Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy

Although trihexyphenidyl is used clinically to treat both primary and secondary dystonia in children, limited evidence exists to support its effectiveness, particularly in dystonia secondary to disorders such as cerebral palsy. A prospective, open-label, multicenter pilot trial of high-dose trihexyphenidyl was conducted in 23 children aged 4 to 15 years with cerebral palsy judged to have secondary dystonia impairing function in the dominant upper extremity. All children were given trihexyphenidyl at increasing doses over a 9-week period up to a maximum of 0.75 mg/kg/d. Trihexyphenidyl was subsequently tapered off over the next 5 weeks. Objective motor assessments were performed at baseline, 9 weeks, and 15 weeks. The primary outcome measure was the Melbourne Assessment of Unilateral Upper Limb Function, tested in the dominant arm. Tolerability and safety were monitored closely throughout the trial. Of the 31 children who agreed to participate in the study, 5 failed to meet entry criteria and 3 withdrew due to nonserious adverse events (chorea, drug rash, and hyperactivity). Three children required a dosage reduction because of nonserious adverse events but continued to participate. The 23 children who completed the study showed a significant improvement in arm function at 15 weeks (P = .045) but not at 9 weeks (P = .985). Post hoc analysis showed that a subgroup (n = 10) with hyperkinetic dystonia (excess involuntary movements) worsened at 9 weeks (P = .04) but subsequently returned to baseline following taper of the medicine. The authors conclude that scientific evidence for the clinical use of trihexyphenidyl in cerebral palsy remains equivocal. Trihexyphenidyl may be a safe and effective for treatment for arm dystonia in some children with cerebral palsy if given sufficient time to respond to the medication. Post hoc analyses based on the type of movement disorder suggested that children with hyperkinetic forms of dystonia may worsen. A larger, randomized prospective trial stratified by the presence or absence of hyperkinetic movements is needed to confirm these results.     

The Premenstrual Syndrome and Fibromyalgia—Similarities and Common Features

The aim of the study was to assess the clinical similarities and common features of fibromyalgia syndrome (FM) and premenstrual dysphoric syndrome (PMDD). Thirty young patients who met the diagnostic criteria for PMDD were included in the study and compared to 26 women belonging to the medical staff of a general psychiatry department. All enrollees were interviewed and examined by a skilled physician. They completed the following nine survey items: demographic information, clinical health assessment questionnaire, fibromyalgia impact questionnaire, sleep and fatigue questionnaires, Sheehan disability scales, SF-36 assessment for quality of life, visual analog scale for pain, Mini International Neuropsychiatric Interview (MINI) questionnaire (assessment of coexistent psychiatric conditions), and the premenstrual severity scale. Additionally, each individual underwent a physical examination measuring the classical tender points and was asked to describe the distribution and continuum of her pain or tenderness. The PMDD group scored significantly higher in the measures pain and tenderness as well as in severity of premenstrual symptoms compared to the control group. Five patients in the PMDD group and none in the control group had FM. Quality of life measured by the SF-36 was higher in the control group than in the PMDD group and correlated with the degree of tenderness reported. Psychiatric comorbidity was significantly more common in the PMDD group, affecting 16 of the 30 PMDD patients compared to only three of the 26 control patients. In this study, patients with PMDD were found to have higher levels of tenderness, higher psychiatric comorbidity, greater level of physical disabilities, and a lower quality of life. These parameters were highly correlated with a lower pain threshold.     

Decision making for nurse staffing: Canadian perspectives

The effectiveness of methods for determining nurse staffing is unknown. Despite a great deal of interest in Canada, efforts conducted to date indicate that there is a lack of consensus on nurse staffing decision-making processes. This study explored nurse staffing decision-making processes, supports in place for nurses, nursing workload being experienced, and perceptions of nursing care and outcomes in Canada. Substantial information was provided from participants about the nurse staffing decision-making methods currently employed in Canada including frameworks for nurse staffing, nurse-to-patient ratios, workload measurement systems, and "gut" instinct. A number of key themes emerged from the study that can form the basis for policy and practice changes related to determining appropriate workload for nursing in Canada. These include the use of (a) staffing principles and frameworks, (b) nursing workload measurement systems, (c) nurse-to-patient ratios, and (d) the need for uptake of evidence related to nurse staffing.     

The Cost-Time Index: a new method for measuring the efficiencies of recruitment-resources in clinical trials

Paid media are important resources used to recruit subjects in clinical trials. An index for evaluating which advertising resource has minimal cost and time requirement for patient accrual, for a given study design, has not been previously introduced. In this communication the authors present a new index, the Cost-Time Index, which represents a measure of the average amount of money and time spent, simultaneously, on a given advertising resource to recruit one analyzable subject. This index can be calculated using retrospective data and may be a useful tool for comparing recruitment efficiencies among various resources. The authors demonstrate the utility of the Cost-Time Index and recommend its use as an additional variable in future studies regarding recruitment strategies in clinical trials.     

Disrupted relationships: adult daughters and father absence

Changes in family structures have resulted in many children growing up in non-traditional families, where their father is not resident in the family home. Father absence that occurs as a result of the breakdown of the parental relationship is associated with life adversity and less than optimal outcomes for children and adolescents. However, little research exists that explores this phenomenon from the perspective of the father absent young person. This phenomenological study was conducted in 2005 and aimed to explore women's perceptions about relationships with their fathers within the context of a father absent childhood. Nine women participated in this study. Findings revealed that growing up without their father present in the family home disrupted the relationship these daughters held with their fathers. Due to the perceived lack of interest these daughters felt from their fathers, they expressed feelings of hurt and diminished respect for their fathers. Furthermore, participants felt that their fathers were unable to provide them with the father-daughter relationship that they sought. The findings of this paper provide insights that can help nurses and other healthcare professionals to recognise the emotional impact that father absence can have on young women. Findings suggest a need for further research to gain greater insights into the experiences of family members who undergo disruption of relationships due to family breakdown.     

Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing

BACKGROUND & AIMS: Muc3 intestinal mucin contains an extracellular cysteine-rich domain with 2 epidermal growth factor (EGF)-like motifs. The aim of this study was to determine the functional properties of Muc3 proteins. METHODS: Glutathione S-transferase-fusion proteins containing both Muc3 EGF-like domains (m3EGF1,2) or truncated versions (m3EGF1 and m3EGF2) were purified from Escherichia coli. Mouse colon (young adult mouse colon) and human A431 and LoVo cells were examined for migration and tyrosine phosphorylation in response to recombinant proteins. LoVo cells were transfected with a human MUC3A transmembrane-EGF1,2 construct and a stable clone was isolated (LhM3c14). Endogenous MUC3A in LoVo was inhibited by specific small interfering RNA transfection. Apoptosis was quantitated by nuclear morphology or terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay. Colitis was induced in mice by oral 5% dextran sodium sulfate or rectal 5% acetic acid, followed by enema treatments. RESULTS: m3EGF1,2 stimulated cell migration in all cell lines, but did not induce proliferation. Migration was inhibited by a tyrosine phosphorylation inhibitor, genistein, but not by the EGF receptor inhibitor, tyrphostin (AG1478). Inhibition of endogenous MUC3A in LoVo reduced baseline migration. Tyrosine phosphorylation of ErbB receptors was not observed after treatment of cells with m3EGF1,2. LoVo cells pretreated with m3EGF1,2 and transfected LhM3c14 cells showed reduced apoptosis in response to tumor necrosis factor alpha or Fas-receptor stimulation. Administration of m3EGF1,2 per rectum significantly reduced mucosal ulceration and apoptosis in experimental acute colitis. Truncated proteins m3EGF1 and m3EGF2 had no effect. CONCLUSIONS: The Muc3 mucin cysteine-rich domain plays an active role in epithelial restitution, and represents a potential novel therapeutic agent for intestinal wound healing.     

Differential activation of insulin receptor isoforms by insulin-like growth factors is determined by the C domain

The actions of IGF-I and IGF-II are thought to be largely due to their activation of the IGF-I receptor. However, IGF-II can also bind with high affinity to, and effectively activate, an isoform of the insulin receptor (IR-A) that lacks a sequence at the carboxyl-terminal end of the extracellular alpha subunit due to the alternative splicing of exon 11. This isoform is poorly activated by IGF-I. Here, we show that IGF-II, but not IGF-I, induces potent autophosphorylation of residues Y1158, Y1162, and Y1163 in the activation loop of the kinase domain and tyrosine 960 in the juxtamembrane region of both IR-A and IR-B (exon 11+) isoforms. We have also found, by using IGF chimeras, that the C domain of IGF-II completely accounts for the ability of IGF-II to stimulate IR autophosphorylation compared with IGF-I. We further show that the C domains are responsible for the differential abilities of IGF-II and IGF-I to activate phosphorylation of insulin receptor substrate-1 and Akt, as well as their ability to induce migration and cell survival via the IR-A. Finally, we show for the first time that IGF signaling through the IR-A can protect cells from butyrate-induced apoptosis. In summary, our studies define the structural determinants that allow potent IGF-II signaling and regulation of cellular functions through the IR-A and provide novel insights into IGF signaling via the IR.     

Cervical and lumbar MRI findings in aviators as a function of aircraft type

BACKGROUND & AIMS: Neck pain and lower back pain (LBP) are frequently reported by military helicopter pilots (HP) and fighter pilots. A small number of studies have used imaging methods to evaluate spinal cervical degenerative findings in pilots exposed to high +Gz, with results indicating an increase in cervical disk protrusions in this population. We evaluated the cervical and lumbar spine with magnetic resonance imaging (MRI) to assess the prevalence of degenerative changes in three subpopulations of pilots. METHODS: Fighter pilots (FP), transport pilots (TP), and HP (10 pilots in each group) underwent cervical and lumbar MRI. Degenerative pathologic changes (disk herniation, cord compression, foraminal stenosis, and the presence of osteophytes) were evaluated in each group by two independent experienced radiologists. RESULTS: Cervical spine degenerative changes seemed to be associated with older age rather then aircraft type, affecting the older group of TP (8/10 pilots) more than the younger FP group who were exposed to high +Gz (3/10 pilots). In contrast, for lumbar spine degenerative changes, we found an uncommon pattern of lumbar spine degeneration in HP, affecting the upper part of the lumbar spine (10/13 disks found at L1-L4). CONCLUSIONS: The results of this study suggest that HP may have detectable degenerative lumbar findings. More research is needed to validate these findings as well as to explore the possible pathophysiological link between occupational exposures and the specific involvement of the upper lumbar spine.     

Etiologic factors for male breast cancer in the U.S. Veterans Affairs medical care system database

The etiology of male breast cancer is largely unknown, reflecting its relative rarity. Although a number of previous studies have suggested relationships with a variety of medical conditions, the results have largely derived from case–control studies and may reflect recall biases. Within the large U.S. Veterans Affairs computerized medical care system database, we had the opportunity to access 26 million hospital discharge records over the period 1969–1996 and to relate various documented medical conditions to the risk of subsequent male breast cancer. This allowed us to calculate relative risks (RR) and 95% confidence intervals (CI) for male breast cancer associated with conditions occurring one or more years after initial hospitalization, adjusted for age, race, calendar year, duration of follow-up, and number of hospital visits. Among 4,501,578 men aged 18–100 years, a total of 642 cases of primary male breast cancer were identified (523 among whites, 119 among blacks). Medical conditions that were significantly related to risk were diabetes (RR 1.30, 95% CI 1.05–1.60), obesity (1.98, 1.55–2.54), orchitis/epididymitis (1.84, 1.10–3.08), Klinefelter syndrome (29.64, 12.26–71.68), and gynecomastia (5.86, 3.74–9.17). Additionally, among black patients, cholelithiasis emerged as a significant risk predictor (3.45, 1.59–7.47). Diseases that have previously been related to male breast cancer risk that were not supported by our study results included thyroid diseases, smoking-related conditions, liver cirrhosis, prostatic hyperplasia, and fractures. After adjustment for obesity, the association with diabetes disappeared, but that with gynecomastia persisted. In multivariate models that simultaneously considered all important medical predictors of risk, significant risks were seen for Klinefelter syndrome (16.83, 6.81–41.62), gynecomastia (5.08, 3.21–8.03), obesity (1.91, 1.50–2.44), and orchitis/epididymitis (1.80, 1.08–3.01). These results support previous speculations that male breast cancer is influenced not only by tissue at risk, but also by hormonal and inflammatory factors.