Nigel Harris - Academia.edu (original) (raw)

Papers by Nigel Harris

Research paper thumbnail of Feature extraction and classification of electrocardiogram (ECG) signals related to hypoglycaemia

Computers in Cardiology, 2003, 2003

Nocturnal hypoglycaemia has been implicated in the sudden deaths of young people with diabetes. E... more Nocturnal hypoglycaemia has been implicated in the sudden deaths of young people with diabetes. Experimental hypoglycaemia has been found to prolong the ventricular repolarisation and to affect the T wave morphology. It is postulated that abnormally low blood glucose could in certain circumstances, be responsible for the development of a fatal cardiac arrhythmia. We have used automatic extraction of both timeinterval and morphological features, from the Electrocardiogram (ECG) to classify ECGs into normal and arrhythmic. Classification was implemented by artificial neural networks (ANN) and Linear Discriminant Analysis (LDA). The ANN gave more accurate results. Average training accuracy of the ANN was 85.07% compared with 70.15% on unseen data. This study may lead towards the demonstration of the possible relationship between cardiac function and abnormally low blood glucose.

Research paper thumbnail of Review Clinical applications of electrical impedance tomography

Journal of Medical Engineering & Technology, 1993

... The lungs can be clearly identified on the EIT image (figure 1). Impedance changes are primar... more ... The lungs can be clearly identified on the EIT image (figure 1). Impedance changes are primarily due to changes in lung resistivity, but there are contributions from associated changes in chest geometry and changes in pulmonary blood volume [20]. Kira et al. ...

Research paper thumbnail of A new minimally invasive technique to show nerve ischaemia in diabetic neuropathy

Diabetologia, 1999

Despite extensive research, the pathogenesis of diabetic neuropathy is far from clear. Most of th... more Despite extensive research, the pathogenesis of diabetic neuropathy is far from clear. Most of the debates have focused on metabolic [1, 2] or vascular factors [3, 4] and the complex interactions between them [5, 6]. The role of microvascular disease in the pathogenesis of diabetic neuropathy has gained support from studies in experimental and human diabetic neuropathy [3]. In human sural nerve, oxygen tension was found to be reduced and the presence of arteriovenous shunting and impaired nerve blood flow shown [7, 8]. These findings have been reinforced by nerve biopsy studies, which have shown a correlation between the presence and the degree of microvascular abnormalities with the presence and severity of diabetic neuropathy [9±10]. In vivo studies involving human nerves have, however, been limited by the invasive nature of the mea-Diabetologia (1999) 42: 737±742

Research paper thumbnail of Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes

Diabetologia, 2004

Aims/hypothesis. Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by ... more Aims/hypothesis. Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by a lengthened QT interval and caused by adrenergic stimulation. However it is less clear whether spontaneous clinical episodes lead to similar changes. We have therefore measured cardiac ventricular repolarization and counterregulatory responses in patients with Type 1 diabetes during hypoglycaemic and euglycaemic nights. Methods. We studied 22 patients with Type 1 diabetes (mean age 40.4±17.2 years, duration of diabetes 17.2±9.3 years, HbA1c 8.2±1.2% overnight). Measurements were taken hourly of blood glucose, plasma potassium, catecholamines and high resolution electrocardiograms. Results. Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights. During overnight hypoglycaemia, QTc interval increased by 27 ms (±15) above baseline, compared with 9 ms (±19) during nights with no nocturnal hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (±0.21) above baseline during hypoglycaemia, compared with −0.05 nmol/l (±0.08) during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant difference between potassium, and noradrenaline concentrations between the two groups. Conclusion/interpretation. QTc interval lengthens significantly during spontaneous nocturnal hypoglycaemia. Increases are generally less than those observed during experimental hypoglycaemia and could reflect attenuated sympathoadrenal responses during clinical episodes. The clinical relevance of these changes is uncertain but is consistent with the hypothesis that clinical hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of cardiac arrhythmia. [Diabetologia (2004) 47:312-315]

Research paper thumbnail of Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes

Diabetologia, 2005

Aims/hypothesis: Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthen... more Aims/hypothesis: Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthening on the ECG; this may be important in the pathogenesis of sudden overnight death in young people with diabetes. Since hypoglycaemic QTc lengthening appears to be mediated through the sympathoadrenal response, we tested the hypothesis that beta 1-blockade will prevent these changes in type 1 diabetic patients and so provide a potential therapeutic intervention. Methods: We studied eight type 1 diabetic adults without cardiovascular or renal complications. Similar hypoglycaemic clamp studies were performed on two occasions, at least 4 weeks apart, but immediately before one visit subjects received atenolol 100 mg daily for 7 days. Following a 60-min euglycaemic (5 mmol/l) period, blood glucose was lowered over 30 min to 2.5 mmol/l, and held for 60 min. High-resolution ECG was recorded at baseline and at 0, 30 and 60 min during each glycaemic plateau. QT interval was measured using a semiautomated tangent method and QTc was derived from QT using the Fridericia formula. Results: Mean (SD) baseline QTc was similar at both visits: control 391 (30) ms, post-atenolol 386 (34) ms; (p=0.33). Without atenolol pretreatment, QTc lengthened during hypoglycaemia to a maximum of 448 (34) ms (p<0.001). On atenolol, QTc lengthening was significantly reduced (peak QTc 413 (27) ms; p=0.004 vs control visit). Conclusions/interpretation: Hypoglycaemic QTc lengthening is blunted by atenolol in patients with type 1 diabetes. Selective beta 1-blockade may help prevent sudden death, if we can identify those at high risk.

Research paper thumbnail of Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy

Diabetologia, 2003

Aims/hypothesis. The pathogenesis of painful diabetic neuropathy remains unknown. As a consequenc... more Aims/hypothesis. The pathogenesis of painful diabetic neuropathy remains unknown. As a consequence we still do not have any effective, rational treatments and a greater understanding of the mechanisms is urgently required. Previous studies have shown no consistent morphological differences in the nerves of patients with and without painful neuropathy. The aim of this study was to compare epineurial haemodynamics in patients with chronic painful and painless neuropathy. Methods. The techniques of microlightguide spectrophotometry and fluorescein angiography were used to measure epineurial intravascular oxygen saturation and blood flow respectively. Eleven patients with painful and eight with painless neuropathy were studied, with the groups matched carefully in terms of severity of neuropathy and diabetes control. Results. Intravascular oxygen saturation was higher in the painful neuropathy group compared to those without pain (median 73.8% vs 67.7%, respectively; p=0.021). Fluorescein rise time was also faster in those with painful symptoms (median 18.3 s vs 53.6 s; p=0.046) indicating higher epineurial blood flow in these subjects. Conclusion/interpretation. These results indicate that there are distinct differences in haemodynamics within the epineurium of the sural nerve in subjects with painful and painless neuropathy. Haemodynamic factors could therefore have an important role in the pathogenesis of neuropathic pain and might offer further insight into potential treatments for this distressing condition.

Research paper thumbnail of Impaired blood flow and arterio-venous shunting in human diabetic neuropathy: a novel technique of nerve photography and fluorescein angiography

Diabetologia, 1993

New techniques of sural nerve photography and fluorescein angiography which are able to provide a... more New techniques of sural nerve photography and fluorescein angiography which are able to provide an index of nerve blood flow have been developed. Under local anaesthetic, 3 cm of sural nerve was exposed at the ankle using an operating microscope. Without disturbing the epineurium, vessels were identified and photographed at a standard magnification (x 30). These were independently graded by an ophthalmologist not otherwise involved with the study. Fluorescein angiography was then carried out on the exposed nerve. The fluorescein appearance time and intensity of fluorescence were quantified, using computer analysis of digitised images. Thirteen subjects with chronic sensory motor neuropathy, five non-neuropathic diabetic and nine normal control subjects were studied. The mean epineurial vessel pathology score of the neuropathic group was significantly higher than the combined normal control and non-neuropathic diabetic groups (p < 0.01). Direct epineurial arteriovenous shunting was observed in six neuropathic and one non-neuropathic diabetic patients and not in any of the normal control subjects. The nerve fluorescein appearance time was significantly delayed in subjects with chronic sensory motor neuropathy (51.5 + 12 s) compared to both normal (34.7 _+ 9 s, p < 0.01) and non-neuropathic diabetic subjects (33.4 + 11 s,p < 0.025). The mean intensity of fluorescence at 96, 252 and 576 s, was significantly lower in subjects with chronic sensory motor neuropathy compared with both of the other groups (p < 0.05). The epineurial vessel pathology score was significantly related to reduced sural (p < 0.01) and peroneal (p < 0.001) nerve conduction velocities, elevated vibration (p < 0.01) and thermal (p < 0.001) perception and the severity of retinopathy (p < 0.002). The fluorescein appearance time was significantly related to reduced sural sensory (p <0.02) conduction velocity, elevated vibration (p < 0.01) perception and epineurial vessel (p < 0.002) pathology score, but it failed to relate to peroneal motor (p = 0.06) conduction velocity, thermal (p = 0.1) perception and the severity ofretinopathy (p = 0.3). Intensity of fluorescence was significantly related to fluorescein appearance time (at 96 s,p < 0.001; at 576 s,p < 0.05) but did not relate to measures of neuropathic severity. These techniques have enabled us to observe that epineurial vessel anatomy is abnormal and that nerve blood flow is impaired in subjects with chronic sensory motor neuropathy. In addition epineurial arterio-venous shunting may be a feature of diabetic neuropathy. These techniques may further be applied to study nerve blood flow in early diabetic neuropathy.

Research paper thumbnail of Exercise-induced conduction velocity increment: a marker of impaired peripheral nerve blood flow in diabetic neuropathy

Diabetologia, 1992

Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive ... more Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive test that will identify those diabetic subjects who will eventually develop neuropathy is essential for early intervention. Sural sensory conduction velocity was recorded (x 3) in 12 non-neuropathic diabetic subjects, 15 diabetic subjects with established neuropathy and 16 age-matched normal control subjects, before and after exercise to 80 % age/sex predicted maximum heart rate. Fixed sural electrodes were used. Subcutaneous temperature was recorded by a needle thermocouple placed near the sural nerve. Sural sensory conduction velocity increased significantly after exercise in normal subjects (p <0.01, mean increase 5.07 m/s) and non-neuropathic diabetic subjects (p < 0.02, mean increase 3.99 m/s) but not in neuropathic subjects (mean increase 0.99 m/s). Subcuta-neous temperature rose significantly in normal subjects (p<0.01, mean increase 2.07~ and non-neuropathic diabetic subjects (p < 0.001, mean increase 2.52 ~ but not in neuropathic subjects (mean increase 0.15 ~ However, sural sensory conduction velocity increased by 1.2 m. s-1 ~ following direct warming of the limb in six neuropathic subjects which was comparable to that of normal and non-neuropathic subjects (1.49 and 1.48 m. s-1. ~ The impairment of exercise conduction increment in diabetic neuropathy suggests impaired nerve blood flow in diabetic neuropathy.

Research paper thumbnail of Prolonged but partial impairment of the hypoglycaemic physiological response following short-term hypoglycaemia in normal subjects

Diabetologia, 1995

Recent studies have reported reduced endocrine and symptomatic responses to hypoglycaemia 18-24 h... more Recent studies have reported reduced endocrine and symptomatic responses to hypoglycaemia 18-24 h after antecedent hypoglycaemia in both non-diabetic subjects and those with insulin-dependent diabetes mellitus. We examined these and peripheral physiological responses in eight nondiabetic subjects aged 23-35 years in the week following antecedent hypoglycaemia. Blood glucose levels were held at plateaus of 5 mmol/1 and 2.5 mmol/1 for 30 min during hyperinsulinaemic (60 mUm -2. min-~) morning clamps on days 1, 3 and 8 of two study periods separated by at least 4 weeks. Measurements were made at time 0, 15 and 30 min of each plateau on each day. On the afternoon of Day 1 we also induced either euglycaemia with a blood glucose level of 5 mmol/1 (control week) or hypoglycaemia of 2.9 mmol/1 (hypo week) for 2 h in random order. The adrenaline response to morning hypoglycaemia (p < 0.01 on all days) was attenuated on Day3 (p < 0.05) and Day 8 (p < 0.05) compared to Day i of hypo week only. Sweating was also attenuated on Day 3 (p < 0.05) and Day 8 (p < 0.02) of hypo week only. Noradrenaline levels and tremor increased during hypoglycaemia on each study day (p < 0.05) but did not differ between days in either week. During hypo week only, the total symptom score response to hypoglycaemia was attenuated on Day 3 (p < 0.03) but not Day 8 (p = 0.10). Autonomic symptoms were similarly affected. In summary, the physiological responses to hypoglycaemia are affected differentially by antecedent hypoglycaemia with sweating and adrenaline responses remaining impaired for at least 5 days.

Research paper thumbnail of Early identification of diabetic foot ulcers that may require intervention using the micro lightguide spectrophotometer

Diabetes Care, 1999

OBJECTIVE: Adequate tissue oxygenation is known to be essential for the healing of diabetic foot ... more OBJECTIVE: Adequate tissue oxygenation is known to be essential for the healing of diabetic foot ulcers, but hypoxia has also been shown to be a potent stimulus for growth. There are no studies looking specifically at ulcer oxygen levels during the healing process. We measured the serial microvascular oxygen saturation (SaO2) of the foot ulcer, the ulcer margin, and a control site using the Erlangen micro lightguide spectrophotometer (EMPHO II; Bodenseewerk Geratetechnik, Erlangen, Germany) to study serial changes during healing. RESEARCH AND DESIGN METHODS: Studied over 9 months were 14 patients with neuropathy with a total of 24 foot ulcer sites. Of these patients, four (seven ulcers) had significant ischemia as determined by the ankle-brachial pressure index (ABPI) and transcutaneous oxygen tension. RESULTS: Of 21 ulcer sites with serial measurements, only 13 ulcers healed. In those ulcers, a significant reduction (P<0.05) in SaO2 occurred with healing. SaO2 dropped from 58% a...

Research paper thumbnail of Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes

Diabetes, 2004

Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and su... more Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and sudden death. This results from both sympatho-adrenal activation and a lowered serum potassium. It has been suggested that cardiac autonomic neuropathy (CAN) might indicate those who are at particular risk. We tested this hypothesis in 28 adults with type 1 diabetes and 8 nondiabetic control subjects. After standard tests of autonomic function and baroreflex sensitivity (BRS) measurement, diabetic participants were divided into three groups: 1) CAN− with normal BRS (BRS+; n = 10), 2) CAN− with impaired BRS (BRS−; n = 9), and 3) CAN+ (n = 9). QTc was then measured during controlled hypoglycemia (2.5 mmol/l) using a hyperinsulinemic clamp. Mean (±SE) QTc lengthened from 377 ± 9 ms (baseline) to a maximum during hypoglycemia of 439 ± 13 ms in BRS+ subjects and from 378 ± 5 to 439 ± 10 ms in control subjects. Peak QTc tended to be lower in CAN+ (baseline, 383 ± 6; maximum, 408 ± 10) and BRS− g...

Research paper thumbnail of Mechanisms of Abnormal Cardiac Repolarization During Insulin-Induced Hypoglycemia

Diabetes, 2003

Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these c... more Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these contribute to sudden death associated with nocturnal hypoglycemia in young people with diabetes. We measured cardiac repolarization (QT interval [QTc] and QT dispersion [QTd]) during experimental hypoglycemia with and without β-blockade and potassium infusion to establish possible mechanisms. Two groups of 10 nondiabetic men (study 1 and study 2) each underwent four hyperinsulinemic clamps: two euglycemic (5 mmol/l) and two hypoglycemic (5 mmol/l and 2.5 mmol/l for 60 min each). Study 1 was performed with and without potassium infusion to maintain normal concentrations and study 2 with and without β-blockade (atenolol, 100 mg/day for 7 days). QTd was unchanged during euglycemia but increased during hypoglycemia (55 ms, P < 0.0001 vs. baseline), which was prevented by potassium (6 ms, P = 0.78). QTc increased significantly during hypoglycemia alone (67 ms, P < 0.0001) and during pota...

Research paper thumbnail of A knowledge-based electrocardiogram-monitoring system for detection of the onset of nocturnal hypoglycaemia in type 1 diabetic patients

Nocturnal hypoglycaemia has been implicated in the sudden deaths of young people with diabetes. E... more Nocturnal hypoglycaemia has been implicated in the sudden deaths of young people with diabetes. Experimental hypoglycaemia has been found to prolong the ventricular repolarisation and to affect the T wave morphology. It is postulated that abnormally low blood glucose could in certain circumstances, be responsible for the development of a fatal cardiac arrhythmia. We have designed a monitoring and alarm system for detection of the onset of spontaneous nocturnal hypoglycaemia through monitoring of the electrocardiogram. The system incorporates expertknowledge in the form of a rule-base. It performs monitoring of two ECG features and raises alarms if abnormalities are detected corresponding to hypoglycaemia. The top performance of the system is 100% and 91.30% for sensitivity and specificity respectively. This study supports the hypothesis proposing a relationship between cardiac function and abnormally low blood glucose.

Research paper thumbnail of Preservation of Physiological Responses to Hypoglycemia 2 Days After Antecedent Hypoglycemia in Patients With IDDM

Diabetes Care, 1997

OBJECTIVE To assess the effects of short-term antecedent hypoglycemia on responses to further hyp... more OBJECTIVE To assess the effects of short-term antecedent hypoglycemia on responses to further hypoglycemia 2 days later in patients with IDDM. RESEARCH DESIGN AND METHODS We studied eight type I diabetic patients without hypoglycemia unawareness or autonomic neuropathy during two periods at least 4 weeks apart. On day 1, 2 h of either clamped hyperinsulinemic (60 mU · m−2 · min−1) hypoglycemia at 2.8 mmol/l or euglycemia at 5.0 mmol/l were induced. Hyperinsulinemic hypoglycemia was induced 2 days later with 40 min glucose steps of 5.0, 4.0, 3.5, 3.0, and 2.5 mmol/l. Catecholamine levels and symptomatic and physiological responses were measured every 10–20 min. RESULTS When compared with the responses measured following euglycemia, the responses of norepinephrine 2 days after hypoglycemia were reduced (peak, 1.4 ± 0.4 [mean ± SE] vs.1.0 ± 0.3 nmol/l [P < 0.05]; threshold, 3.4 ± 0.1 vs. 2.9 ± 0.1 mmol/l glucose [P < 0.01]). The responses of epinephrine (peak, 4.0 ± 1.4 vs. 3.5 ±...

Research paper thumbnail of Using simple technology to prompt multistep tasks in the home for people with dementia: An exploratory study comparing prompting formats

Dementia (London, England), Jan 30, 2015

To investigate the relative effectiveness of different prompts for people with dementia during mu... more To investigate the relative effectiveness of different prompts for people with dementia during multistep tasks in the home, to inform prompting technology design. Nine pairs of participants (one with dementia and a partner or relative) participated at home. The participants with mild to moderate dementia (5M/4F, aged 73-86 years) functioned at the Planned or Exploratory levels of the Pool Activity Level instrument. A touchscreen computer displayed different prompts during two set tasks: "card-and-envelope" and "CD player." The trials were scored to establish the relative effectiveness of the prompts. Individual tasks were also explored. Text and audio prompts were each more effective than video or picture prompts for a card-and-envelope task, but this was not seen in a CD player task. The differences may be related to the type of actions within the tasks; the card-and-envelope actions were easier to convey verbally; the CD player actions lent themselves to visual...

Research paper thumbnail of Personal message cards: An evaluation of an alternative method of delivering simulated presence therapy

Dementia (London, England), Jan 11, 2015

Simulated presence therapy is a technique which utilises a familiar recorded voice to calm and re... more Simulated presence therapy is a technique which utilises a familiar recorded voice to calm and reassure people with dementia who are agitated or anxious. Although simulated presence therapy has shown potential benefits in small-scale studies, practical limitations in making and playing the recordings have restricted its use. An alternative method of delivering a message from an attachment figure is through a personal message card. This was one of seven products used within the Bath Memory Technology Library which was made available free of charge to people affected by dementia and their carers. This paper provides an evaluation of the personal message cards. Although feedback was received on only 10 of the 24 cards that were distributed, for nine people there was evidence that the cards met the goals that had been set either fully or in part, and that people affected by even quite severe levels of dementia could benefit from them.

Research paper thumbnail of Pain and other symptoms of CRPS can be increased by ambiguous visual stimuli - An exploratory study

European Journal of Pain, 2011

Background: Visual disturbance, visuo-spatial difficulties, and exacerbations of pain associated ... more Background: Visual disturbance, visuo-spatial difficulties, and exacerbations of pain associated with these, have been reported by some patients with Complex Regional Pain Syndrome (CRPS). Aims: We investigated the hypothesis that some visual stimuli (i.e. those which produce ambiguous perceptions) can induce pain and other somatic sensations in people with CRPS. Methods: Thirty patients with CRPS, 33 with rheumatology conditions and 45 healthy controls viewed two images: a bistable spatial image and a control image. For each image participants recorded the frequency of percept change in 1 min and reported any changes in somatosensation. Results: 73% of patients with CRPS reported increases in pain and/or sensory disturbances including changes in perception of the affected limb, temperature and weight changes and feelings of disorientation after viewing the bistable image. Additionally, 13% of the CRPS group responded with striking worsening of their symptoms which necessitated task cessation. Subjects in the control groups did not report pain increases or somatic sensations. Conclusions: It is possible to worsen the pain suffered in CRPS, and to produce other somatic sensations, by means of a visual stimulus alone. This is a newly described finding. As a clinical and research tool, the experimental method provides a means to generate and exacerbate somaesthetic disturbances, including pain, without moving the affected limb and causing nociceptive interference. This may be particularly useful for brain imaging studies.

Research paper thumbnail of Microcirculatory responses to electrical spinal cord stimulation in painful diabetic neuropathy and other painful conditions

Diabetes Research and Clinical Practice, 2000

Research paper thumbnail of Early Involvement of the Spinal Cord in Diabetic Peripheral Neuropathy

Diabetes Care, 2006

OBJECTIVE—The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have ... more OBJECTIVE—The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have recently reported a significant reduction in spinal cord cross-sectional area at the stage of clinically detectable DPN. In this study, we investigated whether spinal cord atrophy occurs in early (subclinical) DPN. RESEARCH DESIGN AND METHODS—Eighty-one male type 1 diabetic subjects, 24 nondiabetic control subjects, and 8 subjects with hereditary sensory motor neuropathy (HSMN) type 1A underwent detailed clinical and neurophysiological assessments. Diabetic subjects were subsequently divided into three groups based on neuropathy severity (19 with no DPN, 23 with subclinical DPN, and 39 with clinically detectable DPN). All subjects underwent magnetic resonance imaging of the cervical spine and cord area measurements at disc level C2/C3. RESULTS—Mean corrected spinal cord area index (SCAI) (corrected for age, height, and weight) was 67.5 mm [95% CI 64.1–70.9] in diabetic subjects without D...

Research paper thumbnail of Does the choice of treatment for type 2 diabetes affect the physiological response to hypoglycemia?

Diabetes Care, 2000

References 1. Yamada K, Nonaka K: Diabetic ketoacidosis in young obese Japanese men: atypical dia... more References 1. Yamada K, Nonaka K: Diabetic ketoacidosis in young obese Japanese men: atypical diabetes induced by sugar-containing soft drinks (Letter). Diabetes Care 19:671, 1996 2. Tanaka K, Moriya T, Kanamori A, Yajima Y: Analysis and a long-term follow up of ketosis-onset Japanese NIDDM patients.

Research paper thumbnail of Feature extraction and classification of electrocardiogram (ECG) signals related to hypoglycaemia

Computers in Cardiology, 2003, 2003

Nocturnal hypoglycaemia has been implicated in the sudden deaths of young people with diabetes. E... more Nocturnal hypoglycaemia has been implicated in the sudden deaths of young people with diabetes. Experimental hypoglycaemia has been found to prolong the ventricular repolarisation and to affect the T wave morphology. It is postulated that abnormally low blood glucose could in certain circumstances, be responsible for the development of a fatal cardiac arrhythmia. We have used automatic extraction of both timeinterval and morphological features, from the Electrocardiogram (ECG) to classify ECGs into normal and arrhythmic. Classification was implemented by artificial neural networks (ANN) and Linear Discriminant Analysis (LDA). The ANN gave more accurate results. Average training accuracy of the ANN was 85.07% compared with 70.15% on unseen data. This study may lead towards the demonstration of the possible relationship between cardiac function and abnormally low blood glucose.

Research paper thumbnail of Review Clinical applications of electrical impedance tomography

Journal of Medical Engineering & Technology, 1993

... The lungs can be clearly identified on the EIT image (figure 1). Impedance changes are primar... more ... The lungs can be clearly identified on the EIT image (figure 1). Impedance changes are primarily due to changes in lung resistivity, but there are contributions from associated changes in chest geometry and changes in pulmonary blood volume [20]. Kira et al. ...

Research paper thumbnail of A new minimally invasive technique to show nerve ischaemia in diabetic neuropathy

Diabetologia, 1999

Despite extensive research, the pathogenesis of diabetic neuropathy is far from clear. Most of th... more Despite extensive research, the pathogenesis of diabetic neuropathy is far from clear. Most of the debates have focused on metabolic [1, 2] or vascular factors [3, 4] and the complex interactions between them [5, 6]. The role of microvascular disease in the pathogenesis of diabetic neuropathy has gained support from studies in experimental and human diabetic neuropathy [3]. In human sural nerve, oxygen tension was found to be reduced and the presence of arteriovenous shunting and impaired nerve blood flow shown [7, 8]. These findings have been reinforced by nerve biopsy studies, which have shown a correlation between the presence and the degree of microvascular abnormalities with the presence and severity of diabetic neuropathy [9±10]. In vivo studies involving human nerves have, however, been limited by the invasive nature of the mea-Diabetologia (1999) 42: 737±742

Research paper thumbnail of Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes

Diabetologia, 2004

Aims/hypothesis. Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by ... more Aims/hypothesis. Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by a lengthened QT interval and caused by adrenergic stimulation. However it is less clear whether spontaneous clinical episodes lead to similar changes. We have therefore measured cardiac ventricular repolarization and counterregulatory responses in patients with Type 1 diabetes during hypoglycaemic and euglycaemic nights. Methods. We studied 22 patients with Type 1 diabetes (mean age 40.4±17.2 years, duration of diabetes 17.2±9.3 years, HbA1c 8.2±1.2% overnight). Measurements were taken hourly of blood glucose, plasma potassium, catecholamines and high resolution electrocardiograms. Results. Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights. During overnight hypoglycaemia, QTc interval increased by 27 ms (±15) above baseline, compared with 9 ms (±19) during nights with no nocturnal hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (±0.21) above baseline during hypoglycaemia, compared with −0.05 nmol/l (±0.08) during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant difference between potassium, and noradrenaline concentrations between the two groups. Conclusion/interpretation. QTc interval lengthens significantly during spontaneous nocturnal hypoglycaemia. Increases are generally less than those observed during experimental hypoglycaemia and could reflect attenuated sympathoadrenal responses during clinical episodes. The clinical relevance of these changes is uncertain but is consistent with the hypothesis that clinical hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of cardiac arrhythmia. [Diabetologia (2004) 47:312-315]

Research paper thumbnail of Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes

Diabetologia, 2005

Aims/hypothesis: Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthen... more Aims/hypothesis: Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthening on the ECG; this may be important in the pathogenesis of sudden overnight death in young people with diabetes. Since hypoglycaemic QTc lengthening appears to be mediated through the sympathoadrenal response, we tested the hypothesis that beta 1-blockade will prevent these changes in type 1 diabetic patients and so provide a potential therapeutic intervention. Methods: We studied eight type 1 diabetic adults without cardiovascular or renal complications. Similar hypoglycaemic clamp studies were performed on two occasions, at least 4 weeks apart, but immediately before one visit subjects received atenolol 100 mg daily for 7 days. Following a 60-min euglycaemic (5 mmol/l) period, blood glucose was lowered over 30 min to 2.5 mmol/l, and held for 60 min. High-resolution ECG was recorded at baseline and at 0, 30 and 60 min during each glycaemic plateau. QT interval was measured using a semiautomated tangent method and QTc was derived from QT using the Fridericia formula. Results: Mean (SD) baseline QTc was similar at both visits: control 391 (30) ms, post-atenolol 386 (34) ms; (p=0.33). Without atenolol pretreatment, QTc lengthened during hypoglycaemia to a maximum of 448 (34) ms (p<0.001). On atenolol, QTc lengthening was significantly reduced (peak QTc 413 (27) ms; p=0.004 vs control visit). Conclusions/interpretation: Hypoglycaemic QTc lengthening is blunted by atenolol in patients with type 1 diabetes. Selective beta 1-blockade may help prevent sudden death, if we can identify those at high risk.

Research paper thumbnail of Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy

Diabetologia, 2003

Aims/hypothesis. The pathogenesis of painful diabetic neuropathy remains unknown. As a consequenc... more Aims/hypothesis. The pathogenesis of painful diabetic neuropathy remains unknown. As a consequence we still do not have any effective, rational treatments and a greater understanding of the mechanisms is urgently required. Previous studies have shown no consistent morphological differences in the nerves of patients with and without painful neuropathy. The aim of this study was to compare epineurial haemodynamics in patients with chronic painful and painless neuropathy. Methods. The techniques of microlightguide spectrophotometry and fluorescein angiography were used to measure epineurial intravascular oxygen saturation and blood flow respectively. Eleven patients with painful and eight with painless neuropathy were studied, with the groups matched carefully in terms of severity of neuropathy and diabetes control. Results. Intravascular oxygen saturation was higher in the painful neuropathy group compared to those without pain (median 73.8% vs 67.7%, respectively; p=0.021). Fluorescein rise time was also faster in those with painful symptoms (median 18.3 s vs 53.6 s; p=0.046) indicating higher epineurial blood flow in these subjects. Conclusion/interpretation. These results indicate that there are distinct differences in haemodynamics within the epineurium of the sural nerve in subjects with painful and painless neuropathy. Haemodynamic factors could therefore have an important role in the pathogenesis of neuropathic pain and might offer further insight into potential treatments for this distressing condition.

Research paper thumbnail of Impaired blood flow and arterio-venous shunting in human diabetic neuropathy: a novel technique of nerve photography and fluorescein angiography

Diabetologia, 1993

New techniques of sural nerve photography and fluorescein angiography which are able to provide a... more New techniques of sural nerve photography and fluorescein angiography which are able to provide an index of nerve blood flow have been developed. Under local anaesthetic, 3 cm of sural nerve was exposed at the ankle using an operating microscope. Without disturbing the epineurium, vessels were identified and photographed at a standard magnification (x 30). These were independently graded by an ophthalmologist not otherwise involved with the study. Fluorescein angiography was then carried out on the exposed nerve. The fluorescein appearance time and intensity of fluorescence were quantified, using computer analysis of digitised images. Thirteen subjects with chronic sensory motor neuropathy, five non-neuropathic diabetic and nine normal control subjects were studied. The mean epineurial vessel pathology score of the neuropathic group was significantly higher than the combined normal control and non-neuropathic diabetic groups (p < 0.01). Direct epineurial arteriovenous shunting was observed in six neuropathic and one non-neuropathic diabetic patients and not in any of the normal control subjects. The nerve fluorescein appearance time was significantly delayed in subjects with chronic sensory motor neuropathy (51.5 + 12 s) compared to both normal (34.7 _+ 9 s, p < 0.01) and non-neuropathic diabetic subjects (33.4 + 11 s,p < 0.025). The mean intensity of fluorescence at 96, 252 and 576 s, was significantly lower in subjects with chronic sensory motor neuropathy compared with both of the other groups (p < 0.05). The epineurial vessel pathology score was significantly related to reduced sural (p < 0.01) and peroneal (p < 0.001) nerve conduction velocities, elevated vibration (p < 0.01) and thermal (p < 0.001) perception and the severity of retinopathy (p < 0.002). The fluorescein appearance time was significantly related to reduced sural sensory (p <0.02) conduction velocity, elevated vibration (p < 0.01) perception and epineurial vessel (p < 0.002) pathology score, but it failed to relate to peroneal motor (p = 0.06) conduction velocity, thermal (p = 0.1) perception and the severity ofretinopathy (p = 0.3). Intensity of fluorescence was significantly related to fluorescein appearance time (at 96 s,p < 0.001; at 576 s,p < 0.05) but did not relate to measures of neuropathic severity. These techniques have enabled us to observe that epineurial vessel anatomy is abnormal and that nerve blood flow is impaired in subjects with chronic sensory motor neuropathy. In addition epineurial arterio-venous shunting may be a feature of diabetic neuropathy. These techniques may further be applied to study nerve blood flow in early diabetic neuropathy.

Research paper thumbnail of Exercise-induced conduction velocity increment: a marker of impaired peripheral nerve blood flow in diabetic neuropathy

Diabetologia, 1992

Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive ... more Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive test that will identify those diabetic subjects who will eventually develop neuropathy is essential for early intervention. Sural sensory conduction velocity was recorded (x 3) in 12 non-neuropathic diabetic subjects, 15 diabetic subjects with established neuropathy and 16 age-matched normal control subjects, before and after exercise to 80 % age/sex predicted maximum heart rate. Fixed sural electrodes were used. Subcutaneous temperature was recorded by a needle thermocouple placed near the sural nerve. Sural sensory conduction velocity increased significantly after exercise in normal subjects (p <0.01, mean increase 5.07 m/s) and non-neuropathic diabetic subjects (p < 0.02, mean increase 3.99 m/s) but not in neuropathic subjects (mean increase 0.99 m/s). Subcuta-neous temperature rose significantly in normal subjects (p<0.01, mean increase 2.07~ and non-neuropathic diabetic subjects (p < 0.001, mean increase 2.52 ~ but not in neuropathic subjects (mean increase 0.15 ~ However, sural sensory conduction velocity increased by 1.2 m. s-1 ~ following direct warming of the limb in six neuropathic subjects which was comparable to that of normal and non-neuropathic subjects (1.49 and 1.48 m. s-1. ~ The impairment of exercise conduction increment in diabetic neuropathy suggests impaired nerve blood flow in diabetic neuropathy.

Research paper thumbnail of Prolonged but partial impairment of the hypoglycaemic physiological response following short-term hypoglycaemia in normal subjects

Diabetologia, 1995

Recent studies have reported reduced endocrine and symptomatic responses to hypoglycaemia 18-24 h... more Recent studies have reported reduced endocrine and symptomatic responses to hypoglycaemia 18-24 h after antecedent hypoglycaemia in both non-diabetic subjects and those with insulin-dependent diabetes mellitus. We examined these and peripheral physiological responses in eight nondiabetic subjects aged 23-35 years in the week following antecedent hypoglycaemia. Blood glucose levels were held at plateaus of 5 mmol/1 and 2.5 mmol/1 for 30 min during hyperinsulinaemic (60 mUm -2. min-~) morning clamps on days 1, 3 and 8 of two study periods separated by at least 4 weeks. Measurements were made at time 0, 15 and 30 min of each plateau on each day. On the afternoon of Day 1 we also induced either euglycaemia with a blood glucose level of 5 mmol/1 (control week) or hypoglycaemia of 2.9 mmol/1 (hypo week) for 2 h in random order. The adrenaline response to morning hypoglycaemia (p < 0.01 on all days) was attenuated on Day3 (p < 0.05) and Day 8 (p < 0.05) compared to Day i of hypo week only. Sweating was also attenuated on Day 3 (p < 0.05) and Day 8 (p < 0.02) of hypo week only. Noradrenaline levels and tremor increased during hypoglycaemia on each study day (p < 0.05) but did not differ between days in either week. During hypo week only, the total symptom score response to hypoglycaemia was attenuated on Day 3 (p < 0.03) but not Day 8 (p = 0.10). Autonomic symptoms were similarly affected. In summary, the physiological responses to hypoglycaemia are affected differentially by antecedent hypoglycaemia with sweating and adrenaline responses remaining impaired for at least 5 days.

Research paper thumbnail of Early identification of diabetic foot ulcers that may require intervention using the micro lightguide spectrophotometer

Diabetes Care, 1999

OBJECTIVE: Adequate tissue oxygenation is known to be essential for the healing of diabetic foot ... more OBJECTIVE: Adequate tissue oxygenation is known to be essential for the healing of diabetic foot ulcers, but hypoxia has also been shown to be a potent stimulus for growth. There are no studies looking specifically at ulcer oxygen levels during the healing process. We measured the serial microvascular oxygen saturation (SaO2) of the foot ulcer, the ulcer margin, and a control site using the Erlangen micro lightguide spectrophotometer (EMPHO II; Bodenseewerk Geratetechnik, Erlangen, Germany) to study serial changes during healing. RESEARCH AND DESIGN METHODS: Studied over 9 months were 14 patients with neuropathy with a total of 24 foot ulcer sites. Of these patients, four (seven ulcers) had significant ischemia as determined by the ankle-brachial pressure index (ABPI) and transcutaneous oxygen tension. RESULTS: Of 21 ulcer sites with serial measurements, only 13 ulcers healed. In those ulcers, a significant reduction (P<0.05) in SaO2 occurred with healing. SaO2 dropped from 58% a...

Research paper thumbnail of Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes

Diabetes, 2004

Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and su... more Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and sudden death. This results from both sympatho-adrenal activation and a lowered serum potassium. It has been suggested that cardiac autonomic neuropathy (CAN) might indicate those who are at particular risk. We tested this hypothesis in 28 adults with type 1 diabetes and 8 nondiabetic control subjects. After standard tests of autonomic function and baroreflex sensitivity (BRS) measurement, diabetic participants were divided into three groups: 1) CAN− with normal BRS (BRS+; n = 10), 2) CAN− with impaired BRS (BRS−; n = 9), and 3) CAN+ (n = 9). QTc was then measured during controlled hypoglycemia (2.5 mmol/l) using a hyperinsulinemic clamp. Mean (±SE) QTc lengthened from 377 ± 9 ms (baseline) to a maximum during hypoglycemia of 439 ± 13 ms in BRS+ subjects and from 378 ± 5 to 439 ± 10 ms in control subjects. Peak QTc tended to be lower in CAN+ (baseline, 383 ± 6; maximum, 408 ± 10) and BRS− g...

Research paper thumbnail of Mechanisms of Abnormal Cardiac Repolarization During Insulin-Induced Hypoglycemia

Diabetes, 2003

Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these c... more Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these contribute to sudden death associated with nocturnal hypoglycemia in young people with diabetes. We measured cardiac repolarization (QT interval [QTc] and QT dispersion [QTd]) during experimental hypoglycemia with and without β-blockade and potassium infusion to establish possible mechanisms. Two groups of 10 nondiabetic men (study 1 and study 2) each underwent four hyperinsulinemic clamps: two euglycemic (5 mmol/l) and two hypoglycemic (5 mmol/l and 2.5 mmol/l for 60 min each). Study 1 was performed with and without potassium infusion to maintain normal concentrations and study 2 with and without β-blockade (atenolol, 100 mg/day for 7 days). QTd was unchanged during euglycemia but increased during hypoglycemia (55 ms, P < 0.0001 vs. baseline), which was prevented by potassium (6 ms, P = 0.78). QTc increased significantly during hypoglycemia alone (67 ms, P < 0.0001) and during pota...

Research paper thumbnail of A knowledge-based electrocardiogram-monitoring system for detection of the onset of nocturnal hypoglycaemia in type 1 diabetic patients

Nocturnal hypoglycaemia has been implicated in the sudden deaths of young people with diabetes. E... more Nocturnal hypoglycaemia has been implicated in the sudden deaths of young people with diabetes. Experimental hypoglycaemia has been found to prolong the ventricular repolarisation and to affect the T wave morphology. It is postulated that abnormally low blood glucose could in certain circumstances, be responsible for the development of a fatal cardiac arrhythmia. We have designed a monitoring and alarm system for detection of the onset of spontaneous nocturnal hypoglycaemia through monitoring of the electrocardiogram. The system incorporates expertknowledge in the form of a rule-base. It performs monitoring of two ECG features and raises alarms if abnormalities are detected corresponding to hypoglycaemia. The top performance of the system is 100% and 91.30% for sensitivity and specificity respectively. This study supports the hypothesis proposing a relationship between cardiac function and abnormally low blood glucose.

Research paper thumbnail of Preservation of Physiological Responses to Hypoglycemia 2 Days After Antecedent Hypoglycemia in Patients With IDDM

Diabetes Care, 1997

OBJECTIVE To assess the effects of short-term antecedent hypoglycemia on responses to further hyp... more OBJECTIVE To assess the effects of short-term antecedent hypoglycemia on responses to further hypoglycemia 2 days later in patients with IDDM. RESEARCH DESIGN AND METHODS We studied eight type I diabetic patients without hypoglycemia unawareness or autonomic neuropathy during two periods at least 4 weeks apart. On day 1, 2 h of either clamped hyperinsulinemic (60 mU · m−2 · min−1) hypoglycemia at 2.8 mmol/l or euglycemia at 5.0 mmol/l were induced. Hyperinsulinemic hypoglycemia was induced 2 days later with 40 min glucose steps of 5.0, 4.0, 3.5, 3.0, and 2.5 mmol/l. Catecholamine levels and symptomatic and physiological responses were measured every 10–20 min. RESULTS When compared with the responses measured following euglycemia, the responses of norepinephrine 2 days after hypoglycemia were reduced (peak, 1.4 ± 0.4 [mean ± SE] vs.1.0 ± 0.3 nmol/l [P < 0.05]; threshold, 3.4 ± 0.1 vs. 2.9 ± 0.1 mmol/l glucose [P < 0.01]). The responses of epinephrine (peak, 4.0 ± 1.4 vs. 3.5 ±...

Research paper thumbnail of Using simple technology to prompt multistep tasks in the home for people with dementia: An exploratory study comparing prompting formats

Dementia (London, England), Jan 30, 2015

To investigate the relative effectiveness of different prompts for people with dementia during mu... more To investigate the relative effectiveness of different prompts for people with dementia during multistep tasks in the home, to inform prompting technology design. Nine pairs of participants (one with dementia and a partner or relative) participated at home. The participants with mild to moderate dementia (5M/4F, aged 73-86 years) functioned at the Planned or Exploratory levels of the Pool Activity Level instrument. A touchscreen computer displayed different prompts during two set tasks: "card-and-envelope" and "CD player." The trials were scored to establish the relative effectiveness of the prompts. Individual tasks were also explored. Text and audio prompts were each more effective than video or picture prompts for a card-and-envelope task, but this was not seen in a CD player task. The differences may be related to the type of actions within the tasks; the card-and-envelope actions were easier to convey verbally; the CD player actions lent themselves to visual...

Research paper thumbnail of Personal message cards: An evaluation of an alternative method of delivering simulated presence therapy

Dementia (London, England), Jan 11, 2015

Simulated presence therapy is a technique which utilises a familiar recorded voice to calm and re... more Simulated presence therapy is a technique which utilises a familiar recorded voice to calm and reassure people with dementia who are agitated or anxious. Although simulated presence therapy has shown potential benefits in small-scale studies, practical limitations in making and playing the recordings have restricted its use. An alternative method of delivering a message from an attachment figure is through a personal message card. This was one of seven products used within the Bath Memory Technology Library which was made available free of charge to people affected by dementia and their carers. This paper provides an evaluation of the personal message cards. Although feedback was received on only 10 of the 24 cards that were distributed, for nine people there was evidence that the cards met the goals that had been set either fully or in part, and that people affected by even quite severe levels of dementia could benefit from them.

Research paper thumbnail of Pain and other symptoms of CRPS can be increased by ambiguous visual stimuli - An exploratory study

European Journal of Pain, 2011

Background: Visual disturbance, visuo-spatial difficulties, and exacerbations of pain associated ... more Background: Visual disturbance, visuo-spatial difficulties, and exacerbations of pain associated with these, have been reported by some patients with Complex Regional Pain Syndrome (CRPS). Aims: We investigated the hypothesis that some visual stimuli (i.e. those which produce ambiguous perceptions) can induce pain and other somatic sensations in people with CRPS. Methods: Thirty patients with CRPS, 33 with rheumatology conditions and 45 healthy controls viewed two images: a bistable spatial image and a control image. For each image participants recorded the frequency of percept change in 1 min and reported any changes in somatosensation. Results: 73% of patients with CRPS reported increases in pain and/or sensory disturbances including changes in perception of the affected limb, temperature and weight changes and feelings of disorientation after viewing the bistable image. Additionally, 13% of the CRPS group responded with striking worsening of their symptoms which necessitated task cessation. Subjects in the control groups did not report pain increases or somatic sensations. Conclusions: It is possible to worsen the pain suffered in CRPS, and to produce other somatic sensations, by means of a visual stimulus alone. This is a newly described finding. As a clinical and research tool, the experimental method provides a means to generate and exacerbate somaesthetic disturbances, including pain, without moving the affected limb and causing nociceptive interference. This may be particularly useful for brain imaging studies.

Research paper thumbnail of Microcirculatory responses to electrical spinal cord stimulation in painful diabetic neuropathy and other painful conditions

Diabetes Research and Clinical Practice, 2000

Research paper thumbnail of Early Involvement of the Spinal Cord in Diabetic Peripheral Neuropathy

Diabetes Care, 2006

OBJECTIVE—The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have ... more OBJECTIVE—The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have recently reported a significant reduction in spinal cord cross-sectional area at the stage of clinically detectable DPN. In this study, we investigated whether spinal cord atrophy occurs in early (subclinical) DPN. RESEARCH DESIGN AND METHODS—Eighty-one male type 1 diabetic subjects, 24 nondiabetic control subjects, and 8 subjects with hereditary sensory motor neuropathy (HSMN) type 1A underwent detailed clinical and neurophysiological assessments. Diabetic subjects were subsequently divided into three groups based on neuropathy severity (19 with no DPN, 23 with subclinical DPN, and 39 with clinically detectable DPN). All subjects underwent magnetic resonance imaging of the cervical spine and cord area measurements at disc level C2/C3. RESULTS—Mean corrected spinal cord area index (SCAI) (corrected for age, height, and weight) was 67.5 mm [95% CI 64.1–70.9] in diabetic subjects without D...

Research paper thumbnail of Does the choice of treatment for type 2 diabetes affect the physiological response to hypoglycemia?

Diabetes Care, 2000

References 1. Yamada K, Nonaka K: Diabetic ketoacidosis in young obese Japanese men: atypical dia... more References 1. Yamada K, Nonaka K: Diabetic ketoacidosis in young obese Japanese men: atypical diabetes induced by sugar-containing soft drinks (Letter). Diabetes Care 19:671, 1996 2. Tanaka K, Moriya T, Kanamori A, Yajima Y: Analysis and a long-term follow up of ketosis-onset Japanese NIDDM patients.