Pharmacokinetics and pharmacodynamics of a single dose of sustained-release azithromycin formulation in pigeons.

To date, only a few studies on the azithromycin (AZM) pharmacokinetics in ornamental birds have been published. In the current study AZM concentrations in domestic pigeon (Columba livia domestica) plasma samples were analyzed using a validated ultra-high performance liquid chromatography tandem mass spectrometry method. The aim of the current study was to carry out an analysis of the pharmacokinetics and pharmacodynamics after administration of a single oral dose of a sustained-release AZM formulation and to conduct a simulation of treatment based on selected minimal inhibitory values. The study was performed with 12 healthy adult pigeons, both sexes. The pigeons tolerated AZM very well and no adverse effects were observed in any animal during the study. Based on the observed characteristics of the pharmacokinetics/ /pharmacodynamics profiles of AZM in pigeons, it should be noted that 35 mg/kg per os as a single starting dose and 25 mg/kg every 24 h are recommended for treatment of both suscep- tible and less susceptible pathogens.

Feather analysis as a non-invasive alternative to tissue sampling for surveillance of doxycycline use on poultry farms.

Intensive chicken production leads to overuse of antibiotics on poultry farms. For food safety control, there is great need for means to use non-conventional matrices allowing analysis of antibiotics during poultry breeding. The main goal of this study was to demonstrate feathers as suitable material for non-invasive detection of doxycycline treatment in poultry. Transfer to and depletion of doxycycline in chicken feathers were investigated after therapeutic, spray, and subtherapeutic treatment. For the quantitative determination of doxycycline in feathers, a validated ultra-high-performance liquid chromatography - tandem mass spectrometry method was used. High concentrations of doxycycline in feathers were detectable for 22 D post treatment in each experimental group, and they were much higher than those in muscle and liver. A washing experiment with the same solvent as for extraction showed different ratios between extractable and non-extractable residues in feathers of chickens treated therapeutically, by spraying and subtherapeutically, which demonstrates the ability of feather analysis to distinguish different forms of treatment. After a segmentation procedure, high amounts of doxycycline were found to be deposited in the upper part of feathers in each treatment group. The obtained results showed that chicken feathers are a suitable material for the detection and non-invasive surveillance of doxycycline.

Influence of Clonal Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts on Progression and Survival in Multiple Myeloma Patients After Autologous Peripheral Blood Stem Cell Transplantation in Long-term Observation.

BACKGROUND: High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) remains the mainstay of treatment of eligible patients diagnosed multiple myeloma. The role of clonal plasma cell (CPC) contamination was found as a reason for relapse, but results in terms of survival, progression, and purging were ambiguous. Therefore, the aim of the study was to explore the influence of CPC contamination in the autograft on survival and progression after auto-PBSCT. STUDY DESIGN: The study included 59 patients diagnosed and treated for multiple myeloma in 1998-2004. Cells with coexpression of CD38+++CD138++CD56+ and lacking the expression of CD45, CD19, CD10, CD20, and CD23 were considered CPC in flow cytometry. RESULTS: The risk of death and progression after auto-PBSCT increased significantly by 10% (P < .021) and 8% (P < .034) per 1 × 106/kg of the CPC number, respectively. For CPC number above 2.96 × 106/kg overall survival achieved clinical significance. Two years after auto-PBSCT, the risk of death was independent of CPC number among the patients who survived (P = .70). Analogous conclusions concerned results of progression-free survival at 1 year after auto-PBSCT. CONCLUSIONS: High clonal plasma cell contamination (>2.96 ×1 06/kg; 90th percentile of CPC number) is associated with the worst progression-free survival and overall survival. Therefore purging in vitro might be considered for the patients with the highest CPC contamination. Negative consequences of CPC contamination on the risk of death are observed for only 2 years after auto-PBSCT. Thereafter only those patients who had lower CPC contamination survived.

Azacitidine for Relapse After Allogeneic Stem Cell Transplantation-Single-Center Study.

BACKGROUND: Relapse is the leading cause of treatment failure for myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation. Treatment options are very limited and use of azacitidine is one of the available options. METHODS: This was a retrospective, single-institution study. Of 28 evaluated patients, 18 were males, and the median age was 60 years (range, 15-78). There were 15 patients with acute myeloid leukemia, 8 with myelodysplastic syndrome, 4 with chronic myelomonocytic leukemia, and 1 with primary myelofibrosis. Ten patients received azacitidine for overt relapse, 14 received it as a preemptive therapy, and 4 others received it as maintenance treatment after allo-hematopoietic cell transplant (HSCT). Eleven patients received a donor lymphocyte infusion (DLI). RESULTS: The patients received median 5 (1-9) cycles of azacitidine in preemptive and maintenance therapy and median 2.5 (1-9) cycles in patients with relapse. Thirty-nine percent of patients received DLIs. Median overall survival was 6.1 months (95% CI, 0.7-13) for relapse therapy vs 21.2 months (95% CI, 8.4-inf) for preemptive therapy. Among patients treated for relapse, 30% achieved temporary disease control and underwent the second allo-HSCT. A complete, cytogenetic remission was achieved in 50% of patients and stable minimal residual disease in 14% of patients in a group with preemptive therapy. Toxicity was considerable; neutropenia (71%), anemia (14%), thrombocytopenia (36%), and serious infections (36%) were observed in the preemptive setting. CONCLUSIONS: These data support the notion that azacitidine is best used as a preemptive therapy against relapse for patients after allo-HSCT performed for myeloid malignancy. Applying azacitidine as therapy for ongoing relapse after allo-HSCT may lead to stable disease and allow for better performance of the second allo-HSCT.

Pharmacokinetic depletion phase of doxycycline in healthy and Mycoplasma gallisepticum-infected chicken broilers after coadministration of enrofloxacin traces.

The objective of this study was to investigate the influence of enrofloxacin (ENR) traces on doxycycline (DC) pharmacokinetic depletion phase parameters in plasma and lungs of healthy and Mycoplasma gallisepticum (MG)-infected chicken broilers. The multiple-dose oral administration of DC to chickens which were permanently exposed on ENR traces significantly increased concentration of DC in plasma and lung. It also prolonged the DC elimination time in both healthy and infected animals after final dose. The obtained result indicated that simultaneous administration of DC and ENR in chicken broilers therapy should be avoided.

Correlation between oral fluid and plasma oxytetracycline concentrations after intramuscular administration in pigs.

The penetration of oxytetracycline (OTC) into the oral fluid and plasma of pigs and correlation between oral fluid and plasma were evaluated after a single intramuscular (i.m.) dose of 20 mg/kg body weight of long-acting formulation. The OTC was detectable both in oral fluid and plasma from 1 hr up to 21 day after drug administration. The maximum concentrations (Cmax ) of drug with values of 4021 ± 836 ng/ml in oral fluid and 4447 ± 735 ng/ml in plasma were reached (Tmax ) at 2 and 1 hr after drug administration respectively. The area under concentration-time curve (AUC), mean residence time (MRT) and the elimination half-life (t1/2ß ) were, respectively, 75613 ng × hr/ml, 62.8 hr and 117 hr in oral fluid and 115314 ng × hr/ml, 31.4 hr and 59.2 hr in plasma. The OTC concentrations were remained higher in plasma for 48 hr. After this time, OTC reached greater level in oral fluid. The strong correlation (r = .92) between oral fluid and plasma OTC concentrations was observed. Concentrations of OTC were within the therapeutic levels for most sensitive micro-organism in pigs (above MIC values) for 48 hr after drug administration, both in the plasma and in oral fluid.

Azacitidine Use After Allogeneic Stem Cell Transplantation-Results From the Polish Adult Leukemia Group.

BACKGROUND: Relapse of primary hematologic disease constitutes an important reason for failure of allogeneic hematopoietic stem cell transplantation (alloHSCT). There are very few treatment modalities for this indications. Therefore, there is a need for novel effective therapies and even more for the prevention of relapse. There are scarce data that azacitidine can be used for these purposes. METHODS: At the Polish Adult Leukemia Group, we retrospectively analyzed the results of azacitidine treatment after alloHSCT. Relapsing patients, patients with minimal residual disease/mixed chimerism, and patients in complete remission with high risk of relapse were analyzed separately. There were 17 patients, 6 with myelodysplastic syndrome, 11 with acute myeloid leukemia, 8 male, and overall median age of 56 years (range, 15-78); 7 patients received donor lymphocyte infusion (DLI). RESULTS: Patients treated because of relapse received a median of 3 (range, 1-6) cycles of azacitidine, patients receiving preemptive treatment received a median of 4 cycles (range, 2-6), and those on maintenance received a median of 5 cycles (range, 3-5). Toxicity was considerable, especially in relapse-neutropenia (67%), anemia (67%), thrombocytopenia (100%), serious infections (78%)-and preemptive settings. Median overall survival of patients treated for relapse reached 6.8 months (95% confidence interval [CI], 0.7-∞), with better survival observed in patients with temporary disease control (7.7 vs 4.7 mo) and without previous exposure to azacitidine (7.7 vs 3.4 mo). One-year overall survival reached 75% (95% CI, 13%-96%) for preemptive and 50% (95% CI, 0%-91%) for maintenance treatment. DLI did not aggravate graft-versus-host disease. CONCLUSIONS: Effectiveness of azacitidine in relapsing patients is disappointing. Azacitidine seems to be promising in preemptive and maintenance settings. Toxicity is considerable. Further research is needed.

The influence of Actinobacillus pleuropneumoniae infection on tulathromycin pharmacokinetics and lung tissue disposition in pigs.

A tulathromycin concentration and pharmacokinetic parameters in plasma and lung tissue from healthy pigs and Actinobacillus pleuropneumoniae (App)-infected pigs were compared. Tulathromycin was administered intramuscularly (i.m.) to all pigs at a single dose of 2.5 mg/kg. Blood and lung tissue samples were collected during 33 days postdrug application. Tulathromycin concentration in plasma and lung was determined by high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The mean maximum plasma concentration (Cmax ) in healthy pigs was 586 ± 71 ng/mL, reached by 0.5 h, while the mean value for Cmax of tulathromycin in infected pigs was 386 ± 97 ng/mL after 0.5 h. The mean maximum tulathromycin concentration in lung of healthy group was calculated as 3412 ± 748 ng/g, detected at 12 h, while in pigs with App, the highest concentration in lung was 3337 ± 937 ng/g, determined at 48 h postdosing. The higher plasma and lung concentrations in pigs with no pulmonary inflammation were observed at the first time points sampling after tulathromycin administration, but slower elimination with elimination half-life t1/2el  = 126 h in plasma and t1/2el  = 165 h in lung, as well as longer drug persistent in infected pigs, was found.

Dramatic recurrence of cancer in a patient who underwent kidney transplantation--case report.

BACKGROUND: Besides cardiovascular diseases and infections, cancers are the main cause of death in patients after transplantation of a vascularized organ. After transplantation, usually de novo cancers develop. Recurrences of cancers that had been diagnosed and treated before transplantation are much rarer. In exceptional cases, cancer is transferred with the donor's organ. The epidemiology and the course of post-transplantation de novo neoplasia is relatively well known. However, the issue of recurrence of pre-transplantation cancer, which is significantly rarer and its course more individualized and difficult to predict, poses a challenge to contemporary transplantation. CASE REPORT: This paper presents an unexpectedly rapid recurrence of rare cancer-endometrial stromal sarcoma-that occurred shortly after transplantation of a kidney from a deceased donor to a patient who had undergone cancer treatment 7 years earlier. The dramatic course of the disease, complicated with recurrent massive thrombosis of the inferior vena cava and the right cardiac cavities, as well as pulmonary embolism and serious infectious complications, illustrates the difficulties related to qualifying patients with a history of malignancy for transplantation. CONCLUSIONS: Based on this case report, we attempt to find an answer to the question about the risk of cancer recurrence in patients receiving immunosuppressive therapy and find out how it can be minimized. Answering these questions is particularly important if the recurrent cancer is substantially more aggressive, cancer treatment options are limited, and the prognosis is poor due to lack of immunocompetence.

Hospital outbreak of vancomycin-resistant enterococci caused by a single clone of Enterococcus raffinosus and several clones of Enterococcus faecium.

A mixed outbreak caused by vancomycin-resistant Enterococcus raffinosus and Enterococcus faecium carrying the vanA gene was analysed. The outbreak occurred in a large hospital in Poland and affected 27 patients, most of whom were colonised, in three wards, including the haematology unit. The E. raffinosus isolates had a high-level multiresistant phenotype and were initially misidentified as Enterococcus avium; their unambiguous identification was provided by multilocus sequence analysis. The molecular investigation demonstrated the clonal character of the E. raffinosus outbreak and the polyclonal structure of the E. faecium isolates. All of the isolates carried the same Tn1546-like element containing an IS1251-like insertion sequence, located on a c. 50-kb conjugative plasmid. One of the E. faecium clones, found previously to be endemic in the hospital, was probably the source of the plasmid. The results of the study suggest that difficulties in identification may have led to an underestimate of the importance of E. raffinosus in vancomycin-resistant enterococci (VRE) control strategies.

[Standardized new method for measuring vibration perception]. / Standaryzacja nowej metodyki badania czucia wibracji.

The examination of the vibration perception is one of the basic measurements applied in the evaluation of the peripheral neuropathies in hand-arm vibration syndrome (HAVS) The detailed guidelines on how this kind of examinations should be performed, presented in the 1998 ISO standard, differ substantially from those currently binding in Poland. The aim of this study was to standardize the method of vibration perception measurements, taking account of the parameters consistent with the ISO recommendations, such as algorithm (stimulus presentation method), vibration frequency, the size and contact force of vibrating probe, as well as the comparison of the results obtained by means of both methods (ISO-recommended method and standard Polish method). It was found that the algorithm change (ascending method replaced by Bekesy's technique, recommended by ISO) did not affect the of the vibration perception thresholds values within the wide range of frequencies (32-500 Hz), whereas the decreased size of probe, pressed with smaller contact force, resulted in significantly higher values of perception thresholds within the frequency range of 125-400 Hz. The comparison of the outcomes of the ISO-recommended and Polish standard methods revealed that the perception thresholds did not differ at the frequency of 125 Hz, but at the frequencies of 250 and 400 Hz, the ISO-recommended method produced higher values. Moreover, at the frequencies ranging from 125 to 400 Hz, the results of the perception threshold measurements, taken several times in the same persons (intrasubject variability) by means of both methods, were more scattered. It was revealed that the measurements at the frequency range of 4-125 Hz should be included in the vibration perception examinations, and the certification of the ability to work in the conditions of exposure to hand-arm vibration should be based on their results. It is also essential that in the standard examination, a smaller vibratory probe (phi = 5 mm) and lighter contact force (0.1 N) than those currently used, should be applied.

Endoscopic obliteration for bleeding peptic ulcer.

A group of 133 patients treated for bleeding peptic ulcer in our Department, is reviewed. Within several hours of admission, all patients underwent upper gastrointestinal tract gastroscopy and obliteration of the bleeding ulcer. Bleeding gastric ulcers were found in 41 patients, and duodenal ulcers in 92 patients. Patients were classified according to the Forrest scale: IA - 11 patients, IB - 49 patients, IIA - 35 patients, lIB - 40 patients. In 126 (94.7%) patients the bleeding was stopped, and 7 required urgent surgery: 3 patients with gastric ulcer underwent gastrectomy, and 4 with duodenal ulcer - truncal vagotomy with pyloroplasty and had the bleeding site underpinned. Fifty-five patients underwent elective surgery: gastrectomy and vagotomy (18 patients with gastric ulcer), highly selective vagotomy (25 patients with duodenal ulcer) and truncal vagotomy and pyloroplasty (12 patients with duodenal ulcer). None of the patients was observed to have recurrent bleeding.

Long-term consequences of surgical treatment of peptic ulcer.

Surgical treatment of peptic ulcer may lead to several late postoperative morphological and metabolic abnormalities. Forty two patients (16 females and 26 males) at mean age of 47 years after surgery for peptic ulcer (mean postoperative period of 9 years) were recruited in this study. Following methods have been used for evaluation of those patients: clinical and serum biochemical assessment, UGI tract endoscopy, histology of gastric or duodenal mucosa biopsies, test for H-pylori presence, Ca-P-Mg homeostasis and BMD using DXA-absorptiometry. No clinical and biochemical abnormalities were found. In 60% of examined pts gastritis or duodenitis with various degrees of the reflux were found endoscopicaly. In 64% of pts histology showed signs of mucosal inflammation. Recurrent ulcer was found in 3 pts. H-pylori was present in 16 pts (40%). The significant reduction of BMD, especially of the lumbar spine, in the pts after the PG resection in comparison to the pts with the vagotomy was found. Within several years after gastric operation the patient must be carefully evaluated and adequate supplementation of Ca and vitamin D is strongly recommended.

Long term care insurance.

Long term care is a relatively new employee benefit issue and was virtually unheard of two years ago. Long term care plans have been implemented in a handful of companies and government retirement systems. Long term care has become an employee benefits issue because of the growing awareness of the risks of long term care to the elderly and the costs of long term care. Long term care benefit plans provide a means for protecting against those risks and costs. Although the design and implementation of a long term care benefit plan involve the same general principles as the design and implementation of any employee benefit, there is a basic difference. That difference lies in the fact that employees must be educated about the risks and expenses of long term care so they can make informed judgements about whether to participate in an employer-sponsored long term care benefit plan.