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A 48-year-old Chinese woman developed ascending motor paralysis while visiting Japan, leading to tetraplegia and respiratory failure over 2 weeks. The patient's course was complicated by anoxic encephalopathy. Nerve conduction studies revealed a severely decreased amplitude of compound muscle action potentials and a sural nerve biopsy specimen showed findings consistent with axonal-form Guillain-Barr6 syndrome. An autopsy, excluding the brain, demonstrated small-cell lung cancer that was not detected clinically, axonal-dominant degeneration in the nerve roots and distal peripheral nerves, and the loss of both myelin and axons in the dorsal spinal column. The spinal anterior horn cells were severely decreased and were accompanied by astrocytic reaction in all spinal segments with lymphocytic infiltration. A limited examination of the dorsal root ganglia did not show Nageotte nodules, but the infiltration of T cells was observed. Although the clinical course mimicked axonal-form Guillain-Barré syndrome, the autopsy demonstrated both sensory and motor neuronal involvement, as well as small-cell lung cancer. Although anti-Hu and antiganglioside antibodies were negative in the patient's serum, the para-neoplastic mechanism might have damaged the anterior horn and dorsal root ganglia cells, which subsequently led to secondary axonal degeneration. There has been a report on a case of paraneoplastic subacute motor neuronopathy, but the acute course described here has not been reported before.

Aims: Disseminated intravascular coagulation syndrome (DIC) is a serious complication in elderly patients with systemic inflammatory response syndrome (SIRS). We investigated whether the clinically relevant parameters of atherosclerosis, nutrition and cellular immunity are determining factors for DIC in septic SIRS patients or not. Patients and methods: Forty-four subjects aged 65 years or over were enrolled, all of whom had bacterial sepsis and a high concentration of C-reactive protein (≥ 15.0 mg/dL). Subjects were given gabexate mesilate (GM) following diagnosis of DIC. They were divided into the following groups: N-DIC, subjects with SIRS but not DIC (n = 22); DIC-A, subjects with SIRS and DIC who survived through treatment with GM (n = 6); and DIC-D, subjects who had SIRS and DIC and died despite treatment with GM (n = 16). Results: Subjects with a low hemoglobin or serum albumin concentration, and atrial fibrillation at admission had a significantly high incidence of DIC, which was not high in subjects with myocardial ischemia, past history of overt cerebral infarctions or periventricular lucency. There was no difference in hemoglobin concentration between DIC-A and DIC-D. Differences in increases in CD11b- and CD14-positive mononuclear cells between DIC and N-DIC subjects were not significant. Post-mortem examinations showed that the ratio of the width of the thoracic aorta to that of the abdominal aorta was significantly higher for DIC-D than DIC-A. Conclusion: Nutritional disorders and irregularity in aortic blood flow are significant risks of DIC. Treatment with GM alone is not sufficient to achieve survival in patients with DIC and SIRS.

Plasma atrial (ANP) and brain (BNP) natriuretic peptide levels were compared to determine if transmitral flow velocity pattern is an instantaneous marker of body fluid balance in anuric patients on hemodialysis (HD). We measured plasma ANP and BNP levels and performed Doppler echocardiography in 38 anuric patients before and after HD. Patients with valvular disease, left ventricular systolic dysfunction having a fractional shortening < 0.3, arrhythmia, or left ventricular hypertrophy were excluded. The relationships between plasma ANP or BNP levels and the transmitral flow velocity pattern were evaluated. We also determined if the magnitude of the decrease in plasma ANP level was related to that in the early peak of transmitral flow velocity (peak E). The mean age of the subjects was 61.1 +/- 9.7 years. The ANP level of 213.6 +/- 146.1 pg/mL was related to peak E of 61 +/- 15 cm/s before HD (R = 0.504, P < 0.001), but not after HD. Plasma ANP level was not related to peak late transmitral flow velocity (peak A) or peak E/peak A before or after HD. BNP level was not related to the transmitral flow velocity pattern. The magnitude of decrease in hANP level during HD was significantly related to that in peak E (R = 0.342, P < 0.05). Before HD, peak E was related to the plasma ANP level, reflecting volume overload. Change in peak E showed a weak relationship with that of plasma ANP level in the same HD patient. The measurement of peak E during a HD session may potentially enable the assessment of hydration status during HD.

A 51-year-old man with poliomyelitis was admitted to emergency because of a severe decubitus ulcer on his right hip that was associated with infection. His general condition deteriorated and he was malnourished and dehydrated. Despite adequate hyperalimentation and antibiotic administration, laboratory data indicated pancytopenia 4 days later. He was diagnosed as having secondary hemophagocytosis (HPS) associated with methicillin-sensitive Staphylococcus aureus sepsis due to decubitus inflammation based on bone marrow aspiration and a blood culture. Although granulocyte colony stimulating factor, packed red blood cell transfusions, platelet transfusions, and antibiotics gradually improved the pancytopenia, the patient died of massive gastrointestinal tract bleeding.

Multiple myelomas often occur in elderly people with age-related complications as they age further. A 54-year-old man was first admitted with cerebral infarction and multiple myeloma (IgG kappa, stage IIIA) in November 1989. There was partial remission following chemotherapy. The karyotype of the marrow cells was 46, XY, and no p53 gene mutations were detected by polymerase chain reaction and single-strand conformation polymorphism analysis. In February 1999, chemotherapy (melphalan, vindesine, ranimustine, prednisolone) was administered as a result of aggravation of the myeloma. Later, after daily subcutaneous injection of 50 µg of nartograstim for 6 days to treat febrile neutropenia, the soft tissues around the right eye swelled gradually, but without redness accompanied by an elevation of the serum creatine-kinase concentration. When nartograstim was discontinued, however, the swelling disappeared and the creatine-kinase level normalized. Then in July, on the sixth day of daily subcutaneous injections of 75 µg of filgrastim following the same chemotherapy regimen, similar swelling of the soft tissues occurred around the left eye, and was again reversed by withdrawal of the drug. In July 2000, infusion of dexamethasone was conducted, and following daily subcutaneous-injection of 75 µg of filgrastim for 5 days, the right subclavicular soft tissue became swollen. The patient later died of myocardial infarction and an autopsy revealed an infiltration of myeloma cells into the right subclavicular muscle and bone marrow that was packed with myeloma cells. This case suggests that exposure to granulocyte-colony stimulating factors enables myeloma cells to proliferate and infiltrate into soft tissues.

The significance of labial gland biopsies (LGBs) in the diagnosis of Sjogren’s syndrome (SS) in the elderly has been a controversial subject since it is complicated by age-related histopathological changes. In an attempt to clarify the appropriateness of LGBs in present diagnosis criteria, we evaluated the specificity of LGBs using autopsied tissues. This was done by taking labial, sublingual and submandibular salivary glands from 53 autopsy subjects (24 males and 29 females) with an average age of 84 years, and testing them histopathologically with reference to a previously reported grading system. None had any sicca symptoms (oral dryness or dry eye). In subjects up to 75 years old, acinar atrophy was more frequent in labial glands than in the two major salivary glands ( P =0.0098 for sublingual and P =0.0009 for submandibular glands). Also, while there were significant differences in frequency of such atrophy between the sublingual and submandibular salivary glands of subjects younger and older than 75, the labial glands showed no such variation. Taking grade 3 (focus score of 1) as the diagnosis criterion, two subjects were determined to have SS in which case the specificity was 95%. Using contemporaneous serological test results for anti-SSA/Ro antibodies as a diagnostic criterion raised specificity to 98%. For both major and minor glands, these appeared to be no relationship between degree of lymphocytic infiltration and age. Our results thus suggest that it is appropriate to adopt a focus score of 1 as a diagnostic criterion for SS in the elderly, and that serological test results can improve specificity.

Background: The clinical significance of a slight increase in serum soluble interleukin-2 receptor (sIL2R) concentration in the stable elderly was investigated. Methods: The subjects consisted of 35 residents of nursing homes with physical impairment as a sequela to cerebral infarctions, who had no inflammatory conditions, and were not receiving anodyne or immunological treatment. They were divided into two groups: 24 subjects without overt or suspected malignancy (NC) and 11 with a history of malignancy (CA). Serological screening with measurement of sIL2R concentrations was performed and numbers of lymphocytes with CD4 and CD8 markers were determined. The NC group was subdivided into control subjects (n = 15, sIL2R

The cellular distribution of malondialdehyde (MDA) was assessed immunohistochemically in brain specimens from young and normal elderly subjects as well as patients with Alzheimer's disease (AD). MDA was increased in the cytoplasm of neurons and astrocytes in both normal aging and AD, but was rarely detected in normal young subjects. By electron microscopic immunohistochemistry, neuronal MDA formed cap-like linear deposits associated with lipofuscin, while glial MDA deposits surrounded the vacuoles in a linear distribution. In the hippocampus, neuronal and glial MDA deposition was marked in the CA4 region but mild in CA1. By examination of serial sections stained with anti-MDA and antibodies against an advanced glycation end product, N(epsilon)-(carboxymethyl)lysine (CML), neuronal and glial MDA deposition was colocalized with CML in AD, but only neuronal MDA was colocalized with CML in normal aged brains. Glial MDA, although abundant in the aged brain, typically was not colocalized with CML. In AD cases, MDA was colocalized with tau protein in CA2 hippocampal neurons; such colocalization was rare in CA1. MDA also was stained in cores of senile plaques. Thus, while both MDA and CML accumulate under oxidative stress, CML accumulation is largely limited to neurons, in normal aging, while MDA also accumulates in glia. In AD, both MDA and CML are deposited in both astrocytes and neurons.

Respiratory insufficiency has been reported frequently in patients with myotonic dystrophy (MyD). Recent data support the hypothesis that this respiratory failure results from a primary dysfunction of the central nervous system. The medullary arcuate nucleus (ARC) has been shown to be involved in the regulation of respiration. We performed a quantitative study of neurons in the ARC in eight MyD patients, ten control subjects with other neurological diseases (control group A) and eight control subjects without neurological diseases (control group B). Alveolar hypoventilation of the central type occurred in three of the MyD patients but not in the remaining MyD patients or controls. The density of neurons in the ARC in MyD patients with hypoventilation was significantly lower than in MyD patients without hypoventilation and control groups A and B. There was no significant difference in the neuronal density of the ARC between MyD patients without hypoventilation and control groups A and B. These data suggest that the neuronal loss of the ARC is associated with the presence of hypoventilation in MyD.

Anemia is a common disease in elderly people. However, since hemoglobin concentration often decreases subclinically with aging because of nutritional impairment, its pathological significance is unclear. To investigate the pathological significance of low hemoglobin concentration, we studied the relation between hemoglobin levels and arrhythmia, as well as circulatory parameters. Arrhythmia was detected by Holter type ambulatory electrocardiography in 42 elderly people (aged 60 or over) living in a nursing home. Plasma concentrations of human atrial natriuretic peptide (hANP) after iron therapy were determined by immunoradiometric assay. Changes in circulatory parameters in elderly people with iron deficiency anemia were examined. Supraventricular and ventricular premature contractions significantly increased in elderly people with low hemoglobin concentrations or hematocrit. hANP increased significantly as the hemoglobin concentration decreased in 22 elderly people. Of these 22 subjects, 11 showed a low serum concentration of iron, and were administered ferrous salts. No side effects, such as nausea, occurred. After iron supplementation, the average hemoglobin level increased from 9.0 to 10.5 g/dl, and the average hANP level was reduced from 58.3+/-23.5 to 41.2+/-27.9 pg/ml, which was statistically significant by Wilcoxon's signed rank sum test. The increase in the hemoglobin level inversely correlated with the hANP level. Heart rate, blood pressure and body weight of subjects decreased significantly after iron supplementation therapy. Although hemoglobin levels were increased by iron supplementation therapy after a long period of anemia, the duration of the period with low hemoglobin levels showed no significant relation to initial hANP concentration. In conclusion, low hemoglobin levels induced secretion of hANP, and treatment of iron deficiency might exert favorable effects on the circulatory system.

An 86-year-old man had a history of hypertension and had been treated with calcium antagonist but no medications that could reduce heart rate. As a 12-lead electrocardiogram showed sinus bradycardia, complete right bundle branch block and left anterior fascicular hemiblock on his first visit to our hospital on January 1998, he was admitted to our hospital for further examination and treatment. A 24-hour Holter electrocardiogram demonstrated a total number of 74,182 heartbeats per day with pauses (> 2.0 sec) of 187/day. Overdrive atrial pacing study and His bundle electrogram revealed a prolonged corrected sinus node recovery time (5.820msec at a stimulation rate of 130/min) and H-V conduction time (80msec) with normal A-H conduction time, respectively. We diagnosed these abnormalities as sick sinus syndrome (Rubenstein II). His activity of daily living score was 30 points by the Barthel index on the day of admission. Oral administration of orciprenaline sulfate (30 mg/day), a beta-adrenoceptor agonist, was initially chosen rather than implantation of a cardiac pacemaker to increase his heart rate since he did not have any symptoms due to bradycardia and he did not give us an informed consent for the implantation. Orciprenaline sulfate, however, failed to increase total heartbeats (73,079/day). Then, oral cilostazol (100 mg/day), a phosphodiesterase III inhibitor, was administered. After two weeks of the regimen total heart beats were increased (85,642/day) with no pauses. The increase in heart rate resulted in the improvement of his activity of daily living (Barthel index: 55 points). Cilostazol could be the first line medication for elderly patients with bradyarrhythmia in whom implantation of cardiac pacemaker is not absolutely indicated.

Objective: To clarify the possible relation between the extent of involvement of catecholaminergic neurons and the presence of alveolar hypoventilation in patients with myotonic dystrophy (MyD).Background: Respiratory insufficiency has been reported frequently in MyD patients. Recent data support the hypothesis that this respiratory failure results from a primary dysfunction of the CNS.Methods: The authors performed a quantitative immunoreactive study of tyrosine hydroxylase immunoreactive (TH+) neurons linked to hypoventilation in the dorsal central medullary nucleus (DCMN), the ventral central medullary nucleus (VCMN), and the subtrigeminal medullary nucleus (SMN)-where the automatic respiratory center is thought to be located-in eight MyD patients and in 10 age-matched control subjects. Alveolar hypoventilation of the central type was present in three of the MyD patients but not in the remaining MyD patients or the control subjects.Results: The densities of TH+ neurons of the DCMN, the VCMN, and the SMN in MyD patients with hypoventilation were significantly lower than in those without hypoventilation (p < 0.02, p < 0.01, and p < 0.01, respectively) and control subjects (p < 0.01, p < 0.01, and p < 0.01, respectively).Conclusions: These data suggest that the loss of TH+ neurons of the DCMN, the VCMN, and the SMN is associated with the presence of hypoventilation in MyD and may be an important feature of MyD.

In the previous study [Takeda et al. (1996) Neurosci Lett 221: 17-21], we reported that the advanced glycation end products (AGEs) in the external space of neuronal perikarya (extraneuroperikaryal AGE deposits) were significantly abundant in the Alzheimer's brain. In this study, we investigated the spatial relationship of the extraneuroperikaryal AGE (carboxymethyllysine and pentosidine) deposits in astrocytes and microglial cells in the Alzheimer's disease brain using double immunolabelling for AGEs and astrocyte or microglial cell markers. Most of the extraneuroperikaryal AGE deposits were co-localized with glial fibrillary acidic protein-positive astrocytes. AGE deposit-bearing astrocytes also contained Gomori-positive granules. Furthermore, some of the extraneuroperikaryal AGE deposits were co-localized with microglial cells. These extraneuroperikaryal AGEs may activate astrocyte and microglia, and play a role in pathogenesis of Alzheimer's disease.

It is generally accepted that cancers in the elderly are of low grade malignancy. In order to clarify this point, autopsy cases from a medical center for the elderly between 1982 and 1994 were pathologically analyzed. Three hundred and fifty (160 males, 190 females) out of a total of 871 (361 males, 510 females) autopsy cases were examined. The incidence of cancer in various age groups were found to be as follows:or = 69 years, 24/67 (36%); 70-74 years, 40/102 (39%); 75-79 years, 54/136 (39%); 80-84 years, 79/180 (44%); 85-89 years, 66/172 (38%); 90-94 years, 59/137 (43%); 95-99 years, 17/56 (30%); andor = 100 years, 12/21 (57%). The incidences did not significantly differ among the groups, that is, there was no age-dependency in the incidence of cancer. Furthermore, the incidences of multiple cancers (two or more different malignancies in one patient) also did not differ. However, deaths due to the cancers showed a tendency to decrease with age. The survival periods of clinical cancer cases without a surgical operation history (time period between the date of diagnosis and death), were age-related for female cases. However, the rate of distant metastasis was not age-related. The incidence of latent cancers in individuals over 85 years of age was 79/174 (45.4%) and significantly higher than the value of 69/234 (29.5%) for those under 85. The number of malignant tumors in various organs for the different age groups was also counted and the total numbers of clinical cancers and latent cancers in each organ were, 50 and 23 in the lung, 46 and 20 in the stomach, 41 and 31 in the colon, 0 and 39 in the prostate, and 14 and 0 in the mammary glands, respectively. All prostate cancers were latent cancers, and all mammary cancers were clinical cancers. These findings provide strong evidence that cancers in individuals of advanced age have less malignancy potential.

We recently reported a significantly higher incidence of intracytoplasmic inclusion bodies (IIBs) of the substantia nigra in patients with myotonic dystrophy (MyD) than in age-matched controls. The changes are, per se, not specific, since a small percentage of disease and normal controls also showed similar inclusions. To elucidate the pathological significance of the inclusion in MyD, we studied immunohistochemical characteristics of IIBs of the substantia nigra in eight patients with MyD. Many IIBs showed moderately intense immunoreactivity for ubiquitin, microtubule-associated protein (MAP) 1 and MAP 2. However, the IIBs did not react with any of the following: anti-neurofilament protein antibodies (Abs) (68, 160 and 200 kDa), anti-neuron-specific enolase antibody (Ab), anti-tau Ab, anti-tubulin Abs (alpha and beta), anti-paired helical filament Ab, anti-actin Ab, anti-phosphorylated epitope of neurofilaments Ab, anti-synaptophysin Ab, anti-myelin basic protein Ab, anti-actin Ab and anti-glial fibrillary acidic protein Ab. Our results suggest that IIBs of the substantia nigra in MyD are related to an alteration of neuronal cytoskeleton metabolism affecting microtubular proteins in conjunction with activation of ubiquitin proteolytic systems.

Pathological changes of spinal vascular disease due to dissecting aortic aneurysm, atheroma emboli, cardiac arrest and pencil-shaped softening are described. Spinal cord damage in four patients who developed paraplegia secondary to the dissecting aortic aneurysm varied significantly from case to case. The extent of aortic dissection, the level of radicular artery, the vascular supply pattern in the transverse section of the spinal cord, and the vulnerability to ischemia were suggested to be very important factors contributing to the spinal cord damage. Atheroma emboli of spinal cord vessels were found in 7/604 autopsied cases. Atheroma emboli of spinal cord vessels is one cause of myelopathy in aged persons with hypertension, renal failure, myocardial infarction, or diabetis mellitus. Atheroma emboli were often observed at the vessels of lumbosacral segmental level. Necrosis of the spinal cord was only observed in two cases of atheroma emboli. Ischemic changes of the spinal cord were observed in 7/15 cases in which the cerebral cortex showed lamellar necrosis due to cardiac arrest. The damaged areas were found more predominantly in the lumbosacral segment. In the cross section, the area from the mid-portion of gray matter to the base of the posterior horn was predominantly affected. Histological findings of 13 cases of pencil-shaped softening, in which the spinal cord showed transverse necrosis by compression of extradural metastatic tumors are described. The continuity between the cavity of pencil-shaped softening, the area of transverse necrosis was confirmed. For the pathogenesis of pencil-shaped softening, mechanical compression was considered to be an important factor.

Complications, prognosis, and efficacy of treatments were retrospectively studied in elderly patients, some of whom had lung, stomach, colon, pancreatic, and liver cancers. Hemoglobin concentration and characteristics of erythrocytes were measured for up to sixty months. Eighty-eight patients died of cancer, and malignant tumors were detected before death in 57. The average survival periods were 11 months for patients with gastric cancer. 9 months for those with colon cancer, and 7 months for those with lung cancer. Malignancies of the digestive organs and lung were often detected in elderly patients with anemia. In elderly people who were without cancer for more than 78 months the hemoglobin concentration did not change significantly, but in those with a malignancy the hemoglobin concentration continuously decreased. Patients with colon cancer who were given blood transfusions survived longer than those who were not given the transfusions, but the same was not true of patients with gastric or lung cancers. Iron therapy, however, was generally effective in patients with malignant tumors of the gastrointestinal tract. Among those who were near death, the red cell distribution widths differed significantly between patients with different types of carcinomas, but differences in mean corpuscular hemoglobin and in mean corpuscular volume were not statistically significant. In conclusion, hemoglobin concentration and characteristics of erythrocytes should not be neglected in the diagnosis and treatment of cancers in the elderly.

We measured the platelet distribution width, the mean platelet volume, the volume percentage of platelets, and the platelet-to-large-cell ratio in 15 elderly patients with disseminated intravascular coagulation (DIC). Peripheral venous blood mixed with ehtylenediaminetetraacetic acid was analyzed with a Sysmex E-4000 analyzer. The underlying diseases were sepsis, pneumonia, pyelonephritis, and other inflammatory diseases. The mean duration of survival from the onset of DIC was 16.9 +/- 23.9 days. The distribution of red cell sizes before the onset of DIC did not differ significantly from that in patients without DIC, but fragmentation of erythrocytes on blood films was more common in the early stage of DIC (p < 0.01). Before the onset of DIC, the two groups did not differ significantly in the frequency of giant platelets on blood smears. At the onset of DIC, the platelet distribution width, the mean platelet volume, and the platelet-to-large-cell ratio were significantly higher than in patients without DIC. The concentration of glutamic-oxaloacetic transaminase and those of other serum enzymes did not change significantly, but the serum creatinine concentration and the blood urea nitrogen level increased as the platelet-to-large-cell ratio increased. No significant relation was evident between the levels of serum C-reactive protein and creatinine, between the platelet-to-large-cell ratio and the mean volume of red blood cells, or between the platelet-to-large-cell ratio and the distribution of red cell sizes. These data suggest that studies of platelets are more useful in the diagnosis of DIC at early stages of impaired organ function than are other indicators of inflammation such as the level of C-reactive protein.

The purpose of this study was to assess the background to the longevity of 36 centenarians in Nagoya city and to compare 14 institutionalized centenarians out of those 36 with 202 individuals in the 70-99 age group in our special nursing home, particularly with regard to blood chemistry and immunity tests. The reasons for their social longevity in terms of profile appeared to be attention to eating habits, abstention from smoking and drinking, occupations with adequate exercise. The incidence of dementia was 65.6% among them. We evaluated centenarians from the viewpoint of Hasegawa's Dementia Scale (HDS) and comprehensive functional assessment of the elderly consisted of the revised version of Hasegawa's Dementia Scale (HDSR), and examination of activity of daily living (ADL), physical perception, and social life. All were positively associated. Thus centenarians independent of physical assistance demonstrated significantly higher systolic blood pressure, and respective scores for HDS, HDSR, ADL, physical perception and social life than their dependent counterparts, were less likely to be institutionalized and suffered from fewer disorders. In particular none were diagnosed as positive for cerebral hemorrhage, infarction and dementia. Age demonstrated significant positive or negative correlation with the following values in blood chemistry and immunity tests: blood cell counts, hemoglobin concentration, hematocrit value, albumin, total protein, total cholesterol, low density lipoprotein cholesterol, creatinine, blood cell nitrogen, uric acid, helper T cell, and IgA immunoglobulin.

非小細胞肺癌（NSCLC）に随伴発症した関節リウマチ（RA）を経験した．症例は78歳女性．高血圧で経過観察中，NSCLC（腺癌，stage IIIb）を発症した．診断後から急速に多関節炎が出現し，血清学的検査で抗CCP抗体，抗MMP-3抗体，SLX，NSE，CEAが陽性であった．関節X線写真，関節穿刺液の所見からRA（Class I，Stage I）と診断し，経口プレドニゾロン（20 mg/日）で，多関節痛は速やかに消失し自立歩行が可能となった．癌に随伴する多関節痛では関節炎の鑑別診断が重要である．

The purpose of this study was to clarify aspects of social life in a comprehensive functional assessment of 160 elderly subjects, over 60 years of age, in institutions for the elderly. Five items were assessed: economic conditions, marital status, family conditions, family relationships and group behavior. The institutions were of 4 types: a geriatric hospital, a special nursing home for the aged, a home for the elderly and a home with moderate fees. The assessment of social life demonstrated significant correlation between the revised version of Hasegawa's Dementia Scale, activity of daily living and physical conditions. Inter-institution comparisons revealed significant differences in terms of economic conditions for the home for the elderly, family conditions for the home with moderate fees, and family relationships and group behavior for the geriatric hospital. Total grades across the 5 items were significantly lower for the geriatric hospital cases. This assessment proved useful to illuminate aspects of social life of the elderly in institutions.

Concentrations of nervous tissue-related proteins, including S-100 proteins (alpha and beta), enolase isozymes (alpha and gamma), superoxide dismutase (SOD) isozymes (Cu/Zn SOD and Mn SOD), and GTP-binding proteins (alpha subunits of GO and Gi2) were determined in the four cerebrocortical regions (superior frontal gyrus of frontal lobe, parahippocampal gyrus of temporal lobe, superior parietal lobule of parietal lobe, and calcarine area of occipital lobe) of patients with Alzheimer's disease, and age-matched control and young control patients by means of enzyme immunoassay methods. Although the temporal cortex of some patients with Alzheimer's disease (4/7) showed apparently enhanced S-100 beta with decreased gamma-enolase, concentrations of neuronal (neuron-specific gamma-enolase and the alpha subunit of GO) and glial (S-100 beta, S-100 alpha, and alpha-enolase) marker proteins, and both SODs in each region were not significantly different between patients with Alzheimer's disease and the age-matched controls. Concentrations of Gi2 alpha also showed similar values in the cerebral cortices of young and aged controls and patients with Alzheimer's disease. However, when compared with young controls, S-100 beta in the four regions of patients with Alzheimer's disease and aged controls, and Cu/Zn SOD in frontal cortex of patients with Alzheimer's disease were significantly enhanced (P less than 0.01).

An autopsy case of progressive supranuclear palsy (PSP) associated with central pontine myelinolysis (CPM) is reported. A 73-year-old male patient suffered from gait disturbance for about 5 years. The clinical features were characterized by gradual development of supranuclear ophthalmoplegia, tremor, bradykinesia, rigidity, neck dystonia, dementia and pseudobulbar palsy at the advanced stage of his illness. Treatment with levodopa did not improve his neurological signs and symptoms. PSP or multiple system atrophy was considered as a clinical diagnosis of the patient. He died of pneumonia, acute pancreatitis and liver dysfunction in November 1985. The main neuropathological findings were neuronal loss and gliosis with neurofibrillary tangles of globose type in the globus pallidus, subthalamic nucleus, substantia nigra and dentate nucleus, and at the base of the pons, bilateral and symmetrical demyelination was found. In addition, myelin staining revealed circumscribed pallor in the cerebral white matter. The histologic diagnosis was PSP associated with CPM. An association of PSP with CPM is rare in the elderly and possible etiologic factors of both diseases were discussed.

Scleroderma and eosinophilia often occur together, though the pathogenesis is unclear. We investigated the effect of olopatadine hydrochloride in a series of cases of limited scleroderma (LS). Ten patients with LS and positive eosinophil counts (LSE) were enrolled (average age, 85 years; six men and four women). Serum concentrations of the anti-Scl-70 antibody were positive. Olopatadine hydrochloride was prescribed at 10 mg/day for 3 weeks. Serum concentrations of the anti-Scl-70 antibody significantly decreased, but changes in eosinophil numbers and percentages in peripheral blood were not significant. Factor analysis suggested a correlation between serum concentrations of the anti-Scl-70 antibody and complement C4. Olopatadine could be effective in reducing anti-Scl-70 antibodies in the elderly with LSE.

The effect of rehabilitation and prognosis for elderly cases of cerebrovascular dementia were evaluated by comparing the group of the patients receiving rehabilitation with those who did not receive rehabilitation. There were no significant differences in the age, neurological symptoms, psychotic symptoms, physical complications, ADL and Hasegawa's dementia rating scale between the two groups. The main reason for rehabilitation was recurrence of cerebrovascular attack (42.9%), disuse atrophy (42.9%) and bone fracture and others (14.3%). There was significant improvement of ADL in the patients showing a score of more than 10 on Hasegawa's dementia rating scale and in the patients given drugs to improve cerebral circulation and metabolism, but there was no significant improvement of Hasegawa's dementia rating scale. Concerning the prognosis of patients receiving the rehabilitation, there was no change of ADL and Hasegawa's dementia rating scale. In the group of patients which did not receive rehabilitation, significant decrease of ADL was noted, but there was no change of Hasegawa's dementia rating scale.

A 51-year-old man with poliomyelitis was admitted to emergency because of a severe decubitus ulcer on his right hip that was associated with infection. His general condition deteriorated and he was malnourished and dehydrated. Despite adequate hyperalimentation and antibiotic administration, laboratory data indicated pancytopenia 4 days later. He was diagnosed as having secondary hemophagocytosis (HPS) associated with methicillin-sensitive Staphylococcus aureus sepsis due to decubitus inflammation based on bone marrow aspiration and a blood culture. Although granulocyte colony stimulating factor, packed red blood cell transfusions, platelet transfusions, and antibiotics gradually improved the pancytopenia, the patient died of massive gastrointestinal tract bleeding.

Argyrophilic grain disease (AGD) is a progressive degenerative disease of the human brain, the prevalence of which increases with advancing age. The features of AGD in autopsied brains from 32 centenarians were studied using phosphorylated tau (AT8) immunostaining combined with Gallyas–Braak staining and 4R tau-specific antibody (RD4) immunostaining. Ten of 32 centenarians were diagnosed as AGD, yielding an overall frequency of 31.3%. In the demented group, nine (39.1%) of 23 cases were found with argyrophilic grains (AGs), while in the non-demented group, AGs were found in only one (11.1%) of nine cases, the difference between them being significant (P

To investigate the characteristics of alpha-synucleinopathy in the brains of centenarians, the autopsied brains and spinal cords from 23 cases were studied. Coronal slices were prepared from a section of the cerebral hemisphere, following the guidelines of the Consortium to Establish a Registry for Alzheimer’s Disease (AD) (CERAD) and the consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB). Spinal cord specimens were prepared at each segment from the third cervical to the third sacral segment. In all cases, we performed standard stainings of hematoxylin–eosin, Kluver–Barrera, and Gallyas–Braak combined with Luxol fast blue/cresyl violet, and alpha-synuclein (AS), phosphorylated tau (AT8) and beta-amyloid protein immunostainings. One-way ANOVA analysis, Chi-square or Fisher exact test were used for statistical analysis. Overall, AS-positive structures were found in 8 (34.8%) of our 23 centenarians, 6 (35.3%) of 17 demented patients, and four (40%) out of ten AD patients. The frequencies of AS lesions in the brains with senile plaque (SP) stage 0–A, B, and C were 27.7, 33, and 50%, respectively. No statistical differences were found among the frequencies of AS lesions in the subgroups of NFT stages I–II, III–IV, and V–VI (P=0.478). Most cases showed a widespread distribution of AS-positive structures except for one patient, in whose brain only the medulla was involved. The distribution pattern of AS-positive lesions was similar to that in Parkinson’s disease or DLB, but the pigmented neurons in substantia nigra were relatively well preserved. Our findings indicate that there is a high frequency of alpha-synucleinopathy in centenarians, SP-positive and AS-positive lesions may involve a synergistic interaction.

Multiple myelomas often occur in elderly people with complications due to aging. A 54-year-old man was first admitted with cerebral infarction, and multiple myeloma (IgG kappa, stage IIIA) occurred in November 1989 that was followed by partial remission after chemotherapy. The karyotype of the bone marrow cells was 46, XY, and no p53 gene mutations were detected by polymerase chain reaction and single-strand conformation polymorphism analysis. Chemotherapy (melphalan 10 mg, vindesine 3 mg, ranimustine 150 mg, prednisolone 60 mg for 4 days) was performed in February 1999 because of aggravation of the myeloma. After daily subcutaneous injection of 50 micrograms of nartograstim for six days to treat neutropenia, soft tissues around the right eye were swelled gradually without redness, accompanied by elevation of the serum creatine-kinase concentration. The swelling disappeared, and the enzyme level normalized after discontinuation of nartograstim. In July, on the sixth day of daily subcutaneous injection of 75 micrograms of filgrastim after the same chemotherapy, similar swelling of the soft tissues around the left eye became evident, and again this proved reversible. In July 2000, 40 mg of dexamethasone was infused, and after 5-day subcutaneous-injection of 75 micrograms of filgrastim daily, the right subclavicular soft tissue became swollen. He died of myocardial infarction, and autopsy revealed infiltration of myeloma cells into the right subclavicular muscle and bone marrow packed with myeloma cells. This case suggests that myeloma cells can proliferate and infiltrate into soft tissues on exposure to granulocyte-colony stimulating factors.

The clinical significance of a slight increase of serum soluble interleukin-2 receptor (sIL2R) concentration in the stable elderly was investigated. Thirty-five residents of nursing homes with physical impairment as a sequel to cerebral infarctions, without any inflammatory condition, anodyne or immunological treatment, were divided into two groups: 24 without overt or suspected malignancy (NC) and 11 with a history of malignancy (CA). Serological screening with measurement of sIL2 R concentrations was performed and numbers of lymphocytes with CD4, CD8 markers were determined. The NC group was divided into controls (n = 15, sIL2R < = 883 U/mL) and subjects demonstrating elevation (n = 9, NH), as in a previous study. Differences were found in serum concentrations of albumin, blood urea nitrogen, total cholesterol concentration, Pettigrew's prognostic nutritional index (PNI), as well as the ADL score, but not age or sex between NH and controls. Factor analysis in NC revealed serum creatinine and blood urea nitrogen concentrations to correlate positively, and serum albumin, total cholesterol concentrations, ADL score, PNI to correlate negatively to sIL2R. Differences were found in sIL2R, albumin, total protein, total cholesterol, beta-lipoprotein, PNI between CA and controls, but correlations were not found in CA. Survival rate of controls over twenty-four months was better than that of NH, but not of CA. Our results suggest that a slight increase of concentration of sIL2R is related to subclinical systemic deterioration, especially with regard to nutrition, with a plausible connection to prognosis of the stable elderly without malignancy.

OBJECTIVES: To investigate the significance of low hemoglobin concentration and longevity in older people. DESIGN: Randomized prospective study. SETTING: Nursing home and geriatric hospital ward in a metropolitan welfare center. PARTICIPANTS: Apparently stable older residents from 1990 to 1996. MEASUREMENTS: Survival rates were estimated by statistical analysis. Sixty-three older subjects with low hemoglobin (Hb

The effects of music therapy on natural killer (NK) cell count and activity (NKCA) were studied in 19 persons. Alzheimer's disease, cerebrovessel disease and Parkinson's disease subjects were assigned to a music therapy. Blood samples were drawn at rest and after completion of music therapy. Music therapy did not change the number of circulating lymphocytes. The percentage of NK cells increased during music therapy, along with an increase in the NK cell activity. The proportion of T cells, CD4 and CD8 did not change significantly during music therapy. One hour after the music therapy session, plasma adrenaline increased but cortisol and noradrenalin did not change. The results indicate that music therapy can significantly increase NK cell count and activity. The change in NK cell and function were independent of neuro-degenerative diseases.

The cellular distribution of an advanced glycation end product [Nepsilon-(carboxymethyl)lysine (CML)] in aged and Alzheimer's disease (AD) brains was assessed immunohistochemically. CML was localized in the cytoplasm of neurons, astrocytes, and microglia in both aged and AD brains. Glial deposition was far more marked in AD brains than in aged brains, and neuronal deposition was also increased. On electron microscopic immunohistochemistry, neuronal CML formed granular or linear deposits associated with lipofuscin, and glial deposits formed lines around the vacuoles. Neuronal and glial deposits were prominent throughout the cerebral cortex and hippocampus, but were sparse in the putamen, globus pallidus, substantia nigra, and cerebellum, with glial deposits being far more prominent in AD brains. The distribution of neuronal and glial deposits did not correspond with the distribution of AD pathology. The extent of CML deposits was inversely correlated with neurofibrillary tangle formation, particularly in the hippocampus. Most hippocampal pyramidal neurons with neurofibrillary tangles did not have CML, and most of the neurons with heavy CML deposits did not have neurofibrillary tangles. In the hippocampus, neuronal CML was prominent in the region where neuronal loss was mild. These observations suggest that CML deposition does not directly cause neurofibrillary tangle formation or neuronal loss in AD.

Background: Soluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF binding with receptors on target cells. In a variety of pathologic situations, the concentrations of sTNF receptors (R) increase. Objective: To discuss possible causes of increased risks for infectious disease and cancer seen in the elderly. Methods: The participants were healthy subjects (n = 48) of three age groups (young, middle-aged, and elderly). Patients with senile dementia of Alzheimer type (n = 25) were also studied. For detection of cytokines, interleukin (IL) 1α, IL-1β, IL-6, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor, and TNF-α were measured in serum by enzyme-linked immunosorbent assays, as were soluble (s) IL-1 receptor antagonist (IL-1ra), sIL-6R, p55sTNF-R, and p75sTNF-R. Results: IL-1α, IL-1β, IL-6, and TNF-α were not detected, and sIL-6R and IL-1ra concentrations were not significantly different between the three age groups. However, sTNF-R and M-CSF were increased in sera from the elderly, both healthy and demented. A significant correlation was seen between sTNF-R and M-CSF concentrations. Conclusions: Increased sTNF-R levels may oppose the physiologic and protective effects of TNF by interference with its receptor binding. This interaction may contribute to the susceptibility of the elderly to infectious and neoplastic diseases.

A clinico-pathological evaluation was performed on patients requiring nasogastric nutritional support. As a result, it was found that nasogastric tube feeding was common in patients with cerebrovascular diseases (CVD) and senile dementia of Alzheimer's type (SDAT). Pneumonia was anamnestic in many CVD patients, which was frequently the direct indication for nasogastric tube feeding and the major cause of death in these patients. On the other hand, pneumonia was not common in SDAT in which the major indication of nasogastric tube feeding was abnormal appetite. However, pneumonia was an infrequent cause of death in SDAT compared to CVD patients. The mean age in which nasogastric tube feeding was started was 8 years older in SDAT than CVD patients, however, there was no significant difference in the duration of nasogastric tube feeding ranging from initiation to death. A swallowing study, based on a clinico-pathological evaluation, was performed by video-fluoroscopy on healthy seniors and senior patients neurological diseases. There was no abnormal finding in the healthy seniors. Findings in CVD patients with single-sided neurological diseases indicated that 27.3% had moderate abnormalities and 18.2% had severe abnormalities. In CVD with bilateral defects, 35.7% had moderate abnormalities and 42.9% had severe abnormalities. Though even single-sided CVD defects can frequently cause swallowing disorder, oral food intake was maintained in nearly half of the patients with bilateral CVD, despite high incidence of severe swallowing disorder. In the mild SDAT group, rated on a scale from 0.5 to 1.0 according to the Clinical Dementia Rating (CDR), 11.1% had moderate swallowing disorder. In the CDR 2-3 group, 23.1% had moderate disability and 15.4% had severe disability. It appears that SDAT patients do not suffer from rapid deterioration in swallowing ability, which was relatively retained in this disease group. In Parkinson's disease patients with a Yahr grade of I-II, 55.6% had normal findings and 44.4% had mild abnormalities. In Yahr grade III-IV patients, 28.6% had mild and 28.6% had severe disability. Patients with severe dysfunction had a high incidence of silent aspiration. The swallowing function was maintained in the early course of mild Parkinson's disease patients, however the ability rapidly deteriorated with the course of the disease. The radiological findings of the swallowing study supported the clinico-pathological characteristics of each disease.

Hypersomnia occurs frequently in patients with myotonic dystrophy (MyD). We performed a quantitative immunohistochemical study of serotonin (5-HT)-containing neurons linked to hypersomnia in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) in 8 patients with MyD, 5 of whom showed hypersomnia, and in 12 age-matched controls. The densities of 5-HT neurons in the DRN and the SCN were significantly lower in MyD patients with hypersomnia than in MyD patients without hypersomnia and controls. These data suggest that the loss of 5-HT neurons of the DRN and the SCN is associated with the presence of hypersomnia in MyD.

To study vascular lesions of the spinal cord in the elderly, a pathological study of atheromatous emboli in the spinal cord was done. Among 604 patients examined at autopsy, atheromatous emboli of the spinal cord were found in 7 (1.2%). The average age of these patients was 76 years. The most common underlying disorders in these patients were hypertension, severe aortic atherosclerosis, and diabetes mellitus. Atheromatous emboli were also often found in the arteries of the kidneys, spleen, pancreas, and colon. The small arteries of the spinal arachnoid at the lumbosacral level were most frequently affected by the atheromatous emboli. Two patients had spinal-cord infarctions associated with atheromatous emboli: one had a cystic infarction of the lateral column at the T9 segment, and the other had cystic infarctions of the lateral column at the C7 and T3 segments. The low incidence of spinal cord infarction was attributed to good collateral circulation in the spinal cord. Atheromatous embolism should be considered as a possible cause of vascular lesions of the spinal cord in elderly persons with aortic atherosclerosis.

Intracytoplasmic inclusion bodies of the thalamus in eight patients with myotonic dystrophy (MyD) were studied immunohistochemically. The intracytoplasmic inclusion bodies of the thalamus (thalamic inclusions, TIs) were strongly immunostained with anti-ubiquitin antibody (Ab) and some of them were mildly stained with anti-microtubule associated protein 1 (MAP 1) and anti-MAP 2 antibodies. However, TIs did not react with any of the following: anti-neurofilament protein Ab, anti-tau Ab, anti-paired helical filament Ab, anti-tubulin Abs (alpha and beta), anti-neuron-specific enolase Ab, anti-glial fibrillary acidic protein Ab, anti-synaptophysin Ab, anti-myelin basic protein Ab, anti-actin Ab and anti-phosphorylated epitope of neurofilaments Ab. Thus, our study demonstrates the unique immunohistochemistry of TIs in MyD which differentiates them from other intracytoplasmic inclusions in various neurodegenerative disorders.

A cytoarchitectonic study of spinal ventral horn cells was performed to identify age-related changes. The diameter distribution of ventral horn neurons of the fourth lumbar segment of the spinal cord and their size and topographical distributions were investigated in 14 autopsy cases. These cases represented patients of 18–100 years of age who had died of non-neurological diseases. The results indicate that small neurons widely distributed in the intermediate zone of the ventral horn significantly diminished with aging (P < 0.0005, r = –0.898), whereas medium-sized and large neurons located in the medial and lateral nuclei showed only a slight decrease with advancing age. The total number of neurons in the whole ventral horn was also noted to decrease significantly with aging (P < 0.0005, r = –0.899). While small neurons in the intermediate zone of the ventral horn are thought to be mostly interneurons, their physiological function still remains obscure in many respects. The findings of this study provide insight into age-related cell loss in terms of size and location.

The characteristics of multiple spongy necrosis of the basis pontis (MSN), central pontine myelinolysis (CPM), and cerebrovascular disease (CVD) of the pons developing in the elderly have not been fully clarified. We therefore studied 305 patients (aged 60-107, mean: 83.9) autopsied in Nagoya City Kohseiin Geriatric Hospital. MSN was found in four patients (1.3%). The major histologic finding was multiple necrosis of the basis pontis, characterized by loss of myelin and axons, no reactive astrocytes or inflammatory cells were found. Small foci of spongy necrosis appeared to unite with each other to form larger lesions. The central basis pontis was weakly stained by Kluver-Barrera stain in 15 patients, which suggested the presence of CPM. However, the diagnosis was only confirmed in one patient, (by the myelinolysis, loss of oligodendroglia, infiltration of macrophages, and reactive astrocytosis). With regard to CVD, none of the 305 patients had macroscopic pontine hemorrhage, but histologically small and old hemorrhagic lesions were found in 15. These lesions were associated with hypertensive or arteriosclerotic changes in the pontine vessels. Pontine infarction was evident in 77 patients (25.2%). In most lesions (74%) the area of infarction was smaller than 1 mm2. In 27 of the 74 patients with lacunar or microscopic infarcts, the pontine infarcts were found in areas where the blood was supplied through the short circumferential branch.

The purpose of this study was to assess the background to the longevity of a 115-year-old woman who was the oldest individual in Japan as of September, 1994. The secrets of her social and medical profile appeared to be hereditary factors, well-balanced meals, no smoking or drinking, sufficient sleep and adequate exercise. From the viewpoints of psychological aspects and comprehensive functional assessment of the elderly, she clearly has a tenacious personality. Furthermore, she has maintained independence in her activities of daily living, and did not suffer from senile dementia until 107 years of age. From the medical standpoint, she has suffered from transient hypertension, but her left ventricle function has remained within the normal echocardiography range and no greatly abnormal values have been observed in blood chemistry tests. She has suffered from pneumonia and urinary tract infection many times since the age of 109, and on these occasions she was promptly admitted to our hospital and received appropriate medical treatment. We consider that this also played an important role in her longevity.

A quantitative study of neurons in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) was performed in seven patients with myotonic dystrophy (MyD), five of whom showed hypersomnia, and in eight age-matched controls. The densities of neurons in the DRN and the SCN were significantly lower in MyD patients with hypersomnia than in MyD patients without hypersomnia and control subjects. There was an appreciable positive correlation in the density of neurons between the DRN and the SCN in all MyD patients. These data suggest that the neuronal loss of the DRN and the SCN is associated with the presence of hypersomnia in MyD.

The purpose of this study was to assess the role of institutions for the elderly, and special nursing homes in particular, with regard to senile dementia. The subjects consisted of 81 cases who were institutionalized in our special nursing home from early November, 1992 to late October, 1993. Of these, 37 cases (45.7%) showed clinical dementia at the time of institutionalization. The severity and respective percentages of dementia were as follows: slight degree 32.4%, moderate degree 27.0% and severe degree 40.6%. The severity of dementia demonstrated significant correlation with age. Hasegawa's Dementia Scale, activity of daily living and physical conditions. The admission rate (40.5%) of the demented group for physical diseases was significantly higher than that (22.7%) of the non-demented group. The majority of families of both groups first sought advice at institutions other than our special nursing home and the welfare office in the city, prior to being institutionalized. The referral rate from such institutions was far higher than that for direct entry from their homes. We consider that special nursing homes, in addition to carrying for daily living requirements, should pay great attention to physical diseases in patients suffering from senile dementia, and cooperate with medical institutes, particularly referring hospitals, and other welfare and health facilities, in this regard.

The purpose of this study was to assess possible correlations between paraplegia in flexion and dementia in elderly patients in our special nursing home and geriatric hospital. At the time of our study, 10.5% of all our patients were suffering from paraplegia in flexion, with the ratio increasing with advancing age. Disorders of the nervous system, and in particular disorders caused by cerebrovascular disease were found at a high rate of frequency among the paraplegia in flexion patients, in whom the incidence of dementia was 97.8%. In most cases, the degree of dementia was severe, the types and respective percentages being as follows: vascular type 37.8%, Alzheimer's type 24.4%, mixed type 22.2% and others 15.6%. Many of these patients demonstrated pseudobulbar palsy, frontal sign, Babinski's sign, and typical reflexes of spinal automatism. We think that paraplegia in flexion is probably caused by reflexes of spinal automatism and extensive cerebral lesions.

Sirs: “Pseudopseudohypoparathyroidism (PPHP)” is an entity in which patients with all the features of Albright’s hereditary osteodystrophy (AHO) have normal serum calcium and phosphate, and a normal response to parathyroid hormone (PTH). AHO is a condition in which the characteristic physical findings include a round face, short stature, brachydactyly, and ectopic calcification. AHO was first described in patients with “pseudohypoparathyroidism type Ia (PHPIa)” exhibiting resistance to PTH [1]. PPHP and PHP-Ia are genetically related variants caused by heterozygous loss-of-function mutations within the gene encoding the α-subunit of a stimulatory G protein (Gs α); this protein is necessary for the action of parathyroid and other hormones that act by stimulating the adenylate cyclase-cyclic AMP system [12]. Ossification of the posterior longitudinal ligament (OPLL), a type of paravertebral ligamentous ossification, is recognized as a cause of cervical myelopathy [9]. We describe a case of PPHP with cervical myelopathy caused by OPLL. A 53-year-old Japanese man developed difficulty in walking and limb weakness, and was admitted to our hospital for the first time in 1989. His medical history was notable for the presence of mental retardation, hypothyroidism, cerebral hemorrhage, an episode suggestive of tetany, and a diagnosis of pseudohypoparathyroidism made without further investigation. His medications at that time were L-thyroxine and vitamin D. A general physical examination revealed the typical features of AHO. When his vitamin D therapy was interrupted, serum calcium (4.6 mEq/l, normal range: 4.5–5.5), phosphate (4.0 mg/dl, normal range: 2.5–4.5), PTH (24 pg/ml, normal range: 10–65) and 1a, 25(OH)2 vitamin D (39 pg/ml, normal range: 15–70) levels were all within the normal range. The Ellsworth-Howard test revealed a normal phosphaturic response and a normal cyclic-AMP response. Therefore, the diagnosis of PPHP was confirmed. Under diagnosis and medication for hypothyroidism, antithyroid antibodies were negative; this condition may have resulted from the thyroid tissue deficiency in a Gs α-coupled transduction pathway [10]. Neurological examination revealed intact cranial nerves and mild tetraparesis without rigidity. The deep tendon reflexes were brisk. Walking was unsteady with a spastic gait. Sensation was normal. His verbal and performance IQ were 61 on the Wechsler adult-intelligence scale. CT of the head revealed bilateral and symmetrical intracranial calcifications (Figure A). A lateral radiograph of the cervical spine revealed OPLL between C2 and C5 (Figure B). CT of the cervical spine indicated severe OPLL (Figure C), and MR imaging showed severe spinal-canal stenosis and compression of the spinal cord due to OPLL and disc protrusion (Figure D, E). His symptoms gradually deteriorated over the next 10 years. Further weakness of the legs developed after he had an accidental fall in 1999. Since then, he has been confined to a wheelchair. The common neurological manifestation of PPHP and PHP-Ia is the presence of intracranial calcifications predominantly in the basal ganglia [7]. This finding has usually been reported in association with extrapyramidal symptoms [3, 13, 14]. In our patient, the lesion corresponding to the neurological symptom was cervical myelopathy associated with OPLL rather than the intracranial calcifications. Some cells from ligaments with OPLL have one of several phenotypes characteristic of osteoblasts [8]. In addition, the Gsα gene (GNAS1) has been postulated to be the leading candidate for progressive osseous heteroplasia, which is characterized by severe progressive extraskeletal bone formation within deep connective tissue and normal calcium homeostasis [4]. These features might help to explain why ossification with this particular localization developed in our patient. Although only a few PPHP or PHP-Ia cases complicated by OPLL have been reported [2, 5, 6, 11, 15], we should recognize the cervical myelopathy caused by ectopic ossification as a neurological complication in patients with PPHP.

The localization of two small heat shock proteins, alpha B crystallin and 28-kDa heat shock protein (HSP28), was studied immunochemically and immunohistochemically in cerebral cortex of patients with Alzheimer's disease (AD) and control groups. By specific immunoassays for alpha B crystallin and HSP28, we found that the concentrations of alpha B crystallin are elevated in the temporal and frontal lobes, while those of HSP28 are elevated in the temporal, frontal, and parietal lobes in the AD brains. Immunohistochemically, alpha B crystallin was localized in astrocytes and oligodendrocytes, while HSP28 was present in degenerating neurons in the cerebral cortex of both AD and control brains. However, alpha B crystallin-immunoreactive astrocytes and HSP28-immunoreactive degenerating neurons were more frequently observed in AD brains. The immunoreactivity for HSP28 was also found in the senile plaques in the AD brains. These findings suggest that the increased accumulations of these small heat shock proteins appear to be part of reactive processes of glial cells and neurons under pathologic conditions.

A 78-year-old man with developmental disturbance of the genital organs and eunuchoidism was reported. He also had a high pitched voice, thickness of the lower lip and kyphosis of the thorax. He seemed to be fretful, but his intelligence was normal. Neurological tests revealed bilateral hemianopsia and decreased tendon reflexes. A plain skull radiograph clearly showed an egg shaped calcified mass extending upward from the sella turcica which resembled a ballooning shape. Brain CTs showed a high density round mass which expanded the sella turcica and raised the floor of the third ventricle. The inner part of the tumor showed irregular high density. T1-weighted MR imaging revealed an iso signal intensity, and T2 showed low signal intensity in the mass. These findings strongly supported the diagnosis of calcificated craniopharyngioma. Endocrinological study showed panhypopituitarism caused by the tumor compressing the pituitary gland and the hypothalamus. The main reasons why there were no apparent symptoms of hypopituitarism were because the receptors were up-regulated and secondarily because the thyroid and the adrenal cortical functions decreased while struggling to maintain balance with each other. There was also a possibility that these symptoms might have been masked by normal aging. Benign monoclonal hypergammopathy was also indicated, although we could not find a clear correlation between this finding and others.