Retrievable Günther Tulip Vena Cava Filter in the prevention of pulmonary embolism in patients with acute deep venous thrombosis in perinatal period

Objectives

To evaluate the feasibility and efficacy of the retrievable Günther Tulip Vena Cava Filter in the prevention of pulmonary embolism in patients with acute deep vein thrombosis in the perinatal period and to discuss the technical demands associated with the filter's implantation and retrieval.

Methods

Between 1996 until 2007, eight women (mean age 27.4 years, range 20–42 years) with acute deep iliofemoral venous thrombosis in the perinatal period of pregnancy and increased risk of pulmonary embolism during delivery were indicated for retrievable Günther Tulip Vena Cava Filter implantation. All filters were inserted and removed under local anesthesia from the jugular approach.

Results

The Günther Tulip Vena Cava Filter was implanted suprarenally in all patients on the day of caesarean delivery. In follow-up cavograms performed just before planned filter removal, no embolus was seen in the filter in any patient. In all patients the filter was retrieved without complications on the 12th day after implantation.

Conclusions

Retrievable Günther Tulip Vena Cava Filters can be inserted and removed in patients during the perinatal period without major complications.     

Maturation of neurons in neocortical slice cultures: A light and electron microscopic study on in situ and in vitro material.

Using light and electron microscopic methods, we investigated the development and morphology of neurons in neocortical slice cultures. Slices taken from the visual cortex of 6-day-old rats and cultivated for 14 or 20 days were compared with in situ material of corresponding age (P 20 and P 26). Maturation and differentiation of pyramidal and non-pyramidal cells kept in vitro were found to have progressed considerably. In the light microscope the neurons exhibited a morphological appearance strikingly similar to that of the neurons of the neocortex in situ at the same age. The fine structure of the tissue in vitro also had a mature appearance, corresponding in most respects to the material in situ. Synapses and dendritic spines were well-developed. Sometimes a spine apparatus was contained in the sections and occasionally a myelinated fiber could be seen. GABA-immunoreactive cells making symmetric synaptic contacts were also present. Despite these similarities, some quantitative differences could be observed. In slice cultures, only 52% of the synapses were located on spines (78% in situ). In vitro, a larger proportion of synapses (30%) showed a postsynaptically concave curvature than was the case in situ (12%). The areal density of synapses in vitro reached only about 70% of that in situ. This was probably a side-effect of the larger size of dendritic and axonal profiles on electron micrographs of in vitro-material. The most striking difference was that large synapses and synapses containing a large amount of synaptic vesicles were considerably more frequent in vitro than in situ.     

Effects of (R)α-methylhistamine on experimental colitis

Inflammation Research -     

DNA methylation and mRNA expression of HLA‐DQA1 alleles in type 1 diabetes mellitus

Type 1 diabetes (T1D) belongs among polygenic multifactorial autoimmune diseases. The highest risk is associated with human leucocyte antigen (HLA) class II genes, including HLA‐DQA1 gene. Our aim was to investigate DNA methylation of HLA‐DQA1 promoter alleles (QAP) and correlate methylation status with individual HLA‐DQA1 allele expression of patients with T1D and healthy controls. DNA methylation is one of the epigenetic modifications that regulate gene expression and is known to be shaped by the environment.Sixty one patients with T1D and 39 healthy controls were involved in this study. Isolated DNA was treated with sodium bisulphite and HLA‐DQA1 promoter sequence was amplified using nested PCR. After sequencing, DNA methylation of HLA‐DQA1 promoter alleles was analysed. Individual mRNA HLA‐DQA1 relative allele expression was assessed using two different endogenous controls (PPIA, DRA). We have found statistically significant differences in HLA‐DQA1 allele 02:01 expression (PPIA normalization, P_corr = 0·041; DRA normalization, P_corr = 0·052) between healthy controls and patients with T1D. The complete methylation profile of the HLA‐DQA1 promoter was gained with the most methylated allele DQA1*02:01 and the least methylated DQA1*05:01 in both studied groups. Methylation profile observed in patients with T1D and healthy controls was similar, and no correlation between HLA‐DQA1 allele expression and DNA methylation was found. Although we have not proved significant methylation differences between the two groups, detailed DNA methylation status and its correlation with expression of each HLA‐DQA1 allele in patients with T1D have been described for the first time.     

Activity of pivaloyloxymethyl butyrate, a novel anticancer agent, on primary human tumor colony-forming units

The anti-proliferative effects of pivaloyloxymethyl butyrate (AN-9), a butyric acid (BA) derivative with potent tumor-differentiating properties both in vitro and in vivo, was evaluated against colorectal, breast, lung, ovarian, renal cell, bladder, and other types of tumor colony-forming units in a human tumor cloning assay. A total of 76 evaluable specimens were exposed to AN-9 continuously, 48 of these were also exposed to BA continuously for direct comparison of the two agents, and 20 specimens were exposed to AN-9 for two hours. An in vitro inhibitory response was defined as a 50% decrease in tumor colony formation in treated cells compared to untreated controls. Superior anti-tumor activity was observed with the continuous exposure to AN-9 (39% in vitro response at 100 M and 70% at 200 M) than with the two-hour exposure (20% at 100 M and 25% at 200 M). At a continuous concentration of 200 M, AN-9 demonstrated greater tumor-specific activity than BA against melanoma (100% vs. 67%), ovarian (67% vs. 40%), breast (63% vs. 0%), non-small cell lung (60% vs. 10%), and colorectal tumor colony-forming units (62% vs. 20%). AN-9 is a novel differentiating agent with activity against colony-forming units derived from a variety of primary human tumors, including those that are considered relatively chemoresistant, and may thus provide a therapeutic alternative or addition to standard cytotoxic agents, if appropriate drug concentrations can be achieved in patients.     

Activity of (-)-2'-deoxy-3'-oxacytidine (BCH-4556) against human tumor colony-forming units

Background: BCH-4556 ((-)-2-deoxy-3-oxacytidine) is an L-nucleoside analogue shown to have broad preclinical anticancer activity, particularly against solid neoplasms such as prostate, renal, and hepatoma in vitro and in vivo, in contrast to cytosine arabinoside (ara-C) which is preferentially active against leukemia.Materials and methods: The antitumor activity of BCH-4556 was evaluated using human tumor colony-forming unit (HTCFU) assay, in which fresh tumor specimens were taken directly from patients with and without prior chemotherapy.Results: Overall, in vitro responses (50% or less survival compared to untreated controls) were observed in 11% (two of 18), 29% (five of 17) and 50% (nine of 18) of specimens treated for one hour with BCH-4556 at 1, 10 and 100 µg/ml, respectively; and 16% (nine of 55), 32% (24 of 74), 48% (35 of 73) and 65% (11 of 17) of specimens treated continuously with BCH-4556 at 0.1, 1, 10 and 100 µg/ml, respectively. With the one-hour schedule, a significant difference in response rates was noted between 100 µg/ml and 1 µg/ml (P = 0.02). With the continuous schedule, significant differences in response rates were observed between 1 µg/ml and 0.1 µg/ml (P = 0.02), between 10 µg/ml and 0.1 µg/ml (P = 0.0001), as well as between 10 µg/ml and 1 µg/ml (P = 0.01). A trend suggesting the superiority of continuous exposure was observed in paired specimens (n = 18) at comparable drug concentrations. Activity was noted against ovarian (nine of 16 = 56%), renal (three of four = 75%), and melanoma (two of two = 100%) HTCFU at 10 µg/ml using the continuous schedule. Comparisons between BCH-4556 and paclitaxel were made in 32 specimens at 10 µg/ml using the continuous exposure. Twenty-three specimens showed similar responses with both drugs; seven showed better responses with BCH-4556; and two showed better responses with paclitaxel (P = 0.18).Conclusions: Promising activity was observed with BCH-4556 against ovarian, renal, and melanoma HTCFU. There appeared to be a positive relationship between BCH-4556 concentration and response using both one-hour and continuous exposures. Continuous exposure to BCH-4556 provided high response rates especially at concentrations above 10 µg/ml. For both one-hour and continuous exposures, BCH-4556 had similar, and at times, greater potency than paclitaxel against the same tumor specimens in the present study.     

Identification of a new in-frame deletion of six amino acids in ribosomal protein S19 in a patient with Diamond-Blackfan anemia

Ribosomal protein S19 (RPS19) is currently the only gene associated with Diamond-Blackfan anemia (DBA), a rare congenital pure red cell aplasia characterized by normochromic macrocytic anemia, reticulocytopenia, and normocellular bone marrow with a selective deficiency of erythroid precursors. RPS19 is mutated in 25% of DBA patients, but its role in DBA pathogenesis remains elusive. We have identified a novel heterozygous microdeletion in RPS19 in a DBA patient presenting with profound anemia after birth. The deletion of 18 nucleotides (233-250; A in start codon is +1) in exon 4 leads to the elimination of 6 amino acids 78IYGGRQ83, affecting the most conserved stretch of three amino acids (YGG) in RPS19. The mutated allele was not detected in the patient's family members, indicating de novo mutation. Both alleles were expressed at the same level. Using an immunofluorescence technique, the mutated RPS19 protein localized to nucleoli, and its intracellular distribution did not differ from the wild-type RPS19. The deletion of only a few amino acids of this protein with a preserved reading frame is rare, and this type of a mutation could be very helpful in further experiments to define the role of the RPS19 protein in DBA pathogenesis.     

The significance of portal vein embolization in the treatment of colorectal liver metastases

The first aim of the present paper was to evaluate hypertrophy of liver parenchyma after portal vein embolization in patients after systemic chemotherapy for colorectal carcinoma metastases and planned extensive liver resections. The second aim was to study whether hypertrophy of the liver parenchyma remnant after could influence the postoperative course large liver resections in long-term chemotherapy within complex therapy of colorectal carcinoma.The prospective study comprised of 43 patients with colorectal hepatic metastases in whom liver resections of 4-5 segments were planned (Table 1). All patients underwent complex therapy of colorectal carcinoma, including chemotherapy consisting of 6-12 therapeutic cycles. Time interval between chemotherapy and liver resection was 2-24 months (mean interval of 8 months). Twenty patients whose presumed liver parenchyma remnant was less than 40% of total liver volume were indicated for portal vein embolization (mean liver parenchyma remnant of 29%). This was always embolization of the right portal branch. Twenty-three patients were primarily indicated to liver resection. RESULTS: Hypertrophy of the left liver lobe occurred in all 20 patients. After portal vein embolization, the volume of left liver increased on average from 476 ml (282-754) to 584 ml (380-892) (P < 0.05). Mean hypertrophy of left liver lobe after portal vein embolization was 28.5%. The measured parenchyma remnant after tumor resection increased from 29% up to 38% by hypertrophy. Mean values of ALT and AST in the postoperative period were significantly different in the groups in this study. The values of alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GMT) were lower in patients after portal vein embolization (P < 0.05). Significant differences were in postoperative level of serum bilirubin, bilirubin levels in patients after portal vein embolization were 2-3 times lower than in the group of patients after immediate surgery (P < 0.05). he values of prothrombin time were also significantly lower in patients who underwent surgery without previous portal vein embolization (P < 0.05).