Listeria monocytogenes meningoencephalitis in adults: analysis of factors related to unfavourable outcome.

PURPOSE: To analyse the short-term outcome in patients with Listeria monocytogenes meningoencephalitis (LMME) to improve management and outcome. METHODS: Observational study with adult patients with LMME between 1977 and 2009 at a tertiary hospital in Barcelona, Spain. Parameters that predicted outcome were assessed with univariate and logistic regression analysis. RESULTS: Of 59 cases of LMME, 28 occurred in the last decade. Since 1987, a new protocol has been used and 29/45 patients (64%) treated since then received adjuvant dexamethasone. In patients who received this treatment there was a trend towards fewer neurological sequelae (5 vs 33%; p = 0.052). Antiseizure prophylaxis with phenytoin was administered in 13/45 (28%) patients. Seizures occurred in 7/45 (16%) patients, all in the group who did not receive phenytoin. Hydrocephalus presented in 8/59 (14%). It was never present at admission and five patients needed neurosurgical procedures. Sequelae after 3 months were present in 8/45 (18%), mostly cranial nerve palsy. Rhombencephalitis (RE) was related to the presence of neurologic sequelae (OR: 20.4, 95% CI: 1.76-236). Overall mortality was 14/59 (24%), 9/59 (15%) due to neurological causes related to hydrocephalus or seizures. Mortality was defined as early in 36% and late in 64%. In the multivariate analysis, independent risk factors for mortality were presence of hydrocephalus (OR: 17.8, 95% CI: 2.753-114) and inappropriate empirical antibiotic therapy (OR: 6.5, 95% CI: 1.201-35). CONCLUSIONS: Outcome of LMME may be improved by appropriate empirical antibiotic therapy, suspicion and careful management of hydrocephalus. Use of adjuvant dexamethasone or phenytoin in a subgroup of these patients might have a benefit.

Analysis of stroke care resources in Spain in 2012: have we benefitted from the Spanish Health System's stroke care strategy?

INTRODUCTION: The Spanish Health System's stroke care strategy (EISNS) is a consensus statement that was drawn up by various government bodies and scientific societies with the aim of improving quality throughout the care process and ensuring equality among regions. Our objective is to analyse existing healthcare resources and establish whether they have met EISNS targets. MATERIAL AND METHODS: The survey on available resources was conducted by a committee of neurologists representing each of Spain's regions; the same committee also conducted the survey of 2008. The items included were the number of stroke units (SU), their resources (monitoring, neurologists on call 24h/7d, nurse ratio, protocols), SU bed ratio/100,000 inhabitants, diagnostic resources (cardiac and cerebral arterial ultrasound, advanced neuroimaging), performing iv thrombolysis, neurovascular interventional radiology (neuro VIR), surgery for malignant middle cerebral artery (MCA) infarctions and telemedicine availability. RESULTS: We included data from 136 hospitals and found 45 Stroke Units distributed unequally among regions. The ratio of SU beds to residents ranged from 1/74,000 to 1/1,037,000 inhabitants; only the regions of Cantabria and Navarre met the target. Neurologists performed 3,237 intravenous thrombolysis procedures in 83 hospitals; thrombolysis procedures compared to the total of ischaemic strokes yielded percentages ranging from 0.3 to 33.7%. Hospitals without SUs showed varying levels of available resources. Neuro VIR is performed in every region except La Rioja, and VIR is only available on a 24h/7 d basis in 17 cities. Surgery for malignant MCA infarction is performed in 46 hospitals, and 5 have telemedicine. CONCLUSION: Stroke care has improved in terms of numbers of participating hospitals, the increased use of intravenous thrombolysis and endovascular procedures, and surgery for malignant MCA infarction. Implementation of SUs and telemedicine remain insufficient. The availability of diagnostic resources is good in most SUs and irregular in other hospitals. Regional governments should strive to ensure better care and territorial equality, which would achieve the EISNS objectives.

Matrix metalloproteinases inhibition promotes the polyfunctionality of human natural killer cells in therapeutic antibody-based anti-tumour immunotherapy.

Activation of human natural killer (NK) cells is associated with the cleavage of CD16 from the cell surface, a process mediated by matrix metalloproteinases (MMPs). In this report, we examined whether inhibition of MMPs would lead to improved NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) function. Using an in-vitro ADCC assay, we tested the anti-tumour function of NK cells with three different therapeutic monoclonal antibodies (mAbs) in the presence of MMPs inhibitor GM6001 or its control. Loss of CD16 was observed when NK cells were co-cultured with tumour targets in the presence of specific anti-tumour antibodies, and was found particularly on the majority of degranulating NK responding cells. Treatment with MMPs inhibitors not only prevented CD16 down-regulation, but improved the quality of the responding cells significantly, as shown by an increase in the percentage of polyfunctional NK cells that are capable of both producing cytokines and degranulation. Furthermore, MMPs inhibition resulted in augmented and sustained CD16-mediated signalling, as shown by increased tyrosine phosphorylation of CD3ζ and other downstream signalling intermediates, which may account for the improved NK cell function. Collectively, our results provide a foundation for combining MMPs inhibitors and therapeutic mAbs in new clinical trials for cancer treatment.

Health care resources for stroke patients in Spain, 2010: analysis of a national survey by the Cerebrovascular Diseases Study Group.

INTRODUCTION: Stroke is currently a major social health problem. For this reason, the Spanish Ministry of Health approved the Stroke National Strategy (SNS) in 2008 to improve the prevention, treatment and rehabilitation of stroke patients. This plan intends to guarantee 24-hour, 365-days neurological assistance in the whole country by the end of 2010. Our aim was to analyse the situation of stroke assistance in Spain in 2009. MATERIAL AND METHODS: A committee of neurologists practicing in the different autonomous communities (AC), and who had not participated in the preparation of the SNS, was created. A national survey was performed including the number of stroke units (SU) and their characteristics (monitoring, 24-h/7-day on-call neurology service, nursing staff ratio and the use of protocols), bed ratio of SU/100,000 people, availability of intravenous thrombolysis therapy, neurovascular intervention (NI) and telemedicine. RESULTS: We included data from 145 hospitals. There are 39 SU in Spain, unevenly distributed. The ratio between SU bed/number of people/AC varied from 1/75,000 to 1/1,037,000 inhabitants; Navarra and Cantabria met the goal. Intravenous thrombolysis therapy is used in 80 hospitals; the number of treatments per AC was between 7 and 536 in 2008. NI was performed in the 63% of the AC, with a total of 28 qualified hospitals (although only 1 hospital performed it 24h, 7 days a week in 2009). There were 3 hospitals offering clinical telemedicine services. CONCLUSIONS: Assistance for stroke patients has improved in Spain compared to previous years, but there are still some important differences between the AC that must be eliminated to achieve the objectives of the SNS.

Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis.

Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical HLA class I molecule, the gene for which is transcribed in most tissues. It has recently been reported that this molecule binds peptides derived from the signal sequence of HLA class I proteins; however, no function for HLA-E has yet been described. We show that natural killer (NK) cells can recognize target cells expressing HLA-E molecules on the cell surface and this interaction results in inhibition of the lytic process. Furthermore, HLA-E recognition is mediated primarily through the CD94/NKG2-A heterodimer, as CD94-specific, but not killer cell inhibitory receptor (KIR)-specific mAbs block HLA-E-mediated protection of target cells. Cell surface HLA-E could be increased by incubation with synthetic peptides corresponding to residues 3-11 from the signal sequences of a number of HLA class I molecules; however, only peptides which contained a Met at position 2 were capable of conferring resistance to NK-mediated lysis, whereas those having Thr at position 2 had no effect. Interestingly, HLA class I molecules previously correlated with CD94/NKG2 recognition all have Met at residue 4 of the signal sequence (position 2 of the HLA-E binding peptide), whereas those which have been reported not to interact with CD94/NKG2 have Thr at this position. Thus, these data show a function for HLA-E and suggest an alternative explanation for the apparent broad reactivity of CD94/NKG2 with HLA class I molecules; that CD94/NKG2 interacts with HLA-E complexed with signal sequence peptides derived from "protective" HLA class I alleles rather than directly interacting with classical HLA class I proteins.

NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor.

CD94 is a C-type lectin expressed by natural killer (NK) cells and a subset of T cells. Blocking studies using anti-CD94 mAbs have suggested that it is a receptor for human leukocyte antigen class I molecules. CD94 has recently been shown to be a 26-kD protein covalently associated with an unidentified 43-kD protein(s). This report shows that NKG2A, a 43-kD protein, is covalently associated with CD94 on the surface of NK cells. Cell surface expression of NKG2A is dependent on the association with CD94 as glycosylation patterns characteristic of mature proteins are found only in NKG2A that is associated with CD94. Analysis of NK cell clones showed that NKG2A was expressed in all NK cell clones whose CD16-dependent killing was inhibited by cross-linking CD94. The induction of an inhibitory signal is consistent with the presence of two immunoreceptor tyrosine-based inhibitory motifs (V/LXYXXL) on the cytoplasmic domain of NKG2A. Similar motifs are found on Ly49 and killer cell inhibitory receptors, which also transmit negative signals to NK cells.

[Preliminary study on efficacy and tolerance of a "coupage" of olive oil in patients with chronic kidney disease. Nutritonal evaluation]. / Estudio preliminar sobre eficacia y tolerancia de un "coupage" de aceite de oliva en pacientes con enfermedad renal crónica. Evaluación del estado de nutrición.

The discrepancies among data reported by using olive oil (OO) in humans appear to be due to the great differences between the different OO used. Based on structure/function relationships we have chemically optimized an OO through the rational mixture ("coupage") of several Spanish extra virgin olive oils (methodology "oHo"). Patients with chronic kidney disease (CKD) develop a progressive picture of malnutrition and inflammation that lead them to an elevated risk of cardiovascular disease. In a pilot, randomised trial the nutritional efficacy and safety of "oHo" were evaluated in 32 patients (mean age 60,8 +/- 13,2 years old; 16 women) with CKD (KDIGO stages 4-5) at predialysis. After a 7 days wash out for statins and ACE inhibitors 19 patients had "oHo" at doses of 60 mL/day (20 mL t.i.d) for 30 consecutive days, whilst 13 patients remain as a control group without "oHo". At the end of the study only patients having "oHo" showed significant increases of serum albumin (p<0.05) and not significant increases of total proteins, weight, and BMI. Total cholesterol (p<0.05) and HDL-cholesterol (p<0.01) increased with "oHo". The number of cases with pathologic HOMA-IR in the control group increased from 1 to 2 patients whilst in the "oHo" group decreased from 2 to none. No significant changes of minerals, arterial pressure, hemoglobin, and other parameters related to CKD were seen. After a 30 days follow-up in the "oHo" group all parameters came back to basal ones, excepting for blood pressure that significantly decreased (p<0,05). Tolerance was excellent and constipation significantly diminished (p<0,001) in the "oHo" group. Of importance, none of these biological changes were seen in regular consumers of other conventional olive oils (control group). These intriguing results, seen by the first time, appear to partially satisfy the recent claims ("reverse epidemiology") about the need of a more correct nutrition in CKD patients. However, these data need to be proved in more larger trials as well as in CKD patients under dialysis with harder inflammatory/malnutrition conditions.

[Fistulae or catheter for elderly who start hemodialysis without permanent vascular access?]. / Acceso vascular permanente en pacientes de edad avanzada que inician hemodiálisis: fístula o catéter?

UNLABELLED: Autologous access is the best vascular access for dialysis also in older patients and it should be mature when patient needs hemodialysis. It is not always possible. Surgeon availability and demographic characteristics of patients (age, diabetes, vascular disease...) are factors that determine primary vascular access. AIM: To analyse outcome and vascular access complications in elderly who start hemodialysis without vascular access. PATIENTS AND METHODS: All patients older than 75 years who initiated hemodialysis without vascular access between January 2000 and June 2002 were included, They were divided en two groups depending on primary vascular access. GI: arterio-venous fistulae. GIIl: Tunnelled cuffed catheter. Epidemiological and analytical data, vascular access complications related, as well as patient and first permanent vascular access survival from their inclusion in dialysis up to December 2002 were analysed and compared in both groups. RESULTS: 32 patients were studied. GI: n = 17 (4 men) and GIIl: n =1 5 (8 men), age: 79.9 +/- 3.8 and 81.7 +/- 4 years respectively (ns). There were no differences in sex and comorbidity (diabetes, ischemic heart disease, peripheral vascular disease and hypertension). It took GI 3 months to get a permanent vascular access suitable for using, while it took GIIl 1.3 months (p < 0.005) The number of temporary untunnelled catheters was higher in GI (3.35 vs 1.87 p < 0.05). Vascular access complications: 70.6% of infections occur in GI (incidence (I) = 48 infections/100 patients-year) while only 29.4% were detected in GII (I = 25 infections/100 patients-year). 70% of central venous thrombosis happen in GI (I: 25 CVT/100 patients-year) vs 30% in GIIl (I = 14.4/100 patients-year) (ns). No significant differences neither in bleeding (66.7% vs 33.3%) nor ischemia (75% vs 25%) were found. Dialysis dose (Kt/V) as well as anaemia degree were similar in both groups. Permanent vascular access survival after 2 years was 45.8% in GI and 24% in GII (ns). Patient survival was similar in GI and GII (72% vs 51% ns). CONCLUSIONS: Elderly who start hemodialysis without vascular access took longer to get a suitable permanent vascular access when arterio-venous fistulae is placed than with a tunnelled cuffed hemodialysis catheter. As a consequence, vascular access complications are larger, infection ones are the most common. In these patients a tunnelled catheter should be inserted at the time a peripheral arterio-venous access is created, in order to avoid temporary untunnelled catheters.

[Evolution of the demand for ambulatory neurological care and pathologies attended in neurology clinics in the health care district of Tortosa, Tarragona]. / Evolución de la demanda de asistencia neurológica ambulatoria y patología atendida en la consulta de neurología de la región sanitaria de Tortosa, Tarragona.

AIMS: An analysis was conducted to determine whether there were any changes in the demand for health care, demography and pathologies attended in outpatient departments within the health care district of Tortosa between 1997 and 2003. PATIENTS AND METHODS: Data about the demand for and attendance at first neurology visits over the period 1997 and from March 2003 to February 2004 was collected prospectively. Information concerning age, sex, groups of pathologies, diagnoses, rates of requests for first visits, source of the demand and destination after the visit were compared. RESULTS: Mean age rose from 49 to 56 years (p < 0.001). Patients above 70 years of age increased from 23.7% to 35.9% (p < 0.001), while in the population within the area the figure only rose from 15.8 to 17.1%. The proportion of females went up from 52 to 62% (p < 0.001). Demand (that is, the rate of requests for first visits per 1000 inhabitants per year among those over the age of 15) rose from 8.5 to 9.3, 9.8% (p = 0.03). Demand from primary care increased from 52 to 69% (p < 0.001). Cognitive disorders (6.5% and 15.9%) grew by 144.6% (p < 0.001). Headaches (23.9% and 24.1%), the largest diagnostic group, and non-neurological diagnoses (18% and 18.5%) remained unchanged (p = NS). No changes were observed in the number of discharges in the first visit: 22.8% and 21.1% (p = NS). CONCLUSIONS: The most striking results are the increase in demand (mainly from primary care), the increased age of the population attended and the notable growth in the number of cognitive disorders. These quantitative and qualitative changes in the demand increase the need for resources.

NK phenotypic markers and IL2 response in NK cells from elderly people.

Immunosenescence is a process that primarily affects the T cell compartment of the immune system, although age-associated immunological alterations have also been demonstrated in the NK cell phenotype and function. A significant expansion in the number of NK cells is found in aging. The NK cytotoxic capacity of total peripheral blood lymphocytes is also well preserved, not only in healthy elderly people but also in centenarians. However, NK cell killing of K562 is impaired when considered in a per-cell basis, and this defect is associated with defective signal transduction after activation more than a diminished conjugate formation or killing capacity. We have studied the phenotype of NK cells in elderly donors fulfilling the Senieur criteria. We have also studied the capacity of these cells to be activated by IL2 when different NK cell functions, other than cytotoxicity, are considered. Our results confirm the increased percentage of NK cells in the elderly due to the expansion of the CD56dim subset that also show an altered pattern of activation markers, whereas no differences were found in the CD56bright subset. The response of NK cells to IL2 was found to be impaired when proliferation, expression of CD69, and Ca2+ mobilization were considered, whereas TNF-alpha production was not significantly affected. These results suggest that human NK cells do not escape the aging process, although senescence have a differential effect on distinct NK cell biological functions, ranging from severe to negligible impairment, depending on the parameters considered.

Management of antiretroviral therapy.

In a very short period of time, availability of antiretroviral drugs has increased from one drug with very modest activity to 12 approved drugs with remarkable potency, particularly when used in combination. The additional availability of absolutely quantitative assays with a broad dynamic range to measure plasma HIV-1 RNA has dramatically changed the evaluation of these new antivirals and the management of patients infected with the human immunodeficiency virus (HIV). The approved antiretroviral drugs represent three novel classes including nucleoside analog reverse transcriptase inhibitors, non-nucleoside analog reverse transcriptase inhibitors as well as protease inhibitors. Clinical trials evaluating different combinations of these drugs have resulted in the generation of some basic guidelines for their appropriate use. These guidelines focus on using these drugs in complex, multidrug regimens with the ultimate goal to keep the viral burden, as measured by plasma viral RNA levels, as low as possible and for as long as possible on a drug regimen that is compatible with long-term tolerance and compliance. To maximize the potential of these new drugs and to avoid significant associated toxicities and drug interactions, the treating physician must be completely aware of the pharmacokinetics and unique antiviral properties of these drugs. This review focuses on these unique properties as well as provides general guidelines for their appropriate use.

Validated high-performance liquid chromatographic method for quantitation of neohesperidine dihydrochalcone in foodstuffs.

An analytical method to detect and quantitate neohesperidine dihydrochalcone in foodstuffs has been developed and validated in soft-drink applications. The method was shown to be sufficiently precise, accurate, selective and rugged in quantitating neohesperidine DC both at flavouring (1-5 mg/kg) and sweetening (5-50 mg/kg) levels. Applications of the method to determine neohesperidine DC in foodstuffs other than soft-drinks is also described.

Principles of antibiotic prescribing in the elderly.

Clinicians providing care to elderly patients must appreciate the subtle clinical manifestations that herald the onset of life-threatening infectious disease. Aged patients with an infection may have neither fever nor leucocytosis, making diagnosis challenging. Often, the early features of infectious disease are nonspecific and may resemble inflammatory or neoplastic processes, or there may be insufficient time to await definitive laboratory confirmation, and empirical antimicrobial treatment must be initiated. Aging involves inevitable deleterious alterations in biological processes and, in many elderly patients, this is most strongly characterised by diminished renal functional capacity. This has a major influence on antimicrobial prescribing in the elderly, because therapeutic efficacy must be achieved while minimising the risk of drug-related toxicity. Before prescribing an antibiotic to an aged patient with an infection, the clinician must be cognisant of the patient's drug allergy history and the other drugs that the patient is taking. Ignorance of potential drug-drug interactions can result in ineffective treatment or enhanced toxicity. The therapy of elderly patients with infections is being expanded. To reduce costs and enhance the efficiency of care, systems have been developed to provide antimicrobial care in the home and in long term care facilities. Home healthcare has burgeoned, and drugs that are well tolerated, have a broad spectrum of activity and are simple to administer (e.g. ceftriaxone and fluoroquinolones) appear to be eminently suitable for this therapeutic role. Physicians must also be informed of the factors responsible for the emergence of resistant bacteria that are contributing to infections in institutional and community settings. Clinicians should strive to curb inappropriate antibiotic use to stem the tide of infections that are caused by multidrug-resistant bacteria.

Medium term response to H-R erythropoietin in CAPD patients: the influence of erythropoietin plasmatic levels and the effects on peritoneal transport capacity.

Anemia of CRF has been corrected by use of H-R-EPO both in hemodialysis and CAPD patients. Long term response to subcutaneous EPO and its relationship with serum EPO levels remain to be established. Twenty-five CAPD patients treated with CAPD during 30 +/- 28 (mean +/- SD) months were included in this study. The follow-up period was 6-24 months. All patients have been on CAPD at least 6 months and their Hemoglobin (Hb) level was lower than 8.5 g/dl. Twelve patients received EPO by subcutaneous route, at doses of 20 u./Kg daily and 13 other patients at doses of 2000 units twice a week. Thereafter, these doses were adjusted to obtain a Hemoglobin level ranging 10.5-13 g/dl. In conclusion, our results suggest that the subcutaneous route for H-R-Erythropoietin can be considered as the best choice for CAPD patients. Low doses twice a week seem to improve anemia in 2 months. Later, dose adjustment should be done according to the patient's response. The improvement in nutritional status we observed suggests a new positive aspect for EPO therapy. Our data did not show changes in peritoneal function.

Staphylococcus aureus nasal carrier status (SANCS) in CAPD patients; is it induced or favored by subcutaneous rHu-erythropoietin?

Staphylococcus aureus nasal carriage status (SANCS) has been recognized as a risk factor for patients on CAPD, due to a higher probability of suffering peritoneal catheter infections. The use of subcutaneous drugs (insulin dependent diabetics, drug addicts, HD patients and antiallergic vaccines), has been associated with increased risk of SANCS. On CAPD, erythropoietin (EPO) is almost universally used by the subcutaneous route. The objective of this paper was to evaluate the incidence and prevalence of SANCS in 85 CAPD patients by means of nasal smear and the influence of SANCS on peritoneal and catheter infection rate. Patients were divided in four groups according to diabetic status and EPO treatment (mean dose 2000 u. twice a week). The prevalence of SANCS in control groups was 30% in non-diabetics and 23% in diabetics. EPO treated patients showed a prevalence of SANCS of 39% in non-diabetics and 45% in diabetics due to the presence of 7 and 5 carrier patients respectively. SANCS patients (29% of the population), suffered 45% of peritonitis and 42% of exit-site infections caused by S. aureus. In a prospective part of the study, there was no difference in the frequency of developing positive cultures among EPO and control (30% of patients). No male EPO treated patients developed SANCS. We conclude that it is necessary to monitor S. aureus nasal carrier status periodically in CAPD patients especially in women. Whether or not subcutaneous erythropoietin treatment is implicated pathogenetically with SANCS, is not clarified by our data because of the frequent spontaneous appearance of SANCS among CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of the anemia with human recombinant erythropoietin in CAPD patients.

Three homogenous groups of CAPD patients, all of them with plasma hemoglobin levels lower than 8 g/dl were studied. Group 1 included 8 patients who received EPO by the subcutaneous route (s.c), at doses of 20 u./kg daily; this dose was reduced when a hemoglobin level higher than 10.5 g/dl was reached. Group 2 included 7 patients treated with EPO by subcutaneous route but at doses of 2000 units twice a week. Group 3 was constituted by 4 patients receiving EPO by intraperitoneal route (i.p.), at doses of 4000 u/day, three days a week. All patients showed an increase in hematocrit and Hb levels after three months of treatment, but the mean EPO dose was quite different comparing the groups, maintaining the reached levels at the 9th month; reticulocyte count increased only during the first month. The rest of clinical and biochemical parameters did not suffer any significant modifications. Our features showed a higher profit, that is, higher increase in Hb level with lower dose of EPO in the s.c. group in respect to i.p. group. Furthermore, we have registered a marked increase in the frequency of exogenous peritonitis in these particular patients while using i.p. EPO. In conclusion, we feel that subcutaneous route for H-R-Erythropoietin is an ideal way for this treatment, resulting in a more adequate profit ratio than that described in hemodialysis patients. The intraperitoneal route is more expensive and risky for the peritoneum, probably as a consequence of the increase of manipulations.

[Acute renal failure secondary to hepatic veno-occlusive disease in a bone marrow transplant patient]. / Insuficiencia renal aguda secundaria a enfermedad veno-oclusiva hepática en un paciente con trasplante de médula ósea.

Acute renal failure following bone marrow transplantation is a frequent complication with an incidence ranging 15-30% and with high rates of morbidity and mortality. Numerous potential etiologies can be implicated as chemotherapy regimen, use of nephrotoxic antibiotics, sepsis-induced damage, cyclosporine toxicity and other especific pathologies as graft-v-host disease or veno-occlusive disease of the liver. We report the case of a 41-year-old man who underwent autologous peripheral blood stem cell transplantation and developed and acute renal failure secondary to a fatal veno-occlusive disease of the liver. Incidence, potential predisposing factors, outcome and possibilities of treatment are reviewed.

[Hemodialysis with 2.5 mEq/L of calcium in relative hypoparathyroidism: long-term effects on bone mass]. / Hemodiálisis con 2,5 mEq/L de calcio en el hipoparatiroidismo relativo: efectos a largo plazo en la masa ósea.

Low PTH secretion is known to be associated with Adynamic Bone Disease (ABD). Positive balance calcium by CaCO3 or dialysate calcium (DCa) might play a role in the parathyroid gland suppression and a decrease in DCa to 2.5 mEq-l or lower has been proposed. The long-term effect of this procedure on bone mineral density (BMD) has not been established. The aim was to evaluate the effect of lowering dialysate calcium on bone mass in patients with relative hypoparathyroidism. We studied 20 patients with intact PTH below 120 pg/ml, using 3 mEq/l DCa and CaCO3 as sole phosphate binder. Sex: 10M/10F. Age: 57 +/- 13 yrs. Months on dialysis: 40 +/- 29. None of them had previous renal transplantation, parathyroidectomy nor aluminic toxicity. BMD of the lumbar spine was assessed by Quantitative Computed Tomography (QCT). They were randomized in two groups (GI and GII), with similar age, sex, and time on dialysis. There were no difference in BMD, levels of intact PTH, serum calcium, phosphate and AP (Alkaline Phosphatase) GI (n = 11; 5M/6F) was transferred to 2.5 mEq/l DCa and GII (n = 9; 5M/4F) continued using 3 mEq/l. BMD was measured one year later. Calcium, phosphate and AP were measured monthly and PTH every three months. After one year of hemodialysis with 2.5 mEq/l of calcium dialysate, BMD showed a significant reduction. BMD mg/cc Baseline (B): 146.09 +/- 54; Final (F): 125.42 +/- 54 (p < 0.01). Z-score B: 0.13 +/- 1.89; F: -0.68 +/- 1.89 (p < 0.05). GII did no show change. The mean change: GI: -15 +/- 13%, GII: 1.28 +/- 17% (p < 0.05); Z-Score GI: -0.81 +/- 0.92, GII: 0.27 +/- 0.67 (p < 0.01). A separate analysis of BMD in both sexes (GI) revealed a tendency for females to lose more bone mineral than males: F: = 17.12 +/- 7.1%. M: -12.23 +/- 18.6% (ns). GI: PTH and AP increased: PTH B: 38.75 +/- 41; F: 99 +/- 69 (p < 0.01); AP: B: 118.4 +/- 47; F: 152 +/- 38 (p < 0.01). GII: PTH B: 53.8 +/- 28; F: 79 +/- 5 (ns). AP: B: 125.1 +/- 36; F: 138 +/- 38 (ns). The rate of BMD loss inversely correlated with the increase of PTH (r = -0.61, p < 0.01). Serum calcium and phosphate did not change. In GI CaCO3 doses were: B: 332 +/- 261; F: 537 +/- 260 (as grams of element calcium, every three months, p < 0.01). By multiple lineal regression only delta PTH and DCa were predictors of greater BMD loss. In conclusion, the use of 2.5 mEq/l dialysate calcium resulted in: 1) Loss of trabecular vertebral bone mass. 2) Increase in PTH secretion and biochemical markers of bone formation. 3) A greater CaCO3 dose.

[Beneficial effect of AN69 membranes on anemia in hemodialyzed patients]. / Efecto beneficioso de las membranas de AN69 sobre la anemia de los pacientes en hemodiálisis.

UNLABELLED: Biocompatible hemodialysis membranes induce a smaller inflammatory response in hemodialysis patients, and remove a larger amount of higher molecular weight retention products, then cellulose membranes. These phenomena could improve uremic anemia in hemodialysis patients. The objective was to evaluate the effects of biocompatible AN69 membranes on anemia in hemodialysis patients. Twenty-five stable patients undergoing hemodialysis with cuprophane membrane for more than 6 months were studied prospectively. These patients were stratified in 2 groups. Group I (GI): 14 patients switched over to a more biocompatible dialyzer (from cuprophan to AN69) and Group II (GII): 11 patients continued treatment with the same cuprophan membrane. The study lasted 5 months. Baseline hematocrit (%), ferritin (ng/mL), transferrin saturation (%), KTV, PCR (g/kg/day) and dose of erythropoietin (EPO) (UI/week) were measured and were revised monthly. Target hematocrit was 33%-35%. A significant increase of hematocrit became obvious after 2 months in GI without changes in dose of EPO and intensity of dialysis, meanwhile GII remains stable. CONCLUSION: Hemodialysis using AN69 membranes increases hematocrit without modifying intensity of dialysis.

[Rhabdomyolysis and acute renal failure secondary to statins]. / Rabdomiolisis y fracaso renal agudo secundario a estatinas.

Statins are competitive inhibitors of hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase and are the most commonly used drugs to treat hyperlipidaemia. Muscle toxicity is an adverse effect reported with a low incidence and rarely associated with acute renal failure due to rhabdomyolysis. We describe two patients with chronic renal failure treated with pravastatin and simvastatin who suffered rhabdomyolysis and acute renal failure. One patient started pravastatin several days after cessation of bezafibrate and developed acute renal failure without needing dialysis. The other was treated with simvastatin three years ago and suffered rhabdomyolysis when renal function was impaired after indomethacin was prescribed for backache. He needed hemodialysis because of acute cardiac failure and died from a respiratory infection while on mechanical ventilation. Myopathy was reversible in both patients. We recommend starting statins with the lower doses in chronic renal failure and monitoring muscle enzymes when renal function changes or when new drugs with potential interactions are prescribed.