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Biomedical subjects

A Nicholson

Publications and source records attributed to A Nicholson.

At least 19 recordsLinked to original sources

Evaluation of a new chromogenic agar medium for isolation and identification of Group B streptococci.

AIMS: To evaluate a new chromogenic agar as a screening medium for the isolation of Group B streptococci from high vaginal swabs from pregnant women. METHODS AND RESULTS: The medium was evaluated with 195 high vaginal swabs referred for antenatal screening and compared with blood agar and Granada medium. The new chromogenic medium showed 100% sensitivity for the detection of Group B streptococci, and also showed a positive predictive value of 100%. Granada medium also showed excellent sensitivity and specificity and both media were superior to blood agar. CONCLUSIONS: The new chromogenic medium showed excellent performance for the detection of Group B streptococci from clinical samples. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first chromogenic medium described for the detection of Group B streptococci. The medium offers an effective and convenient alternative to conventional media, currently used in clinical laboratories.

Agar↗

Neonatal sepsis in Jamaican neonates.

AIM: To determine the incidence and causative organisms of bacterial sepsis in neonates at The University Hospital of the West Indies. METHODS: A retrospective review of all neonates with culture-proven sepsis admitted to the hospital between January 1995 and December 2000 was conducted. Incidence rates and antimicrobial susceptibility patterns were determined. RESULTS: There were 4702 admissions to the neonatal unit during the study period. Of these, 135 had culture-proven sepsis and 115 were inborn, giving an incidence of 6.7/1000 live births. There were 89 positive blood cultures, 51 positive urine cultures and two positive CSF cultures. The single most common organism was Klebsiella spp (28%). Other organisms included Escherichia coli (16%), group B Streptococcus (11%) and Enterobacter spp (10%). The aminoglycoside resistance rate of Klebsiella spp was 46% and seven isolates had multiple resistance to antibiotics. There was a case fatality rate of 6.7%. CONCLUSION: Physicians involved in newborn care at The University Hospital of the West Indies need to recognise the important role Klebsiella now plays in neonatal sepsis and its contribution to neonatal mortality. Empirical antibiotic regimens for gram-negative sepsis must take into consideration the high rates of aminoglycoside resistance that are now prevalent.

Anti-Bacterial Agents↗

Routine use of a commercial test, GLABRATA RTT, for rapid identification of Candida glabrata in six laboratories.

When evaluated in six clinical laboratories from six countries with 1,174 fresh isolates, including 715 Candida glabrata and 459 non-C. glabrata strains, GLABRATA RTT (Fumouze Diagnostics, Levallois Perret, France) yielded an overall sensitivity and an overall specificity of 95.8 and 98.9%, respectively. The results were consistent from one laboratory to another. The five false-positive results corresponded to C. parapsilosis (n = 2), C. tropicalis, C. guilliermondii, and C. lusitaniae. GLABRATA RTT allows a rapid, cost-effective, and reliable presumptive identification of C. glabrata.

Candida glabrata↗

A longitudinal magnetic resonance imaging (MRI) study of differences in abdominal fat distribution between normal mice, and lean overexpressers of mitochondrial uncoupling protein-3 (UCP-3).

AIM: To characterize evolution and distribution of abdominal adipose fat between 6 and 18 weeks of age in an animal model of energy consumption based on mice overexpressing the mitochondrial uncoupler protein 3 (UCP-3). METHODS: T2-weighted multislice MRI was performed six times during the 12 week study; visceral, subcutaneous and intermuscular fat depots were quantified. RESULTS: The overexpressor (UCP-3tg) mice consistently have less subcutaneous, visceral, interskeletal muscle and total fat throughout the experiment. Mean (standard error) volumes (ml) of the three distinct depots change between week 6 and week 18 as follows: wild type: subcutaneous 1.93 (0.28) to 6.18 (0.47), visceral 2.15 (0.34) to 6.37 (0.64), intermuscular 0.23 (0.04) to 0.53 (0.03); UCP-3tg: subcutaneous 1.47 (0.17) to 4.07 (0.57), visceral 1.18 (0.04) to 3.69 (0.59), intermuscular 0.23 (0.01) to 0.32 (0.04). Although they eat more (4.3 g compared with 3.4 g per day) the UCP-3tg's always weigh less than controls. In wild-type control animals, increases of all fat pools between week 6 and week 18 is highly significant, as it is for subcutaneous, visceral and total pools in the UCP-3tg animals. The UCP-3tg mice, however, show no significant absolute or relative increase in intermuscular fat; UCP-3 is predominantly overexpressed in skeletal muscle. CONCLUSION: MRI provides an excellent approach to comparative studies of fat distribution in animal models of energy expenditure such as the UCP-3tg mouse.

Abdomen↗

Evaluation of a new chromogenic medium, Uriselect 4, for the isolation and identification of urinary tract pathogens.

AIMS: To compare the performance of a new chromogenic medium, Uriselect 4, with cystine lactose electrolyte deficient (CLED) agar and an established chromogenic agar, CPS ID 2 medium, for detection of urinary tract pathogens. METHODS: Using a semiquantitative culture method, 777 samples were inoculated on to the three test media in duplicate. All bacterial strains that yielded a potentially significant growth were observed for colony colour and identified using standard methods. RESULTS: Of the 777 samples tested, 589 urine samples yielded potentially significant growth of at least one strain. A total of 811 strains were isolated on at least one of the three media. A total of 168 urine samples yielded a mixture of at least two strains. Uriselect 4 medium showed the best sensitivity of the three media and only failed to recover 14 strains (1.7%). CPS ID 2 medium failed to recover 22 strains (2.7%). CLED medium showed the worst recovery and failed to recover 74 strains (9.1%). Both chromogenic media allowed for identification of Escherichia coli with a high degree of specificity (98% for Uriselect 4, 99.7% for CPS ID 2). Inclusion of a spot indole test increased the specificity of both chromogenic media to 100% for E coli. CONCLUSIONS: Uriselect 4 and CPS ID 2 were superior to CLED medium for the isolation of urinary tract pathogens mainly because of their ability to discriminate mixed cultures. Both chromogenic media were also useful for the preliminary identification of the most common urinary tract pathogens.

Agar↗

Wheeze, eczema and rhinitis in 6-7 year old Irish schoolchildren.

The aim of this study was to determine the prevalence of wheeze, eczema and rhinitis in 6-7 year old schoolchildren in Louth and Meath and assess their risk factors. The ISAAC (International Study for Asthma and Allergies in Childhood) questionnaire was used. The response rate was 64.1% (n = 1899). The prevalence rates for wheeze, eczema and rhinitis were 17.4%, 11.2% and 20.2% respectively, with 2.4% of children reported to be suffering from all 3 conditions. The main risk factors for wheeze were male sex and smoking in the home. Ninety-five (28.7%) children with wheeze had no diagnosis of asthma. Of these children 36 (37.9%) had wheeze with exercise, 55 (59.9%) had a dry cough not associated with a cold or flu and 13 (13.7%) reported more than 4 attacks of wheeze in the last year. This study suggests underdiagnosis and undertreatment of atopic illness in this age group. It also suggests decreasing exposure to passive smoking and early recognition and treatment will improve quality of life for many children.

Child↗

Cloning and biochemical analysis of the tetrahymena origin binding protein TIF1: competitive DNA binding in vitro and in vivo to critical rDNA replication determinants.

Cis-acting type I elements regulate the initiation of DNA replication, replication fork movement, and transcription of the Tetrahymena thermophila rDNA minichromosome and are required for cell cycle-controlled replication and developmentally programmed gene amplification. Previous studies identified three in vitro single-stranded type I element binding activities that were proposed to play distinct roles in replication control. Here we describe the cloning of one of these genes, TIF1, and we provide evidence for its association with type I elements in vivo. Furthermore, we show that TIF1 interacts (in vitro and in vivo) with pause site elements (PSE), which co-localize with replication initiation and fork arrest sites, and are shown to be essential. The in vivo accessibility of PSE and type I elements to potassium permanganate suggests that origin regions are frequently unwound in native chromatin. TIF1 contains sequence similarity to the Solanum tuberosum single strand-specific transcription factor, p24, and a related Arabidopsis protein. Antisense inhibition studies suggest that TIF1 competes with other proteins for PSE and type I element binding. TIF1 displays a marked strand bias in vivo, discriminating between origin- and promoter-proximal type I elements. We propose that this bias selectively modulates the binding of a different subset of proteins to the respective regulatory elements.

Amino Acid Sequence↗

Survey on small animal anaesthesia.

OBJECTIVE: To ascertain anaesthetic practices currently for dogs and cats in Australia. METHODS: A questionnaire was distributed to 4,800 veterinarians throughout Australia, seeking data on numbers of dogs and cats anaesthetised per week; drug preferences for anaesthetic premedication, induction and maintenance; use of tracheal intubation, supplemental nitrous oxide and anaesthetic antagonists; and types of vaporisers, breathing systems and anaesthetic monitoring devices used or available. Additional questions concerned proportions of different animal types seen in the practice, and the respondent's university and year of graduation. RESULTS: The response rate was 19%; 95% of respondents graduated from Australian universities, about half since 1985. Most responses (79%) came from mainly small animal practices. On average 16 dogs and 12 cats were anaesthetised each week. Premedication was used more often in dogs than cats, with acepromazine and atropine most favoured in both species. For anaesthetic induction, thiopentone was most preferred in dogs and alphaxalone/alphadolone in cats. Inhaled agents, especially halothane, were preferred for maintenance in both species. Most respondents usually employed tracheal intubation when using inhalational anaesthetic maintenance, but intubation rates were lower during injectable anaesthetic maintenance and a minority of respondents provided supplemental O2. Nitrous oxide was administered regularly by 13% of respondents. The agents most frequently used to speed recovery from anaesthesia were doxapram and yohimbine. The most widely used vaporisers were the Fluotec Mark III and the Stephens machine. Most (95%) respondents used a rebreathing circuit for large dogs and a non-rebreathing system was used for small dogs by 68% of respondents. Most respondents (93%) indicated some form of aid was available to monitor general anaesthesia: the three most mentioned were an apnoea alarm, oesophageal stethoscope and electrocardiogram. CONCLUSION: Diverse approaches were evident, but there appeared to be less variation in anaesthetising dogs: premedication was more frequent and less varied in type, while thiobarbituates dominated for induction and inhalants for maintenance. Injectable maintenance techniques had substantial use in cats, but little in dogs. Evident disparity between vaporisers available and circuits used suggested either confusion in terminology or incorrect use of some vaporisers in-circuit. While most respondents used monitoring equipment or a dedicated observer to invigilate anaesthesia, the common reliance on apnoea alarms is of concern, because of unproven reliability and accuracy.

Anesthesia↗

Meningococcal disease--management of serogroup C clusters in a hyperendemic area.

Recent evidence in Ireland highlights an increased incidence of meningococcal disease, with group B the prominent serogroup. However, in developed countries, 'clusters 'are predominantly group C. To retrospectively analyse all patients with meningococcal disease in the North Eastern Health Board (NEHB) Region (circa 300,000 population) from January 1997 to December 1998 inclusively, and to highlight the occurrence of two 'clusters' of Group C meningococcal disease, one in Drogheda and the other in Monaghan (both of whom received national media attention). We studied clinical, laboratory (including PCR) and epidemiological data on all patients in the NEHB with a diagnosis of meningococcal disease. Blood for PCR (Polymerase Chain Reaction) was sent to the National Meningococcal Reference Laboratory on all suspected cases. Details of two 'clusters' were studied in depth from an epidemiological perspective. 131 patients with meningococcal disease were notified, with three deaths of 53 notifications in 1997 (7.5% mortality) and six deaths of 78 notifications in 1998 (9.8% mortality). The rate of meningococcal disease per 100,00 in 1997 was 13.1 and rose to 18.6 in 1998. This contrasts with a national average of 8.5 per 100,00 for the Republic of Ireland in 1997. Age peaks occurred in those under one year old and between 14-16 years old, with seasonal peaks in the winter and spring months. In 1997, 57.5% were group B and 35% were group C, with 7.5% not grouped. In 1998, 60.3% were group B and 39.7% were group C. There were two linked cases in Drogheda, with both attending a local national school. Both were confirmed group C disease. In Monaghan, in January 1998, a cluster of four cases of group C disease occurred over a 48 hour period. All were males, ranging in age from 11-16 years. Of the four, one died and one received intensive care treatment in a children's hospital. The cluster received intense local and national media attention. One week later, a fifth case of group C disease occurred in Monaghan and this 10 year old boy made an uneventful recovery. The high endemic rate of meningococcal disease is striking, with a four fold rise over the past five years. Clusters of serogroup C meningococcal disease will be of historical interest now that new conjugate C vaccines are incorporated into the vaccination program.

Adolescent↗

Traditional Tongan cures for morning sickness and their mutagenic/toxicological evaluations.

Every year millions of women become pregnant, and more than 60% of them will develop some form of morning sickness. Yet drugs like Thalidomide, Bendectin and other possibly potent teratogens administered for pre-partum nausea have severely limited any medicinal intervention. In Tonga, women have been treated for morning sickness for hundreds of years. Two types of traditional treatments exist, the first one consists of an infusion of fresh leaves, commonly called vai momoko. The second type of treatment is called vai haka, which is made from the boiled bark of several trees. In this paper we describe the results of 6 months of intensive interviews in Tonga regarding the second type of treatment called vai haka. In addition, we tested vai haka for mutagenic and teratogenic effects. Data from the Ames TA-98 mutagenic bioassay clearly indicate that vai haka is not mutagenic with or without S-9 activation. Twenty-six experimental CD-1 white mice were gavaged with 0.1 ml of vai haka (at 540xthe human dose) while the control group of 17 mice were gavaged with 0.1 ml of water to determine teratogenic and developmental effects of the vai haka. No significant teratogenic or developmental anomalies occurred in the mice dosed with vai haka compared to the controls.

Adult↗

Giant lamellar bodies as a feature of pulmonary low-grade MALT lymphomas.

AIMS: Giant lamellar bodies (GLBs) are rare pulmonary inclusions, most frequently described in sclerosing haemangiomas. Following a recent report of their presence in a case of pulmonary lymphoma of MALT origin, our aims were to determine their frequency in pulmonary lymphoproliferative disorders, examine their structure and investigate their aetiology further. METHODS AND RESULTS: We reviewed a series of 29 pulmonary lymphomas (23 low-grade, six high-grade) and 18 cases of reactive pulmonary lymphoid hyperplasia. Five of 23 (22%) low-grade lymphomas contained GLBs, 4/4 of which stained for surfactant apoprotein A but not for surfactant apoprotein B. No GLBs were seen in 18 cases of reactive pulmonary lymphoid hyperplasia or six high-grade primary pulmonary lymphomas. Ultrastructural examination revealed concentrically arranged extracellular material forming roughly spherical structures up to 25 microm in diameter. The GLBs were often surrounded by foamy cells and cholesterol clefts, supporting an origin, at least in part, from products of cell breakdown and surfactant degradation. CONCLUSION: These findings support the idea that the presence of lamellar bodies is in part due to stasis of products arising from degradation of surfactant, in association with certain types of chronic pulmonary pathology. Given their absence in reactive pulmonary lymphoid hyperplasia, the presence of GLBs as an epiphenomenon in a pulmonary lymphoid infiltrate should warrant careful investigation with regard to the diagnosis of low-grade MALT lymphoma.

Aged↗

A brain dead donor model of porcine orthotopic cardiac transplantation for assessment of cardiac allograft preservation.

BACKGROUND: We aimed to develop a large animal model of orthotopic cardiac transplantation, incorporating donor brain death, to assess new methods of preservation of the donor heart. METHODS: Brain death was achieved in the donor pig by inflation of a 20 cc subdural balloon 1 h prior to harvest. The donor heart was stored for 6 h with conventional hypothermic ischaemic preservation. It was then transplanted orthotopically into the recipient pig using the Lower and Shumway technique. One hour after reperfusion, the transplanted heart was weaned from cardiopulmonary bypass with dobutamine support. Dobutamine support was continued for up to 4 h, if required. After 6 h of physiological and biochemical evaluation, the recipient was euthanased and the heart excised for histological assessment. RESULTS: All pigs experienced the classical haemodynamic changes associated with brain death. This resulted in the release of Troponin I, consistent with myocardial injury. The donor operation was successfully completed in 11 out of 13 pigs. Six out of 11 transplanted hearts were successfully weaned from cardiopulmonary bypass, but required ongoing dobutamine support. CONCLUSIONS: This porcine model of orthotopic cardiac transplantation is a relevant and practical large animal model for the assessment of new methods of preservation of the donor heart.

Journal Article↗

Regulation of mitotic homeologous recombination in yeast. Functions of mismatch repair and nucleotide excision repair genes.

The Saccharomyces cerevisiae homologs of the bacterial mismatch repair proteins MutS and MutL correct replication errors and prevent recombination between homeologous (nonidentical) sequences. Previously, we demonstrated that Msh2p, Msh3p, and Pms1p regulate recombination between 91% identical inverted repeats, and here use the same substrates to show that Mlh1p and Msh6p have important antirecombination roles. In addition, substrates containing defined types of mismatches (base-base mismatches; 1-, 4-, or 12-nt insertion/deletion loops; or 18-nt palindromes) were used to examine recognition of these mismatches in mitotic recombination intermediates. Msh2p was required for recognition of all types of mismatches, whereas Msh6p recognized only base-base mismatches and 1-nt insertion/deletion loops. Msh3p was involved in recognition of the palindrome and all loops, but also had an unexpected antirecombination role when the potential heteroduplex contained only base-base mismatches. In contrast to their similar antimutator roles, Pms1p consistently inhibited recombination to a lesser degree than did Msh2p. In addition to the yeast MutS and MutL homologs, the exonuclease Exo1p and the nucleotide excision repair proteins Rad1p and Rad10p were found to have roles in inhibiting recombination between mismatched substrates.

Base Pair Mismatch↗

Impaired gamma interferon responses against parvovirus B19 by recently infected children.

Parvovirus B19 is the causative agent of "fifth disease" of childhood. It has been implicated in a variety of conditions, including unsuccessful pregnancy and rheumatoid arthritis, and is a potential contaminant of blood products. There has been little study of immunity to parvovirus B19, and the exact nature of the protective humoral and cell-mediated immune response is unclear. Immune responses to purified virus capsid proteins, VP1 and VP2, were examined from a cohort of recently infected children and compared with responses from long-term convalescent volunteers. The results demonstrate that antibody reactivity is primarily maintained against conformational epitopes in VP1 and VP2. The unique region of VP1 appears to be a major target for cell-mediated immune responses, particularly in recently infected individuals. We confirm that antibody reactivity against linear epitopes of VP2 is lost shortly after infection but find no evidence of the proposed phenotypic switch in either the subclass of parvovirus B19-specific antibody or the pattern of cytokine production by antigen-specific T cells. The dominant subclass of specific antibody detected from both children and adults was immunoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 production by isolated lymphocytes from children or adults. In contrast, lymphocytes from convalescent adults produced a typical type 1 response associated with high levels of IL-2 and gamma interferon (IFN-gamma). However, we observed a significant (P<0.001) deficit in the production of IFN-gamma in response to VP1 or VP2 from lymphocytes isolated from children. Taken together, these results imply that future parvovirus B19 vaccines designed for children will require the use of conformationally preserved capsid proteins incorporating Th1 driving adjuvants. Furthermore, these data suggest novel mechanisms whereby parvovirus B19 infection may contribute to rheumatoid arthritis and unsuccessful pregnancy.

Adult↗

Systemic phaeohyphomycosis in pregnancy and the puerperium.

Systemic fungal infections are rare. In pregnancy, treatment is problematic because of the risk of possible teratogenic effects of the antifungal drugs. We present the case of a 32 year-old woman who presented during pregnancy with a two-month history of painless subcutaneous nodules. Excision biopsy of one lesion showed dematiaceous fungal elements. Anti-fungal treatment was deferred and the pregnancy proceeded uneventfully. The remaining nodules were excised at the time of caesarean section delivery. Three weeks into the puerperium, she developed generalised seizures and investigations indicated systemic fungal infection with positive cultures for Aureobasidium spp which responded to appropriate antifungal therapy of flucytosine and itraconazole.

Adult↗