Maximum Occlusal Force and Incident Functional Disability in Older Adults: The Tsurugaya Project.

The purpose of the current study was to investigate the association between maximum occlusal force, which is an objective predictor of masticatory performance, and incident functional disability in an elderly Japanese population. A prospective cohort study was conducted targeting 815 (51.7% female) community-dwelling older adults aged ≥70 y residing in the Tsurugaya district, Sendai, Japan. The outcome measurement was incident functional disability, defined as a first certification of long-term care insurance in Japan, which is determined on the basis of a strictly established, uniform, nationwide standard. During a median follow-up of 7.9 y (interquartile range, 4.8-7.9 y), information on long-term care insurance was obtained from the Sendai Municipal Authority. Bilateral maximum occlusal forces of the participants were measured using a horseshoe-shaped pressure-indicating film, and the participants were categorized into quartiles based on occlusal force. Adjusted hazard ratios for functional disability were estimated with Cox proportional hazard models, adjusted for age, sex, body mass index, medical history, smoking status, alcohol consumption, duration of education, depressive symptoms, cognitive impairment, physical functioning, marital status, history of falls, and number of remaining teeth. The multiple-adjusted hazard ratios and 95% confidence intervals (CIs) for incident functional disability compared to the greatest occlusal force quartile were 1.53 (95% CI, 1.02-2.33), 1.64 (95% CI, 1.06-2.55), and 1.64 (95% CI, 1.01-2.68) for the third, second, and first quartiles, respectively ( P for trend = 0.011). A lower maximum occlusal force was significantly associated with an increased risk of functional disability independently of possible confounders, including the number of remaining teeth. Occlusal force may be a useful indicator of the relationship between oral function and geriatric health. Knowledge Transfer Statement:This prospective cohort study demonstrated that lower maximum occlusal force was associated with an increased risk of functional disability in older adults, even after adjustment for possible confounding factors, including the number of remaining teeth. This strengthens the rationale regarding the association between oral function and geriatric health. Particularly in older adults, occlusal force is reduced by several factors other than tooth loss, such as the absence of a dental prostheses, sarcopenia in the masticatory muscle, poor periodontal condition, and orofacial pain. Our findings suggest that maximum occlusal force may be a useful biomarker associated with diverse parameters aside from the number of remaining teeth.

Hypermethylation of CpGs in the promoter of the COL1A1 gene in the aged periodontal ligament.

Although the human periodontal ligament shows age-associated histological alterations, the molecular mechanisms are not yet understood. We previously found that COL1A1 gene expression declines with age. In this study, we asked whether DNA methylation in the regulatory region of the gene alters in the aging process, as a possible cause of the decline. The method used was a bisulfite modification of cytosine and nucleotide sequencing of DNA. While the 1st intron region was kept demethylated at young and old ages, the levels of methylation at most CpG sites in the proximal and distal regions of the promoter showed elevation at older ages. Analysis of the data indicates the possible importance of DNA hypermethylation in the promoter region for the age-associated decrease of COL1A1 gene expression.

Gustatory sweating with special references to its mechanism.

A case of gustatory sweating associated with aneurysm in the right cervical region has been described. Gustatory sweating was observed not only on the right half of the face, but also on the right side of the neck and of the upper part of the frontal chest, on the right shoulder and the lateral side of the right arm. Thermoregulatory sweating was almost completely abolished in the involved area, but the responsiveness to intradermal acetylcholine of the sweat glands in the affected area was increased. Further, it was found that axon reflex sweating was elicited by intradermal injection of nicotine in the gustatory sweating area. Gustatory sweating in the present case can possibly be explained by assuming that an aberrant connection was formed by collateral sprouting from the efferent vagal nerve fibers into the preganglionic sympathetic sweat nerve fibers, very probably at about the level of the subclavian ansa.

Increased endoneurial albumin in diabetic polyneuropathy.

Albumin was measured in the endoneurium of fascicular biopsies of sural nerves and in plasma from diabetic patients with polyneuropathy by solid phase radioimmunoassay, and normalized to total endoneurial and plasma protein, respectively, to obtain an index of the blood-nerve barrier (BNB-Index). Fifteen diabetic patients with polyneuropathy had a mean BNB-Index of 29.7 +/- 12.6% SD, 3.8 times higher than control values (7.8 +/- 2.0% SD, n = 4). These data suggest that the blood-nerve barrier of endoneurial capillaries is impaired in patients with diabetic polyneuropathy.

Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy.

BACKGROUND: Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). OBJECTIVE: To determine whether DMRV and HIBM are allelic. METHODS: The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured. RESULTS: The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity. CONCLUSIONS: DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.

Focally accentuated uptake in an area of increased activity in tc-99m HEDP brain scans.

Brain scans performed with Tc-99m HEDP in two patients with suspected intracranial lesions showed abnormal uptake characterized by a focal area of accentuated concentration in a region of increased radioactivity. Surgery revelaed that the focal uptake represented the attachment of meningioma and the general region of increased activity corresponded to the meningioma itself.

Simple and defined method to detect the SOD-1 mutants from patients with familial amyotrophic lateral sclerosis by mass spectrometry.

Mutations in Cu/Zn superoxide dismutase (SOD1) cause a subset of cases of familial amyotrophic lateral sclerosis (FALS). We established a simple and defined method to detect the mutant SODI in erythrocytes by electrospray ionization mass spectrometry (ESIMS) using materials precipitated with specific antiserum. Hemolysate was mixed with anti-SOD1 antiserum and the generated precipitate, which was soluble in the solvent for MS analysis, was injected on to an LC column connected to an ESI-mass spectrometer. MS spectra of the reduced SOD1 prepared from normal individuals showed ion peaks corresponding to free monomer SOD1. The spectra from FALS patients revealed doublet ion peaks corresponding to normal and mutant components. The ratios of mutant to normal SOD1 were about 1/2 in cases of (G37R) and (A4S), and about 0.15 in a case of (H46R). This method provides for the rapid diagnosis using small amount of specimens, and will contribute to elucidate the pathomechanism of FALS through the quantification of SOD1 mutants in erythrocytes and in tissues of nervous systems.

Functional analyses of the stratum corneum in scars. Sequential studies after injury and comparison among keloids, hypertrophic scars, and atrophic scars.

OBJECTIVE: To characterize the functional properties of the stratum corneum (SC) of various scars. DESIGN: A prospective cohort study. SETTING: University hospital medical center. PATIENTS: Thirty-two consecutive patients surgically treated for various skin diseases and 26 consecutive patients with hypertrophic scars or keloids. MAIN OUTCOME MEASURES: Noninvasive bioengineering measurements of functional properties of the SC, such as transepidermal water loss (TEWL), high-frequency conductance, and SC turnover time. RESULTS: The SC barrier function assessed by TEWL was found to be a better parameter for the functional evaluation of scars than the hydration state of the skin surface measured by high-frequency conductometry. In general, the SC on the scars of deeper wounds in the dermis took longer to normalize functionally than the SC on the scars of superficial wounds, especially on the high compared with the abdomen. Thus, elevated levels of TEWL observed on scars at the donor sites of split-thickness grafts normalized between 200 and 400 days in contrast to fewer than 50 days for those of subepidermal erosions. Both TEWL and high-frequency conductance remained high in hypertrophic scars and keloids, and the SC involved showed a faster turnover time than that of adjacent normal skin. CONCLUSIONS: Scars, a proliferative change of the dermis, can be objectively evaluated according to functional abnormalities of the SC, because the dermis has a close relationship with the epidermis and with the SC. The functional characteristics of the SC of fresh scars and those of hypertrophic scars and keloids resemble those of retinoid-treated skin, rather than those found in epidermal hyperproliferative conditions such as psoriasis and dermatitis.

The therapeutic effects of 4-methylcatechol, a stimulator of endogenous nerve growth factor synthesis, on experimental diabetic neuropathy in rats.

We investigated therapeutic effects of 4-methylcatechol (4-MC), a non-amine catechol compound, on streptozotocin (STZ)-induced diabetic neuropathy in rats. 4-MC is one of the potent stimulators of endogenous nerve growth factor (NGF) synthesis both in vitro and in vivo. Diabetic rats showed a statistically significant reduction in motor nerve conduction velocity (MNCV), mean myelinated axon diameter, and NGF content in the sciatic nerve during the experimental period of 8 weeks. The 4-MC treatment started 4 weeks after the STZ injection resulted in significantly greater NGF content, faster MNCV, and larger mean myelinated nerve fiber diameter and axon diameter than in untreated diabetic rats. These findings suggest that a decreased NGF level in the diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy and that 4-MC treatment could be useful for diabetic neuropathy.

Two novel mutations in the adrenoleukodystrophy gene in two unrelated Japanese families and the long-term effect of bone marrow transplantation.

We identified two novel missense mutations in exon 1 of adrenoleukodystrophy (ALD) gene in two unrelated Japanese families. The first, G(874)C transition results in Arg(163)Pro substitution in the cytoplasmic domain of the ALD protein in adrenomyeloneuropathy family. The second, C(679)G results in Ser(98)Trp substitution in the first transmembrane loop in childhood onset cerebral ALD family. Both mutations cause the substitution of polar amino acid (arginine and serine) with non-polar amino acid (proline and tryptophan). Bone marrow transplantation (BMT) from his non-affected his younger sister was performed on a boy with childhood onset cerebral ALD who showed neurological deficit and brain MRI abnormalities. We evaluated the effect of BMT over a 6-year period in terms of neurological deficit, the level of very-long-chain fatty acids (VLCFA) in plasma and fibroblasts, and brain MRI. After BMT, patient's peripheral white blood cells were replaced by donor's XX ones carrying a normal ALD gene confirmed by in situ hybridization using satellite DNA of the centromere of X and Y chromosomes as probes and the level of VLCFA in lymphocytes was within normal limit. However, his neurological state progressively deteriorated. BMT was not beneficial to him.

Effects of 4-methylcatechol, a stimulator of endogenous nerve growth factor synthesis, on experimental acrylamide-induced neuropathy in rats.

Acrylamide monomer (ACR) causes central-peripheral distal axonopathy. We induced neuropathy in rats by means of ACR injection as an experimental model of the dying-back type of peripheral neuropathy to assess the potential efficacy of 4-methylcatechol (4-MC), a potent stimulator of endogenous nerve growth factor (NGF) synthesis, as a therapeutic agent for the axonal nerve lesion. ACR-induced neuropathy in rats resulted in a dying- back type of axonal degeneration, and a statistically significant reduction in motor nerve conduction velocity (MNCV), and density of large myelinated fibers. We administered 4-MC and ACR together to rats intraperitoneally and found improved clinical signs, and significantly more NGF content in sciatic nerves, faster MNCV, and greater myelinated fiber density than in rats given ACR alone. These findings suggest that 4-MC can prevent the progression of ACR-induced neuropathy and decreased NGF levels may be involved in the pathogenesis of ACR neuropathy.

Angiographic study of cerebral vasospasm following rupture of intracranial aneurysms: Part I. Time of the appearance.

An investigation of the time of appearance of vasospasm as seen angiographically after the onset of subarachnoid hemorrhage was carried out on 797 cases of intracranial saccular aneurysm in which operations were performed. It has been reported that vasospasm often occurs early after the onset of subarachnoid hemorrhage. With only one subarachnoid hemorrhage, vasospasm occurred within three days after the hemorrhage in only 4.2% of the 120 cases in this study. The appearance of vasospasm was most frequently seen angiographically between ten and 17 days. During this period vasospasm was seen in 49.1% of 116 cases. In those cases with a subarachnoid hemorrhage one to 17 days before the last one, vasospasm within three days after the last hemorrhage was seen in 38.7% of 62 cases. During the period between ten and 17 days after the last hemorrhage, vasospasm was seen in only 20% of 25 cases. The preceding subarachnoid hemorrhage, which had occurred between one and 17 days before the last hemorrhage, seemed to be responsible for the high rate of vasospasm within three days after the last hemorrhage, and the low rate of vasospasm in the period between ten and 17 days after the last hemorrhage.

Afferent artery and the site of neck of anterior communicating aneurysms.

The relationship between the afferent artery and the site of aneurysmal neck and hemodynamics in the anterior part of the circle of Willis was investigated from surgical and angiographic findings in 213 patients with anterior communicating artery aneurysms. An afferent artery was limited to the dominant A1 in about 95% of them. The neck of an aneurysm was more than three times greater at the bifurcation of the dominant A1 and the anterior communicating artery than at the bifurcation of the non-dominant A1 and the anterior communicating artery.

Cervical spinal epidural abscess following acupuncture: successful treatment with antibiotics.

A 67-year-old man with poorly controlled diabetes mellitus (DM) had acupuncture several times a month for chronic shoulder muscle stiffness. A few days after acupuncture in the posterior nuchal region, a low-grade fever and backache developed, and subacutely progressed. Finally he complained of gait disturbance, and then respiratory distress appeared. Magnetic resonance imaging (MRI) demonstrated high cervical epidural abscess with massive soft tissue inflammation and vertebral osteomyelitis. Conservative treatment with antibiotics was effective and it was well documented by following serial MRIs. This case suggested that needle acupuncture should be avoided for immunocompromised subjects such as patients with poorly controlled DM.

Bilateral paramedian thalamo-midbrain infarction showing electroencephalographic alpha activity.

A 57-year-old man became unresponsive and mute with bilateral ophthalmoplegia and quadriplegia. Magnetic resonance imaging (MRI) showed bilateral infarctions at the ventral midbrain and the dorsomedial nucleus of the thalamus. Serial studies with MR and vertebral angiography disclosed hypoperfusion and spontaneous reperfusion of the bilateral posterior cerebral arteries at their origin from the basilar artery. Electroencephalographically, a posteriorly distributed alpha rhythm was clearly recorded and it was reactive in response to external stimuli. The findings seen in the present patient suggest that the ventral midbrain and medial dorsal thalamus are not necessary to produce posterior electroencephalographic alpha activity.

Development of severe longitudinal atrophy of thoracic spinal cord following lupus-related myelitis.

A 26-year-old woman suffered from acute myelitis at Th 6 level associated with systemic lupus erythematosus. Methyl-prednisolone pulse therapy, intravenous high-dose immunoglobulin administration and plasmapheresis were not effective. Her neurological signs had persisted in spite of subsequent administration of oral prednisolone and azathiopurine. Magnetic resonance imaging (MRI) of spinal cord at the onset showed a marked swelling with intramedullary high intensity signals on T2WI along the whole thoracic cord. Three years later, MRI demonstrated a severe longitudinal and segmental atrophy of the mid to low thoracic cord which resulted in transverse spinal signs.

A case of varicella complicated by cellulitis and scarlet fever due to Streptococcus pyogenes.

We report a 4-year-old boy with cellulitis and scarlet fever due to streptococcal infection following the onset of varicella. He developed a painful ulcer and subcutaneous induration on the left shoulder and a small, light-red-colored rash on the trunk at approximately the same time as the development of vesicles over the entire body. Streptococcus pyrogenes was isolated from samples from the posterior intranasal space and the ulcer on the shoulder. The clinical symptoms improved with the administration of antibiotics and intravenous drip infusion, but it took approximately one month from the first visit for the subcutaneous induration to disappear and the ulcer to heal with epithelialization. The complication of secondary streptococcal infection in varicella is relatively rare in Japan, but in Western countries there have been many reported cases of life-threatening necrotizing fasciitis and necrotizing pyomyositis due to secondary streptococcal infection following varicella. Close attention should be paid to streptococcal infection as a complication of varicella.

A case of dermatomyositis associated with mechanic's hand.

A 67-year-old man was referred to the Department of Internal Medicine at Tokyo Medical University with interstitial pneumonia in July 1999. He presented with keratotic plaques on both palsm and on the ventral and lateral sides of his fingers. Erythematous keratosis was observed on the dosal aspect of his fingers and metatarsophalangeal (MP) joints. Edematous erythema was seen on the patient's chest, back, and the extensor surfaces of his arms. Electromyography revealed a myogenic pattern and an increased level of myogenic enzymes was found in the blood. Histological findings of the ventral sides of his fingers showed hyperkeratosis and parakeratosis of the dermal tissue and liquefaction degeneration of the basal layer at the papilla. Based on these findings, the patient was given a diagnosis of dermatomyositis associated with mechanic's hand. A systemic examination confirmed interstitial pneumonia and carcinoma of the duodenal papilla. Mechanic's hand is a type of dermatitis associated with myopathy first reported by Stahl et al. in patients with collagen disease. We report herein the first documented case of mechanic's hand in Asians.

The spontaneous LH surge in ovarian hyperstimulation for assisted reproductive technology.

Thirty-seven patients who underwent assisted reproductive technology programme, in vitro fertilisation or embryo transfer and gamete intra-fallopian transfer, were randomised into two groups in order to evaluate frequency of premature spontaneous LH surge when stimulated with different type of hMG. An hMG (FSH:LH = 1:1) was administered for eighteen patients (group A) and the different highly purified hMG (FSH:LH = 19:1) was administered for nineteen patients (group B). Blood samples are drawn from day 3 of the cycle until hCG administration, and serum LH level are measured in the frozen samples. There were no statistical difference in the total amount of hMG used before hCG injection, days of hMG injection and the number of oocytes retrieved between two groups. The premature spontaneous LH surge occurred only one patient in group A (5.6%), but more frequent LH surge was observed in group B (42.1%) (p < 0.05). It is suggested that the different FSH/LH ratio may be the reason for the difference of the incidence of premature spontaneous LH surge.

[A case of hemiballism successfully treated by sulpiride, caused by lesions of the striatum].

A case of hemiballism caused by infarction in the left striatum on MRI was reported. Hemiballism is generally associated with lesions in the subthalamic nucleus. However, hemiballism occasionally occurs as a result of lesions outside the subthalamic nucleus. Hemiballism is a benign condition with spontaneous recovery in most cases, but hemiballism caused by lesions outside the subthalamic nucleus is reported to tend to persist for a long term. In our case without involvement of the subthalamic nucleus, hemiballism so far continued for three months since the onset. Successful pharmacological treatments of ballism with haloperidol or phenothiazines were well known. In our case, the treatments of ballism with these drugs were unsuccessful due to drug-induced hepatic dysfunction. Instead of these drugs, ballism was improved by administration of 150 mg of sulpiride per day with no side effects. Sulpiride may be beneficial for persistent hemiballism caused by the extra subthalamic lesions.