A 60-year-old male patient visited the Oriental Medicine Research Institute of the Kitasato on ***** because of abdominal discomfort. Hangeshashin-to was administered to him and the abdominal discomfort was relieved. He continued to take Hangeshashin-to from June to August 1997. He had chills, high fever, and fatigue from ********. He stopped Hangeshashin-to and took Shosaiko-to for five days because of liver dysfunction. He was admitted to our hospital on ********. Antibiotics and stronger neo-minophagen C were administered to him. A chest roentgenogram revealed a ground-glass shadow on the left upper lung, and Shosaiko-to was discontinued. The patient began to complain of dyspnea and had fine crackles on the chest. A chest roentgenogram and chest CT showed interstitial pneumonitis. Oral predonisolone therapy was started for hypoxemia and the patient improved. A drug lymphocytes stimulation test revealed that lymphocytes were stimulated by Shosaiko-to and its components, Saiko and Ogon. A chest roentgenogram just before ingesting Hangeshashin-to revealed the interstitial change of the lung. Taken all together, this patient suffered from druginduced hepatitis and pneumonitis as a result of ingesting Hangeshashin-to and Shosaiko-to.

Since 1993, we have used a clinical clerkship method in an attempt to improve the undergraduate clinical training in our department. At first, the students were given the opportunity to learn adequate basic clinical procedures (levels 1 to 3), but data on the effect of their training were lacking. Therefore, we conducted a survey to obtain the necessary information. Twenty-nine students (29 % of students in the sixth academic year) participated and wrote their survey reports at the end of the course. The reports were designed to evaluate their problem-solving skills and the effects of self-directed learning in clinical anesthesia and to obtain an overall impression of the training. The results revealed that the educational effect was insufficient for almost all students who participated because they were unable to fully solve the problems of anesthetic management from either a pathophysiologic or pathobiochemical standpoint. From these results and our further experiences from 1994 through 1996, we decided to reform our educational procedures. The important improvements are as follows. 1) Trainees must record the anesthesia course during the assigned anesthetic case and participate in the postoperative ward discussion. 2) A member of the teaching staff must discuss ways to manage and solve problems with trainees at the end of each case. 3) After the discussion, trainees must write a report about how and what they have learned.

The purpose of this study was to examine the effect of physical inactivity, produced by prolonged bed rest, on the excitability of the spinal motor neuron pool in humans, using the activity of soleus H-reflex.
Eight healthy male subjects underwent continuous bed rest with 6 degree head-down tilt for 20 days (BR group) . Ten different healthy male subjects maintained their usual daily life during the observation period for 20 days (control group) . Recruitment curves of H-reflex and M-wave were obtained from every subject. H slope/M slope (H slp/M sip) which shows the excitability of spinal motor neurons was calculated by using data in the recruitment curve.
The H sip/M sip in the BR group significantly increased after BR, compared to the pre-BR values (p<0.05) . In the control group, however, there were no significant differences in the H slp/M sip between the pre and the post-observation values. At the baseline, the H slp/M sip showed no significant differences between the BR group and the control group. After the BR, the H slp/M sip in the BR group significantly increased compared to the control group after the observation period (p<0.05) .
This study suggests that the excitability of the monosynaptic spinal motor neuron pool is facilitated by physical inactivity during BR.

Objective: At Kitasato Institute Hospital, Kitasato University (henceforth, the hospital), the first edition of an antimicrobial use guidebook (henceforth, the guidebook) was produced in 2000.  This time, the Pharmaceutical Department’s members on the hospital’s Infection Control Committee (ICC) took the lead and revised the guidebook so that it better conforms to clinical conditions and assessed the guidebook they created.
Methods: A Working Group (WG) consisting of two ICC Pharmaceutical Department members and two members of the Medical Products Information Office staff examined the items to be listed in the guidebook.  These items were approved by the ICC and then assigned to physicians and pharmacists to be written up.  A questionnaire survey was conducted on the physicians and pharmacists in the hospital as to their assessment of the content and the conditions of use of the guidebook created.
Results: In the revised edition, “Antimicrobials PK/PD,” “TDM,” “Empiric Therapy for Infections in Each Department,” etc. have been added, the physicians wrote “Empiric Therapy for Infections in Each Department” and everything else was written by the WG.  The return rate of the questionnaire was 65.7% (N=99), and the guidebook utilization rate was 75.4%.  Frequently viewed items were “List of Antimicrobials Used In-Hospital,” “How to Administer Medication during Decreased Renal Function,” “Empiric Therapy for Infections in Each Department,” etc. by the internal medicine physicians, “List of Antimicrobials Used In-Hospital” and “How to Administer Medication during Decreased Renal Function,” etc. by the surgeons, and “Classification of Antimicrobials,” “List of Antimicrobials Used In-Hospital,” “When Renal Function is Decreased,” “TDM,” and “Empiric Therapy for Infections in Each Department,” etc. by the residents.  Furthermore, there were no items deemed “not necessary for inclusion” for a clear reason.  As to be expected in this guidebook, 72.3% of all respondents mentioned it was “a source of information on basic antimicrobial use” and next, “a source of information for treating infections outside one’s area of specialty.”
Conclusion: The items listed in the guidebook are thought to be appropriate, and its usage conditions are also good.  As they are specialists on antimicrobials, the pharmacists playing a central role while cooperating with the physicians on the ICC led to the creation of a highly useful guidebook.

OBJECTIVES: The aim of this study was to examine the efficacy, safety, and adherence of ibandronate (IBN) treatment with or without vitamin D supplementation for 3 years in Japanese women with postmenopausal osteoporosis. METHODS: This prospective investigation included 27 patients treated with IBN alone (monotherapy group) and 29 patients receiving IBN and alfacalcidol (ALF) (combination group). Bone metabolism and bone mineral density (BMD) were measured before and at 18, 24, 30, and 36 months of therapy. Treatment discontinuation and fracture occurrence were assessed as well. RESULTS: Lumbar 1–4 BMD (L-BMD) was significantly increased in the monotherapy and combination groups by 3.9% and 7.2%, respectively, at 36 months, with significant gains in total hip BMD (H-BMD) of 3.7% and 4.9%, respectively. There were significant differences in L-BMD improvement between the groups at 18, 24, and 30 months (P < 0.05) and at 36 months (P < 0.01). Compared with pretreatment levels, the percentage changes of L-BMD and H-BMD were significant at all time points in the combination group and at all points apart from L-BMD at 36 months in the monotherapy group. In the monotherapy group, 14 patients dropped out during 3 years and 2 vertebral fractures occurred during the first year. In the combination group, 16 cases dropped out during 3 years and 1 nonvertebral fracture was noted during the first year. CONCLUSIONS: Our findings suggest that combination therapy of IBN and vitamin D is superior to monotherapy with regard to L-BMD improvements for 3 years, with both groups showing comparable safety and adherence to treatment.
Asian Continental Ancestry Group ; Bone Density ; Compliance ; Female ; Hip ; Humans ; Metabolism ; Osteoporosis ; Osteoporosis, Postmenopausal ; Prospective Studies ; Vitamin D

OBJECTIVES: Increasing bone mineral density (BMD) to reduce fracture risk is a primary goal of osteoporosis treatment. This prospective, observational study evaluates the effects of monthly minodronate (MIN; 50 mg) with or without eldecalcitol (ELD) addition in osteoporosis patients with rheumatoid arthritis (RA) during 18 months. METHODS: The cohort was prospectively and randomly split into the MIN monotherapy group (14 cases) and MIN plus ELD group (combination group; 14 cases) due to no reports on the effectiveness and safety of MIN therapy in relation to ELD addition for comparisons of serum tartrate-resistant acid phosphatase (TRACP)-5b, bone alkaline phosphatase (BAP), and BMD of the lumbar 1–4 vertebrae (L-BMD), bilateral total hips (H-BMD; the mean value of the right and left hips), and bilateral femoral necks (FN-BMD) at baseline and at 6, 12, and 18 months of treatment. RESULTS: Baseline values were comparable between the groups apart from a tendency for higher TRACP5b in the combination group. Seven of 14 patients in the combination group had received previous bisphosphonate treatment. BAP was significantly more reduced in the monotherapy group at 6 months, with no other remarkable differences for TRACP5b, L-BMD, H-BMD, or FN-BMD during the observation period. CONCLUSIONS The above findings suggest that regardless of ELD addition, MIN potentially improves BMD during 18 months in osteoporosis patients with RA.

The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin. Angiotensin II is probably the most important stimulator of sodium reabsorption. Proximal tubule AT(1A) receptor is crucial for the systemic pressor effect of angiotensin II. In rodents and rabbits, the effect on proximal tubule NBCe1 is biphasic; at low concentration, angiotensin II stimulates NBCe1 via PKC/cAMP/ERK, whereas at high concentration, it inhibits NBCe1 via NO/cGMP/cGKII. In contrast, in human proximal tubule, angiotensin II has a dose-dependent monophasic stimulatory effect via NO/cGMP/ERK. Insulin stimulates the proximal tubule sodium transport, which is IRS2-dependent. We found that in insulin resistance and overt diabetic nephropathy, stimulatory effect of insulin on proximal tubule transport was preserved. Our results suggest that the preserved stimulation of the proximal tubule enhances sodium reabsorption, contributing to the pathogenesis of hypertension with metabolic syndrome. We describe recent findings regarding the role of proximal tubule transport in the regulation of blood pressure, focusing on the effects of angiotensin II and insulin.
Acidosis, Renal Tubular ; Angiotensin II ; Blood Pressure* ; Diabetic Nephropathies ; Homeostasis ; Humans ; Hypertension ; Insulin ; Insulin Resistance ; Kidney Tubules, Proximal ; Plasma Volume ; Rabbits ; Rodentia ; Sodium ; Sodium-Bicarbonate Symporters

OBJECTIVES: The aim of this study was to examine the discontinuation and occurrence of fracture during denosumab treatment in Japanese women with primary osteoporosis or rheumatoid arthritis (RA) with osteoporosis. METHODS: This retrospective study included 143 patients with primary osteoporosis and 96 patients with RA and osteoporosis who were treated with denosumab. Treatment discontinuation, fracture occurrence, lumbar spine (L1–4) bone mineral density (LS-BMD), and bilateral total hip BMD (TH-BMD) were examined before and at 1 and 2 years after treatment commencement. RESULTS: In the primary osteoporosis group, 32 cases dropped out and no fractures occurred from 0 to 1 year. Eighteen cases were lost to follow-up and no fractures were noted from 1 to 2 years. In the RA with osteoporosis group, 7 cases dropped out and no fracture occurred from 0 to 1 year. Twenty-one cases were lost to follow-up and 2 nonvertebral fractures were noted from 1 to 2 years. In this group, 13 cases dropped out from 1 to 2 years and 16 cases dropped out during the 2-year study period due to economic reasons. LS-BMD and TH-BMD values increased continuously for 2 years of treatment in both primary osteoporosis and RA with osteoporosis groups. CONCLUSIONS: These results suggest that during denosumab therapy, the discontinuation rate is expected to remain low during 2 years of treatment in primary osteoporotic patients. In RA patients with osteoporosis, however, the discontinuation rate may increase due to economic reasons from 1 to 2 years of therapy.
Arthritis, Rheumatoid* ; Asian Continental Ancestry Group* ; Bone Density ; Compliance* ; Denosumab* ; Female ; Hip ; Humans ; Lost to Follow-Up ; Osteoporosis* ; Retrospective Studies ; Spine

The purpose of this study was to consider the cause of the prolonged inflammatory reaction that sometimes appears after endovascular stent-graft repair for dissecting aortic aneurysm. Endovascular stent-grafting was performed in 12 patients (11 men and 1 woman, mean age 60±9.8). Endovascular stent-grafting was indicated to close the entry of type B dissections in 10 patients and to exclude ulcer-like projections (ULP) in 2 patients. On the 7th postoperative day (POD), aortography showed no endoleak in 7 type B cases (A-group), remaining endoleak in 3 type B cases (B-group), and complete exclusion in 2 ULP cases (C-group). The value of FDP-E in the A-group was high on the first POD and then decreased gradually. FDP-E also increased up to the 7th POD in the B-group, and increased very slightly after the operation in the C-group. The values of WBC and CRP increased up to the 3rd POD in all groups, but in the A-group it was still high on the 7th POD. On contrast-enhanced CT performed after the procedure and on the 7th POD, edema (over 10mm in thickness) around the descending thoracic aorta was demonstrated in 5 out of 7 cases in the A-group, but in none of the cases in the B- and C-groups. A segmental atelectasis in the left lung was detected in 6 out of 7 cases in the A-group, but in none of the cases in the Band C-groups. In the A-group, endovascular stent-grafting influenced thrombus formation, and the thickened edema around the descending thoracic aorta and the atelectasis produced in the left lung were prominent more than in the other groups. These results suggest that the Inflammation around aortic wall induced by thrombosis in the false lumen, might contribute to the development of the edema around the descending thoracic aorta and the atelectasis in the left lung. We conclude that the inflammatory reaction might have prolonged the postoperative course in the A-group patients.

AIMIn 11 congenital hypogonadal men, the bone mineral density (BMD) values were determined to assess the effect of long-term androgen replacement therapy (ART) on skeletal integrity.

METHODSEleven congenital hypogonadal men, including 8 isolated gonadotropin deficiency patients, 2 Kallmann's syndrome and 1 vanishing testes syndrome were recruited and treated with 250 mg of testosterone enanthate intramuscularly every 4 weeks for 7-43 years (mean+/-SD: 21.5 +/-13 years). In these patients and a group of 10 healthy young men (controls), the whole and trabecular BMDs were examined at the distal end of radius by means of a peripheral quantitative computerized tomography device.

RESULTSThe whole radial BMD in hypogonadal men was significantly less in the patients than in the healthy men (498+/-115 and 725+/-134 mg/cm(3), respectively; P<0.01); the trabecular BMD was also lower in the hypogonadal men (199+/-80 and 375+/-89 mg/cm(3); P< 0.01). The whole radial BMD values in 10 of 11 hypogonadal men were at least 1 SD below the mean value for healthy young men; 2 hypogonadal men had BMD values more than 2.5 SD lower than the healthy mean. Additionally, the whole radial BMD showed a significant negative correlation with the patient's age at the initiation of ART (r = 0.748, P<0.01). The serum level of bone-specific alkaline phosphatase and the urinary level of deoxypyridinoline were not significantly different between the two groups.

CONCLUSIONOsteopenia persists in the hypogonadal men after long-term ART, suggesting that such patients have a persistent defect in bone development not alleviated by androgen replacement.

Adult ; Age Factors ; Bone Density ; drug effects ; Cryptorchidism ; drug therapy ; Hormone Replacement Therapy ; Humans ; Hypogonadism ; congenital ; drug therapy ; physiopathology ; Injections, Intramuscular ; Kallmann Syndrome ; drug therapy ; Male ; Middle Aged ; Reference Values ; Testosterone ; administration & dosage ; analogs & derivatives ; therapeutic use