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PubMed1983

How effective is perimetry in current practice?

A recent study that sampled the performance of nonphysician perimetrists in community ophthalmic practices revealed that the detection rate for any defect averaged only 69%. Nasal steps were correctly identified more often (77%) than were hemianopic defects (44%). If this relatively low identification rate for hemianopias is representative, then patients with unexplained visual loss should all have CT scans regardless of the result of the visual field examination. Greater accuracy in perimetry may be achieved by improved teaching, by optimizing exploration strategies, and perhaps by automated devices.

False Negative Reactions↗
PubMed2001

Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations.

Seventy-nine unrelated Lebanese patients were tested for 15 mutations in the MEFV gene: A761H, A744S, V726A, K695R, M694V, M694I, M694del, M6801 (G --> C), M680I (G --> A) in exon 10, F479L in exon 5, P369S in exon 3, T267I, E167D and E148Q in exon 2, using PCR digestion, ARMS, DGGE and/or sequencing. Mutations were detected in patients belonging to all communities, most interestingly the Maronite, Greek orthodox, Greek catholic, Syriac and Chiite communities. The most frequent mutations are M694V and V726A (27% and 20% of the total alleles respectively). M694I, E148Q and M680I mutations account respectively for 9%, 8% and 5%. Each of the K695R, E167D and F479L mutations was observed once and all the remaining mutations were not encountered. Of the alleles 33% do not carry any of the studied mutations. The mutation spectra, clinical features and severity of the disease differed among the Lebanese communities. The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations at codon 694 in exon 10 (both M694V and M694I). None of the patients carrying other mutations developed amyloidosis.

Amyloidosis↗
PubMed1999

Safety in infants of SPf66, a synthetic malaria vaccine, delivered alongside the EPI.

The most likely mechanism to deliver a malaria vaccine in African countries is through the Expanded Program of Immunization (EPI). So far only SPf66, a multistage synthetic peptide, has shown any evidence of protection in Phase III field trials. In Tanzania, SPf66 reduced the risk of clinical malaria by 31% in children aged 1-5 years. In order to progress in the critical path of vaccine development and testing towards the implementation of a new vaccine in malaria control programs, we carried out a randomized double-blind placebo controlled efficacy trial of SPf66 when given alongside the EPI scheme. Monitoring of safety and reactogenicity during this trial included detailed clinical and laboratory assessments on 98 infants and assessment of adverse effects within 1 h of vaccination for all 1207 children vaccinated. Surveillance systems monitored attendances as outpatients, admissions to hospital and fatal events in the community. No serious adverse effects were detected more frequently amongst SPf66 recipients compared to placebo. This first assessment in very young infants of a synthetic vaccine provides evidence of a good safety profile.

Double-Blind Method↗
PubMed2003

Health education for nurses in Japan to combat child abuse.

A health education program for nurses was conducted to address the complex problem of child abuse, which has reached epidemic proportions. In Japan, the number of consultations has risen 23-fold over the past 11 years. Maltreatment of children is a public health problem as perilous as any contagious disease. The International Council of Nurses asks for nurses' leadership to strengthen measures to combat abuse throughout the world. The Japanese Nursing Association has published statements for prevention, detection and support. Yet, few community-based education programs with a multidisciplinary perspective have been reported that focus on nurses, the largest group of health providers. More than 200 nurse educators, clinicians and managers met for a one-day program designed to improve understanding of the nurses' role in combatting the abuse and neglect of children and to formulate action plans. This significant health problem is addressed in the context of a health education program's needs, objectives, content and evaluation.

Child↗
PubMed2002

Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics.

Antibiotics such as erythromycin and rifampicin, at low concentrations, alter global bacterial transcription patterns as measured by the stimulation or inhibition of a variety of promoter-lux reporter constructs in a Salmonella typhimurium library. Analysis of a 6,500-clone library indicated that as many as 5% of the promoters may be affected, comprising genes for a variety of functions, as well as a significant fraction of genes with no known function. Studies of a selection of the reporter clones showed that stimulation varied depending on the nature of the antibiotic, the promoter, and what culture medium was used; the response differed on solid as compared with liquid media. Transcription was markedly reduced in antibiotic-resistant hosts, but the presence of mutations deficient in stress responses such as SOS or universal stress did not prevent antibiotic-induced modulation. The results show that small molecules may have contrasting effects on bacteria depending on their concentration: either the modulation of bacterial metabolism by altering transcription patterns or the inhibition of growth by the inhibition of specific target functions. Both activities could play important roles in the regulation of microbial communities. These studies indicate that the detection of pharmaceutically useful natural product inhibitors could be effectively achieved by measuring activation of transcription at low concentrations in high-throughput assays using appropriate bacterial promoter-reporter constructs.

Anti-Bacterial Agents↗
PubMed1991

Women's knowledge of and attitude toward breast cancer in a developing country: implications for program interventions--results based on interviewing 500 women in Saudi Arabia.

We interviewed 500 adult females without personal history of any type of cancer to assess their awareness and attitude toward various aspects of breast cancer. The mean age (SD) of participants was 31.6 (+/- 8.5) years with a range of 18 to 62 years. After control for level of education, age was not found to be a statistically significant factor that influenced participants' performance. Also not statistically significant was the history of having a relative who had cancer. Conversely, education was the only examined factor that correlated with interviewees' awareness and attitude. Individuals with university or higher education (level III) were more knowledgeable (statistically significant) than uneducated or those with only primary schooling (level I), or those participants who only had intermediate or high school education (level II). On the other hand, the responses of those individuals with education level I generally performed in a fashion similar to those at education level II. The general outcome of this exercise was that unacceptably high proportions of females at all education levels were either wrong or uncertain about some fundamental aspects of breast cancer etiology, risk factors, clinical features, detection methods, and management. Also shown was the relatively high percentages of those, particularly in education level I, who held misconceptions about unconventional management or the complications of conventional methods. We conclude that academic education alone is not enough to assure that recommended health behaviors will be adopted. For establishing cancer health education or cancer prevention and early detection programs, primary care physicians and community cancer centers should work jointly. Brief guidelines are proposed.

Adolescent↗
PubMed2000

Methods for estimating gene frequencies and detecting selection in bacterial populations.

Recent breakthroughs in molecular technology, most significantly the polymerase chain reaction (PCR) and in situ hybridization, have allowed the detection of genetic variation in bacterial communities without prior cultivation. These methods often produce data in the form of the presence or absence of alleles or genotypes, however, rather than counts of alleles. Using relative allele frequencies from presence-absence data as estimates of population allele frequencies tends to underestimate the frequencies of common alleles and overestimate those of rare ones, potentially biasing the results of a test of neutrality in favor of balancing selection. In this study, a maximum-likelihood estimator (MLE) of bacterial allele frequencies designed for use with presence-absence data is derived using an explicit stochastic model of the host infection (or bacterial sampling) process. The performance of the MLE is evaluated using computer simulation and a method is presented for evaluating the fit of estimated allele frequencies to the neutral infinite alleles model (IAM). The methods are applied to estimate allele frequencies at two outer surface protein loci (ospA and ospC) of the Lyme disease spirochete, Borrelia burgdorferi, infecting local populations of deer ticks (Ixodes scapularis) and to test the fit to a neutral IAM.

Alleles↗
PubMed1982

Declining mortality from hypertension and stroke.

Recorded mortality from hypertension and stroke has decreased dramatically in most countries during the last 50 to 75 years. The reported reduction in mortality may be due to changes in diagnostic fashions or coding procedures. However, the magnitude and consistency of the decline suggests the occurrence of a true decrease. The possibility that better treatment of hypertension is responsible for the reduction in mortality is attractive. However, based on temporal relationships, it seems more likely that much of the fall has resulted from an alteration in the determinants of blood pressure. Increasing use of antihypertensive drug therapy may account for an acceleration in the decline of stroke mortality during the last decade. If so, this represents one of the first tangible benefits of the massive public health efforts to detect and treat hypertension in the community.

Age Factors↗
PubMed2003

Psychiatric genetics in Australia.

Australian research in psychiatric genetics covers molecular genetic studies of depression, anxiety, alcohol dependence, Alzheimer's disease, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. For each disorder, a variety of clinical cohorts have been recruited including affected sib pair families, trios, case/controls, and twins from a large population-based twin registry. These studies are taking place both independently and in collaboration with international groups. Microarray studies now complement DNA investigations, while animal models are in development. An Australian government genome facility provides a high throughput genotyping and mutation detection service to the Australian scientific community, enhancing the contribution of Australian psychiatric genetics groups to gene discovery.

Alcoholism↗
PubMed2006

Microbial diversity in alpine tundra wet meadow soil: novel Chloroflexi from a cold, water-saturated environment.

Cold, water-saturated soils play important biogeochemical roles, yet almost nothing is known about the identity and habitat of microbes active under such conditions. We investigated the year-round microenvironment of an alpine tundra wet meadow soil in the Colorado Rocky Mountains, focusing on the biogeochemistry and microbial diversity of spring snowmelt--a dynamic time for alpine ecosystems. In situ measurements revealed spring and autumn periods of long-term temperature stability near 0 degrees C, and that deeper soil (30 cm) was more stable than surface soil, with more moderate summers and winters, and longer isothermal phases. The soil was saturated and water availability was limited by freezing rather than drying. Analyses of bioavailable redox species showed a shift from Mn reduction to net Fe reduction at 2-3 cm depth, elevated SO4(2-) and decreased soluble Zn at spring snowmelt. Terminal restriction fragment length polymorphism profiles detected a correlated shift in bacterial community composition at the surface to subsurface transition. Bacterial and archaeal small-subunit rRNA genes were amplified from saturated spring soil DNA pooled along a depth profile. The most remarkable feature of these subsurface-biased libraries was the high relative abundance of novel, uncultivated Chloroflexi-related sequences comprising the third largest bacterial division sampled, and representing seven new Chloroflexi subdivisions, thereby dramatically expanding the known diversity of this bacterial division. We suggest that these novel Chloroflexi are active at near -0 degrees C temperatures, under likely anoxic conditions, and utilize geochemical inputs such as sulfide from upslope weathering.

Bayes Theorem↗
PubMed2005

Health economics of renal replacement therapy: perspectives from Singapore.

The prevalence of end-stage renal disease (ESRD) in Singapore is high and projected to increase sharply due to the aging population and the high prevalence of diabetes. The number of patients treated with dialysis was projected to rise from 2633 in 1999 to nearly 6000 in the year 2010. The cost of dialysis provision was estimated to increase 2.5-fold from US dollar 90 million in 1999 to US dollar 241 million in 2010. To address this, the Singapore Ministry of Health launched three initiatives in the year 2000: First, to reduce the incidence of ESRD through (1) primary prevention of diabetes, (2) community-based screening to facilitate early detection of patients with diabetes, (3) improving glycemic and blood pressure (BP) control of diabetics in the primary care setting, and (4) the establishment of dedicated Renal Retardation clinics to optimize BP control (and glycemic control for diabetics), and reduce the level of proteinuria in patients at high risk of ESRD development. Second, to increase the percentage of ESRD patients treated with continuous ambulatory peritoneal dialysis (CAPD), which is a lower-cost modality compared with hemodialysis; and third, amendments to the existing opt-out legislation for organ procurement for transplantation to increase the supply of kidneys for cadaveric renal transplant.

Humans↗
PubMed2005

Suppression of bladder epithelial cytokine responses by uropathogenic Escherichia coli.

Urinary tract infections are most commonly caused by uropathogenic strains of Escherichia coli (UPEC), which invade superficial bladder epithelial cells via a type 1 pilus-dependent mechanism. Inside these epithelial cells, UPEC organisms multiply to high numbers to form intracellular bacterial communities, allowing them to avoid immune detection. Bladder epithelial cells produce interleukin-6 (IL-6) and IL-8 in response to laboratory strains of E. coli in vitro. We investigated the ability of UPEC to alter epithelial cytokine signaling by examining the in vitro responses of bladder epithelial cell lines to the cystitis strains UTI89 and NU14. The cystitis strains induced significantly less IL-6 than did the laboratory E. coli strain MG1655 from 5637 and T24 bladder epithelial cells. The cystitis strains also suppressed epithelial cytokine responses to exogenous lipopolysaccharide (LPS) and to laboratory E. coli. We found that insertional mutations in the rfa and rfb operons and in the surA gene all abolished the ability of UTI89 to suppress cytokine induction. The rfa and rfb operons encode LPS biosynthetic genes, while surA encodes a periplasmic cis-trans prolyl isomerase important in the biogenesis of outer membrane proteins. We conclude that, in this in vitro model system, cystitis strains of UPEC have genes encoding factors that suppress proinflammatory cytokine production by bladder epithelial cells.

Cell Line, Tumor↗
PubMed2005

Staphylococcus aureus isolates carrying Panton-Valentine leucocidin genes in England and Wales: frequency, characterization, and association with clinical disease.

Staphylococcus aureus isolates carrying the genes that encode for Panton-Valentine leucocidin (PVL), a highly potent toxin, have been responsible for recent outbreaks of severe invasive disease in previously healthy children and adults in the United States of America and Europe. To determine the frequency of PVL-positive isolates sent to the Staphylococcus Reference Unit (United Kingdom) for epidemiological purposes, we tested 515 isolates of S. aureus, and 8 (1.6%) were positive for the PVL locus. A further 470 isolates were selected to explore the association of PVL-positive S. aureus with clinical disease. Of these, 23 (4.9%) were PVL positive and most were associated with skin and soft tissue infections (especially abscesses). The PVL genes were also detected in isolates responsible for community-acquired pneumonia, burn infections, bacteremia, and scalded skin syndrome. Genotyping by pulsed-field gel electrophoresis and multilocus sequence typing revealed that the PVL-positive isolates were from diverse genetic backgrounds, although one prevalent clone of 12 geographically dispersed methicillin-resistant S. aureus (MRSA) isolates was identified (ST80). All 12 isolates were stapylococcal cassette chromosome mec type IVc, had an agr3 allele, and shared a common toxin gene profile (sea-see, seg-sej, eta, etb, and tst negative but etd positive). ST80 strains with similar genetic characteristics have been responsible for community-acquired infections in France and Switzerland. The remaining PVL-positive isolates were mostly methicillin-sensitive S. aureus and belonged to 12 different sequence types, including ST22 and ST30, which are closely related to the most prevalent MRSA clones in United Kingdom hospitals, EMRSA-15 and EMRSA-16, respectively.

Bacterial Toxins↗
PubMed1994

Naturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive for antibody to hepatitis B surface antigen.

Hepatitis B virus (HBV) DNA was extracted from sera of six carriers with hepatitis B e antigen as well as antibody to hepatitis B surface antigen and sequenced within the pre-S regions and the S gene. HBV DNA clones from five of these carriers had point mutations in the S gene, resulting in conversion from Ile-126 or Thr-126 of the wild-type virus to Ser-126 or Asn-126 in three carriers and conversion from Gly-145 to Arg-145 in three of them; clones with Asn-126 or Arg-145 were found in one carrier. All 12 clones from the other carrier had an insertion of 24 bp encoding an additional eight amino acids between Thr-123 and Cys-124. In addition, all or at least some of the HBV DNA clones from these carriers had in-phase deletions in the 5' terminus of the pre-S2 region. These results indicate that HBV escape mutants with mutations in the S gene affecting the expression of group-specific determinants would survive in some carriers after they seroconvert to antibody against surface antigen. Carriers with HBV escape mutants may transmit HBV either by donation of blood units without detectable surface antigen or through community-acquired infection, which would hardly be prevented by current hepatitis B immuneglobulin or vaccines.

Adult↗
PubMed2005

The interrelation of demographic and geospatial risk factors between four common sexually transmitted diseases.

OBJECTIVES: To examine the interrelation between demographic and geospatial risk factors for gonorrhoea, chlamydia, genital warts, and genital herpes. DESIGN: We analysed age, sex, ethnicity, socioeconomic status, and area of residence for Leeds residents aged 15-54 with Neisseria gonorrhoeae, genital Chlamydia trachomatis, first episode genital herpes, and first episode genital warts during 1994-5. The 1991 UK census provided denominator population information. RESULTS: Regression analysis showed that young age (15-24 years), ethnicity (with a gradient of risk black >white >Asian), and residence in inner city areas of deprivation were independent risk factors for all STDs. There were highly significant correlations in the geospatial distribution of incidence rates between the four infections. However, there was variation in the degree of central urban clustering, with gonorrhoea having the most restricted, and genital warts and chlamydia the widest distribution. 31% of all disease occurred in the four inner city census wards, representing 15% of the population. CONCLUSION: These results are in keeping with core group theory applying in a unified manner to the four most common UK sexually transmitted diseases in this urban area. Population based studies are needed to clarify whether ethnicity is associated with differing sexual behavioural or mixing patterns. Our data suggest that chlamydia screening in women <25 years of age could detect 70% of cases in the community, that such programmes should give particular emphasis to implementation in core group areas, and that they could function as unifying strategies for the control of most common STDs within urban areas.

Adolescent↗
PubMed1999

Depression, cerebral atrophy, cognitive performance and incidence of dementia. Population study of 85-year-olds.

BACKGROUND: Hospital-based studies suggest that depression in old age relates to organic brain changes. AIMS: To determine whether these findings are confirmed in a population-based sample. METHOD: A population sample of non-demented 85-year-olds (227 mentally healthy and 62 with DSM-III-R depression were given a neuropsychiatric examination and computerised tomographic scans of the brain, and followed for three years. RESULTS: On the Mini-Mental State Examination, those with a low educational level with major depression performed worse than the mentally healthy; this distinction was not evident among those who had received higher education. Measures of brain atrophy were similar in depressed and mentally healthy individuals. The three-year incidence of dementia was increased in those with early-onset major depression. CONCLUSIONS: Higher education may protect against cognitive symptoms in depressed individuals. The association between depression and cerebral atrophy in the elderly is not very strong. The higher incidence of dementia in those with early-onset major depression may be due to a longer lifetime duration of depression, emphasising the importance of detecting and treating depression in the community.

Aged↗