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Biomedical subjects

J Griffith

Publications and source records attributed to J Griffith.

At least 19 recordsLinked to original sources
PubMed2006

Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition.

OBJECTIVES: This study tested the effect of Epimedium-derived phytoestrogen (PE) on preventing steroid-associated osteonecrosis (ON) in rabbit model. METHODS: Thirty 28-week-old male New-Zealand white rabbits were divided into control group (CON; n=14) and PE group (PE; n=16; 5 mg/kg body weight/day) after receiving an established inductive protocol for inducing steroid-associated ON. Before and after inductive protocol, Dynamic-MRI was employed on bilateral femora for local intra-osseous perfusion, blood samples were examined for coagulation, fibrinolysis and lipid-transportation, and marrow samples were quantified for adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular thrombosis and extravascular fat-cell-size were examined histopathologically. RESULTS: The incidence of ON in the PE group (31%) was significantly lower than that in the CON group (93%). Compared to the CON group, local intra-osseous perfusion was maintained in the PE group. Blocked trunk vessels were seldom found in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell-size were both significantly lower in the PE group than those in the CON group. During the early period after induction, indicator of coagulation, fibrinolysis, lipid-transportation and adipogenesis-gene expression were found with significantly changing pattern in the PE group compared to the CON group. CONCLUSION: PE was able to exert beneficial effect on preventing steroid-associated ON in rabbits with inhibition of both thrombosis and lipid deposition.

Adrenal Cortex Hormones↗
PubMed2006

Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone.

AIMS: The present study employed both static and dynamic imaging modalities to study both intra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS). METHODS: Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 microg/kg). 24 h later, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 h. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for hematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically. RESULTS: Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P<0.05). Compared to baseline, a significant decrease in ratio of tissue-type plasminogen activator/plasminogen activator inhibitor 1, activated partial thromboplatin time and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ON rabbits (P<0.05). Dynamic MRI showed a significant decrease in the perfusion index 'maximum enhancement' in the ON rabbits (P<0.05), and microCT-based microangiography showed blocked stem vessels in ON samples. Overall, 93% of the rabbits (13/14) developed ON, and no rabbits died throughout the experiment period. CONCLUSION: Both intra- and extravascular events were found attributing to the steroid-associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortality in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.

Animals↗
PubMed2003

Cerebral vasomotor reactivity testing in head injury: the link between pressure and flow.

BACKGROUND: It has been suggested that a moving correlation index between mean arterial blood pressure and intracranial pressure, called PRx, can be used to monitor and quantify cerebral vasomotor reactivity in patients with head injury. OBJECTIVES: To validate this index and study its relation with cerebral blood flow velocity and cerebral autoregulation; and to identify variables associated with impairment or preservation of cerebral vasomotor reactivity. METHODS: The PRx was validated in a prospective study of 40 head injured patients. A PRx value of less than 0.3 indicates intact cerebral vasomotor reactivity, and a value of more than 0.3, impaired reactivity. Arterial blood pressure, intracranial pressure, mean cerebral perfusion pressure, and cerebral blood flow velocity, measured bilaterally with transcranial Doppler ultrasound, were recorded. Dynamic cerebrovascular autoregulation was measured using a moving correlation coefficient between arterial blood pressure and cerebral blood flow velocity, the Mx, for each cerebral hemisphere. All variables were compared in patients with intact and impaired cerebral vasomotor reactivity. RESULTS: No correlation between arterial blood pressure or cerebral perfusion pressure and cerebral blood flow velocity was seen in 19 patients with intact cerebral vasomotor reactivity. In contrast, the correlation between these variables was significant in 21 patients with impaired cerebral vasomotor reactivity, whose cerebral autoregulation was reduced. There was no correlation with intracranial pressure, arterial blood pressure, cerebral perfusion pressure, or interhemispheric cerebral autoregulation differences, but the values for these indices were largely within normal limits. CONCLUSIONS: The PRx is valid for monitoring and quantifying cerebral vasomotor reactivity in patients with head injury. This intracranial pressure based index reflects changes in cerebral blood flow and cerebral autoregulatory capacity, suggesting a close link between blood flow and intracranial pressure in head injured patients. This explains why increases in arterial blood pressure and cerebral perfusion pressure may be useful for reducing intracranial pressure in selected head injured patients (those with intact cerebral vasomotor reactivity).

Adolescent↗
PubMed2002

The Adolescent Food Habits Checklist: reliability and validity of a measure of healthy eating behaviour in adolescents.

OBJECTIVE: Amid concerns about the quality of young people's diets, this paper describes the development of a measure of healthy eating behaviour for use with adolescents. DESIGN: Items for the measure were selected from a larger pool on the basis of responses from a pilot study. The 23-item checklist was validated using measures of dietary fat and fibre intake, fruit and vegetable consumption, dietary restraint, nutrition knowledge and a measure of family income. SETTING: Participants came from seven secondary schools in the north-west of England. SUBJECTS: A total of 1822 adolescents aged between 13 and 16 y took part in the study, representing 84% of those invited to participate. RESULTS: Correlations between measures indicate a good level of convergent validity, and the checklist is also shown to have high internal and test-retest reliability. CONCLUSIONS: The focus on choices available to adolescents means that the checklist will provide a useful addition to food frequency-type approaches to the measurement of adolescent eating behaviour. SPONSORSHIP: This research was funded by the Medical Research Council and the Economic and Social Research Council's Health Variations Programme.

Adolescent↗
PubMed2001

Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells.

Immature dendritic cells (DCs) sample their environment for antigens and after stimulation present peptide associated with major histocompatibility complex class II (MHC II) to naive T cells. We have studied the intracellular trafficking of MHC II in cultured DCs. In immature cells, the majority of MHC II was stored intracellularly at the internal vesicles of multivesicular bodies (MVBs). In contrast, DM, an accessory molecule required for peptide loading, was located predominantly at the limiting membrane of MVBs. After stimulation, the internal vesicles carrying MHC II were transferred to the limiting membrane of the MVB, bringing MHC II and DM to the same membrane domain. Concomitantly, the MVBs transformed into long tubular organelles that extended into the periphery of the cells. Vesicles that were formed at the tips of these tubules nonselectively incorporated MHC II and DM and presumably mediated transport to the plasma membrane. We propose that in maturing DCs, the reorganization of MVBs is fundamental for the timing of MHC II antigen loading and transport to the plasma membrane.

Animals↗
PubMed2001

Clinical significance of P-glycoprotein immunohistochemistry and doxorubicin binding assay in patients with osteosarcoma.

In 45 osteosarcoma patients, mean age 18 (4-61) years and followed for 14 (5-48) months, we studied the sensitivity to doxorubicin as well as P-glycoprotein expression, and compared these with the extent of tumour necrosis following chemotherapy. Doxorubicin assay was positive in 37 patients in whom necrosis induced by chemotherapy was good in 20 and poor in 17. Metastases developed in nine patients. In eight patients in whom doxorubicin assay indicated tumour resistance, chemonecrosis was poor and all developed pulmonary metastases. P-glycoprotein was studied in pre-treatment biopsies and post-treatment resection specimens. Its expression was positive in 16 patients in whom the necrosis induced by chemotherapy was good in four and poor in 12. In 29 patients with negative P-glycoprotein expression, necrosis was good in 16 and poor in 13. The doxorubicin sensitivity had a high correlation with chemonecrosis (P=0.006) and the incidence of metastases (P<0.001). However, P-glycoprotein expression at the time of diagnosis did not correlate statistically with chemonecrosis (P=0.066). Doxorubicin sensitivity prior to treatment is a better determinant of the response to chemotherapy and clinical outcome than is the P-glycoprotein expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Laboratory enhanced surveillance for meningococcal disease in Victoria.

OBJECTIVE: To describe the epidemiological and microbiological characteristics and notification patterns of invasive meningococcal disease (IMD) in Victoria between 1990 and 1999. METHODS: Cases of IMD occurring between 1990 and 1995 identified in any of three databases were combined, matching where possible. Statistical modelling provided estimates of cases missing from all datasets. Notification sources for 1999 and 2000 cases were identified. Cases identified from notification and laboratory results provided the data to describe IMD epidemiology between 1990 and 1999. RESULTS: Between 1990 and 1995, 479 cases of IMD were identified. Three individual datasets each identified between 62 and 82% of cases and 47% of cases were identified in all three datasets. Statistical modelling estimated that between 37 and 83 additional cases were not identified by any dataset. Serogroup B and C strains caused 63 and 33% of culture-positive cases, respectively, with a substantial rise in serogroup C cases in 1999. Epidemiological characteristics remained relatively constant between 1990 and 1998, but an increase in patient age was seen in cases with serogroup C disease in 1999. In addition to three clonal strains seen elsewhere, an additional strain was identified that was unique to Victoria. Since January 1999, only 72% of notifications have come from treating doctors. CONCLUSIONS: Meningococcal disease is of increasing public health significance in Victoria. Laboratory enhanced notification has improved case identification and detailed microbiological information has improved our understanding of the changing epidemiology of this disease. Collaboration with laboratories and other agencies, active investigation of putative cases and microbiological monitoring are important elements in supporting public health decisions about the control of IMD.

Age Distribution↗
PubMed2001

What is the impact of early rheumatoid arthritis on the individual?

Rheumatoid arthritis has a significant impact on patients' physical, emotional and social functioning that often occurs very early in the disease with the onset of symptoms. Patients therefore come to their consultation with the rheumatologist, having often experienced these symptoms over a period of some months, with specific expectations (for reassurance and diagnosis) and their own understanding and beliefs about the aetiology and prognosis of their symptoms. Information and advice given by rheumatologists will be rejected by patients if it cannot be accommodated within these lay beliefs. The diagnosis itself can cause a variety of reactions, including relief, disbelief, anger, fear and devastation. Following diagnosis, patients are faced with the problems of adapting to a new self-concept, managing their symptoms and trying to assimilate the large amount of information that they are given about their disease, its treatment, preferred health behaviours, prognosis and so on. There are a number of ways in which health professionals can reduce this impact in early disease. Eliciting patients' lay beliefs about the cause of their symptoms will ensure that information given in the consultation is relevant to individual patients and is presented in a way that has meaning for them. Determining patients' expectations of the rheumatologist will ensure that patients' needs for information and reassurance are met and that unrealistic or inappropriate expectations can be discussed and re-negotiated. Understanding patients' attitudes towards treatment interventions will inform shared clinical decision-making and promote adherence. Obtaining this information in the context of a time-limited consultation can be assisted by the use of validated clinical tools, presented as self-completed questionnaires. Further research is needed to determine the content, frequency, timing and methodology of educational interventions in early rheumatoid arthritis and to improve the understanding of the complex interaction between lay beliefs and disease outcome.

Arthritis, Rheumatoid↗
PubMed2001

Surveillance of antibiotic resistance in invasive isolates of Neisseria meningitidis in Australia 1994-1999.

A total of 1434 strains of Neisseria meningitidis isolated from cases of invasive meningococcal disease (IMD) in Australia between 1994 and 1999 were examined by standard methods for susceptibility to antibiotics used for treatment and prophylaxis. The proportion of isolates fully susceptible to penicillin decreased from 45% in 1994 to 26% in 1999 (P<0.001). All the other isolates were less sensitive to penicillin except for two meningococci with a penicillin MIC of 1 mg/l. The geometric mean penicillin MIC increased from 0.045 to 0.065 mg/l from 1994 to 1999. There was no significant difference in the geometric mean penicillin MICs of serogroup B and serogroup C meningococci. Penicillin susceptibility was significantly associated with a poorer outcome. Isolates from survivors of IMD had a higher geometric mean penicillin MIC (0.06 mg/l) than those from fatal cases (0.048 mg/l) (P< 0.001). This suggests that factors other than the decrease in susceptibility to penicillin observed were more relevant to outcome in IMD. All isolates were fully susceptible to ceftriaxone. Rifampicin resistance was infrequent (eight isolates in 6 years) and sporadic. A single isolate had decreased quinolone susceptibility. Despite the significant shift in susceptibility to penicillin recorded, this group of antibiotics remains a suitable treatment for IMD in Australia.

4-Quinolones↗
PubMed2001

The Neurospora crassa genome: cosmid libraries sorted by chromosome.

A Neurospora crassa cosmid library of 12,000 clones (at least nine genome equivalents) has been created using an improved cosmid vector pLorist6Xh, which contains a bacteriophage lambda origin of replication for low-copy-number replication in bacteria and the hygromycin phosphotransferase marker for direct selection in fungi. The electrophoretic karyotype of the seven chromosomes comprising the 42.9-Mb N. crassa genome was resolved using two translocation strains. Using gel-purified chromosomal DNAs as probes against the new cosmid library and the commonly used medium-copy-number pMOcosX N. crassa cosmid library in two independent screenings, the cosmids were assigned to chromosomes. Assignments of cosmids to linkage groups on the basis of the genetic map vs. the electrophoretic karyotype are 93 +/- 3% concordant. The size of each chromosome-specific subcollection of cosmids was found to be linearly proportional to the size of the particular chromosome. Sequencing of an entire cosmid containing the qa gene cluster indicated a gene density of 1 gene per 4 kbp; by extrapolation, 11,000 genes would be expected to be present in the N. crassa genome. By hybridizing 79 nonoverlapping cosmids with an average insert size of 34 kbp against cDNA arrays, the density of previously characterized expressed sequence tags (ESTs) was found to be slightly <1 per cosmid (i.e., 1 per 40 kbp), and most cosmids, on average, contained an identified N. crassa gene sequence as a starting point for gene identification.

Bacteriophage lambda↗
PubMed2001

Socioeconomic status and weight control practices in British adults.

STUDY OBJECTIVE: Attitudes and practices concerning weight control in British adults were examined to test the hypothesis that variation in concern about weight and deliberate weight control might partly explain the socioeconomic status (SES) gradient in obesity. Higher SES groups were hypothesised to show more weight concern and higher levels of dieting. SETTING: Data were collected as part of the monthly Omnibus Survey of the Office of National Statistics in March 1999. PARTICIPANTS: A stratified, probability sample of 2690 households was selected by random sampling of addresses in Britain. One randomly selected person in each household was interviewed at their home. MAIN RESULTS: As predicted, higher SES men and women had higher levels of perceived overweight, monitored their weight more closely, and were more likely to be trying to lose weight. Higher SES groups also reported more restrictive dietary practices and more vigorous physical activity. CONCLUSIONS: The results are consistent with the idea that part of the protection against weight gain in higher SES groups could be a higher frequency of weight monitoring, a lower threshold for defining themselves as overweight, and a greater likelihood of deliberate efforts at weight control.

Adult↗
PubMed2001

An outbreak of serogroup C meningococcal disease associated with a secondary school.

An outbreak of 3 cases of invasive meningococcal disease occurred in a secondary school on 2 campuses in Victoria. Despite having only one isolate (a C.2a:nst strain), meningococcal DNA was identified by polymerase chain reaction (PCR) in early culture-negative blood specimens of the other 2 cases. Both were subsequently shown by PCR to be capsule serogroup C by PCR. An committee was formed to manage the response to the outbreak. Chemoprophylaxis was offered to family and children who had been in close contact with the cases. As one strain had been confirmed as being of a vaccine-preventable group, vaccination was offered to the whole school community as well as the families of cases. The direct costs of the outbreak to public health, which would have been identical whatever the causative serogroup, was $8,178. Vaccine charges accounted for most of the additional $56,941 cost of vaccinating the target group of 1600 students, staff, and families. No further cases have been associated with this outbreak.

Child↗
PubMed2001

S-adenosylmethionine decarboxylase overexpression reduces invasiveness and tumorigenicity in nude mice of MCF-7 breast cancer cells.

To elucidate the role of S-adenosylmethionine decarboxylase (SAMDC) in breast cancer biology, we have generated SAMDC overexpressing MCF-7 breast cancer cells. SAMDC overexpression did not alter in a major way growth properties of MCF-7 cells in soft agar, either under basal conditions or in response to estrogen and antiestrogen administration. SAMDC-MCF-7 cells, on the other hand, exhibited a markedly reduced invasive ability in matrigel (p=0.013). Furthermore, they were less tumorigenic in nude mice. The odds for control clones to form tumors were 3.13 (C.1.1.2-8.2, p=0.0184) higher than those for SAMDC clones. The odds ratio were identical in the absence and in the presence of estradiol. In addition, the growth rate of established tumors was slower for SAMDC than for control clones. Overall, our results are consistent with the notion that these phenotypic changes induced by SAMDC overexpression are primarily mediated by suppression of cellular putrescine (and, possibly, spermidine) levels.

Adenosylmethionine Decarboxylase↗
PubMed2001

Prokaryote multidrug efflux proteins of the major facilitator superfamily: amplified expression, purification and characterisation.

In bacterial genomes 3-12% of open reading frames are predicted to encode membrane transport proteins. These proteins can be vital for antibiotic efflux, protein/ toxin secretion, cell nutrition, environmental sensing, ATP synthesis, and other functions. Some, such as the multidrug efflux proteins, are potential targets for the development of new antibacterials and also for applications in biotechnology. In general membrane transport proteins are poorly understood, because of the technical difficulties involved in isolating sufficient protein for elucidation of their structure-activity relationships. We describe a general strategy for the amplified expression, purification and characterisation of prokaryotic multidrug efflux proteins of the 'Major facilitator superfamily' of transport proteins, using the Bacillus subtilis multidrug resistance protein, 'Bmr', as example.

Amino Acid Sequence↗
PubMed2000

Monostotic fibrous dysplasia of the spine: report of a case involving the lumbar transverse process and review of the literature.

Monostotic fibrous dysplasia of the spine is rare. We report its clinical, radiologic and histologic features affecting a 47-year-old housewife. She presented with low-back pain of 1-year's duration, and radiographs showed a diffuse expansile lesion in the left transverse process of the fourth lumbar vertebra. The lesion was excised and histologically confirmed to be fibrous dysplasia. The patient remained well 8 years after operation. Including the present case, a total of 22 cases of monostotic fibrous dysplasia of the spine were found in the literature. Combining these reported cases, we found that the condition affects either sex with equal frequency and presents at any age, the mean being 32 years. There is no predilection for any part of the spinal column, though sacral or coccygeal involvement is distinctly rare. It most commonly involves the body and adjacent pedicle, although no part of the vertebra is spared. It is worth noting that a propensity for progressive enlargement, even to the extent of causing graft destruction, exists if the lesion is left untreated or incompletely treated. Complete removal of all involved bone, together with stabilization, should therefore be the treatment of choice for this condition.

Female↗
PubMed2000

Vertebral deformity in chinese men: prevalence, risk factors, bone mineral density, and body composition measurements.

The prevalence and risk factors for vertebral deformity were studied in 396 community-dwelling Chinese men aged 70-79 years. Anterior to posterior (H(a)/H(p)), middle to posterior (H(m)/H(p)) and posterior to posterior (H(p)/H(p - 1) or H(p)/H(p + 1)) ratios from T5 to L5 were derived from lateral spine X-ray films, using standardized digitization methods. Using values of 3 standard deviations (SD) or more below the mean and 4 SD or more below the mean as the cutoff, 16% and 7% of these men, respectively, were deemed to have one or more deformed vertebra. Heavy cigarette smoking, heavy alcohol consumption, and working as a heavy manual worker were risk factors for vertebral deformity. Men with severe vertebral deformity (VHR < mean - 4 SD below mean) had much lower body weight, fat mass, and bone mineral density (BMD) than controls. The odds ratios for severe vertebral deformity was 9.9 (95% CI 2.1-45.7) in the lowest quartile of femoral neck BMD.

Absorptiometry, Photon↗
PubMed2000

Varicella zoster virus infections following allogeneic bone marrow transplantation: frequency, risk factors, and clinical outcome.

Reactivation of varicella zoster virus (VZV) is a common event in patients undergoing allogeneic bone marrow transplantation (BMT) and may lead to life-threatening complications. We retrospectively analyzed the incidence, clinical outcome, and risk factors for VZV infections occurring within the first 5 years of transplantation in 100 consecutive adults undergoing allogeneic BMT between 1992 and 1997. Forty-one patients (41%) developed VZV reactivation a median of 227 days (range 45-346 days) post-transplantation. Twelve percent of VZV reactivation occurred in the first 100 days and 88% within the first 24 months. Among those who survived for 2 or more years after transplantation (n = 47), 59% developed VZV infection. Forty percent of patients with VZV reactivation required admission with a mean hospital stay of 7.2 days. Two patients developed encephalitis, and 1 died despite antiviral therapy. The most frequent complications were post-herpetic neuralgia and peripheral neuropathy (68%). Thoracic dermatomal zoster represented 41% of the infections; disseminated cutaneous involvement was observed in 17% of patients. No clinical or epidemiologic risk factors were associated with recurrence. Administration of ganciclovir for prevention of cytomegalovirus infection delayed the onset of VZV infection beyond 4 months (P = .06). In a further subset analysis, patients with a limited chronic graft-versus-host disease (GVHD) had a lower estimated incidence of VZV reactivation compared with those with extensive chronic GVHD (P = .11). We conclude that complications from reactivation of VZV infection are common and associated with considerable morbidity and mortality in patients undergoing allogeneic BMT.

2-Aminopurine↗