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.

A childhood-onset intestinal toxemia botulism during chemotherapy for relapsed acute leukemia.

BACKGROUND: Botulism is a potentially fatal infection characterized by progressive muscle weakness, bulbar paralysis, constipation and other autonomic dysfunctions. A recent report suggested that cancer chemotherapy might increase the risk for the intestinal toxemia botulism in both adults and children. CASE PRESENTATION: We report a 5-year-old boy, who developed general muscle weakness, constipation, ptosis and mydriasis during the third induction therapy for relapsed acute myeloid leukemia. He had recent histories of multiple antibiotic therapy for bacteremia and intake of well water at home. Repeated bacterial cultures identified Clostridium botulinum producing botulinum neurotoxin A. Botulinum toxin A was isolated from his stools at 17, 21, and 23 days after the onset. Symptoms were self-limiting, and were fully recovered without anti-botulinum toxin globulin therapy. CONCLUSION: This is the second report of a pediatric case with cancer chemotherapy-associated intestinal toxemia botulism. Our case provides further evidence that the immunocompromised status due to anti-cancer treatments increases the risk for the development of botulism at all ages in childhood.

[METABOLIC INTOXICATION IN THERMIC TRAUMA].

In 76 injured persons with deep and superficial burns, having area from 3 to 65% of the total body surface and ageing 5-16 yrs old, there was investigated the impact of early surgical treatment on the metabolic intoxication severity in accordance to content of the oxidatively modified proteins carbonyl groups in the blood serum, and of a ceruloplasmin, what was considered as integral express-index of the organism antioxidant system state. Changes of these indices in ambustial disease of middle severity have witnessed a sufficiently compensated reaction of organism: of severe and extremely severe one--there were noted a deficiency of the organism antioxidant defense; and in stages of toxemia and septicotoxemia--attrition of the organism oxidant reserves and danger of the septic complications occurrence. Conduction of early surgical intervention have guaranteed maintenance of a ceruloplasmin content in stages of toxemia and septicotoxemia on the level of healthy persons, relief of the ambustial disease course, absence of critical metabolic intoxication and carbonyl stress, reduction of the septic complications rate in 1.5 times.

Preeclampsia, pregnancy-related hypertension, and breast cancer risk.

Pregnancy conditions accompanied by high blood pressure, such as preeclampsia and pregnancy-related hypertension, have been associated with a lower risk of breast cancer in several epidemiologic studies. It is unknown whether length of gestation or multiple occurrence of these conditions alters the association with breast cancer. It is also unknown whether the inverse association between preeclampsia and breast cancer risk is modified by menopausal status at breast cancer diagnosis. Using data from a large, population-based case-control study of breast cancer conducted on Long Island, New York, during 1996-1997, the authors examined these questions among ever-parous women (1,310 cases and 1,385 controls) using multivariate logistic models. Preeclampsia was inversely associated with breast cancer (odds ratio = 0.7, 95% confidence interval: 0.5, 1.0); this association was even stronger among women who had multiple occurrences of preeclampsia (odds ratio = 0.3, 95% confidence interval: 0.1, 0.9). The risk reduction was more pronounced among postmenopausal women. Gestation length did not substantially alter the relation between preeclampsia and breast cancer risk. Pregnancy-related hypertension was also inversely associated with breast cancer risk, but the relations were not statistically significant after adjustment for preeclampsia. These data suggest that pregnancy conditions related to hypertension, particularly preeclampsia, play a role in reducing breast cancer risk. Possible biologic mechanisms underpinning these associations should be further explored.

Kraepelin's 'lost biological psychiatry'? Autointoxication, organotherapy and surgery for dementia praecox.

Kraepelin believed that a chronic metabolic autointoxication, perhaps arising from the sex glands, eventually caused chemical damage to the brain and led to the symptoms of dementia praecox. The evolution of Kraepelin's autointoxication theory of dementia praecox is traced through the 5th to 8th (1895 to 1913) editions of his textbook, Psychiatrie. The historical context of autointoxication theory in medicine is explored in depth to enable the understanding of Kraepelin's aetiological assumption and his application of a rational treatment based on it--organotherapy. A brief account of the North American reception of Kraepelin's concept of dementia praecox, its autotoxic basis, and the preferred American style of rational treatment--surgery--concludes the discussion.

Trombose do seio cavernoso: revisão da literatura e relato de caso / Cavernous sinus thrombosis: review of the literature and case report

A trombose séptica do seio cavernoso é uma complicação encefálica decorrente de infecções faciais ou cranianas como sinusites, otites, infecções odontogênicas, oftalmológicas, entre outras. Apesar de rara, apresenta grande importância devido ao alto percentual de óbitos e seqüelas. As infecções odontogênicas, embora não ocupem posição destacada entre os fatores etiológicos dessa doença, podem atuar como focos primários situando o cirurgião-dentista entre os profissionais capazes de elaborar não só o diagnóstico, como sua profilaxia e o correto encaminhamento para tratamento médico especializado. O diagnóstico clínico dessa condição é dificultado pela semelhança com algumas infecções da órbita como a celulite orbital. Esse trabalho revisa a literatura e procura atualizar conceitos que facilitam o diagnóstico, a profilaxia e o tratamento da trombose do seio cavernoso. O trabalho também relata um caso dessa grave doença, originada de uma acne na região do mento, cuja rápida evolução levou o paciente ao óbito em três dias de tratamento. Após essa revisão, podemos afirmar que o diagnóstico dessa condição é clínico, com confirmação em exames de imagem, e quanto mais precoce o tratamento, melhor a chance de sobrevida. Infere-se também a importância da profilaxia antibiótica em cirurgias orais e faciais, atribuindo a ela redução significativa dessa infecção nos últimos tempos.

Increased oxygen consumption after cardiac surgery is associated with the inflammatory response to endotoxemia.

OBJECTIVE: The aim of this study was to determine whether the increase in post-operative oxygen consumption (delta VO2) in cardiac surgery patients is related to endotoxemia and subsequent cytokine release and whether delta VO2 can be used as a parameter of post-perfusion syndrome. DESIGN: Prospective study. SETTING: Operating room and intensive care unit of a university hospital. PATIENTS: Twenty-one consecutive male patients undergoing elective coronary artery bypass surgery without major organ dysfunction and not receiving corticosteroids. MEASUREMENTS AND RESULTS: Plasma levels of endotoxin, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were measured before, during and for 18 h after cardiac surgery. Oxygen consumption, haemodynamics, the use of IV fluids and dopamine, body temperature and the time of extubation were also measured. Measurements from patients with high delta VO2 (> or = median value of the entire group) were compared with measurements from patients with low delta VO2 (< median). Patients with high delta VO2 had higher levels of circulating endotoxin (P = 0.004), TNF (P = 0.04) and IL-6 (P = 0.009) received more IV fluids and dopamine while in the ICU, and were extubated later than patients with low delta VO2. Several hours after delta VO2 the patient's body temperature rose. Forward stepwise regression analysis showed that circulating endotoxin and TNF explained 50% of the variability of delta VO2. CONCLUSIONS: This study demonstrates that patients with high post operative oxygen consumption after elective cardiac surgery have higher circulating levels of endotoxin, TNF and IL-6 and also have more symptoms of post-perfusion syndrome. Early detection of high VO2 might be used as a clinical signal to improve circulation in order to meet the high oxygen demand of inflammation. In addition, continuous measurement of VO2 provides us with a clinical parameter of inflammation in interventional studies aiming at a reduction of endotoxemia or circulating cytokines.

Inhibition of nitric oxide synthesis aggravates reperfusion injury after hepatic ischemia and endotoxemia.

The potential role of nitric oxide (NO) was investigated in the pathophysiology of liver injury after priming with 20 min hepatic ischemia-reperfusion and administration of .5 mg/kg Salmonella enteritidis endotoxin. Liver injury during the early reperfusion phase of 4 h was characterized by severe vascular oxidant stress, lipid peroxidation (LPO), neutrophil infiltration, and a 33% reduction of the microvascular blood flow in the liver. Inhibition of NO synthesis with N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) aggravated liver injury by 90%, reduced LPO, and did not affect liver neutrophils but further impaired microvascular blood flow. Treatment with the NO-donor spermine-NONOate or L-arginine did not affect these parameters in postischemic animals, however, treatment did restore all values of L-NAME-treated animals back to disease control levels. These data suggest that endogenous NO formation is sufficient to limit ischemic liver injury during reperfusion but inhibition of NO synthesis will result in additional ischemic damage. NO may also be involved in scavenging of superoxide in the vasculature and in inducing LPO.

How to deal with a rare entity: the coexistence of a complete mole and a healthy egg in a twin pregnancy?

The association of a normal and a molar egg within a twin pregnancy is extremely rare. The key to diagnosis is the fetal karyotype, thus allowing elimination of its principal differential diagnosis: partial triploid mole. We report a case where the evolution of the pregnancy was complicated by severe toxemia. Interruption of pregnancy was then necessary, even though a conservative attitude had first been considered. Throughout this case, we discuss the means of diagnosis and the clinical handling of this rare entity.

Development of renal failure in endotoxemic rats: can it be explained by early changes in renal energy metabolism?

Endotoxin shock not only causes renal failure, endotoxemia also leads to metabolic impairment, resulting in energy shortage and loss of cellular integrity; therefore, we tested the hypothesis that early changes in renal metabolism contribute to the development of acute renal failure during endotoxin shock. Endotoxin (Escherichia coli 127B8; 8 mg/kg from t = 0 to 60 min) was infused in three groups of 8 rats, in which renal biopsies were taken at t = 30, 50 and 90 min, respectively; a fourth group (n = 8) served as control. In the biopsies, glucose, lactate, ATP, ADP, AMP and creatine phosphate concentrations were determined. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured from the clearances of 131I-hippurate and 125I-thalamate, respectively. We also assayed urine flow (V; catheter in the bladder), cardiac output (CO), blood pressure (MAP), heart rate (HR) and arterial lactate, glucose and creatinine concentrations. During the first 30 min of endotoxemia, we found no systemic hemodynamic or biochemical changes. From t = 30 to t = 90, CO and MAP decreased to 59 and 70%, respectively, while HR and serum levels rose to 110 and 800%, respectively (p < 0.05), indicating progression of shock. Renal function clearly deteriorated from t = 30; at t = 90 RPF, GFR and V had decreased by 86, 84 and 86%, respectively, plasma creatinine being 193% of the baseline value (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of depletion of glucocorticoid receptor in the production of multiple organ failure during endotoxemia].

Endotoxin (20 mg/kg B.W.) was injected intravenously to control (n = 12) and glucocorticoid receptor (GR) depletion rat model (n = 13, in which more than 80 percent of GR were blocked with a potent GR antagonist RU486). Four hours after injection of endotoxin, the changes in serum acid phosphatase (ACP) activity, phospholipase A2 (PLA2) activity and lipid peroxide (LPO) level were determined. The results showed that all of the indices were increased in the control rats after endotoxin injection (ACP 17.6 +/- 1.9 U/dL, PLA2 325.6 +/- 99.1 U, and LPO 6.0 +/- 0.4 nmol MDA.ml-1), but they were increased to even higher levels in the rats injected with both RU486 and endotoxin (ACP 30.1 +/- 7.6 U/dL, PLA2 633.7 +/- 70.6 U, and LPO 8.2 +/- 1.1 nmol MDP.ml-1). Furthermore, after presented multiple organ damage pathologically. These results suggested that the glucocorticoid insufficiency caused by the decrease of GR after severe trauma or shock may exacerbate the damage of endotoxin to the organs, so much so that glucocorticoid insufficiency might result in multiple organ failure. This article also discussed problem of glucocorticoid treatment.

Effect of endotoxin on hypoxic pulmonary vasoconstriction--the role of prostaglandins and leukotrienes.

In this study, we observed the effect of endotoxemia on hypoxic pulmonary vasoconstriction (HPV) in dogs and explored roles played by prostaglandins and leukotrienes in this process. 5 micrograms/kg BW of E. coli endotoxin induced transient rise in pulmonary arterial pressure and pulmonary vascular resistance (PVR). 30 min after injection of endotoxin when PVR tended to decline, pulmonary vasoconstriction response to alveolar hypoxia was lost, and the ratio of TXB2 to 6-keto-PGF1 alpha decreased significantly. HPV was enhanced at 60-100 min and then returned to the control level at 2 h after injection of endotoxin. At these periods the ratio of TXB2 to 6-keto-PGF1 alpha was the same as before use of endotoxin, whereas plasma concentration of leukotrienes was markedly increased. Indomethacin could prevent the early loss of HPV, but no effect on the late increment of HPV was found. Diethylcarbamazine, which blocked the production of leukotrienes after use of endotoxin, could inhibit late increment of HPV. We concluded that the early loss of HPV was related to the vasodilator prostacyclin, and the late increment of HPV was mainly brought about by leukotrienes.

[Experimental study of the protective effects of N-acetylcysteine on endotoxin-induced acute lung injury].

The purpose of this study was to investigate the effects of NAC (N-acetylcysteine) on endotoxin induced acute lung injury in unanesthetized sheep. The results showed that NAC attenuated the responses to endotoxemia, and the rise in pulmonary artery pressure was significantly diminished, and the rise of TXB2 and 6-keto-PGF1 alpha in plasma and lung lymph was less significantly for NAC + E than for E alone. The QL (lung lymph flow), PC (lung lymph protein clearance) and PS (pulmonary capillary surface permeability area) were significantly decreased in NAC + E group. The lipid peroxide contents in artery plasma and lung lymph were not increased in NAC-treated group. We conclude that NAC is capable of attenuating all pathophysiologic changes after endotoxin infusion, blocking the reaction of oxygen free radicals, and protecting lungs from oxidant damage.

Endotoxemia and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke.

To determine whether endotoxemia and release of tumor necrosis factor (TNF-alpha) and/or interleukin 1 alpha (IL-1 alpha) are involved in the pathogenesis of heatstroke, 17 adult patients with a mean rectal temperature of 42.1 +/- 0.2 degrees C were studied. Blood samples were taken on admission and after cooling was completed. TNF-alpha and IL-1 alpha levels were measured by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) content was measured by the chromogenic substrate modification of the Limulus amebocyte lysate. TNF-alpha, IL-1 alpha, and LPS were elevated in all patients [199 +/- 25 (SE) pg/ml, 480.5 +/- 68.3 pg/ml, and 8.60 +/- 1.19 ng/ml, respectively, compared with normal control values of 31.4 +/- 8.4 pg/ml, 53.7 +/- 5.32 pg/ml, and less than 9 pg/ml]. There was no significant correlation between temperature and the circulating concentration of TNF-alpha, IL-1 alpha, and LPS. Postcooling TNF-alpha, IL-1 alpha, and LPS concentrations were significantly decreased but still above normal control values. The findings suggest that these mediators may have a role in the pathogenesis of heatstroke that could change the strategy of management.

Oral contraceptives and myocardial infarction.

The risk of myocardial infarction in contraceptive users is limited to women over 35 years of age who smoke. The cause of myocardial infarction in oral contraceptive users is thrombotic and not atherosclerotic. Minor lipid changes have no clinical relevance to myocardial infarction in contraceptive pill users and do not appear to increase coronary plaques.

PIP: Epidemiologic studies are examined to determine the relationship between oral contraceptives and myocardial infarction. An increased risk for myocardial infarction has been found with oral contraceptive usage in women 35 years in age. An data analysis of 1 study indicated that neither current nor past oral contraceptives, in combination with smoking 15 cigarettes/day, had the highest high relative risk for myocardial infarction; oral contraceptive use amplified the risk associated with smoking. Thus, it is evident that the risk of myocardial infarction in contraceptive users is limited to women over 35 years of age who smoke. The cause of myocardial infarction in oral contraceptive users is thrombotic and not atherosclerotic. 1 study revealed 36% of women using oral contraceptives had diffuse atherosclerosis, whereas 79% not using oral contraceptives had diffuse atherosclerosis. The women undergoing myocardial infarction while taking oral contraceptives did not have atherosclerotic myocardial infarction. Furthermore, autopsy studies have shown that myocardial infarction in women ingesting oral contraceptives was thrombotic and not atherosclerotic. Minor lipid changes, noted mainly with oral contraceptives with a high progestin content, have no clinical relevance to myocardial infarction in contraceptive pill users and do not appear to increase coronary plaques. Actually, it has been demonstrated that estrogen in oral contraceptives may directly protect the coronary arteries from atherosclerosis by inhibiting the entry of LDL cholesterol into blood vessel walls.

[A research on the cholestasis caused by continuous endotoxemia].

Intrahepatic cholestasis is often observed in patients without obstruction of the bile duct, who are suffering from severe prolonged infection in the field of peptic surgery. Clinical data were analyzed in recently experienced 18 cases which showed this kind of jaundice. In those case, high rates of endotoxemia and high rates of gram negative bacilli were seen. This fact made us infer that endotoxins might cause jaundice. In order to clarify the mechanism of the jaundice, we made an experimental model of persistent endotoxemia in rats. Low-dose endotoxin was infused continuously to Donryu-rats and bile-output was observed with external bile-guiding tube for 24 hours. In the endotoxin group, bile-output was significantly decreased whereas it was not changed in the control group. In addition, serum bilirubin was elevated in the endotoxin group, whereas it did not change in the control group. Blood-flow of liver tissue and systemic arterial blood pressure did not show any severe decrease under the continuous endotoxemia. Data of bile-output and bile acid showed bile acid independent flow might be depressed by endotoxin infusion. This model was thought to be under non-shock condition and useful to investigate jaundice seen in patients under continuous endotoxemia.

Gestantes hipertensas e morte fetal: análises de 171 casos / Hypertensive pregnants and fetal death: analysis of 171 cases

Foram abordados neste trabalho alguns aspectos em relaçäo ao manuseio de gestantes hipertensas com morte fetal. Estudaram-se 171 gestantes hipertensas, no período de 1979 a 1982, atendidas no Hospital das Clínicas de Ribeiräo Preto - USP. Foram avaliados: coeficiente de mortalidade fetal por hipertensäo arterial; morte fetal repetitiva; diagnóstico clínico e laboratorial da morte fetal e os recursos utilizados; tempo decorrido entre a informaçäo materna da parada de nmovimentos fetais e a resoluçäo da gravidez; tempo decorrido entre o diagnóstico médico da morte fetal e a resoluçäo da gestaçäo; necessidade e tempo de induçäo/estimulaçäo do parto, assim como os recursos utilizados para tal; tipo de parto e complicaçöes gravídicas e puerperais. O coeficiente de mortalidade fetal hipertensäo arterial foi de 12,8% e, em 43,5% das pacientes hipertensas crônicas, elas referiram pelo menos um feto morto em gestaçäo anterior. Em relaçäo a informaçäo materna, o tempo máximo decorrido até a resoluçäo da gravidez foi de 15 dias, e, em relaçäo ao diagnóstico médico, o tempo máximo foi de sete dias, sendo observado que a grande maioria destas pacientes tiveram seu parto resolvido nos dois primeiros dias. Observou-se ainda que o diagnóstico clínico foi isolado em 42,7% das vezes, sendo necessário recorrer-se a exames complementares em 57,2% dos casos. O parto normal foi o tipo de resoluçäo mais freqüente (77,2%), seguido de embriotomia (11,2%). A complicaçäo mais freqüente nesta casuística foi a retençäo placentária, seguida de descolamento prematuro de placenta, insuficiência renal e endometrite