Infection control and meticillin-resistant Staphylococcus aureus decolonization: the perspective of nursing home staff.

BACKGROUND: Infection control and meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes have started to assume greater importance in practice and policy. AIM: To explore infection control and MRSA decolonization in nursing homes in Northern Ireland from the perspective of nursing home staff. METHODS: Semi-structured interviews with nursing home managers and focus group discussions with nursing home staff were conducted, transcribed verbatim and analysed via the framework method. FINDINGS: Six one-to-one interviews and six focus group discussions (N = 7, 6, 6, 5, 5 and 4 participants, respectively) were conducted. Three overarching themes with inter-related subthemes were identified as influencing infection control and MRSA decolonization in the nursing homes: organizational factors (e.g. time, financial resources, environment, management and culture), external factors [e.g. hospitals, regulation and general practitioners (GPs)], and residents and families. It was reported that when the workload was unmanageable, aspects of infection control were not adhered to and more financial resources were necessary. There was conflict in maintaining an environment that was both 'homely' and clinical, and it was difficult to achieve good infection control practices with confused residents, some families, GPs and members of staff who were resistant to change. Support for MRSA decolonization in nursing homes was tempered by the risk of recolonization, particularly from hospital admissions. CONCLUSIONS: Infection control and MRSA decolonization in the nursing home environment appear to be affected by many factors, some of which may be beyond the direct control of staff.

Mental health problems and medically unexplained physical symptoms in adult survivors of childhood sexual abuse: an integrative literature review.

People sexually abused in childhood are at higher risk than non-abused people of medically unexplained symptoms such as irritable bowel syndrome or chronic pain, with mental ill health and high healthcare use. Friction and frustration, with high, unproductive healthcare costs, can often develop between these patients and health-care professionals such as general practitioners and nursing staff. The aim of this integrative literature review was to seek a sound evidence base from which to develop helpful interventions, improve relationships and identify gaps in knowledge. It found some theories about interconnections among childhood sexual abuse mental health and medically unexplained symptoms, such as 'somatization' or 'secondary gain', were used prejudicially, stigmatizing survivors. Conflicting theories make more difficult the search for effective interventions. Researchers rarely collaborated with sexual abuse specialists. Emphasis on identifying key risk factors, rather than providing support or alleviating distress, and lack of studies where survivors voiced their own experiences, meant very few targeted interventions for this group were proposed. Recommendations to enable effective interventions include making abuse survivors the prime study focus; qualitative research with survivors, to assist doctors and nursing staff with sensitive care; case histories using medical records; prospective studies with sexually abused children; support for the growing field of neurobiological research.

Effects of lapatinib monotherapy: results of a randomised phase II study in therapy-naive patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER-2) tyrosine kinases. This study investigated the pharmacodynamic and clinical effects of lapatinib in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: In total, 107 therapy-naive patients with locally advanced SCCHN were randomised (2 : 1) to receive lapatinib or placebo for 2-6 weeks before chemoradiation therapy (CRT). Endpoints included apoptosis and proliferation rates, clinical response, and toxicity. RESULTS: Versus placebo, lapatinib monotherapy did not significantly increase apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling or caspase-3 assays. A statistically significant decrease in proliferation using Ki67 assay was observed (P=0.030). In a subset of 40 patients that received 4 weeks of lapatinib or placebo, objective response rate (ORR) was 17% (n=4/24) vs 0% (n=0/16). In the lapatinib single-agent responders, all had EGFR overexpression, 50% had EGFR amplification, and 50% had HER2 expression by immunohistochemistry (including one patient with HER2 amplification). However, these patients showed variable modulation of apoptosis, proliferation, and phosphorylated EGFR on drug treatment. Following CRT, there was a statistically non-significant difference in ORR between lapatinib (70%) and placebo (53%). There was no clear correlation between changes in apoptosis or proliferation and response to chemoradiation. Mucosal inflammation, asthenia, odynophagia, and dysphagia were the most commonly reported adverse events with lapatinib. CONCLUSION: Short-term lapatinib monotherapy did not demonstrate apoptotic changes, but provided evidence of clinical activity in locally advanced SCCHN, and warrants further investigation in this disease.

Cluster randomised controlled trial of an infection control education and training intervention programme focusing on meticillin-resistant Staphylococcus aureus in nursing homes for older people.

The aim of this cluster randomised controlled trial was to test the impact of an infection control education and training programme on meticillin-resistant Staphylococcus aureus (MRSA) prevalence in nursing homes. Nursing homes were randomised to intervention (infection control education and training programme; N=16) or control (usual practice continued; N=16). Staff in intervention homes were educated and trained (0, 3 and 6 months) in the principles and implementation of good infection control practice with infection control audits conducted in all sites (0, 3, 6 and 12 months) to assess compliance with good practice. Audit scores were fed back to nursing home managers in intervention homes, together with a written report indicating where practice could be improved. Nasal swabs were taken from all consenting residents and staff at 0, 3, 6 and 12 months. The primary outcome was MRSA prevalence in residents and staff, and the secondary outcome was a change in infection control audit scores. In all, 793 residents and 338 staff were recruited at baseline. MRSA prevalence did not change during the study in residents or staff. The relative risk of a resident being colonised with MRSA in an intervention home compared with a control home at 12 months was 0.99 (95% confidence interval: 0.69, 1.42) after adjustment for clustering. Mean infection control audit scores were significantly higher in the intervention homes (82%) compared with the control homes (64%) at 12 months (P<0.0001). Consideration should be given to other approaches which may help to reduce MRSA in this setting.

Isolation and characterization of mutations in region 1.2 of Escherichia coli sigma70.

Eubacterial RNA polymerase uses the sigma (sigma) subunit for recognition of and transcription initiation from promoter DNA sequences. One family of sigma factors includes those related to the primary sigma factor from Escherichia coli, sigma70. Members of the sigma70 family have four highly conserved domains, of which regions 2 to 4 are present in all members. Region 1 can be subdivided into regions 1.1 and 1.2. Region 1.1 affects DNA binding by sigma70 alone, as well as transcription initiation by holoenzyme. Region 1.2, present and highly conserved in most sigma factors, has not yet been assigned a putative function, although previous work has demonstrated that it is not required for either association with the core subunits of RNA polymerase or promoter-specific binding by holoenzyme. We generated random single amino acid substitutions targeted to region 1.2 of E. coli sigma70 as well as a deletion of region 1.2, and characterized the behaviour of the mutant sigma factors both in vivo and in vitro to investigate the function of region 1.2 during transcription initiation. In this study, we show that mutations in region 1.2 can affect promoter binding, open complex and initiated complex formation and the transition from abortive transcription to elongation.

Heterogeneity in nuclear transport does not affect the timing of DNA synthesis in quiescent mammalian nuclei induced to replicate in Xenopus egg extracts.

Intact G0 nuclei from quiescent mammalian cells initiate DNA synthesis asynchronously in Xenopus egg extracts, despite exposure to the same concentration of replication factors. This indicates that individual nuclei differ in their ability to respond to the inducers of DNA replication. Since the induction of DNA synthesis requires the accumulation of replication factors by active nuclear transport, any variation in the rate of transport among nuclei could contribute to the variability of DNA replication. Using the naturally fluorescent protein allophycocyanin (APC) coupled with the nuclear localization sequence (NLS) of SV40 T antigen, as a marker of nuclear uptake, we show here that individual G0 nuclei differ in their rate of transport over a range of more than 20-fold. Surprisingly, this variation has no direct influence on the timing or extent of DNA synthesis. Similar results were obtained by monitoring the uptake of nucleoplasmin, a nuclear protein present at high levels in egg extracts. These experiments show that the initiation of DNA synthesis is not driven merely by the accumulation of replication factors to some threshold concentration. Instead, some other explanation is needed to account for the timing of initiation.

Spinal stabilization by using crossed-screw anterior-posterior fixation after multisegmental total spondylectomy for thoracic chondrosarcoma. Case report.

The authors describe the case of a 41-year-old man with high-grade chondrosarcoma who presented with a paraspinous mass extending into three thoracic vertebrae (T10-12). Crossfixed long anterior and posterior instrumentation was placed after three complete spondylectomies (T10-12). This technique augments spinal stability with an outrigger effect by using crossfixators placed between paired dorsal rods, as well as between the anterior and posterior hardware components. This technique may be used as an alternative when multiple vertebrae or all three spinal columns are involved by radioresistant malignant tumors in patients in whom there is a relatively long life expectancy.

Glucose levels are not associated with common features-derived prototype memory abstractions.

Elevated glucose levels are associated with increased recall on declarative memory tasks. No previous studies have examined such a relationship using a common features-derived prototype memory abstraction task. 20 participants volunteered, 10 each in an experimental group who were given 40 g of glucose to drink and a control group given an artificially sweetened beverage after fasting. Analysis indicated that common features-derived prototype memory abstractions seem resistant to glucose fluctuations.

Magnetic source imaging and brain surgery: presurgical and intraoperative planning in 26 patients.

OBJECT: The availability of large-array biomagnetometers has led to advances in magnetoencephalography that permit scientists and clinicians to map selected brain functions onto magnetic resonance images. This merging of technologies is termed magnetic source (MS) imaging. The present study was undertaken to assess the role of MS imaging for the guidance of presurgical planning and intraoperative neurosurgical technique used in patients with intracranial mass lesions. METHODS: Twenty-six patients with intracranial mass lesions underwent a medical evaluation consisting of MS imaging, a clinical history, a neurological examination, and assessment with the Karnofsky Performance Scale. Magnetic source imaging was used to locate the somatosensory cortex in 25 patients, the visual cortex in six, and the auditory cortex in four. The distance between the lesion and the functional cortex was determined for each patient. Twenty-one patients underwent a neurosurgical procedure. As a surgical adjunct, a frameless stereotactic navigational system was used in 17 cases and a standard stereotactic apparatus in four cases. Because of the results of their MS imaging examination, two patients were not offered surgery, four underwent a stereotactic biopsy procedure, 10 were treated with a subtotal surgical resection, and seven were treated with complete surgical resection. One patient deteriorated before a procedure could be scheduled and, therefore, was not offered surgery, and two patients were offered surgery but declined. Three patients experienced surgery-related complications. CONCLUSIONS: Magnetic source imaging is an important noninvasive neurodiagnostic tool that provides critical information regarding the spatial relationship of a brain lesion to functional cortex. By providing this information, MS imaging facilitates a minimum-risk management strategy and helps guide operative neurosurgical technique in patients with intracranial mass lesions.

Radiation-induced blood-brain barrier damage in astrocytoma: relation to elevated gelatinase B and urokinase.

Successful management of brain tumors prolongs life, raising the risk of delayed injury secondary to the treatment. Radiation therapy, a mainstay of brain tumor treatment, can damage the cerebral blood vessels. Acutely a breakdown of the blood-brain barrier (BBB) may be seen, but fibrosis complicates radiation injury in the chronic phase. Matrix metalloproteinases (MMPs) and plasminogen activators are two matrix-degrading proteolytic enzymes, which are induced by radiation. They disrupt the basal lamina around cerebral capillaries and open the BBB. We report a patient with an astrocytoma managed by partial resection and external beam irradiation to maximal tolerable doses. The patient later developed malignant brain edema shortly after stereotactic radiosurgery. Tissue obtained during surgical debulking to control the edema showed very high levels of gelatinase B (92 kDa type IV collagenase) and urokinase-type plasminogen activator (uPA). Tumor cells were absent from the biopsy and subsequent autopsy specimens, but necrosis with fibrosis of the blood vessels was seen. If abnormal matrix enzyme function participates in the expression of radiation injury, then inhibitors to such enzymes may provide one strategy for controlling cerebrovascular damage after therapeutic brain radiation.

Reducing alcohol consumption. Comparing three brief methods in family practice.

OBJECTIVE: To compare the effects of three brief methods of reducing alcohol consumption among family practice patients. DESIGN: Patients randomly assigned to one of three interventions were assessed initially and at 3-, 6-, and 12-month follow-up appointments. SETTING: Family practice clinic composed of 12 primary care physicians seeing approximately 6000 adults monthly in a small urban community, population 40,000. PARTICIPANTS: Through a screening questionnaire, 134 men and 131 women were identified as hazardous drinkers (five or more drinks at least once monthly) during an 11-month screening of 1420 patients. Of 265 patients approached, 180 agreed to participate and 159 (83 men and 76 women) actually participated in the study. INTERVENTIONS: Three interventions were studied: brief physician advice (5 minutes), two 30-minute sessions with a physician using cognitive behavioural strategies or two 30-minute sessions with a nurse practitioner using identical strategies. MAIN OUTCOME MEASURES: Quantity and frequency (QF) of drinking were used to assess reduction in hazardous drinking and problems related to drinking over 12 months of follow up. RESULTS: No statistical difference between groups was found. The QF of monthly drinking was reduced overall by 66% (among men) and 74% (among women) for those reporting at least one hazardous drinking day weekly at assessment (N = 96). Men reported drinking significantly more than women. CONCLUSIONS: These results indicated that offering brief, specific advice can motivate patients to reduce their alcohol intake. There was no difference in effect between brief advice from their own physician or brief intervention by a physician or a nurse.

Direct thrombolysis of superior sagittal sinus thrombosis with coexisting intracranial hemorrhage.

We present a case of dural cerebral venous thrombosis with coexisting left frontal hemorrhage that was successfully treated with 13.79 million units of urokinase over a period of 165 hours.

Adoptive immunotherapy of malignant glioma using tumor-sensitized T lymphocytes.

Malignant glioma remains one disease for which there is no curative therapy. Clearly there is a need to explore new and innovative approaches for their treatment. In this report, we review our preclinical trial of a new adoptive immunotherapy protocol using cytotoxic T lymphocytes (CTL) which had been sensitized to glioma in vivo and then activated and their number expanded ex vivo using compounds which enhance signal transduction. These glioma-sensitized lymphocytes, when introduced systemically into rats with either an intracerebral or intradermal glioma, eradicated or slowed the progression of their tumor. These results indicate for the first time that a reproducible and sustained eradication of a malignant glioma could be achieved by the adoptive transfer of tumor-sensitized, ex vivo expanded CTL. A Phase I clinical trial is now underway to test the safety and potential efficacy of this immunotherapy in patients with recurrent malignant glioma.