Evidence for the presence of makisterone A in Drosophila larvae and the secretion of 20-deoxymakisterone A by the ring gland

Ring glands or brain—ring gland complexes from third-instar Drosophila melanogaster larvae secreted ecdysone [(22R)-2β,3β,14α,22,25-pentahydroxy-5β-cholest-7-en-6-one] and two less polar ecdysteroids (LP1 and LP2) in vitro. Radioimmunoassay with different antisera indicated that LP1 and LP2 are side-chain-modified analogues of ecdysone. In high-performance liquid chromatography, the retention time of LP2 was equivalent to that of a precursor of makisterone A [(20R,22R)-2β,3β,14α,20,22,25-hexahydroxy-24-methyl-5β-cholest-7-en-6-one] secreted by Dysdercus fasciatus prothoracic glands in vitro. LP2 was metabolized in vitro by the fat body of Drosophila larvae to a product with the characteristics of makisterone A when analyzed by gas chromatography/mass spectrometry (selected ion monitoring). Evidence was obtained for the presence of makisterone A in Drosophila larvae. These data suggest that LP2 is 20-deoxymakisterone A (24-methylecdysone) and that makisterone A could function as an additional moulting hormone in Drosophila, although 20-deoxymakisterone A production is apparently dependent on the sterol composition of the diet. LP1 has not been identified.     

Ground reaction forces during stair locomotion in pregnancy

Pregnant women experience numerous physical alterations during pregnancy which may place them at an increased risk of falls. The purpose of this study was to examine ground reaction forces (GRFs) during staircase locomotion in pregnant and non-pregnant women.MethodsData were collected on 29 pregnant women in their second and third trimesters, and on 40 control women. Subjects walked at their freely chosen speeds during stair ascent and descent. A force plate imbedded in the second stair, but structurally independent of the staircase, was used to collect GRF data (1080 Hz). A marker placed on the L3/L4 spinal segment was used to determine ascent and descent velocity from a motion-capture system. In the statistical analyses, trimester (control, second trimester, third trimester) and subject were the independent variables. Stance time and ascent/descent velocity were analyzed with an ANOVA. Mediolateral excursion of the COP during the step was analyzed with an ANCOVA. The GRFs were categorized into anterioposterior, mediolateral, and vertical forces. A two factor MANCOVA (subject, trimester) was performed on each GRF category. Mass and velocity served as covariates in each analysis (α = 0.05).ResultsThe mediolateral excursion of the COP during ascent was greater in the third trimester (p = 0.04). The anterioposterior braking impulse was greater in both ascent (p = 0.01) and descent (p = 0.01) during pregnancy. The vertical GRF loading rate during descent was greater in pregnant women than in controls (p = 0.04).ConclusionThese alterations are likely related to increased instability during stairway walking and could contribute to increased fall risk during pregnancy.     

Visual influences on balance

This paper discusses the impact of vision on balance and orientation in patients with vestibular disorders and in anxiety patients with space and motion discomfort (SMD). When the vestibular system is impaired, vision has a greater influence on standing postural control, resulting in greater sway when individuals are presented with erroneous or conflicting visual cues. Studies have shown that individuals with other motion sensitivities, such as motion sickness, also tend to rely on vision for balance and do not disregard erroneous visual cues. Recently, patients with anxiety disorders that include SMD also have been shown to have increased postural sway in conflicting visual environments, similar to patients with vestibular disorders. Thus, while specific vestibular deficits are not always directly associated with SMD, data regarding the impact of vision on balance suggest that some patients with SMD may have an underlying balance disorder.     

The validity of two quality assessment instruments: Monitor and Senior Monitor

This paper is concerned with validity of Monitor and Senior Monitor. The study carried out, which was funded by the Department of Health, attempted to establish the validity of the instruments through a multiple triangulation research design. Monitor and Senior Monitor were compared to another instrument, Qualpacs, and also to other methods that focused on quality of nursing care—observation of patients' activities and interactions with nurses, and interviews with patients and nurses on their perceptions of quality.

The results did not reveal a clear picture. Convergent validity was relatively strong for Senior Monitor and the Monitor DG3 schedule, but not the DG1, DG2 and DG4 schedules, when compared to Qualpacs. The comparison with observation of nurse-patient activities and interactions supported Monitor rather more than Senior Monitor, particularly with respect to frequency of omitted activities. Both instruments showed considerable construct validity in that congruence emerged between their items and the views of patients and nurses on what constitutes quality.     

Safety, pharmacokinetics, and biological pharmacodynamics of the immunocytokine EMD 273066 (huKS-IL2): results of a phase I trial in patients with prostate cancer

This phase 1 clinical trial was conducted to evaluate the safety and to determine the maximum tolerated dose (MTD) of the immunocytokine EMD 273066 huKS-IL2 and, secondarily, to assess its pharmacokinetics, immunogenic potential, and immunologic activity in patients with androgen-independent prostate cancer (n = 22). EMD 273066 was administered in 3-day cycles (separated by 4 weeks) of once-daily, 4-hour intravenous infusions at a dose determined by an escalation protocol (0.4, 0.7, 1.4, 2.8, 4.3, 6.4, or 8.5 mg/m/d). Approximately 2/3 of patients received a second cycle of treatment. The results show that the MTD of EMD 273066 [ie, one dose level below that producing dose-limiting toxicity (DLT) in at least 33% of patients in a dosing group] was 6.4 mg/m/d. EMD 273066 was generally well tolerated up to a dose of 4.3 mg/m/d. No DLTs, defined as drug-related toxicities >OR= Grade 3 occurring during the first treatment cycle, were observed among patients in the 0.4-, 0.7-, 1.4-, or 4.3-mg/m/d dosing groups. Four patients treated with 2.8, 6.4, or 8.5 mg/m/d EMD 273066 experienced DLTs. Titers of both antiimmunocytokine and anti-FcIL-2 antibody responses were observed after the first dose cycle and either decreased or remained stable during a second course of treatment. No hypersensitivity reactions were observed. EMD 273066 exhibited immunologic activity as demonstrated by increases in lymphocyte counts, natural killer cell number and specific activity, and antibody-dependent cellular cytotoxicity activity. On average, Cmax, which was dose-dependent, was achieved within 1 hour after infusion. Mean t(1/2) which was independent of dose, ranged from 4.0 to 6.7 hours across doses. A zero-compartment body model with one-order kinetics best described the concentration-time profiles. These data demonstrate that the novel immunocytokine EMD 273066 is well tolerated at doses above a level of observed systemic biologic activity in patients with androgen-independent prostate cancer.     

Investigation of incidence of superficial peroneal nerve injury following ankle fracture

The aim of this study was to investigate the incidence of superficial peroneal nerve (SPN) injury following ankle fracture and to establish whether this differed between those treated by open reduction and internal fixation (ORIF) and those treated nonoperatively in a cast. Two hundred eighty patients who had been treated for an ankle fracture either surgically (ORIF group) or nonoperatively (cast group) were identified. Patients were invited for review, assessed using the AOFAS scoring system, and examined for any evidence of SPN injury. The surgical approach was documented and all fractures were classified according to the Weber classification. A total of 120 patients returned for review; 56 patients from the ORIF group and 64 patients from the cast group. The mean time from injury to review was 2 years (range, 12-36 months). Overall, 18 patients (15%) had a symptomatic SPN injury and these patients had a significantly lower AOFAS score. In the cast group, 9% of patients had painful symptoms from an SPN injury, compared to 21% of patients in the ORIF group (p < .05). No evidence of SPN injury was found in those who had a posterolateral approach to the ankle. Surgeons should be aware that the SPN is at risk during lateral approach to the fibula and that injury to this nerve can frequently be identified as a cause of chronic ankle pain.