Toshio Onishi

Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma.

Plasma calcitonin (CT) levels were measured serially in 54 patients surgically treated for medullary thyroid carcinoma. Patients with postoperative basal CT levels higher than 1 ng/ml measured within 1 month after surgery had a higher recurrence rate than those with lower CT levels (p < 0.002). Patients with postoperative basal CT levels higher than 2 ng/ml had a lower survival rate than those with lower CT levels (p < 0.01). However, pre-operative basal CT levels had no significant correlation with life expectancy or recurrence during the present observation period. Serial measurements in 23 patients with elevated postoperative CT levels showed exponential increases in basal CT levels in 19 patients (p < 0.05 in nine patients, 0.05 < p < 0.1 in four patients) and slight decreases in four (p < 0.05 in one patient). Doubling time of CT levels calculated from the regression line in each patient showed the highest correlation with 3-year survival, recurrence within 5 years, and time interval between surgery and clinical recurrence of the tumor, allowing quantitative prediction of the prognosis.

Reduction of risk of pneumonia associated with use of angiotensin I converting enzyme inhibitors in elderly inpatients

Pneumonia is a major direct cause of death in the elderly. Although aspiration based on a reduced cough reflex is one of the causes of pneumonia in the elderly, there are few studies of angiotensin-I converting enzyme inhibitors (ACE inhibitors), which are antihypertensive drugs that induce cough, as a factor influencing the incidence of pneumonia in institutionalized elderly subjects. To assess the effect of ACE inhibitors and dihydropiridine calcium-channel blockers on the incidence of pneumonia, we conducted a hospital-based case-control study. Cases were 55 pneumonia patients aged > or = 65 years during a 1-year period. The controls were elderly subjects, frequency matched to the cases by age and gender (n = 220). Data were collected on known risk factors and on medication for hypertension, consisting of ACE inhibitors, calcium-channel blockers, and nonantihypertensive medication. The significance of differences in risk factors was analyzed using univariate and multivariate comparisons of cases and controls. After adjustment for potential confounding factors, the relative risk estimates for pneumonia were 0.38 (95% confidence interval [CI], 0.15-0.97) and 1.84 (95% CI, 0.89-3.78) for ACE inhibitors and calcium-channel blockers, respectively, relative to nonantihypertensive medication. The preventive effect of ACE inhibitors on pneumonia was apparent in long-acting ACE inhibitor users (0.24; 95% CI, 0.07-0.88). We conclude that ACE inhibitor use is an independent factor reducing risk of pneumonia among elderly inpatients.

The effect of oestrogens on human calcitonin secretion after calcium infusion in elderly female subjects.

The effect of oestrogen administration (4–6 weeks) on the response of human calcitonin (hCT) secretion to 5 min calcium infusions was studied in ten elderly women. There was no significant difference in mean basal plasma hCT levels before and after oestrogen administration. However, the mean increment in plasma hCT in response to calcium infusion (ΔhCT) increased significantly (P < 0·001) from 21·9±6·6 (mean ±SE) before treatment, to 79·6±15·5 ng/l after oestrogen administration. Mean serum calcium levels decreased significantly (P < 0·001) from 2·42 ±0·06 before to 2·19·0±07 mmol/l after oestrogen treatment. Mean plasma immunoreactive PTH (iPTH) levels increased significantly (P < 0·05) from 521·41 before to 696·96 ng/l after oestrogen treatment. To exclude out the possibility that the decreased serum calcium level itself might have influenced ΔhCT, 1α‐hydroxycholecalciferol (1α‐OH‐D3) was administered with oestrogens. While this resulted in a slight increase in serum calcium level, there was no significant difference in ΔhCT in response to calcium infusion following oestrogen treatment alone, and after combination therapy of oestrogen and 1 α‐OH‐D3. The primary action of administered oestrogen may be in stimulating hCT secretion which results in a decrease in plasma calcium concentration and an increase in plasma iPTH level.

Topical administration of 1,25-dihydroxyvitamin D 3 for proriasis: Report of five cases

SummaryThe effects of topical administration of 1,25-dihydroxyvitamin D3, as 0.1 and 0.5 μg per g base, and control base applied to contralateral skin lesions in five patients with persistant psoriasis were compared. In all five, definite and in some cases remarkable improvement of the lesions was seen when 1,25-dihydroxyvitamin D3 at concentration of 0.5 μg per g base was applied for two to five weeks. No local or systemic toxicity was detected in any patient. Although the mechanism of the improvement is yet to be elucidated, these results show the possible effectiveness of topical 1,25-dihydroxyvitamin D3 on psoriatic skin lesions.

Effects of prostaglandins on the cytosolic free calcium concentration in vascular smooth muscle cells.

The effects of prostaglandin (PG) F2 alpha and 9,11-epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of thromboxane A2, on the cytosolic free calcium concentration ([Ca2+]i) in vascular smooth muscle cells were studied with a new fluorescent Ca2+ indicator fura 2. PGF2 alpha and STA2, which are strong vasoconstrictors, caused rapid phasic and subsequent tonic increases in [Ca2+]i. PGF2 alpha caused dose-dependent elevation of [Ca2+]i not only in control solution but also in the calcium-free solution. A first stimulation with PGF2 alpha caused dose-dependent decrease in the response of [Ca2+]i to a second stimulation with PGF2 alpha. Pretreatment with 13-Azaprostanoic acid, a receptor level antagonist of thromboxane A2 inhibited the increase of [Ca2+]i induced by STA2. These results suggest that PGF2 alpha induces calcium mobilization followed by smooth muscle contraction through its specific receptors.

Radioimmunoassay of human platelet-derived growth factor using monoclonal antibody toward a synthetic 73-97 fragment of its B-chain

A mouse monoclonal antibody toward a 73-97 fragment of human platelet-derived growth factor (hPDGF) B-chain was used to develop a radioimmunoassay (RIA) for serum hPDGF. By the single step procedure of the double antibody technique, the measurable range was 10-1,000 micrograms/l. The coefficients of variation within and between series were 10.2% and 12.1% respectively, and satisfactory dilution curves were obtained for sera from healthy subjects. The hPDGF levels in all plasma samples from 15 healthy subjects examined were below the detection limit (10 micrograms/l), whereas the mean hPDGF concentration (+/- SD) in serum samples of 60 healthy subjects was 31.9 +/- 20.4 micrograms/l. This value was significantly (p less than 0.01) higher than the mean for 21 patients with idiopathic thrombocytopenic purpura (12.6 +/- 4.5 micrograms/l). There was a significant positive (r = 0.481, p less than 0.01) but not a strong (r2 = 0.23) correlation between the peripheral blood platelet counts and serum hPDGF levels of all subjects. This RIA system should be useful clinically for measurement of serum hPDGF.

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.

1,25-dihydroxyvitamin D3 binds specifically to rat vascular smooth muscle cells and stimulates their proliferation in vitro

Cultured vascular smooth muscle cells (VSMC) derived from rat aorta were found to contain a specific receptor for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Its Kd (5.0 x 10(-11) M) and capacity (22.9 fmol/mg of cytosol protein) for 1,25-(OH)2D3, its sedimentation coefficient on a sucrose density gradient (3.2 S), its relative affinities for various vitamin D3 metabolites [1,25-(OH)2D3 greater than 25-hydroxyvitamin D3 greater than 24,25-dihydroxyvitamin D3 greater than vitamin D3] and its affinity for DNA-cellulose were similar to those reported for the 1,25-(OH)2D3 receptor in other tissues. 1,25-(OH)2D3 at concentrations of more than 10(-10) M caused dose-dependent enhancement of the proliferation of VSMC in DMEM with 10% FCS. 25-Hydroxyvitamin D3 stimulated the proliferation of VSMC only at its highest concentration tested (10(-6) M). These data show that 1,25-(OH)2D3 stimulates the proliferation of VSMC after its binding to a cytoplasmic receptor of the cells in vitro, and support the possibility that VSMC are target cells of the hormone.

Deletion allele of the angiotensin-converting enzyme gene as a risk factor for pneumonia in elderly patients ☆

PURPOSE Aspiration due to an age-related reduction in cough is a major cause of pneumonia in elderly persons. Because the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE) has been associated with the cough reflex, we studied whether this genetic polymorphism was also associated with the risk of pneumonia. SUBJECTS AND METHODS We studied 1011 elderly inpatients (221 men and 790 women, mean [+/- SD] age of 82 +/- 7 years) in a long-term care hospital. The association between the ACE I/D polymorphism and the incidence of pneumonia (defined using specific criteria that included radiographic abnormalities) was assessed during an 8-month period that excluded the winter. Data were analyzed using proportional hazards models, with adjustment for age, sex, and other potential confounders. RESULTS During follow-up, 87 cases (9%) of pneumonia occurred, 38 of which were fatal. The ACE DD allele (vs. ID + II) was associated with an increased risk of pneumonia (relative risk [RR] = 2.9; 95% confidence interval [CI]: 1.7 to 4.8, P < 0.001) and fatal pneumonia [RR = 4.4; 95% CI: 2.1 to 9.0; P < 0.0001). CONCLUSIONS The ACE D allele is an independent risk factor for pneumonia in elderly persons.

Serum calcium regulating hormones in the perinatal period.

SummaryTo clarify perinatal vitamin D metabolism, we measured 25-hydroxyvitamin D (25OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], 1,25-dihydroxyvitamin D [1,25(OH)2D], calcium (Ca), phosphorus (P), parathyroid hormone (PTH), and human calcitonin (CT) in paired maternal, cord, and infant serum. Cord serum 25OHD was significantly lower than the maternal level, and cord serum 24,25(OH)2D was also significantly below the maternal concentrations. Maternal, cord, and infant serum 1,25(OH)2D, on the other hand, was significantly higher than the normal adult level. The serum PTH was low, but the CT concentration was high in the cord. Cord serum Ca and P levels were significantly higher than maternal. The reason for the elevated circulating 1,25(OH)2D level in the perinatal period is uncertain, and we speculate that the possible factors are gonadal steroids, placental lactogen, prolactin, and CT. In addition, serum 24,25(OH)2D and 1,25(OH)2D concentrations are under some control by the fetus.