ETHANOL INDUCES TRANSIENT ARREST OF CELL DIVISION (G2 + M BLOCK) FOLLOWED BY G0/G1 BLOCK: DOSE EFFECTS OF SHORT- AND LONGER-TERM ETHANOL EXPOSURE ON CELL CYCLE AND CELL FUNCTIONS

To study the cytophysiological effects of ethanol systematically,L929 cells, a fibroblastic cell line derived from mouse connectivetissue, were exposed to various concentrations of ethanol (12.5,50, 100 and 200 mM) for short (3 and 6 h) and longer (24 or26 h) durations. Ethartol-induced cellular responses were analysedby a combination of the following assays: number of cells, amountsof DNA and protein, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide) assay and cell cycle. Ethanol dose-dependently suppressedthese cellular functions, except that 12.5 mM exposures forboth 6 and 26 h increased the amount of protein in spite ofalmost no change in other cellular functions, compared to thecontrol. The most marked dose-dependency was observed in a reductionof formazan product in an MTT assay after both 6 and 26 h exposuresto ethanol, being independent of the number of cells and probablyreflecting dose-dependent depression of mitochondrial respiration.A G₂+M block in the cell cycle, an inhibition of cell division,was induced after short-term exposures (3 and 6 h) to 100 and200 mM ethanol, but the block was released before 24 h had passed.Alternatively, prolonged exposures (24 h) to 50–200 mMethanol induced a G₀/G₁ block, resulting in a decrease in theamount of DNA below the control value. Moreover, the percentageof the S phase was decreased gradually and dose-dependentlythroughout the 24 h exposure. Thus, high concentrations of ethanol(50, 100 and 200 mM) perturbed the cell cycle progression bycausing both a transient G₂+M block (an inhibition of mitosis)and a continuous G₀/G₁ block, though the latter was masked bythe G₂+M block during shortterm exposure. The cells seem finallyto acquire some tolerance to ethanol so as to pass through mitosis,but much less tolerance to pass through the checkpoint fromthe G₁ to the S phase, which results in a decline in proliferation.     

Efficacy of hypothermic perfusion using University of Wisconsin solution in extended hepatectomy with hepatic inflow occlusion in a canine model

This study was designed to elucidate the efficacy of University of Wisconsin (UW) solution for preventing liver injury, when used as a hypothermic perfusate infused into the systemic circulation during extended hepatectomy with hepatic inflow occlusion. Adult mongrel dogs (9.5–17.5 kg, n= 14) were subjected to 75% hepatectomy under 60 min hepatic inflow occlusion. The animals were divided into two groups. The UW group (n= 7) underwent hypothermic perfusion using 4°C UW solution (core temperature of the liver: 12.3±0.2°C). The control group designated as the Ringer's lactate (LR) group (n= 7) underwent hypothermic perfusion using 4°C LR solution. The perfusate was introduced into the systemic circulation via the hepatic vein. Blood from the hepatic vein was sampled, and alanine amino-transferase, purine nucleoside phosphorylase activities and the ammonia concentration were measured. The 7 day survival rate was higher in the UW group than in the LR group. The parameters of liver function were less significantly altered in the UW group than in the LR group. The plasma ammonia concentration was significantly (P<0.05) lower 6h after reperfusion in the UW group than in the LR group. A small volume of hypothermic perfusion of the liver using UW solution was safe if it returned to systemic circulation. Hypothermic perfusion of the liver using UW solution may be effective for preventing hepatic tissue injury during extended hepatectomy with hepatic vascular occlusion.     

A Case of a Short-Coupled Variant of Torsades De Pointes with Electrical Storm

TAKEUCHI, T., et al. : A Case of a Short-Coupled Variant of Torsades De Pointes with Electrical Storm. This case report describes a short-coupled variant of Torsades de Pointes with a characteristic ECG pattern consisting of a prominent J wave in leads V₃–V₆, in which an electrical storm was evoked with autonomic receptor stimulation and a blockade test. The patient's frequent VF attacks were triggered by short-coupled premature ventricular contractions with a right bundle branch block morphology and left-axis deviation, and were suppressed by deep sedation followed by a combination therapy using verapamil and mexiletine. Interestingly, with the use of those drugs, the prominent J wave diminished. The mechanism underlying this syndrome is discussed. (PACE 2003; 26[Pt. I]:632–636)     

Pyruvate dehydrogenase complex deficiency with multiple minor anomalies

Pyruvate dehydrogenase complex (PDHC) deficiency is known to cause congenital lactic acidosis. The case of a 9-month-old female infant with PDHC deficiency caused by a mutation in exon 11 of the pyruvate dehydrogenase (PDH) Elα gene is described. Her facial features were as follows: frontal bossing, upslanting palpebral fissures, a short upturned nose, a long philtrum and low set ears. These anomalies are characteristic not only of a malformation syndrome or chromosomal aberration, but also of PDHC deficiency. Because PDHC deficiency requires early treatment, metabolic disorders should be kept in mind in a patient with dysmorphic features. Further, she had multiple minor anomalies including bilateral inguinal herniae, an umbilical hernia and small hands and feet, which have not been described in previous reports.     

Accidental transmission of HCV and treatment with interferon

Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunode?ciency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2–3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.     

Retroperitoneal perforation of a pancreatic cyst during endoscopic retrograde pancreatography

A 70‐year‐old man was admitted to Ueno Municipal Hospital, Ueno, Japan, for evaluation of abdominal distension. Computed tomography showed a 1 × 1 cm cyst at the pancreas tail. Endoscopic retrograde pancreatography (ERP) showed a normal pancreatic duct after the first gentle injection and an enhanced cyst at the pancreas tail. Extravasation of the contrast medium occurred from the pancreatic duct to the superior‐dorsal extrapancreas at the same time of the next low‐pressure manual injection. Computed tomography showed extravasation of the contrast medium from the pancreas cyst to the retroperitoneal space after ERP. It was considered that the cyst wall weakness, in addition to slight elevated pancreatic duct pressure, caused the disruption of the cyst wall.     

Interferon-related mental deterioration after craniotomy for removal of metastatic renal cancer

Interferon-related severe adverse events on the central nervous system are relatively rare, because interferon-alpha (INF-alpha) can not cross an intact blood-brain barrier. We experienced remarkable mental deterioration caused by INF-alpha administration in a 43-year-old man with renal cell carcinoma after surgical removal of a metastatic brain tumor. We detected a high concentration of INF-alpha in a cerebrospinal fluid sample, which was comparable to that in the serum at 24 h after the administration of INF-alpha; 5x10(6) IU i.m., suggesting that the blood-brain barrier was damaged somehow by the craniotomy. The mental deterioration improved shortly after discontinuation of the INF-alpha administration.     

Differentiating early and late-onset depression with multichannel near-infrared spectroscopy

Background: Individuals with late‐life depression can be divided into two categories, those with early and late‐onset depression (EOD and LOD, respectively). It has been reported that LOD has more accentuated subcortical vascular lesions and frontal lobe dysfunction (hypofrontality). The aim of the present study was to examine whether LOD exhibits more prominent hypofrontality than EOD during performance of the word fluency task (WFT) under multichannel near‐infrared spectroscopy (NIRS), a newly developed non‐invasive functional neuroimaging technique. Methods: Eleven patients with EOD, 12 patients with LOD, and 13 healthy controls participated in the study. Clinical symptoms of depression were equivalent in the EOD and LOD groups. Brain magnetic resonance imaging demonstrated more robust subcortical vascular changes in LOD than EOD. The NIRS images were obtained using an ETG‐4000, 52‐channel NIRS system (Hitachi Medical, Tokyo, Japan). Mean changes in oxy‐hemoglobin (oxy‐Hb) were evaluated while the participants performed the phonemic WFT. Results: Healthy controls exhibited clear increases in oxy‐Hb bilaterally throughout the medial to the lateral frontal cortices and the superior temporal areas during the WFT. In contrast, increases in oxy‐Hb were mildly attenuated in EOD and severely attenuated in LOD in most channels. Subsequent analyses revealed that increases in oxy‐Hb in LOD during the WFT was significantly poorer than in EOD in the left lateral portion of the cortex, including the dorsolateral prefrontal and the superior temporal areas. In addition, significant negative correlations were obtained between the age of onset and oxy‐Hb, as well as between subcortical vascular changes and oxy‐Hb in the lateral channels. These findings suggest that the higher the age of onset of depression, and the more prominent the vascular lesions, the greater the attenuation in lateral frontal and temporal activation, as indicated by NIRS. Conclusions: Multichannel NIRS is useful for demonstrating attenuated functional activation in the left lateral prefrontal and temporal areas in LOD and, thus, for differentiating between LOD and EOD. The NIRS findings observed may have useful clinical implications for treatment‐resistant LOD.