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Biomedical subjects

D M Lloyd

Publications and source records attributed to D M Lloyd.

At least 19 recordsLinked to original sources
PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗
PubMed2004

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

Animals↗
PubMed2004

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗
PubMed2004

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Chromosome Mapping↗
PubMed2004

Is intraperitoneal levobupivacaine with epinephrine useful for analgesia following laparoscopic cholecystectomy? A randomized controlled trial.

BACKGROUND AND OBJECTIVE: A randomized controlled trial of patients undergoing laparoscopic cholecystectomy. To evaluate whether the instillation of levobupivacaine, with epinephrine, intraperitoneally, reduces morphine consumption; further, to consider the degree of abdominal and shoulder pain in the presence of local anaesthetic at the site of surgical incision. METHODS: Patients received a standardized procedure and were allocated randomly to receive either (a) 2.5 mg mL(-1) levobupivacaine 30 mL, with epinephrine 5 microg mL(-1), or (b) normal saline 30 mL, with epinephrine 5 microg mL(-1), to the bed of the gall bladder and above the liver, immediately before wound closure. RESULTS: Median (interquartile range) total abdominal pain during inspiration in the levobupivacaine group was significantly (P = 0.041) lower (71 (21-129) mm) than that in the placebo group (123 (71-179) mm). However, there was no significant difference between the two groups with respect to total abdominal pain at rest, right shoulder pain or the consumption of rescue morphine and rescue dihydrocodeine. There were no differences between the two groups with respect to the administration of cyclizine, total nausea and total sedation scores. In addition, the number of episodes of vomiting was not significantly different. CONCLUSIONS: Intraperitoneal administration of levobupivacaine with epinephrine is associated with modest analgesia following laparoscopic cholecystectomy.

Adult↗
PubMed2003

Changing profiles of proteoglycans in the transition of predentine to dentine.

Proteoglycans and their constituent glycosaminoglycans have been proposed to play important roles in matrix mediated formation of mineralised tissues, such as dentine. This study has examined the changing profile of proteoglycan species during the transition of unmineralised predentine to mineralised dentine. Three-week-old calves teeth were collected and proteoglycans purified from the predentine, the predentine/dentine interface and dentine. Decorin and biglycan, together with related degradation products, were identified in the predentine fraction, alongside degradation products of versican, indicating metabolism of the proteoglycan components within this tissue. Decorin and biglycan were also identified as major proteoglycan species within extracts from the predentine/dentine interface and dentine. Analysis of the glycosaminoglycan constituents within each fraction demonstrated significant changes in their composition. Predentine contained a high proportion of dermatan sulfate (DS) (51.5%), with chondroitin sulfate (CS) (17.8%) and hyaluronan (HA) (30.7%) additionally identified. Within the predentine/dentine interface the proportion of CS increased greatly (62.5%), with corresponding decrease in the proportion of DS (21.4%) and HA (16.1%) also evident. CS only was identifiable within the dentine matrix. A four-fold increase in the level of sulfation was identified for glycosaminoglycans extracted from the predentine/dentine interface compared with the predentine and dentine fraction. The ratio of DeltaDi4S:DeltaDi6S was higher for glycosaminoglycans isolated from the predentine fraction. Glycosaminoglycans extracted from the dentine fraction possessed longer chain lengths than those present in the predentine and predentine/dentine fractions. The results indicate that the proteoglycans within each fraction undergo subtle structural modification, particularly at the onset of mineralisation, indicating an active involvement of these macromolecules in the overall mineralisation process.

Animals↗
PubMed2002

Experimental study of large-volume microwave ablation in the liver.

BACKGROUND: Microwave coagulation therapy is useful in the destruction of small, irresectable liver tumours of primary and secondary origin. Unfortunately, the small lesion size produced by currently available equipment makes it difficult and time consuming completely to ablate lesions larger than 3 cm in diameter. A microwave system capable of producing large-volume ablations in very short periods of time has been developed. Using a large-animal model the ability of the equipment to produce large-volume lesions in a safe, predictable and dose-dependent manner was tested. METHODS: Fourteen large white pigs were anaesthetized and underwent multiple microwave treatments. The animals were killed at different timepoints to investigate lesion size and evolution. RESULTS: The microwave system was able to generate large-volume ablations of up to 6.5 cm in diameter in a controlled and dose-dependent manner. CONCLUSION: This novel microwave system allows the ablation of large volumes of liver tissue in a short period of time. The ability to produce lesions reproducibly and safely highlights the potential of this system in the future treatment of irresectable liver tumours.

Analysis of Variance↗
PubMed2000

The physiology and psychology of selective attention to touch.

In this chapter we review psychological and physiological experiments on selective attention to touch stimuli. We explore the role of selective attention in tactile target detection and search, determining those tasks that benefit from attention and those which can be effectively performed pre-attentively. We also try to determine the stage at which attentional selection occurs. We review electrophysiological and human brain imaging (PET, fMRI, MEG, SEP) studies to assess how early in the somatosensory processing pathway attentional modulation occurs. There is some evidence that the primary somatosensory cortex (S1) can show attentional effects. However, a number of studies have suggested that there is a hierarchy to attentional modulation in the somatosensory system, with the greatest effects being observed in secondary and association areas.

Afferent Pathways↗
PubMed2000

Laparoscopic splenectomy: a suitable technique for children and adults

Aims: Splenectomy retains an important role in the management of certain haematological conditions that fail to respond to conventional medical therapy, and has traditionally been performed through a midline or left subcostal incision with patients requiring 5-7 days in hospital. The well recognized benefits of laparoscopic surgery should also apply to splenectomy. This study aimed to develop a safe and effective technique suitable for all age ranges and without the requirement for expensive stapling devices. METHODS: An operative technique evolved over the 5-year period from 1994, from an initial six-port approach with the patient supine, to a four-port approach in a modified right lateral position, with locking surgical clips applied down a 5-mm port to vessels in the hilum, and removal of the spleen within a retrieval bag through a 4-6-cm Pfannanstiel incision. Data were collected prospectively for all patients undergoing laparoscopic splenectomy at Leicester Royal Infirmary, including demographic details, indication for surgery, duration of surgery, length of inpatient stay, transfusion requirement, postoperative complications and the response of the original condition to surgical intervention. RESULTS: A total of 40 patients underwent laparoscopic splenectomy (14 children, 26 adults) for a variety of conditions (idiopathic thrombocytopenia (ITP) (n = 24), haemolytic anaemia (n = 9) or malignancy (n = 7)) with a median operating time of 180 min for the first 20 patients and 100 min for the second 20 (P < 0.0001), and median inpatient stay of 3 days for the first 20 patients and 2 days for the second 20 (P < 0.0003). None of the operations was converted to open surgery, five patients required blood and/or platelet transfusion perioperatively, none of the patients had major postoperative complications, 23 of the 24 patients with ITP developed normal platelet counts after operation, and all nine patients with haemolytic anaemia maintained a normal haemoglobin concentration after operation. CONCLUSION: Laparoscopic splenectomy can be performed safely and effectively in adults and children without the need for stapling devices.

Journal Article↗
PubMed1999

Mechanisms of attention in touch.

A series of experiments demonstrated the role of higher level cognitive processes, such as attention, in tactile perception. The first series of experiments demonstrated that automatic orienting to a tactile stimulus resulted in inhibition of subsequent stimuli at that body site--inhibition of return (IOR). A possible explanation suggests that inhibition of saccades to a body site can cause the inhibition of subsequent stimuli presented to that same site. In contrast, when the subjects strategically oriented attention to the stimulus, the processing of subsequent stimuli at that body site was facilitated. In both of these experiments the skin received exactly the same test stimuli, (100 Hz sine wave presented for 50 ms), but very different effects were observed depending upon attentional strategy. Experimental manipulations showed that this cannot be due to a peripheral masking of the receptors after cue presentation to the target. Rather the results may be explained centrally by cognitive, particularly attentional mechanisms. Cross-modal interactions suggest that tactile processes are facilitated when vision is oriented to the body site receiving stimulation. Possible explanations come from recent findings of spatiotopic maps of different sensory modalities in the superior colliculus of the midbrain and in the parietal lobe. These are integrated with motor systems that control saccades and head orientation towards sensory inputs. Excitatory links among these maps could be the source of the observed facilitation effects.

Adolescent↗
PubMed1998

Effects of intravenous nitric oxide inhibitors on endotoxin-induced fever in prepubertal pigs.

1. The ability of nitric oxide inhibitors to antagonize the febrile effects of lipopolysaccharide (LPS) endotoxin (20 microg/animal i.v.) was assessed in prepubertal pigs in which deep body temperature was measured at 10-min intervals for 180 min. 2. In experiment 1, pigs (n=5) were injected with Nomega-nitro-L-arginine-methyl ester (L-NAME) (30 mg/kg i.v.) or aminoguanidine (27 mg/kg i.v.) 30 min before LPS. There was a marked tendency for L-NAME, but not aminoguanidine, to reduce LPS pyrexia. 3. In experiment 2, pigs (n=7) were injected with 2-amino-4-methylpyridine (1 mg/kg i.v.) 30 min before LPS. This drug tended to increase, rather than reduce, core temperature. 4. In experiment 3, pigs (n=5) were injected with S-methylisothiourea (10 or 15 mg/kg i.v.) concomitantly with LPS. Both doses of the drug produced a small, nonsignificant, reduction in the febrile response. 5. The results indicate that the nitric oxide inhibitors used in this study were relatively ineffective in modifying LPS fever in conscious pigs; these findings are in marked contrast with the actions, in this species, of drugs that inhibit prostaglandin production. In addition, the most effective drug, L-NAME, was the one considered to be the least selective for the inducible form of nitric oxide.

Animals↗
PubMed1997

Laparoscopic treatment of nonparasitic cysts of the liver with omental transposition flap.

BACKGROUND: Between 1991 and November 1994, 18 patients with large, solitary, nonparasitic liver cysts underwent laparoscopic deroofing; the last 13 of them also received an omental transposition flap in addition. METHODS: Using three to four trocars, the cystic contents were first aspirated, and the cyst derooted widely using diathermia. An omental transposition flap was fashioned and stapled into the cyst cavity itself. RESULTS: Postoperative complications included one case of pulmonary atelectasis. Another patient developed a subhepatic bile collection which was aspirated percutaneously. On average, patients were discharged on the 4th (2-14) postoperative day. Follow-up was performed with abdominal ultrasound for 2-43 months (mean 19 months). There were two early cyst recurrences, both in cases without an omental transposition flap (overall recurrence rate, 11%; in patients with omental flap, 0). CONCLUSIONS: Deroofing in combination with an omental transposition flap is a safe and effective therapy for symptomatic solitary liver cysts and can be performed using minimal-access surgical techniques.

Adult↗
PubMed1997

Interrelated adrenocortical and neurohypophysial responses associated with fever in endotoxin-treated pigs.

Low intravenous doses of endotoxin [lipopolysaccharide (LPS), 0.7 microgram/kg] induce monophasic fever, increase anterior and posterior pituitary hormone release, and enhance hypothalamic c-Fos expression in pigs, all of which can be prevented by indomethacin (Ind). The present study shows that the synthetic corticosteroid dexamethasone (Dex, 5 mg/kg) has a similar action to Ind and, when given alone, lowers core temperature. In addition, the corticosteroid synthesis inhibitor metyrapone (Met, 3.3 mg/kg, every one-half hour) reduces LPS fever and amplifies the effect of LPS on vasopressin, but not on oxytocin, release. The similar actions of Dex and Ind suggest that phospholipase A2 pathways controlling prostaglandin synthesis mediate the responses of prepubertal pigs to immunological challenge with LPS. The increased vasopressin release induced when animals receiving Met are also given LPS supports findings in other nonrodent species indicating an inverse relationship between cortisol and vasopressin. The attenuation of LPS fever by Met is suggestive of an endogenous antipyretic mechanism associated with enhanced neurohypophysial vasopressin secretion.

Analgesics, Non-Narcotic↗
PubMed1996

Selection criteria for preoperative endoscopic retrograde cholangiopancreatography in the laparoscopic era.

BACKGROUND: Indicators for cholangiography were originally designed to select patients at risk for common bile duct (CBD) stones for intraoperative cholangiography. OBJECTIVE: To refine these criteria to apply to the much more invasive procedure of preoperative endoscopic retrograde cholangiopancreatography (ERCP). DESIGN: Retrospective review of selection criteria for ERCP in consecutive patients referred over 18 months following the introduction of laparoscopic cholecystectomy. SETTING: Two ERCP units in adjacent teaching hospitals. PATIENTS: Three hundred seventeen patients with gallstones and in situ gallbladders. INTERVENTION: Common bile duct imaging at ERCP. MAIN OUTCOME MEASURES: Abnormalities justifying ERCP. RESULTS: Abnormalities justifying ERCP were found in 66% of patients. This group differed significantly from those with normal ducts, with more being referred with abnormal results of all liver function tests (P < .001), jaundice (P < = .001), a dilated CBD on ultrasound (P < .001), or CBD stones on ultrasound (P < .001). On the other hand, patients with normal ducts were significantly more likely to have been referred with pancreatitis (P = .003) or elevated results of individual liver function tests (P < .001). A logistic regression model using age, presence of jaundice at ERCP, levels of alkaline phosphatase and albumin, and ultrasonography showing dilated ducts or visible CBD stones was found to have a specificity of 75% and a sensitivity of 89%. Past pancreatitis or elevated results of individual liver function tests were not predictive factors. CONCLUSION: The use of such a model rather than individual criteria would improve the selection of patients for preoperative ERCP, optimizing its role in the laparoscopic era.

Adult↗