Neurological manifestations in Japanese Ama divers.

Repetitive breath-hold (BH) diving can lead to accumulation of nitrogen (N2) in blood and tissues, which may give rise to decompression illness (DCI). An unusual condition is "Taravana", the diving syndrome reported by Cross in the 1960s. That report generated wide discussion as to whether BH diving can cause DCI. Paulev was the first person to suggest the link between DCI and BH diving. He, a submarine medical officer developed symptoms of DCI after a series of BH dives, having proceeded the dives by spending time in a hyperbaric chamber at 20 meters for 8 minutes. Recently four professional Japanese BH divers (Ama) with histories of diving accidents were reported. Magnetic resonance imaging of these divers detected cerebral infarcts localized in the watershed areas of the brain. A survey conducted on their island revealed that many Ama divers had experienced stroke-like events. A clinical feature of DCI in BH diving is that the damage is limited to the brain. Although the mechanisms of brain damage in BH diving are unclear, N2 bubbles passing through the lungs or the heart so as to become arterialized are most likely to be the etiological factor.

Relationship between NAT1 genotype and phenotype in a Japanese population.

NAT1, which biotransforms many carcinogens, is genetically polymorphic. This polymorphism has been postulated as a mechanism for susceptibility differences in cancer, possibly due to NAT1 activity differences. However, the relationship between NAT1 genotype and phenotype is not clear. In our study of 110 Japanese, the frequency of the NAT1*10 allele (0.53, 95% confidence interval 0.46-0.59) was higher than others have observed in Caucasians (0.16). From genotype frequency studies, 26.4% of the subjects belonged to the NAT1*10/*10 genotype, 53.6% to the NAT1*4/*10 genotype and 20% to the NAT1*4/*4 genotype. Neither NAT1*3 nor NAT1*11 genotype was seen in these subjects. In female subjects, we found higher NAT1 activity in NAT1*4/*10 subjects than in NAT1*4/*4 subjects (n = 49; 2.63 versus 2.16 nmol/min/mg protein). NAT1 activity-difference between NAT1*4/*10 and NAT1*10/*10 was not statistically significant. Thus, not only the presence of NAT1*10 allele, but also other factors are suspected of increasing NAT1 activities. After full sequencing of 10 subjects, five individuals having the highest activities and five individuals having the lowest activities, we found NAT1*18A and NAT1*18B to be in the high activity group and the low activity group, respectively. The genotypes containing these variants were heterozygous, i.e. NAT1*4/*18A and NAT1*4/*18B. Due to rare frequencies of these variants, they cannot be considered as other effective, genetic factors on NAT1 activity. Age and tobacco smoking did not affect the relationship between NAT1 genotype and phenotype.

Radiotherapy after hyperbaric oxygenation improves radioresponse in experimental tumor models.

We examined the effect of radiotherapy after hyperbaric oxygen (HBO) breathing in experimental tumors using a tumor growth delay assay. Tumor models used were SCCVII (radiobiological hypoxic fraction: approximately 10%) and 9L tumors (containing less hypoxic cells) subcutaneously transplanted into C3H/He mice and Fisher 344 rats, respectively. Irradiation using X-rays was locally administered to the tumors immediately after decompression. HBO breathing enhanced the radiation response in SCCVII tumors but not in 9L ones. In the next experiment using SCCVII tumors, irradiation was administered 5, 15, 30, and 90 min after decompression. A significant growth delay was seen in the treated animals within 30 min after HBO breathing, and the tumor growth delay time was prolonged 1.61 times as long as that in radiotherapy alone. We concluded that: (1) radiotherapy after HBO breathing is effective for tumors with hypoxic cells; and (2) the time lapse from decompression to irradiation is an important factor in improving radiosensitivity. Radiotherapy after HBO breathing can be used to enhance the efficacy of clinical treatments.

Radiotherapy after hyperbaric oxygenation for malignant gliomas: a pilot study.

The results of radiotherapy combined with hyperbaric oxygen in 9 patients with malignant glioma were compared with those of radiotherapy without hyperbaric O2 in 12 patients. This is the first report of a pilot study of irradiation immediately after exposure to hyperbaric O2 in humans. All patients receiving this treatment showed more than 50% regression of the tumor, and in 4 of them, the tumors disappeared completely. Only 4 out of 12 patients without hyperbaric O2 showed decreases in tumor size, and all 12 patients died within 36 months. So far, this new regimen seems to be a useful form of radiotherapy for malignant gliomas.

Human auditory brain stem response during induced hyperthermia.

A continuous monitoring of auditory brain stem response (ABR) and esophageal (Tes) and rectal temperatures (Tre) were recorded in male undergraduate subjects to investigate a relationship between the interpeak latencies (IPLs) and core temperature. The average change of Tes (36.8-39.5 degrees C) was achieved by immersing the subjects in a temperature-controlled water bath (30-42 degrees C). The IPLs became shorter with the rise in body temperature and were correlated with both Tes and Tre. The average slopes for IPL(I-III) and IPL(I-V) were significantly higher than those for IPL(III-V). The present study of humans indicated that changes of IPL(I-III) and IPL(I-V) were 0.11 and 0.16 ms, respectively, per 1 degree C change in core temperature during induced hyperthermia.

In situ arterial and brain tissue PCO2 responses to acetazolamide in cats.

We have studied how in situ arterial (PaCO2) and brain tissue PCO2 (PbCO2) responses to acetazolamide (AZ) are affected by respiratory patterns. Sixteen cats were anesthetized with ketamine. Group 1 cats (n = 7) breathed air spontaneously. Group 2 cats (n = 6) were paralyzed and ventilated mechanically to maintain PaCO2 at 37 +/- 1 Torr before AZ administration; the respiratory rate and depth did not change during the course of measurements. Two CO2 sensors to measure in situ PaCO2 and PbCO2 continuously were used. One was placed through a burr hole into the cerebral white matter 15 mm in depth, and another was inserted into the femoral artery. After intravenous administration of AZ (20 mg/kg), PaCO2 decreased, after a significant transient rise, and then returned gradually to the baseline in group 1, but it increased gradually and reached a new steady state in group 2. PbCO2 and the PbCO2-PaCO2 gradient increased remarkably in the two groups immediately after administration. We conclude that AZ resulted in a large increase in both PbCO2 and the PbCO2-PaCO2 gradient and that there are two distinct in situ PaCO2 responses to AZ in spontaneously breathing vs. mechanically ventilated animals. The mechanisms for these observations are discussed.

Simultaneous hypertensive intracerebral hematomas: two case reports.

We describe two patients (76- and 54-year-old females) with multiple hypertensive intracerebral hematomas occurring simultaneously. One patient had a right thalamic hematoma extending into the internal capsule and basal ganglia together with an other one in the left putamen. The other patient had two hematomas located ipsilaterally in the left putamen and thalamus. Their neurological examinations showed only unilateral deficits. Their magnetic resonance angiograms revealed no vascular malformations. Neuroradiological procedures are essential for the diagnosis of these multiple brain events.

Neurological accidents caused by repetitive breath-hold dives: two case reports.

We report two Japanese male professional breath-hold divers (33 and 39 years of age) who experienced neurological disorders during repetitive dives to over 20 m of seawater. One patient had right homonymous hemianopsia, and the other presented with right hemiparesis with facial involvement and sensory deficit. In addition, they each had a history of neurological problems following such dives. Magnetic resonance images of their brains disclosed multiple T2-weighted hyperintensities corresponding to their neurological symptoms. Their brain lesions suggest a multiple cerebral infarction caused by occlusion of the cerebral arteries. We conclude that the repetitive deep breath-hold dives induced the brain involvement.

Multiple cerebral infarction in Japanese breath-hold divers: two case reports.

We report on two Japanese breath-hold divers (ama) who developed neurological disturbances following more than 3 hours of consecutive dives to 15-25 meters of seawater. Their magnetic resonance images of the brain showed multiple cerebral infarcts which were consistent with their neurological symptoms. The cerebral lesions seem to have been caused by repetitive breath-hold dives for extended periods of time. Immediate recompression is required when neurological symptoms develop after such dives.

Brain pH responses to acetazolamide and hypercapnia in cats.

The involvement of increased brain tissue CO2 tension in acetazolamide-induced brain acidosis was investigated by comparing the brain pH response to acetazolamide with that to hypercapnia. CO2 and pH sensors were placed bilaterally into cerebral white matter to 15 mm depth in cats. Group 1 cats (n = 9) breathed spontaneously, and in situ brain tissue PCO2, and pH (PbCO2 and pHb) were measured after intravenous acetazolamide administration (20 mg/kg). Group 2 cats (n = 9) were paralyzed and ventilated mechanically, and the changes of pHb were investigated by adjusting the ventilation to maintain the same Pbco2 values as in the acetazolamide-treated group. PbCO2 changes were not significantly different between the two groups. However, pHb responses were quite different: the fall in pHb was progressive in Group 1 but transient in Group 2. Brain acidosis after acetazolamide administration is not due to the rise in brain tissue CO2 tension.

Intracranial pressure responses during hyperbaric oxygen therapy.

The responses of intracranial pressure (ICP) to hyperbaric oxygen (HBO) therapy and arterial gas pressures were investigated. ICP was measured through a ventricular or spinal drainage catheter in patients with brain tumor or cerebrovascular disease. Changes in ICP, heart rate (HR), arterial blood pressure (ABP), and transcutaneous partial pressure of carbon dioxide (PtcCO2) or oxygen (PtcO2) were recorded continuously during air or 100% O2 breathing at 1 and 2.5 atmospheres absolute (ATA). HR and PtcCO2 decreased and mean ABP was unchanged during HBO inhalation. ICP was reduced at the beginning and tended to increase gradually during HBO inhalation. The change from air to O2 without altering respiratory frequency and volume caused a gradual increase of ICP and PtcCO2 with a transient ICP reduction in an artificially respirated patient. Intentionally reduced respiration to maintain PtcCO2 at the value at 2.5 ATA with air caused the ICP to return to near the value at 2.5 ATA with air even during HBO inhalation. These findings suggest that reduced ICP is initially due to direct cerebral vasoconstriction caused by hyperoxia and is maintained mainly by induced hypocapnia during HBO inhalation. Care is required when giving HBO therapy to patients with a high ICP and/or who are respirated artificially.

Hyperbaric oxygen therapy adjunctive to mild hypertensive hypervolemia for symptomatic vasospasm.

The efficacy of hyperbaric oxygen (HBO) therapy was evaluated retrospectively in 43 patients who developed symptomatic vasospasm following acute aneurysm surgery. HBO therapy was given as an adjunct to mild hypertensive hypervolemia in 24 patients. Before HBO therapy, 17 patients had no infarct (Group 1), and seven had infarcts (Group 2) caused by vasospasm. A further 19 patients received mild hypertensive hypervolemia alone (Group 3). Cerebral infarcts developed in four Group 1 and 12 Group 3 patients. A good outcome 1 month after surgery was achieved by 13 Group 1 (76%), one Group 2, and seven Group 3 patients (37%). Fifteen of the 24 patients who received HBO therapy responded to HBO exposure, and 12 responding patients (80%) had a good outcome. During HBO exposure, electroencephalographic improvements were all accompanied by neurological improvements. There were no complications related to HBO therapy. HBO therapy adjunctive to mild hypertensive hypervolemia is helpful in preventing cerebral infarction associated with symptomatic vasospasm.

[New approaches in neurosurgery and hyperbaric medicine--the importance of preventive and industrial medicine].

Neurosurgical patients have been mainly treated by surgical procedures over the past decades. In addition, hyperbaric oxygen (HBO) therapy in neurosurgery has been used in patients with ischemic cerebrovascular diseases, head trauma, spinal damage, postoperative brain edema and others. However, the main therapeutic methods for neurosurgical diseases have changed dramatically due to developments in radiological techniques, such as radiosurgery and intravascular surgery. With changes in therapeutic methods, HBO therapy may become a very important treatment option for neurosurgical patients. For example, HBO therapy combined with radiotherapy (UOEH regimen) and anticoagulant therapy appear to be very effective in the treatments of malignant brain tumors and ischemic cerebrovascular diseases, respectively. On the other hand, medical examinations under hyper- and hypobaric environments have not yet been fully studied in the central nervous system compared to those in the cardiopulmonary systems. Moreover, the mechanisms of cerebral lesions in decompression sickness and acute mountain sickness remain unclear. Clinical neurologic approaches are very important in these fields. Hence, clinicians and researchers skilled in both neurosurgery and hyperbaric medicine will be required for advanced treatment and preventive and industrial medicine.

Pirmenol hydrochloride-induced QT prolongation and T wave inversion on electrocardiogram during treatment for symptomatic atrial fibrillation.

Pirmenol hydrochloride is a new orally effective, long-acting antiarrhythmic agent currently used in patients with supraventricular and ventricular tachyarrhythmias. We report on a 56-year-old female who exhibited drug refractory paroxysmal atrial fibrillation, in which marked prolongation of the QT interval and T wave inversion on electrocardiogram was demonstrated reproducibly shortly after the administration of oral pirmenol therapy. The plasma concentration of pirmenol was at a subtherapeutic level and the lymphocyte stimulation test was positive in this patient. Thus, an immunological mechanism might be involved in the mechanism of pirmenol-induced QT prolongation and T wave inversion on the electrocardiogram.

Overnight recordings of intracranial pressure and electroencephalography in neurosurgical patients. Part I: Intracranial pressure waves and their clinical correlations.

Simultaneous overnight recordings of intracranial pressure (ICP) and electroencephalography (EEG) were conducted on 85 neurosurgical patients with intracranial hypertension and/or ventriculomegaly. Intracranial pressure waves were classified into five types according to the pattern of appearance, and their correlation with sleep cycles and clinical conditions of patients were investigated. A-waves appeared exclusively in patients with long-standing intracranial hypertension, and episodic B-waves appeared in patients with chronic hydrocephalus or a postoperative tumor-free condition. When these episodic pressure waves appeared, the patients were conscious and sleep cycles including REM stage were observed. Persistent, high pressure B-waves were seen mostly in patients with an acute phase of intracranial hemorrhages. The consciousness of these patients ranged from drowsy to stupor. EEG showed alternate appearances of light sleep and waking rhythms in accordance with cyclic oscillations of B-waves which coincided with periodic, apneic respiratory rhythms. When markedly regular B-waves of moderately high pressure appeared continuously, the patients were severely impaired in consciousness and were mainly in a subacute phase of intracranial hemorrhages. EEG showed continuous slow activities and sleep stages were not scored in these patients. No characteristic clinical features were found in patients whose ICP remained within normal range without pressure waves throughout the recording.

Overnight recordings of intracranial pressure and electroencephalography in neurosurgical patients. Part II: Changes in intracranial pressure during sleep.

Changes in intracranial pressure (ICP) during sleep were investigated in 37 patients with chronic intracranial hypertension or chronic hydrocephalus, in whom episodic pressure waves characterized by A-waves or episodic B-waves were seen in Part I of this paper. The patients were conscious, and sleep stages including REM sleep were observed in all of them. During non-REM sleep, ICP significantly rose in Stage II on many occasions, and was always lower in Stage IV than in other sleep stages. A marked elevation of ICP was seen in REM sleep. ICP changes during REM sleep were characterized by frequent appearances of the pressure waves; 88.9% of A-waves and 95.1% of episodic B-waves appeared during REM sleep. The initiation of REM sleep scored on EEG began 1 to 2 minutes prior to or at the onset of the episodic pressure waves. The episodic pressure waves are assumed to be induced by the intracranial conditions in REM sleep, when increased brain activity and reduced sympathetic tone are known to occur simultaneously.

[Procainamide-induced skin eruption associated with disseminated intravascular coagulation in a patient with sustained ventricular tachycardia].

A 70-year-old man, who had sustained ventricular tachycardias following a previous anterior myocardial infarction, suffered from skin eruptions and abnormal blood tests after 10 days following the oral administration of 1500 mg/day of procainamide. These abnormalities disappeared early after the discontinuation of oral procainamide. However, similar skin eruptions exhibited again when the procainamide was resumed. These results suggest that oral procainamide therapy induces skin eruptions and serious abnormal blood tests in the patient. No reports have suggested such a serious early complication by procainamide therapy. Careful follow-up is needed after the administration of oral procainamide therapy.

[Thrombosed AVM presenting temporal lobe epilepsy].

A rare case of thrombosed AVM presenting temporal lobe epilepsy is reported. A 27-year old man was admitted to our hospital because of a 7-year history of temporal lobe epilepsy. He had also suffered from generalized seizure since he was 6 years old. No neurological deficit was disclosed. CT scan demonstrated a small calcified mass lesion in the left temporal lobe which was not enhanced by contrast study. Skull X - P and cerebral angiography were normal. Low intensity area on T1-weighted MR image corresponded to the high density area on CT scan. T2-weighted MR image demonstrated that peripheral low intensity area was more prominent and extensive. Conventional EEG showed focal spike discharges from the left fronto-central lead, and subdural EEG recordings showed intermittent spike discharges from the medial side of the left temporal lobe. A 5 cm temporal lobectomy was performed and a thick fibrous mass adjacent to the hippocampoamygdala complex was removed. Histopathological examination demonstrated a thrombosed AVM surrounded by gliotic neural tissue.

[Gliosarcoma associated with von Recklinghausen's disease: a case report].

A very rare case of gliosarcoma with von Recklinghausen's disease is presented. A 51-year-old man was admitted to our hospital in March 1990, because of a 2-month history of personality change and left hemiparesis. Multiple neurofibroma over his whole body with many café au lait spots had been present since early childhood. His mother, brothers and children also had café au lait spots. Neurological examination on admission revealed memory disturbance, left homonymous hemianopsia and left hemiparesis. CT scan showed a large lobular lesion in the right temporoparietal region. The medial hypodense part was sharply demarcated by a ring-like enhancement, while the lateral isodense part was homogeneously enhanced. MRI showed a sharply demarcated high intensity lesion with Gd-EDTA enhancement corresponding to the enhanced area on CT. Faint staining on angiography revealed that the blood supply to the tumor was predominantly dural. At surgery, the tumor was solid and highly vascular, and adhered tightly to the dura. The superficial part of the tumor was well demarcated from the brain tissue, but the demarcation was obscure in the deeper part. Histological findings showed two clearly defined neoplastic components: a gliomatous component that was stained for GFAP, and a sarcomatous component that had spindle-shaped nuclei and eosinophilic fibers. The patient underwent radiotherapy after surgery, but the tumor soon recurred. A second operation was performed, but the tumor had infiltrated into the scalp and he died 10 months after the first operation. This combination is very rare and has not been reported previously.