Biochemical activities of lysosomal acid hydrolases in leukemic cells

The biochemical activities of 8 lysosomal acid hydrolases in leukemic cells from 48 patients were examined. Characteristic alterations were found in α-mannosidase, β-galactosidase and N-acetyl-β-glucosaminidase activities of leukemic cells. The level of α-mannosidase activity was much higher in myelo(mono)genous leukemias (AML, AMoL, AMMoL, CML and CMMoL) than in lymphogenous ones (ALL, T-cell leukemia, hairy cell leukemia and CLL) without exception. The β-galactosidase activity also differed as a result of α-mannosidase, except in T-cell leukemia. In T-cell leukemia it was within the range of normal lymphocytes, but in the other lymphogenous leukemias it was significantly below normal. N-acetyl-β-glucosaminidase activity in myelo(mono)genous leukemic cells was above the range of normal granulocytes. The changes in these enzyme levels were consistent. The lymphocytic or myelocytic nature of three cases of acute undifferentiated leukemia could be determined by enzyme studies. In two cases it was lymphocytic and in one it was myelocytic. The enzymatic abnormalities were also found in morphologically mature neutrophils from patients with not only chronic types (CML, CMMoL) but also acute types (AMoL, AMMoL) of leukemias, and were similar to those of their respective leukemic cells. Analysis of lysosomal enzymes (at least three of those mentioned above), can elucidate one of the biochemical properties of leukemic cells and may be valuable in the differentiation of leukemias.     

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.     

Practical guidelines for physicians in the management of febrile seizures

Recent studies have shown that adequate medication can prevent the recurrence of febrile seizures (FS). It has also been clarified that the vast majority of, though not all, FS patients follow a benign course. Then, questions arise as to whether or not FS should be prevented, particularly in light of the risks of side effects from drugs. Which kinds of FS can be prevented, if necessary? The guidelines presented here are aimed primarily at helping general practitioners in considering how to manage FS most appropriately. The guidelines stress that judgements should be individualized, while referring to a few specific ‘warning factors’. The guidelines follow a ‘laissez-faire’ principle for the majority of FS cases, whereas intermittent therapy with diazepam and continuous medication with either phenobarbital or valproate are indicated in other limited cases meeting respective definite criteria.     

Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Decreased cerebral blood flow with an increased oxygen extraction fraction, the so-called misery perfusion syndrome, suggests a vulnerability to reduction in cerebral perfusion pressure and a tendency to develop cerebral infarction. It is uncertain, however, whether the infarct would occur in the brain region specifically exhibiting this condition. CASE DESCRIPTION: We report the case of a patient with right intracranial internal carotid artery stenosis who presented with mild left hemiparesis resulting from a right frontal watershed infarct. Positron emission tomography 2 months after the stroke showed decreased cerebral blood flow with an increased oxygen extraction fraction in noninfarcted areas of the affected hemisphere. Maximal changes were detected in the watershed area between the middle cerebral artery and the posterior cerebral artery. Three months later, while on antiplatelet therapy, he suffered a new infarct in the right temporo-occipital watershed area that had shown the highest oxygen extraction fraction value on the first positron emission tomographic study. One month after the recurrence of stroke, a second study showed that low perfusion with increased oxygen extraction fraction persisted in the affected hemisphere to a lesser degree than in the first study. CONCLUSIONS: This observation suggests that the area of low perfusion exhibiting the highest oxygen extraction fraction has the highest risk for infarction. Increased oxygen extraction fraction may be an important factor in the development of hemodynamic infarction.     

Direct inactivation of herpes simplex virus type-2 by rat epidermal protein.

Proteins were extracted from corneocytes of skin of 2-day-old rats and fractionated by gel filtration and cation exchange column chromatography. The different protein fractions were tested for direct inactivation of herpes simplex virus infectivity as determined by reduction of plaque formation. The most effective protein fractions against herpes simplex virus were a neutral pH buffer soluble and mol. wts. ranging from 20 K to 30 K. Amino acid composition of the proteins were virtually identical to epidermal histidine-rich proteins. The activity was significantly (P less than 0.001) stronger against type-2 than type-1. The activity was most stable at pH 7.2 and the rate of inhibition increased in a time-dependent manner up to 4 h. The 50% effective dose was estimated as 1.1 micrograms protein/ml.     

A comparative clinical and pharmacokinetic study of a new slow-release versus conventional preparations of valproic acid in children with intractable epilepsy.

Thirteen children with intractable epilepsy were treated by means of three-times-daily administration of a conventional preparation of valproic acid (C-VPA) and twice-daily administration of a new slow-release preparation of VPA (SR-VPA) with the cross-over technique. The frequency of seizures, side effect and steady-state pharmacokinetics of VPA were evaluated. With the change from C-VPA tid to SR-VPA bid, four patients exhibited a significant reduction in seizure frequency. The steady-state minimum concentration (Cmin) was higher, the maximum concentration (Cmax) lower and there were less diurnal fluctuations with SR-VPA, than with the respective values obtained in the C-VPA group, all the differences being statistically significant. Furthermore, a significant difference was unexpectedly found in the area under the curve (AUC) from 0 to 24 hours, the mean AUC in the period of SR-VPA being 9% higher than that with C-VPA. Five of the nine patients under 6 years of age showed more than 10% increase, and all four patients over 6 years of age less than 10% increase or a decrease in AUC. It was concluded that with SR-VPA bid, the pharmacokinetic features were more stable, the age-related AUC value was larger and the clinical effect was better than in comparison to C-VPA tid in children with intractable epilepsy.