Chronic peritoneal dialysis in paediatrics: Experience of a national registry

The results of the first 3 year' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986–1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.     

Long-term outcome of Hodgkin disease patients following high-dose busulfan, etoposide, cyclophosphamide, and autologous stem cell transplantation.

Busulfan (Bu)-based preparative regimens have not been extensively investigated in Hodgkin disease (HD). The purposes of this study were to investigate the toxicity and efficacy of a novel preparative regimen of Bu 14 mg/kg, etoposide 50-60 mg/kg, and cyclophosphamide 120 mg/kg in patients with primary refractory and relapsed HD. One hundred twenty-seven patients with a median age of 33 years (range, 14-67 years) underwent transplantation. The regimen was well tolerated, with 5.5% treatment-related mortality at 100 days after transplantation. With a median follow up of 6.7 years, the 5-year progression-free survival was 48 +/- 5%, and the 5-year overall survival was 51 +/- 5%. A Cox proportional hazards model identified refractory disease at time of transplantation as the only significant factor affecting relapse and overall survival, whereas disease bulk >10 cm affected overall survival. Five patients died between 5.3 and 9.3 years of late complications, including secondary myelodysplasia or acute myeloid leukemia, secondary solid malignancies, and pulmonary toxicity. This novel Bu regimen is comparable to other radiation-free preparative regimens in its effectiveness in the control of HD and with a low-risk of early treatment-related mortality.     

Infection risk associated with anti-TNF-α agents: a review

Introduction: TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenesis of chronic immune-mediated diseases. TNF-α inhibitors can be administered either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) to treat chronic immune-mediated diseases.

Areas covered: Patients receiving TNF-α inhibitors are at high risk of infections. Based on our experience, in this paper, we discuss the risk of infections associated with the administration of TNF-α inhibitors and the strategies for mitigating against the development of these serious adverse events.

Expert opinion: Infliximab more so than etanercept appears to be responsible for the increased risk of infections. Re-activation of latent tuberculosis (LTB) infection and the overall risk of opportunistic infections should be considered before beginning TNF-α inhibitor therapy. A careful medical history, Mantoux test and chest-x-ray should always be performed before prescribing TNF-α inhibitors. Particular attention should be paid to risk factors for Pneumocystis jirovecii infection. Hepatitis B and C virological follow-up should be considered during TNF-α inhibitor treatment. Finally, patients who are at high risk of herpes zoster (HZ) reactivation would benefit from a second vaccination in adulthood when receiving TNF-α inhibitors.     

Genistein accumulates in body depots and is mobilized during fasting, reaching estrogenic levels in serum that counter the hormonal actions of estradiol and organochlorines.

Isoflavones are important dietary compounds that are consumed with the daily diet and elicit important biological actions. Here we report on the ability of genistein to partially accumulate in body depots of male mice, be released following fasting, and modulate the actions of estradiol and environmental estrogens in reproductive and nonreproductive target organs of estrogen-reporter mice (ERE-tK-luciferase). After the consumption of 50 mg/kg/day for 3 days, genistein accumulates in body compartments where it remains at functionally active levels for at least 15 days. Following 48 h of fasting, its concentration increased in serum from 99 +/- 13 to 163 +/- 17 nM. These levels are sufficient to exert an estrogenic effect in the testis and liver, as revealed by a twofold increase in luciferase gene expression. beta-Benzene-hexachloride (betaBHC) given at the concentration of 100 mg/kg/day for 3 days also accumulates in the body and is released by fasting, reaching serum levels of 176 +/- 33 nM, upregulating the luciferase gene in the liver and inhibiting its expression in the testis. When genistein was given in combination with betaBHC at doses sufficient to induce accumulation of both in body depots, the genistein mobilized by fasting reversed the action of the mobilized betaBHC in the testis. Acute administration of nutritional doses of genistein inhibited the action of estradiol and reversed the antiestrogenic action of o,p'-DDT: 1,1,1,-trichloro-2(p-chlorophenyl)-2-(o-chlorophenyl)ethane in the liver and the antiestrogenic action of betaBHC in the testis. Genistein had an additive effect with the ER agonist p,p'-DDT: 1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane in the liver. The observed effects may be relevant to a protective action of phytoestrogens against estrogen receptor-interacting pollutants as well as the dietary modulation of estradiol action.     

Protective effect of erythropoietin and its carbamylated derivative in experimental Cisplatin peripheral neurotoxicity.

PURPOSE: Antineoplastic drugs, such as cisplatin (CDDP), are severely neurotoxic, causing disabling peripheral neuropathies with clinical signs known as chemotherapy-induced peripheral neurotoxicity. Cotreatment with neuroprotective agents and CDDP has been proposed for preventing or reversing the neuropathy. Erythropoietin given systemically has a wide range of neuroprotective actions in animal models of central and peripheral nervous system damage. However, the erythropoietic action is a potential cause of side effects if erythropoietin is used for neuroprotection. We have successfully identified derivatives of erythropoietin, including carbamylated erythropoietin, which do not raise the hematocrit but retain the neuroprotective action exerted by erythropoietin. EXPERIMENTAL DESIGN: We have developed previously an experimental chemotherapy-induced peripheral neurotoxicity that closely resembles CDDP neurotoxicity in humans. The present study compared the effects of erythropoietin and carbamylated erythropoietin (50 microg/kg/d thrice weekly) on CDDP (2 mg/kg/d i.p. twice weekly for 4 weeks) neurotoxicity in vivo. RESULTS: CDDP given to Wistar rats significantly lowered their growth rate (P < 0.05), with slower sensory nerve conduction velocity (P < 0.001) and reduced intraepidermal nerve fibers density (P < 0.001 versus controls). Coadministration of CDDP and erythropoietin or carbamylated erythropoietin partially but significantly prevented the sensory nerve conduction velocity reduction. Both molecules preserved intraepidermal nerve fiber density, thus confirming their neuroprotective effect at the pathologic level. The protective effects were not associated with any difference in platinum concentration in dorsal root ganglia, sciatic nerve, or kidney specimens. CONCLUSIONS: These results widen the spectrum of possible use of erythropoietin and carbamylated erythropoietin as neuroprotectant drugs, strongly supporting their effectiveness.     

Whole body action of xenoestrogens with different chemical structures in estrogen reporter male mice

The present work tested the estrogenic activity of three weak environmental estrogens p,p'DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane], p,p'DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] and betaBHC [beta-benzene-hexachloride] in the transgenic estrogen-reporter mouse model (ERE-tK-LUC). By a time dependent analysis of the transgenic reporter expression (luciferase), we showed that all these chemicals modulated the estrogen receptors (ERs) in the whole body, although with a different efficacy and depending upon the tissue analyzed. Peak activity was registered at 16 h of treatment with 5000 microg/kg of each compound. Organochlorines are lipophylic molecules that accumulate in fat. During weight loss they are mobilized and their concentration increases in blood. We tested whether after experimental accumulation in fat tissue, followed by a 48 h period of fasting, these compounds could be modulated to reach sufficient levels to activate the ERs in target tissues. This experimental setting produced results that were different from those obtained following acute treatments. In loaded mice, fasting induced betaBHC mobilization resulted in strong ER activation in the liver, lung, eye, cerebellum, hypothalamus and cortex. p,p'DDT mobilization had no effect in these tissues, but efficiently acted in the testis, where, on the contrary, betaBHC inhibited reporter expression. During fasting, betaBHC, p,p'DDT and the metabolite p,p'DDE increased in blood concentration, from 2.7 +/- 0.36, 0.65 +/- 0.01 and 0.48 +/- 0.06 microg/ml to 9.51 +/- 1.1, 4.98 +/- 0.77 and 6.0 +/- 0.71 microg/ml, respectively. We conclude that these organochlorines modulate differently the expression of estrogen regulated genes in a tissue- and compound-specific manner and that their action is dependent on the energy balance. Moreover, we show that this mouse model is suitable to detect the estrogenic activity of chemicals with variable structures such as alkyl phenols and polychlorobiphenyls.     

Risk factors for poor renal prognosis in children with hemolytic uremic syndrome

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D^–STEC^– recovered normal renal function compared with 65%–76% of D⁺STEC⁺, D⁺STEC^– and D^–STEC⁺ patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D^– but STEC⁺ patients have a significantly better prognosis.     

Dense soft tissue 3D reconstruction refined with super-pixel segmentation for robotic abdominal surgery

Purpose

Single-incision laparoscopic surgery decreases postoperative infections, but introduces limitations in the surgeon’s maneuverability and in the surgical field of view. This work aims at enhancing intra-operative surgical visualization by exploiting the 3D information about the surgical site. An interactive guidance system is proposed wherein the pose of preoperative tissue models is updated online. A critical process involves the intra-operative acquisition of tissue surfaces. It can be achieved using stereoscopic imaging and 3D reconstruction techniques. This work contributes to this process by proposing new methods for improved dense 3D reconstruction of soft tissues, which allows a more accurate deformation identification and facilitates the registration process.

Methods

Two methods for soft tissue 3D reconstruction are proposed: Method 1 follows the traditional approach of the block matching algorithm. Method 2 performs a nonparametric modified census transform to be more robust to illumination variation. The simple linear iterative clustering (SLIC) super-pixel algorithm is exploited for disparity refinement by filling holes in the disparity images.

Results

The methods were validated using two video datasets from the Hamlyn Centre, achieving an accuracy of 2.95 and 1.66 mm, respectively. A comparison with ground-truth data demonstrated the disparity refinement procedure: (1) increases the number of reconstructed points by up to 43 % and (2) does not affect the accuracy of the 3D reconstructions significantly.

Conclusion

Both methods give results that compare favorably with the state-of-the-art methods. The computational time constraints their applicability in real time, but can be greatly improved by using a GPU implementation.

     

Painful neuropathy in subclinical hypothyroidism: clinical and neuropathological recovery after hormone replacement therapy

We describe a 60-year-old woman complaining of severe burning feet for 3 months. A neurological examination showed absent Achilles tendon reflexes; nerve conduction study demonstrated mild sensory neuropathy, and skin biopsy revealed a length-dependent loss of intraepidermal nerve fibres. Haematological exams demonstrated a subclinical hypothyroidism and hormone replacement therapy was started. Conversely, symptomatic treatments for neuropathic pain were withdrawn after few days because of side effects. During the following months, thyroid function recovered, and the patient experienced a progressive decrease of neuropathic pain intensity. At 6- and 12-month follow-ups, nerve conduction study and clinical examination were normal, whereas skin biopsy demonstrated a complete reinnervation of the epidermis. Subclinical hypothyroidism is a possible cause of sensory neuropathy and hormone replacement therapy can prompt nerve regeneration.