Factors possibly influencing the prognosis of oligodendroglioma

Fifty-seven cases of oligodendroglioma (including eight cases of malignant oligodendroglioma) treated at the University of Tokyo Hospital between 1961 and 1985 were analyzed for factors influencing the survival rate. Factors related to a poor outcome were findings of malignancy and symptoms of dementia. Survival rate and postoperative survival period were not influenced significantly by radiation therapy, extent of resection, tumor characteristics, or ABO blood groups.     

A double-blind clinical evaluation of the effect of Nizofenone (Y-9179) on delayed ischemic neurological deficits following aneurysmal rupture

The effect of Nizofenone (Y-9179), a vertebral protective agent, on delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH) due to aneurysmal rupture was investigated by a cooperative double-blind clinical trials. Delayed ischemic neurological deficits following SAH are closely associated with the occurrence of vasospasm, and the effectiveness of any cerebral protective agent depends on sufficient coverage by the drug over the period around the onset of ischemic insult. Therefore, the study was designed so that the effect of Nizofenone could be analyzed in terms of these two factors. In patients admitted within day 9 of SAH, drug administration was immediately initiated and continued for 5 days. When delayed ischemic neurological deficits occurred, angiography was carried out to confirm the presence of vasospasm, and then drug administration was extended for an additional 5 days. Ten of the 100 cases enlisted in the study were excluded prior to code-breaking because of the occurrence of severe complications not related to vasospasm. Out of the 42 cases of the Nizofenone group and 48 of the placebo group, 25 and 29 developed vasospasm, respectively. Thus Nizofenone did not prevent vasospasm. Of the 25 cases of the Nizofenone group with vasospasm, 13 cases received sufficient drug coverage around the onset of vasospasm. The placebo group, the total Nizofenone group, and the Nizofenone group with sufficient drug coverage were stratified according to the occurrence of vasospasm. The disability status index one month after admission and the neurological functions, such as motor and speech functions, of each group were then compared. In patients who developed vasospasm, only the Nizofenone group with sufficient drug coverage had a significantly better outcome than the placebo group (p less than 0.05). No particular side effect of Nizofenone was observed. Thus, the results indicate that Nizofenone may be useful in the therapy of delayed ischemic neurological deficits following SAH, although the effect of the drug may be considerably influenced by the timing of its administration.     

A Case of Cronkhite–Canada Syndrome markedly improved with mesalazine therapy

We report a 50‐year‐old Japanese woman with typical clinical manifestations of Cronkhite–Canada Syndrome (CCS) and possible novel treatment modality for this disease. The patient was diagnosed as CCS based on the presence of several clinical manifestations, such as a diffuse alopecia, nail deformities, hypogeusia, pigmentation of skin, and abdominal discomfort combined with diarrhea and wasting. In addition, she also had multiple polypoid lesions in the gastrointestinal (GI) tract. She was first treated with hyperalimentation and corticosteroid. While this combination therapy seemed to reduce several clinical manifestations, abdominal symptoms and diarrhea recurred with the beginning of oral nutrition. Endoscopy and histology showed that inflammatory changes remained, especially in the lower intestine. Therefore, mesalazine was started. A few days after this therapy, her clinical symptoms disappeared and the polypoid lesions in the large bowel completely resolved. It was therefore possible to restart oral nutrition. We predict that the administration of mesalazine might be one of the useful therapies for CCS.     

How to diagnose isolated articular cartilage lesions of the knee in a consulting room

Abstract In order to clinically diagnose articular cartilage lesions of the knee in a medical examination, 121 knees (117 cases) with isolated lesions were investigated. Lesions of the patella (PAT), facies patellaris (F-PAT), lateral femoral condyle (LFC), lateral tibial plateau (LTP), medial femoral condyle (MFC), and medial tibial plateau (MTP) were found in 15, 10, 9, 57, 24, and 6 knees, respectively. The lesions often occurred in athletes, but many cases with lesions did not have a history of trauma. Giving way, pain in maximal flexion, pain after exercise, and pseudolocking were relatively common symptoms. Atrophy of the thigh on the involved side was not severe. Mild limitations in both extension and flexion were often found. Hydrarthrosis was frequent in cases with F-PAT, LFC, and MFC lesions. Valgus alignment was found in LTP lesions, while varus alignment was found in MFC and MTP lesions. Findings of fibrillation in PAT, flaps, deep defects, and softening in F-PAT and MFC, deep defects in LFC, and softening and fissuring in LTP were often seen during arthroscopy. Cartilage lesions such as softening were also thought to be related to the symptoms. Increases in joint fluid may suggest lesions in F-PAT, LFC or MFC where deep and wide lesions often occur. Cases with valgus alignment may have LTP lesions and those with varus alignment may have MFC or MTP lesions.     

Lorazepam Is an Independent Risk Factor for Transitioning to Delirium in Intensive Care Unit Patients

Background: Delirium has recently been shown as a predictor of death, increased cost, and longer duration of stay in ventilated patients. Sedative and analgesic medications relieve anxiety and pain but may contribute to patients' transitioning into delirium.

Methods: In this cohort study, the authors designed a priori an investigation to determine whether sedative and analgesic medications independently increased the probability of daily transition to delirium. Markov regression modeling (adjusting for 11 covariates) was used in the evaluation of 198 mechanically ventilated patients to determine the probability of daily transition to delirium as a function of sedative and analgesic dose administration during the previous 24 h.

Results: Lorazepam was an independent risk factor for daily transition to delirium (odds ratio, 1.2 [95% confidence interval, 1.1-1.4]; P = 0.003), whereas fentanyl, morphine, and propofol were associated with higher but not statistically significant odds ratios. Increasing age and Acute Physiology and Chronic Health Evaluation II scores were also independent predictors of transitioning to delirium (multivariable P values < 0.05).     

Insulin binds to specific receptors and stimulates macromolecular synthesis in C 6 glioma cells

Summary The existence of insulin receptors and biological responces to insulin on macromolecular synthesis have been studied in C6 glioma cells. Binding of¹²⁵I-insulin to C6 glioma cells was specific, time-and PH-dependent. Porcine insulin competed for¹¹²⁵I-insulin binding in a dose-dependent manner. Unlabeled polypeptides, including glucagon, bovine growth hormone, bovine prolactin did not compete for¹²⁵I-insulin binding. Scatchard analysis of the binding data gave a curvilinear plot which may indicate negative co-operativity or the existence of both high and low affinity (Ka=7.55 × 10¹⁰ –4.25 × 10⁹) sites.Incubation of cultures with insulin caused a time and dose-dependent stimulation of DNA, RNA and protein synthesis in C 6 glioma cells (measured by³H-thymidine,³H-uridine or³H-leucine incorporation into DNA, RNA, or protein respectively). The increase of macromolecular synthesis was admitted at more than 2 nM concentration of insulin. Maximal stimulation of DNA synthesis (142% of control) occurred 6 hours after incubation with 167 nM insulin. The same concentration of insulin caused a 45% increase in 1 hour on RNA synthesis, a 37% increase in 2 hour on protein synthesis.These results indicate that C 6 glioma cells have specific insulin receptors capable of mediating effects of insulin on macromolecular synthesis. Insulin in the brain and even blood may be an important growth factor in the glioma cells of the patients with disrupted bloodbrain-barrier.Presented on the European Congress of Neurosurgery, September 1987, Barcelona, Spain.     

Cerebral blood flow measured by Xenon enhanced CT in brain tumors

In the management of malignant brain tumors, it is important to know the extent and viability of tumors. However, an ordinary CT scan with iodine enhancement has only a limited ability to distinguish the tumor from surrounding normal tissue. Since the blood flow in tumor tissue was found to be relatively high in a previous experimental report, we have investigated the blood flow in a tumor and the surrounding brain. The Xenon enhanced CT method has several advantages over the conventional isotope method and enables us to evaluate rCBF with the same resolving power as with the CT scan. We evaluated rCBF in 15 brain tumor cases and obtained the following results. Mean rCBF value of the tumor is a little lower than that of gray matter and higher than that of surrounding edema. Our Xe-CT method enables us to distinguish the demarcation between the tumor area and the surrounding edematous area and offers useful information for determining the extent of resection in surgery. Mean lambda value of the tumor which is not obtainable in vivo by radionuclide scanning, was 1.02 +/- 0.06 for gliomas and 0.72 +/- 0.09 for metastatic tumors. rCBF value and lambda value are important elements to know the uptake rate of anticancer drugs into the brain tumors. And to evaluate these value in each brain tumor is useful in the selection of chemotherapeutic agents.     

Inhibitory effect of butylated hydroxyanisole administration on pancreatic carcinogenesis in Syrian hamsters initiated with N-nitrosobis(2-oxopropyl)amine

The modifying potential of butylated bydroxyanisole (BHA) administrationon pancreatic carcinogenesis was evaluated in 70 female Syriangolden hamsters. Groups of animals received saline, 70 mg/kgbody weight of N-nitrosobis(2-oxopropyl)-amine (BOP) or 70 mg/kgplus 20 mg/kg body weight of BOP followed by basal diet or dietcontaining 2% BHA from week 3. Although the body weights ofhamsters receiving the 2% BHA supplement decreased, caloricrestriction was not observed. All hamsters were killed at week18 and histo-pathologically examined for lesion development.The incidences of pancreatic carcinomas in hamsters receiving70 mg/kg plus 20 mg/kg body weight of carcinogen followed by2% BHA was 7.1%, significantly lower than the 64.3% evidentin hamsters given the same doses of BOP followed by basal diet.The total numbers of pancreatic lesions including carcinomas,atypical ductal hyperplasias and ductal hyperplasias and ductularproliferations in the liver were also significantly decreasedin animals receiving BOP followed by 2% BHA. The results thusindicate that both pancreatic and cholangiocellular carcinogenesisinitiated by BOP in Syrian hamsters can be inhibited by 2% BHAtreatment for a relatively short experimental period.     

Substrate specificity of tissue plasminogen activator and urokinase as determined with synthetic chromogenic substrates

Three different synthetic chromogenic substrates )H-glutamylglycyl-L-arginine-p-nitroanilide (S-2227), pyro-glutamyl-glycyl-L-arginine-p-nitroanilide (S-2444), and H-D-isoleucyl-L-prolyl-L-arginine-p-nitroanilide (S-2288] were investigated for use in the measurement of plasminogen activator activity with high molecular weight urokinase (H-UK), low molecular weight urokinase (L-UK), and tissue plasminogen activator (TPA). The three substrates were hydrolyzed by both TPA-type and UK-type plasminogen activator. As regards the amidolytic activity of S-2227, TPA exhibited a weaker amidolytic activity, and L-UK a stronger activity. In the case of the amidolytic activity of S-2444, no great difference between the three activators was observed in terms of Vmax. As regards the amidolytic activity of S-2288, L-UK exhibited a stronger activity, and TPA a weaker activity. It is suggested that the molecular size of the synthetic chromogenic substrate was too small when compared to natural substrate (fibrin), and therefore that fibrin-binding sites around the catalytic site in TPA are not recognized.