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K L Davison

Publications and source records attributed to K L Davison.

At least 19 recordsLinked to original sources

Investigating the aetiology of and evaluating the impact of the Men C vaccination programme on probable meningococcal disease in England and Wales.

The aims were to (1) investigate the aetiology of probable meningococcal disease, where a clinical diagnosis is made in the absence of laboratory data, and (2) evaluate the impact of the Men C vaccination programme in England and Wales. Multiple linear regression analyses were carried out using data reported to Enhanced Surveillance of Meningococcal Disease (ESMD) and laboratory reports of isolates of organisms causing symptoms that mimic meningococcal disease. Confirmed meningococcal disease appeared to be a significant predictor of probable disease. Thus, an additional reduction in meningococcal disease attributable to the serogroup C vaccination campaign was evident in probable disease over and above that observed in confirmed cases alone. Enteroviruses were a significant contributor to cases of probable meningitis and influenza appeared to be a significant contributor to probable cases of septicaemia. This analysis confirms the success seen following the Men C vaccination campaign and gives an indication of the aetiologies of other causes of probable meningitis and septicaemia reported to ESMD.

Adolescent↗

Clusters of meningococcal disease in school and preschool settings in England and Wales: what is the risk?

AIMS: To assess the risk of further cases in educational settings in order to inform policy on managing cases and clusters of meningococcal disease. METHODS: Between 1 April 1995 and 31 March 2001, surveillance in preschool and school settings in England and Wales identified 114 clusters of meningococcal disease. Twenty clusters were reported in preschool settings, 43 in primary, 46 in secondary, and five in independent schools. Seventy three clusters (64%) consisted of two or more confirmed cases, of which 30 had two or more serogroup C cases. Following the introduction of the national meningococcal serogroup C vaccination programme in 1999, no serogroup C clusters were observed between April 2000 and March 2001. RESULTS: The relative risk of further cases in the four weeks after a single case compared with the background rate was raised in all settings, ranging from RR 27.6 (95% CI 15.2 to 39.9) in preschool settings to RR 3.6 (95% CI 2.5 to 4.6) in secondary schools. Absolute risk estimates ranged from 70/100 000 in preschool settings to 3.0/100 000 in secondary schools. The relative risk of clustering was similar for serogroup B and C strains. Most (68%) second cases occurred within seven days of the first case. CONCLUSIONS: Although there was a higher risk of further cases of meningococcal disease in schools and especially in preschool settings, it is not known whether widespread antibiotic use after single cases reduces risk of further cases and if there is a real risk of harm. Evidence of risk reduction is needed to inform public health policy.

Child↗

National enhanced surveillance of meningococcal disease in England, Wales and Northern Ireland, January 1999-June 2001.

Enhanced surveillance of meningococcal disease (ESMD) was implemented nationally across ten regions of England, Wales and Northern Ireland from 1 January 1999. It aims to deliver more sensitive surveillance than laboratory reporting by including clinically diagnosed but laboratory unconfirmed cases. Consultants in Communicable Disease Control (CsCDC) report all clinically diagnosed cases of meningococcal disease (MD) to the Regional Epidemiologist in the relevant regional unit of the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). These reports are reconciled with laboratory data from the PHLS Meningococcal Reference Unit and then forwarded to the national CDSC where further reconciliation with laboratory data takes place. In addition, CsCDC are asked to report any clusters of MD that occur. Between 1 January 1999 and 30 June 2001, 12,074 cases of MD were ascertained through ESMD. The majority (57%) were laboratory confirmed. The estimated incidence of MD fell between 1999 and 2001 from 9.2 to 8.0 per 100,000 population. Of laboratory confirmed cases, the number of cases of serogroups B and W135 increased and of serogroup C and of ungrouped meningococcal infection decreased. Variation between regions was considerable and deserves further investigation. Of 11,522 cases with a reported clinical diagnosis, 53.6% were diagnosed as septicaemia, 32.6% as meningitis, 12.5% as both septicaemia and meningitis, and 13% had other invasive MD. Between 1 January 1999 and 30 June 2001 698 deaths were reported, an overall case fatality rate (CFR) of 5.8%; 567 deaths were in confirmed cases and 131 probable (CFR 8.2% and 2.5%, respectively). CFR was higher in serogroup C (13.5%) than B (5.8%). No peak in serogroup C meningococcal infection occurred in the winter of 2000/1 and no clusters of serogroup C meningococcal infection were reported in the first half of 2001. ESMD provides information about the epidemiology of MD that is more complete than statutory notification and laboratory surveillance and is useful for evaluating the impact of the meningococcal serogroup C vaccination programme and of the other non-vaccine preventable serogroups.

Adolescent↗

Enhanced surveillance scheme for suspected meningococcal disease in five regional health authorities in England: 1998.

Enhanced surveillance of meningococcal disease (ESMD) began in five English regions on 1st January 1998. The aims of the scheme were to obtain accurate incidence data and develop a robust surveillance system with which to monitor the impact of a new meningococcal serogroup C conjugate vaccine. During 1998, 2,314 suspected cases of meningococcal disease were identified. The majority (84%) was classified as invasive meningococcal disease, with infection of N. meningitidis confirmed in 66%. Sixteen per cent of suspected cases were subsequently given an alternative diagnosis. Age differences between those classified as meningococcal disease and those not, implied a higher index of suspicion of meningococcal disease in younger children. Regions with high rates of meningococcal disease were due to a higher rate of serogroup C. ESMD increased ascertainment of meningococcal disease and deaths. Cases were 34% greater than identified through statutory notifications, an additional 6.8% confirmed infections were identified than were reported to the PHLS Meningococcal Reference Unit (MRU) and deaths were 24% greater than death registrations. These data were used to inform the national meningococcal serogroup C conjugate vaccination programme in England and Wales. In 1999 ESMD was extended to all regions of England, Wales and Northern Ireland.

Adolescent↗

Estimating the burden of serogroup C meningococcal disease in England and Wales.

In 1999 a new conjugate vaccine for serogroup C meningococcal disease was licensed for use in the UK. In order for an appropriate vaccination strategy to be developed the burden of serogroup C disease in England and Wales needed to be established. This was done using data from an enhanced surveillance scheme alongside routine laboratory reports and a total of 5,052 cases of serogroup C disease in England and Wales between 1993 and 1998 were estimated. Among these, an estimated 398 died and 1,767 were admitted to intensive care units (ITUs). The greatest burden of disease was in young children and teenagers. The current literature identified four studies reporting sequelae following serogroup C meningococcal disease. These provided estimates of sequelae in the range of 6.5% and 45% and presented some evidence of higher levels than occur following serogroup B meningococcal disease. This information was provided to the Joint Committee on Vaccination and Immunisation to inform policy to implement a serogroup C conjugate vaccination programme in the UK. The vaccination programme has since been justified by the dramatic reduction in serogroup C meningococcal cases.

Adolescent↗

Failure to vaccinate current injecting drug users against hepatitis B in England and Wales.

In most industrialised countries the elimination of hepatitis B infection is highly reliant on effective vaccine delivery to injecting drug users. This paper highlights the very poor vaccine coverage achieved in England and Wales in the ten years since this problem was officially recognised and targeted. This is despite the existence of a comprehensive and well-utilised network of specialist services for injecting drug users.

Communicable Disease Control↗

An outbreak of hepatitis A among young men associated with having sex in public venues.

An increase in hepatitis A virus (HAV) infection was noted among young men in the former Thames regions during 1997. A retrospective case-control study, using a standardised questionnaire at interview, was conducted in the area most affected (London and East Sussex) to investigate the hypothesis that this increase was mainly among homosexual men and to establish the risk factors associated with transmission. Forty-eight cases and 161 controls completed questionnaires. Forty-one cases (85%) described their sexuality as homosexual (p < 0.0001). Cases were more likely than controls to have eaten shellfish (Odds Ratio (OR) 2.4; 95% Confidence Interval (CI) 1.16, 5.04) during the two months before onset of illness. Cases had more sexual partners (p = 0.015), and more casual sexual partners (p = 0.007) than controls. Cases were more likely to have had sex in a gay sauna (OR 3.5; 95% CI 1.53, 8.30), or in a gay club, pub or disco (OR 2.9; 95 CI 1.29, 6.63) than controls. After adjusting for confounding factors, cases were more likely to have eaten shellfish (adjusted [adj] OR 3.0; 95% CI 1.33, 6.59) and to have had sex in a gay sauna (adj OR 3.9; 95% CI 1.42, 10.59). Public health messages need to inform homosexual men about recognised risk factors such as eating shellfish and travel abroad to endemic areas, as well as sexual risks. Homosexual men can benefit from hepatitis A vaccine. We would suggest that in an outbreak situation men who have multiple anonymous partners and have sex in public venues should be targeted as a priority for health education and immunisation.

Adolescent↗

Guidelines for the control of hepatitis A virus infection.

The PHLS Advisory Committee on Vaccination and Immunisation, following a review of the evidence on control measures for preventing hepatitis A virus (HAV) infection and widespread consultation, has prepared the following guidelines. They include a description of the current epidemiology of HAV infection in England and Wales, where most individuals are now susceptible to HAV. HAV infection is uncommon, with around 1000 infections notified per year in England and Wales. Clusters occur in families and in settings where potential for faecal/oral spread is high, e.g. day care centres, nurseries, primary schools. Larger outbreaks have been recorded in men who have sex with men and injecting drug users. Personal hygiene remains the cornerstone of measures for preventing HAV infection and its spread. Those with haemophilia, hepatitis B or C virus infection or liver cirrhosis, intravenous drug users and men who have sex with men should be offered HAV vaccination as a preventive measure. HAV vaccine should be used for preventing secondary cases and outbreaks provided that patients are informed that the latest date the vaccine is most likely to be effective in preventing disease in contacts is probably 7 days from onset of illness in the primary case. Human normal immunoglobulin (HNIG) should be offered in addition or in preference to vaccine for contacts who are more than 7 days from onset of illness in the primary case, and for those at risk of adverse outcome of HAV infection. Individuals at particular risk of an adverse outcome to infection include those more than 50 years old, with liver cirrhosis of any cause, or with pre-existing hepatitis B or C virus infection. HAV vaccine should be used to prevent infection for travellers to countries where HAV infection is a risk. HNIG is no longer indicated for travellers. Children travelling to such countries should be offered vaccine from 5 years and consideration should be given to vaccinating those aged 1-4 years.

Adult↗

Chlorinated dibenzo-p-dioxin and dibenzofuran concentrations in beef animals from a feeding study.

Four calves were fed polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans for 120 days at levels somewhat higher than what may be found in forage near some waste incinerators and manufacturing plants. Four calves were fed identical diets but without the chemicals. Using bioelectrical impedance measurements of total body fat, 30-50% of the dosed 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, and 2,3,4,7,8-PeCDF was estimated to be retained by the animals. Although these same congeners were bioconcentrated in adipose tissue (BCF approximately 10), consumer products such as ribeye showed concentrations less than what were found in the animal feed (BCF approximately 0.1). Distribution of the dioxins and furans into various lipid compartments appeared to be rather uniform in back fat, perirenal fat, and ribeye for tetra to hexa congeners. Ribeye, serum, and liver lipids had higher concentrations of the higher chlorinated congeners, due in part to not reaching a steady state. An unexpected source of dioxin and furan contamination was discovered during the experiment, resulting in the control animals having concentrations of some congeners that were equal to or in some cases greater than those of the dosed animals. Pentachlorophenol-treated wood components in the pole barn where the feeding experiment was conducted were found to have contributed to the animals' exposure.

Adipose Tissue↗

Poor hepatitis B vaccine coverage in injecting drug users: England, 1995 and 1996.

Self-reported data on vaccination status collected in 1995 and 1996 from seven of the 39 drug agencies in England that took part in the unlinked anonymous HIV prevalence monitoring programme of injecting drug users were analysed to estimate hepatitis B vaccine coverage in this population. Twenty-seven per cent (374/1366) of injecting drug users (IDUs) reported vaccination against hepatitis B and 13% (172) reported having received three doses of vaccine. Eighteen per cent of the IDUs who reported vaccination (66/374) were found to have a marker in their saliva of past/current hepatitis B infection (antibody to hepatitis B core (anti-HBc)) compared with 23% (232/992) of those unvaccinated. Over half (760/1366) of all IDUs tested reported not having been vaccinated against hepatitis B were negative for anti-HBc, and therefore remained susceptible to infection. Targeted vaccination for IDUs against hepatitis B in England has had little success so far, suggesting that enhanced or alternative strategies need to be adopted.

Adolescent↗

A surgical model for determination of true absorption and biliary excretion of manganese in conscious swine fed commercial diets.

Some trace elements, such as Mn, Cu and Zn, are absorbed and quickly resecreted into the gut through the bile. When this occurs, the unabsorbed nutrient and the absorbed and resecreted nutrient may mix in the gut, preventing quantitative calculation of either. We have developed a surgical model that prevents this complication. Pigs (20-40 kg) were fitted with cannulas in the bile duct, lumen of the duodenum, portal vein, ileocolic vein and jugular vein. After recovery for 6-8 d, pigs were given an oral dose of 9.25 mBq of 54Mn. The flow rate of blood past the portal vein was determined by infusion of P-amino hippuric acid into the ileocolic vein. Absorption was quantified by multiplying the concentration of 54Mn in the portal blood by the flow rate. Biliary excretion was determined by quantitative collection of bile, and previously collected bile was reinfused into the gut lumen. Urine and feces were also quantitatively collected. A postoperative time of 6-8 d was sufficient for pigs to recover from the effects of surgery and anesthesia, as assessed by several measures of metabolic function and food and water intake. True absorption was calculated to be 0.5%. 54Mn in the urine and bile began to increase after 4 d. When the pigs were killed after 12 d, only 0.5% of the 54Mn remained in the carcass. Results of this study show that pigs surgically modified by the described procedure can recover fully and can serve as a model to study intestinal absorption and biliary excretion of nutrients. Furthermore, initial studies using 54Mn showed that the model is applicable to studying Mn metabolism and suggest the need for a more detailed study of Mn absorption and biliary excretion.

Animals↗

Metabolism of 2-(glutathion-S-yl)hydroquinone and 2,3,5- (triglutathion-S-yl)hydroquinone in the in situ perfused rat kidney: relationship to nephrotoxicity.

2,3,5-(Triglutathion-S-yl)hydroquinone [2,3,5-(triGSyl)HQ] (20 mumol/kg) and 2-(glutathion-S-yl)hydroquinone [2-(GSyl)-HQ] (250 mumol/kg) both cause nephrotoxicity when administered to male rats, although the former is considerably more potent than the latter. To address the issue of the differential potency of these conjugates we investigated the metabolism and toxicity of 2,3,5-(triGSyl)HQ and 2-(GSyl)HQ in the in situ perfused rat kidney. Infusion of 5 and 10 mumol 2,3,5-(triGSyl)HQ into the right renal artery caused a time-dependent elevation in gamma-glutamyl transpeptidase (gamma-GT) excretion into urine produced by both the perfused and the contralateral kidneys. At the lower concentration, gamma-GT excretion was greater from the perfused kidney, whereas gamma-GT excretion from the perfused and contralateral kidneys was the same at the higher concentration. Using HPLC-EC to analyze urine and bile, metabolites of 2,3,5-(triGSyl)HQ (10 mumol) were observed only within the first 30 min of perfusion. At the lower dose (5 mumol) neither parent compound nor metabolites were found in urine or bile. Infusion of 40 mumol 2-(GSyl)HQ into the right renal artery also caused a time-dependent excretion of gamma-GT into urine: excretion being greater from the perfused kidney. HPLC-EC analysis of urine and bile from 2-(GSyl)HQ perfused kidneys demonstrated the formation of three known metabolites; 2-(N-acetyl-cystein-S-yl)HQ (9.2 +/- 0.5 mumol). 2-(cystein-S-ylglycine)HQ (0.8 +/- 0.3 mumol), and 2-(cystein-S-yl)HQ (1.3 +/- 0.3 mumol). Unchanged 2-(GSyl)HQ was detected in the urine and bile (0.8 +/- 0.1 mumol). A greater fraction of the dose (74%) was recovered in urine following infusion of 40 mumol 2-(GSyl)[14C]HQ than of 10 mumol 2,3,5-(triGSyl)[14C]HQ (29%). In contrast, a greater fraction of the dose was retained by the kidney following treatment with 10 mumol 2,3,5-(triGSyl)[14C]HQ than following treatment with 40 mumol 2-(GSyl)[14C]HQ (36 and 11%, respectively). This result suggests that metabolites derived from 2,3,5-(triGSyl)[14C]HQ are more reactive than those derived from 2-(GSyl)[14C]HQ, which is consistent with the finding that 2,3,5-(tricystein-S-yl)hydroquinone exhibits a lower oxidation potential than 2-(cystein-S-yl)hydroquinone. Differences in the reactivity of the metabolites derived from 2,3,5-(triGSyl)[14C]HQ and 2-(GSyl)[14C]HQ probably account for the more potent nephrotoxicity of 2,3,5-(triGSyl)HQ.

Animals↗

Effect of AT-125 on the metabolism of propachlor and the glutathione conjugates of propachlor and bromobenzene in rat.

1. Dosing rats with the gamma-glutamyl-transpeptidase inhibitor AT-125 results in the excretion of free glutathione in the urine of rat: this treatment did not lead to the excretion of glutathione conjugates of orally dosed xenobiotics, neither did AT-125 increase the biliary excretion of glutathione conjugates. 2. Dosing rat with AT-125 prior to dosing with 2-chloro-N-isopropylacetanilide decreased the excretion of 2-methylsulphonylacetanilide metabolites from 23% of the dose to < 0.5%. 3. We conclude that glutathione and glutathione-xenobiotic conjugates are probably not processed in vivo by the same pathway, and that AT-125 can alter the in vivo transport of mercapturic acid pathway metabolites.

Acetanilides↗

Comparative metabolism and elimination of acetanilide compounds by rat.

1. 14C-labelled propachlor, alachlor, butachlor, metolachlor, methoxypropachlor and some of their mercapturic acid pathway metabolites (MAP) were given to rat either by gavage or by perfusion into a renal artery. MAP metabolites were isolated from bile and urine. 2. Rat gavaged with propachlor and methoxypropachlor eliminated 14C mostly in urine, whereas rat gavaged with alachlor, butachlor and metolachlor eliminated 14C about equally divided between urine and faeces. When bile ducts were cannulated, the gavaged rat eliminated most of the 14C in bile for all compounds. The amount of 14C in bile from the propachlor-gavaged rat was less than that for the other acetanilides, with the difference being in the urine. 3. The mercapturic acid metabolites 2-methylsulphinyl-N-(1-methylhydroxyethyl)-N-phenylacetam ide and 2-methylsulphinyl-N-(1-methylmethoxyethyl)-N-phenylacetam ide were isolated from the urine and bile of the methoxypropachlor-gavaged rat. 4. Bile was the major route for 14C elimination when MAP metabolites of alachlor, butachlor and metolachlor were perfused into a renal artery. Urine was the major route for 14C elimination when MAP metabolites of propachlor and methoxypropachlor were perfused. Mercapturic acid conjugates were major metabolites in bile and urine when MAP metabolites were perfused. 5. We conclude that alkyl groups on the phenyl portion of the acetanilide causes biliary elimination to be favoured over urinary elimination.

Acetamides↗

Propachlor-S-cysteine: a major circulating metabolite in the calf, pig and rat after administration of propachlor.

1. Propachlor-S-cysteine was the major metabolite found in systemic blood from rat, pig and calf given propachlor via the stomach. It was also the major metabolite found in the portal blood of pig; the portal blood of rat and calf was not examined. 2. Erythrocytes were the major transporter of propachlor metabolites in rat blood whereas plasma was the major transporter of these metabolites in pig and calf. 3. There was no evidence for metabolism of propachlor-S-cysteine by rat blood or by cytosol from rat, pig and calf erythrocytes.

Acetanilides↗

Glutathione-mediated methylthio-turnover and sex differences in the metabolism of pentachlorothioanisole by rat.

1. Sex differences observed in the metabolism of pentachlorothioanisole in rat were due to: (1) greater excretion in urine by females, and greater biliary excretion by males; (2) formation of pentachlorophenyl mercapturic acid pathway metabolites by females; and (3) redox-cycling between methylthio and methylsulphoxyl oxidation congeners in intermediary metabolites by females. 2. Three methylthio-turnover processes are proposed in the intermediary metabolism of pentachlorothioanisole.

Animals↗

Comparative metabolism of the cysteine and homocysteine conjugates of propachlor by in situ perfused kidneys of rats.

1. 14C-Cysteinyl- and homocysteinylpropachlor were metabolized to their respective mercapturic acids by rat kidneys in situ. First-pass elimination of 14C in urine was 47.5% for the cysteine conjugate and 36% for the homocysteine conjugate. 2. About half of the perfused 14C-labelled material isolated from urine from kidneys perfused with homocysteinylpropachlor was unchanged homocysteinylpropachlor and about half was the corresponding mercapturic acid. However, only the corresponding mercapturic acid and the S-oxide of this mercapturic acid (31.4% and 1.7% of the dose) were found in urine from kidneys perfused with cysteinylpropachlor, indicating that rat kidneys more efficiently acetylated the natural substrate, the cysteine conjugate.

Acetanilides↗