A Difficult Differential Diagnosis of Acute Cholecystitis in a Patient With Steroid-induced Diabetes.

UNLABELLED: An impairment of gallbladder motility due to autonomic neuropathy may cause cholestasis and result in gallbladder stone formation. Diabetes is one of risk factors for acute cholecystitis. Diabetes and steroid use are associated with the susceptibility to bacterial infections, we are apt to diagnose steroid-induced diabetic patients manifesting symptoms of cholecystitis as having acute bacterial infective cholecystitis. Here, we report a very rare steroid-induced diabetic patient complicated with gallbladder torsion-induced necrotizing cholecystitis due to a floating gallbladder. KEYWORDS: Cholecystitis; Diabetes; Floating gallbladder; Torsion.

Association between paraoxonase-1 Q192R polymorphism and lung function among Saskatchewan grain handlers.

INTRODUCTION: Paraoxonase-1 (PON1) is a high-density, lipoprotein-associated, multifunctional antioxidant enzyme that is detected in nonciliated bronchiolar epithelial cells, although its role in the lung has not yet been clarified. We therefore investigated the association between the PON1 Q192R polymorphism and lung function. PATIENTS & METHODS: A total of 216 male Saskatchewan grain handlers provided demographic, occupational and respiratory-symptom information by means of questionnaires, and thereafter underwent PON1 Q192R genotyping and lung-function testing. RESULTS: Mean lung-function values did not differ among the Q192R genotypes. However, current smokers with the Q/Q genotype had a higher mean percent predicted forced expiratory volume in the first second (FEV(1)), and absolute and percent predicted FEV(1) per forced vital capacity (FVC) compared with current smokers with at least one 192R allele (100.9 +/- 11.2% vs 92.0 +/- 15.1%, p = 0.01; 78.0 +/- 5.9% vs 74.1 +/- 6.8%, p = 0.03; and 96.8 +/- 7.1% vs 92.1 +/- 8.3%, p = 0.03; respectively). The incidence of subjects with FEV(1)/FVC less than 70% was significantly higher in current smokers with at least one 192R allele than in nonsmokers with the Q/Q genotype (odds ratio: 5.0; 95% confidence interval: 1.5-17.4). The protective effect of the Q/Q genotype was not found in nonsmokers. The FVC was not influenced by either PON1 genotype or smoking status. CONCLUSION: The results obtained from grain handlers suggest that PON1 may play some role in the protection of the airways against the toxicity of cigarette smoke, and the 192R allele may be a novel genetic risk factor for airway injury.

Tumor necrosis factor alpha and pulmonary function in Saskatchewan grain handlers.

OBJECTIVE: The objective of this study was to estimate the contribution of lifestyle (cigarettes) and tumor necrosis factor (TNF) alpha polymorphisms at position 308 of the tumor necrosis factor alpha gene promotor (TNF-308*1/*2) to pulmonary function among grain handlers. METHODS: Employed male grain handlers (157) provided occupational and respiratory symptom information, pulmonary function measurements, and DNA for genotyping. RESULTS: The genotypes of 101 were TNF-308*1/*1, 47 were *1/*2, and nine were *2/*2. Current smokers whose genotype was *2/*2 or *1/*2 had lower values compared with other combinations of genotype and smoking status. Among *1/*1 homozygotes, current smokers had better percent of predicted forced expiratory volume in 1 second (P = 0.04) mean values than nonsmokers and better percent of predicted forced vital capacity than exsmokers (P = 0.017) or nonsmokers (P = 0.008). CONCLUSIONS: These results indicate the complexity of determining which workers will develop acute and chronic adverse pulmonary conditions in response to exposure to grain dust and the toxins in cigarette smoke interacting with their genotype.

The in-vivo effects of sho-saiko-to, a traditional Chinese herbal medicine, on two cytochrome P450 enzymes (1A2 and 3A) and xanthine oxidase in man.

The Chinese herbal medicine sho-saiko-to is a mixture of seven herbal components (Bupleurum root, Pinellia tuber, Scutellaria root, Jujube fruit, Ginseng root, Glycyrrhiza root and Ginger rhizome) that is widely administered to patients with chronic hepatitis in Japan. We assessed the effects of sho-saiko-to on the activity of cytochrome P450 (CYP) 1A2, CYP3A and xanthine oxidase (XO) in man. Twenty-six healthy subjects were studied to evaluate their baseline activity of CYP1A2 and XO by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine and of CYP3A by a urinary excretion ratio of 6beta-hydroxycortisol (6beta-HC) to free cortisol (FC). Thereafter, the subjects received a twice-daily 2.5-g dose of sho-saiko-to for five days, and underwent the caffeine test on day 1 and day 5. The mean activity of CYP1A2 decreased by 16% on both day 1 and day 5 compared with the baseline (P=0.001). The mean activity of XO also significantly decreased by 25% on day 1 and 20% on day 5 (P<0.0001) compared with the baseline value. The activity of CYP3A tended to be lower on day 5 than the baseline (P=0.146). It is concluded that sho-saiko-to reduces CYP1A2 and XO activity in man.

Essential role of the adhesion receptor LFA-1 for T cell-dependent fulminant hepatitis.

Viral hepatitis affects more than 2 billion people worldwide. In particular, no effective treatment exists to abrogate death and liver damage in fulminant hepatitis. Activation of T cells is an initial and critical event in the pathogenesis of liver damage in autoimmune and viral hepatitis. The precise molecular mechanisms that induce T cell-mediated hepatocyte injury remain largely unclear. In mice, T cell-dependent hepatitis and acute liver damage can be modeled using ConA. In this study, we examined the role of the adhesion receptor LFA-1 in ConA-induced acute hepatic damage using LFA-1(-/-) (CD11a) mice. Massive liver cell apoptosis and metabolic liver damage were observed in LFA-1(+/+) mice following ConA injection. By contrast, LFA-1(-/-) mice were completely resistant to ConA-induced hepatitis and none of the LFA-1(-/-) mice showed any hepatic damage. Whereas activated hepatic T cells remained in the liver in LFA-1(+/+) mice, activated T cells were rapidly cleared from the livers of LFA-1(-/-) mice. Mechanistically, T cells from LFA-1(-/-) mice showed markedly reduced cytotoxicity toward liver cells as a result of impaired, activation-dependent adhesion. Importantly, adoptive transfer of hepatic T cells from LFA-1(+/+) mice, but not from LFA-1(-/-) mice, sensitized LFA-1(-/-) mice to ConA-induced hepatitis. Thus, LFA-1 expression on T cells is necessary and sufficient for T cell-mediated liver damage in vivo. These results provide the first genetic evidence on an adhesion receptor, LFA-1, that has a crucial role in fulminant hepatitis. These genetic data identify LFA-1 as a potential key target for the treatment of T cell-mediated hepatitis and the prevention of liver damage.

The application of a radiotherapy-planning system: consideration from a case of intraoral squamous cell carcinoma that lacked a control.

OBJECTIVE: The purpose of this case study was to present an applied example of a radiotherapy-planning system used during the treatment of a malignant tumor in the oral and maxillofacial region. STUDY DESIGN: The various radiotherapy modalities were performed on a patient with oral squamous cell carcinoma of multiple metachronous recurrences. Estimated radiation dose-distribution curves for each radiotherapy modality were computed by using a commercially available radiotherapy-planning system. A personal computer was used to make the superimposed radiation dose-distribution curve. RESULTS: The 3-dimensional dose-distribution curves were determined with the radiotherapy-planning system. In addition, with the use of superimposition of the dose-distribution curves from all sources of radiotherapy, it was possible to estimate regions receiving extremely high radiation dosages. This information serves as a road map to potential postradiation complication sites at follow-up examinations. CONCLUSION: The radiotherapy-planning system is very useful for the evaluation of a radiotherapy dosage to treat malignant tumors in the oral and maxillofacial region.

A population phenotyping study of three drug-metabolizing enzymes in Kyushu, Japan, with use of the caffeine test.

OBJECTIVE: We assessed in vivo activities of cytochrome P450 1A2 (CYP1A2), N-acetyltransferase 2, and xanthine oxidase in Japanese residents of Kyushu, the southern island of Japan. METHODS: One hundred eighty-two healthy volunteers (108 men and 74 women) received a 150-mg oral dose of caffeine before they went to sleep. The concentrations of caffeine, caffeine metabolites, and uric acid in their overnight urine samples were analyzed. The CYP2A6 genotypes were determined in 66 of the 182 volunteers to assess whether they affected a metabolic ratio for CYP1A2 activity index. RESULTS: The metabolic ratio for CYP1A2 was not polymorphic, but its mean ratio was greater in smokers than in nonsmokers (P <.05). Twenty subjects (11.0%) were found to be slow acetylators. Twenty subjects were determined to be putative poor metabolizers of xanthine oxidase, and the mean urinary uric acid concentration of those subjects was 53% lower than that of the other subjects (P <.0001). The mean ratio for CYP1A2 obtained from 3 subjects with the CYP2A6(*)4C/CYP2A6(*)4C genotype was greater than the mean ratio from subjects with other genotypes (P <.01) or that from subjects with a wild-type CYP2A6(*)1A allele (P <.05). CONCLUSIONS: Our results suggest that putative poor metabolizers of xanthine oxidase activities exist in a Japanese population and that a decreased 1,7-dimethyluric acid formation from caffeine in poor metabolizers of CYP2A6 appears to affect the metabolic ratio used for the assessment of CYP1A2 activity.

Cancer therapy by gene therapy with angiostatin.

Angiostatin, an internal fragment of plasminogen, has been shown to inhibit angiogenesis. A new area of cancer research that has generated excitement is the use of angiostatin to treat cancer. Angiostatin protein therapy has not been pursued because current technology is inadequate to manufacture the needed biologically active proteins in sufficient quantities. It is sufficient for effective therapy with angiostatin to establish angiostatin production in the vicinity of tumors by gene transfer of angiostatin cDNA. There are various methods by which to transfer angiostatin cDNA. One way is to use a viral vector to incorporate the gene into cells. Another way is to use nonviral vectors. In this review, evidence accumulated from many laboratories suggests that angiostatin gene therapy may be an important new cancer therapy as an adjuvant therapy to prevent recurrence. (c) 2001 Prous Science. All rights reserved.