Use of a temporary caval filter in a young man with pulmonary embolism to prevent migration of massive caval thrombus during an attempt of caval thrombolysis.

A 33 year old male with no known risk factors for hypercoagulability developed a massive thrombi in the inferior vena cava (IVC). The patient had a history of both pulmonary embolism and embolism related syncope. The thrombus which extended proximally to the level of the renal vein and distally to the left superficial femoral vein did not respond to anticoagulant therapy or thrombolysis. Thirteen days after admission, we decided to use a temporary caval filter to provide protection from migration of the thrombus while attempting invasive thrombolytic therapy, which was performed using a tissue type plasminogen activator through a coaxial catheter of the temporary filter. This resulted in a marked decrease in the size of the thrombus, and multiple thrombi were found to be trapped in the temporary filter. Although the temporary caval filter was effective in capturing emboli, resulting in a decrease in the thrombus size, the thrombus was not completely dissolved within two weeks, which is the maximal implantation time. A permanent filter was eventually used to prevent pulmonary embolism, which could arise from the remaining thrombus. We have found placement of a temporary caval filter to be a safe and effective adjunct, in select cases, when attempting thrombolysis of massive thrombi in the IVC. Since we inserted the temporary filter 13 days after admission, use of a temporary filter during thrombolysis may have been more effective if conducted earlier in our patient's clinical course.

[An analysis of questionnaires about geriatric medicine/medical education sent to members of the Japanese Society of General Medicine].

Geriatric medical care can be viewed as general medical care for the elderly. We conducted a survey of members of the Japanese Society of General Medicine who belong to a university hospital, on their views of geriatric medicine/medical education. The questionnaires consisted of six categories of items about: (1) the physician's career; (2) whether the physician performs geriatric research in his/her laboratory; (3) whether the physician has an interest in geriatric medicine or medical education; (4) the physician's views on geriatric medicine or medical education; (5) of what pre- and post-graduate medical education on geriatric medicine should consist, from the physician's point of view: and (6) the physician's ideas about geriatric medicine/medical education in view of general medicine. Out of the 181 questionnaires sent, 96 (53%) people replied, of whom 51 (53.1%) were members of a Department of General Medicine, 57 (60%) were teaching staff, 46 (48.4%) had experience in home medical care such as home visits, and 17 (18.1%) belonged to the Japanese Society of Geriatric Medicine. Seventy-six respondents (85.4%) had an interest in geriatric medicine/medical education. Of the respondents, 96.8% recognized the need for pre- and post-graduate medical education concerning geriatrics. Some members of the Japanese Society of General Medicine who answered the questionnaire see geriatric medicine as entirely general medicine, and also that geriatric medicine is important, necessary and special. In addition, they see that the field of geriatric medicine is not yet developed in regard to geriatric medical care and education. Most respondents could not specify which section in a medical university is responsible for teaching the fields of basic and social medicine. This result shows that it may be difficult to incorporate pre-graduate geriatric medical education into the curriculum. As part of the pre-graduate curriculum of medical education on geriatrics, a practical exercise such as inspection of a geriatric hospital and geriatric home was considered most desirable by the respondents. Out of nine items, the top three most important aspects of post-graduate medical education on geriatrics for clinical and social medicine, were (1) studying the medical care and welfare of the elderly, (2) assessing the impaired life function of the elderly, and (3) studying pharmaco- therapy. Out of 6 items, the top three most important aspects of a practical exercise in post-graduate medical education in geriatrics were (1) providing general care to the elderly, (2) giving rehabilitation guidance and (3) providing psychological support for the elderly. Furthermore, 20 of the respondents (22.5%) have performed geriatric medical research on either the activities of daily life of the elderly or living wills, both of which seem to reflect the health and life of elderly people.

[A case of polymyalgia rheumatica with swelling and pitting edema of the distal lower extremities].

We report a case of an 82-year-old woman with polymyalgia rheumatica (PMR) associated with swelling and pitting edema of the lower extremities. The patient had been previously admitted because of PMR in 1990, but there was no history of swollen extremities. In July 1996, at another hospital, she was again diagnosed as having PMR on the basis of pain in the neck, shoulders and lower back. Administration of prednisolone was followed by improvement of the symptoms. Four months later, similar pain recurred and swelling of the lower extremities was noted. On admission, the erythrocyte sedimentation rate was 86 mm/h, and C-reactive protein was 15.5 mg/dl. Reviewing the previous treatment, it was ascertained that her clinical deterioration was due to premature reduction of the steroid dosage. The cause of the swelling of the lower extremities was unlikely to be heart, liver, kidney or endocrine disease. Prednisolone was increased from 2.5 mg to 10 mg daily with marked improvement in all the symptoms including the swelling and pitting edema. In 1996, a study reported distal extremity swelling with pitting edema as a manifestation of PMR, which mostly developed concurrently with proximal symptoms or during relapses of PMR. The swelling responded poorly to non-steroidal antiinflammatory drugs but promptly to corticosteroids. The distal swelling was reported to be tenosynovitis and synovitis of the surrounding structures. The present case appears similar to that report. More studies of PMR need to be done.

Alterations in mRNA expression of duodenal 1,25-dihydroxyvitamin D3 receptor and vitamin D-dependent calcium binding protein in aged Wistar rats.

Previously, we reported that uptake of calcium into isolated duodenal cells and duodenal brush border membrane vesicles decreased in senescence. Decreases in duodenal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptor number and 9k vitamin D-dependent calcium binding protein (CaBP) were also observed in aged rats. In this study, we examined the steady state mRNA levels of duodenal 1,25-(OH)2D3 receptor and CaBP in both adult (6-month-old) and old (24-month-old) rats. We identified one major band of 4.4 kb for 1,25-(OH)2D3 receptor mRNA. The size of the transcript was not affected by age. The content of 1,25-(OH)2D3 receptor mRNA (normalized with poly(A)+RNA) decreased 23% in the aged rat as compared to the adult rat. The expression of CaBP was also examined. A single band of 0.6 kb was observed for CaBP mRNA. The size of CaBP mRNA was not altered with age. However, the abundance of CaBP mRNA (normalized with poly(A)+RNA) was reduced 20% in the senescent rat. Thus, the results in the present study were consistent with our previous findings that the number of 1,25-(OH)2D3 receptors and the level of CaBP declined in the aged rat. However, the precise mechanism leading to the age-related deficit in mRNA expression remains to be elucidated.

Participation of decreased serum cholesteryl ester transfer activity, independent of increased serum lipoprotein(a), in angina pectoris in normolipemic elderly subjects.

The cholesteryl ester transfer activity (CETA) is a measurement of the transfer of cholesteryl ester from HDL to VLDL, LDL or peripheral cells. Its role in the development of early coronary heart disease is not clear. In the present study, serum levels of CETA, lipoprotein(a) [Lp(a)] and other lipid-related factors were compared in 10 normal young subjects, 28 healthy elderly subjects and 14 normolipemic elderly patients with angina pectoris. Compared to the young normals and healthy elderly subjects, the elderly patients with angina pectoris showed significantly decreased mean serum CETA levels, and significantly increased mean serum levels of Lp(a) and apoprotein B. These results may indicate that decreased serum values of CETA participate in the development of angina pectoris in normolipemic elderly patients.

[Presence of circulating suppressive factor for muscarinic acetylcholine receptor in senile dementia].

Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acetylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acetylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean +/- SD age of 77.5 +/- 8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic-subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (3H-QNB), an antagonist for muscarinic acetylcholine receptor, to the rat synaptic membrane, was 18.1 +/- 7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7 +/- 3.8%). However, that in the VD group (8.4 +/- 6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on 3H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r = 0.480, p less than 0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT.

Initial appearance of an ill-defined shadow on a chest roentgenogram in a patient with aortitis syndrome.

A 20-years-old woman with fever and an abnormal shadow on a chest roentgenogram was admitted to our hospital. High grade fever continued even after gradual disappearance of the ill-defined shadow on the right upper lobe (S3) with minor fissure deviation upward, while neck pain and bruit gradually developed. She was diagnosed as aortitis syndrome from a digital subtraction angiography. The initial appearance of an ill-defined shadow on a chest roentgenogram, considered as pulmonary infarction, is rare in the aortitis syndrome and this kind of onset is interesting in relation to the pathogenesis and diagnosis of this syndrome.

[Cognitive function and calcium-related factors in elderly female subjects].

Calcium (Ca)-related factors were evaluated as possible related factors to senile dementia in 60 elderly female subjects (mean age +/- SD: 79 +/- 7 years). These subjects were classified by their score on Hasegawa's Dementia Screening Scale, into a non-dementia group (score 22-32.5, n = 18) and a dementia group (0-21.5, n = 42), and the latter group was further classified by ischemic score into Alzheimer-type dementia (n = 22) and vascular-type dementia (n = 20). There was no significant difference in the mean values of age or serum creatinine among the three groups. In the Alzheimer-type dementia group, the mean serum level of Ca was significantly lower, and the serum level of parathyroid hormone (PTH) and urinary Ca were significantly higher than those in the non-dementia group, respectively. In the group of vascular-type dementia, the mean serum level of calcitonin (CT) was slightly, but not significantly, lower than that in the non-dementia group. The score for cognitive subjects negatively correlated significantly with the values of serum PTH (r = -0.49, p less than 0.05) and urinary Ca excretion (r = -0.38, p less than 0.05), respectively, and positively correlated significantly with that of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] (r = 0.31, p less than 0.05), in the combined group of non-dementia and Alzheimer-type dementia, and positively correlated significantly with the serum CT level (r = 0.40, p less than 0.05) in the combined group of non-dementia and vascular-type dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracellular signal transduction evoked by low-density lipoprotein in vascular smooth muscle cells.

Low-density lipoprotein (LDL) is a well-known causal factor in the development of arteriosclerosis. In the present study, we evaluated LDL-evoked cellular signal transduction in cultured rat vascular smooth muscle cells (VSMC). The addition of LDL at concentrations of more than 50 ng/ml, and apolipoprotein B (Apo-B) at more than 5 ng/ml, induced rapid but transient increases in the inositol 1,4,5-trisphosphate (InsP3) level, and caused rapid phasic and subsequent tonic increases in cytosolic free Ca2+ concentration [( Ca2+]i) in a dose-dependent manner in VSMC. LDL and Apo-B also caused transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of a Na+/H+ exchanger. The enhancement of thymidine incorporation induced by the addition of LDL correlated well with the degree of increment of [Ca2+]i increases by the lipoprotein. These results suggest that an increase in [Ca2+]i mediated by InsP3 and intracellular alkalization may function as an important signal for enhanced DNA synthesis induced by LDL in VSMC.

Exaggerated natri-calci-uresis and increased circulating levels of parathyroid hormone and 1,25-dihydroxyvitamin D in patients with senile hypertension.

Renal handling of Na and Ca in response to physiological saline infusion (20 ml/kg i.v. for 2 h) was compared between 27 hypertensive (mean +/- SD age 79.8 +/- 9.2 years) and 44 normotensive (79.1 +/- 4.1 years) senile females. Compared to the normotensive group, the hypertensive group showed statistically significant decreases in the basal values of serum Ca and PRA, and significant increases in basal circulating levels of parathyroid hormone and 1,25(OH)2D and in urinary excretions of Na, Ca and Pi in the 2-hour urine specimens during the saline infusion. These results suggest that the excessive excretions of Ca and Pi associated with exaggerated natriuresis may participate in aberration of Ca metabolism in low-renin hypertensive seniles.

Interleukin-6 stimulates proliferation of cultured vascular smooth muscle cells independently of interleukin-1 beta.

The effects of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) on proliferation of cultured vascular smooth muscle cells (VSMCs) were investigated. Treatment with IL-6 caused a rapid increase in the c-myc mRNA level, and resulted in increases in DNA synthesis and cell number. IL-1 beta stimulated the DNA synthesis of the cells. EGF showed synergistic and PDGF or IL-1 beta showed additive effects with IL-6 on the DNA synthesis. These results suggest that IL-6, independently of IL-1 beta, may be important in the proliferation of VSMCs.

Effect of elastase in reversing the de-differentiation of rabbit costal chondrocytes in culture induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA).

As elastase is known to affect cell functions in various cell systems, its effects on the functions of control and 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated chondrocytes in vitro were examined. Pretreatment of chondrocytes with TPA (10(-8) M) for 48 h significantly enhanced DNA synthesis, inhibited glycosaminoglycan (GAG) synthesis and inhibited the increase in ornithine decarboxylase (ODC) activity in response to parathyroid hormone (PTH) relative to values in control cultures. Addition of elastase (1, 10 and 50 ng/ml) for 24 h partially inhibited the de-differentiated phenotypes induced by TPA such as the decreased synthesis of GAG and decreased response of ODC activity to PTH without affecting the DNA synthesis. Moreover, elastase significantly increased both the basal level of cyclic AMP and that on PTH treatment of TPA-pretreated cells. These results suggested that elastase partially restored the differentiated phenotypes of de-differentiated chondrocytes probably through its effect in increasing the level of intracellular cyclic AMP.

Nicorandil is a potent dilator of endothelin-induced vascular contraction.

Nicorandil, an antianginal drug, is known to open K+ channel and to increase cGMP production. The effects of nicorandil on vascular contraction induced by endothelin (ET), a potent newly discovered vasoconstrictor peptide, were investigated using helical strips from rat thoracic aorta. ET at a concentration of 5 x 10(-9) M induced strong and persistent contraction in the presence of extracellular Ca2+ and similar persistent but smaller contraction in the absence of extracellular Ca2+. Nicorandil at concentrations greater than 10(-7) M, strongly and dose-dependently inhibited ET-induced contraction in the presence of extracellular Ca2+. Nicorandil also suppressed ET-induced contraction in the presence of 10(-4) M methylene blue, an inhibitor of cGMP production, in the presence of extracellular Ca2+ but not in the absence of extracellular Ca2+. ET-induced contraction was also inhibited to lesser extents by the Ca2+ channel blockers nicardipine and verapamil. Nicorandil also strongly suppressed ET-induced increase in cytosolic free Ca2+ concentration in cultured vascular smooth muscle cells. These results suggest that nicorandil is a potent dilator of ET-induced vasoconstriction.

Stimulatory effect of 1,25-dihydroxyvitamin D3 on transferrin synthesis in primary cultures of adult rat hepatocytes.

The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on protein synthesis was studied in primary cultures of adult rat hepatocytes, in comparison with those of dexamethasone (DEX). The transferrin (TF) level in the culture medium assayed by a radioimmunoassay (RIA), after incubation for 24 hr was increased in the presence of 1,25-(OH)2D3, significantly at concentrations of more than 10(-12) M and maximally to about 140% of that in control cultures at 10(-8) M, without change in the albumin concentrations, assayed by an EIA. Other vitamin D3 metabolites had similar but weaker effects in increasing transferrin synthesis. On the other hand, incubation with 10(-6) M Dex for 24 hr enhanced the syntheses of both transferrin and albumin. Addition of 10(-7) M actinomycin D did not significantly block the effect of 1,25-(OH)2D3, but did suppress that of dexamethasone. These results indicate that 1,25-(OH)2D3 stimulates TF synthesis of cultured rat hepatocytes with different mechanism(s) of action from that of dexamethasone.

Inverse relation between severity of psoriasis and serum 1,25-dihydroxy-vitamin D level.

The serum levels of calcium, inorganic phosphate, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 34 patients with psoriasis vulgaris and compared with the severity of skin lesions. Severity of psoriasis was evaluated by three indices, the area-severity index (ASI), the area index (AI) and the severity index (SI), determined as the product of the area and severity, the area, and the severity of the individual skin lesions, respectively. The mean basal levels of these serum parameters were within the normal range. ASI and SI showed significant inverse correlations (r = -0.387, P less than 0.05 and r = -0.638, P less than 0.01, respectively) with the serum level of 1,25-dihydroxyvitamin D, but not with any other serum parameters, but AI was not correlated with any of these serum parameters. These data suggest that psoriatic patients are not deficient in 1,25-dihydroxyvitamin D, but that development of this skin disease may be related to a slightly decreased level of active metabolites of vitamin D or abnormalities in the responsiveness of the skin cells to them.

Participation of both intracellular free Ca2+ and protein kinase C in tonic vasoconstriction induced by prostaglandin F2 alpha.

The roles of intracellular free Ca2+ and protein kinase C in the tonic contraction induced by prostaglandin were studied. Prostaglandin F2 alpha induced tonic contraction of rat thoracic aorta in both control and Ca2(+)-free solution. Close correlations were observed between the contractile response of aortic strips and the changes in intracellular free Ca2+ concentration in vascular smooth muscle cells assessed with the fluorescent Ca2+ indicator fura 2, both in control and Ca2(+)-free solutions. Prostaglandin F2 alpha also enhanced the production of inositol 1,4,5-trisphosphate in vascular smooth muscle cells before the rise of the intracellular free Ca2+ concentration. Moreover, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, inhibited the tonic contractions induced by PGF2 alpha and 12-O-tetradecanoyl phorbol-13-acetate, a direct activator of protein kinase C, at similar concentrations. These results suggest that both intracellular free Ca2+ and protein kinase C participate in prostaglandin F2 alpha-induced tonic contraction.

Comparison of the production of cyclic AMP in response to parathyroid hormone in fibroblasts from aged subjects and young subjects: lack of an age-dependent decrease.

An age-dependent effect on the ability to produce cyclic AMP in response to parathyroid hormone (PTH) stimulation was examined using culture skin fibroblasts from both young and elderly female subjects. The mean values of both absolute and comparative production of intracellular cyclic AMP due to various concentrations of PTH administration did not differ between the two age groups, although the mean serum PTH level was significantly higher in the elderly subjects. These results indicate that the decreased response of the target organ to PTH in aged subjects can be explained mainly by the decreased number of intact cells rather than a decreased response of individual cells to PTH.

Comparison of the inhibitions of proliferation of normal and psoriatic fibroblasts by 1 alpha,25-dihydroxyvitamin D3 and synthetic analogues of vitamin D3 with an oxygen atom in their side chain.

The inhibitory effects of 1 alpha,25-(OH)2D3 and synthetic oxa-derivatives of vitamin D3 on growth of normal and psoriatic fibroblasts in culture were compared. Proliferation of normal fibroblasts was strongly inhibited by these new compounds in the following order: 22-oxa-1 alpha,25-(OH)2D3 greater than 22-oxa-1 alpha-(OH)D3 greater than 1 alpha,25-(OH)2D3 greater than 20-oxa-1 alpha,25-(OH)2D3. 22-Oxa-1 alpha,25-(OH)2D3 was about 10-times more inhibitory than 1 alpha,25-(OH)2D3. Proliferation of psoriatic fibroblasts was not inhibited by 1 alpha,25-(OH)2D3 at concentrations of up to 10(-6) M, but was suppressed by 10(-8)-10(-6) M 22-oxa-1 alpha,25-(OH)2D3 and 10(-6) M 22-oxa-1 alpha-(OH)D3. These results suggest that oxa-derivatives of vitamin D3, especially 22-oxa-1 alpha,25-(OH)2D3, should be useful in further studies on the cause and treatment of psoriasis.

Clinical evaluation of hypokalemia in anorexia nervosa.

The serum and urinary levels of electrolytes were measured in 25 patients with anorexia nervosa admitted to this hospital. Seven (28%) of these patients vomited, usually surreptitiously. Hypokalemia was detected in 5 (20%) of these patients, all among those who vomited. The urinary chloride/sodium ratios were low in the patients who vomited, and did not overlap the values in patients who did not vomit, indicating that this ratio was a good indication of vomiting. These results suggested that stopping vomiting is most important for correcting hypokalemia.

[Comparison of hypotensive effects of acutely administered human parathyroid hormone (1-34) in normal young and elderly subjects].

The effects of acute administration of human parathyroid hormone (1-34) [PTH(1-34)] on the blood pressure of 15 young (mean age +/- SD, 20.9 +/- 1.7 years; 7 males and 8 females) and 11 elderly (78.1 +/- 5.9 years; 4 males and 7 females) normal subjects were compared. The elderly subjects have a slightly, but significantly higher mean basal systolic blood pressure (132.4 +/- 17.7 mmHg) than the young subjects (118.7 +/- 11.4 mmHg), but the basal diastolic and mean blood pressures of the two groups were similar. Intravenous bolus infusion of PTH(1-34) at a dose of 100 U induced transient, but marked hypotension in all subjects. The mean maximal decrease in systolic blood pressure (-delta SBP was significantly more (p less than 0.01) in the elderly subjects (42.5 +/- 13.9 mmHg) than in the young subjects (8.0 +/- 8.9 mmHg), but the maximal decrease in diastolic blood pressure (-delta DBP) was similar in the elderly (25.6 +/- 13.9 mmHg) and young (27.3 +/- 10.9 mmHg) subjects. The maximal decrease in the mean blood pressure (-delta MBP) was also significantly higher (p less than 0.01) in the elderly subjects (31.9 +/- 8.7 mmHg) than in young ones (20.6 +/- 7.6 mmHg). The corrected serum level of calcium (scCa) was significantly (p less than 0.01) lower in the elderly subjects (9.6 +/- 0.2 mg/dl) than in the young ones (10.0 +/- 0.3 mg/dl), and the serum level of C-terminal parathyroid hormone (C-PTH) was significantly higher in the elderly subjects (270 +/- 80 pg/ml) than in the young ones (150 +/- 80 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)