Morphology of the cockerel's comb after androgen administration.

1. Androgen receptor (AR) expression and morphological changes in blood capillaries were investigated in the comb of cockerels, both untreated controls and after the administration of testosterone (T) or the androgen antagonist flutamide (F) for 7 weeks. 2. Twenty-six male Single Comb White Leghorn roosters were divided into T-treated, F-treated and untreated groups. Tissue sections were examined histologically, immunohistochemically, and comb blood vessel castings were analysed by scanning electron microscopy. 3. Histologically, the capillaries of the peripheral dermis layer in the T-treated group were dilated compared with controls. Many red blood cells were seen in the lumen. Although the capillary diameter in the F-treated group did not show a significant difference as compared with control, blood capillaries with small diameters were often observed, and there were few red blood cells in the capillaries. Some capillary castings were extended markedly in the T treated group, and small blood vessels were observed arborising from the extended blood capillaries. In contrast, all capillaries were slender in the F-treated group, and the casting surface was rough. 4. Immunoreactivity for AR was found in capillary endothelial cells in the peripheral dermis layer of the comb. The intensity of staining in these cells was increased in the T-treated group but was reduced in the F-treated group. 5. It is concluded that immunoreactivity for AR was found in capillary endothelial cells in the peripheral dermis layer of the rooster's comb. The intensity of staining in these cells was increased in the T-treated group but reduced in the F-treated group. Thus, the capillary endothelial cells in the peripheral dermis layer of the comb are androgen targets.

Skin morphology of thyroidectomized rats.

We induced hypothyroidism in rats by conducting a thyroidectomy (TD) and investigated subsequent changes in the morphology of the skin, especially that of the epidermis and hair follicles. The 6 rats in the TD group seemed less active than the 3 rats in the control group and had cold, dry paws. All of the rats in the TD group exhibited retarded hair growth 12 weeks after surgery. Histologically, all of the rats in the TD group exhibited epidermal thinning from 12 weeks after surgery. Many hair follicles were in the telogen phase: the bulbs and papillae were involuted and had migrated towards the epidermis. Hair follicle atrophy involving thinning of the outer root sheath and the inner root sheath was often observed. The immunoreactivities of antithyroid hormone receptors alpha and beta in the outer root sheaths of 5 of the TD rats were weaker than those of control rats. Cell proliferation in hair follicles of TD rats was weaker than in follicles of control rats 4 weeks after surgery. It is suggested that decreased expression of TRs and decreased cell proliferation activity in the hair follicles of rats is associated with a lack of thyroid hormone and results in retardation of hair growth.

Morphology of thyroid follicular cells of methimazole-treated rats.

Thyroids of rats treated with methimazole (MMI) were analysed histologically, immunohistochemically and electron microscopically. Thyroids of MMI-treated rats displayed greater hypertrophy and were heavier than those of control rats. Thyroids of MMI-treated rats were composed of variant or small follicles and contained more columnar cells than those of control rats. Strong staining of thyroid granules by azocarmine G was evident in the apical regions of follicular cells from MMI-treated rats. Anti-thyroglobulin positivity was detected in the apical regions of follicular epithelial cells, especially those of MMI-treated rats. After application of a post-embedding method to detect thyroglobulin, colloidal gold particles were often observed in apical vesicles of MMI-treated rats. Our study suggests that apical vesicles may serve as markers of hyperthyroidism. When the functional state of the thyroid gland is known from histological analysis, use of the Azan stain could provide useful additional information.

Primary involvement of the motor area in association with the nigrostriatal pathway in multiple system atrophy: neuropathological and morphometric evaluations.

To evaluate the changes that occur in the motor and supplementary motor cortices in cases of multiple system atrophy (MSA), we carried out morphological and morphometric studies in 7 cases of MSA and 11 age-matched controls. Neuropathological study revealed presence of glial cytoplasmic inclusions (GCIs) in the cortex and subcortical white matter of the motor and supplementary motor areas, loss of small to medium-sized pyramidal neurons, and astrocytosis in the motor cortex in all cases of MSA, showing a definite predilection in the cortical layers V and VI. The severity of neuronal loss in the motor cortex was highly correlated with the incidence of GCIs and the involvement of the nigrostriatal pathway. Morphometrically, significant reductions of both the thickness of motor cortical layers V and VI and the number of neurons were observed. In addition, a reduction in the number of neurons in the supplementary motor cortex was detected in three out of the seven MSA cases. The results of this study suggest that the motor area is a cardinal target in MSA, and that in association with the nigrostriatal pathway it forms a motor loop degeneration in this disease.

Vascular and metabolic reserve in Alzheimer's disease.

Vascular and metabolic reserve were analyzed in probable Alzheimer's disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.

Can PET data differentiate Alzheimer's disease from vascular dementia?

The present study endeavored to differentiate Alzheimer's disease (AD) from vascular dementia (VaD) by comparing the metabolic and hemodynamic parameters. Positron emission tomographic (PET) studies were carried out in 13 patients with probable AD and 20 patients with VaD. PET findings were not included in the diagnostic criteria of AD or VaD. Using oxygen-15 labeled compounds, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), cerebral blood volume, and vascular transit time (VTT) were measured quantitatively during the resting state. To evaluate vascular reactivity (VR), CBF was also measured during 7% CO2 inhalation. Regional CBF from the parietal cortex positively correlated with the neuropsychological scores in both AD and VaD groups. The typical parietotemporal pattern of hypoperfusion and hypometabolism was observed in the AD group, whereas the frontal lobe including the cingulate and superior frontal gyri were predominantly affected in the VaD group. The occipital cortex was preserved in both groups. A significant increase of the OEF was found in the parietotemporal areas in the AD group. No significant prolongation was seen with VTT. There was a marked difference in VR between the two groups: VR was depleted in the VaD group, whereas VR was normal in the AD group. The increased OEF with preserved vascular reserve seen in AD may implicate participation of a vascular factor in the pathogenesis of AD, possibly at the capillary level. Thus, PET provides important functional information in discriminating AD from VaD by comparing the patterns of hypoperfusion and/or hypometabolism, and in the understanding of the underlying hemodynamic pathophysiology.

Management of pancreatic arteriovenous malformation.

Pancreatic arteriovenous malformations (AVM), while extremely rare, are frequently complicated by gastrointestinal bleeding. The elimination of pancreatic AVM is difficult once portal hypertension has developed. We describe herein a patient with congenital AVM of the pancreatic head presenting with recurrent episodes of melena, in whom pylorus-preserving pancreatoduodenectomy provided a means of definitive management. We also review the literature and focus on the diagnostic and therapeutic approaches. Angiography is always necessary to facilitate tactics of treatment, even if diagnosis has been established by non-invasive imaging modalities. To obtain complete regression, total extirpation of the affected organ, or at least the involved portion, should be performed before this disease leads to the lethal complications of gastrointestinal bleeding and portal hypertension. Transcatheter arterial embolization is the only alternative treatment for the control of hemorrhage.

[Vascular and metabolic reserve in a case of hypoplasia of bilateral internal carotid arteries].

We report a 64-year-old right-handed man who presented with a hypoplasia of bilateral internal carotid arteries (ICAs). The patient complained of a vertigo and was diagnosed as having a benign paroxysmal positional vertigo. Upon neurological examination, he was completely free from neurological deficits. MR angiogram revealed an occlusion of both ICAs. On conventional angiogram, the right ICA was occluded about 3 cm distal from its origin, and the left ICA was occluded at the precavernous portion. There was an abundant collateral blood flow to the frontal, temporal and parietal lobes through the posterior communicating arteries. Both carotid canals were hypoplastic on 3D-CT. The patient was then diagnosed as having a hypoplasia of both ICAs. Using a positron emission tomography (PET), cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and vascular transit time (VTT) were measured during resting state, and the vascular reactivities to carbon dioxide inhalation (VRCO2), and to the intravenous administration of Acetazolamide (VRACZ) were also evaluated. There was no global or focal reduction in CBF and VTT was within normal limit, whereas a global reduction of CMRO2 caused mild decrease in OEF. Moreover, VRACZ was significantly decreased and an intracerebral steal phenomenon was observed in the parietal cortical areas, whereas VRCO2 was preserved. The discrepancy between VRACZ and VRCO2 observed could be related to the differences in the mechanisms underlying the vasodilating effects of carbon dioxide and ACZ.

[Effect of combination chemotherapy with mitomycin C and cisplatin on advanced gastric carcinoma].

A 71-year-old male with advanced gastric carcinoma with paraaortic lymph node metastases underwent distal gastrectomy. Cisplatin (CDDP) 50 mg/body was administered intravenously (i.v.) on day 1 followed by the administration of 5-fluorouracil 500 mg/body/day i.v. on day 2 through day 7. After two courses of this regimen, further enlargement of paraaortic lymph nodes was revealed by CT scan, and chemotherapy was suspended. Multiple liver and lung metastases were diagnosed 6 months after initial diagnosis, and mitomycin C (MMC) 10 mg/body i.v. was administered on day 1 followed by CDDP 50 mg/body i.v. on day 2. After three courses of this regimen, partial response of the liver metastases and complete response of the lung metastases were observed, and the general condition was markedly improved without any adverse effect except slight nausea. Though the patient died of brain metastases one year after initial diagnosis, the combination chemotherapy with MMC and CDDP was nevertheless thought to improve his quality of life.

[A case of unresectable advanced cancer of the gall bladder successfully treated by arterial infusion therapy with cisplatin].

A 70-year-old male was admitted for obstructive jaundice. He was diagnosed as an unresectable advanced cancer of the gall bladder that was stage IV associated with direct extension of the liver (Hinf3) and the bile duct (Binf3), and with enlargement of paraaortic lymph node (N4(+)) by image analyses. Intraarterial infusion therapy with cisplatin (CDDP, 50 mg) was started through the common hepatic artery. Since the primary tumor and the enlarged paraaortic lymph node shrank markedly and the bile duct was completely obstructed, additional arterial infusion with CDDP (50 mg) was made. CT examination thereafter revealed that the paraaortic lymph node enlargement disappeared although thickening of the gall bladder wall still remained. Therefore this case was considered as a complete response (CR). Then, a reservoir for hepatic arterial infusion was implanted and CDDP (a total of 230 mg) was repeatedly infused 5 times. CT scanning images taken 7 months after the start of the treatment showed neither primary tumor nor enlargement of paraaortic lymph node. An extensive cholecystectomy was performed. Histopathological examination revealed signet-ring cell carcinoma located in all layers of the gall bladder. Factors indicating clinicopathological stage were se, hinf1, vs0, bw1, hw0 and ew2 (according to the General Rules for Surgical and Pathological Studies on Cancer of Bile duct).

Misery perfusion with preserved vascular reactivity in Alzheimer's disease.

To elucidate the hemodynamic pathophysiology underlying Alzheimer's disease (AD), cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and oxygen extraction fraction (OEF) were measured with positron emission tomography in 10 patients with probable AD and in 20 age-matched normal volunteers. By the 15O intravenous bolus injection method, CBF was measured during resting state, CO2 inhalation (hypercapnia) and hyperventilation (hypocapnia), and the vascular reactivity (VR) was estimated by comparing the CBF changes (delta CBF%/PaCO2 mmHg) in the hyper- or hypocapnic to the resting state. By the 15O2 single-breath method or 15O steady-state method, CMRO2 and OEF were measured during resting state. Based on 26 regions of interest, local CBF, CMRO2 and OEF were compared statistically between the two groups. As compared with the control group, the mean CBF and CMRO2 decreased to as low as 77.0% and 88.4% of the normal values, respectively, while the mean OEF increased by 12.1% (p < 0.05) in AD patients. These changes were most pronounced in the supramarginal and superior temporal gyri. There was no focal change in VR in the AD group, and no significant difference was seen in VR to either hyper- or hypocapnia between AD and control groups. The results may suggest a vascular involvement, possibly at the capillary level, that might cause a relative misery perfusion syndrome accompanied by preserved vascular reactivity in AD.

Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study.

Cerebral blood flow (CBF), oxygen metabolism (CMRO2), and glucose metabolism (CMRGlc) were measured using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO2 was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is impaired and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy.

Correlation of EEG activities between slow-wave sleep and wakefulness in patients with supra-tentorial stroke.

Using topographic EEG mapping, we studied the relationships between delta activity during slow-wave sleep (SWS) and the background EEG activity during wakefulness, in 11 normal subjects and 35 stroke patients with unilateral supra-tentorial lesions. Delta-1 power during SWS showed a significant positive correlation with alpha-1 power during wakefulness, in both hemispheres. Delta-1 and delta-2 power during SWS correlated positively not only with alpha-2 power, but also with delta-1 and delta-2 power during wakefulness in the affected hemisphere. these figures indicate that the amount of delta activity during SWS can be associated with that of alpha activity during wakefulness. A close negative correlation was observed between delta power during SWS and the age of the subjects in the patient group. The Barthel index showed no significant correlation with delta-1 or delta-2 power in either hemisphere in patient group. Our results suggest that delta activity during SWS may be associated with dysfunction of the cerebral cortex in stroke patients as well as in normal aged subjects.

Scalp topography of SEP late components in patients with supra-tentorial lesions.

Somatosensory evoked potentials (SEP) to simultaneous bilateral median nerve stimulation were recorded in 7 patients with unilateral brain lesions, 8 patients with degenerative dementia, and 5 normal volunteers. Right-left amplitude difference was compared from serial topographic images and the amplitude was compared at homologous electrodes. In patients with unilateral lesions, the amplitude from the frontopolar, frontal, anterior-temporal, and/or occipital electrodes was smaller on the affected side at 240 and 360 msec, regardless of whether the subjects showed sensory deficit or not. No significant laterality was seen in the primary sensorimotor areas. Distribution obtained from the patients with degenerative dementia was quite symmetrical. A significant right-left amplitude difference was seen at the anterior temporal site at 180 and 240 msec in normal controls, although an almost symmetrical distribution was obtained on the topographic images. The late components of SEP are not associated with the primary somatosensory function, but possibly with other cortical pathways.

[Outcomes of effective treatment of cases of metastatic liver tumors by intra-arterial infusion chemotherapy].

We studied the prognoses of unresectable liver tumors, including 31 colorectal cancers and 10 gastric cancers treated by intra-arterial infusion chemotherapy using an implantable reservoir. Adriamycin, epirubicin, or cisplatin were administered intermittently early on. Cisplatin and 5-FU combined therapy were given later. In nine with colorectal metastases and six with gastric metastases, metastatic lesions decreased, and in 4 patients with metastatic lesions could be resected. But in many patients, hepatic and other organ recurrences were observed. We need to try many other treatments.

Infratentorial infarction: correlation of MR findings with neurological and angiographical features.

Using magnetic resonance imaging, we reviewed 141 infratentorial infarcts in 81 consecutive cases: 65 infarcts were seen in the paramedian pons, while 18 in the posterior inferior cerebellar artery (PICA) territory and 17 in the watershed area between PICA and superior cerebellar artery. No comparable sign or symptom was observed for 44 (31.2%) infarcts, whereas 66 (46.8%) infarcts appeared symptomatic and 31 (22.0%) infarcts were regarded as equivocal mainly due to the coexisting supratentorial lesions or non-localizing symptoms. The frequent coexistence of basal ganglionic small infarcts in those with infratentorial small (< 15 mm) infarcts implicated their common pathogenetic background. The fact that atrial fibrillation was seen in 33.3% of those with large (> 15 mm) infarcts whereas it was seen in only 6.5% of those with small infarcts may suggest a cardiogenic embolism as a possible cause of infratentorial large infarcts. Major artery occlusive lesion was seen in 15 of 22 cases with cerebellar infarction, whereas no occlusive lesion was seen in the majority of cases with pontine small infarcts. With MR imaging, infratentorial infarcts were detected more frequently than in the previous studies based on X-ray CT, and they can be considered as a benign condition.

Evolution of crossed cerebellar diaschisis in middle cerebral artery infarction.

To elucidate the evolution of crossed cerebellar diaschisis, cerebral oxygen metabolism was measured repeatedly by positron emission tomography (PET) in 35 consecutive patients with unilateral cerebral infarction within the territory of middle cerebral artery. The crossed cerebellar diaschisis was defined as significant when the laterality ratio of cerebral oxygen metabolism between the left and right cerebellar hemispheres exceeded the control range (mean +/- 2 standard deviations) as derived from 27 age-matched normal volunteers. Significant crossed cerebellar diaschisis was observed in 31 patients (89%) on the initial PET studies. Of these 31 patients, 23 with infarcts involving the frontal sensorimotor cortex persistently had crossed cerebellar diaschisis up to 5 years after onset, whereas the diaschisis disappeared in 8 patients with smaller infarcts mainly in the frontal or parietal lobe without recovery of oxygen metabolism in the infarcted areas. These present results suggest that crossed cerebellar diaschisis can exist persistently even in the late stage in those having a lesion involving the cortical pontine-cerebellar pathways.

Effects of fasudil hydrochloride on cerebral blood flow in patients with chronic cerebral infarction.

To evaluate the effect of the novel intracellular calcium antagonist fasudil hydrochloride, cerebral blood flow (CBF) was measured quantitatively with positron emission tomography following the intravenous administration of fasudil in five patients with chronic cerebral infarction. The hemispheric mean CBF increased significantly on both hemispheres 30, 60, and 90 min after the administration of fasudil when the CBF values were corrected according to PaCO2 level, although there was no significant change in raw CBF data. A significant increase of CBF was seen in the cerebellar hemisphere and thalamus at 30 min and in the occipital cortex at 90 min. There was no significant fall in the systemic blood pressure after the administration of fasudil.