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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Aminophylline does not protect against radiocontrast nephropathy in patients undergoing percutaneous angiographic procedures.

BACKGROUND: Radiocontrast nephropathy (RCN) is one of the leading causes of hospital-acquired acute renal insufficiency. Adenosine, a renal vasoconstrictor, is thought to play a role in RCN. In this study, aminophylline, a non-selective adenosine-competitive inhibitor, was evaluated as a potential agent to protect against RCN. METHODS: Twenty-six patients treated with 200 mg intravenous aminophylline immediately prior to percutaneous coronary and peripheral procedures were individually matched to 26 controls for baseline creatinine (Cr), diabetes mellitus and amount of contrast used. The aminophylline-treated group was also similar to control with respect to baseline ejection fraction, amount of post-procedure hydration, age, blood pressure and the use of nephrotic drugs. RESULTS: There was no significant difference between the change from baseline Cr to peak measured Cr in either cases or controls. Also, when a change in Cr > or =25% from baseline was considered significant, Fisher's exact test did not show a difference between the 2 groups. CONCLUSION: Aminophylline does not appear to add a protective role in preventing against RCN in patients undergoing percutaneous angiographic procedures.

Aged↗

Enhanced primary care items. Their use in diabetes management.

BACKGROUND: The Enhanced Primary Care (EPC) items for care planning and case conferencing provide an opportunity for better quality care for people with chronic disease. OBJECTIVE: To explore the use of the EPC items in the structured care of diabetes based on evidenced based guidelines in general practice. DISCUSSION: Care planning and case conferencing are useful, especially in the structured care of patients who have poor control. The achievement of better health outcome for these patients depends upon a patient oriented and structured approach in collaboration with other health professionals. This needs to be supported by systems within the practice, Division and local community.

Australia↗

Leptin regulates prothyrotropin-releasing hormone biosynthesis. Evidence for direct and indirect pathways.

The hypothalamic-pituitary-thyroid axis is down-regulated during starvation, and falling levels of leptin are a critical signal for this adaptation, acting to suppress preprothyrotropin-releasing hormone (prepro-TRH) mRNA expression in the paraventricular nucleus of the hypothalamus. This study addresses the mechanism for this regulation, using primary cultures of fetal rat hypothalamic neurons as a model system. Leptin dose-dependently stimulated a 10-fold increase in pro-TRH biosynthesis, with a maximum response at 10 nm. TRH release was quantified using immunoprecipitation, followed by isoelectric focusing gel electrophoresis and specific TRH radioimmunoassay. Leptin stimulated TRH release by 7-fold. Immunocytochemistry revealed that a substantial population of cells expressed TRH or leptin receptors and that 8-13% of those expressing leptin receptors coexpressed TRH. Leptin produced a 5-fold induction of luciferase activity in CV-1 cells transfected with a TRH promoter and the long form of the leptin receptor cDNA. Although the above data are consistent with a direct ability of leptin to promote TRH biosynthesis through actions on TRH neurons, addition of alpha-melanocyte-stimulating hormone produced a 3.5-fold increase in TRH biosynthesis and release, whereas neuropeptide Y treatment suppressed pro-TRH biosynthesis approximately 3-fold. Furthermore, the melanocortin-4 receptor antagonist SHU9119 partially inhibited leptin-stimulated TRH release from the neuronal culture. Consequently, our data suggest that leptin regulates the TRH neurons through both direct and indirect pathways.

Animals↗