Inflammatory and bone turnover markers in a cross-sectional and prospective study of acute Charcot osteoarthropathy.

AIMS: To assess markers of inflammation and bone turnover at presentation and at resolution of Charcot osteoarthropathy. METHODS: We measured serum inflammatory and bone turnover markers in a cross-sectional study of 35 people with Charcot osteoarthropathy, together with 34 people with diabetes and 12 people without diabetes. In addition, a prospective study of the subjects with Charcot osteoarthropathy was conducted until clinical resolution. RESULTS: At presentation, C-reactive protein (P = 0.007), tumour necrosis factor-α (P = 0.010) and interleukin-6 (P = 0.002), but not interleukin-1ß, (P = 0.254) were significantly higher in people with Charcot osteoarthropathy than in people with and without diabetes. Serum C-terminal telopeptide (P = 0.004), bone alkaline phosphatase (P = 0.006) and osteoprotegerin (P < 0.001), but not tartrate-resistant acid phosphatase (P = 0.126) and soluble receptor activator of nuclear factor-κß ligand (P = 0.915), were significantly higher in people with Charcot osteoarthropathy than in people with and without diabetes. At follow-up it was found that tumour necrosis factor-α (P = 0.012) and interleukin-6 (P = 0.003), but not C-reactive protein (P = 0.101), interleukin-1ß (P = 0.457), C-terminal telopeptide (P = 0.743), bone alkaline phosphatase (P = 0.193), tartrate-resistant acid phosphatase (P = 0.856), osteoprotegerin (P = 0.372) or soluble receptor activator of nuclear factor-kß ligand (P = 0.889), had significantly decreased between presentation and the 3 months of casting therapy time point, and all analytes remained unchanged from 3 months of casting therapy until resolution. In people with Charcot osteoarthropathy, there was a positive correlation between interleukin-6 and C-terminal telopeptide (P = 0.028) and tumour necrosis factor-α and C-terminal telopeptide (P = 0.013) only at presentation. CONCLUSIONS: At the onset of acute Charcot foot, serum concentrations of tumour necrosis factor-α and interleukin-6 were elevated; however, there was a significant reduction in these markers at resolution and these markers may be useful in the assessment of disease activity.

Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention.

BACKGROUND: Bile acid diarrhoea is a common, under-diagnosed cause of chronic watery diarrhoea, responding to specific treatment with bile acid sequestrants. We previously showed patients with bile acid diarrhoea have lower median levels compared with healthy controls, of the ileal hormone fibroblast growth factor 19 (FGF19), which regulates bile acid synthesis. AIM: To measure serum FGF19 and SeHCAT retention prospectively in patients with chronic diarrhoea. METHODS: One hundred and fifty-two consecutive patients were grouped according to (75) Se-homocholic acid taurine (SeHCAT) 7-day retention: normal (>15%) in 72 (47%) diarrhoea controls; ≤15% in 54 (36%) with primary bile acid diarrhoea, and in 26 (17%) with secondary bile acid diarrhoea. Fasting blood was assayed for FGF19, 7α-hydroxy-4-cholesten-3-one (C4) and total bile acids. RESULTS: FGF19 was significantly lower in the primary bile acid diarrhoea group compared with the diarrhoea control group (median 147 vs. 225 pg/mL, P < 0.001), and also in the secondary group (P < 0.006). FGF19 and SeHCAT values were positively correlated (rs = 0.44, P < 0.001); both were inversely related to C4. Other significant relationships included SeHCAT and body mass index (BMI)(P = 0.02), and FGF19 with age (P < 0.01). The negative and positive predictive values of FGF19 ≤ 145 pg/mL for a SeHCAT <10% were 82% and 61%, respectively, and were generally improved in an index including BMI, age and C4. In a subset of 28 primary patients, limited data suggested that FGF19 could predict response to sequestrant therapy. CONCLUSIONS: Reduced fibroblast growth factor 19 is a feature of bile acid diarrhoea. Further studies will fully define its role in predicting the response of these patients to therapy.

Predicting the development of acute kidney injury in liver cirrhosis--an analysis of glomerular filtration rate, proteinuria and kidney injury biomarkers.

BACKGROUND: The timely diagnosis of acute kidney injury (AKI) in liver cirrhosis is challenging. AIM: To evaluate whether quantification of glomerular filtration rate (GFR), proteinuria and kidney injury biomarkers can accurately predict the development of AKI. METHODS: A prospective cohort analysis of patients with cirrhosis was performed. Measures of baseline kidney function included serum creatinine, iohexol clearance and urine protein:creatinine ratio. Blood and urine samples were collected daily. A retrospective analysis of cystatin C GFR and neutrophil gelatinase-associated lipocalin (NGAL) measured 48 h prior to the diagnosis of AKI was undertaken to evaluate their ability to predict the development of AKI. RESULTS: Eighteen of the 34 cirrhosis patients studied developed AKI. A GFR <60 mL/min/1.73 m(2) was identified in 56% with Iohexol clearance compared to 8% using the four-variable modified diet in renal disease formula (P < 0.0001). Prediction of AKI, 48 h prior to the development of AKI with cystatin C GFR and serum NGAL concentration were similar; area under the receiver operating curve (AUROC) values 0.74 (0.51-0.97), P = 0.04 and 0.72 (0.52-0.92), P = 0.02 respectively. The development of AKI was strongly predicted by urine protein:creatinine ratio above the cut-off of >30 (equivalent to 300 mg/day of proteinuria) sensitivity 82% (57-96) and specificity 80% (52-96), AUROC 0.86 (0.73-0.98), P ≤ 0.0001. [OR 21 (3-133), P ≤ 0.002]. CONCLUSIONS: In patients with liver cirrhosis a urine protein:creatinine ratio >30 predicts AKI. Iohexol clearance and cystatin C formulae identify a greater proportion of patients with a GFR <60 mL/min/1.73 m(2), which also predicts the development of AKI.

Analysis of adipokine concentrations in paediatric non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children. It is important to distinguish children with more severe disease or steatohepatitis (NASH) from those with the less severe simple steatosis (SS) as prognosis differs. The importance of adipokines in the evolution of NASH is well recognized. OBJECTIVE: As adipokines are important in mediating inflammation, they may also be useful biomarkers of disease. METHODS: Plasma from 40 children (30 boys), median age 13.4 years, with liver biopsy-proven NAFLD was analysed. Liver biopsies were scored using the NAFLD activity score and compared with adipokine concentrations. RESULTS: Median body mass index z-score was 2.12 with a median homeostasis model of assessment- insulin resistance of 4.08. Resistin was lower in NASH than in SS (P = 0.03). Monocyte chemoattractant protein 1 (MCP-1) was also lower in NASH (P = 0.04). MCP-1 was higher in children with severe fibrosis (P = 0.008) with an area under the receiver operating characteristic curve (AUROC) of 0.76. Plasminogen activator inhibitor 1 (PAI-1) was also higher in this group (P = 0.011) with an AUROC of 0.78. There were no significant differences in leptin, adiponectin, adipsin, interleukin (IL) 6, IL10 or tumour necrosis factor α between groups. CONCLUSION: PAI-1 MCP-1 and resistin were differentially expressed with increasing severity of NAFLD. Though it is unlikely that this profile alone would serve as a biomarker of disease, differences found may contribute to understanding the role of these mediators in NAFLD.

The use of novel biochemical markers in predicting spontaneously resolving 'pregnancies of unknown location'.

BACKGROUND: 'Pregnancies of unknown location' (PULs) include viable and failing intrauterine and extrauterine pregnancies. The aim of this study was to evaluate the role of novel biochemical markers in the prediction of spontaneous resolution of PULs. METHODS: Serum samples were taken at the first visit to the pregnancy unit for measuring the traditional markers ß-hCG and progesterone, and for inhibin A, inhibin pro-αC-related immunoreactivity (inhibin pro-αC-RI) and insulin-like growth factor-binding protein 1 (IGFBP-1). Follow-up was continued until the pregnancy had resolved, the location of the pregnancy and viability was determined or treatment was required. Outcomes were dichotomized into 'spontaneous resolution' and 'other outcome' categories. RESULTS: One-hundred and nine cases of PUL were included in the data analysis. Spontaneous resolution occurred in 70% and a further scan was required in 30% to reach a diagnosis. Levels of progesterone and inhibin A were significantly lower (both P < 0.001) and levels of IGFBP-1 significantly higher (P = 0.02) in the pregnancies that spontaneously resolved than in those pregnancies that required further intervention. In decision tree analysis, the novel markers were less useful than progesterone and ß-hCG in predicting spontaneously resolving PULs. Inhibin pro-αC-RI and IGFBP-1 were not useful in the prediction of spontaneously resolving PULs. Inhibin A is more predictive than ß-hCG alone, but serum progesterone is the best single marker and progesterone and hCG together continues to be the best way of predicting spontaneously resolving PULs. CONCLUSIONS: These novel biochemical markers are not clinically useful in predicting spontaneously resolving PULs.

Repetitive transcranial magnetic stimulation reduces cortisol concentrations in bulimic disorders.

BACKGROUND: In people with bulimic eating disorders, exposure to high-calorie foods can result in increases in food craving, raised subjective stress and salivary cortisol concentrations. This cue-induced food craving can be reduced by repetitive transcranial magnetic stimulation (rTMS). We investigated whether rTMS has a similar effect on salivary cortisol concentrations, a measure of hypothalamic-pituitary-adrenal axis (HPAA) activity. METHOD: We enrolled twenty-two female participants who took part in a double-blind randomized sham-controlled trial on the effects of rTMS on food craving. Per group, eleven participants were randomized to the real or sham rTMS condition. The intervention consisted of one session of high-frequency rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC). Salivary cortisol concentrations were assessed at four time points throughout the 90-min trial. To investigate differences in post-rTMS concentrations between the real and sham rTMS groups, a random-effects model including the pre-rTMS cortisol concentrations as covariates was used. RESULTS: Salivary cortisol concentrations following real rTMS were significantly lower compared with those following sham rTMS. In this sample, there was also a trend for real rTMS to reduce food craving more than sham rTMS. CONCLUSIONS: These results suggest that rTMS applied to the left DLPFC alters HPAA activity in people with a bulimic disorder.

Antidepressants, but not antipsychotics, modulate GR function in human whole blood: an insight into molecular mechanisms.

Clinical studies have demonstrated an impairment of glucocorticoid receptor (GR)-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depression (GR resistance), and its resolution by antidepressant treatment. Recently, we showed that this impairment is indeed due to a dysfunction of GR in depressed patients (Carvalho et al., 2009), and that the ability of the antidepressant clomipramine to decrease GR function in peripheral blood cells is impaired in patients with major depression who are clinically resistant to treatment (Carvalho et al. 2008). To further investigate the effect of antidepressants on GR function in humans, we have compared the effect of the antidepressants clomipramine, amytriptiline, sertraline, paroxetine and venlafaxine, and of the antipsychotics, haloperidol and risperidone, on GR function in peripheral blood cells from healthy volunteers (n=33). GR function was measured by glucocorticoid inhibition of lypopolysaccharide (LPS)-stimulated interleukin-6 (IL-6) levels. Compared to vehicle-treated cells, all antidepressants inhibited dexamethasone (DEX, 10-100nM) inhibition of LPS-stimulated IL-6 levels (p values ranging from 0.007 to 0.1). This effect was specific to antidepressants, as antipsychotics had no effect on DEX-inhibition of LPS-stimulated IL-6 levels. The phosphodiesterase (PDE) type 4 inhibitor, rolipram, potentiated the effect of antidepressants on GR function, while the GR antagonist, RU-486, inhibited the effect of antidepressants on GR function. These findings indicate that the effect of antidepressants on GR function are specific for this class of psychotropic drugs, and involve second messenger pathways relevant to GR function and inflammation. Furthermore, it also points towards a possible mechanism by which one maybe able to overcome treatment-resistant depression. Research in this field will lead to new insights into the pathophysiology and treatment of affective disorders.

M2-PK as a novel marker in ovarian cancer. A prospective cohort study.

BACKGROUND: Pyruvate kinase isoenzyme M2-PK is instrumental to tumour metabolism and hence over-expressed in tumour cells leading to detectable plasma concentrations. OBJECTIVES: To assess the degree of association between M2-PK plasma concentrations and ovarian cancer and to determine the cut-off values for its sensitivity and specificity for differentiating between benign and malignant ovarian disease. SETTINGS: The Gynaecological Cancer Centre at both King's College and St. Thomas' Hospitals, London, UK. METHODS: Patients with suspected ovarian cancer referred to the above centre were recruited prospectively during the years 2004-2005. Blood samples were collected before surgery for plasma M2-PK assays. Results were assessed with respect to cancer diagnosis, patient and tumour characteristics. Statistical analysis including the receiver operator characteristic (ROC) curve was performed using Analyse-It and SPSS V 13. RESULTS: 100 patients with age range 14-88 years and a median of 57 years were recruited in the study. Of whom 52 were diagnosed with invasive ovarian cancer. Of these 35 (67%) were Stage III and above with two secondary tumours. M2-PK was not related to patient age (p = 0.43). There was a significant correlation between CA125 and M2-PK (p < 0.001). The mean M2-PK concentration in cancer patients was 52 U/ml versus 27 U/ml in patients with benign conditions (p < 0.001). At a cut-off value of 22 U/ml the sensitivity of M2-PK for detecting cancer was 70% with a specificity of 65%. CONCLUSION: M2-PK was significantly raised in ovarian cancer patients, however its role in clinical practice needs further evaluation.

Tumour M2-PK as a predictor of surgical outcome in ovarian cancer, a prospective cohort study.

BACKGROUND: Optimal cytoreduction is a major prognostic factor in ovarian cancer; several clinical, radiological and biochemical predictors have been studied. Tumour M2-PK (TU M2-PK) is over-expressed in tumour cells and can be detected in plasma samples but its role in ovarian cancer has not yet been evaluated. OBJECTIVES: To assess the potential clinical applications of TU M2-PK in ovarian cancer particularly in relation to surgical cytoreduction. SETTINGS: The Gynaecological Cancer Centre at both King's College and St Thomas' Hospitals; London; UK. METHODS: Patients with suspected ovarian cancer were recruited prospectively during the years 2004-2005. Blood samples were collected before surgery for plasma TU M2-PK assays. Data were analysed in relation to cancer diagnosis and outcome. Statistical analysis was performed using Analyse-It' and SPSS' V13. RESULTS: 100 patients were recruited; 52 diagnosed with invasive ovarian cancer, 13 with borderline tumours and 35 patients had benign conditions. The mean M2-PK concentration in cancer patients was 52 U/ml vs 31 U/ml in patients with borderline tumours and 22 U/ml in those with benign conditions (p < 0.001); it was significantly raised in association with late stage disease and higher grade (p < 0.05). Taking 35 U/ml as a reference point, TU M2-PK predicted sub-optimal cytoreduction in advanced stage disease with a sensitivity of 69%, specificity of 60% and overall efficacy of 61% (95% CI: 44-75%). CONCLUSION: TU M2-PK was significantly raised in ovarian cancer patients, particularly those with higher stage disease. The potential clinical application as a predictor of surgical outcome in ovarian cancer needs further evaluation.

Bone mineral density, polyphenols and caffeine: a reassessment.

Several studies have shown beneficial associations between tea consumption and bone mineral density (BMD) and fracture risk. Current investigations into potential mechanisms of benefit are focused upon the F and polyphenol components of tea. However, previous studies have pointed towards caffeine consumption as a potential risk factor for low BMD and high fracture risk. Tea, therefore, represents an interesting paradox as a mildly caffeinated beverage that may enhance bone health. Fruit and vegetable intake has also been associated with BMD, and it is now apparent that several fruit and vegetable components, including polyphenols, may contribute positively to bone health. Evidence surrounding the function(s) of polyphenol-rich foods in bone health is examined, along with more recent studies challenging the relevance of caffeine consumption to in vivo Ca balance. Plant foods rich in polyphenols such as tea, fruit and vegetables, as significant factors in a healthy diet and lifestyle, may have positive roles in bone health, and the negative role of caffeine may have been overestimated. The present review covers evidence of dietary mediation in positive and negative aspects of bone health, in particular the roles of tea, fruit and vegetables, and of caffeine, flavonoids and polyphenols as components of these foods. Since the deleterious effects of caffeine appear to have been overstated, especially in respect of the positive effects of flavonoids, it is concluded that a reassessment of the role of caffeinated beverages may be necessary.

Prevalence of vitamin D inadequacy in osteoporotic hip fracture patients in London.

BACKGROUND: It is well established that vitamin D levels are suboptimal in the elderly and that adults with fragility fracture are more likely to have serum vitamin D levels either lower than those of control patients of similar age, or below the normal range. OBJECTIVES: To investigate the prevalence of vitamin D inadequacy in an elderly population with hip fractures from London (UK) and compare levels with data previously presented from Glasgow (UK). RESEARCH DESIGN AND METHODS: A retrospective patient audit was carried out over a 17-month period (September 2003-January 2005). Patient records were searched for hip fracture admissions and cross matched with vitamin D analysis carried out within 3 days of the hip fracture admission. The resulting records were hand searched to exclude patients with a hip fracture resulting from high impact/trauma. RESULTS: There were data for 103 hip fracture patients, 79.6% of the patients were women (n = 82). The mean age at the time of fracture was 73.4 years, 100% were aged 60 years or over and 41% were aged 75 years or over. Around 20% of the patients were receiving supplementation with calcium and/or vitamin D and were not excluded from the analysis. The mean vitamin D level was 32.1 nmol/L (12.9 ng/mL), SD = 19.4 (7.8), however, it is likely that the true mean is lower since in approximately 15% of cases vitamin D levels were reported as < 12.5 nmol/L, but were transcribed at 12.5 nmol/L in order to allow a numerical value to be calculated. Ninety-nine per cent of patients had a vitamin D level < 80 nmol/L, 94.2% < 70 nmol/L and 81.6% < 50 nmol/L. There were no significant differences by patient age or sex, however, there were significant seasonal differences in vitamin D. In the year from September 2003 to August 2004, 82.8% of summer admissions had vitamin D levels < 70 nmol/L compared with 98.0% in winter (p = 0.04). Mean vitamin D levels in the 30 patients with parathyroid hormone (PTH) levels above the reference range were significantly lower than levels in the 71 patients within the range: mean 19.9 nmol/L, SD = 16.2 versus mean 37.5 nmol/L, SD = 18.5 (p < 0.0001). Furthermore, 50% of the patients with PTH levels above the reference range had vitamin D levels < 12.5 nmol/L, reflecting extremely low levels of vitamin D. CONCLUSIONS: This study confirms almost universal vitamin D inadequacy among 103 patients admitted to hospital with hip fracture in London, although the prevalence of inadequacy is slightly lower than that seen in a similar study carried out in Glasgow.

Expectant management of miscarriage--prediction of outcome using ultrasound and novel biochemical markers.

BACKGROUND: The aim of this study was to examine the value of various ultrasound and biochemical parameters for the prediction of successful expectant management of miscarriage. METHODS: This was a prospective observational study. Clinically stable women with an ultrasound diagnosis of miscarriage were offered expectant management. In all cases, gestational age, size of retained products of conception, serum HCG, progesterone, 17-hydroxyprogesterone, insulin growth factor-binding protein 1 (IGFBP-1), inhibin A and inhibin pro alpha-C RI levels were recorded. Follow-up continued until resolution of the pregnancy. Clinical data, ultrasound findings and biochemical markers were analysed using univariate analysis and decision tree analysis. RESULTS: Fifty-four women underwent expectant management of miscarriage. Thirty-seven (69%) had successful expectant management and 17 (31%) required surgery. The size of retained products, serum HCG, progesterone, inhibin A and inhibin pro alpha-C RI were all significantly different in those pregnancies that resolved spontaneously (P<0.05). Serum inhibin A was the best predictor of a complete miscarriage. CONCLUSION: This study shows that novel biochemical markers may be used to predict the likelihood of successful expectant management of miscarriage.

Results from an ultrasound-based familial ovarian cancer screening clinic: a 10-year observational study.

OBJECTIVES: To assess the use of transvaginal sonography as a screening test for familial ovarian cancer and, secondarily, to determine the value of a family history of malignant disease and the potential role of serum CA 125 levels in the screening procedure. METHODS: Two thousand five hundred self-referred women were studied at the Ovarian Screening Clinic at King's College Hospital, London. These symptom-free women with at least one close relative who had developed ovarian cancer were studied prospectively. Each woman was scanned for the presence of a persistent ovarian lesion and a sample of peripheral blood was taken for the retrospective analysis of serum CA 125. Women with a positive screen result were referred for surgical investigations; those with a negative result but considered to be at high risk were rescreened. The main outcome measures were findings at surgery, the histological classification of ovarian lesions, and cancer reported at follow-up. RESULTS: The women were aged 17 to 78 (mean, 48) years; 65% were premenopausal, 26% were postmenopausal and 9% had undergone hysterectomy. Seven hundred and thirty-eight women (29.5%) had a family history of multiple site cancers and 279 (11.2%) reported cancer specific to the ovary. There were 4231 screenings (2500 first screens, 998 second screens and 733 third or higher order screens). One hundred and four screens gave a positive result (2.5%); 11 cancers were detected (seven (64%) at stage I, four of which were of borderline malignancy). One additional cancer was reported within 12 months of the last scan and classified as a false-negative screen result. Eight cancers (including two peritoneal) were reported at follow-up (> 1-9 years after the last scan). All these women presented at an advanced stage (stage III). Fifteen of 20 cancers occurred in premenopausal women. The overall sensitivity of ultrasound screening was 92% (95% confidence interval, 76-100); the specificity was 97.8%. The prior odds of any woman having a screen-detectable ovarian malignancy during the study period were 1 : 207. The posterior odds subsequent to a positive screen result were 1 : 8.5 (1 : 12.7 at Screen 1; 1 : 3.7 at Screen 2; 1 : 3.0 at subsequent screens); the value was 1 : 11.4 for women with one family relative with ovarian cancer and 1 : 5.0 for women with the site-specific ovarian cancer syndrome. The prior use of a decision level for serum CA 125 >or= 20 U/mL would have reduced the number of women undergoing sonography by 78%; seven of the 12 cancers (58%) would have been detected (63% of all stage I disease, 75% of invasive stage I disease). An alternative cut-off value of 35 U/mL would have resulted in a detection rate of 33%. CONCLUSIONS: Transvaginal sonography can effectively detect intraovarian cancer and tumors of borderline malignancy in women with a family history of the disease. Screening efficacy is related to the type of family history. The level of serum CA 125 can be used to select women for sonography, but the detection rate for early cancers would be reduced.

Validity of PSA, free/total PSA ratio and complexed/total PSA ratio measurements in men with acute urinary retention.

The reliability of serum prostate specific antigen (PSA) measurements in men with acute urinary retention is unclear. Total PSA, free and complexed PSA were measured, and the free/total (f/t) PSA and complexed/total (c/t) PSA ratios calculated, prior to catheterisation and at 48 and 72 h post-catheterisation in 39 men with acute retention. Subsequent histology showed 12 patients had prostate cancer and 27 benign prostatic hypertrophy. Serum free and total PSA fell following catheterisation, while complexed PSA rose during the first 48 h then subsequently fell. The f/t PSA and c/t PSA ratios provided the best discrimination at 48-72 h with 100% sensitivity and 75-82% specificity.Prostate Cancer and Prostatic Diseases (2001) 4, 167-172.

Angiogenic peptides in prostatic disease.

OBJECTIVE: To determine the value of measuring serum concentrations of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with benign prostatic hyperplasia (BPH), advanced and localized prostate cancer, and thus assess the role of angiogenesis factors as markers of malignancy and the formation of metastasis. PATIENTS AND METHODS: Serum was obtained from 106 suitable patients who attended a routine clinic during the study period. A histological diagnosis was confirmed for each patient and a bone scan was positive in those with metastatic disease. The level of serum prostate specific antigen (PSA) was measured and the serum concentrations of VEGF and bFGF measured using a quantitative sandwich immunoassay technique. RESULTS: There was a significant difference (1.6-fold) in the serum concentration of bFGF between patients with local and advanced prostate cancer (P=0.006), but there was no significant difference for either of the growth factors between patients with BPH and metastatic prostate cancer (Mann-Whitney test). CONCLUSION: The serum levels of VEGF and bFGF could not be used to distinguish benign from malignant prostatic disease; the serum PSA level is of more value than either, but the serum concentration of bFGF may be of some value in differentiating patients with local and advanced malignancy.

Influence of investigative and operative procedures on serum prostate-specific antigen concentration.

We determined the effect of cystoscopy (flexible and rigid), transrectal ultrasonography (with and without needle biopsy of the prostate) and transurethral resection of the prostate or bladder tumour on the serum prostate-specific antigen (PSA) concentration. Samples were taken from 60 men before and up to 14 days following these procedures. Flexible cystoscopy did not result in a significant increase in serum PSA concentration, with a median increase of 0.1 microgram/L (P > 0.05). Small but statistically significant increases in serum PSA levels 1 day post-procedure were observed following rigid cystoscopy and transrectal ultrasound without biopsy. The median increase in serum PSA concentration following rigid cystoscopy was 0.15 microgram/L (P = 0.04) and following transrectal ultrasound was 0.3 microgram/L (P = 0.01). In both cases the serum PSA level had normalized by 2 days post-procedure. Transurethral resection of bladder tumours resulted in a variable rise in serum PSA, with a median increase of 2.6 micrograms/L after 1 day, which returned to normal over 7-14 days. Ultrasound-guided needle biopsy of the prostate and transurethral resection of the prostate produced significant increases in serum PSA levels, which took up to fourteen days to return to normal. The median increase in serum PSA following needle biopsy was 6.0 micrograms/L and following transurethral resection of the prostate (TURP) was 13 micrograms/L. Samples for PSA measurement may safely be taken within 24-48 h of flexible cystoscopy and transrectal ultrasonography (TRUS) providing prostatic biopsy is not carried out. For other procedures it is necessary to wait for at least 14 days to ensure that false positive PSA results are not obtained.

The prevalence of alcohol misuse in patients undergoing cataract surgery.

If a factor could be identified which delayed the onset of cataract by 10 years, the number of annual cataract operations worldwide has been estimated to decrease by 45%. A case-control study compared alcohol consumption in 78 patients attending for routine cataract surgery in South East London with data from a large population-based survey. Male cataract patients had a significantly greater risk of being harmful drinkers (odds ratio = 8, p = 0.007) than the controls. The harmful male drinkers were significantly younger than the non-drinkers with cataract (mean difference 15 years, p < 0.007). Female cataract patients were not more likely to be excessive drinkers than controls. The female drinkers with cataract were of a similar age to the non-drinking female patients with cataract. Haematological and biochemical indices of alcohol toxicity indicated five patients who were likely to be harmful drinkers, but who had denied this on direct questioning. Seven (26%) of the male patients had a low serum 25 hydroxycholecalciferol although the levels were normal in the female patients. These results support the view that excess alcohol consumption is related to cataract formation and suggest that alcohol causes premature cataract formation in male, but not female patients. Alcohol consumption is amenable to intervention and suggests that such intervention could have a significant impact on the need for cataract surgery.

Functional, radiographic, and histologic assessment of healing of autogenous osteochondral grafts and full-thickness cartilage defects in the talus of dogs.

A circular (5.5 mm diameter) full-thickness cartilage defect was created on the medial ridge of the talus in 12 skeletally mature dogs. In 6 dogs, the articular surface of the lesion was repaired, using an osteochondral graft obtained from the ipsilateral manus. The graft (digit I, first phalanx, distal articular surface and diaphysis) was contoured to obtain a press fit in the drilled talar recipient site. In 6 dogs, the lesion was not treated and healed by fibrous tissue replacement. Functional assessment (lameness, hock range of motion, joint stability, joint crepitus, and mid-femoral muscle circumference) was completed before surgery and at postoperative weeks 2 through 20. Radiographic assessment (periarticular soft tissue width, joint space width, osteophyte formation, and graft incorporation) was completed before surgery and at postoperative weeks 0, 6, 12, and 20. To facilitate histologic assessment, tissues were stained with toluidine blue and H&E. Histologic assessment of the articular surface on the surgically treated talus, ipsilateral tibia, and contralateral talus was completed, using a modification of the Mankin grading system. Subchondral bone was examined to assess graft viability and incorporation. Analysis of the ordinal data was completed, using a Mann-Whitney rank sum test. All dogs were fully weight bearing by postoperative week 7. Dogs without grafts had significantly (P = 0.036) better clinical function at postoperative week 6. Significant difference in functional assessment was not evident at postoperative week 20. Immediate postoperative radiographic assessment revealed significant (P = 0.005) difference between nongrafted and grafted groups. Significant difference was not observed at postoperative week 6, 12, or 20. All grafts appeared radiographically incorporated by postoperative week 12. All grafts restored joint surface congruity, whereas 3 of 6 nongrafted lesions had poor articular congruity. Of 6 grafts, 4 partially retained normal hyaline cartilage, resulting in significantly (P = 0.014) lower Mankin grades. Significant histologic differences between groups were not apparent when the apposing tibia and control talus were examined. Talar reconstruction by use of a phalangeal osteochondral graft is a viable surgical procedure. These data indicate that normal articular and subchondral architecture are more closely approximated by osteochondral reconstruction than by fibrous tissue repair.

Disseminated aspergillosis in a dog with diskospondylitis and neurologic deficits.

A German shepherd dog was treated initially for signs of urinary tract infection; subsequently, signs of spinal pain and neurologic deficits developed. Fungal hyphae were found in the urine sediment, and spinal radiography revealed changes in the vertebrae and intervertebral disks at the levels of T3 to T8, T12 to T13, L3-4, and L5-6, consistent with diskospondylitis. Fungal cultures of urine and specimens from spinal lesions yielded Aspergillus terreus. Itraconazole (5 mg/kg of body weight, PO, q 24 h) was used to treat this infection, and locomotion improved. Sudden death occurred 4 weeks after treatment was initiated; this was attributed to exsanguination associated with a weakened renal artery. This dog was raised in Florida and resided in central Virginia. The disseminated aspergillosis found in this dog was not limited to the hot arid climates that some reports suggest are optimal conditions for growth.

Prevalence of Parelaphostrongylus tenuis in a sample of hunter-harvested white-tailed deer from a tri-county area in northeastern Wisconsin.

Heads from 78 hunter-harvested white-tailed deer (Odocoileus virginianus) were donated for study during the 1985 Wisconsin gun hunting season. The intra-cranial nervous tissue was examined for Parelaphostrongylus tenuis. Prevalences were calculated for the total sample and for the portion of the sample which had no intra-cranial trauma. The prevalences thus calculated were 58% and 75%, respectively.