bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a Highly Pathogenic H5N1 Avian Influenza A Virus Isolated from Duck Meat
Authors: Tumpey Terrence M. , Suarez David L. , Perkins Laura E. L. , Senne Dennis A. , Lee Jae-gil , Lee Youn-Jeong , Mo In-Pil , Sung Haan-Woo , Swayne David E.
Published: July 2002

Since the 1997 H5N1 influenza virus outbreak in humans and poultry in Hong Kong, the emergence of closely related viruses in poultry has raised concerns that additional zoonotic transmissions of influenza viruses from poultry to humans may occur. In May 2001, an avian H5N1 influenza A virus was isolated from duck meat that had been imported to South Korea from China. Phylogenetic analysis of the hemagglutinin (HA) gene of A/Duck/Anyang/AVL-1/01 showed that the virus clustered with the H5 Goose/Guandong/1/96 lineage and 1997 Hong Kong human isolates and possessed an HA cleavage site sequence identical to these isolates. Following intravenous or intranasal inoculation, this virus was highly pathogenic and replicated to high titers in chickens. The pathogenesis of DK/Anyang/AVL-1/01 virus in Pekin ducks was further characterized and compared with a recent H5N1 isolate, A/Chicken/Hong Kong/317.5/01, and an H5N1 1997 chicken isolate, A/Chicken/Hong Kong/220/97. Although no clinical signs of disease were observed in H5N1 virus-inoculated ducks, infectious virus could be detected in lung tissue, cloacal, and oropharyngeal swabs. The DK/Anyang/AVL-1/01 virus was unique among the H5N1 isolates in that infectious virus and viral antigen could also be detected in muscle and brain tissue of ducks. The pathogenesis of DK/Anyang/AVL-1/01 virus was characterized in BALB/c mice and compared with the other H5N1 isolates. All viruses replicated in mice, but in contrast to the highly lethal CK/HK/220/97 virus, DK/Anyang/AVL-1/01 and CK/HK/317.5/01 viruses remained localized to the respiratory tract. DK/Anyang/AVL-1/01 virus caused weight loss and resulted in 22 to 33% mortality, whereas CK/HK/317.5/01-infected mice exhibited no morbidity or mortality. The isolation of a highly pathogenic H5N1 influenza virus from poultry indicates that such viruses are still circulating in China and may present a risk for transmission of the virus to humans.
The Majority of Infiltrating CD8+T Cells in the Central Nervous System of Susceptible SJL/J Mice Infected with Theiler's Virus Are Virus Specific and Fully Functional
Authors: Kang Bong-Su , Lyman Michael A. , Kim Byung S.
Published: July 2002

Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains, such as SJL/J, and serves as a relevant infectious model for human multiple sclerosis. It has been previously suggested that susceptible SJL/J mice do not mount an efficient cytotoxic T-lymphocyte (CTL) response to the virus. In addition, genetic studies have shown that resistance to Theiler's virus-induced demyelinating disease is linked to theH-2Dmajor histocompatibility complex class I locus, suggesting that a compromised CTL response may contribute to the susceptibility of SJL/J mice. Here we show that SJL/J mice do, in fact, generate a CD8+T-cell response in the CNS that is directed against one dominant (VP3159-166) and two subdominant (VP111-20and VP3173-181) capsid protein epitopes. These virus-specific CD8+T cells produce gamma interferon (IFN-γ) and lyse target cells in the presence of the epitope peptides, indicating that these CNS-infiltrating CD8+T cells are fully functional effector cells. Intracellular IFN-γ staining analysis indicates that greater than 50% of CNS-infiltrating CD8+T cells are specific for these viral epitopes at 7 days postinfection. Therefore, the susceptibility of SJL/J mice is not due to the lack of an early functional Theiler's murine encephalomyelitis virus-specific CTL response. Interestingly, T-cell responses to all three epitopes are restricted by the H-2Ksmolecule, and this skewed class I restriction may be associated with susceptibility to demyelinating disease.
Targeting Adenoviral Vectors by Using the Extracellular Domain of the Coxsackie-Adenovirus Receptor: Improved Potency via Trimerization
Authors: Kim Jin , Smith Theodore , Idamakanti Neeraja , Mulgrew Kathy , Kaloss Michele , Kylefjord Helen , Ryan Patricia C. , Kaleko Michael , Stevenson Susan C.
Published: July 2002

Adenovirus binds to mammalian cells via interaction of fiber with the coxsackie-adenovirus receptor (CAR). Redirecting adenoviral vectors to enter target cells via new receptors has the advantage of increasing the efficiency of gene delivery and reducing nonspecific transduction of untargeted tissues. In an attempt to reach this goal, we have produced bifunctional molecules with soluble CAR (sCAR), which is the extracellular domain of CAR fused to peptide-targeting ligands. Two peptide-targeting ligands have been evaluated: a cyclic RGD peptide (cRGD) and the receptor-binding domain of apolipoprotein E (ApoE). Human diploid fibroblasts (HDF) are poorly transduced by adenovirus due to a lack of CAR on the surface. Addition of the sCAR-cRGD or sCAR-ApoE targeting protein to adenovirus redirected binding to the appropriate receptor on HDF. However, a large excess of the monomeric protein was needed for maximal transduction, indicating a suboptimal interaction. To improve interaction of sCAR with the fiber knob, an isoleucine GCN4 trimerization domain was introduced, and trimerization was verified by cross-linking analysis. Trimerized sCAR proteins were significantly better at interacting with fiber and inhibiting binding to HeLa cells. Trimeric sCAR proteins containing cRGD and ApoE were more efficient at transducing HDF in vitro than the monomeric proteins. In addition, the trimerized sCAR protein without targeting ligands efficiently blocked liver gene transfer in normal C57BL/6 mice. However, addition of either ligand failed to retarget the liver in vivo. One explanation may be the large complex size, which serves to decrease the bioavailability of the trimeric sCAR-adenovirus complexes. In summary, we have demonstrated that trimerization of sCAR proteins can significantly improve the potency of this targeting approach in altering vector tropism in vitro and allow the efficient blocking of liver gene transfer in vivo.
Ty3 Integrase Is Required for Initiation of Reverse Transcription
Authors: Nymark-McMahon M. Henrietta , Beliakova-Bethell Nadejda S. , Darlix Jean-Luc , Le Grice Stuart F. J. , Sandmeyer Suzanne B.
Published: July 2002

The integrase (IN) encoded by the
Saccharomyces cerevisiae
retroviruslike element Ty3 has features found in retrovirus IN proteins including the catalytic triad, an amino-terminal zinc-binding motif, and a nuclear localization sequence. Mutations in the amino- and carboxyl-terminal domains of Ty3 IN cause reduced accumulation of full-length cDNA in the viruslike particles. We show that the reduction in cDNA is accompanied by reduced amounts of early intermediates such as minus-strand, strong-stop DNA. Expression of a capsid (CA)-IN fusion protein (CA-IN) complemented catalytic site and nuclear localization mutants, but not DNA mutants. However, expression of a fusion of CA, reverse transcriptase (RT), and IN (CA-RT-IN) complemented transposition of catalytic site and nuclear localization signal mutants, increased the amount of cDNA in some of the mutants, and complemented transposition of several mutants to low frequencies. Expression of a CA-RT-IN protein with a Ty3 IN catalytic site mutation did not complement transposition of either a Ty3 catalytic site mutant or a nuclear localization mutant but did increase the amount of cDNA in several mutants and complement at least one of the cDNA mutants for transposition. These in vivo data support a model in which independent IN domains can contribute to reverse transcription and integration. We conclude that during reverse transcription, the Ty3 IN domain interacts closely with the polymerase domain and may even constitute a domain within a heterodimeric RT. These studies also suggest that during integration the IN catalytic site and at least portions of the IN carboxyl-terminal domain act in
cis
.
Selective Targeting and Inducible Destruction of Human Cancer Cells by Retroviruses with Envelope Proteins Bearing Short Peptide Ligands
Authors: Gollan Timothy J. , Green Michael R.
Published: July 2002

In the accompanying study, we show how retroviral tropism can be redirected by insertion of short peptide ligands at multiple locations in envelope. Here we use this approach to selectively target and destroy human cancer cells. Many cancer cells overexpress specific cell surface receptors. We have generated Moloney murine leukemia virus (MLV) envelope derivatives bearing short peptide ligands for gastrin-releasing protein (GRP) and human epidermal growth factor receptors. Pseudotyped viruses containing these chimeric envelope derivatives selectively transduce human cancer cell lines that overexpress the cognate receptor. A retrovirus targeting the GRP receptor can deliver the thymidine kinase gene to human melanoma and breast cancer cells, which are killed by the subsequent addition of ganciclovir. Collectively, our results demonstrate that short peptide ligands inserted at appropriate locations in MLV envelope can selectively target retroviruses to human cancer cells and deliver a therapeutically relevant gene.
Densities, Refractive Indices, Speeds of Sound and Shear Viscosities of Diethylene Glycol Dimethyl Ether Methyl Salicylate at Temperatures from 298.15 to 318.15 K
Authors: Aminabhavi Tejraj M. , Phayde Hemant T. S. , Khinnavar Rajashekhar S.
Published: July 2002

Densities, refractive indices, speeds of sound and viscosities of the diethylene glycol dimethyl ether - methyl salicylate system were measured as a function of mole fraction at 298.15, 303.15, 308.15, 313.15 and 318.15 K. The results are fitted by a power series equation involving both the temperature and mole fraction variables. The basic physical data of the mixtures are further used to calculate the excess molar volume VE, changes in isentropic compressibility ∆β, changes in refractivity ∆R and changes in viscosity ∆η. The results are fitted by the Redlich-Kister polynomial relation. The isobaric thermal expansion coefficients of the mixtures are also determined from density measurements. The data are compared with those obtained from equations derived by differentiation of the Lorentz-Lorenz and Eykman relations. Refractive indices of the mixture are used to test the validity of mixing relations. The changes in isobaric thermal expansion coefficients ∆α of the mixtures were examined. Viscosity data were tested in terms of the McAllister, Heric and Auslaender relations.
Oleanane Triterpenoids Functionalized at C-25 and C-26
Authors: Sejbal Jan , Klinot Jiří , Buděšínský Miloš
Published: July 2002

Reaction of 25-oximino-19β,28-epoxy-18α-oleanan-2β-ol (4) with nitrous acid afforded hemiacetal 22 ((25S)-2β,25;19β,28-diepoxy-18α-oleanan-25-ol). Functionalization of 19β,28-epoxy-18α-oleanan-2β-ol (1) with lead(IV) acetate gave 2β,25;19β,28-diepoxy-18α-oleanane (31). A series of derivatives with an oxygen functionality at position 25 has been prepared by modification of the functional groups in compounds 22 and 31. 26-Oximino-19β,28-epoxy-18α-oleanan-2β-ol (7) on reaction with nitrous acid afforded the corresponding nitrimine 10 which could not be converted into derivatives with an oxygen group at C-26: all the attempted preparations led invariably to compounds containing a nitrile group in position 8β. The nitrile groups in positions 10β and 8β appeared to be extremely unreactive.
A New Iterative Method of Construction of the Hammett Acidity Function
Authors: Pytela Oldřich
Published: July 2002

A new iterative algorithm has been devised for construction of the H acidity function. The procedure is based on gradual transformation of the dependence of log I vs acid concentration into the dependence of H vs acid concentration, and it involves four steps. In the first step a continuous acidity function is obtained by taking the average of log I values for the same acid concentrations. The second step of the algorithm is smoothing out of the acidity function by means of smoothing the H value by weighted moving average. In the third step, the mean distances between the log I values and the corresponding values of the smoothed acidity function H are calculated for the given indicator, and in the fourth step these distances are used together with log I values for calculating a new acidity function. The procedure designed was converted into a programme in the Delphi 2 language for PC Pentium and was successfully validated on literature data.
Self-Assembly of 1,1'-Biphenyl-2,2',6,6'-tetracarboxamides. Effect of Substitution at the Amidic Nitrogen
Authors: Holý Petr , Podlaha Jaroslav , Císařová Ivana , Závada Jiří
Published: July 2002

Self-assembly of three 1,1'-biphenyl-2,2',6,6'-tetracarboxamides 2a-2c differing each from the other by substitution at the amidic nitrogens (R = H, ethyl and 1-(R)-phenylethyl, respectively) was investigated by single crystal X-ray diffraction analysis. It was found that the unsubstituted tetracarboxamide 2a gives rise to infinite hydrogen-bonded 2D network composed from chiral cyclotetrameric squares (D4 symmetry). Such self-assembling pattern is suppressed by alkyl substitution in 2b and 2c, which disfavours formation of intermolecular amide-amide hydrogen bonds.
Evidence for the aetiology of injuries in Australian football
Authors: Norton K , Schwerdt S , Lange K
Published: July 2002

Objectives—To determine in Australian football (a) the influence of ground hardness and playing grade (level) on game speed and structure, and (b) player movement patterns throughout the game and across levels.

Methods—The design consisted of several studies. Seventeen games played on grounds of different hardness in 2000 were used to determine game speed and structure. Four first grade and four second grade grand final games (1994, 1996, 1997, 1999) were used to determine the game speed and structure on the same ground but at different levels. Fifty one players (44 first grade and seven second grade) were used to measure movement patterns within games and across levels during the 2000 season.

Results—There was a significant relation between ground hardness and game speed, which could lead to higher injury rates when the ground is harder. There was a 6.7% difference in game speed between the first and second grade levels reflecting differences in injury incidence. The first grade games were also characterised by a greater number of shorter, high intensity play periods and longer stop periods than the second grade games. Midfield players in the first grade games covered about 24% greater distance than their second grade counterparts, and there was a significant difference in their playing speeds.

Conclusions—Over the past 40 years, the game speed in the top level of Australian football has approximately doubled. Over the same time, the number of collisions and the estimated injury incidence have also doubled. This study provides additional support to the suggestion that these variables are strongly linked. Factors such as ground hardness, playing level, and time during the game influence game speed and are therefore important in injury development in Australian football.
Sea level and acute responses to hypoxia: do they predict physiological responses and acute mountain sickness at altitude?
Authors: Grant S , MacLeod N , Kay J W , Watt M , Patel S , Paterson A , Peacock A
Published: July 2002

Objectives: To compare a range of physiological responses to acute sea level hypoxia at simulated altitudes with the same physiological responses and acute mountain sickness (AMS) scores measured at altitude (similar to the simulated altitudes) during a 17 day trek in the Himalayas.

Methods: Twenty men and women aged 18–54 years took part in the study. End tidal CO2tension (Petco2) and saturated oxygen (Sao2) were measured using a capnograph. Observations made at sea level and some simulated altitudes were compared with those in the Himalayas. Pairwise correlations were used to examine the correlation between variables and regression, with 95% prediction intervals providing information on how well one variable could be predicted from another for a given subject.

Results: There was only a significant correlation for a few comparisons. The 95% prediction intervals for individual Sao2values at a range of simulated altitudes were fairly wide going from ± 4% to ± 5%. All of the correlations between laboratory and Himalayan Petco2values were not statistically significant. There was a significant correlation for the relation between Sao2and Petco2at sea level for the laboratory data (r=−0.51; p=0.05). For the Himalayan data, there were significant correlations at Namche Bazaar (3450 m; day 3) (r=−0.56; p=0.01) and Dingboche (4300 m; day 6) (r=−0.48; p=0.03). The correlation between Sao2and Petco2and AMS was generally poor.

Conclusions: The results indicate that limited information can be gained on a subject's response to altitude by assessing physiological variables at sea level and a range of simulated altitudes before the subject carries out a trek at altitude.
Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants
Authors: Ng P C , So K W , Fung K S C , Lee C H , Fok T F , Wong E , Wong W , Cheung K L , Cheng A F B
Published: July 2002

AIM

To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants.

METHODS

A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes.

RESULTS

Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms.

CONCLUSIONS

Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on hyperalimentation. However, until the safety of erythromycin has been confirmed in preterm infants, this treatment modality should remain experimental. Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage.
Inflammatory bowel disease and laterality: is left handedness a risk?
Authors: Morris D L , Montgomery S M , Galloway M L , Pounder R E , Wakefield A J
Published: July 2002

BACKGROUND

Left handedness has been associated with inflammatory bowel disease (IBD) and autoimmune diseases.

AIMS

To determine whether left handedness is associated with IBD in two prospective national birth cohorts.

METHODS

Subjects with Crohn's disease (CD) and ulcerative colitis (UC) were identified from two national longitudinal birth cohorts at age 26 years (1970 British Cohort Study (BCS70), born in 1970) and age 33 years (National Child Development Study (NCDS), born in 1958). Laterality was determined at age 10 (BCS70) or seven (NCDS) years, based on hand preference for writing and foot preference for kicking a ball (BCS70 only). Multiple logistic regression was used to assess the relationship of handedness with CD, UC, and IBD in the cohorts combined and adjusted for sex.

RESULTS

Both cohorts combined showed increased adjusted relative odds of 2.13 (95% confidence interval (CI) 0.97–4.65; p=0.059), 2.13 (95% CI 0.92–4.91; p=0. 077), and 2.13 (95% CI 1.20–3.78; p=0.010) for CD, UC, and IBD, respectively in left handers.

CONCLUSIONS

The study suggests a link between IBD and left handedness which may be genetic and/or environmental in origin.
Narrowing the gap: access to HIV treatments in developing countries. A pharmaceutical company's perspective
Authors: Cochrane James
Published: July 2002

The advent of new antiretroviral medicines means that the effects of HIV can now be curbed, but only one in twenty infected people have so far benefited. For those living in developing countries, the new treatments are practically unattainable. Governments, UNAIDS and pharmaceutical companies recognise this only too well and have rethought established assumption in order to try and overcome the challenges posed by cost, inadequate health services and unreliable local supply of medicines.
When is surgery research? Towards an operational definition of human research
Authors: Margo Curtis E
Published: July 2002

The distinction between clinical practice and surgical research may seem trivial, but this distinction can become a complex issue when innovative surgeries are substituted for standard care without patient knowledge. Neither the novelty nor the risk of a new surgical procedure adequately defines surgical research. Some institutions tacitly allow the use of new surgical procedures in series of patients without informing individuals that they are participating in a scientific study, as long as no written protocol or hypothesis exists. Institutions can justify this practice by viewing human research in narrow terms as an activity outlined in a formal protocol. Application of limited definitions, however, erodes patients' rights and risks losing public confidence in how biomedical research is conducted. I propose an operational definition of human research also be recognised. Enforcing more rigid and less ambiguous guidelines of human research may curtail enrolment into some studies, but it will also protect patients from being used as subjects without their knowledge.
Mental illness: psychiatry's phlogiston
Authors: Szasz Thomas
Published: July 2002

In physics, we use the same laws to explain why airplanes fly, and why they crash. In psychiatry, we use one set of laws to explain sane behaviour, which we attribute to reasons (choices), and another set of laws to explain insane behaviour, which we attribute to causes (diseases). God, man's idea of moral perfection, judges human deeds without distinguishing between sane persons responsible for their behaviour and insane persons deserving to be excused for their evil deeds. It is hubris to pretend that the insanity defence is compassionate, just, or scientific. Mental illness is to psychiatry as phlogiston was to chemistry. Establishing chemistry as a science of the nature of matter required the recognition of the non-existence of phlogiston. Establishing psychiatry as a science of the nature of human behaviour requires the recognition of the non-existence of mental illness.
Electronic communication in ethics committees: experience and challenges
Authors: Eiser Arnold R , Schade Stanley G , Anderson-Shaw Lisa , Murphy Timothy
Published: July 2002

Experience with electronic communication in ethics committees at two hospitals is reviewed and discussed. A listserver of ethics committee members transmitted a synopsis of the ethics consultation shortly after the consultation was initiated. Committee comments were sometimes incorporated into the recommendations. This input proved to be most useful in unusual cases where additional, diverse inputs were informative. Efforts to ensure confidentiality are vital to this approach. They include not naming the patient in the e-mail, requiring a password for access to the listserver, and possibly encryption. How this electronic communication process alters group interactions in ethics committees is a fruitful area for future investigation.
On the theory of individual health
Authors: Danzer G , Rose M , Walter M , Klapp B F
Published: July 2002

On top of elaborate methods and approaches in research, diagnostics, and therapy, medicine is in need of a theory of its own thought and action; without theoretical reflection and referentiality, action becomes blind (and thus costly) and thought takes on a monotonous and circular character. Take the concept of health. The field of medicine, more and more taking its cues from evidence-based medicine (EBM), is onesidedly oriented to concepts of health which are based on notions of standard values for large populations or—in the shadow of the genome project—see health as the outcome of an intact genome, often turning a blind eye to the individual aspects of health. With an eye in particular to Friedrich Nietzsche's philosophy, the present paper looks into some continental European theories of individual health, seeking to determine to what extent they can contribute to reducing medicine's theory deficit and what consequences this may have for research, diagnostics, and therapy.
Cohort study of occupational risk factors of low back pain in construction workers
Authors: Latza Ute , Karmaus Wilfried , Stürmer Til , Steiner Markus , Neth Axel , Rehder Uwe
Published: July 2002

OBJECTIVES

To identify work related risk factors of future low back pain (LBP) in a cohort of construction workers free of LBP at the start of follow up.

METHODS

The Hamburg construction worker study comprises 571 male construction workers who have undergone two comprehensive interview and physical examination surveys. A cohort of 285 subjects without LBP at baseline was identified. After a follow up of 3 years, the 1 year prevalence of self reported LBP was determined in the 230 men followed up (80.7%). Prevalence ratios (PRs) with 95% confidence intervals (95% CIs) of LBP at follow up according to self reported work tasks of construction workers measured at baseline were estimated from Cox's regression models which were adjusted for age, and anthropometric measures.

RESULTS

At follow up 71 out of 230 workers (30.9%) reported LBP during the preceding 12 months. Four work tasks (scaffolding, erecting roof structures, sawing wood, laying large sandstones) with an increased risk of 1 year prevalence of LBP at follow up were further evaluated. After further adjustment for occupation the relative risk was increased for workers who had reported ⩾2 hour/shifts laying large sandstones (PR=2.6; 95% CI 1.1 to 6.5). Work load of bricklayers was additionally estimated by an index on stone load (high exposure: PR=4.0; 95% CI 0.8 to 19.8), and an index for laying huge bricks/blocks (yes/no: PR=1.7; 95% CI 0.5 to 5.7).

CONCLUSIONS

The results suggest that self reported differences in brick characteristics (size and type of stone) and temporal aspects of the work of bricklayers (average hours per shift laying specified stones) can predict the future prevalence of LBP. The data have to be interpreted with caution because multiple risk factors were tested.
Rheumatoid arthritis in workers exposed to silica in the pottery industry
Authors: Turner Susan , Cherry Nicola
Published: July 2002

OBJECTIVE

To investigate the relation between rheumatoid arthritis and occupational exposure to silica in pottery and related industries.

METHODS

Medical records of 8325 men and women born 1916–45 and employed in pottery, refractory material (aluminosilicate or silica), and sandstone industries were examined to identify cases of rheumatoid arthritis. Medical and employment histories were extracted for cases and matched referents. Indices of duration, cumulative exposure, and mean silica concentration were compiled. Conditional logistic regression was used to investigate the relation between rheumatoid arthritis and indices of exposure, having allowed for potential confounders of smoking, employment in the coal mining industry, and number of pregnancies.

RESULTS

58 Cases of rheumatoid arthritis (43 men, 15 women) were identified. Cases had significantly shorter duration of exposure than referents. There was no significant difference between cases and referents in mean silica concentration. Men who had worked in the coal mining industry were particularly at risk (odds ratio 5.36, 95% confidence interval 1.92 to 15.03).

CONCLUSION

There was no evidence of increased risk of developing rheumatoid arthritis after occupational exposure to silica at mean exposures within the current United Kingdom exposure limits.
Occupational seafood allergy: a review
Authors: Jeebhay M F , Robins T G , Lehrer S B , Lopata A L
Published: July 2002

BACKGROUND

Recent years have seen increased levels of production and consumption of seafood, leading to more frequent reporting of allergic reactions in occupational and domestic settings. This review focuses on occupational allergy in the fishing and seafood processing industry.

REVIEW

Workers involved in either manual or automated processing of crabs, prawns, mussels, fish, and fishmeal production are commonly exposed to various constituents of seafood. Aerosolisation of seafood and cooking fluid during processing are potential occupational situations that could result in sensitisation through inhalation. There is great variability of aerosol exposure within and among various jobs with reported allergen concentrations ranging from 0.001 to 5.061(μg/m3). Occupational dermal exposure occurs as a result of unprotected handling of seafood and its byproducts. Occupational allergies have been reported in workers exposed to arthropods (crustaceans), molluscs, pisces (bony fish) and other agents derived from seafood. The prevalence of occupational asthma ranges from 7% to 36%, and for occupational protein contact dermatitis, from 3% to 11%. These health outcomes are mainly due to high molecular weight proteins in seafood causing an IgE mediated response. Cross reactivity between various species within a major seafood grouping also occurs. Limited evidence from dose-response relations indicate that development of symptoms is related to duration or intensity of exposure. The evidence for atopy as a risk factor for occupational sensitisation and asthma is supportive, whereas evidence for cigarette smoking is limited. Disruption of the intact skin barrier seems to be an important added risk factor for occupational protein contact dermatitis.

CONCLUSION

The range of allergic disease associated with occupational exposure to crab is well characterised, whereas for other seafood agents the evidence is somewhat limited. There is a need for further epidemiological studies to better characterise this risk. More detailed characterisation of specific protein antigens in aerosols and associated establishment of dose-response relations for acute and chronic exposure to seafood; the respective roles of skin contact and inhalational exposure in allergic sensitisation and cross reactivity; and the contribution of host associated factors in the development of occupational seafood allergies are important areas for future research.
International business travel: impact on families and travellers
Authors: Espino C M , Sundstrom S M , Frick H L , Jacobs M , Peters M
Published: July 2002

Objectives: Spouses and staff of the World Bank Group (WBG) were questioned about the impact of international business travel on families and travellers. Dependent variables were self reported stress, concern about the health of the traveller, and negative impact on the family. We hypothesised that several travel factors (independent variables) would be associated with these impacts. These travel factors had to do with the frequency, duration, and predictability of travel and its interference with family activities.

Methods: Survey forms were developed and distributed to all spouses of travelling staff as well as a small sample of operational staff. Kendall's tau b correlation coefficients of response frequencies were computed with the data from scaled items. Written responses to open ended questions were categorised.

Results: Response rates for spouses and staff were 24% and 36%, respectively. Half the spouse sample (n=533) and almost 75% of the staff sample (n=102) reported high or very high stress due to business travel. Self reported spouse stress was associated with six out of eight travel factors. Female spouses, those with children, and younger spouses reported greater stress. Self reported staff stress was significantly associated with four out of nine travel factors. Further insight into how business travel affects families and staff (including children's behavioural changes) and how families cope was gained through responses to written questions.

Conclusions: The findings support the notion that lengthy and frequent travel and frequent changes in travel dates which affect family plans, all characteristic of WBG missions, negatively affects many spouses and children (particularly young children) and that the strain on families contributes significantly to the stress staff feel about their travel. Policies or management practices that take into consideration family activities and give staff greater leeway in controlling and refusing travel may help relieve stress.
Galactorrhoea and pituitary mass: a typical prolactinoma?
Authors: Brändle Michael , Schmid Christoph
Published: July 2002

A 21 year old woman presenting with galactorrhoea, hyperprolactinaemia, and a pituitary mass on magnetic resonance imaging (MRI) is described who was referred to us before planned pituitary surgery. Although a thorough history did not suggest hypothyroidism, laboratory studies revealed profound primary hypothyroidism. At that time, pituitary MRI showed homogeneous enlargement of the pituitary gland consistent with pituitary hyperplasia due to primary hypothyroidism. With thyroid hormone replacement therapy the galactorrhoea resolved, concentrations of prolactin and thyroid hormones returned to normal, and the pituitary shrunk to normal size within two months. This case illustrates that primary hypothyroidism can present only with galactorrhoea and pituitary mass, and should therefore be considered in the differential diagnosis of hyperprolactinaemia and pituitary enlargement.
Role of smoking in inflammatory bowel disease: implications for therapy
Authors: Thomas Gareth A O , Rhodes John , Green John T , Richardson Charles
Published: July 2002

The relationship between smoking and inflammatory bowel disease is now firmly established but remains a source of confusion among both patients and doctors. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. In addition, it has opposite influences on the clinical course of the two conditions with benefit in ulcerative colitis but a detrimental effect in Crohn's disease. These differences have been the subject of much interest and scrutiny with the hope that they may offer some insight into the pathogenesis of the two conditions and possibly lead to alternative therapeutic options. Nicotine is probably the principal active ingredient in smoking responsible for the association; trials have shown it to be of some benefit in ulcerative colitis, but further research is required to establish its therapeutic role, and the relevant mechanisms responsible for its action. In this article, we review the role of smoking in inflammatory bowel disease and its implication for therapy.
Update on chronic viral hepatitis
Authors: Walsh K , Alexander G J M
Published: July 2002

Many recent and significant advances in the field of chronic viral hepatitis, including therapy, suggest that an update on chronic hepatitis is timely.

Chronic hepatitis B virus infection remains a significant worldwide cause of liver cirrhosis and hepatocellular carcinoma, despite the wide availability of a long established and effective vaccine. Transmission occurs via perinatal, sexual, and parenteral routes (particularly intravenous drug abuse and although blood products still carry a risk, this is now extremely low in Western countries). Only a minority of infected adult cases develop chronic hepatitis but in children under 1 year, 90% develop chronic hepatitis. The clinical spectrum of chronic liver injury ranges from mild inflammation to end stage liver cirrhosis. Interferon alfa has been the mainstay of treatment for patients with active disease but nucleoside analogues (lamivudine and adefovir) are now available with similar efficacy. Patients with end stage liver disease and hepatocellular carcinoma can be offered transplantation but infection in the graft is commonplace. The combination of hepatitis B immunoglobulin and newer antiviral drugs reduce the incidence and severity of graft infection significantly.

The hepatitis C virus epidemic of the latter half of the 20th century now affects more than 1% of populations worldwide. This RNA virus is spread parenterally and is becoming the leading indication for liver transplantation. The majority of patients develop chronic hepatitis, which may be progressive, evolving to significant liver disease (cirrhosis or hepatocellular carcinoma) in about 20% cases after decades. Treatment with the combination of interferon alfa and ribavirin is successful in up to 40% cases. Liver transplantation is a therapeutic option for some but graft infection is universal and often complicated by progressive liver fibrosis. A vaccine remains a remote prospect so that prevention is crucial.

Hepatitis D virus infection occurs on a background of hepatitis B virus infection and can also cause liver damage. The response to antiviral therapy is poor.

The newer “hepatitis” viruses G and TT do not cause significant liver injury.
Common krait (Bungarus caeruleus) bite in Anuradhapura, Sri Lanka: a prospective clinical study, 1996–98
Authors: Kularatne S A M
Published: July 2002

Common krait (Bungarus caeruleus) is the deadliest snake found commonly in the dry zone of Sri Lanka. In Anuradhapura, 210 farmers bitten by the common krait over a three year period were investigated prospectively from 1 January 1996. The sex ratio was equal, 110 (52%) patients were in the age group 10–30 years. One hundred and one (48%) patients were severely envenomed and needed mechanical ventilation from 12 hours to 29 days (mode two days). The bite occurred at night while the victims were asleep on the floor. In 99 (47%) situations killed specimens were available for identification. The cardinal symptom was abdominal pain developing within hours of the bite. Alteration in the level of consciousness was observed in 150 (71%) patients: drowsy in 91 (43%), semiconscious in 24 (11%), and deep coma in 35 (17%). Autonomic disturbances included transient hypertension, tachycardia, lacrimation, sweating, and salivation. These manifested in 139 (66%) patients with moderate to severe envenomation. One hundred and forty nine (71%) had hypokalaemia and 105 (50%) metabolic acidosis, anterograde memory loss in 84 (40%), and delayed neuropathy in 38 (22%) patients. Polyvalent antivenom had no significant benefit (t = 0.5) in reversing respiratory paralysis and preventing delayed neurological complications. Sixteen (7.6%) patients died and a submucosal haemorrhage in the stomach was seen at necropsy in three cases. Mortality could be minimised with early and free access to mechanical ventilation.
Variations in treatment benefits influence smoking cessation: results of a randomised controlled trial
Authors: Schauffler Helen H , McMenamin Sara , Olson Keri , Boyce-Smith Gifford , Rideout Jeffrey A , Kamil Jeffrey
Published: July 2002

OBJECTIVE

To assess the impact and costs of coverage for tobacco dependence treatment benefits with no patient cost sharing for smokers with employer sponsored coverage in two large independent practice association (IPA) model health maintenance organisations (HMOs) in California, USA.

METHODS

A randomised experimental design was used. 1204 eligible smokers were randomly assigned either to the control group, which received a self-help kit (video and pamphlet), or to the treatment group, which received the self-help kit and fully covered benefits for over the counter (OTC) nicotine replacement therapy (NRT) gum and patch, and participation in a group behavioural cessation programme with no patient cost sharing.

RESULTS

The quit rates after one year of follow up were 18% in the treatment group and 13% in the control group (adjusted odd ratio (OR) 1.6, 95% confidence interval (CI) 1.1 to 2.4), controlling for health plan, sociodemographics, baseline smoking characteristics, and use of bupropion. Rates of quit attempts (adjusted OR 1.4, 95% CI 1.1 to 1.8) and use of nicotine gum or patch (adjusted OR 2.3, 95% CI 1.6 to 3.2) were also higher in the treatment group. The annual cost of the benefit per user who quit ranged from $1495 to $965 or from $0.73 to $0.47 per HMO member per month.

CONCLUSIONS

Full coverage of a tobacco dependence treatment benefit implemented in two IPA model HMOs in California has been shown to be an effective and relatively low cost strategy for significantly increasing quit rates, quit attempts, and use of nicotine gum and patch in adult smokers.
Passive smoking in the home: plasma cotinine concentrations in non-smokers with smoking partners
Authors: Jarvis Martin J , Feyerabend Colin , Bryant Andrew , Hedges Barry , Primatesta Paola
Published: July 2002

BACKGROUND

Risks of lung cancer and of heart disease attributable to passive smoking have been evaluated mainly in non-smokers married to smokers, but there has been little quantitative assessment of the extent of exposure in marriage partners as indicated by markers of inhaled smoke dose.

OBJECTIVE

To relate plasma cotinine concentrations in non-smoking English adults to the smoking behaviour of their partners and to demographic and other factors.

DATA

Population survey. Data from two years (1994 and 1996) of the Health Survey for England.

MAIN OUTCOME MEASURES

Plasma cotinine concentrations in non-smoking adults married to or cohabiting with a partner.

RESULTS

There was a strong dose–response relation between cotinine concentrations in non-smoking adults and the smoking behaviour of their partners, rising from a geometric mean of 0.31 ng/ml in those with non-smoking partners to 1.99 ng/ml in those whose partners smoked 30 or more cigarettes per day. In addition, exposure was greater in men, in the autumn and winter, and in those living in more disadvantaged circumstances, and there was an increasing gradient of exposure from the south to the north of the country. On average, cotinine concentrations in non-smokers with a smoking partner were 0.6–0.7% of those in cigarette smokers.

CONCLUSIONS

If cotinine is taken as a measure of risk relevant dose, the implied increase in risk of lung cancer in non-smokers with smoking partners is consistent with the risk observed in epidemiological studies. Smoking by partners in the home is a major source of non-smoking adults' exposure to passive smoking.
The genetics of tobacco use: methods, findings and policy implications
Authors: Hall W , Madden P , Lynskey M
Published: July 2002

Research on the genetics of smoking has increased our understanding of nicotine dependence, and it is likely to illuminate the mechanisms by which cigarette smoking adversely effects the health of smokers. Given recent advances in molecular biology, including the completion of the draft sequence of the human genome, interest has now turned to identifying gene markers that predict a heightened risk of using tobacco and developing nicotine dependence
Differential and systemic alteration of defence-related gene transcript levels in mycorrhizal bean plants infected with Rhizoctonia solani
Authors: Guillon C , St-Arnaud M , Hamel C , Jabaji-Hare S H
Published: July 2002

The role of arbuscular mycorrhizas in response of plants to soilborne root pathogens is unclear. A time course study was conducted to monitor disease development and expression of mRNA for the defence-related genes phenylalanine ammonia lyase, chalcone synthase, chalcone isomerase, and hydroxyproline-rich glycoprotein in bean (Phasoelus vulgaris L.) plants colonized by the arbuscular mycorrhizal fungus Glomus intraradices Schenck & Smith and postinfected with the soilborne pathogen Rhizoctonia solani Kühn. Precolonization of bean plants by G. intraradices did not significantly reduce the severity of rot symptoms. RNA blot analysis of the defence-related genes revealed a systemic increase in the four defence genes in response to R. solani infections. On the other hand, precolonization of bean plants with G. intraradices elicited no change in phenylalanine ammonia lyase, chalcone synthase, and chalcone isomerase transcripts. A differential and systemic alteration in the expression of all four defence genes was observed in all tissues only during the pathogenic interaction of arbuscular mycorrhizal beans. Depending on the time after infection with R. solani and the tissue examined, varying responses from stimulation to suppression to no change in transcript levels were detected.Key words: induced resistance, defence-related genes, RNA analysis, Rhizoctonia solani, Glomus intraradices.
Enhancer of garnet/δAP-3 is a cryptic allele of thewhitegene and identifies the intracellular transport system for the white protein
Authors: Lloyd Vett K , Sinclair D AR , Alperyn M , Grigliatti T A
Published: July 2002

The white gene encodes an ABC-type transmembrane transporter that has a role in normal eye pigment deposition. In addition, overexpression in Drosophila leads to homosexual male courtship. Its human homologue has been implicated in cholesterol transport in macrophages and in mood disorders in human males. The garnet gene is a member of a group of other Drosophila eye colour genes that have been shown, or proposed, to function in intracellular protein transport. Recent molecular analysis indicates that it encodes the δ subunit of the AP-3 adaptin complex involved in vesicle transport from the trans-Golgi network to lysosomes and related organelles, such as pigment granules. This identification revealed a novel role for intracellular vesicular transport in Drosophila pigmentation. To further analyze this intracellular transport system, we examined the genetic interactions between garnet and a second site enhancer mutation, enhancer of garnet (e(g)). We show here that e(g) is a cryptic allele of the white gene. The white-garnet interaction is highly sensitive to the levels of both gene products but also shows some allele specificity for the white gene. The additive effect on pigmentation and the predicted protein products of these genes suggest that the garnet/AP-3 transport system ensures the correct intracellular localization of the white gene product. This model is further supported by the observation of homosexual male courtship behavior in garnet mutants, similar to that seen in flies overexpressing, and presumably mis-sorting, the white gene product. The we(g)allele also enhances mutations in the subset of other eye-color genes with phenotypes similar to garnet. This observation supports a role for these genes in intracellular transport and leads to a model whereby incorrect sorting of the white gene product can explain the pigmentation phenotypes of an entire group of eye-color genes.Key words: white, garnet, e(g), AP-3, adaptins.