Histopathological studies on the toxicity of ochratoxin A in rats. I. Acute oral toxicity

Traumatic spinal cord lesions in children are infrequent (2 to 5 per cent of all cases admitted to specialised paraplegic centres depending on whether the upper age limit is set at 10 or 15 years). Traffic accidents are responsible for at least 50 per cent of the lesions; playground accidents and various sports add another 35 per cent. A large proportion of the accidents have been found to be related to the child's normal desire for adventure and exploration. The segment most frequently involved in our own series of 18 cases was the cervical and upper thoracic spine. Histopathological studies have shown that splitting of the cartilaginous end-plate in the growth zone of the vertebrae is a common finding. Radiological signs of spinal trauma are less evident than in adults; they may be totally missing. Precise neurological assessment must rely on repeated examination and close clinical observation, especially in the comatous child with a head injury. Spinal cord involvement must be suspected and the child treated as a paraplegic until definite proof of a normal neurological status is available. Due to a highly labile water electrolyte balance in the early post-traumatic stage and considerable fluctuations in plasma volume and temperature regulation, permanent monitoring of the cardiovascular function, body temperature and diuresis is mandatory. In children below the age of 10, deep vein thrombosis and embolism are exceptional (sepsis creates a high-risk situation requiring anticoagulation). In the initial treatment of spinal injury only conservative measures should be considered; there are no indications for laminectomy, nor for spinal fusion. In the tetraplegic child below the age of 6, skull-traction should be avoided and immobilisation of the cervical segment achieved by bilateral padded head-rests.     

Acute cardiovascular effects of insulin-like growth factor I in patients with chronic heart failure

Insulin-like growth factor I (IGF-I) enhances myofibrillar development in cardiomyocytes of rats in culture and in vivo. In addition, IGF-I has vasodilatory effects and improves cardiac function in healthy volunteers. This study was conducted to evaluate the acute hemodynamic effects of IGF-I in patients with chronic heart failure Eight patients with chronic heart failure were randomized to receive recombinant human IGF-I (60 micrograms/kg) or placebo, i.v., over 4 h in a cross-over, double blind study on 2 consecutive days. Electrocardiogram as well as systemic hemodynamics were continuously monitored over 7 h by flow-guided thermodilution and radial artery catheters. IGF-I was well tolerated by all patients, and no pathological changes on electrocardiogram were recorded. Compared with placebo, IGF-I increased the cardiac index by 27 +/- 3.7% (+/- SE; P < 0.0005) and the stroke volume index by 21 +/- 5.6% (P < 0.05), and decreased systemic vascular resistance by 28 +/- 4.4% (P < 0.0002), right atrial pressure by 33 +/- 9.0% (P < 0.003), and pulmonary artery wedge pressure by 25 +/- 6.1% (P < 0.03). Mean systemic and pulmonary artery pressure as well as heart rate and pulmonary vascular resistance were not significantly influenced by IGF-I treatment. Insulin and C peptide levels were decreased by IGF-I, whereas glucose and electrolyte levels remained unchanged. Urinary levels of norepinephrine decreased significantly (P < 0.05) during IGF-I infusion. Thus, acute administration of IGF-I in patients with chronic heart failure is safe and improves cardiac performance by afterload reduction and possibly by positive inotropic effects. Further investigations to establish whether the observed acute effects of IGF-I are maintained during chronic therapy appear to be warranted.     

Acute inhalation toxicity of neutralized chemical agent identification sets (CAIS) containing agent in chloroform

Basic fibroblast growth factor (bFGF) exerts angiogenic and mitogenic properties in human tissue. Since changes in ion currents modulate essential Ca2+-dependent intracellular pathways in endothelial cells, we have investigated a possible contribution of Ca2+-activated K+ channels (BKCa) on bFGF-induced endothelial cell proliferation. The patch-clamp technique was used to identify BKCa and to study their modulation by bFGF in cultured endothelial cells of human umbilical cord veins (HUVEC). Cell counts of HUVEC were carried out on different days to analyze bFGF-induced cell proliferation and its influence by the specific BKCa blocker iberiotoxin (IBX). Using single-channel recordings, we found characteristic BKCa with a single-channel slope conductance of 170.3 +/- 2.1 pS (n = 7), half-maximal activation at internal pCa = 5.7 (n = 5; test potential: 80 mV), and dose-dependent block by IBX (25-100 nmol/l). In cell-attached patches bFGF (50 ng/ml) caused a significant increase in the open-state probability (NPo) after 6 min at test potentials of 80 and 100 mV (n = 28; p < 0.001), respectively, which lasted up to 30 min. After preincubation with pertussis toxin (100 ng/ml; 4 h) bFGF superfusion did not cause a significant increase in BKCa activity until 25 min had passed (n = 20; p < 0.01). Addition of 100 nmol/l IBX to the pipette solution caused a total block of BKCa within 2 min in cell-attached patches, whereas bFGF (50 ng/ml) was not able to activate BKCa. When incubated with IBX (25-100 nmol/l) every 2 days, bFGF-induced proliferation of HUVEC was significantly decreased by 50 (-41%) and 100 nmol/l (-50%) IBX (n = 5; p < 0.001) after 7 days. We conclude that activation of BKCa by bFGF may play an important role in bFGF-induced proliferation of human endothelial cells and thus might be important in the process of angiogenesis and vascular remodelling.     

Acute mucocutaneous toxicity following high-dose hydroxyurea

Three patients with advanced acute myeloid leukemia were treated with oral high-dose hydroxyurea at a dose of 10 g daily for 8-10 days. Severe acute stomatitis developed in all three patients. In addition, two of the patients developed a peculiar acute cutaneous type of toxicity associated with soreness, violet erythema, and edema of the palms and foot soles followed by intense universal hyperpigmentation of the skin. Apparently, the pronounced acute mucocutaneous toxicity was caused by the sustained high daily dose of hydroxyurea, indicating that myelosuppression may not be the dose-limiting toxicity of this drug.     

Acute toxicity and pharmacokinetics of dibekacin mice

The LD50 values of dibekacin to mice were determined following three different methods of administration, namely, intravenous constant infusion, intravenous bolus injection, and intramuscular injection. The serum levels of dibekacin were pharmacokinetically analyzed. The differences in LD50 values between the methods of administration were discussed from the viewpoints of pharmacokinetics. 1) The LD50 value following the intravenous constant infusion was higher than that following the intravenous bolus injection and approached the level of that following the intramuscular injection, when the infusion rate of the drug was decreased by increasing the infusion period. 2) The biological half-life of dibekacin in mice was 24--45 min. 3) The volume of distribution increased as its dose increased, and a linear correlation was noted between log Vd and log (dose). 4) The difference among the maximum serum concentrations calculated with dibekacin following the administration of LD50 was small, which coincided with the results of the experiment that the serum concentrations of dibekacin at the death following the administration of LD100 were almost the same regardless of the method of administration.     

Acute and subacute toxicity of atrazine to carp (Cyprinus carpio L.)

Investigations of acute and subacute atrazine toxicity in carp (Cyprinus carpio L.) were carried out. Acute toxicity was investigated in a semi-static test during a 96-hr exposition. The estimated LC-50 value was 18.8 mg/l. Subacute toxicity was investigated by exposing fish (carp) to different atrazine concentrations (1.5, 3.0, and 6.0 mg/l) for 14 days. Biochemical and histopathological changes in certain organs and tissues were investigated. The results show that atrazine leads to changes of varying intensity depending on the parameter tested, the organs and tissues examined, as well as the atrazine concentration. Biochemical changes were most prominent in the alkaline phosphatase, glutamic-oxaloacetic transaminase, and glutamic-pyruvic transaminase activities whereas the most severe histopathological changes were observed in the gills.     

Acute cyanide toxicity caused by apricot kernel ingestion

A 41-year-old woman ingested apricot kernels purchased at a health food store and became weak and dyspneic within 20 minutes. The patient was comatose and hypothermic on presentation but responded promptly to antidotal therapy for cyanide poisoning. She was later treated with a continuous thiosulfate infusion for persistent metabolic acidosis. This is the first reported case of cyanide toxicity from apricot kernel ingestion in the United States since 1979.     

Acute pulmonary toxicity of urban particulate matter and ozone

We have investigated the acute lung toxicity of urban particulate matter in interaction with ozone. Rats were exposed for 4 hours to clean air, ozone (0.8 ppm), the urban dust EHC-93 (5 mg/m3 or 50 mg/m3), or ozone in combination with urban dust. The animals were returned to clean air for 32 hours and then injected (intraperitoneally) with [3H]thymidine to label proliferating cells and killed after 90 minutes. The lungs were fixed by inflation, embedded in glycol methacrylate, and processed for light microscopy autoradiography. Cell labeling was low in bronchioles (0.14 +/- 0.04%) and parenchyma (0.13 +/- 0.02%) of air control animals. Inhalation of EHC-93 alone did not induce cell labeling. Ozone alone increased (P < 0.05) cell labeling (bronchioles, 0.42 +/- 0.16%; parenchyma, 0.57 +/- 0.21%), in line with an acute reparative cell proliferation. The effects of ozone were clearly potentiated by co-exposure with either the low (3.31 +/- 0.31%; 0.99 +/- 0.18%) or the high (4.45 +/- 0.51%; 1.47 +/- 0.18%) concentrations of urban dust (ozone X EHC-93, P < 0.05). Cellular changes were most notable in the epithelia of terminal bronchioles and alveolar ducts and did not distribute to the distal parenchyma. Enhanced DNA synthesis indicates that particulate matter from ambient air can exacerbate epithelial lesions in the lungs. This may extend beyond air pollutant interactions, such as to effects of inhaled particles in the lungs of compromised individuals.     

Acute solitary gastric erosion (Dieulafoy) (author's transl)

Acute solitary gastric erosion (Dieulafoy) is one rare cause of fulminant, fatal acute gastric haemorrhage. Conservative treatment is usually lethal and elimination of the source of haemorrhage by active surgical intervention is the only possible form of therapy. The key to successful surgical treatment is early preoperative diagnosis by means of emergency gastroscopy.