The relationship between cytokeratin expression in bladder washings and resected tumour specimens.
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Adult↗
Biomedical subjects
A Patterson
Publications and source records attributed to A Patterson.
Acute liver failure in pregnancy associated with maternal MCAD deficiency.
In recent years the association between severe pregnancy complications and fetal fatty acid oxidation (FAO) disorders has been reported. However, there are few descriptions of a maternal FAO disorder leading to these complications. We describe acute liver failure associated with an undiagnosed maternal medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. The previously healthy proband presented at the 39th week with an itchy rash, palmar erythema and trace proteinuria; she was admitted onto a maternity ward. Acute fatty liver was suspected from the blood tests and a Caesarean section was performed, delivering a healthy boy. Cord blood samples were taken at delivery as part of an ongoing research project. The analysis of the cord blood sample showed a high concentration of octanoylcarnitine of 2.3 micromol/L (reference <0.1), suggesting a possible fatty acid oxidation disorder. However, subsequent acylcarnitine analyses of the baby's blood showed a normal pattern. The proband was further evaluated by urine organic acids and acylcarnitine profile. Elevated concentrations of hexanoylglycine in urine and octanoylcarnitine in blood spots were found, consistent with a diagnosis of MCAD deficiency. Mutation analyses confirmed that she was homozygous for c.985A>G (K329E). Even though these pregnancy complications are rare and it is not possible to affirm that the proband's acute liver failure was secondary to an undiagnosed MCAD deficiency, it seems likely.
Acyl-CoA Dehydrogenase↗
Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension.
Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, with subsequent extracellular matrix (ECM) production and smooth muscle cell (SMC) proliferation. Changes in the ECM can modulate vasoreactivity and SMC contraction. Galectin-1 (Gal-1) is a hypoxia-inducible beta-galactoside-binding lectin produced by vascular, interstitial, epithelial, and immune cells. Gal-1 regulates SMC differentiation, proliferation, and apoptosis via interactions with the ECM, as well as immune system function, and, therefore, likely plays a role in the pathogenesis of PH. We investigated the effects of Gal-1 during hypoxic PH by quantifying 1) Gal-1 expression in response to hypoxia in vitro and in vivo and 2) the effect of Gal-1 gene deletion on the magnitude of the PH response to chronic hypoxia in vivo. By constructing and screening a subtractive library, we found that acute hypoxia increases expression of Gal-1 mRNA in isolated pulmonary mesenchymal cells. In wild-type (WT) mice, Gal-1 immunoreactivity increased after 6 wk of hypoxia. Increased expression of Gal-1 protein was confirmed by quantitative Western analysis. Gal-1 knockout (Gal-1(-/-)) mice showed a decreased PH response, as measured by right ventricular pressure and the ratio of right ventricular to left ventricular + septum wet weight compared with their WT counterparts. However, the number and degree of muscularized vessels increased similarly in WT and Gal-1(-/-) mice. In response to chronic hypoxia, the decrease in factor 8-positive microvessel density was similar in both groups. Vasoreactivity of WT and Gal-1(-/-) mice was tested in vivo and with use of isolated perfused lungs exposed to acute hypoxia. Acute hypoxia caused a significant increase in RV pressure in wild-type and Gal-1(-/-) mice; however, the response of the Gal-1(-/-) mice was greater. These results suggest that Gal-1 influences the contractile response to hypoxia and subsequent remodeling during hypoxia-induced PH, which influences disease progression.
Animals↗
The views and practice of oncologists towards nutritional support in patients receiving chemotherapy.
Malnutrition in patients with cancer is common and an adverse prognostic indicator. A questionnaire answered by 357 (72%) UK specialist oncological trainees suggests that they lack the ability to identify factors that place patients at risk from malnutrition. Major barriers to effective nutritional practice included lack of guidelines, knowledge and time.
Adult↗
Carnitine transporter defect: diagnosis in asymptomatic adult women following analysis of acylcarnitines in their newborn infants.
Carnitine transporter defect (CTD) is an autosomal recessive disorder characterized by episodes of non-ketotic hypoglycaemia, hyperammonaemia and liver disease, or by the development of cardiomyopathy, both of which occur in infancy and childhood. Blood carnitine concentrations are extremely low. The diagnosis can be confirmed by finding abnormal fat oxidation and carnitine uptake in skin fibroblasts. The condition has not previously been thought to present later in life or to be benign. We report the identification of four women discovered to have CTD as a consequence of finding low carnitine concentrations in the cord blood or newborn samples from their infants. All four mothers had been asymptomatic and none had a cardiomyopathy.
Adult↗
Role of polymerase chain reaction and immunocytochemistry in the cytological assessment of lymphoid proliferations.
BACKGROUND: Fine-needle aspiration cytology (FNAC) is used as a screening test to evaluate lymphadenopathy. The combined use of genetic analysis and flow cytometry for immunophenotyping has increased the accuracy of diagnosis and correct categorisation of lymphomas on cytological preparations. AIM: To show the utility of immunocytochemistry and polymerase chain reaction (PCR) in the evaluation of cytological preparations of lymph nodes. METHODS: Fine needle aspirates were obtained from 33 patients (initial presentation, n = 27; recurrence, n = 6). Routine examination was undertaken using immunocytochemistry and DNA PCR to detect clonality and specific translocations. The cytodiagnosis and subclassification of lymphoma was correlated with histological diagnosis in the available follow-up biopsies. RESULTS: 14 patients had a cytological diagnosis of non-Hodgkin's lymphoma (NHL), 4 had suspected NHL, 2 had atypical lymphoid proliferation and 13 had reactive hyperplasia. A World Health Organization (WHO) subtype was suggested in 8 patients. Incorporating the results of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements enabled diagnosis of lymphoma in 17 patients, including 5 of the 6 patients suspected to have NHL or an atypical lymphoid proliferation. Identification of the translocations t (14;18) and t (2;5) helped WHO categorisation in 3 of the patients. The cytological findings were confirmed in 12 out of the 13 patients for whom histological follow-up was available. Seven of the 18 lymphoma patients were managed without a subsequent biopsy. We made one false-positive diagnosis of B-cell NHL on cytology. CONCLUSION: The use of immunocytochemistry and PCR is valuable in the definitive diagnosis and subtyping of malignant lymphomas on cytological preparations. The use of these techniques may avoid lymph node biopsies in some cases and allow definitive treatment based on aspirate findings alone.
Biopsy, Fine-Needle↗
Socio-demographic inequalities in the diets of mid-aged Australian women.
OBJECTIVES: This study reports on the distributions of food and nutrient intakes by socio-demographic factors for a large population sample of mid-aged Australian women participating in the Australian Longitudinal Study on Women's Health. DESIGN: This cross-sectional population-based study used the Cancer Council of Victoria food frequency questionnaires to derive estimates of food and nutrient intakes. SETTING: Nationwide community-based survey. SUBJECTS: A total of 10561 women aged 50-55 y, at the time of the survey in 2001. RESULTS: Analysis showed favourable patterns of food intake, with frequent consumption of many foods that are promoted as components of a healthy diet (eg, fresh fruit, leafy green and other vegetables, bread, cereals, milk and meat). Intakes of both foods and nutrients varied significantly across socio-demographic groups, with unmarried women, and women in 'labouring' occupations (eg, cleaner, factory worker, kitchenhand) having poorer nutrient intake. CONCLUSIONS: Although many mid-aged women in this sample had generally healthful diets, women in certain socio-demographic groups (particularly unmarried women and those in labouring occupations) had nutrient intakes of concern. As well as helping to address the dearth of current data on dietary intakes in the Australian population, the results highlight the need for continued targeted public health strategies aimed at improving diet of women from the various socio-economic backgrounds.
Australia↗
A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly.
BACKGROUND: Serum homocysteine increases with age and is also considered a marker for low serum vitamin B(12) and folate. Furthermore, raised serum total homocysteine has been associated with atrophic changes in the brain. An association between serum vitamin B(12)/folate and cognitive impairment would be of considerable public health importance in view of the increasing numbers of elderly people. AIM: To systematically review published studies on the relationship between serum vitamin B(12), folate and total homocysteine and cognitive function in the elderly. DESIGN AND DATA SOURCES: A systematic review was undertaken of published evidence in English, examining the association between low serum vitamin B(12)/folate and raised total homocysteine with cognitive impairment (as indicated by low scores on neuropsychological testing) in subjects aged over 60 years. Sixteen electronic databases and cited articles were searched. Of 383 potential articles, six fulfilled the eligibility criteria: three case control and three cohort studies were identified. 'The Cochrane Non-Randomized Studies Methods Group' guidelines were used for assessment and extraction of data from these studies. RESULTS: All three case control studies found that serum total homocysteine was significantly higher in cases when compared with controls, and there was wide variation for both serum vitamin B(12) and folate in both groups of participants. The relationship of serum folate and vitamin B(12) status with cognitive impairment was heterogeneous and one case control study reported decreasing cognitive scores with increasing serum vitamin B(12). In the cohort studies, although serum total homocysteine could predict the rate of decline in neuropsychological testing, the overall odds ratio/relative risk (RR) of developing cognitive impairment in relation to levels of serum B(12) and serum folate were not significant. Although one study reported a significant RR of developing Alzheimer's disease when both serum folate and B(12) levels were low. One cohort study reported an increased prevalence of Alzheimer's type dementia in subjects who had normal serum vitamin B(12) at baseline. CONCLUSION: Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B(12) or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B(12) or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double-blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.
Aged↗
SM047 immunoreactivity in peritoneal fluids.
SM047 is a recently developed monoclonal antibody generated against an ovarian adenocarcinoma cell line. A recent immunohistochemical study has shown that SM047 is strongly expressed in tissue sections of most ovarian serous adenocarcinomas. This study aimed to ascertain whether SM047 staining is of value in cytological preparations of peritoneal fluid. A total of 206 consecutive peritoneal fluids were stained immunocytochemically with SM047, CA125, monoclonal carcinoembryonic antigen (mCEA), Ber-EP4 and cytokeratins (CK7 and 20). SM047 positivity was present in reactive mesothelial cells in 117 of 141 (83%) benign cases in which these were present. SM047 positive tumour cells were present in 22 of 23 (96%) ovarian serous adenocarcinomas and in small numbers of gastric adenocarcinomas (two of three), mesotheliomas (one of two) and pancreatic adenocarcinomas (one of one). All six colorectal and two breast adenocarcinomas were negative with SM047. Reactive mesothelial cells in all cases were positive with CK7 and in most cases with CA125. They were negative with CEA, Ber-EP4 and CK20. All adenocarcinomas were positive with Ber-EP4 and mesothelial cells were always negative. All colorectal adenocarcinomas were positive with CK20. This study shows that SM047 staining may be of value in the diagnosis of an ovarian serous adenocarcinoma in peritoneal fluids. Negative staining helps to exclude a primary ovarian serous adenocarcinoma and is characteristic of colorectal adenocarcinoma. The small numbers of other malignancies in the study precludes a judgement of the value of SM047 staining in these neoplasms. SM047 staining may be useful, as part of a larger panel, in the work up of patients with peritoneal effusions.
Adenocarcinoma↗
Analyzing refractive changes after anterior segment surgery.
PURPOSE: To present a comprehensive method for analyzing astigmatism after anterior segment surgery and to demonstrate the applicability of this method in evaluating patients having laser in situ keratomileusis (LASIK). METHODS: Calculation of mean refractive power, refractive surgical effect, and preoperative, postoperative, and surgically induced astigmatism is presented using vectorial analysis and matrix formalism. Indices of refractive surgical success, that is, a global index of correction (GIC), a spherical index of correction (SIC), and astigmatic or surgical accuracy (SA), are presented. Interpretation of keratometric data and correlation with regular refractive astigmatism may require normalization of keratometric data, for which a method is provided. RESULTS: There was a significant difference between the mean preoperative (-7.16 +0.95 x 87.86) and postoperative (-0.66 +0.095 x 82) refractive powers (P <.001). The mean refractive surgical effect was 5.64 +0.84 x 178.51, with a mean preoperative (K1), postoperative (K3), and surgically induced (K2) astigmatism of 0.95 diopter (D), 0.095 D, and 0.84 D, respectively. For the refractive data, the mean GIC and SIC were 90% and 90%, respectively, with an SA of 0.75. There was a significant correlation between keratometric and refractive astigmatism (r = 0.52, P <.001) and between the change in the refraction and keratometry (r = 0.94, P <.001). CONCLUSION: The method presented allows a meaningful interpretation of both refractive and keratometric data and calculation of mean refractive power without the need to change the format of the data from conventional notation. While the results pertain to 1 surgeon, LASIK had a greater effect in correcting the spherical component of refractive power than the astigmatic component. The correlation between refractive and normalized keratometric astigmatism indicates that the cornea is a main determinant of astigmatism. The high correlation between the change in myopia and keratometry after LASIK shows that although the cornea may not be the main determinant of myopia, the effect of LASIK in reducing myopia appears to be mediated through a change in corneal curvature.
Adult↗
Assessing surgically induced astigmatism.
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Astigmatism↗
Transcriptome of channel catfish (Ictalurus punctatus): initial analysis of genes and expression profiles of the head kidney.
Analysis of expressed sequence tags (ESTs) is an efficient approach for gene discovery, expression profiling, and development of resources useful for functional genomics studies. As part of the transcriptome analysis in channel catfish (Ictalurus punctatus), we have conducted EST analysis using a cDNA library made from the head kidney. We analysed 2228 EST clones. Orthologues were established for 1495 (67.1%) clones representing 748 genes, of which 545 (36.5%) clones were singletons. The remaining 733 (32.9%) clones represent unknown gene clones, for which the number of genes has not yet been determined.
Animals↗
Listening to deaf speech: does experience count?
Listening for intelligibility in disordered speech involves a complex interaction of factors, including listener experience. This study examines intelligibility as perceived by two groups (experienced and inexperienced listeners) in interpreting deaf speech. Speech samples were gathered from a hearing-impaired child over thirteen months, immediately post cochlear implantation. Results indicate that experienced listeners interpret more of disordered speech than inexperienced, but while experience appears to be a factor in intelligibility judgements, it does not alone guarantee higher intelligibility rating.
Deafness↗
Making it to work: towards employment for the young adult with autism.
In the last few decades there has been an increase in the reported prevalence of autism and its correlates within what is now termed autistic spectrum disorder (ASD): from 20 in every 10,000 children being estimated by Wing and Gould (1979) to 91 in every 10,000 by the National Autistic Society (NAS) (1999). While changes in criteria may account for some of this it is accepted that such children are increasingly being identified and knowledge of autism is growing. Semi-structured interviews were conducted with nine teaching staff from seven different schools for children with special needs to elicit information in relation to preparing young adults with ASD for the world of work. Results indicated educational practices are being modified for children with autism. Currently the most specifically tailored packages are offered in schools for children with severe learning difficulties.
Adolescent↗
Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix.
Hypoxic tumors are known to be more malignant, to be more likely to metastasize, and to have a poor prognosis. They are also radio- and chemoresistant. For this reason, it is desirable that a clinically useful marker of hypoxia is found, so that treatment with radiotherapy and bioreductive chemotherapy can be rationally applied to individual patients. Glut-1 is a facilitative glucose transporter that is ubiquitously expressed in normal tissue and expressed at higher levels in a number of tumors. Its potential as an intrinsic hypoxia marker arises from its dual control in hypoxic conditions by reduced oxidative phosphorylation and the hypoxia-inducible factor (HIF-1) oxygen-sensing pathway. Eppendorf histography, by virtue of its proven predictive qualities, is a suitable gold standard used in our laboratory to validate new hypoxia markers. Using this technique, pretreatment pO(2) measurements were performed on 54 patients with locally advanced cervical carcinoma. Then, immunohistochemical staining was used to detect Glut-1 protein in individual tumor biopsy sections. Both measurements were made before initiation of treatment. By using a low-tech scoring system, pO(2) was found to correlate weakly with Glut-1 score (r = 0.28; P = 0.04). To extrapolate this correlation to the known adverse effects of tumor hypoxia on outcome, we examined the prognostic significance of Glut-1 staining in a retrospective series of 121 patients. An absence of Glut-1 significantly increased the likelihood of metastasis-free survival (P = 0.022) but did not significantly effect disease-free or recurrence-free survival. These findings suggest that Glut-1 be an intrinsic marker of hypoxia that can easily be applied in a clinical setting.
Biomarkers, Tumor↗
A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer.
PURPOSE: Flavopiridol is a potent cyclin-dependent kinase inhibitor with preclinical activity against non-small cell lung cancer (NSCLC), inhibiting tumor growth in vitro and in vivo by cytostatic and cytotoxic mechanisms. A Phase II trial was conducted to determine the activity and toxicity of flavopiridol in untreated patients with metastatic NSCLC. EXPERIMENTAL DESIGN: A total of 20 patients were treated with a 72-h continuous infusion of flavopiridol every 14 days at a dose of 50 mg/m(2)/day and a concentration of 0.1-0.2 mg/ml. Dose escalation to 60 mg/m(2)/day was permitted if no significant toxicity occurred. Response was initially assessed after every two infusions; patients treated longer than 8 weeks were then assessed after every four infusions. Plasma levels of flavopiridol were measured daily during the first two infusions to determine steady-state concentrations. RESULTS: This study was designed to evaluate a total of 45 patients in two stages. However, because no objective responses were seen in the first 20 patients, the early-stopping rule was invoked, and patient accrual was halted. In four patients who received eight infusions, progression was documented at 15, 20, 40, and 65 weeks, respectively. The most common toxicities included grade 1 or 2 diarrhea in 11 patients, asthenia in 10 patients, and venous thromboses in 7 patients. The mean +/- SD steady-state concentration of drug during the first infusion was 200 +/- 89.9 nM, sufficient for cytostatic effects in in vitro models. CONCLUSIONS: At the current doses and schedule, flavopiridol does not have cytotoxic activity in NSCLC, although protracted periods of disease stability were observed with an acceptable degree of toxicity.
Aged↗
Transcriptome analysis of channel catfish (Ictalurus punctatus): genes and expression profile from the brain.
Expressed sequence tag (EST) analysis was conducted using a complementary DNA (cDNA) library made from the brain mRNA of channel catfish (Ictalurus punctatus). As part of our transcriptome analysis in catfish to develop molecular reagents for comparative functional genomics, here we report analysis of 1201 brain cDNA clones. Of the 1201 clones, 595 clones (49.5%) were identified as known genes by BLAST searches and 606 clones (50.5%) as unknown genes. The 595 clones of known gene products represent transcripts of 251 genes. These known genes were categorized into 15 groups according to their biological functions. The largest group of known genes was the genes involved in translational machinery (21.4%) followed by mitochondrial genes (6.2%), structural genes (3.1%), genes homologous to sequences of unknown functions (2.3%), enzymes (2.7%), hormone and regulatory proteins (2.5%), genes involved in immune systems (2.1%), genes involved in sorting, transport, and metal metabolism (1.8%), transcriptional factors and DNA repair proteins (1.6%), proto-oncogenes (1.2%), lipid binding proteins (1.2%), stress-induced genes (0.7%), genes homologous to human genes involved in mental diseases (0.6%), and development or differentiation-related genes (0.3%). The number of genes represented by the 606 clones of unknown genes is not known at present, but the high percentage of clones showing no homology to any known genes in the GenBank databases may indicate that a great number of novel genes exist in teleost brain.
Animals↗
Comprehensive method of analyzing the results of photoastigmatic refractive keratectomy for the treatment of post-cataract myopic anisometropia.
PURPOSE: To assess the efficacy, stability, and safety of photoastigmatic refractive keratectomy (PARK) in treating post-cataract myopic anisometropia to restore binocularity and to describe a comprehensive method for analyzing the results of refractive surgery. SETTING: St. Paul's Eye Center, Royal Liverpool Hospital, Liverpool, United Kingdom. METHODS: Nineteen patients (20 eyes) with post-cataract myopic anisometropia were treated with PARK using a VISX Twenty-Twenty laser and followed for 12 months. Cataract surgery had been performed between 10 and 144 months (mean 43.4 months) previously. A comprehensive method based on Long's matrix formalism and the vech operator of Harris, in addition to the nearest equivalent sphere and cylinder, was used to analyze the refractive data. RESULTS: The mean preoperative refraction in the post-cataract eyes was -4.79 +1.17 x 0.2 and in the fellow eyes, +0.02 +0.31 x 166. Twelve months after PARK, the postoperative refraction in the post-cataract eyes was -0.90 +0.65 x 2, a significant reduction (P = .15). This postoperative refraction was not significantly different from that in the fellow eye (P = .93). The pretreatment mean uncorrected visual acuity was 0.12. It improved to 0.41 at 12 months, at which time 52% of eyes achieved a visual acuity of 0.5 or better without correction. All patients regained binocularity. At 12 months, 2 eyes (11%) showed clinically unacceptable regression; 1 eye with grade 2 haze lost 1 line of corrected visual acuity. CONCLUSIONS: Photoastigmatic refractive keratectomy reduced post-cataract myopic anisometropia, allowing restoration of binocularity in all patients. Overall, the results in this elderly population with previous ocular surgery, posterior capsule thickening, and macular degeneration are not as satisfactory as those obtained from similar treatment of physiological myopia. Stability and postoperative complications are acceptable.
Adult↗