<症例>マムシ (Agkistrodon halys Blomhoffii) 咬傷における少量抗毒素血清投与の経験 : 43症例の検討

Forty-three consecutive patients of venomous snakebite by the Japanese viper (Agkistrodon halys Blomhoffii, "Mamushi" in Japanese) were treated with an uniformly scheduled therapy from 1990 and 1994. The therapy was mainly composed of minimal dose of antivenin, methylprednisolon and cepharanthin. There were two clinical courses, i.e., the minimal envenomation course (Group A, n=14) and the severe one (Group B, n=29). Our treatment was so satisfactory that all patients of both groups fully recovered activities of daily living with neither organic disorders nor sequelae of the bitten extremities. The high appearance ratio of atypical lymphocytes (P < 0. 05) and the increased ratio of lymphocyte count to White blood cell count (P<0. 02) could be indicators that predict hich clinical courses the patients take.1990年から1994年までの5年間に当院で治療したマムシ咬傷43例について検討した. 当院では原則として抗毒素血清, ステロイド, セファランチンの投与を行っているが, 死亡例はなく, 咬傷部の機能障害を示した症例もなかった. 4例（9. 3%）に即効型過敏反応が認められた. 1例は anaphylaxy shock を呈したが治療により即時改善をみた. 遅延型血清病は入院期間中観察されなかった. McCollough らの分類により軽症例（n=14）と重症例（n=29）に分け予後因子を検討した. 治療開始前の WBC, CPK, LDH, BUN, Cr はいずれも重症化指標とはなりえなかったが, 白血球中のリンパ球比率（P<0. 02）, 異型リンパ球出現率（P<0. 05）が高い程, 重症化することが示唆された. 死亡報告が散見されるマムシ咬傷に対し受傷早期の抗毒素血清投与は有用であり, 即効型過敏反応に即座に対応すれば比較的安全に投与できるものと考えられた. しかし, 軽症例に対しての抗毒素血清投与には疑問が残り, 今後は重症化が危倶される症例を的確に選択する必要があると思われた

Dissection of Ire1 Functions Reveals Stress Response Mechanisms Uniquely Evolved in Candida glabrata

Proper protein folding in the endoplasmic reticulum (ER) is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR), is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata Δire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata

Hemodynamic Performance of the Biventricular Bypass System Operated in an Independent Variable Rate Mode

The present study was undertaken to determine whether a biventricular bypass system operated in an independent variable rate (VR) mode can maintain the entire circulation. Two pusher-plate pumps which incorporated the Hall effect position sensors were used to bypass the right and left ventricles in 10 sheep under fibrillation. The flow distributions of the pump output to the carotid and renal arteries were investigated every 6 h using ultrasonic blood flow meters for 24 h in 5 animals, and the controllability of the VR mode was evaluated in 5 long-term experiments. The carotid artery flow ratio to the pump output decreased significantly from 4.7 +/- 0.8% before the bypass to 2.7 +/- 0.9% after 24 h. However, the renal artery flow ratio did not change throughout the experiments. In the long-term experiments, the animals were kept alive from 3 to 48 days (mean 15.6 days). The mean pump output had been maintained at more than 90 ml/min/kg for the first 7 days. After the surgery, the pump driving conditions were not readjusted in any experiment. The results indicate that the biventricular bypass system operated in the independent VR mode automatically maintains the entire circulation at a satisfactory level.</p

Use of ventricular assist devices in patients with postcardiotomy shock.

Over the last three years, we have used ventricular assist devices (VAD) in 7 patients. Of these 7, four patients with combined aortic and mitral valvular disease underwent double valve replacement; one patient with annuloaortic ectasia underwent a Cabrol's operation; another had aortic valve replacement; the last patient had triple coronary artery bypass grafts. The only patient who could be weaned from CPB developed cardiogenic shock after the operation. LVADs supported 6 patients for 4 to 8 days and a BVAD supported one patient for 9 days. All patients survived the weaning procedure. Three were discharged from the hospital and survived 7 to 21 months. The 4 other patients died of multiple organ failure. Three of these four suffered from both renal failure and infection, while one patient had arrhythmia and died of ileus. These data suggest that renal failure and major infection can be serious detrimental complications to VAD support.</p

Doppler echocardiographic evaluation of Bjork-Shiley and St. Jude Medical prostheses in the mitral position.

The left ventricular studies by Doppler echocardiography were performed in 50 patients with a Bjork-Shiley (B-S) mitral valve and 50 patients after implantation of a St. Jude Medical (SJM) mitral valve; the effect of valve replacement on the hemodynamic performance at rest and during bicycle exercise was determined from serial echocardiographic data. Twenty-eight patients (56%) of the B-S group and 42 patients (84%) of the SJM group showed a good response to the exercise. There was no significant difference in the effective orifice area at rest among each sizes of the B-S valve. In the SJM valve, on the contrary, the effective valve orifice area increases in parallel to the size of the SJM valve. There was a clear relation between the valve size and pressure gradient. The pressure gradient directly depends on the valve size and the effective orifice area in the SJM valve. High pressure gradient group in both prostheses had a tendency to take negative values of percent increase in stroke volume. Further, there were no cases showing positive values of percent increase in end-diastolic volume among the patients whose pressure gradients were assumed to be more than 10 mmHg at rest. It is suggested that impairment of inflow caused by the artificial valve, prosthetic valve stenosis, is possibly a significant factor causing left ventricular dysfunction, notably a decrease in stroke volume during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)</p

Mechanical circulatory support with a centrifugal pump after open heart surgery.

Since December 1988, a centrifugal ventricular assist device (VAD) was used to support the circulation in 5 patients who could not be weaned from cardiopulmonary bypass (CPB) or developed cardiogenic shock after removal from CPB. Three patients required a left VAD, one needed a right VAD. One patient had biventricular support using a centrifugal left VAD and a diaphragm type right VAD. The duration of the centrifugal VAD support ranged from 6 to 136 (mean 72)h. All patients were weaned from the VAD, but only 2 patients were discharged from the hospital. Two patients died of multiple organ failure, and one died of cardiogenic shock caused by intractable arrhythmia. Infection occurred in all non-survivors, and 2 of them developed renal failure. We conclude that the centrifugal VAD is effective to recover a failing ventricle. The factors related to the unsuccessful recovery were delayed start of the VAD support and major complications such as infection as infection and renal failure.</p

Successful use of the centrifugal ventricular assist device for postcardiotomy cardiogenic shock.

A centrifugal pump was successfully used as a left ventricular assist device (LVAD) in a 54-year-old female who developed cardiogenic shock following open heart surgery. Cardiac index prior to the LVAD support was 1.4 l/min/m2 and increased to 3.0 l/min/m2 at removal of the device, which assisted for 88h. She resumed her daily activity 10 months after the operation and is in New York Heart Association functional class I.</p

A sheep survived for 48 days with the biventricular bypass type total artificial heart.

A biventricular bypass type total artificial heart (BVB-TAH) utilizing two pusher-plate pumps was developed and implanted in a sheep for 48 days with excellent results. A Hall effect sensor was utilized to operate each pump independently with a full stroke at variable rates (VR). With this system, the animal's hemodynamics was kept physiologically, and all metabolic parameters except hemoglobin and hematocrit returned to normal three weeks after implantation. However, signs of infection appeared on the forty-second day, and consequently the animal fell into a state of shock. Even at that time the BVB-TAH maintained circulation by increasing pumping rate automatically. On the forty-eighth day, the animal could not stand and suffered from anuria; the experiment was then terminated after 1,140 h pumping. At autopsy, there was an enlarged heart with an atrophic change, 1,900 ml of pleural effusion, and 3,100ml of ascites fluid. Blood culture taken on the forty-seventh day yielded Acinetobacter calcoaceticus. The BVB-TAH operated in an independent VR mode maintained entire circulation, and has a capability of substituting the native heart function in any situation.</p