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Biomedical subjects

M Hastings

Publications and source records attributed to M Hastings.

At least 19 recordsLinked to original sources
PubMed2001

The use of liver grafts from donors with bacterial meningitis.

BACKGROUND: The shortage of suitable donors for transplantation is a worldwide problem. The use of cadaveric donors with bacterial meningitis may be associated with an increased risk of sepsis. We report the results of orthotopic liver transplantation (OLT) from 33 such donors between 1989 and 1999. METHODS: The hospital records of recipients from cadaveric donors with meningitis (study group) were retrospectively reviewed and compared with matched recipients from cadaveric donors dying from causes other than meningitis (recipient-matched control group). RESULTS: A total of 34 recipients underwent 21 whole, 10 reduced, and 3 split liver transplants from 33 cadaveric donor livers with bacterial meningitis. The donor meningitis pathogens were Neisseria meningitidis (n=14), Streptococcus pneumoniae (n=4), Haemophilus influenzae (n=1), Streptococcus species (n=2), and unknown (n=12). Twenty-seven patients had an elective OLT and seven patients had an emergency OLT. Adequate antimicrobial therapy before organ procurement and after transplant was administrated. The mean posttransplant follow-up was 37 months (range: 1 day-106 months). There was no difference in recipient and graft survival rates between the study and the recipient-matched groups. In the study group, there were no infectious complications caused by the meningeal pathogens. Overall patient survival rates were 79%, 76%, 72%, and 72% at 1, 6, 12, and 60 months, respectively. Graft survival was 77%, 70%, 65%, and 65% at 1, 6, 12, and 60 months, respectively. The survival rate in elective cases was significantly better than emergency cases (P<0.05). CONCLUSION: Liver transplantation from donors with bacterial meningitis is a safe procedure provided both donors and recipients receive adequate antimicrobial therapy.

Adolescent↗
PubMed2001

Keystone clocks.

Explore the source record for details and available documents.

Animals↗
PubMed2001

Quinolone resistance in neutropenic patients: the effect of prescribing policy in the UK and Pakistan.

Quinolones are increasingly used as prophylaxis in neutropenic patients to prevent serious Gram-negative septicaemias but practice is not uniform because of the controversial evidence as to their effectiveness. It is unclear if they are of real benefit in patients with short episodes of neutropenia such as those resulting from treatment for solid tumours and lymphomas. The concern over the use of ciprofloxacin in such settings is the increasing development of quinolone resistant Gram-negative bacteria. We have retrospectively analysed our bacterial isolate resistance patterns in the Queen Elizabeth Hospital (QE) and in the Haematology Department of the Aga Khan Hospital (AKU), Pakistan where all patients would receive ciprofloxacin prophylaxis when neutropenic. Seven out of 57 (12.2%) and 18 out of 55 (32.7%) Gram-negative organisms isolated from blood cultures at the QE and AKU Haematology Departments, respectively, were resistant to ciprofloxacin (P < 0.01). In the Birmingham community this was significantly lower (P < 0.01) (55 out of 6423: 0.85%). We also showed a higher level of E. coli resistance at the AKU (18 out of 31: 58%) where ciprofloxacin use was more widespread than at the QE (1 out of 11, P < 0.01). We conclude that ciprofloxacin should not be used indiscriminately.

Anti-Infective Agents↗
PubMed2000

Circadian clocks in the mammalian brain.

Daily cycles in physiology and behaviour are probably a universal feature of multicellular organisms. These rhythms are predominantly driven by endogenous clocks with a periodicity approximating to one day, i.e. circadian. In mammals, the circadian clock governing activity/ rest, neuroendocrine and autonomic rhythms lies in the hypothalamus, in the suprachiasmatic nuclei (SCN). Intrinsic circadian oscillators are also present in the retina. The SCN "clockwork" is based on a cell autonomous, genetically determined mechanism. Mammalian homologues of a number of Drosophila genes which encode elements of the fly circadian mechanism have recently been identified. In Drosophila, the protein products of these genes interact in a negative feedback loop, establishing a circadian cycle in gene expression. Characterisation of the roles played by putative mammalian clock genes in the SCN, and how the emergent cellular signal imposes order over the entire neuraxis, will provide a fundamental contribution to our understanding of the molecular basis of behaviour. BioEssays 22:23-31, 2000.

Animals↗
PubMed2000

Recurrent penicillin-resistant pneumococcal sepsis after matched unrelated donor (MUD) transplantation for refractory T cell lymphoma.

Patients who undergo splenectomy and recipients of allogeneic marrow (alloBMT) or peripheral stem cell transplantation are at increased risk of overwhelming infection from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. As prophylaxis against these pathogens splenectomised patients are immunised and may also receive antibiotics for life. We report relapsing overwhelming sepsis caused by penicillin-resistant pneumococcus in a patient who was immunised and received prophylactic phenoxymethylpenicillin for 8 months following splenectomy and matched unrelated donor (MUD) marrow transplantation for refractory T cell lymphoma. No obvious focus of sepsis was found during any of the three episodes and S. pneumoniae serogroup 6, subtype 6B was isolated from blood cultures on each occasion. He was treated with i.v. cephalosporins, as the organisms were resistant to penicillin with a minimum inhibitory concentration (MIC) of 2.0, and there was complete resolution of symptoms each time. In the light of recurrent sepsis with this penicillin-resistant organism the decision was made to give prophylactic levofloxacin for the next 12 months. This case illustrates that the choice of prophylactic regimen and the treatment of sepsis in immunocompromised patients remain difficult and challenging issues.

Adult↗
PubMed1998

Morphological and functional evidence, and clinical importance, of vascular anastomoses in the latissimus dorsi muscle of the sheep.

Mobilisation of the latissimus dorsi muscle as a functional graft necessarily involves division of perforating arteries that enter the distal portion of the muscle, rendering it vulnerable to ischaemic damage when the muscle is stimulated electrically. Using a fluorescent microsphere technique we showed that the blood flow contributed by the thoracodorsal artery decreases in a proximal-to-distal direction, and that of the perforating arteries in a distal-to-proximal direction, but for neither does the flow decline to zero. This is consistent with earlier reports of anastomotic connections between the 2 arterial territories. We went on to use fluorescence microscopy to demonstrate the existence of these vascular anastomoses, the first such evidence obtained under physiological conditions of pressure and flow. In clinical applications, the existence of anastomotic connections offers the prospect of maintaining flow to the distal part of the grafted muscle without the delays inherent in neovascularisation procedures.

Animals↗
PubMed1996

Modeling and measuring lateral line excitation patterns to changing dipole source locations.

In order to determine excitation patterns to the lateral line system from a nearby 50 Hz oscillating sphere, dipole flow field equations were used to model the spatial distribution of pressures along a linear array of lateral line canal pores. Modeled predictions were then compared to pressure distributions measured for the same dipole source with a miniature hydrophone placed in a small test tank used for neurophysiological experiments. Finally, neural responses from posterior lateral line nerve fibers in the goldfish were measured in the test tank to demonstrate that modeled and measured pressure gradient patterns were encoded by the lateral line periphery. Response patterns to a 50 Hz dipole source that slowly changed location along the length of the fish included (1) peaks and valleys in spike-rate responses corresponding to changes in pressure gradient amplitudes, (2) 180 degrees phase-shifts corresponding to reversals in the direction of the pressure gradient and (3) distance-dependent changes in the locations of peaks, valleys and 180 degrees phase-shifts. Modeled pressure gradient patterns also predict that the number of neural amplitude peaks and phase transitions will vary as a function of neuromast orientation and axis of source oscillation. The faithful way in which the lateral line periphery encodes pressure gradient patterns has implications for how source location and distance might be encoded by excitation patterns in the CNS. Phase-shift information may be important for (1) inhibitory/excitatory sculpting of receptive fields and (2) unambiguously encoding source distance so that increases in source distance are not confused with decreases in source amplitude.

Acoustic Stimulation↗
PubMed1995

Circadian rhythms: peering into the molecular clockwork.

Recent developments in our understanding of the molecular basis of circadian rhythms look set to provide one of the most elegant demonstrations of the relationship between the activity of individual genes and the execution of biologically relevant and complex patterns of behaviour. At the same time the lid is being opened on one of the classic 'black boxes' of biology, the circadian clock.

Animals↗
PubMed1994

Circadian rhythms. What makes the clock tick?

The circadian clock affects many aspects of eukaryotic behaviour. A series of studies in fungi, flies and mice have used molecular and genetic approaches to peer into the machinery of the clock.

Animals↗
PubMed1990

Excitotoxic lesions of the lateral hypothalamus made by N-methyl-d-aspartate in the rat: behavioural, histological and biochemical analyses.

The purpose of this study was to determine whether the excitotoxin N-methyl-d-aspartate (NMDA) could be used to make lesions within the lateral hypothalamus and what effect they had on regulatory behaviour. Larger doses of NMDA were effective in the lateral hypothalamus but tended to spread into adjacent structures; smaller doses made lesions which were contained within the lateral hypothalamus and zona incerta. Lesions which damaged the lateral hypothalamus and surrounding tissue had no effect on the concentration of dopamine (or its metabolites) in the dorsal or ventral striatum. The large lesions, including extrahypothalamic damage, were associated with long-term deficits in lab chow and water intake, but rats with lesions restricted to the lateral hypothalamus made good recoveries, eating and drinking normally from around the tenth day post-operation. Body weight gain was normal in these rats, though there was a long-term loss of body weight compared to controls. Unoperated rats with food intake yoked to lesioned rats showed identical long-term changes in body weight, suggesting that the changes in body weight of lesioned rats may be a reflection of changes in eating and drinking rather than a disruption of a body weight set-point mechanism. Motor deficits were not found; all rats were able to consume without difficulty saccharin solutions. All lateral hypothalamic lesioned rats failed to respond to dehydrating, dipsogenic or glucoprivic challenges. It is concluded that NMDA is an effective toxin in the rat lateral hypothalamus, sparing ascending dopamine fibres, and that the main effect of such lesions is an impairment in responding to physiological challenges.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Enhancement of neutrophil chemiluminescence after elective gastrointestinal surgery.

Neutrophil count and luminol-dependent chemiluminescence were measured pre-operatively and on the second, sixth and ninth days after operation in nine patients undergoing major, elective gastrointestinal surgery. The aim of the study was to test the hypothesis that elective surgery as a form of injury has no prolonged deleterious effect on neutrophil activity in non-septic patients. A significant increase in neutrophil count was demonstrated in all patients at Day 2 (P less than 0.01) and Day 9 (P less than 0.01). Neutrophil chemiluminescence increased on Day 2 and Day 6, the increase on Day 6 being significant (P less than 0.02). In the first 9 days after elective gastrointestinal surgery, a biphasic neutrophilia occurs and the metabolic response of neutrophils to an opsonized particle is not impaired. These data would support the hypothesis that major elective surgery has no deleterious effects on neutrophil activity, and indeed that neutrophil activity may be enhanced.

Adult↗