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Biomedical subjects

D A Simpson

Publications and source records attributed to D A Simpson.

At least 55 records · Page 3Linked to original sources
PubMed1994

A variant of adrenomyeloneuropathy in a family with adrenoleukodystrophy and adrenomyeloneuropathy.

A 31-year-old man was seen with addisonian crisis, followed by the abrupt onset of spastic paraparesis and peripheral neuropathy. A workup revealed adrenal insufficiency, for which the patient was aggressively treated. The workup also revealed an increase in very-long-chain fatty acids consistent with the diagnosis of adrenomyeloneuropathy. Abnormal pituitary dysfunction improved with treatment of the Addison's disease. A review of the patient's pedigree revealed two family members in whom multiple sclerosis had been diagnosed but which, in retrospect, was thought to be adrenomyeloneuropathy. No other family member was found to have Addison's disease. A sibling died at age 8 of Schilder's disease, confirming the presence of adrenoleukodystrophy as well as adrenomyeloneuropathy within this family.

Addison Disease↗
PubMed1994

Brain injury patterns in fatally injured pedestrians.

To study the relationship between the severity of impact to the head and the severity and distribution of injury to the brain in fatally injured pedestrians, events in vehicle-pedestrian collisions were reconstructed to determine the peak linear and angular acceleration sustained by the pedestrians' heads. The nature and distribution of injuries to the brain were determined by neuropathologic examination of coronal sections of the brain. Study of 13 cases with occipital impacts and 18 with lateral impacts showed that the brain appeared to be more susceptible to injury from lateral impacts. The frontal and temporal regions appeared to be more susceptible to injury at low accelerations in occipital impacts, providing an explanation for "coup" and "contrecoup" injuries. For occipital impacts, a positive relationship was found between linear acceleration and the extent of injury to the brain, suggesting that there was a threshold for observable and concussive brain injury at about 1500 m/s2 peak linear acceleration. These findings are important for the development of measures for preventing brain injuries.

Accidents, Traffic↗
PubMed1993

Extradural haematoma: trends in outcome over 35 years.

We have reviewed 35 years experience of extradural haemorrhage (EDH) in a large neurosurgical unit, based in two university hospitals, one dealing exclusively with children and the other a general hospital. A steady reduction in the mortality rate from 29 to 8.5% occurred during that period. A trend towards earlier diagnosis is noted and an increasing proportion of rural patients has been evident throughout the study period. During the time-period studied there were many significant developments: the establishment of a modern neurosurgical unit, the evolution of an intensive care unit, the availability of CT head scanning and the formal organization of rapid retrieval to service country areas. However, no single feature could be identified as the major contributor to falling mortality results. Clinical awareness and early diagnosis are the keys to successful management of EDH.

Adolescent↗
PubMed1993

Hunter-McAlpine syndrome: report of a third family.

A 9-year-old girl with craniosynostosis, facial dysmorphism, mental retardation, proportionate short stature and acral abnormalities is described, in whom both clinical and radiological features support a diagnosis of Hunter-McAlpine syndrome. Her mother is mildly affected, confirming previous evidence that this syndrome is dominantly inherited and shows considerable phenotypic variability within families.

Abnormalities, Multiple↗
PubMed1992

Genetic analysis of Pseudomonas aeruginosa adherence: distinct genetic loci control attachment to epithelial cells and mucins.

Infection of mucosal tissues by the opportunistic pathogen Pseudomonas aeruginosa is initiated by attachment of the bacterium to host tissues. To gain a better understanding of this interaction, we used two methods to isolate mutants of P. aeruginosa with altered adherence to cultured A549 cells and to mucins. First, from a population of nonpiliated mutants of P. aeruginosa mutagenized with transposon Tn5G, we have isolated variants that are defective in binding to both A549 cells and respiratory mucins. Using a cloned transposon plus flanking DNA from one such mutant as a DNA probe, we have isolated plasmids from a cosmid bank, which, upon reintroduction to the original mutants, restored adhesion to both A549 cells and mucin. The second strategy to identify genes involved in adhesion used mutagenesis of P. aeruginosa N1G, an rpoN mutant which is unable to bind to either A549 cells or mucin, with transposon Tn5 containing an outward-directed promoter. From this bank of mutagenized P. aeruginosa N1G, two classes of adhesion variants were isolated; one class attached to A549 cells and to mucin, and the other class restored binding of the rpoN mutant to mucin but not to A549 cells. These findings suggest that P. aeruginosa can express at least two adhesins distinct from pili, one recognizing receptors shared by epithelial cells and mucins and the other recognizing mucins alone.

Bacterial Adhesion↗
PubMed1992

Alterations to influenza virus hemagglutinin cytoplasmic tail modulate virus infectivity.

The influenza virus hemagglutinin (HA) contains a cytoplasmic domain that consists of 10 to 11 amino acids, of which five residues have sequence identity for 10 of 13 HA subtypes. To investigate properties of these conserved residues, oligonucleotide-directed mutagenesis was performed, using an HA cDNA of influenza virus A/Udorn/72 (H3N2) to substitute the conserved cysteine residues with other residues, to delete the three C-terminal conserved residues, or to remove the entire cytoplasmic domain. The altered HAs were expressed in eukaryotic cells, and the rates of intracellular transport were examined. It was found that substitution of either conserved cysteine residue within the cytoplasmic domain did not affect the rate of intracellular transport, whereas deletion of residues within the C-terminal domain resulted in delayed cell surface expression. All the altered HAs were biologically active in hemadsorption and fusion assays. To investigate whether the wild-type HA and HAs with altered cytoplasmic tails could complement the influenza virus temperature-sensitive transport-defective HA mutant A/WSN/33 ts61S, the HA cDNAs were expressed by using a transient expression system and released virus was assayed by plaque analysis. The wild-type HA expression resulted in a release of approximately 10(3) PFU of virus per ml. Antibody neutralization of complemented virus indicated that the infectivity was due to incorporation of wild-type H3 HA into ts61S virions. Sucrose density gradient analysis of released virions showed that each of the HA cytoplasmic domain mutants was incorporated into virus particles. Virions containing HAs with substitution of the cysteine residues in the cytoplasmic domain were found to be infectious. However, no infectivity could be detected from virions containing HAs that had deletions in their cytoplasmic domains. Possible roles of the HA cytoplasmic domain in forming protein-protein interactions in virions and their involvement in the initiation of the infection process in cells are discussed.

Amino Acid Sequence↗
PubMed1992

Usefulness of beta 2-transferrin assay in the detection of cerebrospinal fluid leaks following head injury.

The clinical value of analyzing various fluids and exudates for beta 2-transferrin (beta 2-Tfn) to detect cerebrospinal fluid (CSF) leakage following head trauma was reviewed in a series of 11 cases. Qualitative detection of beta 2-Tfn was performed by agarose gel electrophoresis of tears, ear and nose exudates, cerebral cyst fluid, and wound discharge fluid in different cases. In each instance the presence of beta 2-Tfn in the analyzed fluid supported the diagnosis of a CSF leak. Equally, the demonstration of the absence of beta 2-Tfn in the fluid excluded the diagnosis of such a leak. Neither false-positive nor false-negative results were found, as indicated by separate radiological investigations and/or subsequent clinical assessment of patients. The detection of beta 2-Tfn in suspect fluids thus provides a highly sensitive and selective, rapid, and noninvasive test for the detection of CSF leakage in cases of head trauma.

Adolescent↗
PubMed1991

Head injuries in infants and young children: the value of the Paediatric Coma Scale. Review of literature and report on a study.

The normal verbal and motor responses embodied in the standard Glasgow Coma Scale (GCS) are not achievable during the first few years of life. The recent literature contains numerous reports of attempts to devise scales of responses quantitating the conscious level in infants and young children, both for research purposes and as clinical guides; some of these scales incorporate items, e.g. brainstem reflexes, that are not included in the GCS. We have reported on a simple paediatric version of the GCS, which uses the standard scale with minor modifications in the verbal component, and sets realistic age-related normal responses. This has been tested prospectively in a series of 60 head-injured infants and children (age range 0-72 months). Of 6 cases recorded as comatose 6 h after injury, 4 have confirmed or suspected residual disabilities. Of 35 cases considered to be fully conscious at 6 h, 31 have made good recoveries and only 1 has suspected residual disabilities. The study suggests that the scale accords with the realities of neurological immaturity, and confirms that it can be used in routine paediatric practice. For comparative therapeutic trials, the conscious level in infants has limited value as an index of brain injury, and should be complemented by other indices, such as brainstem reflexes.

Brain↗
PubMed1991

Influenza virus ts61S hemagglutinin is significantly defective in polypeptide folding and intracellular transport at the permissive temperature.

The influenza virus hemagglutinin (HA) temperature-sensitive (ts) mutant, ts61S, contains a nucleotide change in RNA segment 4 which leads to an amino acid change at HA1 residue 110 of serine to proline. When ts61S HA is synthesized and maintained at the nonpermissive temperature (39.5 degrees), the HA is defective in transport in the exocytic pathway and is retained in the endoplasmic reticulum (S. Nakajima, D. J. Brown, M., Ueda, K., Nakajima, A. Suguira, A. K. Pattnaik, and D. P. Nayak, 1986, Virology 154, 279-285). In a comparison of the biochemical properties of ts61S HA and A/WSN/33 HA (wt) expressed at the permissive temperature (33 degrees), we have found that ts61S HA is extensively debilitated. A large proportion of ts61S HA fails to gain reactivity with conformation-specific monoclonal antibodies and does not become resistant to protease digestion. In turn, a large population of the molecules are not transported from the ER to the Golgi apparatus or cell surface with the same kinetics or efficiency as wt HA. These data suggest that the serine to proline change at HA1 residue 110 leads to partial impairment of folding at the permissive temperature with complete impairment at the nonpermissive temperature.

Animals↗
PubMed1991

Embolism of cerebral tissue: a cause of coagulopathy and cerebral infarction? Report of a case.

We report a case of potentially survivable closed head injury, which was complicated by disseminated intravascular coagulation and bilateral cerebral infarction. Autopsy disclosed pulmonary emboli composed of cerebral tissue. We suggest that the entry of brain tissue into the systemic blood circulation caused severe disseminated intravascular coagulation, with consequent thrombosis of cerebral veins and spreading infarction.

Brain↗
PubMed1991

Pseudomonas aeruginosa exoenzyme S is an adhesion.

Exoenzyme S from Pseudomonas aeruginosa has been studied as an adhesion for glycosphingolipids and buccal cells. Binding of exoenzyme S to gangliotriosylceramide (GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer), gangliotetraosylceramide (Gal beta 1-3 GalNAcT beta 1-4 Gal beta 1-4Glc beta 1-1Cer), and lactosylceramide (Gal beta 1-4Glc beta 1-1Cer) separated on thin-layer chromatograms was observed. Binding curves for exoenzyme S with dilutions of gangliotetraosylceramide immobilized on plastic plates were similar to previously reported results for the intact bacteria. Binding of exoenzyme S to sialylated counterparts of these glycosphingolipids was not seen, indicating that the addition of a sialic acid residue interferes with binding. Exoenzyme S and monoclonal antibody to exoenzyme S inhibit the binding of P. aeruginosa to buccal cells. The presence of exoenzyme S on the surface of P. aeruginosa was detected by immunogold labeling of bacteria with antibodies to exoenzyme S. Results of these studies led us to conclude that exoenzyme S is an important adhesion of P. aeruginosa.

ADP Ribose Transferases↗
PubMed1991

Pontomedullary tear in a speedboat accident. Report of a case with MRI diagnosis.

A case of atlanto-occipital dislocation with incomplete pondomedullary brainstem tear is reported; it resulted from a high-speed motorboat accident. The 43 year old man exhibited a locked-in syndrome; the diagnosis was made with MRI and verified by autopsy. With modern methods of life support, prolonged survival after such injuries is unfortunately sometimes possible.

Abducens Nerve↗
PubMed1990

Extradural haemorrhage in infancy and childhood. A review of 35 years' experience in South Australia.

One hundred and two paediatric cases of extradural haemorrhage (EDH) were treated in Adelaide, South Australia, during the period 1954-1988; 10 were infants (0-2 years) and 92 were children (2-14 years). There were 9 deaths (mortality 8.8%). Long-term disabilities severe enough to interfere with school and/or employment were seen in 8 (7.8%) survivors. This relatively low number of adverse outcomes is partly an expression of a low incidence (5.9%) of associated intradural haematomas and few high-velocity impacts due to vehicular accidents. There is reason to believe that the results of treatment have improved in the decade 1977-1988. We attribute this in part to early diagnosis by computed tomography (CT), but a contributory factor may be earlier referrals from country centres to a paediatric trauma centre and rapid transfer, by air or road, by medical retrieval teams.

Adolescent↗
PubMed1989

Effect of fluid preloading on cardiovascular variables after spinal anaesthesia with glucose-free 0.75% bupivacaine.

We studied the effect on systemic arterial pressure of fluid preloading with 1 litre of crystalloid fluid before spinal anaesthesia in 40 patients undergoing minor lower abdominal or lower limb surgery. Fluid was given at a rate of either 1 ml min-1 (no preload group), or 1000 ml in the 15 min (preload group) immediately before induction of spinal anaesthesia with 3 ml of 0.75% glucose-free bupivacaine. There was no difference between the groups in the character of anaesthesia or motor block in the lower limbs. The cephalad spread of analgesia ranged from L1 to C8. Analgesia was insufficient for surgery without supplementary analgesia in three patients in each group. The group not given a fluid preload had significantly lower arterial pressures (P less than 0.05) when anaesthesia extended above the T5 dermatome. The mean time before the lowest arterial pressure was recorded was twice as long in the preloaded group as in the non-preloaded group. Glucose-free 0.75% bupivacaine did not give a reliable extent of anaesthesia for lower abdominal surgery.

Abdomen↗
PubMed1989

Road crash cervical injuries. A radiological study of fatalities.

A lateral radiograph of the cervical spine was obtained for 174 of the 207 persons killed in road crashes in Adelaide, South Australia, during the 12-month period of June 1, 1987 to May 31, 1988. Of the total of 57 cases of cervical injury, routine postmortem examination identified 30 cases (52.6%), and the radiographic examinations identified 51 cases (89.5%). In the cases where it was performed, radiography identified 96.2% of injuries. One-half of injuries of level C3 and above were not reported at postmortem examination, compared with 22% of those occurring below this level. This finding correlates with the physical difficulties of examining the upper part of the cervical spine. This study has shown that lateral cervical radiography is a simple and effective method of more accurately identifying significant cervical spinal injuries, thus improving greatly the value of postmortem examinations in determining the patterns and mechanisms of these injuries.

Accidents, Traffic↗
PubMed1989

Pontomedullary tears and other gross brainstem injuries after vehicular accidents.

In a series of 988 autopsied victims of road crashes, there were 36 (3.6%) cases of gross primary brainstem injury. These fell into three groups. The first comprised eight cases of pontomedullary tearing without other gross brain injury: in seven of these, there were associated atlanto-occipital dislocations and/or high cervical fracture-dislocations. The usual cause appeared to be facial impact inducing acute hyperextension. Second, there were 17 cases of pontomedullary tearing associated with other brainstem lacerations and/or major damage elsewhere in the brain: in all, there were fractures of the skull base, typically transverse middle fossa fractures. Most of these injuries appeared to be due to facial impacts transmitting force to the anterior skull base, although hyperextension was also a factor in some. There was a third heterogeneous group of 11 cases with brainstem lacerations in sites other than the pontomedullary junction: in some of these it appeared that the impacts had caused skull base fractures by inducing calvarial torsion. In this series, the proportion of motorcyclists (41.7%) was double the expected figure. The use of a helmet modifies the mechanisms of impact head injury; the overall benefits of helmet use are well established, but there is need for more research on helmet design.

Accidents, Traffic↗