A case of "interval" form of acute carbon monoxide poisoning--brain MRI and therapeutic effect of hyperbaric oxygenation

A 43-year-old female who had suffered from paranoid reaction attempted suicide with city gas. She was admitted to an emergency hospital in a comatose state, regained consciousness the next day and was discharged 12 days after. However, on the 21st day after the poisoning, behavioral anomalies and staggering appeared. She was readmitted into another emergency hospital with the diagnosis of an "interval" form of acute carbon monoxide poisoning. She was performed hyperbaric oxygen therapy 42 times until the 53rd day after the accident. Nevertheless, her symptoms did not improve and remained in a state like an apallic syndrome. With little promise of improvement, she was moved to our hospital, and hyperbaric oxygen therapy further continued for 40 times which resulted in a remarkable recovery. Repeat EEGs were performed. On the 32nd day, EEG showed an abnormality consisting of generalized delta waves. On the 56th day, the abnormal EEG improved slightly with more alpha activity. EEG was normalized 126 days after. The X-ray CT scan on the 32nd day revealed low densities in the bilateral globus pallidus and the deep white matters adjacent to the frontal horns of the lateral ventricle and in the semioval centers. On the 57th day, these low density areas were depicted more clearly by the X-ray CT scan, which became less marked on the 73rd day. MRI was performed 3 times.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

     

Pax-1 in the development of the cervico-occipital transitional zone

The Pax-1 gene has been found to play an important role in the development of the vertebral column. The cervico-occipital transitional zone is a specialized region of the vertebral column, and malformations of this region have frequently been described in humans. The exact embryonic border between head and trunk is a matter of controversy. In order to determine a possible role of Pax-1 in the development of the cervico-occipital transitional zone we studied the expression of this gene in a series of quail embryos and murine fetuses with in situ hybridization and immunohistochemistry. Pax-1 is expressed in all somites of the embryo, including the first five occipital ones. During embryonic days 3–5 the gene is down-regulated in the caudal direction within the first five somites, whereas more caudally Pax-1 is strongly expressed in the cells of the perinotochordal tube. In 5-day-old quail embryos, the cartilaginous anlage of the basioccipital bone has developed and there is no more expression of Pax-1 in this region. The fusion of the dens axis with the body of the axis also coincides with switching off of the Pax-1 gene. More caudally, the gene is continuously expressed in the intervertebral discs of murine embryos and therefore seems to be important for the process of resegmentation. Quail embryos do not possess permanent intervertebral discs. Hyper- or hyposegmentation defects may be explained by an over- or under-expression of Pax-1 during development. We also reinvestigated the border between the head and trunk in chick embryos by performing homotopical grafting experiments of the 5^th somite between chick and quail embryos. Grafted quail cells formed mainly the caudal end of the basioccipital bone. They were also located in the cranial half of the ventral atlantic arch, and only a few cells were found in the tip of the dens axis.     

Physiological levels of estradiol correlate with lipid / lipoprotein profiles in healthy men

In this cross-sectional study, the relationships of the physiological levels of estradiol (E2) and dehydroepiandrosterone-sulfate (DHEA-S) to the lipid and lipoprotein profiles were investigated in 212 apparently healthy men aged from 18 to 59 years old. These subjects were divided into tertiles according to the levels of E2 and DHEA-S, respectively. We performed one-way analysis of variance and analysis of co-variance controlling for age, body mass index, percent body fat, waist to hip ratio, maximal oxygen uptake, alcohol and cigarette consumptions as confounding factors.A lower E2 level was associated with higher concentrations of total cholesterol (TC) and low density lipoprotein cholesterol. A lower DHEA-S level was associated with a lower concentration of high density lipoprotein cholesterol (HDLC) and a higher ratio of TC / HDLC. These correlations remained significant after adjusting for the above confounding factors. Neither free testosterone nor sex hormone-binding globulin was associated with the lipids and lipoproteins. These results suggest that higher levels of E2 and DHEA-S, at least in physiological concentrations, are related to the favorable lipid and lipoprotein levels in men.     

In vitro drug-drug interactions with perospirone and concomitantly administered drugs in human liver microsomes.

In vitro metabolism studies were conducted to assess drug-drug interactions between perospirone, an antipsychotic agent, and concomitantly administered drugs--biperiden, flunitrazepam, haloperidol, and diazepam--using human liver microsomes. The metabolism of perospirone in the presence of 100 microg/ml drugs was decreased to 45-73% of that in their absence, whereas no effects were observed with any of the drugs at 1 microg/ml or lower. The effects of perospirone on the metabolism of concomitantly administered drugs were also assessed, and no inhibitory effect was observed. Thus, the metabolism of perospirone and concomitantly administered drugs did not demonstrate any marked mutual inhibition in the human liver microsomes. On the other hand, the perospirone metabolism was markedly reduced by ketoconazole indicating a major role for CYP 3A4. Based on the inhibition constant (Ki) for perospirone metabolism and the plasma unbound concentration of ketoconazole, in vivo perospirone clearance was estimated to be reduced to 64-90% of the control level. Thus careful attention should be paid to the possibility of increase in unchanged perospirone concentration when perospirone is co-administered with drugs that are known as CYP3A4 inhibitors, including macrolide antibiotics and other imidazole antifungals.     

An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker.

We reported previously that an angiogenesis inhibitor, E7820, inhibits in vitro tube formation of human umbilical vein endothelial cell through the suppression of integrin alpha2 expression. Here we describe the antiangiogenic and antitumor effects of E7820 in mice and discuss the feasibility of using platelet integrin alpha2 expression on platelets as a biological marker of the efficacy of E7820. Oral administration of E7820 significantly inhibited basic fibroblast growth factor-induced angiogenesis in Matrigel implants and human colon WiDr tumor-induced angiogenesis in a dorsal air sac model. Twice-daily treatment with E7820 clearly inhibited the s.c. tumor growth of seven tumor cell lines derived from human colon, breast, pancreas, and kidney, and completely suppressed the growth of human pancreatic KP-1 and human colon LoVo cell lines. Moreover, E7820 significantly inhibited the growth of KP-1 and human colon tumor Colo320DM cells orthotopically implanted in the pancreas and cecum, respectively. The efficacy of E7820 was comparable in the s.c. and orthotopic transplantation models. Immunohistochemical analyses using anti-CD31 antibody showed that E7820 significantly reduced microvessel density in orthotopically implanted KP-1 tumor. E7820 reduced integrin alpha2 expression on a megakaryocytic cell line, Dami cells, induced by phorbol 12-myristate 13-acetate treatment. It also decreased the expression level of integrin alpha2 on platelets withdrawn from mice bearing s.c. KP-1 tumor at a dosage close to that affording antitumor activity. These data demonstrate that E7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E7820.     

Prolonged suppressed thyroid-stimulating hormone levels in hyperthyroidism in a neonate born to a mother with Graves' disease

Abstract We report here a case of neonatal hyperthyroidism born to a mother, whose pregnancy was complicated by poorly controlled Graves' disease. The patient demonstrated exophthalmos and marked goiter at birth, indicating the existence of thyrotoxicosis in utero. The mother's Graves' disease was well controlled in the third trimester, resulting in a slightly lower level of free thyroxine (FT₄) in the umbilical cord blood serum; however, thyroid-stimulating hormone (TSH) was undetectable. Thyroid-stimulating hormone remained undetectable for 2 months, while FT₄ levels varied in the course. This case suggests that severe and prolonged thyrotoxicosis in utero, due to poor control of pregnancy with Graves' disease, might induce unresponsiveness of the hypothalamo-pituitary system in the newborn.     

A case of embolization to a large polycystic kidney with infection

75 year old female who was hospitalized for abdominal pain and fever up on 12th May 1998. She had been followed as a polycystic kidney patient since few years. The swelling of the right kidney and her general condition became gradually worse. On 18th May, the embolization to the right kidney using pure alcohol and gelatin sponge was performed. Within a month, CT scan showed the reduced volume of the right kidney and her blood examination data as well as her general condition became gradually well. And on 17th June, she left our hospital without any complication.     

Suicidal attempts in three postoperative patients with renal cancer after alpha interferon withdrawal

We report 3 cases of suicide attempts in postoperative patients with renal cancer after alpha interferon withdrawal. In the first patient, depression occurred during interferon therapy, and remained after interferon withdrawal. A suicide attempt occurred 7 months after interferon withdrawal. In the second and third patients, depression did not occur during interferon therapy, but suicide attempts occurred 40 days and 7 months after interferon withdrawal, respectively. Depression does not always disappear after interferon is discontinued. Psychiatric supervision should be continued even more frequently after interferon withdrawal. The increased risk of psychiatric side effects due to interferon, as well as their severity, suggest that interferon should be administered with caution.     

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.