Evaluation of a Clinical Cancer Trial Research Training Workshop: Helping Nurses Build Capacity in Southwest Virginia

Residents of Southwest Virginia (SWVA) face significant barriers in accessing the most advanced forms of cancer care, cancer risk reduction, and clinical trials involvement. A collaboration between the University of Virginia (UVA) Cancer Center and UVA School of Nursing was forged with oncology caregivers in this region to build community capacity to support Cancer Clinical trials (CCT) by strengthening the workforce, and thus improving health outcomes for this underserved region of Appalachia. The UVA School of Nursing designed an educational workshop focusing on the basics of CCT to facilitate the development of a skilled nursing workforce in the SWVA region that could provide care to patients on protocol and/or to encourage residents to participate in trials. The goal of the workshop was to offer a CCT training session for oncology nurses that fostered the knowledge and skills necessary to facilitate and support CCT infrastructure across this high‐risk region. This evaluation reports the learning outcomes of the CCT training on 32 nurse participants from SWVA. Evaluations of the training program showed high rates of satisfaction, increased comfort level with CCTs, and increased knowledge and attitude toward CCTs. These findings provide information about a curriculum that could be useful in educating other oncology nurses and student nurses how to care for patients who may be enrolled in a clinical trial. Nurses can also be advocates for participation in clinical trials once they have the knowledge and are comfortable in their own understanding of a trial's usefulness. Educating the nursing workforce is an essential component of building capacity and infrastructure to support clinical trials research.     

Do Ethical Principles Explain Moral Norm? A Test for Consent to Organ Donation

Moral norm is a strong predictor of intention with respect to certain behaviors. In the context of a study of organ donor consent, the goal was to enrich the ethics construct with the help of the following three dimensions: autonomy, beneficence, and justice. The results indicated that theinterrelations among the ethics variables were significant. However, the results also indicated that moral norm was influenced only by beneficence. Conducting other studies in different cultural contexts and verifying other behaviors would shed light on whether beneficence still influences moral norm.     

Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a mycobacterial adhesin

Although it generally is accepted that the interaction of Mycobacterium tuberculosis with alveolar macrophages is a key step in the pathogenesis of tuberculosis, interactions with other cell types, especially epithelial cells, also may be important. In this study we describe the molecular characterization of a mycobacterial heparin-binding hemagglutinin (HBHA), a protein that functions as an adhesin for epithelial cells. The structural gene was cloned from M. tuberculosis and bacillus Calmette–Guérin, and the sequence was found to be identical between the two species. The calculated M_r was smaller than the observed M_r when analyzed by SDS/PAGE. This difference can be attributed to the Lys/Pro-rich repeats that occur at the C-terminal end of the protein and to a putative carbohydrate moiety. Glycosylation of HBHA appears to protect the protein from proteolytic degradation, which results in the removal of the C-terminal Lys/Pro-rich region responsible for binding of HBHA to sulfated carbohydrates. Evidence suggests that glycosylation is also important for HBHA-mediated hemagglutination and for certain immunologic properties of the protein. Finally, the absence of a signal peptide in the coding region of HBHA raises the possibility that this protein is not secreted via the general secretion pathway.     

Coordination of motor pools controlling the ankle musculature in adult spinal cats during treadmill walking

The coordination of the motor pools of two ankle plantar-flexor, i.e. the soleus (Sol) and medial gastrocnemius (MG), and an ankle dorsiflexor, i.e. the tibialis anterior (TA) was quantified by comparing the EMG amplitude relationships in muscle pairs in normal and trained adult spinalized cats during treadmill walking across a range of relatively slow speeds (0.1 to 1.0 m/s). The effects of increased tactile stimulation or loading on locomotor performance were also studied in the spinal cats. Joint probability density distributions in the spinalized cats showed a low level of MG activation relative to Sol which did not change as speed increased. In general, the coordination between Sol and MG was similar in normal and spinal cats. However, towards the final phase of the extensor burst, the MG EMG amplitude decayed prematurely in spinal cats, particularly at higher speeds. Preferential elevation of MG relative to Sol activity was seen as a result of tactile stimulation. An elevated load resulted in a higher level of MG activation relative to Sol, prolonged MG activity at the end of the extensor burst, and the reduction in the clonic pattern of EMG typical of spinal cats. Spinalized cats showed an increased incidence of Sol-TA coactivation, especially at the higher speeds, due in part to the tonic activity in the TA. However, the overall reciprocal relationship between these antagonists was maintained. This reciprocity was preserved, but the high level of coactivation was unaffected by tactile stimulation. An elevated load, however, resulted in less Sol-TA coactivation. These results suggest that the coordination between synergists (Sol-MG) and between antagonists (Sol-TA and MG-TA), as well as the level of activation are modulated in the adult spinal cat similar to that observed in the normal cat. Further, there are specific types of proprioceptive-cutaneous information that can affect selected phases of the step cycle such that full weight-supporting stepping is significantly improved.     

Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice

The toxicity and efficacy of two oximes, HLö-7 and pyrimidoxime, were evaluated in mice and compared to those obtained with HI-6. HLö-7 and pyrimidoxime produced 24 h LD₅₀ values of 356 and 291 mg/kg (i.p.), respectively. In combination with atropine (17.4 mg/kg, i.p.), HLö-7 was a very efficient therapy against poisoning by 3×LD₅₀ dose of soman, sarin and GF and 2×LD₅₀ dose of tabun with ED₅₀ values of 12.4, 0.31, 0.32 and 25.2 mg/kg, respectively. In contrast, pyrimidoxime was a relatively poor therapy which resulted in ED₅₀ values of >150, 5.88, 100 and 71 mg/kg against poisoning by soman, sarin, GF and tabun, respectively. HLö-7 produced significant (p <0.05) reactivation of phosphorylated acetylcholinesterase, in vivo, resulting in 47, 38, 27 and 10% reactivation of sarin, GF, soman and tabun inhibited mouse diaphragm acetylcholinesterase, respectively. HLö-7 also antagonized sarin-induced hypothermia in mice suggesting that it reactivated central acetylcholinesterase. The potential of HLö-7 as a replacement oxime for the treatment of nerve agent poisoning is discussed.     

Stereoselective pharmacokinetics of ifosfamide and its 2- and 3-N-dechloroethylated metabolites in female cancer patients

 The pharmacokinetics of the R and S enantiomers of ifosfamide (IFF) and of its 2- and 3-N-dechloroethylated metabolites (2-DCE-IFF and 3-DCE-IFF) were investigated in 14 cancer patients treated with a 3-h infusion of (R,S)-IFF (3 g/m²) with mesna uroprotection. An enantioselective gas chromatographic-mass spectrometric (GC-MS) assay was used to determine the concentrations in plasma and urine. The AUCs of (R)-IFF were significantly larger than those of (S)-IFF (2480±200 vs 1960±150 μM . h). The terminal half-lives (7.57±0.99 h) and mean residence times (11.17±1.10 h) of (R)-IFF were significantly longer than those of (S)-IFF, 6.03±0.82 h and 9.37±0.88 h, respectively. The mean volume of distribution at steady state of (R)-IFF (25.68±0.80 l/m²) was slightly smaller than that of (S)-IFF (27.35±0.89 l/m²). While the renal clearances of (R)-IFF and (S)-IFF were similar, the nonrenal clearance was significantly lower for (R)-IFF (30.20±2.70 vs 41.40±3.55 ml/m² per min) as was total clearance (41.52±2.90 vs 52.37±3.75 ml/m² per min). The AUC values for all of the DCE metabolites from (S)-IFF were significantly greater than those from (R)-IFF with 47% of the measured AUC accounted for by DCE from (S)-IFF compared to only 20% for (R)-IFF. Therefore, the enantioselective difference in IFF elimination can be partially explained by differences in N-dechloroethylation. Received: 13 December 1994/Accepted: 14 May 1995     

Clinical and genetic study of chronic (types II and III) childhood onset spinal muscular atrophy

We have conducted a retrospective study of 63 patients affected by chronic forms of spinal muscular atrophy (SMA) to better document the natural history of this disease. Thirty-nine patients had type II and 24 type III SMA. These patients had manual muscle testing (MMT) and forced vital capacity (FVC) studies done every six to 12 months over follow up periods ranging from six to 140 months. A decline in FVC was seen in both types of SMA but there was no significant change in MMT in either group. Genetic studies were also done in a subset of 17 families (23 patients) included in this study. Homozygous deletions in the telomeric survival motor neuron (SMN) and the neuronal apoptosis inhibitory protein (NAIP) genes were observed in 100% and 11.8% of the patients tested respectively.