Resolution of a leg ulcer after hysterectomy for huge uterine myoma

Venous ulcers are the most common type of leg ulcers, accounting for 80% to 90% of cases. We report a large, therapy-resistant ulcer present for three months on the right leg of a 44-year-old woman who also had a huge uterine myoma. Without any other treatment, the leg ulcer regressed spontaneously three months after a hysterectomy for the uterine myoma that had been demonstrated in a CT image to be compressing the right common iliac vein in the pelvis. Uterine myoma can become the cause of venous insufficiency of the leg, when it is big enough to disturb the blood circulation in the pelvis in individuals who have incompetent perforating veins.     

High-concentration (20 mug/g) tacalcitol ointment therapy on refractory psoriasis vulgaris with low response to topical corticosteroids

The efficacy and safety of the application of high-concentration (20 mug/g) tacalcitol ointment once daily for 12 weeks to psoriasis vulgaris lesions which showed low response to topical corticosteroids, were evaluated in a prospective, multicenter, open-label study. Eighty patients were enrolled in the safety analysis of the test drug, and 54 of the 80 patients in the efficacy analysis. The efficacy rate based on the number of cases graded as "moderate improvement" or better in the final global improvement rating of the 54 cases included in the efficacy analysis, was 88.9% (95% CI: 77.4-95.8%). Significant improvement in erythema, thickness, and scaling was observed from 2 weeks of treatment onward (p < 0.001). Five local adverse reactions (2 events of irritation, 2 events of itching, and 1 event of redness) were observed in 3 of the 80 patients included in the safety analysis. There were no significant changes in mean serum calcium values. Tacalcitol 20 mug/g ointment is concluded to be effective and safe for the treatment of refractory psoriasis vulgaris with low response to topical corticosteroids.     

Relationship Between Gelation Rate of Controlled-release Acetaminophen Tablets Containing Polyethylene Oxide and Colonic Drug Release in Dogs

Purpose. We hypothesized that sufficient gelation of orally administered hydrophilic matrix tablets before they reach the colon could, as a result of continuous erosion of the gelated matrix, prevent the decrease in colonic drug release which normally occurs here. The purpose of this study was to elucidate the effect of gelation of hydrophilic matrices containing polyethylene oxide on colonic drug release in dogs using controlled-release (CR) acetaminophen tablets. Methods. Two types of CR tablets were prepared, a slow gelling tablet (SG) and a rapid gelling tablet (RG) containing an extra highly water soluble filler. In vitro and in vivo performance were examined. Results. SG and RG showed similar drug release behavior in vitro. In oral administration to dogs, the two formulations showed similar gastrointestinal transit, reaching the colon within 2–4 h after oral dosing. Further, they showed similar maximum plasma levels (Cmax) and time to Cmax (Tmax). In contrast, however, the two tablets produced different plasma levels from 2 h post-dosing, with plasma levels of RG higher than those of SG and with smaller individual variation. Directly observed colonic drug release behavior of RG was similar to in vitro drug release, whereas that from SG was suppressed. Conclusions. Colonic drug release is closely related to the gelation of hydrophilic matrix, and rapid gelation provides continuous in vivo drug release.     

Scintigraphic evaluation of a novel colon-targeted delivery system (CODES) in healthy volunteers

The purposes of this study are to investigate the gastrointestinal transit and release properties of a novel, colon-targeted delivery system (CODES) administered to healthy volunteers using gamma scintigraphy and to confirm that lactulose functions to promote disintegration in the colon. Two placebo formulations were studied: one was CODES, which consisted of a lactulose containing core overcoated with both Eudragit E and Eudragit L designed to rapidly disintegrate in the colon, the other was lactulose-free reference formulation (LFRF) that consisted of lactulose-free tablet core overcoated with the same materials. Transit and disintegration of the radiolabeled formulations were followed by gamma scintigraphy. In the fasted state, scintigraphic images indicated that CODES started to disintegrate in the ascending colon in the majority of subjects at 7.11 +/- 2.01 h post-dose. Disintegration was complete within 1 h following commencement of in vivo release. In contrast, LFRF presented with prolonged in vivo disintegration properties. In the fed state, the disintegration period of CODES was almost comparable to that observed in the fasted state. Gamma scintigraphic studies clearly showed that CODES provides for rapid target site release in the colon regardless of the ingestion of food.     

Renoprotective effect of triple therapy with low-dose angiotensin receptor blocker,low-dose diuretic and Ca-antagonist in hypertensive type 2 diabetic patients with overt nephropathy

Combination therapy with angiotensin receptor antagonist(ARB) plus angiotensin converting enzyme inhibitor(ACE-I) (ARB/ACE-I) was efficacious in reducing proteinuria in patients with progressive renal disease. However, this therapy may be associated with the worsening of anemia and hyperkalemia. The present study addressed whether or not triple therapy with low-dose ARB, low-dose diuretic (D) and calcium channel blocker(CCB) (ARB/D/CCB) is as effective as therapy with low-dose ARB/ACE-I in retarding the progression of overt diabetic nephropathy. In the triple therapy, the patients were initially subjected to monotherapy with CCB for 24 weeks. Low-dose ARB and low-dose D were added to the treatment for an additional 24-week period. In parallel, patients undergoing double therapy were initially treated with low-dose ACE-I alone for 24 weeks, and then low-dose ARB was added for an additional 24-week period. The results were as follows: 1) In the triple therapy, blood pressure was reduced by 9 mmHg in systole and 5 mmHg in diastole (not significant) compared to monotherapy with CCB. There was a significant decline in proteinuria (3.3 +/- 1.2 g/day in the CCB-treated period vs. 2.1 +/- 1.0 g/day in the ARB/D/CCB-treated period, n = 12, p = 0.0143). Furthermore, a significant improvement in the slope of reciprocal serum creatinine concentration(1/Cr) was found in response to triple therapy(1/Cr: -0.0118 +/- 0.0009 in the CCB-treated vs. -0.0035 +/- 0.0028(I/mg/dl/month) in the ARB/D/CCB-treated period, n = 12, p < 0.001). There was neither a worsening of anemia nor an increase in the serum potassium(K) concentration. 2) In the double therapy, blood pressure was reduced by 12 mmHg in systole(p = 0.0079, n = 11) and 6 mmHg in diastole(n = 11, p = 0.0037) compared to the monotherapy with ACE-I. A significant improvement in the slope of 1/Cr was found in the double therapy(1/Cr: -0.0095 +/- 0.0052 in the ACE-I treated period vs. -0.0029 +/- 0.0028(I/mg/dl/month) in the ARB/ACE-I, n = 11, p < 0.001). In addition, there was a substantial reduction in hematocrit and increase in serum K concentration. The present result suggests that triple therapy consisting of ARB/D/CCB is as efficacious as double therapy with ARB/ACE-I in protecting the kidney from the progression in patients with diabetic overt nephropathy. The former may be expected to have less adverse effects.     

Analysis of tolerance induction using triple chimeric mice: major histocompatibility complex-disparate thymus, hemopoietic cells, and microenvironment

BACKGROUND: Although bone marrow transplantation (BMT) has become a valuable strategy for the treatment of various intractable diseases in recent years, success rates remain low in elderly patients because of low thymic function. We have previously shown that fetal thymus transplantation (TT) with BMT is effective for elderly recipients in mice. METHODS: We performed fully major histocompatibility complex (MHC)-mismatched fetal TT from B6 (H-2) mice plus allogeneic BMT from C3H/HeN (H-2) mice by intra-bone marrow-BMT (IBM-BMT) using congenitally athymic nude (nu/nu) BALB/c (H-2), or BALB/c adult-thymectomized recipients to obtain triple chimeras. We next carried out the IBM-BMT+TT using senescence-accelerated mouse P1 strain (SAMP1) to examine whether this method would be applicable to aging mice. RESULTS: Triple chimeric mice survived for a long period with sufficient T-cell functions comparable to the mice treated with BMT plus MHC-matched TT, whereas those without TT survived for a short period with insufficient T-cell reconstitution. Almost all the hematolymphoid cells were derived from donor bone marrow cells. Interestingly, they showed tolerance to all three types of MHC determinants with donor-derived thymic dendritic cells in TT. Triple chimeric SAMP1 also survived for long periods with T-cell functions restored in contrast to non-TT SAMP1 recipients. CONCLUSION: These findings suggest that third party combined TT with allogeneic IBM-BMT may be more advantageous for elderly recipients with low thymic function, than IBM-BMT alone (without TT).     

Automatic global and regional phase analysis from gated myocardial perfusion SPECT imaging: application to the characterization of ventricular contraction in patients with left bundle branch block

Although many patients with heart failure benefit from cardiac resynchronization therapy (CRT), predicting which patients will respond to CRT remains challenging. Recent evidence suggests that the analysis of mechanical dyssynchrony using gated myocardial perfusion SPECT (MPS) may be an effective tool. The aim of this study was to evaluate global and regional gated MPS dyssynchrony measurements by comparing parameters obtained from patients with a low likelihood (LLk) of conduction abnormalities and coronary artery disease and patients with left bundle branch block (LBBB). METHODS: A total of 86 consecutive patients with LLk and 72 consecutive patients with LBBB, all without prior myocardial infarction or sternotomy, were studied using gated MPS. Global (histogram SD [sigma], bandwidth [beta], and entropy [epsilon]) and regional (wall- and segment-based differences of means [Deltamicro(W) and Deltamicro(S), respectively] or modes [DeltaM(W) and DeltaM(S), respectively]) dyssynchrony measures were calculated by Fourier harmonic phase-angle analysis of local myocardial count variations over the cardiac cycle for each patient, and then unpaired t tests were used to determine which parameters were sex-specific and how well they discriminated between the LLk and LBBB populations. Receiver-operating-characteristic analysis was also performed to calculate the area under the curve (AUC), sensitivity (Ss), specificity (Sp), and optimal threshold (Th). RESULTS: Global parameters were found to be sex-specific, whereas regional differences were sex-independent. All parameters studied showed statistically significant differences between the groups (all global, P < 0.05; all regional, P < 0.0001). Receiver-operating-characteristic analysis yielded higher AUC, Ss, and Sp for epsilon and regional parameters (epsilon: AUC = 0.95/0.96, Ss = 94%/88%, Sp = 89%/91%, and Th = 53.9%/60.6% for women/men; Deltamicro(W): AUC = 0.93, Ss = 88%, Sp = 86%, and Th = 10.5 degrees ; Deltamicro(S): AUC = 0.94, Ss = 90%, Sp = 94%, and Th = 9.2 degrees ; DeltaM(W): AUC = 0.95, Ss = 90%, Sp = 94%, and Th = 15 degrees ; and DeltaM(S): AUC = 0.95, Ss = 88%, Sp = 90%, and Th = 10.5 degrees ) than for global parameters (sigma: AUC = 0.75/0.67, Ss = 81%/66%, Sp = 63%/64%, and Th = 16.5 degrees /22.2 degrees for women/men; beta: AUC = 0.80/0.72, Ss = 71%/71%, Sp = 79%/64%, and Th = 69 degrees /81 degrees for women/men). CONCLUSION: The computed parameters all discriminate effectively between LLk and LBBB populations. Measurements that are less dependent on the shape of the phase-angle distribution histogram provided higher sensitivity and specificity for this purpose. Further study is needed to evaluate these parameters for the purpose of predicting response to CRT.     

Crossed forelimb extension produced in thalamic cats by injection of putative transmitter substances into the paralemniscal pontine reticular formation

To analyze the descending pathways of the paralemniscal pontine reticular formation (PLRF), a technique was used for the selective activation of cell bodies by localized injection of putative neurotransmitters in the PLRF. When a small amount (less than 0.1 microliter) of 0.1 M glutamate was injected into the PLRF unilaterally in thalamic cats, the forelimb contralateral (c-forelimb) to the injection was extended, and occasionally the ipsilateral forelimb was flexed. These responses were similar to those obtained by electrical stimulation of the PLRF, but were relatively weaker. Unit spikes of PLRF neurons were increased in frequency following administration of glutamate. The latent periods and durations of increases in spike frequency varied depending on the concentration and quantity of the glutamate solution, and were roughly similar to those of the extensor EMG in the c-forelimb. Since the firing of PLRF neurons preceded the EMG with 11 ms latency, the unit spike of PLRF neurons could be used as a triggering signal to observe a spike triggered averaged EMG response in the extensor muscle of the c-forelimb. Results similar to those with glutamate were observed upon administration of quisqualate, kainate and aspartate. The most effective compound was quisqualate. Application to the PLRF of 1-naphthylacetyl spermine (1-NA-Spm), an analogue of the natural spider toxin JSTX-3 and an antagonist of glutamate, suppressed both the PLRF neuron activity and the extensor EMG of the c-forelimb. These observations suggest that extensor muscles of the forelimb are excited by the contralateral PLRF, perhaps via the crossed reticulospinal tract from the PLRF. PLRF neurons may be activated by glutamate (quisqualate) receptors.