The impact of immigration on tuberculosis rates in the United Kingdom compared with other European countries.

OBJECTIVE: To investigate whether trends in tuberculosis (TB) rates across Europe are linked to patterns of migration. DESIGN: Descriptive analysis of Organisation for Economic Co-operation and Development population statistics and EuroTB data for 21 European countries for 1996-2005. RESULTS: TB notification rates increased in only three of the 21 countries: the United Kingdom, Norway and Sweden. In all three countries, approximately three quarters of cases were foreign-born. The UK had the third highest number of foreign nationals overall, but the highest number from a country with a TB incidence > or =250 cases/100000 (219000, 13%). European countries with declining TB rates had varying patterns of migration, but did not generally receive migrants from very high-incidence countries and/or had a smaller proportion of their total TB cases in their migrant population. CONCLUSIONS: The increase in the rate of TB in the UK, which contrasts with most other European countries, may, at least in part, be due to the fact that a high proportion of UK cases occur in the foreign-born, coupled with a comparatively large number of foreign nationals from countries with a very high incidence of TB.

Tuberculosis in non-UK-born persons, England and Wales, 2001-2003.

SETTING: England and Wales, 2001-2003. OBJECTIVES: To describe demographic and clinical characteristics of tuberculosis (TB) in non-UK-born persons and compare with UK-born cases to inform public health action and health service provision. DESIGN: Analysis of surveillance data. RESULTS: Among the 67% of cases who were non-UK-born, TB incidence was 88/100000 compared to 4/100000 among the UK-born. UK-born minority ethnic groups were also at increased risk of TB. Although the highest TB incidence occurred in recent entrants to the UK, nearly half the cases had been resident for >or=5 years. The majority of non-UK-born cases originated from South Asia (48%) and sub-Saharan Africa (35%). The demographic characteristics of non-UK-born and UK-born cases differed. In addition, non-UK-born cases were less likely to have pulmonary TB than the UK-born (52% vs. 73%, chi(2) P<0.001), but were more likely to have isoniazid-resistant disease (8% vs. 6%, chi(2) P=0.002), depending on region of birth. CONCLUSIONS: During 2001-2003, most TB cases were non-UK-born. TB services need to take the characteristics of TB in this group into account. Furthermore, awareness of the risk of disease is required among the non-UK-born for many years after arrival into the UK, and among UK-born minority ethnic groups.

Modelling the hepatitis B vaccination programme in prisons.

A vaccination programme offering hepatitis B (HBV) vaccine at reception into prison has been introduced into selected prisons in England and Wales. Over the coming years it is anticipated this vaccination programme will be extended. A model has been developed to assess the potential impact of the programme on the vaccination coverage of prisoners, ex-prisoners, and injecting drug users (IDUs). Under a range of coverage scenarios, the model predicts the change over time in the vaccination status of new entrants to prison, current prisoners and IDUs in the community. The model predicts that at baseline in 2012 57% of the IDU population will be vaccinated with up to 72% being vaccinated depending on the vaccination scenario implemented. These results are sensitive to the size of the IDU population in England and Wales and the average time served by an IDU during each prison visit. IDUs that do not receive HBV vaccine in the community are at increased risk from HBV infection. The HBV vaccination programme in prisons is an effective way of vaccinating this hard-to-reach population although vaccination coverage on prison reception must be increased to achieve this.

Hepatitis A vaccination--a prison-based solution for a community-based outbreak?

In December 2001, an increase in cases of hepatitis A was observed in South Yorkshire. Cases were predominantly young males who reported injecting drug use. A community-based vaccination programme was introduced in November 2002, but new cases continued to occur. In March 2003, a vaccination campaign was implemented in the local prison for a four-week period. One thousand two hundred and thirty-six (91%) prisoners were vaccinated. Two thirds (895/1,363) of the prisoners came from the area affected by the outbreak and 52% (465/895) reported injecting drugs. The median age of injectors was 25 years. Notifications of cases of hepatitis A from South Yorkshire ceased in August 2003. Although on this occasion the prison vaccination campaign was probably implemented too late to have had a significant impact on the local outbreak, a large number of young male injectors from the local area were successfully vaccinated. This suggests that a prison-based intervention offers a potentially effective way of immunising the IDU population and interrupting a community-based outbreak.

Increasing hepatitis B vaccine coverage in prisons in England and Wales.

The most frequently reported risk factor for hepatitis B infection in England and Wales is injecting drug use (38%). Since approximately 61% of injecting drug users (IDUs) had been imprisoned and less than 40% had received hepatitis B vaccine, a prison based hepatitis B vaccination programme was set up in 2001. At the 42 establishments participating in this study, all prisoners were offered vaccine at reception. Prisoners over 18 years were vaccinated using the 0, 7 and 21 days schedule and those under 18 years, using the 0, 1 and 2 months schedule. As far as possible a fourth dose was given to all after 12 months. In 2003, 14,163 prisoners received at least one dose of vaccine and altogether 26,265 doses were administered. A further 1111 prisoners reported they had already been vaccinated against hepatitis B. The median vaccine coverage rate was 17% (range 0-94%). Despite low coverage levels, the vaccination programme in prisons can be said to have vaccinated a sizable number of young, male prisoners, a group that have previously been shown to be at high risk of infection. The prisons which achieved vaccine coverage levels over 50% had designated nursing staff who ran the vaccination clinics.

Total ear canal ablation in the cat: indications, morbidity and long-term survival.

Fifty-two total ear canal ablation (TECA) procedures in 44 cats were reviewed. The indication for surgery was neoplasia in 41 per cent of the cats, 86 per cent of which had ceruminous gland adenocarcinoma. Chronic inflammatory or polypoid disease accounted for 50 per cent of surgical procedures. Postoperative complications included Horner's syndrome (42 per cent) and facial paralysis (56 per cent) and these were permanent in 14 per cent and 28 per cent of cases, respectively, with the rest resolving in the ensuing weeks or months. The higher incidence of Horner's syndrome and facial paralysis in the cat, compared to the dog, was attributed to greater fragility of the feline tympanic plexus and facial nerve. The median survival time of cats with ceruminous gland adenocarcinoma was 50-3 months, and did not differ significantly from that for inflammatory or polypoid disease. A potential prognostic indicator for this tumour was the mitotic index (MI): cases with MI < or = 2 survived significantly longer than those with MI > or = 3.

Daniel L. Gilbert: explorer of life.

From the time Dan was 12 years old to the present, he always was the explorer of life. He was very fortunate in having an opportunity to see how life exists in several human societies around the world. His many professional foreign travels are presented. Dan went to a 1959 meeting in Argentina, to England in 1963, and to Chile in 1963. After he married Claire, she accompanied him on his 44 day around the world trip in 1965 and on all his later foreign trips. In 1966, there was a Latin American trip on the way to doing research at a laboratory in Chile. Next on his travels was being a consultant in Venezuela in 1969 and attending a meeting in Russia in 1972. His son Raymond joined in trips to France in 1977, to Australia in 1983, to a 1990 trip to a Peruvian meeting, and finally joined the 1991 meeting to a meeting in Japan, with a side trip to China where Dan gave lectures. The last 2 foreign trips for Dan with Claire, but not with Raymond, were the meetings in 1994 in Buenos Aires, Argentina, and the 1998 meeting, which was held in both Israel and Jordan.

CD4 cell counts in adults with newly diagnosed HIV infection: results of surveillance in England and Wales, 1990-1998. CD4 Surveillance Scheme Advisory Group.

OBJECTIVES: To describe the distribution and changes in CD4 cell counts (both initial and subsequent) in HIV-infected persons over time and determine the factors influencing these counts. DESIGN: Reports were requested from laboratories measuring CD4 cell counts in England and Wales. Initial counts were analysed and median counts were followed over time. METHODS: Time trends and the relationship between initial CD4 cell count and age, sex, and HIV risk category were studied using quantile regression methods or chi-square tests. RESULTS: Between 1990 and 1998, 9553 adults were newly diagnosed with HIV infection and had a CD4 cell count within 6 months of HIV diagnosis. Over 50% of initial CD4 cell counts in each major risk category were below 350 cells/mm3. Older age (P < 0.001), male sex (P < 0.013) and heterosexual risk (P < 0.001) were independently associated with lower initial CD4 cell counts. For heterosexually infected adults, the median initial CD4 cell count was significantly negatively associated with the year of diagnosis (P = 0.03) and the median age increased through the time period examined (P < 0.001), whereas for men who have sex with men (MSM), there was no significant change in these values over time. For each year cohort of newly diagnosed individuals, the median CD4 cell count in subsequent years decreased until 1996 and then increased thereafter, consistent with a treatment effect. CONCLUSION: Across all major risk groups, a large proportion of HIV-infected adults are being diagnosed late in the course of HIV disease. For the heterosexually infected, the data suggest an ageing cohort effect, whereas for MSM the data are consistent with continuing transmission.

Molecular biology of varicella-zoster virus. A review prepared for the UK Advisory Group on Chickenpox.

Varicella-zoster virus (human herpesvirus 3; VZV) is one of eight herpes viruses that routinely infect humans. It is classified as a member of the genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae. Of the other human herpes viruses it is most closely related to the herpes simplex viruses (also members of the Alphalerpesvirinae). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar membrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.

Activation of macrophages and B lymphocytes by an oligodeoxynucleotide derived from an acutely pathogenic simian immunodeficiency virus.

Certain CpG-containing DNA sequences from bacteria, viruses, or invertebrates elicit responses in the vertebrate innate immune system. These responses also account for many nonspecific effects of oligodeoxynucleotides used for antisense approaches. Here we describe a sequence from an acutely pathogenic simian immunodeficiency virus (SIV) that induces release of cytokines from macrophages and B lymphocyte proliferation. Furthermore, several similar sequences in other immunodeficiency viruses were found that also activate macrophages. These results led to the question if CpG-containing DNA, which is thought to play an immunostimulatory role in bacterial infections, has a similar role in infections by immunodeficiency viruses.

Director of nursing finance: controlling health care costs.

Vice Presidents of Nursing in 250 hospitals throughout the United States were asked whether they have someone who is responsible for the nursing division budget as well as coordinating all the department's financial matters. Job duties believed to be relevant to a Director of Nursing Finance position were explored as well as who within the hospital's organizational structure typically performs these job duties.

Subtype-specific signaling mechanisms of somatostatin receptors SSTR1 and SSTR2.

Somatostatin regulates diverse cellular effectors, including adenylyl cyclase, ion channels, and ion exchangers. We expressed two somatostatin receptor subtypes, SSTR1 and SSTR2, stably in mouse fibroblast Ltk- cells and transiently in human embryonic kidney HEK293 cells to investigate subtype-specific pharmacological and functional properties. The effects of GTP gamma S and pertussis toxin on [125I-Tyr11]somatostatin-14 binding indicated that SSTR2 may couple exclusively to pertussis toxin-sensitive G proteins, whereas SSTR1 may couple to both pertussis-sensitive and -insensitive G proteins. When expressed either stably or transiently, both receptor subtypes mediated somatostatin inhibition of cAMP accumulation by a pertussis toxin-sensitive mechanism. In contrast, only SSTR1 mediated somatostatin inhibition of Na(+)-H+ exchange activity, and this action was insensitive to pertussis toxin. We generated two chimeric receptors by replacing sequential residues of SSTR2 with cognate sequences of SSTR1 to identify molecular determinants unique to SSTR1 that may confer coupling to the exchanger. SSTCR4 included a SSTR1 segment encompassing determinants within the fifth and sixth hydrophobic domains and the entire third cytoplasmic loop, while SSTCR5 contained a SSTR1 segment spanning the second through sixth hydrophobic domains, including both second and third cytoplasmic loops. Although both chimeric receptors mediated somatostatin inhibition of cAMP accumulation, only SSTCR5 mediated the inhibition of Na(+)-H+ exchange activity, and this effect was pertussis-insensitive. These findings demonstrate both pharmacological and functional differences between SSTR1 and SSTR2. The ability of SSTR1 to selectively attenuate Na(+)-H+ exchange activity requires determinants outside the third cytoplasmic domain.

G alpha 13 stimulates Na-H exchange.

Activity of the ubiquitous Na-H exchanger (NHE1) is regulated by a number of receptors with tyrosine kinase activity as well as by several classes of receptors coupled to heterotrimeric GTP-binding proteins. We previously demonstrated that the beta 2-adrenergic receptor and other receptors that stimulate adenylyl cyclase by activating Gs stimulate NHE1 by a guanine nucleotide-dependent mechanism that is independent of receptor coupling to Gs. Now we report that a recently identified G alpha subunit, alpha 13, activates the exchanger. Transient expression of mutationally activated alpha 13 constitutively stimulates Na-H exchange; moreover, an alpha 13/alpha z chimera, designed to respond to stimulation by Gi-coupled receptors, mediates stimulation of Na-H exchange by one such receptor, the dopamine2 receptor. Mutationally activated alpha 13, however, does not stimulate adenylyl cyclase activity or phosphoinositide hydrolysis, indicating that its action on NHE1 occurs independently of these two effector pathways. These findings reveal the first known signaling function of alpha 13 and identify a new G protein involved in the regulation of NHE1.

Inhibition of varicella-zoster virus replication by an inhibitor of protein myristoylation.

Inhibitors of myristoylation and analogues of myristic acid inhibit the replication of some retroviruses including human immunodeficiency virus, but no studies with other virus families have been reported. We have shown that replication of varicella-zoster virus (VZV) in tissue is inhibited by DL-2-hydroxymyristic acid at concentrations similar to those required for inhibition with acyclovir. Protein synthesis is not inhibited, but protein myristoylation is non-specifically reduced. Despite this lack of specificity, DL-2-hydroxymyristic acid inhibits VZV replication without apparent cytotoxicity. This is in agreement with our earlier suggestion that non-specific inhibitors of myristoylation could have antiviral effects without toxicity to cells due to the stability of cellular myristoylproteins. This supports suggestions that myristoylation inhibitors have potential as antiviral drugs against the many viruses that produce myristoylproteins.

Neuropsychological deficit in chronic alcoholism: early detection and prediction by analysis of verbal behavior.

The content analysis of five-minute speech samples obtained from detoxified chronic alcoholic patients is a valid test for measuring cognitive impairment during the course of treatment. Such cognitive impairment scores six months after hospital discharge can be predicted using the variables of age, educational level, certain drinking patterns and cognitive impairment scores at the time of hospital admission. Patients who abstain for six months following hospital discharge have less cognitive impairment than those patients who resume drinking.

Cognitive impairment and other psychological scores derived from the content analysis of speech in detoxified male chronic alcoholics.

Sober chronic alcoholic males, sober nonalcoholic males, and intoxicated nonalcoholic males were assessed along several psychological dimensions by means of the content analysis of speech. Average cognitive impairment scores were significantly greater among intoxicated nonalcoholics than sober chronic alcoholics and significantly greater in sober chronic alcoholics than in sober nonalcoholics. Sober chronic alcoholics, also, had a significantly higher score than sober nonalcoholics on depression, social alienation-personal disorganization (schizoid traits), separation, guilt, and diffuse anxiety, and hostility inward. The general mental health, including cognitive function, of sober chronic alcoholics is clearly impaired when compared to sober nonalcoholic individuals.