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2004 Lowbury Lecture: the Western Australian experience with vancomycin-resistant enterococci - from disaster to ongoing control.

The first hospital outbreak of a vancomycin-resistant enterococcus (VRE) in Western Australia (WA) started in the Royal Perth Hospital in July 2001 and initially involved the Intensive Care Unit (ICU) and the Nephrology and Dialysis Units. The outbreak was caused by vancomycin-resistant Enterococcus faecium (VREF) of the vanB genotype. Pulsed-field gel electrophoresis and plasmid analysis of the isolates demonstrated a single-strain outbreak. Despite the isolation of carriers and implementation of all the additional precautions recommended to control VRE, VREF spread rapidly. Two months after the index patient was detected, the epidemic strain had spread to 22 wards and units and one outpatient unit (Satellite Dialysis). Four patients were infected and 64 were colonized. A Hospital VRE Executive Group, which included the Chief Executive and Directors of Clinical Services and Nursing, was formed to eradicate the outbreak and to prevent the epidemic strain from becoming endemic in the hospital. The WA Department of Health agreed to provide substantial extra funding to enable the hospital to use expensive enhanced infection control practices, as follows. Control was handicapped by the slowness of conventional laboratory methods, which took four to five days to identify VRE and allowed environmental contamination and nosocomial transmission to occur before carriers were detected and isolated. A laboratory procedure to make rapid provisional identification of VRE within 30-48h was developed by performing multiplex polymerase chain reaction (PCR) for vanA and vanB genes directly on 24-h selective enrichment broth cultures. On average, four rectal swabs, each collected on separate days, were needed to detect >90% of carriers. In total, 1977 ward contacts were screened after discharge from hospital and 54 (2.73%) were found to be carrying VREF. The electronic labelling and active follow-up of ward contacts resulted in a significant number of carriers being detected who otherwise posed a risk of initiating further outbreaks in hospital if they were re-admitted. The outbreak was terminated after five months and the cost of the enhanced infection control practices was 2,700 000 Australian dollars (1,000,000 pounds sterlings). Ongoing control has been facilitated by targeted active surveillance cultures: on admission to high-risk units (ICU, Burns, Nephrology, Haematology, Bone Marrow Transplant Unit), on transfer out of the ICU to other hospital units, by monthly screening of patients regularly attending Dialysis Units, and by opportunistic laboratory screening of inpatient faecal specimens submitted for Clostridium difficile culture and toxin. Vigilance needs to be maintained as the epidemic strain of VREF remains in the Perth community. Ward contacts of the first outbreak have caused small outbreaks in two hospitals, and seven to 19 sporadic new carriers have been detected annually since the first outbreak. The key elements of the VRE control programme are as follows: To date, this programme has prevented VRE from becoming established in any WA hospital.

Bacterial Proteins↗

Lowbury Lecture 2005: infection control from a global perspective.

All healthcare settings around the world face the problem of healthcare-associated infections (HCAIs). Rates of infection vary between countries and within the same country depending on resources, interest of caregivers and healthcare staff, and patients' socio-economic situation. According to recent publications, 10-70% of HCAIs are preventable. Failure to comply with guidelines on hand hygiene, glove and gown use, and barrier nursing is a problem and unnecessary infection control measures are costly. National legislations and regional, national and international standards and guidelines associated with infection control also have an impact for countries that are not directly involved. They should be based on the assessment of infection risk, and should not increase costs unnecessarily. The International Federation of Infection Control and national infection control societies play an important role in continuing the education of infection control specialists.

Cross Infection↗

G. Paul Moore Lecture: Unifying the disciplines of our voice smorgasbord.

A look at the many disciplines working with voice over the past 50 years is provided from the perspective of a speech-language pathologist (SLP). Some of the earliest collaborations between medicine and speech-language pathology were seen in the management of cleft palate and velopharyngeal inadequacy problems and observed, also, in laryngectomee rehabilitation. The earlier concern of the SLP for the emotional and psychological aspects of patients with voice disorders appeared replaced with the rise of symptomatic therapy. Dramatic improvement in instrumentation assisted by computer analyses increased our awareness and understanding of both normal and disordered phonation. Although instrumentation today allows for many forms of visual feedback in voice training and therapy, this may be often at the expense of providing needed kinesthetic-proprioceptive and auditory feedback. Particular voice therapy approaches (cognitive, gestalt-holistic, imagery, resonant therapy, muscle training, and symptomatic therapy) used today are described. Suggestions are given for improving educational requirements and clinical experience in voice for SLPs.

Cleft Palate↗

Second Annual Mario S. Verani, MD, Memorial Lecture: Nuclear cardiology, the next 10 years.

The nuclear cardiology of the future will be based on new clinical and biologic targets. It will be driven by modern concepts of molecular and cell biology and molecular genetics. A major effort involves detection of atherosclerosis and vascular vulnerability. Approaches include targeting proliferating smooth muscle cells, angiogenesis, vascular injury, inflammation through a variety of mechanisms, defining cell death and protease activation, and imaging gene expression. Another new clinical target involves imaging stem cells and various progenitor cells. To meet these new objectives, advanced imaging technology is required. This involves the development of micro-single photon emission computed tomography and micro-positron emission tomography systems as well as fusion technology involving radiologic computed tomography imaging together with nuclear imaging. Vascular lesion detection imaging may require intravascular detectors. The future of nuclear cardiology, based on molecular imaging, is extraordinarily exciting. The newly defined biologic targets will allow the answering of many of the key clinical questions that will dominate cardiovascular care in cardiovascular investigation over the next decade.

Animals↗

Survey of 1264 patients with orbital tumors and simulating lesions: The 2002 Montgomery Lecture, part 1.

OBJECTIVE: To determine the incidence of specific orbital tumors based on patients referred to an ocular oncology center. DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 1264 consecutive patients referred to an ocular oncology service because of space-occupying orbital lesions. METHODS: A retrospective chart review was carried out for 1264 consecutive patients referred for a suspected orbital mass over a 30-year period. The lesions were grouped into general categories, as shown in "Results." The specific diagnosis in each case was based on clinical findings, computed tomography scan results, magnetic resonance imaging results, and histopathologic analysis results, when available. The number and percentage of benign and malignant tumors per age group also was determined. MAIN OUTCOME MEASURES: The incidence of orbital tumors and pseudotumors. RESULTS: Among 1264 consecutive patients, the number and percentage of lesions in each general category were as follows: cystic, 70 cases (6%); vasculogenic, 213 cases (17%); peripheral nerve lesions, 23 (2%); optic nerve and meningeal tumors, 105 (8%); fibrocytic lesions, 13 (1%); osseous and fibro-osseous tumors, 21 (2%); cartilaginous lesions, 1 (<1%); lipocytic and myxoid lesions, 64 (5%); myogenic tumors, 36 (3%); lacrimal gland lesions, 114 (9%); primary melanocytic lesions, 11 (<1%); metastatic tumors, 91 (7%); lymphoma and leukemia lesions, 130 (10%); secondary orbital tumors, 142 (11%); histiocytic lesions, 17 (1%); thyroid-related orbitopathy, 67 cases (5%); other inflammatory lesions, 133 cases (11%); and miscellaneous other lesions, 13 (1%). The most common diagnoses were: lymphoid tumor (139 cases;11%), idiopathic orbital inflammation (135 cases; 11%), cavernous hemangioma (77 cases; 6%), lymphangioma (54 cases; 4%), meningioma (53 cases; 4%), optic nerve glioma (48 cases; 4%), metastatic breast cancer (44 cases;4%), orbital extension of uveal melanoma (41 cases; 3%), capillary hemangioma (36 cases;3%), rhabdomyosarcoma (35 cases; 3%), dermolipoma (31 cases; 3%), herniated orbital fat (30 cases; 2%), dermoid cyst (26 cases; 2%), varix (26 cases; 2%), dacryops (19 cases; 2%), and other less common lesions. Of the 1264 lesions, 810 (64%) were benign and 454 (36%) were malignant. The percentage of malignant lesions was 20% in children (age range, 0-18 years), 27% in young adults and middle-aged patients (age range, 19-59 years), and 58% in older patents (age range, 60-92 years). Rhabdomyosarcoma was the most common malignancy in children, representing 3% of all orbital masses, and lymphoma was the most common malignancy in older patients, representing 10% of cases. CONCLUSIONS: A variety of tumors and pseudotumors can involve the orbit. In this series of 1264 lesions, 64% were benign and 36% were malignant. The percentage of malignant tumors increased with age, with malignancies being common in older patients because of the higher incidence of lymphoma and metastasis in the elderly.

Adolescent↗

Melanocytoma of optic disc in 115 cases: the 2004 Samuel Johnson Memorial Lecture, part 1.

PURPOSE: To report clinical variations and the natural course of melanocytoma of the optic disc. PATIENTS AND METHODS: A retrospective study was conducted on a consecutive series of patients with melanocytoma of the optic disc who were evaluated at the Ocular Oncology Service at Wills Eye Hospital. Demographic information and variations in appearance and size of the tumor and local ocular complications were noted. Frequency of tumor growth and malignant transformation was recorded. Clinical factors, including patient data and tumor features, were analyzed for their impact on visual acuity loss of 2 or more Snellen lines and the tumor growth, using Cox proportional hazards regression models. Kaplan-Meier survival estimates of probability of visual acuity loss of 2 or more Snellen lines and probability of tumor growth were performed as a function of time from the initial examination. MAIN OUTCOME MEASURES: Visual acuity loss of 2 or more Snellen lines, tumor growth, and malignant transformation of the tumor. RESULTS: There were 115 patients (116 eyes) with melanocytoma of the optic disc. The mean age at diagnosis was 50 years; 38% of patients were male and 62% of patients were female; 65% of patients were white, 29% of patients were African American, and 6% of patients were Asian, Hispanic, Indian, or Arabic. The lesion was unilateral in 99% of patients. Visual symptoms that seemed to be related to the melanocytoma were present in 24% of patients, and an afferent pupillary defect was noted in 9% of patients. Associated ocular abnormalities included ocular melanocytosis (8%), racial melanosis (7%), optic nerve hypoplasia (2%), and retinitis pigmentosa (1%). The melanocytoma was dark brown to black in 100% of patients. The mean tumor diameter was 2 mm and the mean thickness was 1 mm. Associated findings included a choroidal component (54%), retinal component (30%), optic disc edema (25%), retinal edema (16%), localized subretinal fluid (14%), retinal exudation (12%), retinal hemorrhage (5%), vitreous seeds (4%), and retinal vein obstruction (3%). Fluorescein and indocyanine green angiography typically showed persistent hypofluorescence of the lesion. Using Kaplan-Meier survival curves, related visual loss occurred in 18% of patients by 10 years, and minor tumor enlargement occurred in 11% of patients by 5 years and in 32% of patients by 10 years. Malignant transformation was documented in 2 patients (2%). CONCLUSIONS: Although melanocytoma of the optic disc generally is considered to be a benign, stationary lesion, it can produce several local complications, can cause visual loss, can grow slowly, and, rarely, can undergo malignant transformation into melanoma. Patients with optic disc melanocytoma should undergo periodic ocular examination.

Adolescent↗

IFPA 2005 Award in Placentology Lecture. Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? -- a review.

Intrauterine growth restriction is associated with a range of alterations in placental transport functions: the activity of a number of transporters is reduced (Systems A, L and Tau, transporters for cationic amino acids, the sodium-proton exchanger and the sodium pump), placental glucose transporter activity and expression are unchanged whereas the activity of the calcium pump is increased. In contrast, accelerated fetal growth in association to diabetes is characterized by increased activity of placental Systems A and L and glucose transporters. Evidence suggests that these placental transport alterations are the result of specific regulation and that they, at least in part, contribute to the development of pathological fetal growth rather than representing a consequence to altered fetal growth. One interpretation of this data is that the placenta functions as a nutrient sensor, altering placental transport functions according to the ability of the maternal supply line to provide nutrients. Placental transporters are subjected to regulation by hormones. Insulin up-regulates several key placental transporters and maternal insulin may represent a "good nutrition" signal to increase placental nutrient transfer and the growth of the fetus. Preliminary evidence suggests that placental mammalian target of rapamycin, a protein kinase regulating protein translation and transcription in response to nutrient stimuli, may be involved in placental nutrient sensing.

Amino Acid Transport Systems↗