Health promotion in Local Health Unit 4 Chiavarese--Liguria Region, Italy. "Unplugged" project: needs, methodology and implementation.

AIM: The aim of this paper was to use and evaluate the unplugged project, a school-based program of proven effectiveness aimed at the prevention of substance abuse based on social influence. METHODS: This project was conducted during the school-year 2011/2012; it involved the Local Health Unit (LHU)'s personnel specifically and adequately formed and was addressed to teachers working in the three districts of the LHU4 Chiavarese. The courses involved teachers in three consecutive days and provided both theoretical inputs and practical exercises designed to enpower skills and to make the same effective. As a whole, 25 teachers of the secondary schools (public and private) of first and second level were trained. Following the training, 14 curricular courses have been launched and 286 students have been involved. RESULTS: The teachers have mainly worked on personal and social components of their students, stimulating their critical assessment of standards and skills potentially transferable in everyday life. The benefits for students have been: establishment of the classroom, positive relationship with the teacher, empathy, decrease of conflicts, increased self-awareness and self-esteem, better school results. Besides, teachers benefit from increased respect, self-reliance and confidence, as well as acquisition of new skills. CONCLUSION: Both the interest shown by teachers and the results achieved in classrooms have stimulated school leadership and personnel belonging to LHU4 Chiavarese to plan a new edition of the program the next autumn.

Cataract surgery in the United Kingdom: a postal survey.

PURPOSE: A postal questionnaire study to evaluate the current practice of cataract surgery delivery in the United Kingdom including strategies for postoperative review was performed. METHODS: A cataract questionnaire was sent to all hospital departments delivering ophthalmic services in the United Kingdom based on a list from the Royal College of Ophthalmologists. It included questions about the staffing level, number of cases operated on per list, and the different strategies employed postoperatively. The results were statistically analyzed. RESULTS: A total of 248 questionnaires were sent and 106 (43%) replies were received. The mean number of consultant teams was 11 (2-20). The average number of cases per list was 6-7 (range 4-9). In 65 hospitals, all patients are reviewed postoperatively in the hospital and some consultant teams review patients postoperatively in 18 hospitals. In 15 hospitals, patients were seen by the community optician. Most hospitals review their patients postoperatively within the first 3 weeks with more hospitals seeing them at 2-3 weeks. A wide variety of health professionals review the postoperative cases and they include doctors, nurses, and opticians (in house and community). CONCLUSIONS: There are varied practices for cataract surgery in the United Kingdom including the number of cases on the list and postoperative review protocols. There is room for better service organization in some hospitals in terms of patient flow and better use of medical staff time to improve output.

Cytokines in breast cancer.

In recent decades many advances have occurred in the understanding of the role of cytokines in breast cancer. New signalling pathways of interleukin (IL)-1 family, IL-6, IL-11, IL-18, interferons (IFNs) and interferon regulatory factors 1 (IRF-1) and 2 (IRF-2) have been found within tumour microenvironments and in metastatic sites. Some cytokines (IL-1, IL-6, IL-11, TGFbeta) stimulate while others (IL-12, IL-18, IFNs) inhibit breast cancer proliferation and/or invasion. Similarly, high circulating levels of some cytokines seem to be favourable (soluble IL-2R) while others are unfavourable (IL-1beta, IL-6, IL-8, IL-10, IL-18, gp130) prognostic indicators. So far IL-2, IFNalpha, IFNbeta and occasionally IFNgamma, IL-6, IL-12 have been the cytokines used for anti tumour treatment of advanced breast cancer either to induce or increase hormone sensitivity and/or to stimulate cellular immunity. Disappointing results occurred in most trials; however, two long-term pilot studies suggest that IL-2 and IFNbeta, when used appropriately can have a positive effect on clinical benefit and overall survival of patients with minimal residual disease after chemotherapy or with disseminated disease controlled by conventional endocrine therapy.

Skin blood flowmotion and microvascular reactivity investigation in hypercholesterolemic patients without clinically manifest arterial diseases.

Fourier spectral analysis of forearm skin laser Doppler flowmetry (LDF) signal was performed in fifteen hypercholesterolemic patients (HP), without clinically manifest arterial diseases, and in fifteen age-matched healthy control subjects (CS), in order to investigate skin blood flowmotion (SBF). The LDF frequency intervals studied were: 0.01-1.6 Hz total spectrum, as well as 0.01-0.02 Hz (endothelial), 0.02-0.06 Hz (sympathetic), 0.06-0.2 Hz (myogenic), 0.2-0.6 Hz (respiratory) and 0.6-1.6 Hz (cardiac). Skin microvascular reactivity (MVR) to acetylcholine (ACh) and to sodium nitroprusside (SNP) iontophoresis was also investigated. HP showed a lower post-ACh increase in power spectral density (PSD) of the 0.01-0.02 Hz SBF subinterval compared to CS (1.80+/-1.73 PU(2)/Hz vs 3.59+/-1.78 PU(2)/Hz, respectively; p<0.005), while they did not differ in MVR from CS. In eleven HP the 0.01-0.02 Hz SBF subinterval showed a higher post-ACh PSD increase near to the statistical significance after 10 weeks of rosuvastatin therapy (10 mg/day) compared to pretreatment test (3.04+/-2.95 PU(2)/Hz vs 1.91+/-1.94 PU(2)/Hz; p=0.07). The blunted post-ACh increase in PSD of the 0.01-0.02 Hz SBF subinterval in HP suggests a skin endothelial dysfunction in these patients. This SBF abnormality showed a tendency to improve after rosuvastatin therapy in eleven treated patients.

Study of skin vasomotion during phollicular and luteal phase in young healthy women.

The aim of this study was to evaluate if changes in female sex hormones associated to follicular phase (FP) and luteal phase (LP) may affect skin vasomotion in women with evidence of ovulatory cycle. Nine healthy non-smoker women aged 25+/-4 years, with regular menstrual cycle of 28+/-2 days and evidence of ovulation (indicated by a mid-luteal serum progesterone concentration > 5 ng/ml) (group-1) and six healthy non-smoker healthy women aged 24+/-2 years with evidence of an-ovulatory cycle (group-2) were enrolled in the study. At the times 1 (7th-10th day from the beginning of the last menstrual cycle) and at the time 2 (18th-22th day from the beginning of the last menstrual cycle) forearm skin vasomotion was investigated by means of spectral Fourier analysis of the skin laser Doppler flowmetry (LDF) tracing registered under basal conditions and following acetylcholine (ACh) iontophoresis. The power spectral density (PSD) of the 0.01-0.02, 0.02-0.06 and 0.06-0.2 Hz LDF tracing frequency intervals (related to endothelial-, sympathetic- and myogenic-dependent vasomotion, respectively) was measured in PU2 (LDF perfusion unit)/Hz (1 PU = 10 mV). At the same times skin blood flux response (percentage change from baseline) to ACh and to sodium nitroprusside (SNP) iontophoresis was also investigated. Basal and ACh-stimulated skin vasomotion did not significantly differ between time 1 and time 2 in PSD of the three frequency intervals investigated in both groups, as well as between the two groups at each time of investigation. Similarly, no significant changes were observed in skin vasodilator response to ACh and SNP iontophoresis between time 1 and 2 in each group. These results suggest that the female sex hormone changes associated to the FP and LP in young women with ovulatory cycle do not affect basal and ACh stimulated skin vasomotion as well as the endothelial- and non-endothelial-dependent skin vasoreactivity.

Immunotherapy prolongs the serum CEA-TPA-CA15.3 lead time at the metastatic progression in endocrine-dependent breast cancer patients: a retrospective longitudinal study.

In metastatic breast cancer tumour markers' increase predicts, by a few months (lead time) disease progression. In breast cancer patients with endocrine dependent metastatic disease, we reported a prolonged clinical benefit and overall survival when first line conventional antiestrogen hormone therapy was started at the lead time and also when an immunotherapy schedule was added to the same conventional hormone treatment. Thirty-two of these last patients were considered (group a). In 27 (group b) of these 32 patients who progressed during first line salvage hormone plus immunotherapy the lead time at the progression of metastatic disease during therapy was compared with that at the onset of metastases when the same patients were without treatment and with that of a control group (group c) who did not receive immunotherapy. At disease progression, CEA-TPA-CA15.3 sensitivity was 92.5% in the group b (studied patients) and 88.5% in the group c (controls). At the progression in the group b, CEA-TPA-CA15.3 lead time (m+/-sd, months) was significantly longer than in group c (12.1+/-12.9 vs 2.4+/-4.0) (P=0.000). Besides, in group b the lead time was significantly longer at the progression than at the metastatic onset (P=0.003) while in the group c the difference was near to significance (P=0.05). The CEA-TPA-CA15.3 tumour marker panel accurately predicted metastatic disease progression and immunotherapy significantly prolonged the CEA-TPA-CA15.3 lead time. This can be used for anticipating salvage treatment in these patients.

Thyroid fine needle aspiration: how to improve clinicians' confidence and performance with the technique.

Studies from single institutions report an acceptable accuracy rate for thyroid fine needle aspiration (FNA). However, FNA accuracy is much lower in many other centers in Europe and the USA and large multicenter studies indicate that the clinicians' confidence in the FNA technique remains low. One explanation for this is that there is an excess of inadequate and indeterminate findings for a follicular nodule at FNA cytology. In a University Hospital with large and qualified experience on thyroid nodule diagnosis, a review of 320 slides with an FNA diagnosis of indeterminate follicular nodule from different minor Italian Hospitals led to a different diagnosis in 61%. Since ancillary thyroid imaging may be overutilized and only a few authors report a proportion of excised nodules lower than 10%, we suspect that use of the FNA procedure is suboptimal. Several techniques are reported to improve the performance of thyroid FNA. Among these are tumor markers and large needle aspiration biopsy (LNAB). Immunodetection of the tumor marker galectin-3 has been evaluated by large multinational studies. Analysis of LNAB specimens reduces the number of inadequate FNA findings, improves the diagnostic determination of indeterminate follicular FNA findings and represents a better substrate for the determination of galectin-3. Therefore, we propose that clinical practice guidelines reflect these adjuvant techniques to thyroid FNA in order to improve selection criteria for thyroid nodule surgery.

Skin vasomotion investigation: a useful tool for clinical evaluation of microvascular endothelial function?

Skin vasomotion is the rhythmic variation of skin microvessel diameter responsible for skin microcirculatory blood flow oscillation, the so called skin blood flowmotion. It can be easily investigated by means of the spectral analysis of skin laser Doppler flowmetry (LDF) signal. Experimental and clinical findings suggest that vasomotion is partially dependent on microvascular endothelial activity. Based on this, investigation of skin vasomotion, using spectral analysis of skin LDF signal has been recently proposed for the investigation of microvascular endothelial function in clinical setting. Clinical studies have demonstrated that the LDF technique coupled with spectral analysis of skin LDF tracing is a useful and accurate method for the measurement of skin microvascular endothelial-dependent vasomotion in patients with different pathological conditions. In these studies skin vasomotion investigation showed a higher sensitivity in the evaluation of skin microvascular endothelial function than tests based on the simple LDF measurement of skin blood flow response to different stimuli. Further studies are needed to evaluate whether the investigation of skin endothelial-dependent vasomotion can predict clinical and therapeutic outcomes of patients with vascular diseases.

Insulin resistance and low urinary citrate excretion in calcium stone formers.

Epidemiological data suggest an association between kidney stones and some features of metabolic syndrome such as an overweight condition, arterial hypertension or glucose intolerance. However, mechanisms remain to be elucidated. This study aimed to evaluate insulin resistance, as assessed by homeostasis model assessment (HOMA-IR), and urine composition analysis in patients affected by calcium nephrolithiasis. A cohort of 61 (38 male, 29-57 years of age) non-diabetic calcium stone formers was studied. Data about body mass index, arterial blood pressure, serum biochemistry including parathyroid hormone and calcitriol were recorded in all the patients; fasting glucose and insulin were determined to calculate HOMA-IR value and accordingly the patients were grouped into tertiles. Urine pH and urinary excretion of calcium, citrate, phosphate, oxalate, uric acid, urea and creatinine were measured on 24h urine samples. Patients of the highest HOMA-IR tertile showed lower urine citrate levels than patients of the lowest HOMA-IR tertile (475+/-243 vs. 630+/-187 mg/24h, p<0.05), whereas no difference was detected as far as urinary oxalate, calcium, uric acid, phosphate, and urine pH and urine volume output were concerned. HOMA-IR values were positively related to uric acid serum levels (r=0.31, p<0.05) and negatively to urinary citrate excretion (r=-0.26, p<0.05). Hypocitraturic patients showed higher levels of HOMA-IR than normocitraturic ones (3.03+/-0.92 vs. 2.25+/-1.19, p<0.05). This study shows that a higher level of insulin resistance is associated with lower urinary citrate excretion, and that hypocitraturic patients show a greater insulin resistance than normocitraturic calcium stone formers. This may be related to changes in citrate, Na(+)-K(+) and H(+) renal tubule transports, which have been described in insulin resistance. In conclusion, insulin resistance may contribute to an increased risk of calcium stone formation by lowering urinary citrate excretion. This finding suggests the need for a careful metabolic assessment in patients known to form calcium stones in order to ensure stone recurrence prevention and cardiovascular protection.

Absent post-ischemic increase of blood flowmotion in the cutaneous microcirculation of healthy chronic cigarette smokers.

The aim of the study was to investigate whether chronic cigarette smoke habit is associated with changes of laser Doppler (LD) skin blood flowmotion (SBF). We performed spectral analysis of skin forearm LD signal detected by a LD flowmetry (Periflux PF4, Perimed, Sweden) before and during forearm post-ischemic hyperaemia, in 14 healthy chronic smoker subjects and 14 age and sex matched nonsmoker subjects. Forearm skin ischemia was obtained by a pneumatic cuff, positioned at the right arm and inflated for 3 minutes to 30 mmHg above systolic blood pressure. Power spectral density (PSD) of the SBF total spectrum (0.009-1.6 Hz), as well as 0.009-0.02 Hz , 0.02-0.06 Hz, 0.06-0.2 Hz, 0.2-0.6 Hz and 0.6-1.6 Hz frequency intervals (FI), referred to endothelial, sympathetic, myogenic, respiratory and heart activity, respectively, were measured in LD conventional perfusion units (PU)/Hz. Smokers showed a basal SBF total spectrum PSD mean values not significantly different from nonsmokers (2.14+/-1.58 PU/Hz and 1.93+/-1.35 PU/Hz, respectively). Following ischemia, PSD mean value of SBF total spectrum, as well of five FI considered, significantly increased in nonsmokers (p<0.01), while it did not significantly change in smokers. Smokers and nonsmokers did not differ in basal and post-ischemic skin LD perfusion mean values. The absent post-ischemic increase of the SBF and of its FI related to endothelial and myogenic activity in smokers can be an early sign of skin microcirculatory impairment, suggesting an endothelial and smooth muscle skin microvascular dysfunction associated with the chronic smoking habit.

Progress in the preoperative diagnosis of thyroid nodules: managing uncertainties and the ultimate role for molecular investigation.

The preoperative evaluation of thyroid nodules currently relies on a clinical assessment of risk factors and an algorithm based on imprecise tests. With serum TSH, thyroid ultrasound and fine-needle aspiration (FNA) with or without ultrasound guide, accounting for the routine initial evaluation, indeterminate aspirates remain the major obstacle for confidently advising patients whether to have surgery or not. Recent clinical guidelines have attempted to settle various controversies but many inherent errors of clinical testing result in delayed diagnosis and unnecessary surgery. A better solution may ultimately involve the use of molecular markers of thyroid carcinogenesis but further research is still needed regarding the basic biology of thyroid cancer.

Serum thyroglobulin measurement: clinical background and main methodological aspects with clinical impact.

It is worldwide recognized that circulating thyroglobulin (Tg) measurement represents a fundamental tool in the follow-up of patients affected by differentiated thyroid cancer (DTC). In the last American and European Consensus Conferences, a surveillance guideline has been extended to the use of thyrotropin (TSH)-stimulated Tg levels for thyroidectomized patients without clinical evidence of residual tumor with Tg below 1 microg/l during TSH suppression. Therefore, sensitivity of the methods is critical to detect small amounts of Tg and/or to observe minimal changes in Tg concentration in the management of DTC patients. It has been proposed that only methods providing the greatest distinction between the lower limit of euthyroid reference range (approximately 3.0 microg/l) and the functional sensitivity limit (at least 1 microg/l) of the assay may offer a suitable clinical sensitivity for detecting small amounts of functioning thyroid tissue in TSH-suppressed state (1 g of normal thyroid tissue results in a serum Tg of approximately 1 microg/l when TSH is normal and about 0.5 microg/l when TSH is suppressed). In the last 30 years sensitivity of Tg measurements has been greatly improved, nowadays methods can achieve very good analytical and functional sensitivity to give reliable results also in the very low concentration range (between 0.1 and 1 microg/l). In addition, with the introduction of fully automated assays, results can be readily available to the clinician while patients are still in the ambulatory area. However, despite the large clinical use of Tg measurement, wide differences (by threefold) still remain between results produced in different laboratories due to poor standardization, heterogeneity of circulating Tg, interference from auto-antibodies, differences in the epitope recognition by antibodies used in the assays.

Electrochemotherapy a novel approach to the treatment of metastatic nodules on the skin and subcutaneous tissues.

Electrochemotherapy (ECT) is a new treatment for metastatic nodules of solid tumors on the skin or subcutaneous tissue. ECT is a combination of a physical effect, cell membrane poration, and cytotoxic drug administration. Cell membrane poration is achieved by applying short intense electric filed pulses. Pore formation on the cell membrane allows low permeant drugs like bleomycin or cisplatin to enter the cell and thus locally increase their toxicity: up to 10.000 times for bleomycin and 80 times for cisplatin. ECT has been investigated in a multicenter study European Standard Operating Procedures for Electrochemotherapy (ESOPE) that demonstrates how by ECT over 80% of the cutaneous or subcutaneous metastatic nodules can be healed, thus confirming the results of previous studies. ECT efficacy is independent of tumor histology. The experience gathered in the ESOPE study allowed to prepare standard operating procedures that are key to the dissemination of the technology. ECT is safe effective, the treatment is completed in one session usually on an out-patient basis with minimum side-effects. ECT is cost-effective and, although palliative, it ameliorates patients' quality of life. ECT is the treatment of choice for tumors refractory to conventional treatment, can be used in form of cytoreductive therapy before conventional treatment for organ sparing and functions saving, finally can be adopted to treat hemorrhagic or painful nodules, it can be applied in previously irradiated areas.

Effects of molecular weight and surface functionalization on surface composition and cell adhesion to Hyaluronan coated titanium.

This paper describes the effect of surface functionalization on surface composition and cell adhesion to titanium samples by high and low molecular weight Hyaluronan (HA). HA was covalently linked to aminated Ti surfaces obtained by two different surface functionalization techniques, that is polyethyleneimine (PEI) adsorption and deposition from allylamine plasma. The two approaches yield very different surface densities of available amino groups, affecting this way the number and frequency of surface-HA bonds and the configurational freedom of the latter. Results of cell adhesion test are dependent on the surface functionalization approach adopted, low molecular weight HA coupled to PEI functionalized Ti does not yield the same degree of resistance to cell adhesion found on other samples. These results indicate that the details of the surface functionalization step are crucial for surface engineering of implant devices by biological molecules.

The investigation of skin blood flowmotion: a new approach to study the microcirculatory impairment in vascular diseases?

Skin blood flow oscillation, the so called flowmotion, is a consequence of the arteriolar diameter oscillations, i.e. vasomotion, and it is thought to play a critical role in favoring the optimal distribution of blood flow in the skin microvascular bed. Investigation of skin blood flowmotion, using spectral analysis of the skin laser Doppler flowmetry (LDF) signal, showed different flowmotion waves of endothelial, sympathetic or myogenic mediated vasomotion origin. Using this method in peripheral arterial obstructive disease (PAOD) patients an impairment of all the three flowmotion waves was found at level of the diseased leg following ischemia in the II stage of the disease and basally in critical limb ischemia. In patients with essential arterial hypertension (EHT) forearm skin blood flowmotion showed a post-ischemic impairment of myogenic and sympathetic components in newly diagnosed patients, and of endothelial and sympathetic components in long standing patients. In diabetic patients there was a selective impairment of skin flowmotion wave mediated by sympathetic activity in basal conditions. Investigation of skin blood flowmotion in response to different vasoactive substances demonstrated an important role of nitric oxide (NO) in controlling the endothelial component of vasomotion and an insulin action on smooth muscle cells of skin microvessels. All these data suggest that the study of skin blood flowmotion can become a method to early and easily detect skin microvascular impairment in vascular diseases and to investigate the mechanisms of substances active on skin microvascular bed.

Effects of systemic glucocorticoid administration on tenocytes.

The effects of systemic administration of glucocorticoids (GC) on Achilles tendons of rats was studied. After the animal euthanasia, Achilles tendons were removed in sterile conditions from Sprague Dawley adult female rats to isolate tenocytes. Animals have been daily treated for 8 weeks with 4 mg/kg methylprednisolone or Sham-treated with saline solution. In vitro, cell proliferation (WST-1), extra-cellular matrix (ECM) synthesis (collagen type I, CICP; proteoglycans, PG; and fibronectin, FBN), and transforming growth factor (TGF-beta1) were evaluated at 3 and 7 days of culture. The effect of glucocorticoids (GC) on tenocytes was evident both at 3 and 7 days of culture, and caused a significant decreases in cell proliferation (P<0.01), CICP (P<0.01) and PG synthesis (P<0.01) as compared to NT tenocytes. In conclusion, GC systemic treatment seems to compromise the normal proliferation rate and synthetic activity of cultured tenocytes. This study was helpful in understanding the fundamental biological processes that occur during corticosteroid systemic administration and tenocyte cultures may be used to further study to improve knowledge of these cell behaviour also in the ambit of tendon tissue-engineered therapies.

Thyroid nodule evaluation: what have we really learned from recent clinical guidelines?

Recent guidelines for the evaluation of thyroid nodules clarify the diagnostic algorithm while also reporting important differences. The performance of fine needle aspiration (FNA) for cytological examination follows serum TSH determination and thyroid ultrasonography. Thyroid scintigraphy is recommended following a low TSH value and/or FNA yielding an indeterminate follicular cytology. The use of thyroid ultrasonography is the source of some controversy: though it is recommended as a principal first test, its real-time use to guide FNA ranges from routine to only following an FNA yielding an inadequate or nondiagnostic cytological result. In clinical practice, the proportion of physicians utilizing ultrasonography, scintigraphy and FNA varies and frequently deviates from recommended guidelines. The development of guidelines is necessary to bring about consistency and optimization to the diagnostic work-up of thyroid nodules. It is likely that novel diagnostic procedures, such as molecular markers, large needle aspiration biopsy and thyroid imaging with tracers beyond conventional radioactive iodine or (99m)Tc pertechnetate, will lead to improved performance and implementation of guidelines.

Heart rate variability and QT dispersion in patients with subclinical hypothyroidism.

UNLABELLED: The effect of subclinical hypothyroidism (SH) on cardiovascular autonomic function and ventricular repolarization has not been yet elucidated. The aim of the present study was to evaluate the dispersion of QT interval, i.e. an index of inhomogeneity of repolarization, and heart rate variability (HRV), i.e. a measure of cardiac autonomic modulation, in SH patients. METHODS: The study included 42 patients (29 women and 13 men; mean age 53.2+/-14.2 years; body surface area 1.76+/-0.14 m2) with SH, as judged by elevated serum TSH levels (>3.6 mIU/l; range, 3.8-12.0) and normal free thyroid hormones (FT4 and FT3) and 30 euthyroid volunteer. Subjects with cardiac, metabolic, neurological disease or any other systemic disease that could affect autonomic activity were excluded from the study. Patients with SH and control subjects underwent a full history, physical examination, standard 12-lead ECG, and 24-h ambulatory ECG monitoring. To evaluate the effect of treatment with L-thyroxine on QT dispersion and HRV, 15 patients with SH were randomly assigned to receive therapy with L-thyroxine. All the subjects were evaluated at enrolment and after 6 months. RESULTS: Patients with SH showed higher QT dispersion and lower HRV measures than healthy controls (P<0.01 for all). In SH patients, the standard deviation of N-Ns (SDNN) was negatively related to TSH (r=-0.42, P=0.006), while low frequency (LF)/high frequency (HF) ratio was positively related to TSH (r=0.42, P=0.006). Moreover, in SH patients both QT dispersion and QTc dispersion were positively related to TSH (r=0.64 and r=0.63, P<0.001 for both). After 6 months, the patients treated with L-tiroxine exhibited a reduction of QT dispersion and an increase of HRV parameters. CONCLUSION: The results of the present study demonstrated that SH can alter autonomic modulation of heart rate and cause increased inhomogeneity of ventricular recovery times. Accordingly, early L-thyroxine treatment may be advised not only to prevent progression to overt hypothyroidism but also to improve abnormal cardiac autonomic function and ventricular repolarization inhomogeneity.

C-reactive protein in patients on chronic hemodialysis with different techniques and different membranes.

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and cardiovascular mortality. The aim of the present study was to evaluate CRP levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities and dialyzed with different membranes, at baseline and after 6 months. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 3 months and were prospectively followed in their initial dialytic modality for 6 months. Patients were treated with conventional bicarbonate dialysis (N = 127) or hemodiafiltration (N = 120). Patients treated with conventional bicarbonate dialysis were dialyzed with different membranes: Cuprophane (N = 51), low-flux cellulose modified membrane (N = 37) and synthetic membranes (N = 39). Hemodiafiltration was performed in post-dilution mode with polysulfone (N = 66) and polyacrylonitrile (N = 54) membranes. Analysis of baseline CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (upper limit in normal subjects). The mean +/- S.D. CRP values were significantly higher (P < 0.05) in hemodiafiltration with infusion volumes < 10 l per session (14.6+/-3.1 mg/l) than in standard hemodialysis (5.1 +/- 2.1 mg/l) and hemodiafiltration with infusion volumes > 20 l per session (4.9 +/- 2.1 mg/l). These values did not significantly change after 6 months of follow-up. Concerning the membranes, the highest levels of CRP were observed in patients dialyzed with Cuprophane with a significant increase from 15.1 +/- 3.6 to 21.2 +/- 3.1 mg/l after 6 months (P < 0.05); a significant reduction of CRP levels was observed in patients dialyzed with polysulfone in the same follow-up period (from 13.5 +/- 2.9 to 8.1 +/- 2.4 mg/l; P < 0.05). The CRP increase following low volume HDF can be related to back-filtration of bacterial derived contaminants.; moreover, an important effect on CRP of the hemodialysis membrane is observed and new synthetic membranes can be used to decrease these levels.

Safety and effects on the lipid and C-reactive protein plasma concentration of the association of ezetimibe plus atorvastatin in renal transplant patients treated by cyclosporine-A: a pilot study.

Ezetimibe (E) is a new cholesterol adsorption inhibitor which prevents the adsorption of dietary and biliary cholesterol by binding to a recently described cholesterol transporter. This pilot study was performed to evaluate the safety and the low-density lipoprotein (LDL)-C and C-reactive protein lowering efficacy of atorvastatin (A) and of the association of A plus E in five renal transplant patients with hypercholesterolemia and mild renal functional impairment receiving cyclosporine-A (CsA). Patients received for three periods, each of 3 weeks, A at a dose of 20 mg/day; A at a dose of 10 mg/day and finally, A 10 mg plus E 10 mg daily. The medications were well-tolerated and no important clinical or laboratory (muscle enzyme, creatinine clearance and CsA concentration) abnormalities were observed throughout the study period. A alone lead to target LDL-C values only in two of five patients and did not significantly reduce the mean CRP values. The combination of E plus A produced the lowest lipid levels and significantly reduced CRP mean values and allowed all patients to attain target levels of LDL-C: total cholesterol decreased from 240 +/- 42 (mean +/- S.D.) to 171 +/- 34 mg/dl, LDL-C from 129 +/- 32 to 87 +/- 21 mg/dl, plasma triglycerides from 330 +/- 54 to 194 +/- 71 mg/dl and CRP from 6.2 +/- 1.9 to 3.9 +/- 2.4 mg/l (P < 0.05 for all). This pilot study suggests that the co-administration of E and A at 10 mg/day in renal transplant patients receiving CsA is well-tolerated and effective in reducing important cardiovascular risk factors.