Optimum pain relief with continuous epidural infusion of local anesthetics shortens the duration of zoster-associated pain

OBJECTIVE: To investigate effects of continuous epidural infusion (CEI) of 0.5% bupivacaine added to intermittent epidural boluses (IEB) on the duration of zoster-associated pain (ZAP), as compared with continuous infusion of normal saline placebo added to IEB. DESIGN: A prospective, double-blind, randomized, placebo-controlled study. SETTING: A university hospital and an affiliated clinic in Japan from 1996 through 1999. PATIENTS: 56 immunocompetent herpes zoster (HZ) patients, 50 years or older, within 10 days of rash onset and with severe pain and eruption. INTERVENTIONS: Patients were hospitalized and randomly allocated into 2 groups. CEI group given CEI of 0.5% bupivacaine (0.5-1.0 mL/h) plus IEB of 0.5% bupivacaine 4 times daily (n = 29). IEB group given normal saline infusion plus IEB of 0.5% bupivacaine 4 times daily (n = 27). All patients received oral acyclovir 800 mg, 5 times daily, for 7 days. OUTCOME MEASURES: The number of days required for complete cessation of ZAP and the proportion of subjects with allodynia beyond 30 days. RESULTS: The median time to cessation of ZAP was significantly shorter in the CEI group than in the IEB group (29 days vs. 40 days, P = 0.002). The number of patients whose allodynia persisted beyond 30 days of treatment was significantly lower in the CEI group than in the IEB group (10% vs. 37%, P = 0.027). CONCLUSIONS: CEI of 0.5% bupivacaine plus IEB was associated with a shorter duration of ZAP and fewer patients with allodynia beyond 30 days, compared with IEB plus normal saline infusion. Patients at high risk for developing postherpetic neuralgia (PHN) can be managed with intensive therapies at the early stage of disease, such as CEI, which maintains effective analgesia and may reduce the burden of PHN.     

Clinical characteristics relevant to myocardial cell apoptosis: analysis of pericardial fluid

We investigated the pro-apoptotic potential of pericardial fluids from patients with different clinical conditions on cultured neonatal rat cardiomyocytes. Pericardial fluids were obtained during open heart surgery from 88 patients with ischemic heart disease (n=44), valvular heart disease (n=32), or aortic disease (n=12). The terminal deoxynucleotidyl transfer-mediated end labeling fragmented nuclei assay was performed on primary cardiac myocytes from neonatal rats in the presence of 1% pericardial fluid from each patient. We evaluated relations between these patients' clinical characteristics and the extent of myocardial cell apoptosis. Induction of myocardial cell apoptosis by pericardial fluids was observed in 29 of the 88 patients (33.0%). The prevalence of myocardial cell apoptosis was significantly influenced by diabetes mellitus (DM) (53.6% with vs. 23.3% without, P<0.005), acute coronary syndrome (ACS) (64.7% with vs. 25.4% without, P<0.005), and poor left ventricular systolic function (60.0% with vs. 25.0% without, P<0.005). Multivariate stepwise logistic regression analysis revealed that the presence of DM, ACS, and poor left systolic function were significant predictors of myocardial cell apoptosis. DM, ACS and left ventricular dysfunction may play important roles in the pathogenesis of myocardial cell apoptosis in the clinical setting.     

Graciloplasty for internal and external sphincteric resection of lower rectal cancer

Anal sphincteric resection for rectal cancer is most commonly followed by colostomy in the lower abdominal wall, which enforces quite a poor quality of life due to a permanent stoma. For surgeons treating lower rectal cancer, the goal is to achieve defecation via the anus without placing a stoma. Internal sphincteric resection, partial external sphincteric resection and coloanal anastomosis have been reported for the treatment of lower rectal cancer with avoiding a colostoma. Extended resection of the external sphincter, however, limits patient's daily activities because of poor functional results and necessitates reconstruction of damaged anal function. This paper describes a case of graciloplasty for postoperative anal dysfunction that yielded a good clinical outcome in a 65-year-old female who had undergone very low anterior resection with complete internal and partial external sphincteric resection for lower rectal cancer.     

Increased aqueous flare intensity in eyes with liquefied after-cataract

PURPOSE: To describe aqueous flare intensity in eyes with white liquefied after-cataract. SETTING: Department of Ophthalmology, Toyama Medical and Pharmaceutical University, Toyama, Japan. METHODS: Seven patients with unilateral liquefied after-cataract and another 10 unaffected patients with an intraocular lens (IOL) were examined. The eyes were divided into 3 groups. The first group was composed of 7 eyes with liquefied after-cataract. The second group included the fellow eyes of the patients with unilateral liquefied after-cataract; 4 had an IOL, and 3 had cataract. The third group included 10 additional eyes without liquefied after-cataract. All patients underwent cataract operations consisting of phacoemulsification/aspiration with continuous curvilinear capsulorhexis and acrylic IOL implantation in the capsular bag. Aqueous flare was measured using a laser flare-cell meter. RESULTS: The mean +/- SD of aqueous flare intensity was significantly higher in the first group (11.8 +/- 1.8 photon counts/msec) than in the second group (6.4 +/- 0.8 photon counts/msec) and in the third group (6.3 +/- 0.7 photon counts/msec). CONCLUSION: It is possible that liquefaction of after-cataract and disruption of the blood-aqueous barrier may be related.     

Synthesis of novel 26-substituted milbemycin A4 derivatives and their acaricidal activities

A series of novel 26-substituted milbemycin A4 derivatives was synthesized from 5-O-t-butyldimethylsilyl-26-hydroxymilbemycin A4 prepared by selenium dioxide oxidation of 5-O-t-butyldimethylsilyl-milbemycin A4. Their acaricidal activities were assessed against the organophosphorus-sensitive two-spotted spider mite (Tetranychus urticae) on the primary leaves of cowpea plants (Vigna sinesis Savi species) by spraying.     

Inhibition of P-glycoprotein function by tea catechins in KB-C2 cells

We studied the effects of tea catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG) on the P-glycoprotein (P-gp) function in multidrug-resistant P-gp over-expressing KB-C2 cells. EC did not have any effects on cellular accumulation of P-gp substrates, rhodamine-123 and daunorubicin, but the other catechins increased the accumulation in the order of EGC < ECG < EGCG. The effects of EGCG were larger than those of verapamil and quercetin. Since these catechins inhibited the efflux of P-gp substrates, the elevation of substrate accumulation seemed to be induced by the inhibition of the efflux transporter. The results showed that the inhibitory effects of the catechins did not depend on their total hydrophobicity, but significantly depended on their chemical structure. The presence of the galloyl moiety on the C-ring markedly increased the n-octanol/PBS partition coefficients of the catechins and their activity on P-gp. On the other hand, the presence of the trihydric pyrogallol group as the B-ring decreased the partition coefficients but increased the activity on P-gp, compared with the action of the corresponding catechins with a dihydric catechol B-ring.     

Extracellular ATP inhibits apoptosis and maintains cell viability by inducing autocrine production of interleukin-4 in a myeloid progenitor cell line

Interleukin-3 (IL-3)-dependent myeloid progenitor cell FDC.P2 is induced to undergo apoptotic cell death upon IL-3 depletion. Extracellular adenosine triphosphate (ATP) was found to prevent apoptosis and maintain cell viability of FDC.P2 cells upon IL-3 withdrawal. The antiapoptotic effect of ATP required extracellular Ca2+. Furthermore, FK506, a specific inhibitor of calcium/calmodulin-dependent protein phosphatase calcineurin, inhibited the antiapoptotic effect of ATP. As one of cytokines whose expression is dependent on the activation of calcineurin, interleukin-4 (IL-4) played a critical role in ATP-mediated cell survival of FDC.P2 cells because neutralizing antibody against IL-4 effectively abrogated the antiapoptotic activity of ATP. Moreover, ATP treatment induced a significant amount of secreted IL-4 that was sufficient to maintain cell viability. Taken together, our present results demonstrate that extracellular ATP triggers autocrine production of IL-4 through calcium-dependent activation of calcineurin and secreted IL-4 substitutes IL-3 in protecting FDC.P2 cells from apoptosis even in the absence of IL-3.