The impact of improved compliance with a weekly contraceptive transdermal system (Ortho Evra) on contraceptive efficacy

OBJECTIVE: The contraceptive efficacy of perfect dosing cycles and imperfect dosing cycles has not been described previously. Method compliance determines the proportion of perfect and imperfect dosing cycles, and together can form the basis for evaluating differences in efficacy based on differences in compliance. MATERIALS AND METHODS: The transdermal contraceptive delivery system (Ortho Evra) has been studied in a North American randomized trial vs. an oral contraceptive (OC) and in total has been evaluated in 3319 women in contraceptive clinical trials. This article explores the impact of perfect vs. imperfect compliance with the contraceptive method on contraceptive efficacy. Previously published data for a transdermal system (Patch, n = 812) and OC (Triphasil, n = 605) users from the North American comparative study were reanalyzed to determine the effect of imperfect use on the contraceptive efficacy of the different methods. RESULTS: Contraceptive efficacy was significantly better (p = 0.007) in cycles with perfect dosing (Pearl Index = 0.83) compared to those with imperfect dosing (Pearl Index = 6.32) for both methods. This difference is homogeneous (p = 0.62) across the Patch and OC groups. Pooled data for all Patch users confirm that perfect dosing cycles are associated with significantly better efficacy than imperfect dosing cycles (p = 0.047). In addition, compliance did not vary by age in the pooled Patch data, which are in agreement with the previously published Patch data from the comparative study. In the comparative study, the percentage of cycles with perfect dosing was significantly higher with the Patch than with the OC (88.7% vs. 79.2%, p < 0.001), and was consistently high in all age groups (range, 89.6-91.8%). By contrast, among OC users, the percentage of cycles with perfect dosing increased with increasing age (p < 0.001) from 67.7% in users aged 18-20 years to more than 80% in those aged 30 years and older. CONCLUSION: In conclusion, deviations from perfect use (whether corrected or not) of a transdermal contraceptive system and of an OC increase contraceptive failures by approximately 5-10-fold when compared to perfect use. The weekly change schedule of the transdermal contraceptive delivery system is associated with a significantly greater proportion of cycles in which there is perfect dosing compared to an OC.     

Decreased quality of peripheral blood progenitors collected after a peripheral blood progenitor transplant

The purpose of this study was to determine the quality of peripheral blood progenitor cells (PBPC) collected after an initial autologous PBPC transplant. Tandem autologous transplants have been used in the treatment of several malignancies. Routinely, PBPC have been collected prior to the first transplant and used for both transplants. In the current study, PBPC harvested prior to the first high-dose therapy (HDT) were used as a source of progenitors for transplant 1, and a combination of bone marrow harvested prior to the first course of HDT and PBPC collected approximately 85 days after the first transplant were used to support the second HDT. We analyzed the quality of the PBPC collected 85-120 days after HDT and autologous PBPC transplant. CD34 and colony-forming units granulocyte-macrophage (CFU-GM) contents of those collections were poor, and hematopoietic recovery was more consistent with recovery from a bone marrow transplant than a PBPC transplant. Thirteen of 15 patients received both transplants. Days to absolute granulocyte count of 500 was 10 +/- 1.5 for the first transplant and 13.3 +/- 3.7 for the second (p < 0.01). The number of days to platelet count of 20,000 was 14.3 +/- 10.7 for the first transplant and 18 +/- 7 for the second transplant (p = 0.066). The number of days of total parenteral nutrition (TPN) and intravenous morphine used by patients for the first and second transplants was similar, whereas the length of hospitalization was 21.8 +/- 3.6 for the first transplant and 27.6 +/- 7.8 for the second transplant (NS). In conclusion, it appears that the quality of PBPC collected following a previous PBPC transplant may be compromised.     

Evidence for a novel gene for familial febrile convulsions, FEB2, linked to chromosome 19p in an extended family from the Midwest

Febrile convulsions are a common form of childhood seizure. It is estimated that between 2 and 5% of children will have a febrile convulsion before the age of 5. It has long been recognized that there is a significant genetic component for susceptibility to this type of seizure. Wallace, Berkovic and co-workers recently reported linkage of a putative autosomal dominant febrile convulsion gene to chromosome 8q13-21. We report here another autosomal dominant febrile convulsion locus on chromosome 19p. Linkage analysis in this large multi- generational family gave a maximum pairwise lod score of 4.52 with marker Mfd120 at locus D19S177. Linkage to the chromosome 8 locus was excluded in this family. Haplotype analysis using both affected and unaffected family members indicates that this febrile convulsion gene, which we call FEB2 , can be localized to an 11.7 cM, 1-2 Mb section of chromosome 19p13.3, between loci D19S591 and D19S395.      

Activation of PAR2 receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint

Background and Purpose

The PAR₂ receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR₂ activation in the rat knee joint.

Experimental Approach

PAR₂ in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR₂ with its activating peptide, 2-furoyl-LIGRLO-NH₂ (1–100 nmol·100 μL⁻¹, via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR₂ activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR₂ activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH₂ or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK₁) receptors in the PAR₂ responses were assessed using the selective antagonists, SB366791 and RP67580 respectively.

Key Results

PAR₂ were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH₂ increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH₂ also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH₂ alone).

Conclusions and Implications

PAR₂ receptors play an acute inflammatory role in the knee joint via TRPV1- and NK₁-dependent mechanisms involving both PAR₂-mediated neuronal sensitization and leukocyte trafficking.     

鸟氨酸α酮戊二酸强化营养对大鼠癌性恶病质的作用:切除肿瘤可以提高营养支持的作用

探讨鸟氨酸α酮戊二酸对负荷肝细胞瘤Morris7777大鼠的作用。大鼠分别接受等氮、热卡的含鸟氨酸α酮戊二酸或甘氨酸的饲料。鸟氨酸α酮戊二酸已用于其它一些分解代谢状态（如创伤、败血症）。肿瘤植入自然生长3周后达11g／（100g体重），此时可以引起进行性的厌食、负氮平衡以及机体和组织的消耗。与甘氨酸比较，鸟氨酸α酮戊二酸既没有影响肿瘤的生长也没有改变肿瘤引起的宿主分解代谢变化。认为本研究以及当肿瘤占宿主体重4％～30％的报告中，强化营养支持效果欠佳的原因是由于肿瘤夺取了宿主的氨基酸。本实验证明肿瘤植入3周后，肿瘤自身的蛋白积累和对氨基酸氧化分解占宿主每日摄入蛋白量的～70％。由于临床工作中肿瘤总是在较小时被诊断并行初次治疗的。本实验进一步研究了手术切除肿瘤以限制疾病阶段后强化营养的作用。大鼠术前3天和术后3天或6天分别接受鸟氨酸α酮戊二酸或甘氨酸的饲料。鸟氨酸α酮戊二酸强化营养的大鼠其氮平衡、肌肉谷氨酰胺和支链氨基酸浓度、小肠蛋白积累高于甘氨酸强化营养的大鼠（P＜0．05）。本实验证明不切除肿瘤仅行营养支持其效果欠佳，而且为进一步实验研究建立了恰当的动物模型。     

Lack of agreement in classification of the severity of acute asthma between emergency physician assessment and classification using the National Asthma Council Australia guidelines (1998)

Aims: To determine the level of agreement in classification of the severity of acute asthma at presentation to the emergency department, between emergency physician global assessment and severity classification according to the National Asthma Council Guidelines, Australia 1998 (NACG). Methods: Prospective observational study in emergency departments throughout Australia, participating in the Asthma Snapshot 2000 project. Patients between the ages of one and 60 years presenting to participating emergency departments with acute asthma between 21 August and 3 September 2000 were included. Data collected were emergency physician global assessment of asthma severity and severity classification according to the National Asthma Council Guidelines and disposition. Results: Five hundred and five subjects had completed data for emergency physician assessment of severity and for calculation of severity classification according to the National Asthma Council Guidelines. Weighted kappa for agreement in classification was 0.48 (95% confidence interval: 0.40, 0.56). Emergency physicians assess asthma as less severe compared to the National Asthma Council Guidelines assessment. Conclusions: Agreement between physician assessment of severity of acute asthma and severity classification according to National Asthma Council Guidelines is only moderate. This may have implications in treatment and disposition. This also suggests that emergency physicians may be using other methods to classify acute asthma than the National Asthma Council Guidelines classification.     

Update on Percutaneous Mechanical Mitral Commissurotomy

A reusable metallic valvotomy device has been developed with the goals of improving the results of percutaneous mitral valvotomy and increasing the cost-effectiveness of the procedure. The device consists of a detachable and reusable metallic dilator with two articulated bars screwed at the distal end of a catheter. Using transseptal catheterization, the device is placed across the valve over a traction guidewire and then opened gradually by means of pliers up to a maximum of 40 mm. To date, the device was used in 168 patients with a broad spectrum of mitral valve disease. The procedure was successful in 95% of cases and resulted in an increase in mitral valve area from 1.01 ± 0.8 to 2.20 ± 0.7 cm². No increase in mitral regurgitation was noted in 87% of cases. Bilateral splitting of the commissures was observed in 89%. Complications included the following: 2 severe mitral regurgitations (one requiring surgery), 1 pericardial tamponade, 1 transient cerebrovascular embolic event. The maximum number of consecutive patients treated with the same device was 35. The results obtained are at least comparable to those of current balloon techniques and confirm the possibility of safe multiple reuses of the device after sterilization.