Comparative analysis of risk factors for pathological fracture with femoral metastases

A number of risk factors based upon mostly retrospective surgical data, have been formulated in order to identify impending pathological fractures of the femur from low-risk metastases. We have followed up patients taking part in a randomised trial of radiotherapy, prospectively, in order to determine if these factors were effective in predicting fractures. In 102 patients with 110 femoral lesions, 14 fractures occurred during follow-up. The risk factors studied were increasing pain, the size of the lesion, radiographic appearance, localisation, transverse/axial/circumferential involvement of the cortex and the scoring system of Mirels. Only axial cortical involvement >30 mm (p = 0.01), and circumferential cortical involvement >50% (p = 0.03) were predictive of fracture. Mirels' scoring system was insufficiently specific to predict a fracture (p = 0.36). Our results indicate that most conventional risk factors overestimate the actual occurrence of pathological fractures of the femur. The risk factor of axial cortical involvement provides a simple, objective tool in order to decide which treatment is appropriate.     

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

OBJECTIVE: To determine the absorption, excretion and metabolism of kaempferol in humans. DESIGN: A pharmacokinetic study of kaempferol from endive over 24 h. SUBJECTS: Four healthy males and four healthy females. RESULTS: Kaempferol, from a relatively low dose (9 mg), was absorbed from endive with a mean maximum plasma concentration of 0.1 microM, at a time of 5.8 h, indicating absorption from the distal section of the small intestine and/or the colon. Although a 7.5-fold interindividual variation between the highest and lowest maximum plasma concentration was observed, most individuals showed remarkably consistent pharmacokinetic profiles. This contrasts with profiles for other flavonoids that are absorbed predominantly from the large intestine (eg rutin). An average of 1.9% of the kaempferol dose was excreted in 24 h. Most subjects also showed an early absorption peak, probably corresponding to kaempferol-3-glucoside, present at a level of 14% in the endive. Kaempferol-3-glucuronide was the major compound detected in plasma and urine. Quercetin was not detected in plasma or urine indicating a lack of phase I hydroxylation of kaempferol. CONCLUSIONS: Kaempferol is absorbed more efficiently than quercetin in humans even at low oral doses. The predominant form in plasma is a 3-glucuronide conjugate, and interindividual variation in absorption and excretion is low, suggesting that urinary kaempferol could be used as a biomarker for exposure.     

Evaluation of reliability for urine mucopolysaccharidosis screening by dimethylmethylene blue and Berry spot tests

BACKGROUND: The mucopolysaccharidosis (MPS) are a group of inherited metabolic disorders resulting from the deficiency of the enzyme responsible for intralysosomal catabolism of glycosaminoglycans (GAGs). GAGs are progressively accumulated in multiple tissues and released into the corporal fluids. The first laboratory approximation to MPS diagnosis is the identification of an increased urinary GAG excretion. For this, several semiquantitative and quantitative methods have been developed. The aim of this retrospective statistical study was to evaluate the reliability of MPS urine screening for the semiquantitative Berry spot test (BST) and the quantitative dimethylmethylene blue test (DMB). METHODS: The 24-h-urine samples (n = 246) were tested through BST, DMB, and for GAG excretion pattern by one-dimensional electrophoresis or thin layer chromatography. RESULTS: the 204 samples that demonstrated a normal GAG excretion pattern were considered as non-MPS samples. Forty-two samples presented an abnormal GAG excretion pattern. Enzyme analysis was available for 31 out of 42 patients (31/42), confirming that all were affected by MPS. Urinary GAG concentrations of MPS patients by DMB were increased 1.04- to 7.1-folds, compared to age-related normal levels. The sensitivity was 100% for DMB and 93.6% for BST. DMB demonstrated a specificity of 74.5%, while BST a specificity of 53.9%. The specificity of MPS screening increased to 84.3%, considering conjunctly DMB and BST. CONCLUSION: The DMB is a sensitive method, however, inclusion of BST could increase the specificity of MPS urine screening.     

Repair of UV dimers in skin DNA of patients with basal cell carcinoma

Epidemiologic studies suggest that exposure to sunlight is the primary etiologic agent for basal cell carcinoma. Formation of UV-induced DNA damage is believed to be a crucial event in the process leading to skin cancer. In this study, repair of photoproducts in DNA was followed in the skin of patients with basal cell carcinoma and control subjects. The subjects were exposed to 800 J/m(2) Commission Internationale de 1'Eclairag of solar-simulating radiation on buttock skin. Biopsies were taken at 0 hour, 24 hours, and 3 weeks after the exposure. Two cyclobutane pyrimidine dimers, TT=C and TT=T, were measured using a sensitive (32)P-postlabeling assay. Initial levels of both TT=C and TT=T differed between individuals in both groups. The levels of TT=T in patients with basal cell carcinoma and controls were similar (9.9 +/- 4.0 and 9.2 +/- 2.9 products per 10(6) normal nucleotides), whereas the level of TT=C was significantly lower in controls than in patients with basal cell carcinoma (6.2 +/- 3.1 versus 10.9 +/- 4.5 products per 10(6) normal nucleotides). The fractions of TT=T remaining after 24 hours and 3 weeks were significantly higher in patients with basal cell carcinoma (72% and 11%) compared with controls (48% and 5%). A slower removal in patients with basal cell carcinoma than in controls was indicated also for TT=C (52% versus 42% remaining at 24 hours); however, the difference between groups was not significant. When including data from our previously reported small-scale study, the fraction of dimers remaining at 24 hours was significantly higher in patients with basal cell carcinoma for both TT=C and TT=T. The data suggest that patients with basal cell carcinoma have a reduced capacity to repair UV-induced DNA lesions.     

Home blood pressure measurement: a systematic review

The purpose of this research was to review the literature on home blood pressure measurement (HBPM) and to provide recommendations regarding HBPM assessment. Observational studies on HBPM, published after 1992, as identified by PubMed, EMBASE, and Cochrane literature searches were reviewed. Studies were selected if they met the following criteria: 1) self-measurements had been performed with validated devices; 2) measurement procedures were described in sufficient detail; and 3) papers clearly explained how final HBPM results were calculated upon which conclusions and/or treatment decisions were based. Office blood pressure measurement (OBPM) yields higher blood pressure values than HBPM. For systolic blood pressure, differences between OBPM and HBPM increase with age and the height of office pressure. Differences also tend to be greater in men than in women and greater in patients without than in those with antihypertensive treatment. Furthermore, HBPM can diagnose normotension with almost absolute certainty; it correlates better with target organ damage and cardiovascular mortality than OBPM, it enables prediction of sustained hypertension in patients with borderline hypertension, and it proves to be an appropriate tool for assessing drug efficacy. Despite some limitations and although more data are needed, HBPM is suitable for routine clinical practice.     

Comparison of randomization techniques for clinical trials with data from the HOMERUS-trial

Background. Several methods of randomization are available to create comparable intervention groups in a study. In the HOMERUS-trial, we compared the minimization procedure with a stratified and a non-stratified method of randomization in order to test which one is most appropriate for use in clinical hypertension trials. A second objective of this article was to describe the baseline characteristics of the HOMERUS-trial. Methods. The HOMERUS population consisted of 459 mild-to-moderate hypertensive subjects (54% males) with a mean age of 55 years. These patients were prospectively randomized with the minimization method to either the office pressure (OP) group, where antihypertensive treatment was based on office blood pressure (BP) values, or to the self-pressure (SP) group, where treatment was based on self-measured BP values. Minimization was compared with two other randomization methods, which were performed post-hoc: (i) non-stratified randomization with four permuted blocks, and (ii) stratified randomization with four permuted blocks and 16 strata. In addition, several factors that could influence outcome were investigated for their effect on BP by 24-h ambulatory blood pressure monitoring (ABPM). Results. Minimization and stratified randomization did not lead to significant differences in 24-h ABPM values between the two treatment groups. Non-stratified randomization resulted in a significant difference in 24-h diastolic ABPM between the groups. Factors that caused significant differences in 24-h ABPM values were: region, centre of patient recruitment, age, gender, microalbuminuria, left ventricular hypertrophy and obesity. Conclusion. Minimization and stratified randomization are appropriate methods for use in clinical trials. Many outcome factors should be taken into account for their potential influence on BP levels. Recommendation. Due to the large number of potential outcome factors that can influence BP levels, minimization should be the preferred method for use in clinical hypertension trials, as it has the potential to randomize more outcome factors than stratified randomization.     

Dynamic sentinel node biopsy in penile carcinoma: evaluation of 10 years experience

PURPOSE: The aim of this study was to evaluate the results of 10 years dynamic sentinel node biopsy experience in penile carcinoma at our institute. PATIENTS AND METHODS: 140 patients with clinically node-negative groins were prospectively included. Lymphoscintigraphy was performed after injection of 99mTechnetium-nanocolloid around the primary tumour. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma ray detection probe. Lymph node dissection was performed only if sentinel node metastasis was found. Median follow-up was 52 months (range 5-129). RESULTS: Lymphoscintigraphy visualized at least 1 sentinel node in 138 patients. Sentinel node metastasis was found in 37 inguinal regions of 31 patients. The sentinel node was the only tumour-positive node in 78% (29/37) of the dissection specimens. Complications occurred in 8% (17/206) of the operated groins. False-negative results were encountered in 6 patients resulting in a false-negative rate of 16% (6/37 patients). 5-year disease-specific survival was 96% and 66% for patients with a tumour-negative sentinel node and tumour-positive sentinel node, respectively (p=0.001). CONCLUSION: Dynamic sentinel node biopsy in penile carcinoma is of important diagnostic, prognostic, and therapeutic value at the cost of only minor morbidity.     

Person-related predictors of employment outcomes after participation in psychiatric vocational rehabilitation programmes

Background   

There is increasing recognition of the importance of psychiatric vocational rehabilitation (PVR) programmes in helping individuals with severe mental illnesses to find and secure jobs. However, little is known concerning the factors related to PVR outcomes.