Evaluation of gastrointestinal toxicity following cytostatic chemotherapy

Summary A number of clinical and chemical parameters related to the gastrointestinal tract in patients treated with intensive chemotherapy for disseminated malignant melanoma were evaluated in order to find quantitative indicators for gastrointestinal toxicity and to investigate the cause of diarrhea after chemotherapy.In 11 patients 17 courses of polychemotherapy with bleomycin, DTIC, vindesine, and actinomycin D were administered, while the patients received complete liquid enteral nutrition. As clinical parameters for toxicity the diarrhea grading system according to the WHO criteria and the daily fecal consistency were used. Furthermore, in the feces Na⁺, K⁺, and Cl^- (mmol/24 h), Na⁺/K⁺ ratio, dry and wet weight (g/24h), lactate and bile acids (mmol/24 h), fat (g/24 h), pH, and osmolarity were determined.Both clinical parameters were closely correlated. The most important effects of the chemotherapy on the chemical parameters were an increased fecal fluid, K⁺, and fat excretion. The fecal wet weight and K⁺ excretion showed a high correlation with the two clinical parameters for gastrointestinal toxicity. We conclude that mucosal injury resulting from chemotherapy probably leads to increased small intestinal fluid and electrolyte secretion inducing diarrhea and that fecal wet weight and K⁺ excretion are probably the best quantitative indicators for gastrointestincal toxicity.     

Management of a child with acute thyroxine ingestion

We report a case of thyroxine overdose in a child. Despite extremely high thyroxine (T4RIA) levels on admission, the patient's only symptoms were mild hypertension and tachycardia. Both symptoms responded to propranolol, with a drop in pulse rate and a decrease in blood pressure to normal levels. After four days of cardiac monitoring, the patient was released and received propranolol for five additional days as an outpatient.     

Amiodarone-induced pulmonary toxicity in the rat

A rat model of amiodarone-induced pulmonary toxicity is described. The rats were fed, by gavage, 175 mg/kg/day of amiodarone hydrochloride suspended in methyl cellulose. Controls received methyl cellulose alone. Groups of rats were examined after 1, 3, 6, 9, and 12 weeks of feeding. We found that drug-fed rats had significantly more macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage (BAL). The early increase in cellularity was due to an increase in macrophages, and the macrophage count peaked after 6 weeks of drug treatment. The number of neutrophils in the experimental animals remained high throughout the course of the experiment. An increasing number of lymphocytes was seen in the BAL between 6 and 12 weeks of drug treatment. Protein in the lavage fluid was significantly elevated after 12 weeks of amiodarone exposure. Histologic sections were abnormal after 3 weeks of drug treatment, characterized by interstitial thickening with accumulation of mononuclear cells and alveoli packed with large foamy macrophages. There was only minimal evidence of fibrosis. This model appears to be very similar to human amiodarone-induced pulmonary toxicity and should be useful for the study of the pathogenesis of amiodarone-induced toxicity.     

Lidocaine toxicity following subcutaneous administration

A case of a 2-year-old girl who survived grand mal seizures secondary to toxicity from massive subcutaneous administration of lidocaine is presented. She was treated with intravenous diazepam and was intubated. After 24 hours of observation she was discharged, and there have been no sequelae or recurrence of seizure activity during ten months follow up. Central nervous system, cardiac, and hematologic effects of lidocaine toxicity are discussed. Drug interactions that may potentiate lidocaine toxicity are listed.     

Fatal cardiac arrhythmias and shock following yew leaves ingestion

A 40-year-old woman presented with vomiting and abdominal pain following voluntary ingestion of 150 yew leaves. She developed ventricular conduction defects and arrhythmias unresponsive to medical treatment after admission. She expired five hours after yew ingestion from irreversible cardiogenic shock. More attention should be given to this rare but severe intoxication for which no effective therapy is known.     

Simple battery armor to protect against gastrointestinal injury from accidental ingestion

Inadvertent battery ingestion in children and the associated morbidity and mortality results in thousands of emergency room visits every year. Given the risk for serious electrochemical burns within hours of ingestion, the current standard of care for the treatment of batteries in the esophagus is emergent endoscopic removal. Safety standards now regulate locked battery compartments in toys, which have resulted in a modest reduction in inadvertent battery ingestion; specifically, 3,461 ingestions were reported in 2009, and 3,366 in 2013. Aside from legislation, minimal technological development has taken place at the level of the battery to limit injury. We have constructed a waterproof, pressure-sensitive coating, harnessing a commercially available quantum tunneling composite. Quantum tunneling composite coated (QTCC) batteries are nonconductive in the low-pressure gastrointestinal environment yet conduct within the higher pressure of standard battery housings. Importantly, this coating technology enables most battery-operated equipment to be powered without modification. If these new batteries are swallowed, they limit the external electrolytic currents responsible for tissue injury. We demonstrate in a large-animal model a significant decrease in tissue injury with QTCC batteries compared with uncoated control batteries. In summary, here we describe a facile approach to increasing the safety of batteries by minimizing the risk for electrochemical burn if the batteries are inadvertently ingested, without the need for modification of most battery-powered devices.Battery ingestion in the pediatric population has been documented for decades and results in an estimated 5,000 emergency room visits per year (1). Of particular concern are button batteries, which can lodge in the esophagus and lead to serious complications, including death. The U.S. Consumer Product Safety Commission has analyzed data from 1997 to 2010 and estimated that 40,400 children younger that 13 years received treatment in hospital emergency departments for battery-related injuries, with 14 battery-related deaths in children from 7 mo to 3 y in age (1). Recent data from the National Capital Poison Center note that 3,366 reported battery ingestions occurred in 2013, with 2,277 occurring in the <6 y age group, and with 8% of these leading to adverse events, including major clinical complications, including death (2, 3). To help protect children from battery accidents, the Consumer Product Safety Improvement Act of 2008 was passed, which mandates toy safety standards (known as F963-11) and requires batteries to be inaccessible in all toys intended for children younger than 3 years. Unfortunately, additional legislation to further regulate the safety associated with button cell batteries (the Button Cell Battery Safety Act of 2011) introduced on June 9, 2011, in a previous session of Congress, was not enacted. This new legislation would have required warning labels and more secure battery compartments on a wide range of products, including watches, cameras, calculators, laptops, and smart phones. Although progress has been made to regulate safety by restricting battery access, improving the safety of batteries themselves has not been addressed. In fact, newer, higher-voltage batteries such as the 3V lithium-ion batteries, particularly in the ≥20-mm format, which can also be modified using the described approach, are recognized as leading causes of complications if ingested (4).Injuries and sequelae from inadvertent battery ingestion include vocal cord paralysis, esophageal strictures, esophageal perforation, tracheoesophageal fistula, and aortoesophageal fistula leading to death (1, 5–8). It has been recognized for more than 30 y that esophageal impaction is associated with the most severe morbidity (7). Battery-induced injuries are proposed to occur via three mechanisms: ischemic necrosis from direct pressure, leakage of caustic alkaline electrolytes, and the generation of an external electrolytic current generating hydroxide at the negative pole of the battery (1, 3, 8–10). It is this last mechanism that leads to significant tissue injury (3). Because the interval from ingestion to injury is only 2 h (11), current management guidelines recommend endoscopic evaluation for foreign body retrieval in all cases of battery ingestion (5, 12).To mitigate injuries caused by battery ingestion, here we report the development of pressure-sensitive, waterproof quantum tunneling composite coated (QTCC) button batteries based on off-the-shelf components. A QTC was applied to the anode of conventional button batteries to impart pressure-sensitive conductive properties. QTCs consist of conductive metal microparticles suspended in an insulating polymer matrix. Nanoscale roughness on the microparticle surface enhances the electric field gradient, such that when the particles come into close proximity (less than 1–5 nm), electrons can tunnel through the insulator, separating them to conduct current (13, 14). Given that quantum tunneling does not require contact between the metal particles, the polymer matrix can remain continuous, and therefore waterproof (13, 14). Because of the low water permeability of silicone, the time to water ingress exceeds gastrointestinal transit time. A conductive paste affixes the QTC to the button battery anode, and an additional waterproof insulating polymer covers the remainder of the anode and gasket so that the button battery will not short circuit in conductive fluids below the compressive stress (σ_c) level required for QTC conduction, avoiding the generation of external electrolytic currents if ingested. To evaluate the improved safety of QTCC batteries, we tested the batteries in a large-animal model simulating esophageal impaction. The pressure at which the QTCC batteries conduct is directly proportional to the coating thickness for a given density of conductive microparticles. When the microparticles have higher average spacing at zero stress, greater axial compression is required to bring them into close enough proximity to achieve conduction. Because the QTCCs are affixed to the rigid battery housing, compression is restricted to the axial direction. Therefore, the required pressure for conduction is not diameter-dependent and can be applied to any diameter button battery without significant design modification. Moreover, given that conduction is directly proportional to coating thickness and particle density, significant tunability exists for triggering conduction. QTCCs impart weatherproofing of batteries, expanding the possible applications beyond accidental ingestion scenarios to include using batteries in high humidity or more corrosive environments that would otherwise affect the battery structure.     

Corrosive oesophageal strictures following acid ingestion: Clinical profile and results of endoscopic dilatation

There are several reports on oesophageal strictures caused by alkali ingestion, but information on oesophageal strictures due to acid ingestion is scarce. Endoscopic dilatation, which has been found to be quite safe and effective in the treatment of benign oesophageal strictures of other aetiology, has also not been evaluated adequately in the treatment of these strictures. Over a period of 2 years, of 47 patients treated at this centre of benign oesophageal strictures, 17 (36.2%) patients had strictures following ingestion of corrosive agents. Thirteen patients had ingested acids and only four gave a history of alkali ingestion. The age range of these 13 patients was 14-50 years (mean = 25.5 years, s.d. = 2.6). The amount of acid ingested varied from 10 to 100 ml (median = 50 ml). The interval between acid ingestion and presentation to hospital ranged from 1 to 60 months (median = 2 months). Ten patients had multiple strictures, and the most common site of involvement was the upper third followed by the lower third of the oesophagus. Only five of these 13 patients had evidence of gastric involvement in the form of antral stricture (four) and hour glass deformity (one). Strictures were dilated using Eder-Puestow metal olives passed over a guide wire. The total number of sittings required to achieve adequate dilatation in this group ranged from 1 to 30 (median = 14). Most patients were managed successfully with dilatation (good response 63.6%, satisfactory response 18.2%). On follow-up, recurrence of dysphagia was seen in a high number of patients (66%), but this could be managed easily with repeat dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute exogenous lipoid pneumonia caused by accidental kerosene ingestion in an elderly patient with dementia: A case report

Acute exogenous lipoid pneumonia is an uncommon condition caused by aspiration of oil‐based substances, occurring mainly in children. Here, we report the case of an 83‐year‐old patient with Alzheimer's disease who presented with coughing and hypoxia. The diagnosis of acute exogenous lipoid pneumonia caused by accidental kerosene ingestion was made on the basis of the patient's clinical history, and typical radiological and cytological findings. The patient's cognitive impairment and an unsafe environment, in which the patient's 91‐year‐old husband stored kerosene in an old shochu bottle, were responsible for the accidental ingestion. Acute exogenous lipoid pneumonia should be considered in the differential diagnosis for acute respiratory disorders in the rapidly aging population. Geriatr Gerontol Int 2013; 13: 222–225.     

Probable gastrointestinal toxicity of kombucha tea

Kombucha tea is a health beverage made by incubating the Kombucha “mushroom” in tea and sugar. Although therapeutic benefits have been attributed to the drink, neither its beneficial effects nor adverse side effects have been reported widely in the scientific literature. Side effects probably related to consumption of Kombucha tea are reported in four patients. Two presented with symptoms of allergic reaction, the third with jaundice, and the fourth with nausea, vomiting, and head and neck pain. In all four, use of Kombucha tea in proximity to onset of symptoms and symptom resolution on cessation of tea drinking suggest a probable etiologic association.     

Prolonged toxicity following massive ingestion of sustained-release theophylline preparation

Massive ingestion of sustained-release theophylline preparations in three patients was treated with gastric lavage and repeated dosages of orally-administered activated charcoal. Therapy was initiated promptly; however, two patients had their highest theophylline levels documented six to 12 hours after ingestion, and theophylline levels on arrival at the hospital were significantly lower than the maximal level documented. All three patients had prolonged elevations of the level, with markedly delayed half-lives of the drug. Overdosages due to sustained release preparations may lead to prolonged toxicity and require aggressive and continuous therapy.