Dialysis dose and frequency.

BACKGROUND: From the beginning of the dialysis era, the issue of optimal dialysis dose and frequency has been a central topic in the delivery of dialysis treatment. METHODS: We undertook a discussion to achieve a consensus on key points relating to dialysis dose and frequency, focusing on the relationships with clinical and patient outcomes. RESULTS: Traditionally, dialysis adequacy has been quantified referring to the kinetics of urea, taken as a paradigm of all uraemic toxins, and applying the principles of pharmacokinetics using either single- or double-pool variable volume models. An index of dialysis dose is the fractional clearance of urea, which is commonly expressed as Kt/V. It can be calculated from blood urea concentration and haemodialysis (HD) parameters, according to the respective urea kinetic model or by means of simplified formulas. Similar principles are applicable to peritoneal dialysis (PD), where weekly Kt/V and creatinine clearance are used. Recommended minimal targets for dialysis adequacy have been defined by both American and European guidelines (DOQI and European Best Practice Guidelines, respectively). The question of how to improve the severe outcome of dialysis patients has recently come back to the fore, since the results of two recent randomized controlled trials led to the conclusion that, in thrice weekly HD and in PD, increasing the dialysis dose well above the minimum requirements of current American guidelines did not improve patient outcome. Daily HD (defined as a minimum of six HD sessions per week), in the form of either short daytime HD or long slow nocturnal HD, is regarded as a possibility to improve dialysis patient outcome. The results of the studies published so far indicate excellent results with respect to all outcomes analysed: optimal blood pressure control, regression of left ventricular hypertrophy and amelioration of left ventricular performance, improvement of renal anaemia, optimal hyperphosphataemia control, improvement of nutritional status, reduction in oxidative stress indices and improvement in quality of life. The basis for these beneficial effects is thought to be a more physiological clearance of solutes and water, with reduced pre- and post-HD solute concentrations and interdialytic oscillation, compared with traditional HD. Apart from concerns regarding reimbursement and organizational issues, no serious adverse effects have been described with daily HD. However, the evidence accumulated is limited mainly to retrospective cohorts, with small patient numbers and no adequate controls in most instances. Therefore, large prospective studies with adequate controls are required to make daily HD accepted by reimbursing authorities and patients. CONCLUSIONS: Given the available observational and interventional body of evidence, there is no reason to reduce arbitrarily dialysis dose, particularly dialysis treatment time in HD patients treated three times weekly. Daily HD represents a very promising tool for improving dialysis outcomes and quality of life, although its impact on patient survival has not yet been proven definitively.     

Obesity-associated lymphoedematous mucinosis

Background: Mucin deposition on the shins is considered as an indicator of pretibial myxoedema, which is typically seen in patients with Graves' disease.
Objective: The purpose of this study was to report the clinical and histopathological features of a group of patients with pretibial mucinosis in the absence of thyroid disease.
Methods: Five patients are included in this series and studied both clinically and histologically and compared with similar cases in the literature.
Results: All patients were middle aged or elderly. Four patients were women. They were characterized clinically by morbid obesity and bilateral lower extremity pitting oedema sparing the feet. Semitranslucent papules and/or nodules and sometimes vesicles were found on the shins. Characteristic histological features include (i) hyperorthokeratosis with epidermal atrophy and effacement of the rete ridge pattern, (ii) oedema in the papillary and upper part of the reticular dermis with mucin deposition stained positively with alcian blue and colloidal iron, (iii) angioplasia in the upper part of dermis with upward-running, increased and thickened capillary vessels and (iv) variable fibrosis in the reticular dermis with separation of collagen bundles and increased stellate or linear fibroblasts. A hypocaloric diet was given in two cases, and an important weight loss was observed, which was accompanied by a marked improvement of the pretibial mucinosis.
Conclusions: Pretibial mucinosis is a histological feature associated with morbid obesity and lymphoedematous features of the legs that should be distinguished from true pretibial myxoedema. The term of 'obesity-associated lymphoedematous mucinosis' seems to be appropriate for this condition.     

Congenital mesoblastic nephroma with hypercalcemia. Pathogenetic role of prostaglandins

A case of mesoblastic nephroma, hypercalcemia, and raised levels of prostaglandins in a 2-month-old female infant is reported. Plasma parathyroid hormone (PTH) was normal and urinary prostaglandins were raised. During surgery a prostaglandin arteriovenous gradient was demonstrated. A large quantity of PGE was extracted from the tumor by radioimmunoassay after incubation. Both blood calcium and urinary prostaglandins returned to normal after nephrectomy. These results show that this tumor produced prostaglandins, the mediators of hypercalcemia in this patient.     

The incidence of unknown common bile duct calculosis in videolaparoscopic cholecystectomy and usefulness of routine intraoperative cholangiography]

BACKGROUND: The aim of this study is to show the utility of intraoperative cholangiography IOC in detecting unknown common bile duct calculosis during VLS cholecystectomy. METHODS: The General Surgery Unit of Carlo Poma Hospital in Mantova, carried out a retrospective study considering 288 VLS executed from January 1996 to May 1999. The study excluded the following categories of patients: those with an already known choledocholitiasis, those who underwent preoperative curative ERCP, and those with a preoperative cholangio RMN. RESULTS: The IOC has detected a hepatocholedochocalculosis in 31 patients (11.4% and in 7 cases there was a suspected calculosis. Twenty of the 31 patients did not present any element that could give the suspect of calculosis. In personal experience IOC showed in 11.4% an unknown hepatic choledochal calculosis after pre-operative echography routine examinations. The percentage of success of the intraoperative cholangiography was of 90%, the meantime for this procedure 15 minute. CONCLUSIONS: The routinary execution of IOC during VLC is useful also considering its low costs.     

Airway control via the Cobrapla™ during percutaneous dilatational tracheotomy in five patients

PURPOSE: To evaluate the use of the new supraglottic airway device CobraPLA (CPLA) for performing percutaneous dilatational tracheotomy (PDT) utilizing continuous fibreoptic visualization of the larynx and trachea and uninterrupted airway control. CLINICAL FEATURES: The percutaneous tracheotomies were carried out in five patients (four males and one female; mean age 72 yr, mean height 164.6 cm, mean weight 74 kg) following the Griggs technique under continuous fibreoptic vision and airway control provided by the CPLA. The mean time required for removal of the ETT, positioning of the CPLA, and confirmation of adequate ventilation and cuff seal was 78 sec. The mean time for the entire PDT procedure was six minutes and 57 sec. In one patient a 7-mm tracheostomy cannula was used, and in the other four patients an 8-mm cannula was used.The hemodynamic and respiratory variables remained stable during the entire procedure; there were no adverse events.At no point was there any significant difficulty in placing the CPLA or in providing ventilation or oxygenation. Each procedure could be observed easily in its entirety through the FOB. CONCLUSIONS: This technique can be considered simple and safe because it is video-assisted and ensures a continuous airway control. The CPLA offers several advantages over some other supraglottic devices when performing this surgical procedure.     

Efficacy and Safety of Oral Lactoferrin Supplementation in Combination with rHuEPO‐β for the Treatment of Anemia in Advanced Cancer Patients Undergoing Chemotherapy: Open‐Label,Randomized Controlled Study

Advanced‐stage cancer patients often suffer from anemia that closely resembles the anemia of chronic inflammatory diseases characterized by specific changes in iron homeostasis and absorption. i.v. iron improves the efficacy of recombinant human erythropoietin (rHuEPO) in anemic cancer patients undergoing chemotherapy. We report the results of an open‐label, randomized, prospective trial aimed at testing the efficacy and safety of treatment with oral lactoferrin versus i.v. iron, both combined with rHuEPO, for the treatment of anemia in a population of 148 advanced cancer patients undergoing chemotherapy. All patients received s.c. rHuEPO‐β, 30,000 UI once weekly for 12 weeks, and were randomly assigned to ferric gluconate (125 mg i.v. weekly) or lactoferrin (200 mg/day). Both arms showed a significant hemoglobin increase. No difference in the mean hemoglobin increase or the hematopoietic response, time to hematopoietic response, or mean change in serum iron, C‐reactive protein, or erythrocyte sedimentation rate were observed between arms. In contrast, ferritin decreased in the lactoferrin arm whereas it increased in the i.v. iron arm. In conclusion, these results show similar efficacy for oral lactoferrin and for i.v. iron, combined with rHuEPO, for the treatment of anemia in advanced cancer patients undergoing chemotherapy.     

Overexpression of GAP‐43 modifies the distribution of the receptors for myelin‐associated growth‐inhibitory proteins in injured Purkinje axons

Neurons with enhanced intrinsic growth capabilities can elongate their axons into non‐permissive territories, but the mechanisms that enable the outgrowing processes to overcome environmental inhibition are largely unknown. To address this issue, we examined adult mouse Purkinje cells that overexpress the axonal growth‐associated protein GAP‐43. After injury, these neurons exhibit sprouting along the intracortical neuritic course and at the severed stump in the white matter. To determine whether GAP‐43‐overexpressing Purkinje cells are responsive to extrinsic inhibitory cues, we investigated the content and subcellular localization of major receptors for myelin‐associated inhibitory proteins, PlexinB1 and the Nogo receptor (NgR) with the related co‐receptors LINGO‐1 and p75. Expression of these molecules, estimated by measuring perikaryal immunostaining intensity and Western blot, was not different in wild‐type or transgenic mice, and it was not overtly modified after axotomy. Following injury, however, the content of PlexinB1 was significantly reduced in GAP‐43‐overexpressing neurites. Furthermore, in the same axons the distribution of both PlexinB1 and NgR was altered, being inverse to that of GAP‐43. Labelling for the two receptors was conspicuously reduced on the axonal surface and it was almost undetectable in the outgrowing sprouts, which showed strong GAP‐43 immunoreactivity. These observations indicate that although GAP‐43 overexpression does not modify the expression of receptors for myelin‐associated inhibitory factors, it interferes with their subcellular localization and exposure on the neuritic membrane. Therefore, GAP‐43 promotes axon growth by multiple synergistic mechanisms that potentiate the intrinsic motility of the elongating processes, while reducing their sensitivity to environmental inhibition.