Von Hippel-Lindau syndrome with microscopic hemangioblastomas of the spinal nerve roots. Case report

The authors describe a case of von Hippel-Lindau syndrome diagnosed at autopsy in a 49-year-old woman. She died suddenly following hemorrhage from a cerebellar hemangioblastoma. Other autopsy findings included a retinal hemangioblastoma, an adrenal pheochromocytoma, and a clear-cell renal tumor. The case was distinguished by the unexpected finding of multiple microscopic hemangioblastomas of the spinal nerve roots. The case is discussed with emphasis on the incidence of spinal hemangioblastomas in von Hippel-Lindau syndrome.     

Pharmacological studies with beclobrate, a new hypolipidemic agent

A new diphenylmethane derivative with potent hypolipidemic activity, ethyl-(+/-)-2-[[alpha-(p-chlorophenyl)-p-tolyl]-oxy]-2-methylbutyrate (Sgd 24774, beclobrate) has been investigated in animals. From a comparison of the ED25 values of beclobrate and clofibrate, the new drug is 11 times more potent with respect to its hypocholesterolemic activity and 36 times more hypotriglyceridemic in normally fed rats, and lowers fructose-induced hypertriglyceridemia in rats 20 times as effectively as does clofibrate. On a similar basis of comparison, the hepatomegalic effect of beclobrate in rats is 22 times that of clofibrate. High doses of beclobrate did not reveal any other peripheral or central effects in a wide range of pharmacological tests, indicating a high specificity of the action of the drug on blood lipids. On the basis of the results of interaction studies performed with beclobrate in animals, administration of the substance in man should be largely free from risk.     

Serum magnesium levels and acute exacerbation of chronic obstructive pulmonary disease: a retrospective study

A decrease in serum Mg(+2) is associated with airway hyper-reactivity and impaired pulmonary function. The purpose of this study was to determine if decreased serum Mg(+2) levels in patients with chronic obstructive pulmonary disease (COPD) are associated with acute exacerbations. In a retrospective study, the charted serum Mg(+2) levels in 100 COPD patients were examined. These included 50 patients who presented with an acute exacerbation of COPD and 50 stable patients. Chart review was sequential within both groups. Serum Mg(2+) levels in the stable COPD patients averaged 0.91+/- 0.10 mmol/L (mean+/- SD) with a 95% CI of 0.88 - 0.94 mmol/L. Patients undergoing an exacerbation had significantly lower serum Mg(+2) levels (0.77+/- 0.10 mmol/L; CI, 0.74 - 0.79; p<0.0001). Logistic regression of the dichotomous outcomes as a function of serum Mg(+2) concentration demonstrated a highly significant association (chi(2)=41.26; p<10(-5)). These data were subjected to receiver-operator characteristic (ROC) analysis for decision levels (DL) and the area under the ROC curve was determined to be 0.85+/- 0.04 (CI, 0.78 - 0.93). The optimum DL was determined to lie between 0.80 mmol/L (OR=14.33; sensitivity 70%; specificity 86%) and 0.84 mmol/L (OR=11.16; sensitivity 84%; specificity 68%). These data suggest that at the lower range of the reference interval, serum Mg(+2) levels are associated with an increased risk of exacerbation of symptoms in COPD patients. Furthermore, they suggest a DL that is useful for predicting clinical outcomes in these patients and serving as a target value for therapy.     

Randomized trials of breast-conserving therapy versus mastectomy for primary breast cancer: a pooled analysis of updated results

We have undertaken a pooled analysis of the 6 major randomized trials comparing mastectomy (MT) and breast-conserving therapy (BCT) in the treatment of primary breast cancer. Specifically, these trials compared the 2 most widely used options in local treatment: mastectomy and axillary dissection (MT) versus breast-conserving surgery, axillary dissection, and breast radiotherapy (BCT). The early results of these 6 trials formed the basis for a 1990 National Institutes of Health Consensus statement. However, most of these trials have recently published long-term follow-up results, and this pooled analysis incorporates the updated results of these 6 trials. For each of these trials, the observed number of treatment events was compared with that expected under the null hypothesis, given the number of patients per arm and the total number of events. Approximate odds ratios were computed using the observed and expected number of events, and the variance of the observed number of events. These were then pooled across trials to give overall odds ratios for the risk of locoregional recurrence, total recurrence, and death. Four of the 6 trials show that MT significantly reduces the risk of locoregional recurrence when compared with BCT, and the pooled odds ratio also shows a significant benefit for MT (odds ratio [OR], 1.561; 95% confidence interval [CI], 1.289-1.890; P < 0.001). However, only 1 trial shows a statistically significant benefit for MT in reducing mortality, and the pooled odds ratio shows no significant difference between MT and BCT (OR, 1.070; 95% CI, 0.935-1.224; P = 0.33). This pooled analysis confirms that MT and BCT have comparable effects on mortality, even after long-term follow up. However, BCT is associated with a significantly greater risk of locoregional recurrence.     

Comparison of trace metal concentrations in malign and benign human prostate

Imbalance in the composition of trace metals, recognized to be essential to normal human homeostasis, besides the accumulation of potentially toxic or nonessential trace metals, may cause disease. Thus, there is a need for their analysis in cancerous and noncancerous human tissues to examine the relationship between cancer and these elements. Trace metal concentrations including Cd, Ni, Zn, Cu, Fe, Mg, and Ca in both malign and benign prostate samples were determined by atomic absorption spectrophotometry. The tissues were digested by using microwave energy. In contrast to the literature data for zinc, the concentrations of calcium and zinc in the malign human prostate were found to be significantly higher than those in the benign human prostate (p < 0.05 for both metals). Similarly, the concentrations of iron, nickel, and magnesium in the malign prostate were also found to be higher than those in the benign prostate (p 相似文献   

Induction of apoptosis and necrosis by resistance modifiers benzazoles and benzoxazines on tumour cell line mouse lymphoma L5718 Mdr+cells

Eighteen new fused heterocyclic compounds of benzazoles and benzoxazines were investigated for induction and inhibition of apoptosis on tumor cells (L5718, mouse lymphoma cell line containing the human mdr-1 gene). For evaluation of apoptosis, the cells were stained with FITC-labelled Annexin-V and propidium iodide and the results were analysed by flow cytometry. Nine of these substances were also checked for reversal of multidrug resistance. The reversal of multidrug resistance was determined by measuring the rhodamine-123 accumulation in the cancer cells. Rhodamine-123 shows a green fluorescence and its intracellular concentration correlates well with the inhibition of efflux pump activity. Three of the tested compounds, 5-(p-nitrobenzamido)-2-benzylbenzoxazole (BD-3), 6-methyl-2-(o-chlorophenyl) benzoxazole (A-9) and 5-(p-nitrophenoxyacetamido)-2-phenylbenzoxazole (D-30), showed an increased apoptotic effect on mouse lymphoma cells. Moreover, compounds BD-3, A-9 and 5-(2-thienylcarboxyamido)-2-phenylbenzoxazole (D-24) also amplified the apoptosis effect of 12H-benzo(a)phenothiazines (M-627). However, D-24, alone was not effective. Additionally, 2-(p-nitrobenzyl)benzoxazole (B-11), was also found to increase the apoptotic effect of M-627. On the other hand, 5-(p-nitrophenylacetamido)-2-phenylbenzoxazole (D-7) showed an anti-apoptotic effect. No positive correlation was found between the increased drug accumulation effect and the programmed cell death induced by the compounds studied.     

Cytarabine-induced fever complicating the clinical course of leukemia

The aim of this study is to assess the frequency and clinical characteristics of cytosine arabinoside-induced fever in patients with acute myeloid leukemia in remission, receiving high-dose (3 g/m2) consolidation therapy. We have investigated 77 consolidation cycles over a study period of 4 years. A strict definition of cytosine arabinoside-induced fever (i.e. patients without neutropenia and with negative blood cultures during the fever episodes) was used. Of the 77 consolidation cycles, fever due to cytarabine was detected in 33 cycles (43%). Median time of onset of fever from the beginning of first chemotherapy dose was 22 h and maximum temperature was in the range 38.0-39.7 degrees C (mean+/-SD: 38.8+/-0.5 degrees C). Median duration of fever was 10.15 h and did not exceed 72 h. There was no difference with regard to neutrophil and white blood cell counts between cycles with or without cytarabine fever. The cost of investigation of fever source was about US$2137. Our analysis suggests that 'cytarabine fever' is a frequent and often a self-limiting complication of high-dose cytosine arabinoside consolidation therapy, and cost-reductive approaches could be structured based on this background.