Suspected lamotrigine-induced toxic epidermal necrolysis

OBJECTIVE: To describe a patient who developed toxic epidermal necrolysis (TEN) possibly secondary to lamotrigine use. CASE SUMMARY: A 74-year-old white man with a history of probable complex partial seizures was admitted to the neurology service for a prolonged postictal state. His antiepileptic regimen was changed while he was in the hospital to include lamotrigine. After 19 days of hospitalization and 14 days of lamotrigine therapy, the patient became febrile. The next day he developed a rash which progressed within 4 days to TEN, diagnosed by skin biopsy. All suspected drugs were discontinued, including lamotrigine. The patient was treated with hydrotherapy in the burn unit. His symptoms improved and he was discharged from the hospital 26 days after the rash developed. DISCUSSION: During lamotrigine's premarketing clinical trials, the manufacturer reported several cases of Stevens-Johnson syndrome and TEN. There are several published case reports of lamotrigine-induced severe skin reactions. All of these reports included patients being treated with both valproic acid and lamotrigine. Our patient was exposed to phenytoin, carbamazepine, clindamycin, and lamotrigine, but not valproic acid. The patient reported prior use of phenytoin with no skin rash. Carbamazepine was the antiepileptic drug the patient was maintained on prior to his hospital admission, and the symptoms of TEN resolved while he was still receiving carbamazepine. The patient received only two doses of clindamycin, which makes this agent an unlikely cause of TEN. CONCLUSIONS: Because of the temporal relationship of the onset of the patient's rash and several drugs that are known to cause severe rashes, it is not certain which drug was the definite culprit. However, based on the evidence from the literature, lamotrigine appears to be the causative agent.     

Screeing of toxic isolates of Fusarium poae and Fusarium sporotrichiodes involved in causing alimentary toxic aleukia

A total of 131 isolates of Fusarium poae and F. sporotrichioides from overwintered cereals, which were associated with the alimentary toxic aleukia toxicoses in the Soviet Union, were tested for their ability to produce T-2 toxin [4 beta, 15 diacetoxy-8alpha-(3-methylbutyryloxy)-12,13-epoxytrichothec-9-en 3alpha-ol]. The presence of T-2 toxin was determined by thin-layer chromatography, gas-liquid chromatography, spectroscopic analyses, and the rabbit skin test. A good correlation was demonstrated between T-2 toxin dectetion by thin-layer chromatography and inflammatory skin reactions of rabbits.     

Bacterial biosensors for monitoring toxic metals

Biosensors utilize biological components to provide selectivity for monitoring compounds of environmental, clinical and industrial importance. A number of biosensors based on bacteria have recently been developed for monitoring toxic metals in the environment. The advantages and disadvantages of these types of biosensors are discussed.     

Perioperative monitoring of potentially toxic drugs

A list of drugs considered to have a narrow therapeutic margin are discussed. These potentially toxic drugs will be reviewed, including recommended therapeutic ranges, when therapeutic levels should be obtained, and additional laboratory studies that may be required for patients on these medications who are preparing to undergo surgery.     

Compatibility of toxic Chinese medicines]

This article expounds the suitable compatibility and incompatibility in using toxic Chinese medicines in respects of reducing toxicity, raising curative effect, enhancing toxicity and reducing curative effect. Meanwhile it discusses the compatibility mechanism of toxic Chinese medicines in combination with the studies of clinical and modern experiments.     

Acute toxic effects of fragrance products

To estimate the prevalence of urinary stone disease in Koreans, and to determine the inter-relationships between urinary stone disease and various epidemiological factors, 1,521 controls and 1,177 cases with urinary stones were evaluated. Of special interest in this study were: 1) proportion of past urinary stone history among controls; 1.9% 2) the point prevalence rate of urinary stones among controls; 0.2% 3) the recurrence rate of urinary stones (the proportion of past history of urinary stone) among cases; 56.8% 4) high incidences (76.3%) in the thirties to the fifties among cases 5) the risk factors for urolithogenesis; obesity [higher than 25 of BMI (body mass index, weight/height2)], more than 10 year-experience as a production worker, past stone history, familial stone history, low physical activity (< 2,000 Kcal/day), and low intake of fruit. However, the well-known risk factors for urinary stones; over intake of meat or fish and milk or dairy products, perspiration, amount and kind of drinking water, and stress unexpectedly were not significantly different between the controls and the cases.     

Gelatinases in drug-induced toxic epidermal necrolysis

BACKGROUND: The matrix metalloproteinases (MMPs) MMP2 and MMP9 play a significant role in epidermal detachment, inflammation and re-epithelialization. We have evaluated their activity in toxic epidermal necrolysis (TEN). DESIGN: The level and pattern of activity of MMP2 and MMP9 were investigated by measuring the degradation of 3H-labelled gelatin and by zymography in blister fluid from six TEN patients and compared the results with three other blistering conditions: bullous pemphigoid (n = 6), second-degree burn (n = 13) or suction blister (n = 3). RESULTS: A higher amount of MMP2 was found in TEN blister fluid with the constant presence of a significantly larger proportion of the activated forms of MMP2, a particular feature of TEN, than the other blistering diseases studied. CONCLUSION: This study emphasizes the potential role of MMP2 in the specific inflammatory reaction and reparation process in TEN skin.     

An integrated process for the production of toxic catechols from toxic phenols based on a designer biocatalyst

We describe the biocatalytic production of 3-phenylcatechol from 2-phenylphenol with the whole cell biocatalyst Escherichia coli JM101 (pHBP461). The recombinant produces 2-hydroxybiphenyl 3-monooxygenase, an enzyme from Pseudomonas azelaica HBP1. This enzyme introduces a hydroxyl-group at the C3-position of a variety of 2-substituted phenols, such as 2-phenylphenol. This permits the biocatalytic production of 3-substituted catechols, which are difficult to synthesize chemically. Both 2-phenylphenol and 3-phenylcatechol are highly toxic to E. coli. The toxic effects of 2-phenylphenol were minimized by feeding this substrate to the reactor at a rate slightly below the maximum biooxidation rate. As a result, the substrate concentration in the reactor remained below toxic levels during the bioconversion. The toxic product formed was removed by continuous adsorption on the solid resin Amberlite XAD-4. To this end the reaction mixture, containing the biocatalyst, was pumped continuously through an external loop with a fluidized bed of the resin. This resin efficiently and quantitatively adsorbed both 3-phenylcatechol and the remaining trace amounts of 2-phenylphenol. Consequently, the concentrations of these compounds were kept at subtoxic levels (below 100 mg L-1) and gram amounts of 3-phenylcatechol were produced with space-time yields of up to 0.39 g L-1 h-1. The product was recovered from the resin by acidic methanol elution and purified by recrystallization from n-hexane resulting in overall yields exceeding 59%. The optimized system served as a surprisingly simple and efficient integrated process, that allows the bioconversion of toxic substrates to toxic products with whole cell biocatalysts.     

Streptococcal toxic shock syndrome complicating preseptal cellulitis

PURPOSE: To document the static nature of crystalline deposits in talc retinopathy. METHOD: Case report. RESULTS: A 38-year-old woman with a remote history of intravenous drug abuse showed the incidental finding of fine, irregularly shaped refractile deposits in the retinal microvasculature. At 2-year follow-up, fundus findings were identical to the initial manifestation with respect to the distribution and position of crystalline deposits in each fundus. CONCLUSION: This case documents the static nature of crystalline deposits in talc retinopathy.     

Genome-linked toxic responses to dietary iron overload

Genome-related differences to Fe overload between and within rodent species were evaluated in the present study. Male B6C3F1 mice, yellow and black C5YSF1 mice, and Fischer 344 (F344) rats were fed AIN-76A diets containing 35 (control), 1,500, 3,500, 5,000, or 10,000 micrograms carbonyl Fe/g for 12 wk. No effects on body weight gain were observed in the B6C3F1 and black C5YSF1 mice, whereas at all doses of Fe above the control, weight gain was reduced in yellow C5YSF1 mice and F344 rats. At the 10,000 micrograms Fe/g dose, 9 of 12 rats died, but there was no mortality among the mice. In all animals, there was a dose-related increase in liver nonheme Fe, and the Fe was stored in hepatocytes predominantly in the periportal region. There was significant hypertrophy of the hepatocytes in both B6C3F1 mice and F344 rats fed the 10,000 micrograms Fe/g diet. PCNA assays showed significant stimulatory effects of the high dose of Fe on hepatocyte proliferation in the F344 rats and the C5YSF1 mice but not in the B6C3F1 mice. In the rat, there was pancreatic atrophy with loss of both endocrine and exocrine tissue. Morphometric evaluation of pancreas showed fewer beta cells in B6C3F1 and yellow C5YSF1 mice but not in the black C5YSF1 mice. There were fewer islets in the yellow C5YSF1 mice, and total and mean islet areas were smaller than in the control mice. Rats in the 10,000 micrograms Fe/g dose group had markedly exacerbated dose-dependent nephropathy and changes in glomerular and tubular epithelium associated with Fe accumulation. The rats also showed degeneration of the germinal epithelium of the testis, formation of multinucleated giant cells, and lack of mature sperm.     

Surgical management of toxic goitre in Khartoum

Seventy patients with toxic goitre treated surgically in two surgical firms in Khartoum during a 10-years period were studied. Of these patients 62.9% had diffuse goitres, 34.3% nodular and 2.8% hot clinically solitary nodules. The age ranged between 15 and 54 years and the M:F ratio was 1.0:6.7. Ninety per cent of the patients had large size goitres (grade III). Preoperative carbimazole and inderal were found to be superior to other drug combinations. Subtotal thyroidectomy was the standard procedure and no serious postoperative complications were noted. Fifteen patients had postoperative hectic period i.e. fever, headache and tachycardia that responded to temporary inderal and steroids. Surgical treatment of toxic goitre in developing countries could be extended to include more patients since drug availability and patient compliance are minimal.