The impact of abdominal aortic aneurysm on muscle mass and energy expenditure: A novel preliminary investigation.

OBJECTIVE: Vascular surgical patients, including those with abdominal aortic aneurysm (AAA), are nutritionally vulnerable. The aim of this study was to compare resting energy expenditure (REE) of patients with AAA relative to age- and gender-matched controls and explore relationships between aneurysm size and muscle mass. METHODS: Twenty patients with AAA underwent assessment of REE using indirect calorimetry. Mid-arm circumference and triceps skinfold thickness were measured and corrected arm muscle area calculated. Twenty gender- and age-matched controls were assessed using the same procedures. RESULTS: Mean (SD) age of participants with AAA was 74.7 (7.7) years, size of AAA ranged from 45 to 70 mm. Median (IQR) REE was significantly higher than controls [5990 (5469, 7017) kJ/day versus 5086 (4536, 5886) kJ/day, p = .011; or 69 (64, 80) kJ/kg/day versus 66 (61, 69) kJ/kg/day, p = .046]. While weight-adjusted REE was independent of aneurysm size (r = .200; p = .397), as aneurysm size increased, weight-adjusted corrected arm muscle area decreased (r = -.576; p = .008). CONCLUSION: The raised REE and decline in muscle mass associated with larger AAA suggest that early detection and attention to nutritional requirements of patients with AAA may be warranted.

A comparison of flow-mediated dilatation and peripheral artery tonometry for measurement of endothelial function in healthy individuals and patients with peripheral arterial disease.

OBJECTIVE: Flow-mediated dilatation (FMD) and peripheral artery tonometry (PAT) are commonly used methods for assessing endothelial function in a research setting but it is unclear how well they correlate. This study aimed to compare and correlate these methods in patients with peripheral arterial disease (PAD) and in healthy individuals. MATERIALS AND METHODS: FMD and PAT measurements were obtained as samples of convenience from 26 patients with PAD and 25 healthy subjects. FMD was defined as the percentage increase in the brachial artery diameter after distal occlusion and PAT was measured using the reactive hyperaemia index (RHI). RESULTS: Patients with PAD had a significantly lower FMD than healthy subjects (2.43% vs. 5.80%, p < 0.001). No difference was found in RHI between the two groups. No correlation was found between the FMD and RHI in subjects with PAD (r = 0.284, p = 0.160), in healthy subjects (r = 0.153, p = 0.464) or when both groups were combined (r = 0.174, p = 0.22). CONCLUSION: The lack of change in RHI in PAD patients suggests that PAT is not a sensitive measure of endothelial function. The lack of correlation suggests that FMD and PAT are not interchangeable. PAT should not be used as a substitute for FMD as a measure of endothelial function.

Clinical medical sciences for undergraduate dental students in the United Kingdom and Ireland - a curriculum.

The technical aspects of dentistry need to be practised with insight into the spectrum of human diseases and illnesses and how these impact upon individuals and society. Application of this insight is critical to decision-making related to the planning and delivery of safe and appropriate patient-centred healthcare tailored to the needs of the individual. Provision for the necessary training is included in undergraduate programmes, but in the United Kingdom and Ireland there is considerable variation between centres without common outcomes. In 2009 representatives from 17 undergraduate dental schools in the United Kingdom and Ireland agreed to move towards a common, shared approach to meet their own immediate needs and that might also be of value to others in keeping with the Bologna Process. To provide a clear identity the term 'Clinical Medical Sciences in Dentistry' was agreed in preference to other names such as 'Human Disease' or 'Medicine and Surgery'. The group was challenged to define consensus outcomes. Contemporary dental education documents informed, but did not drive the process. The consensus curriculum for undergraduate Clinical Medical Sciences in Dentistry teaching agreed by the participating centres is reported. Many of the issues are generic and it includes elements that are likely to be applicable to others. This document will act as a focus for a more unified approach to the outcomes required by graduates of the participating centres and act as a catalyst for future developments that ultimately aim to enhance the quality of patient care.

Development of ocular disease in patients with mucous membrane pemphigoid involving the oral mucosa.

AIM: To determine the rate of development of ocular disease in patients presenting with mucous membrane pemphigoid (MMP) involving their oral mucosa. METHODS: Diagnosis of oral MMP was made on the basis of clinical signs, histology, and direct and indirect immunofluorescence. Age, race, sex, age at diagnosis, progression of eye signs, duration of follow up, and time to progression of ocular disease were recorded. RESULTS: 30 patients with established oral MMP were reviewed. The mean age at diagnosis was 65.2 years (range 46-84 years) and 16/30 (53%) were male. At initial ocular review nine (30%) patients showed ocular signs of pemphigoid, of whom two had mild (IIA IIIB), four moderate (IIB IIIC), and three severe (IIC IIID) disease. The mean interval between diagnosis of oral MMP and first ophthalmic review was 19.3 months (range 0-144). Over the period of follow up two (7%) patients developed ocular disease at 19 months and 48 months, respectively, despite having had no evidence of ocular involvement at presentation. In total, 11 (37%) patients with oral disease eventually showed ocular disease with a calculated incidence rate for the development of ocular disease of 0.03 per person year over 5 years. CONCLUSIONS: MMP may affect different tissues at different stages, often separated by many years. Patients with MMP involving their oral mucosa are at significant risk of developing ocular disease and should remain under ophthalmic review.

Review article: oral ulceration--aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic.

Oral ulceration is a common complaint of patients attending out-patient clinics. The aim of this review is to provide the gastroenterologist with a differential diagnosis of oral ulceration, and a practical guide for the management of recurrent aphthous stomatitis, including topical and systemic therapy. The association of recurrent aphthous stomatitis with Behçet's disease and other systemic disorders, including coeliac disease, is discussed. Recent evidence concerning the immunopathogenesis of Behçet's disease is reviewed, including renewed interest in the role of Streptococcus sanguis and possible infectious triggering of an inappropriate immunoinflammatory response, resulting in tissue damage. The efficacy and limitations of conventional treatment for this mutisystem disorder are outlined together with the potential role of novel biological agents, such as anti-tumour necrosis factor-alpha therapy. Oral ulceration, as a manifestation of inflammatory bowel disease and a complication of drug therapy, is described. Guidance is given concerning indications for referral of patients with oral ulceration to an oral physician/surgeon for further investigations, including biopsy if appropriate.

Placental compressibility: implications for indirect diagnosis of posterior placenta previa.

A number of problems beset the indirect diagnosis of posterior placenta previa using transabdominal ultrasound. We add a new potential complicating factor. In 128 pregnancies at or beyond 30 weeks' gestation, measurements were taken from the fetal skull to the maternal sacrum before and after compression. Up to 69% compressibility of the placenta was found in vivo and in vitro. Modified fetal skull to maternal sacrum measurement criteria were devised from the results. Placenta previa is highly unlikely if the measurement from the fetal skull to maternal sacrum is less than 10 mm before compression or less than 7 mm after compression. Placenta previa is probable if the measurement is greater than 20 mm before compression or greater than 15 mm after compression. In 40% of the cases, posterior placenta previa could not be excluded. We conclude that placental compressibility is an additional confounding problem for indirect ultrasound assessment of posterior placenta previa and that indirect assessment should be attempted only if maneuvers to image the lower uterine segment directly are unsuccessful.

Gallstone prevalence in Christchurch: risk factors and clinical significance.

AIMS: To determine the frequency, risk factors and clinical significance of gallstones in a New Zealand population. METHODS: One thousand names were randomly selected from the Christchurch electoral rolls to recruit controls for a study on the prevalence of gallstones in diabetics. Three hundred and eighteen subjects (169 females, 149 males) were recruited and in this study we analyse this control group for gallstone disease. All subjects completed a questionnaire, provided a fasting blood sample and underwent an ultrasound examination of their gallbladder unless they had previously undergone a cholecystectomy. RESULTS: Overall gallstone disease, defined as previous cholecystectomy or a positive scan for gallstones was seen in 20.75% of the 318 subjects recruited. Gallstone disease was more frequent in females (23.1%) compared to males (18.1%) but this difference was not statistically significant. For both genders there was a significant increase in gallstones with age. On univariate analysis, risk factors for gallstone disease included age, increased body mass index, family history of gallstones and decreased alcohol intake in females. However, only age and family history were significant on multiple logistic regression. There was no difference in the frequency of dyspeptic symptoms or abdominal pain between those with or without gallstones confirmed on scanning. The ratio of cholecystectomy to silent gallstones was higher in females (46.2%) than in males (22.2%). CONCLUSION: Gallstones are prevalent in the New Zealand Community (20.8% overall). Risk factors are increasing age and family history. Gallstones detected on scanning were not associated with an increased incidence of dyspeptic symptoms or abdominal pain.

Direct healthcare costs and predictors of costs in patients with primary Sjogren's syndrome.

OBJECTIVES: To analyse the healthcare usage, direct healthcare costs and predictors of cost in primary Sjögren's syndrome (PSS) in the UK and to compare the findings with the data from healthy control groups and rheumatoid arthritis (RA) patients. METHODS: A total of 129 patients with PSS (American-European criteria), 91 with RA and 92 controls, were included in the study. All groups were age-matched females and all completed questionnaires on health status (SF-36) and healthcare utilization (economic component of the Stanford Health Assessment Questionnaire). Annual direct healthcare costs were calculated (and expressed in 2004 UK pound sterling) and predictors of costs for each patient group were determined by regression analyses. Age, health status, disease duration and anti-Ro/La antibody positivity were used as potential predictor variables. RESULTS: Mean age was similar in the PSS (59.2 yrs, S.D. 11.6), RA (60.3 yrs, S.D. 10.5) and control groups (57.7 yrs, S.D. 12.5). The mean disease duration was 5.4 yrs (S.D. 4.8) in the PSS group and 13.4 yrs (S.D. 11.4) in the RA group. The mean annual total direct cost per patient [95% confidence interval (CI)] was 2188 pounds sterling (1831 and 2546 pounds sterling) in the PSS group, 2693 pounds sterling(2069 and 3428 pounds sterling) in the RA group and 949 pounds sterling (741 and 1156 pounds sterling) in the control group. The costs in the PSS group were greater than for the RA and control groups for visits to all healthcare professionals (total) as well as visits to the dentist, dental hospital and ophthalmologist. The costs in the PSS and RA groups were higher than in controls for diagnostic tests and visits to hospital and the accident and emergency (A&E) department. The PSS group also incurred higher costs than controls, but lower costs than the RA group, for visits to a rheumatologist, urine and blood tests, assistive devices and drug therapy. Regression analysis identified the SF-36 physical function subscale as the best predictor of costs in PSS patients as well as controls and the mental health subscale in RA patients. CONCLUSION: This is the first study to evaluate direct healthcare costs in patients with PSS. PSS has a significant impact on the healthcare system, similar to that of RA, by more than doubling costs compared with control patients.

Binding of protein chemotactic factors to the surfaces of neutrophil leukocytes and its modification with lipid-specific bacterial toxins.

The binding to neutrophil leukoyctes of human serum albumin (HSA), which is chemokinetic for leukocytes, i.e. influences their rate of locomotion, and of alkali-denatured HSA, which is chemotactic for leukocytes, i.e. influences their direction of locomotion, was studied. Native serum albumin showed low affinity binding to the neutrophil surface. Denatured serum albumin showed saturable binding with a Ka of approximately 1-(6) litres per mole to about 10(6) binding sites per cell. Another protein chemotactic factor, alpha5-casein, gave similar binding. These results exclude that chemotactic reactions to denatured proteins are mediated in a completely non-specific manner and suggest the presence on the cell of a restricted number of defined recognition sites. Binding was reduced following treatment of the cells with either of two lipid-specific bacterial toxins, perfringolysin, the theta-toxin of Clostridium perfringens, an oxygen-labile cholesterol-specific toxin, and Staphylococcus aureus Sphingomyelinase C. Both have previously been shown to reduce chemotactic reactions and both were used at doses which did not reduce cell viability. These results suggest an important, and possiblly direct, role for membrane lipid in the binding sites for chemotactic factors. Visual analysis of the behaviour of perfringolysin-treated neutrophils showed that these cells were still capable of chemotactic locomotion. The cells appeared to be less efficient than normal in detecting chemotactic gradients only when at a distance from the gradient source, a finding which is consistent with reduced binding of the chemotactic factor to the cell surface.

Efficacy of fetal part elevation to visualise internal cervical os.

The diagnosis or exclusion of placenta previa is best achieved by direct visualisation of the relationship of the lower edge of the placenta to the internal cervical os. In later pregnancy, the presenting fetal part frequently obscures this area. Elevation of the presenting part was attempted in 56 consecutive pregnancies of greater than 30 weeks gestation, with a success rate of 71%. This confirms that in a minority of pregnancies, other manoeuvres or ultrasound techniques are necessary to visualise the lower placental margin directly.

Diagnosis of obstructive hydronephrosis in infants: comparison sonograms performed 6 days and 6 weeks after birth.

OBJECTIVE: The purpose of this study was to compare the usefulness of renal sonograms obtained 6 days and 6 weeks after birth in differentiating obstruction from nonobstruction in patients with antenatal pyelocaliceal dilatation shown by sonography and to establish sonographic criteria to determine the degree of postnatal pyelocaliceal dilatation that warrants further investigation. MATERIALS AND METHODS: Criteria for an infant to enter the study were fetal pyelectasis of 4 mm or greater, two postnatal sonograms with the second showing persisting pyelectasis extending at least into the infundibula, and a voiding cystourethrogram showing normal findings. One hundred thirty kidneys in 100 infants met the study criteria. The first postnatal sonogram was obtained at a mean age of 6 days (range, 1-14 days) and the second at a mean age of 6.6 weeks (range, 3-16 weeks). The degree of pyelectasis was measured in the anteroposterior direction on the transverse postnatal sonograms. The diagnosis of obstruction was made by excretory urography in 99 infants and nephrostography in one infant. Kidneys were categorized as definitely obstructed, possibly obstructed (anatomic features of obstruction on excretory urogram but functionally not obstructed), or not obstructed. Receiver-operating-characteristic (ROC) curves based on renal pelvic diameters were plotted for both sonograms; the ability to detect definite obstruction or possible obstruction was compared for the two time periods; and optimal cutoff points were determined. RESULTS: The mean diameter of the renal pelvis was not significantly different between the sonogram obtained at 6 days and the sonogram obtained at 6 weeks for the 86 nonobstructed kidneys. For the 27 kidneys that were obstructed, the mean pelvic diameter increased from 18 mm (range, 5-54 mm) on the sonogram obtained at 6 days to 22 mm (range, 11-60 mm) on the sonogram obtained at 6 weeks. The mean pelvic diameter of 17 kidneys categorized as possibly obstructed increased from 6 mm (range, 0-11 mm) to 10 mm (range, 6-20 mm) between the first and second sonograms. The ROC curves for all sonograms obtained at 6 weeks provided cutoff points with greater sensitivity and specificity than did the curves for the sonograms obtained at 6 days. The optimal cutoff points were 6 mm for possible obstruction (sensitivity, 100%; specificity, 57%) and 11 mm for definite obstruction (sensitivity, 100%; specificity, 57%) and 11 mm for definite obstruction (sensitivity, 100%; specificity, 96%). CONCLUSION: Renal obstruction may be underestimated or missed on a renal sonogram obtained 6 days after birth. A sonogram obtained 6 weeks after birth is more specific for detecting obstruction.

Inhibition, by anaesthetic agents, of human leucocyte locomotion towards chemical attractants.

The effects of local, i.v. and volatile anaesthetic agents on locomotion of human blood leucocytes were studied in vitro. Blood neutrohpils and monocytes and PHA-activated lymphocytes were allowed to migrate in filters towards standard chemotactic agents and the effect of adding anaesthetic agents to the system was measured. The results showed that locomotion of all cell types was depressed reversibly by all classes of anaesthetics used at clinical concentrations. The pattern of depression varied according to the cell type under study and the class of anaesthetic used. The action of anaesthetics on chemically stimulated locomotion of leucocytes was analysed. It was concluded that the principal action of these drugs is primarily on the mechanism of locomotion itself, rather than on the capacity of the cells to detect and respond to concentration gradients of attractants. Serum albumin can protect against the inhibitory action of anaesthetics.

Vesicoureteric reflux in the newborn: relationship to fetal renal pelvic diameter.

There has been a low yield of primary vesicoureteric reflux (VUR) from screening the fetal urinary tract during obstetric sonography. We sought to determine whether changing the cut-off level of fetal renal pelvic diameter from 10 mm to 4 mm would improve the yield of VUR. In a prospective community-based study, a fetal renal pelvic diameter of 4 mm or more on a transverse view of the fetal renal hilum at obstetric sonography after 16 weeks' gestation was found in 426 fetuses from 9,800 consecutive pregnancies. After birth, renal sonography was performed on 386 of the 426 babies. Of the 386 babies, 264 (187 boys) had a voiding cystourethrogram (VCUG) at a mean age of 9 weeks. Primary VUR was detected in 33 (16 boys) of the 264 infants (13%), and secondary VUR in another 5 (2%). Only 5 of the 33 (15%) babies with primary VUR would have been detected if a cut-off point of 10 mm for fetal renal pelvic diameter had been used. The prevalence of reflux was similar at each cut-off level of antenatal renal pelvic diameter from 4 to 10 mm. Neither calyceal nor ureteric dilatation was helpful in differentiating those with from those without VUR. The postnatal renal sonogram did not distinguish whether reflux was present or not. More infants with primary VUR, particularly girls, were found by changing the cut-off point for fetal renal pelvic diameter from 10 mm to 4 mm, and performing a VCUG on all such infants even if the postnatal renal sonogram was normal. Of the 33 infants with primary VUR, 9 (27%, 5 boys) had an abnormal dimercaptosuccinic acid scan. Our findings support the screening of the obstetric population for a fetal renal pelvic diameter of 4 mm or more, and then investigating the infants for VUR after birth.

Dissolution of gallstones with simvastatin, an HMG CoA reductase inhibitor.

The aim of this study was to determine whether 12 months of therapy with Simvastatin, an HMG CoA reductase inhibitor, would dissolve gallstones. Twenty-seven subjects entered the study, all had a fasting oral cholecystogram, ultrasound examination, and fasting serum lipids prior to therapy. In addition, 22 subjects had their gallbladder ejection fraction, after CCK, determined by radionucleotide scanning. Eleven subjects had the cholesterol saturation index (CSI) of bile calculated before and at the end of 12 months of therapy. Of the 27 subjects, 26 completed 12 months of treatment with Simvastatin 20 mg daily. There was a significant fall in the total serum cholesterol (27%, P < 0.0001), LDL cholesterol (31%, P < 0.0001), triglyceride (34%, P < 0.0001) but no change in HDL after 12 months of therapy. Simvastatin treatment resulted in a 28% fall in the CSI of bile at the end of therapy (P < 0.01). The concentrations of individual bile acids did not change with therapy, and apart from a slight but significant increase in arachidonate, there were no other significant changes in the fatty acid composition of the biliary phospholipids. After 12 months of Simvastatin therapy there was a small decrease in the gallstone diameter but complete dissolution of gallstones was not achieved in any subjects. In conclusion 12 months of therapy with Simvastatin was effective in lowering the serum lipids and the CSI of bile but was not effective in dissolving gallstones.

Gallbladder polyps: prospective study.

The aim of this study was to describe the natural history of gallbladder polyps. Thirty-eight subjects who had been previously identified as having gallbladder polyps in an epidemiologic study of gallstone prevalence in 627 diabetic subjects and matched controls were followed longitudinally. Follow-up sonograms were obtained on 33 and 22 of the 38 subjects at 2 and 5 years, respectively. Prevalence for gallbladder polyps in this population was 6.7%, with a marked male predominance (odds ratio 2.3). No statistical difference in prevalence was found between diabetic subjects and nondiabetic controls. Ninety percent of the polyps were less than 10 mm in diameter, with no polyp being larger than 12 mm. During the follow-up period no changes suggestive of malignant transformation were observed. In conclusion, we found that gallbladder polyps were relatively common and that few significant changes occurred over a 5 year period. In asymptomatic subjects in whom gallbladder polyps less than 10 mm in diameter are found incidentally, the likelihood of malignant transformation is low.

Prevalence of gallbladder disease in diabetes mellitus.

A study was undertaken to compare the prevalence of gallstone disease (gallstones observed on ultrasound or history of cholecystectomy) in 308 diabetics and 318 controls. There was a higher prevalence of gallstone disease (GSD) in diabetics (32.7%) compared to controls (20.8%; P < 0.001 chi-squared test). However, when gender was taken into account, the difference was only significant in females (diabetics 41.8% versus controls 23.1%; P < 0.001). Analysis by type of diabetes revealed that subjects with non-insulin-dependent diabetes mellitus (NIDDM) had a higher prevalence of GSD than controls for both genders: males-controls 18.1%, NIDDM 33.3% (P < 0.05), IDDM 15.6% ns; females-controls 23.1%, NIDDM 48.6% (P < 0.001), IDDM 36.3% (P < 0.05). On univariate analysis the following risk factors were associated with gallstones (P < 0.1): increased age, body mass index (BMI), triglycerides, LDL cholesterol, decreased HDL cholesterol, alcohol intake, family history of GSD, and female parity > 3. Using stepwise multiple, logistic regression, the following variables were identified as independently predictive of gallstones for each gender/diabetic combination: Males-NIDDM (N = 54), increased age, and decreased HDL; IDDM (N = 90), age and family history; Females-NIDDM (N = 74), increased age, diabetes, increased BMI, and decreased alcohol; IDDM (N = 91), increased BMI, age, decreased alcohol and family history. The proportion of subjects who underwent cholecystectomy was higher in females (46.7%) compared to males (21.7%; P < 0.01) but there were no differences between diabetics and controls in either sex. In conclusion, there was a higher prevalence of GSD in diabetics compared to controls. However, GSD is multifactorial and only in NIDDM females was diabetes an independent risk factor. The proportion of diabetics and controls with GSD who underwent cholecystectomy was equivalent.

Gallbladder volume: comparison of diabetics and controls.

Diabetics are known to have an increased prevalence of gallstones. The aim of this study was to investigate whether diabetics have increased gallbladder volumes that would predispose to stasis, nucleation of cholesterol crystals, and gallstone formation. The gallbladder volume of 271 diabetic subjects and 277 controls was determined by ultrasound using the ellipse formula. Gallbladder volume was also determined by the sum of the cylinders method in 143 cases with a strong correlation (r = 0.89) between the two methods. Using analysis of variance, gallbladder volume was influenced by both diabetic type (NIDDM = 33.68 cm3, IDDM = 26.84 cm3, controls = 29.05 cm3; P = 0.018) and the presence of gallstones (gallstones = 32.04 cm3, no gallstones = 27.58 cm3; P = 0.018). The variation in gallbladder volume between NIDDM, IDDM, and control subjects was influenced by the presence of gallstones (P = 0.024, interaction term from ANOVA). Significant differences (P < 0.001) were only found between NIDDM vs IDDM and NIDDM vs control in the nongallstone group (NIDDM = 34.33 cm3, IDDM = 25.08 cm3, control = 25.17 cm3). Males had significantly larger gallbladder volumes than females: 31.98 cm3 vs 27.74 cm3 (P = 0.023). After the inclusion of BMI, HDL cholesterol, triglyceride, and age in a statistical model with gender and diabetic type in those without gallstones, significant differences were still found between NIDDM and IDDM (P = 0.013) and NIDDM and controls (P = 0.005), demonstrating that NIDDM is an independent predictor for increased gallbladder volume.