Effect of arachnoid plasty using fibrin glue membrane after clipping of ruptured aneurysm on the occurrence of complications and outcome in the elderly patients.

BACKGROUND: In elderly patients with aneurysmal subarachnoid hemorrhage (SAH), complications including vasosopasm, subdural effusion, and late hydrocephalus, are liable to occur even after aneurysmal surgery. We examined prospectively the efficacy of arachnoid plasty using fibrin glue membrane during surgery of ruptured aneurysms in the elderly patients for preventing complications. The effects on the modified Rankin scale (mRS) and the Glasgow outcome scale (GOS) 3 months after SAH were noted. METHODS: Total of 31 patients aged more than 70 years selected from a consecutive series of patients with aneurysmal SAH, were divided into two groups alternately, a group with arachnoid plasty (n = 16) and a control group without arachnoid plasty (n = 15). Statistical analyses were performed to assess relationships among various clinical and neuroradiological variables, especially between arachnoid plasty and occurrence of symptomatic vasospasm, subdural effusion, late hydrocephalus, or outcome such as mRS and GOS 3 months after onset. FINDINGS: Statistical analyses revealed that arachnoid plasty were associated with late hydrocephalus and subdural effusion negatively, but with better mRS at 3 months after SAH. A tendency to be associated with less frequent symptomatic vasospasm was also noted. CONCLUSION: Arachnoid plasty using fibrin glue is suggested to be effective in preventing complications associated with SAH and aneurysmal surgery. A better outcome in the elderly patients can be achieved.

Brain-derived neurotrophic factor modulates glucagon secretion from pancreatic alpha cells: its contribution to glucose metabolism.

AIM: Brain-derived neurotrophic factor (BDNF) reduces plasma glucose levels in obese db/db diabetic mice and is speculated to produce its effects via the hypothalamus, the regulatory centre of satiety and the autonomic nervous system. The potential effect of BDNF directly on peripheral endocrine organs, however, remains to be clarified. Here we report the effects of BDNF on hormonal secretion from pancreatic islets of Langerhans using their isolated culture. METHODS AND RESULTS: In an immunohistochemical study, mouse pancreatic alpha cells were stained specifically with the anti-TrkB (a specific receptor for BDNF) antibody. After 7 days culture of isolated islets of the normal mouse pancreas, 10 ng/ml BDNF decreased the secretion of glucagon per 6 h significantly less than that of the control (p = 0.016). In contrast, there were no significant changes in insulin secretion or glucagon and insulin contents in the islets cultured under the same conditions. In vivo administration of BDNF (10 mg/kg/day) to normal mice for 7 days significantly decreased their food consumption (p < 0.05). The fasting plasma glucose levels were decreased on day 7 compared with day 1 more significantly in BDNF-treated mice (p = 0.043) than in pair-fed control mice (p = 0.14). In newborn BDNF-knockout mice, fasting plasma glucose levels increased in the order of homozygote, heterozygote and wild type (p = 0.033). No apparent immunohistochemical abnormality was observed for pancreatic glucagon in the BDNF-knockout mice. CONCLUSION: These data suggest that BDNF affects glucose metabolism not only with its anorectic effect but also with modulated glucagon secretion from pancreatic alpha cells.

Insulin inhibits glucagon-induced glycogenolysis in perivenous hepatocytes specifically.

Hepatocytes form the hepatic acinus as the unit of microcirculation. Following the bloodstream, at least 2 different zones can be discerned: the periportal and perivenous zones. Two types of hepatocytes, periportal hepatocytes (PPHs) and perivenous hepatocytes (PVHs), have been thought to be functionally heterogeneous, with PPHs being predominantly gluconeogenic and PVHs being glycolytic. We therefore investigated the region-specific functional effects of insulin on glycogen synthesis, glycolysis, glycogenolysis, and gluconeogenesis in isolated PPHs and PVHs prepared by using the digitonin-collagenase method. Glycogen synthesis from 5 to 20 mmol/L glucose did not differ between the PPHs and PVHs of fed rats during 60 minutes of incubation. Lactate release induced by 5 to 20 mmol/L glucose was 3 times greater from PVHs than from PPHs (P <.01). The addition of insulin did not accelerate either glycogen synthesis or lactate release during 60 minutes of incubation. Insulin did not inhibit glucose release from gluconeogenic substrates with or without 0.2 nmol/L glucagon in either the PPHs or the PVHs of fasting rats. Insulin antagonized the 0.1 nmol/L glucagon-induced increase in glucose release from the PVHs of fed rats during 30 minutes of incubation (to 56.1% +/- 7.2%, P <.01) but not that from the PPHs (to 81.8% +/- 7.3%, P =.10). Thus the antagonizing effect was greater in PVHs than in PPHs (P <.01). Insulin binding did not differ between the PPHs and PVHs of fed rats. It was confirmed that PVHs are actually glycolytic. An acute metabolic effect of insulin was observed only in antagonizing glucagon-induced glycogenolysis in PVHs specifically. The specific effect of insulin on PVHs might depend on the differences in intracellular characteristics between PPHs and PVHs rather than hormone binding.

Side-to-side arterial anastomosis model in the rat internal and external carotid arteries.

Microvascular anastomosis has become a general and essential technique in the field of vascular reconstructive surgery. Side-to-side microvascular anastomosis is rarely performed by microsurgeons. Laboratory training models are essential for the development and refinement of microsurgical techniques. A new experimental model of a side-to-side "arterial" anastomosis in the rat internal and external carotid arteries is presented, in which 100 percent patency was accomplished immediately, and was maintained 7 days after anastomosis. This model can provide an experimental and training tool for side-to-side anastomosis of small arteries.

Hormone-specific combinations of isoforms of adenylyl cyclase and phosphodiesterase in the rat liver.

Since many isoforms of adenylyl cyclase and adenosine 3', 5'-monophosphate (cAMP) phosphodiesterase have been cloned, it is likely that receptors of each hormone have a specific combination of these isoforms. Types I, III and VIII adenylyl cyclases are reported to be stimulated by Ca(2+)-calmodulin, type I phosphodiesterase by Ca(2+)-calmodulin, but types IV and VII (cAMP-specific) phosphodiesterases by Co2+. In the present study, we examined different effects of Ca2+ and Co2+ on hormone-induced cAMP response in the isolated perfused rat liver.The removal of Ca2+ from the perfusion medium (0 mM CaCl(2 ) + 0.5 mM EGTA) did not affect glucagon (0.1 nM)-responsive cAMP but reduced secretin (1 nM)-, vasoactive intestinal polypeptide (VIP, 1-10 nM)- and forskolin (1 microM)-responsive cAMP considerably. The addition of 1 mM CoCl2 reduced glucagon- and secretin-responsive cAMP considerably, forskolin-responsive cAMP partly, did not affect 1 nM VIP-responsive cAMP, but enhanced 10 nM VIP-responsive cAMP. Forskolin- and VIP-responsive cAMP was greater in the combination (0 mM CaCl(2) + 0.5 mM EGTA + 3 mM CoCl2) than in the Ca(2+)-free perfusion alone. These results suggest that secretin, VIP1 and VIP2 receptors are linked to Ca(2+)-calmodulin-sensitive adenylyl cyclase; glucagon receptor to Ca(2+)-calmodulin-insensitive adenylyl cyclase; VIP1 receptor to Ca(2+)-calmodulin-dependent phosphodiesterase; glucagon, secretin and VIP2 receptors to cAMP-specific phosphodiesterase, respectively, in the rat liver.

Impaired neural regulation of insulin secretion related to the leptin receptor gene mutation in Wistar fatty rats.

The Wistar fatty (WF) rat is a model of obese Type 2 diabetes mellitus (DM). These rats were bred by crossing Zucker fatty (ZF) and Wistar-Kyoto (WKY) rats. A homo-allelic leptin receptor gene mutation has been reported in ZF rats. We report here how these genetic factors contribute to plasma insulin regulation. The fasting plasma insulin levels were higher in WKY and Wistar lean (WL) rats than in Zucker lean (ZL) rats (p<0.05). The levels in WF and ZF rats were higher than in their respective lean littermates, WL and ZL rats (p<0.05). After intragastric glucose load, the plasma insulin increase was reduced upon pretreatment by intracerebroventricular (i. c.v.) methylatropine (an antagonist of the cholinergic receptor) injection in WL rats (p<0.05) but not in WF rats. Plasma glucagon-like peptide-1 (GLP-1) response to intragastric glucose load was not affected by methylatropine. After selective hepatic-vagotomy, plasma insulin levels increased in wild-type ZL rats (p<0.05). This increase was not observed in heterozygote ZL rats. Surprisingly, this response of plasma insulin was not shown in wild-type WL and WKY rats. ZF and WF rats did show a prominent decrease in insulin response (p<0.05). These results indicate that the genetic factor in ZF rats is associated with impaired vagal nerve-mediated control of insulin secretion. The genetic factor in WKY rats may diminish sensitivity to the vagal information of insulin release and contribute to insulin resistance. Therefore, we conclude that the presence of both genetic factors in a homo-allelic state is important to the development of DM in WF rats.

Hypocaeruloplasminaemia with heteroallelic caeruloplasmin gene mutation: MRI of the brain.

We present two patients with hypocaeruloplasminaemia and a heteroallelic caeruloplasmin gene mutation (HypoCPGM). These patients had diabetes mellitus and tremor of the hands, respectively. T2-weighted fast spin-echo MRI showed mildly reduced intensity of the putamen, much more marked on echo-planar imaging.

Sequential changes and recoveries of the motor evoked potential in experimental hypertension.

The D- and I-waves of the motor evoked potential (MEP) were investigated as a monitor for acute intracranial hypertension in 20 dogs. Intracranial pressure (ICP) was raised bvy inflation of an extradural balloon. The MEP elicited by electrical transcortical stimulation were recorded during inflation and deflation of the balloon. The D-waves were linearly suppressed according to the ICP level, however, the I-waves and the ICP level did not correlate. Each wave disappeared in the animals kept about 50 mmHg or more, whose pupils were dilated. In the animals kept under 60 mmHg, the amplitude of the D-wave recovered proportionate to the period during which the amplitude was suppressed less than 50%. The changes of the MEP have some relation to histopathological changes. The results demonstrate that the D-wave of MEP is a useful monitor for intracranial hypertension.

Effects of glucagon on glycogenolysis and gluconeogenesis are region-specific in periportal and perivenous hepatocytes.

It has been established, mainly by histochemical and immunohistochemical studies, that liver cells are functionally heterogeneous, with periportal hepatocytes (PPHs) being predominantly gluconeogenic and perivenous hepatocytes (PVHs) being glycolytic. We therefore investigated the region-specific functional effects of glucagon on glycogenolysis and gluconeogenesis in isolated PPHs and PVHs prepared by the digitonin-collagenase method. BB rats, a model of insulin-dependent diabetes, were used to study the region-specific heterogeneity of gluconeogenesis in the diabetic state. Although glycogen content was not different between PVHs and PPHs in rats fed the normal diet, basal glucose release was 1.37 times greater in PVHs than in PPHs (P <.05). The increase in glucose release stimulated by 0.01 to 0.1 nmol/L glucagon was 1.52 times greater in PVHs than in PPHs (P < .05), whereas no differences were seen in response to 1 to 100 nmol/L glucagon. Glucose release from gluconeogenic substrates was 1.57 times greater in the PPHs than in the PVHs of fasted normal rats (P < .05), whereas the increase in gluconeogenesis produced by glucagon was not different between PPHs and PVHs. The glucagon-binding capacity, the cAMP release, and the increase in intracellular Ca2+ stimulated by glucagon were not different between PPHs and PVHs in the fed or fasted states. Gluconeogenesis from gluconeogenic substrates was 1.52 times greater in the PPHs than in the PVHs of fasted nondiabetic BB rats (P < .05). After the development of diabetes, the gluconeogenic capacity in PVHs increased to the level observed in PPHs, but that in PPHs did not change. Thus there was no difference in gluconeogenesis between the PPHs and PVHs of diabetic BB rats. In both the PPHs and PVHs of diabetic BB rats, the 0.01 to 100 nmol/L glucagon-induced increase in gluconeogenesis was greater than that in PPHs from nondiabetic BB rats (2.30 and 3.07 times, P < .01, respectively). We conclude that PPHs and PVHs of normal rat liver express region-specific differences in their glycogenolytic and gluconeogenic responses to glucagon. In diabetic BB rats, the difference in the gluconeogenic capacity between PPHs and PVHs disappeared, whereas glucagon-induced gluconeogenesis was enhanced.

Identification of a novel mutation of the CPO gene in a Japanese hereditary coproporphyria family.

Hereditary coproporphyria (HCP) is an autosomal dominant disease characterized by a deficiency of coproporphyrinogen oxidase (CPO) caused by a mutation in the CPO gene. Only 11 mutations of the gene have been reported in HCP patients. We report another mutation in a Japanese family. Polymerase chain reaction-single strand conformational polymorphism and direct sequence analyses demonstrated a C to T substitution in exon 1 of the CPO gene at nucleotide position 85, which lies in the putative presequence for targeting to mitochondria. This mutation changes the codon for glutamine to a termination codon at amino acid position 29. MaeI restriction analysis showed two other carriers in the family. The C-T mutation is located within a recently proposed putative alternative translation initiation codon (TIC-1), supporting that TIC-1 is the real TIC rather than TIC-2.

Impaired vagus nerve-mediated control of insulin secretion in Wistar fatty rats.

It has been reported that hyperglycemia in the portal venous blood suppresses afferent activity of the hepatic branch of the vagus nerve, which in turn accelerates efferent activity of the pancreatic branch of the vagus nerve to stimulate insulin secretion. The present study examined this neural control mechanism in genetically obese diabetic male Wistar fatty (fa/fa) rats. Adult (aged 12 to 14 weeks) Wistar fatty rats were obese, hyperinsulinemic, and hyperglycemic. Young (aged 5 to 6 weeks) Wistar fatty rats were slightly obese and hyperinsulinemic, but were euglycemic compared with the lean littermates. In both adult and young lean littermates, the plasma insulin response after an intragastric glucose load (1 g/kg) was diminished by intracerebroventricular (i.c.v.) atropine methylbromide (methylatropine 10 nmol) pretreatment, and a transient increase in plasma insulin was observed after selective hepatic vagotomy, as reported in normal rats. In contrast, in both adult and young Wistar fatty rats, the plasma insulin response after an intragastric glucose load was not diminished by i.c.v. methylatropine pretreatment, and plasma insulin decreased slightly after selective hepatic vagotomy. Further, afferent discharges of the hepatic vagal branch decreased and efferent discharges of the celiac/pancreatic vagal branch increased when 10 mg glucose was infused into the portal vein in the 9-week-old lean littermates, as reported in normal rats. In 7-week-old Wistar fatty rats, afferent discharges of the hepatic vagal branch decreased but efferent discharges of the celiac/pancreatic vagal branch did not increase after intraportal glucose infusion. It is concluded that the vagus nerve-mediated regulation of insulin secretion is impaired from an early stage of life in Wistar fatty rats. Efferent discharges of the vagus nerve to the pancreas seem not to be suppressed by afferent discharges from the hepatic vagus branch, which may lead to insufficient insulin secretion in response to nutrient ingestion followed by a delayed peak. These abnormalities may thus lead to the insulin resistance and fasting hyperinsulinemia that characterize the Wistar fatty rat model.

Hyperglycemia is a factor for an increase in serum ceruloplasmin in type 2 diabetes.

OBJECTIVE: To examine if there is a correlation between high blood glucose and serum ceruloplasmin (Cp) levels. RESEARCH DESIGN AND METHODS: Serum Cp levels were measured in 637 patients with type 2 diabetes (all type 2 diabetes group). For the follow-up type 2 diabetes group, 161 patients who had not had any changes in their situation during the last year that are known to influence serum Cp levels were reexamined 1 year later. The control group was composed of 158 healthy individuals. Serum Cp and blood HbA1c levels were measured by radial immunodiffusion and high-performance liquid chromatography assays, respectively. RESULTS: Serum Cp levels in the all type 2 diabetes group were significantly higher than those in the control group (P < 0.0001), although the serum Cp levels did not correlate with the blood HbA1c levels in the all type 2 diabetes group (r = 0.055, P = 0.351). Then we evaluated those factors (delta-log Cp and delta-HbA1c) in the follow-up type 2 diabetes group to minimize changes from the genetic differences and to exclude any known factors influencing serum Cp levels. This indicated that the delta-HbA1c had a positive correlation to the delta-log Cp (r = 0.304, P < 0.0001). CONCLUSIONS: A persistent high blood glucose (namely HbA1c) is associated with an increase in serum Cp levels over 1 year.

A novel mutation of coproporphyrinogen oxidase (CPO) gene in a Japanese family.

Hereditary coproporphyria (HCP) is an autosomal dominant disease characterized by a deficiency of coproporphyrinogen oxidase (CPO). Only 11 mutations of the gene have been reported to date as the mutations responsible for HCP. We report here a novel mutation of the gene responsible for the disease in a Japanese family. Analysis of the polymerase chain reaction (PCR) amplified DNA fragments of the gene by direct-sequencing and/or cloning-based sequencing methods revealed the gene abnormality responsible for the disease. The mutation found was a single base deletion of T at nt position 526, which results in frame shift and truncation of coded protein at amino acid position 204. Screening of pre-symptomatic cases seemed to be possible by PCR restriction analysis using restriction enzyme Xcm I.

Early potentials of direct cortical responses: experimental study in dogs and pathophysiological and clinical implications.

OBJECTIVE: The characteristics of the early component of the direct cortical response have not been well studied, although direct cortical response recording is a common method of brain function monitoring. METHODS: In this experimental study, we sought conditions affording the clearest recording of the early potential, by varying the polarity and low-cutoff filter setting, and we confirmed that the early potential consists of two components, P1 and P2. RESULTS: When subcortical damage was induced by local cerebral compression or saline injection, transient changes in P1 and permanent disappearance of P2 were observed. P2 also disappeared when the fiber connections between the cortex and the basal ganglia, including the thalamus, were destroyed by wire insertion. With deep recording, both P1 and P2 exhibited potential reversal at a level histologically confirmed to be in Layer V of the cortex. CONCLUSION: These findings suggest that P1 is a spike reflecting the activity of pyramidal cells evoked by electrical stimulation of the brain surface and that P2 is a potential arising in Layer V of the cortex and is related to afferent fibers from the thalamus. Recording of P2 may be useful for monitoring for subcortical damage.

Relative contribution of Ca2+-dependent mechanism in glucagon-induced glucose output from the liver.

Divalent cations are known to affect the activity of the cAMP-generating system. By observing the effects of the addition of cobalt (Co2+) and the depletion of calcium (Ca2+), this study tried to determine the relative contribution of Ca2+-dependent mechanism in glucagon-induced glucose output from the isolated perfused rat liver. Co2+ (1 mM) completely suppressed glucose and cAMP output induced by 0.1 nM glucagon and partly suppressed those induced by 1 to 10 nM glucagon. Co2+ (1-5 mM) did not inhibit 125I-labeled glucagon binding to hepatic cell membrane. Phenylephrine- or angiotensin II-induced glucose output was not affected by 1 mM Co2+. Co2+ (1 mM) inhibited a glucagon-induced increase in [Ca2+]i in isolated rat hepatocytes but did not inhibit a phenylephrine-induced increase in [Ca2+]i. The removal of Ca2+ from the perfusion medium impaired phenylephrine- or angiotensin II-induced glucose output, but did not impair glucagon-induced glucose output. When glucagon-induced cAMP production was inhibited by Co2+, the glucose output produced by 1 to 10 nM glucagon was impaired further in the Ca2+-free perfusion. Addition of 0.1 mM IBMX increased the glucose output produced by 1 nM glucagon but did not increase that produced by 10 nM glucagon in the Co2+-containing Ca2+-free perfusion. These results suggest that Co2+ inhibits the glucagon-responsive adenylyl cyclase system directly, resulting in impaired glucose output. Glucagon increases [Ca2+]i through a mechanism different from that of phenylephrine. Glucagon (0.01-10 nM)-induced glucose output from the liver is derived mainly through a cAMP-dependent mechanism. Only when glucagon-induced cAMP production was inhibited by Co2+ was the Ca2+ dependency observed in high concentrations (>/=1 nM) of glucagon-induced glucose output, and it approximated 30% of the glucose output produced by 10 nM glucagon.

Sequential changes in CGRP-like immunoreactivity in NIDDM model Otsuka Long-Evans Tokushima Fatty (OLETF) rat pancreatic islets.

We describe the changes in B cells and calcitonin gene-related peptide (CGRP)-like immunoreactivity in the pancreatic islets of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of human non-insulin-dependent diabetes mellitus (NIDDM). In the OLETF rat pancreatic islets, CGRP immunoreactivity was seen in the nerve fibers with multiple varicosities and in endocrine cells that were identical to somatostatin-containing cells, but some somatostatin-immunoreactive cells lacked CGRP immunoreactivity. In the OLETF rats, plasma insulin levels were significantly higher than in the control rats (Long-Evans Tokushima Otsuka; LETO) only at 7 weeks of age. From 7 through 32 weeks of age, OLETF rats had a greater B-cell area than LETO rats. The length of CGRP-immunoreactive nerve fibers per area and the numbers of CGRP-immunoreactive cells per area did not differ between the groups at 7 weeks of age. After 16 weeks of age, both of these CGRP parameters in the OLETF rats became increasingly higher than in the LETO rats. These results suggest that CGRP is a B-cell growth factor and probably an inhibitory factor for insulin secretion.

Hypoglossal nerve paresis caused by spontaneous dissection of kinked internal carotid artery--case report.

A 54-year-old male presented with pure hypoglossal nerve paresis. Angiography and magnetic resonance (MR) imaging showed the characteristic findings of left internal carotid artery (ICA) dissection. He received aspirin and his symptoms gradually disappeared. Repeat angiography and MR imaging showed that the lesion had completely disappeared. This case supports the hypothesis that hypoglossal nerve paresis is due to nerve stretching and compression by intramural hematoma of the dissected ipsilateral ICA, and severe tortuosity of the ICA may be a related phenomenon.

[Clinical effects of sodium ozagrel and urokinase in patients with acute cerebral infarction in the territory of the internal carotid artery].

In this study, the clinical effects were compared between a thromboxane synthetase inhibitor (sodium ozagrel) and a thrombolytic agent (urokinase) in patients with acute cerebral infarction. The subjects consisted of 598 patients admitted on the day of the onset of the cerebral infarction in the territory of the internal carotid artery who showed a low density area on CT images within 5 days. Of these patients, 300 were treated with sodium ozagrel and classified as Group Oz, while the remaining 298 were treated with urokinase and classified as Group Ur. The results were as follows: 1. In group Oz, complete recovery of motor impairment was seen in 209 (69.7%) patients. Complete recovery within 3 weeks after onset was seen in 186 (62.0%) patients. In group Ur, complete recovery of motor impairment was seen in 175 (58.7%) patients. Complete recovery within 3 weeks after onset was seen in 120 (40.3%) patients. Therefore, a higher incidence of complete recovery of the motor impairment was noted in group Oz [p < 0.001: chi 2 test]. Similarly, complete recovery within 3 weeks after onset was more frequent in group Oz [p < 0.001: chi 2 test]. 2. In group Oz, complete recovery was made contribution statistically by Anosognosia (Ag) and unilateral neglect (UN) on admission [multivariate analysis: p < 0.01]. In group Ur, complete recovery was made contribution statistically by Ag (p < 0.01), UN (p < 0.01) and aphasia (p < 0.05). 3. Progressive stroke was observed in 29 (9.5%) patients in the group Oz and in 71 (23.0%) patients in group Ur. There was a higher incidence of progressive stroke in group Ur [p < 0.001: chi 2 test] 4. All patients with progressive stroke had initial evidence of deterioration of neurological deficits within 6 days after the onset in group Oz, and within 5 days after the onset in group Ur. The maximal period from the beginning to the end of the deterioration of neurological deficit was 7 days. 5. In group Oz, progressive stroke was only seen in 29 (29.9%) of the patients who were admitted with motor disturbances and unilateral neglect. In group Ur, progressive stroke was seen in 8 (4.3%) of the 187 patients with motor disturbances without higher cortical dysfunction, in 17 (47.2%) of the 36 patients with motor disturbances and higher cortical dysfunction without unilateral neglect and was seen in 46 (61.3%) of the patients with motor disturbances and unilateral neglect. 6. Hemorrhagic infarction was observed in 14 (4.6%) patients in group Oz and in 31 (10.0%) patients in group Ur. There was a higher incidence of hemorrhagic infarction in group Ur [p < 0.001: chi 2 test]. 7. In group Oz, there was a higher incidence of hemorrhagic infarction among patients with atrial fibrillation (Af) on the ECG [p < 0.001: chi 2 test]. Similarly, in group Ur, hemorrhagic infarction was more frequent among patients with atrial fibrillation (Af) on the ECG [p < 0.001: chi 2 test]. Therefore, sodium ozagrel was clinically more efficient and safer than urokinase in patients with acute cerebral infarction.

Case report: interferon induced coma in Sheehan's syndrome.

A 54-year-old woman who was being treated with 10 million units (mu) of natural interferon (IFN)-alpha per day for chronic active hepatitis C at a local clinic, developed coma on the fourth day of treatment. On admission to Yamagata University Hospital, she was still in a state of semicoma with severe hyponatraemia (122 mEq/L) and hypochloraemia (89 mEq/L). After the administration of electrolytes, her condition improved remarkably. Endocrinological loading tests showed a hypofunction of the anterior pituitary gland. In consideration of these results, and her past experiences of haemorrhage during childbirth and subsequent amenorrhoea, we diagnosed her illness as a coma as a result of Sheehan's syndrome which had become overt during IFN therapy. She recovered completely after treatment with hydrocortisone and l-thyroxine.