Gd-DTPA2)-enhanced MRI of femoral knee cartilage: a dose-response study in healthy volunteers.

The negatively charged contrast agent Gd-DTPA2- distributes inversely to the cartilage fixed charged density. This enables structural cartilage examinations by contrast-enhanced MRI. In line with the development of a clinically applicable protocol for such examinations, this study describes the temporal pattern of Gd-DTPA2- distribution in femoral knee cartilage at three different doses in healthy volunteers. Nineteen volunteers (ages 21-28 years) were examined with a 1.5T MRI system. Quantitative relaxation rate measurements were made in weight-bearing central parts of femoral cartilage using sets of five turbo inversion recovery images with different inversion times. The cartilage was analyzed before and four times (1-4 h) after an intravenous injection of Gd-DTPA2- at single, double, and triple doses: 0.1, 0.2, and 0.3 mmol/kg body weight, respectively. The increase in R1 postcontrast was linearly dose-related at all times. The highest R1 values were registered at 2 and 3 h postcontrast, suggesting 2 h to be optimal in the clinical situation. The triple dose indicated a subtle compartmental difference in men, with higher contrast distribution medially than laterally. Results suggest that the triple dose is needed to detect minor cartilage matrix differences.     

Salvage cryotherapy using an argon based system for locally recurrent prostate cancer after radiation therapy: the Columbia experience

PURPOSE: Cryosurgical ablation of the prostate has been reported as potential treatment for radioresistant clinically localized prostate cancer. We report our experience with the safety and efficacy of salvage cryosurgery using the argon based CRYOCare system (Endocare, Inc, Irvine, California). MATERIALS AND METHODS: Between October 1997 and September 2000, 38 men with a mean age of 71.9 years underwent salvage cryosurgery for recurrent prostate cancer after radiation therapy failed. All patients had biochemical disease recurrence, defined as an increase in prostate specific antigen (PSA) of greater than 0.3 ng./ml. above the post-radiation PSA nadir. Subsequently prostate biopsy was positive for cancer. Pre-cryosurgery bone scan demonstrated no evidence of metastatic disease. In addition, these patients received 3 months of neoadjuvant androgen deprivation therapy before cryotherapy. RESULTS: The PSA nadir was 0.1 or less, 1 or less and greater than 1 ng./ml. in 31 (81.5%), 5 (13.2%) and 2 (5.3%) patients, respectively. Biochemical recurrence-free survival calculated from Kaplan-Meier curves was 86% at 1 year and 74% at 2 years. Reported complications included rectal pain in 39.5% of cases, urinary tract infection in 2.6%, incontinence in 7.9%, hematuria in 7.9% and scrotal edema in 10.5%. The rate of rectourethral fistula, urethral sloughing and urinary retention was 0%. CONCLUSIONS: Our study supports cryosurgery of the prostate as safe and effective treatment in patients in whom radiation therapy fails. Using the CRYOCare machine resulted in a marked decrease in complications.     

Prostatic expression of hensin, a protein implicated in epithelial terminal differentiation

OBJECTIVES: Hensin induces terminal differentiation in rabbit kidney collecting tubule cells. Rabbit hensin and human DMBT1 result from alternative splicing of the same gene. The human DMBT1 gene is located on chromosome 10q25-26, a region often deleted in prostate cancer. In this study we examined the potential role of this gene in terminal differentiation of prostate, as well as its role in prostatic carcinogenesis. METHODS: We searched for deletions of this gene in prostatic cells cultured from cancer and benign tissues using PCR and cDNA cloning. The expression of hensin/DMBT1 in cultured cells and during prostate development was characterized by immunochemistry. RESULTS: No deletions of hensin/DMBT1 similar to those found in glioblastomas, lung and esophageal cancers were observed in prostate cancer or BPH cells. Hensin/DMBT1 protein was localized in intracellular vesicles of epithelial cells in neonatal and 6-week-old mouse prostates. By 6 weeks, hensin/DMBT1 began to localize in the basal lamina of the prostate and vas deferens. In matured 6-month-old prostates, there was extensive deposition of hensin/DMBT1 in the basal lamina. CONCLUSIONS: There is no evidence that hensin/DMBT1 is implicated in prostatic carcinogenesis. The localization of hensin/DMBT1 during maturation raises the possibility that hensin/DMBT1 is involved in terminal differentiation of the prostate and vas deferens.     

Prostaglandin E1 treatment of leg ulcers caused by venous or arterial incompetence

An open and a double-blind study were undertaken on patients with leg ulcers caused mainly by venous (VI) or arterial incompetence (AI). They were treated with intravenous infusions or injections of prostaglandin E1 (PGE1). Eight of 10 patients in the open study experienced relief of pain and a complete or almost complete healing of their ulcers. In the double-blind study (20 patients) 4 out of 5 patients with a history of leg ulcers due to VI for more than 5 year responded to the PGE1 treatment, compared with one of 5 treated with saline. In the saline group 3 more patients with VI of shorter duration improved. In 3 of 5 patients of PGE1 with ulcers due to AI the original ulcer area was reduced by 78--65% after 70 days, while in the 2 remaining cases healing occurred later on. No effect was noted in the 2 patients with ulcers due to AI who received saline infusions. The results indicate the beneficial effect of PGE1 on pain and healing in leg ulcers caused by peripheral vascular disease.     

Guidelines for the management of vitiligo: the European Dermatology Forum consensus

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence‐based and expert‐based recommendations (S1 level).     

Reliability of anthropometric measurements in overweight and lean subjects: consequences for correlations between anthropometric and other variables

OBJECTIVE: To estimate the reliability of anthropometric measurements in overweight and lean subjects, and to examine the influence of this reliability on correlations to other variables, since low reliability leads to underestimation of correlations. DESIGN: Replicate measurements by two observers in 26 overweight and 25 lean subjects measured at two occasions. MEASUREMENTS: Sagittal abdominal diameter (SAD), waist circumference (waist), waist-to-hip ratio (W/H) and skinfold measurements. RESULTS: Intra-class correlation coefficients (ICCs) for SAD and waist were higher than for W/H (0.98 vs. 0.90, P<0.001, and 0.97 vs. 0.90, P = 0.001, respectively). For waist, the ICC was lower for overweight than for lean subjects (0.85 vs 0.95, P=0.030), but the ICC values were comparable for SAD and W/H (0.92 vs. 0.95 and 0.78 vs. 0.83, respectively). Intra-observer variations (IOV) for SAD and waist were lower than for W/H (coefficients of variation; 1.6%, 1.4% and 2.3%, respectively), as were intra-subject variations (ISV) (2.7%, 3.0% and 3.4%, respectively). ICC values ranged from 0.84 to 0.93 and were lower for overweight than for lean subjects for biceps, subscapular and umbilical skinfolds (P=0.031, P<0.001 and P=0.048, respectively). Coefficients of variations for skinfold measurements ranged between 7.3% and 16.0% for IOV and between 14.9% and 20.8% for ISV. CONCLUSIONS: The low ICC values imply that correlations can be underestimated in overweight groups. We propose that, because of their higher reliability, SAD and waist have a higher predictive capacity for cardiovascular risk than W/H. SAD is the only measurement with high reliability in both weight groups and its use is recommended.     

Low and high circulating cortisol levels predict mortality and cognitive dysfunction early after stroke

OBJECTIVE: Elevated cortisol levels are associated with confusion and poor outcome after stroke. Dehydroepiandrosterone sulphate (DS), the most abundant adrenal androgen may act as an anti-glucocorticoid. An altered regulation of these steroids may affect numerous brain functions, including neuronal survival. The purpose of this study was to investigate serum cortisol and DS levels and the cortisol/DS ratio early after stroke and relate our findings to the presence of disorientation and mortality. DESIGN: Patients with acute ischaemic stroke (n = 88, 56 men and 32 women) admitted to a stroke unit were investigated with repeated clinical assessments and scores for degree of confusion, extent of paresis and level of functioning. Serum cortisol (C) and DS were measured on day 1 and/or day 4. Data for 28-day and 1-year mortality are presented. A control group of 65 age-matched healthy individuals was used. Multivariate analyses of mortality rates in the different tertiles or sixtiles of serum cortisol were performed with logistic regression, adjusting for age, sex, diabetes and level of consciousness. RESULTS: There was no difference in serum cortisol levels on day 1 for stroke patients when compared with control group values. Initial cortisol levels were significantly higher in the patients with acute disorientation versus orientated patients (P < 0.05). Cortisol levels on day 1 were an independent predictor of 28-day mortality, and patients with low cortisol levels (<270 nmol L(-1)) and increased levels (>550 nmol L(-1)) both had an increased 1-year mortality. DS levels on day 1 were significantly elevated in stroke patients. CONCLUSION: Hypercortisolism is associated with cognitive dysfunction early after ischaemic stroke. High and low circulating cortisol levels are associated with increased mortality after stroke. DS levels were not associated with clinical outcome.