Therapeutic drug monitoring of antitubercular agents for disseminated Mycobacterium tuberculosis during intermittent haemodialysis and continuous venovenous haemofiltration.

WHAT IS KNOWN AND OBJECTIVE: There is a lack of data regarding therapeutic drug monitoring (TDM) of antitubercular agents in the setting of continuous venovenous haemofiltration (CVVH). We describe TDM results of numerous antitubercular agents in a critically ill patient during CVVH and haemodialysis. CASE SUMMARY: A 49-year-old man was initiated on treatment for disseminated Mycobacterium tuberculosis. During hospital admission, the patient developed critical illness and required renal replacement therapy. TDM results and pharmacokinetic calculations showed adequate serum concentrations of rifampin, ethambutol and amikacin during CVVH and of rifampin, pyrazinamide, ethambutol and levofloxacin during intermittent haemodialysis. WHAT IS NEW AND CONCLUSION: The presence of critical illness and renal replacement therapy can induce pharmacokinetic changes that may warrant vigilant TDM to ensure optimal therapy. To our knowledge, this is the first report to describe TDM for several antitubercular agents during CVVH in a critically patient with disseminated M. tuberculosis.

Nanowire networks and hollow nanospheres of Ag-Au bimetallic alloys at room temperature.

Due to their physicochemical properties, metallic nanoalloys have potential applications in biomedicine, electrocatalysis and electrochemical sensors, among many other fields. New alternative procedures have emerged in order to reduce production costs and the use of toxic substances. In this study we present a novel low-toxicity synthesis method for the fabrication of nanowire networks (NWNs) and Ag-Au hollow nanospheres. The synthesis process is performed at room temperature without any sophisticated equipment, such as special cameras or furnaces, etc. Transmission electron microscopy showed that the NWNs contain random alloys with a diameter of between 10-13 nm. The radius for the hollow nanospheres is approximately located between 70-130 nm. The absorption bands in the UV-vis spectrum associated with the surface plasmon in Ag-Au bimetallic nanoparticles are highlighted at 385 nm for the NWNs and 643 nm for the hollow nanospheres. The study was performed with low-toxicity substances, such as rongalite, ascorbic acid and sucrose, and showed high efficiency for the fabrication of these types of nanostructures, as well as good stability for long periods of time.

Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial.

OBJECTIVE: To evaluate the effect of short-term hormone replacement therapy with 0.625 mg conjugated estrogens daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. METHODS: We performed a double-blinded, randomized, controlled trial over 3 years. Randomization was performed using computer-generated sorting. All participants were blinded to the use of conjugated equine estrogens (CEE) or placebo and FMD was assessed by a blinded examiner, before and after 28 days of medication. A total of 64 healthy postmenopausal women were selected and randomly assigned into two groups of treatment: 0.625 mg of CEE or placebo. RESULTS: FMD values were statistically different between the groups (p = 0.025): the group receiving CEE showed a FMD value of 0.011 compared to the placebo group (FMD = -0.082). The two groups were additionally evaluated for homogeneity through the Shapiro-Wilk test in respect to variables that could interfere with endothelial function such as age (p = 0.729), body mass index (p = 0.891), and time since menopause (p = 0.724). Other variables were excluded during selection of the participants such as chronic vascular conditions, smoking, and sedentary lifestyle. CONCLUSION: Our results demonstrate that the administration of 0.625 mg CEE for 28 days is effective in improving vascular nitric oxide-dependent dilation assessed by FMD of the brachial artery in postmenopausal women. CLINICAL TRIAL REGISTRATION: NCT01482416.

Short-term tibolone does not interfere with endothelial function: a double-blinded, randomized, controlled trial.

Objective To evaluate the effect of short-term hormone replacement therapy with tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. Methods We performed a randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women were randomly allocated to receive tibolone (n = 50) or placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was performed before and after the use of tibolone and placebo. Results A total of 31 women completed the study in the tibolone group, and 32 women completed the study in the control group. The results of the FMD measurements obtained from the women in the two groups before treatment were similar (0.018 and 0.091, for tibolone and placebo, p = 0.57). The values of the FMD in women who used tibolone and placebo, before and after the treatment, were similar in both groups. The numbers of women who presented an increase in the values of the FMD in both groups were also similar. Conclusion Our results demonstrate that the administration of 2.5 mg tibolone to healthy postmenopausal women for 28 days does not promote endothelial-dependent vasodilation, measured by FMD of the brachial artery.

[Stress level assessment of the nursing staff in the Intensive Care Unit of a university hospital]. / Nivel de estrés del personal de enfermería de la Unidad de Cuidados Intensivos de un hospital clínico universitario.

The objective was to determine the work stress level among nursing staff in the Intensive Care Unit of a university hospital and to analyse its relationship with the various sociodemographic and working variables of the studied sample. A study was designed using a quantitative, descriptive and cross-sectional approach. The target population of the study was the nursing staff selected by non-random sampling. The instrument used was the Job Content Questionnaire. Data analysis was performed using SPSS 20. The mean, ranges and standard deviation for each of the variables were calculated. A bivariate analysis was also performed on the social and occupational variables of the sample. The participation rate was 80.90% (N=89). The mean of the Social support dimension was 3.13±0.397, for the Psychological demands at work dimension it was 3.10±0.384, with a mean of 2.96±0.436 being obtained for the Control over the work dimension. In the analysis of sociodemographic and work variables of the sample, only the professional category was significant, with nurses recording higher values in perception of job demands and control over their work compared to nursing assistants. In conclusion, there is a moderate perception of work stress in the analysed group of professionals. Among the sources of stress in the workplace was the low control in decision-making by practitioners, as well as the need to continually learn new things. On the other hand, the support received from colleagues is valued positively by the sample.

Best practices for the care of pregnant people living with TB.

BACKGROUND: Each year more than 200,000 pregnant people become sick with TB, but little is known about how to optimize their diagnosis and therapy. Although there is a need for further research in this population, it is important to recognize that much can be done to improve the services they currently receive.METHODS: Following a systematic review of the literature and the input of a global team of health professionals, a series of best practices for the diagnosis, prevention and treatment of TB during pregnancy were developed.RESULTS: Best practices were developed for each of the following areas: 1) screening and diagnosis; 2) reproductive health services and family planning; 3) treatment of drug-susceptible TB; 4) treatment of rifampicin-resistant/multidrug-resistant TB; 5) compassionate infection control practices; 6) feeding considerations; 7) counseling and support; 8) treatment of TB infection/TB preventive therapy; and 9) research considerations.CONCLUSION: Effective strategies for the care of pregnant people across the TB spectrum are readily achievable and will greatly improve the lives and health of this under-served population.

Green Synthesis for Carbon Quantum Dots via Opuntia ficus-indica and Agave maximiliana: Surface-Enhanced Raman Scattering Sensing Applications.

In this study, we present an alternative method for synthesizing carbon quantum dots (CQDs) using a green synthesis approach via extracts from Agave maximiliana and Opuntia ficus-indica(Ofi). The extracts from both plants were used as the carbon source for the CQDs. The synthesis method employs mesoporous zeolite 4A as a refractory for the thermal treatment of the samples. Transmission electron microscopy analysis established that the size of the CQDs shows a narrow distribution centered around 2 nm with a maximum size of less than 3 nm for both cases. The CQDs exhibit absorption bands associated with π-π* transitions located around 220 nm. In both cases, photoluminescence (PL) phenomenon was detected by irradiating the samples with a UV wavelength and detecting emissions close to the blue wavelength. Additionally, both kinds of CQDs were tested as surface-enhanced Raman scattering (SERS) substrates against methylene blue (MB), indicating an enhancement associated with ring deformation and stretching modes of the v(C-C) and v(C-N) bonds located around 1400 and 1620 cm-1, respectively. Complementarily, in the framework of density functional theory, H2nC2(2m+1) structures (with n = 3-5 and m = 1-3) were used as a theoretical representation of CQDs in interaction with the MB molecule. It is used for developing the analysis of charge transfer effects between both systems and for specifying elements that generate the SERS effect associated with the chemical enhancement mechanism.

Detection of hantaviruses in Brazilian rodents by SYBR-Green-based real-time RT-PCR.

Current knowledge of the pathogenic hantavirus indicates that wild rodents are its primary natural reservoir. Specific primers to detect the presence of viral genomes were developed using an SYBR-Green-based real-time RT-PCR protocol. One hundred sixty-four rodents native to the Atlantic Forest biome were captured in São Paulo State, Brazil, and their tissues were tested. The presence of hantavirus RNA was detected in sixteen rodents: three specimens of Akodon montensis, three of Akodon cursor, two of Necromys lasiurus, one of Juliomys sp., one of Thaptomys nigrita, five of Oligoryzomys nigripes, and one of Oryzomys sp. This SYBR Green real-time RT-PCR method for detection of hantavirus may be useful for surveying hantaviruses in Brazil.

Immunopathological evaluation of recombinant mycobacterial antigen Hsp65 expressed in Lactococcus lactis as a novel vaccine candidate.

Bovine tuberculosis (TBB) is a zoonotic disease distributed worldwide and is of great importance for public health and the livestock industry. Several experimental vaccines against this disease have been evaluated in recent years, yielding varying results. An example is the Bacillus Calmette-Guérin (BCG) vaccine, which has been used extensively in humans and tested in cattle showing mixed results related to protection (0-80%) against Mycobacterium bovis. In this study, we used the food-grade bacterium Lactococcus lactis as an expression system for production of mycobacterial protein Hsp65. For this purpose, the construction of a replicable plasmid in strain NZ9000 L. lactis (pVElepr) was conducted, which expressed the Mycobacterium leprae Hsp65 antigen, and was recognized by traded anti-Hsp65 antibodies. The strain NZ9000-pVElepr was applied to calves that were negative to tuberculin test and the immune response was monitored. The results showed that immune response was not significantly increased in calves with NZ9000-pVElepr with respect to control groups, and no injury was observed in any lung or lymph of the calves. Finally, this study suggest that the recombinant NZ9000 strain of L. lactis may protect against the development of M. bovis infection, although studies with longer exposure to this pathogen are necessary to conclude the matter.

Evaluation of albendazole prodrugs in experimental trichinellosis.

BACKGROUND: Two albendazole (ABZ) prodrugs, N-methoxycarbonyl-N'-[(2-nitro-4-propylthio) phenyl] thiourea (compound 2), and N-methoxycarbonyl-N'-[(2-nitro-5-propylthio) phenyl] thiourea (compound 3) have recently been synthesized. These compounds showed greater solubility than ABZ itself. METHODS: In order to evaluate the biotransformation of compounds 2 and 3 to ABZ and/or ABZ-sulphoxide (ABZ-SO), plasma samples taken from mice treated with the prodrugs were analyzed by HPLC. Also, the anthelmintic activity of compounds 2 and 3 against Trichinella spiralis was evaluated in the mice experimentally infected with the parasite. RESULTS: The presence of ABZ and/or ABZ-SO was demonstrated in plasma samples taken at different time intervals after prodrug administration, although their levels were low compared to those reached in mice treated with ABZ. Additionally, prodrugs 2 and 3 were also detected in these samples. In regard to the anthelmintic activity of ABZ prodrugs, it was shown that compound 3 was more active than compound 2. Additionally, it was as effective as ABZ against T. spiralis pre-adult, adult, and female fecundity. However, compound 3 was not as active as ABZ against the muscle stage of the parasite. CONCLUSIONS: Compound 3 had better anthelmintic activity against T. spiralis than compound 2. The bioconversion of compounds 2 and 3 to ABZ and/or ABZ-SO was demonstrated by HPLC, but they did not reach equivalent concentrations to that of ABZ. Prodrugs 2 and 3 were also present in plasma samples, suggesting that prodrugs were not efficiently reduced in the intestine of mice.

Hemocytopenia as initial manifestation of systemic lupus erythematosus. Prognostic significance.

In 1960 Rabinowitz and Dameshek emphasized the close relationship between idiopathic thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE) and suggested that ITP is often a prodrome of SLE. On the basis of tis observation, the present study was designed to investigate the prevalence of SLE in patients with the initial diagnosis of ITP, autoimmune hemolytic anemia (AIHA), Fisher-Evans' syndrome (F-E) and idiopathic aplastic bone marrow (IABM) and to investigate the salient clinical manifestations and prognosis of these patients. We studied 62 patients, 35 with ITP, 16 with AIHA, 9 with F-E and 2 with IABM. Seventeen developed four or more ARA criteria for SLE within 6 of 14 years after the initial hematologic manfestations (IHM). Mucocutaneous symptoms predominated in all groups. None developed renal failure and only 2 had central nervous system involvement. When these patients were matched by age, sex and duration of illness with 24 SLE patients without hematologic abnormalities, the everity and therapeutic indices of the former showed a significantly (p 0.001) milder course. Eight of the 9 patients that required splenectomy are at present without treatment. SLE patient with IHM have a more benign course which is not worsened by splenectomy.

FasL and Bax genes are differentially expressed in acinar epithelium and inflammatory cells of primary Sjögren salivary glands.

AIM: Assess the expression of FasL, Bax, TNFa and IL-6, genes in salivary glands of primary Sjögren patients. METHODS: Twenty minor salivary glands from patients with primary Sjögren syndrome were studied by in situ hybridization with cDNA fluorescent probes. An equal number of control biopsies were included. RESULTS: Sjögren salivary glands differentially display the inflammatory cytokines and pro-apoptotic mRNAs as follows: mononuclear infiltrating cells exhibited IL-6 and TNFa, whereas the ductal epithelium and acinary cells mainly expressed FasL and Bax. Control biopsies were negative. CONCLUSION: Present data suggest that local production of inflammatory cytokines would induce the Fas and Bax pathways committing the ductal epithelium and the acinary cells to apoptosis.

Antifungal activity of some Cuban Zanthoxylum species.

Ethanolic extracts of the trunk bark of Zanthoxylum fagara, Z. elephantiasis and Z. martinicense showed activity against different species of fungi. No antibacterial activity was detected.

Accidental radiation injury to the hand: anatomical and physiological considerations.

A case study describing an accident in Mexico caused by failure to de-energize an x-ray spectrometer prior to repair is presented. The evolution, medical management, and outcome of the radiation injury to the hand are briefly reviewed. A discussion follows, with radiation injury and thermal burns compared and contrasted. The anatomy and physiology of thick skin and the vascular system of the hand are reviewed so that the reader will have a better understanding of the role of vascular injury in the pathological process that leads to tissue atrophy and radiation necrosis. Hyperbaric oxygen therapy, sympathectomy, and other techniques for improving circulation in involved areas are reviewed.

Possible role of Hsp70 in autoantigen shuttling to the dermo-epidermal junction in systemic lupus erythematosus.

The lupus band is the result of immune complex deposition along the dermo-epidermal junction; such complexes are formed in situ by the interaction of antinuclear antibodies with their respective autoantigens. Dermal autoantigens are released after sun exposure, concurrently a heat shock protein production take place and would participate in autoantigen transfer to the dermo-epidermal junction. In this work the presence of Hsp70 along with the lupus band was investigated by immunofluorescence in twenty SLE skin biopsies. Immune deposits were mainly composed by IgM, IgG and C3 and were found in all lupus biopsies at the dermo-epidermal junction. Immunoreagents were also present into papillary vessels and, with less extent, into epidermal keratinocytes. Hsp70 was present in 60% of lupus biopsies, and was mainly distributed along dermo-epidermal junction and around papillary vessels. Furthermore, by double fluorescence labelling assays, we found that immuno-reactants are co-localized with Hsp70. Our results suggest that Hsp70 would shuttle autoantigens to the dermo-epidermal junction.

Drug-induced agranulocytosis treated with granulocyte-macrophage colony stimulating factor.

Drug induced agranulocytosis (DIA) is a potentially lethal disorder characterized by selective neutropenia. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been utilized for its treatment. We report four cases of DIA treated with GM-CSF at the dose of 5 micrograms/kg/day. The patients presented infectious diseases at diagnosis. Median days to obtain 1 x 10(9)/L neutrophils and a normal neutrophil count (NNC), were 7(5-9) and 7.5 (6-10) days, respectively. The infectious disease at diagnosis improved and all patients are alive at the moment of this report. No other adverse effects than thrombocytosis (two cases) and thrombocytopenia (one case) were observed. We consider that GM-CSF could be a safe and effective alternative in the treatment of DIA.

Diagnostic laparotomy in fever of unknown origin.

Twenty five consecutive patients with fever of unknown origin (FUO) who underwent diagnostic laparatomy (DL) are reviewed. There were 14 females and 11 males, with a mean age of 34 years. The main symptoms and signs besides fever were malaise, weight loss, varied abdominal complaints, peripheral lymph nodes enlargement, hepatomegaly and splenomegaly. The main laboratory abnormalities were: anemia, leukocytosis, and mild alterations in liver function tests. CT scan was performed in 14 patients: hepatomegaly, splenomegaly and or retroperitoneal nodes were found in 10 of them. During laparotomy, an extensive exploration of intra-abdominal organs was performed, taking multiple biopsies for histopathologic and microbiologic analysis. Splenectomy was performed in 17 patients, prophylactic appendectomy in four, and cholecistectomy in one. Laparotomy was useful to establish a diagnosis in 64 percent of cases. The most frequently diagnosed pathologies were lymphoma and tuberculosis. Postoperative morbidity was 12% and mortality was 4%. Mean follow-up was 29 months. When preoperative data were analyzed, no predictive factors were found for a laparotomy with diagnostic success. It is concluded that DL is a useful last-step procedure in the diagnostic work-up for patients with FUO.

[Seroprevalence of viral markers of hepatitis B among health professionals. Multicenter study in Mexico]. / Seroprevalencia de marcadores virales de hepatitis B en profesionales de la salud. Estudio multicéntrico en México.

To determine the prevalence of serological markers for hepatitis B infection among health care workers (HCW) in Mexico we surveyed 1072 volunteers from 26 hospitals in 12 states, from which only 1017 fulfilled the inclusion criteria: 82 patients (8.1%) were excluded because of lipemic and/or hemolyzed serum, leaving 935 persons in the study. The study population consisted of physicians, nurses, laboratory chemists, health laboratory technicians and odontologists. All of them had been working in their respective fields and in contact with biological materials for at least 12 months. None of them had been vaccinated for hepatitis B. We determined the presence of HBsAg and anti-HBs by the ELISA method. The participants' mean age was 31.4 years (range: 18-72) and their mean working time was 7.8 years. 615 were female and 320 male. The HBsAg was positive in 11 (1.2%) and the anti-HBs in 91 cases (9.7%). These results suggest that HCW in Mexico have a greater relative risk of becoming infected with the HB virus than the general population. Relative risks were particularly higher for the health laboratory technicians and the physicians. These results confirm that biohazard measures must be reinforced and that the application of HB virus vaccine could be recommended for health care workers.

[Secondary polycythemia and gasometric changes in chronic bronchopneumopathies with respiratory insufficiency]. / Poliglobulia secundaria y alteraciones gasométricas en bronconeumópatas crónicos con insuficiencia respiratoria.

42 patients with chronic bronchopneumopathy were divided into 2 groups: one with polyemia (15 patients) and the other without polyemia (27 patients). There was no statistical significant differences in median age, clinical evolution nor basal medium arterial PO2 value (43 +/- 12 and 48 +/- 11 mm Hg); while there was an increase of median basal PCO2 in patients with polyemia (54 +/- 8.4 and 48 +/- 9.3; P < 0.025). There was direct correlation between PCO2 and Hb levels in the whole series (r = 0.42; P < 0.01) and equal correlation in the limit of statistical signification between PCO2 and red cells (r = 0.29; P = 0.05). The correlation between these hematic values and the PO2 values of the whole series was not significant, this taking into account the logical inverse relation between them, because of the important role of hypoxia in developing polyemia. The correlation between PO2 and PCO2 was inverse and significant (r = -0.33; P < 0.05). These findings show the apparent influence of CO2 retention to produce polyemia, apart from the effects of hypoxia, being the opposite of the results in experimental studies which showed a stoppage of the erythropoietin production by CO2 effects. The probable explanation is that patients with more PCO2 had more intense respiratory malfunction than lower PCO2 patients, producing night episodes of more basal hypoxia, this being a major stimulus of polyemia.

[Liver transplantation in Mexico. Report of the first successful case]. / Trasplante de hígado en México. Informe del primer caso exitoso.

This article reports the first successful human orthotopic liver transplantation performed in Mexico. The recipient was a 41 year old white male, with a history of essential hypertension and hepatitis in 1975. The diagnosis of postnecrotic cirrhosis was made in 1985 by liver biopsy. The HBsAg was negative and the functional reserve of the liver was limited (Stage "C" of the Child-Pugh classification). A liver graft was obtained through the National Cadaver Organ Transplant Program on May 2, 1988 and an orthotopic liver transplantation was performed without incidents, using the portosystemic veno-venous bypass. Inmunosuppression was carried out with triple drug therapy, cyclosporine, azathioprine, and prednisone. His postoperative course was characterized by idiopathic cholestasis, one episode of acute rejerction, arterial hypertension, renal dysfunction, esophageal herpes and inguinal lymphocele, all of which resolved. Currently the patient is alive 22 months postransplantation with normal liver function and adequate quality of life.