Simultaneous Parenchyma-Preserving Liver Resection, Cytoreductive Surgery and Intraperitoneal Chemotherapy for Stage IV Colorectal Cancer.

BACKGROUND: The outcome of stage IV colorectal cancer (CRC) has improved with modern systemic therapy. However, the concomitant presence of liver metastases (LM) and peritoneal carcinomatosis (PC) remains associated with a dismal prognosis and surgery in this context remains exceptional. METHODS: Stage IV CRC patients with LM and PC undergoing simultaneous cytoreductive surgery, intraperitoneal chemotherapy (IPC) and liver resection/ablation were identified from prospectively collected databases. We assessed response to neoadjuvant chemotherapy (NACT), postoperative complications, progression free survival (PFS), and overall survival (OS). RESULTS: Twenty-one patients with resectable disease were treated between 2007 and 2014. In 16 patients (76%), NACT was administered and tumour response defined their selection. The remaining 5 (24%) were selected according to the pattern of recurrence. Median peritoneal cancer index was 5 (range: 3-10.5). Liver surgery included 34 wedge resections, 5 ablations and one bisectionectomy to treat a total of 45 hepatic lesions with a median of 2 per patient (range: 1-2) and a median size of 1.35 cm (range: 0.8-2). Tumour regression grade 4 (fibrosis but residual cancer cells predominate) was seen in 50% of the resected metastases after NACT. Median hospital stay was 17 days (range: 14-24); severe morbidity (Clavien-Dindo grade 3-4) occurred in 24% and no perioperative mortality (0-90 days) was recorded. The median OS was 44 months (range: 31-57) while the median PFS was 10 months (range: 8-12). CONCLUSIONS: Combined parenchyma-preserving liver resection, cytoreductive surgery and IPC in patients with LM and PC from CRC can be performed safely and results in promising mid-term overall survival.

Clinical and laboratory features of South American rattlesnake (Crotalus durissus terrificus) envenomation in children.

The venom of the South American rattlesnake Crotalus durissus terrificus was first reported to have mainly haemolytic and neurotoxic physiopathological activities. Later studies demonstrated the systemic myotoxic action of the venom, characterized by the release of myoglobin from damaged skeletal muscle into serum and urine, and a recent report ruled out the presence of intravascular haemolysis in 3 patients, one child and 2 adults. The present paper describes the clinical-laboratory evolution of 10 children bitten by C. durissus terrificus; 2 developed acute renal failure and one died. The myotoxic activity of the venom was evaluated by measuring serum lactic dehydrogenase, creatine kinase and aspartate aminotransferase, by detection of myoglobin in serum and urine, and by muscle biopsy. Haemolytic activity was evaluated by serial measurements of serum haemoglobin and haptoglobin and by detection of urine haemoglobin. We conclude that the signs and symptoms exhibited by patients bitten by C. durissus terrificus are due only to the myotoxic and neurotoxic action of the venom. The only patients with major morbidity were those who initially received subcutaneous antivenin and did not receive definitive antivenin therapy until later.

Acute myocardial infarction-like enzyme profile in human victims of Crotalus durissus terrificus envenoming.

The clinical signs and symptoms of Crotalus durissus terrificus envenoming are due to the neurotoxic, myotoxic systemic and thrombin-like coagulating effects of the venom. The rhabdomyolysis observed after envenoming caused by snakes, the venom of which has a systemic myotoxic activity, has been limited thus far to skeletal muscle, with no reports of myocardial damage. In the present paper we report serial measurements of serum creatine kinase (CK), lactic dehydrogenase (LD) and of CK-MB and LD1 isoenzymes in human victims of Crotalus bites. The results were similar to those reported for acute myocardial infarction even though the clinical evolution, electrocardiogram and echocardiogram findings did not show any involvement of cardiac muscle. The enzymatic profile detected, as well as the pattern of focal involvement observed in muscle biopsies obtained from these patients, suggest that there may be a type of skeletal muscle fibre that is preferentially damaged by C. durissus terrificus venom, i.e., type I and/or IIa fibres, the composition of which is richer in CK-MB and LD1, and is similar to that of cardiac fibres.

Evidence that Crotalus durissus terrificus (South American rattlesnake) envenomation in humans causes myolysis rather than hemolysis.

The venom of the South American rattlesnake Crotalus durissus terrificus was originally reported to have a pathophysiological activity mainly involving hemolysis and neurotoxicity. The systemic myotoxic action of this venom was demonstrated in 1985. In the present paper we report clinical and laboratory data concerning three patients bitten by C. durissus terrificus and treated at the University Hospital of Ribeirão Preto, University of São Paulo. The normal haptoglobin levels detected in the serum of these patients during the first 48 hr after the accident, as well as the absence of hemoglobin in darkened urine samples as evaluated by immunodiffusion against anti-hemoglobin serum, rule out the occurrence of intravascular hemolysis. These data permit us to conclude that the signs and symptoms observed in human envenomation with C. durissus terrificus are due to a myotoxic and neurotoxic action of the venom.

Myonecrosis, myoglobinuria and acute renal failure induced by South American rattlesnake (Crotalus durissus terrificus) envenomation in Brazil.

The venom of the Brazilian rattlesnake Crotalus durissus terrificus is know to have hemolytic and neurotoxic physiopathological activities which may cause acute renal failure with hemoglobinuria and/or methemoglobinuria. As far as we know, no report has been published on the ability of the venom of this rattlesnake species to cause rhabdomyolysis. In the present paper we demonstrate that the venom of Brazilian snakes of the genus Crotalus can induce systemic myonecrosis. Clinical, laboratory and anatomo-pathological data for two patients referred to the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, 24 hr after a rattlesnake bite, are presented. In both cases, exaggerated elevation of serum levels of the enzymes creatine phosphokinase, lactate dehydrogenase and glutamic-oxaloacetic transaminase were detected, as well as data suggesting acute hypercatabolic renal failure. Immunoelectrophoresis of the serum and urine of these patients, carried out against specific anti-myoglobin serum (Behringwerke), demonstrated myoglobinemia and myoglobinuria, confirming injury to muscle tissue. Electron microscopy of a calf muscle biopsy taken from the leg contralateral to the bite from one patient revealed foci of myonecrosis.

Electron-microscopic study of systemic myonecrosis due to poisoning by tropical rattlesnake (Crotalus durissus terrificus) in humans.

This article describes the ultrastructural study of skeletal muscle biopsy specimens from five patients following envenomization by tropical rattlesnake (Crotalus durissus terrificus). All the patients were bitten in the leg and the biopsy specimens were obtained from the contralateral gastrocnemius muscle in the middle of the lower leg. A wide spectrum of detailed ultrastructural changes involving muscle fibers and microvasculature was demonstrated. Essentially, such lesions included widespread necrotic myofibers intermixed with intact fibers, accompanied by changes in the endothelial lining of the intramuscular blood capillaries and small arterial vessels, reducing their lumens. Since these alterations were observed in biopsy specimens from the limb contralateral to the site of the bite, they clearly demonstrate the systemic myonecrotic action of the venom of a tropical rattlesnake. On the basis of these data, the mechanism of venom-induced myopathy is described. It is postulated that the pathogenesis of systemic myonecrosis due to poisoning by C durissus terrificus is a complex one, probably due to direct damage to cells by the myotoxins of the venom, as well as indirect effects due to ischemia.

Severe scorpion envenomation in Brazil. Clinical, laboratory and anatomopathological aspects.

Scorpion stings in Brazil are important not only because of their incidence but also for their potential ability to induce severe, and often fatal, clinical situations, especially among children. In this report we present the clinical and laboratory data of 4 patients victims of scorpion stings by T. serrulatus, who developed heart failure and pulmonary edema, with 3 of them dying within 24 hours of the sting. Anatomopathologic study of these patients revealed diffuse areas of myocardiocytolysis in addition to pulmonary edema. The surviving child presented enzymatic, electrocardiographic and echocardiographic changes compatible with severe cardiac involvement, which were reversed within 5 days. These findings reinforce the need for continuous monitoring of patients with severe scorpion envenoming during the hours immediately following the sting.

[Immediate hypersensitivity reactions after intravenous use of antivenin sera: prognostic value of intradermal sensitivity tests]. / Reações de hipersensibilidade imediatas após uso intravenoso de soros antivenenos: valor prognóstico dos testes de sensibilidade intradérmicos.

The frequency and class of immediate-type hypersensitivity manifestations were studied in 494 snakebitten and scorpion stung patients who were treated with intravenous injections of antivenom sera. These patients were admitted to HC-FMRPUSP from 1983 to 1988. The effectiveness of a hypersensitivity skin test was also investigated. Eighty two out of 320 patients admitted following snake bites (25.6%) had immediate-type reactions consisting of isolated skin lesions (40%), skin lesions plus respiratory manifestations (19%) and gastrointestinal involvement (17%). Anaphylactic shock occurred in ten patients (12%). Thirteen out of 174 patients admitted following scorpion stings had immediate-type reactions (7.5%). There was also a preponderance of skin reactions. Anaphylactic shock was observed in one patient. The positive predictive value of hypersensitivity skin test was 31.8% and its sensibility was 54.8%. These data show that a hypersensitivity skin test is ineffective in predicting immediate-type hypersensitivity manifestations in patients given snake and scorpion antivenom. Considering these results, this test should be eliminated as a routine procedure when treating victims of poisonous animals. These studies indicate that prior to the administration of antivenom anti-histamine (H1- and H2-antagonists) as well corticosteroids should be given by i.v. route in order to prevent or reduce hypersensitivity reactions. Antivenom sera must always be given under continuous medical surveillance by an intravenous route, without dilution, drop by drop for 15-30 minutes.

Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application.

An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a negative SST result may lead the health team to a feeling of false safety that no adverse reaction will occur, but this is not true for the anaphylactoid reactions. The decision to use premedication, which is based on knowledge about anaphylaxis and on the pharmacology of the medication used, is left to the judgment of health professionals, who should always be prepared for eventual untoward events.

[Crotalid bites in children: clinical, laboratory, epidemiologic aspects and treatment approach]. / Acidente crotálico na infância: aspectos clínicos, laboratoriais, epidemiológicos e abordagem terapêutica.

At the Hospital of Clinics of the Faculty of Medicine of Ribeirão Preto/USP during the years 1980-1989 21 children have been attended after rattlesnake bite: 16 severe and 5 with moderate envenomation. Four (20%) developed acute tubular necrosis 2 necessitating dialysis. One patient died 13 days after the bite and grave complications including digestive hemorrhage and acute respiratory insufficiency. All patients preserved clinical laboratory and epidemiological characteristics of Crotalus durissus terrificus envenomation. We also comment on the correct management of such patients specially related to antivenin dosage and the prevention of acute tubular the most serious complication of such an accident.

[Levels of contaminant zinc in solutions routinely used in rehydration and/or parenteral feeding]. / Conteúdo do zinco contaminante nas soluções rotineiramente utilizadas em hidratação e/ou alimentação parenteral.

With the objective to evaluate the zinc needs of children submitted to rehydration and/or parenteral nutrition, the content of contaminating zinc was determined in intravenous solutions utilized at University Hospital of Ribeirão Preto, SP, Brazil. Zinc was measured in 40 bottles containing deionized water and submitted to the routine treatment for industrialization of serum for parenteral use, according to the standards of the University Hospital of Ribeirão Preto, Industrial Pharmacy. The effect of the sealing material employed (polished red stopper and unpolished black stopper) was observed, as well as time of contact between the solutions and rubber stoppers and latex slides, and the method of bottle conditioning (vertical or horizontal position) which permits contact of the solutions with the rubber stoppers. The gluco-saline solutions prepared in our Hospital and stored in glass bottles with unpolished black rubber stoppers and latex slide showed substantial zinc levels (1,220 to 4,860 micrograms/ml, n = 30). The same solutions kept in glass vials or plastic bottles were zinc free. The highest zinc levels were observed in the amino acid solutions placed in sealed bottles with unpolished black rubber stoppers (11,690 to 24,310 micrograms/ml, n = 20). It is important to be aware of these contaminating zinc levels to provide proper treatment involving this micronutrient.

Abdominal compartment syndrome: an underrated complication in pediatric kidney transplantation.

The transplantation of a large kidney in small children can lead to many complications, including an underrated complication known as abdominal compartment syndrome (ACS), which is defined as intra-abdominal pressure (IAP)≥20 mm Hg with dysfunction of at least one thoracoabdominal organ. Presenting signs of ACS include firm tense abdomen, increased peak inspiratory pressures, oliguria, and hypotension. Between June 1, 1985, and September 30, 2013, our center performed 420 kidney transplants (deceased/living related donors: 381/39) in 314 pediatric recipients (female/male: 147/167). ACS occurred in 9 pediatric patients (weight<15 kg) who received a large kidney from adult donors. In 1 case, the patient underwent abdominal decompression with re-exploration and closure with mesh in the immediate postoperative period. In a second case, the patient developed a significant respiratory compromise with hemodynamic instability necessitating catecholamines, sedation, and assisted ventilation. For small children transplanted with a large kidney, an early diagnosis of ACS represents a critical step. From 2005 we have measured IAP during transplantation via urinary bladder pressure, and immediately after wound closure we use intraoperative and postoperative duplex sonography to value flow dynamics changes. We recommend that bladder pressure should be routinely checked in small pediatric kidney recipients who are transplanted with a large graft.

Vitamin A deficiency among Brazilian school-aged children in a healthy child service.

BACKGROUND/OBJECTIVES: Vitamin A deficiency (VAD) is a world public health problem contributing to the increase in childhood morbidity and mortality in developing countries and severe deficiency of vitamin A may lead to xerophthalmia and blindness. The objective of this study was to determine the prevalence of VAD among Brazilian school-aged children attended at a primary health unit and to verify if some considered risk factor was associated with VAD in this group. SUBJECTS/METHODS: A descriptive prospective transverse study was conducted on 103 randomly selected children. A total of 54 boys and 49 girls aged 5.5-11 years had the relative dose-response (RDR) test performed on. Possible ocular alterations related to vitamin A and the status of anemia, serum zinc, some acute-phase proteins, and anthropometric situation were determinate by an analytic design. RESULTS: No child presented xerophthalmia. Serum retinol values lower than 1.05 and 0.7 micromol l(-1), respectively were found in 26.2 and 5.8% of the children. The prevalence of hypovitaminosis detected by RDR test was 20.4%. The following variables and their relationship with VAD were evaluated: sex (P=0.33; 95% confidence interval 0.61-4.34), weight and height (P> or =0.5), hemoglobin (P=0.15), C-reactive protein (P=0.56; 95% confidence interval 0.75-18.26), alpha-1-acid-glycoprotein (P=0.56; 95% confidence interval 0.15-15.42) and serum zinc (P=0.31). None of these variables was related to VAD. CONCLUSIONS: In this population, the prevalence of VAD detected could be considered a public health problem. School-aged children can be considered at risk for VAD mainly of a subclinical level, even without some associated risk factors.

'Reversible cardiomyopathy' in patients with severe scorpion envenoming by Tityus serrulatus: evolution of enzymatic, electrocardiographic and echocardiographic alterations.

Severe scorpion envenoming is characterized by cardiocirculatory failure which may lead to pulmonary oedema. These are the major causes of death among victims of scorpion stings. Involvement of the heart has been attributed to the massive release of catecholamines and/or to a direct toxic effect of the venom on cardiac fibres, while pulmonary oedema has been considered to be of cardiogenic or non-cardiogenic origin. We present here the clinical, laboratory, electrocardiographic and echocardiographic data of 12 victims of severe Tityus serrulatus stings. These patients had important echocardiographic evidence of moderate to severe left ventricular (LV) dysfunction with diffuse LV hypokinesia and reduced ejection fraction. Seven developed pulmonary oedema. The clinical course of all the patients was satisfactory and the laboratory, electrocardiographic and echocardiographic changes returned to normal, usually within 1 week of the sting. The important alterations detected by echocardiography as early as during the 1st few hours after the sting, taken together with the enzymatic and electrocardiographic data, confirm that LV dysfunction is responsible, either alone or in combination with other factors, for the cardiac insufficiency and pulmonary oedema encountered in scorpion envenoming.

Stabilization of proteins by guanidination.

Earlier studies have indicated the marked resistance of two pronase endopeptidases to denaturation in high concentrations of urea or guanidine hydrochloride (Siegel, S., and Awad, W. M., Jr. (1973) J. Biol. Chem. 248, 3233--3240). One component has only a single residue of lysine and the other has none. The consideration arose that lysine-containing peptide segments may be less stable than those containing arginine because of the fluctuations of the side groups of the former residue. The small epsilon amino groups may not be able to sustain solvation of the hydrophobic arm in an aqueous medium. Arginine residues have shorter hydrophobic arms, larger hydrophilic groups, and higher pKa values and, thus may be less motile than lysine. The hypothesis was tested by guanidination of seven globular proteins (bovine carbonic anhydrase, chymotrypsinogen, alpha-lactalbumin, serum albumin, ribonuclease, hen egg lysozyme, and horse heart cytochrome c). Conversion of lysine residues to homoarginine was between 90 and 99%. Tritium-hydrogen isotope exchange revealed that all proteins except lysozyme demonstrated reduced out-exchange after guanidination. The results with lysozyme were not unexpected since only this protein has a high arginine to lysine ratio. These findings suggest that high arginine to lysine ratios contribute to protein stability.

Reações de hipersensibilidade imediatas apos uso intravenoso de soros antivenenos: valor prognostico dos testes de sensibilidade intradermicos / Immediate hypersensitivity reactions after intravenous use of antivenin sera: prognostic value of intradermal sensitivity tests

Foram admitidos no Hospital das Clinicas da FMRPUSP, durante os anos de 1983 a 1988, 494 pacientes vitimas de acidentes ofidicos e escorpionicos que receberam soro antiveneno (SAV) e nos quais foi avaliada a frequencia e tipo das manifestacoes imediatas, bem como o valor prognostico do teste de sensibilidade. Do total de pacientes vitimas de ofidismo, 82 (25,6 por cento) apresentaram reacoes imediatas, das quais as mais comuns foram as cutaneas, isoladas (40 por cento) ou associadas com sintomas respiratorios (19 por cento), seguidas de manifestacoes gastrintestinais (17 por cento). Choque anafilatico foi detectado em 10 pacientes (12 por cento). Em relacao aos acidentes escorpionicos, reacoes imediatas foram observadas em 13 pacientes (7,5 por cento), tambem com predominio de lesoes cutaneas. Sintomatologia cardiocirculatoria foi detectada em apenas 1 paciente. Devido ao baixo valor preditivo positivo (31,8 por cento) e a baixa sensibilidade (54,6 por cento), propomos que o teste de sesibilidade intradermico seja abolido da rotina de atendimento de urgencia aos pacientes vitimas de acidentes por animais peconhentos. Anti-histaminicos (bloqueadores dos receptores "H IND. 1" e "H IND. 2") e corticosteroides devem ser administrados por via parenteral anteriormente a soroterapia, no sentido de prevenir...

Metales pesados en agua de bebederos de presión / Heavy metals in water of drinking fountains

The purpose of this study was to analyze the levels of lead (Pb), cadmium (Cd), aluminum (Al), zinc (Zn), cooper (Cu) and chromium (Cr) in the water of drinking fountains distributed in the Campus of the University of São Paulo. Ribeirão Preto, Brazil. Thirty random samples were collected in different parts of the Campus that were analyzed by Atomic Absorption Spectrophotometry. According to WHO's Drinking Water Guidelines; lead, cadmium and zinc were found in concentrations higher than those recommended in 40 per cent, 20 per cent and 13 per cent of the samples, respectively. The results were analyzed considering nutritional and toxicological aspects related to the presence of essential and toxic elements for the human being. Reviewing the regulatory limits established in ten countries of America, authors focus in the necessity to find a consensus in the establishment of the higher levels of heavy metals in potable water. The tolerable daily intake, have to be the basis to assure the prevention of diseases associated with a long-term ingestion of these elements through foods.