In situ split liver transplantation using a donor with a recent history of HELLP syndrome.
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Adult↗
Biomedical subjects
Michael Crawford
Publications and source records attributed to Michael Crawford.
A distinctive fatty acid profile in circulating lipids of Korean gestational diabetics: a pilot study.
Gestational diabetes mellitus (GDM) is a transient metabolic disorder that is a strong predictor of type 2 diabetes and cardiovascular disease. Previously, GDM was associated with reduced red cell long-chain omega-6 and omega-3 fatty acids in population (British) with high intake of total and saturated fat. The aim of the study was to examine blood fatty acids status of GDM patients (n=12) and normoglycaemic women (control, n=12) from South Korea where typical diet retains high omega-3 fat with low total fat intake. Subjects were matched for BMI and gestation week. Blood obtained at delivery were analyzed for plasma triacylglycerols (TG), phosphatidylcholine (PC), sphingomyelin (SM), and red cell PC, phosphatidylethanolamine (PE) and SM fatty acids. GDM patients had lower total saturated fatty acids (SFA) in the plasma TG (p<0.05) and PC (p<0.0001), and higher omega-6 and omega-3 metabolites in the plasma PC (p<0.05) than the controls. Conversely, the red cell PC and PE of the GDM contained higher proportions of palmitic (p<0.05) and SFA (p<0.05) but lower arachidonic (p<0.05) and docosahexaenoic (p>0.05) acids compared with the controls. Interestingly, red cell PC arachidonic acid level was comparable between Korean and British women whereas docosahexaenoic acid level decreased in the order of Korean control (5.5+/-0.9)>Korean GDM (3.5+/-2.1)=British control (3.9+/-2.9)>British GDM (2.8+/-2.3) (p<0.05). The similarity in the plasma and red cell fatty acids profile between Korean and British cohort suggests that the reduced membrane arachidonic and docosahexaenoic acids in GDM might be attributed to the effect of the disease itself regardless of ethnicity, obesity, or diet.
Adult↗
Primary open-angle glaucoma patients have reduced levels of blood docosahexaenoic and eicosapentaenoic acids.
The aetiology of primary open-angle glaucoma (POAG), which is the commonest cause of non-remediable blindness and visual impairment, is not well understood. Nevertheless, increased intraocular pressure, and vascular factors such as ocular blood flow deficits are thought to be risk factors. There is evidence of decreased optic nerve blood velocity and increased red blood cell aggregability in POAG. These factors are influenced by fatty acids. We have investigated if glaucoma patients have abnormal blood fatty acid composition. Patients with POAG (n=10) and their healthy siblings (n=8) were enrolled. Compared with their healthy siblings, the glaucoma patients had reduced eicosapentaenoic (EPA, P<0.01), and docosahexaenoic (DHA, P<0.05) fatty acids and total omega3 long-chain polyunsaturated fatty acids (LCPUFA) (P<0.05) in red cell choline phosphoglycerides (CPG); decreased EPA (P<0.05) in ethanolamine phosphoglycerides (EPG); lower EPA (P<0.05) and total omega3 LCPUFA (P<0.05) in serine phosphoglycerides (SPG). Similarly, they had reduced EPA, DHA and total omega3 LCPUFA in plasma CPG (P<0.005) and triglycerides (P<0.05). These findings may be significant, since EPA and DHA could modulate impaired systemic microcirculation and ocular blood flow and optic neuropathy, which are the main physiological changes associated with glaucoma.
Adult↗
Nutrient intake of women with and without gestational diabetes with a specific focus on fatty acids.
OBJECTIVE: Diet therapy is the cornerstone for the management of gestational diabetes mellitus (GDM). Women with GDM are commonly given dietary advice that broadly focuses on a reduction of total energy and fat consumption. We compared nutrient intake and specifically fatty acids of women with GDM who had received individualized nutritional counseling with those of non-diabetic women who did not. METHOD: Women with GDM (n=44) and healthy pregnant women (n=44) with uncomplicated singleton pregnancies were recruited during the third trimester. Women with GDM were given consultation on diet, health, and macronutrient content of foods commonly consumed by the individual. The non-diabetic group did not receive any dietary advice. Both groups were asked to keep a detailed record of all of foods and fluid consumed over a 4-d period. RESULTS: After dietary counseling, the GDM group had lower intakes of energy (P<0.05), refined sugar (P<0.0001), total and saturated fats (P<0.0001), and monounsaturated (P<0.01) and trans (P<0.0001) fatty acids and higher levels of docosahexaenoic acid and fiber (P<0.05) compared with the non-diabetic group. CONCLUSIONS: Individualized dietary advice was associated with a lower consumption of the target nutrients in women with GDM. Another benefit of the advice was a slight increase in intake of eicosapentaenoic and docosahexaenoic acids, although consumption of omega-3 fatty acids by both groups was well below the recommendations for pregnancy. There is evidence that docosahexaenoic acid modulates insulin resistance and that it is vital for neurovisual development. We suggest that dietary management for women with GDM should foster the current recommendations for essential fatty acids in pregnancy.
Adult↗
The in vitro metabolism of irinotecan (CPT-11) by carboxylesterase and beta-glucuronidase in human colorectal tumours.
AIMS: Irinotecan (CPT-11) is a prodrug that is used to treat metastatic colorectal cancer. It is activated to the topoisomerase poison SN-38 by carboxylesterases. SN-38 is metabolized to its inactive glucuronide, SN-38 glucuronide. The aim of this study was to determine, the reactivation of SN-38 from SN-38 glucuronide by beta-glucuronidase may represent a significant pathway of SN-38 formation. METHODS: The production of SN-38 from irinotecan and SN-38 glucuronide (2.4, 9.6 and 19.2 microm) was measured in homogenates of human colorectal tumour, and matched normal colon mucosa from 21 patients). RESULTS: The rate of conversion of irinotecan (9.6 microm) was lower in tumour tissue than matched normal colon mucosa samples (0.30+/-0.14 pmol min-1 mg-1 protein and 0.77+/-0.59 pmol min-1 mg-1 protein, respectively; P<0.005). In contrast, no significant difference was observed in beta-glucuronidase activity between tumour and matched normal colon samples (4.56+/-6.9 pmol min-1 mg-1 protein and 3.62+/-2.95 pmol min-1 mg-1 protein, respectively, using 9.6 microm SN-38 glucuronide; P>0.05). beta-Glucuronidase activity in tumour correlated to that observed in matched normal tissue (r2>0.23, P<0.05), whereas this was not the case for carboxylesterase activity. At equal concentrations of irinotecan and SN-38 glucuronide, the rate of beta-glucuronidase-mediated SN-38 production was higher than that formed from irinotecan in both tumour and normal tissue (P<0.05). However, at concentrations that reflect the relative plasma concentrations observed in patients, the rate of SN-38 production via these two pathways was comparable. CONCLUSIONS: Tumour beta-glucuronidase may play a significant role in the exposure of tumours to SN-38 in vivo.
Antineoplastic Agents, Phytogenic↗
Neurological status of low-risk Vietnamese newborns: a comparison with a British newborn cohort.
A shortened version of the Dubowitz newborn neurological examination, recently reassessed in rural Thailand, was applied to a group of 58 Vietnamese newborns. The aim was to establish the neurological status of newborns in this population for use in further studies and to compare with groups previously studied. Compared to the original British cohort, the Vietnamese newborns showed significantly lower scores in 10 of 25 items, including several related to truncal tone. Evidence was sought of thiamine and long-chain fatty acid deficiency as a possible cause for these findings, but no correlation was found between the neurological status and the maternal or infant blood levels of these nutritional indicators. The findings suggest that the neurological status of low-risk Vietnamese newborns appears to lie between that of British newborns and those ethnic minority Karen newborns in refugee camps on the Thai-Burmese border tested previously. Although no specific nutritional cause has been identified in the study, the findings may still reflect sub-optimal intake of some important nutrients.
Adult↗
Abnormality of erythrocyte membrane n-3 long chain polyunsaturated fatty acids in sickle cell haemoglobin C (HbSC) disease is not as remarkable as in sickle cell anaemia (HbSS).
Sickle cell disease (SCD) is a group of inherited blood disorders in which clinical illness results from the presence of erythrocytes with sickled haemoglobin (HbS). Blood vessel occlusion is a fundamental pathological process in SCD. Sickle cell haemoglobin C (HbSC) disease and sickle cell anaemia (HbSS) share some pathophysiology and clinical manifestations. However, the former is generally less severe. Erythrocytes of HbSC patients have longer life span, reduced haemolysis, and lower propensity to adhere to vascular endothelium than those of their HbSS counterparts. The structure and function of erythrocytes are strongly modulated by membrane long chain polyunsaturated fatty acids (LCPUFA). We have tested the possibility that HbSC and HbSS patients have different membrane fatty acid composition consistent with the difference in their clinical severity. Steady-state patients, 9 HbSC and 28 HbSS, and 15 HbAA were studied. The HbSC patients had a higher level of linoleic (LA, P<0.05) and docosahexaenoic (DHA, P<0.05) acids, and lower arachidonic acid (AA, P<0.01) and AA/eicosapentaenoic acid (EPA) ratio (P<0.05) in erythrocyte choline phosphoglycerides (CPG) compared with the HbSS group. Similarly, the level of EPA was higher and AA/EPA ratio (P<0.01) lower in serine phosphoglycerides of the HbSC patients. In contrast to the HbSC, the HbSS group had lower levels of EPA (P<0.001), DHA (P<0.05), total n-3 metabolites and total n-3 fatty acids (P<0.001) in erythrocyte CPG compared with the healthy HbAA controls. Moreover, the HbSS patients with disease complications compared with those without complications had reduced DHA and total n-3 fatty acids (P<0.005) in erythrocyte CPG. The abnormalities in erythrocyte in LCPUFA which is manifested by an increase in AA and a decrease in EPA and DHA in HbSS relative to HbSC disease observed in this study are consistent with the contrast in clinical severity between the two entities.
Adult↗
Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease.
Leukocyte adhesion to vascular endothelium contributes to vaso-occlusion and widespread organ damage in sickle cell disease (SCD). Previously, we found high expression of the adhesion molecules alphaMbeta2 integrin and L-selectin in HbSS individuals with severe disease. Since membrane n-6 and n-3 polyunsaturated fatty acids modulate cell adhesion, inflammation, aggregation and vascular tone, we investigated the fatty acid composition of mononuclear cells (MNC) and platelets of HbSS patients in steady state (n=28) and racially matched, healthy HbAA controls with similar age and sex distribution living in the same environment (n=13). MNC phospholipids of the patients had lower levels of docosahexaenoic acid (DHA, p<0.01) and increased arachidonic acid (AA, p<0.005) relative to HbAA controls. Similarly, platelets from HbSS patients had less eicosapentaenoic acid (EPA, p<0.05) and more AA (p<0.05) in choline phosphoglycerides (CPG), with reduced DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in SCD patients with complications compared to those without (p<0.05). Reduced cell content of EPA and DHA relative to AA favours the production of aggregatory and proinflammatory eicosanoids that activate leukocytes and platelets. This facilitates inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD.
Adult↗
Steady-state haemoglobin level in sickle cell anaemia increases with an increase in erythrocyte membrane n-3 fatty acids.
The aim of the study was to investigate, whether (a) patients with homozygous sickle cell disease (SCD, HbSS) have abnormal blood fatty acids; (b) the abnormality, if it exists, affects all the plasma and erythrocyte lipids or it is restricted to a particular lipid moiety; (c) there is an association between levels of membrane n-3 or n-6 long-chain polyunsaturated fatty acids (LCPUFA) and the degree of anaemia. Fatty acids of erythrocyte choline (CPG), serine (SPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SPM); and plasma CPG, triglycerides and cholesterol esters of 43 steady-state HbSS patients and 43 ethnically matched, healthy, HbAA controls were analysed. The levels of the n-6 LCPUFA, arachidonic (AA), adrenic and docosapentaenoic acids in erythrocyte CPG (P<0.001) and EPG (P<0.01) were higher in the patients compared with the controls. In contrast, the proportions of eicosapentaenoic acid (EPA) in CPG and EPG (P<0.001) and docosahexaenoic acid (DHA) and total n-3 metabolites in CPG (P<0.001) were lower in the patients. The steady-state haemoglobin level of the patients correlated with erythrocyte DHA (r=0.55, P<0.01), EPA (r=0.38, P<0.05) and total n-3 metabolites (r=0.51, P<0.001) in CPG. Also, it correlated with erythrocyte EPA (r=0.64, P<0.01) and total n-3 metabolites (r=0.42, P<0.01) in EPG. The study revealed an imbalance between n-3 and n-6 LCPUFA in erythrocyte and plasma lipid moieties of the HbSS group. Furthermore, it suggested that correction of the imbalance by supplementation with EPA and DHA could ameliorate anaemia in the patients. This observation is consistent with the results of pilot studies, which demonstrated that treatment with n-3 fatty acids confers clinical benefit to sickle cell patients.
Anemia↗
Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance.
BACKGROUND: Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids. OBJECTIVE: We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs). DESIGN: We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed. RESULTS: The difference in maternal plasma triacylglycerol FAs between groups was not significant. However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 +/- 0.9%; P < 0.01) than did the control group (5.2 +/- 1.6%). Likewise, RBC DHA was lower in the type 1 [choline: 3.4 +/- 1.5% (P < 0.01); ethanolamine: 5.9 +/- 2.5% (P < 0.05)] and type 2 [choline: 3.5 +/- 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 +/- 2.2%; ethanolamine: 7.5 +/- 2.5%). Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group. CONCLUSIONS: Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.
Adult↗
Asymptomatic postoperative deep vein thrombosis and the development of postthrombotic syndrome. A systematic review and meta-analysis.
Perioperative antithrombotic clinical regimens have reduced the incidence of postoperative deep venous thrombosis (DVT). Long-term effects of asymptomatic postoperative DVT have been studied in a number of clinical trials and the present review describes the clinical significance of asymptomatic postoperative DVT regarding the possible development of postthrombotic syndrome (PTS). We performed a systematic review of reference databases focusing upon studies including patients suspected of having postoperative DVT and reporting subsequent cases of PTS at the end of a well-defined follow-up period. The included studies were stratified according to type of screening method and applied statistics. Over-all evaluation included meta-analyses based upon the Cochrane software package. The overall relative risk of developing PTS was 1.58 (95% confidence intervals: 1.24-2.02) in patients suffering from asymptomatic DVT as compared to patients without DVT (p<0.0005). In conclusion, asymptomatic postoperative DVT is associated with an increased risk of late development of PTS. The finding emphasizes that postoperative DVT, diagnosed by means of well-defined objective measures, remains the correct scientific endpoint in trials evaluating the efficacy of preoperative antithrombotic treatment regimens.
Data Collection↗
Liver retransplantation in an infant requiring cavoportal hemi transposition.
Historically inability to achieve portal inflow to the liver allograft operatively was felt to be a contraindication to orthotopic liver transplantation (OLTx). Cavoportal hemi transposition has been utilized more recently in adult OLTx recipients but rarely in pediatric recipients. Here we report the case of a 10-month-old male with biliary atresia, who required urgent retransplantation with an in situ split cadaver donor allograft for failure of his first liver allograft from portal vein thrombosis. At the time of retransplantation, cavoportal hemi transposition was required to effect portal vein inflow to the allograft because of extensive thrombosis of the recipients portomesenteric venous system.
Biliary Atresia↗
Small bowel tumours: a 10 year experience in four Sydney teaching hospitals.
BACKGROUND: Small bowel tumours are uncommon and can have a long delay prior to diagnosis. The present study aims to compare the use of computed tomography (CT) and contrast small bowel series (SBS) in their diagnosis and to outline the clinical features of small bowel tumours. METHODS: A retrospective, case note study was conducted between 1990 and 2000 in four Sydney teaching hospitals. The data collected included clinical features, investigations and tumour characteristics. RESULTS: One hundred and sixty-six people with small bowel tumours were identified (91 malignant; 75 benign). Malignant tumours consisted of adenocarcinomas (31%), carcinoid tumours (12%), lymphomas (7%) and leiomyosarcomas (5%). Benign tumours consisted of adenomas (22%), hamartomas (13%), leiomyomas (4%), inflammatory polyps (4%) and hyperplastic polyps (2%) and a benign schwannoma (1%). Adenocarcinomas were mainly located in the duodenum (P < 0.001) and carcinoid tumours in the ileum (P < 0.001). Malignant tumours were associated with a higher proportion of symptoms (P < 0.01), signs (P < 0.001) and episodes of small bowel obstruction (P < 0.01). Abdominal CT scans demonstrated a greater sensitivity (87.7%) than SBS (72.9%) with a slightly improved sensitivity when both investigations were used (89.3%). Abdominal ultrasound had a lower sensitivity than both of the above investigations of 65%. Gastroduodenoscopy had a sensitivity of 90% for diagnosing duodenal tumours. Operative procedures were performed on 92 patients with a preoperative diagnosis made in 77%. Metastatic spread of malignant tumours was evident in 46%. The sites of spread were to lymph nodes (23%), liver (21%) and distant locations (2%) at diagnosis. CONCLUSIONS: Malignant small bowel tumours are more likely to produce symptoms and signs than benign tumours, particularly caused by small bowel obstruction. Abdominal CT is the best radiological investigation for small bowel tumours and has a slight complimentary effect with SBS in improving the chances of detection. Gastroduodenoscopy remains the best investigation of duodenal tumours.
Adolescent↗
Liver transplantation from controlled non-heart-beating donors: an increased incidence of biliary complications.
BACKGROUND: Hepatic allografts from non-heart-beating donors (NHBD) have been cited as a means to expand the supply of donor livers. Concern exists that donor warm ischemic time in addition to subsequent cold ischemia-reperfusion injury may result in damage to sensitive cell populations within the liver. Because the biliary epithelium is sensitive to ischemia-reperfusion injury, the authors surmised that an increased incidence of biliary complications might occur among recipients of an NHBD allograft. METHODS: This study was a retrospective evaluation of NHBD recipients compared to a group of heart-beating donor (HBD) recipients from a single institution. RESULTS: Fifteen patients received a hepatic allograft from a controlled NHBD donor. NHBD and HBD (n=221) graft survival did not differ at 1 (71.8% vs. 85.4%, P=0.23) or 3 years (71.8% vs. 73.9%, P=0.68). Patient survival at 1 (79% vs. 90.9%, P=0.16) and 3 years (79.0% vs. 77.7%, P=0.8) was also similar. Major biliary complications occurred in five (33.3%) NHBD recipients; 66.6% of the NHBD biliary complications consisted of intrahepatic strictures versus 19.2% among HBD recipients (P<0.01). Major biliary complications in the NHBD recipients resulted in multiple interventional procedures, retransplantation, and death. CONCLUSIONS: Donor warm ischemic time may predispose hepatic allografts to an increased incidence of ischemic type strictures. Although graft and patient survival was similar to a cohort of HBD recipients, caution is urged with the use of these organs.
Adult↗
Hox genes as synchronized temporal regulators: implications for morphological innovation.
In vertebrates, clusters of Hox genes express in a nested and hierarchical fashion to endow the embryo's segments with discrete identities. Later in development, members of the same gene family are employed again to pattern the limb, intestinal, and reproductive systems. A careful analysis of the morphologies of Hox mutant mice suggests that the genes provide qualitatively different cues during the specification of segments than they do during the development of more recently derived structures. In addition to the regulatory differences noted by others, the activity of Hox genes during specification of the vertebrate metameres in some recent deletion experiments is inconsistent with a role for them as strictly spatial determinants. On the contrary, the phenotypes observed are suggestive of a role for them as elements of a generic time-keeping mechanism. By contrast, the specification of more recent evolutionary structures appears to be more spatial and gene-specific. These differences in role and effect may suggest some simple mechanisms by which the Hox clusters operate, and rules by which gene networks can be diverted to create new structures over the course of evolution. Specific predictions and experiments are proposed.
Animals↗
Delayed visual maturation in Karen refugee infants.
Thirty-eight babies born to Karen mothers living in camps for displaced persons in north-western Thailand have delayed visual maturation (DVM type 1) that recovers within 6 months. Vitamin A concentrations were deficient in 16% of breast-milk samples from lactating mothers and vitamin B(1) concentrations were deficient in 60% of plasma samples. Infantile beriberi was common in this population. The levels of fatty acids in plasma and milk in Karen women were excellent at birth and in the postpartum period. The degree of deficiencies in these vitamins and the concentration of essential fatty acids in cord blood and maternal breast-milk did not correlate significantly with visual impairment in the infants. DVM might be caused by nutritional deficiency or toxic effects during critical periods of gestation that lead to delayed cortical myelination or structural defects which impinge on parietal cortex function.
Adolescent↗
Suicide in ethnic minority groups.
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Ethnicity↗
Inequality of international public health.
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Developed Countries↗