HYPOTHALAMIC DYSFUNCTION—A Review of Experimental and Clinical Observations of Cardiac and Renal Aspects

The nuclear cell masses of the hypothalamus act as autonomic regulators for visceromotor function. Through the correlation of impulses arising in or about the hypothalamus with the changes in cellular chemistry, there is provided, by mediation of the endocrines, a balanced control of water metabolism, renal function and cardiac action.Derangement of hypothalamic regulation causes specific clinical syndromes described by the general term “diencephalohypophyseal dystrophy.” Cardiac abnormalities attributable to hypothalamic dysfunction include alterations in rate and various arrhythmias. Alteration in renal function includes hematuria, polyuria or relative anuria, and specific effects on electrolyte and nitrogen output.     

CEREBRAL VASCULAR DISEASES—Certain Clinical and Electroencephalographic Aspects

In a preliminary study of 52 patients with cerebral vascular disease, clinical and electroencephalographic evaluations were compared. Most of the patients were in the sixth and seventh decade of life and had had symptoms of cerebral vascular disease for over a year. Seventeen of the patients had clinical evidence of intermittent cerebral ischemia. When routine electroencephalographic techniques were used, 47 per cent of the records were within normal limits. Twenty patients with cerebral vascular disease, eight of whom had clinical cerebral vascular insufficiency, were studied during posturally induced hypotension. No activation was detected in any of these 20 patients. It would appear that other methods of activation, including tilt-table studies, and serial recordings should be further explored and evaluated in these disorders if more clinically useful information is to be gained.     

Daunoxome® Treatment of Solid Tumors: Preclinical and Clinical Investigations

Abstract

Daunorubicin has been entrapped into small unilamellar vesicles (50-80 nm dia) composed of a 2:1 mole ratio of highly purified DSPC:cholesterol. In earlier studies, liposomes of this size and composition had been demonstrated to deliver their entrapped contents selectively to a wide range of solid tumors in vivo. Preclinical and initial clinical investigations of these daunorubicin liposomes (DaunoXome) are discussed. In one murine solid tumor model (P1798 lymphosarcoma), a ten-fold increased delivery of entrapped daunorubicin to tumor tissue was observed. Efficacy studies in the same model indicated improved tumor regression and extended life spans that correlated with the observed degree of enhanced tumor drug delivery. In a second tumor model (MA16C mammary adenocarcinoma), a ten-fold enhancement in efficacy again was demonstrated. In terms of median survival times and long term survival rate, DaunoXome dosed at 2 mg/kg (daunorubicin) demonstrated an efficacy comparable to free drug at 20 mg/kg. Clinical pharmacokinetics paralleled findings from animal studies. In humans, DaunoXome produced daunorubicin plasma AUC levels that were more than 35-fold greater than those reported for comparable doses of free drug at 80 mg/m². Response rates above 50% have been shown for treatment of Kaposi's sarcoma. A low incidence of side effects has been observed and HIV positive patients have been able to continue antiviral therapy during DaunoXome treatments. Cardiotoxicity has not manifested clinically even for patients receiving in excess of 1 gram/m² cumulative daunorubicin.     

ESOPHAGEAL HIATAL HERNIA—Some Aspects of Surgical Treatment

Patients with esophageal hiatal hernia often have an array of distressing complaints and physical signs that are difficult to interpret. Physiologic and anatomic studies of the gastroesophageal area in the region of the esophageal hiatus of the diaphragm indicate the existence of a three-in-line sphincter group, consisting of the inferior esophageal constrictor, diaphragmatic pinchcock and cardioesophageal junction. These mechanisms, acting in unison, prevent regurgitation in normal persons.It also can be deduced from clinical, radiologic and experimental data that anatomic disturbances at the esophageal hiatus account for physiologic alterations. A reasonable explanation for the symptoms and signs of esophageal hiatal hernia can be made on the basis of the functional competence of the three-in-line sphincter mechanisms.     

Physicochemical Aspects of Reaction of Ozone with Galactolipid and Galactolipid–Tocopherol Layers

The impact of reaction of galactolipids with ozone on the physicochemical properties of their monolayers was examined. In Megli and Russo (Biochim Biophys Acta, 1778:143–152, 2008), Cwiklik and Jungwirth (Chem Phys Lett, 486:99–103, 2010), Jurkiewicz et al. (Biochim Biophys Acta, 1818:2388–2402, 2012), Khabiri et al. (Chem Phys Lett, 519:93–99, 2012), and Conte et al. (Biochim Biophys Acta, 1828:510–517, 2013), the properties of layers formed from model mixtures composed of chosen lipids and selected oxidation products were studied, whereas in this work, question was raised as to how the oxidation reactions taking place in situ affect the physical properties of the galactolipid layers. So, set experiment should take into account the effect of all reaction products. The mechanical characteristics of monolayers of monogalactosyldiacyl-glycerol (MGDG) and digalactosyldiacylglycerol (DGDG) were determined by Langmuir trough technique, and the electrical properties of liposomes formed from these lipids by measuring their electrophoretic mobility. Considerable loss of galactolipid molecules forming monolayers was found at ozone concentrations (in aqueous medium) higher than 0.1 ppm with a stronger effect measured for MGDG. That goes along with the greater amounts of MDA found in the extracts of oxidized MGDG films compared with DGDG. Based on this, it was concluded that an additional galactose group present in DGDG molecules acts protectively under oxidative conditions. The surface tension of the solutions (of small volume) contacting the oxidized galactolipids films was significantly reduced, indicating the presence of soluble in polar media, surface active reaction products. The presence of α-tocopherol in mixtures with tested galactolipids at a molar ratio of lipid to tocopherol equal to 1.7:1 caused some inhibition of lipid oxidation, reducing the decrease of amount of lipid particles forming the monolayer. Here, also protective effect of α-tocopherol was greater for the MGDG compared to DGDG.     

Physiological Aspects of Photosynthesis–Respiration Interrelations

Russian Journal of Plant Physiology - The review discusses up-to-date concepts of interrelations between photosynthesis and respiration. It considers the quantitative ratio of the processes in the...     

Development and Clinical Evaluation of Clotrimazole–β-Cyclodextrin Eyedrops for the Treatment of Fungal Keratitis

Fungal keratitis is a serious corneal disease that may result in loss of vision. There are limited treatment options available in Iraqi eye hospitals which might be the main reason behind the poor prognosis of many cases. The purpose of this study was to prepare and pharmaceutically evaluate clotrimazole–β-cyclodextrin (CTZ–β-CD) eyedrops then clinically assess its therapeutic efficacy on fungal keratitis compared with extemporaneous amphotericin B eyedrops (0.5% w/v). A CTZ–β-CD ophthalmic solution was prepared and evaluated by various physicochemical, microbiological, and biological tests. The prepared formula was stable in 0.05 M phosphate buffer pH 7.0 at 40 ± 2°C and 75 ± 5% RH for a period of 6 months. Light has no significant effect on the formula’s stability. The CTZ–β-CD eyedrops efficiently complied with the isotonicity, sterility, and antimicrobiological preservative effectiveness tests. Results of the clinical study revealed that 20 (80%) patients showed a favorable response to the CTZ–β-CD eyedrops, while 16 patients (64%) exhibited a favorable response to amphotericin B (P > 0.05). The mean course of treatment was significantly (P < 0.05) less in the CTZ treatment group than in the amphotericin group (21.5 ± 5.2 vs. 28.3 ± 6.4 days, respectively). The CTZ formulation was significantly (P < 0.05) more effective in the management of severe cases and also against Candida sp. than amphotericin B. There was no significant difference (P < 0.05) between both therapies against filamentous fungi. The CTZ–β-CD formulation can be used alternatively to other ophthalmic antimycotic treatment options in developing countries where stability, cost, or efficacy is a limiting factor.Key words: clotrimazole, β-cyclodextrin, eyedrops, fungal keratitis, Iraq     

American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis — 2016--Executive Summary

Abbreviations:AACE = American Association of Clinical EndocrinologistsAFF = atypical femur fractureASBMR = American Society for Bone and Mineral ResearchBEL = best evidence levelBMD = bone mineral densityBTM = bone turnover markerCBC = complete blood countCI = confidence intervalDXA = dual-energy X-ray absorptiometryEL = evidence levelFDA = U.S. Food and Drug AdministrationFLEX = Fracture Intervention Trial (FIT) Long-term ExtensionFRAX® = Fracture Risk Assessment ToolGFR = glomerular filtration rateGI = gastrointestinalHORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once YearlyIOF = International Osteoporosis FoundationISCD = International Society for Clinical DensitometryIU = international unitsIV = intravenousLSC = least significant changeNBHA = National Bone Health AllianceNOF = National Osteoporosis Foundation25(OH)D = 25-hydroxy vitamin DONJ = osteonecrosis of the jawPINP = serum carboxy-terminal propeptide of type I collagenPTH = parathyroid hormoneR = recommendationRANK = receptor activator of nuclear factor kappa-BRANKL = receptor activator of nuclear factor kappa-B ligandRCT = randomized controlled trialRR = relative riskS-CTX = serum C-terminal telopeptideSQ = subcutaneousVFA = vertebral fracture assessmentWHO = World Health Organization     

Differential Globalization of Industry- and Non-Industry–Sponsored Clinical Trials

Background

Mapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry–sponsored clinical trials and its evolution over time.

Methods

We analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank''s income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry–sponsored international trials.

Results

119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry–sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry–sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry–sponsored trials (from 42.4% to 37.2%).

Conclusions

Based on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry–sponsored clinical research. Only 3% of academic trials but 30% of industry trials are international. The latter appeared to be conducted in preferentially selected countries.     

Evaluation of Etest Performed in Mueller–Hinton Agar Supplemented with Glucose for Antifungal Susceptibility Testing of Clinical Isolates of Filamentous Fungi

Although reference broth microdilution protocol is currently available for filamentous fungi antifungal susceptibility testing (AFST), simpler alternatives as Etest^® tend to be favoured in clinical routine, making their validation of utmost importance. In this study, Etest^® method using 2 % glucose supplemented Muller–Hinton agar was compared to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 protocol for filamentous fungi AFST. The echinocandins, caspofungin and anidulafungin, the azoles voriconazole and posaconazole, and the polyene amphotericin B were tested against 48 Aspergillus spp., seven Fusarium spp., one Beauveria bassiana and three Paecilomyces lilacinus isolates. The majority of the isolates were susceptible to the antifungals tested, and the overall level of agreement between the CLSI and Etest methods was 71.9 % for one dilution and 99.7 % when using two dilutions. Since interpretative breakpoints for filamentous fungi employing the CLSI or Etest methods are not available yet, the established epidemiological cut-off values for Aspergillus spp. were used to distinguish wild-type isolates from those with acquired resistance mechanisms. Forty-five Aspergillus strains did not evidence resistance mutations.