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Biomedical subjects

L Davies

Publications and source records attributed to L Davies.

At least 109 records · Page 6Linked to original sources
PubMed1993

The target of ammonia action in dictyostelium.

The weak base ammonia is implicated in a number of key processes in Dictyostelium development, notably aggregation and culmination. To determine its intracellular site of action, we compared its biological potency with that of other weak bases. All the bases inhibited these developmental processes effectively, but differed manyfold in potency in accordance with their activity in dissipating pH gradients, as measured by in vivo 31P NMR with pH-sensitive phosphonate probes. These results indicate that weak bases influence development by raising the pH of an intracellular acidic compartment.

Alkalies↗
PubMed1993

Identification, synthesis and properties of 5-(aziridin-1-yl)-2-nitro-4-nitrosobenzamide, a novel DNA crosslinking agent derived from CB1954.

5-(Aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide, the active form of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), can react spontaneously with oxygen, and in aqueous solution yields 5-(aziridin-1-yl)-2-nitro-4-nitrosobenzamide and hydrogen peroxide. Mild biological reducing agents such as NAD(P)H, reduced thiols and ascorbic acid rapidly re-reduced the nitroso compound to the hydroxylamine. Both compounds were equally efficient at inducing cytotoxicity and DNA interstrand crosslinking in cells when exposed in phosphate-buffered saline (PBS). Neither agent was capable of inducing cross-links in isolated DNA. When acetyl coenzyme A was included in the incubation, crosslink formation was seen with the hydroxylamine, but not with the nitroso compound. Thus, the nitroso compound is acting as a prodrug for the hydroxylamine, and needs to be reduced to this compound to exert its cytotoxic effects. In vivo anti-tumour tests showed that neither compound was effective in its own right. This may be due to the rapid reduction of the nitroso to the hydroxylamine, and the reaction of the hydroxylamine with serum proteins. The chemical synthesis of the 5-(aziridin-1-yl)-2-nitro-4-nitrosobenzamide, and an improved synthesis of 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is described. These results emphasize the potential efficacy of the in situ activation of prodrugs such as CB1954 either by endogenous enzymes such as DT diaphorase, or by antibody directed enzyme prodrug therapy (ADEPT).

Animals↗
PubMed1993

What is BS5750?

Explore the source record for details and available documents.

Dental Care↗
PubMed1993

Variation in firing order of human soleus motoneurons during voluntary and reflex activation.

The activation of motoneurons in a muscle pool is said to proceed as an ordered array in response to both dorsal root stimulation and voluntary activation, with small motoneurons being recruited before larger ones. We have examined 19 voluntarily recruited soleus motor units in 5 normal subjects and found that in 18 cases, the lowest threshold motor unit recruited by slowly increasing 'tonic' voluntary activity was different from the lowest threshold unit recruited by electrical stimulation of the tibial nerve in the popliteal fossa (phasic Hoffman reflex). The initially recruited voluntary units were, however, part of the pool influenced by the stimulated afferents because, during tonic activation, the timing of their discharge could be shown to be altered by electrical stimulation at a lower intensity than that required for H recruitment at rest. These findings suggest that the pool of soleus motoneurons responding to the voluntary command "tonically plantar flex your ankle" differs somewhat, in order of activation, from the pool responding to phasic stimulation of the largest diameter fibers in the tibial nerve, perhaps because of inhomogeneities in the distribution of descending or segmental inputs to the soleus motoneuron pool. Whether this partitioning is functional or a reflection of minor, random variations in synaptic density remains to be determined.

Action Potentials↗
PubMed1993

Discharge properties of single motor units in patients with spinal cord injuries.

To study neurophysiological correlates of spastic paresis, we analyzed the discharge pattern of single motor units (SMUs) during sustained voluntary contraction from muscles weakened by spinal cord injury (SCI) and from muscles of near normal strength just at or above the level of injury. The average firing rate of SMUs was reduced in patients' biceps brachii and tibialis anterior muscles compared with controls, but not in the triceps brachii. Floating serial correlation coefficients obtained from successive interdischarge intervals were significantly more positive in patients than in controls in all three muscles. One statistical measure of regularity of discharge, akin to a coefficient of variation, was best able to differentiate patient and control SMUs. Increased discharge variability in muscles just above the level of injury suggested that subtle effects of traumatic SCIs were more extended than was clinically apparent. Although consistent statistical differences could be measured, these changes were not specific to SCI, nor were all SMUs equally affected.

Humans↗
PubMed1993

Portable system for quantifying motor abnormalities in Parkinson's disease.

In order to quantify motor disabilities in Parkinson's disease (PD), we designed a compact, portable, neurophysiological system based upon a personal computer to measure tremor, bradykinesia, and muscle tone. Tremor was detected by solid state accelerometers and translated into a digital signal. The system displayed the root mean square displacements and frequency distribution of the tremor in the horizontal and vertical planes, along with a reconstructed graphic image of the displacement. Bradykinesia was measured using a panel that detects release and depression of switches in response to auditory and visual signals; the system calculated subjects' reaction times and movement times in milliseconds. Tone at the elbow was measured by strapping the upper extremity to a lightweight low-friction cradle and then passively moving the cradle with an instrumented handle. Signals representing torque and arm angle were processed by the computer and displayed in real time on the screen with stiffness as a mean slope in Nm/degree. In clinical tests, quantitative measures of tremor, movement time and rigidity were significantly abnormal in PD patients compared to control subjects. We conclude that this system is a convenient and accurate method to quantitate important aspects of the parkinsonian syndrome, and may be applied to quantitate other movement disorders.

Adult↗
PubMed1993

Rectal methohexital for sedation of children during imaging procedures.

OBJECTIVE: Brevital (methohexital), administered as a solution per rectum, provides safe, rapid, and effective sedation for induction of surgical anesthesia. This study was undertaken to evaluate rectal Brevital as a sedative for children undergoing imaging procedures. MATERIALS AND METHODS: In a review of patients' records, we found that, during a 1-year period, 190 children from 1 month to 14 years old were sedated for CT or MR imaging. Sedation was required for 94 CT and 96 MR imaging studies. Rectal Brevital was used in 102 patients (mean age, 25 +/- 2 months), and oral chloral hydrate was used in 88 (mean age, 28 +/- 3 months). RESULTS: Sleep was achieved in 81% of patients who received Brevital and in 80% of those who received chloral hydrate. Induction time was shorter (p = .0001) with Brevital (9 +/- 1 min) than with chloral hydrate (28 +/- 2 min). The mean duration of sleep was 46 min with Brevital and 66 min with chloral hydrate (p = .0001). Brevital provided adequate sedation in 89 (87%) of 102 imaging studies, and chloral hydrate did so in 73 (83%) of 88 studies. No cardiorespiratory complications or allergic reactions occurred with either drug. Significantly fewer patients were discharged fully awake and alert after sedation with chloral hydrate than with Brevital (p < .002). Children sedated with chloral hydrate also required a longer period of observation in the radiology department (p < .04). CONCLUSION: We conclude that rectal Brevital produces sedation of adequate duration for most imaging procedures in children. Ease of administration, wide margin of safety, rapid and pleasant induction, and short recovery time make this drug a favorable alternative to other commonly used sedatives.

Adolescent↗
PubMed1993

The pulmonary response to sublethal thoracic irradiation in the rat.

An animal model of radiation-induced lung disease was established using male Wistar rats given sublethal bilateral thoracic irradiation (15 Gy). The rats were studied for up to 20 weeks and compared to sham-irradiated controls. Three distinct syndromes were identified. Two weeks after irradiation there was an increase in wet lung weight without an increase in dry lung weight. Interstitial edema was confirmed ultrastructurally, but aside from minor abnormalities of endothelial cells, both capillary and alveolar basement membranes were intact and there was no alveolar protein leak. At 4 weeks after irradiation, there was an abrupt increase in both wet and dry lung weights, as well as intra-alveolar macrophages, lymphocytes, polymorphs, and protein. These changes persisted for periods of up to 8 weeks. Electron microscopy at 4 weeks revealed prominent interstitial edema and severe endothelial cell damage. There was patchy thickening of the cytoplasm of type I cells as well as some cells which appeared to be transforming from type II to type I cells, suggesting previous epithelial denudation. Mast cell density increased in perivascular and peribronchial areas from 4 weeks, and this and parenchymal mast cell density peaked at 7 weeks. The total collagen content of the lungs (determined biochemically) rose by up to 50% above control values from 5 weeks after irradiation, the bulk of the increase having occurred by 12 weeks. Further increases up to 20 weeks were similar to that seen in growing control animals. Collagen deposition (as defined by electron microscopy and Picrosirius polarization) was prominent in peribronchial and perivascular areas in all animals, but in alveolar walls it was increased severalfold above controls by 20 weeks after irradiation. In summary, this model provides sequential changes of interstitial edema, alveolitis, and interstitial fibrosis which can be studied independently. The temporal relationship between the appearance of mast cells and increased collagen deposition supports the hypothesis that mast cells are intimately related to the development of fibrosis.

Animals↗
PubMed1993

The effect of steroids on radiation-induced lung disease in the rat.

We have used a model of bilateral radiation-induced lung disease in the rat to study the effects of corticosteroids. This model is characterized by interstitial edema at 2 weeks after radiotherapy followed by florid alveolitis with an alveolar protein leak which peaks at 4 weeks. Mast cell density peaks at 7 weeks, and there is a progressive increase in lung collagen (fibrosis) from 5 to 20 weeks. Intraperitoneal corticosteroids or saline were given at the time of irradiation or sham irradiation (protocol 1), every second day during weeks 3 and 4 (protocol 2), or three times weekly during weeks 3 to 8 (protocol 3). In protocol 1, steroids protected the lung from interstitial edema at 2 weeks, delayed the alveolitis without reducing its intensity, and significantly reduced the alveolar protein leak. However, radiation fibrosis was not reduced at 20 weeks. Longer steroid administration (protocol 2) suppressed the alveolar protein leak and delayed and significantly reduced the severity of the inflammatory cell response. Although the tissue mast cell and fibrotic responses were suppressed during and for at least 3 weeks after steroids, the ultimate fibrotic reaction was the same in both irradiated groups. In protocol 3, steroids suppressed the alveolitis and delayed the rise in tissue mast cell density, but did not affect the fibrotic response at 20 weeks. These studies suggest that steroids can suppress the alveolitis provided they are used throughout the period of alveolitis. Although they also delay the tissue mast cell response to radiation, the ultimate fibrosis is not altered. This provides further evidence for the dissociation of alveolitis and fibrosis after lung irradiation and has potential implications for management of radiation-induced lung disease in humans.

Animals↗
PubMed1992

An active covalently linked dimer of human interferon-gamma. Subunit orientation in the native protein.

We have constructed and expressed a covalently linked head to tail dimer of human interferon-gamma (IFN-gamma) in which two monomers are joined head to tail via a rigid peptide hinge using genetic engineering techniques. The hinge was derived from the human immunoglobin IgA1 sequence (Hallewell, R.A., Laria, I., Tabrizi, A., Carlin, G., Getzoff, E.D., Tainer, J.A., Cousens, L.S., and Mullenbach, G.T. (1989) J. Biol. Chem. 264, 5260-5268). Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the polypeptide produced by this construction migrates as a 30,000 polypeptide species. The protein elutes as a single species by molecular sieve chromatography under native conditions. The covalently linked dimer exhibits one-half the antiviral activity of native dimeric IFN-gamma; receptor binding assays show the covalently linked dimer binds to the IFN-gamma receptor with one-half the avidity of native IFN-gamma. This difference is not due to conformational differences between the two molecules, as the aromatic region of the NMR spectrum of the purified covalently linked dimer is identical with that of the wild type protein. From these data, we suggest that human IFN-gamma associates in a head to tail dimer in its active configuration. Regions of IFN-gamma are contiguous with the amino and carboxyl termini and are obscured by the hinge peptide in the covalently linked dimer. Our studies demonstrate that these regions may be important for receptor-ligand interaction.

Amino Acid Sequence↗
PubMed1992

Recumbent tic.

A 59-year-old man with a 30-year history of an unusual movement disorder characterised by involuntary axial spasms that occur only in recumbency is described. Clinical and electrophysiological evidence suggest that this disorder is best characterised as a simple tic of unusual form. We have coined the term "recumbent tic" to describe this disorder.

Abdominal Muscles↗
PubMed1992

The economics of femorocrural reconstruction for critical leg ischemia with and without autologous vein.

It is well established that primary arterial reconstruction, even to crural vessels, is cheaper than amputation. Reintervention increases expenditure and may produce mean costs exceeding those of primary amputation. Furthermore, secondary amputation may eventually become necessary. Femorocrural grafts have the highest average "reconstruction policy" cost (i.e., primary procedure and all further operations necessary during follow-up). We must therefore seek support for this potentially expensive form of treatment. In conjunction with health economists we have compared the average policy cost of 130 reconstructions with grafts exceeding 70 cm in length (89 vein grafts, 41 polytetrafluoroethylene grafts with a distal vein collar) with 67 vascular amputations, at mean follow-up of 3 years. One-month mortality rate after reconstruction was less than 1% but was 10% after amputation. At 3 years, however, 20% of both groups were dead. Overall 3-year patency is 65% (72% for vein grafts, 48% for polytetrafluoroethylene grafts). Ninety-seven percent of irreversible graft occlusions resulted in amputation in these patients. After autologous vein grafting reintervention, our follow-up showed increased mean costs from $6898 to $15,024 per patient. After prosthetic grafting, the higher reintervention rate increased from $6898 to $20,416. These mean costs remained less than amputation, reintervention, and additional mobility costs, which amounted to a mean of $21,726 per patient. Important differences in outcome were observed: 70% of patients undergoing amputation were confined to the home compared with only 9% of patients undergoing reconstruction; 30% of patients undergoing amputation were confined to bed or had to use a wheelchair compared with 1% of patients undergoing reconstruction.

Amputation, Surgical↗
PubMed1992

Confidants and companions: choices in later life.

This study examines and compares the correlates of considering each of the following as a confidant or a companion: spouse, children, siblings, other relatives, friends. Using a Canadian sample of 400 respondents aged 65 and over, we found evidence of substitution among the previously married and childless; more extensive ties to children and more intimate ties to friends among women; the importance of geographic proximity to children for confiding and companionship, and to siblings for confiding; the relevance of family size to confiding in siblings; and the precariousness of friendship as one reaches very old age. Predictors of who serve as confidants and as companions are similar, but important differences emerge. We compared our results to those of studies in Australia and the United States and to an earlier analysis of network composition and concluded that the confiding and companionate relations of older persons are best understood by combining the results of relationship-specific and network composition analyses.

Aged↗
PubMed1992

Correlates of using mental health services: implications of using alternative definitions.

BACKGROUND: Studies using varying definitions of mental health visits result in widely divergent estimates. This analysis examines the stability of a predictive model using three varying definitions based on provider type, diagnosis, psychotherapy, and psychotropic medication use. METHODS: Interview and questionnaire data and claims records from the RAND Health Insurance Experiment are used to test these models among 3138 enrollees. RESULTS: Estimates of visits, and factors associated with them, are highly sensitive to definitions. Depression was the only symptom/life situation variable, and education the only sociodemographic measure, predictive across all three models. Risk indicators such as suicide thoughts and drinking problems were only significant for the traditional (mental health specialty) model. While patients within the traditional model definition were significantly younger than other enrollees, those within the model using the most expansive definition were significantly older. Varying the definition also led to different results in respect to experimental manipulations, geographic sites and some specific types of comorbidity. CONCLUSIONS: A reasonable definition, consistent with medical standards, requires, at least, a mental health diagnostic judgment and some form of psychotherapeutic or drug treatment. Studies of the content of mental health care are needed.

Adult↗
PubMed1991

Economic analysis alongside clinical trials. Revisiting the methodological issues.

Controlled clinical trials are recognized as the best source of data on the efficacy of health care interventions and technologies. Because economic evaluation is dependent on the quality of the underlying medical evidence, clinical trials have increasingly been viewed as a natural vehicle for economic analysis. However, the closer integration of economic and clinical research raises many methodological issues. This paper discusses these issues in trial design, collection of resource use data, collection of outcome data, and interpretation and extrapolation of results. Some guidelines are suggested for economic analysts wishing to undertake evaluations alongside clinical trials.

Clinical Trials as Topic↗
PubMed1991

Vasculitic neuropathy. A clinical and pathological study.

The clinical, electrophysiological and pathological features and prognosis of 34 patients with peripheral neuropathy caused by necrotizing vasculitis were evaluated. The causes included polyarteritis nodosa and its Churg-Strauss variant, rheumatoid arthritis, undifferentiated connective tissue disease, Wegener's granulomatosis, primary Sjögren's disease, and chronic lymphocytic leukaemia with cryoglobulinaemia; 2 patients had no evidence of systemic vasculitis. Mononeuritis multiplex was the most common clinical manifestation, followed by asymmetrical polyneuropathy and distal symmetrical polyneuropathy. Pain was a frequent symptom. Nerve conduction studies were abnormal in all cases, and in 3 patients there was conduction block or severe slowing of motor conduction. Necrotizing vasculitis was present in sural nerve biopsies of most cases, and severe active axonal degeneration was a dominant feature. Immunofluorescent staining of blood vessels for immunoglobulin, C3 and fibrinogen was positive in all cases in which it was performed, even when there was no cellular infiltration. All patients were treated with prednisone alone or in combination with other immunosuppressive agents, or with plasmapheresis. Long-term follow-up studies demonstrated that although the peripheral neuropathy usually improved and caused only mild to moderate functional disability, the long-term prognosis of the systemic disease was poor with a 5-yr survival of only 37%.

Adult↗
PubMed1991

HIV prevalence and risk behaviours for HIV transmission in South Australian prisons.

During the latter half of 1989, HIV prevalence in South Australian prisoners was 1.4%. The prevalence of HIV infection across the prison system did not change significantly during 1989 but there was clustering of HIV-infected prisoners in some prisons. Almost half the prisoners from all of the South Australian prisons agreed to participate in our studies, from which we estimate that about 42% of prisoners engage in risk behaviours at least once while incarcerated. Prisoners estimated that 36% of all prisoners inject drugs intravenously at some stage during their stay and that 12% engage in anal intercourse at least once. Interviews with former prisoners who had a history of intravenous drug use revealed that about half had injected themselves while in prison, 60% shared needles and most did not clean shared needles adequately. Most of these prisoners injected themselves once a month or less frequently. The conditions for spread of HIV within the prison system exist but at the current prevalence of infection, transmission can be expected to be infrequent. The opportunity exists now to improve and expand preventive measures.

Adult↗