Regarding Newton's laws (Editorial, Eye, May 2006).
Explore the source record for details and available documents.
Models, Theoretical↗
Biomedical subjects
N Davies
Publications and source records attributed to N Davies.
An unusual cause of acute lid swelling.
Explore the source record for details and available documents.
Acute Disease↗
Portal vein embolisation prior to hepatic resection for colorectal liver metastases and the effects of periprocedure chemotherapy.
Portal vein embolisation (PVE) is an effective method of increasing future liver remnant (FLR) but may stimulate tumour growth. The effect of periprocedure chemotherapy has not been established. 15 consecutive patients underwent PVE prior to hepatic resection for colorectal liver metastases with a FLR <30% of tumour-free liver (TFL). Liver and tumour volumes pre-PVE and 6 weeks post-PVE were calculated by CT or MRI volumetry and correlated with the periprocedure chemotherapy regimen. PVE increased the FLR from 18+/-5% of TFL to 27+/-8% post-PVE (p<0.01). Post-PVE chemotherapy did not prevent hypertrophy of the FLR but the volume increase with chemotherapy (median 89 ml, range 7-149 ml) was significantly reduced (median 135 ml, range 110-254 ml without chemotherapy) (p = 0.016). Tumour volume (TV) decreased in those receiving post-PVE chemotherapy (median TV decrease 8 ml, range -77 ml to +450 ml) and increased without chemotherapy (median TV increase 39 ml, range -58 ml to +239 ml). Of the 15 patients, eight underwent resection; four were not resected due to disease progression and three due to insufficient hypertrophy of the FLR. PVE increased the FLR by an average of 9% allowing resection in 50% of patients. Periprocedure chemotherapy did not prevent but did reduce hypertrophy. A trend towards tumour regression was observed.
Aged↗
The selective modulation of endothelial cell mobility on RGD peptide containing surfaces by YIGSR peptides.
The ability of the biomimetic peptides YIGSR, PHSRN and RGD to selectively affect adhesion and migration of human microvascular endothelial cells (MVEC) and vascular smooth muscle cells (HVSMC) was evaluated. Cell mobility was quantified by time-lapse video microscopy of single cells migrating on peptide modified surfaces. Polyethylene glycol (PEG) hydrogels modified with YIGSR or PHSRN allowed only limited adhesion and no spreading of MVEC and HVSMC. However, when these peptides were individually combined with the strong cell binding peptide RGD in PEG hydrogels, the YIGSR peptide was found to selectively enhance the migration of MVEC by 25% over that of MVEC on RGD alone (p<0.05). No corresponding effect was observed for HVSMC. This suggests that the desired response of specific cell types to tissue engineering scaffolds could be optimized through a combinatory approach to the use of biomimetic peptides.
Adsorption↗
Spinal injuries admitted to a specialist centre over a 5-year period: a study to evaluate delayed admission.
STUDY DESIGN: Retrospective study of 432 patients admitted to our institution with a spinal injury over a 5-year period. OBJECTIVES: To present epidemiological data relating to this spinal population, reporting specifically on delayed admission and length of hospitalisation. SETTING: Royal National Orthopaedic Hospital, Stanmore, UK. METHODS: A total of 432 traumatic spinal injuries admitted between March 1998 and March 2003 were analysed with respect to age, gender, mechanism of injury, level of bony injury, neurological level (complete, incomplete and intact), Injury Severity Score (ISS), date of injury, referral and admission independently and length of hospitalisation. The delays between injury and referral (>3 days) and between referral and admission (>7 days) were correlated to the length of hospitalisation. A detailed analysis of the cause of delay at both junctures was undertaken. RESULTS: There were 322 males (average age, 38.6 years) and 110 females (average age, 41.8 years) in our study. Classification of neurological severity disclosed 108 complete injuries, 115 incomplete and 209 intact. The average time between injury and referral was 5.5 days (range 0-94), and between referral and admission was 10.7 days (range 0-130). A total of 161 patients (37%) experienced a delay between injury and referral, of whom 59 (37%) were subsequently also delayed to admission. The principal reason for delay between injury and referral was the treatment of concurrent injuries. Even patients with complete injuries (15/43) experienced delayed referral. In all, 112 patients (26%) experienced a delay between referral and admission. Principal reasons included the provision of beds (Intensive care, acute and rehabilitation) and physiological stabilisation of other injuries particularly thoracic trauma. CONCLUSIONS: Provision of beds remains the most common preventable reason for delay between referral and admission and is associated with increased hospitalisation. Early liaison with a designated spinal injuries unit, particularly those with cord injury remains vitally important.
Adult↗
Secondary amenorrhoea due to Leydig cell tumour.
Explore the source record for details and available documents.
Adrenal Glands↗
Obstructive jaundice secondary to neuroendocrine tumour in a patient with von Recklinghausen's disease.
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, with variable clinical manifestations and unpredictable course, associated with an increased incidence of various tumours. Plexiform neurofibromas are hallmark lesions of NF1; they are slow-growing tumours, which account for substantial morbidity, including disfigurement and functional impairment, and may even be life-threatening. Neuroendocrine tumours (NETs), a rare diverse group of neoplasms, are occasionally associated with neurofibromatosis. Pancreatic NETs are tumours with an incidence of less than 1/100 000 population/year and complex patterns of behaviour, which often need complicated strategies for optimal management. We present the case of a young adult with NF1, having a unique concurrence of plexiform neurofibroma involving the liver with an ampullary NET, and we discuss step by step the management in a specialist centre.
Adult↗
Population differentiation and Wolbachia phylogeny in mosquitoes of the Aedes scutellaris group.
Mosquito species of the Aedes (Stegomyia) scutellaris (Walker) group (Diptera: Culicidae) are distributed across many islands of the South Pacific and include major regional vectors of filariasis, such as Aedes polynesiensis (Marks). Analysis of populations of Ae. polynesiensis at the extremes of its range, from Fiji and from Moorea, French Polynesia, using the rDNA ITS2 (internal transcribed spacer 2) region and six microsatellite markers showed considerable genetic differentiation between them (F(ST) = 0.298-0.357). Phylogenetic analysis of the Wolbachia endosymbionts in three members of the complex revealed that based on the wsp gene they are all very similar and belong to the Mel subgroup of the A clade, closely related to the Wolbachia strain present in the gall wasp Callyrhytis glandium (Giraud) (Hymenoptera: Cynipidae). By contrast they are only distantly related to the A-clade Wolbachia in Aedes albopictus (Skuse), a species closely allied to the Ae. scutellaris group. There was very low differentiation between the Wolbachia in the Moorea and Fiji populations of Ae. polynesiensis.
Aedes↗
Early impact of centralization of oesophageal cancer surgery services.
BACKGROUND: In response to national guidance, oesophageal surgery from four hospitals within Wessex was centralized to a single site, with a provision for surgeons to travel to the centre to operate if they wished. This study assessed the clinical impact of this change. METHODS: Data for patients who had oesophageal cancer surgery at the single site were collected prospectively for 1 year from May 2002 and compared with the Wessex Oesophageal Cancer Audit (WOCA) data for the four hospitals from 1999 to 2000. RESULTS: Thirty-three patients underwent surgery on the single site compared with 40 patients from the four hospitals during the WOCA. Age, sex, co-morbidity, tumour site, and preoperative tumour and node stage were similar in the two groups. Six patients from the WOCA underwent 'open and close' laparotomy compared with none in the single-site group (P = 0.020). There were four anastomotic leaks in the WOCA group and two in the single-site group. Overall complication rates in those undergoing resection were similar in the two groups, but the in-hospital mortality rate was significantly higher in the WOCA group (five versus no patients; P = 0.022). Pathology reporting was incomplete in significantly more patients in the WOCA group (15 versus three; P = 0.001). The mean node harvest was greater in the single-site group (30.5 versus 19). CONCLUSION: Centralization of oesophageal surgery resulted in better preoperative staging, a lower 30-day mortality rate and more complete pathological reporting.
Adult↗
Liver transplant and obstetrics.
Explore the source record for details and available documents.
Acetaminophen↗
Agouti-related protein (83-132) is a competitive antagonist at the human melanocortin-4 receptor: no evidence for differential interactions with pro-opiomelanocortin-derived ligands.
Interactions between pro-opiomelanocortin (POMC)-derived peptides, agouti-related protein (AGRP) and the melanocortin-4 receptor (MC4-R) are central to energy homeostasis. In this study we have undertaken comprehensive pharmacological analysis of these interactions using a CHOK1 cell line stably transfected with human MC4-R. Our main objectives were (1) to compare the relative affinities and potencies of POMC-derived peptides endogenously secreted within the hypothalamus, (2) to investigate the potency of AGRP(83-132) antagonism with respect to each POMC-derived peptide and (3) to determine whether AGRP(83-132) and POMC-derived peptides act allosterically or orthosterically. We have found that beta melanocyte-stimulating hormone (betaMSH), desacetyl alpha MSH (da-alphaMSH) and adrenocorticotrophic hormone all have very similar affinities and potencies at the MC4-R compared with the presumed natural ligand, alphaMSH. Moreover, even MSH precursors, such as beta lipotrophic hormone, showed significant binding and functional activity. Therefore, many POMC-derived peptides could have important roles in appetite regulation and it seems unlikely that alphaMSH is the sole physiological ligand. We have shown that AGRP(83-132) acts as a competitive antagonist. There was no significant difference in the potency of inhibition by AGRP(83-132) or agouti(87-132) at the MC4-R, regardless of which POMC peptide was used as an agonist. Furthermore, we have found that AGRP(83-132) has no effect on the dissociation kinetics of radiolabelled Nle4,D-Phe7 MSH from the MC4-R, indicating an absence of allosteric effects. This provides strong pharmacological evidence that AGRP(83-132) acts orthosterically at the MC4-R to inhibit Gs-coupled accumulation of intracellular cAMP.
Agouti-Related Protein↗
Fusion of interleukin-2 to subunit antigens increase their antigenicity in vitro due to an interleukin-2 receptor beta-mediated antigen uptake mechanism.
Subunit vaccines, based on one or more epitopes, offer advantages over whole vaccines in terms of safety but are less antigenic. We investigated whether fusion of the cytokine interleukin-2 (IL-2) to influenza-derived subunit antigens could increase their antigenicity. The fusion of IL-2 to the subunit antigens increased their antigenicity in vitro. Encapsulation of the subunit antigen in liposomes also increased its antigenicity in vitro, yet encapsulation of the subunit IL-2 fusion did not. The use of anti-IL-2 receptor beta (IL-2Rbeta) antibody to block the receptor subunit on macrophages suggested that the adjuvancy exerted by IL-2 in our in vitro system is due to, at least in part, a previously unreported IL-2Rbeta-mediated antigen uptake mechanism.
Adjuvants, Immunologic↗
Extent of foveal tritanopia in diabetes mellitus.
AIM: To use a colour matching technique to test the hypothesis that the foveal tritanopic zone is increased in size in diabetes mellitus. METHOD: A Wright tristimulus colorimeter was adapted for small field colour matching and colour matches were performed on bipartite fields in the range 12' to 60' of arc. The reference stimulus was 490 nm desaturated with 650 nm and the matching stimulus consisted of either two wavelengths (530 nm and 650 nm) or three (460 nm, 530 nm, and 650 nm). The size of the zone of foveal tritanopia was measured using two alternative forced choice presentations of dichromatic and trichromatic matches made by the observer for different field sizes. 21 diabetic and 12 controls performed the experiment. RESULTS: The results for the controls show a normal distribution, with a median foveal tritanopic zone of 18' of arc. The median for the diabetic patients was also 18' of arc, but the distribution showed a significant skew to the right. A non-parametric test shows a significant difference in comparison with the controls (p = 0.01), with several subjects having extensive zones of foveal tritanopia, reaching up to 1 degree. CONCLUSIONS: In the majority of diabetic subjects the extent of foveal tritanopia is normal; however, there is good evidence that in a small number of subjects the size of the zone is significantly increased. This indicates S-cone pathway damage that is sufficiently severe to lead to dichromatic colour vision in the fovea.
Adult↗
Novel ligands for the investigation of imidazoline receptors and their binding proteins.
New ligands for imidazoline receptors are described so that these receptors can be more fully explored and understood. BU224, (2-(4,5-dihydroimidaz-2-yl)-quinoline, shows high affinity and is selective for the imidazoline-2 (I(2)) class of receptors. BU224 was tested in the rat Porsolt forced swim paradigm where it was found to decrease time spent immobile and increase the time spent swimming, consistent with an antidepressant profile. BU224 was tritiated and, in radioligand binding studies, was found to label a single population of saturable sites with high affinity. In vitro brain autoradiography with [(3)H]BU224 also showed a pattern of distribution similar to the known labeling of I(2) receptors. A new series of four 2BFI (2-(benzofuranyl)-2-imidazoline) derivatives were investigated as potential ligands for imaging brain I(2) receptors using positron emission tomography (PET). At least two, BU20012 and BU20013, retained high affinity and moderate selectivity and penetrated the brain when administered peripherally in the mouse. 2BFI has undergone the Mannich reaction to immobilized diaminodipropyl amine to fabricate an affinity column, which was used to isolate a protein from rabbit brain; this protein was sequenced and identified as the enzyme creatine kinase.
Animals↗
The effects of depot long-acting somatostatin analog on central aortic pressure and arterial stiffness in acromegaly.
Acromegaly is associated with increased cardiovascular risk. Although conventional risk factors such as glucose intolerance, hypertension, and dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I excess on the vasculature. To study the effects of GH excess on the vasculature, we have assessed arterial stiffness in acromegalic subjects with and without active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6 females) and 8 healthy controls were studied. Of the acromegalic subjects, eight had active disease (group A), and eight were cured (GH < 2.5 mU/liter; group B). The three groups were age, sex, and blood pressure matched. Group A subjects were restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was assessed by analyzing central arterial pressure waveforms derived from measured radial artery waveforms. This allowed determination of the augmentation of central pressure and the augmentation index. Lipids, glucose, and IGF-I were also measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index was higher in group A (28 +/- 12 vs. 12 +/- 13%; P < 0.01) but not in group B (22 +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in group A (50.3 +/- 21.2 nmol/liter; P < 0.01), compared with group B (22.5 +/- 8.9 nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I concentration was identified as a strong independent predictor of the augmentation index (beta = 0.50; P = 0.007). There were no significant differences in aortic systolic pressure, aortic diastolic pressure, lipids, or glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P < 0.05), but at 6 months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months (P < 0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P < 0.05). In conclusion, acromegaly is associated with changes in the central arterial pressure waveform, suggesting large artery stiffening. This may have important implications for cardiac morphology and performance in acromegaly as well as increasing the susceptibility to atheromatous disease. Large artery stiffness is reduced in cured acromegaly and partially reversed after pharmacological treatment of active disease.
Acromegaly↗
Transsphenoidal surgery for acromegaly in wales: results based on stringent criteria of remission.
We retrospectively analyzed 90 patients who underwent transsphenoidal surgery (performed by three surgeons) in our center as initial therapy for acromegaly. We used a combination of modern, evidence-based remission criteria including mean day curve GH less than 2.5 micro g/liter (5 mU/liter), a nadir GH less than 1.0 micro g/liter (2 mU/liter) after an oral glucose tolerance test, and normal age-related IGF-I levels (where available). Fifty-seven of 90 (63%) patients remained in remission after surgery. Seventy-nine percent of patients with microadenomas but only 56% of patients with macroadenomas achieved remission (P < 0.001). Eighty-six percent of patients with preoperative GH levels below 10 micro g/liter (day profile or after oral glucose tolerance test) went into remission, compared with 51% of patients with GH levels above 25 micro g/liter at diagnosis (P < 0.002). The remission rate was also related to the period of surgery that was significantly higher in 1998-2001 (76%; P < 0.05) compared with 1990-1997 (54%) and 1980-1989 (63%). There were no recurrences or perioperative deaths. Meningitis occurred in 3% of patients, cerebrospinal fluid rhinorrhea in 7%, and permanent diabetes insipidus in 15%. The proportion of patients who developed new anterior pituitary hormone deficiencies and panhypopituitarism was significantly less in the period 1998-2001 (P < 0.001) when compared with the periods from 1990-1997 and 1980-1989. Transsphenoidal surgery is a safe and effective treatment for acromegaly, and our results compare favorably with those from published series. The presence of an intrasellar lesion and low preoperative GH levels is a good predictor of remission in the long term, but historically in our center this can only be achieved in a significant proportion of patients at the expense of some degree of hypopituitarism. However, surgical outcome in our center, including a reduced frequency of hypopituitarism, has improved significantly over time, coincident with the arrival of a dedicated pituitary neurosurgeon and the use of selective adenomectomy as the preferred surgical approach wherever possible.
Acromegaly↗
The Klippel-Trenaunay syndrome in pregnancy.
Explore the source record for details and available documents.
Adult↗
Engineering of vascular ingrowth matrices: are protein domains an alternative to peptides?
Anastomotic intimal hyperplasia and surface thrombogenicity are the main reasons for the high failure rate of prosthetic small-diameter vascular grafts. While anastomotic intimal hyperplasia is a multifactorial event, ongoing surface thrombogenicity is primarily caused by the lack of an endothelium, even after years of clinical implantation. After decades of poorly performing synthetic artery-grafts, tissue engineering has emerged as a promising approach to generate biologically functional bio-synthetic hybrid grafts mimicking native arteries regarding the presence of an endothelial lining on the blood surface. "In vitro endothelialization" represented the first generation of such tissue-engineered vascular grafts, utilising cell culture techniques for the creation of a confluent autologous endothelium on ePTFE grafts. The clinical long-term results with this method in almost 200 patients are highly encouraging, showing patencies equal to vein grafts. Since "in vitro endothelialization" requires cell culture facilities, it will always be confined to large centres. Therefore, research of the 1990s turned to the development of spontaneously endothelializing implants, to make tissue-engineered grafts amenable to the entire vascular-surgical community. Apart from scaffold designs allowing transmural ingrowth, biological signalling through a facilitating ingrowth matrix holds a key to spontaneous endothelialization. In biological signalling, the increasingly deeper understanding of bio-active molecules and the discovery of domains and peptide sequences during the 1980s created the expectation in the 1990s that peptide signalling may be all that is needed. This present review highlights the possible problems associated with such a reductionist approach. Using the fibronectin molecule, we demonstrated that domains may be more suitable modules in tissue engineering than peptide sequences.
Animals↗