Comparison of leuprolide acetate and triptorelin in assisted reproductive technology cycles: a prospective,randomized study

OBJECTIVE: To compare the use of two depot GnRH-a, leuprolide and triptorelin, in long-suppression GnRH-a protocols. DESIGN: Prospective, randomized study. SETTING: An IVF unit of an academic medical center.Fifty-two women who underwent controlled ovarian hyperstimulation and IVF. INTERVENTION(S): Patients were prospectively randomized to receive 3.75 mg depot formulations of either leuprolide or triptorelin on days 21-23 of the menstrual cycle. Stimulation with gonadotropins was initiated after pituitary desensitization was achieved. MAIN OUTCOME MEASURE(S): The stimulation pattern and cycle outcomes were compared between the two groups. RESULT(S): Twenty-six patients were included in each group. No significant differences were observed in the patient age, estrogen, and P levels on day of hCG administration, gonadotropin dosage, number of oocytes retrieved, fertilization rate, percentage of high-quality embryos, and number of embryos transferred. However, significantly higher clinical implantation and pregnancy rates were found in the leuprolide group compared with the triptorelin group. CONCLUSION(S): A depot preparation of leuprolide is associated with higher implantation and pregnancy rates than a depot preparation of triptorelin when it is used in the midluteal phase as part of the long-suppression GnRH-a protocol in IVF.     

Modulation of the hydrophobic domain of polymyxin B nonapeptide: effect on outer-membrane permeabilization and lipopolysaccharide neutralization

Polymyxin B nonapeptide (PMBN), a cationic cyclic peptide derived from the antibacterial peptide polymyxin B, is capable of specifically increasing the permeability of the outer membrane (OM) of Gram-negative bacteria toward hydrophobic antibiotics. In this study, we evaluated the contribution of the hydrophobic segment of PMBN (i.e., D-Phe(5)-Leu(6)) to this activity. Accordingly, we synthesized four analogs of PMBN by replacing D-Phe(5) with either with D-Trp or D-Tyr and Leu(6) with Phe or Ala and evaluated their ability to bind cell-free lipopolysaccharide (LPS) and increase bacterial OM permeability. Compared with PMBN, [D-Tyr(5)]PMBN and [Ala(6)]PMBN possessed reduced LPS affinity (IC(50) = 2.5, 25, and 12 microM, respectively) and significantly reduced OM permeability and LPS neutralization activity. [Phe(6)]PMBN exhibited rather similar affinity to cell-free LPS (IC(50) = 5 microM) and the same OM permeability capacity as PMBN. However, [D-Trp(5)]PMBN, despite its similar affinity to cell-free LPS (IC(50) = 4 microM), had moderately reduced OM permeability capacity. These results demonstrate the significant role of the PMBN hydrophobic segment in promoting biological activity.     

Economic analysis of filgrastim use for patients with acute myeloid leukaemia in the UK: a comparison of collection methods of resource use data

BACKGROUND: A clinical trial of patients with de novo acute myeloid leukaemia (AML) showed that haematopoietic support with filgrastim (granulocyte colony-stimulating factor, G-CSF) following induction and consolidation chemotherapy accelerated recovery from neutropenia. The clinical benefits included reductions in infections, anti-infective therapy and length of hospital stay. OBJECTIVE: The objective of this economic analysis is 2-fold. First, it aims to determine if the observed clinical benefits from the use of filgrastim would lead to cost savings from the perspective of a healthcare institution in the UK. Second, the analysis compares the results of two methods on collection of resource use data. DESIGN: A retrospective cost-minimisation analysis was undertaken based on the clinical results of all UK patients enrolled in the trial. Two cost models were developed: a model based only on the medical resource use collected in the case report forms (the CRF model); and a model based on all medical resources collected from patient medical files (the PF Model). Treatment costs of AML between filgrastim and the placebo arm were compared for the first induction cycle as well as the first induction and the first consolidation cycles combined. Results from the two models were compared. SETTING AND PATIENTS: The CRF model was applied to two samples of patients: all UK patients (n = 82) and patients enrolled at one centre [the Manchester Royal Infirmary (MRI) (n = 30)], whereas the PF model was applied to the MRI patient sample only. RESULTS: For all UK patients, using the CRF model, the filgrastim-treated arm produced cost savings of 747 pounds sterling (9.0%) and 2135 pounds sterling (14.4%) [1998 values] per patient in the first induction cycle and in the induction and consolidation cycles combined, respectively. For the patients at MRI the CRF model resulted in cost savings with filgrastim of 177 pounds sterling (2.2%) and 414 pounds sterling (3.2%) per patient respectively. Using the PF model the savings at MRI were 910 pounds sterling (8.6%) and 1285 pounds sterling (8.0%) per patient, respectively. CONCLUSION: Use of filgrastim in the treatment of AML in the UK may result in net cost savings. A retrospective analysis using total resources obtained through patient files produced higher cost savings estimates than that obtained by resources noted in the CRFs. The models based on PF resource data may be more reliable because they are more comprehensive. However, the cost estimates in this study may have been impacted by sample size, site characteristics, disease and treatment settings. Therefore, further evaluation on the methods for collecting resource use data in larger, multicentred studies is warranted.     

Performance of infusion pumps during hyperbaric conditions

BACKGROUND: Many hyperbaric facilities use infusion pumps inside the chamber. It is therefore important to ensure that this equipment will perform accurately during hyperbaric conditions. The authors tested the function and accuracy of the Imed 965 and Infutec 520 volumetric infusion pumps, the Easy-pump MZ-257 peristaltic infusion pump, and the Graseby 3100 syringe pump. METHODS: The authors calculated the deviations of infused volumes at low and high rates (12-18 and 60-100 ml/h) on three different hyperbaric protocols (up to 2.5, 2.8, and 6 atmospheres absolute [ATA]), resembling a standard hyperbaric oxygen treatment and US Navy treatment tables used for decompression illness and for arterial gas embolism. Two examples of each pump model were examined in every experiment. RESULTS: The Easy-pump MZ-257 failed to function completely beyond a chamber pressure of 1.4 ATA, making it unsuitable for use inside the hyperbaric chamber. The Graseby 3100 failed to respond to all keyboard functions at 2.5-2.8 ATA, making it unsuitable for use in most hyperbaric treatments. The Imed 965 performed within an acceptable volume deviation (< or =10%) during most hyperbaric conditions. During the compression phase of the profiles used, and for the low infusion rates only, exceptional volume deviations of 20-40% were monitored. The Infutec 520 demonstrated an acceptable deviation (within 10%) throughout all the hyperbaric profiles used, unaffected by changes in ambient pressure or infusion rate. CONCLUSIONS: Commercially available infusion pumps operating during hyperbaric conditions demonstrate substantial variations in performance and accuracy. It is therefore important that the hyperbaric facility staff make a careful examination of such instruments to anticipate possible deviations in the accuracy of the equipment during use.     

Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study

OBJECTIVE: The prevalence of cigarette smoking among schizophrenia patients is significantly higher than in the general population; this may reflect self-medication of symptoms and/or adverse effects of neuroleptics. The authors examined the prevalence of cigarette smoking in apparently healthy adolescents later hospitalized for schizophrenia. METHOD: Each year, a random sample of male Israeli military recruits, who have been screened and found not to be suffering from major psychopathology, complete a smoking questionnaire. Through the Israeli National Psychiatric Hospitalization Case Registry, 14,248 of these adolescents were followed to determine later psychiatric hospitalization. RESULTS: Of the 14,248 adolescents assessed, 4,052 (28.4%) reported smoking at least one cigarette a day. Over a 4-16-year follow-up, the prevalence of schizophrenia in the entire cohort was 0.3% (N=44). Smokers were at greater risk for later schizophrenia; the adjusted relative risk was 1.94, and the 95% confidence interval (CI) was 1.05-3.58. The number of cigarettes smoked was significantly associated with the risk for schizophrenia. Compared to nonsmokers, adolescents who smoked 1-9 cigarettes/day were 1.38 times (95% CI=0.48-4.00) as likely to be hospitalized later for schizophrenia, and adolescents who smoked 10 cigarettes/day or more were 2.28 times (95% CI=1.19-4.34) as likely; the latter difference was statistically significant. CONCLUSIONS: Taken together with the existing data on abnormalities in nicotinic transmission in patients and their relatives, this higher prevalence of smoking in future schizophrenia patients, before the onset of their illness, might indicate that impaired nicotinic neurotransmission is involved in the pathophysiology of schizophrenia.     

Eruption cysts: a clinical report of 24 new cases

The eruption cyst (EC) occurs within the mucosa overlying a tooth that is about to erupt. In the past EC was considered a type of dentigerous cyst (DC) occuring in the soft tissues. Twenty four patients (mean age 4.44 years, range 1.0 month-12 years) with EC were diagnosed and treated. EC was associated with natal teeth in two (8.3%) cases, with primary teeth in 10 (41.6%) cases and with permanent teeth in 12 (50%) cases. There was a gender predilection, the male to female ratio was 2:1. The primary mandibular central incisors and the permanent first molars were the most common site affected. The clinical appearance was a raised, bluish gingival mass on the alveolar ridge. The size was variable and dependent on the size and number of the associated teeth. The type of treatment provided was one of the following: no treatment (10 cases, 42%), extraction (2 cases, 8%) and marsupialization (12 cases, 50%). All surgical specimens underwent histopathologic examination. EC should be recognized as a separate entity from DC and a conservative treatment approach is recommended.