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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 55 records · Page 3Linked to original sources
PubMed2001

Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity and oropharyngx characterised by fibrosis in the submucosa leading to progressive limitation of the mouth opening. Interferon gamma (IFN-gamma) is a known anti-fibrotic cytokine. In this study we have investigated: a) the effect of IFN-gamma on collagen synthesis by arecoline-stimulated OSF fibroblasts in vitro (n=5), b) the effect of intra-lesional IFN-gamma on the fibrosis of OSF patients (n=29) and c) the immunohistochemical analysis of pre- and post-treatment inflammatory cell infiltrates and cytokine levels in the lesional tissue (n=29). The results show that the increased collagen synthesis in vitro in response to arecoline was inhibited in the presence of IFN-gamma (0.01-10.0 U/ ml) in a dose-related way. In an open uncontrolled study intra-lesional IFN-gamma treatment showed improvement in the patients mouth opening from an inter-incisal distance before treatment of 21 +/- 7 mm, to 30 +/- 7 mm immediately after treatment and 30 +/- 8 mm 6-months later, giving a net gain of 8 +/- 4 mm (42%) (range 4-15 mm). Patients also reported reduced burning dysaesthesia and increased suppleness of the buccal mucosa. The post-treatment immunohistochemistry showed a decreased amount of inflammatory cell infiltrate and an altered level of cytokines compared with the pre-treatment lesional tissue. The effect of IFN-gamma on collagen synthesis appears to be a key to the treatment of these patients, and intra-lesional injections of the cytokine may have a significant therapeutic effect on OSF.

Areca↗
PubMed2001

Follicular lymphoid hyperplasia of the hard palate and oral mucosa: report of three cases and a review of the literature.

AIMS: To bring to wider attention this uncommon, poorly understood entity which may closely resemble, clinically and morphologically, follicular lymphoma. METHODS AND RESULTS: We report three cases of follicular lymphoid hyperplasia of the hard palate and oral mucosa which caused diagnostic difficulties for the referring pathologists. The clinicopathological features are described and integrated into a review of the 16 previously recorded cases. The condition most commonly presents as a slowly growing mass situated in the posterior hard palate but may present with multicentric oral lesions and lymphadenopathy. Morphologically, it is characterized by a dense follicular lymphoid infiltrate within the lamina propria which may show the classical features of benign reactive hyperplasia, but not uncommonly, indistinct germinal centres, ill-defined mantles and a lack of tingible-body macrophages are features which may lead to an erroneous diagnosis of follicular lymphoma. CONCLUSIONS: Follicular lymphoid hyperplasia of the palate is a poorly recognized entity which is frequently confused with follicular lymphoma. Awareness of the entity combined with the use of immunohistochemistry for immunoglobulin light chains and bcl-2 protein allows a correct diagnosis to be made avoiding extensive investigation and aggressive treatment to the patient.

Aged↗
PubMed2001

A study of four cases of extra-orbital giant cell angiofibroma with documentation of some unusual features.

AIMS: To document the clinical, light microscopic, immunohistochemical and ultrastructural features of four cases of extra-orbital giant cell angiofibromas. METHODS AND RESULTS: Sections of formalin-fixed paraffin-embedded specimens were studied by haematoxylin and eosin, reticulin and immunohistochemical stains. Electron microscopy was carried out in two cases on tissue fixed in formalin. The age of the patients ranged from 30 to 41 years. Two patients presented with a soft tissue swelling in the left groin, one patient had a left axillary soft tissue lump and one patient presented with a parotid lump. All lesions were well circumscribed and contained variably cellular and vascularized tissue composed of round to spindle cells with a patternless arrangement, scattered multinucleate giant cells and pseudovascular spaces conforming to the description of giant cell angiofibroma. Mononuclear and multinucleate tumour cells were both positive for vimentin and CD34; one tumour exhibited focal S100 protein and GFAP positivity. Both of the tumours examined by electron microscopy showed fibroblastic features, but in addition one contained cells having Schwannian features. All four patients were well without recurrent disease on follow-up (average 25 months). CONCLUSION: Giant cell angiofibroma shares many features with solitary fibrous tumour and giant cell fibroblastoma and shows a wider distribution than initially recognized. Rarely, Schwannian differentiation may be observed in these tumours.

Adult↗
PubMed2001

Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment.

OBJECTIVE: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids. METHODOLOGY: A cross-sectional comparison of lumbar spine-bone mineral density (LS-BMD) was undertaken in 76 subjects after stratifying them according to dosage and administration route of corticosteroid. RESULTS: Weight was the only independent predictor of LS-BMD (r(2) = 0.38). Children receiving greater than 800 microg/day of inhaled corticosteroid plus intermittent oral corticosteroid had a significantly lower weight-adjusted LS-BMD than children treated with 400-800 microg/day of inhaled corticosteroid (mean difference: 0.06 g/cm(2), 95% confidence interval (CI): - 0.02 to - 0.10). A significant difference in weight-adjusted LS-BMD persisted when all children receiving greater than 800 microg/day of inhaled corticosteroid, irrespective of additional oral corticosteroid treatment, were compared with children receiving 400-800 microg/day of inhaled corticosteroid (mean difference: - 0.05 g/cm(2), 95%CI interval: -0.02 to - 0.09). Bone mass was similar in children not receiving any inhaled corticosteroid and those treated with 400-800 microg/day of inhaled corticosteroid. CONCLUSIONS: A reduced bone mass in prepubertal asthmatic children receiving high doses of inhaled corticosteroids may predetermine a compromised peak bone mass and increase osteoporotic fracture risk in adulthood.

Absorptiometry, Photon↗
PubMed2001

Hepatocellular carcinoma and chemoembolization.

BACKGROUND: Chemoembolization is often used in the treatment of hepatocellular carcinoma; however, there are limited data on its efficacy in an Australian setting. AIMS: To review retrospectively the experience of 21 patients with hepatocellular carcinoma who collectively had 36 chemoembolizations performed between October 1995 and February 1999 in a teaching hospital and liver transplant centre in Victoria. METHODS: Selective catheterization of the right or left hepatic arteries was performed. A mixture of cisplatin 50 mg, epirubicin 50 mg, mitomycin C 10 mg, Lipiodol and gelfoam was injected. Computed tomography (CT) scans were performed at baseline and at 1-3 months after chemoembolization. Outcome measures included response rates, toxicity, progression-free and overall survival. RESULTS: CT response rates: partial response 19% (n = 7), median duration 11 months (range 2+ to 37+); minor response 17% (n = 6), median duration 7 months (1+ to 12+); stable disease 42% (n = 15), median duration 3 months (1+ to 15 months); and progressive disease 22% (n = 8). Major toxicities included one case each of acute renal failure, contrast encephalopathy, gastric ulceration and hepatorenal failure. Median progression-free survival was 3 months (range 0-37+). Median overall survival was 15 months (range 6-50+). CONCLUSION: Chemoembolization has a role in the palliative treatment of hepatocellular carcinoma. Our response rates and toxicity data are consistent with those in the published literature. However, new treatments are needed and prevention of disease by reduction in the prevalence of chronic hepatitis B and C will be required to significantly reduce mortality from this tumour.

Adult↗
PubMed2001

Aprotinin reduces blood loss and the need for transfusion in orthognathic surgery.

A randomized, placebo-controlled, double-blind trial (n= 15 in each group) showed that patients given aprotinin intravenously (200 ml, [2000000 kallikrein inactivator units] before the operation and then 50 ml per h until the end of the operation) during simultaneous maxillary Le Fort 1 and mandibular sagittal split osteotomies, lost 52% less blood than controls (calculated by subtracting the volume of saline irrigant used from the volume of blood collected in the aspirator bottle and surgical drains). Patients given aprotinin lost a mean (SD) of 473 (190) ml compared with 986 (356) ml in controls. They also required significantly less transfused blood (1 was given 2 units in the aprotinin group compared with 9 given a mean of 1.5 units (range 1-4) in the control group). There were no complications attributable to this drug.

Adult↗
PubMed2001

It's All a Matter of Timing: Sign Visibility and Sign Reference in Deaf and Hearing Mothers of 18-Month-Old Children.

The signed and spoken language produced by 14 mothers to their 18-month-old children during free play was analyzed. All the children had profound prelingual deafness. Seven of the mothers were profoundly deaf and fluent users of British Sign Language (BSL) or Auslan. The other seven were hearing and had enrolled in a signing program. Maternal signed utterances were classified according to whether they were made in the child's line of sight and whether they had a salient context; that is, they referred to an object or event at the child's current focus of attention. Spoken utterances were coded by word length. Comparisons between the two groups showed that both deaf and hearing mothers produced a majority of single-sign utterances (rather than utterances containing two or more signs). Deaf mothers also produced a majority of single-word spoken utterances, whereas the hearing mothers produced a significantly greater proportion of multiword utterances. As predicted, deaf mothers were more successful than hearing mothers in presenting signed utterances with a salient context that were visible to their children. Across the group as a whole, the total number of visible and salient signed utterances produced in 10 minutes was positively correlated with the total number of occasions on which mothers successfully redirected their child's attention or the child spontaneously turned to look at the mother. This suggests that deaf children who are visually attentive to their mothers receive a greater number of visible signed utterances with a salient context. I argue that this provides a more secure context for early language development.

Journal Article↗
PubMed2001

Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplantation.

BACKGROUND: Ovarian failure is a common sequel to chemo/radiotherapy in patients successfully treated for cancer. Harvesting, cryopreserving and subsequently re-implanting ovarian cortical grafts can be used to re-establish reproductive potential in women with cancer. The safety issue, however, is of great concern because residual disease in autografted ovarian tissues might cause recrudescence of disease. METHODS: A total of 30 non-obese diabetic severe combined immunodeficient (NOD/LtSz-SCID) mice were individually xenografted s.c. with frozen-thawed ovarian tissue from 18 patients with lymphoma [13 Hodgkin's lymphoma (HL) and 5 non-Hodgkin's lymphoma (NHL)]. The animals were autopsied at 16 weeks, or earlier if cachectic. The xenograft, liver, spleen, sternum, para-aortic lymph nodes and thymus were prepared for histology, immunohistochemistry and human DNA microsatellite analysis. RESULTS: None of the animals grafted with ovarian tissue from lymphoma patients developed disease. However, all 3 animals grafted with lymph node tissue from an NHL patient developed B-cell lymphomas that were confirmed as human in origin by DNA microsatellite analysis. CONCLUSION: Ovarian tissue harvested before high-dose chemotherapy for HL or NHL may not carry a risk of disease transmission by autotransplantation, although the possibility is difficult to exclude completely.

Adult↗
PubMed2001

A validation of two orthognathic model surgery techniques.

In order to create an evidence-based orthognathic surgery planning protocol, an investigation of two popular model surgery techniques, the Lockwood keyspacer and the Eastman anatomically-orientated system was carried. This determined (a) the accuracy of positioning of the maxillary cast according to the prescribed treatment plan and (b) the relocation of the maxilla after a simulated Le Fort I down fracture osteotomy using the intermediate wafer as a guide. Fifteen patients-five Class II division 1, five Class II division 2, and five Class III-were included in the study. All the measurements were taken with Erickson's vertically mounted electronic caliper and variations from the treatment plan were analysed. The mean model surgery positioning errors +/- SD (mm) were: (i) vertical plane-Lockwood -0*8 +/- 1*6 and Eastman 0*00 +/- 1*0 (P = 0*0001); (ii) anteroposterior plane-Lockwood 1*2 +/- 1*8 and Eastman -0*1 +/- 1*4 (P = 0*05); and (iii) transverse plane-Lockwood 0*9 +/- 0*9 and Eastman 1*0 +/- 0*9 (P = 0*34). After the simulated osteotomy, the mean errors +/- SD were: (i) vertical plane-Lockwood -0*5 +/- 1*5 and Eastman 0*3 +/- 1*1 (P = 0*001); (ii) in anteroposterior plane-Lockwood 0*8 +/- 2*0 and Eastman 0*7 +/- 1*0 (P = 0*89); and (iii) transverse plane-Lockwood 0*8 +/- 0*6 and Eastman 0*7 +/- 0*5 (P = 0*83). The Eastman technique was relatively better especially in the vertical plane. The variations from the treatment plan were on the whole anatomically small, but in some cases could be clinically significant.

Dental Articulators↗
PubMed2001

Targeted disruption of the methionine synthase gene in mice.

Alterations in homocysteine, methionine, folate, and/or B12 homeostasis have been associated with neural tube defects, cardiovascular disease, and cancer. Methionine synthase, one of only two mammalian enzymes known to require vitamin B12 as a cofactor, lies at the intersection of these metabolic pathways. This enzyme catalyzes the transfer of a methyl group from 5-methyl-tetrahydrofolate to homocysteine, generating tetrahydrofolate and methionine. Human patients with methionine synthase deficiency exhibit homocysteinemia, homocysteinuria, and hypomethioninemia. They suffer from megaloblastic anemia with or without some degree of neural dysfunction and mental retardation. To better study the pathophysiology of methionine synthase deficiency, we utilized gene-targeting technology to inactivate the methionine synthase gene in mice. On average, heterozygous knockout mice from an outbred background have slightly elevated plasma homocysteine and methionine compared to wild-type mice but seem to be otherwise indistinguishable. Homozygous knockout embryos survive through implantation but die soon thereafter. Nutritional supplementation during pregnancy was unable to rescue embryos that were completely deficient in methionine synthase. Whether any human patients with methionine synthase deficiency have a complete absence of enzyme activity is unclear. These results demonstrate the importance of this enzyme for early development in mice and suggest either that methionine synthase-deficient patients have residual methionine synthase activity or that humans have a compensatory mechanism that is absent in mice.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2001

Evidence of nerve sheath differentiation and high grade morphology in sclerosing epithelioid fibrosarcoma.

Sclerosing epithelioid fibrosarcoma is a recently described sarcoma in which ultrastructural evidence of fibroblastic differentiation forms part of the diagnostic criteria. This report describes a further case of this tumour, which showed evidence of both fibroblastic and perineurial differentiation by immunohistochemistry and electron microscopy, and which had areas of high grade morphology. The tumour metastasised and the patient died of disease 12 months after presentation. The relevance of these findings to diagnosis and differentiation in these tumours is discussed.

Cell Differentiation↗
PubMed2001

Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling.

Starvation causes a rapid reduction in thyroid hormone levels in rodents. This adaptive response is caused by a reduction in thyrotropin-releasing hormone (TRH) expression that can be reversed by the administration of leptin. Here we examined hypothalamic signaling pathways engaged by leptin to upregulate TRH gene expression. As assessed by leptin-induced expression of suppressor of cytokine signaling-3 (SOCS-3) in fasted rats, TRH neurons in the paraventricular nucleus are activated directly by leptin. To a greater degree, they also contain melanocortin-4 receptors (MC4Rs), implying that leptin can act directly or indirectly by increasing the production of the MC4R ligand, alpha-melanocyte stimulating hormone (alpha-MSH), to regulate TRH expression. We further demonstrate that both pathways converge on the TRH promoter. The melanocortin system activates the TRH promoter through the phosphorylation and DNA binding of the cAMP response element binding protein (CREB), and leptin signaling directly regulates the TRH promoter through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). Indeed, a novel Stat-response element in the TRH promoter is necessary for leptin's effect. Thus, the TRH promoter is an ideal target for further characterizing the integration of transcriptional pathways through which leptin acts.

Animals↗
PubMed2001

Outpatient management of low-velocity gunshot-induced fractures.

This prospective study evaluated the efficacy of an outpatient management protocol for patients with a gunshot-induced fracture with a stable, nonoperative configuration. Forty-one patients (44 fractures) with a grade I or II open, nonoperative fracture secondary to a low-velocity missile comprised the study population. Patients were treated by a standard protocol, which included 1 g of cefazolin administered in the emergency room and a 7-day course of oral cephalexin. Follow-up visits were performed until complete wound and fracture healing were achieved. Thirty-two (78%) of 41 patients underwent full follow-up. Average follow-up was 5.2 months. One (2.8%) fracture (distal fibula) developed a superficial infection, which responded to an additional week of oral antibiotics, and no patient developed a deep infection. There was 1 delayed union and 2 patients with painful retained shrapnel. These results demonstrate that patients with stable, low-velocity, gunshot-induced fractures can be managed effectively and safely on an outpatient basis using this protocol.

Adult↗
PubMed2001

Factors associated with frequent admission to hospital for patients with chronic airflow limitation.

BACKGROUND: Chronic airflow limitation (CAL) is a common cause of admission and readmission to hospital. This study has explored associated factors with repeat hospital admission in patients with CAL. METHOD: A retrospective file review of patients admitted more than once to hospital during the 1999 calendar year, with a diagnosis of CAL. RESULTS: Two hundred and two patients admitted with CAL accounted for 284 admissions and 1815 bed days. Of these, 46 patients were admitted more than once accounting for 115 (40.5%) admissions and 730 (39.8%) bed days. The study found evidence of general practice involvement in 35 (30.5%) admissions immediately before presentation at the hospital emergency department (ED). The discharge summary following that admission revealed only 67 (54%) were referred back to their general practitioners for follow up. The number of admissions attending the ED between the hours of 9.00 am and 5.00 pm were 62 (53.9%) and 96 (83.5%) between the hours of 7.00 am and 10.00 pm. CONCLUSION: Treatments given in hospital were similar, in most cases, to what could be provided at home with appropriate community based support. General practitioners were involved in approximately one-third of those patients requiring admission or re-admission to hospital.

Female↗