Open Label Randomized Controlled Comparison of Three Alternative Regimes of Ciprofloxacin, Azithromycin and Cefixime for Treatment of Uncomplicated Typhoid Fever in Bangladesh.

Multi-drug resistant Typhoid fever (resistant to previously used chloramphenicol, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole) has been commonly described in the South East Asia region and a recent report suggests that the salmonella typhi have reduced response to fluoroquinolones (nalidixic acid-resistant). The optimum treatment protocol for this type of serovar has not been established. This study compared different antimicrobial regimens for the treatment of uncomplicated typhoid fever which was conducted in the medicine ward of Dhaka Medical College Hospital (DMCH) and outdoor setting in private practice in Dhaka metropolitan city, Mymensingh and Sylhet town from January 2017 to December 2017. Bangladeshi adults with uncomplicated typhoid fever were included in this an open-label randomized controlled trial. Ciprofloxacin (20mg/kg of body weight/day for 14 days), azithromycin (20mg/kg/day for 14 days), and Cefixime (16mg/kg/day for 14 days) were compared. Of the 81 enrolled patients, 62 were eligible for analysis (61 S. enterica serovar Typhi, 1 Salmonella enterica serovar paratyphi A). Of the S enterica serovar Typhi isolates, 88.7% (55/62) were MDR and 93.5% (58/62) were nalidixic acid resistant (NAR). The clinical cure rate was 62% (13/21) with ciprofloxacin, 71% (15/21) with Cefixime, and 85% (17/20) with azithromycin (p=0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with cefixime (7.1 days [6.2 to 8.1 days]) and ciprofloxacin (8.2 days [7.2 to 9.2 days]) (p<0.001). All three antibiotics were well tolerated. A 7-day course of azithromycin can be successfully used in uncomplicated typhoid fever due to isolates of MDR S enterica serovar Typhi.

Induction of apoptosis in A431 skin cancer cells by Cissus quadrangularis Linn stem extract by altering Bax-Bcl-2 ratio, release of cytochrome c from mitochondria and PARP cleavage.

Skin is generally damaged through genetic and environmental factors such as smoking, exposure to xenobiotics, heat, hormonal changes, and ultraviolet light. These factors can cause skin diseases. Cissus quadrangularis Linn. (CQ) has been used in folk medicine for the treatment of skin diseases since ancient times. Taking in to consideration the medicinal properties exhibited by this genus, it was decided to investigate the anti-cancer activity of CQ. Extracts obtained from CQ and their phenolic contents were subjected to in vitro evaluation of anticancer activity by using A431 (skin epidermoid carcinoma, human) cell line. The A431 cells were treated with different extracts of CQ in a dose dependent manner. Out of five extracts, the acetone extract demonstrated significant anti-cancer activity in the A431 cell line. Hexane, chloroform, ethyl acetate and methanol extracts also exhibited cytotoxicity but to a comparatively lesser extent than the acetone extract. The GI(50) value of the acetone extract was found to be 8 µg mL(-1), whereas GI(50) value of purified fraction of acetone extract, termed as AFCQ (active acetone fraction of CQ) with respect to A431 cells, was found to be 4.8 µg mL(-1). Furthermore, the mechanism of anticancer activity exhibited by AFCQ was investigated by comparing its effect with the standard anticancer drug Doxorubicin (DOX) by evaluating the status of apoptotic markers after treatment of A431 cells with AFCQ and DOX. Bax-Bcl-2 ratio along with the release of cytochrome c from mitochondria to cytoplasm, which is a hallmark of apoptosis, was also evaluated. Cleavage of PARP revealed that AFCQ induces apoptosis in A431 cells with reference to DOX.

Antioxidant capacities and total polyphenol contents of hydro-ethanolic extract of phytococktail from trans-Himalaya.

The aim of this study was to evaluate the in vitro antioxidant potential of hydro-ethanolic extract of a novel phytococktail comprising of sea buckthorn, apricot, and Rhodiola (SAR) from trans-Himalaya. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) activity of the extract increased in a dose-dependent manner (upto 0.1 mg/mL), and was found to be about 38% of that of ascorbic acid at 0.1 mg/mL. The hydro-ethanolic extract of SAR also scavenged the ABTS(.+) radical generated by ABTS/potassium persulfate (PPS) system and was found to be about 62% of that of ascorbic acid at 0.1 mg/ mL. The total antioxidant power of the extract was determined by ferric reducing antioxidant power (FRAP) assay. Total phenolic content was found to be 1.28016 × 10(-3) mol gallic acid equivalent (GAE)/g extract. Total flavonoid and flavonol contents were estimated to be 2.5970 × 10(-4) mol and 4.87 × 10(-4) mol quercetin equivalent/g extract, respectively. The hydro-ethanolic extract of this phytococktail indicated presence of essential phytoconstituents of polyphenols, flavonoids, flavonols, and ascorbic acid, which contributed significantly to its antioxidant capacity. The combination of the 3 plants may well support their use in traditional medicine to combat oxidative stress and high-altitude sickness.

Hepatoprotective and antioxidant effects of Argyreia speciosa in rats.

The present study has been designed to evaluate the liver protective and in-vivo antioxidant role of Ethanolic extract (EtAS) and Ethyl acetate extract (EAAS) of roots of Argyreia speciosa, an important 'rasayana' herb in Indian System of medicine, in CCl(4)-induced hepatotoxicity and oxidative stress in rats. Animals were treated with EtAS and EAAS at doses of 200 mg and 400 mg/kg body weight p.o. along with CCl(4) (0.7 ml/kg in olive oil, 1:1 v/v i.p. on every alternate days) for seven days. Serum biochemical parameters such as SGOT, SGPT, ALP, cholesterol, total and direct bilirubin were determined. Antioxidant status in liver was determined by measuring the activities of Super oxide dismutase (SOD), catalase and peroxidase. Histopathological study of isolated liver specimens was also carried out to know the protection offered by the extracts. There was a significant rise in the levels of serum GOT, GPT, and ALP and other biochemical parameters, decrease in the levels of SOD, catalase and peroxidase after administration of CCl(4). Suspensions of EtAS and EAAS (200 and 400 mg/kg) successfully prevented the alterations of these effects in rats (p< 0.001). Histopathological examination demonstrated that CCl(4) treated group induces ballooning degeneration and centrilobular necrosis. Groups treated with EtAS and EAAS showed recovery on ballooning degeneration and centrolobular bridging necrosis was occasionally present. Data also showed that these extracts possessed strong antioxidant activity, and were comparable to Silymarin, a well known liver protecting herbal formulation.

Bioturbation-induced phosphorous release from an insoluble phosphate source.

The influence of bioturbation caused by common carp fry in 5 L jars (5 L each) in the laboratory and in 150 L outdoor vats in increasing the fertilizer value of phosphate rock was evaluated. Soluble reactive phosphate (SRP) was determined to quantify the effects of bioturbation, fish excrements and soil. The level of SRP was always lowest in the control series. Introduction of common carp fry resulted in a net increase of 0.09-0.10 mg L(-1) of SRP attributable to the effect of fish excrement. Bioturbation caused by common carp resulted in a 64.8-90% influx of phosphate from bottom soil in the presence of phosphate rock but only about 6.3-7.2% in the absence of phosphate rock. The bioturbation that occurred in these treatments resulted in a significant release of phosphorous into the overlying water from the apatite source. The results confirm the benefits of the application of environmentally friendly phosphate rock in fish farming ponds at low cost.

A polyherbal vaginal pessary with spermicidal and antimicrobial action: evaluation of its safety.

A polyherbal vaginal pessary (Praneem) has been formulated that has antimicrobial properties against genital pathogens in addition to spermicidal action. Thus, it has dual potential as a barrier method for contraception and for providing protection against some sexually transmitted infections. The present study reports the findings of a multicentre trial that was conducted to evaluate the safety of this product. Trials were carried out in 23 women in three centres in India: the Postgraduate Institute of Medical Education and Research, Chandigarh; Safdarjang Hospital, New Delhi; and Kamla Nehru Memorial Hospital, Allahabad. Thorough clinical and pelvic examinations were carried out as well as cervical cytology, blood biochemistry and haematology before and after use of the polyherbal pessary intravaginally once daily for 7 consecutive days. No toxicity was observed on clinical examination or by laboratory investigations. Daily intravaginal use of this pessary for 7 days had no adverse effects on cervical cytology or on metabolic and organ functions.

A method of MRI-based thermal modelling for a RF phased array.

Magnetic Resonance Imaging (MRI) is an attractive method of temperature monitoring in vivo due to its non-invasive nature. The natural extension of this temperature monitoring is to implement temperature control. This work outlines a method of MRI-based thermal modelling for multi-source phased array heating systems that can potentially be employed, in the future, for real time temperature prediction and control. This method is based on Pennes bioheat equation. It employs the superposition of an empirically acquired basis set of temperature distributions that define the heating system's temperature response. MR thermal images based on the proton resonance frequency shift (PRFS) technique are used to acquire this basis set. The feasibility of this approach is tested in phantom using a radiofrequency (RF) heating system. The results show that this method can accurately reproduce measured temperature distributions outside of the basis set.

3D numerical reconstruction of the hyperthermia induced temperature distribution in human sarcomas using DE-MRI measured tissue perfusion: validation against non-invasive MR temperature measurements.

Essential to the success of optimized thermal treatment during hyperthermia is accurate modelling. Advection of energy due to blood perfusion significantly affects the temperature. Without accurate estimates of the magnitude of the local tissue blood perfusion, accurate estimates of the temperature distribution can not be made. It is shown here that the blood mass flow rate per unit volume of tissue in the Pennes' bio-heat equation can be modelled using a relative perfusion index (RPI) determined with dynamic-enhanced magnetic resonance imaging (DE-MRI). Temperature distributions in two patients treated with hyperthermia at Duke University Medical Center for high-grade leg tissue sarcomas are modelled, and the resultant temperatures are compared to measured temperatures using a non-invasive MR thermometry technique. Significant correlations are found between the DE-MRI perfusion images, the MR temperature images, and the numerical simulation of the temperature field. The correlation between DE-MRI measured values and advective heat loss in tissue is used to scale the perfusion distribution, thereby allowing the continuum model to account for the local thermal impact of vasculature in the tumour. Large vessels in tumour and neighbouring healthy tissue need to be taken into account in order to accurately describe the complete temperature distribution.

Effects of beta-adrenergic blocking therapy on left ventricular diastolic relaxation properties in patients with dilated cardiomyopathy.

BACKGROUND: The hemodynamic mechanism for the improvement in left ventricle (LV) end-diastolic pressure in cardiomyopathy patients treated with beta-adrenergic blocking agents is controversial. We hypothesized that the salutary effect of this kind of therapy on LV end-diastolic pressure would be indicative of an improvement in late, passive diastolic relaxation properties. METHODS AND RESULTS: We studied 14 cardiomyopathy patients in normal sinus rhythm with no arteriographic evidence of coronary artery disease and an LV ejection fraction of

Electromagnetic thermal therapy power optimization for multiple source applicators.

The optimization of power deposition for electromagnetic (EM) thermal therapy is investigated. Several goal or objective functions are examined using a generalized mathematical formulation. These include maximization of: (1) target power absorption, (2) the ratio of target to non-target power absorption, (3) target power absorption weighted by the ratio of target to non-target power absorption, and (4) target power absorption subject to the constraint that the non-target high power volume ('hot spot' volume) is below a chosen level. The merit of these functions was retrospectively tested using an anatomic data base containing 38 cancer patients that were clinically heated with EM phased arrays. CT and/or MRI image data were used to define relevant anatomic geometries and tissue properties for finite element numerical models. Power optimization is achieved by variation of seven available control parameters (four amplitudes and three phases) for these clinical array devices. The results indicate that site dependent improvements in target power absorption can be achieved using these goal functions relative to a configuration that utilizes equal phase and amplitude for the sources. The relative merit among these various functions favours an optimization strategy that maximizes the target power absorption weighted by the ratio of target power to non-target power absorption.

Computational techniques for fast hyperthermia temperature optimization.

Hyperthermia temperature optimization involves arriving at a temperature distribution which minimizes a stated goal function, the goal function having a biological basis in maximizing tumor cell kill while not exceeding normal tissue toxicity. This involves the computationally intensive process of multiple evaluations of the temperature goal function, requiring repeated evaluations of the power deposition and its corresponding temperature distribution. Two computational schemes are proposed to expedite the temperature optimization process: (1) temperature distribution evaluation by superpositioning precomputed distributions, and (2) using representative tissue groups (rather than every point in the domain) to evaluate the goal function. The application of these schemes is illustrated with a typical optimization problem, as applied to symmetric and asymmetric, heterogeneous models. Application of these schemes reduced the optimization time on a DEC Alpha 1000 4/266 (Alpha is a registered trademark of Digital Equipment Corporation.) from several h to min, with little difference in results. The computational schemes, though demonstrated in the context of electromagnetic hyperthermia, are generally applicable to other forms of nonionizing radiation employed in hyperthermia therapy.

Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy.

In the mouse, the attachment reaction between the blastocyst trophectoderm and the receptive uterine luminal epithelium occurs at 2200-2300 h on day 4 of pregnancy and is rapidly followed by transformation of stromal cells into decidual cells (decidual cell reaction). This process can also be induced experimentally (deciduoma) by intraluminal oil infusion in the uterus on day 4 of pseudopregnancy. The decidual cell reaction is associated with up- and down-regulation of many genes in a cell-specific manner. Using mRNA differential display, we identified cyclin D3 as one of the genes that is upregulated in the uterus at the sites of blastocyst apposition during the attachment reaction. The levels of expression were low in the morning of days 1-4 as determined by Northern hybridization. In situ hybridization analysis showed that on days 1 and 2, signals were primarily localized in uterine epithelial cells, while signals were detected in both the stromal and epithelial cells on days 3 and 4. In contrast, with the initiation and progression of decidualization on days 5, 6 and 7, the levels of cyclin D3 mRNA were remarkably upregulated in stromal cells both at the mesometrial and the antimesometrial poles. However, on day 8, signals were primarily localized in stromal cells at the mesometrial decidual bed. Implanting blastocysts on these days also expressed cyclin D3 mRNA. In the progesterone-treated delayed implanting mice, the uterine levels of cyclin D3 mRNA were modest at the sites of blastocyst apposition, but were upregulated with the onset of implantation by estradiol-17beta. However, the decidual expression of cyclin D3 mRNA was not dependent on the presence of blastocysts, since increased expression also occurred in experimentally induced deciduoma in the absence of blastocysts. The importance of cyclin D3 in decidualization was further examined in Hoxa-10-deficient mice which show defective decidualization. The expression of cyclin D3 mRNA in Hoxa-10(-/-) uteri on day 5 was severely compromised after application of a deciduogenic stimulus on day 4 of pseudopregnancy. Collectively, the results suggest that cyclin D3 could be important for the process of decidualization.

Short-term macrophage interleukin-1 response to injected silicone in a rat model.

The short-term effects of silicone particles on the ability of splenic and peritoneal macrophages to produce Interleukin-1 (IL-1) were assessed. Lewis rats were divided into three groups. Group 1 animals (n=12) were injected subcutaneously with 2.5 ml of sterile saline; Group 2 animals (n=12) received 2.5 ml of Freund's Complete Adjuvant (FCA); Group 3 animals (n=12) received subcutaneous injections (2.5 ml) of a sonicated slurry comprised of equal parts of FCA and silicone. At days 1, 4, and 7 single-cell suspensions of splenic (10(8) cells/ml) and peritoneal (10(6) cells/ml) macrophages of four animals from each group were prepared. The supernatants from macrophages cultured in the presence or absence of lipopolysaccharide (LPS) were added to IL-1 dependent mouse thymocytes for 72 hrs, and subsequently pulsed with 3H-thymidine. Radioactivity incorporation was determined after 18 hrs. Peritoneal macrophage culture supernatants had significantly higher activity than splenic macrophages and all macrophages stimulated with LPS had significantly higher activity. At days 1 and 7, there were no significant differences in 3H-thymidine uptake. At day 4 there was an elevation of 3H-thymidine uptake from supernatant of peritoneal macrophages treated with FCA/silicone suggesting subcutaneous silicone injection has short-term effects.

Partial characterization of guinea pig cholinephosphotransferase cDNA.

An alternative molecular biology strategy is needed to characterize cholinephosphotransferase (CPT) gene because of the complexity of the problem associated with the solubilization of the membrane-bound enzyme without denaturation. We have synthesized five heterologous oligonucleotide probes based on the published yeast CPT gene sequence. Each probe (24 to 30 mers) was used as either forward or reverse flanking primers in combination with lambda gt11 primers to amplify a segment of DNA from a guinea pig liver 5'cDNA library by polymerase chain reaction (PCR). We detected several clones of varied size (0.1 kb to 2.2 kb) by subjecting the PCR products to 1.2% agarose gel electrophoresis. Southern blot of a 0.7 kb PCR product did hybridize with a 32P-labeled internal probe. Slot blot hybridization of guinea pig liver total RNA with the 32P-labeled 0.7 kb PCR product yielded positive transcripts with intensities proportional to the concentration of RNA. Furthermore, a 0.1 kb clone was sequenced and the observed sequence shared 96% homology with the yeast CPT gene sequence.

Incidence and significance of cardiac arrhythmia in geriatric oral surgery patients.

We recorded heart rhythms of 40 older patients (20 medicated for cardiovascular disease and 20 not medicated for cardiovascular disease) during an outpatient oral surgery visit to determine overall arrhythmia incidence and severity, differences in incidence associated with cardiovascular medication status, and the impact of surgical intervention on arrhythmia incidence. We hypothesized that both groups would show similar arrhythmia numbers and types during surgical visits and that a history of medication for cardiovascular disease would not be an indicator of cardiac arrhythmia. Enrollment remained open until 20 patients older than 60 years of age from each group agreed to participate. Data were analyzed using the chi square statistic and Fisher's exact test (2-tailed). Included in the study were 24 women and 16 men; their mean age was 70.5 years (range, 60 to 86 years). Arrhythmias were detected in 17 patients and 33 of the 160 recorded rhythms. None of the detected arrhythmias were considered life-threatening. Significantly more arrhythmias occurred before administration of anesthesia than during administration of epinephrine-containing local anesthetics (p = 0.0001), and a greater number of rhythm disturbances were seen during the surgical procedure when compared with anesthesia administration (p = 0.0170). No differences in arrhythmia incidence were seen with increasing age, when male patients were compared with female patients, or when patients pharmacologically treated for cardiovascular disease were compared with patients not taking cardiovascular therapeutic medications. We conclude that although arrhythmias in this ambulatory population are common, they are typically benign in character and cardiovascular medication status is not indicative of their presence. In addition, minor oral surgery intervention with local anesthetics used in recommended dosages has no effect on cardiac arrhythmia status in the ambulatory geriatric population.

Hyperthermia treatment planning and temperature distribution reconstruction: a case study.

While a great deal of effort has been applied toward solving the technical problems associated with modelling clinical hyperthermia treatments, much of that effort has focused on only estimating the power deposition. Little effort has been applied toward using the modelled power depositions (either electromagnetic (EM) or ultrasonic) as inputs to estimate the hyperthermia induced three-dimensional temperature distributions. This paper presents a case report of a patient treated with hyperthermia at the Duke University Medical Center where numerical modelling of the EM power deposition was used to prospectively plan the treatment. Additionally, the modelled power was used as input to retrospectively reconstruct the transient three-dimensional temperature distribution. The modelled power deposition indicated the existence of an undesirable region of high power in the normal tissue. Based upon this result, amplitudes and phases for driving the hyperthermia applicator were determined that eliminated the region of high power and subsequent measurements confirmed this. The steady-state and transient three-dimensional temperature distributions were reconstructed for four out of the seven treatments. The reconstructed steady-state temperatures agreed with the measured temperatures; root-mean-square error ranged from 0.45 to 1.21 degrees C. The transient three-dimensional tumour temperature was estimated assuming that the perfusion was constant throughout the treatment. Using the computed three-dimensional transient temperature distribution, the hyperthermia thermal dose was computed. The equivalent minutes at 43 degrees C achieved by 50% (T50Eq43) of the tumour volume was computed from the measured data and the three-dimensional reconstructed distribution yielding T50Eq43 = 40.6 and 19.8 min respectively.

Simulation of electromagnetically induced hyperthermia: a finite element gridding method.

A finite element gridding method for simulating electromagnetically (EM) induced hyperthermia is presented. The method uses patient CT data as its primary input, with critical structures manually outlined (on a graphics workstation) for explicit demarcation. The paper outlines the various stages involved in mesh creation, including procedures for conforming the finite element representation of critical structures to their smooth boundaries, modelling of heating equipment, and modelling of the outer boundaries. The procedure for generating the finite element model is illustrated for an example treatment. Additionally, the results of computing the SAR in six patients are compared to measured values. The comparison reveals agreement between the model prediction and actual treatment within the limits of measurement error.

Verification of a hyperthermia model method using MR thermometry.

Simulation of hyperthermia induced power and temperature distributions is becoming generally accepted and finding its way into clinical hyperthermia treatments. Such simulations provide a means for understanding the complete three-dimensional temperature distribution. However, the results of the simulation studies should be regarded with caution since modelling errors will result in differences between the actual and simulated temperature distribution. This study uses a diffusion weighted magnetic resonance (MR) based technique to measure hyperthermia induced temperature distributions in a three-dimensional space in a non-perfused phantom. The measured data are used to verify the accuracy of numerical simulations of the same three-dimensional temperature distributions. The simulation algorithm is a finite element based method that first computes the electromagnetic induced power deposition then the temperature distribution. Two non-perfused phantom studies were performed and qualitatively the MR and simulated distributions agreed for steady-state. However, due to the long MR sampling time (approximately 4 min), poor agreement between the simulations and MR measurements were obtained for thermal transients. Good agreement between the simulations and fibreoptic thermometry measurements were obtained. The fiberoptic measurements differed from the simulations by 0.11 +/- 0.59 degrees C and -0.17 +/- 0.29 degrees C (mean +/- standard deviation for the two studies).

Toxic effects of fatty acid anilides on the oxygen defense systems of guinea pig lungs and erythrocytes.

Toxic oil syndrome (TOS) is caused by ingestion of denatured edible oils. Even though the etiology and pathogenesis of this disease are not fully known, it is quite clear that generation of free radicals caused by ingestion of fatty acid anilides is responsible for the pathogenetic mechanism in many TOS patients. Fatty acid anilides may also alter the free radical status of lungs and erythrocytes; this possibility may shed some light on understanding toxic oil syndrome. The present study describes the effects of oral administration of fatty acid anilides on the activities of major enzymes involved in the oxygen defense systems of lungs and erythrocytes. Feeding fatty acid anilides caused an increase in the superoxide dismutase (SOD) activity in erythrocytes, whereas it caused a decrease in the SOD activity in lungs. GSH-Px activity was not significantly changed in erythrocytes but was decreased in lungs. Although the activity of catalase was increased only by a higher dose in the erythrocytes, it was not affected in the lung at any dosage. Even though the ingestion of fatty acid anilides caused an increase in the SOD activity in the erythrocytes and a decrease in the SOD activity in the lungs, there was an increase in the lipid peroxidation in both cases. The increase in lipid peroxidation in erythrocytes is probably caused by the accumulation of H2O2, and that in the lungs is due to the accumulation of superoxide anion.