Synthetic cathinones and cardiotoxicity risks.

Abstract: Recently, there has been a worldwide rise in the popularity and abuse of synthetic cathinones. The spectrum of side effects caused by the intake of these drugs of abuse is very wide since they act on different systems with various mechanisms of action, they appear to be involved in different cardiac events, including myocardial infarction and sudden cardiac death due to fatal arrhythmias. Overall, khat users have a higher risk of death, recurrent myocardial ischemia, cardiogenic shock, ventricular arrhythmia, and stroke compared with non-khat user.

Sildenafil-associated hepatoxicity: a review of the literature.

Sildenafil citrate (Viagra®) is a vasoactive agent available worldwide since 1998 for the treatment of male erectile dysfunction. It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. When sildenafil is orally administered, it is rapidly absorbed with a maximum plasma concentration achieved within 1 h and has a terminal half-life of between 3 to 6 h. The drug is extensively and rapidly metabolized by the liver, primarily by the CYP3A4 enzyme. Although the drug is well tolerated, specific adverse events have been observed, like flushing, headaches, dyspepsia, and visual disturbances. Liver toxicity related to sildenafil consumption has been considered a very rare event. However, in the last decade, some cases of sildenafil-associated hepatotoxicity have been reported. Furthermore, some hepatic intoxications have been reported after the intake of "natural" or "herbal" aphrodisiac supplements sold through Internet, sex shops, social media, and by word-of-mouth found to contain sildenafil and other phosphodiesterase type 5 (PDE-5) inhibitors. Studies investigating a possible link between sildenafil use and liver damage are limited, and the underlying mechanism responsible for hepatotoxicity is still missing. Studies in animals evidence that the hematopoietic function of the liver may have severely been affected as a result of a probable toxic effect of sildenafil. Here, the studies reporting liver toxicity by sildenafil in humans and in animals are reported and discussed.

Tuberculosis in prisoners and their contacts in Chile: estimating incidence and latent infection.

SETTING: Contact investigation of tuberculosis (TB) patients in Chilean prisons. OBJECTIVE: 1) To estimate TB incidence and the prevalence of latent tuberculous infection (LTBI) among prisoners and their contacts; and 2) to determine factors associated with disease transmission. DESIGN: Cross-sectional study conducted in 46 prisons (51% of the total prison population) to assess the prevalence of and risk factors for LTBI among contacts of prisoners newly diagnosed with pulmonary TB. We used in vitro interferon-gamma release assays to establish LTBI and a questionnaire to address risk factors. RESULTS: During the 1-year follow-up, we studied 418 contacts of 33 active TB cases. We found high TB incidence (123.9 per 100,000 prisoners) and high LTBI prevalence (29.4%) among contacts. LTBI rates are significantly higher in prison inmates than in non-prisoners (33.2% vs. 15.6%). Male sex, illicit drugs, malnutrition, corticosteroid use, low educational level and sharing a cell with a case increase the risk of LTBI. Multivariate analyses showed that corticosteroid use, duration of incarceration and overcrowding are the most relevant determinants for LTBI among all contacts. CONCLUSIONS: Our results confirm that incarceration increases the risk of tuberculous infection and TB disease, and that it was associated not only with origin from vulnerable groups, but also with the prison environment. Reinforcing TB control is essential to prevent TB transmission in prisons.

Assessment of the stability of exogenous gamma hydroxybutyric acid (GHB) in stored blood and urine specimens.

OBJECTIVE: The aim of this work is to test the stability of exogenous GHB in whole blood and urine samples collected from living and deceased GHB free-users, spiked with known concentrations of GHB and stored at different temperatures (-20°C, 4°C and 20°C) up to 4 weeks. MATERIALS AND METHODS: GHB was added to GHB-free ante-mortem blood and urine samples at the concentration of 5 and 10 mg/L, respectively whereas in post-mortem blood and urine specimens at 50 and 10 mg/L respectively. All samples were stored at three different temperatures: -20°C, 4°C and 20°C and extracted and analyzed at three days, 1 week, 2 weeks, 3 and 4 weeks in duplicate. No preservatives were added. GHB was quantified by GC-MS after LLE according to a previously published method. RESULTS: Post-mortem blood specimens showed a reduction of GHB levels higher than 10% only after a period of 4 weeks of storage for samples kept at +4°C and +20°C, whereas samples stored at -20°C showed a mean reduction of 8.7%. In post-mortem urine samples, there was a mean reduction of GHB levels higher than 20% at all storage temperatures, after 4 weeks of storage. Ante-mortem blood samples showed a reduction of GHB levels lower than 10% only after 3 days of storage at -20°C and at +4°C (samples stored at +20°C showed a mean reduction of 10.4%). After 4 weeks of storage, there was a mean reduction of GHB concentrations higher than 20% at all storage temperatures. Ante-mortem urine samples showed a reduction of GHB levels higher than 10% after just 3 days of storage for samples kept at all tested temperatures. After 4 weeks of storage, there was a mean reduction of GHB concentrations higher than 25% at all storage temperatures. CONCLUSIONS: According to our findings, it would be useful to perform GHB analysis both in blood and urine specimens within 3 days of sampling and the specimens should be stored at -20°C or 4°C in order to avoid instability issues.

A rare case of a scuba diver's death due to propeller injuries of a desalination pump.

Water skiing, boat racing, skin and scuba diving, as well as pleasure boat cruising are becoming increasingly popular hobbies. As a result, the incidence of injuries secondary to motor propellers is becoming more frequent. Injuries by propellers, amputation, death by drowning, and bleeding are rare reported events in forensic literature. The most common circumstances surrounding boat-propeller-related injuries are concerned with getting into or out of the boat, personal watercraft use or water skiing, and falling or being thrown from the boat. A case of a scuba diver's death that occurred during an illegal scuba fishing trip around a desalination plant is presented. A complete autopsy and histological study of all organs and surfaces of dismembered cadaveric sections, performed in order to determine the phases of death, are reported. An underwater scene investigation was conducted by an engineering team studying the mouth of the pump and the dynamic characteristic of rotating propeller blades.

Endometrial carcinoma: MR staging and causes of error.

PURPOSE: This study was undertaken to prospectively determine the diagnostic capabilities of magnetic resonance (MR) imaging in detecting myometrial and cervical invasion and lymph node involvement in endometrial carcinoma and to identify the causes of errors in staging endometrial carcinoma. MATERIALS AND METHODS: Twenty consecutive patients with a histological diagnosis of endometrial carcinoma underwent preoperative MR imaging. MR findings were compared with surgical staging, considered as the standard of reference. RESULTS: In assessing myometrial invasion, MR imaging showed 70% accuracy, 80% sensitivity, 40% specificity, 80% positive predictive value (PPV), and 40% negative predictive value (NPV). In detecting cervical invasion, MR imaging had 95% accuracy, 100% sensitivity, 94.4% specificity, 66.7% PPV, and 100% NPV. In evaluating lymph node involvement, MR imaging showed 100% accuracy, sensitivity, specificity, PPV and NPV. Errors in evaluating myometrial invasion were caused by polypoid tumour, adenomyosis and leiomyomas, whereas those in evaluating cervical invasion were caused by dilatation and curettage. CONCLUSIONS: MR imaging is a reliable technique for preoperative evaluation of endometrial carcinoma. Its main limitation is differentiating between stage IA and IB carcinomas, which is not highly important for surgical planning. Cooperation between the gynaecologist and radiologist is mandatory to avoid staging errors.

Cellular distribution of bovine leukemia virus proteins gp51SU, Pr72(env), and Pr66(gag-pro) in persistently infected cells.

Monoclonal antibodies (mAbs) against bovine leukemia virus (BLV) mature proteins and precursors were used to map the localization of these proteins in persistently infected non-lymphocytic cell lines using immunofluorescence assay (IFA) and immuno-electron microscopy. IFA staining was observed in the basolateral surface of live FLK-BLV cells. When using a mAb against Pr66(gag-pro), mottled pinpoint fluorescence was seen in the cell surface of polarized cells, but no reaction was observed in cells undergoing mitosis. However, a mAb against Pr72(env) stained only mitotic cells and cellular fragments. Additionally, in these dividing cells, this envelope (Env) precursor polyprotein was not evenly distributed but concentrated predominantly in only one daughter cell. To the best of our knowledge, this observation has not been reported previously, either for BLV or for other retroviruses. The results of immunogold electron microscopy confirmed the specificity of the mAbs in the intracellular level. In infected cells, Pr72(env) and gp51SU were seen in proximity at the plasma membrane in incipient budding sites. Additionally, the mAb against Pr72(env) also reacted with Env precursor polyproteins in the mitochondria of BLV-bat(2) ultrathin sections. These mAbs may be used as a tool for mapping virus excretion sites in the cell surface of naturally or in vitro infected cells in the different stages of the cell cycle.

[20210G/A mutation of prothrombin gene in a patient with deep venous thrombosis ad pulmonary embolism without other risk factors of thrombosis]. / Mutación 20210G/A del gen de la protrombina en un paciente con trombosis venosa profunda y embolia pulmonar sin otros factores de riesgo trombótico.

A new genetic anomaly predisposing to venous thrombosis was described in 1996, namely the transition of guanine (G) to adenine (A) at position 20210 in the 3-untranslated region of the prothrombin gene. This mutation is associated with high levels of plasma prothrombin and increased risk of thrombotic events in the venous system. We report the case of a man who, lacking known risk factors for thrombosis, suffered a massive pulmonary embolism and deep venous thrombosis in both lower legs. Thrombophilic analysis confirmed that the patient and close relatives were carriers of the heterozygotic 20210G/A variant of the prothrombin gene. Two relatives with the genetic defect had also suffered some type of deep venous thrombosis.

[Molecular characterization of thalassemias in the Valencia community and its relationship with the hematological phenotype]. / Caracterización molecular de las talasemias en la Comunidad Valenciana y su relación con el fenotipo hematológico.

PURPOSE: The aim of the study is to present the first results of molecular characterization of thalassaemias in Valencian Community and their relationship with the haematological parameters. PATIENTS AND METHODS: The study includes 87 thalassemic patients: 30 alpha-thalassaemias, 40 beta-thalassaemias and 17 delta beta-thalassaemias. The molecular alterations were studied in white cell blood DNA, either following different PCR methods or by testing the digestion of the amplified PCR products with selective restriction enzymes. RESULTS: The molecular characterization of beta-thalassaemias was achieved in 94% of the subjects, being the transition C-->T in CD-39 the most frequent (44%) of the mutations studied. 94% of the delta beta-thalassaemias studied corresponded to the delta beta-Spanish type. All the alpha thalassaemias characterized (64%) corresponded to the -alpha 3.7 deletion. The reamining 36% were negative for the alpha 0 deletions --MED, --20.5, or the non deletional mutations Hph I and NocI. DISCUSSION: In the Valencian Community, like what has been described for the beta-thalassaemias in other Mediterranean regions of Spain (Barcelona, Granada and Mallorca), a high incidence in C-->T transition in CD-39 was observed, in contrast with central and south-western regions of Spain, where the G-->A IVS-I-1 is the most frequent mutation. Our study supports that the IVS-I-6 mutations is the one with lower repercussions on the haematological parameters. Our study confirms the Spanish type of delta beta-thalassaemia as the most frequent in the Valencian Community, and that the 3.7 kb alpha deletion is the most frequent mutation for the alpha-thalassaemia, although alpha thalassaemia is also the poorly characterized form of thalassaemia.

[Primary polycythaemia vera in the elderly]. / La policitemia vera en el anciano.

We present an 86-years-old woman's case with paralysis in her left hand of abrupt apparition, accompanied by arterial hypertension and dizziness. The investigation revealed erythrocytosis, leukocytosis, thrombocytosis, with normal arterial O2 saturation (O2 SAT), increased of his red cell volume and blood viscosity. The polycythaemia vera (PV) was diagnose and the paralysis disappeared, when 24 hours before a phlebotomy was practiced, and the function was recovered by the hand. We analysed the presents diagnostics criteria of the disease defined by Polycythaemia Vera Study Group (PVSG). The different treatments for PV are discussed; in addition to venesection, conventional treatment include chemotherapy with hydroxyurea and pipobroman, as well as the erythropheresis, -interferon and aspirin. All of the treatments are associated with complications; thrombotic in the case of phlebotomy; malignancies and gastrointestinal bleeding in the case of myelosuppressive treatments and aspirin. We think the optimal treatment for PV is a judicious combination of the available alternatives, depending on the phase of the disease, and the age of the patient.

[Efficiency of essential oil (Satureja montana) in controlling the ascospherosis in the honey bee (Apis mellifera) under field conditions.]. / Eficacia del aceite esencial de ajedrea (Satureja montana) en el control de la ascosferosis de la abeja (Apis mellifera) en condiciones de campo.

With the aim of testing its effect in the control of ascosphaerosis in bees, the essential oil of ajedra was incorporated into three types of feed in five different concentrations. Syrup (water and honey) with 0.1% were the best tolerated by the bees, with no colonial changes after a single feed. Later, the ascosphaerosis was introduced in a controlled manner into eight hives. For this, a 10 e6/ml spore suspension was applied by nedulisor three times a week for four weeks to ensure its abundant presence inside the hives. This was continued for the next four weeks period, and at the same time portions of brood-comb in a known state (24 h before operculation) were removed from the hives and heat shocked for 24 h (22 -/+ 2 degrees C), then replaced in the hives for their opercultion, finally removing them and maintaining them at 35 degrees C and 70% relative humidity until the appearance of typical disease symptoms (mummification of the larvae).The hives were randomly divided into two groups of four. One group received 500 ml of syrup with 0.1% oil of ajedra, twice a week for four weeks. The other was kept as the control, receiving syrup without medication. 27.6% of the selected larvae in the treated hives showed mummification, compared with 79.1% in the control hives. The treatment was perfectly tolerated by the bee colonies, showing no changes in their subsequent development.

[New markers of atherogenic risk: hemorrheological profile in children and adolescents with familial hypercholesterolemia]. / Neuvos marcadores de riesgo aterogénico: perfil hemorreológico en niños y adolescentes con hipercolesterolemia familiar.

OBJECTIVE: Recent studies in adults have shown that hemorrheological alterations are predictive of early cardiovascular disease, but it is unknown if they are related to hyperlipemia or are secondary to an established atherosclerotic process and if they appear during childhood. PATIENTS AND METHODS: Several rheological parameters have been studied in 36 patients with familial hypercholesterolemia (FH). These patients were between 2 and 16 years of age and 12 of them were being treated with cholestyramine. Thirty-five controls (CG) were individually matched for age and sex. RESULTS: The FH patients treated with cholestyramine did not show significant differences in any of the six rheological parameters that were studied when compared to the other patients. Therefore, the results of the FH group were analyzed as a whole when they were compared with the CG. The following significant differences were found: Index of erythrocyte aggregation at stasis 5.0 +/- 1.2 vs 3.6 +/- 1.0 (p < 0.001), index of erythrocyte aggregation at low rate of blood shears 8.1 +/- 1.7 vs 6.9 +/- 1.4 (p < 0.001) and plasma viscosity 1.19 +/- 0.11 vs 1.16 +/- 0.04 mPA/s (p < 0.01). There were no significant differences in the plasma fibrinogen nor in the blood viscosity at shear rats of 230/s and 23/s. Carotic echo-doppler was taken in the HF patients which was normal, indicative of the absence of atherosclerosis lesions in the fibrous plaque phase. CONCLUSIONS: These results indicate that there are hemorrheological alterations in absences of established atherosclerotic lesions, which are associated with hypercholesterolemia and that emerge in the pediatric population. Therefore, research in FH patients offers new data to evaluate the atherogenic risk and its complications.

Efficacy of low doses of the polyethylene glycol derivative of interleukin-2 in modulating the immune response of patients with human immunodeficiency virus type 1 infection.

Interleukin-2 (IL-2) is a key cytokine in cellular immunity. Human immunodeficiency virus type 1 (HIV-1)-infected individuals lack IL-2 because of low CD4+ T lymphocyte numbers. In an attempt to enhance cellular immunity, low-dose recombinant human (rh) IL-2 at 10 micrograms or 180,000 units or its polyethylene glycol (PEG) derivative at 9 micrograms or 36,000 units was given by intracutaneous injection to 8 HIV-1-infected men for 30 days. Participants had no evidence of opportunistic infection and received concurrent zidovudine. IL-2 treatment was nontoxic and elicited a local cellular response resembling classic delayed-type hypersensitivity (DTH) with local interferon-gamma production, even in anergic patients. Systemic responses included enhanced DTH responses to recall antigens, improved in vitro proliferative responses to mitogen, and enhanced NK cell activity. Peripheral leukocyte phenotype and virus titers were unchanged. Long-term studies of low-dose IL-2 are warranted to determine whether immunoenhancing effects can be sustained and if they are associated with improved clinical course.

Prolonged immunostimulatory effect of low-dose polyethylene glycol interleukin 2 in patients with human immunodeficiency virus type 1 infection.

13 patients with human immunodeficiency virus type 1 infection class II-IV, but without opportunistic infection or neoplasm, received 6 micrograms (3.6 x 10(4) IU) of polyethylene glycol recombinant human interleukin 2 (PEG IL-2) intradermally twice a week for 4 mo were then followed for an additional 6 mo. Clinical, immunological, and viral parameters were monitored in the patients, all of whom were taking zidovudine. The cutaneous administration of PEG IL-2 resulted in an indurated zone resembling a delayed-type hypersensitivity response of 26 +/- 1 mm diameter (676 mm2) at 72-96 h after injection throughout the 4 mo of administration. This dose, which was appreciably lower than in most previous trials, was not associated with local or systemic toxicity. No increase in the viral burden of circulating leukocytes or plasma occurred. A number of immunological functions were stimulated by this course of therapy. All patients demonstrated high levels of lymphokine-activated killer cell activity by cells freshly removed from the circulation and in the absence of in vitro exposure to IL-2. Natural killer cell activity was also enhanced. Limiting dilution analysis revealed an increase in the frequency of IL-2-responsive cells from abnormally low to levels above normal during the course of injections. In a subgroup of four patients with > or = 400 CD4+ T cells/microliter at entry, there was a trend to sustained increases in CD4+ T cell numbers. However, this increase did not reach statistical significance. This subset of patients also exhibited higher proliferative responses to phytohemagglutinin as mitogen. Several of these effects persisted for 3-6 mo after cessation of therapy. In conclusion, low-dose IL-2 regimens lead to sustained immune enhancement in the absence of toxicity. We suggest pursuit of this approach for further clinical trials both as prophylaxis and therapy.