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Biomedical subjects

D Bruce

Publications and source records attributed to D Bruce.

At least 19 recordsLinked to original sources

Late MRI after head injury in children: relationship to clinical features and outcome.

To characterize the brain pathology in relation to long-term outcome after pediatric head injury, 55 children were studied by magnetic resonance imaging (MRI) at least 3 months after sustaining moderate to severe closed head injury (CHI). Thirty-nine of the patients had abnormal signal intensity consistent with residual brain lesions, including 28 children with lesions involving the frontal lobes. The clinical features of children with frontal lesions, extrafrontal lesions, and diffuse injury were compared. The analysis disclosed that children with frontal lobe lesions were more frequently disabled than children who sustained diffuse injury. Our MRI findings indicate that residual brain lesions are more common after moderate to severe CHI in children than previously thought and that the frontal lobes are most frequently involved. Further investigation is indicated to elucidate whether distinctive cognitive and behavioral sequelae are associated with frontal lobe lesions in children.

Adolescent

Corpus callosum lesions after closed head injury in children: MRI, clinical features and outcome.

Thirty-four children who sustained moderate to severe closed head injury underwent magnetic resonance imaging (MRI). Eight (24%) had MRI evidence of corpus callosum injury, most commonly within the posterior body and splenium. In contradistinction to reports in adults, there was no definite relationship between callosal injury and lower initial Glasgow Coma Scale scores, nor was there a significantly higher incidence of primary brain-stem lesions, diffuse axonal shear injury or intraventricular hemorrhage. In none of these 8 children did the initial admission computed tomography show evidence of callosal injury. Callosal injuries on MRI are not necessarily a poor prognostic finding, the majority of the 8 children showing good functional recovery.

Adolescent

Narrative discourse after closed head injury in children and adolescents.

This study examined narrative discourse in 20 children and adolescents at least 1 year after sustaining a head injury. Narratives were analyzed along the dimensions of language structure, information structure, and flow of information. Severity of impaired consciousness was associated with a significant reduction in the amount of language and information. The most important finding which emerged was the disruption in information structure. This pattern confirms the impression of disorganized discourse in severely injured children. Explanations for the disruption in information structure are explored in terms of the role of vocabulary, memory, and localization of lesion according to magnetic resonance imaging. In view of recent evidence that frontal lobe damage is associated with discourse formulation deficits in adults and is the most common site of focal lesion in closed head injury, we examined discourse patterns in individual patients with frontal lobe lesions. Preliminary data from our single-case studies suggest discourse patterns similar to those reported for adults with frontal lobe injuries.

Adolescent

Molecular biology for platelet alloantigen typing.

Hitherto, full investigation of patients with alloimmunization to platelet-specific antigens has been difficult due to the limited availability of both typing reagents and panels of typed platelets. Following recent advances in the understanding of the molecular and genetic basis of platelet alloantigens, it is now possible to genotype individuals for the alleles coding for the epitopes of four platelet antigen systems (HPA-1-4). This is based on the finding that the two alleles differ by only a single base pair substitution, resulting in one amino acid difference in the relevant platelet glycoprotein. The technique involves amplification of the relevant segments of genomic DNA from any nucleated cell by the polymerase chain reaction, followed by restriction fragment length polymorphism analysis. The technique allows investigation of thrombocytopenic individuals and fetuses/neonates, and can be readily applied to large-scale typing of platelet donors.

Alleles

Reversibility of cerebral atrophy after head injury in children.

Reversible cerebral atrophy in humans has been documented by computed tomography in alcoholics and has been described as an incidental finding after head injury in children. Two children were studied who had sustained a severe closed head injury, 1 and 5 years previously, after which cerebral atrophy had developed, according to subacute computed tomography. Reversible cerebral atrophy was seen on magnetic resonance images of both patients. Despite normal appearance on magnetic resonance images more than 1 year after injury, both patients exhibited residual neuropsychological impairment on a broad range of cognitive and memory tests.

Brain Edema

The incidence of dysfunctional antithrombin variants: four cases in 210 patients with thromboembolic disease.

210 patients, with a history of venous thrombosis, have undergone prothrombotic investigations. In nine cases a consistent deficiency of antithrombin was identified. In five there was a reduction in the plasma antigenic concentration of antithrombin and in a further four cases deficiency was due to the presence of a dysfunctional antithrombin variant. The variants have all been characterized by DNA analysis and in three the mutations have been confirmed by peptide sequencing (antithrombin Basel (41 Pro to Leu). Hamilton (382 Ala to Thr). Cambridge I (384 Ala to Pro) and Cambridge II (384 Ala to Ser). The incidence of antithrombin deficiency in patients with a history of venous thrombosis has previously been quoted at between 2% and 3%: there is no published data available on the incidence of antithrombin variants. In our series 5% of patients who presented before the age of 40 years had antithrombin deficiency, and 2% of the total number of patients investigated had a dysfunctional variant. Our figures indicate that a significant number of cases of antithrombin deficiency are due to dysfunctional variants and that the true incidence of antithrombin deficiency in patients with a history of venous thrombosis is in the order of 5%.

Adult

Availability and category-frequency estimation.

Individuals judged how often examples of taxonomic categories had occurred in a study list. An availability hypothesis was tested--that frequency estimates are based on the retrieval of instances. Cued (by category names) recall of the examples served as an index of availability. The hypothesis was confirmed--there were strong positive correlations between frequency judgments and recall (with the influence of actual frequency removed)--given one or more of the following conditions: List instances were not categorized aloud as they were presented; frequency estimation was preceded by cued recall; frequency estimation was delayed by a week. Limitations on availability occurred under other conditions--notably, when individuals, during list presentation, named the categories to which items belonged and received feedback about their categorizations. Under these circumstances, correlations of frequency estimation and recall were often not significantly different from zero, and frequency judgments and recall sometimes reacted differently to changes in independent variables (e.g., frequency judgments of young and elderly subjects did not differ reliably, even though cued recall of young persons markedly exceeded that of elderly subjects).

Adult

Antithrombin Dublin (-3 Val----Glu): an N-terminal variant which has an aberrant signal peptidase cleavage site.

Antithrombin Dublin is an electrophoretically fast variant of antithrombin which has normal heparin affinity. Direct sequencing of amplified exon 2 revealed a Val----Glu substitution at position -3. N-terminal sequencing of antithrombin from two individuals, heterozygous for the Dublin mutation, showed the presence of a truncated antithrombin in which the N-terminal dipeptide is absent. We propose that the prepeptide mutation redirects signal peptidase cleavage to a site two amino acids downstream into the mature protein.

Adult

Use of oxonol V as a probe of membrane potential in proteoliposomes containing cytochrome oxidase in the submitochondrial orientation.

Absorbance changes in the anionic dye bis[3-phenyl-5-oxoisoxazol-4-yl]pentamethineoxonol (oxonol V) can be used to monitor the membrane potential of liposomes and cytochrome c containing cytochrome oxidase proteoliposomes (c-loaded COV). Diffusion potentials (positive inside the vesicles) cause an increase in the dye extinction, with a maximum at 640 nm. A similar increase is seen upon energization of internally facing cytochrome oxidase molecules in c-loaded COV. Both "passive" and "active" responses are only seen when the dye is fully bound to the vesicle membrane. Calibration curves using potassium or n-butyltriphenylphosphonium ion (BTPP+) diffusion potentials are linear up to 100 mV and pass through the origin. Diffusion potentials (positive inside) also cause an increase and red shift in the oxonol V fluorescence emission spectrum. However, potentials of the same sign induced by cytochrome oxidase turnover induce a large fluorescence quenching in c-loaded COV. A similar anomaly has been observed with submitochondrial particles [Smith, J. C., Russ, P., Cooperman, B. S., & Chance, B. (1976) Biochemistry 15, 5094-5105]. A model is proposed consistent with these responses. It is suggested that the dye molecules move further into the membrane phase upon energization, causing the absorbance increase. In the presence of active enzyme, anionic dye molecules are attracted to a positive dipole on each enzyme molecule, causing self-quenching of the fluorescence.

Calibration

State transitions in a phycobilisome-less mutant of the cyanobacterium Synechococcus sp. PCC 7002.

State transitions were investigated in the cyanobacterium Synechococcus sp. PCC 7002 in both wild-type cells and mutant cells lacking phycobilisomes. Preillumination in the presence of DCMU induced State 1 and dark-adaptation induced State 2 in both wild-type and mutant cells as determined by 77 K fluorescence emission spectroscopy. Light-induced transitions were observed in the wild-type after preferential excitation of phycocyanin (State 2) or preferential excitation of Chl a (State 1). Light-induced transitions were also observed in the phycobilisome-less mutant after preferential excitation of short-wavelength Chl a (State 2) or carotenoids and long-wavelength Chl a (State 1). We conclude that the mechanism of the light-state transition in cyanobacteria does not require the presence of the phycobilisome. Our results contradict proposed models for the state transition, which require phosphorylation of, and an active role for, the phycobilisome.

Chlorophyll

The role of radiation therapy in the management of childhood craniopharyngioma.

Between 1965 and 1986, 31 children were treated for craniopharyngioma at the Children's Hospital of Philadelphia. Total removal was attempted in all patients. Some patients received radiation therapy following subtotal removal. Of the patients whose first resection was subtotal, five received radiation and seven did not. Four of the 5 patients who were radiated (80%) are stable (median 89 months, range 42-155 months) and one recurred at 42 months, failed salvage with total removal, and subsequently died of disease. Of the seven who were not irradiated, all had recurrences (median 12 months, range 3-192 months) and one died of disease. Nineteen patients initially had total removal and none received adjuvant radiation. One patient died postoperatively. Of the 18 remaining patients, 6 had recurrences (median 24 months, range 7-100 months) and 12 (66%) are stable (median 42 months, range 9-133 months). One of these stable patients died of endocrine complications 24 months after initial surgery. Fourteen of the 31 patients recurred. Two died with recurrence and one required no further treatment. Eleven had second resections following initial surgical removal. Seven of these 11 went on to receive radiation and four did not. All seven who were radiated are stable (median 33 months, range 1-228 months); whereas 1 of the 4 who were not radiated recurred again at 18 months. This patient had a third resection followed by radiation therapy and is now stable at 20 months. After initial surgery (and before radiation, when given) 26 of 31 patients had panhypopituitarism, 4 had partial deficits, and 1 was normal. Severe diencephalic syndrome, loss of visual acuity, and intellectual deficits were no more frequent in patients treated with total removal, subtotal removal, and in patients who received radiation. We conclude that radiation has an important role following subtotal removal and for salvage treatment after initial surgery. Aggressive attempt at total removal does result in prolonged progression-free survival in some patients. Extensive resections may result in significant mortality and endocrine morbidity. This review suggests that subtotal removal and radiation results in outcomes at least as favorable as treatment with total removal alone.

Adolescent

Continuous intracranial pressure monitoring and serial electroencephalographic recordings in severely asphyxiated term neonates.

We report our observations from intensive intracranial pressure (ICP) monitoring and serial clinical neurologic and electroencephalographic examinations in ten asphyxiated full-term neonates, of whom five died and at least two survivors had multiple severe neurologic handicaps. Direct measurements of ICP were obtained by a newly developed infant subarachnoid bolt and/or a transfontanelle pressure transducer. Simultaneous ICPs were recorded and correlated when possible. We noted a dependence of transfontanelle ICP values on application technique and force. In infants with no bleeding diathesis, the subarachnoid bolt was safe and no complications were encountered. Only six infants experienced pathologic elevations of ICP following birth asphyxia, and of these infants only two had sustained, marked increases of ICP. We also noted abundant fluctuations of cerebral perfusion pressure (mean arterial blood pressure minus ICP), but the majority of fluctuations were accounted for by mean arterial pressure changes rather than ICP changes. We found no deterioration of clinical neurologic function as measured by serial mental status examinations and electroencephalogram samples at the time the maximum ICP was measured. We also noted very little change in ICP during most electrographic seizures. In these infants ICP did increase after birth but major ICP elevations were uncommon and did not appear to introduce any acute functional neurologic disturbances. Most changes in cerebral perfusion pressure were attributed to blood pressure rather than ICP changes. It appears unlikely that cerebral edema and elevated ICP play a major role in determining neurologic outcome in some asphyxiated term infants.

Asphyxia Neonatorum

Numerical classification of campylobacters by DNA-restriction endonuclease analysis.

Reference strains from five different species of Campylobacter were examined by DNA-restriction endonuclease analysis. The DNA profiles were resolved as absorbence peaks and converted to numerical values which were analysed by a Sirius microprocessor. The percentage similarity between each profile was calculated and the strains clustered together by the computer on shared similarities and the results displayed as an abbreviated dendrogram. Each of the species of Campylobacter were clearly separated from each other and the different biotypes within a species could also be differentiated.

Bacterial Typing Techniques

Lashley's shift from bacteriology to neuropsychology, 1910-1917, and the influence of Jennings, Watson, and Franz.

From 1910 to 1917, Karl S. Lashley's research moved from bacteriology to neuropsychology through intermediate stages of zoology, comparative psychology, and the psychology of learning. This shift is examined with particular reference to Lashley's associations with John B. Watson, Shepherd I. Franz, and Herbert S. Jennings. Watson's impact was substantial, for he attracted Lashley to comparative psychology and was the source of many of his later research interests. The bridge to neuropsychological research was provided by Franz who trained Lashley in the lesion method of investigating the brain bases of learning. The influence of Jennings, Lashley's Ph.D. supervisor, was most evident in the divergence of the post-1915 interests of Lashley and Watson. Lashley's search for brain mechanisms of learning, as contrasted with Watson's concern with behavioral prediction and control, mirrored a similar earlier difference between Jennings and Jacques Loeb.

Animals

Measurement of pregnancy associated plasma protein A (PAPP-A).

A method is described for measuring pregnancy associated plasma protein A (PAPP-A) in the maternal circulation during the 3rd trimester of pregnancy. The method used is a modification of Laurell's electroimmunodiffusion technique.

Antibody Specificity

Computed tomography of craniocerebral injury in the abused child.

Computed tomography (CT) was performed in 26 infants and children with craniocerebral trauma related to abuse during a 41-month period. The pattern of brain injury differed from that seen in the nonabused traumatized infant or child. Parieto-occipital acute interhemispheric subdural hematoma (AIHSH) with associated parenchymal injury was the most frequent finding (58%). Follow-up by CT in patients with AIHSH demonstrated infarction in half and cerebral atrophy in all.

Brain Injuries