Pancreatic pseudocysts drained through a percutaneous transgastric approach: further experience

Percutaneous transgastric placement of a drainage catheter under ultrasonographic and fluoroscopic guidance was performed in 12 patients with pancreatic pseudocysts. Complete resolution of the pseudocysts was obtained in eight patients, and the result was indeterminate in one patient due to early death from unrelated causes. Surgical intervention followed in two patients, one with a multiloculated pseudocyst that was incompletely drained and another with a pseudocyst that became infected following drainage. In one patient with metastatic tumor to the head of the pancreas the pseudocyst resolved initially, but a pseudocyst later recurred. There were no pancreaticocutaneous fistulas or other major complications. The transgastric route of pseudocyst drainage is safe and effective, and it offers a low risk of recurrence and fistula formation.     

Peptide-induced deletion of CD8 T cells in vivo occurs via apoptosis in situ

The ultimate fate of T cells undergoing antigen-induced cell death in vivo remains controversial. Whereas apoptosis of CD4+ T cells driven by superantigen is readily detectable in lymphoid organs, CD8+ T cells have been reported to disappear from the lymphoid organs and accumulate in the liver where they undergo apoptosis. Using transgenic mice that produce large numbers of ovalbumin-specific CD8+ T cells (OT-I cells), we were able to investigate the events that follow soluble peptide administration in an independent CD8+ T cell system. Here we show that the OT-I cells undergo proliferation and apoptosis in situ in lymphoid organs in response to antigenic stimulation with no evidence for liver involvement. This is similar to the course of events found for CD4+ T cell activation and counters the view that the liver is a general site for CD8+ T cell clearance following antigen-specific activation.      

Bone marrow transplantation for refractory acute leukemia in 34 patients with identical twins

Thirty-four patients aged 4-67 yr (median 17) with acute lymphocytic leukemia (ALL) (18 patients) or acute nonlymphocytic leukemia (ANL) (16 patients) who failed to enter complete remission (CR) or relapsed on conventional chemotherapy were treated with cyclophosphamide (CY), 60 mg/kg/day for 2 days, 1000 rad total body irradiation, and a marrow transplant from a genotypically identical normal twin. Sixteen of the patients received additional chemotherapy within the week before CY. After the transplant, 23 patients received immunotherapy consisting of killed autologous leukemic cells and/or normal twin peripheral blood lymphocytes, 16 as part of a prospectively randomized study. One moribund patient died before engraftment. Nine patients (6 ALL, 3 ANL) continued to have detectable leukemic cells. Twenty-four patients (70%) achieved CR. One of them died of viral hepatitis at 1 mo and another of viral interstitial pneumonitis at 4 mo in CR. Fourteen patients (7 ALL, 7 ANL) relapsed 2-16 mo (median 4) after transplantation. However, 8 patients (24%) (3 ALL, 5 ANL) remain in CR without any maintenance chemotherapy at 29-103 mo (median 80) after the transplant. The end results were not signficantly influenced by the type of leukemia, the immediated pre-CY chemotherapy, or the immunotherapy. The results show that this approach, even when applied to endstage patients with acute leukemia in relapse, causes tolerable morbidity, rare nonleukemic deaths, and frequent remissions, some of which represent cures.     

Association between hepatitis B surface antibody seropositivity and coronary artery disease

BACKGROUND: Specific infectious agents have been found to be related to the pathogenesis of coronary atherosclerosis. AIMS: We assessed the possible association between angiographically proven coronary artery disease (CAD) and hepatitis B surface antibody (HBS Ab) seropositivity in a population with relatively high prevalence of hepatitis B virus (HBV) infection. SETTING AND DESIGN: This was a cross-sectional study. MATERIALS AND METHODS: We analyzed data from 830 consecutive subjects undergoing coronary angiography, including angiographic results reported by two cardiologists for inter-observer reliability and assessment of HBS Ab status determined by enzyme-linked immunosorbent assay (ELISA). STATISTICAL ANALYSIS USED: Chi-square test or Fisher's exact test, independent two-sample t test and the Pearson's Correlation Coefficient test were used, as required. Statistics were performed using SPSS software version 13 (SPSS, Chicago, IL). RESULTS: Two hundred forty-nine (30%) subjects had normal angiogram or minimal CAD, and 581 (70%) had significant CAD in at least one major coronary artery. In patients with CAD and in patients without angiographic evidence of significant atherosclerosis, 28.7% and 28.9% respectively were positive for HBV (P=0.954). Mean C-reactive protein levels in subjects with positive and negative HBS Ab were 10.77+/-8.37 mg/L versus 10.33+/-7.64 mg/L respectively (P=0.465). However, C-reactive protein levels in CAD group were significantly higher (P<0.001). CONCLUSIONS: Our results suggested hepatitis B surface antibody seropositivity has no relationship with coronary artery disease. Moreover, no significant linear correlation exists between HBS Ab and C-reactive protein levels. However, as previously shown, C-reactive protein level in patients with coronary artery disease is significantly higher than in patients with normal coronary arteries.     

Factors in the liquid portion of stored blood inhibit the proliferative response in mixed lymphocyte cultures

The transfusion of blood may suppress the immune responses of patients with renal transplants and with malignant disorders. To study the in vitro suppressive effects of banked blood, 4 units of blood were stored in CPDA-1 and ADSOL at 4 degrees C for 14 days. Lymphocytes and plasma or ADSOL supernatants were harvested on Days 0, 4, 7, 10, and 14. Subpopulations of lymphocytes were enumerated by flow cytometry. Recalcified and heat-treated plasma and supernatants from the units of blood were added to mixed lymphocyte cultures (MLC) composed of cells from normal individuals. No significant changes were noted in the proportions of T or B cells from blood stored under these conditions. A 60 +/− 3 percent inhibition in the proliferative response was observed when plasma from CPDA-1 units was added to MLCs (p less than 0.02). Supernatants from ADSOL units demonstrated a 29 +/− 4 percent inhibition (p less than 0.10) of the proliferative response, and this inhibition of response was observed on all 14 days of the study. When appropriate concentrations of dextrose or adenine were added to other MLCs, adenine (at the concentration found in ADSOL) caused a significant inhibition of the proliferative response. This inhibition was not, however, as marked as that observed with recalcified, heat- treated plasma from CPDA-1 units. We conclude that adenine plus some additional factor(s) found in the liquid portion of stored blood inhibits the proliferative response of normal lymphocytes. It is possible that these factors contribute to the immune suppression observed in vivo in some patients who receive blood transfusions.     

Efficacy of gabapentin on subjective idiopathic tinnitus: a randomized, double-blind, placebo-controlled trial

Tinnitus can cause extreme morbidity. Despite many attempts to find a treatment for idiopathic cases, they remain difficult to manage. Because nerve injury is one of the suspected etiologies of tinnitus and because gabapentin has been found to be effective in treating nerve injuries, some authors have attempted to determine if gabapentin has a role in treating tinnitus. Although gabapentin was found to be ineffective for tinnitus in these previous studies, to the best of our knowledge no studies have been performed that took into consideration the presence of various accompanying factors and concomitant diseases that might influence its effect. We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial of gabapentin for idiopathic tinnitus. We treated 40 patients with gabapentin and measured its effectiveness by comparing differences between pre- and post-treatment Tinnitus Severity Index (TSI) values and tinnitus loudness scores. We also compared these outcomes with those of a group of 40 matched placebo controls. At study's end, we found no significant differences between the gabapentin and control groups in mean decreases in TSI value and loudness score (p=0.85 and p=0.12, respectively). However, we did find that patients with hypertension, diabetes, and/or dyslipidemia showed a better response to gabapentin than did those with tinnitus alone (p=0.01). We conclude that although there was no statistically significant difference between gabapentin and placebo in treating isolated tinnitus or tinnitus overall, patients with concomitant hypertension, diabetes, and/or dyslipidemia may benefit from gabapentin.     

Defective NOTCH signaling drives increased vascular smooth muscle cell apoptosis and contractile differentiation in bicuspid aortic valve aortopathy: A review of the evidence and future directions

Bicuspid aortic valve (BAV) disease remains the most common congenital cardiac disease and is associated with an increased risk of potentially fatal aortopathy including aortic aneurysm and dissection. Mutations in the NOTCH1 gene are one of only a few genetic anomalies identified in BAV disease; however evidence for defective NOTCH signaling, and its involvement in the characteristic histological changes of VSMC apoptosis and differentiation in ascending aortae of BAV patients is lacking. This review scrutinizes the evidence for the interactions of NOTCH signaling, cellular differentiation and apoptosis in the context of aortic VSMCs and provides focus for future research efforts in the diagnosis of BAV aortopathy and prevention of catastrophic complications through NOTCH signaling manipulation.     

Optimization of freeze-drying condition of amikacin solid lipid nanoparticles using D-optimal experimental design

Amikacin as an aminoglycoside antibiotic was chosen to be loaded in a cholesterol carrier with nanoparticle size and sustained release profile to increase the dose interval of amikacin and reduce side-effects. To support the stability of solid lipid nanoparticles (SLNs), freeze-drying was suggested. Factors affecting the freeze-drying process in the present study included the type and concentration of cryoprotectants. Pre-freezing temperature effects were also studied on particle size of SLNs of amikacin. In some preliminary experiments, important factors which influenced the particle size of SLNs after lyophilization were selected and a D-optimal design was applied to optimize the freeze-drying conditions in the production of SLNs with minimum particle size growth after freeze-drying. Zeta potential, DSC thermograms, release profiles and morphology of the optimized particles were studied before and after freeze-drying. Results showed sucrose changed the particle size of SLNs of amikacin from 149 ± 4 nm to 23.9 ± 16.7 nm; in that situation, the absolute value of zeta potential changed from 1 ± 0.7 mV to 13 ± 4 mV. The release profiles showed a sustained release behavior of the loaded drug that did not change significantly before and after freeze-drying, but a burst effect was seen after it in the first 2 h. DSC analysis showed chemical interaction between amikacin and cholesterol.