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Biomedical subjects

M McGill

Publications and source records attributed to M McGill.

At least 19 recordsLinked to original sources
PubMed2005

Which diabetic patients should receive podiatry care? An objective analysis.

INTRODUCTION: Diabetes is the leading cause of lower limb amputation in Australia. However, due to limited resources, it is not feasible for everyone with diabetes to access podiatry care, and some objective guidelines of who should receive podiatry is required. METHODS: A total of 250 patients with neuropathy (Biothesiometer; Biomedical Instruments, Newbury, Ohio, USA) ( > 30, age < 65)) but no active foot lesion, and 222 without neuropathy matched for age, type of diabetes, gender and duration, was followed prospectively for 2 years. Sensation was also tested using a 10 g Semmes Weinstein monofilament (Royal Prince Alfred Hospital Diabetes Centre). After the baseline examination, patients were contacted at 6 months and thereafter yearly to determine ulcer status. Incidence of foot ulceration across different risk categories was calculated using Kaplan-Meier survival curve. Log-rank test and Cox's proportional model were used to compare groups. The Number Needed to Treat (NNT) to prevent one ulcer per year was calculated using the standard formulae. RESULTS: During the follow-up period, 34 new ulcers occurred in the neuropathy group and three ulcers in the control group (chi2 (1df) = 21.3; P < 0.0001), equating to an annual incidence of 6.3% and 0.5%, respectively. Fifty-four per cent of the ulcers were due to trauma from footwear. Further stratification of the neuropathy group showed annual incidence of ulceration to be 4% for those with abnormal biothesiometer reading, but who could still feel the monofilament, 10% for those who cannot feel the monofilament and 26% for those with previous ulceration or amputation. Predictors of ulceration were past history of ulceration/amputation (chi2 = 27.8; P < 0.0001) and the presence of neuropathy (chi2 = 4.7; P = 0.03). Assuming a 55% relative risk reduction in ulceration from podiatry care (mean of estimates from 10 reports), the NNT to prevent one foot ulcer per year was: no neuropathy (vibration perception threshold (VPT) < 30)), NNT = 367; neuropathy (VPT > 30) alone, NNT = 45; +cannot feel monofilament, NNT = 18; +previous ulcer/amputation, NNT = 7. CONCLUSION: Provision of podiatry care to diabetic patients should not be only economically based, but should also be directed to those with reduced sensation, especially where there is a previous history of ulceration or amputation.

Age Factors↗
PubMed2001

Clustering of cardiovascular risk factors with diabetes in Chinese patients: the effects of sex and hyperinsulinaemia.

OBJECTIVE: This study was designed to investigate factors which affect the clustering of cardiovascular risk factors with diabetes in Chinese patients. RESEARCH DESIGN AND METHODS: Six hundred and fifty-four patients with diabetes were assessed comprehensively for diabetes complications and cardiovascular risk factors in a metropolitan hospital in Beijing, China. Insulin resistance and secretion were also evaluated by measurement of glucose and insulin levels before and after a meal tolerance test. Results were analysed according to patient groups stratified by the number of cardiovascular risk factors coexisting with diabetes. RESULTS: Cardiovascular risk factors were common in Chinese diabetic patients. The clustering of three or more of these factors with diabetes occurred more often than by chance alone and was associated with postprandial hyperinsulinaemia. Patients with a high number of risk factors were more prone to macrovascular events but did not have higher albuminuria. Using the commonly adopted lower threshold for diagnosing obesity and central obesity in women, there were more women with multiple risk factors. However, this disappeared if the same criteria were used for men and women. Even in the presence of diabetes, cardiovascular risk factors were inadequately controlled in most patients. CONCLUSIONS: The concurrence of diabetes and other cardiovascular risk factors which constitute the metabolic syndrome is a common phenomenon in urban Chinese diabetic patients. It is associated with hyperinsulinaemia and possibly the female sex. This study emphasises the importance of public health measures to control cardiovascular risk factors in patients with diabetes.

Aged↗
PubMed2001

Oral care for people with advanced cancer: an evidence-based protocol.

Poor oral health is an extremely common problem in patients with advanced cancer and, because of its impact on quality of life, promoting oral care should be regarded as a priority by every hospice and palliative care team. At Accord Hospice, Paisley, UK, a protocol for oral care has been developed which is simple, inexpensive and evidence-based. Evaluation of the protocol has shown that it can lead to significant and consistent improvements in oral health and comfort. A survey of mouth-care practices in other Scottish hospice units reveals that although much agreement exists, certain practices that are unsupported by research evidence are still undertaken.

Adult↗
PubMed2000

Response of Charcot's arthropathy to contact casting: assessment by quantitative techniques.

AIMS/HYPOTHESIS: This study used two different methods of quantitative bone scanning to study the relation between activity of Charcot's arthropathy and clinical variables over 12 months. METHODS: Skin temperature of affected and unaffected feet was measured at baseline and every 3 months for 12 months in 17 subjects. Eight subjects underwent a three-phase quantitative bone scan at baseline and 3 monthly for 12 months. Bone isotope uptake in a standard rectangular area over the foot and tibia was analysed by the bilateral scan method (the ratio of isotope uptake of affected and unaffected feet) and the unilateral scan method (the ratio of isotope uptake of affected foot and ipsilateral tibia). The affected foot was placed in a contact cast for an average of 8 months. RESULTS: At presentation the affected foot was hotter than the unaffected foot but the temperature became progressively cooler over 12 months. Median isotope uptake in the affected foot was 2.1% of the injected dose (interquartile range, IQR 1.9-3.0). In both scanning methods the ratio of uptake decreased after casting but at 12 months the affected foot still had more isotope uptake. There was a strong correlation between temperature difference and the ratio of uptake in the bilateral scan method (r = 0.90; p < 0.0001) but when using the unilateral scan method this relation was not significant (r = 0.1;p = 0.6). A strong relation existed between perfusion of the affected foot in the dynamic phase and isotope uptake in the delayed phase of the scans (r = 0.92; p < 0.0001). CONCLUSION/INTERPRETATION: Bone activity and skin temperature of Charcot's arthropathy can be measured quantitatively and both improve over 12 months with contact casting. There is a strong relation between perfusion and disease activity in this condition.

Aged↗
PubMed1999

Possible sources of discrepancies in the use of the Semmes-Weinstein monofilament. Impact on prevalence of insensate foot and workload requirements.

OBJECTIVE: The purpose of this study was to evaluate the effects of different testing sites and buckling strengths on the sensitivity and specificity of using the Semmes-Weinstein monofilament to detect patients with insensate foot. The impact on workload required to educate and follow up these high-risk individuals was estimated by modeling in our patient population with a documented status of neuropathy. RESEARCH DESIGN AND METHODS: Using the 5.07/10-g monofilament, one observer tested 132 randomly selected subjects with diabetes at five sites on the right foot. The sensitivity and specificity of each site and combinations of sites in detecting vibration perception threshold > 40 was calculated. In addition, two monofilaments, one with a buckling force of 5 g and the other with a force of 15 g, were compared by testing 200 randomly selected patients. An estimate of the prevalence of insensate foot and workload was made by modeling the findings to the 5,270 patients with neuropathy status registered on our computerized database. RESULTS: Specificity of the 5.07/10-g monofilament to detect insensate foot at each of the five sites is high, at approximately 90%, but there is considerably more variation and lower sensitivity, ranging from 44-71%. Data derived from the use of different combinations of sites showed that more stringent criteria are associated with lower sensitivity but higher specificity. If the foot is considered insensate when either of sites 3 and 4 (plantar aspect of the first and fifth metatarsal heads, respectively) cannot feel the monofilament, there is reasonable sensitivity and specificity (80-86%, respectively). By modeling on our diabetes center population, it can be demonstrated that the choice of different methodologies leads to different conclusions about the prevalence of severe neuropathy, ranging from 3.4 to 29.3%. CONCLUSIONS: Using a combination of sites 3 and 4 for monofilament testing gives a reasonable compromise for time, sensitivity, and specificity. Minor changes in sensitivity and specificity can lead to major changes in the prevalence of neuropathy, with implications for workload.

Australia↗
PubMed1998

Use of the Semmes-Weinstein 5.07/10 gram monofilament: the long and the short of it.

The Semmes-Weinstein monofilament has been developed for the detection of patients at risk of neuropathic ulceration. In this study we evaluated how the physical characteristics of the monofilaments can impact on their performance. Commercially purchased monofilaments from the Hansen's Disease Center (HDC) and a batch produced 'in-house' (RPAH) were calibrated using a Mettler Balance. To assess the effects of varying lengths on buckling force, the monofilaments were tested repeatedly while the length of the filament was reduced stepwise from 4.1 to 3.1 cm. The correct length of the monofilament to generate a buckling force of 10 g was also determined theoretically by applying the Euler's Buckling Equation. Results showed neither batch of monofilaments buckled at a strength of 10 g (HDC 6.8 g, CI 5.7-7.9, and RPAH 7.2 g, CI 7.1-7.3). In addition HDC showed a wide interfilament variation range, 4.1-10.3 g with CV 29% versus corresponding figures of range 7.1-7.9 g, CV 4.9% for the RPAH monofilaments. As predicted by Euler's Buckling Theory, buckling force can be increased by reducing the length of the filament. These results demonstrate that the physical characteristics of the monofilament are important determinants of buckling force and are not necessarily uniform in commercial filaments. The clinical relevance of variance in buckling force remains to be determined.

Diabetic Neuropathies↗
PubMed1998

Better glycaemic control and risk reduction of diabetic complications in Type 2 diabetes: comparison with the DCCT.

OBJECTIVE: To construct dose response curves relating the development of diabetic complications (retinopathy and microalbuminuria) to mean glycaemic exposure in a cohort of Type 2 patients followed over a period of several years. This allows a comparison with similar data on Type 1 subjects reported by the Diabetes Control and Complications Trial (DCCT) and provides a rational basis for deciding what levels of glycaemic control should be aimed for in advising individual patients and in setting guidelines for conducting health services. RESEARCH DESIGN AND METHODS: This was an analysis of data prospectively collected in our computerized data base for Type 2 patients who attended and were followed up at the Complications Assessment Service of our Diabetes Center. The initial development of retinopathy and microalbuminuria was analyzed with respect to the mean HbA1c during the follow up period. Statistical procedures identical to those employed in the DCCT were used to construct the dose response curve. RESULTS: A smooth relationship between the development of retinopathy with increasing hyperglycaemia was found. For every 10% decrease in HbA1c, there was a 24%) (confidence interval (CI): 16-32) reduction in relative risk, about 2/3 of that reported for insulin-dependent diabetes mellitus (IDDM) patients. The relationship between microalbuminuria and HbAc was more linear and less steep with a relative risk reduction of 9% (CI: -2-19%) for any 10% fall in HbA1c, about 1/3 of that reported for IDDM subjects. No threshold of HbA1c can be found for the relative risk of developing complications. However, more cases of complications are prevented by the same degree of improvement in glycaemic control at higher levels of HbA1c. CONCLUSIONS: The development of diabetic retinopathy in Type 2 subjects is also related to the magnitude of hyperglycaemia although the degree of dependence is less than that in Type 1. Glycaemic control has less influence on microalbuminuria in Type 2. In terms of relative risk, no threshold of 'safe HbA1c' can be found but in absolute terms more cases of diabetic complications can be prevented by improving the glycaemic control of the very hyperglycaemic patients.

Albuminuria↗
PubMed1997

Demonstration of insulin production and storage in insulinomas by in situ hybridization and immunocytochemistry.

Twelve cases of insulinoma were studied to assess the amount of hormone synthesis and hormone storage by the tumour and to see what effect a hormone-producing tumour has on the adjacent normal islets. This was investigated by performing in situ hybridization, which detects hormone messenger RNA, thus giving an indication of the degree of hormone synthesis by the tumour, and immunocytochemistry, which detects the hormone itself, thus giving an indication of the amount of hormone stored in the tumour cells. It was found that in most cases there was less hormone stored within the tumour cells than in adjacent islet cells. In a minority of cases, this decrease in stored hormone was associated with reduced hormone synthesis, but the majority of cases showed either equivalent or increased levels of hormone mRNA in the tumour cells compared with adjacent islets. In addition, it was noted that, unlike some other endocrine organs, the presence of a hormone-producing tumour within the pancreas did not appear to inhibit hormone synthesis in the adjacent normal tissue.

Aged↗
PubMed1997

A search for evidence of viral infection in pancreases of newly diagnosed patients with IDDM.

Techniques were developed to look for evidence of viral infection in formalin-fixed paraffin-embedded autopsy pancreatic tissues from patients who had died of recent-onset insulin-dependent diabetes mellitus. DNA extracted from 47 pancreases in which good DNA preservation was confirmed was analysed by a polymerase chain reaction for Epstein-Barr virus and by a nested polymerase chain reaction for cytomegalovirus. Histological sections from 29 pancreases in which there was good RNA preservation were tested for the presence of enterovirus and Epstein-Barr virus using in situ hybridization techniques. Seventy-five pancreases were analysed immunohistochemically for the presence of mumps virus. None of these viruses could be detected in any of the diabetic pancreases studied. Control studies suggested that the techniques employed were as sensitive as culture done at the time of autopsy. Pancreas was available for study in 9 infants who had died of myocarditis; enterovirus was demonstrable in islets in 5 of these cases. An acute or persisting infection in the pancreas at the time of clinical onset of insulin-dependent diabetes by any of the 4 virus included in this study seems unlikely.

Adolescent↗
PubMed1997

Detection and treatment of hypertension in patients with non-insulin-dependent diabetes mellitus: does the 'rule of halves' apply to a diabetic population?

The extent to which hypertension is detected and adequately treated in the general population is often described by the 'rule of halves', but corresponding figures for patients with non-insulin-dependent diabetes mellitus (NIDDM), based on current American Diabetes Association (ADA) criteria, have not been previously reported. This study looked at the detection and management of hypertension among 2331 consecutive patients with NIDDM attending for annual complications assessment. Hypertension was defined according to ADA criteria, i.e. systolic blood pressure (sBP) > 140 mmHg and/or diastolic blood pressure (dBP) > 90 mmHg. A total of 69% of patients were hypertensive, with proportionately more women in the hypertensive group (48 versus 39%, P < 0.002). Among those with hypertension, 59% were taking antihypertensive drugs but only 31% of treated hypertensives were adequately controlled. Thus, hypertension affects roughly two-thirds of patients with NIDDM and compared with treatment strategies reported in the literature for the non-diabetic population (summarised in the 'rule of halves'), proportionately more hypertensive patients with NIDDM are treated with BP-lowering drugs (59%) but proportionately less (31%) have adequate BP control.

Australia↗
PubMed1996

Expression of the human heat shock protein 60 in thyroid, pancreatic, hepatic and adrenal autoimmunity.

Heat shock proteins (hsps) have been proposed to play a role in autoimmune disease. Their highly conserved nature and role as a common antigenic determinant throughout phylogeny has raised the possibility that they may act as cellular targets of an autoimmune response when their expression is altered in stressed tissue cells. Using an antibody to human hsp60 we have demonstrated a wide tissue distribution in normal tissues, including thymus, the degree of staining reflecting the content of mitochondria in the cells, consistent with the known mitochondrial location of this protein. Enhanced staining was also demonstrated in oncocytes (deeply eosinophilic cells which have greatly increased numbers of mitochondria) in both thyroid and adrenal autoimmune disease and also in unrelated conditions where oncocytic change was identified. No enhancement was demonstrated in target cells in organ specific autoimmune diseases where oncocytic change was not seen, for example islet cells in diabetes and bile duct cells in primary biliary cirrhosis. Thus, no alteration of hsp60 expression was demonstrated which was specific to the autoimmune diseases studied.

Adrenal Glands↗
PubMed1996

Management of neuropathic ulceration.

Patients with diabetes who develop neuropathic foot ulcers are often managed with prolonged bed-rest or given a total contact cast. As these methods are not ideal for many patients, we examined a boot cast as an alternative approach to treating intractable neuropathic ulcers. Fourteen diabetic patients with a total of 16 neuropathic ulcers have been treated. The boot cast is a fibreglass, removable cast, tailor-made for individual patients. For treatment of neuropathic ulcers, a window is cut over the area of the ulcer site to reduce weight-bearing pressure. Despite the long pre-existing duration of the ulcers studied (mean 912 days), ulcers that reached 100% healing did so by 130 days. The mean period in which there has been no recurrence to date is 218 days. The boot cast was found to be an effective treatment in the management of diabetic foot problems. It allows patients to remain ambulant and reduces risk factors for amputation.

Casts, Surgical↗
PubMed1994

Lack of immunohistological changes in the islets of nondiabetic, autoimmune, polyendocrine patients with beta-selective GAD-specific islet cell antibodies.

We examined the pancreases from three nondiabetic, autoimmune, polyendocrine patients with islet cell antibodies (ICAs) and glutamic acid decarboxylase (GAD) antibodies who died without developing insulin-dependent diabetes mellitus (IDDM). All three patients had the beta-selective GAD-specific ICA subtype and antibodies to the GAD-derived 50 kD tryptic fragment. None had whole islet ICA or antibodies to the non-GAD-derived 37k islet antigen, which appear to be more closely associated with IDDM than antibodies to GAD. The three patients also were negative for insulin autoantibodies. Islets within pancreas from patients 1 and 2 appeared well preserved as assessed by hematoxylin and eosin staining. In these two patients, insulin content, as assessed by indirect immunofluorescence on cryostat sections, was normal. Patient 3 had a prolonged postmortem time, and the islet insulin content was reduced slightly. In all three pancreases, no evidence was found of increased human leukocyte antigen class I or de novo class II molecule expression on islet cells, and islet infiltration by T- or B-cells or macrophages was not detected. Islet capillary endothelial cells did not show signs of hypertrophy. No immunoglobulin or complement deposition within or around islets was found. These data indicate that humoral GAD autoimmunity does not necessarily associate with visible beta-cell damage.

Adenocarcinoma↗
PubMed1993

A single visit diabetes complication assessment service: a complement to diabetes management at the primary care level.

Modern diabetes management emphasizes the early detection and prompt treatment of diabetic complications. However it is difficult to organize comprehensive screening at the primary care level. To address this problem we established a complication assessment service whereby all the major diabetes-specific complications were assessed in a single 3 h visit. A report with results and recommendations was sent to the general practitioner (GP). Being philosophically a complication-specific service, no attempt was made to intervene with metabolic management. This paper describes our experience with the first 743 patients of whom 92% had been referred from GPs. Of the diabetes-specific complications, 22% of patients had one, 5% had two, and 1% had three major complications. Many of the patients were unaware of the presence of these complications. One hundred and three people had attended the service on more than one occasion with an average time between visits of 1.7 years. The results demonstrated that GPs were very good at following a recommendation to refer a patient for ophthalmic assessment (85% of cases) and improving hypertension but were less successful in treating hyperlipidaemia. This service has proven to be an excellent forum for the collection of data and the teaching of health professionals. It is a move away from the traditional format of hospital-based clinics providing comprehensive diabetes management.

Australia↗
PubMed1992

Expression of TTK, a novel human protein kinase, is associated with cell proliferation.

We have isolated the full-length sequence for a unique human kinase, designated TTK. TTK was initially identified by screening of a T cell expression library with anti-phosphotyrosine antibodies. The kinases most closely related to TTK are the SPK1 serine, threonine and tyrosine kinase, the Pim1, PBS2, and CDC2 serine/threonine kinases, and the TIK kinase which was also identified through screening of an expression library with anti-phosphotyrosine antibodies. However, the relationships are distant with less than 25% identity. Nevertheless, TTK is highly conserved throughout phylogeny with hybridizing sequences being detected in mammals, fish, and yeast. TTK mRNA is present at relatively high levels in testis and thymus, tissues which contain a large number of proliferating cells, but is not detected in most other benign tissues. Freshly isolated cells from most malignant tumors assessed expressed TTK mRNA. As well, all rapidly proliferating cell lines tested expressed TTK mRNA. Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine. Taken together, these findings suggest that expression of TTK, a previously unidentified member of the family of kinases which can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, is associated with cell proliferation.

Amino Acid Sequence↗
PubMed1992

The distribution of immunoreactive interferon-gamma-containing cells in normal human tissues.

An immunohistochemical technique has been used to study the distribution of lymphocytes expressing interferon-gamma in normal adult tissues. The greatest concentrations of these cells were seen in mucosal sites exposed to a resident microflora. It is proposed that such organisms, by eliciting immune responses, provide the stimulus for the production of 'physiological' interferon-gamma. This in turn may act to preserve the 'tone' or readiness of the immune system.

Adult↗
PubMed1991

Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells.

This study sought to determine, firstly, the relative frequency of lymphocytes and macrophages and, secondly, the percentage of lymphocytes containing interferon-gamma in inflamed islets (insulitis) of patients with type 1 (insulin-dependent) diabetes. Autopsy pancreases of 12 patients who had died of recent-onset type 1 diabetes and one pre-diabetic patient who had died of cardiomyopathy were examined immunohistochemically. In the 87 islets that were studied, the lymphocyte macrophage ratio was 9.7:1 and approximately 40 per cent of the lymphocytes contained interferon-gamma. Interferon-gamma release in the insulitis process may be involved in the pathogenesis of type 1 diabetes.

Adolescent↗