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Biomedical subjects

K Nakatsuka

Publications and source records attributed to K Nakatsuka.

At least 19 recordsLinked to original sources
PubMed1996

Comparison of three intravenous regimens of clodronate in Paget disease of bone.

We compared the effects of three different regimens of intravenous clodronate in a retrospective study of 60 patients with Paget disease. A total dose of 1500 mg of clodronate was given as 300 mg for 5 consecutive days (n = 20), 1500 mg as a single infusion (n = 20), or 300 mg as a single infusion for 5 consecutive months (n = 20). The response to treatment and the duration of the effect were assessed from sequential changes in the activity of serum alkaline phosphatase. Treatment with clodronate induced a significant response in 85% of patients. The response rate was comparable in patients treated with 5 daily infusions (90%), with a single infusion (75%), and with 5 monthly infusions (90%). The median duration of response from the start of treatment was 11 months for those treated with five daily infusions and 12 months for the other two regimens. At one year, 22, 40, and 44% of patients had maintained their response in the daily, single, and monthly infusion regimen, respectively (NS). Six patients (32%) treated with 5 daily infusions achieved a remission (complete response) compared with 3 patients treated with a single infusion and 5 monthly infusions, respectively (16 and 15% respectively, NS). Patients attaining a complete response had a significantly longer duration of response compared with partial responders (median time 15.0 versus 11.5 months, respectively, p < 0.05). We conclude that intravenous clodronate (total dose 1500 mg) suppresses disease activity in the majority of patients with Paget disease of bone. The degree and duration of response were similar for the three regimens. Thus, in the treatment of Paget disease, the choice of regimen is a matter of convenience.

Aged↗
PubMed1996

Duration of response with oral clodronate in Paget's disease of bone.

We studied retrospectively 51 patients with Paget's disease of bone treated with oral clodronate, 1600 mg daily given for 1 (n = 23), 3 (n = 13), or 6 months (n = 15), to compare the effect of a variable length of treatment on the response rate to treatment and the duration of disease suppression. Activity of alkaline phosphatase and urinary hydroxyproline excretion were measured before treatment at monthly intervals for a year and every 3 months thereafter until biochemical relapse. Before treatment, patients given the three regimens had similar disease activity as judged by serum alkaline phosphatase and urinary hydroxyproline values. There was no significant difference in the time to response between groups (median = 2 months). The proportion of patients attaining normal values of alkaline phosphatase activity was significantly higher in patients treated for 6 months (71%, p < 0.03) compared with those treated for 1 or 3 months (23% and 39%, respectively). The time to relapse from the start of treatment was significantly shorter in patients treated for 1 month compared with those treated for 3 or 6 months (median = 11, 18, and 23 months, respectively). Thus, at 2 years all patients treated for 1 month had relapsed, whereas 31% and 40% were still relapse-free in patients receiving treatment for 3 and 6 months, respectively. The length of treatment was the only variable identified by stepwise linear regression that significantly affected the duration of response. We conclude that oral clodronate (1600 mg daily) suppresses disease activity in the vast majority of patients with Paget's disease of bone. The magnitude of the response and its duration depend on the duration of treatment or the total dose administered, so that several months of treatment with oral clodronate are required when a durable response is desired.

Administration, Oral↗
PubMed1996

Simplified procedure for aesthetic improvement of facial contour by maxillary augmentation using a porous hydroxyapatite graft for maxillofacial deformity.

A simplified procedure of maxillary augmentation with a porous hydroxyapatite block graft in the anterior aspect of the maxillary parapiriformis area is described. This procedure is an alternative for maxillary advancement osteotomy and is simple to perform for maxillofacial deformity of cleft lip and palate and other deformities. It is effective for facial aesthetics in association with mandibular surgery, such as mandibular setback by sagittal splitting osteotomy, mandibular segmental osteotomy with premolar extraction, bimaxillary osteotomy, and/or genioplasty. We used this procedure on 21 patients (15 for cleft lip and palate jaw deformity and 6 for aesthetic reasons). Although postoperative infection requiring removal of the hydroxyapatite block occurred in one cleft deformity patient, satisfactory results were obtained in all patients.

Adult↗
PubMed1996

Measurement of bone-specific alkaline phosphatase by an immunoselective enzyme assay method.

We evaluated a new immunoselective enzyme assay of bone-specific alkaline phosphatase (ALP). The monoclonal antibody used in this assay was raised against purified bone-specific ALP obtained from SAOS-2 human osteosarcoma cell line. Calibration was based on the enzyme's own activity. The relative activity of the antibody was 100% with bone ALP, 8.7% with liver ALP, and 0% with placental and intestinal ALPs. Intra- and inter-assay coefficients of variation were less than 4%. The sensitivity of the assay was 0.7 U/L, and the linearity extended from 2 to 140 U/L. The recovery of bone-specific ALP standard added to serum was 94-106%. The correlation coefficient between this method and the polyacrylamide gel (PAG) electrophoretic method was 0.94. The mean value of bone-specific ALP in 89 healthy adults (mean age 29 years, SD 5 years) was 18.5 U/L (SD 4.1 U/L). Interestingly, mean bone-specific ALP activities in 60 premenopausal women (mean age 39 years, SD 8 years) and 70 postmenopausal women (mean age 57 years, SD 5 years) were 20.3 U/L (SD 6.5 U/L) and 31.1 U/L (SD 11.1 U/L), respectively. The age-related increase in bone-specific ALP was significant and more pronounced in women (P < 0.01). We conclude that this new immunoassay of bone-specific ALP would be useful for clinical investigation of patients with osteoporosis or other metabolic diseases of bone.

Adult↗
PubMed1996

[Biochemical markers of bone formation in osteoporosis].

We measured circulating bone Gla-protein(BGP) changes following short-term(2 weeks) active vitamin D treatment in elderly men with osteoporosis (73.0 +/- 9.4 years, n = 9) to evaluate osteoblastic function. We also measured serum levels of BGP(n = 245) and bone specific ALP(B-ALP) in women (n = 113) with normal lumbar bone mineral density, and evaluated the difference in clinical significance between these markers of bone formation. Serum BGP was significantly increased at the end of the first and 2nd week of daily oral 2 micrograms of 1 alpha(OH)D3 administration. BGP measurement is a clinically useful method to detect osteoblastic function after active vitamin D3 treatment. Significant positive correlations were found between age and BGP (r = 0.402, p < 0.01) or B-ALP (r = 0.494, p < 0.01). These markers were significantly higher in postmenopausal women compared with age-matched premenopausal women. The z-score of the difference in B-ALP was 1.47 and that of BGP was 0.7. Although B-ALP and P1CP in sera remained stable even at room temperature for at least 4 hours, the BGP level was significantly lower when the blood sample was kept at room temperature for more than 1 hour. These findings suggest that B-ALP is a more sensitive and stable marker than BGP in evaluating bone formation, although both markers have significant correlations with each other, and BGP is useful to detect the active vitamin D3 effect on osteoblastic function.

Aged↗
PubMed1995

Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro.

Adult T-cell leukemia (ATL) is a human T-cell leukemia virus type I (HTLV-I)-infected lymphoproliferative disorder that shows a characteristic nodular infiltration into various tissues, hypercalcemia, and subsequent rapid increase of peripheral ATL cell number. ATL cells and HTLV-I-infected T-cell lines also make cluster formation rapidly after the non-stimulative culture. However, the mechanism of the acute proliferation of ATL cells remains to be understood. We report the following novel features of homotypic adhesion via leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pathway that suggest a role for it in cytokine production and rapid proliferation of ATL cells: (1) ATL cells show clustering in a calcium dependent manner, even at the higher concentration; (2) ATL cells consistently and highly express ICAM-1 and an active form of LFA-1, whereas integrin expression, except for LFA-1, is rather lower compared with that of normal CD4+ T cells; (3) ATL cells make conjugate formation within 6 minutes and clustering within 48 hours, both of which are inhibited by the addition of monoclonal antibodies (MoAbs) against LFA-1 and ICAM-1; (4) spontaneous mRNA transcription and protein secretion of both interleukin-1 and parathyroid hormone-related protein are observed consistently in ATL cells, and these productions are inhibited by anti-LFA-1 and anti-ICAM-1 MoAbs but are markedly increased by cross-linking of LFA-1 and ICAM-1 by the immobilized specific MoAbs; and (5) proliferative responses of ATL cells are also inhibited by these MoAbs. We propose that ATL cells proliferate in sequential events: the homotypic and calcium-dependent adhesion through LFA-1/ICAM-1, the signal transduction through these adhesion molecules, the production of cytokines, and the proliferation.

Bone Resorption↗
PubMed1995

Sebaceous carcinoma responds to radiation therapy.

We describe a patient with an eyelid tumor that responded well to radiation therapy. The histopathological diagnosis was poorly differentiated sebaceous carcinoma. The patient received 52 Gy electron beam irradiation in a 5-week period; thereafter, the tumor diminished. The histopathological findings after radiation showed that most tumor cells underwent massive necrosis with hyalinized obstructive vessels. The tumor was under control at the 9-month follow-up examination.

Aged↗
PubMed1995

[The variability of blood velocity in the ophthalmic artery with color Doppler imaging].

Non-invasive measurements of blood velocities of the ophthalmic artery (BVA) in color Doppler imaging (CDI) are increasingly used to assess the influence of disease on the hemodynamics of the eye. Such measurements are only valid when compared to spontaneous variability. Therefore, the aim of this study was to examine the variability of BVA in healthy subjects. Within-a-day short-term variability was assessed from measurements obtained during one day from 5 healthy young male subjects as the coefficient of variation (CV) of 10 consecutive measurements. Between-days variability was assessed by comparing measurements made on three different days at one month intervals. The left and right BVA were measured five consecutive times to evaluate the difference in BVA between left and right eyes in 5 healthy young male subjects. In the within-a-day variability, mean CV in maximum systolic BVA (V max), minimum end diastolic BVA (V min), time-averaged BVA (V mean), resistive index (RI), and pulsatility index (PI) were found to be 6.6%, 14.0%, 14.9%, 3.2%, and 17.4%, respectively. The between-days variability was just as high as the within-a-day variability. There was significant difference in BVA between left and right eyes in two of the five subjects. We concluded that the within-a-day variability and the between-days variability of BVA measured using CDI are reproducible. The CDI can be used to assess the influence of disease and drugs on the hemodynamics of the eye.

Adult↗
PubMed1994

[Osteoporosis].

Patients with established osteoporosis visit physicians with various complaints including back pain and weakness of their back, although recent mass screening increases number of osteopenic patients without symptoms. Long-term outcomes of patients with inadequate treatment result in fractures of lumbar spines, femoral necks and/or radial bones. Some patients show friction sound caused by ribs and pelvic bone, and others show skin eruption of abdomen. The psychological problems caused by intolerable pain or fear for the future fractures are also clinically important. The symptomatic improvement are influenced not only by the power of the drugs but also by the psychological condition.

Cardiovascular Diseases↗
PubMed1994

[Exercise and physical therapy in osteoporosis].

Initial studies demonstrated that an adequate amount of continuous exercise such as weight-bearing and aerobic training slow down bone loss, maintain bone mineral density, or even increase bone density in the young adulthood though the magnitude of mechanical loading of the bone. However, it remains unclear whether physical activity is also beneficial for bone health in postmenopausal and elderly women with osteoporosis whose exercise endurance capacity is commonly decreased. Recent longitudinal studies showed that 1-2 years of moderate to intensive exercise can increase postmenopausal bone mass, although the amounts of bone gain are relatively modest and site-specific. Thus, weightbearing exercise should be recommended not only to inhibit loss of bone mass but also to increase muscle strength in the elderly, which definitely lead to prevention of falls and decrease the incidence of new fractures.

Adult↗
PubMed1993

Effect of aminohydroxypropylidene diphosphonate on the bone metabolism of patients with parathyroid adenoma.

Aminohydroxypropylidene diphosphonate (APD), a potent inhibitor of bone resorption, is used to control hypercalcemia in various diseases. It is less effective, however, in the management of hypercalcemia induced by primary hyperparathyroidism. We investigated the effect of APD on the bone metabolism of five patients with parathyroid adenoma. Before parathyroidectomy, 30 mg of APD was administered intravenously. Serum calcium decreased in all cases one to two days after APD administration, although it did not decrease to the normal range. Serum phosphorus also decreased. Urine calcium and hydroxyproline excretion, markers of osteoclasts activity, decreased dramatically. Serum alkaline phosphatase (ALP) and osteocalcin, markers of osteoblast activity, decreased after APD administration. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxy-vitamin D (1,25[OH]2D) increased. These results indicate that APD is partially effective in the management of preoperative serum calcium level in patients with parathyroid adenoma. As osteoclasts activity is inhibited by APD, osteoblasts activity is also suppressed. Elevation of PTH and 1,25(OH)2D after APD-induced decrease in serum calcium level may explain the partial and limited effect of APD on lowering serum calcium in patients with parathyroid adenoma.

Adenoma↗
PubMed1993

Serum anti-streptococcal IgA, IgG and IgM antibodies in IgA-associated diseases.

Serum anti-streptolysin-O antibody (ASO) and anti-streptococcal polysaccharide antibody (ASP) of IgA, IgG and IgM classes were measured using an enzyme-linked immunosorbent assay in 41 children with IgA nephropathy (Group A), 15 children with uncomplicated anaphylactoid purpura (Group B) and 13 children with purpura nephritis (Group C). The serum concentrations of the IgA, IgG and IgM classes were measured by single radial immunodiffusion. When compared with sex- and age-matched controls, the concentrations of serum IgA (but not of IgG or IgM) were significantly increased in the three groups studied. The titers of ASO of the IgA and IgM classes, and those of ASP of the IgA and IgG classes, were significantly increased in Group A. In Group B, only the ASP titers of the IgA class were significantly increased. No significant difference was noted in the titers of either ASO or ASP of any class in Group C. Thus, increased antibody response in IgA nephropathy is not restricted to IgA. Anaphylactoid purpura with or without renal disease appears to be different in its humoral anti-streptococcal response from IgA nephropathy.

Adolescent↗
PubMed1993

[Propranolol for prophylaxis of first hemorrhage in cirrhotic patients with esophageal varices--a controlled study comparing with sclerotherapy].

To compare the efficacy of oral propranolol and sclerotherapy in the prevention of first hemorrhage from esophageal varices, 65 cirrhotic patients with moderate to large esophageal varices and no history of bleeding were included in the prospective controlled trial. After randomization, 33 patients received propranolol at a does reducing the heart rate by 25%; 32 patients were treated with intra-variceal and extra-variceal injection of ethanolamine oleate. On entry to the trial, the two groups were comparable in terms of clinical and biological parameters. The patients were observed for up to 60 months, with an average of 31 months. Nine patients bled (5 in propranolol and 4 in sclerotherapy) during follow-up. No significant difference were observed between propranolol and sclerotherapy in the cumulative bleeding rate and survival. The multivariate Cox model indicated that drug compliance in the propranolol group and high portal pressure in the sclerotherapy group were factors predictive of the first hemorrhage. These data support that propranolol and sclerotherapy are of comparable value in preventing the first hemorrhage in cirrhotic patients with esophageal varices.

Aged↗
PubMed1992

Biological potency of a fluorinated vitamin D analogue in hypoparathyroidism.

Several in vivo experiments have revealed that a synthesized fluorinated analogue of vitamin D, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3) has a higher and longer-lasting biological activity than 1,25(OH)2D3 in calcium regulating actions. We evaluated the biological potency and the availability for clinical use of this compound in hypocalcemia associated with hypoparathyroidism. In an experimental setting, daily administration of 650 pmol/kg of 26,27-F6-1,25(OH)2D3 showed an equivalent effect to that of 3250 pmol/kg of 1,25(OH)2D3 in elevating whole blood ionized calcium levels in parathyroidectomized rats. Furthermore, an additional clinical study demonstrated that 0.5-1.5 micrograms/day of 26,27-F6-1,25(OH)2D3 were considered adequate maintenance doses in various types of hypoparathyroidism and that changes of medication to the same doses of 1,25(OH)2D3 resulted in prompt decline of urinary calcium excretion and of whole blood ionized calcium levels, and in recurrence of symptoms related to hypocalcemia. Although the mechanism responsible for the high potency of this analogue remains unclear, our experience confirms that 26,27-F6-1,25(OH)2D3 has higher biological activities in bone calcium mobilization and is more potent than 1,25(OH)2D3 in correcting hypocalcemia of hypoparathyroidism in a hospital setting.

Animals↗