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Biomedical subjects

A C Hayward

Publications and source records attributed to A C Hayward.

At least 19 recordsLinked to original sources
PubMed2005

The interpretation of nucleic acid amplification tests for tuberculosis: do rapid tests change treatment decisions?

OBJECTIVES: To describe changes in treatment decisions after receipt of nucleic acid amplification (NAA) test for the diagnosis of M. tuberculosis. METHODS: Retrospective notes review of treatment decisions in patients receiving a NAA test for suspected pulmonary or non-pulmonary tuberculosis at the Royal Free Hospital in London between March 2001 and February 2002. Notes were sought on a 50% random sample of patients with both smear and NAA negative specimens and all patients with other specimen results. RESULTS: Two hundred and fifty patients were tested with NAA; clinical details were obtained on 138; 61 were ever treated. Seventeen (17/18) smear-negative patients were started on treatment after a positive NAA; none of six smear-negative patients treated prior to a negative NAA result had treatment stopped. Seventeen (17/21) smear-positive patients were treated prior to NAA result and all were NAA positive; treatment was delayed in four smear-positive patients until receipt of an NAA and one NAA-negative patient was not treated. CONCLUSIONS: In routine practice a positive test in an untreated smear-negative patient leads to decision to treat in almost all, but the proportion testing positive is low (8% or 17/219). In patients already on treatment negative tests did not lead to decisions to stop.

Adolescent↗
PubMed2004

Explaining risk factors for drug-resistant tuberculosis in England and Wales: contribution of primary and secondary drug resistance.

Drug-resistant tuberculosis can be transmitted (primary) or develop during the course of treatment (secondary). We investigated risk factors for each type of resistance. We compared all patients in England and Wales with isoniazid- and multidrug-resistant tuberculosis in two time-periods (1993-1994 and 1998-2000) with patients with fully sensitive tuberculosis, examining separately patients without and with previous tuberculosis (a proxy for primary and secondary drug-resistant tuberculosis). Patients with previous tuberculosis smear positivity and arrival in the United Kingdom <5 years were strongly associated with multidrug resistance and isoniazid resistance. In patients with no previous tuberculosis HIV infection, residence in London and foreign birth were risk factors for multidrug resistance, and non-white ethnicity, residence in London and HIV infection for isoniazid resistance. Risk factors for each type of resistance differ. Elevated risks associated with London residence, HIV positivity, and ethnicity were mainly seen in those without previous tuberculosis (presumed transmission).

Adolescent↗
PubMed2004

Reasons for low reported treatment success in notified tuberculosis patients from a London hospital according to new outcome reporting.

In January 2002 the Communicable Disease Surveillance Centre (CDSC) introduced outcome reporting for tuberculosis 12 months after start of treatment. To determine whether outcome could change with longer and more detailed follow up, we examined this at 12 months and two years for a cohort notified in 2000 at a central London hospital. At 12 months 61/94 (65%) notified patients had completed treatment, 10 (16%) had died, 11 (12%) were lost to follow up, six (6%) were transferred to another service in the UK, four (4%) were still on treatment, and treatment for one (1%) patient had been stopped. After a mean follow up of two years, 65 (69%) had completed treatment. In this London service with a high prevalence of HIV infection (at least 23%), low treatment success was due to deaths, transfers and losses to follow up. The last of these was often due to patients returning to their country of origin (7 of 11). Tuberculosis was the primary or contributing cause of death in at least 4/94 (4%) cases. Completion rates need to be interpreted with caution particularly in specialist units with highly mobile populations. This has implications for national targets as well as for models of care.

Adolescent↗
PubMed2003

Risk factors for drug resistant tuberculosis in Leicestershire--poor adherence to treatment remains an important cause of resistance.

In the light of rising numbers of tuberculosis (TB) cases in the United Kingdom, the problem of anti-tubercular drug resistance remains a significant concern. Drug resistant TB cases are more difficult and costly to treat, and require appropriate treatment and control mechanisms. This matched case control study aimed to investigate risk factors for resistance in Leicestershire, using data for laboratory isolates of Mycobacterium tuberculosis identified from 1993 to 1998. Each case, defined as culture positive laboratory isolates resistant to at least one first-line drug, was matched to four fully sensitive controls on age, sex and ethnic group. Twenty-three cases and 81 controls were included in the analysis. Drug resistance in Leicestershire was found to be associated with poor adherence to treatment (OR 4.8, 95% CI 1.6-14.4, P=0.005) and with previous TB (OR 3.7, 95% CI 1.2-11.8, P=0.022). These findings emphasize the need to provide support to patients taking treatment in order to maximize adherence.

Antitubercular Agents↗
PubMed2003

Epidemiology and control of tuberculosis in Western European cities.

SETTING: Major cities of Western Europe. OBJECTIVE: To describe major variations in the epidemiology and control of tuberculosis in large Western European Cities. DESIGN: Postal survey using contacts identified through the EURO-TB surveillance network. RESULTS: Twenty cities responded. In most cities, notification rates were substantially higher than national rates. Rates ranged from less than 10 per 100,000 in Reykjavik and Belfast to over 70 per 100,000 in Lisbon. MDR-TB ranged from less than 1% of cases in many cities to over 5% in Rome and Milan. The proportion of patients estimated to be HIV-positive ranged from less than 5% in many countries to over 20% in Milan. These variations in epidemiology were accompanied by major variations in control policy, particularly in approaches to new entrant screening and BCG vaccination. CONCLUSION: In Western Europe, tuberculosis is primarily a problem of large cities. Some of these cities have very high rates of tuberculosis. There is little consensus about the best approaches to control. The evidence base for the effectiveness of different aspects of TB control needs to be strengthened.

Antitubercular Agents↗
PubMed2002

The molecular epidemiology of tuberculosis in inner London.

The study used DNA fingerprint typing (spoligotyping and Heminested-lnverse-PCR) of Mycobacterium tuberculosis from all culture-confirmed inner London patients over a 12-month period to describe transmission. The methodology was evaluated by comparison with standard IS6110 typing and by examining its ability to identify known household clusters of cases. Isolates sharing indistinguishable typing patterns using both techniques were defined as clustered. Clusters were investigated to identify epidemiological links. The methodology showed good discriminatory power and identified known household clusters of cases. Of 694 culture-confirmed cases, 563 (81%) were typed. Eleven (2%) were due to laboratory cross-contamination and were excluded. Of the remaining 552 isolates 148 (27%) were clustered. Multivariate analysis indicated that clustering was more common in those with pulmonary smear positive disease (P < 0.02); those born in the United Kingdom (P < 0.0003) and in patients living in south London (P = 0.02). There was also a trend towards clustering being more common in those not known to have HIV infection (P = 0.051). The results suggest that in inner London, recent local transmission makes an important contribution to notification rates.

Adolescent↗
PubMed2002

Primary care referral protocol for carpal tunnel syndrome.

Carpal tunnel syndrome is an extremely common upper limb nerve compression syndrome, widely distributed in the community. There are a variety of treatment options which may be applied to the syndrome, depending on the severity of symptoms. Some options are available in a primary care setting, others require secondary referral. This paper is a detailed review of the available literature and provides a protocol that could be used to assist in the referral of patients from primary care.

Carpal Tunnel Syndrome↗
PubMed2001

Excess hospital admissions for pneumonia and influenza in persons > or = 65 years associated with influenza epidemics in three English health districts: 1987-95.

OBJECTIVES: To study the association between community influenza activity and acute hospital admissions for pneumonia and influenza among elderly persons. DESIGN: Multiple regression analysis of acute hospital admissions against community influenza activity, air temperature and seasonal and long-term trends. SETTING: Three English health districts: 1987-95. SUBJECTS: Persons aged > or = 65 years. OUTCOME MEASURES: Acute hospital admissions for pneumonia and influenza (ICD9: 480-487); excess hospital admissions during epidemic periods. RESULTS: The final regression model explained 70% of the total variation in hospital admissions for pneumonia and influenza, including 14% due to community influenza activity. However, most variation was explained by long-term and seasonal changes unrelated to influenza. In the large influenza epidemic of 1989/90 a typical health district (500,000 total population) experienced 56 excess admissions for pneumonia and influenza attributable to epidemic influenza among persons aged > or = 65 years, requiring 672 additional bed-days. However the figure varied widely between seasons and over the whole study period, the average winter excess was 17.5 admissions per health district, requiring an additional 210 bed-days. CONCLUSIONS: Influenza epidemics exert a variable impact on acute hospital admissions for pneumonia and influenza among elderly persons, which in the past have been poorly quantified. Although the absolute numbers of excess admissions is modest, their impact on bed availability may be considerable because of the duration of hospital stay in elderly persons.

Age Factors↗
PubMed2001

Use of ribotyping and random amplified polymorphic DNA to differentiate isolates of Burkholderia andropogonis.

AIMS: The aim of this study was to determine the genetic diversity among isolates of Burkholderia andropogonis from various host plant species and geographic locations. METHODS AND RESULTS: Both random amplified polymorphic DNA (RAPD) and ribotyping analyses were used to assess the diversity of B. andropogonis isolates and compare these results with pathogenicity assays carried out on a number of common hosts of the organism. CONCLUSIONS: Both RAPD and ribotyping analyses revealed a high level of genetic diversity between isolates of B. andropogonis. Both methods demonstrated a similar clustering of isolates. However, there was no strict correlation between the genetic diversity revealed and the original host, geographic location or pathogenicity of the isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the genetic diversity of isolates of B. andropogonis. The great degree of diversity revealed in this study contrasts with the lack of phenotypic diversity within this species.

Bacterial Typing Techniques↗
PubMed2001

Investigation and control of a large outbreak of multi-drug resistant tuberculosis at a central Lisbon hospital.

An increase in the number of new cases of tuberculosis (TB) combined with poor clinical outcome was identified among HIV-infected injecting drug users attending a large HIV unit in central Lisbon. A retrospective epidemiological and laboratory study was conducted to review all newly diagnosed cases of TB from 1995 to 1996 in the HIV unit. Results showed that from 1995 to 1996, 63% (109/173) of the Mycobacterium tuberculosis isolates from HIV-infected patients were resistant to one or more anti-tuberculosis drugs; 89% (95) of these were multidrug-resistant, i.e., resistant to at least isoniazid and rifampicin. Eighty percent of the multidrug-resistant strains (MDR) available for restriction fragment length polymorphism (RFLP) DNA fingerprinting clustered into one of two large clusters. Epidemiological data support the conclusion that the transmission of MDR-TB occurred among HIV-infected injecting drug users exposed to infectious TB cases on open wards in the HIV unit. Improved infection control measures on the HIV unit and the use of empirical therapy with six drugs once patients were suspected to have TB, reduced the incidence of MDR-TB from 42% of TB cases in 1996 to 11% in 1999.

AIDS-Related Opportunistic Infections↗
PubMed2000

Tuberculosis drug resistance in England and Wales. How much is 'home-grown'?

The fact that a substantial proportion of tuberculosis drug resistance (especially multidrug resistance) is due to transmission of resistant strains or treatment failure in the UK underlines the need to strengthen control in this country. Early identification and effective treatment of cases (including measures to support adherence and appropriate use of initial treatment regimes involving at least four drugs in those at risk of isoniazid resistance) would help to control the problem [1].

Antitubercular Agents↗
PubMed2000

Hospitals in England are failing to follow guidance for tuberculosis infection control - results of a National Survey.

Tuberculosis outbreaks can occur in hospitals if adequate infection control is not in place. UK guidelines on the prevention of tuberculosis transmission have recently been published. A national survey of acute NHS Trusts in England was conducted to evaluate whether tuberculosis infection control in hospitals is consistent with the new guidance. There was a 72% response rate (144 NHS Trusts). Sixty percent of Trusts had updated their tuberculosis infection control plans since the new guidance was published. Even trusts with updated plans failed to meet guidance in many areas. Thirty-five percent of Trusts had negative pressure facilities for the isolation of infectious tuberculosis patients. Depending on the risk category of the patient, 45-67% of Trusts met guidelines for isolation of infectious patients. Patients frequently left isolation for non-medical reasons. Only a minority of Trusts complied with guidance for respiratory protection of staff and visitors. These findings suggest that many Trusts remain at risk of outbreaks of tuberculosis and therefore need to re-examine infection control procedures and the availability of isolation facilities.

Data Collection↗
PubMed1999

Differences in signaling properties of the cytoplasmic domains of the insulin receptor and insulin-like growth factor receptor in 3T3-L1 adipocytes.

Insulin and insulin-like growth factors (IGFs) elicit distinct but overlapping biological effects in vivo. To investigate whether differences in intrinsic signaling capacity of receptors contribute to biological specificity, we constructed chimeric receptors containing the extracellular portion of the neurotrophin receptor TrkC fused to the intracellular portion of the insulin or IGF-I receptors. Chimeras were stably expressed in 3T3-L1 adipocytes at levels comparable to endogenous insulin receptors and were efficiently activated by neurotrophin-3. The wild-type insulin receptor chimera mediated approximately 2-fold greater phosphorylation of insulin receptor substrate 1 (IRS-1), association of IRS-1 with phosphoinositide 3-kinase, stimulation of glucose uptake, and GLUT4 translocation, compared with the IGF-I receptor chimera. In contrast, the IGF-I receptor chimera mediated more effective Shc phosphorylation, association of Shc with Grb2, and activation of mitogen-activated protein kinase compared with the insulin receptor chimera. The two receptors elicited similar activation of protein kinase B, p70S6 kinase, and glycogen synthesis. We conclude that the insulin receptor mediates some aspects of metabolic signaling in adipocytes more effectively than the IGF-I receptor, as a consequence of more efficient phosphorylation of IRS-1 and greater recruitment/activation of phosphoinositide 3-kinase.

3T3 Cells↗
PubMed1998

Nucleotide sequence of the nifH gene coding for nitrogen reductase in the acetic acid bacterium Acetobacter diazotrophicus.

The nifH gene sequence of the nitrogen-fixing bacterium Acetobacter diazotrophicus was determined with the use of the polymerase chain reaction and universal degenerate oligonucleotide primers. The gene shows highest pair-wise similarity to the nifH gene of Azospirillum brasilense. The phylogenetic relationships of the nifH gene sequences were compared with those inferred from 16S rRNA gene sequences. Knowledge of the sequence of the nifH gene contributes to the growing database of nifH gene sequences, and will allow the detection of Acet. diazotrophicus from environmental samples with nifH gene-based primers.

Acetobacter↗
PubMed1997

Two naturally occurring insulin receptor tyrosine kinase domain mutants provide evidence that phosphoinositide 3-kinase activation alone is not sufficient for the mediation of insulin's metabolic and mitogenic effects.

We have recently reported (1) that two naturally occurring mutants of the insulin receptor tyrosine kinase domain, Arg-1174 --> Gln and Pro-1178 --> Leu (Gln-1174 and Leu1178, respectively), both found in patients with inherited severe insulin resistance, markedly impaired receptor tyrosine autophosphorylation, with both mutant receptors being unable to mediate the stimulation of glycogen synthesis or mitogenesis by insulin when expressed in Chinese hamster ovary cells. However, these mutations did not fully prevent IRS-1 phosphorylation in response to insulin in these cells, suggesting that IRS-1 alone may not be sufficient to mediate insulin's metabolic and mitogenic effects. In the present study, we have demonstrated that these mutations also impair the ability of the insulin receptor to activate the transcription factor Elk-1 and promote GLUT4 translocation to the plasma membrane. Although at low concentrations of insulin, the mutant receptors were impaired in their ability to stimulate the tyrosine phosphorylation of IRS-1, at higher insulin concentrations we confirmed that the cells expressing the mutant receptors showed significantly increased tyrosine phosphorylation of IRS-1 compared with parental nontransfected cells. In addition, at comparable insulin concentrations, the association of the p85alpha subunit of phosphoinositide 3-kinase (PI3-kinase) with IRS-1 and the enzymatic activity of IRS-1-associated PI3-kinase were significantly enhanced in cells expressing the mutant receptors. In contrast, no significant stimulation of the tyrosine phosphorylation of Shc, GTP loading of Ras, or mitogen-activated protein kinase phosphorylation was seen in cell lines expressing these mutant receptors. Thus, no activation of any measurable mitogenic or metabolic response was detectable, despite significant insulin-induced phosphorylation of IRS-1 and its association with PI3-kinase in cells stably expressing the mutant insulin receptors. These findings suggest that PI3-kinase activation alone may be insufficient to mediate a wide range of the metabolic and mitogenic effects of insulin. Additionally, the data provide support for the notion that insulin activation of Ras is more closely linked with Shc, and not IRS-1, phosphorylation.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Insulin receptor/IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting.

The insulin receptor (IR) and type 1 insulin-like growth factor (IGF-I) receptor (IGFR) are both widely expressed in mammalian tissues, and are known to be capable of heteromeric assembly as insulin/IGF hybrid receptors, in addition to the classically described receptors. By selective immunoadsorption of radioligand/receptor complexes and by immunoblotting we have determined the fraction of insulin receptors and IGF receptors occurring as hybrids in different tissues. Microsomal membranes were isolated from tissue homogenates and solubilized with Triton X-100. Solubilized receptors were incubated with 125I-IGF-I, and radioligand/receptor complexes bound by IR-specific and IGFR-specific monoclonal antibodies were quantified. The fraction of IGF-I binding sites behaving as hybrids (anti-IR-bound/anti-IGFR-bound) was approx. 40% in liver and spleen, 70% in placenta, and 85-90% in skeletal muscle and heart, similar results being obtained in rabbit and human tissues. There was no correlation between the proportion of hybrids and the ratio of 125I-insulin/125I-IGF-I binding in different tissues. The fraction of 125I-insulin bound to hybrids was too low for accurate quantification, because of the relatively low affinity of hybrids for insulin. The fraction of insulin receptors present in hybrids was therefore determined by immunoblotting. Receptors in solubilized human placental microsomal membranes were precipitated with IR-specific or IGFR-specific monoclonal antibodies, and after SDS/PAGE, blots were prepared and probed with IR-specific and IGFR-specific antisera. It was found that 15% of IR and 80% of IGFR were present in hybrids. Consistent with these figures, the overall level of IR was estimated, by blotting with the respective antibodies at concentrations shown to give equal signals with equal amounts of receptor, to be 4-fold greater than IGFR. Overall it was concluded that a significant fraction of both IR and IGFR occurs as hybrids in most mammalian tissues, including those that are recognized targets of insulin and IGF action. The fraction of hybrids in different tissues was not a simple function of the relative levels of IR and IGFR, possibly because of heterogeneity of receptor expression in different cell types. However, in placenta the proportions of IR, IGFR and hybrids were consistent with a process of random assembly reflecting the molar ratio of IR and IGFR half-receptors.

Animals↗