Biomedical subjects
Publications and source records attributed to M Hobbs.
It is clear that oxidative stress is associated with compromises to the lens. Recent literature indicates that antioxidants may ameliorate that risk and may actually decrease risk for cataract. This article will briefly review the etiology of cataract. It will also review the epidemiologic information with emphasis on roles for vitamins C and E and carotenoids. More thorough recent reviews are available.
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BACKGROUND: The revolution in coronary care in the mid-1980s to mid-1990s corresponded with monitoring of coronary heart disease (CHD) in 31 populations of the WHO MONICA Project. We studied the impact of this revolution on coronary endpoints. METHODS: Case fatality, coronary-event rates, and CHD mortality were monitored in men and women aged 35-64 years in two separate 3-4-year periods. In each period, we recorded percentage use of eight treatments: coronary-artery reperfusion before, thrombolytics during, and beta-blockers, antiplatelet drugs, and angiotensin-converting-enzyme (ACE) inhibitors before and during non-fatal myocardial infarction. Values were averaged to produce treatment scores. We correlated changes across populations, and regressed changes in coronary endpoints on changes in treatment scores. FINDINGS: Treatment changes correlated positively with each other but inversely with change in coronary endpoints. By regression, for the common average treatment change of 20, case fatality fell by 19% (95% CI 12-26) in men and 16% (5-27) in women; coronary-event rates fell by 25% (16-35) and 23% (7-39); and CHD mortality rates fell by 42% (31-53) and 34% (17-50). The regression model explained an estimated 61% and 41% of variance for men and women in trends for case fatality, 52% and 30% for coronary-event rates, and 72% and 56% for CHD mortality. INTERPRETATION: Changes in coronary care and secondary prevention were strongly linked with declining coronary endpoints. Scores and benefits followed a geographical east-to-west gradient. The apparent effects of the treatment might be exaggerated by other changes in economically successful populations, so their specificity needs further assessment.
This paper describes the construction and characterisation of a cDNA library from wheat endosperm tissue during the early stages of grain filling. Developing wheat endosperm tissue was characterised with respect to standard measures including dry weight, cytological appearance and timing of expression of major sources of mRNA such as the seed storage protein genes. In addition, the full complement of proteins present at mid-endosperm development was examined using 2D-electrophoretic techniques. Based on this characterisation, endosperm from the developing grain 8-12 days post-anthesis was chosen for isolating mRNA and preparing cDNA. At this stage in development the mRNA population is not yet dominated by the accumulation of mRNA from seed storage protein genes. A cDNA library, not normalised, containing a high percentage of full length cDNA clones was constructed and 4,319 clones sequenced ("single-pass"). Partitioning of the cDNA sequences into gene families and singletons provided the basis for quantifying the accumulation of sequence classes relative to the total number of sequences determined. The accumulation of gene families/singletons was not linear. However, mathematical modeling of the data suggested that the maximum number of different genes expressed is within the range of 4,500-8,000 (detailed in the Appendix). If an average is taken of these extremes, approximately 27% of the gene products were visible as proteins in the 2D-electrophoretic analysis. Analysis of a functional class of genes relevant to wheat grain end-use, namely the glutenin/gliadin seed storage protein class of genes, revealed a new category of gene characterised by a distinctive N-terminal domain and a reduced central repetitive domain.
We conducted interviews with 85 randomly selected general practitioners (GPs) in Central Sydney to examine patterns of referral of women with breast cancer, satisfaction with local services, awareness of evidence-based guidelines and suggestions for local support. Previous experience was the most frequently cited factor influencing choice of specialist (n = 80, 94%) followed by personal knowledge of the consultant's expertise (n = 72, 85%). Only one third of respondents agreed women wanted to be more involved in choosing the specialist (n = 28, 33%). Of 79 women recently diagnosed with breast cancer, the majority (96%) had been referred to a male surgeon (n = 71, 96%). While only 35% of the GPs rated the care received by women with breast cancer in local facilities as 'excellent', significantly fewer rated communication between GPs and specialists as 'excellent' (35% v 19%, p < 0.01). Younger GPs were less likely to rate communication as 'excellent' compared with GPs aged 55 years or older (p = 0.01). Only 18% of GPs considered their patients as having been 'very well informed' about their treatment choices. Younger GPs were more likely than older GPs to recall all available breast cancer guidelines (p = 0.02). Significantly more GPs (68%) requested seminars with experts than any other types of educational support (p < 0.001). To improve outcomes for women with breast cancer, mechanisms to support communication between GPs and specialists are recommended. Seminars for GPs with experts who emphasize evidence-based guidelines should be funded and evaluated, especially for impact in meeting the needs of older GPs.
BACKGROUND: Psychological debriefing is widely used for trauma victims but there is uncertainty about its efficacy. We have previously reported a randomised controlled trial which concluded that at 4 months it was ineffective. AIMS: To evaluate the 3-year outcome in a randomised controlled trial of debriefing for consecutive subjects admitted to hospital following a road traffic accident. METHOD: Patients were assessed in hospital by the Impact of Event Scale (IES), Brief Symptom Inventory (BSI) and questionnaire and re-assessed at 3 months and 3 years. The intervention was psychological debriefing as recommended and described in the literature. RESULTS: The intervention group had a significantly worse outcome at 3 years in terms of general psychiatric symptoms (BSI), travel anxiety when being a passenger, pain, physical problems, overall level of functioning, and financial problems. Patients who initially had high intrusion and avoidance symptoms (IES) remained symptomatic if they had received the intervention, but recovered if they did not receive the intervention. CONCLUSIONS: Psychological debriefing is ineffective and has adverse long-term effects. It is not an appropriate treatment for trauma victims.
Although immune response control of herpes simplex virus (HSV) has been well demonstrated, numerous HSV-2 strains are neurovirulent in immunocompetent mice. Using an RNase protection assay and an ELISA, we found that HSV-2-infected mice exhibited a deficient IFN-gamma response, an inability to clear virus, and eventual death. An HSV-based amplicon vector expressing mouse IFN-gamma was constructed and packaged into HSV-1-helper virus (HSV(pIFN-gamma)). In mice treated with HSV(pIFN-gamma), (i) the LD50 of HSV-2(G) increased 5000-fold, (ii) intracerebral IFN-gamma expression increased 10-fold, and (iii) HSV titer rapidly decreased. We suggest that the deficient IFN-gamma response is a basis for HSV-2 neurovirulence in mice.
In view of the relative risk of intracranial haemorrhage and major bleeding with thrombolytic therapy, it is important to identify as early as possible the low risk patient who may not have a net clinical benefit from thrombolysis in the setting of acute myocardial infarction. An analysis of 5434 hospital-treated patients with myocardial infarction in the Perth MONICA study showed that age below 60 and absence of previous infarction or diabetes, shock, pulmonary oedema, cardiac arrest and Q-wave or left bundle branch block on the initial ECG identified a large group of patients with a 28 day mortality of only 1%, and one year mortality of only 2%. Identification of baseline risk in this way helps refine the risk-benefit equation for thrombolytic therapy, and may help avoid unnecessary use of thrombolysis in those unlikely to benefit.
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Susceptibility of Neisseria gonorrhoeae to gentamicin, the primary treatment for gonorrhea in Malawi since 1993, was determined by using agar dilution MICs, E-test MICs, disc diffusion, and clinical cure rate. Agar dilution MICs were slightly higher in 1996 than in 1993 isolates, with a concomitant drop in the clinical cure rate. E-test MICs were substantially lower than agar dilution determinations, with only 77.4% within 1 log2 concentration.
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One of the main hypotheses of the World Health Organization (WHO) MONICA Project is that trends in the major coronary disease risk factors are related to trends in rates of fatal and non-fatal coronary disease events. The units of study are populations rather than individuals. The WHO MONICA Project involves continuous monitoring of all coronary disease events in the populations over a 10-year period and periodic risk factor surveys in random samples of the same populations. Estimation of associations between average annual changes in mortality and risk factor levels is illustrated with the use of data from a subset of MONICA centers. Crude estimates of regression coefficients are compared with estimates obtained by weighting for standard errors in both the outcome and explanatory variables. The results show that the strength of association may be either underestimated or overestimated if these errors are not taken into account.
Gene nomenclature for bacterial surface polysaccharides is complicated by the large number of structures and genes. We propose a scheme applicable to all species that distinguishes different classes of genes, provides a single name for all genes of a given function and greatly facilitates comparative studies.
Colanic acid (CA) is an extracellular polysaccharide produced by most Escherichia coli strains as well as by other species of the family Enterobacteriaceae. We have determined the sequence of a 23-kb segment of the E. coli K-12 chromosome which includes the cluster of genes necessary for production of CA. The CA cluster comprises 19 genes. Two other sequenced genes (orf1.3 and galF), which are situated between the CA cluster and the O-antigen cluster, were shown to be unnecessary for CA production. The CA cluster includes genes for synthesis of GDP-L-fucose, one of the precursors of CA, and the gene for one of the enzymes in this pathway (GDP-D-mannose 4,6-dehydratase) was identified by biochemical assay. Six of the inferred proteins show sequence similarity to glycosyl transferases, and two others have sequence similarity to acetyl transferases. Another gene (wzx) is predicted to encode a protein with multiple transmembrane segments and may function in export of the CA repeat unit from the cytoplasm into the periplasm in a process analogous to O-unit export. The first three genes of the cluster are predicted to encode an outer membrane lipoprotein, a phosphatase, and an inner membrane protein with an ATP-binding domain. Since homologs of these genes are found in other extracellular polysaccharide gene clusters, they may have a common function, such as export of polysaccharide from the cell.
As the cochlea develops, the cells in the basal cochlea become sensitive to progressively higher frequencies. To identify features of cochlear morphology that may underlie the place code shift, measurements of infant and adult gerbil cochleas were made at both the light and electron microscopic levels. The measurements included areas of the cochlear duct, basilar membrane, and organ of Corti, height and width of the basilar membrane, thickness of the tympanic cover layer, thickness of the upper and lower basilar membrane fiber bands, and optical density of the basilar membrane. The results indicated that basilar membrane dimensions do not change as the place code shifts and that regions that code for the roughly the same frequency (e.g., approximately 11.2 kHz) at different ages can have basilar membranes of very different dimensions. In contrast, the size of the organ of Corti and the thickness of fiber bands inside the basilar membrane do change in ways consistent with the shift in the frequency map.
3,6-dideoxyhexose (DDH) sugars occur in some of the O antigens of Salmonella enterica and Yersinia pseudotuberculosis, but are otherwise rarely found in nature. Y. pseudotuberculosis DDH biosynthetic genes rfbS (encoding CDP-paratose synthetase) and rfbE (encoding CDP-tyvelose epimerase) were amplified and cloned, and their sequences determined. Comparisons with the equivalent genes of S. enterica show that the genetic arrangement of DDH genes is very similar; however, in Y. pseudotuberculosis there is no suggestion that paratose producing strains are derived from tyvelose-producing strains by inactivation of rfbE, which is the case in S. enterica. The previously determined DNA sequence of the rfb region of an abequose-producing strain was re-examined. It contains the remnants of an insertion sequence (IS) adjacent to a truncated and non-functional rfbE gene. This suggests that the IS was involved in recombination events contributing to O-antigen antigenic diversity in Y. pseudotuberculosis.
Polyomavirus was originally isolated by Ludwick Gross from a mixture that also contained a murine retrovirus. A possible pathogenic interaction between polyomavirus and an endogenous mouse retrovirus locus (mtv-7) in polyomavirus-induced cancer has also been reported. To study potential interactive effects of polyomavirus (Py) and Moloney murine leukemia retrovirus (M-MuLV), newborn Balb/c and NIH Swiss mice were infected with high titer wild-type Py (A2 strain) and M-MuLV. Dramatically stunted growth (runting) occurred in 100% of the doubly inoculated mice, while much lower frequency of runting occurred in animals infected with Py alone and not at all with M-MuLV-infected mice. In situ hybridization for Py DNA showed ongoing Py replication and inflammation in kidneys (atypical of most mice singly infected by Py) of runted doubly inoculated mice. In addition, high Py viral replication continued well past the usual acute stage termination. M-MuLV replication was also initially inhibited in bone marrow by simultaneous Py infection. No M-MuLV replication was seen in singly or doubly infected mouse kidneys. Runting was very rapid, observable within 2 days after co-infection, arguing against an adaptive or antigen-specific immunological mechanism. One possibility was that a cytokine-driven acute response mechanism was involved. Supporting this view, RNAse protection assays for various cytokine RNAs showed that several were specifically elevated in kidneys of doubly infected mice. Three patterns were observed: (1) IL-6 was elevated in doubly infected mice early after infection (7 days), but it declined at later times (19 days); (2) IFN-gamma, IL-1 beta, and IL-10 were elevated at both early and late times; and (3) TNF-alpha, IL-12p40, and possibly TNF-beta were elevated only at late times. While the cytokines in the third category might be indicative of infiltrating inflammatory cells, it seems possible that cytokines in the first or second categories might be involved in establishing runting and ongoing polyoma DNA replication in the doubly infected mice.
St. Jude Medical Center, a Sisters of St. Joseph Health System Corporation in Fullerton California, in their efforts at work redesign, realized that the success of a patient-centered care delivery system largely depended upon successful selection of the most suitable team members. The interviewing and selection process used at St. Jude Medical Center includes a structured interview process with integration of both situational and behavioral styles in conjunction with objective rating scales and values driven questions. A common thread woven into the hiring criteria for all levels of personnel in the patient-centered care delivery model was creativity, adaptability, interpersonal skills and compatibility of values. Additionally, the clinical competence of the caregiver within the scope of practice/responsibility was essential for their expanded role. Management and leadership abilities for the managers are also addressed in the interview and selection process to provide the best team members for the overall success of the patient-care redesign.