Percutaneous treatment of liver hydatid cysts: comparison of direct injection of albendazole and hypertonic saline solution

OBJECTIVE: The purpose of this study was to compare the effect of intracystic injection of albendazole and hypertonic saline in patients with liver hydatid disease. MATERIALS AND METHODS: Fifty-nine patients with a total of 109 hydatid cysts were treated percutaneously. In all cases, local anesthesia was applied. Twenty percent hypertonic saline was used in 31 patients (40 cysts, group 1) as the scolicidal agent, and albendazole solution was used in 28 patients (69 cysts, group 2). The PAIR (percutaneous puncture, aspiration, injection, reaspiration) method was applied in group 1. In group 2, we used a different procedure that could be called the PAI (percutaneous aspiration and injection) method. After this procedure, routine sonography and CT examinations were conducted. The results of both groups were compared. RESULTS: Follow-up examinations showed that liver hydatids expanded approximately to their original size after a significant reduction during the first month. In the follow-up period, fluid contents totally disappeared; thickening and irregularities were also observed in the cyst walls and a solid, hyperechogenic, heterogeneous pseudotumor appearance representing a degenerated membrane was seen in all patients. Hypertonic saline solution inactivated the scolices from the beginning of the treatment. However, scolices were inactive in the cysts aspirated 1 month after the procedure in group 2. A significant correlation was noted between elapsed time after the treatment and the cyst size using Wilcoxon's signed rank test (p = 0.000). No difference was seen between two groups in the amount of cyst size reduction using the Mann-Whitney test (p =0.521). CONCLUSION: In addition to its oral use, albendazole may be injected intracystically as we did in our study. It sterilizes the cyst cavity and affects scolices as well.     

Carboxymethylcellulose-stabilized collagenous rhOP-1 device-a novel carrier biomaterial for the repair of mandibular continuity defects

Human recombinant osteogenic protein-1 (rhOP-1) is osteoinductive. Efforts are made to develop carrier biomaterials with improved space-keeping properties. Bovine collagen type I matrix charged with rhOP-1 was suggested to be an advantageous device of relative liquid quality. We hypothesized that the addition of carboxymethylcellulose (CMC) may stabilize the device and facilitate the regeneration of mandibular continuity defects without further addition of mineralized carrier materials. To test this hypothesis, the anatomical shape, functional remodeling, and mechanical stability of such bony regenerates were evaluated in the course of an animal experiment. Mandibular continuity defects of 5 cm in size were created in five G?ttingen minipigs on one side (contralateral hemimandible: control) and bridged with titanium plates. Four animals were treated with the rhOP-1 device (3000 microg rhOP-1, 2 g collagen, 1 g CMC), and one animal was treated with a placebo device omitting rhOP-1. After 12 weeks of experimental period, bony continuity was reestablished in rhOP-1-treated hemimandibles. The bony regenerates were of good anatomical shape, volume, and functional remodeling. Placebo treatment led to insufficient bony regenerates of significant lower bone volume (volume in 3D-CT scan 29.81 cm(3) vs 8.85 cm(3)). To produce 1 mm of bending, 1972 N were needed for rhOP-1-treated hemimandibles, 2617 N for control hemimandibles, and 642 N for the placebo treated hemimandible. CMC stabilization of collagen carrier biomaterials for rhOP-1 provides good plasticity as well as excellent space-keeping properties and may not interfere with osteoinduction. The results of this preliminary study suggest that the applied rhOP-1 device offers a potential option for further studies on the reconstruction of mandibular defects.     

Syntheses and neuraminidase inhibitory activity of multisubstituted cyclopentane amide derivatives

In further studies aimed toward identifying effective and safe inhibitors of influenza neuraminidases, we synthesized a series of multisubstituted cyclopentane amide derivatives. Amides prepared were 14 examples of N-substituted alkyl or aralkyl types from primary amines, 13 examples of the N,N-disubstituted alkyl, aralkyl, or substituted-alkyl type from secondary amines, and 12 examples from cycloaliphatic or substituted cycloaliphatic secondary amines. These compounds bearing two chiral centers, at position-1 in the ring and position-1' in the side chain attached at position 3, were tested for their ability to inhibit A and B forms of influenza neuraminidase. The 1-ethylpropylamide, diethylamide, dipropylamide, and 4-morpholinylamide showed very good inhibitory activity (IC(50) = 0.015-0.080 microM) vs the neuraminidase A form, but modest activity (IC(50) = 3.0-9.2 microM) vs the neuraminidase B form. Since the parent amides bear two chiral centers (C-1 and C-1'), three of the better inhibitors were tested at higher levels of diastereomeric purity. The diastereomers corresponding to the active forms of the 1-(ethyl)propylamide, the diethylamide, and the dipropylamide (all of the same configuration at the C-1' chiral center), and the diastereomer of the diethylamide representing the active form at both C-1' and C-1 were isolated or synthesized from precursors that were isolated as diastereomers. These diastereomers showed some improvement in neuraminidase inhibition over the parent diastereomeric mixtures. 1-Carboxy-1-hydroxy derivatives of the best active compounds, the diethylamide and the dipropylamide, were also prepared. These compounds were not as active as the compounds without the 1-hydroxy group. In an in vivo study, the C-1' active isomer of the diethylamide from the 1-carboxy series was tested in influenza-infected mice by oral and intranasal administration and found to be very effective only intranasally in preventing weight loss at doses as low as 0.1 (mg/kg)/day.     

Influence of enhancers on the absorption and on the pharmacokinetics of cefodizime using in-vitro and in-vivo models

In the development of novel antibiotics, more and more compounds have been found that cannot be absorbed orally and, therefore, must be administered intravenously or intramuscularly. Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability has received much attention in pharmaceutical research. Cefodizime, a novel third-generation cephalosporin with significant advantages in the parenteral treatment of common infections, was used as a model drug. Cefodizime behaves as a highly hydrophilic compound, as shown from its extremely low partition coefficient. The effect of cationic absorption enhancers (hexadecyldimethylbenzylammonium chloride, N-hexadecylpyridinium bromide, dodecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide) on the lipophilicity of cefodizime was investigated by means of the n-octanol/water system. Results showed that the counter-ions had a positive influence on the solubility of cefodizime. These results on partitioning coefficients in the n-octanol/buffer system were confirmed using an in-vitro transport model with artificial and biological membranes (Caco-2-cells). Furthermore, the physiological compatibility of the absorption enhancers was investigated using the active D-glucose transport. The pharmacokinetic profile of cefodizime was evaluated in rabbits after intraduodenal administration with and without an absorption enhancer.     

N-Acetylaspartate synthase is bimodally expressed in microsomes and mitochondria of brain

N-Acetylaspartate (NAA) is an abundant amino acid derivative of the central nervous system that is localized primarily in neurons and has found widespread use in clinical NMR spectroscopy (MRS) as a non-invasive indicator of neuronal survival and/or viability. Its function, although still obscure, is thought to reflect its unusual metabolic compartmentalization wherein NAA synthase occurs in the neuron and aspartoacylase, the hydrolytic enzyme that removes the acetyl moiety, occurs in myelin and glia. The NAA synthase enzyme, acetyl-CoA/l-aspartate N-acetyltransferase (ANAT), was previously shown to function in mitochondria (MIT), although other subcellular fractions were apparently not examined. In this study we confirmed its presence in MIT but also found significant activity in rat brain microsomes (MIC). The reaction mixture, consisting of [(14)C]aspartate plus acetyl-CoA in Na-phosphate buffer (pH 7), gave rise to [(14)C]NAA that was separated and quantified by TLC. Reaction rates were 29.0+/-0.46 and 6.27+/-0.27 nmol/h/mg for MIC and MIT, respectively. K(m) values and pH optima were similar, and both fractions showed modest enhancement of ANAT activity with the detergents Triton CF-54 and CHAPS. Our tentative conclusion is that ANAT is bimodally targeted to MIT and a component of MIC-likely endoplasmic reticulum. ANAT activity increased in both MIC and MIT between 29 and 60 days of age but differed thereafter in that only MIT ANAT showed a decrease after 1 year.     

Selective reovirus killing of bladder cancer in a co-culture spheroid model

Up to 50% of the transitional cell carcinomas (TCC) express an activated EGF pathway involving MAP/MEK and RAF kinase thus providing a novel means to selectively eliminate transformed cells expressing such proteins. This EGF pathway expression phenotype was also confirmed in our MGH-U3 and room temperature-112 human TCC cell lines, which makes them a suitable model target for the reovirus oncolysis. We report here on an in vitro assay of co-culture spheroids using either human or rat TCC cells with their corresponding fibroblasts to examine the potential of viral selective lysis for TCC. Reovirus, a respiratory enteric orphan virus, which mammals are exposed to early in life, was used in this study. Selective killing of transformed versus normal cells was assayed by time-lapse photography, vital dye staining, immunohistochemistry, and MTT assay. In this in vitro bladder cancer model, reovirus selectively destroyed the transformed cells by lysis or induction of apoptosis. Based on these findings we have initiated an in vivo pre-clinical study on intravesical administration of reovirus in an animal model to further explore the effect of reovirus-mediated oncolysis of TCC.     

Leiomyosarcoma of the bladder in a retinoblastoma patient

We report a rare case of leiomyosarcoma in the bladder which occurred in an 18-year-old female with a prior history of retinoblastoma (RB). Molecular characterization of this tumor displayed a homozygous RB deletion and a reduced P53 expression. These results suggest that the loss of RB and P53 may have contributed to the initiation and/or progression of the leiomyosarcoma of the bladder in this patient.     

Using cuffed and tunnelled central venous catheters as permanent vascular access for hemodialysis: a prospective study

BACKGROUND: Adequate care of a hemodialysis patient requires constant attention to the need to maintain vascular access (VA) patency. VA complications are the main cause of hospitalization in hemodialysis patients. The native arteriovenous fistula (NAVF), synthetic arteriovenous grafts fistula (GAVF) and silastic cuffed central venous catheters (CVCs) are used for permanent vascular access (PVA). CVCs are primary the method of choice for temporary access. But using this access modality is increasing more and more for PVA in elderly hemodialysis patients and when other PVA is not possible. The primary aim of this study is to investigate survivals and complications of the CVCs used for long-term VA. METHODS: We prospectively looked at 92 CVCs (Medcomp Ash Split Cath, 14 FR x 28 cm (Little, M.A.; O'Riordan, A.; Lucey, B.; Farrell, M.; Lee, M.; Conlon, P.J.; Walshe, J.J. A prospective study of complications associated with cuffed, tunnelled hemodialysis catheters. Nephrol. Dial. Transplant. 2001, 16 (11), 2194-2200) with Dacron cuff) inserted in 85 (50 females, 35 males) chronic hemodialysis patients (the mean age: 56.6 +/- 14.1 years) from July 1999 to January 2002. The overall survival and complications were followed up. Furthermore, the patients were evaluated for demographic and clinical characteristics. Data were analysed by chi-square, Wilcoxon rank and Kaplan-Meier survival tests. RESULTS: The median duration of CVC survival was 289 days (range: 10-720). Eleven (11.9%) CVCs were removed due to complications. In 79 (92.9%) patients, 1, in 5 (5.8%) patients, 2 and in 1 patient, 3 CVCs were inserted. Of the 85 patients, 56 have CVCs functioning. In addition, 27 (31.76%) patients have CVCs functioning for over 12 months, 17 (20%) patients have CVCs functioning for 6 months. The total incidence of CVC related infections was 0.82 episodes/1000 catheter days. Besides, thrombosis was occurred in 10 (10.8%) CVCs. The most frequent indications for CVC removal were patient death (69.4%), thrombosis (16.6%) and CVC-related infections (13.8%). CONCLUSIONS: CVCs are primarily used for temporary access. But this study indicates that CVC may be a very useful alternative permanent vascular access for hemodialysis patients when other forms of vascular access are not available.