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The incidence of Gram-positive bloodstream infections has been increasing steadily. The virulence of coagulase-negative staphylococci is based mainly on their ability to produce biofilms, and thus cause infections of intravascular devices and foreign bodies, which must be removed to resolve the infection. Staphylococcus aureus is the leading cause of endocarditis, and it is important to recognize patients at risk of the complications of S. aureus bloodstream infections. The rate of meticillin resistance is higher in healthcare-related infections, although clones of community-acquired meticillin-resistant S. aureus carrying the Panton-Valentine leukocidin have recently emerged. Vancomycin minimum inhibitory concentration (MIC) creep gives cause for concern, and MICs >1 microg/mL are associated with higher failure rates and mortality in patients with S. aureus bacteraemia treated with vancomycin. Daptomycin should be considered the optimal empirical treatment for S. aureus bloodstream infections in settings with medium to high prevalence of meticillin-resistant Staphylococcus aureus infections. Enterococci are the third leading cause of Gram-positive bacteraemia in our institution. Management of this disease is difficult because of its intrinsic resistance to antibiotics, mainly in Enterococcus faecium infections. The recently described synergism of ampicillin plus ceftriaxone is a good therapeutic option for Enterococcus faecalis bacteraemia and endocarditis caused by high-level aminoglycoside-resistant strains.

This article aims to review herpes simplex, herpes zoster and cytomegalovirus and to summarize the main characteristics of the antiviral drugs available to treat those infections. The review of each drug focuses on dosage according to the treatment indication, dose adjustment in patients with impaired renal or hepatic function, the main pharmacokinetic features, and the most significant adverse effects and drug interactions.

BACKGROUND: Solid-organ transplant (SOT) recipients are classically considered to be at increased risk for listeriosis. However, risk factors for this infection have not been assessed. METHODS: We carried out a multicenter, matched case-control study (1:2 ratio) from January 1995 through December 2007. Control subjects were matched for center, transplant type, and timing. Conditional logistic regression was performed to identify independent risk factors. Clinical features and outcomes for all case patients were reviewed. RESULTS: Thirty patients (0.12%) with cases of listeriosis were identified among 25,997 SOT recipients at 15 Spanish transplant centers. In a comparison of case patients with 60 matched control subjects, the following independent risk factors for listeriosis were identified: diabetes mellitus (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.6-19.6; ), P = .007 history of cytomegalovirus infection or disease within the preceding 6 months (OR, 35.9; 95% CI, 2.1-620; P = .014), receipt of high-dose prednisone within the preceding 6 months (OR, 6.2; 95% CI, 1.8-21.1; P = .003), and trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (OR, 0.07; 95% CI, 0.006-0.76; P = .029). Twenty-six patients (86.7%) had bacteremia, and 7 had shock at presentation. Other manifestations included meningoencephalitis (10 cases), spontaneous peritonitis (2), pleural empyema (1), brain abscesses (1), and liver abscesses (1). The 30-day mortality rate was 26.7% (8 of 30 patients died). CONCLUSIONS: Listeriosis in SOT recipients is uncommon but causes high mortality. Diabetes mellitus, cytomegalovirus infection or disease, and receipt of high-dose steroids are independent risk factors for this infection, whereas TMP-SMZ prophylaxis is a protective factor.

Mannose-binding lectin (MBL) is a C-type lectin produced mainly by the liver that binds to a wide range of pathogens. Polymorphisms at the promoter and exon 1 of the MBL2 gene are responsible for low serum levels of MBL and have been associated with an increased risk of infections. We prospectively analyzed 95 liver transplant recipients. Well-known functionally relevant polymorphisms of the MBL2 gene of the liver donor were examined by gene sequencing. Infectious events were collected prospectively. No differences in the incidence of infections were found according to the donor MBL2 genotypes. Survival was lower in patients receiving a liver graft from a donor with an exon 1 MBL2 variant genotype, and they had higher infection-related mortality (50% versus 14%, P = 0.040). No differences were found according to other polymorphisms involving the promoter and 5'-untranslated region. When we analyzed bacterial infection episodes, we found that patients receiving a liver from a donor with an exon 1 variant genotype had a higher incidence of septic shock (46% versus 11%, P = 0.004). Independent variables associated with graft or patient survival were as follows: receiving a graft from a donor with an exon 1 MBL2 variant genotype [adjusted hazard ratio (aHR), 9.64; 95% confidence interval (CI), 2.59-36.0], the Model for End-Stage Liver Disease score (aHR, 1.14; 95% CI, 1.05-1.23), and bacterial infections (aHR, 11.1; 95% CI, 2.73-44.9). Liver transplantation from a donor with a variant MBL2 exon 1 genotype was associated with a worse prognosis, mainly because of infections of higher severity.

Background. It is necessary to clarify the incidence of and risk factors for tuberculosis (TB) among solid-organ transplant (SOT) recipients as well as changes in the chronology, clinical presentation, and prognosis of the disease. Methods. A total of 4388 SOT recipients were monitored prospectively at 16 transplant centers included in the Spanish Network for Research in Infectious Diseases (REIPI). TB episodes were studied, and the incidence rate was calculated. Certain variables were analyzed, by Cox regression analysis, as potential risk factors for TB. Results. Among the 4388 SOT recipients, 21 cases of TB were reported (0.48%). The median duration of follow-up was 360 days (range, 0-720 days). The global incidence of TB was 512 cases per 10(5) patients per year (95% confidence interval [CI], 317-783), which was higher than that in the general population in Spain (18.9 cases per 10(5) inhabitants per year; relative risk [RR], 26.6). The highest incidence (2072 cases per 10(5) patients per year; 95% CI, 565-5306) was observed among lung transplant recipients (RR, 73.3). Of the TB cases, 95% occurred within the first year after transplant, and 76% were pulmonary forms. Crude mortality was 19.0%, and attributable mortality was 9.5%. Multivariate analysis identified recipient age (RR, 1.05; 95% CI, 1.0-1.1) and receipt of a lung transplant (RR, 5.6; 95%, 1.9-16.9) as independent risk factors. Conclusions. TB incidence is increased among SOT recipients. The risk factors identified were age and receipt of a lung transplant. TB-attributable mortality (9.5%) is still high.

To evaluate inflammatory markers (C reactive protein [CRP], interleukina-1beta [IL-1beta], IL-6 and tumoral necrosis factor [TNF-alpha]) as predictors of bloodstream infection in elderly patients with systemic inflammatory response syndrome (SIRS).Blood cultures and markers were performed at admission and on day 4.Eighty-two patients were included, 34% with positive blood cultures. TNF-alpha and IL-6 values at admission were higher in patients with positive blood cultures (84.5 vs. 28.5 pg/mL [P = .001] and 192.5 vs. 113, [P = .017], respectively). TNF-alpha values on day 4 were higher in patients with positive cultures (50.5 vs. 30; P = .017).High TNF-alpha and IL-6 values at admission, and TNF-alpha values on day 4 correlated with bloodstream infection.

Electron microscopy of skin specimens was performed in 4 patients (age range, 7 months-40 years) with glycogenosis III and revealed consistent abnormalities. Massive glycogen storage was observed in epithelial secretory cells of eccrine sweat glands and, less markedly, in smooth muscle fibers from the erector pili. Other cells, including Schwann cells of myelinated and unmyelinated fibers, were not affected. The extent of glycogen storage was similar in all patients and unrelated to age or duration of disease. The extralysosomal nature and selectivity of glycogen deposits, sparing fibroblasts and other cells, differ clearly from the findings in skin from patients with glycogenosis II. The purpose of this study was to show that glycogen deposits in glycogenosis III are not restricted to skeletal muscle and liver, and to assess the usefulness of skin biopsy in this disorder.

The best immunosuppressive regimen in HIV-infected renal transplant recipients has not been established. Thymoglobulin has been associated with an increased risk of serious bacterial infections in HIV-negative patients and, for this reason, there is some concern over its use in the HIV-infected population. We describe three consecutive HIV-infected renal transplant recipients who received thymoglobulin as induction therapy, and we compared their progress with a cohort of 23 HIV-negative recipients. Median follow-up was 24 and 11 months, respectively. Nadir lymphocytopenia was observed at 1 week in both groups, and their absolute lymphocyte count recovery was similar. An early and deep (30 cells/mm(3)) CD4(+) T cell lymphocytopenia was seen in two of the three HIV-infected patients. No opportunistic infections were diagnosed in HIV-positive patients. One HIV-positive patient had a bacterial infection and five HIV-negative patients had one or more bacterial infections. Thymoglobulin was safe in our three HIV-infected renal transplant recipients. Until those data are confirmed in larger studies, close monitoring is recommended during the thymoglobulin-induced CD4(+) T cell lymphocytopenia period.

BACKGROUND: With the introduction of prolonged prophylaxis with valganciclovir in cytomegalovirus (CMV) donor/recipient serodiscordance (D+/R-) patients, concerns about a high incidence of late and invasive CMV disease associated with mortality have emerged. We compared the characteristics of CMV disease in D+/R- patients receiving prolonged valganciclovir prophylaxis with R+ patients. METHODS: We prospectively followed all solid organ transplant recipients from January 2004 to December 2005. CMV prophylaxis with valganciclovir or ganciclovir was administered as follows: donor- recipient serodiscordance (D+/R-), 12 weeks; induction with antithymocyte globulin or acute rejection episodes requiring steroid pulses, 15 to 30 days; and CMV R+ double kidney-pancreas, 15 days. Transplant characteristics and the development of CMV disease variables were collected for all patients. We defined 2 groups according to the risk of CMV disease: CMV donor/recipient mismatch (D+/R-) and recipient CMV-positive (R+) groups. RESULTS: During the study period we performed 481 solid organ transplantations: 237 kidney, 34 kidney-pancreas, 157 liver, 38 heart, 13 liver-kidney, and 2 heart-kidney. Overall, 36 patients developed CMV disease (7.5%). CMV donor-recipient mismatch (D+/R-) was associated with a greater risk of CMV disease compared with CMV-positive recipients (16% vs 7%; P = .036). Prophylaxis against CMV was longer in the D+/R- group (mean days 73 vs 15; P < .001). CMV disease appeared later in the D+/R- than in R+ group (mean days 123 vs 59; P < .001). We observed a trend toward a lower incidence of tissue-invasive CMV disease among the D+/R- group compared with the R+ group without significance (14% vs 41%; P = .382). Three patients died in the first 30 days after the onset of CMV disease, all of them in the R+ group. CONCLUSIONS: In our setting, high-risk patients (D+/R-) receiving prolonged prophylaxis with valganciclovir developed later CMV disease, but this was neither more tissue-invasive nor more life-threatening than in the R+ group.

BACKGROUND: Cytomegalovirus (CMV) disease is associated with an increased net immunosuppressive state in solid organ transplant recipients, leading to more bacterial and fungal infections. The release of pro- and anti-inflammatory cytokines could be one of the responsible factors. METHODS: We prospectively included all patients undergoing solid organ transplantation between April and November 2004. During follow-up, plasma samples were collected in the immediate postsurgical period, at the first and second months, at the time of maximum antigenemia during CMV disease, and at 6 months posttransplantation. We determine the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Log-transformed data were compared by a nonparametric Wilcoxon test for related variables. RESULTS: During the study period, we monitored 146 recipients of solid organ transplantation: 77 kidneys, 8 kidney-pancreas, 46 liver, 11 heart, 2 liver-kidney, and 2 heart-kidney. No differences were observed between the TNF-alpha and IL-10 levels in the immediate postsurgical period or during CMV disease. TNF-alpha and IL-10 levels during CMV disease were higher than levels during the first month (mean TNF-alpha first month = 12.71 pg/mL vs CMV disease = 22.71 pg/mL, P = .028; mean IL-10 first month = 3.47 pg/mL vs CMV disease = 19.2 pg/mL, P = .018). Th1/Th2 ratio (measured as TNF-alpha/IL-10) was 1.75 in the immediate postsurgical period, 7.5 during the first month, 1.86 at the time of CMV disease, and 4.61 at the sixth month. The difference in Th1/Th2 ratio during CMV disease and in the first month was statistically significant (P = .043). CONCLUSION: During CMV disease, we observed an increase in TNF-alpha and IL-10 release, which was similar to that during the postsurgical period. An imbalance toward an anti-inflammatory pattern was noted in these two periods. This could reflect a cooperative factor increasing the net state of immunosuppression during CMV disease.

In 1995 a specialized home care service for infectious diseases was created in our institution. The aim was to improve the quality of life of patients with prolonged parenteral antimicrobial therapy requirements, reduce the length of hospital stay, and improve the care received after discharge by clinical and analytical surveillance. This study reviews the experience of this service from 1995 to 2002 using prospectively recorded data.An analysis was performed of the number of patients included in the home care program per year, number of patients with HIV infection, infectious disease diagnosed, department referring the patient, antimicrobial treatment administered, destination at discharge, and reason for hospital re-admission.The number of patients included each year from 1995 to 2002 was 52, 55, 77, 232, 213, 321, 280 and 219, respectively. The percentage of HIV-infected patients decreased from 90% in 1995 to 23% in 2002. The main reason for referral to the program changed from substitution of day-care hospital treatment to early discharge from hospitalization. Whereas CMV infection was the most frequent infection treated during the 1995-1998 period, bacterial infections predominated in the following years. In 148 episodes, self-administration or a portable infusion pump was used for drug administration. Self-administration was associated with a greater risk of complications (24% vs. 12%, OR 2.3, 95% CI 1.5-3.6, P0.001) and catheter-related sepsis (4% vs. 0%, OR 12.9, 95% CI 10.9-15.3, P0.001). HIV-infected patients were re-hospitalized due to complications unrelated to the home care service more frequently than HIV-uninfected patients.The percentage of HIV-infected patients included in the infectious disease home care service has progressively decreased since 1996, a fact likely to be related to the introduction of highly active antiretroviral therapy and better control of opportunistic infections. Currently, bacterial infections are the most frequent infections treated in the service. Early hospital discharge is now the main reason for referral to the home program.

The prognosis of HIV infection has dramatically improved in recent years with the introduction of combined antiretroviral therapy. Currently, liver disease is one of the most important causes of morbidity and mortality, even more so given the high rate of hepatitis C virus co-infection in countries where drug abuse has been an important HIV risk factor. Survival of HIV-co-infected patients with end-stage liver disease (ESLD) is poor and shorter than that of the non-HIV-infected population. One-year survival of HIV-infected patients with ESLD is only around 50-55%. HIV infection is no longer a contraindication to transplantation, which is becoming a standard therapy in most developed countries. The HIV criteria used to select HIV-infected patients for liver transplantation are quite similar in Europe and North America. Current criteria state that having had an opportunistic infection (e.g. tuberculosis, candidiasis, PCP) is not a strict exclusion criterion. However, patients must have a CD4 count above 100 cells/mm3 and a plasma HIV-1 RNA viral load that is suppressible with antiretroviral treatment. More than 200 orthotopic liver transplants (OLT) in HIV-infected patients have been published in recent years and the mid-term (3-year) survival was similar to that of HIV-negative patients. The main problems in the post-transplantation period are the pharmacokinetic and pharmacodynamic interactions between antiretroviral and immunosuppressive agents and the recurrence of HCV infection, which is the principal cause of post-transplantation mortality. There are controversial results regarding mid-term survival of HIV-HCV co-infected patients compared with HCV mono-infected patients. However, one study showed a trend of poorer 5-year survival of HIV-HCV co-infected patients. There is little experience with the treatment of recurrent HCV infection. Preliminary studies showed rates of sustained virological response ranging between 15% and 20% in HIV-HCV co-infected recipients. Liver transplantation in HIV-HBV co-infected patients had a good prognosis because HBV recurrence can be successfully prevented using immunoglobulins and anti-HBV drugs. Finally, this field is evolving continuously and the indications for liver transplantation or the management of HCV co-infection may change in the future as more evidence becomes available.

Genetically defined deficiencies in key components of the innate immune system have been associated with a greater risk of infection. The aim of this study was to assess the influence of genetic variability of innate immune receptors (mannose-binding lectin [MBL], mannose-associated serine-protease-2 [MASP-2], and Toll-like receptors [TLR4]) in the risk of infections after a kidney transplantation.All patients undergoing a kidney or kidney-pancreas transplantation during a 3-year period were included. Functionally relevant mutations in MBL2, MASP2, and TLR4 genes were determined by DNA sequencing. The incidence of major bacterial infections, asymptomatic cytomegalovirus (CMV) infection, and CMV disease were compared among groups.There were no differences regarding major transplant characteristics among groups. Older age, requirements for posttransplant hemodialysis, and pretransplant diabetes, but not gene polymorphisms, were associated with a greater number of bacterial infections. In univariate analysis, low-MBL genotypes were associated with CMV disease in pretransplant CMV seropositive patients (P=0.015), whereas the TLR4 mutation was associated with higher risk of CMV primary infection (P=0.024). TLR4 mutation was an independent factor associated with CMV disease (odds ratio 5.84, 95% confidence interval 1.35-25.20, P=0.018).Polymorphisms of innate immunity receptors, especially TLR4 mutation, were associated with higher risk of CMV disease, while susceptibility to other infectious disorders was not observed.

We studied the main clinical features, outcome, and laboratory parameters in a group of solid organ transplant (SOT) patients with immunohistochemically proven cytomegalovirus (CMV) disease. Confirmed CMV cases were obtained through databases. Demographics, clinical data, transplantation type, immunosuppressive regimens, donor and recipient CMV serostatus, therapy, outcome and laboratory results, pp65 antigenemia, and qualitative polymerase chain reaction (PCR) for CMV were analyzed. From 1995 to 2004, 31 cases with complete medical records were identified. Disease appeared between 24 and 2538 days after transplantation but most cases presented in the first 100 days. Gastrointestinal CMV disease was the most frequent form (71%), while thrombocytopenia was present in 50% of cases, and leukopenia was less common (35.5%). CMV pp65 antigenemia was positive in 58% of patients, but its sensitivity increased to 71% if performed during the first 6 months. A qualitative CMV PCR technique gave similar results during this period (71.4%). Most patients were treated with intravenous ganciclovir (n=25; 80.6%). In 4 cases (19.4%), use of foscarnet alone or a sequential regimen with ganciclovir-foscarnet was deemed necessary. Surgical procedures were necessary in 5 patients (16%). The death rate reached 13%. CMV end-organ disease can be a life-threatening infection in SOT patients. Gastrointestinal disease was the most frequent end-organ disease. CMV antigen detection is best suited for the early period after transplantation.

Infection can lead to graft loss and death in patients undergoing kidney and double kidney-pancreas transplantation. In this review, the prophylactic measures, the post-transplant timeline for the development of infections, and the most frequent infectious complications in patients with kidney and pancreas transplantation are described. Although great advances have been achieved in the prevention of infections, new problems have developed. Nosocomial bacterial infection with multidrug-resistant bacteria is an emerging complication. Cytomegalovirus is still the most frequent viral infection despite the advances in prevention measures. Moreover, in recent years polyomavirus type BK infection has been recognized as a major cause of renal graft loss. Knowledge of the infectious complications associated with these transplants and the risk factors for their occurrence will allow optimal therapeutic management of this patient population.

México posee una gran diversidad de especies con el Metabolismo Ácido de las Crasuláceas (CAM). Las especies con este metabolismo pueden crecer en sitios donde la disponibilidad de agua es infrecuente, como son las zonas áridas y semiáridas y las copas de los árboles, o como hidrofitas en sitios con poca disponibilidad de CO2. Esta revisión presenta aspectos metodológicos, evolutivos, ecológicos y fisiológicos de este tipo de fotosíntesis. Además, se presentan datos de estudios recientes relacionados con la influencia de las condiciones ambientales en el ciclo diario de la fotosíntesis CAM. Finalmente, se presenta una reflexión sobre la falta de estudios en la fisiología de plantas CAM en México a pesar de su enorme diversidad.

Human herpesvirus 6 (HHV-6) infection is potentially life-threatening to immunosuppressed patients. There is a lack of information regarding the risk and the clinical manifestations of primary HHV-6 infection in solid-organ transplant recipients. We prospectively evaluated patients undergoing solid organ transplantation with negative immunoglobulin (Ig) G antibodies against HHV-6 by means of HHV-6 quantitative polymerase chain reaction. Among 193 recipients, seven were HHV-6 seronegative (prevalence 3.6%). We detected a positive HHV-6 viral load in only one patient, and four patients seroconverted after one year posttransplantation. The patient with a positive HHV-6 viral load developed cholestatic hepatitis without fever and did not experience severe end-organ disease. In conclusion, our findings show a low incidence of symptomatic primary HHV-6 infection among seronegative solid-organ transplant recipients.

An otherwise healthy 48-year-old man was admitted to the hospital after a sudden fever and loss of consciousness. Cranial CT revealed dilatation of the ventricular system and diffuse cerebral edema. The patient also had right hypoglossal-nerve palsy, shown in a video.

The characterization of deletions in the SMN gene provides a helpful tool to confirm the diagnosis of spinal muscular atrophy (SMA). However, there may be homozygous deletions of the SMN gene in some unaffected siblings of SMA type II and III patients. We present two SMA families with affected siblings demonstrating a homozygous deletion of the SMN gene with extremely different phenotypes. We propose a preclinical category of an SMA patient with homozygous deletion of the SMN gene: those with minimal expression of the disease including cramps and EMG abnormalities that may develop the complete SMA phenotype in the future.

A 29-year-old Spanish man presented with chronic intestinal pseudo-obstruction, progressive external ophthalmoplegia, peripheral neuropathy, and diffuse leukoencephalopathy. This combination of clinical features is characteristic of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Genetic analysis revealed a novel 18-base pair (bp) duplication (5044–5061dup) in exon 8 of the thymidine phosphorylase (TP) gene. The mutation is predicted to produce a 6 amino acid insertion in the alpha‐beta-domain of the protein. This 18-bp insertion in the thymidine phosphorylase gene is the first duplication mutation identified in MNGIE. D 2004 Elsevier B.V. All rights reserved.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects motor neurons. It is caused by mutations in the survival motor neuron gene 1 (SMN1). The SMN2 gene, which is the highly homologous SMN1 copy that is present in all the patients, is unable to prevent the disease. An SMN2 dosage method was applied to 45 patients with the three SMA types (I-III) and to four pairs of siblings with chronic SMA (II-III) and different phenotypes. Our results confirm that the SMN2 copy number plays a key role in predicting acute or chronic SMA. However, siblings with different SMA phenotypes show an identical SMN2 copy number and identical markers, indicating that the genetic background around the SMA locus is insufficient to account for the intrafamilial variability. In our results, age of onset appears to be the most important predictor of disease severity in affected members of the same family. Given that SMN2 is regarded as a target for potential pharmacological therapies in SMA, the identification of genetic factors other than the SMN genes is necessary to better understand the pathogenesis of the disease in order to implement additional therapeutic approaches.

Infection is the leading cause of complication after liver transplantation, causing morbidity and mortality in the first months after surgery. Allograft rejection is mediated through adaptive immunological responses, and thus immunosuppressive therapy is necessary after transplantation. In this setting, the presence of genetic variants of innate immunity receptors may increase the risk of post-transplant infection, in comparison with patients carrying wild-type alleles. Numerous studies have investigated the role of genetic variants of innate immune receptors and the risk of complication after liver transplantation, but their results are discordant. Toll-like receptors and mannose-binding lectin are arguably the most important studied molecules; however, many other receptors could increase the risk of infection after transplantation. In this article, we review the published studies analyzing the impact of genetic variants in the innate immune system on the development of infectious complications after liver transplantation.

We studied a patient with ptosis, ophthalmoparesis, and exercise intolerance who showed in her muscle biopsy ragged-red fibers and combined defects of the complexes I and IV of the mitochondrial respiratory chain. Molecular analysis revealed a T3273C transition in the mitochondrial DNA tRNALeu(UUR) gene. The mutation was heteroplasmic and very abundant in muscle from the proposita, less abundant in her other tissues studied, and still less abundant in blood from her maternal relatives. Single muscle fiber analysis showed significantly higher levels of mutant genomes in ragged-red fibers than in normal fibers. The T3273C mutation affects a strictly conserved base pair in the anticodon stem and was not found in controls, thus satisfying the accepted criteria for pathogenicity.

Mutations in the muscular voltage-dependent chloride channel gene (CLCN1), located at 7q35, lead to recessive and dominant myotonia congenita. We report four novel mutations identified in this gene, after clinical, electromyographic, and genetic studies performed on 13 unrelated families. Two of the four mutations (2512insCTCA and A218T) were identified in families with Thomsen's disease, one (Q658X) in a family with Becker's disease, and the fourth (R669C) in a presumably sporadic patient with the Becker phenotype. Although identification of the mutations allows us to establish some genotype/phenotype correlations, this does not wholly account for the clinical heterogeneity and the inheritance patterns of the disease.

We have identified a novel missense mutation in the myophosphorylase gene in a Spanish patient with McArdle's disease. The patient was homozygous for a T-to-C transition at codon 115 (L115P) in exon 3, which changed an encoded leucine (CUG) to a proline (CCG). This is the first mutation to be described in exon 3 and in a protein domain related to dimer contact. These data further emphasize the importance of private mutations in McArdle's disease, some of which are associated with specific ethnic arouns.

Hirano bodies constitute eosinophilic intracytoplasmic inclusions, typically seen in the central nervous system, where they are related to senility and certain dementias such as Alzheimer's disease or the Parkinson-dementia complex. They have been found in different tissues of experimental animals and, on rare occasions, in extraocular muscles of elderly individuals. However, to our knowledge they have not been described in skeletal muscle in locations other than extraocular muscles or associated with muscle pathology. Glycogenosis II or Pompe's disease, is a metabolic disorder caused by acid maltase deficiency and is characterized by glycogen accumulation in lysosomes in various tissues, including skeletal muscle. There are three clinical forms depending on age at onset, the most frequent being the childhood form. We present the histopathological and ultrastructural findings of a muscle biopsy performed in a case of the adult form of glycogenosis II which showed, in addition to characteristic lysosomal glycogen storage, paracrystalline mitochondrial inclusions and, as an exceptional finding, intracytoplasmic Hirano bodies in some muscle fibres.

Motor neuron disease is still one of the most dramatic neurological conditions; it reflects a range of which one end encompasses patients with the bulbar form of amyotrophic lateral sclerosis who have dysarthria and dysphagia and have a dramatically shortened life expectancy. For patients with probable or definite motor neuron disease according to established criteria, the recent introduction of the antiglutamate drug riluzole gives a mean prolongation of life after diagnosis of some 3 months.1 The other end of the range of motor neuron disease is formed by patients with so called multifocal motor neuropathy. This is characterised by lower motor neuron dysfunction in the areas of selected motor nerves. Neurophysiological demonstration of conduction block over these nerves is pivotal for the diagnosis.2 Before the discovery of multifocal motor neuropathy as a separate and treatable condition, patients with …

Genetic anticipation – increasing severity and a decrease in the age of onset with successive generations of a pedigree – is clearly present in autosomal dominant cerebellar ataxia (ADCA). Anticipation is correlated with expansion of the CAG/CTG repeat sequence to sizes above those in the normal range through the generations of a pedigree. Genetic heterogeneity has been demonstrated for ADCA, with four cloned genes (SCA1, SCA2, SCA3/MJD, and SCA6) and three mapped loci (SCA4, SCA5 and SCA7). Another related dominant ataxia, dentatorubral-pallidoluysian atrophy (DRPLA), presents anticipation with CAG/CTG repeat expansions. We had previously analysed ADCA patients who had not shown repeat expansions in cloned genes for CAG/CTG repeat expansions by the repeat expansion detection method (RED) and had detected expansions of between 48 and 88 units in 17 unrelated familial cases. We present here an analysis of 13 genes and expressed sequence tags (ESTs) containing 10 or more CAG/ CTG repeat sequences selected from public databases in the 17 unrelated ADCA patients. Of the 13 selected genes and ESTs, 9 were found to be polymorphic with heterozygosities ranging between 0.09 and 0.80 and 2 to 17 alleles. In ADCA patients none of the loci showed expansions above the normal range of the CAG/CTG repeat sequences, excluding them as the mutation causing ADCA.

Introduccion y objetivos La endocarditis infecciosa predispone al absceso esplenico, de incidencia mal definida y que aumenta la morbimortalidad. No esta estandarizado el momento para esplenectomia cuando se requiere intervencion por endocarditis. Se describe la experiencia con endocarditis y patologia esplenica asociada e indicacion quirurgica valvular y esplenica. Material y metodos Revision retrospectiva de la base de datos prospectiva de endocarditis, definida por criterios modificados de Duke. Analisis de pacientes diagnosticados de infarto/absceso esplenico mediante imagen/estudio post mortem. En los casos de esplenectomia, se practico en la misma intervencion despues del procedimiento valvular. Resultados Entre enero de 1995 – julio de 2011 se recogieron 737 episodios de endocarditis; 62 (8,41%) pacientes presentaron infarto/absceso esplenico con fiebre persistente y dolor abdominal; 6 (8,9%) requirieron esplenectomia; 5 (83%) eran varones. La edad media fue 52 (27–72). EuroSCORE logistico medio fue 37,42% (18,83–60,93%). La endocarditis fue mitral (3), aortica (2) y multivalvular (mitral y tricuspide). Se aislaron Enterococcus spp (2), Staphylococcus aureus (1), estreptococos del grupo viridans (1), Kingella kingae (1) y hemocultivos negativos (1). El absceso esplenico se diagnostico por tomografia (4); en 2 la intervencion fue urgente, sin imagen. Se practico sustitucion valvular. Tres (50%) fallecieron. En los 6 se confirmo absceso esplenico por histopatologia. El seguimiento de los supervivientes a la intervencion con esplenectomia fue de 16, 22 y 36 meses, sin recidiva. Conclusiones Debe sospecharse absceso esplenico en los pacientes con endocarditis, fiebre y dolor abdominal. La esplenectomia y la intervencion valvular pueden realizarse en el mismo acto dependiendo de la condicion del paciente.

Objetivos Investigar los resultados de la cirugia por endocarditis infecciosa en pacientes con cirrosis hepatica. Metodos Se incluyeron pacientes consecutivos con endocarditis y cirrosis (enero de 1998 – febrero de 2011), utilizando los criterios modificados de Duke para diagnosticar la endocarditis, la clasificacion Child-Turcotte-Pugh y la puntuacion model end-stage liver disease (MELD) para la cirrosis. Se realizo analisis univariado de los predictores de mortalidad. Resultados Cuarenta y ocho de 610 (8%) pacientes con endocarditis eran cirroticos; se practicaron 24 operaciones en 22 (46%). Veinte eran varones (mediana de edad 50,5). La cirrosis fue viral (9–41%), alcoholica (9–41%) y desconocida (4–18%). Las clases Child-Turcotte-Pugh fueron A (8) B (12) y C (4). Los estafilococos (29%) fueron predominantes. Las intervenciones fueron programadas, urgentes y de urgencia vital en 11, 5 y 8 casos. La intervencion incluyo sustitucion aortica (11), mitral (2), tricuspide (2), raiz aortica (3) aortica + mitral (3) y extraccion de marcapaso (1). Siete pacientes tenian absceso perivalvular, 5 fistula cavitaria. Los implantes fueron mecanicos (3), pericardicos (10), homoinjertos aorticos (7) y mitrales (2). EuroSCORE logistico confirmo una mortalidad esperada de 36%. La mortalidad hospitalaria fue 54% (intervalo de confianza [IC] 95%: 33–76%); la mortalidad por la clase Child-Turcotte-Pugh fue: A, 3 (37,5%); B, 7 (58%); C, 3 (75%) (p = 0,390). Los fallecidos tenian una puntuacion MELD mas alta (19,83 ± 7,46 vs 13,8 ± 2,78; p = 0,122). Las causas predominantes de fallecimiento fueron sepsis y fallo multiorganico. Conclusiones Los pacientes con endocarditis y cirrosis son los de mas riesgo. EuroSCORE no fue util para la estratificacion del riesgo. En pacientes con cirrosis avanzada la cirugia debe ofrecerse solo en casos seleccionados.

Introduccion. El fingolimod es el primer farmaco modificador de la enfermedad disponible por via oral para pacientes con esclerosis multiple remitente recurrente. Objetivos. Revisar el mecanismo de accion del farmaco y su relacion con el desarrollo de infecciones, proponer medidas preventivas para aquellos pacientes que van a recibir o ya estan recibiendo un tratamiento con fingolimod, y discutir el papel de fingolimod en el desarrollo de leucoencefalopatia multifocal progresiva segun los ultimos avances en el conocimiento de esta infeccion oportunista. Desarrollo. El mecanismo de accion del fingolimod se basa en un efecto antagonico sobre los receptores de la esfingosina 1-fosfato, que impedira la migracion de linfocitos naive y centrales de memoria de tejido linfoide a sangre, preservando la recirculacion de linfocitos T efectores de memoria. Este efecto se traducira en una linfopenia en la sangre periferica. El efecto del fingolimod es una linfopenia redistributiva, selectiva y reversible. No se ha descrito un numero mayor de infecciones convencionales u oportunistas con el uso de fingolimod en comparacion con placebo o interferon beta-1a. Sin embargo, en dos pacientes se produjeron infecciones herpeticas graves. Conclusiones. El fingolimod induce una linfopenia selectiva y reversible que, con los datos disponibles en la actualidad, no parece incrementar el riesgo de infecciones oportunistas, debido a que la inmunovigilancia esta preservada. El riesgo de infeccion herpetica debe tenerse en cuenta y realizar estudios adicionales para confirmar si existe una relacion con el tratamiento.

Experimental models have shown that Chiari I malformation is a primary paraaxial mesodermal insufficiency occurring after the closure of the neural folds takes place. According to these hypotheses, a small posterior fossa caused by an underdeveloped occipital bone would be the primary factor in the formation of the hindbrain hernia. The main objective in the surgical treatment of Chiari I malformation and related syringomyelia is directed to restore normal cerebrospinal fluid dynamics at the craniovertebral junction. The most widely accepted surgical approach is to perform a craniovertebral decompression of the posterior fossa contents with or without a dural graft. It has been emphasized that suboccipital craniectomy should be small enough to avoid downward migration of the hindbrain into the craniectomy. This slump of the hindbrain has been verified by studies using postoperative assessment by magnetic resonance imaging. Our aim in this study is to present a modification of the conventional surgical technique, which we have called posterior fossa reconstruction (PFR). Ten patients were operated on using this technique and compared with a historical control group operated on with the classic approach of making a small suboccipital craniectomy, opening the arachnoid, and closing the dura with a graft. To evaluate the morphological results in both groups objectively, preoperative and postoperative measurements of the relative positions of the fastigium and upper pons above a basal line in the midsagittal T1-weighted magnetic resonance images were obtained. In those cases with syringomyelia, syringo-to-cord ratios were calculated. The mean age of the PFR group was 35 +/- 16 years (mean +/- SD); in the control group it was 35.2 +/- 12 years. In the PFR group, the formation of an artificial cisterna magna was observed in every case; it was observed in only one case in the control group. An upward migration of the cerebellum was seen in all cases in the PFR group, with a mean ascent of the fastigium of 6.2 mm. A significant downward migration of the cerebellum was observed in seven cases in the control group. No significant differences were found in both groups when comparing syringo-to-cord ratios. This leads us to conclude that PFR is more effective than conventional surgical approaches in restoring the normal morphology of the craniovertebral junction. This allows cranial ascent of the hindbrain verified by magnetic resonance imaging and good short-term clinical results. Because PFR is mainly an extraarachnoidal approach, complications related to surgery using this technique can be kept to a minimum.

A 9-year-old boy presented with acute sensory neuronopathy, a condition generally associated with poor recovery. Although sensory nerve action potentials were abolished and sural nerve biopsy showed marked loss of myelinated fibers, he eventually made an almost complete clinical recovery.

This article aims to review herpes simplex, herpes zoster and cytomegalovirus and to summarize the main characteristics of the antiviral drugs available to treat those infections. The review of each drug focuses on dosage according to the treatment indication, dose adjustment in patients with impaired renal or hepatic function, the main pharmacokinetic features, and the most significant adverse effects and drug interactions.

IE and 1,110 cases of IE due to other pathogens (non-SA NVIE). Twogroup comparisons and adjusted survival analysis were performed. Results: Compared to non-SA NVIE, SA NVIE occurred more frequently in older subjects (p = 0.01). It was less often community-acquired (p < 10 4), more frequently diagnosed within the first month of symptoms onset (p < 10 4) and associated with comorbidities (p < 10 4). SA NVIE was more often complicated with stroke (p = 0.0009) and emboli (p = 0.008). By contrast the frequencies of cardiac failure and intracardiac abscess were the same in the two groups. EVS and 60day in-hospital mortality rate were lower (34.2% vs. 50.1%, p < 10 4) and higher (26.5% vs. 11.9%, p < 10 4), respectively. In multivariate analysis, when compared to non-SA NVIE: (1) the probability of EVS was significantly lower in SA NVIE (HR 0.66, 95 CI 0.54 0.80, p < 0.0001); (2) the probability of in-hospital death was significantly higher (HR 1.68, 95 CI 1.28 2.22, p < 0.0001), which was true both in operated and non-operated patients. Conclusion: This study confirms that SA NVIE is associated with higher rates of comorbidities and mortality. It is also associated with a lower rate of EVS, which is neither explained by a higher frequency of comorbidities/complications that would contraindicate surgery nor by a lower frequency of conditions that would require surgery.