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Biomedical subjects

M Hughes

Publications and source records attributed to M Hughes.

At least 19 recordsLinked to original sources

The determinants of compliance with an early intervention programme for high-risk babies in India.

BACKGROUND: Early intervention is known to improve outcomes for babies at risk for growth and developmental problems. Such programmes usually have a prolonged course and require frequent contacts with the service providers. As a consequence of poverty, illiteracy and lack of communication facilities in developing countries, treatment adherence can suffer. METHODS: The present study is an analysis of a clinic-based early intervention programme for high-risk babies in a developing society in Goa, India. A sample of 152 neonates and their parents were offered an early intervention programme and followed up until their first birthday. The primary outcome under study was the uptake of the programme. Various socio-demographic, programmatic and infant-related variables that could affect compliance were examined. RESULTS: Compliance with the intervention programme was only moderate, with 59.2% of infants brought for three or more sessions. Higher maternal educational levels and proximity of the place of residence of the family to the early intervention clinic were significantly associated with better compliance. CONCLUSIONS: Early intervention programmes that go into homes have a greater chance of reaching high-risk infants, compared with those provided at a distant centre. Better-educated mothers are more likely to be convinced about the benefits of such inputs. The authors conclude with recommendations for future practice and research.

Adolescent↗

Bortezomib in relapsed multiple myeloma complicated by extramedullary plasmacytomas.

A 58-year-old man suffered relapse of multiple myeloma complicated by large intra-abdominal extramedullary plasmacytomas and severe hepatic impairment secondary to biliary obstruction. Previous treatment had included two types of combination chemotherapy and high-dose therapy with autologous stem cell transplant. Combination therapy with bortezomib and dexamethasone resulted in partial response of the plasmacytomas and complete resolution of his hepatic impairment. Extramedullary plasmacytomas are rare. This report lends support to the efficacy of bortezomib in the treatment of plasmacytoma and describes the safe use of bortezomib despite hepatic upset.

Antineoplastic Combined Chemotherapy Protocols↗

Dual diagnoses of hereditary hyperferritinaemia-cataract syndrome and hereditary haemochromatosis.

A 30-year-old woman was found to have hyperferritinaemia after presenting with menorrhagia and lethargy. Serum iron studies did not confirm iron overload. Further investigations revealed two distinct genetic mutations of iron haemostasis--homozygosity for C282Y mutation of the HFE gene on chromosome 6 and heterozygosity for A40G mutation in the iron response element of ferritin light chain on chromosome 19. These mutations are responsible for the diseases hereditary haemochromatosis (autosomal recessive) and hereditary hyperferritinaemia-cataract syndrome (autosomal dominant) respectively. This is the first description of such a patient.

Adult↗

A tiered risk-based approach for predicting diffuse and point source phosphorus losses in agricultural areas.

Implementation of the European Union Water Framework Directive requires an assessment of the pressures from human activity, which, combined with information on the sensitivity of the receiving waterbody to the pressures, will identify those water bodies at risk of failing to meet the Directive's environmental objectives. Part of the process of undertaking the risk assessment for lakes is an assessment of diffuse agricultural phosphorus (P) pressures. Three approaches of increasing sophistication were developed for this purpose: a basic 'risk screening' approach (tier 1) applicable to all lakes in Great Britain (GB) and based on export coefficients for different land cover classes and animal types; the Pressure Delivery Risk Screening Matrix approach (tier 2) that differentiated between pressures in surface water and groundwater river basins; and the Phosphorus Indicators Tool (PIT), a simple model of locational risk and P delivery potential (tier 3). Application of the three approaches to a range of lake catchments in England demonstrated that a tiered risk assessment approach was appropriate which was tailored to the quality of the available data. A step-wise procedure was developed whereby if the tier 1 and 2 approaches showed a catchment to be at high risk of failing to meet the Directive's environmental objectives with regard to P, it was justifiable to undertake a more detailed assessment using the tier 3 approach. The tier 1 approach was applied to all lakes in GB greater than 1 ha in size on the assumption that the boundary between the good/moderate status classes under the Water Framework Directive guidelines represented a doubling of the total P (TP) reference conditions. The initial outputs suggested that 51% of lakes in GB are predicted to not meet the TP targets identified for high or good status and must, therefore, be considered at risk. There were regional differences in numbers of lakes at risk. Scotland appeared to have the fewest sites at risk (18%); England the most (88%), with Wales having an intermediate percentage (56%). A comparison of P pressures on freshwaters using the tier 2 approach with other pressures on waterbodies (e.g. nitrate, sediment) in GB is shown as risk maps on the Environment Agency website at: . The tier 3 approach was applied to data-rich catchments and identified at the 1 km(2) areas of relatively high risk of P delivery to water.

Agriculture↗

Positron emission tomography does not add to computed tomography for the diagnosis and staging of pancreatic cancer.

BACKGROUND: Positron emission tomography (PET) has been proposed for pancreatic cancer diagnosis and staging. METHODS: 112 patients with suspected pancreatic cancer underwent 18F-fluoro-2-deoxy-D-glucose gamma camera PET and computed tomography (CT), of whom 62 also had laparoscopic ultrasonography and 70 underwent abdominal exploration for potential resection. The final diagnosis was malignancy in 78 and benign disease in 34 patients (25 with chronic pancreatitis). RESULTS: The diagnostic sensitivity and specificity for PET were 73 and 60% compared to 89 and 65% for CT respectively (Cohen's kappa = 0.59). In 30 patients CT was equivocal with cancer in 14 and benign disease in 16. PET correctly diagnosed 13 of these patients (cancer in 6 and benign disease in 7), interpreted 4 as equivocal (cancer in 3 and benign disease in 1) but was incorrect in the remaining 13 patients (cancer in 5 and benign disease in 8). The sensitivity and specificity for detecting small volume metastatic disease were 20 and 94% for CT and 22 and 91% for PET, respectively. CONCLUSION: PET had a similar accuracy to that of CT for imaging pancreatic cancer but it did not provide any additional information in patients with equivocal CT findings and currently would seem of little benefit for the staging of pancreatic cancer.

Adult↗

Early and late complications after pancreatic necrosectomy.

BACKGROUND: Surgery for pancreatic necrosis is associated with a high morbidity and mortality. The aim of this study was to review the incidence of early and late complications after pancreatic necrosectomy in a large contemporary series of patients. METHODS: The clinical outcomes of 88 patients who underwent pancreatic necrosectomy between 1997 and 2003 were reviewed. RESULTS: The median age was 55.5 (range, 18-85) years, 54 (61%) were males, 68 (77%) had primary pancreatic infection, 71 (81%) had >50% necrosis, and the median admission Acute Physiology and Chronic Health Evaluation score was 9 (range, 1-21). Median time to surgery was 31 (range, 1-161) days; 47 patients underwent minimally invasive necrosectomy and 41 open necrosectomy; 81 (92%) of patients had complications postoperatively, and 25 (28%) died. Multiorgan failure (odds ratio = 3.4, P = .05) and hemorrhage (odds ratio = 6.1, P = .03) were the only independent predictors of mortality. During a median follow-up of 28.9 months, 39 (62%) of 63 surviving patients had one or more late complications: biliary stricture in 4 (6%), pseudocyst in 5 (8%), pancreatic fistula in 8 (13%), gastrointestinal fistula in 1 (2%), delayed collections in 3 (5%), and incisional hernia in 1 (2%); intervention was required in 10 (16%) patients. Sixteen (25%) of 63 surviving patients developed exocrine insufficiency, and 19 (33%) of 58 without prior diabetes mellitus developed endocrine insufficiency. CONCLUSIONS: Almost all patients undergoing necrosectomy developed significant early or late complications or both. Multiorgan failure and postoperative hemorrhage were independent predictors of mortality. Long-term follow-up was important because 62% developed complications, and 16% of those with complications required surgical or endoscopic intervention.

APACHE↗

Basis and lattice polarization mechanisms for light transmission through nanohole arrays in a metal film.

The extraordinary light transmission through double-hole and elliptical nanohole arrays in a thin gold film is investigated for different orientations of the holes relative to the lattice. Even though these bases have similar symmetry characteristics, the polarization follows the orientation of the basis for the ellipse but remains fixed along a lattice vector for the double holes. Furthermore, the maximum transmitted intensity for linearly polarized light is constant for the ellipse, but decreases for the double holes as they are rotated away from being aligned with the lattice. Finite-difference time-domain simulations agree well with the experimental findings. These experiments show how the basis determines both the coupling into the surface plasmon waves and the evanescent transmission through the nanoholes. Both of these effects need to be considered when designing nanophotonic devices using the extraordinary transmission phenomenon.

Anisotropy↗

Successful treatment of a patient with chronic lymphocytic leukaemia (CLL) presenting with bony metastases with aggressive antibody and chemotherapy.

Osteolytic lesions are rare in chronic lymphocytic leukaemia (CLL) and thought to result from Richter's transformation or metastatic disease from nonlymphoid malignancies. We report a patient who presented with a large femoral metastatic lesion and hypercalcaemia caused by CLL itself. Complete remission of CLL with resolution of the osteolytic lesion was achieved with rituximab and cyclophosphamide, adriamycin, oncovin and prednisolone [CHOP (R-CHOP)] combination chemotherapy.

Aged, 80 and over↗

Refugia, dispersal and divergence in a forest archipelago: a study of Streptocarpus in eastern South Africa.

We describe a scenario of plant speciation across a relict forest archipelago in South Africa involving Pleistocene habitat expansion-contraction cycles, dispersal and adaptation to lower temperatures. This is the first population level study using molecular data in South African forests and has significant implications for conservation efforts in this area. Populations of the mesophytic forest floor herbs Streptocarpus primulifolius sensu lato and Streptocarpus rexii were sampled throughout their range in the naturally fragmented forests of eastern South Africa in order to investigate population genetic and phylogenetic patterns within the species complex, using nuclear microsatellites, nuclear ribosomal ITS (internal transcribed spacer) sequences and chloroplast genome sequences. S. primulifolius harbours high levels of genetic diversity at both the nuclear (mean HE = 0.50) and the chloroplast level (each population fixed for a unique haplotype). This is consistent with populations of these coastal species being Pleistocene relicts. In contrast, populations of S. rexii in cooler habitats at higher altitudes and lower latitudes harbour little or no nuclear genetic diversity (mean HE = 0.09) and most share a common chloroplast haplotype. The split of S. rexii from populations intermediate between the two species (S. cf. primulifolius) occurred between 0 and 0.44 million years ago according to the calibrated ITS phylogeny of the taxa. The low genetic diversity and homogeneity of S. rexii is congruent with this species having reached its current range during the Holocene. We found no evidence of monophyly of any of the taxa in this study, which we consider a consequence of recent evolution in a fragmented habitat.

Conservation of Natural Resources↗

Fungal infection but not type of bacterial infection is associated with a high mortality in primary and secondary infected pancreatic necrosis.

INTRODUCTION: Knowledge of microbiology in the prognosis of patients with necrotizing pancreatitis is incomplete. AIM: This study compared outcomes based on primary and secondary infection after surgery for pancreatic necrosis. METHOD: From a limited prospective database of pancreatic necrosectomy, a retrospective case note review was performed (October 1996 to April 2003). RESULTS: 55 of 73 patients had infected pancreatic necrosis at the first necrosectomy. 25 of 47 patients had resistant bacteria to prophylactic antibiotics (n = 21) or did not receive prophylactic antibiotics (n = 4), but this was not associated with a higher mortality (9 of 25) compared to those with sensitive organisms (4 of 22). Patients with fungal infection (n = 6) had a higher initial median (95% CI) APACHE II score compared to those without (11 (9-13) verus 8.5 (7-10), p = 0.027). Five of six patients with fungal infection died compared to 13 of 47 who did not (p = 0.014). With the inclusion of secondary infections 21 (32%) of 66 patients had fungal infection with 10 (48%) deaths compared to 11 (24%) of 45 patients without fungal infection (p = 0.047). CONCLUSION: Whether associated with primary or secondary infected pancreatic necrosis, fungal but not bacterial infection was associated with a high mortality.

Bacterial Infections↗

Laparoscopy and laparoscopic ultrasound in the evaluation of pancreatic and periampullary tumours.

BACKGROUND AND AIMS: The pre-operative determination of resectability of pancreatic and peri-ampullary neoplasia assists the selection of patients for surgical or non-surgical treatment. This study investigated whether the addition of laparoscopy with laparoscopic ultrasound to dual-phase helical CT could improve the accuracy of assessment of resectability. PATIENTS AND METHODS: Prospective study of 305 patients referred to a single unit for consideration of pancreatic resection who underwent dual-phase helical CT scanning +/- laparoscopy with laparoscopic ultrasound. Data were collected on patient demographics, CT findings, assessment of operability, laparoscopic assessment (LA), surgical procedures and histology. RESULTS: LA was undertaken in 239/305 patients, 190 of whom were considered CT resectable, and 49 CT unresectable. Of the 190 CT resectable patients, LA correctly identified unresectability in 28 (15%: metastases in 15; vascular encasement in 6; anaesthesia for laparoscopy found 7 unfit for major resection) and incorrectly in 2 (vascular encasement), but did not identify unresectability in 33; LA correctly confirmed resectability in the remainder (prediction improved, chi(2) = 9.73, p < 0.01). Of the 49 CT unresectable patients, LA correctly identified resectability in 4, and incorrectly in 12, and correctly identified unresectability in the remaining 33. Sixty-six of the 305 patients did not undergo LA, of whom 23 underwent resection. CONCLUSION: When added to dual-phase helical CT, laparoscopy with laparoscopic ultrasound provides valuable information that significantly improves the selection of patients for surgical or non-surgical treatment.

Adult↗

Hereditary pancreatic endocrine tumours.

The two main types of hereditary pancreatic neuroendocrine tumours are found in multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), but also in the rarer disorders of neurofibromatosis type 1 and tuberous sclerosis. This review considers the major advances that have been made in genetic diagnosis, tumour localization, medical and surgical treatment and palliation with systemic chemotherapy and radionuclides. With the exception of the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can be treated medically. The role of surgery however remains controversial ranging from no intervention (except enucleation for insulinoma), intervening for tumours diagnosed only by biochemical criteria, intervening in those tumours only detected radiologically (1-2 cm in diameter) or intervening only if the tumour diameter is > 3 cm in diameter. The extent of surgery is also controversial, although radical lymphadenectomy is generally recommended. Pancreatic tumours associated with VHL are usually non-functioning and tumours of at least 2 cm in diameter should be resected. Practice guidelines recommend that screening in patients with MEN-1 should commence at the age of 5 years for insulinoma and at the age of 20 years for other pancreatic neuroendocrine tumours and variously at 10-20 years of age for pancreatic tumours in patients with VHL. The evidence is increasing that the life span of patients may be significantly improved with surgical intervention, mandating the widespread use of tumour surveillance and multidisciplinary team management.

Endocrine Gland Neoplasms↗

Influence of opioid use on surgical and long-term outcome after resection for chronic pancreatitis.

BACKGROUND: The outcome of pancreatic resection for chronic pancreatitis in patients with preoperative opioid use is not well described. METHODS: During 1997 to 2003, 112 of 231 patients referred with chronic pancreatitis underwent pancreatic resection. The outcome of patients who had preoperative opioid use (N=46) was compared with those without (N=66). RESULTS: Patients who used opioids presented at a younger age and had a younger age of symptom onset, longer symptom duration, more hospitalizations, a higher frequency of diabetes mellitus, a higher pain score, and more restriction in daily activity (all P<.05). Twenty-one (46%) patients with opioid use had a total pancreatectomy compared with 9 (14%) without opioid use (P=.0002); the 21 patients also had a higher frequency of postoperative bleeding and early reoperation (8 vs 2, P<.02; 11 vs 3, P=.003, respectively). Mortality and overall morbidity was not significantly different between the 2 groups (4 vs 1, 27 vs 34, respectively). Pain scores improved postoperatively in both groups (P=.001) and was not significantly different between the groups from 12 months onward (median follow-up of 12 months, range, 3-60 months). Twenty percent of patients who used preoperative opioids however reverted to morphine use compared with 6% of patients who had not used opioids. CONCLUSIONS: Patients who used opioids had more advanced disease than patients without opioid use, accounting for part of the postoperative morbidity. Although long-term pain relief was comparable between the 2 groups, maintaining opioid withdrawal was more problematic in those with preoperative opioid use. Earlier referral for resection may be warranted in this group of patients.

Abdominal Pain↗

Double resection for patients with pancreatic cancer and a second primary renal cell cancer.

BACKGROUND: Reports of synchronous or metachronous double kidney-pancreas cancers are very rare. METHODS: We present 2 patients with renal cell carcinoma and synchronous (1 patient) or metachronous (1 patient) primary pancreatic ductal adenocarcinoma. The patients underwent resection for both cancer types with a worthwhile outcome. RESULTS: The appearance of different primaries in an individual may indicate a genetic predisposition to different neoplasms. The study of double primary cancers is important because it might provide understanding of a shared genetic basis of different solid tumors. CONCLUSIONS: The association between these two cancers demands more detailed epidemiological and molecular investigation. From a clinical viewpoint a resectional policy is recommended.

Adenocarcinoma↗

Increasing age and APACHE II scores are the main determinants of outcome from pancreatic necrosectomy.

BACKGROUND: The aim of this study was to identify factors associated with death after surgery in patients with extensive pancreatic necrosis. METHODS: Sixty-four patients who underwent pancreatic necrosectomy between 1996 and 2002 were studied. RESULTS: The median age was 60.5 (95 per cent confidence interval (c.i.) 57 to 64) years and 40 patients (62.5 per cent) were tertiary referrals. The initial median Acute Physiology And Chronic Health Evaluation (APACHE) II score was 9 (95 per cent c.i. 7.9 to 10.1) and there were 21 deaths (32.8 per cent). Twenty-eight patients (43.8 per cent) underwent minimally invasive retroperitoneal pancreatic necrosectomy (MIRP) and the remainder had open pancreatic necrosectomy (OPN); 44 (72.1 per cent) of 61 patients had infected pancreatic necrosis at the time of the first procedure. Seven patients who underwent MIRP died compared with 14 after OPN (P = 0.240). Patients who died were older than those who survived, with higher APACHE II scores at presentation, and before and after surgery (P = 0.001). Survivors had significantly longer times to surgery than those who died (P = 0.038). All 21 patients who died required intensive care compared with 26 of 43 survivors (P < 0.001). Thirty of 36 patients who had the OPN procedure required intensive care compared with only 17 of 28 patients who had MIRP (P = 0.042). Logistic regression analysis showed that only postoperative APACHE II score was an independent predictor of increased mortality (P = 0.031). CONCLUSION: Advanced age and increasing APACHE II score, and a need for postoperative intensive care, were the most important predictors of outcome after pancreatic necrosectomy.

APACHE↗

Role of Src homology 2-containing-inositol 5'-phosphatase (SHIP) in mast cells and macrophages.

The haemopoietic-restricted Src homology 2-containing inositol 5'-phosphatase (SHIP) acts as a negative regulator of myeloid cell proliferation, survival and end-cell activation. It does so, at least in part, by hydrolysing the phosphoinositide 3-kinase (PI3K)-generated second messenger, PtdIns(3,4,5) P (3) (PI-3,4,5-P(3)) to PtdIns(3,4) P (2). As a result, the myeloid progenitors in SHIP-knockout mice display enhanced survival and proliferation and the mice have increased numbers of neutrophils and monocytes/macrophages. Interestingly, although SHIP is not required for mast cell or macrophage development, it restrains their differentiation since progenitors from SHIP(-/-) mice differentiate into mature mast cells and macrophages significantly faster than their wild-type counterparts. This could suggest that elevated PI-3,4,5-P(3) levels accelerate myeloid differentiation. In bone-marrow-derived mast cells, SHIP prevents degranulation by IgE alone, restrains IgE-antigen-induced degranulation and limits the production of inflammatory cytokines. On the other hand, in peritoneal macrophages, SHIP is a positive regulator of NO production, since SHIP(-/-) peritoneal macrophages produce 5-10-fold less NO than their wild-type counterparts, even though they show greater lipopolysaccharide/interferon-gamma-induced nuclear factor kappa B activation and more rapid inducible NO synthase (iNOS) generation. This is a result of 10-fold higher levels of arginase I in the SHIP(-/-) macrophages, which redirects the iNOS substrate, L-arginine, from NO to ornithine production. This suggests that the chronically elevated PI-3,4,5-P(3) levels in SHIP(-/-) mice may convert M1 (killing) macrophages, which produce NO to kill micro-organisms and tumour cells, into M2 (healing) macrophages, which produce ornithine to promote host cell growth and fibrosis.

Animals↗