A registry of haemodialysis patients and the progress of haemodialysis services in Lithuania.

Background. Until 1990, haemodialysis (HD) in Lithuania wasunderdeveloped, but after independence, development of HD started.Until 1996, no precise data about HD patients in Lithuania wereavailable. In order to create a registry of HD, we started tocollect data about dialysis services and HD patients in 1996.Every collection of data was followed by distribution and discussionof the results within the nephrological community. This studydescribes the changes of Lithuanian HD between 1996–2002. Methods. Between 1996 till 2002 all HD centres in Lithuaniawere annually visited and data were collected about all HD patients(response rate of 100%). The evaluation of the results duringour observational study was made according to the European BestPractice Guidelines. During annual conferences for nephrologists,the guidelines and data of our HD registry were presented. Results. There was an increase in the number of HD stations(from 25 p.m.p. to 75 p.m.p., P<0.001), in HD patients (from60 p.m.p. to 237 p.m.p., P<0.001) and in the incidence ofnew HD patients (from 54.3 p.m.p. to 103 p.m.p., P<0.01).The mean age of HD patients increased from 47.2±16.1years in 1996 to 56.0±14.9 in 2002 (P<0.001). Themain underlying cause of ESRD was chronic glomerulonephritis,but its rate decreased from 54.5% in 1996 to 27.5% in 2002 (P<0.001).The percentage of diabetics increased from 7.1% to 16.4%, P<0.05,and in hypertensive nephropathy from 3.1% to 10.9%, P<0.05.We observed improvement of the quality of HD in Lithuania duringthese 5 years. The percentage of patients on bicarbonate HDincreased from 7.1% in 1996 to 100% in 2002 (P<0.001). Thepercentage of patients receiving more than 12 h HD/week increasedfrom 30.8% in 1996 to 53.5% in 2002 (P<0.001). The mean Kt/Vin 1999 was 0.81±0.53, but it increased in 2002 to 1.22±0.27,P<0.001. In 2002, 84.6% of all HD patients were examinedfor HB_sAg, 82.3% for anti–HCV, 31.2% for anti-HB_s and57.1% for anti-HB_c. The percentage of patients receiving phosphatebinders increased from 65.2% in 1996 to 84.4% in 1997 and 90.5%in 2002. Serum parathyroid hormone (PTH) levels were measuredin 27.3% of HD patients in 1999 but in 85.2% of patients in2002. The mean haemoglobin (Hb) concentration increased from92±15.4 g/l to 105±14.7 g/l; the percentage ofpatients with Hb>100 g/l increased from 27.5% to 64% in 2001.The percentage of HD patients receiving epoetin was 94.6% in2001 as compared with 78% in 1997. There was a marked increasein the use of intravenous iron (from 7.5% patients in 1997 to70.8% in 2000). The mean weekly dose of Epo was lower in HDpatients receiving intravenous iron than in patients receivingoral iron. Conclusions. Over the period of 1996–2002 the HD servicessignificantly expanded in Lithuania. The introduction of EuropeanBest Practice Guidelines and the establishment of a HD registrywith feedback of the results stimulated the significant progressin the quality of HD and in the management of the patients.     

The influence of orthognathic surgery on ventilation during sleep

Orthognathic surgery has varying effects on respiratory parameters. The authors undertook a prospective study of patients requiring mandibular advancement, mandibular setback and maxillary Le Fort I advancement, and surgically assisted rapid maxillary expansion (SARME). Breathing parameters were monitored in a sleep laboratory the night before the operation and in a mean of 9.5 months after the operation. In patients treated with mandibular advancement, the respiratory disturbance index (RDI), oxygen desaturation index (ODI), and number of obstructive apnoeas (OAs) improved significantly. In patients treated with mandibular setback and maxillary Le Fort I advancement, the RDI, ODI, index of flow limitations (IFL), number of obstructive hypopnoeas (OHs), OA, and oxygen saturation deteriorated. In contrast, patients treated with SARME improved only mildly. These results indicate that bimaxillary surgery for Class III malocclusion increased upper airway resistance, probably because of a more dorsal positioning of the base of the tongue, representing an iatrogenic obstructive sleep apnoea (OSA). A young person would probably be able to balance such a decline in respiratory function using different adaptative mechanisms. Mandibular advancement significantly improved respiratory parameters during sleep. The possible effect of orthognathic surgery on the upper airways should be incorporated into the treatment plan.     

Childhood and adulthood traumatic experiences in patients with psoriasis

It is well known that several psychiatric disorders may be related to childhood psychological trauma. Recent studies have associated childhood exposure to trauma to some skin diseases. Our study aimed at exploring whether psoriasis is related to the reported positive and negative traumatic life events in different age intervals beginning from early childhood to adulthood. Furthermore, we investigated differences between psoriatics with early and late onset according to traumatic experiences in different age intervals. Also, we investigated the possible correlation of traumatic experiences with the disease severity. One hundred patients with psoriasis and 101 controls (patients with skin conditions considered to be "non-psychosomatic") were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences (Traumatic Antecedents Questionnaire, TAQ). The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The severity of psoriasis was estimated according to the Psoriasis Area and Severity Index (PASI), a standardized measuring instrument. The amount of positive experiences did not differ significantly among groups, except for safety scores that were higher in controls compared with both psoriatic groups (early and late onset). On the other side, negative traumatic experiences appeared more frequently in patients with psoriasis during all developmental periods. We found no correlation between severity of psoriasis and traumatic experiences. The present study demonstrates an increased history of childhood and adulthood negative traumatic experiences in patients with psoriasis compared to the control group. Our findings suggest a relationship between retrospectively reported negative traumatic experiences and psoriasis.     

Decreased arachidonic acid liberation participates in the anti-aggregatory effect of the histamine H 1 -receptor antagonist Bromadryl

The in vitro effect of the histamine H 1 -receptor antagonist Bromadryl on aggregation of human blood platelets was studied. Bromadryl inhibited stimulated platelet aggregation in a dose-dependent way. Depending on the aggregation stimulus used, its mean inhibitory concentrations were 16 micro mol/litre (thrombin), 18 micro mol/litre (A23187), 92 micro mol/litre (adrenaline) and 395 micro mol/litre (adenosine diphosphate). The inhibitory effect was most pronounced in aggregation stimulated with phorbol 12-myristate 13-acetate (IC 50 = 3 micro mol/litre), suggesting interference of Bromadryl with protein kinase C activity. In Bromadryl-treated platelets, a very good correlation was found between aggregation and liberation of arachidonic acid; the correlation coefficients calculated for thrombin- and A23187-stimulated platelets were 0.94123 and 0.98611, respectively. This indicates that interaction of Bromadryl with phospholipase A 2 (an enzyme liberating arachidonic acid) may be involved in the anti-aggregatory effect. However, in platelets stimulated with thrombin, thromboxane formation was decreased at a lower mean inhibitory concentration of Bromadryl (6 micro mol/litre) than arachidonic acid liberation (72 micro mol/litre); thus, phospholipase A 2 does not seem to be the only site in the arachidonate metabolism cascade affected by Bromadryl. Although specific interference of Bromadryl with histamine receptors could not be excluded, alterations in platelet membrane structure and functions are supposed to be principal in the anti-aggregatory effect of Bromadryl.     

The importance of micelle-bound states for the bioactivities of bifunctional peptide derivatives for delta/mu opioid receptor agonists and neurokinin 1 receptor antagonists

To provide new insight into the determining factors of membrane-bound peptide conformation that might play an important role in peptide-receptor docking and further biological behaviors, the dodecylphosphocholine (DPC) micelle-bound conformations of bifunctional peptide derivatives of delta-preferring opioid agonists and NK1 antagonists (1: Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-O-3,5-Bzl(CF 3) 2; 2: Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-3,5-Bzl(CF 3) 2; 3: Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-Bzl) were determined based on 2D NMR studies. Although the differences in the primary sequence were limited to the C-terminus, the obtained NMR conformations were unexpectedly different for each compound. Moreover, their biological activities showed different trends in direct relation to the compound-specific conformations in DPC micelles. The important result is that not only were the NK1 antagonist activities different (the pharmacophore located at the C-terminus)but the opioid agonist activities (this pharmacophore was at the structurally preserved N-terminus) also were shifted, suggesting that a general conformational change in the bioactive state was induced due to relatively small and limited structural modifications.     

Non‐leukemic pediatric mixed phenotype acute leukemia/lymphoma: Genomic characterization and clinical outcome in a prospective trial for pediatric lymphoblastic lymphoma

Rare cases of hematological precursor neoplasms fulfill the diagnostic criteria of mixed phenotype acute leukemia (MPAL), characterized by expression patterns of at least two hematopoietic lineages, for which a highly aggressive behavior was reported. We present a series of 11 pediatric non‐leukemic MPAL identified among 146 precursor lymphoblastic lymphomas included in the prospective trial Euro‐LBL 02. Paraffin‐embedded biopsies of 10 cases were suitable for molecular analyses using OncoScan assay (n = 7), fluorescence in situ hybridization (FISH; n = 7) or both (n = 5). Except for one case with biallelic KMT2A (MLL) breaks, all cases analyzed by FISH lacked the most common translocations defining molecular subsets of lymphoblastic leukemia/lymphomas. Two non‐leukemic B‐myeloid MPALs showed the typical genomic profile of hyperdiploid precursor B‐cell lymphoblastic leukemia with gains of chromosomes 4, 6, 10, 14, 18, and 21. One B‐T MPAL showed typical aberrations of T‐cell lymphoblastic lymphoma, such as copy number neutral loss of heterozygosity (CNN‐LOH) at 9p targeting a 9p21.3 deletion of CDKN2A and 11q12.2‐qter affecting the ATM gene. ATM was also mutated in a T‐myeloid MPAL case with additional loss at 7q21.2‐q36.3 and mutation of NRAS, two alterations common in myeloid disorders. No recurrent regions of CNN‐LOH were observed. The outcome under treatment was good with all patients being alive in first complete remission after treatment according to a protocol for precursor lymphoblastic lymphoma (follow‐up 3‐10 years, median: 4.9 years). In summary, the present series of non‐leukemic MPALs widely lacked recurrently reported translocations in lymphoid/myeloid neoplasias and showed heterogeneous spectrum of chromosomal imbalances.