Metástasis cutáneas de un carcinoma transicional vesical productor de β-HCG

In spite of the high incidence of transitional cell carcinoma, cutaneous metastases are infrequent, especially when they are the first sign of metastatic spread, with a low survival rate.Thirty five per cent of transitional cell carcinoma of the bladder have ectopic beta- human chorionic gonadotropin (β-HCG) production. It has been related with high grade tumors, advanced stage, metastatic disease, radioresistent tumors and low survival rate because of its effect as a growth modulator with a probably antagonist action in the apoptotic cascade. We present a thirty six years old woman affected by a transitional cell carcinoma of the bladder producing β-HCG that showed two cutaneous metastases as first sign of metastatic disease. The exceptional coincidence of these two circumstances announced a very aggressive tumor behaviour and bad prognostic, with a quickly multiple metastatic dissemination including a pericardic metastases.     

Improvement in antipsychotic-related metabolic disturbances in patients with schizophrenia switched to ziprasidone

PURPOSE: This study evaluated changes in weight, glucose and lipid metabolism in patients with schizophrenia and antipsychotic-related metabolic disturbances who were switched to ziprasidone. METHODS: Eighty-four outpatients with schizophrenia or schizoaffective disorder also having glucose intolerance, diabetes, dyslipidemia or weight gain related to their antipsychotic treatment were switched to ziprasidone. Clinical status was assessed using the Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I) scales and the Positive and Negative Syndrome Scale (PANSS). Assessment scales, weight, glucose and lipids were measured at baseline and at three and six months of ziprasidone treatment. RESULTS: Significant baseline to endpoint reductions were seen in mean weight (-5.1 kg), Body Mass Index (BMI; -1.6 kg/m(2)), serum glucose (-14.0 mg/dL), total cholesterol (-24.1 mg/dL), and triglyceride leves (-46.2 mg/dL). Mean PANSS total score improved 13.9% after 6 months of treatment with ziprasidone. A proportion (34.3%) of patients were classified as much improved in the CGI-I. CONCLUSIONS: Switching patients with schizophrenia to ziprasidone when metabolic disturbances are detected may improve these side effects and result in an improved overall outcome.     

Alcohol dehydrogenase 2 genotype and allelic variants are not associated with the risk for essential tremor

OBJECTIVE: To investigate the possible association between alcohol dehydrogenase 1B, beta-polypeptide (ADH2) genotype and allelic variants and the risk for developing essential tremor (ET). METHODS: Leukocytary DNA from 204 ET patients and 200 healthy controls was studied for the genotype ADH2 and the occurrence of ADH2 allelic variants using allele-specific polymerase chain reaction amplification and MslI-restriction fragment length polymorphism's analyses. RESULTS: The frequencies of the ADH2*1/ADH2*2 genotype and of the allelic variant ADH2*2 did not differ significantly in ET patients when compared with those of the controls. The mean age at onset of ET did not differ significantly between patients with genotypes ADH2*1/ADH2*2 and ADH2*1/ADH2*1. The frequencies of the genotype ADH2*1/ADH2*2 and of the allelic variant ADH2*2 in patients with voice, tongue, and chin tremors did not differ from those of the controls, whereas patients with voice tremor showed lower frequencies of mutated genotypes and ADH2*2 alleles. The frequencies of ADH2 genotypes and ADH2 alleles did not differ significantly between patients who did not drink ethanol and those who reported improvement, no improvement, or unknown response of tremor to ethanol. CONCLUSIONS: These results suggest that ADH2 genotype and allelic variants are not associated with the risk for ET in white Spanish people.     

Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients

Surveillance of drug resistance mutations in antiretroviral-experienced HIV(+) patients may provide useful information regarding options available for rescue interventions. All resistance tests performed from 1999 to 2005 on antiretroviral-experienced individuals at one reference laboratory in Madrid were examined. Only mutations associated with drug resistance recorded at the September 2006 IAS-USA list were considered. A total of 2137 specimens were analyzed. Overall, 71.1% showed resistance mutations to at least one drug class, 56.1% to at least two, and 21% to all three drug families. Resistance mutations were 65% for NRTI, 44.4% for NNRTI, and 42.5% for PI. Mutations T215Y/F, M184V, and M41L were the most frequent for NRTI. Their rate significantly declined since 1999. K65R significantly increased since 1999 (0.8%) to 2003 (7.3%) but declined up to 3.3% in 2005. For NNRTI, K103N significantly increased from 21.8% in 1999 to 29.5% in 2005 (p < 0.01). The most frequent PI resistance mutations were L90M (24.3%), V82X (19.9%), M46I/L (19.5%), and I54V (17.1%). The presence of five or more was 58.8% in 1999 but declined to 22.2% in 2005. The rate of drug resistance mutations causing NRTI and PI resistance has steadily declined in antiretroviral-experienced patients since 1999. The availability of a large number and/or more convenient NRTI as well as the wide use of ritonavir-boosted PI could explain these observations. However, broad PI cross-resistance was seen in nearly 25% of antiretroviral-experienced patients in 2005. Therefore, there is a still need for new antiretrovirals with different resistance profiles.     

Efficacy and safety of a once daily regimen with efavirenz, lamivudine, and didanosine, with and without food, as initial therapy for HIV Infection: the ELADI study

The combination of didanosine (ddI) and lamivudine (3TC) is attractive considering its low cost, potency, tolerability, and convenience (once daily administration), but it is not recommended as first-line therapy for HIV infection. A prospective, multicenter, open, comparative trial was conducted in HIV-infected, antiretroviral-naive persons in Spain who begun a QD regimen with efavirenz (EFV), 3TC, plus ddI, the latter with or without food. A total of 103 patients were recruited in the study. Median baseline CD4 count was 229 cells/microl and plasma HIV-RNA was 4.9 logs copies/ml. In an intent-to-treat analysis, 78 (75.8%) had undetectable viremia at week 48 of therapy, without significant differences when comparing patients on and without fasting ddI (75% vs. 76.6%, respectively). The mean CD4 increase was of 199 cells/microl, with no significant differences between groups. Overall, 29 adverse events were recorded in 23 patients, the majority associated with neuropsychiatric symptoms of EFV. Treatment was discontinued in 10 (9.7%) patients due to adverse events. Virological failure was recognized in only six patients, four taking ddI with and two without food (p = 0.3). Drug resistance mutations were recognised in four of them. Plasma ddI concentrations did not differ significantly between groups. Mitochondrial DNA within peripheral blood mononuclear cells tended to increase in most subjects over 48 weeks of therapy regardless of treatment group. A QD regimen with ddI, 3TC, and EFV shows potency and tolerance similar to that reported using other currently recommended regimens in drug-naive HIV-infected patients. Its efficacy does not seem to be compromised when ddI is administered with food. Therefore, this regimen merits further investigation in larger comparative trials.     

Diabetic macular edema and its relationship to renal microangiopathy: a sample of Type I diabetes mellitus patients in a 15-year follow-up study

PURPOSE: In the present study, our objective was to determine the epidemiological risk factors for the development of diabetic macular edema, especially attendant on renal diabetic lesion (microalbuminuria or overt nephropathy) in 112 Type I diabetic patients after 15 years. METHODS: This is a 15-year follow-up study of a cohort of 112 consecutive Type I (insulin-dependent) diabetes mellitus patients without diabetic retinopathy or nephropathy who were enrolled in 1990. We studied the incidence of diabetic macular edema and its risk factors. The epidemiological risk factors included in the study were as follows: gender, diabetes duration, glycated hemoglobin (HbA1c) levels, arterial hypertension, macroangiopathy, triglyceride levels, fractions of cholesterol [high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol], and cigarette smoking. RESULTS: The incidence of diabetic macular edema after 15 years was as follows: the focal form of diabetic macular edema was present in 13 (11.6%) patients and the diffuse form of macular edema was present in 10 (8.9%) patients, among 23 (20.5%) patients. The following factors were significant in the development of diabetic macular edema: high levels of LDL-cholesterol (P=.013), high levels (>7.5%) of HbA1c (P=.021), the presence of macroangiopathy (P=.022), the severity of diabetic retinopathy (P=.029), the presence of arterial hypertension (P=.037), and the presence of overt nephropathy (P=.047). Microalbuminuria was not significant in logistic regression (P=.587), and cigarette smoking was not significant (P=.976). The relationship between diabetic macular edema and duration of diabetes presented two peaks of incidence: first in patients with 15-20 years' duration of diabetes mellitus, and second in patients with >35 years' duration. CONCLUSIONS: In summary, our data suggest that better control of glycemia, LDL-cholesterol levels, and blood pressure in Type I diabetes mellitus patients may be beneficial in reducing the incidence of diabetic macular edema. Finally, our data validate the current guidelines for ophthalmologic care for the detection of diabetic macular edema over the long-term course of diabetes.     

Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice

Insulin resistance is present in almost all patients with nonalcoholic steatohepatitis (NAFLD), and mitochondrial dysfunction likely plays a critical role in the progression of fatty liver into nonalcoholic steatohepatitis. Rosiglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARgamma), is an insulin sensitizer drug that has been used in a number of insulin-resistant conditions, including NAFLD. The aim of this study was to analyze the effects of rosiglitazone on the liver histology and mitochondrial function in a model of NAFLD. All studies were carried out in wild-type and leptin-deficient (ob/ob) C57BL/6J mice. Ob/ob mice were treated with 1 mg/kg/day, and activity of mitochondrial respiratory chain (MRC), beta-oxidation, lipid peroxidation, glutathione content in mitochondria, and 3-tyrosine-nitrated proteins in mitochondria were measured. In addition, histological and ultrastructural changes induced by rosiglitazone were also noted. Rosiglitazone treatment increased liver steatosis, particularly microvesicular steatosis. In these animals, mitochondria were markedly swollen with cristae peripherally placed. In ob/ob mice, this drug increased PPARgamma protein expression and lipid peroxide content in liver tissue and decreased glutathione concentration in mitochondria. Rosiglitazone suppressed the activity of complex I of the MRC in ob/ob mice, but did not affect beta-oxidation. 3-Tyrosine nitrated mitochondrial proteins, significantly increased in ob/ob mice, were not modified by rosiglitazone treatment. CONCLUSION: Treatment of ob/ob mice with rosiglitazone did not reverse histological lesions of NAFLD or improve MRC activity. On the contrary, rosiglitazone reduced activity of complex I and increased oxidative stress and liver steatosis.     

Isolated CNS Whipple disease: acute onset and relapsing-remitting course

Isolated CNS Whipple disease (WD) carries a poor prognosis, particularly if untreated. We describe 2 patients with isolated CNS WD who presented unusually with an acute onset followed by a relapsing-remitting course. Neither was diagnosed with WD until they had had several relapses.