Chondroitin sulphate inhibits NF-κB activity induced by interaction of pathogenic and damage associated molecules.

OBJECTIVE: To evaluate the anti-inflammatory mechanism of action of Chondroitin Sulphate (CS). DESIGN: THP-1 macrophages were cultured with a range of sizes and concentrations of HA fragments with TLR4 (LPS in a physiologically relevant concentration determined by analyses of sera of a community clinic ascertained knee osteoarthritis (OA) cohort) or TLR2 (heat killed listeria bacteria) agonists and varying concentrations of CS in a physiologically relevant range (10-200 µg/ml). We measured IL-1ß release, intracellular IL-1ß, proIL-1ß, caspase-1 and NF-κB activity and DNA binding activity of NF-κB transcription factors from nuclear and cytoplasmic extracts. RESULTS: Serum LPS was significantly associated with radiographic knee joint space narrowing (JSN) (P = 0.02) in the OA cohort (n = 40). The priming dose of LPS used for these experiments (10 ng/ml) was below the lowest serum concentration of the OA cohort (median 47.09, range 14.43-81.36 ng/ml). Priming doses of LPS and HA fragments alone did not elicit an inflammatory response. However, primed with LPS, HA fragments produced large dose-dependent increases in IL-1ß that were inhibitable by CS. CS did not inhibit caspase-1 activity but in physiologically achievable concentrations, attenuated NF-κB activity induced by either the TLR4 (LPS 1000 ng/ml) or TLR2 agonists alone or in combination with HA fragments. LPS induced and CS significantly reduced activity of canonical NF-κB transcription factors, p65, p50, c-Rel and RelB. CONCLUSIONS: Subinflammatory concentrations of pathogenic (LPS, listeria) and damage associated (HA) molecules interact to induce macrophage-related inflammation. CS works upstream of the inflammasome by inhibiting activation of NF-κB transcription factors.

Catastrophic flood of the Mediterranean after the Messinian salinity crisis.

The Mediterranean Sea became disconnected from the world's oceans and mostly desiccated by evaporation about 5.6 million years ago during the Messinian salinity crisis. The Atlantic waters found a way through the present Gibraltar Strait and rapidly refilled the Mediterranean 5.33 million years ago in an event known as the Zanclean flood. The nature, abruptness and evolution of this flood remain poorly constrained. Borehole and seismic data show incisions over 250 m deep on both sides of the Gibraltar Strait that have previously been attributed to fluvial erosion during the desiccation. Here we show the continuity of this 200-km-long channel across the strait and explain its morphology as the result of erosion by the flooding waters, adopting an incision model validated in mountain rivers. This model in turn allows us to estimate the duration of the flood. Although the available data are limited, our findings suggest that the feedback between water flow and incision in the early stages of flooding imply discharges of about 10(8) m(3) s(-1) (three orders of magnitude larger than the present Amazon River) and incision rates above 0.4 m per day. Although the flood started at low water discharges that may have lasted for up to several thousand years, our results suggest that 90 per cent of the water was transferred in a short period ranging from a few months to two years. This extremely abrupt flood may have involved peak rates of sea level rise in the Mediterranean of more than ten metres per day.

Eating through time: Understanding dietary practices across late prehistory in the northeastern Iberian Peninsula.

OBJECTIVE: This study seeks to contribute to the current understanding of dietary variation in the late Prehistory of the northeastern Iberian Peninsula by examining buccal dental microwear patterns alongside archeological data from the same populations. MATERIALS AND METHODS: Teeth from 84 adult individuals from eight distinct samples spanning the Middle-Late Neolithic to the Middle Bronze Age (Cova de l'Avi, Cova de Can Sadurní, Cova de la Guineu, Cova Foradada, Cova del Trader, Roc de les Orenetes, Cova del Gegant, Cova dels Galls Carboners) were analyzed using optical microscopy to examine buccal dental microwear patterns. RESULTS: The analysis did not reveal clear chronological contrasts in the dietary habits of these samples. Nevertheless, significant differences emerged among the samples, leading to their classification into two distinct sets based on the abrasiveness of the diet informed by the microwear patterns. These findings offer similarities and differences among samples in the Iberian Peninsula, shedding light on the diverse lifestyles of these individuals. DISCUSSION: Integrating our new results with other available proxies points to a multifaceted specialization in dietary patterns among these samples, influenced by factors such as habitat, resource selection, and available technology. By contextualizing the results within the broader context of the Iberian Peninsula, this research discerns shared characteristics and distinctive adaptations in the dietary practices and subsistence strategies of these groups. Ultimately, this study contributes to a deeper understanding of the intricate interplay between culture and environment in shaping human diets throughout late Prehistory.

Antioxidant, antiinflammatory and neuroprotective actions of chondroitin sulfate and proteoglycans.

The antiinflammatory and antiapoptotic effects of chondroitin sulfate (CS) are being used to treat osteoarthritis. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the central nervous system (CNS). We review here such evidence. Perineuronal nets (PNNs) formed by chondroitin sulfate proteoglycans (CSPGs) may have a neuroprotective action against oxidative stress potentially involved in neurodegeneration. On the other hand, in human neuroblastoma SH-SY5Y cells CS has antioxidant and neuroprotective effects by activating the signaling pathway PKC/PI3K/Akt and inducing the antioxidant enzyme hemoxygenase-1. Consistent with this is the observation that protein kinase C (PKC) blockade overcomes inhibition of neurite outgrowth elicited by CSPGs. In addition, CS protects cortical neurons against excytotoxic death by phosphorylation of intracellular signals and the suppression of caspase-3 activation. Of interest is the finding that a disaccharide derived from CSPG degradation (CSGP-DS) protects neurons against toxicity both in vitro and in vivo. Furthermore, CSGP-DS efficiently protects against neuronal loss in experimental autoimmune encephalomyelitis and uveitis, decreases secretion of tumor necrosis factor-alpha (TNF-alpha) and block necrosis factor kappa B (NF-kappaB) translocation. In conclusion, CS may have neuroprotective properties linked to its antioxidant and antiinflammatory effects.

Effectiveness of chondroitin sulphate in patients with concomitant knee osteoarthritis and psoriasis: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The aim of the trial was to assess the efficacy of chondroitin sulphate (CS) on symptomatic knee osteoarthritis (OA) associated to psoriasis. METHODS: In this randomized, double-blind, placebo (PBO)-controlled clinical trial 129 patients with symptomatic knee OA and concomitant psoriasis were randomized into two groups receiving 800 mg daily of CS or PBO for 3 months. The primary efficacy outcome for knee OA was the Huskisson's visual analogue scale (VAS) and for psoriasis was the Psoriasis Area and Severity Index (PASI). Additionally, other secondary efficacy criteria for both conditions were assessed. RESULTS: After 3 months of treatment, CS was more effective than PBO, relieving pain VAS (CS -26.9+/-24.8 vs PBO -14.23+/-20.8mm, P<0.01), decreasing the Lequesne index (CS -4.8+/-3.4 vs PBO -3.3+/-3.5, P<0.05) and reducing the number of patients using acetaminophen as rescue medication (CS 43% vs PBO 64%, P<0.05). Regarding PASI, Overall Lesion Severity Scale and Physician's Global Assessment of Change no statistically significant changes were detected in front of PBO. However, CS improved plantar psoriasis compared to PBO (CS 87% vs PBO 27%, P<0.05). Quality of life improved significantly in CS-treated patients according to the Short Form-36 health survey and the Dermatology Life Quality Index (DLQI). CS tolerability was excellent. Adverse events were infrequent and evenly distributed among groups. The incidence of psoriatic flares did not increase after treatments. CONCLUSIONS: This study confirms the efficacy and safety of CS as a symptomatic slow-acting drug in patients with knee OA and shows that CS improves plantar psoriasis. The use of CS could represent a special benefit in patients with both pathologies since non-steroidal anti-inflammatory drugs have been reported to induce or exacerbate psoriasis.

Deep Seated Density Anomalies Across the Iberia-Africa Plate Boundary and Its Topographic Response.

The modes in which the lithosphere deforms during continental collision and the mechanisms involved are not well understood. While continental subduction and mantle delamination are often invoked in tectonophysical studies, these processes are difficult to be confirmed in more complex tectonic regions such as the Gibraltar Arc. We study the present-day density and compositional structure of the lithosphere along a transect running from South Iberia to North Africa crossing the western Gibraltar Arc. This region is located in the westernmost continental segment of the African-Eurasian plates, characterized by a diffuse transpressive plate boundary. An integrated and self-consistent geophysical-petrological methodology is used to model the lithosphere structure variations and the thermophysical properties of the upper mantle. The crustal structure is mainly constrained by seismic experiments and geological data, whereas the composition of the lithospheric mantle is constrained by xenolith data. The results show large lateral variations in the topography of the lithosphere-asthenosphere boundary. We distinguish different chemical lithospheric mantle domains that reproduce the main trends of the geophysical observables and the modeled P and S wave seismic velocities. A sublithospheric body colder than the surrounding mantle is needed beneath the Betics-Rif to adjust the measured potential fields. We link this body to the Iberian slab localized just to the east of the profile and having some effect on the geoid and Bouguer anomalies. Local isostasy allows explaining most of the topography, but an elastic thickness higher than 10 km is needed to explain local misfits between the Atlas and the Rif Mountains.

Effect of chondroitin sulphate in a rabbit model of atherosclerosis aggravated by chronic arthritis.

BACKGROUND AND PURPOSE: Among the agents employed to manage osteoarthritis, chondroitin sulphate (CS) is a natural glycosaminoglycan with an anti-inflammatory effect on joint cells. CS might also influence the inflammatory component of atherosclerosis. Our aim was to examine the effect of CS administration on vascular injury and on markers of systemic inflammation in a rabbit model of atherosclerosis aggravated by systemic inflammation provoked by chronic antigen-induced arthritis. EXPERIMENTAL APPROACH: Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidaemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intraarticular injections of ovalbumin in previously immunized rabbits. A group of these rabbits were treated prophylactically with CS (100 mg kg(-1)day(-1)) and when the animals were killed, serum and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, femoral arteries and thoracic aorta were used for gene expression studies and histological examination. KEY RESULTS: CS administration reduced the concentration of the proinflammatory molecules C-reactive protein and IL-6 in serum. Likewise, CS inhibited the expression of CCL2/monocyte chemoattractant protein (MCP)-1 and cyclooxygenase (COX)-2 in PBMC, and reduced the nuclear translocation of nuclear factor-kappaB. In the femoral lesion, CS also diminished the expression of CCL2 and COX-2, as well as the ratio of the intima/media thickness. Moreover, CS decreased the percentage of rabbits with atherosclerosis and chronic arthritis that developed vascular lesions in the aorta. CONCLUSIONS AND IMPLICATIONS: These findings suggest that CS treatment may to some extent impede the progression of atherosclerosis.

Size-scaling behaviour of the electronic polarizability of one-dimensional interacting systems.

Electronic polarizability of finite chains is accurately calculated from the total energy variation of the system produced by small but finite static electric fields applied along the chain direction. Normalized polarizability, that is, polarizability divided by chain length, diverges as the second power of length for metallic systems but approaches a constant value for insulating systems. This behaviour provides a very convenient way to characterize the wave-function malleability of finite systems as it avoids the need of attaching infinite contacts to the chain ends. Hubbard model calculations at half filling show that the method works for a small U = 1 interaction value that corresponds to a really small spectral gap of 0.005 (hopping t = -1 is assumed). Once successfully checked, the method has been applied to the long-range hopping model of Gebhard and Ruckenstein showing 1/r hopping decay (Gebhard and Ruckenstein 1992 Phys. Rev. Lett. 68 244; Gebhard et al 1994 Phys. Rev. B 49 10926). Metallicity for U values below the reported metal-insulator transition is obtained but the surprise comes for U values larger than the critical one (when a gap appears in the spectral density of states) because a steady increase of the normalized polarizability with size is obtained. This critical size-scaling behaviour can be understood as corresponding to a molecule which polarizability is unbounded. We have checked that a real transfer of charge from one chain end to the opposite occurs as a response to very small electric fields in spite of the existence of a large gap of the order of U for one-particle excitations. Finally, ab initio quantum chemistry calculations of realistic poly-acetylene chains prove that the occurrence of such critical behaviour in real systems is unlikely.

Chondroitin sulfate and hyaluronic acid (500-730 kda) inhibit stromelysin-1 synthesis in human osteoarthritic chondrocytes.

Chondroitin sulfate (CS) and 500-730 kDa hyaluronic acid (HA) are symptomatic slow-acting drugs for the treatment of osteoarthritis (OA). In addition, a growing body of evidence suggests a role for CS and this specific HA as modifiers of the course of OA. The therapeutic efficacy of CS and HA lies in their different mechanisms of action. Stromelysin-1 (metalloprotease-3 [MMP-3]) is a cartilage proteolytic enzyme, which induces cartilage destruction and acts as a mediator of the inflammatory response. However, there are few studies evaluating the in vitro effect of CS and HA on MMP-3 synthesis in human chondrocyte cultures from OA patients. Thus, the aim of the present study was to analyze the effect of CS and HA (500-730 kDa) on MMP-3 synthesis induced by interleukin-1beta (IL-1beta) in chondrocytes from patients with hip OA. Chondrocyte cultures were incubated for 48 h with IL-1beta (2.5 ng/ml) in the absence or presence of different HA 500-730 kDa (Hyalgan, Bioibérica Farma, Barcelona, Spain) concentrations, or alternatively, CS (Condro.san, Bioibérica Farma) at concentrations of 10, 50, 100, 150, 200 and 1,000 microg/ml. The results revealed that both CS and HA (500-730 kDa) inhibited MMP-3 synthesis induced by IL-1beta in human OA chondrocytes. Specifically, CS and HA (500-730 kDa) reduced MMP-3 expression levels at all tested concentrations. Therefore, our study provides new data on the mechanism of action of these drugs, which could help to explain their clinical efficacy in OA patients.

Can model Hamiltonians describe the electron-electron interaction in π-conjugated systems? PAH and graphene.

Model Hamiltonians have been, and still are, a valuable tool for investigating the electronic structure of systems for which mean field theories work poorly. This review will concentrate on the application of Pariser-Parr-Pople (PPP) and Hubbard Hamiltonians to investigate some relevant properties of polycyclic aromatic hydrocarbons (PAH) and graphene. When presenting these two Hamiltonians we will resort to second quantisation which, although not the way chosen in its original proposal of the former, is much clearer. We will not attempt to be comprehensive, but rather our objective will be to try to provide the reader with information on what kinds of problems they will encounter and what tools they will need to solve them. One of the key issues concerning model Hamiltonians that will be treated in detail is the choice of model parameters. Although model Hamiltonians reduce the complexity of the original Hamiltonian, they cannot be solved in most cases exactly. So, we shall first consider the Hartree-Fock approximation, still the only tool for handling large systems, besides density functional theory (DFT) approaches. We proceed by discussing to what extent one may exactly solve model Hamiltonians and the Lanczos approach. We shall describe the configuration interaction (CI) method, a common technology in quantum chemistry but one rarely used to solve model Hamiltonians. In particular, we propose a variant of the Lanczos method, inspired by CI, that has the novelty of using as the seed of the Lanczos process a mean field (Hartree-Fock) determinant (the method will be named LCI). Two questions of interest related to model Hamiltonians will be discussed: (i) when including long-range interactions, how crucial is including in the Hamiltonian the electronic charge that compensates ion charges? (ii) Is it possible to reduce a Hamiltonian incorporating Coulomb interactions (PPP) to an 'effective' Hamiltonian including only on-site interactions (Hubbard)? The performance of CI will be checked on small molecules. The electronic structure of azulene and fused azulene will be used to illustrate several aspects of the method. As regards graphene, several questions will be considered: (i) paramagnetic versus antiferromagnetic solutions, (ii) forbidden gap versus dot size, (iii) graphene nano-ribbons, and (iv) optical properties.

Extrahepatic metabolism of frusemide in anaesthetized rabbits.

1. Frusemide is removed from the body by biotransformation and renal secretion, but since frusemide metabolism is not altered in patients with hepatic cirrhosis, the role of the liver may be questioned. The aim of the study was to investigate which organs contribute to the first-pass metabolism and systemic clearance of frusemide. 2. Groups of anaesthetized New Zealand rabbits were administered frusemide proximally (prox) and distally (dist) to different organs, and blood was sampled from the abdominal aorta. The area under frusemide plasma concentrations-time curve (AUC0-infinity) was calculated and frusemide extraction by an organ was estimated from the ratio (AUCdist-AUCprox)/AUCdist. The small intestine extracted 83% of the absorbed dose of frusemide but the first-pass uptake by the liver and lungs was negligible. 3. To assess the contribution of the intestine and the kidneys to the systemic clearance of frusemide, it was injected into the jugular vein and blood was sampled proximal and distal to each organ. The kidneys extracted 24% of frusemide circulating in the renal arteries; on the other hand, the ability of the intestine to extract frusemide from the systemic circulation could not be detected. 4. The lungs did not metabolize frusemide in vitro; the rate of metabolism of frusemide in vitro by kidneys was similar to that estimated in the intestine, and both rates were faster (P < 0.05) than that observed in the liver. 5. It is concluded that in rabbits, presystemic metabolism of frusemide is carried out by the intestine, and that systemic clearance of frusemide is mainly performed by the kidneys, although other organs, such as the intestine and the liver, must contribute to it.

Antioxidant status in a squirrel monkey (Saimiri sciureus) with chronic pancreatitis and degenerative myopathy.

A squirrel monkey (Saimiri sciureus) presented with wasting, vomiting and diarrhoea. Haematology revealed elevation of creatinine phosphokinase, lactic dehydrogenase, alanine aminotransferase, amylase and lipase, together with azotaemia and hypoalbuminaemia. Prominent findings were chronic pancreatitis with acinar and ductal plugs, granulomatous and necrotizing peripancreatic steatitis, degenerative myopathy, testicular atrophy, candidiasis and bacterial necrotizing glossitis. Antioxidant analyses revealed low concentrations of serum vitamin E (and apparently A), hepatic selenium and hair zinc. Pancreatitis may have caused malabsorption and maldigestion, associated with deficiency of multiple antioxidants.

Butterfat in rations for pigs fed skimmed whey: Growth rate, feed conversion, economics, carcass evaluation and fat quality.

An experiment was carried out, using 81 castrated male pigs, to estimate the effect of adding butterfat (70% fat, 30% buttermilk), as an energy supplement, to the rations of pigs fed skimmed whey ad libitum. The rations were fed daily in a restricted amount and butterfat added to rations at two levels: T-2 and T-3, 140 and 280 g/day/animal, respectively. In treatment T-1, no butterfat was added. The pigs were weighed every 21 days until they reached average liveweights of 100 (group 1) or 120 kg (group 2), when they were killed for carcass studies. There were significant differences in liveweight gains and feed conversion for the pigs supplemented with butterfat. A negative result, from an economical point of view, was obtained due to the relatively high price of the butterfat. A higher yield of carcass weight on field liveweight was obtained in treatments T-2 and T-3, reflecting the higher degree of fatness. The relative carcass length, muscle depth and percentage of defatted ham were higher in T-1. Conversely, the relative depth of fat was more marked in the groups and treatments that consumed butterfat with their rations. Both groups of T-1 yielded the highest percentage of muscle and the lowest of fat in their carcasses, the differences from T-2 and T-3 being significant. T-2 and T-3 did not differ significantly from one another. There were significant differences in the fatty acid composition due to sampling location. The differences due to treatment were statistically significant in respect of the concentrations of 14:0, 16:1, 17:0, 17:1, 18:0 and 18:1 fatty acids. The unusually low concentration of 18:2 in the dissected fat tissues produces high quality porcine fats, for use in manifactured and prepared foods.

[New therapy for Peyronie's disease: superoxide dismutase by ionization. Comparison with an earlier classical series]. / Nouveau traitement de la maladie de La Peyronie: la superoxyde dismutase par ionisations. Comparaison avec une série ancienne classique.

Due to the poor results obtained in the treatment of Peyronie's disease by ionophoresis and ultrasound, using the classical buffer solution of the cortisone thiomucase type, the authors have experimented ionophoresis with a new product: orgoteine a dismutase superoxide. Austrian authors have already demonstrated the value of this product. Its mechanism of action is still uncertain but it has an experimentally well demonstrated antiinflammatory activity. The good results are obvious not only on the pain, but also on the induration and incurvation, permitting the resumption of sexual intercourse in more than 75% of cases.

[Value of adjuvant chemotherapy in infiltrating tumors of the bladder]. / Intérêt d'une chimiothérapie adjuvante dans les tumeurs infiltrantes de la vessie.

Two populations of patients with invasive epithelial bladder carcinoma are considered. Group A includes 26 patients with P greater than or equal to 2 MO lesions who, prospectively, received adjuvant postoperative chemotherapy with methotrexate, adriamycin, 5 fluoro-uracil and cisplatinum. Group B includes 24 patients treated in the same institution but without chemotherapy. In group A, 6 patients died from distant metastases. One death was not related to disease progression. The 3-year-disease-free survival rate is 67.7%. Acceptability and tolerance of chemotherapy are satisfactory. In group B, a retrospective analysis after the same radiosurgical approach found in one patient a regional recurrence leading to death 5 years after diagnosis. Twenty patients died from distant metastases. The 3-year-disease-free survival rate is 18.5%. No treatment related deaths occurred in either group. Although biased selection in such conditions is inevitable, the benefit of adjuvant chemotherapy looks rather impressive and encouraging.

[Value of an ostomy club for patient followup after total cystectomy]. / Intérêt d'un club d'urostomisés pour le suivi des malades après cystectomies totales.

Patients using stoma appliances after a total cystectomy undergo a considerable psychological shock. The creation of groups of ostomates helps in the dissemination of information concerning the use of stomal appliances and in the building up of user confidence, thereby facilitating a return to a normal everyday life. Our main aim is to organize regular meetings of stoma appliance users, with frequent visits from former cystectomy patients. The usefulness of these clubs has been amply demonstrated by the introduction of the training of enterostomal therapists, the collaboration offered by the appliance manufacturers and the interest manifested by surgeons and urologists.

[A bifid ureter with a blind branch. Apropos of a case]. / L'uretère bifide à branche borgne. A propos d'un cas.

A case of bifid ureter with a blind branch exhibiting no parenchymal connections is reported. Diagnosis was established by excretory urography. Less than twenty cases diagnosed in this way have been reported previously, the embryogenesis of the normal and bifid ureter is reviewed. Symptoms, which are inconsistently present, are described. Excision of the blind branch is required and should be accompanied with antireflux reimplantation of the normal ureter if called for.

[The limits of conventional imagery in urology: the prostate and the kidney]. / Les limites de l'imagerie conventionnelle en urologie: prostate et rein.

Despite the progress in conventional medical imaging it retains certain limitations particularly in two areas: 1) the detection of prostatic cancer: the specificity and sensitivity of transrectal ultrasonography are too poor to justify the use of this modality for screening or for diagnosis. 2) Small renal tumours, which are detected increasingly frequently on ultrasound examinations. Computed tomography is the most reliable examination for determining the benign or malignant nature of the lesion. The other modalities are disappointing and an excessive repetition of medical imaging should be avoided.

[Value of radiotherapy in the treatment of prostatic cancers in the initial stages. Apropos of 111 cases]. / Intérêt de la radiothérapie dans le traitement des cancers de la prostate. aux stades initiaux. A propose de 111 cas.

The authors report on their experience with high energy radiation therapy in early-stage (I/II) carcinomas of the prostate. Among 191 cases of biopsy-proved carcinomas of the prostate, there were 111 stage I and II tumors, including 83 T1, T2 intracapsular tumors. 78 of the 111 patients received curative radiation therapy. Delivered doses did not exceed 65 to 70 grays to the prostate and 50 grays to the pelvis. High energy radiation was used. Extension of the lesions was determined using lymphography, abdominal and pelvic CT, and surgical removal of lymph nodes. Among the 78 irradiated patients, success rates at five years were 65% for the 52 T1-T2 tumors and 38% for the 26 T3 N0 tumors. Selection of patients, technical conditions and long term results are discussed, as well as the problems met in determining the stage of the tumor accurately. High energy radiation therapy can control localized carcinomas with a satisfactory quality of survival.

[Primary vesico-uretero-renal reflux in adults: therapeutic outcome. Apropos of 68 cases]. / Reflux vésico-urétéro-rénal primitif de l'adulte: évolution thérapeutique. A propos de soixante-huit observations.

The authors compare two series of adult patients presenting with primary vesico-uretero-renal reflux. The first series was treated before 1974, and the second, over the past ten years. The salient feature of this comparison is the reduction in the number of renal failures. More systematic investigation of the reflux highlights a greater number of cases which will evolve without further impairment of renal function. This point has a considerable bearing on operative indications.