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Biomedical subjects

R Hirsch

Publications and source records attributed to R Hirsch.

At least 19 recordsLinked to original sources

Carpal canal pressures after volar plating of distal radius fractures.

Elevated pressures within the carpal canal are known to occur after distal radius fractures. Controversy exists regarding prophylactic carpal tunnel release after open reduction with internal fixation of distal radius fractures. The purpose of this study was to determine the tissue pressures within the carpal canal after volar plating of distal radius fractures. This study was a prospective, observational, IRB approved research study. Ten consecutive patients undergoing volar plating of distal radius fractures were enrolled. After the distal radius fractures were reduced and fixed with volar plates, slit catheters were inserted into the carpal canals for continuous postoperative pressure monitoring for 24 hours. The maximum recorded pressure was 65 mmHg, which occurred in the only patient with fracture blisters. Peak pressures remained at 40 mmHg or less (range 16-40, mean 29) in all patients without fracture blisters. At the conclusion of data collection, all pressures were at 31 mmHg or less. No patient complained of median nerve dysfunction during the study period. Routine prophylactic carpal tunnel release is not recommended after volar plating of distal radius fractures based on these pressure recordings.

Adult↗

Angiopoietin-like-4 is a potential angiogenic mediator in arthritis.

Our previous studies of gene expression profiling during collagen-induced arthritis (CIA) indicated that the putative angiogenic factor Angptl4 was one of the most highly expressed mRNAs early in disease. To investigate the potential involvement of Angptl4 in CIA pathogenesis, Angptl4 protein levels were assessed at early stages of disease and its cellular sources were determined. In addition, the functional effects of mouse Angptl4 on endothelial cells were assessed. Angptl4 protein levels were higher in arthritic joints as compared to normal joints. In situ hybridization localized Angptl4 mRNA to stromal fibroblast-like cells within the inflamed synovium. Temporal expression of Angptl4 mRNA during CIA was similar to that of key angiogenic factors, including structurally related angiopoietin 1. Recombinant mouse Angptl4 promoted endothelial cell survival and formation of tubule-like structures. These functional effects of Angptl4, combined with very high expression at early stages of CIA, suggest a role for Angptl4 in angiogenesis in arthritis.

Angiopoietin-1↗

General and oral health implications of cannabis use.

Cannabis, commonly known as marijuana, is the most frequently used illicit drug in Australia. Therefore, oral health care providers are likely to encounter patients who are regular users. An upward trend in cannabis use is occurring in Australia, with 40 per cent of the population aged 14 and above having used the drug. There are three main forms of cannabis: marijuana, hash and hash oil, all of which contain the main psychoactive constituent delta-9-tetrahydrocannabinol (THC). Cannabis is most commonly smoked, however it can be added to foods. THC from cannabis enters the bloodstream and exerts its effects on the body via interaction with endogenous receptors. Cannabis affects almost every system of the body, particularly the cardiovascular, respiratory and immune systems. It also has acute and chronic effects on the mental health of some users. Therefore, chronic abuse is a concern because of its negative effects on general physical and mental health. Cannabis abusers generally have poorer oral health than non-users, with an increased risk of dental caries and periodontal diseases. Cannabis smoke acts as a carcinogen and is associated with dysplastic changes and pre-malignant lesions within the oral mucosa. Users are also prone to oral infections, possibly due to the immunosuppressive effects. Dental treatment on patients intoxicated on cannabis can result in the patient experiencing acute anxiety, dysphoria and psychotic-like paranoiac thoughts. The use of local anaesthetic containing epinephrine may seriously prolong tachycardia already induced by an acute dose of cannabis. Oral health care providers should be aware of the diverse adverse effects of cannabis on general and oral health and incorporate questions about patients' patterns of use in the medical history.

Cannabis↗

Gene expression in juvenile arthritis and spondyloarthropathy: pro-angiogenic ELR+ chemokine genes relate to course of arthritis.

OBJECTIVE: To evaluate the ability of microarray-based methods to identify genes with disease-specific expression patterns in peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) of juvenile arthritis patients and healthy controls. METHODS: Microarray data (Affymetrix U95Av2) from 26 PBMC and 20 SFMC samples collected from patients with active disease (classified by course according to ACR criteria) were analysed for expression patterns that correlated with disease characteristics. For comparison, PBMC gene expression profiles were obtained from 15 healthy controls. Real-time PCR was used for confirmation of gene expression differences. RESULTS: Statistical analysis of gene expression patterns in PBMC identified 378 probe sets corresponding to 342 unique genes with differing expression levels between polyarticular course patients and controls (t test, P<0.0001). The genes represented by these probe sets were enriched for functions related to regulation of immune cell functions, receptor signalling as well as protein metabolism and degradation. Included in these probe sets were a group of CXCL chemokines with functions related to angiogenesis. Further analysis showed that, whereas angiogenic CXCL (ELR+) gene expression was elevated in polyarticular PBMC, expression of angiostatic CXCL (ELR-) chemokines was lower in polyarticular SFMC compared with corresponding pauciarticular samples (t test, P<0.05). CONCLUSIONS: This pilot study demonstrates that juvenile arthritis patients exhibit complex patterns of gene expression in PBMC and SFMC. The presence of disease-correlated biologically relevant gene expression patterns suggests that the power of this approach will allow better understanding of disease mechanisms, identify distinct clinical phenotypes in disease subtypes, and suggest new therapeutic approaches.

Adolescent↗

The effects of a tea tree oil-containing gel on plaque and chronic gingivitis.

BACKGROUND: [corrected] This clinical study assessed the effects of topically applied tea tree oil (TTO)-containing gel on dental plaque and chronic gingivitis. METHODS: This was a double-blind, longitudinal, non-crossover study in 49 medically fit non-smokers (24 males and 25 females) aged 18-60 years with severe chronic gingivitis. Subjects were randomly assigned to three groups and given either TTO-gel (2.5 per cent), chlorhexidine (CHX) gel (0.2 per cent), or a placebo gel to apply with a toothbrush twice daily. Treatment effects were assessed using the Gingival Index (GI), Papillary Bleeding Index (PBI) and plaque staining score (PSS) at four and eight weeks. RESULTS: No adverse reactions to any of the gels were reported. The data were separated into subsets by tooth (anterior and posterior) and tooth surface (buccal and lingual). The TTO group had significant reduction in PBI and GI scores. However,,TTO did not reduce plaque scores, which tended to increase over the latter weeks of the study period. CONCLUSION: Although further studies are required, the anti-inflammatory properties of TTO-containing gel applied topically to inflamed gingival tissues may prove to be a useful non-toxic adjunct to chemotherapeutic periodontal therapy.

Adult↗

Quantitation using GC-TOF-MS: example of bromazepam.

Time-of-flight mass spectrometry (TOF-MS) offers new perspectives for forensic toxicology. Qualitative and quantitative analyses of a mixture of three selected benzodiazepines (diazepam, nordazepam and bromazepam) were used to compare gas chromatography (GC-TOF-MS, quadrupole GC-MS, GC-ECD) and liquid chromatography (HPLC-DAD) data. Method validation parameters like LOD, LOQ, S/N-ratios reflect the capabilities of GC-TOF-MS. Five-point calibrations for bromazepam in human peripheral blood (50, 100, 160, 200, 300 ng/ml) using medazepam as internal standard (1000 ng/ml) were performed. The calibrations using GC-TOF-MS (using the fragments of m/z 236 and 288), GC-ECD (dual system) and HPLC-DAD (at 235 nm) all showed correlation coefficients close or superior to 0.99. Quadrupole GC-MS data was not used in the comparison of extracted samples due to the low sensitivity in the full scan mode. Two analyses of real cases concerning bromazepam are presented. In the first case, the presence or absence of bromazepam could not be established with both HPLC-DAD and GC-ECD due to background signals. The extracted ion chromatograms and spectrum traces after the analysis with the GC-TOF-MS could clearly excluded the presence of bromazepam. The second case illustrates the quantitation of bromazepam, where both HPLC-DAD and GC-ECD were unable to give satisfactory results, again due to interfering background signals. The analyses performed on the GC-TOF-MS-system demonstrated high sensitivity and also high selectivity due to the high quality of mass spectra obtained. The advantages of GC-TOF-MS make it a promising analytical technique for forensic toxicology.

Anti-Anxiety Agents↗

NK cells secrete high levels of IFN-gamma in response to in vivo administration of IL-2.

Interleukin-2 is an immunotherapeutic agent for the treatment of metastatic tumors. Administration of recombinant human IL-2 (rhIL-2) in vivo activates lymphocytes and cell-mediated immune responses. In mice, we have recently observed a dramatic increase of serum IFN-gamma levels in response to in vivo administration of rhIL-2, which was necessary for the observed protective effects of IL-2 against the development of collagen-induced arthritis. To explore further the basis of this phenomenon, the kinetics and source of IFN-gamma in response to IL-2 was investigated. Highest serum levels of IFN-gamma were observed within 3 h of IL-2 administration, with levels decreasing over time. Anti-IL-2 receptor beta antibody blocked this IFN-gamma induction. Multiple doses of rhIL-2 resulted in corresponding increases in circulating IFN-gamma. IFN-gamma induction was dose-dependent between doses of 240 to 30,000 U of rhIL-2. Analysis of the cellular source of IFN-gamma secretion using NK- and T cell-deficient mice demonstrated that NK cells are the likely source of IFN-gamma. Furthermore, IFN-gamma secretion in response to IL-2 administration was not affected by the absence of IL-12, the pivotal cytokine for determination of Th1 responses. These results suggest that effects of IL-2 on immune responses in vivo may be mediated by IFN-gamma.

Animals↗

Expression of angiogenic factors in juvenile rheumatoid arthritis: correlation with revascularization of human synovium engrafted into SCID mice.

OBJECTIVE: Although increased vascularity was noted in early histopathologic studies of juvenile rheumatoid arthritis (JRA) synovium, the available data on angiogenesis in JRA are very limited. The main purposes of this study were to assess expression of the key angiogenic factors in JRA synovium, and to evaluate a SCID mouse model of JRA as an approach to study in vivo regulation of the expression of these factors in JRA. METHODS: RNase protection assay was used to assess the expression of the key angiogenic factors in fresh JRA synovium and in JRA synovial tissue fragments that had been minced and then implanted into SCID mice. Vascularity of the samples was assessed by immunohistochemical staining for von Willebrand factor. Synovial specimens obtained from patients with osteoarthritis (OA) or other noninflammatory arthropathies were used as controls. RESULTS: Detectable levels of messenger RNA for vascular endothelial growth factor and angiopoietin 1 and their respective receptors, as well as endoglin and thrombin receptors, were present in all JRA tissue specimens studied. The levels of expression of these factors in JRA tissues were significantly higher than those in tissues obtained from patients with OA or other noninflammatory arthropathies. Furthermore, increased expression of the key angiogenic factors in the fresh JRA tissues correlated with the exuberant revascularization of JRA minced tissue fragments implanted into SCID mice. This was in sharp contrast to the poor revascularization of implanted OA tissues. CONCLUSION: JRA synovium is characterized by high angiogenic activity. SCID mouse-human JRA synovium chimeras may provide a good approach to study the in vivo regulation of angiogenesis in JRA.

Angiopoietin-1↗

MR imaging of murine arthritis using ultrasmall superparamagnetic iron oxide particles.

The objective of this work was to determine the ability of magnetic resonance (MR) imaging with ultrasmall superparamagnetic iron oxide (USPIO) particles to provide quantitative measures of inflammation in autoimmune arthritis. Mice were injected intravenously or intra-articularly with USPIO followed by magnetic resonance and histological assessment of the knee joint. Comparisons were made between MR microimages and histology in naïve mice and mice with collagen-induced arthritis.Following intravenous administration, accumulation of USPIO was observed in the popliteal lymph nodes, but not the joint. Administration of USPIO intra-articularly resulted in signal loss in the joint. The MR signal intensity could be quantified and correlated with iron staining in the synovial lining. A marked increase in USPIO uptake and a corresponding decrease in signal intensity were observed in arthritic, compared to naïve mice. Areas of focal signal loss corresponded to foci of iron staining by histology. These studies may provide a basis for the clinical application of USPIO in arthritis for assessing disease severity and monitoring response to therapy.

Animals↗

Low-dose aspirin therapy and periodontal attachment loss in ex- and non-smokers.

BACKGROUND, AIMS: This study investigated the periodontal status of non-smokers and ex-smokers in relation to their intake of low-dose aspirin. METHODS: A self-selected sample of 392 males aged 50 years and over was recruited from the general population. Subjects were included in the study if they had a minimum of 6 or more natural teeth, took aspirin (300 mg or less per day) for at least 2 years and were either ex- or non-smokers. Controls were subjects who did not take aspirin regularly. A questionnaire was used to record demographic data, medical and dental histories. Individuals who had diabetes or other systemic diseases were excluded from the study. Periodontal attachment loss (PAL) was calculated by adding measurements of gingival recession and periodontal pocket depth made by a single examiner at 6 sites around each tooth using non-pressure sensitive periodontal probes. Plaque and gingival bleeding indices were also scored. Subjects were divided into 4 groups: aspirin non-smokers, aspirin ex-smokers, no aspirin non-smokers and no aspirin ex-smokers. Data were analysed using two-way ANOVA with age as the covariate. Severity and extent of mean PAL and the cumulative distribution of the mean of the most severe sites (MSS) of PAL were analysed. RESULTS: Controlling for age, mean PAL in aspirin takers was significantly less 2.6+/-0.08 (se) mm than non-aspirin takers 2.9+/-0.06 (se) mm; this association was independent of smoking history. Ex-smokers had significantly more mean PAL 3.9+/-0.07 (se) mm than non-smokers 2.6+/-0.08 (se) mm, irrespective of aspirin status. When MSS-PAL was analysed, these differences became more pronounced; MSS-PAL in aspirin takers was significantly less 3.9+/-0.1 (se) mm than non-aspirin takers 4.2+/-0.08 (se) mm. Ex-smokers had significantly more MSS-PAL 4.3+/-0.08 (se) mm than non-smokers 3.8+/-0.08 (se) mm. Aspirin apparently had a protective association on PAL and it is hypothesised that low-dose aspirin may have reduced the rate of attachment loss. CONCLUSIONS: This hypothesis needs to be confirmed by a prospective study. The results of this study suggest that individuals aged over 50 years, particularly ex-smokers, may benefit by taking low-doses of aspirin daily to reduce their risk of periodontal attachment loss.

Aged↗

Severity of upper and lower extremity functional limitation: scale development and validation with self-report and performance-based measures of physical function. WHAS Research Group. Women's Health and Aging Study.

OBJECTIVES: To better understand disablement and transitions from impairment to disability, discrete valid measures of functional limitation are needed. This study reports the development and criterion-related validity of scales that quantify severity of upper and lower extremity functional limitation. METHODS: Data are from 3,635 cognitively intact community-dwelling women aged 65 years and older and 1,002 moderately to severely disabled participants in the Women's Health and Aging Study. Scales assessing severity of upper and lower extremity functional limitation were constructed from commonly available questions on functional difficulty. Criterion-related validity was evaluated with self-report and performance-based measures. RESULTS: The upper and lower extremity scales range from 0 to 6 and 0 to 9, respectively. Scale scores were well distributed in the disabled group and discriminated limitations in the broader community. For both scales, rates of difficulty for all ADL and IADL increased (p<.001) with increasing severity score, and percent able and mean performance on respective upper and lower extremity tasks decreased (p<.01). DISCUSSION: These scales, constructed from commonly used self-report measures of function, provide discrete measures of upper and lower functional limitation. Because these scales are distinct from measures of disability and impairment, their use should facilitate increased understanding of the disablement process.

Activities of Daily Living↗

Observation of feeding in the diagnosis of posttraumatic feeding disorder of infancy.

OBJECTIVES: To delineate diagnostic criteria for posttraumatic feeding disorder (PTFD) of infancy and to differentiate PTFD from infantile anorexia (IA) via observation of feeding interactions. METHOD: Three groups of infants (aged 6-32 months) participated: PTFD (n = 30), IA (n = 30), and healthy eater controls (n = 30). The three groups were matched with regard to age, gender, ethnicity, and socioeconomic status. Child psychiatrists used infants' medical and feeding histories and observed 20-minute mother-infant feeding interactions to determine diagnoses and group placement. Feeding interactions were also videotaped, and two raters assessed infants' resistance to feeding situations and to swallowing, as well as specific qualities of mother-infant feeding interactions. RESULTS: Overall, the clinical groups (PTFD and IA) demonstrated more problematic feeding interactions than did the control group. However, the PTFD group exhibited more resistance during feeding interactions than did the other two groups. In particular, the PTFD group displayed the most resistance to swallowing food. CONCLUSIONS: Infants' medical and feeding histories, as well as observations of feeding, are important to making the diagnosis of PTFD and differentiating it from other feeding disorders. Implications for treatment of PTFD are discussed.

Child, Preschool↗

Autologous stem cell transplantation for pediatric rheumatic diseases.

The National Institute of Allergy and Infectious Disease, National Institutes of Health, convened a workshop entitled The Next Step: Protocol Development for Autologous Stem Cell Transplantation for Pediatric Rheumatic Disease, June 2000, co-chaired by Drs. Karyl Barron and Carol Wallace. The goal of the workshop was to focus on the scientific rationale for stem cell transplantation therapy in the pediatric diseases, unique aspects of this therapy in the pediatric rheumatic diseases, transplantation issues and options, regulatory issues, and development of a DNA repository for these diseases.

Child↗