Richard L. Ollerton

Intranasal Insulin: the Effects of Three Dose Regimens on Postprandial Glycaemic Profiles in Type II Diabetic Subjects

In both fasting normal and diabetic subjects, nasally administered insulin achieves significant falls in plasma glucose concentrations. Repeated administration before and during a meal has been necessary to lower postprandial glycaemic excursion in subjects with NIDDM. We have studied the use of Novolin® Nasal which employs a non‐irritant, lecithin‐based enhancer as a vehicle for human insulin, on postprandial glucose profiles in NIDDM subjects to determine efficacy, optimal dose frequency, and tolerability. Seventeen NIDDM subjects (15 men, 2 women) participated in a randomized, partially blinded, placebo‐controlled, crossover trial of three active treatment regimens (nasal insulin, 120 U at 0 min, 60 U at 0 and +20 min or 120 U at +20 min) in relation to a standardized mixed meal given at 0 min. All active treatments significantly reduced postprandial glucose concentrations compared to placebo. Intranasal insulin given at 0 min at a dose of 60 U or 120 U resulted in a 50% reduction in postprandial incremental glucose compared to placebo over the first 2 h, whereas treatment with 60 U both at 0 and 20 min lead to a 70% reduction over the 240 min postprandial period. Post‐prandial intravenous insulin was the least effective. There were no episodes of symptomatic hypoglycaemia. Local tolerability was excellent with only four reports of transient nasal irritation out of a total of 68 doses. The delivery device was accurate with intra‐device CV of delivered dose of 4.8%. We conclude that nasal insulin is effective in reducing postprandial glycaemia in subjects with NIDDM and is well tolerated. Repeated dosing achieved the greatest reduction in postprandial glycaemic responses to a mixed meal.

Effects of three approaches to standardized oral hygiene to reduce bacterial colonization and ventilator associated pneumonia in mechanically ventilated patients: A randomised control trial

BACKGROUND Ventilator associated pneumonia remains an important concern in the intensive care unit (ICU). An increasing body of evidence shows that mortality and morbidity can be reduced by implementing a range of preventive strategies, including optimizing oral hygiene. AIM The aim of this feasibility study was to test two oral hygiene strategies on the effects of microbial colonization of dental plaque with respiratory pathogens (primary outcome) and incidence of ventilator associated pneumonia (secondary outcome). METHODS A single blind randomised comparative study was conducted in a 20-bed adult intensive care unit in a university hospital. Patients with an expected duration of mechanical ventilation more than 48 h were eligible. Patients were randomised to one of three study regimens (Group A control, second hourly oral rinse with sterile water, Group B sodium bicarbonate mouth wash second hourly, and Group C twice daily irrigations with chlorhexidine 0.2% aqueous oral rinse and second hourly irrigations with sterile water). All study options included cleaning with a toothbrush and non foaming toothpaste. RESULTS Data from a total of 109 patients were analyzed. Group A 43, Group B 33 and Group C 33 (mean age: 58 ± 17 years, simplified acute physiology score II: 44 ± 14 points). On admission no significant differences were found between groups for all clinical data. While Group B showed a greater trend to reduction in bacterial colonization no significant differences could be demonstrated at Day 4 of admission (p=0.302). The incidence of ventilator associated pneumonia was evenly spread between Groups B and C (5%) while Group A was only 1%. CONCLUSIONS While a number of studies have advocated the use of various mouth rinses in reducing colonization of dental plaque a standardized oral hygiene protocol which includes the use of mechanical cleaning with a toothbrush may be a factor in the reduction of colonization of dental plaque with respiratory pathogens. This feasibility study provides data to inform future adequately powered studies.

A glimpse of the ‘natural history’ of established Type 2 (non-insulin dependent) diabetes mellitus from the spectrum of metabolic and hormonal responses to a mixed meal at the time of diagnosis

The reported glucose and immunoreactive insulin (IRI) responses to oral and intravenous glucose in subjects with Type 2 diabetes have not always been consistent. This may have resulted from variations in the method of glucose administration, the ethnic backgrounds of subjects, the diagnostic criteria applied, the duration of the disease or IRI assay methods. The use of a mixed meal rather than glucose has been shown to provide a more physiological stimulus to the pancreatic beta-cell due to both glucose and non-glucose secretagogues. We have analysed the metabolic and hormonal responses of 188 newly diagnosed Caucasian subjects with Type 2 diabetes and 38 non-diabetic subjects to a 500 kcal mixed meal. The diabetic subjects were stratified according to fasting plasma glucose (FPG) (< 9, 9-12, 12-15 and > or = 15 mmol/l) and body mass index (BMI) (< 26.5, 26.5-30 and > or = 30 kg/m2). Increasing FPG was associated with higher peak glucose concentrations and increasing failure to achieve basal glucose levels by 4 h. Median fasting IRI concentrations were similar to those of normal subjects, but all diabetic subjects had reduced early-phase insulin secretion. Diabetic subjects with FPG < 9 mmol/l showed augmented IRI area under the curve (AUC) at 2 and 4 h, whereas those with FPG > 9 mmol/l had progressive falls in IRI AUC to below that of the normal subjects (P < 0.0001 for the trend). Peak IRI concentrations declined progressively with increasing FPG. Despite equivalent glucose exposure simple trends of increasing AUC, IRI with increasing BMI were statistically significant (P < 0.001, P < 0.02, P < 0.001 and P < 0.01, respectively for each FPG group). Both fasting and AUC non-esterified fatty acid concentrations increased significantly with FPG regardless of BMI (P < 0.001 for the trends). These results using a more physiological mixed meal challenge in a large number of recently diagnosed Type 2 diabetic subjects demonstrate a marked and increasing loss of beta-cell secretory function with increasing fasting hyperglycaemia aggravated by insulin resistance with increasing obesity.

Nebulized Furosemide for the Management of Dyspnea: Does the Evidence Support Its Use?

Dyspnea is a common and distressing symptom associated with multiple chronic illnesses and high levels of burden for individuals, their families and health care systems. The subjective nature dyspnea and a poor understanding of pathophysiological mechanisms challenge the clinician in developing management plans. Nebulized furosemide has been identified as a novel approach to dyspnea management. This review summarizes published studies, both clinical and experimental, reporting the use of nebulized furosemide. The search criteria yielded 42 articles published in the period 1988 to 2004. Although nebulized furosemide appeared to have a positive influence on dyspnea and physiological measurements, caution must be taken with the results primarily coming from small-scale clinical trials or observation trials. Despite the limitations of the studies reported, given the range of conditions reporting effectiveness of nebulized furosemide, further investigation of this potential novel treatment of dyspnea is warranted.

Is human type 2 diabetes maternally inherited? : insights from an animal model

Aims  Patients with Type 2 diabetes mellitus more often report a history of an affected mother than father. However, in the few studies where both parents and offspring have been directly tested, this apparent maternal excess has not been confirmed. Rodent models of diabetes have the advantage that all parents and offspring can undergo glucose tolerance testing at a specific age in adult life. The aim of this study was to gain insights into the inheritance of human Type 2 diabetes by using a rat model.

Reduced sampling protocols in estimation of insulin sensitivity and glucose effectiveness using the minimal model in NIDDM

Recent work in healthy subjects, the aged, and subjects with gestational diabetes or drug-induced insulin resistance using minimal model analysis of the tolbutamide-modified frequently sampled intravenous glucose tolerance test suggested that a reduced sampling regimen of 12 time points produced unbiased and generally acceptable estimates of insulin sensitivity (SI) and glucose effectiveness (SG) compared with a full sampling schedule of 30 time points. We have used data from 26 insulin-modified frequently sampled intravenous glucose tolerance tests in 21 subjects with NIDDM to derive and compare estimates of SI and SG from the full sampling schedule (SI(30), SG(30)) with those estimated from the suggested 12 time points (SI(12), SG(12)) and those estimated with the addition of a 25-min time point (SI(13), SG(13)). Percentage relative errors were calculated relative to the corresponding 30 time-point values. A statistically significant bias of 15% (97% confidence interval from 7.4 to 25.6%, interquartile range 25%) was introduced by the estimation of SI(12) but not SI(13) (1%, 97% confidence interval from –9.4 to 9.3%, interquartile range 21%). Results for SG(12) (–12%, 97% confidence interval from –46.7 to 1.2%, interquartile range 49%) and SG(13) (–5%, 97% confidence interval from –27.8 to 6.8%, interquartile range 37%) were statistically equivocal. The precision of estimation of SI(12), SG(12), and SG(13) measured by the interquartile range of the percentage relative errors was poor. The precision of determination measured by the median minimal model coefficient of variation was 18, 29, and 27% for SI(30), SI(12), and SI(13) and 9, 11, and 11% for SG(30), SG(12), and SG(13), respectively. Thus, the application of minimal model analysis to the 12 time-point protocol of the insulin-modified IVGTT for the estimation of SI and SG in NIDDM may necessitate an inordinately large number of subjects. Although the 13 time-point protocol may be more acceptable for the assessment of SG in population studies, we recommend retention of the full sampling schedule where feasible.

Disaster medical assistance teams: what psychosocial support is needed?

OBJECTIVE The objective of this preliminary study was to evaluate the perceptions of internationally deployed Disaster Medical Assistance Team (DMAT) personnel regarding the psychosocial support needs of these teams. METHODS The DMAT questionnaire was sent to 34 members of Australian medical teams involved in deployments to the 2004 Southeast Asian tsunami and the 2006 Java earthquake. Twenty personnel (59%) completed this survey, which reviewed key deployment stressors, specific support strategies, and the support needs of team members, their families, and team leaders. A key aspect of the survey was to determine whether the perceived psychosocial needs would be supported best within with existing provisions and structures, or if they would be enhanced by further provisions, including the deployment of mental health specialists. RESULTS There was strong support for brief reviews of stress management strategies as part of the pre-deployment briefing, and access to written stress management information for both team members and their families. However, more comprehensive provisions, including pre-deployment, stress-management training programs for personnel and intra-deployment family support programs, received lower levels of support. The availability of mental health-related training for the team leader role and access to consultation with mental health specialists was supported, but this did not extend to the actual deployment of mental health specialists. CONCLUSIONS In this preliminary study, clear trends toward the maintenance of current mental health support provisions and the role of the DMAT leader were evident. A follow-up study will examine the relationship between team-leader, psychosocial support strategies and team functioning.

Some useful integer arrays for the teaching of generalization skills

involved. Many of the basic concepts of numerical linear algebra are to be found in the Simultaneous Iteration method, especially when the basic process is extended by the inclusion of an inverse iteration cycle. It can be introduced to students at different levels, depending on their mathematical expertise. For first and second year students it is a natural extension to the Power Method and implementing it in Maple1 worksheets allows usage of a wider range of standard commands in a practical context. For higher level classes further investigations are both possible and necessary. Merely taking the number of iterations as a measure of efficiency is too simplistic and the additional workload involved by including an inverse iteration phase must be quantified. Using more trial vectors than the order of eigensolution sought can prove beneficial and needs further investigation. Theoretical proofs of the validity of the method in all situations must also be generated but nevertheless Simultaneous Iteration is a useful teaching medium and allows students to see how mathematical research can feed directly into the learning environment.

Partial row-sums of Pascal's triangle

Formulae for binomial coefficient sums of the form are developed by use of generating functions.

Extensions of Generalized Binomial Coefficients

Bondarenko gives an excellent account of the history and properties of the generalized binomial coefficient [2] . He describes this coefficient, written \({\left( {\begin{array}{*{20}{c}} n \\ m \\ \end{array}} \right)_S}\) for n, m ≥ 0 and s ≥ 1, as the number of ways m objects can be placed in n cells, each of which holds a maximum of s - 1 objects. The ordinary binomial coefficients are obtained when s = 2. This description tacitly assumes that empty cells produce distinct arrangements, that the objects are placed in the cells in a given order and that the order of the objects within the cells is not important.