkage of HRAS and the neighboring region of 11p15 to breast cancer susceptibility in 12 high-risk families. Linkage could be excluded within 17 cM of HRAS; the lod score for close linkage to HRAS was -19.9. In addition, rare HRAS alleles segregated independently of breast cancer in 8 families in which both occurred. Among unrelated breast cancer patients not selected for family history, rare HRAS alleles were slightly, but not significantly, more frequent than among controls (0.11 vs 0.04, P = 0.11). The HRAS region of 11p is not the site of a primary alteration leading to breast cancer.

Alleles↗

Effects of responses to depression on the remediation of depressive affect.

The effects of different types of responses to a depressed mood on the duration and severity of the mood were examined. On the basis of Nolen-Hoeksema's (1987) response styles theory of depression, it was hypothesized that distracting, active responses would be more effective in alleviating a depressed mood than would ruminative, passive responses. A depressed mood was induced in 35 male and 34 female Ss, and subjects were randomly assigned to engage in 1 of 4 types of responses: an active task that distracted them from their mood; a passive, distracting task; an active task designed to lead to ruminations about their mood; or a passive, ruminative task. As predicted, the greatest remediation of depressed mood was found in Ss in the distracting-active response condition, followed in order by the distracting-passive, ruminative-active, and ruminative-passive response conditions. Degree of rumination had a greater impact on remediation of depressive affect than level of activity, with greater rumination leading to lesser remediation of depressive affect. In addition, the effects of the response tasks were limited to depressed mood. The implications of these results for interventions with depressed persons are discussed.

Adaptation, Psychological↗

Primary and secondary deviational salience: predictors, consequences, symptoms and strategies.

In this article, the model of deviational salience [italics added], which explains the relationship between self-perceptions and perceptions in general is extended. Original analysis indicated that when individuals evaluate themselves as deviating negatively from their perception of the norm of a salient environmental stimulus, that stimulus becomes more meaningful. Reexamination of the original data indicates that this outcome also occurs when an individual's self-perceptions are incongruent with quantifiable objective norms. Furthermore, interaction between the two sufficient antecedent conditions of primary deviational salience, negative self-perceptions and incongruence, produces secondary deviational salience. The major dysfunctional consequences of both primary and secondary classifications have been examined. Those most debilitating involve misattribution based on the salient feature and obsessive concern over the feature. Finally, several rational-emotive approaches aimed at reducing deviational salience along with the maladaptive behavioral symptoms have been proposed.

Adaptation, Psychological↗