Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center.

Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach. Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting. Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18-44) underwent allo-SCT between 2002 and 2020. Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%. Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.

Is suturing of the bladder defect in benign Enterovesical fistula necessary?

BACKGROUND: Enterovesical fistula (EVF) is a abnormal connection between the intestine and the bladder. The aim of the study was to analyze whether closure of the defect in the bladder wall during surgery is always necessary. METHODS: Fifty-nine patients with benign EVF undergoing surgical treatment were enrolled. A one-stage surgical procedure was performed in all patients. After the separation of the diseased bowel segment, methylene blue was introduced. Through a catheter into the bladder. Only patients with urinary bladder leakage were sutured. RESULTS: The most common intestinal fistula involving the urinary bladder was colovesical fistula, observed in 53% of cases. Two-thirds of patients had diverticular disease as the underlying pathology. There was no relationship between suturing of the bladder and perioperative complications. Recurrent EVF was observed in one patient with bladder suturing and in two patients without suture. CONCLUSIONS: These findings suggest that closure of the bladder defect is not necessary in cases where a leak is not demonstrated from the bladder intraoperatively. This study is limited by its retrospective design and small numbers and a randomized controlled trial is recommended to answer this question definitively.

Sleep disturbance and disease activity in adult patients with inflammatory bowel diseases.

The aim of the study was to identify whether poor quality of sleep is connected to inflammatory bowel disease (IBD) and if so, whether sleep disturbances are related to disease activity. Prospective, observational cohort study was performed. In all enrolled adult patients, the disease activity was assessed by using Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. All patients were also asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). Sixty-five patients were enrolled in our study: n = 30 with CD and n = 35 with UC. The poor sleep was noted in 78% (40/51) patients with clinically exacerbation and in 35% (5/14) patients in remission (P = 0.002; OR 6.5, 95% confidence interval, 1.8 - 23.6). A global PSQI score of 5 points yielded a sensitivity of 84%, a specificity of 39%, and a positive predictive value of 89% for discriminating participants with exacerbation of IBD from those in clinical remission; PSQI higher than 6 indicates the exacerbation of IBD with 77% sensitivity and 62% specificity. The poorest sleep quality was reported in IBD patients with severe exacerbations (9.1 ± 2.9). Sleep disturbance was confirmed in adult IBD patients, both in CD and UC. Confirmation of the relationship between sleep abnormalities and IBD may show the new pathway in pathophysiology, course and treatment of IBD.

Impact of obesity and nitric oxide synthase gene G894T polymorphism on essential hypertension.

Hypertension is a multifactorial disease caused by environmental, metabolic and genetic factors, but little is currently known on the complex interplay between these factors and blood pressure. The aim of the present study was to assess the potential impact of obesity, and angiotensin-converting enzyme (ACE) I/D polymorphism and endothelial nitric oxide synthase gene (NOS3) 4a/4b, G894T and -T786C variants on the essential hypertension. The study group consisted of 1,027 Caucasian adults of Polish nationality (45.5 ± 13.6 years old), of which 401 met the criteria for hypertension. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides were determined by standard procedures. The ACE I/D polymorphism and three polymorphisms in NOS3 gene (4a/4b, G894T, -T786C) were detected by the PCR method. Multivariable logistic regression demonstrated that age above 45 years, diabetes, dyslipidemia, smoking and male sex are important risk factors for hypertension and no significant influence of variants in ACE and NOS3 genes on this risk was recognized. Obese subjects had a 3.27-times higher risk (OR = 3.27, 95% CI: 2.37 - 4.52) of hypertension than non-obese, and in obese the NOS3 894T allele was associated with 1.37 fold higher risk of hypertension (P = 0.031). The distribution of NOS3 G894T genotypes supported the co-dominant (OR = 1.35, P = 0.034, Pfit = 0.435) or recessive (OR = 2.00, P = 0.046, Pfit = 0.286), but not dominant model of inheritance (P = 0.100). The study indicates that in obese NOS3 G894T polymorphism may enhance hypertension risk. However, in the presence of such strong risk factors as age, diabetes and smoking, the impact of this genetic variant seems to be attenuated. Further studies are needed to reveal the usefulness of G894T polymorphism in hypertension risk assessment in obese.

Enzymatic mineralization of gellan gum hydrogel for bone tissue-engineering applications and its enhancement by polydopamine.

Interest is growing in the use of hydrogels as bone tissue-engineering (TE) scaffolds due to advantages such as injectability and ease of incorporation of active substances such as enzymes. Hydrogels consisting of gellan gum (GG), an inexpensive calcium-crosslinkable polysaccharide, have been applied in cartilage TE. To improve GG suitability as a material for bone TE, alkaline phosphatase (ALP), an enzyme involved in mineralization of bone by cleaving phosphate from organic phosphate, was incorporated into GG hydrogels to induce mineralization with calcium phosphate (CaP). Incorporated ALP induced formation of apatite-like material on the submicron scale within GG gels, as shown by FTIR, SEM, EDS, XRD, ICP-OES, TGA and von Kossa staining. Increasing ALP concentration increased amounts of CaP as well as stiffness. Mineralized GG was able to withstand sterilization by autoclaving, although stiffness decreased. In addition, mineralizability and stiffness of GG was enhanced by the incorporation of polydopamine (PDA). Furthermore, mineralization of GG led to enhanced attachment and vitality of cells in vitro while cytocompatibility of the mineralized gels was comparable to one of the most commonly used bone substitute materials. The results proved that ALP-mediated enzymatic mineralization of GG could be enhanced by functionalization with PDA.

Synthesis of prostacyclin and its effect on the contractile activity of the inflamed porcine uterus.

The goal of the study was to estimate the content of prostacyclin (PGI(2)), the levels of PGI synthase (PTGIS) and receptor (PTGIR) protein expression, and the cellular localization of these factors in the inflammatory-changed porcine uterus. The effect of PGI(2) on the contractility of the inflamed uteri was also determined. On Day 3 of the estrous cycle (Day 0 of the study), 50 mL of either saline or Escherichia coli suspension (10(9) colony-forming units/mL) were injected into each uterine horn. Acute endometritis developed in all bacteria-inoculated gilts, however on Day 8 of the study a severe form of acute endometritis was noted more often than on Day 16. Bacteria injections increased the contents of 6-keto-prostaglandin F(1α) in endometrium, myometrium, washings, and the level of PTGIS in endometrium on Days 8 and 16, and the content of PTGIR in endometrium on Day 16. In the inflamed uteri on both study days, stronger immunoreactivity for PTGIS was observed in part of the luminal and glandular epithelial cells and in a portion of the endometrial arteries, and for PTGIR in part of the luminal epithelium and endothelial cells in a portion of the endometrial arteries. On Day 8, PGI(2) decreased contraction intensity in endometrium/myometrium and myometrium of the saline-treated uteri and increased the contraction intensity in both types of strips from the inflamed organs. Our study reveals that inflammation of the porcine uterus upregulates PGI(2) synthesis and that PGI(2) increases contractility, which suggests that PGI(2) might be essential for the course of uterine inflammation.

Characterization and sequence analysis of the replicator region of the novel plasmid pALC1 from Paracoccus alcaliphilus.

The replicator region of a low-copy-number plasmid, pALC1, of Paracoccus alcaliphilus JCM 7364 was cloned in a form of the minireplicon pALC100 (3.6 kb). The host range of the minireplicon embraces several species of genus Paracoccus, as well as Agrobacterium tumefaciens, Rhizobium leguminosarum, and Rhodobacter sphaeroides (all belonging to alpha-Proteobacteria), but not Escherichia coli. The complete nucleotide sequence of the replicator region (2276 bp) revealed the presence of one complete open reading frame coding for the 28.4-kDa protein (RepA) with similarity to replication proteins of plasmid pSW500 of Erwinia stewartii and pVS1 of Pseudomonas fluorescens. The iteron-like region was identified upstream of the repA gene and consisted of two clusters of repeated sequences (17 bp long) separated by a putative DnaA box. Analysis of the predicted amino acid sequence of two adjacent incomplete ORFs suggests the localization of repA between genes involved in conjugation (traG) and partitioning (parA) within the pALC1 genome.

Plasmid occurrence and diversity in the genus Paracoccus.

The results of screening for the occurrence of plasmids in several strains representing 11 out of 13 species of the genus Paracoccus are presented. We show that plasmids (ranging in size from 2.7 to above 450 kb) are widely distributed in this genus. Only one tested strain (P. alkenifer) appears to be plasmid-free. The majority of the strains harbour at least two plasmids, one of which usually fits into the class of megaplasmids.

Excess benign melanocytic naevi in renal transplant recipients.

BACKGROUND: Some studies indicate that malignant melanoma occurs more frequently in renal transplant recipients than in the normal population. The development of excess benign melanocytic naevi is regarded as an indicator of the risk for malignant melanoma. OBJECTIVE: This study was undertaken to evaluate the prevalence of benign melanocytic naevi in adult renal transplant patients. METHOD: All benign melanocytic naevi irrespective of size were counted in 76 patients with renal transplants and were compared to naevus counts in 55 sex- and age-matched healthy controls. RESULTS: The mean total number of benign melanocytic naevi was significantly higher (p < 0.001) in renal transplant patients than in the control group: 93.6 +/- 52.2 and 36.1 +/- 29.9, respectively. The most evident increase occurred on the palms/soles and back/buttocks. A positive, although not significant, correlation between naevus counts and duration of immunosuppression was found. CONCLUSION: Renal transplant recipients have an increased number of benign melanocytic naevi and should be considered as a risk group for malignant melanoma.

Construction of mobilizable cloning vectors derived from pBGS18 and their application for analysis of replicator region of a pTAV202 mini-derivative of Paracoccus versutus pTAV1 plasmid.

Two mobilizable cloning vectors, designated pABW1 and pAWB2, were constructed basing on the E. coli vector pBGS18 and oriT originating from RK2. In pABW2 the kanamycin resistance gene was replaced by a novel tetracycline resistance cassette derived from Tn1721. Both vectors, specific for E. coli, allow to perform the cloning steps in E. coli and then to efficiently transfer the constructs by conjugation to the host of choice. A vector which cannot propagate in the given host can be applied for identification of the host specific plasmid replicator regions. With the use of pABW2 we defined the minimal replicator region of pTAV202-a mini-derivative of the large pTAV1 plasmid of P. versutus. We also proved that RepC' encoded on this fragment is the principal initiator replication protein and that oriV is located along its coding sequence.

Complete nucleotide sequence of the replicator region of Paracoccus (Thiobacillus) versutus pTAV1 plasmid and its correlation to several plasmids of Agrobacterium and Rhizobium species.

The complete nucleotide sequence of the replicator region of pTAV1, a cryptic, low copy number plasmid of Paracoccus versutus, was determined. The minimal replicon sequence (3149 bp) included in pTAV203/18 contains two open reading frames with coding capabilities for putative polypeptides of 23.8 (RepX) and 46 kDa (RepC'). The two genes have the same transcriptional polarity and both seem to be essential for replication of pTAV203. The predicted amino acid sequence of RepC' shows significant homology with the major replication-associated proteins of several Agrobacterium and Rhizobium plasmids. A probable origin of replication (oriV) was proposed to be localized at the 3' terminal end of the repC' gene.

Antimutagenic activity of anthocyanins isolated from Aronia melanocarpa fruits.

Anthocyanins belong to the flavonoid family and are ubiquitous in plants, especially in flower petals and fruit peels. We established that anthocyanins isolated from fruits of Aronia melanocarpa markedly inhibited the mutagenic activity of benzo(a)pyrene and 2-amino fluorene in the Ames test. In the Sister Chromatid Exchanges (SCEs) test with human blood-derived lymphocytes cultured in vitro, a significant decrease of SCEs frequency induced by benzo(a)pyrene was observed in the presence of anthocyanins. In the case of mitomycin C the effect of anthocyanins on SCEs frequency was smaller but still noticeable. Anthocyanins markedly inhibited the generation and release of superoxide radicals by human granulocytes. The results suggest that the antimutagenic influence of anthocyanins is exerted mainly by their free-radicals scavenging action as well as by the inhibition of enzymes activating promutagens and converting mutagens to the DNA-reacting derivatives. These preliminary data seem to be important in the aspect of a possible antimutagenic and anticarcinogenic potency of anthocyanins commonly present in fruits and vegetables.

[T lymphocytes from patients with Hodgkin's disease suppress erythroid progenitor growth from autologous marrow]. / Limfocyty T chorych na ziarnice zlosliwa hamuja wzrost klonalny prekursorów erytroidalanych szpiku autologicznego.

The effect of peripheral blood T lymphocytes from 42 patients with advanced Hodgkin's disease (grade III and IV) on the autologous marrow erythroid colony formation was studied in diffusion chamber culture. It was found, that unfractionated T lymphocytes suppress the BFU-E--(burst forming unit erythroid) and CFU-E--(colony forming unit erythroid)--derived colony formation by releasing an inhibitory activity. The suppression of colony formation was noted already at 0.25 x 10(5) cell concentration. In experiments with 0.5 x 10(5) and 1.0 x 10(5) T cells the inhibitory effect was increased. Subsequently it was shown, that this inhibition was generated by radioresistant, CD8+ and HLA-DR- subset of T cells. In control experiments, T lymphocytes from healthy subjects had no influence on the erythroid colony formation.

Lectin-binding glycoproteins in nuclear fractions from hamster liver and Kirkman-Robbins hepatoma.

As a further step toward characterizing the major nuclear glycoproteins from hamster liver and Kirkman-Robbins hepatoma (Lipinska A. and Gaczynski M. Int. J. Biochem. 4, 1385-1390, 1992) its intranuclear localization was studied. The glycoprotein patterns of examined nuclear fractions of hamster liver and hepatoma revealed some cell specificity observed especially in nuclear matrix preparations. Our results show the extensive presence of envelope glycoproteins in the nuclear matrix.

[Comparative evaluation of treatment results in advanced multiple myeloma with the help of polychemotherapy with vincristine, doxorubicin, dexamethasone (VAD) or only with dexamethasone]. / Ocena porównawcza wyników leczenia zaawansowanych postaci szpiczaka mnogiego za pomoca polichemioterapii winkrystyna, doksorubicyna i deksametazonem (VAD) oraz wylacznie deksametazonem.

A prospective clinical trial was undertaken to determine the therapeutical effectiveness of multidrug chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) or only high dose of dexamethasone (D) in 56 patients with multiple myeloma (MM). The group of patients included 41 with intermediate (II) and 15 with high (III) tumor mass. The final evaluation was performed in 19 patients treated with D and in 19 receiving VAD regimen. Improvement was defined by at least 50% reduction of serum myeloma protein concentration or disappearance of light chain proteinuria. The VAD regimen was more effective giving improvement in 90% of patients with no prior therapy and in 44% of patients with reflectory myeloma. In this respect, cytoreduction of the same magnitude was noted both in stages II and III. Higher therapeutical effect of VAD regimen was observed independently of the immunological type of MM. The treatment with D has given the improvement in 56% of patients with no previous therapy. Our results support the usefulness of VAD regimen in MM-patients with no prior therapy and with refractory myeloma. High frequency of therapy-related complications, however, indicates that VAD treatment should rather be reserved for the patients with resistant MM.

Transformation of Thiobacillus versutus with plasmid DNA.

The representative of the facultatively chemolithotrophic thiobacilli, Thiobacillus versutus has been successfully transformed for the first time with plasmid DNA. The plasmid used for the transformation study was pKK2, a derivative of the broad host range pSa plasmid conferring Km resistance being effectively expressed in T. versutus. Different methods inducing an artificial state of competence were tested. Transformants were obtained at the efficiency of about 10(3) per micrograms of DNA. pKK2 appeared to be compatible with T. versutus indigenous plasmids, but for stable maintenance it required constant selective pressure.

Wavelength referencing in single-mode microbend sensors.

The strong wavelength dependence of microbending losses in single-mode fibers is utilized in wavelength referencing for fluctuation-free microbend sensors. Through fiber size and microbend periodicity, optimization of the wavelength dependence can be increased dramatically. The reference and signal wavelengths can be provided through the spectrum of a light-emitting diode.