Alternative pathway complement activation induces proinflammatory activity in human proximal tubular epithelial cells

Background. Proximal tubular epithelial cells express a surface C3-convertase activity which induces C fixation and insertion of the C5b-9 membrane attack complex (MAC) into the cell plasma membrane. The physiopathological consequences of this phenomenon are unknown. Methods. The effect of C fixation on the production of inflammatory mediators by human proximal tubular epithelial cells in culture was explored. Results. Proximal tubular epithelial cells incubated with a sublytic amount of normal human serum as a source of C, but not with heat-inactivated human serum, showed a time-dependent calcium influx and a concomitant release of ¹⁴C-arachidonic acid (¹⁴C-AA). Eicosanoid synthesis following the arachidonic acid mobilization was studied as prostaglandin E2 release. Mg²⁺/EGTA, which did not prevent C activation by the C3-convertase, and p-bromodiphenacyl bromide, a phospholipase A2-inhibitor, inhibited mobilization of ¹⁴C-AA. These results suggest the activation of an extracellular Ca²⁺-dependent, phospholipase A2. Complement fixation was associated with the synthesis of proinflammaotry cytokines such as IL-6 and TNF-&agr;. Experiments with C6-deficient sera indicated that the release of ¹⁴C-AA and the production of cytokines were dependent on the insertion of the terminal components of complement in the plasma membrane. Indeed, the reconstitution of normal haemolytic activity of C6-deficient sera with purified C6 restored also the release of ¹⁴C-AA and the production of cytokines. Conclusion. In vitro complement activation on the proximal tubular cell surface triggers the generation of proinflammatory mediators, which may potentially contribute to the pathogenesis of tubulointerstitial injury.     

A critical appraisal of daclizumab use as emerging therapy in multiple sclerosis

Introduction: Daclizumab (DAC) is a mAb that binds to CD25, a receptor on the surface of lymphocytes for IL-2, a chemical messenger in the immune system. This prevents activation and proliferation of lymphocytes, which are involved in the immune attack in multiple sclerosis (MS).

Areas covered: In this review, we will focus on newly emerging DAC-high-yield process (HYP) therapy for MS. Based on published original articles and citable meeting abstracts, we will discuss its mode of action as well as data on efficacy and safety.

Expert opinion: DAC has been observed to have multiple (biological) effects, which may contribute to beneficial effects in immune-related disease and particularly in relapsing-remitting MS. The positive results in the clinical studies represent achievement of an important milestone in the development of DAC-HYP as a potential new treatment option for MS patients. The benefit/risk ratios of this new biological agent in MS therapy are still being evaluated. Soon, DAC-HYP might qualify as MS therapy. A safety monitoring program is recommended in the clinical practice.     

Urinary incontinence in the elderly: relation to cognitive and motor function

Urinary incontinence is a common problem in older subjects, very often wrongfully accepted as a normal part of the aging process. A total of 520 subjects (208 males and 312 females; mean age 74.8 +/- 11.8 years), from both private- and nursing-home dwelling populations, were included in this study aimed to estimate the incidence of urinary incontinence and identify factors associated with condition, in aged subjects. The incidence and type of urinary incontinence (stress, urge or mixed incontinence) were assessed by structured questionnaires and diagnosis was confirmed by a seven-day consecutive voiding diary. Assessment of physical, cognitive and emotional functions was performed on each subject using the Mini Mental State Examination (MMSE), Instrumental Activities of Daily Living Scale (IADL), Tinetti Scale (gait), Tinetti Scale (balance) and Geriatric Depression Scale (GDS) instruments. In the total population sample the incidence of urinary incontinence was 47.9%. The incontinence cases were classified, according to the different types, as: stress incontinence (males: 3.4%; females: 8.7%; males+females: 6.5%); urge incontinence (males: 27.4%; females: 31.4%; males+females: 29.8%); mixed incontinence (males: 20.2%; females: 5.8%; males+females: 11.5%). In the total population sample, no significant relationship was found between age and prevalence of urinary incontinence. In the elderly female group, age significantly correlated in a direct manner with urge incontinence (P<0.01) and inversely with stress incontinence (P<0.001). Only in the male sex group age significantly correlated with mixed incontinence (P<0.005). Multiple linear regression analysis showed that the dependent variable 'incontinence' could be predicted by MMSE (P<0.001) in the male sex group and by the Tinetti Scale (gait) (P<0.001) in the female sex group.     

Reverse rim sign on CEUS

Abdominal Radiology -     

Urinary calcium excretion in a population of children living in Southern Italy]

BACKGROUND: Very few studies have evaluated the role of urinary calcium excretion as marker of bone metabolism in children. Normative data are lacking in these age groups. METHODS: In a group of 122 children (66 females e 56 males), mean age 108.13 +/- 18.73 months, attending a primary school in Nocera Superiore (Southern Italy) the following parameters were evaluated: sex, age, weight, height, BMI (weight/height2), urinary calcium excretion which was measured as the urinary calcium/creatinine concentration ratio (Uca/cr) in extemporaneous sample of the second urine in the morning. The Uca/cr ratio was not normally distributed in this childhood population. Natural logarithmic transformation was used to analyze the data. RESULTS: The mean value of Uca/cr was 0.125 +/- 0.102 mg/mg. A significant correlation was found between the Uca/cr ratio and sex. The Uca/cr ratio values were higher in girls than in boys. Mean Uca/cr was 0.144 +/- 0.113 mg/mg in females while it was 0.102 +/- 0.083 mg/mg in males ("t"-test: p < 0.05). No correlation was found between the Uca/cr ratio and other variables such as age, height, weight and BMI either in the simple or in the multiple linear regression analysis correcting both for the sex and the age. Data by age-group and sex were reported as percentile tables. CONCLUSIONS: The discussed variations of the Uca/cr in children from different areas and sex confirm the need for reference standards calculated in the different population groups.     

Prevention of venous thromboembolism in spinal surgery

Deep vein thrombosis (DVT), and its most feared complication, pulmonary embolism (PE), still have a high incidence with high risk for patients health. Proven prophylactic measures are available but are generally underused, and DVT is still considered the most common cause of preventable death among hospitalized patients. The rationale for prophylaxis of venous thromboembolism is based on the clinically silent nature of the disease, the relatively high prevalence among hospitalized patients and the potentially tragic consequences of a missed diagnosis. During the last 15–20 years, spine surgery has changed radically, developing into a well-defined area of specialist surgery, and some attention is now being given to DVT events in spine surgery. The incidence of DVT during spine surgery is not documented in the literature, because only case reports or retrospective studies are reported. It would therefore be very helpful to initiate a multicenter study in order to understand this problem better and to develop, if possible, some guidelines on prophylactic measures in spine surgery. In doing so, we need to consider each patients pattern, any risk factors and every kind of surgical technique related to DVT, in order to improve the outcome of the patient and to reduce any medicolegal problems that could arise from a thrombotic complication or an epidural hematoma, with its high potential for irreversible consequences.     

A new molecular and cytogenetic approach to sterility. A review of the literature

In the therapeutic procedure of conjugal fertility, the use of intracytoplasmic sperm injection (ICSI) has opened new possibilities when conventional in vitro fertilization (IVF) techniques are unsuccessful. Cytogenetic studies showed the presence of genetic anomalies in foetuses conceived with this technique. Starting from these considerations, through a data collection of the literature, the authors report the latest scientific findings on this problem. They show the limits of the knowledge about genetic risks linked to these techniques, increasingly imposing rigorous medical behavior and conscious choices of the couple.     

QT interval dispersion in young women with anorexia nervosa

OBJECTIVES: To evaluate the degree of QT dispersion in a group of young women in the starvation phase of anorexia nervosa (AN) and its relation to left ventricular (LV) mass. STUDY DESIGN: Sixteen patients with self-induced starvation were matched with 16 women of normal weight and 16 constitutionally thin women (body mass index <20 kg/m2). Starving patients and control patients underwent an electrocardiogram and echocardiogram. QT intervals were measured from surface electrocardiograms and QT dispersion was defined as the difference between maximum QT and minimum QT occurring in any of the 12 leads. RESULTS: LV-chamber mass was significantly less in women with AN than in thin and normal-weight women. QT dispersion was significantly greater in AN than in the thin and control groups (QT dispersion: 50 +/- 14 vs 34 +/- 9 and 37 +/- 11 ms, P <.001; QT interval dispersion corrected for heart rate: 49+12 vs 34 +/- 9 and 36 +/- 7 ms, P <.01, respectively). A significant relation between QT dispersion and LV-mass index (r = -0.726, P <.01), and between QTc dispersion and LV mass index (r = -0.693, P < 0.01) were found only in the patients with AN. CONCLUSION: Starving patients show an increased QT dispersion related to reduced LV mass. This result could represent a useful indicator of arrhythmic risk and sudden death in AN.