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Biomedical subjects

K J Hardy

Publications and source records attributed to K J Hardy.

At least 19 recordsLinked to original sources
PubMed2004

Methicillin resistant Staphylococcus aureus in the critically ill.

Methicillin resistant Staphylococcus aureus (MRSA) is endemic within many hospitals worldwide. Critically ill patients on intensive care units have increased risk factors making them especially prone to nosocomially acquired infections. This review addresses the current situation regarding the evolution of MRSA and the techniques for identifying and epidemiologically typing it. It discusses specific risk factors, the morbidity and mortality associated with critically ill patients, and possibilities for future antibiotic treatments.

Critical Illness↗
PubMed2004

Distribution and characterization of staphylococcal interspersed repeat units (SIRUs) and potential use for strain differentiation.

Variable-number tandem repeats (VNTRs) have been shown to be a powerful tool in the determination of evolutionary relationships and population genetics of bacteria. The sequencing of a number of Staphylococcus aureus genomes has allowed the identification of novel VNTR sequences in S. aureus, which are similar to those used in the study of the evolution of Mycobacterium tuberculosis clades. Seven VNTRs, termed staphylococcal interspersed repeat units (SIRUs), distributed around the genome are described, occurring in both unique and multiple sites, and varying in length from 48 to 159 bp. Variations in copy numbers were observed in all loci, within both the sequenced genomes and the UK epidemic methicillin-resistant S. aureus (EMRSA) isolates. Clonally related UK EMRSA isolates were clustered using SIRUs, which provided a greater degree of discrimination than multi-locus sequence typing, indicating that VNTRs may be a more appropriate evolutionary marker for studying transmission events and the geographical spread of S. aureus clades.

Bacterial Typing Techniques↗
PubMed2003

Hypertension, anti-hypertensive drug therapy and erectile dysfunction in diabetes.

AIMS: Erectile dysfunction (ED) is common in diabetes and may be related to the high prevalence of hypertension and consequent anti-hypertensive drug therapy in diabetic patients. The risk factors for ED were studied with particular reference to hypertension and anti-hypertensive drugs. METHODS: We performed a retrospective case note analysis of 763 consecutive male patients (34% Type 1 diabetes, 65% Type 2 diabetes) attending an adult diabetic clinic to collect data on risk factors for ED. We specifically recorded the use of anti-hypertensive drugs. RESULTS: Two hundred and ninety-nine (39%) patients had ED. Mean age of patients with ED (61 years) was higher than those without (mean age 51 years, P < 0.001). The mean age of hypertensive patients was also significantly higher than those without. On multivariate regression analysis, age (P < 0.001), macrovascular disease (P < 0.001), sensorimotor neuropathy (P < 0.001) and HbA1c (P < 0.05) predicted ED. Neither hypertension nor any anti-hypertensive medication independently predicted ED. CONCLUSION: Our data suggest that ED in diabetic patients with hypertension may be related to the higher age and prevalence of macrovascular disease rather than hypertension or its treatment.

Adolescent↗
PubMed2003

Comparison of repaglinide vs. gliclazide in combination with bedtime NPH insulin in patients with Type 2 diabetes inadequately controlled with oral hypoglycaemic agents.

AIMS: This open-label randomized controlled clinical trial compared the effect on glycaemic control and weight gain of repaglinide vs. gliclazide combined with bedtime NPH insulin in patients with Type 2 diabetes inadequately controlled with oral hypoglycaemic therapy [HbA1c>7.0% (DCCT aligned assay, normal range 4.6-6.2%)]. METHODS: Eighty subjects with Type 2 diabetes were randomized to 13 weeks' open-label treatment with repaglinide 4 mg t.i.d. or gliclazide 160 mg b.i.d. in combination with bedtime NPH insulin (initial dose 0.5 units/kg). The fasting blood glucose (FBG) target was < or =6.0 mmol/l. RESULTS: Baseline characteristics were similar for age, sex, weight, BMI, FBG and HbA1c. Glycaemic control improved similarly in both groups-insulin/gliclazide by (mean) 1.0%, from 9.2 to 8.2% (P=0.001) and by 0.9%, from 9.4 to 8.5% in the insulin/repaglinide group (P=0.005) (P=0.83 between groups). Weight gain averaged (mean +/- sem) 4.1 +/- 0.5 and 3.4 +/- 0.4 kg in the insulin/gliclazide and insulin/repaglinide groups, respectively (P<0.0001 for both groups from baseline) (P=0.29 between groups). The mean number of hypoglycaemic episodes experienced per patient was 2.95 +/- 0.82 (insulin/gliclazide) and 2.3 +/- 0.52 (insulin/repaglinide) (P=0.81 between groups). Both treatments were associated with significant improvements in Diabetes Treatment Satisfaction [Diabetes Treatment Satisfaction Questionnaire-potential range 0 (min) to 36 (max)]; in the insulin/gliclazide group, by 4.9 +/- 1.1 points to 33.3 +/- 0.6 (P<0.0001) and by 3.0 +/- 0.9 points to 34.6 +/- 0.4 (P=0.0006) in the insulin/repaglinide group (P=0.29 between groups). CONCLUSIONS: Over 13 weeks, both repaglinide and gliclazide, when combined with bedtime NPH insulin produce similar significant improvements in glycaemic control (-1%) and similar weight gain.

Administration, Oral↗
PubMed2002

Evaluation of a district-wide screening programme for diabetic retinopathy utilizing trained optometrists using slit-lamp and Volk lenses.

BACKGROUND: Debate exists about the optimum way to screen for diabetic retinopathy. Cameras produce a permanent record, but offer patients less choice about when and where to be screened. Optometrists offer flexibility but sensitivity and specificity of schemes have varied considerably, perhaps because of variability in screening methodology and that there is frequently no quality assurance programme. AIMS: To audit our district-wide (population 340000) screening programme for diabetic retinopathy against national targets: sensitivity > 80%, specificity > 95% and referral to review < 3 months. METHODS: Trained optometrists performed slit-lamp examination with Volk lenses (78 dioptre) with standardized reporting. Audit was by ophthalmologist with slit-lamp and Volk lenses through dilated pupils. RESULTS: We examined 872 eyes of 439 patients; 64% were normal, 29% background diabetic retinopathy, 7% sight-threatening eye disease (STED). Sixty-three percent of patients were seen within 6 months of the original screen. Of these, sensitivity for any retinopathy was 72%, specificity 77%, positive predictive value (PPV) 53%, negative predictive value (NPV) 88%. For STED, in this group, sensitivity was 87% and specificity 91%, PPV 30%, NPV 99%. Median interval referral to ophthalmological review was 11.5 weeks with 73% reviewed in under the 13-week target. Of those referred 25% received laser therapy. Eleven patients found to have referable eye disease at their initial screen were not referred to an ophthalmologist by their GP. CONCLUSIONS: We conclude that effective district-wide screening for diabetic retinopathy by optometrists using slit-lamp and Volk lenses is possible; however, only 36% of identified people with diabetes in the district were screened over a 4-year period.

Diabetic Retinopathy↗
PubMed2001

Information given to patients before appointments and its effect on non-attendance rate.

PROBLEM: Wasted outpatient appointments as a result of clinic non-attendance, exacerbating outpatient waiting times. DESIGN: Single centre, prospective, non-randomised, controlled study. BACKGROUND AND SETTING: Diabetes clinic in a district general hospital run by a consultant, one or two diabetes nurse specialists, a dietitian, and a podiatrist. Clinic receives 10-15 new referrals a week in a health district with a population of 340 000. KEY MEASURE FOR IMPROVEMENT: Non-attendance rate in 325 new patients who attended after the intervention compared with 1336 historical controls from the same clinic in the three years before the scheme. STRATEGY FOR CHANGE: Two weeks before their outpatient appointment new patients were sent an information pack telling them when and where to come, where to park, what to bring, who they will see, and what to expect. One week before the appointment they received a supplementary phone call. EFFECTS OF CHANGE: Telling patients what to expect reduced non-attendance rate overall from 15% (201/1336) to 4.6% (15/325), P<0.0001. Non-attendance rate was 7.3% (13/178) in those sent a pack but not phoned and 1.4% (2/147) in those sent a pack and phoned, P=0.01. LESSON LEARNT: Giving new patients detailed information reduces non-attendance to almost 1%.

Appointments and Schedules↗
PubMed2001

17-beta-estradiol suppresses IL-2 and IL-2 receptor.

Interleukin-2 (IL-2) plays an important role in adaptive immune responses. These responses differ between females and males and may be due to the sex steroid estrogen. In this investigation we show that estrogen suppresses IL-2 production from activated peripheral blood T cells and CD4+ T cell lines at the transcriptional level. Suppression of IL-2 occurred at short term, high 17-beta-estradiol concentrations as well as longer term lower 17-beta-estradiol concentrations. In CD4+ Jurkat T cells, suppression of IL-2 was associated with decreased nuclear binding of two important IL-2 promoter transcription factors: NFkappaB and AP-1. The decreased nuclear binding of NFkappaB occurred in the setting of estrogen-induced increases in IkappaBalpha protein levels, an important inhibitor of NFkappaB nuclear translocation. 17-beta-Estradiol was also shown to inhibit IL-2 receptor (IL-2R) expression in activated peripheral blood T cells. Estrogen-induced suppression of IL-2 and its receptor may have many ramifications for our understanding of immune and autoimmune sexual dichotomies, immune responses during pregnancy, and potential therapeutic intervention with hormone agonists and antagonists.

Active Transport, Cell Nucleus↗
PubMed2001

Randomized clinical trial comparing totally extraperitoneal inguinal hernia repair with the Shouldice technique.

BACKGROUND: The optimal technique for inguinal hernia repair remains contentious. This study compared the Shouldice repair with the totally extraperitoneal endoscopic (TEP) method in a randomized clinical trial, with quality of life (QoL) and cost analysis. METHODS: Two hundred patients were randomized to Shouldice or TEP repair. Patients were assessed after operation by questionnaire to determine operative outcomes, complications, QoL, and return to work and normal lifestyle. RESULTS: There were 117 TEP and 115 Shouldice repairs. Median operating time was longer for TEP repair (70 versus 56 min; P = 0.0001), but patients were discharged earlier (68 versus 48 per cent within 1 day; P = 0.0065), and had a quicker return to work (14 versus 30 days; P = 0.0001) and normal lifestyle (21 versus 35 days; P = 0.0001). Open repair was nearly 40 per cent cheaper. Late follow-up in 171 patients (86 per cent) at a median of 1.3 years found that TEP repair led to fewer complications at 1 year (9 versus 21 per cent; P = 0.05) and was associated with significant improvement for the QoL components of work performance and satisfaction, physical symptoms and sense of well-being. CONCLUSION: TEP repair results in fewer complications and an earlier return to work and normal lifestyle, but is more expensive and takes longer to perform.

Costs and Cost Analysis↗
PubMed2001

Local inhibition of nitric oxide temporarily stimulates aldosterone secretion in conscious sheep in vivo.

The effect of localized blockage of endogenous nitric oxide (NO) on basal aldosterone secretion was studied in conscious sheep with autotransplanted adrenal glands. We have shown that infusion of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 130 microg/l blood flow) significantly stimulated basal aldosterone secretion rate (ASR). This stimulatory effect was seen up to 4 h of infusion. Beyond this time point, however, the elevated ASR level was not sustained, and it was seen to drop markedly to lower than control values at 5 h. L-NAME had no effect on cortisol secretion rate (FSR) during the first 4 h of infusion, but a significant reduction in FSR was seen by the 8-h time point. Adrenal blood flow was consistently decreased in association with long L-NAME infusion. Additionally, L-NAME was shown to have no effect on aldosterone secretion when infused systemically. We conclude that the relationship between NO and aldosterone secretion is an inhibitory one, in which NO seems to have a negative effect on basal aldosterone secretion.

Adrenal Glands↗
PubMed2001

The hepatic artery: a reminder of surgical anatomy.

This study was carried out to document the anatomy of the hepatic artery with the purpose of reminding surgeons of the need for this essential knowledge in order to practice safe hepatobiliary surgery. Repeated surgical mistakes on patients referred to our unit prompted the study. One hundred and eighty consecutive livers procured for transplantation was studied, and the anatomy drawn immediately after dissection. The left hepatic artery arose from the left gastric artery in 15%, and either the splenic, gastroduodenal artery or the aorta in 4% of cases. The right hepatic artery arose from the superior mesenteric artery in 15%, the gastroduodenal, right gastric artery or aorta in 10% of cases. There was a major variation of the coeliac axis in 9% of cases studied. Overall, there was an abnormality in 43% of dissections: 48% were multiple and 27% had more than two vascular variations. A constant pattern of abnormalities occurred in the anatomy of the hepatic artery. Realisation of this vascular pattern should make identification of the anatomy easier. When there is one vascular variation, there is a high chance of there being multiple variations.

Adolescent↗
PubMed2000

Implementation of antithrombotic management in atrial fibrillation.

The aim of the study was to assess the extent to which published recommendations on the antithrombotic management of atrial fibrillation had been adopted into clinical practice in a busy district general hospital, and the impact of clinical audit on subsequent management. In the initial audit, 185 consecutive patients with atrial fibrillation were studied using their case notes to identify any further clinical risk factors for stroke. A management algorithm stratified patients with atrial fibrillation into high, moderate, or low risk of stroke according to the individual stroke risk factors. For patients at high risk, the correct treatment is warfarin unless there are specific contraindications. For patients at moderate risk, the correct management is aspirin unless there are specific contraindications. Patients at low risk should receive no thromboprophylaxis. The clinical risks of stroke and thromboprophylaxis on discharge from hospital were recorded. An extensive education programme on stroke prevention in atrial fibrillation was undertaken. Six months later a further 185 consecutive patients with atrial fibrillation were audited. Overall, a large proportion (306/370; 83%) of patients were at high risk of stroke. In the initial audit, antithrombotic management was correct in 89 patients (48%). In the follow up audit, antithrombotic management was correct in 135 patients (73%) (p < 0. 00001). If this improvement in management were extrapolated to all hospital patients in the United Kingdom, approximately 1400 strokes/year could be avoided. Despite broad consensus in recent publications, antithrombotic management of atrial fibrillation remains imperfect, with many patients exposed to unnecessarily high risk of stroke.

Aged↗
PubMed2000

Effect of adrenomedullin infusion on basal and stimulated aldosterone secretion in conscious sheep with cervical adrenal autotransplants.

In vivo and in vitro studies have shown conflicting effects of adrenomedullin (ADM) on the secretion of steroid hormones from the adrenal gland. While some investigators report no effect of this peptide on the output of various hormones, others have reported both stimulatory and inhibitory roles for ADM. We have shown that basal aldosterone secretion rate (ASR), in conscious sheep with cervical adrenal autotransplants, did not change when ADM was infused directly into the adrenal arterial supply. While not affecting basal ASR, ADM did produce pronounced increases in adrenal blood flow (BF). This elevation of BF in association with ADM infusion was seen in all subsequent experiments. When aldosterone output was acutely stimulated by angiotensin II (AngII), potassium chloride (KCl) and adrenocorticotrophic hormone (ACTH), ADM was seen to drastically reduce the secretion of aldosterone with all agonists studied. After pre-exposure to ADM, all three agonists increased ASR but the magnitude of the responses were somewhat blunted. ADM did not have the same effect on cortisol secretion stimulated by ACTH, suggesting that the ability of this peptide to influence adrenal gland function is limited to the zona glomerulosa. In conditions of chronic elevation of aldosterone levels, such as in Na deficiency, ADM did not display the same inhibitory abilities seen in the acute stimulation experiments. Hence, ADM has been shown to have a direct, inhibitory role on the acute stimulation of aldosterone by AngII, KCl and ACTH while not affecting basal or chronic aldosterone secretion or cortisol secretion stimulated by ACTH.

Adrenal Glands↗