Search PubMed⌕ Search

Biomedical subjects

H Munro

Publications and source records attributed to H Munro.

At least 19 recordsLinked to original sources
PubMed2004

Acute hepatitis C virus seroconversion in a Scottish blood donor: HCV antigen is not comparable with HCV nucleic acid amplification technology screening.

BACKGROUND AND OBJECTIVES: This study was conducted to analyse the usefulness of hepatitis C virus (HCV) core antigen tests for the confirmation of HCV infection in a donor presenting as nucleic acid amplification technology (NAT) positive but negative for antibodies to HCV (anti-HCV). MATERIALS AND METHODS: Blood donations were screened, in parallel, for anti-HCV using the Abbott PRISM HCV Chemiluminescent immunoassay (ChLIA) and an 'in-house' HCV NAT (pools of up to 95 donations). An HCV NAT-positive antibody-negative donor was identified. Twelve follow-up samples were obtained and tested with various HCV antigen (including the recently marketed Trak-C second-generation assay) and HCV antibody assays. RESULTS: The single HCV NAT-positive, antibody-negative donation was identified from 1 117 681 donations screened in the 4-year period, July 1999 to June 2003. The index donation was positive by Ortho HCV core antigen enzyme immunoassay (EIA) and Ortho Trak-C (second-generation HCV core antigen EIA). An archive sample, taken 127 days prior to the index donation, was negative for all HCV markers. Subsequent samples demonstrated a loss of reactivity in the Ortho HCV core antigen EIA and reduced activity in the Ortho Trak-C until day 69. Immunoblot (Ortho RIBA-3) and HCV PRISM became positive on day 62, whilst Ortho HCV ELISA was not positive until day 132 or Biorad HCV ELISA until day 160. An alternative immunoblot (Innogenetics Innolia III) was positive from day 55. RNA levels fluctuated considerably during the follow-up period, being completely undetectable by routine screening methods at the time-point around seroconversion; subsequently, antibody was detected using all assays investigated. CONCLUSIONS: This HCV-converting blood donor provided a unique panel of samples for using to assess current (and future) HCV assay systems. The overall test results led to the conclusion that individual HCV antigen testing should not be considered as equivalent to HCV NAT minipool screening. Trak-C antigen testing may be considered as a suitable confirmatory assay for isolated HCV NAT reactivity.

Acute Disease↗
PubMed2004

The epidemiology of subacute sclerosing panencephalitis in England and Wales 1990-2002.

AIM: To assess the impact of measles/mumps/rubella (MMR) vaccine on the epidemiology of subacute sclerosing panencephalitis (SSPE) in England and Wales. METHODS: Cases of SSPE resident in England and Wales with onset between 1990 and 2002 were reviewed. RESULTS: A total of 47 cases were identified, 31 male and 16 female. There was an average annual decline of 14% in SSPE onset over the period, consistent with the decline in notified measles over the last 20 years. A history of measles was present in 35 (median age 1.3 years), the most recent recorded date being 1994; the interval from measles to onset of SSPE ranged from 2.7 to 23.4 years. Four children with a history of receipt of a measles containing vaccine were reported not to have had measles; two of these cases had a brain biopsy, and nucleotide sequence data confirmed wild measles infection. Brain biopsy specimens from a further three cases with a history of measles, of whom two had also had a history of vaccination, showed wild-type strain. CONCLUSION: The prevention of endemic circulation of measles virus in England and Wales through the high coverage achieved with MMR vaccine, together with the measles/rubella vaccination campaign of 1994, has resulted in the near elimination of SSPE. However, the recent decline in MMR vaccine coverage, with the associated increase in localised measles outbreaks and cases in young infants, is of concern. It underlines the importance of maintaining high vaccine coverage in order to protect indirectly those most vulnerable to SSPE, namely infants too young to be vaccinated.

Adolescent↗
PubMed2002

Hepatitis B vaccinees may be mistaken for confirmed hepatitis B surface antigen-positive blood donors.

BACKGROUND AND OBJECTIVES: Hepatitis B surface antigen (HBsAg) test sensitivities have gradually increased, and neutralizable weak HBsAg-positive donations, with no other hepatitis B virus (HBV) markers, have occasionally been found in our donor population. On investigation, these donors have admitted to receiving hepatitis B vaccine up to 5 days previously. A study was therefore initiated to monitor HBsAg reactivity amongst volunteers after receiving their first dose of hepatitis B vaccine. MATERIALS AND METHODS: Eight volunteers were tested using three HBsAg assays (Abbott Auszyme, Ortho HBsAg-3 and Abbott/Murex GE34/36) on days 0, 3, 5, 7 and 10 after administration of hepatitis B vaccine. RESULTS: Two HBsAg tests (Abbott Auszyme and Ortho HBsAg-3) did not detect HBsAg reactivity amongst the volunteers, although the Abbott Auszyme test results reached 70-80% of the manufacturer's cut-off at day 3 in two volunteers. The most recently launched assay (Abbott/Murex GE 34/36) detected seven (87%) of the eight volunteers as HBsAg reactive on day 3, and two (25%) volunteers were still reactive on day 5. CONCLUSION: The Abbott/Murex GE 34/36 assay demonstrated HBsAg reactivity in most volunteers on day 3 and in some on day 5 after vaccination. It is therefore recommended that individuals who have recently been vaccinated with hepatitis B be deferred from blood donation for at least 7 days.

Blood Donors↗
PubMed2001

HTLV antibody screening using mini-pools.

At the present time, the UK blood transfusion services do not screen blood donations for anti-HTLV. This presentation describes a pilot study to ascertain the feasibility of HTLV antibody screening using mini-pools and also provides an estimate of HTLV prevalence within our donor population in Scotland and Northern Ireland. The Abbott/Murex HTLV I/II GE80/81 ELISA was selected for the trial. Thirty confirmed HTLV positive library samples were tested at various dilutions and five were shown to be nonreactive at a dilution of 1:100. Residues of mini-pools (of up to 95 individual donations) prepared for HCV NAT testing were tested with the Abbott/Murex GE80/81 assay. Of 6666 mini-pools (equivalent to 570 609 donations) tested, six were repeatedly reactive. All six mini-pools were confirmed HTLV antibody positive by line immunoassay. Four were confirmed to be HTLV-I positive, one HTLV-II positive and one HTLV positive (unable to type). Dilutions (1:100) of the five HTLV "nonreactive" positive samples were included in each test plate and used to determine a grey-zone cut-off. Using this grey-zone system an additional six (0.09%) mini-pool samples gave repeatedly reactive grey-zone results, none of which were confirmed. The minimum Scottish/Irish HTLV donor prevalence was shown to be 1:95 000.

Blood Donors↗
PubMed2001

Pain management in children with and without cognitive impairment following spine fusion surgery.

BACKGROUND: We compared pain assessment and management practices in children with and without cognitive impairment (CI) undergoing spine fusion surgery. METHODS: The medical records of 42 children (19 with CI and 23 without) were reviewed and data related to demographics, surgery, pain assessment and management, and side-effects were recorded. RESULTS: Fewer children with CI were assessed for pain on postoperative days (POD) 0-4 compared to those without CI (P < 0.002). Self-report was used for 81% of pain assessments in children without CI, while a behavioural tool was used for 75% of assessments in cognitively impaired children. Children with CI received smaller total opioid doses on POD 1-3 compared to those without CI (P < or = 0.02). Furthermore, children without CI received patient/nurse-controlled analgesia for more postoperative days than children with CI (P=0.02). CONCLUSION: Our data demonstrate a discrepancy in pain management practices in children with and without CI following spine fusion.

Analgesia, Patient-Controlled↗
PubMed2000

Postoperative nausea and vomiting in children.

The prevention and treatment of postoperative nausea and vomiting (PONV) in children remains an important challenge for the pediatric anesthesiologist. Despite a clearer understanding of the physiology of emesis and with the development of new anesthetic and antiemetic agents, PONVis still an important cause of morbidity. The approach to minimizing this complication is multifactorial and includes proper preoperative preparation, a rational approach to intraoperative antiemetic prophylaxis, choice of appropriate anesthetic agents and techniques, and a definitive plan for postoperative care. This review gives a brief account of the numerous classes of antiemetics available to treat this condition and the various strategies that can be used to reduce PONV.

Antiemetics↗
PubMed2000

Parental involvement in perioperative anesthetic management.

Parents desire increased input into their child's health care and are taking a larger role in their medical treatment. They are present for a greater amount of time during the hospitalization of their child by staying at the bedside, being physically present during critical events such as cardiac arrest and invasive procedures, and participating in the medical decision-making process. This review discusses the pros and cons of parental presence during the perioperative anesthesia care of the pediatric patient.

Adult↗
PubMed1998

Benefit of dynamic over static incubation in the detection of a low-level HBsAg (chronic carrier) bone donor.

BACKGROUND: Hepatitis B infection can be transmitted by organ or tissue transplantation. CASE REPORT: A 40-year-old man received a bone graft from a donor who tested negative for HbsAg with a static-mode assay. The same donor, on a subsequent donation, was found to be HbsAg-positive with a dynamic mode assay. The archival sample from the initial donation also tested HbsAg-positive with the dynamic-mode assay. The recipient of the bone, who had received HBV vaccine in the past, did not develop clinical or laboratory evidence of HBV infection. CONCLUSIONS: This case highlights the importance of sensitive microbiological test protocols in the context of tissue banking.

Adult↗
PubMed1996

Relevance of RIBA-3 supplementary test to HCV PCR positivity and genotypes for HCV confirmation of blood donors.

HCV antibody screening of 624,910 blood donations resulted in 3,832 samples being referred for confirmation. All were tested by RIBA-3 with 2,710 negative, 945 indeterminate and 177 positive results. HCV RNA was detected by PCR in an average of 69.5% of RIBA-3 positives (4 bands 84.1%; 3 bands 74.1%; 2 bands 34.1%) and only 0.53% of RIBA-3 indeterminates. Eighty-four percent of samples with a total RIBA-3 band intensity score (maximum 16) of > or = 8 were PCR positive compared with only 22% of those with a score of < 8. Total mean band intensities for HCV genotype 1 samples (n = 65) were 13.2, genotype 2 (n = 17) 11.4 and genotype 3 (n = 65) 11.2 with type 1 samples showing greater reactivity with c100 and c33 antibodies. No PCR positive type 1 samples were found with RIBA-3 total band scores less than 8, no PCR positive type 2 samples less than 6, whilst PCR positive type 3 samples were found with scores as low as 2. NS5 indeterminates were the most common (40.2%) single band pattern but yielded no PCR positive samples, followed by c33 (23.3%) with one PCR positive and c100 (20.2%) with one PCR positive whilst c22 indeterminates were least common (16.3%) but included three PCR positive donors. All five RIBA-3 indeterminate PCR positive donors were type 3.

Blood Donors↗
PubMed1996

Third-generation recombinant immunoblot assay: comparison of reactivities according to hepatitis C virus genotype.

BACKGROUND: Recombinant immunoblot assay (RIBA) is widely used as a supplemental test in hepatitis C virus (HCV) confirmatory algorithms. As this assay is based on HCV type 1, its performance was examined with the common European HCV genotypes (1, 2, and 3). STUDY DESIGN AND METHODS: A study was performed to retest in third-generation RIBA (RIBA-3) all 146 second-generation RIBA (RIBA-2)-positive polymerase chain reaction-positive samples detected by second-generation enzyme-linked immunosorbent assays and having known HCV genotypes (74 HCV type 1, 21 type 2, 51 type 3). RIBA band intensities were examined according to HCV genotype. An additional 90 RIBA-3-confirmed PCR-positive samples (47 HCV type 1, 5 type 2, 38 type 3) detected by third-generation enzyme-linked immunosorbent assays were also examined. RESULTS: In the first group of 146 samples, the RIBA-3 NS4 (c100p) band showed a marked improvement in sensitivity for the detection of HCV types 2 and 3 over that of the c100 antigen of RIBA-2, but the mean band intensities of HCV types 2 and 3 remained significantly lower than those of type 1. Improved sensitivity of the NS3 band of RIBA-3 to HCV type 3 was also apparent, but, again, the mean band intensity measured was lower for type 3 than for either type 1 or type 2. The c22 band of RIBA-2 and RIBA-3 exhibited equal sensitivity for all HCV genotypes. These differences were also apparent when RIBA-3 was used in conjunction with third-generation enzyme-linked immunosorbent assays. CONCLUSION: The current RIBA-3 lacks sensitivity to the NS4 antibody for HCV types 2 and 3. The incorporation of type-specific components to other genotypes for NS4 (and NS3) antigens should be considered by the manufacturers.

Blood Donors↗
PubMed1993

Confirmation of hepatitis C virus antibody in blood donors.

Of 103,203 donations collected in Scotland and Northern Ireland over a 3-month period and screened for HCV antibody by Ortho or Abbott second-generation ELISAs, 340 were found repeatedly reactive. Supplementary testing with RIBA-2 resulted in 77 being classified as positive, 130 as indeterminate, and 133 as negative. PCR analysis of the positives and indeterminates indicated viraemia in 65 (84%) of the positives and 7 (5.5%) of the indeterminates. To determine if PCR analysis could be eliminated or reduced by further serological testing, all RIBA-2 positives and indeterminates were tested by UBI and Wellcozyme ELISAs and Innolia and RIBA-3 immunoblots. All RIBA-2 positives with bands to more than 1 gene product were detected in all 4 systems, but > 60% of RIBA-2 indeterminates were negative in those tests that contain either recombinant antigens or synthetic peptides derived independently from those used by Ortho/Abbott tests. A comparison of data from the 79 reactive with the core (c22) region revealed only 16 samples reactive in all 4 systems as well as Ortho and Abbott. These 16 included all 6 of the PCR positives in the 79 c22 indeterminate samples. ELISAs and immunoblots using independently derived antigens can offer a useful method of screening out nonspecific reactions in Ortho or Abbott ELISAs, hence reducing the need for PCR testing. Some caution is required as all such tests do not contain identical mixes of antigenic material.

Antigens, Viral↗
PubMed1993

The ferritin genes: their response to iron status.

Iron is a required nutrient which, at high concentrations, can peroxidize cell lipids and other cellular components. To prevent excess iron from damaging cells, it is stored in ferritin, which consists of a shell of protein subunits of two related types, H (heavy) and L (light), surrounding a cavity in which the iron can be deposited. In order to prepare for a rapid increase in ferritin in response to a rise in cellular iron, a large number of dormant ferritin mRNAs are accumulated in the cytoplasm. These can be rapidly activated to yield a large population of ferritin subunits. Regulation is achieved through a 28-nucleotide "stem-and-loop" structure near the beginning of the H- and L-ferritin mRNAs. When this structure is associated with a binding protein (iron regulatory element binding protein, IRE-BP), translation of the ferritin mRNA cannot proceed. However, when intracellular iron accumulates, IRE-BP releases its hold and translation of the mRNA then takes place. IRE-BP has been identified as a cytosolic form of aconitase, containing several fourfold iron-sulfur clusters. Within each cluster one iron atom is labile; this may be the mechanism by which IRE-BP responds to intracellular iron levels. Finally, transcription of the L- and H-genes shows that L is preferentially transcribed in response to increased iron intake, whereas H responds to cell differentiation and other factors. More work is needed to define independent transcription of the individual genes, including regulation of components other than the 28-nucleotide segment.

Animals↗
PubMed1987

Translation of ferritin light and heavy subunit mRNAs is regulated by intracellular chelatable iron levels in rat hepatoma cells.

Acute administration of iron to rats has been previously shown to induce liver ferritin synthesis by increasing the translation of inactive cytoplasmic ferritin mRNAs for both heavy (H) and light (L) subunits by mobilizing them onto polyribosomes. In this report rat hepatoma cells in culture are used to explore the relationship of this response to intracellular iron levels. After adding iron as ferric ammonium citrate to the medium, latent ferritin H- and L-mRNAs were extensively transferred to polyribosomes, accompanied by increased uptake of [35S]methionine into ferritin protein. Because total cellular levels of L- and H-mRNA were not significantly changed by exposure to iron, the increased ferritin mRNAs on polyribosomes most probably come from an inactive cytoplasmic pool, consistent with the inability of actinomycin-D and of cordycepin to inhibit iron-induced ferritin synthesis. When deferoxamine mesylate, an intracellular iron chelator, was added after the addition of iron to the medium, ferritin mRNA on the polyribosomes was reduced, while the free messenger pool increased, and ferritin synthesis diminished. In contrast, the extracellular iron chelator diethylenetriaminepentaacetic acid failed to inhibit the induction of ferritin protein synthesis. Addition of iron in the form of hemin also caused translocation of mRNA to polyribosomes, a response that could be similarly quenched by deferoxamine. Because hemin does not release chelatable iron extracellularly, we conclude that the level of chelatable iron within the cell has a regulatory role in ferritin synthesis through redistribution of the messenger RNAs between the free mRNA pool and the polyribosomes.

Animals↗
PubMed1986

An autocrine/paracrine role for insulin-like growth factors in the regulation of human placental growth.

Tissue derived from preterm (9-19 weeks gestation) and term (38-41 weeks gestation) human placentae were examined for their ability to synthesize and secrete insulin-like growth factors (IGFs) in organ culture. IGF-I was measured by a specific RIA, and IGF-II by a rat placental membrane radioreceptor assay. First, explants of placental tissue were maintained in organ culture. These explants secreted immunoreactive IGF-I (IR-IGF-I). There were no differences in the IR-IGF-I content of media conditioned by term and preterm placentae under these conditions. The similarity of this material to authentic human IGF-I was supported by parallel displacement in a specific RIA and coelution during Sephadex G-50 gel filtration. Second, monolayer cultures of fibroblasts from normal human preterm placentae (15-19 weeks gestation) were established. Confluent monolayers of these fibroblasts secreted IR-IGF-I (3-10 pg/10(5) cells X 40 h). IR-IGF-I secretion was reversibly inhibited by 5.3 microM cycloheximide, suggesting that the IR-IGF-I was the result of de novo protein synthesis. IR-IGF-I secretion was stimulated 5-fold by platelet-derived growth factor (0.6 U/ml). The response of monolayers of placental fibroblasts to IGF-I also was tested. IGF-I stimulated alpha-[3H]aminoisobutyric acid transport in these fibroblasts, with half-maximal stimulation occurring at 2-3 ng/ml. Stimulation of alpha-[3H]aminoisobutyric acid uptake by IGF-I correlated with specific binding of [125I]iodo-IGF-I. Half-maximal inhibition of [125I]iodo-IGF-I binding occurred at 2-3 ng/ml IGF-I. Placental tissue also secreted IGF-II-like activity, as measured by radioreceptor assay. Media conditioned by placental explants contained 15-20 ng/mg protein X 48 h, and media conditioned by placental fibroblasts contained 3-7 ng/10(5) cells X 40 h IGF-II determined by radioreceptor assay. These data support the hypothesis that the human placenta produces IGFs (IGF-II and/or IGF-I) that act locally to regulate placental growth.

Aminoisobutyric Acids↗
PubMed1985

Filaroides hirthi in a British bred beagle dog.

Filaroides hirthi was identified in large numbers in the lungs of a British bred beagle dog that had received 10 monthly intra-articular injections of a corticosteroid. The dog was terminally hyperpnoeic and eosinophil and reticulocyte counts were raised. At autopsy, the lungs failed to collapse and minute black and red foci were found throughout the lung parenchyma. These foci were identified histologically as parasites and focal haemorrhage. Migrating larvae were found in the liver and mesenteric lymph nodes. F hirthi has not previously been definitively identified in British dogs and the principal features of its identification and control are discussed.

Administration, Topical↗
PubMed1985

Two tissue-specific isozymes of creatine kinase have closely matched amino acid sequences.

Creatine kinase activity is associated with different isozyme species. We have examined two of these: the cytoplasmic brain (B) isozyme that is expressed in many tissues and is reported to be induced by estrogen and the developmentally regulated cytoplasmic muscle (M) isozyme that is found predominantly in differentiated muscle tissue. Recently, we cloned and sequenced the cDNA for the M isoenzyme of rabbit creatine kinase. We now report the isolation of B-isozyme cDNAs and the deduced primary structure of the polypeptide. The translated cDNA nucleotide sequence was cross-checked by fast-atom bombardment/mass spectrometry of tryptic fragments from the protein. The sequence is exactly colinear with the rabbit M isozyme and the two isozymes have 80% nucleotide and amino acid sequence identity. There are blocks of 36 and 41 amino acids where the amino acid sequence is conserved exactly. The colinearity of the two sequences and the extent of their identity makes it unlikely that either isozyme has unique polypeptide domains that account for specialized functions. The rationale for the existence of these creatine kinase isozymes, with distinct biological features, evidently is at the level of regulation of individual isozyme expression.

Amino Acid Sequence↗