The effect of mammographic screening on invasive breast cancer in Western Australia

Objective: To determine whether mammographic screening has affected the presentation of invasive breast cancer in Western Australia. Design: Population-based reviews of the presentation of all invasive breast cancers diagnosed in Western Australia in 1989 and 1994. Setting: Western Australia (population 1.8 million), Active recruitment of women aged 50-69 years for mammographic screening began in 1989. Main outcome measures: Size and stage of invasive breast cancers at diagnosis. Results: From 1989 to 1994, the age-standardised incidence rose from 109 to 123 per 100 000 woman-years, based on 584 and 750 cases, respectively. The proportion of all invasive breast cancers detected as a result of a mammogram increased from 9.2% in 1989 to 34.5% in 1994. Among the cases where relevant information was recorded, the proportion of impalpable tumours increased from 7.7% in 1989 to 27.6% in 1994, and the average size of palpable tumours fell. There was an unexpected increase in the proportion of tumours that were negative on assays for oestrogen and progesterone receptors. Conclusions: A relatively simple and inexpensive clinical review has boosted confidence that the outlay of public monies required to establish and conduct screening in Australia appears likely to yield the reductions in mortality from breast cancer that would be predicted on the basis of the earlier controlled trials of mammography.

Regarding "Edema and leg volume: Methods of assessment" (Letters to the Editor)

I noted with interest the article by Drs Perrin and Guex, entitled &dquo;Edema and leg volume: Methods of assessment,&dquo; published in Angiology 51:9-12, 2000. This was a timely and comprehensive review of the various methods in clinical use for the assessment of peripheral edema, notably in the leg. I would like to take this opportunity to alert readers to a further technique useful for this purpose, namely, bioelectrical impedance analysis. An early reportl described its use for the measurement of edema in the leg, but other than its successful use for the assessment of edema in the arm following masteCtoMy,2,1 the potential of the method remains to be fully realized. This is unfortunate since the method directly and quantifiably measures edema.

Initial results of ultrasound screening for aneurysm of the abdominal aorta in Western Australia: relevance for endoluminal treatment of aneurysm disease

Background. Increased life expectancy in men during the last thirty years is largely due to the decrease in mortality from cardiovascular disease in the age group 29-69 yr. This change has resulted in a change in the disease profile of the population with conditions such as aneurysm of the abdominal aorta (AAA) becoming more prevalent. The advent of endoluminal treatment for AAA has encouraged prophylactic intervention and fuelled the argument to screen for the disease. The feasibility of inserting an endoluminal graft is dependent on the morphology and growth characteristics of the aneurysm. This study used data from a randomized controlled trial of ultrasound screening for AAA in men aged 65-83 yr in Western Australia for the purpose of determining the norms of the living anatomy in the pressurized infrarenal aorta. Aims. To examine (1) the diameters of the infra-renal aorta in aneurysmal and non-aneurysmal cases, (2) the implications for treatment modalities, with particular reference to endoluminal grafting, which is most dependent on normal and aneurysmal morphology, and (3) any evidence to support the notion that northern Europeans are predisposed to aneurysmal disease. Methods. Using ultrasound, a randomized control trial was established in Western Australia to assess the value of a screening program in males aged 65-83 yr, The infra-renal aorta was defined as aneurysmal if the maximum diameter was 30 mm or more. Aortic diameter was modelled both as a continuous tin mm) and as a binary outcome variable, for those men who had an infra-renal diameter of 30 mm or more. ANOVA and linear regression were used for modelling aortic diameter as a continuum, while chi-square analysis and logistic regression were used in comparing men with and without the diagnosis of AAA. Findings. By December 1998, of 19.583 men had been invited to undergo ultrasound screening for AAA, 12.203 accepted the invitation (corrected response fraction 70.8%). The prevalence of AAA increased with age from 4.8% at 65 yr to 10.8% at 80 yr (chi (2) = 77.9, df = 3, P<0.001). The median (IQR) diameter for the non-aneurysmal group was 21.4 mm (3.3 mm) and there was an increase (<chi>(2) = 76.0, df = 1, P<0.001) in the diameter of the infra-renal aorta with age. Since 27 mm is the 95th centile for the non-aneurysmal infra-renal aorta, a diameter of 30 mm or more is justified as defining an aneurysm. The risk of AAA was higher in men of Australian (OR = 1.0) and northern European origin (OR = 1.0, 95%CL: 0.9. 1.2) compared with those of Mediterranean origin (OR = 0.5, 99%CL: 0.4, 0.7). Conclusion. Although screening has not yet been shown to reduce mortality from AAA. these population-based data assist the understanding of aneurysmal disease and the further development and use of endoluminal grafts for this condition. (C) 2001 Published by Elsevier Science Ltd on behalf of The International Society for Cardiovascular Surgery.

The preparation and execution of self-initiated and externally-triggered movement: A study of event-related fMRI

Studies of functional brain imaging in humans and single cell recordings in monkeys have generally shown preferential involvement of the medially located supplementary motor area (SMA) in self-initiated movement and the lateral premotor cortex in externally cued movement. Studies of event-related cortical potentials recorded during movement preparation, however, generally show increased cortical activity prior to self-initiated movements but little activity at early stages prior to movements that are externally cued at unpredictable times. In this study, the spatial location and relative timing of activation for self-initiated and externally triggered movements were examined using rapid event-related functional MRI. Twelve healthy right-handed subjects were imaged while performing a brief finger sequence movement (three rapid alternating button presses: index-middle-index finger) made either in response to an unpredictably timed auditory cue (between 8 to 24 s after the previous movement) or at self-paced irregular intervals. Both movement conditions involved similar strong activation of medial motor areas including the pre-SMA, SMA proper, and rostral cingulate cortex, as well as activation within contralateral primary motor, superior parietal, and insula cortex. Activation within the basal ganglia was found for self-initiated movements only, while externally triggered movements involved additional bilateral activation of primary auditory cortex. Although the level of SMA and cingulate cortex activation did not differ significantly between movement conditions, the timing of the hemodynamic response within the pre-SMA was significantly earlier for self-initiated compared with externally triggered movements. This clearly reflects involvement of the pre-SMA in early processes associated with the preparation for voluntary movement. (C) 2002 Elsevier Science.

Effects of restricted cochlear lesions in adult cats on the frequency organization of the inferior colliculus

Restricted cochlear lesions in adult animals result in plastic changes in the representation of the lesioned cochlea, and thus in the frequency map, in the contralateral auditory cortex and thalamus. To examine the contribution of subthalamic changes to this reorganization, the effects of unilateral mechanical cochlear lesions on the frequency organization of the central nucleus of the inferior colliculus (ICC) were examined in adult cats. Lesions typically resulted in a broad high-frequency hearing loss extending from a frequency in the range 15-22 kHz. After recovery periods of 2.5-18 months, the frequency organization of ICC contralateral to the lesioned cochlea was determined separately for the onset and late components of multiunit responses to tone-burst stimuli. For the late response component in all but one penetration through the ICC, and for the onset response component in more than half of the penetrations, changes in frequency organization in the lesion projection zone were explicable as the residue of prelesion responses. In half of the penetrations exhibiting nonresidue type changes in onset-response frequency organization, the changes appeared to reflect the unmasking of normally inhibited inputs. In the other half it was unclear whether the changes reflected unmasking or a dynamic process of reorganization. Thus, most of the observed changes were explicable as passive consequences of the lesion, and there was limited evidence for plasticity in the ICC. The implications of the data with respect to the primary locus of the changes and to the manner in which they contribute to thalamocortical reorganization are considered. (C) 2003 Wiley-Liss, Inc.

Breast cancer in Western Australia: clinical practice and clinical guidelines

Objectives: To review changes in patterns of care for women with early invasive breast cancer in Western Australia from 1989 to 1999, and compare management with recommendations in the 1995 National Health and Medical Research Council guidelines. Design and setting: Population-based surveys of all cases listed in the Western Australian Cancer Registry and Western Australian Hospital Morbidity Data System. Main outcome measures: Congruence of care with guidelines. Results: Data were available for 1649 women with early invasive breast cancer (categories pT1 or pT2; pN0 or pN1; and M0). In 1999, 96% had a preoperative diagnosis by fine-needle aspiration or core biopsy (compared with 66% in 1989), with a synoptic pathology report on 95%. Breast-conserving surgery was used for 66% of women with mammographically detected tumours (v 35% in 1989) and 46% of those with clinically detected tumours (v 28% in 1989), with radiotherapy to the conserved breast in 90% of these cases (83% in 1989). Adjuvant chemotherapy was given to 92% of premenopausal women with node-positive disease and 63% with poor-prognosis node-negative tumours (v 78% and 14%, respectively, in 1989). Among postmenopausal women with receptor-positive tumours, tamoxifen was prescribed for 91% of those with positive nodes (85% in 1989) and 79% of those with negative nodes (30% in 1989). Among postmenopausal women with receptor-negative tumours, chemotherapy was prescribed for 70% with positive nodes (v 33%) and 58% with negative nodes (v none). Conclusions: Patterns of management of women with early invasive breast cancer in Western Australia during the 1990s changed significantly in all respects toward those recommended in the 1995 guidelines.

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p < 0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p < 0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p = 0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p = 0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes. (C) 2004 Elsevier Ltd. All rights reserved.

Refining the perfusion-diffusion mismatch hypothesis

Background and Purpose-The Echoplanar Imaging Thrombolysis Evaluation Trial ( EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. Methods-Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient ( ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2(Day) (90-vol)-DWIAcute-vol) were also assessed. Results-Mean age was 68 +/- 11, time to MRI 4.5 +/- 0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P < 0.001). Mismatch >= 20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s ( relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R= -0.51; P = 0.009). Conclusions-Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.

Impact of photodynamic therapy on inflammatory cells during human chronic periodontitis

The aim of this study was to evaluate the effects of the photodynamic therapy (PDT) on the inflammatory infiltrate and on the collagen network organization in human advanced chronic periodontitis Two different drug delivery systems (DDS) were tested (liposomes and nanoemulsions) to determine if the effects of PDT could differ according to the DDS used Sixteen patients presenting two teeth with chronic advanced periodontitis and Important tooth mobility with clinical indication of extraction were included in the group liposomes (group L n = 8) or in the group nanoemulsions (group N n = 8) in order to compare the effects of each DDS Seven days before extractions one tooth of each patient was treated with PDT using phthalocyanine derivatives as photosensitizers and the contralateral tooth was taken as control In group L the density of gingival collagen fibers (66 +/- 19%) was significantly Increased (p < 0 02) when compared to controls (35 +/- 21%) Concerning the antigen-presenting cells PDT had differential effects depending on the drug delivery system the number of macrophages was significantly decreased (p < 0 05) in group L while the number of Langerhans cells was significantly decreased in group N (p < 0 02) These findings demonstrate that PDT presents an impact on gingival Inflammatory phenomenon during chronic periodontitis and leads to a specific decrease of antigen-presenting cells populations according to the drug delivery system used (C) 2010 Elsevier B V All rights reserved

Mechanical loading modulates glutamate receptor subunit expression in bone

The cellular mechanisms coupling mechanical loading with bone remodeling remain unclear. In the CNS, the excitatory amino acid glutamate (Glu) serves as a potent neurotransmitter exerting its effects via various membrane Glu receptors (GluR). Nerves containing Glu exist close to bone cells expressing functional GluRs. Demonstration of a mechanically sensitive glutamate/aspartate transporter protein and the ability of glutamate to stimulate bone resorption in vitro suggest a role for glutamate linking mechanical load and bone remodeling. We used immunohistochemical techniques to identify the expression of N-methyl-D-aspartate acid (NMDA) and non-NMDA (AMPA or kainate) ionotropic GluR subunits on bone cells in vivo. In bone sections from young adult rats, osteoclasts expressed numerous GluR subunits including AMPA (GluR2/3 and GluR4), kainic acid (GluR567) and NMDA (NMDAR2A, NMDAR2B and NMDAR2C) receptor subtypes. Bone lining cells demonstrated immunoexpression for NMDAR2A, NMDAR2B, NMDAR2C, GluR567, GluR23, GuR2 and GluR4 subunits. Immunoexpression was not evident on osteocytes, chondrocytes or vascular channels. To investigate the effects of mechanical loading on GluR expression, we used a Materials Testing System (MTS) to apply 10 N sinusoidal axial compressive loads percutaneously to the right limbs (radius/ulna, tibia/fibula) of rats. Each limb underwent 300-load cycles/day (cycle rate, 1 Hz) for 4 consecutive days. Contralateral, non-loaded limbs served as controls. Mechanically loaded limbs revealed a load-induced loss of immunoexpression for GluR2/3, GluR4, GluR567 and NMDAR2A on osteoclasts and NMDAR2A, NMDAR2B, GluR2/3 and GluR4 on bone lining cells. Both neonatal rabbit and rat osteoclasts were cultured on bone slices to investigate the effect of the NMDA receptor antagonist, MK801, and the AMPA/kainic acid receptor antagonist, NBQX, on osteoclast resorptive activity in vitro. The inhibition of resorptive function seen suggested that both NMDAR and kainic acid receptor function are required for normal osteoclast function. While the exact role of ionotropic GluRs in skeletal tissue remains unclear, the modulation of GluR subunit expression by mechanical loading lends further support for participation of Glu as a mechanical loading effector. These ionotropic receptors appear to be functionally relevant to normal osteoclast resorptive activity. (C) 2005 Elsevier Inc. All rights reserved.

Perioperative Temporary Occlusion of the Internal Iliac Arteries as Prophylaxis in Cesarean Section at Risk of Hemorrhage in Placenta Accreta

Purpose The purpose of this study was to describe the preliminary results of prophylactic temporary balloon occlusion of the internal iliac arteries for bleeding control in patients with placenta accreta during cesarean hysterectomy. Methods From May 2006 to March 2010, 21 patients diagnosed with placenta accreta using ultrasound and/or magnetic resonance imaging were submitted to prophylactic balloon occlusion before hysterectomy. Fluoroscopy, balloon occlusion time, surgical duration, intraoperative blood loss, transfusion volume, and procedure complications were analyzed. Results The mean age was 30.5 years with a mean of 3.6 previous gestations. Imaging studies revealed that all patients had placenta accreta and all were submitted to cesarean hysterectomy. One hysterectomy was due to previous diagnosis of fetal death and another due to cesarean with uterine curettage. Mean fluoroscopy time was 7.5 min, balloon occlusion time was 164 min, and surgery duration was 260 min. Estimated blood loss was 1,671.5 ml with mean reposition fluids of 3,538 ml of crystalloids, 309.5 ml of colloids, and 1.24 ml of packed red blood cells. Two patients were submitted to thromboembolectomy due to prolonged surgical time. There was no maternal or fetal mortality related to the procedure. Conclusions The results demonstrated that prophylactic balloon occlusion of internal iliac artery is a safe method and appears to reduce blood loss and transfusion requirements in patients diagnosed with placenta accreta who undergo cesarean hysterectomy. Antenatal imaging diagnosis of placenta accreta enables preoperative planning.

Heart Transplantation in Arrhythmogenic Right Ventricular Dysplasia: Case Reports

Objective. Arrhythmogenic right ventricular dysplasia (ARVD) is a myocardial disease of familiar, origin where the myocardium is replaced by fibrofatty tissue predominantly in the right ventricle. Herein we have presented the clinical courses of 4 patients with ARVD who underwent orthotopic heart transplantation. Patients and Methods. Among 358 adult patients undergoing heart transplantation, 4 (1.1%) displayed ARVD. The main indication for transplantation was the progression to heart failure associated with arrhythmias. All 4 patients displayed rapid, severe courses leading to heart failure with left ventricular involvement and uncontrolled arrhythmias. Results. In all cases the transplantation was performed using a bicaval technique with prophylactic tricuspid valve annuloplasty. One patient developed hyperacute rejection and infection, leading to death on the 7th day after surgery. The other 3 cases showed a good evolution with clinical remission of the symptoms. Pathological study of the explanted hearts confirmed the presence of the disease. Conclusions. ARVD is a serious cardiomyopathy that can develop malignant arrhythmias, severe ventricular dysfunction with right ventricular predominance, and sudden cardiac death. Orthotopic heart transplantation must always be considered in advanced cases of ARVD with malignant arrhythmias or refractory congestive heart failure with or without uncontrolled arrhythmias, because it is the only way to remit the symptoms and the disease.

Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids. (C) 2008 Elsevier B.V. All rights reserved.

Risk Profiles and Penetrance Estimations in Multiple Endocrine Neoplasia Type 2A Caused by Germline RET Mutations Located in Exon 10

Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609-620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected. Hum Mutat 32:51-58, 2011. (C) 2010 Wiley-Liss, Inc.

The role of vaccines in the control of STDs: HPV vaccines

Prophylactic vaccines for genital human papillomavirus (HPV) infection have been shown to be feasible in animal models, and suitable vaccine material based on virus-like particles can be produced in bulk at reasonable cost. Initiation of phase III clinical trials will follow definition of trial outcome measures through further epidemiological studies, and development-of assays of host protective immunity. Vaccines could in principle eliminate HPV-related disease, as the human race is the only natural host for the relevant papillomaviruses (PVs). Therapeutic vaccines for genital HPV infection are also possible, but have not yet been demonstrated as feasible in practice because the choice of vaccine antigens is difficult, the method of their optimal delivery is uncertain, and the nature of the relevant antiviral immunity is unknown. PV species specificity will require trials to be conducted in man, which will slow definition of an ideal vaccine.