Shoshi Takamoto

Alterations of bone mineral density of the femurs in hemiplegia

We evaluated the bone mineral density (BMD) of the bilateral femurs in 112 patients with hemiplegia using dual-energy X-ray absorptiometry in order to elucidate the effect of disuse and immobilization. BMD of the paretic side was significantly reduced compared with that of the nonparetic side in hemiplegic patients (femoral neck 0.582±0.014 g/cm2 versus 0.623±0.014 g/cm2 and total femur 0.645±0.02 g/cm2 versus 0.702±0.017 g/cm2; mean±SEM, P<0.01, respectively). Femoral BMD in both the paretic and nonparetic limb had significantly (P<0.01) lower values than in age- and sex-matched controls, but the paretic side had a more significant reduction of BMD; femoral neck-20% versus -14% and total femur -24% versus -18%. In addition, patients with impaired activities of daily living (ADL), evaluated by a mobility score, had significantly decreased BMD ratios of paretic/nonparetic side than patients with improved ADL (femoral neck 91% versus 97%, P<0.01 and total femur 89% versus 94%, P<0.05). Our results indicated that BMD of both femurs of patients with hemiplegia was reduced, although the paretic side showed a greater BMD decrease. This decrease might be prevented or reduced by improvement of ADL.

Effect of 1α-hydroxycholecalciferol on psoriasis vulgaris: a pilot study

SummaryWe carried out a clinical trial of 1α-hydroxycholecalciferol [1α(OH)D3] at a dose of 1.0 μg a day on 7 patients with psoriasis vulgaris. These patients had been treated by topical applications of corticosteroids before this study without improvement, and during the clinical trial, treatment of topical corticosteroids was continued on 6 of the 7 patients. Four of 7 patients showed complete remission and marked improvement and 2 additional patients showed minimal improvement of their skin lesions during and after the treatment with 1α(OH)D3. No adverse reactions were noted during the treatment period. The mechanism of the phenomenon we observed has yet to be elucidated. Controlled trials of large numbers of patients with psoriasis vulgaris treated with 1α(OH)D3 are under way.

Endothelin-1 in cerebrospinal fluid in elderly patients with hypertension and dementia.

Endothelin-1, a potent endothelium-derived vasoconstrictive peptide, is also known to exist in the central nervous system. We determined endothelin-1-like immunoreactivity in cerebrospinal fluid by a radioimmunoassay in 32 normotensive or hypertensive elderly subjects (79 +/- 8 years old) with or without multi-infarction dementia. The mean value of endothelin-1-like immunoreactivity in cerebrospinal fluid was significantly (P < .05) elevated in subjects with essential hypertension (> or = 160/95 mm Hg, n = 5, 79 +/- 9 years old) compared with those with borderline hypertension (140-159/90-94 mm Hg, n = 4, 78 +/- 5 years old) and normotensive subjects (< 140/90 mm Hg, n = 23, 79 +/- 8 years old). The value of endothelin-1-like immunoreactivity in cerebrospinal fluid was significantly (P < .05) positively correlated with both systolic (r = .38) and diastolic (r = .42) blood pressures in all subjects. On the other hand, mean values of endothelin-1-like immunoreactivity in cerebrospinal fluid were also significantly (P < .05) elevated in the groups of patients with multi-infarction dementia that had profoundly decreased Mini-Mental State scores (< or = 10, n = 6) and moderately decreased Mini-Mental State scores (11 to 20, n = 14) compared with those values in subjects with normal cognitive function (score for Mini-Mental State > or = 21, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ipriflavone on bone mineral density and calcium-related factors in elderly females

SummaryThe effects of ipriflavone (7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one) on bone mineral density (BMD) of the 3rd lumbar vertebra and on calcium (Ca)-related factors, including serum calcitonin (CT) levels before and after rapid calcium infusion (4 mg/kg for 5 minutes), were studied in 11 elderly female subjects (80 ± 2 years of age, mean ± SE). Ipriflavone (IP) administration (600 mg/day, 7 months) resulted in inhibition of BMD loss in 7 patients (responders, mean change of BMD value 2.2 ± 2.3%), whereas 4 patients showed a loss of BMD (nonresponders, mean change of BMD value -13.1 ± 2.6%) compared with pretreatment values. The responder group showed a significant increase in mean pretreatment serum CT levels (from 20 ± 2 pg/ml to 42 ± 7 pg/ml,P < 0.05) after treatment with IP, and a significant decrease in the mean basal serum level of corrected Ca (from 9.6 ± 0.2 mg/dl to 8.7 ± 0.1 mg/dl,P < 0.01) after treatment with IP; nonresponders did not show these changes. For responders, both the percentage of change and the maximal value of serum CT in response to Ca infusion were maintained at rather high levels, both before and after IP treatment; nonresponders showed almost no response to a stimulation test for CT. These findings suggest that IP inhibits bone loss in elderly female subjects possibly through the mechanism of increasing CT secretion.

Effects of 1, 25-dihydroxyvitamin D3 on the synthesis of DNA and glycosaminoglycans by rat aortic smooth muscle cells in vitro

Abstract Studies were made on the effects of 1, 25-dihydroxyvitamin D 3 [1, 25-(OH) 2 D 3 ] on the syntheses of DNA and glycosaminoglycans (GAG) by rat aortic smooth muscle cells (SMC) in vitro . DNA synthesis in cell cultures without fetal calf serum (FCS) was stimulated by incubation for 24 hr with 1, 25-(OH) 2 D 3 at concentrations of more than 10 −12 M, stimulation being maximal at a concentration of 10 −8 M. On the other hand, GAG synthesis was inhibited dose-dependently by 1, 25-(OH) 2 D 3 at concentrations of more than 10 −11 M. Other vitamin D 3 metabolites had similar, but weaker effects on the syntheses of DNA and GAG by SMC, which were proportional to their affinities for the 1, 25-(OH) 2 D 3 receptor. These effects of 1, 25-(OH) 2 D 3 were not seen after short-term incubation (1 hr). These findings suggested that 1, 25-(OH) 2 D 3 stimulated the proliferation of SMC independent of growth factors in FCS, and that its effects were dependent on its specific receptor. Excess 1, 25-(OH) 2 D 3 might cause arteriosclerosis not only by stimulating proliferation but also by suppressing GAG synthesis.

Serum phosphate, parathyroid hormone and vitamin D metabolites in patients with chronic renal failure: effect of aluminum hydroxide administration.

Patients with chronic renal failure showed the existence of phosphate retention, secondary hyperparathyroidism, and reduced production of 1,25-(OH)2D. In order to determine the effect of correction of hyperphosphatemia on secondary hyperparathyroidism and vitamin D metabolism in those patients, 7 nondialyzed patients with chronic renal failure were treated with large doses of A1(OH)3 (15-18 g/day) to correct their high levels of serum phosphate. After treatment with A1(OH)3, serum phosphate fell significantly (p less than 0.005) from 6.3 +/- 1.3 (mean +/- SD) to 3.7 +/- 0.5 mg/dl. Serum parathyroid hormone decreased significantly (p less than 0.02) from 2.87 +/- 1.64 to 1.85 +/- 1.26 ngEq/ml. Serum 1,25-(OH)2D was low compared to the normal mean level before A1(OH)3 administration and decreased significantly (p greater than 0.02) from 19.4 +/- 6.1 to 11.4 +/- 4.3 pg/ml after the treatment. Aluminum levels increased significantly (p greater than 0.02) from 1.7 +/- 1.0 to 3.6 +/- 1.5 micrograms/dl. Serum calcium, calcitonin, and 25-(OH)D showed no significant change. Our data suggested that the suppression of secondary hyperparathyroidism by A1(OH)3 treatment results in a decrease of the 1,25-(OH)2D level in patients with chronic renal failure, even though their hyperphosphatemia has been corrected. We speculate that aluminum loading might play a role in diminishing the secretion of parathyroid hormone and the production of 1,25-(OH)2D in humans.

SPONTANEOUS FRACTURES OF LONG BONES ASSOCIATED WITH JOINT CONTRACTURES IN BEDRIDDEN ELDERLY INPATIENTS: CLINICAL FEATURES AND OUTCOME

To the editor: It was recently reported that influenza A was cultured in 62 double rooms at the Wisconsin Veterans Home over six seasons. The roommate was infected in 12 (19.4%). During 3,294 resident-seasons, influenza was cultured in 208 single rooms (6.3%). Those who lived in double rooms with a culture-positive roommate had a 3.07 relative risk (95% confidence interval 5 1.61–5.78) of acquiring influenza A. Identical methodology was used to analyze the 1992/ 1993 influenza season, in which influenza B was encountered. Case finding was based on intense prospective surveillance by research staff and has been previously described. This study compared the relative risk of influenza B in residents whose roommate had a positive culture with that of those who resided in single rooms. It is possible that a second infected roommate became infected outside of the room. To control for this possibility, the number of single rooms and the number of cases in single rooms each year were determined for comparison. Influenza B was introduced to 29 double rooms. A second culture-confirmed case was noted in 10 (34%). The second cases occurred 0 to 11 days (mean 3.9 days) after the initial case. Seven of these second cases had been vaccinated (70%). Overall, 85% of residents were vaccinated. During 489 resident-seasons in single rooms, influenza was cultured in 65 rooms (13%). Those who lived in a double room with a culture-positive roommate had a relative risk of 2.6 (95% CI 5 1.2–5.6) of acquiring influenza B compared to those who resided in single rooms As expected, the data confirm a greater relative risk of acquiring influenza B in roommates of residents with influenza B than in residents who did not have roommates. The excess risk associated with having a culture-positive roommate is troublesome because it has been demonstrated that culture-confirmed influenza B was associated with an excess 30-day mortality of 3.9% over baseline mortality (1.5%/30 days) in nursing home residents. A private room is optimal, but this is not possible in most nursing homes. Other interventions might include using any curtain or barrier that may exist between roommates. The roommates should be counseled to maintain hand hygiene and 3-foot separation with extra environmental hygiene provided by staff. The unaffected roommate should probably be offered chemoprophylaxis with a neuraminidase inhibitor, even if the entire unit is not placed on chemoprophylaxis.

Comparison of renal responses to synthetic human PTH(1-34) administration in normal young and elderly male subjects

SummaryA parathyroid hormone (PTH) loading test with synthetic human PTH(1–34) was performed in 7 young and 6 elderly normal males. The elderly subjects had significantly higher mean basal levels of serum PTH than the young subjects (0.262±0.035(SE) vs 0.097±0.012 ng Eq/ml,P<0.001). When human PTH(1–34) at a dose of 100 U was administered to these subjects, the mean increases in urinary excretions of adenosine cyclic 3′, 5′-monophosphate(cAMP) and inorganic phosphorus (Pi), expressed as increases in absolute amounts per unit time, were significantly lower in the elderly subjects. (3.65±1.02 vs 7.41±1.05 μmol/h,P<0.05 for cAMP and 14.7±6.3 vs 41.8±8.6 mg/2h,P<0.05 for Pi) and an inverse correlation was found between the serum PTH levels and the increases in urinary cAMP excretion (μmol/hr; r=−0.63,P<0.05). However, when corrected for the glomerular filtration rate (GFR) and the units of PTH administered per kg body weight, the increases were not significantly different in the two groups (elderly 52.1±7.5 vs young 60.0±19.2 nmol·kg/100 ml GFR·U·h for cAMP and 0.315±0.061 vs 0.186±0.044 mg·kg/100 ml GFR·U·2 h respectively for Pi). These results indicated that the decreased response of the kidney to PTH in elderly subjects can be explained mainly by the decreased functional mass of the kidney, possibly with some contribution of down-regulation of PTH receptors owing to increase in the blood level of endogenous PTH in elderly subjects. Further investigations are needed to ascertain why there was decreased response of the kidney to PTH in elderly people.

Effects of valinomycin on calcium mobilization in vascular smooth muscle cells induced by angiotensin II

The effect of the specific potassium (K+) ionophore valinomycin on increase in intracellular calcium concentration [( Ca2+]i) was studied in vascular smooth muscle cells (VSMC). Valinomycin at more than 10(-9) M dose-dependently suppressed phasic increase in [Ca2+]i in VSMC induced by angiotensin II (AII) in both control and Ca2+-free solution, indicating that it suppressed the release of Ca2+ from intracellular Ca2+ stores. Nicorandil and cromakalim, which are both K+ channel openers, also suppressed the increases in [Ca2+]i induced by AII in the Ca2+ free solution. However, valinomycin did not suppress AII-induced production of inositol 1,4,5-trisphosphate (IP3), which is known to mediate the release of Ca2+. These results indicate that decrease of intracellular K+ induced by valinomycin suppressed the release of Ca2+ from intracellular Ca2+ stores induced by IP3.

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.