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Biomedical subjects

C Hill

Publications and source records attributed to C Hill.

At least 109 records · Page 6Linked to original sources

[The different meanings of the word stratification].

In clinical research, stratification has three different meanings. In its first meaning, it describes the natural distribution of patients into subgroups, for instance patients may be stratified by stage. In its second meaning, stratification controls the random allocation of the treatments in a clinical trial, for instance the randomisation can be stratified on stage. Lastly, in its third meaning, stratification of a trial analysis consists into taking into account patients' characteristics in the analysis. This three meanings will be illustrated with a basic example.

Humans↗

First hemodialysis access selection varies with patient acuity.

Timely placement of a reliable permanent vascular access is essential for hemodialysis care quality; National Kidney Foundation Dialysis Outcomes Quality Improvement (NKF-DOQI) guidelines emphasize native arterio-venous (AV) fistulae as preferred access for incident patients. As part of Network One's Vascular Access Quality Improvement Project (QIP) we investigated whether patients' course to end-stage renal disease (ESRD) influenced vascular access selection. Baseline information was obtained for incident (1998) dialysis patients from 6 centers participating in the Network QIP. Patients were subdivided into 3 predefined clinical groups: KNOWN (known chronic renal disease, seen by a nephrologist, with predictable progression to ESRD), CRISIS (KNOWN but with unanticipated medical crisis precipitating ESRD), and UNKNOWN (not known to have chronic renal insufficiency or never seen by a nephrologist before developing ESRD). Two hundred forty patients were identified (median age 69.9, 42% diabetic). Only 43% of the entire population experienced an orderly progression to renal insufficiency. The most frequent initial access was a catheter (54%), followed by a fistula (29%) and a graft (16%), but selection of initial access differed significantly by patient group, with 46% of KNOWN patients receiving a fistula (P <.001). After 2 months of dialysis, the initial access supported dialysis in only 53.7% of the KNOWN patients, and in 59.4% and 45.7% of the CRISIS and UNKNOWN patients, respectively. We conclude that unpredicted, new ESRD patients are common and are less likely to receive a fistula as initial hemodialysis access. Studies should define optimum access management when dialysis requirement is unforeseen.

Acute Kidney Injury↗

Rotavirus gastroenteritis among paediatric patients at Tralee general hospital.

Rotavirus infection among paediatric patients in Tralee general hospital was monitored over 4 years (1994 - 1998). A total of 2,319 specimens from gastroenteritis patients less than 7 years old were tested by latex agglutination assay, of which 203 (8.75%) were deemed positive. An inverse correlation was observed between age and susceptibility to infection, with the very young (under 2 years) most frequently infected. The virus was almost equally distributed among males (53%) and females (47%) testing positive for rotavirus. A distinctive early Spring peak of infection was evident annually, although the largest peak was identified in December 1997. This correlated with a significant change in circulating genotype as determined by RT-PCR based genotyping analysis of 45 rotavirus samples. In 1997, rotavirus accounted for 64% of all identified paediatric enteric agents at Tralee General for which an infectious agent could be identified. The average hospital stay was 3.2 days, and the direct hospital costs for rotavirus associated gastroenteritis was estimated at pounds sterling 31,232 per annum.

Age Distribution↗

Extensive post-translational modification, including serine to D-alanine conversion, in the two-component lantibiotic, lacticin 3147.

Lacticin 3147 is a two-component bacteriocin produced by Lactococcus lactis subspecies lactis DPC3147. In order to further characterize the biochemical nature of the bacteriocin, both peptides were isolated which together are responsible for the antimicrobial activity. The first, LtnA1, is a 3,322 Da 30-amino acid peptide and the second component, LtnA2, is a 29-amino acid peptide with a mass of 2,847 Da. Conventional amino acid analysis revealed that both peptides contain the thioether amino acid, lanthionine, as well as an excess of alanine to that predicted from the genetic sequence of the peptides. Chiral phase gas chromatography coupled with mass spectrometry of amino acid composition indicated that both LtnA1 and LtnA2 contain D-alanine residues and amino acid sequence analysis of LtnA1 confirmed that the D-alanine results from post-translational modification of a serine residue in the primary translation product. Taken together, these results demonstrate that lacticin 3147 is a novel, two-component, D-alanine containing lantibiotic that undergoes extensive post-translational modification which may account for its potent antimicrobial activity against a wide range of Gram-positive bacteria.

Alanine↗

The relationship between acid stress responses and virulence in Salmonella typhimurium and Listeria monocytogenes.

All pathogenic bacteria possess the ability to evade or surmount body defenses (stresses, as experienced by the bacterium) long enough to cause a sufficient reaction, which is then manifested as a disease or illness. While opportunistic pathogens will only cause illness in the event of a predisposing weakness in these defenses, many pathogens must take on and overcome intact defenses. This is particularly true of gastrointestinal pathogens such as Listeria monocytogenes and Salmonella spp., which must circumvent many different stresses in order to arrive at the site of infection. These include the acid barrier of the stomach, the physical barrier of the epithelial cells lining the gastrointestinal tract, and various immune defenses including the initial onslaught of macrophages. Thus, these organisms have developed elaborate systems for sensing stress, and for responding to those stresses in a self-protective fashion. One well characterised adaptive response is to acid stress, the so-called acid tolerance response (ATR). The ATR is a complex phenomenon, involving a number of changes in the levels of different proteins and presumably, many allied events at the level of gene regulation. A number of molecular approaches have identified numerous interesting chromosomal loci involved both in sensing and responding to stress and in virulence. The identity of some of these genes, and their impact on stress responses and virulence will be discussed.

Adaptation, Physiological↗

In situ inversion of the conjugative transposon Tn916 in Enterococcus faecium DPC3675.

Enterococcus faecium DPC3675 is a derivative of E. faecium DPC1146 which contains a single copy of the conjugative transposon Tn916. Although the transposon is observed to be oriented in one direction in individual colonies, DNA extracted from cultures grown from these colonies contains the transposon in both orientations, as determined by PCR analysis and sequencing of the transposon/chromosome junctions. Therefore, Tn916 possesses a hitherto unreported ability to invert within a particular insertion site during growth in broth.

Base Sequence↗

The use of the laryngeal mask airway for inter-hospital transport of infants with type 3 laryngotracheo-oesophageal clefts.

Type 3 laryngotracheo-oesophageal clefts are rare congenital anomalies with a high mortality. In the past, transport of such infants to tertiary centres for surgical correction has proved extremely difficult, with the child's ventilatory status often deteriorating to such an extent that ultimate surgical intervention has not proved possible. We describe two cases of successful inter-hospital transfer of infants with type 3 laryngotracheo-oesophageal clefts using the laryngeal mask airway.

Emergency Service, Hospital↗

Pathophysiological Role of Growth Factors in Diabetic Kidney Disease: Focus on Innovative Therapy.

Various growth factors have been proposed to be players in the development of diabetic microvascular complications. In particular, the growth hormone/insulin-like growth factor system and the transforming growth factor beta system have measurable effects on the development of diabetic kidney disease through a complex intrarenal system. Recent findings indicating that these growth factors might be responsible for early renal changes in diabetes have provided insight into processes that might be relevant to the future development of new drugs useful in the treatment of diabetic kidney disease.

Journal Article↗

Lacticin 3147 displays activity in buffer against gram-positive bacterial pathogens which appear insensitive in standard plate assays.

Lacticin 3147 is a broad-spectrum bacteriocin produced by Lactococcus lactis subsp. lactis DPC3147, which has been shown to be active against a range of food-borne bacteria. The reported inhibitory range for lacticin is extended to include methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, penicillin-resistant Pneumococcus, Propionibacterium acne and Streptococcus mutans. This extended host range is not obvious from traditional agar plate-based methods, but reductions in bacterial cell numbers by up to 6 log10 cfu ml-1 was observed after 2 h in time-kill curve studies conducted in broth, suggesting that the bacteriocin may have potential as a therapeutic agent in the treatment of human infections.

Bacterial Proteins↗

Inhibition of Listeria monocytogenes in cottage cheese manufactured with a lacticin 3147-producing starter culture.

The efficacy of using a lacticin 3147-producing starter as a protective culture to improve the safety of cottage cheese was investigated. This involved the manufacture of cottage cheese using Lactococcus lactis DPC4268 (control) and L. lactis DPC4275, a bacteriocin-producing transconjugant strain derived from DPC4268. A number of Listeria monocytogenes strains, including a number of industrial isolates, were assayed for their sensitivity to lacticin 3147. These strains varied considerably with respect to their sensitivity to the bacteriocin. One of the more tolerant strains, Scott A, was used in the cottage cheese study; the cheese was subsequently inoculated with approximately 10(4) L. monocytogenes Scott A g-1. The bacteriocin concentration in the curd was measured at 2560 AU ml-1, and bacteriocin activity could be detected throughout the 1 week storage period. In cottage cheese samples held at 4 degrees C, there was at least a 99.9% reduction in the numbers of L. monocytogenes Scott A in the bacteriocin-containing cheese within 5 d, whereas in the control cheeses, numbers remained essentially unchanged. At higher storage temperatures, the kill rate was more rapid. These results demonstrate the effectiveness of lacticin 3147 as an inhibitor of L. monocytogenes in a food system where post-manufacture contamination by this organism could be problematic.

Antibiosis↗

Changes in serotonin2A and GABA(A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex.

Having shown a decrease in serotonin2A receptors in the dorsolateral prefrontal cortex (DLPFC) from schizophrenic subjects, we have now determined if this change was reflective of widespread changes in neurochemical markers in DLPFC in schizophrenia. In Brodmann's area (BA) 9 from 19 schizophrenic and 19 control subjects, we confirmed a decrease in the density of [3H]ketanserin binding to serotonin2A receptors in tissue from the schizophrenic subjects [39 +/- 3.3 vs. 60 +/- 3.6 fmol/mg estimated tissue equivalents (ETE); p < 0.005]. In addition, the density of [3H]muscimol binding to GABA(A) receptors was increased in the schizophrenic subjects (526 +/- 19 vs. 444 +/- 28 fmol/mg ETE; p < 0.02). [3H]YM-09151-2, N-[1-(2-thienyl)cyclohexyl]-3,4-[3H]piperidine, [3H]SCH 23390, [3H]mazindol, and N(G)-nitro-L-[3H]arginine binding to BA 9 did not differ between groups, and there was no specific binding of [3H]raclopride or 7-hydroxy-2-(di-n-[3H]propylamino)tetralin to BA 9 from either cohort of subjects. This suggests the density of dopamine D1-like and NMDA receptors, the dopamine transporter, and nitric oxide synthase activity are not altered in BA 9 from schizophrenic subjects. The selective nature of the changes in serotonin2A and GABA(A) receptors in DLPFC could indicate that these changes are involved in the pathology of schizophrenia.

Adult↗

A technique for repair of the 'unrepairable' cleft palate.

The 'unrepairable' cleft palate may be described as one in which the width of the cleft exceeds the sum of the widths of the palatal shelves. A report of such a case is presented, and the technique used to repair the cleft using bilateral buccinator musculomucosal flaps is described. It is offered as a suggested technique for the management of such cases in the future.

Cleft Palate↗

Long term outcome of early active mobilization following flexor tendon repair in zone 2.

We reviewed 34 patients with 65 zone 2 flexor tendon injuries in 39 digits whose outcome had been prospectively studied in an earlier investigation at a mean of 10.6 years after repair. Grip strength was assessed using a Jamar dynamometer. Outcome of grip strength in relation to normal data indicated an excellent or good outcome in 94% of patients, fair in 3% and poor in 3%. Using the grading system recommended by the American Society for Surgery of the Hand, the active range of motion was graded as excellent or good in 75% of digits, fair in 15% and poor in 10%. These results compare favourably with those of the original study with 5/39 of digits showing an improvement from good to excellent. Sixteen of the 34 of patients continued to suffer from cold sensitivity.

Adolescent↗

Paediatric hand injuries caused by spiked railings.

We report five cases of hand injuries caused by spiked palisade railings. One patient sustained an open fracture of the distal phalanx with a disruption of the nail bed, and two patients had digital nerve injuries. Two patients presented with the railing still impaled in the fingers, one of whom had an ischaemic digit at presentation. All patients were male, between 9 and 12 years of age, and presented in the course of 1 month. Railings of this type would appear to be a significant cause of hand injuries, which may be prevented by legislation or a change in railing design.

Accidents↗

The relationship between adult happiness and self-appraised childhood happiness and events.

The primary purpose of the present research was to relate questionnaire-assessed self-reported childhood happiness and events to adulthood happiness in 387 non-clinical participants. Although childhood happiness and adult happiness were found to be significantly correlated (r = .28, p < .001), there was little relationship between reported adult happiness and reported specific childhood events and circumstances. Childhood events and circumstances, however, were much more highly correlated with childhood happiness (R = .64). Thirty-four percent of the persons who said they were unhappy or very unhappy as a child, but only 9% who said they were happy or very happy as a child, reported that they were unhappy or very unhappy as adults.

Adult↗