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1.
BMC Med Educ ; 24(1): 43, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38191382

ABSTRACT

BACKGROUND: Imposter Phenomenon (IP) is a subjective feeling of intellectual fraudulence and self-doubt experienced by individuals in goal-orientated high-achieving professions. The impact of IP within healthcare has been associated with individual physical and mental health and concerns around training, career progression and DEI at an institutional level. To effectively address IP in healthcare, this scoping review aims to explore educational interventions designed to empower high-achieving individuals with the tools needed to confront and overcome IP. METHODS: The scoping review adhered to a predetermined protocol informed by the JBI methodology and PRISMA-ScR guidelines in order to identify educational interventions addressing IP in high-achieving industries. Articles were searched across multiple databases, including MEDLINE (Ovid), PsychINFO, SCOPUS, and Web of Science, alongside grey literature, without imposing any time constraints. A systematic approach including a thematic analysis allowed for a nuanced exploration and interpretation of the identified educational interventions and their impact on addressing IP. RESULTS: Seventeen articles were incorporated into the review, with the majority originating from the USA and majority being published since 2020. Ten studies targeted healthcare professionals, undergraduate and postgraduate healthcare students. Majority of studies aimed at addressing IP, featured a larger number of female participants than males. Workshops with self-reflection and group-guided exercises to overcome IP were the most popular educational interventions. Coaching and structured supervision were also suggested. Across all papers, three themes emerged for coping strategies: individual, peer-to-peer, and institutional. CONCLUSIONS: This scoping review suggests how group and individual interventions such as workshops, small group discussions and coaching can be used to overcome IP in healthcare. Institutional changes like diversity promotion, supervisor education, and support networks are crucial in addressing IP. Further long term and speciality specific assessments are needed to measure impact. Overall, the review highlights how educational awareness and a variety of strategies can be implemented to create a supportive environment for professionals dealing with IP, promoting their well-being and success.


Subject(s)
Anxiety Disorders , Health Personnel , Self Concept , Female , Humans , Male , Anxiety Disorders/therapy , Emotions , Students, Health Occupations , Psychotherapy, Group , Health Personnel/psychology
2.
Int J STD AIDS ; 31(10): 920-938, 2020 09.
Article in English | MEDLINE | ID: mdl-32718268

ABSTRACT

This guideline is an update of a previous version published in 2013. In this new version, we have reflected changes in the way sexual health services are now provided by assuming an integrated Sexual Health/Sexual and Reproductive Healthcare service. There are new recommendations for online testing, female genital mutilation (FGM), chemsex and considerations for transgender (and non-binary) individuals. Previous versions rather assumed a cis-gender clientele and so we have taken a more mechanistic approach to sex and risk without assuming gender identification. We have updated our gender terminology in line with the British Association for Sexual Health and HIV 'sexual health standards for trans, including non-binary, people' although have retained the terminology of 'men' and 'women' in a few cases where it related to other guidelines, e.g. human papillomavirus vaccination and FGM.


Subject(s)
Guidelines as Topic , HIV Infections/diagnosis , Medical History Taking/standards , Referral and Consultation/standards , Sexual Behavior , Sexual and Gender Minorities/statistics & numerical data , Sexually Transmitted Diseases/diagnosis , Adult , Female , Humans , Male , Sexual Health , Sexual and Gender Minorities/psychology , Substance-Related Disorders/complications , Treatment Outcome , United Kingdom
3.
Mol Genet Metab ; 130(1): 77-86, 2020 05.
Article in English | MEDLINE | ID: mdl-32178982

ABSTRACT

In recent years the oxysterol species cholestane-3ß, 5α, 6ß-triol (C-triol) has found application as a diagnostic biomarker for Niemann-Pick disease type C. Other studies have described increased C-triol in patients with Niemann-Pick disease type A/B and milder increases in lysosomal acid lipase deficiency (LALD), whereas they note normal C-triol levels in Smith-Lemli-Opitz syndrome (SLOS) and familial hypercholesterolaemia (FH) patients. Herein, we review data collected in our laboratory during method evaluation along with 5 years of routine analysis and present findings which differ from those reported by other groups with respect to LALD, SLOS and FH in particular, whilst providing further evidence regarding the clinical sensitivity and specificity of this biomarker, which are difficult to accurately assess. All of our Wolman disease (severe LALD) patients have demonstrated gross elevations of C-triol at diagnosis, with reduction to normal levels after induction of enzyme replacement therapy. In diagnostic specimens from SLOS patients we observed very low or undetectable C-triol levels whereas in post-therapeutic SLOS patients demonstrated normalised levels; we also describe a homozygous FH patient in which C-triol is significantly elevated. Upon investigation, we found that C-triol was formed artefactually from cholesterol during our sample preparation, i.e. this is a false positive of analytical origin; at present it is unclear whether similar effects occur during sample preparation in other laboratories. Our data demonstrates clinical sensitivity of 100% during routine application to diagnostic specimens; this is in keeping with other estimates, yet in a small proportion of patients diagnosed prior to C-triol measurement, either by Filipin staining of fibroblasts or molecular genetics, we have observed normal C-triol concentrations. Clinical specificity of C-triol alone is 93.4% and 95.3% when performed in conjunction with lysosomal enzymology. These performance statistics are very similar to those achieved with Filipin staining of cultured fibroblasts in the 5 years preceding introduction of C-triol to routine use in our laboratory. It is increasingly apparent to us that although this analyte is a very useful addition to the diagnostic tools available for NPC, with considerable advantages over more invasive and time-consuming methods, the interpretation of results is complex and should be undertaken only in light of clinical details and results of other analyses including enzymology for lysosomal acid lipase and acid sphingomyelinase.


Subject(s)
Cholestanols/blood , Niemann-Pick Disease, Type C/diagnosis , Wolman Disease/diagnosis , Adolescent , Adult , Aged , Biomarkers/blood , Child , Child, Preschool , Cholestanols/chemistry , Cholesterol/blood , Chromatography, Liquid , Enzyme Replacement Therapy , Fibroblasts/metabolism , Homozygote , Humans , Hyperlipoproteinemia Type II/blood , Infant , Infant, Newborn , Limit of Detection , Middle Aged , Niemann-Pick Disease, Type C/blood , Oxysterols/blood , Sensitivity and Specificity , Tandem Mass Spectrometry , Wolman Disease/blood , Wolman Disease
4.
J Hosp Infect ; 97(4): 430-432, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28602706

ABSTRACT

The car parks at the study hospital are accessed using re-usable, machine-read tickets. In the initial phase of this study, 598 staff members were observed entering the car park, and 21.6% of them put their parking ticket in their mouth. Ultraviolet dye was used to demonstrate card-to-card cross-contamination. Swabs of the ticket machine yielded commensal bacteria: coagulase-negative staphylococci and a Bacillus sp. After placing a poster on the ticket-reading machine highlighting the potential risk of infection, a further 1366 observations demonstrated a significant and persistent decline in the proportion of staff who put their ticket in their mouth (P<0.001).


Subject(s)
Bacillus/isolation & purification , Disease Transmission, Infectious/prevention & control , Environmental Microbiology , Staphylococcus/isolation & purification , Humans
5.
Mol Genet Metab ; 112(2): 160-70, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24726177

ABSTRACT

Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.


Subject(s)
Chondroitinsulfatases/genetics , Chondroitinsulfatases/metabolism , Mucopolysaccharidosis IV/genetics , Mutation , Cells, Cultured , Child , Child, Preschool , Female , Genetic Association Studies , Genetic Testing , Genotype , Glycosaminoglycans/metabolism , Humans , Infant , Lysosomes/metabolism , Male , Mucopolysaccharidosis IV/diagnosis , Polymorphism, Single Nucleotide
6.
Ir J Med Sci ; 183(2): 277-81, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23959770

ABSTRACT

OBJECTIVE: To describe the relationship between parents with gender identity disorder (GID) and their child(ren) as described by the parent and to understand how being a parent affects transitioning from one gender to the other. METHODS: Fourteen parents with GID underwent a semi-structured interview and completed the Index of Parental Attitudes (IPA). An IPA score of greater than 30 indicates parent­child relationship difficulties (range 0­100). The authors also conducted the SCID-I to establish other Axis I disorders. RESULTS: We assessed 12 male to female and two female to male parents with GID residing in Ireland. In total, 14 GID parents had 28 children. Three children had no relationship with their GID parent. The other 25 children, as reported by the parent, had good relationships with their children. In addition, these 25 children average score IPA score was 6.4 (range 0­25). Twelve GID parents (86 %) believed that being a parent had no effect on their desired level of transitioning, while two were influenced not to transition. Eleven GID parents (79 %) reported that being a parent had increased the time taken to commence transitioning, two have stopped transitioning altogether, while one cited no effect on time. CONCLUSION: Parents with GID report positive relationships or no relationship with their children and the IPA revealed no clinical problems. Being a parent can prolong transitioning time in people with GID and can affect overall achieved level of transitioning.


Subject(s)
Child of Impaired Parents/psychology , Parent-Child Relations , Transgender Persons/psychology , Transsexualism/psychology , Adolescent , Adult , Adult Children/psychology , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult
7.
Mol Genet Metab ; 103(3): 300-2, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21514195

ABSTRACT

We describe the case of a boy recently diagnosed with an attenuated form of mucopolysacchararidosis VI (MPS VI, Maroteaux-Lamy syndrome). The Y210C mutation has not been described previously in the homozygous state, although this is a common ARSB mutation. His phenotype is essentially musculoskeletal. Urine screening tests based on measuring total GAG may miss this presentation as total GAGs were not elevated in the patient (although the electrophoresis pattern was clearly abnormal). In this phenotype the benefit of ERT remains to be established.


Subject(s)
Homozygote , Mucopolysaccharidosis VI/genetics , Mutation/genetics , N-Acetylgalactosamine-4-Sulfatase/genetics , Adolescent , Humans , Male , Mucopolysaccharidosis VI/diagnostic imaging , Phenotype , Radiography
8.
Bone Marrow Transplant ; 39(4): 207-10, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17220904

ABSTRACT

Hurler Syndrome is corrected by allogeneic BMT by the action of donor enzyme on recipient tissue. In this paper, we describe monitoring of 39 patients transplanted in two centres to determine donor chimerism, enzyme level and residual substrate - expressed as dermatan sulphate to chondroitin sulphate ratio. We show that in fully engrafted recipients, the enzyme level, expressed as mumol/g total protein/h, post-transplant is 24.2 from an unrelated donor and 10.2 from a heterozygote family donor (P<0.0001). There is a tight relationship between mean post-transplant enzyme level and residual substrate - Spearman's rank correlation coefficient (Rho) was -0.76 and -0.80 at 12 and 24 months, respectively (P<0.0001). We propose that these differences affect patient outcome. As unrelated donor transplant outcomes improve and especially given the higher levels of donor cell engraftment following cord transplants, our data might influence donor selection where only heterozygote-matched family members are available.


Subject(s)
Chimerism , Hematopoietic Stem Cell Transplantation , Iduronidase/metabolism , Mucopolysaccharidosis I/therapy , Chondroitin Sulfates/metabolism , Chondroitin Sulfates/urine , Cord Blood Stem Cell Transplantation , Dermatan Sulfate/metabolism , Dermatan Sulfate/urine , Glycosaminoglycans/urine , Heterozygote , Histocompatibility Testing , Humans , Transplantation, Homologous/physiology , Treatment Outcome
9.
J Inherit Metab Dis ; 25(6): 491-500, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12555942

ABSTRACT

Although it is often perceived as a paediatric disorder, significant numbers of patients with Niemann-Pick disease type C present for the first time in adult life or survive into adult life. The presentation in these patients differs from that seen in the classical juvenile form of the disease. Adult patients are often referred to clinicians with psychosis or other major psychiatric problems. The dystonia with preserved intellectual functioning can be mistaken for other basal ganglia disorders such as Wilson disease. The presence of vertical gaze palsy is an important clinical clue and, in the presence of a modest increase in plasma chitotriosidase activity, can be very helpful in the differential diagnosis. The diagnosis should be confirmed in suspected cases by filipin staining of cultured fibroblasts, as well as cholesterol esterification studies and DNA mutation analysis.


Subject(s)
Niemann-Pick Diseases/physiopathology , Adolescent , Adult , Ataxia/etiology , Child , DNA/genetics , Disease Progression , Fatal Outcome , Female , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Hepatitis/pathology , Humans , Infant, Newborn , Intelligence Tests , Male , Niemann-Pick Diseases/genetics , Niemann-Pick Diseases/psychology , Pregnancy , Psychotic Disorders/etiology , Seizures , Splenomegaly/etiology , Tremor/physiopathology
10.
Biol Reprod ; 60(4): 828-38, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10084955

ABSTRACT

Human first-trimester floating mesenchymal villi explanted onto gels of collagen I or Matrigel were observed to undergo de novo development of anchoring sites. These consisted of cytotrophoblast columns that formed by proliferation of stem villous cytotrophoblast cells, as revealed by whole-mount and thin-section microscopy and incorporation of bromodeoxyuridine into DNA. Column formation occurred exclusively at the distal tips of the villi. No column formation was observed in tissue explanted onto agarose. On Matrigel, the developing columns penetrated downwards into the matrix, whereas on collagen I, cytotrophoblast sheets spread across the surface of the gel and merged to form a shell. The developing columnar cytotrophoblast up-regulated integrins alpha1beta1 and alpha5beta1 and produced an extracellular matrix containing oncofetal fibronectin, as in vivo. Function-blocking antibodies were used to investigate the role of the integrin-fibronectin interaction in anchoring villus development on collagen I. Antibodies to fibronectin and the integrin subunits alpha5 and beta1, added at 24 h, all changed the pattern of cytotrophoblast outgrowth. Anti-fibronectin caused cell rounding within the cytotrophoblast sheet and increased the population of single cells at its periphery. Anti-integrin alpha5 caused rounding and redistribution of cells within the outgrowth. In the presence of anti-integrin beta1, cell-collagen interactions within the sheet were destabilized, often leading to the appearance of an annulus of aggregated cells at the periphery. These results show that 1) mesenchymal villi retain the potential to form anchoring sites until at least the end of the first trimester, 2) adhesion to a permissive extracellular matrix stimulates cytotrophoblast proliferation and differentiation along the extravillous lineage, 3) integrin alpha5beta1-fibronectin interactions contribute significantly to anchorage of the placenta to uterine extracellular matrix. We suggest that as the developing placenta ramifies, new sites of anchorage form whenever peripheral villi contact decidua. This process is predicted to contribute to the stability of the placental-decidual interface.


Subject(s)
Fibronectins/physiology , Receptors, Fibronectin/physiology , Trophoblasts/physiology , Animals , Cell Differentiation , Cell Division , Collagen , Culture Techniques , DNA/biosynthesis , Drug Combinations , Extracellular Matrix/physiology , Female , Humans , Keratins/analysis , Laminin , Mice , Microscopy, Electron , Pregnancy , Proliferating Cell Nuclear Antigen/analysis , Proteoglycans , Rabbits , Rats , Trophoblasts/cytology
11.
Biochem J ; 332 ( Pt 2): 491-8, 1998 Jun 01.
Article in English | MEDLINE | ID: mdl-9601079

ABSTRACT

BeWo is a choriocarcinoma cell line that generates an extracellular matrix (ECM) rich in laminin and is a useful model for human trophoblast. Immunofluorescence with monoclonal antibodies demonstrates that BeWo ECM contains laminin subunits beta1 and gamma1. Immunoprecipitation from conditioned medium shows that the cells secrete two distinct laminin trimers both containing beta1 and gamma1 but with alpha subunits of approx. 400 and 450 kDa. The culture medium also contains a species thought to be beta1 gamma1 dimer. Immunoprecipitation with monoclonal antibody 4C7, previously thought to recognize the alpha1 subunit, isolates complexes containing only the smaller alpha subunit. A second complex containing the larger alpha subunit along with beta1, gamma1 and a 150 kDa polypeptide is precipitated from 4C7-depleted medium with an anti-(laminin 1) polyclonal antibody. Peptide sequencing demonstrates that the 4C7-reactive species is alpha5, which is present as two similarly sized polypeptides. mRNA species encoding laminin subunits alpha1, alpha5, beta1, beta2 and gamma1 are all present in the cells. These results demonstrate the secretion of a novel laminin isoform, laminin 10, the subunit composition of which is alpha5 beta1 gamma1. Laminin 1 is also produced. No evidence for the secretion of beta2-containing laminin isoforms could be derived despite the presence of beta2 mRNA. Analysis with reverse transcriptase-mediated PCR also showed the presence of laminin alpha5 in first-trimester placenta and decidua.


Subject(s)
Choriocarcinoma/chemistry , Laminin/chemistry , Antibodies, Monoclonal/metabolism , Culture Media, Conditioned/chemistry , Decidua/chemistry , Extracellular Matrix/chemistry , Female , Fluorescent Antibody Technique , Humans , Placenta/chemistry , Polymerase Chain Reaction , Precipitin Tests , RNA, Messenger/chemistry , Sequence Analysis , Tumor Cells, Cultured
12.
Mol Hum Reprod ; 4(2): 185-93, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9542978

ABSTRACT

The endothelins are signalling peptides that act via two receptors, ET(A) and ET(B). In the human endometrium, endothelin receptors have been demonstrated in glands and stroma and have been shown to vary during the course of the menstrual cycle. The present study was undertaken to determine whether or not expression of endothelin receptors changes during pregnancy or after administration of exogenous progestagens. The expression of the receptors was correlated with the appearance of basement membrane components during decidualization of the endometrial stroma. Decidual specimens (n = 15) were obtained during the first trimester of pregnancy and 10 at term. Sixteen pairs of endometrial biopsies were obtained from women with menorrhagia before and after exposure to exogenous progestagens. A total of 15 hysterectomy specimens were used as controls for the expression of stromal basement membrane proteins in the absence of decidualization. Autoradiography was carried out with selective ligands for ET(A) ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of ligand binding was then compared with the distribution of laminin alpha2 light chain and collagen IV. ET(A), ET(B), laminin alpha2 light chain, and collagen IV were expressed in stromal decidual cells in the first trimester of pregnancy. ET(B) was also found on endometrial glandular epithelium. Quantitative macro-autoradiography and multiple regression analysis demonstrated a highly significant positive correlation (P < 0.001) between expression of ET(B) and laminin alpha2 light chain. In the third trimester qualitative examination suggested a reduction of ET(A) in the stroma. Progestagen-induced decidua exhibited a similar pattern to that found in first trimester decidua. This study has demonstrated up-regulation of ET(B) during the progesterone-dependent process of decidualization and suggests a paracrine or autocrine role for endothelins in the decidua.


Subject(s)
Decidua/metabolism , Receptors, Endothelin/biosynthesis , Abortion, Induced , Biopsy , Collagen/biosynthesis , Decidua/drug effects , Female , Humans , Laminin/biosynthesis , Levonorgestrel/therapeutic use , Ligands , Menorrhagia/drug therapy , Menorrhagia/metabolism , Norethindrone/therapeutic use , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Third , Progesterone Congeners/therapeutic use
13.
J Surg Res ; 70(1): 66-8, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9228930

ABSTRACT

The impact of problem-based learning on surgery residents' education is unknown. In this study we measured the impact of a weekly structured problem-based learning conference on surgery residents' ABSITE scores and compared it to traditional clinical conferences and self-studying. A questionnaire was designed to determine the perceived quality of the basic (PQCB), and the clinical (PQCC) conferences as well as self-studying (PQCS). The Pearson correlation between PQCB, PQCC, PQCS, and attendance at the basic science conference and each of the ABSITE total score (ABSITE), basic science (BS) and clinical science (CS) component scores were calculated. PQCS (4.2) was significantly higher than PQCB (2.9) and PQCC (2.5) (P = 0.0002). PQCS and PQCB correlated highly with each of ABSITE, CS, and BS while PQCc did not show any correlation. A high correlation was also observed between attendance at basic science and each of ABSITE, CS, and BS but narrowly missed significance. It was also observed that BS scores highly correlated to the CS scores at all postgraduate levels (P = 0.0001). We conclude that performance on all components of the ABSITE is mostly dependent on individual residents. This individual factor is boosted by self-studying which can be motivated by instituting a problem-based learning technique within the program. Traditional conferences even if popular among residents have no impact on measurement tests.


Subject(s)
Educational Measurement , General Surgery/education , Internship and Residency , Problem-Based Learning , Perception , Surveys and Questionnaires
15.
Lab Invest ; 74(1): 21-32, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8569185

ABSTRACT

During pregnancy, the resident stromal cells of the endometrium differentiate to become decidual cells and produce a pericellular basement membrane. We used immunofluorescence and Western blotting with a panel of monoclonal Ab specific for various laminin subunits to examine the composition of decidual laminin. The stromal cell basement membrane contained subunits alpha 2 (M), beta 1 (B1), beta 2 (S), and gamma 1 (B2). Low levels of alpha 1 could also be detected. The glandular and vascular basement membranes of decidual tissue contained subunits alpha 1 (A), beta 1, and gamma 1. An extract was produced from decidual extracellular matrix. Western blots of nonreducing gels showed the presence of high molecular weight complexes containing alpha 2, beta 1, beta 2, and gamma 1. These data indicated that laminins 2 and 4 are coexpressed by decidual cells. Laminin 1 was present in the extract as a minor component. In contrast, cultured stromal cells expressed laminin 1 as the major secreted variant. Immunolocalization was carried out using tissue from various stages of the nonpregnant cycle. The alpha 2 chain polypeptide was absent in the proliferative phase of the cycle but present in late secretory phase in perivascular areas where predecidual differentiation occurs. Reverse transcriptase-PCR experiments confirmed the presence of alpha 2 chain mRNA in decidua but showed that this transcript is detectable throughout the nonpregnant cycle. The results showed that laminins 2 and 4 are hormonally regulated products of decidual cells. The composition of the vascular and epithelial basement membranes remained constant throughout the cycle.


Subject(s)
Decidua/metabolism , Laminin/biosynthesis , Blotting, Western , Cells, Cultured , Decidua/chemistry , Decidua/cytology , Endometrium/chemistry , Endometrium/cytology , Endometrium/metabolism , Female , Humans , Immunohistochemistry , Laminin/chemistry , Laminin/genetics , Peptides/metabolism , Pregnancy , RNA, Messenger/analysis , Stromal Cells/metabolism
16.
Neurotoxicology ; 14(2-3): 359-64, 1993.
Article in English | MEDLINE | ID: mdl-8247409

ABSTRACT

Lead toxicity is known to be subject to individual susceptibility. This study compares two lead-exposed subjects, one (A; blood Pb 1800 micrograms/L) who remained totally asymptomatic, the other (B; blood Pb 1610 micrograms/L) who showed symptoms of toxicity. We have assessed the speciation of lead in the intra-erythrocyte proteins in these patients and have examined its significance in relation to clinical toxicity. Chromatographic separations of erythrocyte haemolysates from these patients showed a metallothionein-like lead containing protein. It was demonstrated that in patient A, most (approximately 70%) of the erythrocyte lead was associated with this protein, whilst in patient B the protein only contained about 20% of the total lead, with significant amounts bound to high molecular weight proteins, including Hb. Further purification of this protein from each patient showed it to contain a number of constituents, one in particular being the major lead-binding species. This component was more abundant in patient A and, relative to patient B, contained a higher proportion of lead. These results suggest that this protein may act to sequester lead into a non-bioavailable form, hence protecting the body from lead toxicity as with patient A.


Subject(s)
Erythrocytes/drug effects , Lead Poisoning/blood , Occupational Exposure , Adult , Carrier Proteins/blood , Erythrocytes/metabolism , Female , Humans , Male , Metallothionein/blood , Middle Aged , Protein Binding
17.
J Inorg Biochem ; 49(1): 55-68, 1993 Jan.
Article in English | MEDLINE | ID: mdl-8433087

ABSTRACT

We have studied the erythrocytes from 24 workers occupationally exposed to inorganic lead, one asymptomatic lead worker showing exceptionally high exposure, and eight control subjects (blood lead 300-750, 1800, and < 100 micrograms/L, respectively). High performance protein chromatography, electrophoresis, and trace metal analysis have identified a low M.Wt., copper, and zinc-containing protein in all cases. This protein (designated protein M) bound lead on in vitro incubation with buffered lead nitrate. Purified samples of protein M were found to show characteristics consistent with metallothionein (M.Wt. approximately 6500, low pI, and greater UV absorbance at 254 nm). Amino acid analysis found a composition of 33% cysteine but no aromatic amino acids. The highly exposed subject showed endogenous lead binding to protein M, which on further purification by ion exchange was found to be associated with one particular constituent (protein M5). Protein M5 was present in much lower quantities in control subjects. These findings suggest the existence of a metallothionein-like protein in erythrocytes which binds lead, sequestering it into a nonbioavailable form and hence protects against lead toxicity.


Subject(s)
Erythrocytes/metabolism , Lead/blood , Metallothionein/blood , Adult , Carrier Proteins/blood , Carrier Proteins/isolation & purification , Humans , In Vitro Techniques , Isoelectric Point , Lead Poisoning/blood , Male , Metallothionein/isolation & purification , Molecular Weight , Occupational Diseases/blood , Occupational Exposure , Protein Binding
18.
Age Ageing ; 18(6): 398-402, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2629488

ABSTRACT

Thyroid function was assessed by measurement of free thyroid hormones and thyrotrophin (TSH) in 78 acutely ill elderly patients and in a control group without acute illness. Abnormal results with any test were more frequently found in the acutely ill group than in controls. In particular, abnormal TSH values were found in 40% of the acutely ill group and in only 8% of controls (p less than 0.001). Seven acutely ill subjects had very low TSH levels (less than 0.04 mU/l) and a blunted response to thyroid-releasing hormone (TRH). With few exceptions these abnormalities could not be attributed to thyroid disease. This suggests that pituitary TSH secretion can be impaired in euthyroid sick old people. High sensitivity TSH assays may therefore be inappropriate as first-line tests of thyroid function, at least in this select group.


Subject(s)
Acute Disease , Thyroid Diseases/epidemiology , Age Factors , Aged , Aged, 80 and over , Female , Humans , Male , Mass Screening , Predictive Value of Tests , Prospective Studies , Sex Factors , Thyroid Diseases/blood , Thyroid Diseases/diagnosis , Thyroid Function Tests/methods , Thyrotropin/blood
19.
Tubercle ; 68(4): 261-6, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3455567

ABSTRACT

Serum 25-hydroxycholecalciferol (25-(OH)D3), calcium and albumin have been measured in 27 patients undergoing treatment for pulmonary tuberculosis. Patient 25-(OH)D3 was significantly lower than controls pre-treatment. Throughout the period of treatment patient median 25-(OH)D3 remained below 10 ng/ml, significantly lower than levels in matched healthy controls. Patients' median serum levels varied between 35% and 66% of controls' values during treatment, but rapidly rose to equal control values once treatment had been stopped. Patients' serum calcium, corrected for albumin, remained virtually identical with control values throughout treatment. Clinicians should be aware that standard anti-tuberculosis chemotherapy may depress Vitamin D stores and that this may be important for patients who are already at risk from osteomalacia.


Subject(s)
Antitubercular Agents/therapeutic use , Calcium/metabolism , Tuberculosis, Pulmonary/metabolism , Vitamin D/metabolism , Adult , Aged , Antitubercular Agents/metabolism , Calcifediol/blood , Calcium/blood , Female , Humans , Male , Middle Aged , Serum Albumin/analysis , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/drug therapy
20.
Eur J Respir Dis ; 71(5): 341-4, 1987 Nov.
Article in English | MEDLINE | ID: mdl-3443156

ABSTRACT

Reports of raised serum calcium in the presence of tuberculosis have tended to be from centres where sunlight is plentiful. U.K.-based data have suggested that normocalcaemia prevails. In a prospective study of 15 African patients with pulmonary tuberculosis, resident in East Africa, corrected serum calcium was significantly lower in a control healthy group (2.59 mmol/l +/- 0.08 and 2.49 +/- 0.06 mmol/l respectively: P less than 0.001). Serum 25-hydroxy vitamin D was significantly lower in the patient group (median, 15.9 ng/ml, range 6.7-35.7) compared with the control group (median 26.2 ng/ml, range 10.5-45.9, P less than 0.05). No significant difference was found between patients and controls for 1,25-dihydroxy vitamin D or parathyroid hormone. No correlation was found between serum calcium and 1,25 (OH)2 D3. Serum albumin showed a negative correlation with radiographic extent of disease and with extent of cavitation. Where sunlight is plentiful, relatively high serum 25-hydroxy Vitamin D may give rise to raised serum calcium in the presence of tuberculosis.


Subject(s)
Hypercalcemia/etiology , Tuberculosis, Pulmonary/blood , Adult , Calcium/blood , Humans , Male , Parathyroid Hormone/blood , Serum Albumin/metabolism , Vitamin D/blood
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