An apparently anomalous relationship between insulin and C-peptide concentrations in their initial response to intravenous glucose.

Intravenous glucose tolerance tests (IVGTTs) with determination of plasma glucose, insulin, and C-peptide concentrations were performed in 136 men and 154 women. It was found that in 4% of men and 12% of women the plasma concentration of insulin exceeded that of C-peptide during the initial response to glucose. Subjects exhibiting this phenomenon had lower fasting and post-glucose C-peptide concentrations than those who did not; however, there were no statistically significant differences in glucose or insulin concentrations. The phenomenon was age-related, being absent from individuals aged 35 years and under, while in older age groups it appeared to be more prevalent in women than in men, suggesting an additional effect of menopause. However, in three follow-up IVGTTs performed in a subgroup of postmenopausal women over a period of 18 months, the phenomenon failed to recur in any of the individuals who first exhibited it, although it did occur in others. Our observations suggest the existence of an age-related but intermittent decrease in pancreatic insulin secretion, which does not lead to any significant change in plasma insulin concentrations, possibly as a result of reduced hepatic uptake of insulin. One consequence appears to be an excess of insulin over C-peptide during the early part of the IVGTT, which is probably related to the different distributional kinetics of the two peptides.     

p16INK4A and p15INK4B gene deletions in primary leukemias

The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene.     

First myocardial infarction in patients under 60 years old: the role of exercise tests and symptoms in deciding whom to catheterise.

OBJECTIVE--To determine the role of exercise tests and assessment of angina in the detection of potentially threatening disease in young patients with infarcts. DESIGN--Elective readmission of patients at a mean (SD) of 60 (30) days after acute myocardial infarction for assessment of angina, treadmill exercise tests, and cardiac catheterisation. SETTING--Cardiology department of a teaching hospital. PATIENTS--186 consecutive survivors, aged under 60 years and discharged from the coronary care unit after a first myocardial infarction. MAIN OUTCOME MEASURES--Coronary arteriography, presence of angina, result of exercise tests, and referral for revascularisation. RESULTS--31% of patients had either two vessel disease (with proximal left anterior descending involvement), three vessel disease, or left main stem disease. 49% of all patients had angina. Of the 173 patients who had an exercise test 34% had 1 mm and 24% had 2 mm of exercise induced ST depression. Thirty percent had no angina and a negative exercise test: after a mean (SD) follow up of 16 (4) months none of this symptom free sub-group had died, had experienced a further myocardial infarction, or had been referred for revascularisation. 79% of patients with either two vessel disease (with proximal left anterior descending involvement), three vessel disease, or left main stem disease had either angina or a 1 mm ST depression during the exercise test. CONCLUSION--Patients without cardiac pain after myocardial infarction and without ST changes during an exercise do not need arteriography.     

Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease

Acetylcholine causes endothelium-dependent dilation of normal arteries in most animal species. The effect of acetylcholine on normal human coronary arteries is controversial. Pathologic studies and epicardial echocardiography have shown that diffuse atherosclerosis is often present despite angiographic evidence of discrete coronary artery disease (CAD). Therefore, we postulated that acetylcholine would cause vasoconstriction of coronary arteries that are angiographically normal in patients with CAD. Coronary artery diameter, measured by automated quantification of digitized cineangiograms, was determined before and after the intracoronary infusion of 0.2 mM acetylcholine at 0.8-1.6 ml/min. The diameter of stenotic or irregular segments of six atherosclerotic coronary arteries decreased from 1.80 +/- 0.42 mm before acetylcholine to 1.26 +/- 0.46 mm after acetylcholine (p = 0.0025). Acetylcholine had a significantly different effect on the diameter of two groups of coronary arteries that are angiographically normal. Acetylcholine caused a 0.16 +/- 0.09-mm increase in the diameter of 14 normal coronary arteries in patients without CAD, whereas it caused a 0.26 +/- 0.12-mm decrease in the diameter of 14 normal coronary arteries in patients with CAD (p less than 0.01). Thus, the normal response to intracoronary acetylcholine is vasodilation, suggesting that endothelium-derived relaxing factor is released from normal human coronary endothelium. The vasoconstrictive effect of acetylcholine in the angiographically normal coronary arteries of patients with CAD suggests the presence of a diffuse abnormality of endothelial function.     

Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders

Nonalcoholic fatty liver is frequently observed in obese individuals, yet the factors that predict its development and progression to liver disease are poorly understood. We proposed that proton magnetic resonance spectroscopy ((1)H-MRS) might allow noninvasive assessment of hepatic lipid composition. Lipid saturation (SI) and polyunsaturation (PUI) indices measured by (1)H-MRS were in agreement with those expected in oils of known composition. Hepatic triglyceride concentration (HTGC) and composition were then measured in healthy lean (LEAN) men, obese men with normal HTGC (OB), and obese men with hepatic steatosis (OB+HS). The effect of marked changes in dietary fat consumption on hepatic lipids were also compared in lean men after 67 hours of a normal mixed (NM) diet versus a low-carbohydrate, high-saturated-fat (LCHF) diet. SI was significantly higher in OB+HS (0.970 +/- 0.004) and OB (0.944 +/- 0.008) versus LEAN (0.818 +/- 0.025) (P < 0.01 for both). PUI was significantly lower in OB+HS (0.003 +/- 0.001) and OB (0.022 +/- 0.005) versus LEAN (0.120 +/- 0.021) (P < 0.01), and significantly lower in OB+HS versus OB (P < 0.05). LCHF diet did not alter HTGC, SI, or PUI (P > 0.05). The (1)H-MRS method provides for rapid, qualitative assessment of lipid composition. Application of this technique in the liver produces results that are consistent with biopsy-based approaches demonstrating that relative hepatic lipid saturation increases and polyunsaturation decreases with obesity. Obesity-related hepatic steatosis is characterized by further depletion of polyunsaturated hepatic lipids. CONCLUSION: This readily available and noninvasive approach should promote further study into interactions between hepatic and whole-body lipid metabolism and help to elucidate the pathogenesis of disorders characterized by lipid accumulation within the liver.     

Comparison of activities of daily living (ADLs) in two different one arm drive wheelchairs: a study of individuals/participants with hemiplegia

Aims: This pilot study measured activities of daily living performance in individuals/participants with hemiplegia propelling both a standard dual handrim Action 3 wheelchair and a standard Action 3 wheelchair with a Neater Uni-Wheelchair kit attachment. The kit consists of a steerable front. Research questions: Does the use of the NUW affect the performance quality of activities of daily living in individuals/participants with hemiplegia. Is there a difference in the motor and process skills during activities of daily living performance, and in the time taken to complete the activities. Methods: Four individuals/participants with hemiplegia were used in a cross over, repeated measures trial. Assessment of Motor and Process Skills of users undertaking making a bed and laying a table “Swedish style”, tasks were measured and time taken to complete each task were recorded. Results: Bed making completion time was quicker in the Neater Uni-wheelchair (p?p?Conclusion: Activities of daily living tasks in the Neater Uni-wheelchair were completed more efficiently with no loss in quality of motor and process skills performance. This suggests that the Neater Uni-wheelchair is a viable alternative to current one arm drive provision.

• Implications for Rehabilitation

• Inappropriate wheelchair provision can result in capacity limitation and poorer quality of ADL motor skill as well-lowered process performance skill.

• AMPS can help to explain motor and process skill differences in complex activities.

     

The prevalence of psychological distress in a sample of facial trauma victims. A comparative cross-sectional study between UK and Australia

Aim

The potential psycho-social sequelae of traumatic facial injury have received increasing attention in recent years, however there remains paucity of cross-national comparative data on the prevalence of psychological distress following such trauma. The aim of the present study was to investigate and compare the prevalence of anxiety and depression in an adult patient group who have been treated for maxillofacial trauma, and who attend a follow-up clinic in either the West Midlands, UK or New South Wales (NSW), Australia. By using an identical methodological and statistical approach, we hoped to add to the available information on the incidence of early psychological distress in patients following facial trauma.

Method

This was a comparative cross-sectional study. A sample of fifty consecutive adult victims of facial trauma in the West Midlands UK, was compared to a group of fifty-two facially injured patients in NSW, Australia. Demographic data was collected, following which the Hospital Depression and Anxiety Scale (HADS) were applied to both groups of patients.

Results

Psychometric scores suggestive of anxiety and depressive state were common in both groups of patients. The mean HADS depression subscale score for UK patients compared to Australian patients was not significantly different (5.94 versus 5.54 p = 0.62). This was also the case for the HADS anxiety subscale (5.96 versus 5.94 p = 0.98). Although the number of patients achieving scores suggestive of a ‘caseness’ for co-morbid psychological state was higher within the UK sample when compared to the Australian group (20% versus 11.5% for HADS depression subscale, and 20% versus 15% for HADS anxiety subscales respectively); these differences did not reach statistical significance.

Conclusion

This cross-national comparative study has shown that anxiety and depression in facial trauma victims were comparable in both settings.