Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects (n=400) were selected by sex and age stratum from the full list of residents born in 1910–1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects (P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.     

Differentiation of blast cells from a Down's syndrome patient with transient myeloproliferative disorder

A male neonate with Down's syndrome and congenital myeloproliferative disorder was studied. His blood picture showed the unique coexistence of leukocytosis with matured cells and a large number of blast cells. The in vitro proliferation and differentiation of blast cells into various lineages in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM) was examined by using a liquid culture and a methylcellulose culture system. The differentiation of blast cells into myeloid cells was confirmed by specific cytochemical stainings, electron microscopy, and an immunologic study. No specific factors in the plasma of the patient promoted the proliferation or differentiation of blast cells. The cellular composition of colonies grown in methylcellulose culture from single blast cells was studied by a micromanipulation technique. High plating efficiency was observed. Of 136 cultures, 78 showed colony growth. Half of the blast cells were colony-forming cells that could proliferate and differentiate into basophils, neutrophils, eosinophils, macrophages, and erythrocytes in the presence of PHA-LCM. Using the blast cells with a high differentiation capacity to the basophil pathway, we studied the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM- CSF). Recombinant GM-CSF support neutrophils, eosinophils, and macrophages but not typical basophils. These findings of the cell differentiation of blast cells into various kinds of cells in vitro were in agreement with the finding of neutrophilia, eosinophilia, basophilia, and thrombocythemia in this patient.     

Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.     

Effects of hypertension and type 2 diabetes mellitus on the risk of total cardiovascular events in Japanese patients with hypercholesterolemia: implications from the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia, hypertension, and diabetes mellitus (DM) are well-established risk factors for cardiovascular disease. We analyzed the cardiovascular events in hyperlipidemic patients with or without DM who were administered open-labeled simvastatin in groups stratified by blood pressure level using data from the Japan Lipid Intervention Trial (J-LIT). Hyperlipidemic patients with DM (n=6,288) had significantly more cardiovascular events than those without DM (n=33,933). The incidence rates of total cardiovascular events in the Non-DM and DM groups were 15.40 and 25.76 per 1,000 patients for the 6-year period, respectively. The relative risk of total cardiovascular events in the DM vs. the Non-DM group was 1.68, and the relative risk was significantly higher in the DM than in the Non-DM group. The relative risks of total cardiovascular events were significantly higher in DM and Non-DM patients whose systolic blood pressure (SBP) was greater than or equal to 130 mmHg compared to that of Non-DM patients whose SBP was less than 130 mmHg, and in DM and Non-DM patients whose diastolic blood pressure (DBP) was greater than or equal to 80 mmHg compared to that of Non-DM patients whose DBP was less than 80 mmHg. In all groups stratified by SBP and DBP, relative risks of total cardiovascular events were higher in DM patients than in Non-DM patients. For patients with hypercholesterolemia and DM, blood pressure should be strictly controlled in order to prevent both coronary events and stroke. These results are in good agreement with the JNC 7 and the ESH/ESC guidelines for DM patients, which recommended that the SBP and DBP be less than 130 and 80 mmHg, respectively.     

Permanent prostate brachytherapy for Japanese men: Results from initial 100 patients with prostate cancer

OBJECTIVE: To evaluate the initial results of brachytherapy for prostate cancer with permanent iodine-125 implant in Japan. METHODS: The results obtained with brachytherapy in the initial 100 Japanese patients treated at Nagano Municipal Hospital were reviewed. Patients with a prostate-specific antigen (PSA) level of less than 10 ng/mL and a Gleason's scores of 5, 6, 3 + 4 were classified as having a low risk of recurrence. Patients with a PSA level of 10-20 ng/mL and/or a Gleason's score of 4 + 3 were classified as having an intermediate risk for recurrence. Seventy-eight of the low-risk patients and 19 of the intermediate-risk patients were treated by seed implants alone, or seed implants combined with preceding external radiation, respectively. A total of 53 patients received neoadjuvant hormone therapy. The efficacy and morbidity of brachytherapy were investigated using the serum PSA, International Prostate Symptom Score, quality of life score and uroflowmetry data. RESULTS: The average V100 and D90 obtained by post-implant dosimetry was 94.3 and 113.7%, respectively. Serum PSA decreased gradually after treatment, although it had still not reached a nadir after 1 year. There was little difference of the PSA level between the patients with and without neoadjuvant hormone therapy even at 1 year after seed implantation. There were no PSA biochemical failure or clinical recurrence during the follow-up period. Voiding symptoms worsened until 3 months after treatment, and then gradually improved. Acute urinary retention occurred transiently in one patient (1%). Rectal bleeding and severe diarrhea did not occur. CONCLUSION: Brachytherapy is a feasible and effective option for the treatment of prostate cancer in Japanese men. Brachytherapy may have a different effect in Japanese patients with respect to voiding symptoms. Urinary retention was rare, but voiding symptoms were persistent in Japanese patients. Neoadjuvant hormone therapy deserves investigation to determine whether it can achieve better results, especially in patients with an intermediate risk.     

Impact of unilateral interposition sural nerve graft on the recovery of sexual function after radical prostatectomy in Japanese men: A preliminary study

PURPOSE: To determine the effect of an interposition nerve graft on sexual function after radical prostatectomy. METHODS: This study includes 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation. Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle. Twenty-one and 31 patients underwent bilateral nerve-sparing (BNS) and unilateral nerve-sparing (UNS) surgery without a nerve graft, respectively. As the age of patients was significantly younger in the UNG group than in the other groups, age-matched analysis also was conducted. Sexual function, evaluated by a self-administered questionnaire using the University of California Los Angeles-Prostate Cancer Index, was compared statistically among the three groups. RESULTS: In the age-matched analysis, the postoperative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months postoperatively. The difference in the SXF score between the UNG and UNS groups began to appear after 6 months postoperatively and increased steadily with time. However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of comorbidities were different between the UNG and UNS groups. CONCLUSIONS: The difference of the SXF score between the UNG and UNS groups increased with time after 6 months postoperatively. However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.     

Evaluation of cardiac function during KCl-induced paralytic attack in the patients with normokalemic periodic paralysis

Some reports have been written about hypokalemic periodic paralysis dealing with cardiac dysfunction and arrhythmia during the paralytic attack. However, no reports have been written about the cardiac function during the attack in cases of normokalemic periodic paralysis. So, we investigated cardiac function in two patients with normokalemic periodic paralysis. A 3.0 g dose of KCl was administered orally to the patients (1 male, 1 female) and 10 healthy volunteers (5 males, 5 females). Cardiac function by using ejection time (ET)/pre-ejection period (PEP), grasping power, and the level of plasma catecholamine were measured during the paralytic attack. Changes in the patients were compared with those in the volunteers. Next, a 3.0 g dose of KCl was administered to the patient, followed by intravenous dosing of 10% NaCl (50 ml) after which ET/PEP and grasping power measured. Lastly, a 60 mg dose of diltiazem, a 10 mg dose of nifedipine or a 80 mg dose of verapamil were administered, followed by a 3.0 g dose of KCl after which ET/PEP and grasping power were measured again. Thirty minutes after the administration of KCl, the grasping power decreased remarkably, from 32.0 kg to 17.0 kg in the male patient and from 30.0 kg to 20.0 kg in the female patient. By contrast, the ET/PEP showed a clear increase, from 3.47 to 6.17 in the male patient and from 2.84 to 5.45 in the female patient. Grasping power of the volunteers, however, did not change remarkably (avg. 40.3 kg before vs. 40.9 kg after in the males and avg. 26.9 kg before vs. 26.0 kg after in the females) and ET/PEP of the volunteers did not change remarkably (avg. 3.37 before vs. 3.17 after in the males and avg. 3.30 before vs. 3.43 after in the females). No significant changes were found in the levels of plasma catecholamine during the paralytic attack.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of alpha-1-blocking agent in the treatment of detrusor sphincter dyssynergia

Effects of adrenergic alpha-1-blocking agent, prazosin, in the treatment of detrusor external-sphincter dyssynergia (DSD) were evaluated in both experimental and clinical aspects. Experimentally, in the urethral pressure profile in dogs, the maximum urethral closing pressure was depressed after intravenous injection of 1 mg prazosin. When experimental DSD was obtained in dogs by stimulating electrically the unilateral 2nd sacral root, intra-venous injection of 1 mg prazosin inhibited contraction of the external urethral sphincter. Clinically, 74 patients with DSD based on neurogenic bladder from cerebral vascular attack (CVA) (13 cases) and spinal cord injury (61 cases) were retrospectively surveyed in terms of therapeutical effects of prazosin for DSD. Spinal cord injury was subdivided to 4 groups for clinical evaluation; cervical cord injury (C) with complete paralysis, thoracic cord injury (Th) with complete paralysis, lumbar cord injury (L) with complete paralysis and spinal cord injury with incomplete paralysis. Patients with CVA and spinal cord injury with incomplete paralysis showed good response rates in subjective improvement, 69% and 60% respectively. However, those with spinal cord injury with complete paralysis showed a poor response (28% for C, 23% for Th and 14% for L). The amount of residual urine significantly decreased after treatment, in all the groups except that of lumbar cord injury with complete paralysis. In all the groups, however, even after the drug treatment the amount of residual urine ranged from 80 to 170 ml and the rates of needing clean intermittent catheterization unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)