Absence of Toxemia in Clostridioides difficile Infection: Results from Ultrasensitive Toxin Assay of Serum.

Clostridioides difficile infection (CDI) is caused by Toxins A and B, secreted from pathogenic strains of C. difficle. This infection can vary greatly in symptom severity and in clinical presentation. Current assays used to diagnose CDI may lack the required sensitivity to detect the exotoxins circulating in blood. The ultrasensitive single molecule array (Simoa) assay was modified to separately detect toxin A and toxin B in serum with a limit of detection at the low picogram level. When applied to a diverse cohort, Simoa was unable to detect toxins A or B in serum from patients with CDI, including many classified as having severe disease. The detection of toxin may be limited by the inference of antitoxin antibodies circulating in serum. This result does not support the hypothesis that toxemia occurs in C. difficile infection, conflicting with the findings of other published reports.

Hyponatraemia compounding pre-eclamptic toxaemia in a patient with type 1 diabetes.

We report a case of profound, symptomatic hyponatraemia in association with pre-eclamptic toxaemia (PET) in a 38-year-old nulliparous woman with type 1 diabetes mellitus. This patient developed hypertension and proteinuria at 31+6 weeks' gestation and was admitted for management of pre-eclampsia. Severe headache, visual disturbance and nausea were associated with a hyponatraemia of 115 mmol/L followed by ketoacidosis. This was reversed through fluid restriction, supplementation with 1.8%-3.0% hypertonic saline and a volume-reduced variable-rate insulin infusion. Clinical stability was achieved and she was subsequently worked up for an induction of labour for worsening pre-eclampsia. Hyponatraemia in the context of PET has been previously reported as rare. However, it has complications that may significantly compound the sequelae of severe PET. We propose that specific and focused monitoring of serum sodium levels should become common practice in the management of women with this condition to allow for timely, measured correction of abnormalities.

Adult Intestinal Toxemia Botulism.

Intoxication with botulinum neurotoxin can occur through various routes. Foodborne botulism results after consumption of food in which botulinum neurotoxin-producing clostridia (i.e., Clostridium botulinum or strains of Clostridiumbutyricum type E or Clostridiumbaratii type F) have replicated and produced botulinum neurotoxin. Infection of a wound with C. botulinum and in situ production of botulinum neurotoxin leads to wound botulism. Colonization of the intestine by neurotoxigenic clostridia, with consequent production of botulinum toxin in the intestine, leads to intestinal toxemia botulism. When this occurs in an infant, it is referred to as infant botulism, whereas in adults or children over 1 year of age, it is intestinal colonization botulism. Predisposing factors for intestinal colonization in children or adults include previous bowel or gastric surgery, anatomical bowel abnormalities, Crohn's disease, inflammatory bowel disease, antimicrobial therapy, or foodborne botulism. Intestinal colonization botulism is confirmed by detection of botulinum toxin in serum and/or stool, or isolation of neurotoxigenic clostridia from the stool, without finding a toxic food. Shedding of neurotoxigenic clostridia in the stool may occur for a period of several weeks. Adult intestinal botulism occurs as isolated cases, and may go undiagnosed, contributing to the low reported incidence of this rare disease.

Hospital-acquired intestinal toxemia botulism in a newly diagnosed adult colon cancer patient.

This manuscript reports a case of intestinal toxemia botulism in an adult with recently diagnosed metastatic colon cancer in whom botulism symptoms began 23 days after hospital admission. Representing the rarest form of botulism presentation in clinical practice, this infectious disease may have developed due to a cluster of predisposing factors that favored Clostridium botulinum colonization and the endogenous production of neurotoxins, among which are previous use of broad-spectrum antibiotics and colon changes related to the development of the neoplasia. This case highlights the importance of considering intestinal toxemia botulism in the differential diagnosis of a patient presenting with symmetrical descending flaccid paralysis, since immediate treatment with botulinum antitoxin may improve clinical outcomes.

Identification of toxemia in patients with Clostridium difficile infection.

Toxemia can develop in Clostridium difficile-infected animals, and correlates with severe and fulminant disease outcomes. Circumstantial evidence suggests that toxemia may occur in patients with C. difficile infection (CDI), but positive diagnosis is extremely rare. We analyzed the potential for C. difficile toxemia in patients, determined its characteristics, and assessed challenges. C. difficile toxins in serum from patients were tested using an ultrasensitive cell-based assay and further confirmed by Rac1 glucosylation assay. The factors that hinder a diagnosis of toxemia were assessed, including investigation of toxin stability, the level of toxins-specific neutralizing antibodies in sera and its effect on diagnosis limits. CDI patients develop detectable toxemia in some cases (2.3%). Toxins were relatively stable in stored sera. Neutralizing anti-toxin antibodies were present during infection and positively correlated with the diagnosis limits. Thus, the masking effect of toxin-specific neutralizing antibodies is the major obstacle in diagnosing C. difficile toxemia using cell-based bioassays.

Botulism toxemia following laparoscopic appendectomy.

We describe a case of botulism infection in a patient who had undergone laparoscopic appendectomy, an occurrence not previously described in the literature. This case exemplifies the need for coordination between clinical and public health personnel to ensure the immediate recognition and treatment of suspected botulism cases.

Fever without source: evaluation of a guideline.

OBJECTIVE: To evaluate the applicability of a standardized guideline for children up to 36 months of age with fever without source (FWS). METHODS: Prospective cohort study involving children with FWS treated at the emergency department of Hospital Universitário, Universidade de São Paulo, São Paulo, Brazil, from June 2006 to May 2007. The guideline classifies the risk of serious bacterial infection (SBI) according to the presence or absence of toxemia, age, and temperature. Laboratory screening was based on risk assessment: complete blood count, blood culture, urinalysis, urine culture, and, if necessary, chest radiography, cerebrospinal fluid, and coproculture. RESULTS: We studied 251 children and, of these, 215 were followed up until the final diagnosis. Toxemia was found in 20 children, and 195 were well-appearing (30 up to 3 months old and 165 from 3 to 36 months old). Among those children from 3 to 36 months without toxemia, 95 had axillary temperature > 39 degrees C. In 107 (49.8%) children, there was spontaneous resolution of fever; in 88 (40.9%), benign self-limited disease was identified; and in 20 (9.3%), there was SBI. Among the cases of SBI, we identified 16 urinary tract infections, three cases of pneumonia and one occult bacteremia. Of the 215 children, 129 (60%) received no antibiotics, and 86 received antibiotics at some point (45 empirically). Empirical antibiotic treatment was maintained for an average of 72 hours. CONCLUSION: The guideline was shown to be appropriate to follow up these children using simple laboratory tests that can be carried out at most health facilities. The most frequent SBI in this sample was urinary tract infection.

Febre sem sinais localizatórios: avaliação de um protocolo de atendimento / Fever without source: evaluation of a guideline

OBJETIVO: Avaliar a aplicabilidade de um protocolo de atendimento padronizado para crianças de até 36 meses de idade com febre sem sinais localizatórios (FSSL). MÉTODOS: Estudo de coorte prospectivo em crianças com FSSL atendidas no Pronto-Socorro do Hospital Universitário da Universidade de São Paulo, São Paulo (SP), de junho de 2006 a maio de 2007. O protocolo estratifica o risco de infecção bacteriana grave (IBG) de acordo com a presença ou não de toxemia, idade e valor da temperatura. Conforme avaliação de risco, indicava-se triagem laboratorial: hemograma, hemocultura, sedimento urinário, urocultura e, se necessário, radiografia torácica, liquor e coprocultura. RESULTADOS: Foram estudadas 251 crianças das quais 215 foram acompanhadas até o diagnóstico final. Vinte crianças apresentavam toxemia, e 195 estavam em bom estado geral (30 com idade de até 3 meses, e 165, de 3 a 36 meses). Nas crianças de 3 a 36 meses não toxêmicas, 95 tinham temperatura axilar > 39 ºC. Em 107 crianças (49,8 por cento), houve melhora espontânea do quadro febril; em 88 (40,9 por cento), foi identificada doença benigna autolimitada; e em 20 (9,3 por cento), IBG. Dentre as IBG, identificamos 16 infecções urinárias, três pneumonias e uma bacteremia oculta. Das 215, 129 (60 por cento) não receberam qualquer antibioticoterapia, e 86 receberam antibiótico em algum momento (45, empiricamente). O antibiótico empírico foi mantido por, em média, 72 horas. CONCLUSÃO: O protocolo aplicado mostrou-se adequado para o seguimento destas crianças que fizeram coleta de exames simples e passíveis de serem realizados na maioria dos serviços. A infecção urinária foi a IBG mais frequente nas crianças com FSSL.

OBJECTIVE: To evaluate the applicability of a standardized guideline for children up to 36 months of age with fever without source (FWS). METHODS: Prospective cohort study involving children with FWS treated at the emergency department of Hospital Universitário, Universidade de São Paulo, São Paulo, Brazil, from June 2006 to May 2007. The guideline classifies the risk of serious bacterial infection (SBI) according to the presence or absence of toxemia, age, and temperature. Laboratory screening was based on risk assessment: complete blood count, blood culture, urinalysis, urine culture, and, if necessary, chest radiography, cerebrospinal fluid, and coproculture. RESULTS: We studied 251 children and, of these, 215 were followed up until the final diagnosis. Toxemia was found in 20 children, and 195 were well-appearing (30 up to 3 months old and 165 from 3 to 36 months old). Among those children from 3 to 36 months without toxemia, 95 had axillary temperature > 39 ºC. In 107 (49.8 percent) children, there was spontaneous resolution of fever; in 88 (40.9 percent), benign self-limited disease was identified; and in 20 (9.3 percent), there was SBI. Among the cases of SBI, we identified 16 urinary tract infections, three cases of pneumonia and one occult bacteremia. Of the 215 children, 129 (60 percent) received no antibiotics, and 86 received antibiotics at some point (45 empirically). Empirical antibiotic treatment was maintained for an average of 72 hours. CONCLUSION: The guideline was shown to be appropriate to follow up these children using simple laboratory tests that can be carried out at most health facilities. The most frequent SBI in this sample was urinary tract infection.

Pregnancy and liver disease.

Liver dysfunction can appear at any point of pregnancy and causes great anxiety to the patient, her family and sometimes her medical attendants. This review concentrates on conditions specific to pregnancy (hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, toxemia of pregnancy, HELLP syndrome) and provides a guide in diagnosis and management of hepatobiliary conditions that are probably related to pregnancy (e.g., gallstones, Budd-Chiari syndrome) or that are not specific to pregnancy (e.g., acute viral hepatitis), and also the situations in which pregnancy occurs during pre-existing liver disease (e.g., chronic active hepatitis, cirrhosis, Dubin-Johnson syndrome, Wilson's disease).

[Endogenous intoxication in patients with stomach cancer observed immediately after surgery].

Severe endogenous intoxication (El) can trigger immediately after surgery many complications right up to multiple organ failure. The evaluation of El according to a degree of toxemia is most objective up to now. The purpose of the case study was to follow up the dynamics of the main El laboratory indices and to evaluate the correlation between them in patients with stomach cancer during the early postoperative period. The El parameters were determined in 2 hours before surgery as well as on days 1, 3, 5, 7 and 14 after surgery. The below indices were determined in blood of patients: toxicity index (TI), count of mean weight molecules (MWM), leukocytic intoxication index (LII) and total count of leukocytes (TCL). The study showed that, when patients with stomach cancer are admitted for surgical treatment, they have pronounced El, which intensifies even more postoperatively. The investigated laboratory indices are independently significant in the evaluation of the El degree. A reliable but faint correlation was found between the parameters of MWM and IT, and MWM and LII. TCL does not correlate reliably with other studied El parameters except for LII. The full-fledged evaluation of the El nature must be used in choosing purposefully detoxication methods with the aim of promoting the quality of postoperative treatment of patients with stomach cancer.

[Criteria for assessment of endogenous intoxication in burn trauma]. / Kriterii otsenki éndogennoi intoksikatsii pri ozhogovoi travme.

Registered in patients with burn trauma was the presence of endogenous intoxication (EI), which was determined by a higher value of coefficient CLP/AOS, a higher contents of medium-molecular peptides (MMP), a lower total and effective concentration of albumin (TAC and EAC) and by a reserve of the binding albumin ability. Intoxication coefficients, i.e. IC MMP/EAC and IC C/EAC showing the deposition and binding of toxic ligands, were acknowledged as the most informative EI parameters.

[Endogenic intoxication markers: data from capillary electrophoresis of trichloroacetic acid supernatant]. / Markery éndogennoi intoksikatsii po dannym kapilliarnogo élektrophoreza TKhU-supernatanta.

Capillary electrophoresis is suggested for characterization of trichloroacetic acid (TCA) supernatant in various visceral diseases involving endogenous intoxication. The technique of electrophoresis is described. Examples of electrophoregrams are offered with extrapolation to common clinical laboratory values. The appearance of a positive "cationic peak" instead of a negative systemic peak observed in health is a specific electrophoretic sign of endogenous intoxication. The area of the peak (proportionate to intoxication) and its ratio to the group undivided peak observed in the distal part of electrophoregram (minutes 8-14, anionic constituents) are significant. The values of the latter peak characterize the defense characteristics of the organism and are in proportion to them. Capillary electrophoresis is a perspective diagnostic method.

[Diagnostic significance of evaluating erythrocyte membrane permeability as an intoxication syndrome criterion]. / Diagnosticheskaia tsennost' otsenki pronitsaemosti membran éritrotsitov v kachestve kriteriia intoksikatsionnogo sindroma.

Twenty-five patients with pyoinflammatory maxillofacial diseases treated in an inpatient setting in the Regional Dentistry Clinic of Krasnodar and 8 healthy volunteers were examined. After opening and draining of the purulent focus the patients were divided into 2 groups. Group 1 consisted of 21 patients treated by intravenous 0.04% sodium hypochlorite (SHC) and intravenous infusions of SHC-oxidized autoblood for 2-3 days. Group 2 (6 pts) was treated by intravenous infusions of SHC-oxidized autoblood for 6 days. The criteria of intoxication were erythrocyte resistance tests in hypotonic sodium chloride and at different concentrations of urea in isotonic medium. A new method for evaluating erythrogram deviations from reference values is proposed, which helps adequately assess the severity of intoxication.

[A method for determining plasminogen with a Russian chromogenic substrate and its diagnostic significance]. / Metod opredeleniia plazminogena s otechestvennym khromogennym substratom i ego diagnosticheskoe znachenie.

Measurement of plasminogen, the key component of fibrinolysis system, is one of the basic methods for estimation of fibrinolysis. Methods based on the use of chromogenic substrates are often used in diagnosis. Plasminogen measurements are important for laboratory diagnosis of thrombophilia caused by deficiency or abnormalities of this fiber, for detection and evaluation of the DIC syndrome, and for monitoring the treatment by fibrinolytic preparations (streptokinase, t-PA, urokinase, etc.). An original chromogenic substrate having no foreign analogs has been created at Institute of Genetics and Selection of Industrial Microorganisms and Research Center of Hematology (Moscow). Unlike previously described plasmin substrates, pNa has been obtained by microbiological methods with Russian commercial enzymes subtilisine 72 and megaterine. This paper presents the results of plasminogen measurements in patients with DIC with the use of the original chromogenic substrate. The results were compared with those of tests with Berihrom-Plasminogen diagnostic kit (Behringwerke AG).

[Clinical examinations of gilts with puerperal septicemia and toxemia]. / Klinische Erhebungen bei Sauen mit puerperaler Septikämie und Toxämie.

In a clinical examination on 78 gilts suffering from feverish puerperal illness the signs were documented. 42 gilts without puerperal disturbances out of the same farms (n = 22) were used as a control. Data for statistics were recorded in minute-books, listing 38 parameters, partly divided in three or four subunits. Within the first 24 hours after parturition 60% of the probands were registered, the other gilts up to the 72nd hour after parturition. 42.3% of the patients beared for the first or second time. Duration of partus averaged more than six hours in 85.9% of patients with consequent puerperal illness, whereas probands of the same age in the control group finished parturition in less than three hours (78.8%; p < or = 0.01). Frequency of obstetrical intervention measured 27% in the group of patients, in the group of probands 9.5% (p < or = 0.05). Gilts with following puerperal illness delivered 1.1 piglets more than healthy individuals (p < or = 0.05) and showed an increased stillbirth rate (p < or = 0.01). Signs of clinical interest in puerperal illness were increase of body temperature (p < or = 0.01), cardiac rate (p < or = 0.01) and respiratory frequency (p < or = 0.01). Approximately 75% of the patients showed anorexia, 66% abnormal faecal consistency. 24.4% of the diseased animals showed exclusively signs of mastitis, in 29.5% there was a combination of mastitis and inflammatory affection of the genital system to be diagnosed, in 46.1% of the cases a solitary infection of the reproductive tract was to be stated. Predominantly E. coli, followed by Staphylococcus spp. and Streptococcus spp. were isolated from the genital tract. The results of this study emphasize the clinical necessity to differentiate between isolated mastitis and puerperal septicaemia respectively toxaemia in cases of feverish puerperal illness. Puerperal septicaemia and toxaemia can, but do not have to be associated with mastitis in gilts.

[New methods for assessing the severity of endogenous intoxication in surgical patients]. / Novye metody otsenki tiazhesti éndogennoi intoksikatsii u khirurgicheskikh bol'nykh.

New methods (a reticulocytic test, inhibition of erythrocyte sedimentation, registration of the frog's heart rate) were used in studying the toxicity of the serum, blood plasma and urine of surgical patients. The most informative methods for the assessment of the toxemia degree are thought to be the reticulocytic test and registration of the frog's heart rate. The maximum time for the determination of endotoxicity is 15 minutes. The pathological process severity can be estimated not only by the toxemia degree but also by its dynamics. The determination of endotoxicity is of value for choosing the methods for the individual detoxication therapy.

Management of a femoral fracture complicated by clostridial myositis.

A clinical case of clostridial myositis secondary to a comminuted femoral fracture is described. This case is unusual because, despite the severe degree of obvious muscle necrosis and gas production, the dog had minimal signs of systemic toxicity. Union of the fracture was achieved but six months postoperatively muscular contracture had resulted in permanent stifle extension.

High plasma levels of von Willebrand factor as a marker of endothelial perturbation in cirrhosis: relationship to endotoxemia.

The aim of this study was to evaluate whether there is endothelial dysfunction in patients with cirrhosis and to detect the mechanism that may account for it. We measured plasma levels of von Willebrand factor (vWF), a marker of endothelial perturbation, and endotoxin, which releases vWF from endothelial cells in vitro, in 32 patients (18 men, 14 women, aged 39-70 years) with cirrhosis classified as mild (class A, n = 10), moderate (class B, n = 16), or severe (class C, n = 6) according to Child-Pugh's classification. vWF antigen (P < .0001) and endotoxemia (P < .0001) progressively increased from A to class C; but the increase of vWF antigen was not strictly related to liver failure, as shown by the lack of correlation between vWF and several indexes of liver protein synthesis. Analysis of the vWF subunit showed no sign of proteolytic fragmentation of the molecule. Multimeric analysis indicated intact vWF multimeric structure. In all patients, there was a strong correlation between vWF antigen and endotoxemia (rho = .92; P = .0001). In 20 selected patients, vWF antigen and endotoxemia were measured before and after 7 days of standard therapy (n = 10) or standard therapy plus nonabsorbable antibiotics. There was a significant decrease of vWF antigen (P < .02) concomitantly with the decrease of endotoxemia (P < .006) in patients taking nonabsorbable antibiotics. Human umbilical vein endothelial cells incubated in vitro with 125 to 500 pg/mL endotoxin released vWF antigen into the medium dose dependently. These results demonstrate that there is endothelial perturbation in cirrhosis and that endotoxemia may play a key role in its occurrence.

Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass.

OBJECTIVE: To examine the relationship between gastric intramucosal pH, intestinal permeability, endotoxemia, and oxygen delivery in patients undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective, observational study. SETTING: Tertiary care center. PATIENTS: Fifty patients undergoing elective cardiac surgery and 10 patients awaiting elective cardiac surgery. INTERVENTIONS: Patients received chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) as a marker of intestinal permeability; insertion of a nasogastric tonometer to measure intramucosal pH (pHi); insertion of a pulmonary artery catheter to measure systemic oxygen delivery and consumption variables; arterial blood sampling for plasma endotoxin by the Limulus amebocyte lysate assay; and blood and urine sampling for measurement of 51Cr-EDTA. MAIN OUTCOME MEASURES: Systemic oxygen delivery, duration of gastric mucosal acidosis, absorption of 51Cr-EDTA, appearance of systemic endotoxemia, renal dysfunction, and duration of hospital stay. RESULTS: Median (range) 24-hour urinary recovery of 51Cr-EDTA in patients was 10.6% (2.1% to 40.2%) while that in controls was 1.2% (0.7% to 2.0%, P<.001). Intestinal permeability increased during CPB. The median (range) for the lowest pHi after bypass was 6.98 (6.74 to 7.17). The pHi did not decline until CPB was discontinued and the heart took over the load of the circulation. Endotoxin was detectable (>0.2 endotoxin unit per milliliter) in the plasma of 21 patients (42%) during the study, most of whom were endotoxemic by the end of CPB. There was no evident relationship between the degree of gut permeability, endotoxemia, gut ischemia, or systemic oxygen dynamics. CONCLUSIONS: Cardiopulmonary bypass is associated with increases in gut permeability, which precede gut mucosal ischemia. In cardiac surgical patients, a low pHi is not necessarily indicative of an adverse clinical outcome. Endotoxemia as measured by the Limulus amebocyte lysate assay is common. The increased intestinal absorption of 51Cr-EDTA and gastric mucosal acidosis occur as independent phenomena and are not related in severity or time of onset.