[Oral diagnosis of vitamin B12 deficiency due to long-term metformin treatment: a case report]. / Diagnostic buccal d´une carence en vitamine B12 due à un traitement au long court avec le metformine: à propos d´un cas.

Metformin is the first line treatment for type 2 diabetes. It is also indicated in patients with insulin-resistant type 1 diabetes. It has several benefic effects on carbohydrate metabolism, weight loss and vascular protection. However, it can also cause serious adverse reactions such as the risk of anemia associated with long term use. It has been reported that long-term metformin use might reduce serum vitamin B12 levels. Oral signs combining Hunter glossitis and stomatodynia may be revelatory and lead to early diagnosis of vitamin B12 deficiency. We here report the case of a female patient who had had these oral signs for 2 years and whose laboratory tests revealed normocytic anemia with iron and vitamin B12 deficiency. The diagnosis of vitamin B12 deficiency due to long-term metformin was suspected while excluding other potential causes. Intramuscular hydroxocobalamin injection associated with oral iron led to the normalization of serum levels and to the disappearance of clinical signs. The patient was referred to a specialized center for further etiological assessment. This clinical case highlights the essential role of dentists in early diagnosis of vitamin B12 deficiency and the prevention of its progression, which can be dramatic in the case of late discovery.

Metabotropic glutamate receptor 5 contributes to inflammatory tongue pain via extracellular signal-regulated kinase signaling in the trigeminal spinal subnucleus caudalis and upper cervical spinal cord.

BACKGROUND: In the orofacial region, limited information is available concerning pathological tongue pain, such as inflammatory pain or neuropathic pain occurring in the tongue. Here, we tried for the first time to establish a novel animal model of inflammatory tongue pain in rats and to investigate the roles of metabotropic glutamate receptor 5 (mGluR5)-extracellular signal-regulated kinase (ERK) signaling in this process. METHODS: Complete Freund's adjuvant (CFA) was submucosally injected into the tongue to induce the inflammatory pain phenotype that was confirmed by behavioral testing. Expression of phosphorylated ERK (pERK) and mGluR5 in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were detected with immunohistochemical staining and Western blotting. pERK inhibitor, a selective mGluR5 antagonist or agonist was continuously administered for 7 days via an intrathecal (i.t.) route. Local inflammatory responses were verified by tongue histology. RESULTS: Submucosal injection of CFA into the tongue produced a long-lasting mechanical allodynia and heat hyperalgesia at the inflamed site, concomitant with an increase in the pERK immunoreactivity in the Vc and C1-C2. The distribution of pERK-IR cells was laminar specific, ipsilaterally dominant, somatotopically relevant, and rostrocaudally restricted. Western blot analysis also showed an enhanced activation of ERK in the Vc and C1-C2 following CFA injection. Continuous i.t. administration of the pERK inhibitor and a selective mGluR5 antagonist significantly depressed the mechanical allodynia and heat hyperalgesia in the CFA-injected tongue. In addition, the number of pERK-IR cells in ipsilateral Vc and C1-C2 was also decreased by both drugs. Moreover, continuous i.t. administration of a selective mGluR5 agonist induced mechanical allodynia in naive rats. CONCLUSIONS: The present study constructed a new animal model of inflammatory tongue pain in rodents, and demonstrated pivotal roles of the mGluR5-pERK signaling in the development of mechanical and heat hypersensitivity that evolved in the inflamed tongue. This tongue-inflamed model might be useful for future studies to further elucidate molecular and cellular mechanisms of pathological tongue pain such as burning mouth syndrome.

[Severe skin reaction with mucous membrane inflammation during MINE chemotherapy]. / Réaction cutanée sévère avec mucite au cours d'une chimiothérapie de type MINE.

BACKGROUND: MINE chemotherapy is used to treat refractory Hodgkin's disease. Cutaneous adverse effects of MINE regimen are uncommon and chiefly consist of erythema and oedema of the extremities. More recently, a number of cases of panniculitis and subcutaneous inflammatory oedema have been described. OBSERVATION: We report the case of a 17-year-old girl developing acute and painful oedema of the limbs with panniculitis of the trunk. This incident was associated with inflammatory lesions of mucous membrane, in particularly in the genital area and on the tongue. These signs occurred 7 days after initiation of MINE chemotherapy, with no other drugs being introduced. A drug-induced reaction was suspected due to the absence of any other aetiology, particularly infectious disease. The condition gradually improved with symptomatic pain therapy. The patient's chemotherapy was subsequently modified. DISCUSSION: The chronology of the symptoms, spontaneous improvement after the end of treatment, and the absence of other potential causative factors resulted in a hypothesis of a cutaneous adverse reaction to the MINE regimen. The signs could be due to capillary leak syndrome resulting from the toxicity of vinorelbine on endothelial cells. Dermatologists should be aware of these cutaneous adverse effects and of the inflammatory lesions of mucous membrane newly described herein.

Massive tongue swelling in refractory status epilepticus treated with high-dose pentobarbital.

INTRODUCTION: The potential causes of acquired macroglossia are extensive. The authors report two cases of subacute marked tongue swelling resulting in airway compromise in patients with refractory status epilepticus requiring prolonged pentobarbital coma. METHOD: The hospitalization histories of the reported patients were retrospectively reviewed. RESULT: The tongue swelling completely resolved in one case and significantly improved in the other after discontinuation of pentobarbital infusion or switching to phenobarbital. The authors speculate that the causes were multifarious, likely a combination of localized angioedema due to barbiturate vehicle and triggered by an initial tongue bite. CONCLUSION: Progressive tongue swelling causing airway obstruction can occur well beyond the acute phase of status epilepticus and may potentially cause problems with extubation in nontracheotomized patients.

Adverse events associated with chlorhexidine use: results from the Department of Veterans Affairs Dental Diabetes Study.

BACKGROUND: The authors report adverse events (AEs) related to the use of chlorhexidine gluconate mouthrinse in a clinical trial of the efficacy of periodontal treatment in older adults with diabetes. METHODS: Participants were U.S. veterans with uncontrolled diabetes (hemoglobin A(1c) value > or =8.5 percent) and periodontal disease. Treatment included periodontal scaling, 0.12 percent chlorhexidine lavage during ultrasonic scaling and use of chlorhexidine mouthrinse at home. RESULTS: Forty-four (31 percent) of 140 subjects reported having AEs. Most common were taste changes and tooth staining, sore mouth and/or throat, tongue irritation and wheezing/shortness of breath; the latter was reported more commonly before chlorhexidine use than after. Only body mass index greater than 30 was significantly related to AEs. CONCLUSIONS: AEs are common among subjects using chlorhexidine mouthrinse. Most AEs (taste change and staining) were resolved easily by subjects' discontinuing mouthrinse use and receiving dental prophylaxis. No serious AEs were reported. CLINICAL IMPLICATIONS: Clinicians should advise patients using chlorhexidine mouthrinse of possible side effects. If necessary, patients should discontinue mouthrinse use and obtain medical care. Careful monitoring of AEs in patients using chlorhexidine is warranted.

Effect of food on the pharmacokinetics of erlotinib, an orally active epidermal growth factor receptor tyrosine-kinase inhibitor, in healthy individuals.

The effects of food on the pharmacokinetics of erlotinib were investigated in two open-label, randomized studies. In a single-dose crossover study (n = 18), 150 mg of erlotinib was administered under either fasting or fed conditions. In the first period, an approximate doubling in the area under the plasma concentration-time curve was evidenced by the geometric mean ratio (GMR) of 2.09 observed under fed conditions; whereas, in the second period there was a decrease, with a GMR of 0.93. In a multiple-dose parallel study (n = 22), 100 mg of erlotinib was administered daily for 8 days, either 7 days of fasting followed by feeding on day 8, or the reverse sequence. In this study, food resulted in an increase in the plasma concentration-time curve on day 1, with a GMR of 1.66 (P = 0.015). In contrast, there was only a 37% increase on day 7, with a GMR of 1.34 (P = 0.252). These studies indicate that food can substantially increase plasma exposure to erlotinib. Given the maximum tolerated dose of erlotinib used in clinical practice, we recommend that erlotinib be taken under conditions of fasting.

[Stomatitis, glossitis, and esophagitis in a patient treated with minocycline]. / Stomatitis, Glossitis und Osophagitis unter Minocyclin.

After 10 days of minocycline therapy, stomatitis, glossitis and esophagitis were seen in a 62-year-old male patient, who had previously tolerated minocycline for > 20 years without complications. This typical side effect of minocycline was initially misinterpreted in the differential diagnosis and was only diagnosed, when the patient was reexposed to a new 7-day minocycline therapy. Healing was achieved by termination of the minocycline therapy and the initiation of antimycotic treatment.

[Tongue angioedema associated with angiotensin-converting enzyme inhibitor (diagnosis, differential diagnosis, treatment)]. / Liezuvio saknies angioedema, kuria sukele angiotenzina konvertuojancio fermento inhibitorius (diagnostika, diferencine diagnostika, gydymas).

Angioneurotic edema is a rare (0.1-0.2%) but potentially life-threatening side effect of angiotensin-converting enzyme inhibitors. It can result in serious respiratory distress, airway obstruction and death. Angiotensin-converting enzyme inhibitors associated angioedema is clinically poorly recognized and frequently underestimated condition. A case history of patient with angioneurotic edema due to treatment with ramipril is presented. A 51-year-old man has been sequentially treated for two years with atenolol, indapamide, enalapril, and fosinopril due to primary arterial hypertension. When the treatment was switched to ramipril 5 mg twice a day the fourth dose of the drug was followed by swelling of lips, tongue, and pharynx without symptoms of airway obstruction. Ramipril was discontinued, prednisolone 120 mg and loratidine 10 mg were given. Symptoms of angioedema gradually disappeared. Mechanisms of angioedema are not fully clear. Pharmacological action of angiotensin-converting enzyme inhibitors on bradykinin and substance P, immunological mechanisms and disarrangements in complement system are discussed. Treatment includes immediate withdrawal of angiotensin-converting enzyme inhibitors and acute therapy with epinephrine 0.3-0.5 ml subcutaneous, 50 mg diphenhydramine s/c or i/v, 40-50 mg methylprednisolone. Future treatment with angiotensin-converting enzyme inhibitors is contraindicated.

A review of drug-induced oral reactions.

Every drug can produce untoward consequences, even when used according to standard or recommended methods of administration. Adverse drug reactions can involve every organ and system of the body and are frequently mistaken for signs of underlying disease. Similarly, the mouth and associated structures can be affected by many drugs or chemicals. Good oral health, including salivary function, is very important in maintaining whole body health. Regarding different parts of the oral system, these reactions can be categorized to oral mucosa and tongue, periodontal tissues, dental structures, salivary glands, cleft lip and palate, muscular and neurological disorders, taste disturbances, drug-induced oral infection, and facial edema. In this article, the drugs that may cause adverse effects in the mouth and related structures are reviewed. The knowledge about drug-induced oral adverse effects helps health professionals to better diagnose oral disease, administer drugs, improve patient compliance during drug therapy, and may influence a more rational use of drugs.

Topical administration of a doxorubicin-specific monoclonal antibody prevents drug-induced mouth apoptosis in mice.

One of the most severe side effects of anti-tumour chemotherapy is mucositis due to drug toxicity for rapidly dividing cells. We show here that anti-DXR monoclonal antibodies can prevent DXR-induced damage. Indeed, apoptosis, confined to the proliferative compartment of the basal mucosa, observed in the tongue of DXR-treated mice was completely inhibited by topical application of the anti-DXR antibodies.

A form of stomatitis induced by excessive peppermint consumption.

This paper reports on a form of stomatitis and glossitis associated with extremely prominent circumvalate papillae in two patients who consumed excessive amounts of mint-flavoured sweets.

Oral side-effects of the most frequently prescribed drugs.

Oral side-effects and their respective prevalence rates for the 200 most frequently prescribed drugs for 1992, as measured by IMS America's National Prescription Audit is reviewed. Accounting for duplication due to brand and generic name listings, the actual number of different medications covered was 131. The results of this review are presented in a table and include the oral side-effects and prevalences as reported in the literature. The three most frequent side-effects encountered with these medications were xerostomia (80.5%), dysgeusia (47.5%), and stomatitis (33.9%). The included table should fill the need for a ready reference for dentists in monitoring and counseling patients regarding the potential oral side-effects of the medications.

[Cytostatic-induced stomatitis]. / Zytostatika-induzierte Stomatitis.

45 patients with oral cancer preoperatively received regional intraarterial chemotherapy (RIAC). All patients developed stomatitis or glossitis limited to the region of cytostatic perfusion. Between 1 and 19 days (median 4 days) after RIAC the tumor was removed by hemiglossectomy, partial resection of the floor of the mouth etc. The tissue alterations induced by chemotherapy in these surgical specimens were analyzed histomorphologically. Stomatitis due to RIAC was characterized by necrosis, ulceration and severe epithelial dysplasia of mucous membranes. Approximately 2 weeks after chemotherapy both the inflammatory changes and the dysplasia had disappeared completely. The differences between spontaneous premalignant dysplasia of the oral cavity and dysplasia induced by RIAC are discussed.