Novel responses of peripheral lymphocytes of cancer patients to chemical induction of sister chromatid exchanges

Sensitivities to sister chromatid exchange (SCE) induction by chemicals of peripheral lymphocytes from 26 cancer patients were estimated under conditions identical to those for healthy humans which had been reported (Cancer Res., 43: 439-442, 1983). The sensitive individual was defined as one whose cells give a mean induced SCE frequency more than 2 standard deviation units above the population mean of induced SCEs in cells from the healthy humans. When cells were treated with 3-amino-1-methyl-5H-pyrido[4, 3-b]indole in the presence of rat liver S9 mix, 8 in 10 stomach cancer patients, 4 in 4 colon cancer patients, 3 in 9 lung cancer patients, 0 in 3 patients bearing other cancers, and 0 in 9 non-cancerous individuals were sensitive. The corresponding frequency of individuals in the healthy population, reported previously, was 1 in 33 persons. Thus, the frequency of sensitive individuals in the combined group of stomach and colon cancer patients was very significantly higher than were frequencies in control groups. Three in 10 patients with stomach cancer and 4 in 16 patients with other cancers were sensitive to induction of SCE by methyl methanesulfonate. Six in these 7 methyl methanesulfonate-sensitive patients were also 3-amino-1-methyl-5H-pyrido[4,3-b]indole sensitive. The frequency of methyl methanesulfonate-sensitive individuals in the healthy populations was 2 in 50. There was no patient who was sensitive to SCE induction by 4-nitroquinoline 1-oxide. The frequency was not significantly different from the healthy population, in which 3 in 50 persons were sensitive. These results suggest that a particular cancer correlates with the sensitivity of peripheral lymphocytes to SCE induction by particular chemicals.     

Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders.

We evaluated regional blood flow and oxygen metabolism in the cerebral and cerebellar cortices of 15 patients with unilateral major cerebral artery occlusive disorders with PET. These patients showed a cortical blood flow asymmetry in middle cerebral artery distribution. Only subcortical abnormalities were detected on computed tomography. Nine patients showed crossed cerebellar hypoperfusion, a reduction in contralateral cerebellar blood flow, while six did not. No difference in the degree of cerebral blood flow asymmetry existed between the two patient groups. However, oxygen metabolism asymmetry was more pronounced and was more closely matched to blood flow asymmetry in patients with crossed cerebellar hypoperfusion. These findings suggest that a major cause of cerebral cortical blood flow reduction is reduced metabolic demand in patients with crossed cerebellar hypoperfusion. Crossed cerebellar hypoperfusion may have clinical significance as a reflection of the cerebral metabolic state on blood flow images.     

Deep vein thrombosis in the psychiatric patients under physical restraint]

Pulmonary thromboembolism induced by deep vein thrombosis (DVT), which is known as economy-class syndrome, is one of sudden death in psychiatric patients under physical restraint. (1) A decrease in venous blood flow, (2) damage to vessel walls, and (3) the enhancement of blood clotting are the major risk factors for DVT (Virchow triad). It has been speculated that physical restraint inhibits venous blood flow, and that antipsychotic drugs facilitate blood clotting. In order to prevent sudden death due to DVT, prophylactic measures and early diagnosis are crucial. Whereas Doppler ultrasonography and contrast venography are the gold standards for the diagnosis of DVT, more simplified methods are now under development. Of those, D-dimer measurement, which can be conducted with a small blood sample, is the most potent candidate for the biochemical diagnosis of DVT. Although there are many prophylactic measures, including anticoagulant medications and physical therapies, it is not clear which is the most effective and suitable in psychiatric practice. Psychiatric professionals should pay closer attention to DVT in psychiatric patients under physical restraint.     

Preoperative identification of subthalamic nucleus for deep brain stimulation using three-dimensional phase sensitive inversion recovery technique.

PURPOSE: We assessed the feasibility of utilizing three-dimensional (3D) phase sensitive inversion recovery (IR) images for preoperatively determining deep brain stimulator position. METHODS: We measured geometric distortion with a grid phantom and evaluated images of 3 volunteers to determine optimum imaging parameters for 3D phase sensitive IR. RESULTS: Geometric distortion measured less than 1.0%. Respective inversion and recovery times, which provided high T(1) contrast between the subthalamic nucleus and adjacent tissue, were 200 and 4000 ms. In studies of 3 volunteers and 2 patients, the subthalamic nucleus was clearly depicted in 3D phase sensitive IR images. The measured coordinates of the subthalamic nucleus agreed well with those calculated by conventional estimation from midpoint of the anterior and posterior commissure. CONCLUSION: Three-dimensional phase sensitive inversion recovery was useful in visualizing the subthalamic nucleus for effective deep brain stimulation.     

Severely calcified constrictive pericarditis simulating a mediastinal tumor and obstructing the right ventricular inflow tract.

We report a rare case of constrictive pericarditis that stimulated a large mediastinal tumor obstructing the right ventricular inflow tract. A 58-year-old woman was referred to our hospital because of a recent increase of dyspnea and facial edema. Computed tomography revealed severely thickened calcification, including a low-density area, presenting as a mediastinal tumor, compressing the right ventricular inflow tract. A complete resection was performed, and her symptoms dramatically improved. Idiopathic constrictive pericarditis was diagnosed pathologically.     

Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.     

Differential protective effects of varying degrees of hypoxia on the cytotoxicities of etoposide and bleomycin

Summary Oxygen is thought to be involved both directly and indirectly in the mechanisms of action of several anticancer agents. We studied the effects of various oxygen concentrations on the cytotoxicities of the following drugs: bleomycin (BLM), etoposide (VP-16), doxorubicin (DOX), and mitomycin C (MMC). Human sarcoma cells, MESSA, were exposed to drug for 1 h at one of several oxygen concentrations: less than 1%, 2.5%, 5%, 21%, and 95%. Cytotoxicity was assessed by cellular incorporation of ³H-thymidine into DNA 5 days after drug exposure. Control experiments varying oxygen concentration without drugs demonstrated toxicity only at the highest concentration (95%). Three different responses of drug sensitivity to varying oxygen tensions were observed. BLM, which has been shown to utilize oxygen as a substrate in generating free radicals and producing DNA scission, demonstrated a progressive increase in cytotoxicity over the entire range of increasing oxygen concentrations. This is consistent with the model of a BLM-cation-oxygen complex and catalytic reduction of oxygen. VP-16, which also produces DNA strand breakage but by interaction with topoisomerase II, exhibited a threshold response. VP-16 toxicity was ameliorated by anoxic conditions (less than 1% O₂), but not by oxygen concentrations of 2.5%–95%. The reason for this protective effect of anoxia with VP-16 is not clear. In contrast, acute anoxia had no effect on the cytotoxicities of DOX and MMC. We conclude that acute hypoxia protects cells from both BLM and VP-16 but that the nature of that protection is different. VP-16 toxicitiy is blunted only by severe anoxia, wheaeas BLM exhibits a dose response effect over the entire range of oxygen concentrations.Supported by NIH grant CA-27478 from the US Department of Health and Human Services, and by the American Lung Association. Dr. Sikic is a recipient of a Faculty Development Award in Clinical Pharmacology from the Pharmaceutical Manufacturer's Association Foundation.     

Clinical study of primary carcinoma of the fallopian tube: experience with 14 cases

Between 1950 and 1986, 14 cases of primary carcinoma of the fallopian tube were treated and diagnosed at the Cancer Institute Hospital. These cases constituted 0.13% of the total number of gynecologic malignancies at the hospital during the period. The clinical/pathological findings and prognoses were described. Of the 14 cases, the average age was 56.0 years. The most frequent symptom was atypical genital bleeding, seen in 11 cases (79%). Massive watery discharge was seen in four cases (29%). In preoperative cytologic examination of vaginal smears, six cases (43%) were positive for cancer. All cases underwent operation as therapy. Postoperative irradiation, adjuvant chemotherapy, and/or second-or third- look operation was also used. Histopathologically, all materials were found to be adenocarcinoma. Four cases were well differentiated, seven were moderately differentiated, and three were poorly differentiated. Two patients with stage III and IV cancers died of the disease. Nine patients were still alive at the end of this study. The five-year survival rate was 57% (4/7). In stage I cancers, the five-year survival rate was 80% (4/5). The prognosis of stage I cancer patients was estimated as rather good.     

Prediction of spinal cord ischemia with a retrievable stent graft on endovascular treatment for a case of thoracic aortic aneurysm

Multiple aortic aneurysms in Behçet’s disease were repaired with transluminaly placed endovascular stent grafts. Before deploying the stent graft device for permanent implantation for the saccular aneurysm located in the descending thoracic arota, from which feeding arteries for the spinal cord possibly branched, a retrievable stent graft was inserted and evoked spinal cord potential (ESP) were monitored in order to predict spinal cord ischemia. The original retrievable stent graft, constructed of a self-expandable Z-shaped stainless steel stent covered with e-PTFE, can be easily withdrawn into a 18 Fr. sheath after deployment. Blood flow into intercostal arteries branching from that part of the descending aorta where the permanent stent graft is planned to be implanted, is intercepted by the retrievable stent graft. A change of ESP during the temporary implantation of the device indicates that spinal cord ischemia would be caused by permanent implantation of the stent graft. In this case, no change of ESP was observed and the patient showed no postoperative paraplegia.The retrievable stent graft was useful for prediction of spinal cord ischemia before endoluminal stent graft repair of the descending aortic aneurysm. However, the device is not flexible enough to fit a severely tortuous aorta, therefore we are obliged to select patients to some extent. Further improvement of the device is required to make prediction of spinal cord ischemia with the retrievable stent graft possible in all cases.     

Effects of flunarizine therapy on intractable epilepsy

In an open trial the antiepileptic effects of flunarizine were studied in 64 patients with intractable epilepsy, and the following results were obtained: 1. Seizures disappeared completely in 2 cases, with a 50% decrease in 6 cases. 2. Of the 25 patients who had accompanying psychiatric symptoms 8.0% showed an improvement in these symptoms. 3. While no marked side-effects were observed, some cases showed an increase in frequency of seizures and the trial was stopped for 8 cases. 4. "Global evaluation" showed an overall improvement rate of 9.4%. In 47 cases, in which changes in frequency of seizure were confirmed and dosage of flunarizine was subsequently changed, improvement rate was 12.8%. 5. The above results suggest that the effectiveness of flunarizine in this open trial was very low.