Moderate Ingestion of Alcohol Is Associated With Acute Ethanol‐Induced Suppression of Circulating CTX in a PTH‐Independent Fashion

The “J shape” curve linking the risk of poor bone health to alcohol intake is now well recognized from epidemiological studies. Ethanol and nonethanol components of alcoholic beverages could influence bone remodeling. However, in the absence of a solid underlying mechanism, the positive association between moderate alcoholic intake and BMD remains questionable because of confounding associated social factors. The objective of this work was to characterize the short‐term effects of moderate alcohol consumption on circulating bone markers, especially those involved in bone resorption. Two sequential blood‐sampling studies were undertaken in fasted healthy volunteers (age, 20–47 yr) over a 6‐h period using beer of different alcohol levels (<0.05–4.6%), solutions of ethanol or orthosilicic acid (two major components of beer), and water ± calcium chloride (positive and negative controls, respectively). Study 1 (24 subjects) assessed the effects of the different solutions, whereas study 2 (26 subjects) focused on ethanol/beer dose. Using all data in a “mixed effect model,” we identified the contributions of the individual components of beer, namely ethanol, energy, low‐dose calcium, and high‐dose orthosilicic acid, on acute bone resorption. Markers of bone formation were unchanged throughout the study for all solutions investigated. In contrast, the bone resorption marker, serum carboxy terminal telopeptide of type I collagen (CTX), was significantly reduced after ingestion of a 0.6 liters of ethanol solution (>2% ethanol; p ≤ 0.01, RM‐ANOVA), 0.6 liters of beer (<0.05–4.6% ethanol; p < 0.02), or a solution of calcium (180 mg calcium; p < 0.001), but only after calcium ingestion was the reduction in CTX preceded by a significant fall in serum PTH (p < 0.001). Orthosilicic acid had no acute effect. Similar reductions in CTX, from baseline, were measured in urine after ingestion of the test solutions; however, the biological variability in urine CTX was greater compared with serum CTX. Modeling indicated that the major, acute suppressive effects of moderate beer ingestion (0.6 liters) on CTX were caused by energy intake in the early phase (～0–3 h) and a “nonenergy” ethanol component in the later phase (～3 to >6 h). The early effect on bone resorption is well described after the intake of energy, mediated by glucagon‐like peptide‐2, but the late effect of moderate alcohol ingestion is novel, seems to be ethanol specific, and is mediated in a non–calcitonin‐ and a non–PTH‐dependent fashion, thus providing a mechanism for the positive association between moderate alcohol ingestion and BMD.     

METHYLATION STATUS OF BCL6 DISTINGUISHES DNA SAMPLES FROM BENIGN AND MALIGNANT LYMPHOPROLIFERATIVE DISORDERS

INTRODUCTION: Core biopsy of the breast has become the method of choice for tissue diagnosis of screen detected microcalcifications and some mass lesions in many breast assessment centres. Biopsy results are not available until the following day. Imprint cytology of fresh breast core samples allows same-day reporting and patient counselling.
AIM: To determine the accuracy of core imprint cytology when compared with core biopsy diagnosis when used in a breast assessment centre setting.
METHODS: Core imprints (CI) were prepared and reported on all fresh core biopsies (CB) performed at the Sir Charles Gairdner Hospital Breast Centre from May to December 2000. Fresh core samples were placed on a glass microscope slide. Core radiographs were taken for microcalcification lesions (MC). A laboratory technician gently and quickly rolled the cores on the slide with fine forceps. The cores were fixed in formalin, processed and reported next day. The imprint slide was air dried and stained with DiffQuik. CI were reported using four categories: Insufficient, Benign, Indeterminate and Malignant. Counselling and planning for management were possible on the same day in women with malignant diagnoses. Clinicians were advised not to discuss negative or indeterminate CI results with women and to defer to the final CB report.
RESULTS: Cores were performed on 381 lesions. There were 83 carcinomas (38 in MC and 45 in masses) and 56 were called malignant on CI (absolute sensitivity 67.5%; 78.9% for MC and 57.8% for masses). 3 malignancies on CB were negative on CI giving a false negative rate of 3.6%. There were no false positive diagnoses. The predictive value of a benign diagnosis was 95.3%. There were no adverse effects in the histology of CB.
CONCLUSION: CI was an accurate method of providing an immediate diagnosis of malignancy in two thirds of malignancies confirmed on CB.     

CD14 expression is increased on monocytes in patients with anti‐neutrophil cytoplasm antibody (ANCA)‐associated vasculitis and correlates with the expression of ANCA autoantigens

Monocyte subsets with differing functional properties have been defined by their expression of CD14 and CD16. We investigated these subsets in anti‐neutrophil cytoplasm antibody (ANCA)‐associated vasculitis (AAV) and determined their surface expression of ANCA autoantigens. Flow cytometry was performed on blood from 14 patients with active AAV, 46 patients with AAV in remission and 21 controls. The proportion of classical (CD14^highCD16^neg/low), intermediate (CD14^highCD16^high) and non‐classical (CD14^lowCD16^high) monocytes and surface expression levels of CD14 and CD16 were determined, as well as surface expression of proteinase 3 (PR3) and myeloperoxidase (MPO) on monocyte subsets. There was no change in the proportion of monocytes in each subset in patients with AAV compared with healthy controls. The expression of CD14 on monocytes from patients with active AAV was increased, compared with patients in remission and healthy controls (P < 0·01). Patients with PR3‐ANCA disease in remission also had increased monocyte expression of CD14 compared with controls (P < 0·01); however, levels in patients with MPO‐ANCA disease in remission were lower than active MPO‐ANCA patients, and not significantly different from controls. There was a correlation between CD14 and both PR3 and MPO expression on classical monocytes in AAV patients (r = 0·79, P < 0·0001 and r = 0·42, P < 0·005, respectively). In conclusion, there was an increase in monocyte CD14 expression in active AAV and PR3‐ANCA disease in remission. The correlation of CD14 expression with ANCA autoantigen expression in AAV may reflect cell activation, and warrants further investigation into the potential for increased CD14 expression to trigger disease induction or relapse.     

Metallic Surface Treatment Using Electrochemical Polishing Decreases Thrombogenicity and Neointimal Hyperplasia of Coronary Stents

An abundant healing response resulting in a more pronounced neointimal hyperplasia compared to conventional balloon angioplasty remains the most important clinical problem after coronary stent implantation. In the present study the potential beneficial effect of metal surface treatment using electrochemical polishing on stent thrombogenicity and neointimal hyperplasia was evaluated in a rat A‐ V model and a porcine coronary model. An electrochemical polishing system was developed to improve surface characteristics of stainless steel stents. Topographic scanning of the stent surface using a profilometer type Taylor Holson Form Taylsurf 120L showed a significant effect on R, (arithmetic mean of the roughness height) (0.14 vs 0.04 μm: P < 0.001) and R_t (maximum rouhgness height between a peak and a valley for the sampling length) (1.44 vs 0.43 μm: P < 0.001). Thrombogenicity of polished stents (n = 6) was compared to nonpolished stents (n = 5) in a rat A ‐ V shunt model using ¹²⁵I fibrinogen and ⁵¹Cr‐labeled platelets. Total clot weight after 30 minutes was significantly lower in the polished stents (32.1 + 2.8 vs 18.1 + 4.4: P < 0.001). Also ¹²⁵I fibrinogen deposition was significantly lower in the polished stents (1.30 + 0.07 vs 0.66 + 0.04: P < 0.001). Platelet deposition, however, was not significantly reduced (12.7 + 3.4 vs 9.87 + 1.9, NS). Subsequently, the effect of electrochemical polishing on neointimal hyperplasia was evaluated in a porcine coronary model. Polished (n =10) and nonpolished stents (n =10) were randomly implanted in the right coronary artery of healthy pigs. Neointimal hyperplasia was significantly decreased in the polished stents (0.6 + 0.28 vs 0.9 + 0.34 mm²: P <0.01). Electrochemical polishing oj coronary stents results in decreased thrombogenicity and neointimal hyperplasia after stent implantation in different animal models.     

Overnight glucose metabolism in obese non-insulin-dependent diabetic patients and in healthy lean individuals

Summary. Increased fasting hepatic glucose production is present in NIDDM patients, and has been shown to be due to increased gluconeogenesis. In order to determine the contribution of the cycling between glucose and three-carbon compounds (Cori and glucose-alanine cycles) to the increased hepatic glucose production, glucose kinetics measured overnight in seven obese NIDDM patients and six lean healthy subjects with both 6, 6 ²H glucose and U-¹³C glucose were determined. At 0500 h obese NIDDM subjects showed a 40% increase in glucose appearance calculated from 6, 6 ²H glucose, whereas glucose appearance calculated from U-¹³C glucose was similar compared to lean subjects, indicating increased glucose cycling. Non-oxidative glucose disposal was also increased three-fold in NIDDM patients. Glucose cycling was increased by 111% in NIDDM patients (118 ± 18 μmole min^-1 vs. 56 ± 11 in controls, P<0–05) and was positively correlated with plasma glucose concentration (r= 0–831, P<0–001) and with non-oxidative glucose disposal (r= 0–714, P<0–01). Four NIDDM patients were studied again after 3 days of insulin therapy. Insulin restored near-normoglycaemia (7–4 ± 0–8 mmole 1^-1) and normalized rates of glucose appearance and glucose cycling. It is concluded that increased glucose cycling in obese NIDDM patients accounts for a major part of the increased fasting hepatic glucose production and non-oxidative glucose disposal in obese NIDDM subjects.     

The double puncture: an effective percutaneous technique for removing complex, multiple renal calculi

Percutaneous nephrostolithotomy, which can require a double puncture, is presently the method of choice in our institution for the removal of renal stones. Patients that underwent this procedure were evaluated to identify the possible reasons for the double puncture. Of 200 patients evaluated, 14 needed a second tract. The three variables that determined whether a second puncture was needed, in order of importance, were number and size of the stones, with second tracts needed in patients with multiple stones and staghorn calculi; anatomical variations of the renal collecting system itself, with bifid systems the most significant anatomic variation; and the dexterity of the radiologist in performing the puncture and the ability of the urologist to extract the stone. Second tracts were needed more frequently in patients who presented with stones in both the lower and middle poles of the collecting systems.