Amelioration of methotrexate-induced malabsorption by vitamin A

Since the early 1960s the Brief Psychiatric Rating Scale (BPRS) has been one of the most frequently used standardized methods in international psychiatric research. The BPRS is used mainly for the rating of psychopathological symptoms of schizophrenic subjects. According to the results of factorial analyses, the original version of the BPRS is divided into five subscales, which have been preserved in the German translation. The validity of this original scale structure for the German BPRS version has not been investigated, however. A principal-components analysis of the 18 BPRS items carried out on the data of 301 schizophrenics yielded four factors that are comparable with four of the original subscales: Thought disturbance, Hostility/suspiciousness, Anxiety/depression, and Anergia. These results are compared with earlier findings and similarities and differences are discussed.     

Preventive effects of germinated barley foodstuff on methotrexate-induced enteritis in rats

The preventive effects of the dietary germinated barley foodstuff (GBF), which increases the contents of protein, RNA and DNA in the intestinal mucosa of rats on the mucosal damage and diarrhea were examined in a methotrexate (MTX)-induced enteritis model in rats. Sprague-Dawley rats intraperitoneally injected with MTX (10 mg/kg body weight) were used as an enteritis model. After consumption of diets containing GBF, glutamine or a glutamine-rich stuff (gluten), mucosal damage, contents of mucosal protein, RNA and DNA, myeloperoxidase (MPO) activity, bacterial translocation and DNA synthetic activity in the small intestine were assessed. GBF more effectively prevented diarrhea and mucosal damages, and increased mucosal protein, DNA and RNA contents than glutamine or gluten. The bacterial trans-location and elevation of MPO activity induced by MTX were depressed only by the consumption of GBF. GBF has a potential as therapeutic diet to decrease the adverse effects of anti-cancer chemotherapy.     

Vesicular stomatitis in the horse

Inactivation of the mitochondrial respiratory chain in response to iron-induced oxidative stress has been studied in cultured cells. Iron loading resulted in malonaldehyde production, decreased levels of glutathione and reduced specific activities of both complexes I and IV of the respiratory chain. These results are discussed with respect to idiopathic Parkinson's disease, which is associated with increased iron levels and a specific decrease in complex I activity in the substantia nigra.     

Chronic ulcerative stomatitis

Chronic ulcerative stomatitis (CUS) has recently been described as a new disease entity characterized by chronic ulceration of oral mucosa which responds to treatment with hydroxychloroquine. It has a particular type of stratified epithelium-specific, antinuclear autoantibody as an immunological marker. Twelve cases have been reported in the literature. We present a 40-year-old woman with an 11-year history of chronic oral ulcerations. Other dermatological diseases, including oral lichen planus, pemphigus vulgaris and cicatricial pemphigoid, as well as bullous lupus erythematosus, were excluded. The clinical diagnosis of CUS was confirmed on the grounds of the immunological and ultrastructural findings. The lesions initially responded to high doses of systemic corticosteroids but relapsed promptly after dose reduction. Dapsone was ineffective. Hydroxychloroquine, given at a dosage of 200-400 mg/day, led to a complete and long-lasting remission.     

Allopurinol blocks shock-wave-induced rises in cytosolic calcium levels in MDCK cells

OBJECTIVE: To evaluate physicians' probability estimates of acute appendicitis based on structured collection of clinical data. DESIGN: Open prospective study. SETTING: District hospital, Norway. SUBJECTS: 304 patients admitted with suspected acute appendicitis. INTERVENTIONS: Initial diagnostic accuracy of physicians was compared with corresponding results from a computer model. MAIN OUTCOME MEASURES: The estimated probabilities of appendicitis in different testing groups were analysed using receiver operating characteristic (ROC) curves. RESULTS: Physicians' estimates had a mean area under ROC-curve of 0.81 (95% CI 0.79 to 0.82), not significantly different from the computer model. Both correlated well with the actual rate of appendicitis, but the physicians tended to overestimate the probability by 10%. CONCLUSION: Physicians' probability estimates perform rather well. Further attempts to implement a probabilistic approach in the diagnostic process of acute appendicitis therefore seem justified.     

Allopurinol hypersensitivity syndrome: hypersensitivity to oxypurinol but not allopurinol

OBJECTIVE: We assessed the clinical, histological, and virological features of anogenital human papillomavirus (HPV) infection, according to their immune status in HIV-1 infected men, referred for an anogenital examination or treatment, in comparison with immunocompetent patients. METHODS: The study population comprised 33 HIV-1 infected heterosexual or homosexual men and 38 HIV negative men seen in a screening and treatment centre for anogenital HPV infections. All patients were examined with a colposcope. Biopsies were carried out on all subjects with anogenital lesions for histological studies and HPV detection by Southern blot. RESULTS: The HIV infected patients had a balanopreputial HPV infection in 70%, anal in 30%, and urethral in 37%, while HIV negative patients had balanopreputial lesion in 72%, anal in 26%, and urethral in 16%. Diffuse anogenital lesions were present in 33% of the HIV infected cases and in 10.5% of HIV negative cases (p < 0.02). Among the HIV infected patients, the genital HPV lesions were condylomatous in 67.5% of the cases and dysplastic in 57%. HIV negative patients had condylomatous lesions in 86% of the cases and dysplasic in 14%. The condylomatous lesions of HIV infected patients had a low grade malignant histological aspect in 36% of the cases and high grade histological criteria were found in 22% of the dysplasias. Oncogenic HPVs were detected more frequently in HIV infected patients (35% v 12%) and more than one HPV type was found in 21.5% of cases. Neither the anogenital diffusion of the HPV lesions nor their morphological, histological, and virological features differed significantly in patient with CD4 cell counts > or < 200 x 10(6)/l. In contrast, patients with CD4 cell counts < 50 x 10(6)/l had a higher risk of several types of HPVs and of developing a diffuse anogenital infection. CONCLUSION: HIV-1 infected patients had an increased frequency of high grade anogenital dysplastic lesions and a higher frequency of HPV infection with multiple and diffuse sites of involvement. These characteristics of HPV infection were independent of the patients' immune status up to CD4 cell counts > 50 x 10(6)/l but showed an increased risk when the CD4 cell count was < 50 x 10(6)/l. The higher frequency of diffuse anogenital infections among HIV infected men calls for rapid treatment, laser or surgery, given the association of histological features of intraepithelial neoplasia and the presence of multiple HPV infection sites which may be the consequence of immune disturbances, most of which are transmissible potentially oncogenic HPVs.     

Granulocyte macrophage-colony-stimulating factor mouthwashes heal oral ulcers during head and neck radiotherapy

Methylglyoxal was demonstrated to be a substrate for the isozymes E1, E2 and E3 of human aldehyde dehydrogenase. Pyruvate was the product from the oxidation of methylglyoxal by the three isozymes. At pH 7.4 and 25 degrees C, the major and minor components of the E3 isozyme catalyzed the reaction with Vmax of 1.1 and 0.8 mumol NADH min-1 mg-1 protein, respectively, compared to 0.067 and 0.060 mumol NADH min-1 mg-1 protein for the E1 and E2 isozymes, respectively. The E2 isozyme had a K(m) for methylglyoxal of 8.6 microM, the lowest compared to 46 microM for E1 and 586 and 552 microM for the major and minor components of the E3 isozyme, respectively. Both components of the E3 isozyme showed substrate inhibition by methylglyoxal, with Ki values of 2.0 mM for the major component and 12 mM for the minor component at pH 9.0. Substrate inhibition by methylglyoxal was not observed with the E1 and E2 isozymes. Methylglyoxal strongly inhibited the glycolaldehyde activity of the E1 and E2 isozymes. Mixed-type models of inhibition were employed as an approach to calculate the inhibition constants, 44 and 10.6 microM for E1 and E2 isozymes, respectively.     

Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction

PURPOSE: Methotrexate nephrotoxicity can lead to delayed methotrexate elimination and the development of life-threatening toxicity, which may not be preventable with the standard rescue agent leucovorin. In preclinical studies, we previously demonstrated that carboxypetidase-G2 (CPDG2) rapidly hydrolyzes methotrexate to nontoxic metabolites. A protocol for the compassionate use of CPDG2 in patients who develop nephrotoxicity while receiving high-dose methotrexate was therefore developed. The pharmacologic and clinical outcome of CPDG2 rescue administered with thymidine and leucovorin in 20 patients is presented here. METHODS: Patients with high-dose methotrexate-induced renal dysfunction received one to three doses of CPDG2, 50 U/kg body weight intravenously (i.v.), thymidine 8 g/m2/d by continuous i.v. infusion, and standard pharmacokinetically guided leucovorin rescue. Plasma concentrations of methotrexate and its inactive metabolite 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) were measured before and after CPDG2 using high-pressure liquid chromatography (HPLC). Tolerance of CPDG2 and thymidine, development of methotrexate toxicities, and recovery of renal function were monitored. RESULTS: Twenty patients who received high-dose methotrexate for osteosarcoma (n = 11), lymphoid cancers (n = 8), and gastric cancer (n = 1) developed nephrotoxicity (median serum creatinine, 3.2 mg/dL) and elevated plasma methotrexate concentrations (median, 201 mumol/L at hour 46). CPDG2 and thymidine rescue was well tolerated and resulted in a rapid 95.6% to 99.6% reduction in the plasma methotrexate concentration. Methotrexate-related toxicity was mild to moderate. Serum creatinine returned to normal values at a median of 22 days. CONCLUSION: CPDG2, thymidine, and leucovorin rescue was highly effective in 20 patients at high risk for developing life-threatening methotrexate toxicity after the onset of methotrexate-induced nephrotoxicity and delayed methotrexate excretion.     

In Trinidad: angular stomatitis and pregnancy

Riboflavin deficiency is endemic in Trinidad. A syndrome is observed peculiar to pregnancy. It occurs in the second trimester in women with low blood riboflavin levels. Treatment with riboflavin gives clinical improvement in mothers and raises fetal blood levels. Early biochemical diagnosis and treatment of subclinical deficiency is of value to the Trinidadian mother but protection to the fetus is doubtful. This is because of the effect of multiple limiting factors in which the mother is deficient.     

Thalidomide and recurrent aphthous stomatitis: a follow-up study

AIM: To investigate the effects of dipfluzine (Dip), a new derivative of cinnarizine (Cin), first developed by China, upon 5-hydroxytryptamine (5-HT)-induced contractions in cerebral arteries. METHODS: Compared Dip, flunarizine (Flu), and Cin antagonistic effects and actions on 2-component contractions evoked by 5-HT in isolated pig basilar artery. RESULTS: Dip showed a greater concentration-dependent antagonistic effect on 5-HT-evoked contraction than Cin and Flu in pig basilar artery rings. The order of potency (IC50) was Dip (4.0 mumol.L-1) > Flu (15.6 mumol.L-1) > Cin (25.2 mumol.L-1). All the Dip, Flu, and Cin inhibited 2-components of 5-HT-induced contraction. The antagonistic effects of Dip and Cin on the initial fast-phase contraction (FPC) were greater than that on the sustained tonic-phase contraction (STC), but Flu showed no difference between inhibiting effects on 2-component contractions. CONCLUSION: Dip was more potent than both of Flu and Cin on cerebrovascular dilation, associated mainly with the inhibition of intracellular calcium release.     

Severe erosive stomatitis: association with immunological diseases?

This report presents a 63-year-old Caucasian woman with a malignant blue nevus, which is an extremely rare form of melanoma originating from or associated with a preexisting blue nevus. The background blue nevus on the left upper arm, which had been present for 5 to 6 years, increased in size and darkened in color for 3 months prior to histological diagnosis of malignant blue nevus. Although the tumor looked much like a nodular melanoma clinically, the diagnosis of malignant blue nevus was established histologically. The patient had a poor outcome due to metastatic spread of the tumor to the visceral organs 1 year following the initial excision of the tumor. To distinguish this rare tumor from other melanocytic lesions, strict histological criteria are needed to make the diagnosis of malignant blue nevus. Differential diagnosis includes cellular blue nevus, atypical cellular blue nevus, primary malignant melanoma, and metastatic melanoma to the dermis. Malignant blue nevus is most commonly seen on the scalp. The tumor has an aggressive behavior and metastasizes in the majority of patients. This paper describes the second reported case of malignant blue nevus involving the upper arm. Clinical and histological features of this uncommon tumor are presented, along with a review of the literature.     

Response to fluconazole and itraconazole of Candida spp. in denture stomatitis

The significance of Candida albicans in the development of denture stomatitis (DS), as well as the clinical and microbiological efficacy of treatment with fluconazole and itraconazole was studied in 115 patients affected with DS and 200 controls (100 healthy patients with dental prosthesis and 100 healthy patients without prosthesis). Specimens were taken from all patients; subsequently all patients with positive culture of the DS group were treated with fluconazole. A second specimen was taken after 15 days of treatment with fluconazole, and if the results were positive again, treatment with itraconazole was instituted and the patients were given appointments for taking a third specimen. The incidence of C. albicans was 92% in the group of patients with DS. After treatment with fluconazole, a clinical cure of 97% and a microbiological cure of 78% was obtained in the patients with DS. In 3.2% of the cases strains resistant to fluconazole were found. The cases of microbiological resistance to fluconazole were treated with itraconazole resulting in a clinical cure of 100% and a microbiological cure of 77%. The results show the poor correlation of the clinico-microbiological response after treatment with these antifungal agents in denture stomatitis.     

Irritant contact stomatitis: a review of the condition

Several different types of interactions are possible between a chemical, a mixture of chemicals, and associated extrinsic factors (i.e., mechanical irritation) in the oral mucosa. These interactions can be broadly classified as irritative or allergenic in nature. In each case, the pathology usually includes mucosal inflammation. The information compiled and reviewed in this article suggests that, given the broad definition of surface lesions/mucosal abnormalities, there may be a continuum of irritation that can be termed "irritant contact stomatitis." This may be due to the fact that the mouth is lined with highly vascular mucosa that turns over rapidly compared to the skin, and may or may not be covered by keratin. Some regions in the mouth are uniquely sensitive to irritants because they can penetrate through the tissue easily. Key factors involved in the potential development of irritation are: inherent irritation potential of the agent, amount of exposure (concentration, duration, and frequency), ability to penetrate the tissue, and inherent reactivity of the subject as well as other extrinsic factors. Irritation leading to oral mucosal alterations is a common occurrence caused by a wide variety of exposures and insults to the oral cavity. Various irritants such as foods, chemicals, friction, thermal/mechanical injury, metals, spices, and oral care products have been documented to cause irritant reactions in susceptible individuals, particularly if used under exaggerated exposure conditions. It is important to note that most irritation in the oral cavity tends to reverse quickly when the causative agent is removed. Oral irritation is a commonly occurring phenomenon. Thus, it is important that the clinician be aware of the clinical manifestations and etiology of the condition.     

In vitro studies of the effect of antiseptic-containing mouthwashes on the formation and viability of Streptococcus sanguis biofilms

The aims of this study were to evaluate the growth of Streptococcus sanguis on hydroxyapatite, bovine enamel and polytetrafluoroethylene substrata in a constant depth film fermentor, and to determine the effects of three antimicrobial-containing mouthwashes on biofilm formation and bacterial viability on hydroxyapatite and enamel. There was little difference in the final cell density (5 x 10(4) cfu mm-2) of the Strep. sanguis biofilm on the three substrata. When hydroxyapatite-grown biofilms were exposed to the mouthwashes for 1 min, the one containing triclosan (T) proved the most effective. The chlorhexidine-containing mouthwash (CX) also achieved significant kills. The T-containing mouthwash was the most effective at killing biofilms grown on enamel. Pre-treatment of hydroxyapatite with CX, cetylpyridium chloride (CPC) or T for 1 min resulted in undetectable biofilm formation after 8 h. After 8 h of growth, only biofilms grown on enamel discs pre-treated with CX showed a reduction in the number of viable organisms. In conclusion, the results of this study have shown that while growth of Strep. sanguis on hydroxyapatite and enamel were similar, the ability of antimicrobial agents to prevent the accumulation of viable bacteria depended on the nature of the substratum.