The Limulus amoebocyte gelation test was first proposed by Levin and Bang in 1970 for assaying endotoxin (Et) in the human bloodstream. This highly sensitive and specific assay technique has been used to detect Et in various samples apart from in mammalian blood. When the Limulus test is applied to detect Et in human blood, Etactivated lysate gelation is not observable. This is thought to be hampered by certain inhibiting proteins in plasma. Several pretreatment procedures of plasma have been tried to eliminate this inhibition by plasma. Chloroform extraction, dilution plus heating, and acidification by perchloric acid (PCA) or trifluoroacetic acid (TFA) are representative. Recently Iwanaga et al clarified the mechanism of Et-activated lysate gelation, and developed a new quantitative technique of Limulus test by measuring optic density using a chromogenic substrate. In this technique, plasma pretreatment is also necessary. Chloroform extraction is not suitable because the sample may become too turbid to measure the optic density. Dilution and heating are not the best methods, either, because the optic density values are unstable. If the acidification technique is employed, most Et combined with protein should be precipitated; thus the amount of Et in the supernatant must be extremely small. Therefore, the determined Et concentration may be too low. Thus these methods for eliminating the inhibition of plasma are not perfect. However, the Limulus test, an outstanding assay technique for bacterial Et, will be used until a better assay technique is proposed. We must await an improved technique for eliminating the inhibition caused by plasma.

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Benzodiazepines exert a neuroinhibitory effect by enhancing γ-aminobutyric acid (GABA)-mediated neurotransmission in the central nervous system. We attempted to measure endogenous benzodiazepine activity in the sera of 6 patients with anoxic encephalopathy who had been resuscitated after cardiopulmonary arrest following asphyxia, drowning, hemorrhagic shock, shock at anesthesia or arrhythmias in acute myocardial infarction. Consciousness levels, according to the Glasgow coma scale (GCS), were 3 in 3 patients, 6 in 2 and 1 in 1, none of whom had taken any synthetic benzodiazepines. To confirm the presence of the endogenous benzodiazepine-like compound, the effects of the benzodiazepine antagonist flumazenil were studied while monitoring the consciousness level, electroencephalogram (EEG) and electrooculogram (EOG). Benzodiazepine receptor assay was applied to measure serum benzodiazepine-receptor binding activity. Consciousness level, EEG and EOG were evaluated continuously for 20 minutes after intravenous bolus injection of 0.5mg of flumazenil. In 4 of 6 patients, serum benzodiazepine-receptor binding activities were detected and ranged from 80 to 650ng/ml as the diazepam equivalent concentration. In 3 patients, the administration of flumazenil induced transient improvements in the consciousness level, from 1 to 4, in the eye opening score as assessed by the GCS. The degree of anoxic encephalopathy on EEG improved from stage III-b to stage III-a, from V-a to III-b, and from V-a to IV-a in 3 of 6 patients and electromyographic artifacts were recorded on EEG in 3 patients after the administration of flumazenil. EOG showed slow eye movements before the administration of flumazenil and changed to slow eye movements overlapped by rapid eye movements after administration of the drug to 2 patients. The clinical and electrophysiological effects occurred in less than 1 minute and lasted for about 15 minutes after drug administration. These findings suggest that an endogenous benzodiazepine-like compound may be induced and may contribute to consciousness disturbance in patients with anoxic encephalopathy.

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The clinical characteristics of 14 cases of prosthetic valve dysfunction (13 patients: 6 males, 7 females, mean age 48.5 years) were retrospectively analyzed. There were 8 cases of mitral (3 porcine, 4 Hall-Kaster and 1 Björk-Shiley), 5 of aortic (3 Hall-Kaster and 2 Björk-Shiley) and 1 of tricuspid (Hall-Kaster) prosthetic dysfunction. There were 4 cases of immediate post-operative dysfunction, of which 2 were caused by impingement of the oversized valve while 2 had valves closed stuck due to a chordal remnant. Electromechanical dissociation was invariably seen in these 4 cases and resulted in low output syndrome or difficulty in weaning from cardiopulmonary bypass. Immediate re-operation was successful in 3 cases. The causes of 10 cases of late prosthetic dysfunction included thrombus in 4, infectious endocarditis in 3, underlying aortic disease in 2 and degeneration of a porcine bioprosthesis in 3 (1 stenosis, 2 regurgitation). Late prosthetic dysfunction of any cause can happen at any time after the first valve replacement. The most common cardiac symptom, congestive heart failure, was seen in all patients. Auscultation revealed either a new murmur or diminished/absent opening/closing clicks in all cases. Repeat surgical intervention was performed in 9 of 10 cases, and was successful in all. Thus, it is important to perform adequate diagnostic tests including fluoroscopy, echocardiography and catheterization without delay, once prosthetic valve dysfunction is clinically suspected. Surgical intervention should be immediately considered if hemodynamically indicated.

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Disseminated thrombotic processes in the microcirculation are considered to be an important cause of multiple organ failure in sepsis patients. In this study, we sought alterations in fibrinolytic parameters [tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)] in 43 sepsis patients who fulfilled the criteria for systemic inflammatory response syndrome (SIRS). Of these 43 patients, 20 developed organ failure and 23 did not. We compared the maximal levels of plasma PAI-1 and t-PA between the two groups. We found that the plasma PAI-1 levels [540.1±435.3ng/ml (mean±SD)] were significantly higher in the sepsis patients with organ failure than in those without organ failure (52.6±47.5ng/ml) (p<0.01). In contrast, only a few patients demonstrated elevated levels of t-PA even among those with organ failure, and no difference in plasma t-PA levels was noted between the two groups. To assess the mechanism of PAI-1 elevation, we also measured circulating levels of interleukin 6 (IL-6) and polymorphonuclear leukocyte elastase (PMN-E). The results indicate positive correlation between plasma PAI-1 and IL-6 (r=0.81, p<0.01) and between PAI-1 and PMN-E (r=0.34, p<0.05). The increases in IL-6 and PMN-E were followed by the increase in PAI-1. These data indicate that PAI-1 production is stimulated by inflammatory mediators. We also measured plasma lactate levels which revealed a relationship between the hypofibrinolytic state and microcirculatory damage. As a result, a positive correlation was observed between PAI-1 and the lactate level (r=0.70, p<0.01). Furthermore, daily measurement of the arterial ketone body ratio (AKBR) and lactate levels confirmed synchronized movement with PAI-1. We conclude that decreased fibrinolytic activity in severe sepsis may contribute to the progression of organ failure via damage to the microcirculation.

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A 27-year-old man was admitted with a complaint of severe headache. CT scans obtained on admission showed not only subarachnoid hemorrhage but also small intracerebral low density lesions. Right carotid angiograms demonstrated an aneurysm at the right IC bifurcation, but no other noticeable abnormalities. By 13 days after onset, the aneurysm was obliterated by a right frontotemporal craniotomy. However, postoperatively, the patient did not fully awaken from anesthesia and left hemiparesis was noted. A CT scan taken at that time showed a large intracerebral hematoma in the right hemisphere. Emergency evacuation of the hematoma was performed, and the clipping proved to be complete. Postoperatively, to investigate the cause of the intracerebral hematoma, the preoperative angiograms were reexamined and sinus occlusions were identified; the main route of venous drainage was via the sylvian veins and the sphenoparietal sinus. These venous abnormalities strongly suggested that the most likely mechanism of the postoperative hemorrhage was exacerbation of poor venous return caused by constriction of an already disturbed venous system, and that the low density areas on CT scans were probably due to previous hemorrhagic changes. After two months of physical rehabilitation, the patient was discharged with left hemiparesis.

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A 6-year-old boy diagnosed with posttraumatic rhinorrhea was successfully treated by recognition of the cerebrospinal fluid leakage pathway using magnetic resonance imaging (MRI). He fell down from the third floor. His consciousness deteriorated after admission due to the elevated intracranial pressure, and barbiturate therapy was performed. Transcranial Doppler sonography suggested hyperemia on the first day and vasospasm due to the traumatic subarachnoid hemorrhage on the fifth day after injury. Posttraumatic rhinorrhea appeared 12 hours after injury and gradually deteriorated. Moderate meningitis occurred, and antibiotic therapy was started. Right anterior cranial base fracture was detected by bone window CT. The axial view of conventional CT scan revealed pneumocephalus in the bifrontal lobe, traumatic subarachnoid hemorrhage in the right sylvian fissure and cerebral contusion in the right frontal region. The craniogram revealed bone fracture on the frontal base but did not show the fistula. MRI showed incarceration of the right rectal gyrus into the right ethmoid sinus and defect of the cortical substance of the frontal bone. Closure of the fistula and repair of the injured dura mater were performed on the sixth day, and bone defect in the right lamina cribrosa and incarceration of the rectal gyrus were recognized by MRI. His postoperative course was excellent. The rhinorrhea disappeared and the meningitis improved. He was discharged on the 34th day after the accident with no complaint except for right blindness due to optic canal fracture.

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Severe accidental hypothermia is associated with marked depression of the brain and cardiovascular function and carries a high risk of mortality. We present three such cases with core temperatures between 18 and 27°C. Two of these patients had cardiac arrest on arrival at the emergency department. Rapid rewarming and successful recovery of spontaneous circulation was accomplished by a combination of direct cardiac compression and continuous irrigation of the pericardial cavity with warm fluids (42°C) in one of the patients with cardiac arrest. The best choice of treatment for severe hypothermia complicated by cardiac arrest is partial cardiopulmonary bypass, but this modality is not readily available in many settings. In such cases, a combination of direct cardiac compression and continuous pericardial irrigation is the best available alternative. Other rewarming modalities for severe hypothermia syndrome are also reviewed.

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We describe a patient with brainstem dysfunction who developed alpha coma after cardiac arrest due to traumatic asphyxia. A 22-year-old man was brought to our hospital in deep coma after being resuscitated. Neurological examination revealed no brainstem reflexes except breathing. The results of a CT scan of the brain were unremarkable. The initial EEG was flat, but BAEPs showed no abnormal findings. On hospital day 3 the patient was still comatose with tetraplegia and bilateral facial palsy, but the brainstem reflexes had returned. An EEG showed a 12Hz alpha rhythm of about 50μV with preponderance over the anterior regions. SEPs showed prolonged latency upon stimulation of left median nerve and left posterior tibial nerve. The blink reflexes showed a normal R₁ latency, but a prolonged R₂ latency, directly and indirectly. MRI of the brain showed no abnormal findings. Two weeks later, the patient assumed a decorticate posture. Serial CTs showed moderate cerebral atrophy, and serial EEGs showed that low-amplitude delta activity had supervened. One year later, the patient was able to wink and swallow, but still suffered tetraplegia. Residual SEP abnormalities had improved, however, the prolonged R₂ latency remained unchanged. Serial neurological and electrophysiological findings suggested that alpha coma occurs not as a result of damage to the brainstem, but of extensive damage to the cerebrum.

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A 10-year-old boy suspected of being in septic shock associated with perforation of the appendix was transferred to our hospital for emergency laparotomy. After appendectomy, drainage and antibiotic therapy, the clinical signs and symptoms of septic shock showed some improvement, but ventilatory assist and high-dose catecholamine drip infusion were still necessary. As there was a strong suspicion of Fournier's syndrome, especially with signs of increasing redness and edema around the scrotum, which became severe, emergency surgical debridement of the necrotic scrotal tissue was performed under general anesthesia on the second postoperative day. Following this operation, the catecholamine dose was tapered and the patient was weaned from ventilatory assist. The patient was discharged from the ICU to the ward on the 6th postoperative day without any complications. E. coli was isolated from the pus that had played an etiologic role in the septic shock. A high mortality rate has been reported in Fournier's syndrome, and it requirs early diagnosis and surgical intervention. We also emphasize that it should be remembered that peritonitis due to appendicitis can cause Fournier's syndrome even in children.

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A case of “overwhelming postsplenectomy infection” is reported. The patient was a 34-year-old laborer who was splenectomized for trauma 5 years prior to the present illness. He went to work with a chill in the morning and came home with a high fever, vomiting and diarrhea at noon. Upon visiting an emergency center at 9p.m. that night, he was found to be in shock. In the ambulance on the way to our hospital, he became pulseless and unconscious. After a short period of stable blood pressure following CPR, he became hypotensive, and died the next morning. The initial examination showed that WBC, RBC and platelet counts were 8, 800, 520×10⁴ and 1.7×10⁴/mm³, respectively. Sepsis and DIG were suspected. Autopsy and blood culture revealed that the patient had developed pneumococcal sepsis and Waterhouse-Friderichsen syndrome. Immunochemical analysis showed that the amount of antibody to pneumococcal capsular polysaccharides had been reduced to a subnormal level. Splenectomized patients should be recognized as immunocompromized hosts and the high morbidity and mortality risk from sepsis in these patients should also be kept in mind.

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The subject, a 26-year-old male diabetic, came out of a diabetic coma. On the 6th day post coma, he complained of slight headache, followed by lethargy the next day. Brain CT revealed low density regions in the bilateral occipital lobes which were suspected to be the result of cerebral infarction. Neurologic examination on the 7th day revealed blindness agnosia (Anton's symptom). Adiadochokinesis and other cerebellar ataxic symptoms were observed on the 13th day. After several days, Gerstmann's syndrome, including left-right agnosia, agraphia, acalculia and finger agnosia also occurred. Agraphia was marked with respect to hiragana. All of the above neurological deficits had appeared temporally. Perimetry revealed a right homonymous hemianopsia and bilateral expasion of Mariotte's blind spot; figures drawn by complications disappeared completely by the 30th post-coma day. With no sequelae, the patient was discharged from the hospital on the 38th post-coma day. Judging from the findings of gradual recovery of eyesight and the size reduction in the low density regions in the bilateral occipital lobes, we attributed the patient's disorder to a transient regional cerebral edema. It remains unknown why the present subject alone, unlike many other diabetic ketoacidosis patients, followed this unique disease course, and why the disorder occurred during the clinically and hematologically stable stage.

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An operative case of intracranial hematoma associated with congenital factor XIII deficiency is reported. A 22-year-old male was admitted to our service on November 2, 1993, because of progressive headache with scintillating scotoma for the previous 3 days. Initial CT scan showed a right occipital subcortical hematoma. Cerebral angiography disclosed a right occipital mass lesion only. Routine laboratory studies on admission, including hematological examination, were all normal. His condition gradually deteriorated until the 7th hospital day. An occipital craniotomy was thus performed. Exceptional bleeding forced us to transfuse fresh blood during the operation. The hematoma was successfully evacuated. The postoperative course was uneventful and the patient was discharged without neurological deficits. Detailed hematological postoperative studies revealed that the patient was deficient in factor XIII, deficiency of which was detected in his mother as well, thus confirming the diagnosis of congenital factor XIII deficiency. Diagnosis and treatment of the disease are discussed herein. Quantitative analysis of coagulation factors is recommended in all patients with unexplained non-traumatic intracerebral hemorrhage.

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We report the case of a 31-year-old woman who was admitted for an inhalation injury and second degree burn (11% TBSA) with multiple fractures. On day 4 after the injury, we detected Candida albicans in her sputa, urine and wounds. Informed consent for HIV testing was obtained and the test result was positive. She was diagnosed as having AIDS (acquired immunodeficiency syndrome) with candidiasis on the basis of laboratory evidence of HIV (human immunodeficiency virus) infection. We continuously examined her CD4+T-lymphocyte counts. The CD4+T-lymphocyte counts were 296cells/μl on day 11 after injury and had recovered to 459cells/μl by day 24 after injury. By hospital day 31, her burn wounds had healed. We conjectured that her base CD4+T-lymphocytes were low due to the HIV infection and that trauma had markedly diminished CD4+T-lymphocytes and caused candidiasis. We suggest that the injured HIV-positive patient must be treated more aggressively for opportunistic infection.

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