Clostridioides difficile carriage in animals and the associated changes in the host fecal microbiota.

The relationship between the gut microbiota and Clostridioides difficile, and its role in the severity of C. difficile infection in humans is an area of active research. Intestinal carriage of toxigenic and non-toxigenic C. difficile strains, with and without clinical signs, is reported in animals, however few studies have looked at the risk factors associated with C. difficile carriage and the role of the host gut microbiota. Here, we isolated and characterized C. difficile strains from different animal species (predominantly canines (dogs), felines (cats), and equines (horses)) that were brought in for tertiary care at North Carolina State University Veterinary Hospital. C. difficile strains were characterized by toxin gene profiling, fluorescent PCR ribotyping, and antimicrobial susceptibility testing. 16S rRNA gene sequencing was done on animal feces to investigate the relationship between the presence of C. difficile and the gut microbiota in different hosts. Here, we show that C. difficile was recovered from 20.9% of samples (42/201), which included 33 canines, 2 felines, and 7 equines. Over 69% (29/42) of the isolates were toxigenic and belonged to 14 different ribotypes including ones known to cause CDI in humans. The presence of C. difficile results in a shift in the fecal microbial community structure in both canines and equines. Commensal Clostridium hiranonis was negatively associated with C. difficile in canines. Further experimentation showed a clear antagonistic relationship between the two strains in vitro, suggesting that commensal Clostridia might play a role in colonization resistance against C. difficile in different hosts.

Understanding and interpreting community sequencing measurements of the vaginal microbiome.

Community-wide high-throughput sequencing has transformed the study of the vaginal microbiome, and clinical applications are on the horizon. Here we outline the three main community sequencing methods: (1) amplicon sequencing, (2) shotgun metagenomic sequencing, and (3) metatranscriptomic sequencing. We discuss the advantages and limitations of community sequencing generally, and the unique strengths and weaknesses of each method. We briefly review the contributions of community sequencing to vaginal microbiome research and practice. We develop suggestions for critically interpreting research results and potential clinical applications based on community sequencing of the vaginal microbiome. TWEETABLE ABSTRACT: We review the advantages and limitations of amplicon sequencing, metagenomics, and metatranscriptomics methods for the study of the vaginal microbiome.

Cryogenic STM in 3D vector magnetic fields realized through a rotatable insert.

Spin-polarized scanning tunneling microscopy (SP-STM) performed in vector magnetic fields promises atomic scale imaging of magnetic structure, providing complete information on the local spin texture of a sample in three dimensions. Here, we have designed and constructed a turntable system for a low temperature STM which in combination with a 2D vector magnet provides magnetic fields of up to 5 T in any direction relative to the tip-sample geometry. This enables STM imaging and spectroscopy to be performed at the same atomic-scale location and field-of-view on the sample, and most importantly, without experiencing any change on the tip apex before and after field switching. Combined with a ferromagnetic tip, this enables us to study the magnetization of complex magnetic orders in all three spatial directions.

Long spin lifetime and large barrier polarisation in single electron transport through a CoFe nanoparticle.

We have investigated single electron spin transport in individual single crystal bcc Co30Fe70 nanoparticles using scanning tunnelling microscopy with a standard tungsten tip. Particles were deposited using a gas-aggregation nanoparticle source and individually addressed as asymmetric double tunnel junctions with both a vacuum and a MgO tunnel barrier. Spectroscopy measurements on the particles show a Coulomb staircase that is correlated with the measured particle size. Field emission tunnelling effects are incorporated into standard single electron theory to model the data. This formalism allows spin-dependent parameters to be determined even though the tip is not spin-polarised. The barrier spin polarisation is very high, in excess of 84%. By variation of the resistance, several orders of magnitude of the system timescale are probed, enabling us to determine the spin relaxation time on the island. It is found to be close to 10 µs, a value much longer than previously reported.

Dimensions of depressive symptoms and cingulate volumes in older adults.

Clinical depression and subthreshold depressive symptoms in older adults have been linked to structural changes in the cingulate gyrus. The cingulate comprises functionally distinct subregions that may have distinct associations with different types, or symptom dimensions, of depression. This study examined the relationship between symptom dimensions of depression and gray matter volumes in the anterior cingulate, posterior cingulate and isthmus of the cingulate in a nonclinical sample. The study included 41 community-dwelling older adults between the ages of 55 and 81. Participants received a structural magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale. Subscale scores for depressed mood, somatic symptoms and lack of positive affect were calculated, and Freesurfer was used to extract cingulate gray matter volumes. Regression analyses were conducted to examine the relationship between depressive symptoms and volumes of cingulate subregions while controlling for sex, age and estimated total intracranial volume. Higher scores on the depressed mood subscale were associated with larger volumes in the left posterior cingulate and smaller volumes in the isthmus cingulate. Higher scores on the somatic symptoms subscale were significantly related to smaller volumes in the posterior cingulate. A trend was observed for a positive relationship between higher scores on the lack of positive affect subscale and larger volumes in the anterior cingulate cortex. These results are consistent with previous findings of altered cingulate volumes with increased depressive symptomatology and suggest specific symptom dimensions of depression may differ in their relationship with subregions of the cingulate.

Barriers to hepatitis C virus treatment in a Canadian HIV-hepatitis C virus coinfection tertiary care clinic.

BACKGROUND: Despite demonstrated efficacy in HIV-hepatitis C virus (HCV) coinfection, not all patients initiate, complete or achieve success with HCV antiviral therapy. PATIENTS AND METHODS: All HIV-HCV coinfected patient consults received at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) between June 2000 and September 2006 were identified using a clinical database. A descriptive analysis of primary and contributing factors accounting for why patients did not initiate HCV therapy, as well as the therapeutic outcomes of treated patients, was conducted. RESULTS: One hundred two consults were received. Sixty-seven per cent of patients did not initiate HCV therapy. The key primary reasons included: HIV therapy was more urgently needed (22%), loss to follow-up (12%), patients were deemed unlikely to progress to advanced liver disease (18%) and patient refusal (12%). Many patients had secondary factors contributing to the decision not to treat, including substance abuse (23%) and psychiatric illness (14%). Overall, 59% of untreated patients (40 of 68) were eventually lost to follow-up. Thirty-three per cent of referred patients started HCV therapy. Twenty-seven of 42 courses (64%) were interrupted prematurely for reasons such as virological nonresponse (48%), psychiatric complications (10%) and physical side effects (7%). Of all treatment recipients, 12 of 42 full courses of therapy were completed and three remained on HCV medication. Overall, eight of the 102 coinfected patients studied (8%) achieved a sustained virological response. DISCUSSION: Not all HIV-HCV coinfected patients who are deemed to be in need of HCV treatment are initiating therapy. Only a minority of patients who do receive treatment achieve success. Implementation of HIV treatment, patient retention, attention to substance abuse and mental health care should be the focus of efforts designed to increase HCV treatment uptake and success. This can be best achieved within a multidisciplinary model of health care delivery.

Endothelin-1 levels predict 3-year survival in patients who have amputation for critical leg ischaemia.

BACKGROUND: Most patients with critical leg ischaemia (CLI) have co-existing coronary heart disease, which is the main cause of their increased mortality rate. The aim of this study was to investigate whether any markers of endothelial function could predict death in these patients. METHODS: In a cohort of 39 patients with CLI who were scheduled for lower-limb amputation, blood levels of vascular endothelial growth factor, homocysteine, endothelin (ET) 1, von Willebrand factor and vascular cell adhesion molecule 1 were measured, as well as forearm vascular responses to the endothelium-dependent vasodilator acetylcholine. RESULTS: Levels of ET-1 were significantly higher in patients who subsequently died within 3 years than in those who were still alive (P = 0.002) and Cox proportional hazards regression analysis demonstrated that ET-1 was an independent predictor of all-cause mortality:hazard ratio 3.53 (95 per cent confidence interval (c.i.) 1.29 to 9.70; P = 0.007) and cardiovascular mortality:hazard ratio 4.15 (95 per cent c.i. 1.30 to 13.23); P = 0.014. CONCLUSION: ET-1 was an independent predictor of death in these patients with CLI.

Investigation of platelet glycoprotein IIIa polymorphism using flow cytometry in patients with rheumatoid arthritis.

OBJECTIVES: Previous work has shown that the human platelet antigen (HPA) 1b polymorphism of platelet glycoprotein IIIa (GPIIIa) is implicated in the development of ischaemic vascular disease. HPA1b positive platelets have a lower threshold for activation and may exert a greater thrombotic tendency than those without the 1b allele. However, platelets heterozygous for the polymorphism are also more sensitive to aspirin than those homozygous for the 1b allele, which have a similar sensitivity to those without the 1b allele. A flow cytometric method has become available to identify this polymorphism. The aim of our study was to evaluate the use of this assay in patients with rheumatoid arthritis (RA) and to determine the incidence of the 1b allele in these patients. We also compared platelet aggregation and platelet/white blood cell interaction in patients with or without this polymorphism. METHODS: We enrolled 99 patients and measured platelet aggregation in whole blood and platelet-rich plasma (prp), platelet/white blood cell interaction and C-reactive protein (CRP). RESULTS: Thirty-four of the 99 patients were unsuitable for analysis because their baseline expression of GPIIIa was outwith the normal range, making the results outwith the limits of the flow cytometric method. The incidence of the 1b allele in the patients was 29%, with incidence being higher in females, although this failed to reach statistical significance. The number of circulating platelet aggregates and adenosine diphosphate (ADP)-induced aggregation in prp was significantly higher in those patients with the 1b allele. CONCLUSIONS: This method may be of use as an initial screening test.

Elevated soluble cell adhesion molecules E-selectin and intercellular cell adhesion molecule-1 in type-2 diabetic patients with and without asymptomatic peripheral arterial disease.

AIM: Cell adhesion molecules may serve as markers of endothelial cell activation, and they may well have a role in the pathogenesis of atherosclerotic vascular disease in diabetes mellitus. EXPERIMENTAL DESIGN: a cross sectional, comparative study. SETTING: a teaching University Hospital. Patients and controls. A cohort of diabetic patients with absent peripheral arterial pulses but no history of cardiovascular or cerebrovascular disease i.e. asymptomatic (n=29), median age 68 (36-80) years, (range), diabetes duration 10 (1-43) years and HbA1c 7.7% (4.8-9.6). They were compared to 12 age and sex matched normal non-diabetic controls. INTERVENTION: none. MEASURES: soluble cell adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1) and E-selectin levels measured by ELISA methods. RESULTS: The 29 patients with diabetes, as a whole, were found to have significantly higher median plasma sICAM-1 and sE-selectin of 283 ng/ml (154-1000) (range), and 65.8 ng/ml (20.6-145) vs 237 (147-312.4) and 37.7 (19.8-46.6) respectively, Mann Whitney U test p<0.02, and p<0.002. In the diabetic group, E-selectin correlated with ICAM-1, age and HbA1c: r=0.524 p<0.01, r=0.385 p<0.05 and r=0.393 p<0.05 respectively (Spearman correlation coefficient). CONCLUSION: These results confirm that elevated levels of adhesion molecules, E-selectin and ICAM-1 occur in Type-2 diabetes early in the course of asymptomatic peripheral arterial occlusive disease, and this is related to glycemic control. This suggests that adhesion molecules may have a role in the pathogenesis of atherosclerotic vascular disease in diabetes.

Sudden unexpected death in heart failure may be preceded by short term, intraindividual increases in inflammation and in autonomic dysfunction: a pilot study.

OBJECTIVE: To see whether sudden unexpected death in chronic heart failure is preceded by intraindividual worsening in inflammation and in ECG criteria. DESIGN AND SETTING: Prospective cohort study conducted in the community. PATIENTS: 34 patients with chronic heart failure were studied. Their mean (SD) age was 68 (8) years, 29 were men, mean (SD) left ventricular ejection fraction was 29 (9)%, and they were in New York Heart Association functional class II (n = 20), III (n = 11), and IV (n = 3). The patients were examined monthly over 24 months, with sequential measurement of C reactive protein and neutrophil counts and 24 hour ambulatory ECG monitoring measuring heart rate variability, mean heart rate, and arrhythmias. Intraindividual changes in these parameters were related to subsequent cardiac deaths. RESULTS: During follow up, nine patients died: five patients had a sudden unexpected death (SUD) and four died of progressive heart failure (PHF). There were significant intraindividual changes in neutrophil counts (p = 0.02), C reactive protein (p = 0.039), and heart rate variability (p < or = 0.018) in those who died of SUD and PHF. In contrast no significant changes were seen in ventricular extrasystoles, ventricular tachycardia episodes, brain natriuretic peptide, or aldosterone in the SUD group, but all of these parameters did increase as expected in those who died of PHF. CONCLUSIONS: This is preliminary evidence that SUD may be preceded by intraindividual increases in both inflammation and autonomic dysfunction. Both may be causal in genesis but, even if they are not, intraindividual increases in either may be convenient markers to identify patients at high risk of impending SUD. Larger studies are needed to confirm the observation from this pilot study.

Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses with equine Cushing's disease.

REASONS FOR PERFORMING STUDY: The mechanisms underlying the increased risk of laminitis in horses with equine Cushing's disease (ECD) are poorly understood. HYPOTHESIS: That abnormalities in glucose homeostasis, similar to those which cause microvascular dysfunction in human diabetics, contribute to development of laminitis in horses with ECD. METHODS: Thirty-one aged horses were divided into 3 groups based on clinical signs and dexamethasone suppression testing (DST). Group 1 (n = 12) had clinical ECD as evidenced by hirsutism. Group 2 (n = 10) had a positive DST but no hirsutism. Group 3 (n = 9) were controls without ECD, with a negative DST and no clinical evidence of ECD. Biochemical indices of glucose metabolism, vascular function and oxidative stress were determined in single morning blood samples. RESULTS: Group 1 had abnormalities in glucose homeostasis, including increased levels of glucose and insulin, compared to Groups 2 and 3. Groups 1 and 2 had significantly lower plasma thiol (PSH) levels and nonsignificantly lower albumin-corrected PSH levels than Group 3, consistent with oxidative stress. CONCLUSIONS AND POTENTIAL RELEVANCE: The observed abnormalities in glucose metabolism and oxidative stress could potentially contribute to development of laminitis in horses with ECD, by similar mechanisms to those that cause microvascular dysfunction in human diabetics. The absence of inter-group differences in the biochemical indices of vascular function precludes their use as preclinical diagnostic indicators of vascular dysfunction. The study also highlighted limitations in the premortem diagnosis of ECD.

Influence of the hormonal changes during the normal menstrual cycle in healthy young women on soluble adhesion molecules, plasma homocysteine, free radical markers and lipoprotein fractions.

AIM: Female sex hormones are known to exert a protective role on the vascular endothelial function, but the exact mechanisms of such protection is not known. We aimed to study the possible regulatory role of the female sex hormones changes during the normal menstrual cycle on soluble adhesion molecules E-selectin and ICAM-1, plasma homocyteine, free radical markers and lipoproteins in healthy young women. EXPERIMENTAL DESIGN: a cross sectional study of healthy female volunteers studied during a single normal menstrual cycle at 3 specific time points. SETTING: North Staffordshire Hospitals NHS Trust. SUBJECTS: 20 healthy young menstruating women, aged (mean +/- SEM) 34 +/- 1 years, with normal menstruation, defined as a menstrual cycle of 21-35 days were studied at 3 time points of the same menstrual cycle. First in the early follicular phase (M-phase), at mid-follicular phase (F-phase), and during the luteal phase (L-phase). INTERVENTION: none. MEASUREMENT: serum levels of soluble E-selectin, ICAM-1, plasma homocysteine, vitamin E and malondialdehyde (MDA), as well as lipoprotein fractions were measured at each time points. RESULTS: The mean percentage change for E-selectin between the M-phase and L-phase, F-phase and L-phase were 6% and 4%, respectively, p<0.005, p<0.066. Levels of ICAM-1, vitamin E and malondialdehyde did not vary through the cycle. Homocysteine was not different between M-phase and F-phase (10.39 +/- 0.68 micromol/l vs 10.33 +/- 0.65), nor between M-phase and L-phase (10.39+/-0.68 vs 9.77 +/- 0.75 micromol/l). Although the mean percentage decrease in homocysteine between F- and L-phases was significant (5.36 +/- 0.53%, p=0.029), the absolute decrease in concentrations was not (p=0.07). There were no cyclical changes in total, LDL, HDL cholesterol, triglycerides, apo A-I, apo B or Lp(a). Using a linear regression model, after correction for age, smoking, body mass index (BMI) and waist/hip ratio (WHR), oestrogen levels were the only predictor of E-selectin during the L-phase p<0.005. There were no significant correlations between oestrogen with lipids, apolipoproteins or homocysteine. There was an interesting significant univariate correlation between homocysteine with low-density-lipoprotein (LDL) cholesterol and apo B throughout all phases of the cycle, which persisted after correction for the effects of age, BMI, WHR and smoking history. Multiple regression analysis with all these factors showed homocysteine to be a significant predictor of apo B concentration during M (p=0.030) and L-phases (p=0.023) of the cycle and of LDL cholesterol in the M-phase (p=0.033). CONCLUSION: Female sex hormones may have small, though significant modulating role on E-selectin and homocysteine metabolism in healthy premenopausal women. Furthermore, the correlation between homocysteine, LDL and apo B levels suggests that induction of cholesterol synthesis by homocysteine, shown previously in vitro, may be of relevance in vivo.

A study of whole blood platelet and white cell aggregation using a laser flow aggregometer.

Both platelet aggregation and white blood cell aggregation are involved in pathological processes such as thrombosis, atherosclerosis and chronic inflammation. People in older age groups are likely to suffer from cardiovascular diseases and may have increased white cell and platelet aggregation which could contribute to this increased risk. This study aimed to compare white cell and platelet aggregation between different age and gender groups. Whole blood white cell aggregation and platelet aggregation were carried out on healthy volunteers using cytometric techniques. It was found that both white cell and platelet aggregation in the elderly group (white cell aggregation median value, 0.08; range, 0.02-0.14; platelet aggregation median value, 0.32; range, 0.1-0.39) were significantly higher (P = 0.017 for white cell aggregation, P = 0.007 for platelet aggregation) than in the younger group (white cell aggregation median value, 0.05; range, 0.01-0.14; platelet aggregation median value, 0.18; range, 0.07-0.36). No significant differences were found between the gender groups.

Evaluation of a combined laser Doppler flowmetry and iontophoresis technique for the assessment of equine cutaneous microvascular function.

A combined laser Doppler flowmetry and iontophoresis (LDFI) technique, used routinely to assess human microvascular function, was evaluated as a noninvasive technique for assessment of equine microvascular function, to facilitate the study of diseases such as laminitis. Baseline and vasoactive agonist-induced (acetylcholine and nitroprusside) microvascular flux was quantified at 2 sites (on the dorsal pastern adjacent to the coronary band and over the gluteals) in 6 clinically normal horses on 5 or 6 separate occasions under standardised conditions. Both agonists significantly increased microvascular flux. Skin pigmentation significantly attenuated the baseline flux, but not the magnitude of the agonist-mediated vasodilatory response. While LDFI was simple to perform, its value as a clinical and research tool for assessing the equine cutaneous microcirculation is limited by its poor reliability, as indicated by the marked intra- and intersubject variability in baseline and agonist-mediated microvascular flux.

Vascular endothelial growth factor in patients with critical limb ischemia before and after amputation.

BACKGROUND: It is known that levels of vascular endothelial growth factor (VEGF) in biological fluids increase with inflammation and vascular proliferation. Theraputic angiogenesis by injection of VEGF or genes encoding for it may be a promising strategy for treatment of critical limb ischemia. However growth factors are also implicated in the development of vascular disease by smooth muscle cell proliferation. METHODS: We have previously shown VEGF levels to be increased in juvenile diabetic subjects with no clinical evidence of vascular disease. We have measured serum VEGF using an enzyme linked immunosorbent assay and cellular VEGF expression using flow cytometry in patients with critical limb ischemia prior to and 6 months postamputation to determine whether removal of the ischemic limb leads to changes in systemic endothelial cell function. RESULTS: Baseline VEGF levels were significantly increased in the patient group compared to controls with levels returning to control levels at 6 months postsurgery. Monocyte and neutrophil VEGF expression was significantly reduced in the patient group. Platelet expression of VEGF was also reduced but this failed to reach statistical significance. CONCLUSIONS: The results suggest that it may be useful to determine the balance between VEGF production and cellular receptor expression prior to treatment.

Faecal carriage of verocytotoxin-producing Escherichia coli O157 in cattle and sheep at slaughter in Great Britain.

A 12-month abattoir survey was conducted between January 1999 and January 2000, to determine the prevalence of faecal carriage of verocytotoxin-producing Escherichia coli O157 (VTEC O157) in cattle and sheep slaughtered for human consumption in Great Britain. Samples of rectum containing faeces were collected from 3939 cattle and 4171 sheep at 118 abattoirs, in numbers proportional to the throughput of the premises. The annual prevalence of faecal carriage of VTEC O157 was 4.7 per cent (95 per cent confidence interval 4.1 to 5.4) for cattle and 1.7 per cent (1.3 to 2.1) for sheep, values which were statistically significantly different from each other (P < 0.001). The organisms were recovered from both cattle and sheep slaughtered throughout the year and at abattoirs in all regions of the country, but the highest prevalence was in the summer. The most frequency recovered VTEC O157 isolates were phage types 2, 8 and 21/28 in cattle and 4 and 32 in sheep, the five most frequently isolated phage types associated with illness in people in Great Britain during the same period.

Biochemical and biophysical markers of endothelial dysfunction in adults with hypopituitarism and severe GH deficiency.

Adult hypopituitarism is known to be associated with reduced life expectancy related to excess vascular events, and endothelial dysfunction is present in patients with this condition. We studied the relationship between biophysical and biochemical markers of endothelial dysfunction, including E-selectin, intercellular cell adhesion molecule-1, von Willebrand factor, and thrombomodulin in 52 adult patients with hypopituitarism and severe GH deficiency (<2 ng/ml on provocative testing) compared with 54 age-, sex-, and smoking-matched normal controls. We also examined endothelium-dependent dilatation of the brachial artery to postischemic occlusion and carotid artery morphology (intima-media thickness) by high-resolution ultrasonography. The patients were stable on conventional hormone replacement therapy but not on GH therapy, and none of the subjects had a known risk factor for vascular disease. Levels of E-selectin [57 +/- 3 vs. 49 +/- 2 ng/ml (mean +/- SEM)] (P < 0.043), intercellular cell adhesion molecule-1 (308 +/- 11 vs. 266 +/- 10 ng/ml) (P < 0.001), thrombomodulin (49 +/- 3 vs. 35 +/- 2 ng/ml) (P < 0.001), and von Willebrand factor (132 +/- 7% vs. 105 +/- 5%) (P < 0.004) were significantly higher in patients than in controls. Brachial artery endothelium-dependent dilatation was significantly lower in patients than in controls [4.7% (0.00-9.77) vs. 10.5% (6.4-16.2) (median, interquartile range)] (P < 0.001). This difference in endothelium-dependent dilatation was more marked in female patients than in controls (P < 0.003), although it disappeared when estrogen-sufficient female patients were compared with controls (P = 0.31). However, the female patients who were not replaced with estrogen continued to show a striking difference compared with estrogen-deficient control females (P < 0.004). There was no difference in carotid intima-media thickness between patients of either sex and controls. On univariate analysis, brachial artery endothelium-dependent dilatation correlated inversely with intercellular cell adhesion molecule-1 (r = -0.225, P < 0.033). Intercellular cell adhesion molecule-1 correlated positively with E-selectin (r = 0.466, P < 0.0001) and negatively with IGF-I (r = -0.238, P < 0.016). E-selectin correlated with thrombomodulin (r = 0.215, P < 0.034) and von Willebrand factor (r = 0.218, P < 0.03) and negatively with IGF-I (r = -0.255, P < 009). Thrombomodulin correlated positively with von Willebrand factor (r = 0.422, P < 0.0001) and inversely with IGF-I (r = -0.266, P < 0.008). These correlations persisted after correction for age, sex, body mass index, and waist to hip ratio, with the exception of IGF-I, which now correlated with thrombomodulin only. These results confirm significant endothelial dysfunction in hypopituitarism and provide insight into the relationship of biochemical and biophysical markers of early atherosclerosis in hypopituitary GH-deficient adults. The negative correlation of IGF-I with some biochemical markers of endothelial dysfunction and the predictive nature of GH deficiency in stepwise regression analysis in this study supports the hypothesis that GH deficiency may play a role in these abnormalities. Future studies will determine whether GH treatment can reverse these abnormalities. Furthermore, the more significant endothelium-dependent dilatation abnormality in the female estrogen-deficient subjects compared with those who were estrogen replete suggests that estrogen replacement in these patients is a crucial element in protecting against vascular disease.

Type III tibial spine avulsions treated with arthroscopic Acutrak screw reattachment.

Type III fractures of the tibial spine require open reduction and internal fixation when conservative treatment fails. The Acutrak cannulated screw system has been used successfully for arthroscopic reduction and fixation of these injuries. It was used in four children and two adults; all patients have returned to their preinjury exercise status. The use of a tent peg technique in children allows preservation of the proximal tibial physis, which prevents premature epiphysiodesis.

Knee osteoarthritis and obesity.

OBJECTIVES: To assess the risk of knee osteoarthritis (OA) attributable to obesity, and the interactions between obesity and other established causes of the disorder. METHODS: We performed a population-based case-control study in three health districts of England (Southampton, Portsmouth and North Staffordshire). A total of 525 men and women aged 45 y and over, consecutively listed for surgical treatment of primary knee OA, were compared with 525 controls matched by age, sex and family practitioner. RESULTS: Relative to a body mass index (BMI) of 24.0-24.9 kg/m(2), the risk of knee OA increased progressively from 0.1 (95% CI 0.0-0.5) for a BMI<20 kg/m(2) to 13.6 (95% CI 5.1-36.2) for a BMI of 36 kg/m(2) or higher. If all overweight and obese people reduced their weight by 5 kg or until their BMI was within the recommended normal range, 24% of surgical cases of knee OA (95% CI 19-27%) might be avoided. As a risk factor for knee OA obesity interacted more than additively with each of Heberden's nodes, earlier knee injury and meniscectomy. In comparison with subjects of normal weight, without Heberden's nodes, and with no history of knee injury, people with a combination of obesity, definite Heberden's nodes and previous knee injury had a relative risk of 78 (95% CI 17-354). CONCLUSIONS: Our findings give strong support to public health initiatives aimed at reducing the burden of knee OA by controlling obesity. People undergoing meniscectomy or with a history of knee injury might be a focus for targeted advice.

The effect of hormone replacement therapy and route of administration on selected cardiovascular risk factors in post-menopausal women.

BACKGROUND: There is increasing use of hormone replacement therapy (HRT) by post-menopausal women. Observational epidemiological studies have shown reductions in cardiovascular risk factors in HRT users in the USA, but no randomized controlled trials of HRT have been carried out in the primary practice setting. Previous studies of cardiovascular risk factors have shown a variety of responses according to type of progestagen and oral or topical administration. None has examined the effect of route using an identical progestagen. OBJECTIVES: Our aim was to establish differences, if any, in alteration in cardiovascular risk factors with HRT in post-menopausal women according to route of administration of HRT, oral, transdermal and implant, using first oestrogen alone then oestrogen plus norethisterone, or testosterone for implant. METHODS: Subjects were recruited by letter of invitation to women aged 50-65 years from lists in general practices local to the Charing Cross Hospital Lipid Clinic in West London. Their menopausal status was confirmed and they were randomized to one of three treatment groups or acted as controls. They attended for three visits; at baseline, HRT was initiated as oestrogen alone, oral or transdermal. At the 3-month visit, HRT with the progestagen, norethisterone, was given cyclically, continuously or transdermally until the final visit at 6 months. A separate group of women from the menopause clinic at Chelsea and Westminster Hospital were studied on oestrogen implant then on implanted oestrogen and testosterone. The outcome measures studied were the separate effects of the four regimes as compared with controls on lipoproteins, glucose, insulin, fibrinogen, factor VII and E-selectin, together with weight, waist:hip ratio and blood pressure. RESULTS: The continuous combined oestrogen-progestagen therapy had similar effects on cardiovascular risk factors as oestrogen with cyclical progestagen. All regimes lowered low-density lipoprotein cholesterol, the oral route being more potent than the parenteral; the effect of transdermal HRT was similar to the implant. Lp(a) was reduced only with the oral route. Reductions in factor VII and E-selectin were observed in both the oral and transdermal routes. There was no increase in body mass index, waist:hip ratio, blood pressure or glucose and insulin levels with any of the HRT regimes used. Systolic blood pressure was reduced with the transdermal route. CONCLUSIONS: This study supports the evidence that oestrogen-progestagen HRT, both oral and transdermal, although attenuating some of the benefit of oestrogen alone on fibrinogen and high-density lipoprotein, significantly reduces cardiovascular risk factors, which should diminish post-menopausal risk of coronary disease.