Investigating unexpected INRs: in search of the culprit--adherence, interactions, genetics, and superwarfarin.

Treatment with coumarin derivatives is highly individualised due to high intra- and inter-individual variation in dose response and risks of severe bleeding or thromboembolic complications. Treatment focuses on reaching and maintaining a stable target international normalised ratio (INR). However, unexpected INRs that are not explained by noncompliance or vitamin K intake may occur. Here we describe seven cases of unexpected INRs, and provide clues that clarify the underlying mechanism.

Nystatin allergy. Petrolatum is not the optimal vehicle for patch testing.

Testing with various bases in a case of contact allergy to nystatin showed that polyethylene glycol is preferable to petrolatum as a test vehicle. The literature on nystatin allergy is reviewed.

Tissue concentrations after a single-dose, orally administered ofloxacin in patients with diabetic foot infections.

We studied the penetration of orally administered ofloxacin at the site of diabetes-related foot infections in patients with a planned debridement of the lesion. A total of nine patients received 800 mg of oral ofloxacin 120 to 150 minutes before surgery. During surgery, vital margin tissue and a serum sample were obtained. Serum and tissue concentrations of ofloxacin were measured. From seven patients sufficient amounts of tissue were obtained. Mean serum concentration was 7.0+/-3.5 mg/liter; mean tissue concentrations was 11.5+/-8.4 mg/kg. Mean serum and tissue concentrations exceed the minimal inhibitory concentration90 (MIC90) of commonly involved pathogens. This indicates that orally administered ofloxacin can be an effective treatment for infected diabetic foot lesions.

[Contact allergy to eyedrops containing beta-blockers]. / Contactallergie voor oogdruppels met beta-blokkers.

In six patients (4 women aged 80, 62, 43 and 52 years and 2 men aged 58 and 51 years), who used eyedrops containing beta-blockers for the treatment of glaucoma, allergic contact dermatitis of the eyelids was diagnosed. Three were allergic to metipranolol, 2 to levobunolol and 1 to timolol. In literature, less than 50 cases of hypersensitivity to beta-blockers in eye medication have been reported. There are, however, reasons to assume that sensitization is more frequent: (a) not all patients are referred by the ophthalmologist to the dermatologist; (b) false-negative reactions to patch tests with the commercial preparations and with beta-blockers are not infrequent; (c) they are not routinely tested because beta-blockers are difficult to obtain in pure form; (d) cross-reactions with other beta-blockers are infrequent, and changing to another preparation therefore usually solves the clinical problem. Nevertheless it is advisable to test a battery of beta-blockers (befunolol, levobunolol, metipranolol, timolol) in allergic patients. A test preparation of 2% in water or 3%-10% in petrolatum may be suitable. Control testing in non-exposed individuals is necessary to exclude irritation reactions.

[Factitious insulinoma]. / Nagebootst insulinoom.

A 32-year-old woman was admitted with signs of recurrent hypoglycaemia. Within 72 hours hypoglycaemia was successfully provoked by prolonged fasting. Also, blood samples demonstrated high levels of serum insulin and C-peptide and the insulin-glucose ratio was abnormally high. An insulinoma was strongly suspected. However, extensive imaging displayed no tumour in the pancreas. The patient also had extensive psychological and social problems. The psychiatrist suggested a factitious disorder. High serum concentrations of insulin and C-peptide in combination with the psychiatric disorder led to the suspicion of abuse of sulfonylurea derivatives by the patient. This was confirmed by toxicological screening. A patient with unexplained hypoglycaemia, especially if an insulinoma cannot be detected, should be suspected of abusing sulfonylurea derivatives.

Pharmacogenetics: from bench to byte.

Despite initial enthusiasm, the use of pharmacogenetics has remained limited to investigation in only a few clinical fields such as oncology and psychiatry. The main reason is the paucity of scientific evidence to show that pharmacogenetic testing leads to improved clinical outcomes. Moreover, for most pharmacogenetic tests (such as tests for genetic variants of cytochrome P450 enzymes) a detailed knowledge of pharmacology is a prerequisite for application in clinical practice, and both physicians and pharmacists might find it difficult to interpret the clinical value of pharmacogenetic test results. Guidelines that link the result of a pharmacogenetic test to therapeutic recommendations might help to overcome these problems, but such guidelines are only sparsely available. In 2001, an early step was taken to develop such guidelines for the therapeutic use of antidepressants, and these included CYP2D6-related dose recommendations drawn from pharmacokinetic study data. However, the use of such recommendations in routine clinical practice remains difficult, because they are currently outside the ambit of the clinical environment and are not accessible during the decision-making process by physicians and pharmacists, namely the prescription and dispensing of drugs.

Contact allergy to furazolidone.

A case of occupational contact allergy to furazolidone, used as an animal feed additive and as an antimicrobial drug in veterinary medicine, is described. The patient did not react to furazolidone 2% pet. Using PEG-400 and alcohol as patch test vehicles resulted in positive patch test reactions. No cross-reactions were observed to other nitrofuran derivatives (nitrofurazone, nitrofurantoin) or to furfural. The literature on contact allergy to nitrofurans is reviewed.

Systemic allergic contact dermatitis from intravesical instillation of the antitumor antibiotic mitomycin C.

6 cases of contact allergy to the antitumor antibiotic mitomycin C from intravesical instillation are described. Reports suggest that up to 9% of patients treated with mitomycin C for chemoresection/prevention of superficial bladder cancer will develop cutaneous side-effects. Patients may present either with vesicular dermatitis of the hands and feet and/or dermatitis of the genitals, or with more widespread eruptions. Probably most, if not all, skin reactions are caused by contact allergy. The distribution is suggestive of systemic contact dermatitis from mitomycin C absorbed from the vesical mucosa.