Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction.

Left ventricular noncompaction cardiomyopathy (LVNC) is a clinically heterogeneous disorder characterized by a trabecular meshwork and deep intertrabecular myocardial recesses that communicate with the left ventricular cavity. Several genetic causes of LVNC have been reported, with variable modes of inheritance, including autosomal dominant and X-linked inheritance, but relatively few responsible genes have been identified. A NGS workflow, based on a panel of 95 genes developed for sequencing most prevalent sudden cardiac death-causing genes, was used to make a rapid and costless molecular diagnosis in two siblings with a severe noncompaction cardiomyopathy starting prenatally and leading to rapid cardiac failure. For the first time, a total homozygous PKP2 deletion was identified. This molecular defect was further confirmed by MLPA and array-comparative genomic hybridization (CGH). Heterozygous PKP2 mutations are usually reported in a significant proportion of Arrhythmogenic Right Ventricular Cardiomyopathy cases. Our results show, for the first time, the involvement of PKP2 in severe cardiomyopathy with ventricular non compaction.

The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment.

The European Union has determined that from 2016 breast cancer patients should be treated in Specialist Breast Units that achieve the minimum standards for the mandatory quality indicators as defined by Eusoma. The existing standard for axillary lymph node staging in breast cancer is sentinel node biopsy (SNB), performed using Technetium-sulphur colloid (99m Tc) alone or with blue dye. The major limits of radioisotope consist in the problems linked to radioactivity, in the shortage of tracer and nuclear medicine units. Among existing alternative tracers, SentiMag® , which uses superparamagnetic iron oxide particles, can represent a valid option for SNB. We conducted a paired, prospective, multicentre study to evaluate the non-inferiority of SentiMag® vs. 99m Tc. The primary end point was the detection rate (DR) per patient. The study sample consists of 193 women affected by breast carcinoma with negative axillary assessment. The concordance rate per patients between 99m Tc and SentiMag® was 97.9%. The DR per patient was 99.0% for 99m Tc and 97.9% for SentiMag® . SentiMag® appears to be non-inferior to the radiotracer and safe. While 99m Tc remains the standard, SentiMag® DR appears adequate after a minimum learning curve. In health care settings where nuclear medicine units are not available, SentiMag/Sienna+® allows effective treatment of breast cancer patients.

Hyperthermic isolated perfusion with tumor necrosis factor-alpha and doxorubicin for the treatment of limb-threatening soft tissue sarcoma: the experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO).

BACKGROUND: Tumor necrosis factor-alpha (TNFalpha)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFalpha dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFalpha. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFalpha dose and doxorubicin (Dx). PATIENTS AND METHODS: HILP with TNFalpha (at a dosage of either 1 mg) and Dx was administered to 75 patients with limb-threatening STS: 37 males and 38 females; median age 50 years; tumor in the lower and upper limbs in 58 and 17 patients, respectively; primary and recurrent tumors in 45 and 30 patients, respectively. Most tumors (77%) were high grade. Tumor resection was carried out 6 to 8 weeks after HILP. RESULTS: The grade of limb toxicity was mild to moderate in the vast majority of patients (76%). Grades IV and V were observed, but only when high muscle temperatures were recorded and high TNFalpha dosages were employed. Systemic toxicity was also mild to moderate and there were no postoperative deaths. Complete and partial tumor responses were 34% and 48%, respectively, with an overall response of 82% . Limb sparing surgery was carried out in 85.3% of patients. At a median follow-up of 28 months, 16 recurrences (21.3%) were recorded, with a 5-year locoregional disease-free survival of 63% . The 5-year disease-free survival and overall survival were 36.7% and 61.6%, respectively. CONCLUSION: HILP with 1 mg of TNFalpha is an effective neoadjuvant therapy resulting in a high rate of limb sparing in limb-threatening STS, with acceptable local reactions and negligible systemic toxicity.

Prognostic factors influencing tumor response, locoregional control and survival, in melanoma patients with multiple limb in-transit metastases treated with TNFalpha-based isolated limb perfusion.

BACKGROUND: In isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNFalpha) and interferon (IFN)-gamma, pioneered by Lienard and Lejenne in 1988, TNFalpha was empirically employed at a dosage (3-4 mg) ten times higher than the systemic maximum tolerable dose (MTD). We previously conducted a phase I/II study in 20 patients with in-transit melanoma metastases, using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. The dose of 1 mg of TNFalpha was identified as optimal in terms of both efficacy and toxicity. The aim of the present study was to describe our experience with 113 stage IIIA/IIIAB melanoma patients treated with a TNFalpha-based ILP and identify prognostic factors for response, locoregional control and survival. PATIENTS AND METHODS: Patients at stage IIIA-IIIAB (presence of in-transit metastases and/or regional node involvement) were considered eligible. The disease was bulky (>or=10 nodules3 cm) in 42.5% of the patients and unresectable in 33% . Forty patients were treated with a TNFalpha dosage of >1 mg and 73 with 1 mg. Patients with tumors in the upper and lower limbs were submitted to ILP via axillary and iliac vessels, respectively. TNFalpha was injected in the arterial line of an extracorporeal circuit at the pre-established dose, followed by melphalan (13 and 10 mg/l of limb volume for the upper and lower limbs, respectively) 30 minutes later. RESULTS: Complete responses (CR) and partial responses (PR) were 63% and 24.5%, respectively, with an objective response (OR) of 87.5%. No change (NC) was observed in only 12.5% of the patients. Upon multivariate analysis, only bulky disease maintained its independent value for tumor response with an odds ratio of 4.07 and a p-value of 0.02. The 5-year locoregional disease-free survival was 42.7%. Upon multivariate analysis, the only prognostic factors were stage, age and bulky disease. The 5-year overall survival was 49%. Multivariate analysis showed that only sex, stage and CR maintained their independent values. CONCLUSION: TNFalpha-based ILP was proven to be an effective treatment for melanoma patients with in-transit metastases. The TNFalpha dosage of 1 mg was as effective as 3-4 mg, with lower toxicity and cost. We propose that TNFalpha and melphalan-based ILP should be employed for bulky tumors or after failure of melphalan-based ILP.

De novo malignancy after solid organ transplantation in children.

The aim of this study was to assess the prevalence of de novo malignancy after solid organ transplantation in childhood. A retrospective questionnaire-based survey was sent to 9 referral centers for pediatric organ transplantation in France. Among 1326 children who underwent solid organ transplantation since 1996, 80 (6%) presented with de novo malignancy posttransplantation during childhood: posttransplant lymphoproliferative disease was the most common (5% of pediatric recipients) comprising 80% of all tumors, with a disproportionately high prevalence among combined liver and small bowel recipients (18%). Various solid tumors were observed mainly among kidney recipients. No skin cancer was reported.

[Do convective treatments significantly reduce morbidity and mortality?]. / I trattamenti convettivi riducono significativamente morbilita' e mortalita'?

Standard hemodialysis is a far from ideal treatment for uremia since the morbidity and mortality of patients on hemodialysis are still significantly higher than those of non-hemodialyzed subjects with similar demographic characteristics. Because it has been suggested that the cause could lie in the inadequate removal of ''middle molecules'' by standard hemodialyis, two alternative treatments have been proposed: high-efficiency hemodialyis and high-flux hemodialyis. The 2002 results of the HEMO study showed that both these treatments are associated with a non-significant reduction in the relative risk of death (4% and 8%, respectively). The MPO study, which - unlike the HEMO study - enrolled only incident cases and not did not allow reuse of dialyzers, evaluated the mortality rate with high-flux and low-flux hemodialysis in a sicker population, i.e., patients with hypoalbuminemia, and showed a significant reduction in the relative risk of death especially in patients with diabetes. In an attempt to define the clinical impact of hemodiafiltration, some of the efficacy data from clinical studies are reviewed in light of a number of factors that may be related to the high mortality among hemodialysis patients. The current state of affairs suggests it is reasonable to prefer high-flux hemodialysis in sicker patients, especially diabetics. Moreover, the use of ultrapure dialysis fluid is recommended to reduce chronic inflammation and its consequences.

[Intravenous thrombolysis in pediatric arterial ischemic stroke: a case report and a review of the literature]. / L'utilisation de la thrombolyse intraveineuse dans l'infarctus cérébral artériel aigu de l'enfant, en dehors de la période néonatale : à propos d'un cas et revue de la littérature.

Pediatric arterial ischemic stroke (AIS) is little known by pediatricians, as it is rare and difficult to diagnose. Current therapeutic approaches include platelet aggregation inhibitors, anticoagulation using heparin or thrombolysis with rt-PA, and therapeutic abstention in the absence of consensus, in contrast with stroke in adults. We report the case of a 3-year-old child who benefited from intravenous thrombolysis with rt-PA 2h after a major AIS of the anterior and middle left arteries due to embolism from the heart. Neurological progression was marked by a persistent, severe functional deficiency, in spite of the early use of thrombolysis. No hemorrhagic complication occurred. This observation raises the problem of therapeutic indications in childhood AIS and more particularly the question of the use of intravenous thrombolysis. Currently, few studies exist on this subject and only a few case report of children and teenagers having received effective intravenous or intra-arterial thrombolysis further to an AIS are available in the literature. A single study describes 46 cases of children with AIS having received thrombolysis but reports numerous complications. However, the absence of symptomatic hemorrhagic complications is noteworthy. There is currently insufficient evidence to recommend thrombolysis in pediatric AIS; nevertheless it can be proposed in certain rare cases, similar to the observation reported herein.

Sentinel node biopsy in cutaneous melanoma: correlations between melanoma prognostic factors and sentinel node status.

This study aims to correlate the most important prognostic factors of primary melanoma with sentinel node (SN) positive for metastases. We have enrolled 84 patients subjected to sentinel node biopsies for cutaneous melanomas of Breslow's thickness > or = 0.75 mm by using an intra-operative gamma probe after lymphoscintigraphy, without blue dye support. SN metastases were reported in 27% of cases (14% by histology and 13% by immunohistochemistry). By chi-square test Breslow's thickness > 2mm (p= 0.004), IV and V Clark's level (p= 0.02), ulceration (p= 0.05) and high mitotic rate (p= 0.05) were statistically significant (p < 0.05) with reference to SN positive for metastases, unlike the site of cutaneous melanoma, vertical growth phase, tumour infiltrating lymphocytes, regression and vascular invasion. Breslow's thickness remains the first prognostic factor to be considered for sentinel node biopsy in cutaneous melanoma, but other markers must be carefully estimated.

120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study.

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.

Organocatalytic route for the synthesis of propionylated starch.

In recent years acetylated, propionylated and butyrylated starches have received special attention due to their capacity to deliver specific short chain fatty acids (SCFAs) to the colon in a sustained and predictable manner, and thus contribute to maintaining the normal physiologic function of the large bowel and preventing specific diseases. In the current contribution a non-conventional organocatalytic solventless route for the eco-friendly propionylation of corn starch is proposed. The catalyst used in the acylation is a naturally occurring α-hydroxy acid (l-tartaric acid). Propionylated starches with degree of substitution (DS) in the 0.05-1.59 interval were obtained and characterized in terms of chemical structure, morphology, crystallinity, thermal stability and hydrophilicity. Results showed that by the proposed methodology propionylated starch with the DS required for clinical use (i.e. 0.2-0.3) could be obtained within 2-3h of reaction. Characterization results evidenced the progressive loss of crystallinity of starch granules as higher substitution levels were conferred.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

[Evolution of the Fontan operation and results in patients with single ventricles or mixed congenital malformations]. / Evolution et résultats des opérations de Fontan dans les cardiopathies congénitales univentriculaires ou assimilées.

STUDY OBJECTIVES: To examine the results of right heart derivations and clinical outcomes according to preoperative characteristics and operative strategy implemented. METHODS: Fontan operations were performed in 65 patients (mean age = 10.3 years, 41 males). The majority of cardiopathies were single ventricles (SV) with (49% of patients) or without (26%) tricuspid atresia. A palliative bidirectional cavo-pulmonary (BCP) anastomosis was performed prior to Fontan in 15 patients. Intra-atrial Fontan tunnelling was performed in 43 patients, Kreutzer-type operations in 10, and extracardiac tubes were used in 8 patients. The mean duration of follow-up was 6.1 +/- 0.3 years. RESULT: The 30-day mortality was 13.8%. Early mortality was higher among patients with SV with than without tricuspid atresia (P < 0.01), and among patients < 4 years old. Early reoperations were required in 5 patients, including dismounting in 1, BCP anastomosis after Kreutzer procedure in 1, and tube thrombosis in 1 patient. A single death occurred past 30 days, and late adverse events included protein-losing enteropathy in 1 patient, complete atrioventricular block in 1, and tube thrombosis treated with heparin in 2 patients. At the end of follow-up, 75% were in New York Heart Association functional class I. CONCLUSION: Our intermediate-term results of Fontan-type operations were satisfactory, and steadily improving. The prognosis was better in patients operated at age 4 or older. A prior BCP anastomosis improved the results. A higher morbidity was observed with intra- than with extra-atrial Fontan procedures. The merit of fenestration procedures with respect to morbidity remains the be evaluated.

[Use of dialysate conductivity to obtain neutral sodium balance in chronic hemodialysis patients]. / L'utilizzo della conduttività del dialisato per il conseguimento del bilancio fisiologico del sodio nei pazienti in trattamento emodialitico periodico.

In order to assure a zero sodium balance in hemodialysis patients, attaining 'constant' values of total body water and plasma water sodium concentration at the end of each dialysis session is a basic pre-requisite. This is achieved by matching the ultrafiltration to the inter-dialytic weight gain and by individualizing dialysate sodium concentration at each dialysis session by making use of a kinetic model. Clinical results suggest that the single pool variable volume sodium kinetic model allows the targeted end-dialysis plasma water sodium concentration to be obtained. Nevertheless, this model is not suitable for routine clinical application, because of difficulties in the real-time determination of initial plasma water sodium concentration and 'effective' sodium dialysance. Measuring dialysate conductivity at the inlet and outlet ports of the dialyzer allows the estimation of sodium transfer during dialysis, if the function of concentration versus conductivity is known. If sodium transfer is measured at two different inlet dialysate conductivities, it is possible to determine ionic dialysance and systemic plasma water conductivity, which can be used routinely to apply the single pool sodium kinetic model. Given that ionic dialysance and plasma water conductivity can be measured easily repeatedly and inexpensively at each dialysis session without the need for blood sampling or laboratory determinations, it can be expected that conductivity kinetic models will soon become a part of everyday clinical practice.

Dry weight and sodium balance.

To achieve good blood pressure control and minimal intradialytic patient discomfort, it is very important to define the correct dry weight and individualize the "adequate" dialysate sodium concentration. Given the highly variable amounts of sodium introduced during interdialytic periods, the use of the sodium and conductivity kinetic models guarantees adequate sodium removal in each patient with each treatment. According to our data, the imprecision of the sodium kinetic model was less than 0.84 mEq/L; that of the conductivity kinetic model, which has the advantage not requiring blood or dialysate samples, was less than 0.14 mS/cm. In paired filtration dialysis (PFD), the corresponding figures were less than 1.1 mEq/L and less than 0.1 mS/cm. A multicenter prospective, controlled and randomized trial has demonstrated that the application of the conductivity kinetic model in PFD makes it possible to improve cardiovascular stability in patients prone to dialysis hypotension. The sodium kinetic model is difficult to apply in routine clinical practice because of the need for blood and dialysate samples, but this may be overcome by the conductivity kinetic model, which is a very promising tool for achieving a zero intradialytic sodium balance and improving cardiovascular stability.

Relevance of the conductivity kinetic model in the control of sodium pool.

Changes in the body sodium pool caused by dialytic treatment have very important clinical implications, mainly in terms of intradialytic cardiovascular instability and interdialytic hyperhydration and hypertension with long-term cardiac hypertrophy and dilation. A kinetic model could be helpful in order to define the dialysate sodium concentration needed to match intradialytic hydrosodium removal with interdialytic sodium and water intake, but unfortunately, none of the sodium kinetic models are suitable for routine clinical application. Two conductivity kinetic models (one for hemodialysis and one for paired filtration dialysis) have been developed on the basis of the linear relationship between the sodium content and conductivity of every saline solution and plasma water and according to basic theory for ionic dialysance determination. These models make it possible to know at the start of each session the dialysate conductivity needed to obtain the desired final plasma water conductivity or to know the latter when the former is known. Clinical evaluations showed that conductivity kinetic models are very precise and accurate and may be used instead of sodium kinetic models. Furthermore, they are suitable for routine use because they do not require blood sampling or laboratory determinations. Clinical application of the conductivity kinetic model has shown that the reduced variability of end-dialysis plasma water conductivity obtained when using the model to identify dialysate conductivity significantly reduces cardiovascular instability, even without any changes in average sodium removal. Given that ionic dialysance can be easily, inexpensively, and repeatedly measured at each dialysis session, it seems realistic to expect that conductivity kinetic modeling will soon become a part of everyday clinical practice.

Electrolyte disorders and substitution fluid in continuous renal replacement therapy.

Electrolyte balances during acute renal failure treated with continuous convective techniques, such as continuous arteriovenous hemofiltration (CAVH) and its pumped variants, are largely dependent on the eloctrolyte plasma concentration available for ultrafiltration, the ultrafiltration rate and the composition of the replacement solution. As blood sodium concentrations measured by potentiometry (Na +P) and the total ultrafiltrate sodium concentration are very similar, Na +P can be taken as the value of ultrafilterable sodium when choosing the correct sodium concentration in the substitution fluid. In CAVH, the ultrafiltrate contains about 3 m Eq/liter of calcium and 1 m Eq/liter of magnesium that must be replaced by the substitution fluid in order to prevent hypocalcemia and hypomagnesemia. In addition, if plasma potassium levels are normal, 3 to 4 mEq/liter of potassium should be added to the replacement fluid to avoid hypokalemia. Although convection and diffusion are combined in continuous hemodialysis, solute transport is largely mediated by convection; however, the net removal of sodium and calcium is significantly influenced by their concentrations in the dialysate, and the risk of hypomagnesemia and hypokalemia can be attenuated by adjusting magnesium and potassium concentrations in the dialysis solution to levels near to the plasma water values. Since critically ill patients are prone to developing dialysis-induced hypophosphatemia, phosphorous must be monitored and supplemented if necessary, Since CRRT works continuously, serious derangement in fluid and electrolyte homeostasis may occur in the absence of careful prescription and extremely vigilant monitoring.

CT-guided biopsy of lung lesions.

CT is the most accurate method for guiding fine needle biopsies in deep and/or small sized lung and mediastinic lesions. The authors have performed 2109 CT-guided lung biopsies (FNAB). The results are given in terms of sensitivity, specificity and rate of complications. In ever examination, Westcott or Chiba needles (22 or 21 gauge) were used. From 2109 lung examinations performed, 1413 (66.99%) were positive, 538 (25.5%) negative, 15 (0.7%) suspicious and 143 (6.78%) inadequate for diagnosis, 267 patients underwent surgical or clinical follow-up and, in all cases, the cytological diagnosis was confirmed. Other considerations were made on lesion topography, histological type, dimensions, complication rate, sensitivity, specificity and diagnostic accuracy. CT, of course, is the best method for guiding fine needle biopsy of the lung for its high spatial resolution and excellent anatomical definition, so that samples with smaller than 2 cm lesions, even in continuity with large vessels or other critical organs, are performed. Nevertheless, the result quality depends on the ability of the operator.

Changes in the clinical condition of haemodialysis patients.

The characteristics of the dialytic population have substantially changed over the past 30 years, becoming older and with a greater number of coexisting diseases. The considerable evolution in treatment modalities has lead to a significant increase in the efficacy and tolerability of dialysis. However, physicians have to deal with illnesses in long term dialysis survivors that may be a consequence of inadequate renal replacement therapy rather than of the dialysis procedure per se. Cardiovascular diseases are the leading cause of death and, although many of the risk factors are the same as in the general population (i.e. hypertension), some appear to be specific to CRF (i.e. hyperparathyroidism, anaemia). Age is the most important demographic factor associated with increased mortality. The increasing incidence of ESRD diabetic patients, as well as malnutrition, also contribute to higher mortality in RRT. The therapeutic answer to a worsening in clinical condition is adequate medical care (starting in the conservative phase), with particular attention being given to correcting anaemia, hypertension, volume overload and hyperparathyroidism, and preventing malnutrition. Treatment modalities also play a crucial role. Data suggest that adequate dialytic dose (and possibly time) can reduce morbidity and mortality, and on-line sodium and potassium modelling can improve intradialytic cardiovascular stability and reduce arrhythmias. Long-term treatment with synthetic high-flux membranes may confer some beneficial effect on beta2-m amyloidosis-related morbidity and may also reduce mortality. Family and social support greatly affect the quality of life of the patients. However technologically advanced, no procedure can succeed unless it is performed in the context of humanised health care directed towards patient needs.

Effect of sodium pool changes on blood pressure in patients undergoing PFD: design of a prospective randomized multicenter trial.

Blood pressure control is important during dialysis and the interdialytic period because of the frequency and potential seriousness of hypotension and hypertension. Water and sodium removal play an important role in the genesis of intradialytic cardiovascular instability or hypertension. Changing dialysate sodium concentrations without the aid of a kinetic model can sometimes give good results but is only an empirical approach. Therefore, this clinical trial was designed to prospectively investigate the advantages of changes in the sodium pool on the blood pressure profile of patients undergoing paired filtration dialysis (PFD). The hypothesis to be tested is whether using a dialysate conductivity which, according to the conductivity kinetic model, ensures that the conductivity of the ultrafiltrate at the end of each dialysis session is 0.3 mS/cm more (B) or less (C) than the mean during the run-in period, improves blood pressure control either in patients prone to intradialytic hypotension or patients who are hypertensive or normotensive with antihypertensive treatment. Patients will be randomly allocated to one of two treatment sequences (where treatment A is standard PFD): AABB or ABAA for patients with intradialytic hypotension; AACC or ACAA for hypertensive patients. During the experimental phase arterial blood pressure will be measured and symptoms reported by the patients will be recorded.

Virological characteristics of hepatitis C virus infection in chronic hemodialysis patients: a cross-sectional study.

Detection of hepatitis C virus viremia (HCV RNA) in serum of hemodialysis (HD) patients is crucial for documenting ongoing infection because the clinical and epidemiological importance of anti-HCV positivity is not clear. HCV viremia was studied in 104 HD patients by reverse transcription polymerase chain reaction (RT PCR) using primers localized in the 5' non-coding region of the viral genome. We used two different methods to detect HCV RNA: a direct PCR amplification of HCV RNA from human serum, and a standard RT PCR procedure (requiring the RNA extraction step). There were 50 (48%) anti-HCV positive patients in this population. Twenty-two (21.1%) out of 104 patients showed HCV RNA in serum by standard RT PCR technique: they belonged to the anti-HCV positive patient group, whereas all anti-HCV negative patients were HCV RNA negative. Prevalence of HCV RNA was more than doubled when standard RT PCR was used compared to direct RT PCR protocol. There was a good association between serum HCV RNA and circulating anti-HCV antibodies, tested by second-generation ELISA and RIBA assays. HCV viremia was not associated with either the presence or the absence of a particular RIBA antibody specificity. AST and ALT levels had no predictive value for HCV viremia, because they were repeatedly normal in the majority of viremic patients (16/22: 73%).(ABSTRACT TRUNCATED AT 250 WORDS)