Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma

The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of Ullrich disease with distinct pathological change of muscular dystrophy

A case of Ullrich disease was presented. The patient was a 3-year-old girl with torticollis, generalized muscle weakness and acroatonia since birth. High-arched palate, protruded calcaneus, and mild contracture of proximal joints were also recognized. Intellectual development was normal. Serum level of CPK was slightly increased. In histological and histochemical examinations of quadriceps femoris muscle, proliferated connective tissue, marked variation in the muscle fiber diameter, and a lot of degenerated and regenerated fibers were recognized. Minimal injury easily causes subcutaneous hemorrhage, but no abnormality was found in the structure of collagen.     

Changes in immune regulation in response to examination stress in atopic and healthy individuals

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.     

Acute leriche syndrome due to paradoxical embolism.

Paradoxical embolism, describing the passage of venous or right-sided cardiac thrombus into the arterial or systemic circulation through patent foramen ovale, is an uncommon cause of acute arterial occlusion. Here, we report acute Leriche syndrome in a young woman attributable to paradoxical embolism. Ischaemia, patent foramen ovale, and venous thrombosis were the triad of evidence for paradoxical embolism.     

The high prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma

BACKGROUND: Although many histopathologic factors in squamous cell carcinoma of the tongue predict the prognosis, the major predictive factors have not been identified clearly. This study analyzed the prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma. METHODS: The clinicopathologic features of 124 consecutive patients seen between January 1985 and December 1999 with previously untreated squamous cell carcinoma of the tongue were reviewed. Their mean age was 58.5 years (range: 23-90) and the male-female ratio was 1.8: 1 (79 men and 45 women). There were 41, 40, 30, and 13 cases at stage I to stage IV, respectively. The clinicopathologic factors, especially the histologic grade at the deep invasive front (invasive front grade, IFG), were analyzed to determine factors predicting prognosis. RESULTS: The 5-year disease-free survival rate of the patients treated with curative aim only was 66.7%. Clinicopathologic factors significantly associated with the prognosis were T classification, tumor size, stage classification, tumor depth, macroscopic appearance, cervical lymph node metastasis (nodal metastasis), microvascular invasion, and IFG. In a multivariate analysis, patients with tumor depth >/=4 mm, IFG >/=8 points, and nodal metastasis had a reduced disease-free survival and IFG >/=11 points had a predictive value for nodal metastasis (odds ratio: 7.34; P = 0.0019). CONCLUSION: This study found that a high IFG malignancy score had a high prognostic value for squamous cell carcinoma of the tongue.