Histological analysis of the influence of certain extremal factors on the postradiational changes in the tissues of experimental animals

NASA Technical Reports Server (NTRS)

Sutulov, L. S.; Gaydamakin, N. A.; Sutulov, Y. L.

1975-01-01

Protons with energies of 120 MeV at a dose of 640 rads or gamma-neutron radiation at a dose of 300 rads produce radiation sickness of moderate severity in rats. The significance of toxemia and disturbances to the endocrine regulatory system in the development of metabolic processes in various stages of radiation sickness are discussed.

[Pregnancy toxemia. Oxygen input/extraction in preeclampsia-eclampsia].

PubMed

Rodríguez-Badillo, R F; Noriega-R, T; Audifred-Salomón, J R; García-Lara, E

1996-07-01

We tried to determine if the toxemia of pregnancy has during its clinical evolution a dependent DO2/VO2 relationship and determine its critical DO2 and finally define if this has a prognostic value. There were included patients with diagnosis of preeclampsia/eclampsia that were enter at the Intensive Care Unit for treatment and monitoring. It was placed a catheter in the pulmonary artery and it was determine the cardiac output and by means of standard formulas the DO2, VO2 and EO2 were calculated. The critical delivery of oxygen was stablished in agree at the Gutiérrez's method. At the same time it was monitorised the base excess which was gotten from arterial and venous blood gases. 36 patients (29 with preclampsia and 7 with eclampsia) were included, with a mean age of 26.3 years old. The mean gestational age was 36.1 weeks. The critical delivery for preeclamptic patients was stablished in 924 mL/min and at the eclamptic patients in 830 mL/min: both values had prognostic correlation with survival and nonsurvival patients (p < 0.001, x2 = 28.29). In survival patients it was a dependent DO2/VO2 relationship during the first 72 hours of study and then it was independent; this fact was accompaniment of a positive increase in the base excess and a decreasing in the EO2 values (< 27%). In the nonsurvival group, these mainteined a DO2/VO2 relationship in a dependent way during all the study and it was accompaniment with a continuous negative base excess with values of EO2 > 30%. The toxemia of pregnancy had a behaviour like state accompaniment of a dependent DO2/VO2 relationship causing an important oxygen deficient that was improved was improved in the survival patients that reach values over the critical delivery. These facts suggesting the presence of a metabolic blockade in variable degree that can improve or increase agree a therapeutic manipulations in the critic DO2.

In Defense of the Obstetrician and Obstetrics

PubMed Central

Hoffman, Ralph L.

1965-01-01

Changes and advances in obstetrics are emphasized by the comparative study of private and one hospital practice in 1939 and 1964. Education, prenatal care, anesthesia, antibiotics, transfusions have all been instrumental. Old problems—abortion, toxemia, prematurity, developmental abnormalities—remain with us. New developments, both professional and economic, some not desirable, face us and demand that active practicing obstetricians take an active role in helping direct their course. PMID:5847740

Botulinum and Tetanus Neurotoxin Induced Blockage of Synaptic Transmission in Networked Cultures of Human and Rodent Neurons

DTIC Science & Technology

2015-11-28

preliminary feasibility studies, neat samples of centrifu- gation-clarified milk, green bean juice , or non-alcoholic apple cider were added to ESN...2008). International outbreak of severe botulism with pro- longed toxemia caused by commercial carrot juice . Clin. Infect. Dis. 47, 1245–1251. Simpson...derived from induced plu - ripotent stem cells develop mature phenotypes typical of en- dogenous spinal motoneurons. J. Neurosci. 35, 1291–1306. Van

Subclinical Pregnancy Toxemia-Induced Gene Expression Changes in Ovine Placenta and Uterus

PubMed Central

Kasimanickam, Ramanathan K.

2016-01-01

The objective was to elucidate gene expression differences in uterus, caruncle, and cotyledon of ewes with subclinical pregnancy toxemia (SCPT) and healthy ewes, and to identify associated biological functions and pathways involved in pregnancy toxemia. On Day 136 (±1 day) post-breeding, ewes (n = 18) had body condition score (BCS; 1–5; 1, emaciated; 5, obese) assessed, and blood samples were collected for plasma glucose and β-hydroxybutyrate (BHBA) analyses. The ewes were euthanized, and tissue samples were collected from the gravid uterus and placentomes. Based on BCS (2.0 ± 0.02), glucose (2.4 ± 0.33), and BHBA (0.97 ± 0.06) concentrations, ewes (n = 10) were grouped as healthy (n = 5) and subclinical SCPT (n = 5) ewes. The mRNA expressions were determined by quantitative PCR method, and prediction of miRNA partners and target genes for the predicted miRNA were identified using miRDB (http://mirdb.org/miRDB/). Top ranked target genes were used to identify associated biological functions and pathways in response to SPCT using PANTHER. The angiogenesis genes VEGF and PlGF, and AdipoQ, AdipoR2, PPARG, LEP, IGF1, IGF2, IL1b, and TNFα mRNA expressions were lower in abundances, whereas hypoxia genes eNOS, HIF1a, and HIF 2a, and sFlt1 and KDR mRNA expressions were greater in abundances in uterus and placenta of SCPT ewes compared to healthy ewes (P < 0.05). The predicted miRNA and associated target genes contributed to several biological processes, including apoptosis, biological adhesion, biological regulation, cellular component biogenesis, cellular process, developmental process, immune system process, localization, metabolic process, multicellular organismal process, reproduction, and response to stimulus. The target genes were involved in several pathways including angiogenesis, cytoskeletal regulation, hypoxia response via HIF activation, interleukin signaling, ubiquitin proteasome, and VEGF signaling pathway. In conclusion, genes associated with blood vessel remodeling were lower in abundances and that the genes associated with hypoxic conditions were greater in abundances in the uteroplacental compartment of SCPT ewes. It is obvious that the factors that influence placental vascular development and angiogenesis as noted in this study set the course for hemodynamic changes and hence have a major impact on the rate of transplacental nutrient exchange, fetal growth, and health of the dam. PMID:27626035

Relationships of maternal blood lead and disorders of pregnancy to neonatal birthweight.

PubMed

Kaul, P P; Srivastava, R; Srivastava, S P; Kamboj, M; Chand, S

2002-12-01

Transient complications of pregnancy (anemia, toxemia, proteinuria, arterial hypertension and hyperemesis) were studied in pregnant women from the general population reporting to local hospitals. Comparison of blood lead levels (PbB) was made between women with normal pregnancies and those with complications. Significantly higher PbB were found in women with pregnancy complications as compared to those with normal pregnancies. Increments in the PbB levels were accompanied by statistically significant decrements in neonate birthweights. Complications of pregnancy may be induced by higher PbB and may also compound the adverse effects of decrements of neonate birthweights

A pilot study of an anti-MRSA bio-engineered lacteal complex (anti-MRSA BLC) in a murine septicemia model.

PubMed

Stoff, Jesse A; Nix, David E; DeYoung, D W

2006-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen of humans and other animals, causing septicemia, abcessation, toxemia, and other infectious diseases. Refined bioengineered lacteal complex (BLC), made specifically against MRSA, is a novel complex of low molecular weight immunogenic and antimicrobial molecules. It was evaluated in vivo using a mouse model of MRSA-induced peritonitis. Intraperitoneal dosing of anti-MRSA BLC demonstrated a therapeutic effect (83% survival) against an intraperitoneal MRSA challenge that caused 100% mortality in untreated animals. Anti-MRSA BLC is a promising therapeutic modality for MRSA infection.

Development of Protective Immunity in New Zealand White Rabbits Challenged with Bacillus anthracis Spores and Treated with Antibiotics and Obiltoxaximab, a Monoclonal Antibody against Protective Antigen.

PubMed

Henning, Lisa N; Carpenter, Sarah; Stark, Gregory V; Serbina, Natalya V

2018-02-01

The recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax protective antigen (PA), is licensed under the U.S. Food and Drug Administration's (FDA's) Animal Rule for the treatment of inhalational anthrax. Because of spore latency, disease reemergence after treatment cessation is a concern, and there is a need to understand the development of endogenous protective immune responses following antitoxin-containing anthrax treatment regimens. Here, acquired protective immunity was examined in New Zealand White (NZW) rabbits challenged with a targeted lethal dose of Bacillus anthracis spores and treated with antibiotics, obiltoxaximab, or a combination of both. Survivors of the primary challenge were rechallenged 9 months later and monitored for survival. Survival rates after primary and rechallenge for controls and animals treated with obiltoxaximab, levofloxacin, or a combination of both were 0, 65, 100, and 95%, and 0, 100, 95, and 89%, respectively. All surviving immune animals had circulating antibodies to PA and serum toxin-neutralizing titers prior to rechallenge. Following rechallenge, systemic bacteremia and toxemia were not detected in most animals, and the levels of circulating anti-PA IgG titers increased starting at 5 days postrechallenge. We conclude that treatment with obiltoxaximab, alone or combined with antibiotics, significantly improves the survival of rabbits that received a lethal inhalation B. anthracis spore challenge dose and does not interfere with the development of immunity. Survivors of primary challenge are protected against reexposure, have rare incidents of systemic bacteremia and toxemia, and have evidence of an anamnestic response. Copyright © 2018 Henning et al.

Induction of Listeria monocytogenes infection by the consumption of ponderosa pine needles.

PubMed Central

Adams, C J; Neff, T E; Jackson, L L

1979-01-01

An infectious microorganism, identified as Listeria monocytogenes, has been isolated from the bloodstream of pregnant mice fed a diet containing Pinus ponderosa needles. When the isolate was injected into pregnant mice, reproductive dysfunction and other changes, including speckled livers, spleen atrophy, and hemorrhagic intestines, appeared to mimic the signs of the disease in pregnant mice fed pine needles. Moreover, these pathological changes are similar to those observed in cattle and other mammals experiencing abortions or toxemia, or both, attributed to the ingestion of P. ponderosa needles, suggesting that L. monocytogenes may be a part of the etiology of "pine needle abortion." PMID:113341

Anthrax lethal and edema toxins in anthrax pathogenesis

PubMed Central

Liu, Shihui; Moayeri, Mahtab; Leppla, Stephen H.

2014-01-01

The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use CMG2 as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection. PMID:24684968

[Associated factors in newborns with intrauterine growth retardation].

PubMed

Thompson-Chagoyán, Oscar C; Vega-Franco, Leopoldo

2008-01-01

To identify the risk factors implicated in the intrauterine growth retardation (IUGR) of neonates born in a social security institution. Case controls design study in 376 neonates: 188 with IUGR (weight < 10 percentile) and 188 without IUGR. When they born, information about 30 variables of risk for IUGR were obtained from mothers. Risk analysis and logistical regression (stepwise) were used. Odds ratios were significant for 12 of the variables. The model obtains by stepwise regression included: weight gain at pregnancy, prenatal care attendance, toxemia, chocolate ingestion, father's weight, and the environmental house. Must of the variables included in the model are related to socioeconomic disadvantages related to the risk of RCIU in the population.

Behavioral outcome including attention deficit hyperactivity disorder/hyperactivity disorder and minor neurological signs in perinatal high-risk newborns at 4-6 years of age with relation to risk factors.

PubMed

Sato, Masuko; Aotani, Hirofumi; Hattori, Ritsuko; Funato, Masahisa

2004-06-01

Diagnostic problems with the criteria of attention deficit hyperactivity disorder (ADHD) in the Diagnostic Statistical Manual, 4th edn, have been identified. The aim of this study was to clarify whether the minor neurological signs test (MNT) the authors had previously reported was a predictor for the criteria of ADHD or hyperactivity disorder (HD) in perinatal risk children at 4-6 years of age and what kind of risk factors related to MNT. A total of 136 children discharged from neonatal intensive care units were examined at the age of 4-6 years by a developmental neuropediatrician using both MNT and diagnostic criteria of DSM-IV ADHD/ICD-10 (International Classification of Diseases, 10th edn) HD. SPSS base and professional were used for statistical analysis. On comparison of diagnostic criteria between ADHD (11.0%) and HD (27.5%), the incidence in the same subjects showed significant difference. MNT scores showed significant correlation with criteria of ADHD (P < 0.01) and HD (P < 0.05). Diagnostic validity of MNT for predicting ADHD was demonstrated with 78% sensitivity and 79% specificity. High positive rates on MNT did not show a significant difference between the very low birthweight (VLBW) and non-low birthweight (NLBW) groups. Behavioral outcome with relation to risk factors were analyzed using multiple regression analysis. Apgar 5 in the NLBW group and toxemia of pregnancy and small for gestational age (SGA) in VLBW group were highly correlated with behavioral outcome. Minor neurological signs test score was a significant predictor for criteria of ADHD and HD. High incidences of positive MNT were suspected in not only VLBW children but also NLBW children and Apgar 5 in NLBW children and toxemia of pregnancy and SGA in VLBW children influenced behavioral outcome.

[Experimental approach to the prophylaxis and treatment of acute lung injury syndrome with proteinase inhibitors and corvitin].

PubMed

Moĭbenko, O O; Kubyshkin, A V; Kharchenko, V Z; Horokhova, N Iu; Semenets', P F

2003-01-01

The results of a combined study of the proteolysis on a model of post-ischemic toxemia in rats showed a decrease in antiproteinase potential and an activation of proteolysis. The activation of proteolysis and inhibition of antiproteinases was observed not only in the blood, but also in the bronchoalveolar secretion. Those changes were accompanied with the changes in the morphological structure of the lungs. The data obtained have shown a high effectiveness of proteinase inhibitor (contrical) and an antioxidant of flavonoid group (corvetine). Those drugs decreased the morphological changes in the lungs and prevented the development of imbalance in proteinase-inhibitor system. The prophylactic effect was more considerable when both drugs were used in a combined way.

PATHOPHYSIOLOGICAN AND CLINICAL ASSESSMENT OF CHANGES OF ERYTHROCYTE RESISTANCE TO SAPONIN IN THE PROCESS OF ROENTGEN THERAPY (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krylov, A.A.

1961-04-01

In 40 patients undergoing roentgen therapy dynamic studies were made concerning the resistance of erythrocytes to saponin. A method of kinelysis was employed with a Soviet photoelectric colorimeter FEK-M. In the majority of patients subject to deep roentgen therapy there was noted a considerable rise of erythrocyte resistance to saponin, which is considered as a manifestation of compensatory mechanisms. A rapid decline of the resistance ("saponin disruption'') was preceded, as a ruls, by radiation toxemia and served as a signal of the necessity of repeated blood transfusions. The technique referred to is recommended as an objective index of the statemore » of regulatory mechanisms in the process of irradiation. (auth)« less

Intestinal volvulus with coagulative hepatic necrosis in a chicken.

PubMed

Haridy, Mohie; Goryo, Masanobu; Sasaki, Jun; Okada, Kosuke

2010-04-01

A 7-week-old SPF chicken inoculated at 4 weeks of age with chicken anemia virus was puffed up depressed and had ruffled feathers and a good body condition. Intestinal volvulus involving the jejunum and part of the duodenum forming two loops with one knob was observed. Microscopically, venous infarction of the obstructed loops, periportal and sublobular multifocal coagulative hepatic necrosis and granulomatous inflammation of the cecal tonsils were observed. Gram staining revealed no bacteria in hepatic tissue; however, gram-positive bacilli were detected in the necrotic debris in the intestinal lumen. Immunosuppression might have predisposed the chicken to intestinal and cecal tonsil infection that then progressed to volvulus. Loss of the mucosal barrier in infarction might allow bacterial toxins and vasoactive factors to escape into the systemic circulation (toxemia) and be responsible for the hepatic necrosis.

THE REFRIGERATION TREATMENT OF CHRONIC OSTEOMYELITIS

PubMed Central

Bingham, Robert

1951-01-01

Systemic penicillin therapy plus refrigeration at the site of the lesion, with operation if necessary, was used in the treatment of chronic osteomyelitis. Nine patients with disease of long standing were treated. For three, bed rest, chemotherapy and refrigeration were sufficient. Surgical treatment in addition was carried out in six cases. Operations consisted of unroofing the abscess cavity, multiple drilling for sievelike perforation of the abscessed bone, and primary suture of the incision. Solutions of penicillin, 500 to 1,000 units per cubic centimeter, were used for local irrigation at the time of closure. In all cases the lesions healed and there was no recurrence within a period of two years. The period of hospitalization did not exceed 14 days in any case. Refrigeration of the infected area before and after operation reduced pain, swelling, infection and toxemia. PMID:14801722

Detection of septicemia in chicken livers by spectroscopy,.

PubMed

Dey, B P; Chen, Y R; Hsieh, C; Chan, D E

2003-02-01

To establish a procedure for differentiating normal chickens from chickens with septicemia/toxemia (septox) by machine inspection under the Hazard Analysis and Critical Control Point-Based Inspection Models Project, spectral measurements of 300 chicken livers, of which half were normal and half were condemned due to septox conditions, were collected and analyzed. Neural network classification of the spectral data after principal component analysis (PCA) indicated that normal and septox livers were correctly differentiated by spectroscopy at a rate of 96%. Analysis of the data established 100% correlation between the spectroscopic identification and the subset of samples, both normal and septox, that were histopathologically diagnosed. In an attempt to establish the microbiological etiology of the diseased livers, isolates from 30 livers indicated that the poultry carcasses were contaminated mostly with coliforms present in the environment, hindering the isolation of pathogenic microorganisms. Therefore, to establish the cause of diseased livers, a strictly aseptic environment and procedure for sample collection is required.

Anthrax vaccines: present status and future prospects.

PubMed

Kaur, Manpreet; Singh, Samer; Bhatnagar, Rakesh

2013-08-01

The management of anthrax remains a top priority among the biowarfare/bioterror agents. It was the Bacillus anthracis spore attack through the US mail system after the September 11, 2001, terrorist attacks in the USA that highlighted the potential of B. anthracis as a bioterrorism agent and the threat posed by its deliberate dissemination. These attacks invigorated the efforts toward understanding the anthrax pathogenesis and development of more comprehensive medical intervention strategies for its containment in case of both natural disease and manmade, accidental or deliberate infection of a non-suspecting population. Currently, efforts are directed toward the development of safe and efficacious vaccines as well as intervention tools for controlling the disease in the advanced fulminant stage when toxemia has already developed. This work presents an overview of the current understanding of anthrax pathogenesis and recent advances made, particularly after 2001, for the successful management of anthrax and outlines future perspectives.

Decidual vascular changes in early pregnancy as a marker for intrauterine pregnancy.

PubMed

Lichtig, C; Korat, A; Deutch, M; Brandes, J M

1988-09-01

Endometrial vascular changes similar to atherosclerosis of toxemia of pregnancy were described and graded in 217 consecutive endometrial biopsies of known early intrauterine pregnancy. Severe vascular changes were found in 23.5% of cases. Control material consisting of endometrial biopsies of patients with known cases of tubal ectopic pregnancy and various non-pregnancy menstrual disorders showed minimal or no changes except in one case. A parallel study of Aria-Stella phenomenon in 110 cases of uterine pregnancy showed significant changes in only 3.6% of patients. It is obvious that in these cases of positive Arias-Stella findings, the possibility of an extrauterine pregnancy could not be discarded on histologic grounds alone. The authors suggest the use of the vascular changes of the more severe histologic degree as described in this article as a positive or strongly suspicious marker for intrauterine pregnancy whenever this is needed.

[The comparative efficacy of a new hydrogel enterosorbent in the detoxification therapy of combined radiation-thermal lesions].

PubMed

Nurkhanov, B M

1990-01-01

The detoxification effect of a new hydrogen sorbent Ikhant, synthesized on basis of piperidol homo- and copolymers, was studied on a model of combined radiation-thermal damage (CRTD). Wistar male rats were irradiated by a dose of 7.5 Gr and a IIIB degree burn was inflicted to 15% of their body surface. Intra-abdominal injection of Ikhant in the dose of 0.1 g per rat was given immediately and 24 hours after CRTD. Parallel studies of the effect of known carbon and silicon-containing sorbents on the development of toxemia in CRTD were conducted. High effectiveness of Ikhant as a measure of detoxification therapy in CRTD was established on grounds of the experimental data. By binding and discharging the toxins through the intestine, the new enterosorbent facilitates improvement of certain biochemical values of hepatic, function and, on the whole, reduces the level of the organism's autointoxication.

Extensive Chest Wall Tissue Loss and its Management by Vertical Rectus Abdominis Myocutaneous Flap

PubMed Central

Basu, Sandip Kanti; Bain, Jayanta; Chattopadhyay, Debarati; Majumdar, Bijay Kumar

2017-01-01

Extensive electric burn around the chest in children is rare and this type of injury always poses a great challenge for its management. A 12-year-old male child with extensive electric burn of the chest wall was admitted to hospital. It was a neglected case of 9 days old burn; the young boy was in critical condition having systemic features of toxemia with widespread necrosis of the skin, subcutaneous tissues, and muscles along with exposed bones (ribs and sternum) with the risk of impending rupture of pleura through the exposed intercostal spaces. After initial resuscitation, a thorough debridement of all necrotic tissues was done. Thereafter, a superiorly based vertical rectus abdominis myocutaneous flap was harvested to cover the exposed bones and intercostal spaces. The remaining raw areas were skin grafted. The child made an excellent recovery with good outcome. PMID:28082777

Cell-wall preparation containing poly-γ-D-glutamate covalently linked to peptidoglycan, a straightforward extractable molecule, protects mice against experimental anthrax infection.

PubMed

Candela, Thomas; Dumetz, Fabien; Tosi-Couture, Evelyne; Mock, Michèle; Goossens, Pierre L; Fouet, Agnès

2012-12-17

Bacillus anthracis is the causative agent of anthrax that is characterized by septicemia and toxemia. Many vaccine strategies were described to counteract anthrax infection. In contrast with veterinary live vaccines, currently human vaccines are acellular with the protective antigen, a toxin component, as the main constituent. However, in animal models this vaccine is less efficient than the live vaccine. In this study, we analyzed the protection afforded by a single extractable surface element. The poly-γ-D-glutamate capsule is covalently linked to the peptidoglycan. A preparation of peptidoglycan-linked poly-γ-D-glutamate (GluPG) was tested for its immunogenicity and its protective effect. GluPG injection, in mice, elicited the production of specific antibodies directed against poly-glutamate and partially protected the animals against lethal challenges with a non-toxinogenic strain. When combined to protective antigen, GluPG immunization conferred full protection against cutaneous anthrax induced with a fully virulent strain. Copyright © 2012 Elsevier Ltd. All rights reserved.

Proportional mortality: A study of 152 goats submitted for necropsy from 13 goat herds in Quebec, with a special focus on caseous lymphadenitis.

PubMed

Debien, Elaine; Hélie, Pierre; Buczinski, Sébastien; Lebœuf, Anne; Bélanger, Denise; Drolet, Richard

2013-06-01

The objectives of this study were to determine the main causes of mortality, with a special focus on caseous lymphadenits as a cause of death or wasting in caprine herds from Quebec. Goats (n = 152) from 13 herds were submitted for necropsy; the cause of mortality, and the presence, location, and cause of abscesses (if present) were recorded. Proportional mortalities were distributed as: Clostridium perfringens type D enterotoxemia (17.1%), pneumonia (13.8%), paratuberculosis (10.5%), listeriosis (6.6%), pregnancy toxemia (5.3%), caprine arthritis-encephalitis (4.6%), and caseous lymphadenitis (3.9%). Caseous lymphadenitis was diagnosed in 24.3% of the submitted goats, but was not a major cause of wasting or mortality. Abscesses were localized internally in 54.1% of the cases. Paratuberculosis was diagnosed in 29 goats (16 as cause of death) and was considered a major cause of wasting and/or mortality.

Botulism from chopped garlic: delayed recognition of a major outbreak.

PubMed

St Louis, M E; Peck, S H; Bowering, D; Morgan, G B; Blatherwick, J; Banerjee, S; Kettyls, G D; Black, W A; Milling, M E; Hauschild, A H

1988-03-01

Diagnosis of botulism in two teenaged sisters in Montreal led to the identification of 36 previously unrecognized cases of type B botulism in persons who had eaten at a restaurant in Vancouver, British Columbia, during the preceding 6 weeks. A case-control study implicated a new vehicle for botulism, commercial chopped garlic in soybean oil (P less than 10(-4)). Relatively mild and slowly progressive illness, dispersion of patients over at least eight provinces and states in three countries, and a previously unsuspected vehicle had contributed to prolonged misdiagnoses, including myasthenia gravis (six patients), psychiatric disorders (four), stroke (three), and others. Ethnic background influenced severity of illness: 60% of Chinese patients but only 4% of others needed mechanical ventilation (P less than 10(-3]. Trypsinization of serum was needed to show toxemia in one patient. Electromyography results with high-frequency repetitive stimulation corroborated the diagnosis of botulism up to 2 months after onset. Although botulism is a life-threatening disease, misdiagnosis may be common and large outbreaks can escape recognition completely.

Prenatal knowledge and informational priorities of pregnant adolescents.

PubMed

Smith, P B; Levenson, P M; Morrow, J R

1985-01-01

One hundred and forty-six indigent pregnant adolescents (12 to 18 years of age) were asked to complete a questionnaire concerning their prenatal care priorities (Scale I) and their knowledge of correct perinatal behaviors (Scale II). On Scale I, over 75% of teens considered parenting skills, infant care, and diet extremely important. On Scale II correctly answered items focused on the need to avoid substance abuse and smoking during pregnancy, visit the doctor, and eat balanced meals. The mean number of correct answers, however, was only 11.8 out of a total possible scale of 18 items. Less than 50% correctly answered statements about the effects of weight gain and other health behaviors on risk for high blood pressure and toxemia, safety of laxatives during pregnancy, possibility of becoming pregnant again before resuming menstruation, and the safety of various physical activities. Performance on both knowledge and health priority scales showed correct health information was limited to basic concrete facts. Abstract and technical aspects of health care did not appear to be easily assimilated.

THE EFFECT OF SODIUM CHLORIDE ON THE CHEMICAL CHANGES IN THE BLOOD OF THE DOG AFTER PYLORIC AND INTESTINAL OBSTRUCTION.

PubMed

Haden, R L; Orr, T G

1923-06-30

Experiments to determine the effect of furnishing an ample supply of sodium chloride on the toxemia of pyloric and intestinal obstruction are reported. A fall in chlorides is the first and seemingly most significant change to take place in the blood after pyloric and intestinal obstruction. The chloride is apparently utilized by the body as a protective measure against the primary toxic substance. Two dogs with pyloric obstruction were given 50 cc. of 10 per cent NaCl subcutaneously daily. One lived 3 days, the other 4. The blood showed little change, except a marked terminal rise in chlorides. Animals given a like amount of distilled water or 25 per cent glucose showed the changes typical of untreated animals. The obstruction of the pylorus was released in six dogs 48 to 72 hours after the initial operation. Two died within 24 hours after the second operation with a high non-protein nitrogen in the blood. Two survived but showed a high level of non-protein nitrogen in the blood and a high nitrogen excretion in the urine, low blood chlorides, and a marked alkalosis. One dog in such a state died on the 13th day from peritonitis, arising in a wound infection. The other showed a marked fall in non-protein nitrogen in the blood following the administration of 10 gm. of sodium chloride by mouth, but died following the intravenous injection of 25 per cent sodium chloride. Two animals were given 50 cc. of 10 per cent NaCl subcutaneously, at the time of the second operation. The blood rapidly returned to normal and complete recovery followed. Two dogs with the duodenum obstructed by section and inversion of the cut ends were treated with 10 per cent sodium chloride after the obstruction had existed for 48 hours and the characteristic blood changes had developed. The non-protein nitrogen returned to normal within 48 hours after treatment was begun. One dog died following a lateral anastomosis for relief of the obstruction. A second operation was not attempted in the other animal. Two dogs in which the duodenum was obstructed by section and inversion of the cut ends were given 500 cc. of 0.85 per cent NaCl subcutaneously on the day of operation and each day thereafter until death. One dog lived 21 days, the other 28. Both dogs showed a marked alkalosis, but never any rise in the non-protein nitrogen of the blood. The animals at autopsy showed intussusception of the ileum with extensive ulceration. In one there was a perforation and terminal peritonitis. The operation wounds healed normally. Three dogs with section of the duodenum were given 500 cc. of distilled water every day. One died in 24 hours, one in 48 hours, and the third in 72 hours. Autopsy showed no cause for death other than toxemia. One dog with section of the duodenum was given 500 cc. of 2 per cent glucose every day. The blood showed a rapid rise in non-protein nitrogen and carbon dioxide-combining power, and a fall in chlorides. The animal died 72 hours after operation. Three dogs with section of the duodenum were given 500 cc. of 1 per cent sodium bicarbonate every day. One dog died in 72 hours, one lived 7 days, and the third lived 9 days. All developed a high non-protein nitrogen in the blood and two showed marked clinical symptoms of an alkalosis. These results demonstrate that solutions of sodium chloride have a marked effect in preventing and controlling the toxemia of pyloric and intestinal obstruction as shown in clinical symptoms and in chemical changes in the blood. Dogs given an abundant supply of distilled water died more quickly than untreated control animals. Solutions of glucose have no specific value, and sodium bicarbonate solutions prolong life only a short while. Good therapeutic results have been obtained with very concentrated sodium chloride solutions, and with dry sodium chloride given by mouth. It seems evident that sodium chloride has a specific action in preventing and possibly in controlling the changes produced by the toxic body. Sodium chloride is a valuable therapeutic agent in pyloric and high intestinal obstruction.

Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects

PubMed Central

Di Bella, Stefano; Ascenzi, Paolo; Siarakas, Steven; Petrosillo, Nicola; di Masi, Alessandra

2016-01-01

Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies. PMID:27153087

Pregnancy hormone concentrations across ethnic groups: implications for later cancer risk.

PubMed

Potischman, Nancy; Troisi, Rebecca; Thadhani, Ravi; Hoover, Robert N; Dodd, Kevin; Davis, William W; Sluss, Patrick M; Hsieh, Chung-Cheng; Ballard-Barbash, Rachel

2005-06-01

A variety of in utero factors have been associated with risk of adult cancers, particularly birth weight, toxemia, and gestational age. These factors are thought to reflect hormonal exposures during pregnancy. We hypothesized that the prenatal hormonal milieu may explain part of the variation in cancer rates across ethnic groups, for example, the higher incidence of breast cancer in the Caucasian compared with Hispanic women and the higher incidence of prostate and lower incidence of testicular cancers among African-Americans compared with Caucasians. We measured hormones in early pregnancy blood samples from three ethnic groups in a health care plan in Boston, MA. Mean levels of androstenedione, testosterone, estrone, and prolactin were significantly lower in Caucasian women compared with Hispanic women. Although not statistically significant, estradiol levels were lower in Caucasian compared with Hispanic or African-American women. Concentrations of androstenedione, testosterone, and progesterone were notably higher in African-American compared with Caucasian or Hispanic women. These data are consistent with hypotheses that in utero hormonal exposures may explain some of the ethnic group differences in cancer risk.

[Effects of zinc deficiency in pregnancy on the mother and the newborn infant].

PubMed

Favier, A; Favier, M

1990-01-01

There seems to be a zinc deficiency during pregnancy in view of the low serum zinc levels, but especially low zinc levels in hair and leucocytes. The need for zinc supplements is still ill-defined but represents at least 5 mg per day which are not covered by the diet and taken from the maternal reserves. Therefore the risk of deficiency is real and its manifestations are numerous. There is a risk of spontaneous abortion, gravidic toxemia, treatment-resistant anemia, abnormally prolonged gestation and difficult delivery for the mother. As for the fetus, with zinc deficiency there is a risk of hypotrophism and malformations with potentialization of the teratogenic effect of alcohol and many medications. Besides, in animals, zinc deficiency during pregnancy results in late effects several months after birth: decrease immunity, learning or memory disorders. In view of all these consequences, administration of supplements is imperative and must be evaluated providing that it does not exceed 50 mg of zinc per day. Besides, it seems preferable to provide balanced multisupplements in minerals and vitamins, since supplement in iron alone results in zinc deficiency.

Clinical mimics of infant botulism.

PubMed

Francisco, Ann Marie O; Arnon, Stephen S

2007-04-01

Since 1992, Human Botulism Immune Globulin has been provided by the California Department of Health Services to infants with probable infant botulism, the intestinal toxemia form of human botulism. Human Botulism Immune Globulin became available in California in 1992-1997 within a randomized, controlled, double-blinded, pivotal clinical trial and subsequently became available nationwide in 1998-2003 in an open-label study until its licensure in October 2003 as BabyBIG. Thereafter, Human Botulism Immune Globulin remained available nationwide as an approved orphan-drug product. To achieve prompt neutralization of circulating botulinum toxin, the decision to treat with Human Botulism Immune Globulin has been based on clinical criteria that include a consistent history and physical findings of bulbar palsies, hypotonia, and weakness. After licensure, the charts of patients who did not have laboratory-confirmed infant botulism were reviewed to identify their actual diagnoses. The approximately 5% of 681 patients treated with Human Botulism Immune Globulin who did not have infant botulism fell into 5 categories: spinal muscular atrophy, metabolic disorders, other infectious diseases, miscellaneous, and probable infant botulism lacking laboratory confirmation.

[Fever in pediatric office practice].

PubMed

Murahovschi, Jayme

2003-05-01

To determine how to select a child who requires in depth laboratory investigation, defining the most appropriate laboratory screening tests, and to detect the individual who requires immediate therapy, when fever is the main symptom presented by the child seen in an outpatient clinic, or at the physician's office. Additionally, this review aims at providing suggestions on how to deal with fever, and with the anxiety it causes. Bibliographic review using Medline database and previously selected manuscripts. Fever may cause both negative and positive outcomes, none of major consequence. Age group, fever magnitude and duration, shivering, appetite decrease or behavioral changes (toxemia), and other localizing symptoms should be investigated through the patient's medical history. Laboratory screening tests should include complete blood count, erythrocyte sedimentation rate, C-reactive protein, urinalysis (white cells count and gram stain of the sediment), and in some cases, lumbar puncture and blood culture. The treatment should include antipyretic medications and, occasionally, physical methods (cool baths, sponging) in order to reduce discomfort caused by the fever. Children with fever request both scientific expertise, as well as empathy from the pediatrician, so that they can receive individualized therapy.

The centenary of Lester Dragstedt--fifty years of therapeutic vagotomy.

PubMed Central

Modlin, I. M.; Darr, U.

1994-01-01

Lester Reynolds Dragstedt was trained initially as a physiologist and subsequently became a surgeon. He achieved renown not only because of his intellectual and technical skills, but because he was able to utilize physiological principles to define the development of surgical procedures. A humble upbringing in Anaconda, Montana was followed by a scientific education in Chicago. His brief background in surgery was obtained during a two year period spent mostly in Vienna and Budapest. At the University of Chicago, he pioneered the development of therapeutic vagotomy in the treatment of peptic ulcer disease. His research interests were many and varied, ranging from the toxemia of intestinal obstruction to the quest for a pancreatic hormone which might regulate fat metabolism. After retiring as Chairman of Surgery at the University of Chicago, he assumed a research position in surgery at the University of Florida in Gainesville. Dragstedt was a creative scientist, a superlative clinical surgeon, and a teacher honored by his pupils. The example of his life confirms the benefit of scientific inquiry when applied to clinical and surgical practice. Images Figure 1 Figure 2 Figure 3 Figure 5 PMID:7502534

Anthrax Toxin-Expressing Bacillus cereus Isolated from an Anthrax-Like Eschar.

PubMed

Marston, Chung K; Ibrahim, Hisham; Lee, Philip; Churchwell, George; Gumke, Megan; Stanek, Danielle; Gee, Jay E; Boyer, Anne E; Gallegos-Candela, Maribel; Barr, John R; Li, Han; Boulay, Darbi; Cronin, Li; Quinn, Conrad P; Hoffmaster, Alex R

2016-01-01

Bacillus cereus isolates have been described harboring Bacillus anthracis toxin genes, most notably B. cereus G9241, and capable of causing severe and fatal pneumonias. This report describes the characterization of a B. cereus isolate, BcFL2013, associated with a naturally occurring cutaneous lesion resembling an anthrax eschar. Similar to G9241, BcFL2013 is positive for the B. anthracis pXO1 toxin genes, has a multi-locus sequence type of 78, and a pagA sequence type of 9. Whole genome sequencing confirms the similarity to G9241. In addition to the chromosome having an average nucleotide identity of 99.98% when compared to G9241, BcFL2013 harbors three plasmids with varying homology to the G9241 plasmids (pBCXO1, pBC210 and pBFH_1). This is also the first report to include serologic testing of patient specimens associated with this type of B. cereus infection which resulted in the detection of anthrax lethal factor toxemia, a quantifiable serum antibody response to protective antigen (PA), and lethal toxin neutralization activity.

Crossing of the epithelial barriers by Bacillus anthracis: the Known and the Unknown

PubMed Central

Goossens, Pierre L.; Tournier, Jean-Nicolas

2015-01-01

Anthrax, caused by Bacillus anthracis, a Gram-positive spore-forming bacterium, is initiated by the entry of spores into the host body. There are three types of human infection: cutaneous, inhalational, and gastrointestinal. For each form, B. anthracis spores need to cross the cutaneous, respiratory or digestive epithelial barriers, respectively, as a first obligate step to establish infection. Anthrax is a toxi-infection: an association of toxemia and rapidly spreading infection progressing to septicemia. The pathogenicity of Bacillus anthracis mainly depends on two toxins and a capsule. The capsule protects bacilli from the immune system, thus promoting systemic dissemination. The toxins alter host cell signaling, thereby paralyzing the immune response of the host and perturbing the endocrine and endothelial systems. In this review, we will mainly focus on the events and mechanisms leading to crossing of the respiratory epithelial barrier, as the majority of studies have addressed inhalational infection. We will discuss the critical gaps of knowledge that need to be addressed to gain a comprehensive view of the initial steps of inhalational anthrax. We will then discuss the few data available on B. anthracis crossing the cutaneous and digestive epithelia. PMID:26500645

Linden flower (Tilia spp.) as potential vehicle of Clostridium botulinum spores in the transmission of infant botulism.

PubMed

Bianco, M I; Lúquez, C; De Jong, L I T; Fernández, R A

2009-01-01

Infant botulism is an intestinal toxemia caused principally by Clostridium botulinum. Since the infection occurs in the intestinal tract, numerous food products have been investigated for the presence of C. botulinum and its neurotoxins. In many countries, people use linden flower (Tilia spp) tea as a household remedy and give it to infants as a sedative. Therefore, to help provide a clear picture of this disease transmission, we investigated the presence of botulinum spores in linden flowers. In this study, we analyzed 100 samples of unwrapped linden flowers and 100 samples of linden flowers in tea bags to determine the prevalence and spore-load of C. botulinum. Results were analyzed by the Fisher test. We detected a prevalence of 3% of botulinum spores in the unwrapped linden flowers analyzed and a spore load of 30 spores per 100 grams. None of the industrialized linden flowers analyzed were contaminated with botulinum spores. C. botulinum type A was identified in two samples and type B in one sample. Linden flowers must be considered a potential vehicle of C. botulinum, and the ingestion of linden flower tea can represent a risk factor for infant botulism.

Streptococcus bovis/S. equinus complex septicemia in a group of calves following intramuscular vaccination.

PubMed

Clarke, Lorelei L; Fathke, Robert L; Sanchez, Susan; Stanton, James B

2016-07-01

Organisms previously classified as Streptococcus bovis (i.e., the S. bovis/S. equinus complex) are common in cattle feces, but may also act as opportunistic pathogens. In the current work, Streptococcus infantarius subsp. coli, a member of this complex, was associated of a cluster of calves that died within hours of injection with a modified live viral vaccine. Within 12 h of vaccination of 46 calves at a cow/calf operation, 4 calves had died, 3 calves were ill, and 1 unvaccinated cow was dead. Autopsies were performed on the cow, 2 dead calves, and 1 affected surviving calf, which was euthanized ~24 h after vaccine administration. The animals had similar gross anatomic and microscopic lesions, including subcutaneous and intramuscular dark hemorrhage on the caudal neck, multiorgan ecchymosis and petechiation, and alveolitis to interstitial pneumonia. Gram-positive cocci were in the vasculature of the lung and skeletal muscle, and S. infantarius subsp. coli was cultured from tissues and from the vaccines used on affected animals, but not in vials used on unaffected animals. Together, these findings suggest death caused by streptococcal septicemia and toxemia as a result of contamination. © 2016 The Author(s).

Observation of an organism found in patients with gestational trophoblastic disease and in patients with toxemia of pregnancy.

PubMed

Lueck, J; Brewer, J I; Aladjem, S; Novotny, M

1983-01-01

This is an initial descriptive report of observations of multiple forms of an organism found in patients with gestational trophoblastic disease and in patients with preeclampsia-eclampsia. The worm-like forms most frequently observed have an average length of 1.0 to 1.5 mm. Larva-like forms have an average length of 150 mu; primordial eggs and egg-like forms in developmental stages range from 7 to 43 mu in diameter; and sperm-like forms are 3.5 mu or slightly smaller in size. These forms have been observed in contact smears prepared from 3 ml samples of peripheral circulating blood from both groups of patients, from trophoblastic tumor tissue, from contact smears prepared from placentas of patients with preeclampsia-eclampsia, and from umbilical cord blood of infants delivered of patients with preeclampsia-eclampsia. The various forms of this organism share morphologic characteristics of several orders of helminths, i.e., hookworms, roundworms and tapeworms. The taxonomy of these forms has not yet been determined. Until the time of taxonomic classification, the various forms will be referred to as Hydatoxi lualba. We have experimental evidence that this organism has biologic activity in BALB/c mice and in beagle dogs.

[Mortality in the perinatal period].

PubMed

Gutiérrez Avila, J H; Villalobos Olivas, A; Contreras Lemus, J

1980-01-01

A comparative study was conducted between 1978-79 in the pediatric department of the Mexican General Hospital to investigate social and physiopathological conditions leading to neonatal mortality. 100 newborn infants who had survived the first week of life were compared to 100 who had died. Social variables such as maternal age, education, socioeconomic status, marital status, and prenatal care were investigated, as well as physiopathological characteristics such as toxemia, length of gestation, diabetes, bleeding during the last trimester of pregnancy, type of presentation at delivery, congenital malformations, length of delivery, fetal cardiac frequency, and Apgar scores. Considerable social risk factors were identified in unmarried mothers (45.2% of those whose babies died, as compared to 21.4% in the control group), and lack of prenatal care (73.7% versus 41.1%). Physiopathological risk factors were low birth weight (80.5% versus 22%), probable diabetes of the mother (57.3% versus 8.7%), gestation of less than 37 weeks (70.4% versus 17.7%), low Apgar scores at 5 minutes of life (71.0% versus 10.3%), and fetal bradycardia (68.3% versus 6.3% in the control group). Abdominal or cesarean delivery seemed to represent a lesser risk than the use of forceps or the need for manual maneuvers. The need for comprehensive prenatal care programs, especially among the economically poor, is stressed.

Home visits during pregnancy: consequences on pregnancy outcome, use of health services, and women's situations.

PubMed

Blondel, B; Bréart, G

1995-08-01

This review of eight randomized controlled trials assessed two different types of home visits during pregnancy: (1) those offering social support to high-risk women; and (2) those providing medical care to women with complications. In both categories, pregnancy outcome was not improved when women received home visits. The summary odds ratio for preterm delivery (< 37 weeks) was 1.0 (95% CI: 0.8 to 1.1). Nor did the home visits decrease the rate of hospital admission for women with complications (mainly threatened preterm labor or toxemia); the corresponding summary odds ratio was 0.9 (95% CI: 0.7 to 1.2). Nevertheless in some trials home visits had positive effects on women (medical knowledge, support levels, health habits, and satisfaction). The randomized controlled trials provide little evidence that programs offering home visits are effective in improving either pregnancy outcome or the use of health services. A better integration of hospital and home services might allow a more rational use of health services for women with complications. In addition, we need to define more precisely the content of home visits providing social support. For this, further research is required on how emotional support, health education, and advice influence the health of women and infants and mother-child interactions.

Countermeasures to the bioterrorist threat of smallpox.

PubMed

Jahrling, Peter B; Fritz, Elizabeth A; Hensley, Lisa E

2005-12-01

Variola, the agent of smallpox, is a bioterrorist threat, as is monkeypox virus, which also occurs naturally in Africa. Development of countermeasures, in the form of improved vaccines, antiviral drugs, and other therapeutic strategies are a high priority. Recent advances in molecular biology and in animal model development have provided fresh insight into the virulence determinants for smallpox and the pathophysiology of disease. The complex replication cycle for orthopoxviruses, and the pivotal role for viral-specific immunomodulatory proteins which contribute to escape from immunologic surveillance, provide many unique targets for therapeutic intervention. The "toxemia" of smallpox has been elucidated in part by variola-infected primate studies which revealed the central role of apoptosis and the evolution of a cytokine storm leading to hemorrhagic diathesis, resembling fulminent "black" smallpox. This suggests a potential role for therapeutic strategies developed for septic shock, in treatment of smallpox. Drugs licensed for other viruses which share molecular targets with orthopoxviruses (e.g. Cidofovir) or cancer drugs (e.g. Gleevec and other tyrosine kinase inhibitors) have immediate application for treatment of smallpox and monkeypox and provide leads for second generation drugs with higher therapeutic indices. Recent advances in identification of virulence determinants and immune evasion genes facilitate the design of alternative vaccines to replace live vaccinia strains that are unsuitable for a large proportion of individuals in a mass immunization campaign.

[Delivery after a previous cesarean in the Gyneco-Obsteric Hospital Garza Garcia, N.L].

PubMed

de la Garza Quintanilla, C; Celaya Juárez, J A; Hernández Escobar, C

1997-04-01

One hundred and four patients who delivered after a previous cesarean section, at Hospital de Ginecoobstetricia de Garza García, N.L., from February 1, 1994 to January 31, 1995, were reviewed. The objective for this study was to know materno-fetal morbi-mortality at our hospital. Age, parity weeks of gestation, cause for previous section, delivery culmination, weight and Apgar of products, as well as, materno-fetal morbi-mortality, were analyzed. Average age group was 21 to 30 years with 68.5%. As to parity nulliparae predominated with 48.1%. As to weeks of gestation, the most frequent was 37 to 40 weeks, 85.5%. Previous section indication was: 1. Pelvic presentation, 2. Fetal stress, 3. Cefalo-pelvic disproportion, 4. Premature rupture of membranes, 5. Toxemia. As to deliveries outcome, there was dystocia in 86.5%, by profilactic low forceps application in 81.7%; and mid low in 4.8%. Eutocic delivery, 13.5%. Product weight was 3,000 to 3,500 g, with 51%. Apgar in 94 products was 8 and 9 at one minute. Maternal morbidity was 15.3% being most frequent vaginal tears. There was one case of uterine atonia, and one case of dura mater adverted puncture. There were no uterine dehiscence nor rupture. Perinatal morbidity was 5.6%. There was no perinatal death.

Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring.

PubMed

Akitake, Yoshiharu; Katsuragi, Shinji; Hosokawa, Masato; Mishima, Kenichi; Ikeda, Tomoaki; Miyazato, Mikiya; Hosoda, Hiroshi

2015-01-01

Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible. Copyright © 2015 Elsevier Inc. All rights reserved.

[Social and psychological aspects of contraception in adolescents].

PubMed

Fortier, L

1976-09-01

Reasons for the high adolescent birthrate in the U.S., medical, psychological, and social repercussions of teenage pregnancy, and facts and myths about sex education and contraception for young people are discussed. About 30% of U.S. women under 20 become pregnant outside marriage, and many more are pregnant when they marry. The reasons for the high pregnancy rates in young people include recent early menarch, which accounts for 94% fertility in 17.5-year-olds, better health, and ignorance about contraception and basic facts about reproduction. Pregnant adolescents risk toxemia, anemia, puerperal morbidity, prematurity, neonatal mortality, and congenital defects such as mental retardation in the baby. They face family alienation, loss of educational and employment opportunities, forced marriage, and high suicide rates in addition to the trials of puberty. Many girls believe that their fertile period is during menses, that pills are dangerous, that they are not fertile. Studies have shown that sex education can lower repeat pregnancies 67%. Recent research has negated the belief that many young women desire pregnancy unconsciously. Current information shows that supplying contraception will not encourage young people to begin having intercourse. Most sex education courses in the U.S. are given after the average teenagers become active sexually. It is believed that contraception should be provided universally for young people, and that parental authorization of contraception would probably mend family ties, certainly better than would unwanted pregnancy.

A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.

PubMed

Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

2015-12-01

The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. © 2015 John Wiley & Sons Ltd.

A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence

PubMed Central

Reardon-Robinson, Melissa E.; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

2016-01-01

Summary The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. PMID:26294390

Global occurrence of infant botulism, 1976-2006.

PubMed

Koepke, Ruth; Sobel, Jeremy; Arnon, Stephen S

2008-07-01

To summarize the worldwide occurrence of reported infant (intestinal toxemia) botulism cases since first recognition of the disease in 1976. We collected information on infant botulism cases by active and passive surveillance, by provision of therapeutic Human Botulism Immune Globulin to suspected cases, and by searching the medical literature. We defined a case as laboratory-confirmed botulism that occurred in an infant

Improved porcine model for Shiga toxin-producing Escherichia coli infection by deprivation of colostrum feeding in newborn piglets.

PubMed

Sato, Toshio; Hamabata, Takashi; Takita, Eiji; Matsui, Takeshi; Sawada, Kazutoshi; Imaoka, Taishi; Nakanishi, Nobuo; Nakayama, Keizo; Tsukahara, Takamitsu

2017-05-01

Porcine edema disease (ED) is a toxemia caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC). ED occurs most frequently during the weaning period and is manifested as emaciation associated with high mortality. In our experimental infection with a specific STEC strain, we failed to cause the suppression of weight gain in piglets, which is a typical symptom of ED, in two consecutive experiments. Therefore, we examined the effects of deprivation of colostrum on the sensitivity of newborn piglets to STEC infection. Neonatal pigs were categorized into two groups: one fed artificial milk instead of colostrum in the first 24 h after birth and then returned to the care of their mother, the other breastfed by a surrogate mother until weaning. The oral challenge with 10 11  colony-forming units of virulent STEC strain on days 25, 26 and 27 caused suppression of weight gain and other ED symptoms in both groups, suggesting that colostrum deprivation from piglets was effective in enhancing susceptibility to STEC. Two successive STEC infection experiments using colostrum-deprived piglets reproduced this result, leading us to conclude that this improved ED piglet model is more sensitive to STEC infection than the previously established models. © 2017 Japanese Society of Animal Science.

Association between Endocrine Disrupting Phenols in Colostrums and Maternal and Infant Health

PubMed Central

Yi, B.; Kim, C.; Park, M.; Han, Y.; Park, J. Y.; Yang, M.

2013-01-01

Bisphenol A (BPA) and alkylphenols (APs) are well-known endocrine disrupting chemicals (EDCs) which may threat the next generations' health. We performed biomonitoring of these phenols in colostrums to assess risk of the phenols in breast-fed neonates. Study subjects were the lactating mothers who delivered babies within 2 weeks (N = 325; 30.67 ± 3.45 years) and their neonates (N = 326; embryonic period, 39.1 ± 1.5 weeks). BPA, nonylphenol (NP), and octylphenol (OP) in colostrums were quantified with LC/MS/MS. Information for environmental exposure sources of the phenols was obtained by questionnaires. As results, median level of BPA in colostrums was 7.8 ng/mL, while most NP or OP was not detected. Regarding health risks of phenols, levels of total NP in colostrums were elevated among sick mothers with toxemia, thyroid disorders, gastritis, and so forth than health mothers (3.51 ± 4.98 versus 2.04 ± 3.71 ng/mL, P = 0.02). Dairy products intake and detergents use were positively correlated with total BPA levels (Ps < 0.05). In conclusion, we estimate most neonates who are exposed to BPA rather than NP or OP via colostrums and recommend continuous biomonitoring of the phenols to clarify their suspected health risk on neonates and pregnant or gestation mothers. PMID:23737772

Efficacy of ETI-204 monoclonal antibody as an adjunct therapy in a New Zealand white rabbit partial survival model for inhalational anthrax.

PubMed

Biron, Bethany; Beck, Katie; Dyer, David; Mattix, Marc; Twenhafel, Nancy; Nalca, Aysegul

2015-04-01

Inhalational anthrax is characterized by extensive bacteremia and toxemia as well as nonspecific to mild flu-like symptoms, until the onset of hypotension, shock, and mortality. Without treatment, the mortality rate approaches 100%. Antibiotic treatment is not always effective, and alternative treatments are needed, such as monotherapy for antibiotic-resistant inhalational anthrax or as an adjunct therapy in combination with antibiotics. The Bacillus anthracis antitoxin monoclonal antibody (MAb) ETI-204 is a high-affinity chimeric deimmunized antibody which targets the anthrax toxin protective antigen (PA). In this study, a partial protection New Zealand White (NZW) rabbit model was used to evaluate the protective efficacy of the adjunct therapy with the MAb. Following detection of PA in the blood, NZW rabbits were administered either an antibiotic (doxycycline) alone or the antibiotic in conjunction with ETI-204. Survival was evaluated to compare the efficacy of the combination adjunct therapy with that of an antibiotic alone in treating inhalational anthrax. Overall, the results from this study indicate that a subtherapeutic regimen consisting of an antibiotic in combination with an anti-PA MAb results in increased survival compared to the antibiotic alone and would provide an effective therapeutic strategy against symptomatic anthrax in nonvaccinated individuals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax.

PubMed

Yamamoto, Brent J; Shadiack, Annette M; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N; Gonzales, Nestor; O'Connor, Edward; Casey, Leslie S; Serbina, Natalya V

2016-10-01

The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery. Copyright © 2016 Yamamoto et al.

Evaluation of a point-of-care glucose and β-hydroxybutyrate meter operated in various environmental conditions in prepartum and postpartum sheep.

PubMed

Hornig, Katlin J; Byers, Stacey R; Callan, Robert J; Holt, Timothy; Field, Megan; Han, Hyungchul

2013-08-01

To compare β-hydroxybutyrate (BHB) and glucose concentrations measured with a dual-purpose point-of-care (POC) meter designed for use in humans and a laboratory biochemical analyzer (LBA) to determine whether the POC meter would be reliable for on-farm measurement of blood glucose and BHB concentrations in sheep in various environmental conditions and nutritional states. 36 pregnant mixed-breed ewes involved in a maternal feed restriction study. Blood samples were collected from each sheep at multiple points throughout gestation and lactation to allow for tracking of gradually increasing metabolic hardship. Whole blood glucose and BHB concentrations were measured with the POC meter and compared with serum results obtained with an LBA. 464 samples were collected. Whole blood BHB concentrations measured with the POC meter compared well with LBA results, and error grid analysis showed the POC values were acceptable. Whole blood glucose concentrations measured with the POC meter had more variation, compared with LBA values, over the glucose ranges evaluated. Results of error grid analysis of POC-measured glucose concentrations were not acceptable, indicating errors likely to result in needless treatment with glucose or other supplemental energy sources in normoglycemic sheep. The POC meter was user-friendly and performed well across a wide range of conditions. The meter was adequate for detection of pregnancy toxemia in sheep via whole blood BHB concentration. Results should be interpreted with caution when the POC meter is used to measure blood glucose concentrations.

Blackleg in cattle: A case report of fetal infection and a literature review.

PubMed

Abreu, Camila C; Edwards, Erin E; Edwards, John F; Gibbons, Philippa M; Leal de Araújo, Jeann; Rech, Raquel R; Uzal, Francisco A

2017-09-01

Clostridium chauvoei causes blackleg in cattle. The disease has been reported worldwide, and although it can be prevented by vaccination, sporadic cases and occasional outbreaks still occur. We describe a case of blackleg in a 2-y-old, pregnant Gyr cow with in utero transmission to the fetus. The cow had characteristic gross and microscopic lesions of blackleg including widespread necrohemorrhagic and emphysematous skeletal and myocardial myositis, and fibrinous pericarditis. Her uterus contained a near-term, markedly emphysematous fetus with skeletal muscle and myocardial lesions similar to those seen in the dam. Histopathology of dam and fetal tissues revealed numerous gram-positive bacilli, many of them with sub-terminal spores, in multiple tissues. These bacilli were identified as C. chauvoei by immunohistochemistry. Anaerobic culture and fluorescent antibody tests performed on skeletal muscle from both the dam and fetus were positive for C. chauvoei, confirming a diagnosis of blackleg. Blackleg is a so-called endogenous infection, and the currently accepted pathogenesis involves ingestion of spores that are transported to muscle tissues where they lie dormant until anaerobiosis prompts germination. Germinating bacteria are histotoxic, producing severe, local necrosis and ultimately lethal toxemia. This model, however, has not been confirmed experimentally and also fails to explain some cases of the disease. A presumptive diagnosis of blackleg is based on clinical, gross, and histologic findings. Diagnostic confirmation necessitates the detection of C. chauvoei by culture, PCR, or immunodetection methods.

Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax

PubMed Central

Yamamoto, Brent J.; Shadiack, Annette M.; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N.; Gonzales, Nestor; O'Connor, Edward; Casey, Leslie S.

2016-01-01

The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery. PMID:27431219

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits.

PubMed

Weiss, Shay; Altboum, Zeev; Glinert, Itai; Schlomovitz, Josef; Sittner, Assa; Bar-David, Elad; Kobiler, David; Levy, Haim

2015-12-01

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Immunization with recombinant bivalent chimera r-Cpae confers protection against alpha toxin and enterotoxin of Clostridium perfringens type A in murine model.

PubMed

Shreya, Das; Uppalapati, Siva R; Kingston, Joseph J; Sripathy, Murali H; Batra, Harsh V

2015-05-01

Clostridium perfringens type A, an anaerobic pathogen is the most potent cause of soft tissue infections like gas gangrene and enteric diseases like food poisoning and enteritis. The disease manifestations are mediated via two important exotoxins, viz. myonecrotic alpha toxin (αC) and enterotoxin (CPE). In the present study, we synthesized a bivalent chimeric protein r-Cpae comprising C-terminal binding regions of αC and CPE using structural vaccinology rationale and assessed its protective efficacy against both alpha toxin (αC) and enterotoxin (CPE) respectively, in murine model. Active immunization of mice with r-Cpae generated high circulating serum IgG (systemic), significantly increased intestinal mucosal s-IgA antibody titres and resulted in substantial protection to the immunized animals (100% and 75% survival) with reduced tissue morbidity when administered with 5×LD(100) doses of αC (intramuscular) and CPE (intra-gastric gavage) respectively. Mouse RBCs and Caco-2 cells incubated with a mixture of anti-r-Cpae antibodies and αC and CPE respectively, illustrated significantly higher protection against the respective toxins. Passive immunization of mice with a similar mixture resulted in 91-100% survival at the end of the 15 days observation period while mice immunized with a concoction of sham sera and respective toxins died within 2-3 days. This work demonstrates the efficacy of the rationally designed r-Cpae chimeric protein as a potential sub unit vaccine candidate against αC and CPE of C. perfringens type A toxemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chapter 29: Unproved and controversial methods and theories in allergy-immunology.

PubMed

Shah, Rachna; Greenberger, Paul A

2012-01-01

Unproved methods and controversial theories in the diagnosis and management of allergy-immunology are those that lack scientific credibility. Some definitions are provided for perspective because in chronic medical conditions, frequently, nonscientifically based treatments are developed that can have a very positive psychological effect on the patients in the absence of objective physical benefit. Standard practice can be described as "the methods of diagnosis and treatment used by reputable physicians in a particular subspecialty or primary care practice" with the understanding that diagnosis and treatment options are consistent with established mechanisms of conditions or diseases.(3) Conventional medicine (Western or allopathic medicine) is that which is practiced by the majority of MDs, DOs, psychologists, RNs, and physical therapists. Complementary medicine uses the practice of conventional medicine with complementary and alternative medicine such as using acupuncture for pain relief in addition to opioids. Alternative medicine implies use of complementary and alternative practices in place of conventional medicine. Unproved and controversial methods and theories do not have supporting data, validation, and sufficient scientific scrutiny, and they should not be used in the practice of allergy-immunology. Some examples of unproven theories about allergic immunologic conditions include allergic toxemia, idiopathic environmental intolerance, association with childhood vaccinations, and adrenal fatigue. Unconventional (unproved) diagnostic methods for allergic-immunologic conditions include cytotoxic tests, provocation-neutralization, electrodermal diagnosis, applied kinesiology assessments, and serum IgG or IgG(4) testing. Unproven treatments and intervention methods for allergic-immunologic conditions include acupuncture, homeopathy ("likes cure likes"), halotherapy, and autologous urine injections.

The demographic cost of early marriage.

PubMed

1978-01-01

The IPPF Biomedical Workshop held in London in November 1977, heard 16 speakers present papers on widely varied aspects of the problem of pregnancy during adolescence. These expert studies found that over the world teenagers face greater risks from pregnancy and the infants greater risks from low birth weight and birth defects. Moslem countries show particularly high rates of teenage marriage, ranging from 31% in Egypt to 73% in Pakistan. Religious beliefs and economic incentives, particularly gifts to the family of the bride, play a part. Demography also increases adolescent marriage. In Iran the sex ratio in 1970 was 100 women to every 109 men, which meant a nationwide shortage of 2 million women. As soon as a girl reaches puberty she is sought as a bride. In the U.S. in 1975 girls aged 15-19 experienced 1 million pregnancies, most of them unintended. This means 1 in 10 adolescents and 1 in 4 sexually active teenagers conceived. 11% of babies born to 15-17 year olds had low birth weight as did 9% of those born to women aged 17-19. These young mothers also had higher rates of toxemia, neonatal deaths, and maternal mortality than women in the optimal childbearing age bracket of 20-30. The social problems encountered, including lack of schooling, few job opportunities, and low income prospects, also hamper both mother and child. The problem in the U.S. seems to be acceptance and concern over the pregnancy rate but a refusal to face the sexual activity which leads to it. Sex education at younger ages is recommended.

Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox.

PubMed

Jahrling, Peter B; Hensley, Lisa E; Martinez, Mark J; Leduc, James W; Rubins, Kathleen H; Relman, David A; Huggins, John W

2004-10-19

Smallpox virus (variola) poses a significant threat as an agent of bioterrorism. To mitigate this risk, antiviral drugs and an improved vaccine are urgently needed. Satisfactory demonstration of protective efficacy against authentic variola will require development of an animal model in which variola produces a disease course with features consistent with human smallpox. Toward this end, cynomolgus macaques were exposed to several variola strains through aerosol and/or i.v. routes. Two strains, Harper and India 7124, produced uniform acute lethality when inoculated i.v. in high doses (10(9) plaque-forming units). Lower doses resulted in less fulminant, systemic disease and lower mortality. Animals that died had profound leukocytosis, thrombocytopenia, and elevated serum creatinine levels. After inoculation, variola was disseminated by means of a monocytic cell-associated viremia. Distribution of viral antigens by immunohistochemistry correlated with the presence of replicating viral particles demonstrated by electron microscopy and pathology in the lymphoid tissues, skin, oral mucosa, gastrointestinal tract, reproductive system, and liver. These particles resembled those seen in human smallpox. High viral burdens in target tissues were associated with organ dysfunction and multisystem failure. Evidence of coagulation cascade activation (D dimers) corroborated histologic evidence of hemorrhagic diathesis. Depletion of T cell-dependent areas of lymphoid tissues occurred, probably as a consequence of bystander apoptotic mechanisms initiated by infected macrophages. Elaboration of cytokines, including IL-6 and IFN-gamma, contribute to a cytokine storm formerly known as "toxemia." A more precise understanding of disease pathogenesis should provide targets for therapeutic intervention, to be used alone or in combination with inhibitors of variola virus replication.

The safe motherhood initiative: a call to action.

PubMed

Mahler, H

1987-03-21

A conference on Safe Motherhood, convened in Nairobi in February 1987 by the World Bank, World Health Organization, and United Nations Fund for Population Activities, has issued a call to reduce maternal mortality in developing countries by 50% in 1 decade. Of the 500,000 maternal deaths that occur each year, 99% are in developing countries. This has been a seriously neglected problem, largely because its victims are those with the least power and influence in society--they are poor, rural peasants, and female. The roots of mush maternal mortality lie in discrimination agianst women, in terms of legal status and access to education, financial resources and health care, including family planning. It is essential that all women are ensured access to maternal health and family planning services, especially obstetric care for life-threating conditions such as obstructed labor, eclampsia, toxemia, infection, and complications from spontaneous and induced abortion. The primary health care system at the district and subdistric leveles needs strengthening to provide adequate prenatal care and family planning services and to upgrade district hospitals and maternity centers so they can perform emergency care in pregnancy and childbirth. Since illegal abortion from unwanted pregnancy accounts for 25-50% of maternal deaths, access to family planning services and safe procedures is particularly important. In his remarkes to the conference, Halfdan Mahler, Director-General of WHO, outlined a 4-part strategy to combat maternal mortality: 1) adequate primary health care and an adequate share of available food for females from infancy to adolescence, and universally available family planning; 2) good prenatal care, including nutrtion, with early detection and referral of those at high risk; 3) the assistance of a trained person at all births; and 4) access to the essential elements of obstetric care for women at higher risk.

External cephalic version for breech presentation at term.

PubMed

Rauf, Bushra; Nisa, Mehrun-; Hassan, Lubna

2007-09-01

To assess the success rate of External Cephalic Version (ECV) at term and its effects on measures of pregnancy outcome. A quasi-experimental study. The study was conducted at Hayatabad Medical Complex, Peshawar, from December 2003 to January 2005. A total of 40 patients were offered ECV over a period of fourteen months. All singleton breech presentations with an otherwise normal antenatal course between 36-41 weeks of gestation were included in the study. Exclusion criteria included contraindications to ECV i.e. multiple pregnancy, oligohydramnios, growth retardation, antepartum hemorrhage, rupture of membranes toxemias of pregnancy, non-reassuring fetal monitoring pattern, previous uterine scar, bad obstetric history, any contraindication to vaginal delivery, labour and patient wishes after thorough counseling. Overall success rate of the procedure and its effect on maternal and fetal outcome was determined. Significance of results was determined using Chi-square test. A total of 40 patients were recruited for the trial. Overall success rate was 67.5% with only 30% being primi-gravida (p < 0.05). Multi-gravida showed higher success rate of 80%. Following successful ECV, spontaneous vaginal delivery was attained in 77.7% (n=21), while caesarean section was performed due to various indications in about 6 cases (p < 0.05). Following failed version, 61.5% (n=8) had elective C/S and only 5 delivered vaginally. Route of delivery did not affect the perinatal outcome except for congenital abnormalities. Following successful ECV, there was only one stillbirth. Overall live births associated with successful version was 96.2% (p < 0.05), while in failed version, there were no fetal deaths. ECV at term appears to be a useful procedure to reduce the number and associated complications of term breech presentation. It is safe for the mother and the fetus and helps to avoid a significant number of caesarean sections.

Inhibitory effect of baicalin on iNOS and NO expression in intestinal mucosa of rats with acute endotoxemia.

PubMed

Feng, Aiwen; Zhou, Guangrong; Yuan, Xiaoming; Huang, Xinli; Zhang, Zhengyuan; Zhang, Ti

2013-01-01

The mechanism by which baicalin modulated the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the mucosa of distal ileum was investigated in a rat model of acute endo-toxemia induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). The experiment demonstrated that LPS upregulated iNOS mRNA and protein expression as well as NO produc-tion (measured as the stable degradation production, nitrites). LPS not only increased toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor gamma (PPARγ) content, but also activated p38 and activating transcription factor 2 (ATF2) and inactivated PPARγ via phosphorylation. Inhibition of p38 signalling pathway by chemical inhibitor SB202190 and small interfering RNA (siRNA) ameliorated LPS-induced iNOS generation, while suppression of PPARγ pathway by SR-202 boosted LPS-elicited iNOS expression. Baicalin treatment (I) attenuated LPS-induced iNOS mRNA and protein as well as nitrites generation, and (II) ameliorated LPS-elicited TLR4 and PPARγ production, and (III) inhibited p38/ATF2 phosphorylation leading to suppression of p38 signalling, and (IV) prevented PPARγ from phosphorylation contributing to maintainence of PPARγ bioactivity. However, SR-202 co-treatment (I) partially abrogated the inhibitory effect of baicalin on iNOS mRNA expression, and (II) partially reversed baicalin-inhibited p38 phosphorylation. In summary, baicalin could ameliorate LPS-induced iNOS and NO overproduction in mucosa of rat terminal ileum via inhibition of p38 signalling cascade and activation of PPARγ pathway. There existed a interplay between the two signalling pathways.

Inhibitory Effect of Baicalin on iNOS and NO Expression in Intestinal Mucosa of Rats with Acute Endotoxemia

PubMed Central

Yuan, Xiaoming; Huang, Xinli; Zhang, Zhengyuan; Zhang, Ti

2013-01-01

The mechanism by which baicalin modulated the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the mucosa of distal ileum was investigated in a rat model of acute endo-toxemia induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). The experiment demonstrated that LPS upregulated iNOS mRNA and protein expression as well as NO produc-tion (measured as the stable degradation production, nitrites). LPS not only increased toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor gamma (PPARγ) content, but also activated p38 and activating transcription factor 2 (ATF2) and inactivated PPARγ via phosphorylation. Inhibition of p38 signalling pathway by chemical inhibitor SB202190 and small interfering RNA (siRNA) ameliorated LPS-induced iNOS generation, while suppression of PPARγ pathway by SR-202 boosted LPS-elicited iNOS expression. Baicalin treatment (I) attenuated LPS-induced iNOS mRNA and protein as well as nitrites generation, and (II) ameliorated LPS-elicited TLR4 and PPARγ production, and (III) inhibited p38/ATF2 phosphorylation leading to suppression of p38 signalling, and (IV) prevented PPARγ from phosphorylation contributing to maintainence of PPARγ bioactivity. However, SR-202 co-treatment (I) partially abrogated the inhibitory effect of baicalin on iNOS mRNA expression, and (II) partially reversed baicalin-inhibited p38 phosphorylation. In summary, baicalin could ameliorate LPS-induced iNOS and NO overproduction in mucosa of rat terminal ileum via inhibition of p38 signalling cascade and activation of PPARγ pathway. There existed a interplay between the two signalling pathways. PMID:24312512

Antibody Response to Shiga Toxins in Argentinean Children with Enteropathic Hemolytic Uremic Syndrome at Acute and Long-Term Follow-Up Periods

PubMed Central

Fernández-Brando, Romina J.; Bentancor, Leticia V.; Mejías, María Pilar; Ramos, María Victoria; Exeni, Andrea; Exeni, Claudia; Laso, María del Carmen; Exeni, Ramón; Isturiz, Martín A.; Palermo, Marina S.

2011-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with a broad spectrum of clinical manifestations that include diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Systemic Stx toxemia is considered to be central to the genesis of HUS. Distinct methods have been used to evaluate anti-Stx response for immunodiagnostic or epidemiological analysis of HUS cases. The development of enzyme-linked immunosorbent assay (ELISA) and western blot (WB) assay to detect the presence of specific antibodies to Stx has introduced important advantages for serodiagnosis of HUS. However, application of these methods for seroepidemiological studies in Argentina has been limited. The aim of this work was to develop an ELISA to detect antibodies against the B subunit of Stx2, and a WB to evaluate antibodies against both subunits of Stx2 and Stx1, in order to analyze the pertinence and effectiveness of these techniques in the Argentinean population. We studied 72 normal healthy children (NHC) and 105 HUS patients of the urban pediatric population from the surrounding area of Buenos Aires city. Using the WB method we detected 67% of plasma from NHC reactive for Stx2, but only 8% for Stx1. These results are in agreement with the broad circulation of Stx2-expressing STEC in Argentina and the endemic behavior of HUS in this country. Moreover, the simultaneous evaluation by the two methods allowed us to differentiate acute HUS patients from NHC with a great specificity and accuracy, in order to confirm the HUS etiology when pathogenic bacteria were not isolated from stools. PMID:21559455

Dietary omega-3 fatty acids for women.

PubMed

Bourre, Jean-Marie

2007-01-01

This review details the specific needs of women for omega-3 fatty acids, including alpha linoleic acid (ALA) and the very long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fatty acids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fatty acid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood. ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fatty acids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fatty acids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes. The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola), walnuts and so-called "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs.

Revisiting the Concept of Targeting Only Bacillus anthracis Toxins as a Treatment for Anthrax.

PubMed

Glinert, Itai; Bar-David, Elad; Sittner, Assa; Weiss, Shay; Schlomovitz, Josef; Ben-Shmuel, Amir; Mechaly, Adva; Altboum, Zeev; Kobiler, David; Levy, Haim

2016-08-01

Protective antigen (PA)-based vaccines are effective in preventing the development of fatal anthrax disease both in humans and in relevant animal models. The Bacillus anthracis toxins lethal toxin (lethal factor [LF] plus PA) and edema toxin (edema factor [EF] plus PA) are essential for the establishment of the infection, as inactivation of these toxins results in attenuation of the pathogen. Since the toxins reach high toxemia levels at the bacteremic stages of the disease, the CDC's recommendations include combining antibiotic treatment with antitoxin (anti-PA) immunotherapy. We demonstrate here that while treatment with a highly potent neutralizing monoclonal antibody was highly efficient as postexposure prophylaxis treatment, it failed to protect rabbits with any detectable bacteremia (≥10 CFU/ml). In addition, we show that while PA vaccination was effective against a subcutaneous spore challenge, it failed to protect rabbits against systemic challenges (intravenous injection of vegetative bacteria) with the wild-type Vollum strain or a toxin-deficient mutant. To test the possibility that additional proteins, which are secreted by the bacteria under pathogenicity-stimulating conditions in vitro, may contribute to the vaccine's potency, we immunized rabbits with a secreted protein fraction from a toxin-null mutant. The antiserum raised against the secreted fraction reacts with the bacteria in an immunofluorescence assay. Immunization with the secreted protein fraction did not protect the rabbits against a systemic challenge with the fully pathogenic bacteria. Full protection was obtained only by a combined vaccination with PA and the secreted protein fraction. Therefore, these results indicate that an effective antiserum treatment in advanced stages of anthrax must include toxin-neutralizing antibodies in combination with antibodies against bacterial cell targets. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

WILD PIG ATTACKS ON HUMANS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, J.

Attacks on humans by wild pigs (Sus scrofa) have been documented since ancient times. However, studies characterizing these incidents are lacking. In an effort to better understand this phenomenon, information was collected from 412 wild pig attacks on humans. Similar to studies of large predator attacks on humans, data came from a variety of sources. The various attacks compiled occurred in seven zoogeographic realms. Most attacks occurred within the species native range, and specifically in rural areas. The occurrence was highest during the winter months and daylight hours. Most happened under non-hunting circumstances and appeared to be unprovoked. Wounded animalsmore » were the chief cause of these attacks in hunting situations. The animals involved were typically solitary, male and large in size. The fate of the wild pigs involved in these attacks varied depending upon the circumstances, however, most escaped uninjured. Most human victims were adult males traveling on foot and alone. The most frequent outcome for these victims was physical contact/mauling. The severity of resulting injuries ranged from minor to fatal. Most of the mauled victims had injuries to only one part of their bodies, with legs/feet being the most frequent body part injured. Injuries were primarily in the form of lacerations and punctures. Fatalities were typically due to blood loss. In some cases, serious infections or toxemia resulted from the injuries. Other species (i.e., pets and livestock) were also accompanying some of the humans during these attacks. The fates of these animals varied from escaping uninjured to being killed. Frequency data on both non-hunting and hunting incidents of wild pig attacks on humans at the Savannah River Site, South Carolina, showed quantitatively that such incidents are rare.« less

The problem of teenage pregnancy.

PubMed

McGrew, M C; Shore, W B

1991-01-01

In this question and answer dialogue along with a case study, the psychosocial issues and medical aspects of teenage pregnancy are discussed. Suggestions for improving the situation included 1) developing a community based approach which utilizes school sex education integrated with parent, church, and community groups, 2) increasing teenage knowledge of contraception, and 3) providing counseling and medical and psychological health, education, and nutrition of the mother and father in order to reduce low birth weight babies and the school dropout rates. Advice to providers is to involved in supporting community based adolescent pregnancy and childbearing programs, and serving the needs of of teenagers by providing contraceptive information in confidence, and providing nonjudgmental information to parents and teenagers on sexuality, pregnancy and birth control. The cost of teenage childbearing is estimated at 16.6 billion for 1985, with the U.S. fertility rate, birth and abortion rates higher than Canada, France, the Netherlands, Great Britain and Sweden. Within 1 month of 1st initial intercourse, 20% result in teenage pregnancy. 50% will give birth to a second child. The health risk to the mother and child due to poor nutrition, toxemia conditions, while psychosocial effect is the cycle of failure and low self-esteem. For disadvantaged youth, a baby appears as a reachable achievement, and for those with an additional child, the goal of security and financial independence is less likely. Financial and emotional support from family or social services and family planning practices can lead to completion of H.S., limitation in family size, and independence. Of those receiving public assistance in 1969, 66% were independent, and only 12% receiving assistance between 1969 and 1974 were still receiving assistance. Teen fatherhood has not been adequately addressed, and findings suggest that parenting and contraceptive education, job training, support to stay in school are receptive ideas to fathers and also impact favorable on mothers and children.

Gene-Trap Mutagenesis Identifies Mammalian Genes Contributing to Intoxication by Clostridium perfringens ε-Toxin

PubMed Central

Ivie, Susan E.; Fennessey, Christine M.; Sheng, Jinsong; Rubin, Donald H.; McClain, Mark S.

2011-01-01

The Clostridium perfringens ε-toxin is an extremely potent toxin associated with lethal toxemias in domesticated ruminants and may be toxic to humans. Intoxication results in fluid accumulation in various tissues, most notably in the brain and kidneys. Previous studies suggest that the toxin is a pore-forming toxin, leading to dysregulated ion homeostasis and ultimately cell death. However, mammalian host factors that likely contribute to ε-toxin-induced cytotoxicity are poorly understood. A library of insertional mutant Madin Darby canine kidney (MDCK) cells, which are highly susceptible to the lethal affects of ε-toxin, was used to select clones of cells resistant to ε-toxin-induced cytotoxicity. The genes mutated in 9 surviving resistant cell clones were identified. We focused additional experiments on one of the identified genes as a means of validating the experimental approach. Gene expression microarray analysis revealed that one of the identified genes, hepatitis A virus cellular receptor 1 (HAVCR1, KIM-1, TIM1), is more abundantly expressed in human kidney cell lines than it is expressed in human cells known to be resistant to ε-toxin. One human kidney cell line, ACHN, was found to be sensitive to the toxin and expresses a larger isoform of the HAVCR1 protein than the HAVCR1 protein expressed by other, toxin-resistant human kidney cell lines. RNA interference studies in MDCK and in ACHN cells confirmed that HAVCR1 contributes to ε-toxin-induced cytotoxicity. Additionally, ε-toxin was shown to bind to HAVCR1 in vitro. The results of this study indicate that HAVCR1 and the other genes identified through the use of gene-trap mutagenesis and RNA interference strategies represent important targets for investigation of the process by which ε-toxin induces cell death and new targets for potential therapeutic intervention. PMID:21412435

Diversity of flora used for the cure of equine diseases in selected peri-urban areas of Punjab, Pakistan

PubMed Central

2013-01-01

Background Plants have widely been used and documented for their therapeutic potential in many parts of the world. There are, however, few reports on the use of plants for the treatment of diseases of equines. To this end, participatory epidemiology and rapid rural appraisal techniques were used to document the plants having pharmacotherapeutic significance against different ailments of equines in selected population of Punjab, Pakistan. Methods A survey was conducted to interview a total of 450 respondents (150 from each of the districts of Faisalabad, Lahore and Sargodha of Pakistan) to collect information about disease recognition of the equines and their treatment on a well − structured questionnaire. A total of 60 plants belonging to 40 families were documented. An inventory was developed depicting detailed information of plants used in treatment of different conditions of equines. Results The top ten species of plants used were: Allium cepa, Zingiber officinale, Vernonia anthelmintica, Capsicum annum, Brassica campestris, Trachyspermum ammi, Anethum graveolens, Picrorhiza kurroa, Azadirachta indica, and Citrullus colocynthis. Seeds were the most frequently used (n = 16/60) parts, followed by leaves (n = 12/60) and fruits (n = 11/60) of plants. Based on the combination of different parts of plants used in different ratios and variation in their dose or mode of preparation led to a large number of recipes/remedies against wounds, lameness, bronchitis, colic, anorexia, dermatitis, weakness, parasitism (internal & external), fever, heat stress, urine retention, swelling, toxemia, and indigestion. Conclusions This study generated lot of data on phytomedicinal approach for the treatment of ailments in the equines in some selected areas. It would, therefore, be imperative to expand similar studies in other parts of Pakistan and elsewhere. Moreover, use of the documented plants may be validated employing standard scientific procedures, which may have their application in the drug discovery/development by the pharmaceutical industry. PMID:24283263

Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens ε-toxin.

PubMed

Ivie, Susan E; Fennessey, Christine M; Sheng, Jinsong; Rubin, Donald H; McClain, Mark S

2011-03-11

The Clostridium perfringens ε-toxin is an extremely potent toxin associated with lethal toxemias in domesticated ruminants and may be toxic to humans. Intoxication results in fluid accumulation in various tissues, most notably in the brain and kidneys. Previous studies suggest that the toxin is a pore-forming toxin, leading to dysregulated ion homeostasis and ultimately cell death. However, mammalian host factors that likely contribute to ε-toxin-induced cytotoxicity are poorly understood. A library of insertional mutant Madin Darby canine kidney (MDCK) cells, which are highly susceptible to the lethal affects of ε-toxin, was used to select clones of cells resistant to ε-toxin-induced cytotoxicity. The genes mutated in 9 surviving resistant cell clones were identified. We focused additional experiments on one of the identified genes as a means of validating the experimental approach. Gene expression microarray analysis revealed that one of the identified genes, hepatitis A virus cellular receptor 1 (HAVCR1, KIM-1, TIM1), is more abundantly expressed in human kidney cell lines than it is expressed in human cells known to be resistant to ε-toxin. One human kidney cell line, ACHN, was found to be sensitive to the toxin and expresses a larger isoform of the HAVCR1 protein than the HAVCR1 protein expressed by other, toxin-resistant human kidney cell lines. RNA interference studies in MDCK and in ACHN cells confirmed that HAVCR1 contributes to ε-toxin-induced cytotoxicity. Additionally, ε-toxin was shown to bind to HAVCR1 in vitro. The results of this study indicate that HAVCR1 and the other genes identified through the use of gene-trap mutagenesis and RNA interference strategies represent important targets for investigation of the process by which ε-toxin induces cell death and new targets for potential therapeutic intervention.

Generation and characterization of recombinant bivalent fusion protein r-Cpib for immunotherapy against Clostridium perfringens beta and iota toxemia.

PubMed

Das, Shreya; Majumder, Saugata; Kingston, Joseph J; Batra, Harsh V

2016-02-01

Clostridium perfringens beta (CPB) and iota (CPI) toxaemias result in some of the most lethal forms of haemorrhagic and necrotic enteritis and sudden death syndrome affecting especially neonates. While CPB enterotoxemia is one of the most common forms of clostridial enterotoxemia, CPI enterotoxemia though putatively considered to be rare is an emerging cause of concern. The similarities in clinical manifestation, gross and histopathology findings of both types of toxaemias coupled to the infrequency of CPI toxaemia might lead to symptomatic misidentification with Type C resulting in therapeutic failure due to habitual administration of CPB anti-toxin which is ineffective against CPI. Therefore in the present study, to generate a composite anti-toxin capable of neutralizing both toxaemias, a novel bivalent chimera r-Cpib was constructed by splicing the non-toxic C terminal binding regions of CPB and CPI, via a flexible glycine linker (G4S) by overlap-extension PCR. The fusion protein was characterized for its therapeutic abilities toward CPI and CPB toxin neutralizations. The r-Cpib was found to be non-toxic and could competitively inhibit binding of CPB to host cell receptors thereby reducing its cytotoxicity. Immunization of mice with r-Cpib generated specific antibodies capable of neutralizing the above toxaemias both in vitro and in vivo. Caco-2 cells exposed to a mixture of anti-r-Cpib sera and native CPI or CPB, displayed significantly superior protection against the respective toxins while passive challenge of mice with a similar mixture resulted in 83 and 91% protection against CPI and CPB respectively. Alternatively, mice exposed to a mixture of sham sera and native toxins died within 2-3 days. This work thus demonstrates r-Cpib as a novel bivalent fusion protein capable of efficient immunotherapy against C. perfringens CPI and CPB toxaemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Dormant Microbial Component in the Development of Preeclampsia

PubMed Central

Kell, Douglas B.; Kenny, Louise C.

2016-01-01

Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one. PMID:27965958

Arrangement of the Clostridium baratii F7 Toxin Gene Cluster with Identification of a σ Factor That Recognizes the Botulinum Toxin Gene Cluster Promoters

DOE PAGES

Dover, Nir; Barash, Jason R.; Burke, Julianne N.; ...

2014-05-22

Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bontmore » gene that is part of a toxin gene cluster that includes several accessory genes. In this paper, we sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ 70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. Finally, this TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.« less

Consequences of early childbearing.

PubMed

Monroy De Velasco, A

1982-12-01

By 2000, developing countries will have an estimated 1 billion adolescents who are physically old enough to reproduce themselves but far too young to be responsible, healthy parents of healthy children. Governments must become involved in the issues surrounding adolescent pregnancy and both custom and the laws must change to reflect the needs of young people. The consequences of early childbearing are felt by society as well as the families directly affected. The incidence of births to very young women, both married and unmarried is growing; each year approximately 13 million children are born to young mothers. The percentage of live births to mothers under the age of 20 ranges from 20% in some African and Caribbean countries, to 10-15% in many Latin American countries, 5-10% in Asia, and 1% in Japan. Increased out-of-wedlock adolescent pregnancy is due to many factors: earlier sexual maturity from better childhood health and nutrition, a trend toward later marriage, increased opportunity for opposite sex interaction in schools and in the labor force, and rapid urbanization which weakens traditional family structures and social and cultural controls. Early childbirth is especially dangerous for adolescents and their infants. Compared to women between the ages of 20-35, pregnant women under 20 are at a greater risk for death and disease including bleeding during pregnancy, toxemia, hemorrhage, prolonged and difficult labor, severe anemia, and disability. Life-long social and economic disadvantages may be a consequence of teenage birth. Educational and career opportunities may be limited, as may be opportunities for marriage. Teen mothers tend to have larger completed family sizes, shorter birth intervals resulting in both poorer health status for the family, and a more severe level of poverty. The children also suffer; teens mothers have a higher incidence of low birth weight infants which is associated with birth injuries, serious childhood illness, and mental and physical disabilities. Adolescents' access to family planning information and services is limited. Government programs in developing countries have focused on older women to limit family size. In addition, national laws and local customs often prohibit minors from consenting to medical services. Both the number and proportions of abortions performed for young women have been increasing. Abortions are more physically traumatic for young women who tend to request services later in pregnancy.

An architecture for a continuous, user-driven, and data-driven application of clinical guidelines and its evaluation.

PubMed

Shalom, Erez; Shahar, Yuval; Lunenfeld, Eitan

2016-02-01

Design, implement, and evaluate a new architecture for realistic continuous guideline (GL)-based decision support, based on a series of requirements that we have identified, such as support for continuous care, for multiple task types, and for data-driven and user-driven modes. We designed and implemented a new continuous GL-based support architecture, PICARD, which accesses a temporal reasoning engine, and provides several different types of application interfaces. We present the new architecture in detail in the current paper. To evaluate the architecture, we first performed a technical evaluation of the PICARD architecture, using 19 simulated scenarios in the preeclampsia/toxemia domain. We then performed a functional evaluation with the help of two domain experts, by generating patient records that simulate 60 decision points from six clinical guideline-based scenarios, lasting from two days to four weeks. Finally, 36 clinicians made manual decisions in half of the scenarios, and had access to the automated GL-based support in the other half. The measures used in all three experiments were correctness and completeness of the decisions relative to the GL. Mean correctness and completeness in the technical evaluation were 1±0.0 and 0.96±0.03 respectively. The functional evaluation produced only several minor comments from the two experts, mostly regarding the output's style; otherwise the system's recommendations were validated. In the clinically oriented evaluation, the 36 clinicians applied manually approximately 41% of the GL's recommended actions. Completeness increased to approximately 93% when using PICARD. Manual correctness was approximately 94.5%, and remained similar when using PICARD; but while 68% of the manual decisions included correct but redundant actions, only 3% of the actions included in decisions made when using PICARD were redundant. The PICARD architecture is technically feasible and is functionally valid, and addresses the realistic continuous GL-based application requirements that we have defined; in particular, the requirement for care over significant time frames. The use of the PICARD architecture in the domain we examined resulted in enhanced completeness and in reduction of redundancies, and is potentially beneficial for general GL-based management of chronic patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Contribution of genome-environment interaction to pre-eclampsia in a Havana Maternity Hospital.

PubMed

Lardoeyt, Roberto; Vargas, Gerardo; Lumpuy, Jairo; García, Ramón; Torres, Yuselis

2013-07-01

Pre-eclampsia is a major cause of morbidity and mortality during pregnancy worldwide and is among the leading causes of maternal mortality in Cuba. It is a complex, multifactoral disease, in which interaction of genetic and environmental factors should not be overlooked if the goal is proper risk assessment to support personalized preventive genetic counseling and more effective prenatal care to prevent pregnancy complications. Determine the contribution to pre-eclampsia of interaction between a predisposing genome and adverse environmental factors in pregnant women in a Havana maternity hospital. This was the exploratory phase of a hospital-based case-control study, using January 2007-December 2009 patient records from the Eusebio Hernández University Hospital, a provincial maternity hospital in Havana. Eighty pregnant women diagnosed with pre-eclampsia and 160 controls were studied. The main variables were age, parity, nutritional status (measured by BMI), alcohol use, tobacco use, and history of pre-eclampsia in relatives of the pregnant woman (proband) or of her partner. Pearson chi square and Fisher exact test were used to assess statistical significance of associations between variables and odds ratio as a measure of association strength. Familial aggregation was studied and a case-control design used to assess gene-environment interaction, using multiplicative and additive models. Among the environmental risk factors studied, alcohol showed the strongest effect on pre-eclampsia risk (OR 3.87, 95% CI 1.64-9.13). Familial pre-eclampsia clustering was observed; risk was increased for both first-degree (OR 2.43, 95% CI 1.62-3.73) and second-degree (OR 1.89, 95% CI 1.34-2.68) relatives as well as for husband's relatives (OR 2.32, 95% CI 1.40-3.86). There was evidence of interaction between alcohol consumption and family history. Familial aggregation of the disorder was demonstrated, the first Cuban epidemiological evidence of genetic and enviromental contributions to pre-eclampsia risk. Familial clustering among the husband's relatives demonstrates the fetal genome's importance in genesis of pre-eclampsia. The interaction of environmental risk factors with genetic ones produces increased pre-eclampsia risk, compared to expectations based on independent action of these variables. KEYWORDS Pre-eclampsia, toxemia of pregnancy, pregnancy outcome, environment, genetics, genome-environment interaction, genetic epidemiology, Cuba.

Definition of prepartum hyperketonemia in dairy goats.

PubMed

Doré, V; Dubuc, J; Bélanger, A M; Buczinski, S

2015-07-01

A prospective cohort study was conducted on 1,081 dairy goats from 10 commercial herds in Québec (Canada) to define prepartum hyperketonemia based on optimal blood β-hydroxybutyrate acid threshold values for the early prediction of pregnancy toxemia (PT) and mortality in late-gestation dairy goats. All pregnant goats had blood sampled weekly during the last 5wk of pregnancy. The blood was analyzed directly on the farm for β-hydroxybutyrate acid quantification using a Precision Xtra meter (Abbott Diabetes Care, Saint-Laurent, QC, Canada). Body condition scores on the lumbar region and sternum were noted. Each goat was classified as being at low (n=973) or high risk (n=108) of having PT by producers based on a standardized definition. The optimal threshold for predicting a PT diagnosis or mortality for each week before kidding was determined based on the highest sum of sensitivity and specificity. The association between hyperketonemia and subsequent PT was tested using a multivariable logistic regression model considering hyperketonemia at wk 4 prepartum, litter size, and body condition score at wk 4 prepartum as covariates, and herd and parturition cohort as random effects. The association between mortality and hyperketonemia was also tested using a logistic regression model accounting for the presence or absence of treatment during the last month of pregnancy. The hyperketonemia definition based on PT varied between ≥0.4 and ≥0.9mmol/L during the last 5wk prepartum. Goats affected by hyperketonemia at wk 4 prepartum and with a large litter size (≥3 fetuses) had 2.1 and 40.5 times the odds, respectively, of subsequent PT than other goats. Hyperketonemia definitions based on mortality varied between ≥0.6 and ≥1.4mmol/L during the last 4wk prepartum, and was ≥1.7mmol/L during the first week postpartum. Goats affected by hyperketonemia and treated by producers had 3.4 and 11.8 times the odds, respectively, of subsequent mortality than did other goats. These results showed that prepartum hyperketonemia could be defined in dairy goats using subsequent risks of PT or mortality during the last month of pregnancy. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comparison of two treatment strategies for cows with metritis in high-risk lactating dairy cows.

PubMed

Armengol, Ramon; Fraile, Lorenzo

2015-05-01

Acute puerperal metritis (APM) and clinical metritis (CM) are uterine diseases frequently diagnosed in dairy cows. These diseases are responsible for important economic loss because of their effect not only on reproductive performance but also on milk production. The objective of this study was to assess the impact of two different treatments for metritis on dairy cows by measuring their reproductive performance in the next gestation. The end points to measure the reproductive performance included the conception rate at the first artificial insemination, the number of days at conception, and the proportion of nonpregnant cows at over 150 days after beginning milk production. The study was carried out in a high production dairy cow farm located in Lleida (northeast Spain). Recordings of 1044 parturitions of 747 Holstein cows were controlled in this farm from 2009 to 2014. Cows were diagnosed as suffering from metritis (APM or CM) if the following parameters were observed: an abnormally enlarged uterus; a fetid, watery, reddish brown uterine discharge with (APM) or without (CM) fever (>39.5 °C); and presence (APM) or absence (CM) of signs of systemic illness (decreased milk production, dullness, or other signs of toxemia) within 21 days postpartum. Afterwards, cows suffering from metritis (APM or CM) were randomly assigned and balanced to two groups: (1) animals receiving parenteral amoxicillin intramuscularly plus intrauterine infusion with oxytetracycline (P + I group) and (2) animals receiving only parenteral amoxicillin intramuscularly (P group). Furthermore, reproductive performance of cows without metritis was used as reference (control group). Metritis was diagnosed in 27.5% of the total parturitions included in the study (288 of 1044). In particular, metritis was diagnosed in 30.5% (118 of 387) and 25.9% (170 of 657) of parturitions from heifers and multiparous cows, respectively. Reproductive performance was not significantly affected by the parity, the season at the first artificial insemination, the season at conception, the bull, or the inseminator. The P + I treatment was able to significantly reduce the number of days at the first insemination and at conception when compared with the P treatment in heifers. In multiparous cows, this significant effect was only observed for days at conception. Additionally, the P + I treatment was able to significantly increase the percentage of pregnant animals at the first insemination and decrease the percentage of nonpregnant cows at greater than 150 days in milk production for both heifers and multiparous cows when compared with the P treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Medical treatment for botulism.

PubMed

Chalk, Colin; Benstead, Tim J; Keezer, Mark

2011-03-16

Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key but the role of other medical treatments is unclear. To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events in botulism. We searched the Cochrane Neuromuscular Disease Group Specialized Register (10 January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (10 January 2010 in The Cochrane Library, Issue 4 2010), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011). We reviewed bibliographies, and contacted authors and experts. We included randomized and quasi-randomized controlled trials examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism and adult intestinal toxemia). Medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin, plasma exchange, 3,4-diaminopyridine and guanidine. Two authors selected studies, assessed risk of bias and extracted data independently onto data extraction forms.Our primary outcome was in-hospital death from any cause occurring within four weeks. Secondary outcomes were death occurring within 12 weeks, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events. A single randomized controlled trial met the inclusion criteria. This trial evaluated human-derived botulinum immune globulin for the treatment of infant botulism. This study included 59 treatment patients and 63 control patients. There were no deaths in either group making any treatment effect on mortality inestimable. There was a significant benefit in the treatment group on duration of hospitalization (mean difference (MD) 3.10 weeks, 95% confidence interval (CI) 1.68 to 4.52), mechanical ventilation (MD 2.60 weeks, 95% CI 1.14 to 4.06), and tube or parenteral feeding (MD 6.40 weeks, 95% CI 2.80 to 10.00) but not on risk of adverse events or complications (relative risk reduction 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11). There is good evidence supporting the use of human-derived botulinum immune globulin in infant intestinal botulism. A single randomized controlled trial demonstrated significant decreases in the duration of hospitalization, mechanical ventilation and tube or parenteral feeding among treated patients. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.

Machine vision process monitoring on a poultry processing kill line: results from an implementation

NASA Astrophysics Data System (ADS)

Usher, Colin; Britton, Dougl; Daley, Wayne; Stewart, John

2005-11-01

Researchers at the Georgia Tech Research Institute designed a vision inspection system for poultry kill line sorting with the potential for process control at various points throughout a processing facility. This system has been successfully operating in a plant for over two and a half years and has been shown to provide multiple benefits. With the introduction of HACCP-Based Inspection Models (HIMP), the opportunity for automated inspection systems to emerge as viable alternatives to human screening is promising. As more plants move to HIMP, these systems have the great potential for augmenting a processing facilities visual inspection process. This will help to maintain a more consistent and potentially higher throughput while helping the plant remain within the HIMP performance standards. In recent years, several vision systems have been designed to analyze the exterior of a chicken and are capable of identifying Food Safety 1 (FS1) type defects under HIMP regulatory specifications. This means that a reliable vision system can be used in a processing facility as a carcass sorter to automatically detect and divert product that is not suitable for further processing. This improves the evisceration line efficiency by creating a smaller set of features that human screeners are required to identify. This can reduce the required number of screeners or allow for faster processing line speeds. In addition to identifying FS1 category defects, the Georgia Tech vision system can also identify multiple "Other Consumer Protection" (OCP) category defects such as skin tears, bruises, broken wings, and cadavers. Monitoring this data in an almost real-time system allows the processing facility to address anomalies as soon as they occur. The Georgia Tech vision system can record minute-by-minute averages of the following defects: Septicemia Toxemia, cadaver, over-scald, bruises, skin tears, and broken wings. In addition to these defects, the system also records the length and width information of the entire chicken and different parts such as the breast, the legs, the wings, and the neck. The system also records average color and miss- hung birds, which can cause problems in further processing. Other relevant production information is also recorded including truck arrival and offloading times, catching crew and flock serviceman data, the grower, the breed of chicken, and the number of dead-on- arrival (DOA) birds per truck. Several interesting observations from the Georgia Tech vision system, which has been installed in a poultry processing plant for several years, are presented. Trend analysis has been performed on the performance of the catching crews and flock serviceman, and the results of the processed chicken as they relate to the bird dimensions and equipment settings in the plant. The results have allowed researchers and plant personnel to identify potential areas for improvement in the processing operation, which should result in improved efficiency and yield.

Crude glycerin decreases nonesterified fatty acid concentration in ewes during late gestation and early lactation.

PubMed

Polizel, D M; Susin, I; Gentil, R S; Ferreira, E M; de Souza, R A; Freire, A P A; Pires, A V; Ferraz, M V C; Rodrigues, P H M; Eastridge, M L

2017-02-01

Crude glycerin is a gluconeogenic substrate in ruminants and may help to decrease the occurrence of pregnancy toxemia. The objective in this trial was to determine the effects of feeding a diet containing crude glycerin on DMI, milk yield, milk composition, and blood metabolites in periparturient ewes and lamb performance. One hundred eighteen 90 (±1.1)-d pregnant Santa Inês ewes were used. After lambing, 32 ewes (62.8 ± 1.3 kg BW) were allotted in a randomized complete block design defined by prelambing diet, BW, BCS, lambing date, type of birth (single or twin), and sex of offspring. Diets were isonitrogenous (13.0 ± 0.3% CP, DM basis), composed of concentrate and raw sugarcane bagasse (70:30 ratio, DM basis), and fed ad libitum daily. Crude glycerin (83.6% glycerol) levels were 0 or 10% (DM basis), corresponding to the experimental diets G0 and G10, respectively. From 8 until 56 d of lactation, DMI was determined. In the same period, once a week at 1000 h, the ewes were separated from the lambs and mechanically milked after intravenous administration of 10 IU of synthetic oxytocin. Three hours after the first milking, ewes were milked again and milk yield and composition were determined. Glucose, NEFA, and β-hydroxybutyrate (BHBA) were determined at -14, -7, 0, 7, 14, 28, and 56 d relative to lambing and insulin was determined at -14, -7, 0, and 7 d. Crude glycerin did not affect DMI (2.2 kg/d for G0 vs. 2.2 kg/d for G10; = 0.93) or milk production (171 g/3 h for G0 vs. 164 g/3 h for G10; = 0.66). However, there was a decrease ( = 0.01) in milk fat percentage (8.1% for G0 vs. 7.0% for G10) for ewes fed glycerin. Ewes fed the G10 diet had decreased ( < 0.01) NEFA concentration (0.27 mmol/L for G0 vs. 0.18 mmol/L for G10). There was an interaction between diet × time for glucose ( = 0.04), insulin ( = 0.05), and BHBA ( = 0.01); feeding glycerin increased glucose (5.61 mmol/L for G0 vs. 7.42 mmol/L for G10; < 0.01) and insulin concentrations (10.5 μIU for G0 vs. 24.5 μIU for G10; < 0.01) at parturition compared with G0. The BHBA was less ( = 0.02) on the day of lambing (0.40 mmol/L for G0 vs. 0.29 mmol/L for G10) and it was greater ( < 0.01) on d 56 for ewes fed the G10 diet (0.46 mmol/L for G0 vs. 0.61 mmol/L for G10). There was no effect of diets fed to ewes on lamb growth from birth to weaning. Crude glycerin improved energy balance of periparturient ewes, suggesting a reduced risk of developing clinical metabolic-related disorders. Crude glycerin can be added at 10% of ewes' diets without affecting DMI and milk yield.

Maternal and foetal risk factor and complication with immediate outcome during hospital stay of very low birth weight babies.

PubMed

Mannan, M A; Jahan, N; Dey, S K; Uddin, M F; Ahmed, S

2012-10-01

This prospective study was done to find out the maternal and foetal risk factors and complications during hospital stay. It was conducted in Special Care Neonatal Unit (SCANU), Department of Child Health, Bangabandhu Memorial Hospital (BBMH), University of Science and Technology Chittagong (USTC) from1st October 2001 to 30th March 2002 and cases were 35 very low birth weight (VLBW) newborns. Common complications of VLBW babies of this series were frequent apnea (40%), Septicemia (25.71%), Hypothermia (17.14%), NEC (14.28%), Convulsion (11.43%), Hyper-bilirubinaemia (8.57%), Anemia (5.71%), IVH (5.71%), RDS (2.86%), HDN (2.86%), CCF (2.86%), ARF (2.86%), either alone or in combination with other clinical conditions. Newborns 62.86% male, 37.14% female & their mortality rate were 40.91% & 38.46% respectively; Preterm 88.57% & their mortality (41.93%) were higher than term babies (25.00%); AGA 62.86%, SGA 37.14% & mortality rate of AGA babies (45.46%) were higher than of SGA (30.77%) babies. The mortality rate of VLBW infants of teen age (≤ 18 years) mothers (57.14%) & high (≥ 30 years) aged mothers (50.00%) were higher than average (19-26 yrs) maternal age mothers (33.33%). Mortality rate was higher among the babies of primi (41.67%) than multiparous (36.36%), poor socioeconomic group (53.33%) than middle class (30.00%) & mothers on irregular ANC (47.83%) than regular ANC (25.00%). It has been also noted the mortality rate of home delivered babies (50.00%) higher than institutional delivered (34.78%) babies; higher in LUCS babies (46.15%) than normal vaginal delivered babies (31.58%); higher in the babies who had antenatal maternal problem (48.15%) than no maternal problems babies (12.50%); higher in the babies who had fetal distress (50.00%) and twin (46.67%) than no foetal risk factors (28.57%) during intrauterine life; higher in the babies who had problems at admission (46.67%) than no problems (35.00%); and mortality higher in twin (46.67%) than singleton babies (35.00%). Maximum VLBW babies who died during hospital stay had multiple problems and mortality was varied from ?60-100%. The babies who had frequent apnea have been carried relative better outcome (mortality rate 35.72%). In this study out of total 35 studied baby 21(60.00%) survived and 14(40.00%) died. Frequent apnea, sepsis, hypothermia, NEC, convulsion, jaundice, anemia, IVH, and RDS are common complications in VLBW babies. Male sex, prematurity, primiparity, average (middle) socio-economic status, irregular ANC, preterm labor, toxemia of pregnancy, prolonged rupture of membrane, malnutrition, multiple gestations and foetal distress are risk factor for VLBW delivery. Clinical outcome depends on maturity, birth weight, centile for weight, maternal age, parity, maternal nutrition & socio-economic status, ANC, place & mode of delivery, maternal problems during antenatal & perinatal period, number of gestation, fetal condition, presentation at admission, postnatal problems, time of start of management & referral and level of care.

Medical treatment for botulism.

PubMed

Chalk, Colin H; Benstead, Tim J; Keezer, Mark

2014-02-20

Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key but the role of other medical treatments is unclear. This is an update of a review first published in 2011. To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events in botulism. On 30 March 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register (30 March 2013), CENTRAL (2013, Issue 3) in The Cochrane Library, MEDLINE (January 1966 to March 2013) and EMBASE (January 1980 to March 2013). We reviewed bibliographies and contacted authors and experts. Randomized and quasi-randomized controlled trials examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin, plasma exchange, 3,4-diaminopyridine and guanidine. Two authors independently selected studies, assessed risk of bias and extracted data onto data extraction forms.Our primary outcome was in-hospital death from any cause occurring within four weeks. Secondary outcomes were death occurring within 12 weeks, duration of hospitalization, mechanical ventilation, tube or parenteral feeding and risk of adverse events. A single randomized controlled trial met the inclusion criteria. We found no additional trials when we updated the searches in 2013. This trial evaluated human-derived botulinum immune globulin (BIG) for the treatment of infant botulism and included 59 treatment participants as well as 63 control participants. The control group received a control immune globulin which did not have an effect on botulinum toxin. In this trial there was some violation of intention-to-treat principles, and possibly some between-treatment group imbalances among those participants admitted to the intensive care unit (ICU) and mechanically ventilated, but overall we judged the risk of bias to be low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a significant benefit in the treatment group on mean duration of hospitalization (BIG: 2.60 weeks, 95% CI 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) 3.10 weeks, 95% CI 1.68 to 4.52), mechanical ventilation (BIG: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD 2.60 weeks, 95% CI 1.14 to 4.06), and tube or parenteral feeding (BIG: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD 6.40 weeks, 95% CI 2.80 to 10.00) but not on risk of adverse events or complications (BIG: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11). There is evidence supporting the use of human-derived botulinum immune globulin (BIG) in infant intestinal botulism. A single randomized controlled trial demonstrated significant decreases in the duration of hospitalization, mechanical ventilation and tube or parenteral feeding with BIG treatment. This evidence was of moderate quality for effects on duration of mechanical ventilation but was otherwise of high quality. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.

A multiple-scenario assessment of the effect of a continuous-care, guideline-based decision support system on clinicians' compliance to clinical guidelines.

PubMed

Shalom, Erez; Shahar, Yuval; Parmet, Yisrael; Lunenfeld, Eitan

2015-04-01

To quantify the effect of a new continuous-care guideline (GL)-application engine, the Picard decision support system (DSS) engine, on the correctness and completeness of clinicians' decisions relative to an established clinical GL, and to assess the clinicians' attitudes towards a specific DSS. Thirty-six clinicians, including residents at different training levels and board-certified specialists at an academic OB/GYN department that handles around 15,000 deliveries annually, agreed to evaluate our continuous-care guideline-based DSS and to perform a cross-over assessment of the effects of using our guideline-based DSS. We generated electronic patient records that realistically simulated the longitudinal course of six different clinical scenarios of the preeclampsia/eclampsia/toxemia (PET) GL, encompassing 60 different decision points in total. Each clinician managed three scenarios manually without the Picard DSS engine (Non-DSS mode) and three scenarios when assisted by the Picard DSS engine (DSS mode). The main measures in both modes were correctness and completeness of actions relative to the PET GL. Correctness was further decomposed into necessary and redundant actions, relative to the guideline and the actual patient data. At the end of the assessment, a questionnaire was administered to the clinicians to assess their perceptions regarding use of the DSS. With respect to completeness, the clinicians applied approximately 41% of the GL's recommended actions in the non-DSS mode. Completeness increased to the performance of approximately 93% of the guideline's recommended actions, when using the DSS mode. With respect to correctness, approximately 94.5% of the clinicians' decisions in the non-DSS mode were correct. However, these included 68% of the actions that were correct but redundant, given the patient's data (e.g., repeating tests that had been performed), and 27% of the actions, which were necessary in the context of the GL and of the given scenario. Only 5.5% of the decisions were definite errors. In the DSS mode, 94% of the clinicians' decisions were correct, which included 3% that were correct but redundant, and 91% of the actions that were correct and necessary in the context of the GL and of the given scenario. Only 6% of the DSS-mode decisions were erroneous. The DSS was assessed by the clinicians as potentially useful. Support from the GL-based DSS led to uniformity in the quality of the decisions, regardless of the particular clinician, any particular clinical scenario, any particular decision point, or any decision type within the scenarios. Using the DSS dramatically enhances completeness (i.e., performance of guideline-based recommendations) and seems to prevent the performance of most of the redundant actions, but does not seem to affect the rate of performance of incorrect actions. The redundancy rate is enhanced by similar recent findings in recent studies. Clinicians mostly find this support to be potentially useful for their daily practice. A continuous-care GL-based DSS, such as the Picard DSS engine, has the potential to prevent most errors of omission by ensuring uniformly high quality of clinical decision making (relative to a GL-based norm), due to the increased adherence (i.e., completeness) to the GL, and most of the errors of commission that increase therapy costs, by reducing the rate of redundant actions. However, to prevent clinical errors of commission, the DSS needs to be accompanied by additional modules, such as automated control of the quality of the physician's actual actions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

NASA Astrophysics Data System (ADS)

Popov, Dmitri

Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally found in the umbilical cord and bone marrow as hematopoietic cells, a subset of mesenchymal stem cells, endothelial progenitor cells, endothelial cells of blood vessels, etc. [Beutler et al. 2000 ] Potential mechanisms responsible for radiation-acquired marrow cell failure include direct toxicity , direct damage of hematopoietic multipotential cells or cellular or humoral immune suppression of the marrow multipotential cells. [ Beutler et al. 2000] Methods: These studies were conducted at several different research institutions and laboratories listed as follows: Kazan All-Union Scientific Research Veterinary, Biotechnology Centre of Russian Academy of Science (North Osetia), Institute Belarussian Scientific and Research Institute for Radiobiology in Gomel, the St. Petersburg Veterinary Institute, the Advanced Medical Technology and Systems Inc., Ontario, Canada. The studies were approved by the Animal Care and Use Committee for ethical animal research equivalent, at each institution. A critically important volume of purified Radiation Toxins (RT) was isolated from larger mammalian irradiated animals. Subsequently the RT were characterized chemically and biologically. The experimental design of later studies compared relative toxicity, potential for development of acute radiation hematopoietic syndrome, and potential cloning disorder of multipotential hematopoietic progenitors and their derivative and lethality after intravenous or intramuscular injections of SRD containing Hematopoietic Radiation Toxins. These experiments have employed a wide variety of experimental animals. The animals were irradiated in RUM-17, Puma, and Panorama devices. The dose varied from 0.7Gy to 100Gy. The methods of immune depletion, immuno-lympho plasmasabsorption, as well as direct extraction, were used to refine and purify the specific Radiation Toxins from the central lymph of animals with Hematopoietic forms of Radiation Toxins. Experiments include administration of Hematopoietic Radiation Toxins (SRD-4) to radiation naive animals in doses 0.1 mg/kg; 0,5 mg/kg; 1 mg/kg; 2 mg/kg; 3 mg/kg up to 30 mg/kg. Results: After I/V or I/M administration of Hematotoxic Radiation Toxins to radiation -naive animals the induction of specific clinical signs was observed- including thrombocytopenia, lymphocytosis followed by lymphocytopenia, granulocytopenia , aplastic anemia, and the clinical manifestations- ecchymosis, hemorrhage and coagulopathy. These observed clinical signs mimic the acute/hematopoietic acute radiation syndrome. Conclusions: Administration of Hematopoietic Radiation Toxins (SRD-4) to radiation naive animals in doses 0.1 mg/kg;0,5 mg/kg; 1 mg/kg; 2 mg/kg; 3 mg/kg up to 30 mg/kg produced specific toxic reactions with the development of signs and symptoms consistent with the hematological form of Acute Radiation Syndromes. Administration of high doses of Hematopoietic Radiation Toxins developed a clinical picture identical to severe Acute Radiation Exposure Syndrome and induces Toxic Multiple Organ Failure (TMOF) and Toxic Multiple Organ Involvement (TMOI) {i.e. pneumonitis, renal failure, renal hypo-perfusion, acute tubular necrosis, hepatic failure, etc.} essentially as which occurs as an acute consequence of radiation toxemia. Aplastic anemia is an important clinical and pathological process which develops after animals receive high doses of both radiation and administered radiation toxins.