Effect of flumazenil on hypoglossal and phrenic nerves activities in rabbits

BACKGROUND: Upper airway obstruction and inadequate ventilation often arise during sedation and anesthesia by benzodiazepines (Bz). Flumazenil antagonizes these effects of active benzodiazepines on the central nervous system. To estimate the influence of flumazenil on the endogenous Bz system related respiratory control, we studied the effect of flumazenil and diazepam on the neural activity and the respiratory response caused by a brief (60 sec) respiratory arrest (RA) manifested in the hypoglossal nerve (HG) and the phrenic nerve (PH) activities in rabbits. METHODS: Experiments were performed on adult rabbits which were vagotomized, paralyzed and artificially ventilated with 50% N2O, 50% oxygen and 0.5% sevoflurane. We evaluated and compared the effects of the sequential administrations of flumazenil and diazepam on the peak amplitude (AMP) as well as the root mean square (RMS) of HG and PH, and respiratory cycle (Tc). RESULTS: Flumazenil by itself increased HG activity more than PH activity with no influence on Tc. But it was not dose-related. Previous administration of flumazenil in total dose of 0.25 mg x kg(-1) could not prevent the anticipated respiratory depression caused by diazepam 2.0 mg x kg(-1). These depressions are greater in HG activity than in PH activity. Additional flumazenil 0.15 mg x kg(-1) following the administration of diazepam promptly reversed these inhibitory effects on HG activity beyond the control level. The same dose of flumazenil, however, did not reverse PH activity sufficiently. RA response was characterized by raised AMPs and augmented RMSs (deltaAMPs, deltaRMSs) with marked prolongation in Tc (deltaTc). Flumazenil and diazepam did not seem to have any influence upon these RA responses. There was a significant change in cardiovascular parameters with the tested dosages of flumazenil and diazepam, but the change was in the normal physiological range. CONCLUSIONS: These results suggest the possibility that the endogenous benzodiazepine system is likely to play an inhibitory role in the regulation of respiration, especially in the maintenance of upper airway patency but the system is unrelated to the chemosensitive-respiratory control.     

Primary cardiac malignant lymphoma diagnosed intraoperatively during aortic valve repair; report of a case

A 58-year-old male who complained of chest oppression on effort was diagnosed as aortic regurgitation by echocardiography. The cardiac catheterization was showed moderate aortic regurgitation. He was referred to our hospital for aortic valve replacement. We considered preoperatively that the aortic regurgitation is due to infective endocarditis or aortitis syndrome. We have not noticed cardiac tumor at all until aortic valve replacement. Postoperative pathological diagnosis of the tumor was malignant lymphoma. The tumor had a characteristic architecture of a cardiac MICE (mesothelial/monocytic incidental cardiac excrescence). After the operation, additional chemotherapy using doxorubicin and cysplatin was performed. The patient has been doing well for 5 years after operation.     

Implementation of a common clinical path for transurethral resection of prostate (TURP) in multiple hospitals

PURPOSE: To investigate the length of hospitalization and medical charges when a common clinical path for TURP (transurethral resection of prostate) was implemented in multiple hospitals. PATIENTS AND METHODS: This study included 310 patients in 2001 and 298 in 2002, who were diagnosed with benign prostatic hyperplasia and who underwent TURP in seven hospitals in Japan. While the patients were treated according to the managing methods of each hospital in 2001, the patients were managed using a common clinical path in 2002, on which we conferred and established in 2001. We investigated the change of various outcome indicators before and after implementation of the common clinical path. RESULTS: The background of patients and surgical outcome in 2002 were equal to those in 2001, except in incidence of preoperative urinary tract infection, general anesthesia and blood transfusion, and number of surgeons. Implementation of a common clinical path shortened the pre- and postoperative hospital stay, duration of bed rest, administration of antibiotics and Foley catheter indwelling, and reduced the standard deviation of these indicators. The total medical charge decreased from 515,439 to 491,935 yen. However, outcomes were considerably different among the seven hospitals. Multivariate analyses identified the hospitals, cognitive impairment, preoperative indwelling catheter and preoperative variance as the factors affecting preoperative hospital stay, and the hospitals, co-existing disease, blood transfusion, postoperative urinary tract infection and postoperative variance as factors affecting postoperative stay. Based on these analyses, we determined four exclusion criteria against using a common clinical path: 1) patients requiring examination or surgery other than TURP simultaneously, 2) patients whose ADL disturbance, cognitive impairment, past history and/or coexisting disease are expected to affect postoperative convalescence, 3) patients with a preoperative indwelling catheter just before operation, and 4) patients with preoperative urinary tract infection. By excluding 122 (39.4%) and 129 (43.3%) patients fulfilling the above criteria in 2001 and 2002, respectively, there were reduction in the length of pre- and postoperative hospital stay, and the total admission fee. Furthermore, there were decrease in their standard deviations. CONCLUSIONS: A common clinical path was valid for reducing variance of the critical indicators affecting the clinical course of TURP and shortening the pre- and postoperative stay in the multiple hospitals. It is mandatory to establish the standard perioperative management for TURP from the viewpoint of urologists, under the circumstances of the impending introduction of the Diagnosis Procedure Combination (DPC).     

Reference ranges of total serum and free testosterone in Japanese male adults

PURPOSE: To establish reference range of serum Total Testosterone (T-T) and Free Testosterone (F-T) in Japanese male adults. SUBJECTS AND METHOD: Among 1,172 male adults, who daily lived their healthy life, 1,143 subjects in the year range from 20 to 77 years old, who had serum LH concentration within its reference range (For 20-70 years old: 1.1-25.9 mIU/mL), were selected. As diurnal rhythm of both T-T and F-T was observed, blood samples were collected in the morning when T-T and F-T concentration were relatively stable at their high concentration levels. The collected samples were stored at -20 degree C until they were used for assays. RESULTS: Reference range for T-T has decided to express by the mean +/- 2SD calculated from the entire test results, because influence of aging on the results was negligible, Reference range of T-T has established as 2.01-7.50 ng/mL. The other hand, reference ranges of F-T classified for every decade have decided to express by the mean +/- 2SD of each decade subgroup, because great influence of aging on F-T was observed. For each decade from 20 years on and > 70 years, reference ranges of F-T have established as: 8.5-27.9 pg/mL, 7.6-23.1 pg/mL, 7.7-21.6 pg/mL, 6.9-18.4 pg/mL, 5.4-16.7 pg/mL, and 4.5-13.8 pg/ mL, respectively. Conclusion: Reference ranges of serum T-T and F-T in Japanese male adults have established. And the value of Young Adult Mean (YAM) of F-T calculated for a group of the ages between 20 and 39 years have been proposed as a guideline of requirement for the Androgen Replacement Therapy (HRT). The value of 80% and 70% of YAM were 12.4 pg/mL and 10.9 pg/mL, respectively.     

Change in parameters before and after alpha-1-blocker therapy for men with lower urinary tract symptoms using color doppler ultrasound urodynamics: possible application for prediction of clinical outcome

INTRODUCTION: We previously developed a noninvasive video urodynamic study using color Doppler ultrasonography. We sought the best flow velocity-related parameter which would allow prediction of an improvement in lower urinary tract symptoms (LUTS) after alpha 1-blocker treatment. METHODS: Twenty-two men with benign prostatic hyperplasia who were treated with a nonselective alpha 1-blocker (urapidil) were included. Subjective symptoms were evaluated using the International Prostate Symptom Score (IPSS) before and after alpha 1-blocker treatment. We measured the flow velocities using a transperineal ultrasound technique in the distal prostatic urethra just proximal to the external urethral sphincter (V1) and in the sphincteric urethra (V2), and used them to obtain the velocity ratio (VR=V1/V2). The corresponding functional cross-sectional areas of the urethra at these two sites (A1 and A2) were calculated as Q(max)/V. All these parameters obtained by the velocity-flow urodynamics were compared before treatment and after 4 weeks. RESULTS: After treatment, V1 and VR were decreased, and A1 was increased. V2 correlated best with the change in IPSS before and after alpha 1-blocker therapy, with Spearman's rho of 0.584. All men with V2 exceeding 50 cm/s did not show an improvement in the LUTS. CONCLUSIONS: The maximum flow velocity at the sphincteric urethra (V2) can predict the subjective outcome of alpha 1-blocker treatment. The velocity-flow parameters changed after alpha 1-blocker treatment. We confirmed that the transperineal ultrasound urodynamic study is not only noninvasive but also informative.     

A Case of Graft Infection 10 Years After Ascending Aorta Replacement

A 52-year-old man was admitted with anemia and slight fever, which he had for the last 2 months. He had undergone replacement of the ascending aorta for acute aortic dissection 10 years previously. Echocardiography demonstrated a flailing thin structure in the anterior wall of the ascending aorta corresponding to the proximal portion of the prosthetic graft. This abnormal echocardiographic finding led us to repeat blood cultivation. We finally detected Enterococcus facium and Staphilococcus epidermidis in his blood sample. We diagnosed this as a graft infection and prepared for surgical re-replacement of the infected graft. While he was waiting for the operation, an infectious aneurysm of a tibialis posterior artery ruptured and an emergency operation was done. Replacement of the infected ascending aorta graft was done thereafter. In surgery, 2-cm-long vegetation was found. It stuck to the graft wall near the former hole used for air removal in the first surgery. The patient recovered fully and left our hospital after 3 months of postoperative antibiotics therapy. This rare case of aortic graft infection long after the original replacement surgery suggests the importance of thorough echocardiographic investigation of prosthetic graft infection as a possible cause of fever of unknown origin.     

Bone mass increase specific to the female in a line of transgenic mice overexpressing human osteoblast stimulating factor-1

We have reported that transgenic mice overexpressing human osteoblast stimulating factor-1 (osf1) under the control of the human osteocalcin promoter have a significantly higher bone mineral content and density than nontransgenic littermates. Consequently, bone mass loss due to estrogen deficiency was compensated for in ovariectomized female mice. Here, we show that in this transgenic line, the bone mass increase was evident in female, but not male, mice, as evaluated using the ash assay, double-emission X-ray analysis, and calcein double-labeling to determine the bone formation rate. To elucidate a possible influence on gene expression, we analyzed genomic structures of the inserted transgene and its flanking regions in mouse chromosomes. The results revealed that the transgene was integrated in the mouse repetitive sequences, 234-bp-long -satellite repeats, as inverted multiple (5 + 8) copies. Twelve copies at most seemed to be functional, but no direct evidence supporting female-specific mRNA synthesis of the transgene was obtained.     

Effect of interferon-alpha on chromosome abnormalities in treated chronic myelogenous leukemia patients

To investigate the relationship of chromosomal aberrations at blastic crisis (BC) in chronic myelogenous leukemia (CML), with previous therapies and with atomic bomb (AB) exposure, we studied 114 CML patients who developed BC, including 23 AB survivors in Hiroshima. In total, only 45.6% showed major-route abnormalities, which figure was far lower than those previously reported, implying possibility of geographical difference. Occurrence of major-route abnormality was not associated with either duration of chronic phase or survival time after BC. Patients treated with interferon-alpha (IFNalpha) showed lower frequency of major-route abnormalities and lower number of abnormal chromosomes than did patients treated with busulfan (Bu). The frequency of trisomy 8 was lower and monosomy 7 was higher in IFNalpha-treated than in Bu-treated patients. The frequency of unusual abnormalities at BC in IFNalpha-treated patients was indistinguishable from those in Bu-treated patients and, notably, a more common (40%) feature in IFNalpha-treated patients was no change in the cytogenetic picture. Thus, we conclude that IFNalpha action on chromosome aberration is basically quite neutral and that IFNalpha does not induce any specific aberrations, including unusual ones at BC, with an exception of deletion of chromosome 7. Atomic bomb exposure status did not make any difference in secondary abnormalities at BC.     

Evaluation of groEL gene analysis for identification of Borrelia burgdorferi sensu lato

The nucleotide sequences of the groEL genes, the flagellin genes, and the 16S rRNA genes from 22 reference strains of Borrelia were compared. groEL sequence analysis is useful not only in interspecies differentiation but also in intraspecies differentiation of Borrelia afzelii and Borrelia garinii isolates.