Treatment of advanced bladder cancer with intra-arterial infusion of cisplatinum (CDDP) and aclacinomycin (ACR), combined with angiotensin II

Ten patients with advanced bladder cancer were treated with intra-arterial infusion therapy. The patients consisted of nine males and one female between 55 and 82 years old (median: 70 years). In all patients, cisplatinum (CDDP) (2 mg/kg), aclacinomycin (ACR) (0.5 mg/kg) and Angiotensin II (25 mg) were infused via the internal iliac artery for a period of about 30 minutes. Seven patients also received X-ray therapy with a linac. The efficacy of this therapy was assessed by computed tomographic scanning, sonography and cystoscopy. As a result of this assessment, 2 patients were rated complete response "(CR)", 6 partial response (PR) (showing 50% or more reduction in the lesion) and 2 no change "(NC)". To compare the efficacy of this therapy for two histopathologically defined groups of patients (patients with grades 2 and 3 cancer), one patient was rated "CR", four "PR" and two "NC" in the grade 3 group (total 7 patients), while one was rated "CR" and two "PR", in the grade 2 group (total 3 patients). In effective cases, pollakiuria and miction pain disappeared shortly following intra-arterial infusion therapy. As for side effects of the therapy, mild nausea or vomiting was observed in all patients, while leukopenia was noted in one patient.     

Can random bladder biopsies be eliminated after bacillus Calmette–Guérin therapy against carcinoma in situ?

Purpose

Intravesical bacillus Calmette–Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy.

Methods

We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens.

Results

According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p?=?0.116, and p?<?0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%.

Conclusion

RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).

     

Combined treatment with vitamin k2 and bisphosphonate in postmenopausal women with osteoporosis

Vitamin K2, as well as bisphosphonates, such as etidronate, alendronate, and risedronate, is widely used in the treatment with osteoporosis in Japan. Etidronate increases the lumbar bone mineral density (BMD), and prevents new vertebral fractures, in patients with osteoporosis, while alendronate and risedronate increase the lumbar and femoral neck BMDs, and prevent new vertebral and femoral neck fractures. Vitamin K2 enhances gamma-carboxylation of bone glutamic acid residues and the secretion of osteocalcin, sustains the lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis. Bisphosphonates, such as alendronate and risedronate, rather than vitamin K2, should be initially chosen for the treatment of osteoporosis, because they are more efficacious than vitamin K2. Available evidence suggest that risedronate prevents deterioration of the connectivity of the trabeculae in ovariectomized rats, whereas vitamin K2 increase the trabecular thickness, and that a combination of risedronate and vitamin K2 has a synergistic effect on preventing the deterioration of trabecular bone architecture induced by estrogen deficiency. Some studies have shown that combined treatment with etidronate and vitamin K2 appears to be more effective than etidronate alone in the prevention of new osteoporotic vertebral fractures. Based on these findings, combined treatment with vitamin K2 and bisphosphonates may be more efficacious in the prevention new vertebral fractures than a single treatment with bisphosphonate in postmenopausal women with osteoporosis. Thus, this combined treatment should be recommended for the treatment of postmenopausal osteoporosis. It is proposed that the role of vitamin K2 should be emphasized, when used in combination with bisphosphonates, especially in patients with vitamin K deficiency.     

Acoustic evaluation of postoperative hoarseness in adult patients

The present study was performed to evaluate postoperative hoarseness quantitatively by means of acoustic wave form analysis. Pitch and amplitude perturbation (PPQ, and APQ), and normalized noise energy (NNE) were measured along with the frequency characteristics in 51 adult patients undergoing elective surgery. The normal values for these acoustic parameters were less than 0.5%, less than 2.0%, and less than -10 dB, respectively. Vowel sound "E" was recorded and evaluated before the induction of anesthesia and on the morning of the day after the surgery. PPQ increased from 0.39% to 1.00% (P less than 0.05), APQ increased from 3.34% to 6.62% (P less than 0.05), and NNE increased from -9.19 dB to -4.74 dB (P less than 0.05). Eighteen percent of the patients showed abnormal values in all parameters preoperatively, but 45% of the patients postoperatively (P less than 0.05). These findings suggest that even the short term intubation resulted in the postoperative hoarseness, and this method is a useful and non-invasive bed-side test to evaluate postoperative hoarseness quantitatively.     

Experimental and clinical evaluation of the splenic capping method in the treatment of injured spleens

Polyglycolic acid elastic mesh was tailored and wrapped around the entire surface of experimentally injured spleens in 11 dogs, while carefully avoiding the splenic hilum, like a "hair-net", to achieve complete hemostasis by compression. All 11 dogs survived the experiment with no postoperative bleeding observed. Histological examination, performed 6 weeks postoperatively, revealed histiocytes, fibroblastic proliferation with collagen and cellular collagenized fibrous tissue forming a neocapsule covering the spleen. Hematologically, the platelet count was increased at 2 weeks postoperatively, but subsequently decreased to within the normal levels by 4 weeks. We employed this splenic capping method clinically in four cases to avoid splenectomy and sufficient hemostasis with ultimate splenic recovery was achieved in each case without any abscess formation, postoperative bleeding, or complications related to the use of the mesh. These experimental and clinical results thus indicate the efficacy and safety of the splenic capping method for preserving the injured spleen.     

Assessment of high-energy phosphorus compounds in the rat kidney by in situ31P nuclear magnetic resonance spectroscopy: effect of ischemia and furosemide

Summary ³¹P nuclear magnetic resonance (NMR) spectroscopy of the in situ rat kidney was performed by a surface coil method, and the effects of ischemia and furosemide infusion were assessed.³¹P NMR spectra of the kidney subjected to 30 min of ischemia returned completely to the pre-ischemic level after 60 min of reperfusion. But the³¹P NMR spectra after 60 min of ischemia did not recover, even after 120 min of reperfusion. Levels of -ATP and inorganic phosphate (Pi) decreased and the chemical shift of Pi increased after intravenous infusion of furosemide. This increase in chemical shift might signal an alkalotic change in intracellular pH. Furosemide infusion prior to ischemia is thought to protect the kidney from injury induced by 60 min of warm ischemia. The chemical shift of Pi returned to the pre-ischemic level earlier than -ATP and Pi. In conclusion, according to the findings of³¹P NMR spectroscopy, furosemide infusion prior to ischemia may be effective in protecting the kidney against ischemic injury. But the change in Pi peak and the causes of the dissociation of Pi and -ATP should be examined further.     

Pharmacological effects of concomitant administration of β-adrenoceptor blocker and agonist in normal subjects: characterization by heart rate response to exercise

The effects of a combination regimen of metoprolol and ₁-adrenoceptor agonist denopamine on resting and exercise heart rate have been studied in 10 normal volunteers. Maximal ramp upright bicycle exercise was performed three times at 1-week intervals. Two hours before each exercise test, 5 mg metoprolol plus 20 mg denopamine, 5 mg metoprolol plus a denopamine placebo, or two placebos were orally administered in a double-blind fashion.During exercise after placebo administration, heart rate increased in parallel with the exercise intensity. Compared to the placebo values, resting heart rate was significantly decreased by an average of 10 beats · min^–1 by 5 mg metoprolol, whereas it was not altered by the combination regimen. During exercise, however, both the combination regimen and metoprolol alone showed a significant negative chronotropic effect, decreasing peak exercise heart rate by an average of 14 and 21 beats · min^–1, respectively. Peak oxygen uptake was also significantly decreased by both regimens.We conclude that concomitant administration of 5 mg metoprolol and 20 mg denopamine exerts an effective -adrenoceptor blocking action during exercise but a minimal effect at rest in normal subjects. The combination regimen appears to have a favourable pharmacological profile for -adrenoceptor blocker therapy in patients with chronic heart failure.     

Two-dimensional photon counting imaging and spatiotemporal characterization of ultraweak photon emission from a rat's brain in vivo

The process of metabolic reactions within living cells leads to spontaneous ultraweak light emission. The development of a system for highly sensitive imaging and spatiotemporal analysis of ultraweak photon emission from a rat's brain is reported in this paper. The equipment used in this experiment consists of a two-dimensional photon-counting tube with a photocathode measuring 40 mm in diameter, a highly efficient lens system, and an electronic device to record time series of a photoelectron train with spatial information. The sensitivity and ability to extract spatiotemporal information from sequential data of a single photoelectron train were examined. The minimum detectable radiant flux density of the system was experimentally estimated to be 9.9 x 10(-17) W/cm2 with a 1-s observation time. Spontaneous photon emission was demonstrated from an exposed rat's cortex in vivo without adding any chemical agent or employing external excitation. An image of ultraweak photon emission was compared with one obtained after cardiac arrest. The intensity after cardiac arrest was depressed to approximately 60% of before that. The regional properties of time courses of emission intensity were also demonstrated, indicating the potential usefulness for spatiotemporal characterization of photon emission with mapping of physiological information such as oxidative stress. This technology constitutes a novel method, with the potential to extract pathophysiological information from the central nervous system.     

Fractal dimensions in the occurrence of miniature end-plate potential in a vertebrate neuromuscular junction

1. Occurrence of miniature endplate potentials (MEPP) in the sartorius muscle of Rana catesbiana in high Mg2+ Ringer solution were observed in standard intracellular recording. Intervals and amplitudes of sequentially occurring MEPP were registered and analyzed. 2. Interval histograms of a time series of MEPP showed exponential-like pattern as reported in the classical study by Fatt and Katz (1952). The cumulative distribution of the intervals plotted in logarithmic axes showed two distinct phases. In shorter intervals (< 1s), curve along exponential decay was observed, and in longer intervals (> or = 1s) linear decay can be seen. The latter power-law relation gave dimensions of 4.111 +/- 0.812 (mean and S.D.). Self-similarity in longer range implies a time-scale invariant nature and may suggest fractal nature in restoration process of synaptic vesicles, while exponential decay in the short time interval range implies random release of transmitter packet from the readily releasable pool. 3. Fluctuation of amplitudes in sequentially occurred MEPP were analyzed according to Higuchi's cumulative route-length analysis. The estimates for sequential amplitude curve showed the power-law relation in a logarithmic plot whose inclination (= D) estimated with linear regression analysis was 1.996 +/- 0.007 (mean and S.D.). This results indicate that fluctuation in the amplitude of MEPP shows possible maximum complexity as a graphic curve in 2-D plane. Similar result was obtained for fluctuation of intervals of successively occurring MEPP.