Cuff inflation to aid nasotracheal intubation using the C-MAC videolaryngoscope.

A preliminary report is presented of a technique for using the C-MAC videolaryngoscope to carry out nasopharyngeal intubations. The main thrust of the technique is that cuff inflation of the endotracheal tube is used to lift the endotracheal tube off the posterior pharyngeal wall and thus direct it towards the glottis. The technique was used successfully in 5 consecutive patients needing nasotracheal intubation. Indeed a couple of these patients might have been difficult to intubate using conventional laryngoscopy. The full technique is described together with pictures at the various stages of intubation.

Lack of effect of furfural on unscheduled DNA synthesis in the in vivo rat and mouse hepatocyte DNA repair assays and in precision-cut human liver slices.

The ability of furfural to induce unscheduled DNA synthesis (UDS) in hepatocytes of male and female B6C3F(1) mice and male F344 rats after in vivo administration and in vitro in precision-cut human liver slices has been studied. Preliminary toxicity studies established the maximum tolerated dose (MTD) of furfural to be 320 and 50 mg/kg in the mouse and rat, respectively. Furfural was dosed by gavage at levels of 0 (control), 50, 175 and 320 mg/kg to male and female mice and 0, 5, 16.7 and 50 mg/kg to male rats. Hepatocytes were isolated by liver perfusion either 2-4 h or 12-16 h after treatment, cultured in medium containing [3H]thymidine for 4 h and assessed for UDS by grain counting of autoradiographs. Furfural treatment did not produce any statistically significant increase or any dose-related effects on UDS in mouse and rat hepatocytes either 2-4 h or 12-16 h after dosing. In contrast, UDS was markedly induced in mice and rats 2-4 h after treatment with 20 mg/kg dimethylnitrosamine and 12-16 h after treatment of mice and rats with 200 mg/kg o-aminoazotoluene and 50 mg/kg 2-acetylaminofluorene (2-AAF), respectively. Precision-cut human liver slices from four donors were cultured for 24 h in medium containing [3H]thymidine and 0-10 mM furfural. Small increases in the net grain count (i.e. nuclear grain count less mean cytoplasmic grain count) observed with 2-10 mM furfural were not due to any increase in the nuclear grain count. Rather, it was the result of concentration-dependent decreases in the mean cytoplasmic grain counts and to a lesser extent in nuclear grain counts, due to furfural-induced cytotoxicity. In contrast, marked increases in UDS (both net grain and nuclear grain counts) were observed in human liver slices treated with 0.02 and 0.05 mM 2-AAF, 0.002 and 0.02 mM aflatoxin B(1) and 0.005 and 0.05 mM 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. This study demonstrates that furfural does not induce UDS in the hepatocytes of male and female B6C3F(1) mice and male F344 rats after oral treatment at doses up to the MTDs. Moreover, human liver slice studies suggest that furfural is also not a genotoxic agent in human liver.

Is ethanol genotoxic? A review of the published data.

A great many studies have been carried out on the toxicology of ethanol, the majority in the context of the effects of the consumption of alcohol in beverages. Published information relevant to the assessment of the possible genotoxic potential of ethanol has been reviewed and evaluated in terms of the safety of ethanol as an industrial chemical, rather than as a component of beverages. The available data on ethanol from standard genotoxicity test methods are incomplete. There is clear evidence that ethanol is not a bacterial or mammalian cell mutagen but in vitro assays for chromosome aberration, although mostly negative, have generally not included exogenous metabolic activation. Evidence from the use of ethanol as a vehicle control suggests that it is not mutagenic or clastogenic in vitro. Reported tests for chromosome aberration induction in vivo are all negative and only a minority of micronucleus tests are positive. Conflicting results have been reported for the dominant lethal assay, although an inter-laboratory study performed to OECD guidelines was negative. There is some evidence that ethanol induces SCE in vivo and can also act as an aneugen at high doses. Many in vivo studies were designed to model alcoholism and used very high doses, sometimes for long periods. Outcomes may have been affected by disturbances of metabolism giving rise to secondary effects. It is concluded that there is no significant evidence that ethanol is a genotoxic hazard according to the criteria normally applied for the purpose of classification and labelling of industrial chemicals. Some degree of genotoxicity may result from excessive alcohol drinking, but this is not considered relevant to any conceivable exposure obtainable by either inhalation or dermal exposure in the workplace.

Embolization of a mesenteric arteriovenous fistula following pancreatic allograft: the steal effect.

The first pancreatic transplant was performed in 1966 by Kelly and Lillehei at the University of Minnesota (1, 2). Nearly 30 years later, Ozaki et al., published the first occurrence of an arteriovenous fistula (AVF) in a transplanted allograft bundle (3). From its early days as a radical and experimental procedure in the treatment of insulin-dependent diabetes mellitus, this operation has progressed to become routine in many major medical centers. However, the incidence of technical complications remains relatively high, ranging from 10 to 40% (1). The list of potential complications includes allograft pancreatitis, vascular thrombosis, hemorrhage, pseudoaneurysm formation, anastomotic leaks, intra-abdominal infections, and, al. though rare, AVF. Lowell et al., in 1993, reported this last complication in 3 of 90 consecutive pancreatic recipients (4). These same authors promoted the theory that AVF formation was directly related to procurement technique: a nonspecific "blind ligation" of mesenteric vessels along the inferior pancreatic border. However, this approach continues to be used commonly. We have identified the occurrence of an allograft superior mesenteric artery-superior mesenteric vein (SMA-SMV) AVF in a pancreas-after-kidney (PAK) transplant recipient.

Drug therapy for hyperthyroidism in pregnancy: safety issues for mother and fetus.

Hyperthyroidism (thyrotoxicosis) in pregnancy and the child bearing years is usually attributable to Graves' disease. This is an autoimmune condition in which thyroid-stimulating immunoglobulins (TSI) cause hyperthyroidism. As a rule, pregnancy complicates the management of hyperthyroidism, rather than vice versa. However, patients who remain thyrotoxic during pregnancy are at increased risk of maternal and fetal complications, particularly miscarriage and stillbirth. Therefore, bodyweight loss, eye signs and a bruit over the thyroid gland in a pregnant woman warrant thyroid investigation. Investigations should include measurement of serum free thyroid hormone levels [free thyroxine (T4) and free triiodothyronine (T3)] rather than total T4 and T3 levels, because total T4 and T3 levels may be raised in euthyroid pregnancies due to the presence of increased levels of thyroxine binding globulin (TBG). By 20 weeks' gestational age, the fetal thyroid is fully responsive to TSI and to antithyroid drugs. Maternal T4 and T3 and thyrotropin pass across the placenta in small and decreasing amounts as gestation progresses, but thyrotropin releasing hormone, TSI, antithyroid drugs, iodides and beta-blockers are readily transferred to the fetus from the mother. Hyperthyroidism is usually treated throughout pregnancy with an antithyroid drug, preferably propylthiouracil. The smallest dose which controls the disease is given with careful monitoring of free T4 and T3 levels to minimise the risk of fetal hypothyroidism and goitre. Bilateral subtotal thyroidectomy may be an option for a small number of patients with hyperthyroidism in pregnancy.

Anhydrous ammonia burns case report and review of the literature.

Chemical burns are associated with significant morbidity, especially anhydrous ammonia burns. Anhydrous ammonia is a colorless, pungent gas that is stored and transported under pressure in liquid form. A 28 year-old patient suffered 45% total body surface area of second and third degree burns as well as inhalational injury from an anhydrous ammonia explosion. Along with fluid resuscitation, the patient's body was scrubbed every 6 h with sterile water for the first 48 h to decrease the skin pH from 10 to 6-8. He subsequently underwent a total of seven wound debridements; initially with allograft and then autograft. On post burn day 45, he was discharged. The injuries associated with anhydrous ammonia burns are specific to the effects of ammonium hydroxide. Severity of symptoms and tissue damage produced is directly related to the concentration of hydroxyl ions. Liquefactive necrosis results in superficial to full-thickness tissue loss. The affinity of anhydrous ammonia and its byproducts for mucous membranes can result in hemoptysis, pharyngitis, pulmonary edema, and bronchiectasis. Ocular sequelae include iritis, glaucoma, cataracts, and retinal atrophy. The desirability of treating anhydrous ammonia burns immediately cannot be overemphasized. Clothing must be removed quickly, and irrigation with water initiated at the scene and continued for the first 24 h. Resuscitative measures should be started as well as early debridement of nonviable skin. Patients with significant facial or pharyngeal burns should be intubated, and the eyes irrigated until a conjunctivae sac pH below 8.5 is achieved. Although health care professionals need to be prepared to treat chemical burns, educating the public, especially those workers in the agricultural and industrial setting, should be the first line of prevention.

Comparative in vitro and in vivo effects of antioxidants.

We have investigated the effects of reactive oxygen species (ROS) in a wide variety of systems, both in vitro and in vivo, with particular attention to their genetic effects. Some of the results of these studies, as they relate to the protective effects of antioxidants, are discussed.

Appendiceal diverticulitis.

Diverticulitis has long been known to affect the right colon, and in recent years, our understanding has evolved in regard to the underlying cause. Appendiceal diverticulitis has yet to gain widespread recognition despite the fact that it was first described in 1893. Commonly dismissed by surgeons and pathologists as a variant of true appendicitis, appendiceal diverticulitis is a discrete clinical process that must be considered in the appropriate setting. We describe a case of appendiceal diverticulitis in a previously healthy 59-year-old man and review the literature.

Development of a colocutaneous fistula in a patient with a large surface area burn.

A 61 year old female sustained a large surface area burn, complicated by inhalation injury. One month before the incident, she had undergone a left hemicolectomy with colorectal anastomosis for diverticular disease. Due to the severity of her burns, multiple surgical debridement and skin grafting procedures were required, including a large fascial debridement of her flank and back. Her hospital course was complicated by recurrent episodes of pulmonary and systemic infection, as well as pre-existing malnutrition. Prior to her discharge to a rehabilitation center, stool began to drain from her left posterior flank. This complication represented a colonic fistula arising from the recent colon anastomosis. The fistula was managed nonoperatively and gradually closed. To our knowledge, this is the first report of a colocutaneous fistula spontaneously draining from the abdomen via the retroperitoneum in a burn victim, not related to direct thermal injury to the peritoneal cavity.

Recreational-outdoor burns: the impact and severity--a retrospective review of 107 patients.

INTRODUCTION: Campfires, bonfires and barbecues play a prominent role in outdoor activities and serve a variety of decorative and functional purposes. Given all of it's various forms, uses and benefits, the outdoor fire can turn dangerous in a matter of seconds: a stumble or fall (the child running that trips) leads to direct contact with the flames and subsequent burn injury. With it's everyday occurrence, we were surprised to find a paucity of information regarding this type of burn in the literature, including the NBIE analysis. METHODS: A retrospective review of 107 patients admitted to the Maricopa Medical Bum Center, from 1987 to 1996, was conducted. Each chart was analyzed for the patient demographics, mechanism of injury, percent total body surface area burned, operative versus non-operative treatment and overall outcome. RESULTS: An average burn injury involved 5.7% TBSA, with a wide range from 1 to 47%. The majority of our population involved either small children or intoxicated adults and a total of 50 patients required 92 operations. Severe morbidity, including 4 amputations and 2 mortalities, were seen. The average hospital stay was 14.3 days, ranging from 1 to 52 days. CONCLUSIONS: Recreational outdoor burns were extremely common injuries leading to loss of functional employment and prolonged physical therapy requirements. Small children and intoxicated adults comprised the majority of our study population. The impact and severity of such outdoor fires could be greatly affected by appropriate attention to prevention.

The effects of vitamin C supplementation on biomarkers of oxygen radical generated damage in human volunteers with "low" or "high" cholesterol levels.

A human volunteer study was conducted to test the effect of vitamin C supplementation on biomarkers of oxygen radical-mediated damage in individuals with a range of serum cholesterol levels. A group of 48 non-smokers, 24 men and 24 women, was selected from a panel of over 100 volunteers to give as wide a range of serum cholesterol levels as possible. None of the volunteers was taking medication to control cholesterol levels and they maintained their normal dietary habits so as not to compromise their cholesterol status. Volunteers were allocated to three groups of 16, each consisting of four males with low cholesterol levels (< 6 mmol/L) matched for age and build with four males with high cholesterol levels (> 6 mmol/L) and eight females matched in the same way. A three-treatment, three-treatment period, cross-over design was adopted to take account of any temporal differences in response. The three treatments given were placebo, 60 mg vitamin C/day (the recommended daily allowance) and 6 g vitamin C/day. Each treatment was given for 14 days with 6 weeks between the treatment periods. All procedures were performed to the standards of Good Clinical Practice. Blood samples were taken at the end of each treatment period. Serum was assayed for cholesterol whilst vitamin C, total antioxidant capacity, lipid peroxidation breakdown products and ras p21 protein levels were measured in plasma. Lymphocytes were examined for DNA damage using the Comet assay and chromosome aberration test. The Comet assay was conducted with and without challenge with hydrogen peroxide and the chromosome aberration test with and without challenge with bleomycin. Vitamin C supplementation caused a statistically significant increase in plasma vitamin C concentrations and total antioxidant capacity but did not affect cholesterol levels or ras p21 protein levels. There was a non-significant dose-related decrease in lipid peroxidation breakdown products with vitamin C supplementation. No effect on DNA damage was observed in the Comet assay, either with or without hydrogen peroxide challenge, or in the chromosome aberration test without bleomycin. However, a statistically significant increase in bleomycin-induced aberrations was found after vitamin C supplementation. This may be due to effects of vitamin C on iron status. Comparison of male and female subjects showed statistically significant differences in plasma vitamin C levels, the antioxidant capacity of the plasma and the number of chromosome aberrations induced by bleomycin challenge of lymphocytes in vitro. The results were the same for both low and high cholesterol subjects. This study provides no evidence of a beneficial effect on any of the biomarkers studied of vitamin C supplementation over a short-term supplementation period of 2 weeks in a population of healthy, non-smoking individuals eating a nutritionally adequate diet.

A study of the toxic hazard that might be associated with the consumption of green potato tops.

Eating green potatoes has reportedly led to poisoning attributed to potato glycoalkaloids (PGA), primarily alpha-solanine and alpha-chaconine. Concentrations of PGA increase during the greening of potatoes but are reportedly much higher in potato tops (leaves). As it is known that members of the UK Bangladeshi community consume potato tops, a study of the toxic hazard that may be associated with the consumption of green potato tops has been carried out. PGA in seven potato varieties were determined by HPLC. Tubers protected from light contained 0.05-0.65 mg/100 g alpha-solanine and 0.3-0.63 mg/100 g alpha-chaconine. Concentrations in leaf samples ranged from 0.64 to 22.6 mg alpha-solanine/100 g and 0.06 to 55.7 mg alpha-chaconine/100 g. Aqueous leaf extracts were cytotoxic to Chinese hamster ovary cells and lysed human, rat and hamster blood cells with no difference in sensitivity among species. Oral administration of potato tops to rats, mice and Syrian hamsters had no adverse effects at the highest practicable dose. A mixture of alpha-solanine and alpha-chaconine (1:1, w/w) given orally at doses of up to 50 mg/kg body weight to hamsters had no effect, but a single ip injection of 25 mg/kg body weight or greater was lethal, with bleeding in the gut. High concentrations of cytotoxic PGA were found in some potato tops, but their effect in laboratory animals was minimal. It is concluded that the consumption of moderate quantities of potato tops (2-5 g/kg body weight/day) is unlikely to represent an acute health hazard to humans.

Development of cell culture techniques for assessment of the toxicity of plant products.

Plant products consumed by humans contain a wide variety of both beneficial and toxic compounds. Studies have been undertaken to explore the utility of cell culture techniques in testing plant products for toxicity and antitoxicity. Preliminary results are reported on the cytotoxic effects of aqueous and methanol extracts of a range of conventional and herb teas and a variety of vegetables. The teas were tested in primary cultures of rat hepatocytes, using lactate dehydrogenase release and inhibition of protein synthesis as endpoints of cytotoxicity. Toxicity was detected in aqueous preparations but not in methanol extracts. Korean green tea and a conventional black tea were more toxic than herb teas such as comfrey and ragwort, which are thought to contain hepatotoxic pyrrolizidine alkaloids. Extracts of five vegetables were tested using the same assays and also the MTT assay in hepatocytes and the Kenacid blue assay in Chinese hamster ovary (CHO) cells. Toxicity to hepatocytes was low but most extracts were more toxic to CHO cells. The toxicity of cabbage was reduced by cooking and that of potato was increased by greening, which increases the levels of glycoalkaloids and other toxins in the tubers. The results suggest a number of ways in which cell culture tests may be useful for detecting and assessing the effects of toxins and antitoxins in plant products.

Induction of polyploidy in human lymphocytes in vitro by excess adenine, but not by adenosine.

It is known that high levels of DNA precursors can be both clastogenic and mutagenic in cultured cell lines and in vivo. The purpose of the present study was to examine at an observational level the cytogenetic effects of adenine and adenosine in primary human cell cultures. Human peripheral blood lymphocytes from four donors were cultured and treated with a range of concentrations of adenine and adenosine. Although no increase in sister chromatid exchange (SCE) frequency was observed with either compound, there was a statistically significant, dose-related increase in the proportion of polyploid cells in cultures treated with adenine, but not in those treated with adenosine. Some of the polyploid metaphases found after adenine treatment contained diplochromosomes, suggesting that endoreduplication might have been involved in polyploid formation in these cells. It is concluded that a high level of adenine can cause genetic changes in human lymphocytes by interfering with mitosis, perhaps by disturbing the balance of DNA precursor pools.