Experience of sentinel node biopsy alone in early breast cancer without further axillary dissection in patients with negative sentinel node

AIMS: The aims of surgical therapy of breast cancer are loco-regional tumour control and staging. Axillary staging is still considered the single most important prognostic indicator in breast cancer. Surgical removal of axillary nodes remains the standard way to assess their involvement in most centres. The morbidity associated with axillary dissection (AD) is well recognized. In recent years sentinel node biopsy (SNB) has evolved. Multiple studies suggest it has the same accuracy as AD in axillary staging and less morbidity in early breast cancer (EBC). SNB has become the standard of practice in EBC in many parts of the world. In Australia, the preference has been to wait for the results of the Sentinel Node versus Axillary Clearance (SNAC) trial as well as other international trials before accepting SNB as a standard of care. The experience of a single surgeon with SNB alone in EBC without further completion axillary dissection (CAD) in negative sentinel node (SLN) is described in the present paper. METHODS: An audit was done of the senior author's prospective data from the Royal Australasian College of Surgeons database. Other information was added retrospectively from case notes. RESULTS: Between December 2000 and December 2003, 154 EBC cases (153 patients) underwent SNB alone. An average of four SLN was removed. Of these cases, 31.8% had positive SLNs (excluding 2.6% cases that had isolated tumour cells), of these, 93.9% had metastases (39.1% micro- and 60.9% macro-metastases) in axillary-SLN (ASLN) and almost all of these had CAD. ASLNs were the only positive nodes in 73.9%. Extra-ASLN retrieved in 68.8% of 34% demonstrated on lymphoscintigraphy. Of these, 12.1% were positive (6.1% micro- and macro-metastases each), all internal mammary. Mean follow up was 22.1 months. There was one local-regional-systemic and one systemic recurrence over this time. CONCLUSION: SNB has a valid role in staging of the axilla particularly in low-risk patients. After adequate self audit, SNB offers a minimal morbidity and reliable method of axillary staging. Patients choosing SNB alone must understand that the long-term results of the randomized controlled trial are still pending for level I evidence of long-term efficacy.     

The mechanism of pause-induced torsade de pointes in long QT syndrome

INTRODUCTION: Torsade de pointes (TdP), is often preceded by a short-long cycle length sequence. However, the causal relationship between the pause associated with a short-long cycle length sequence and TdP is not completely understood. This study tests the hypothesis that a pause enhances both dispersion of repolarization and EAD formation; however, EADs that form where APD is longest will be less likely to initiate TdP. METHODS AND RESULTS: We used optical mapping to measure transmural action potentials from the canine left ventricular wedge preparation. D-sotalol and ATX-II were used to mimic LQT2 and LQT3, respectively. The pause significantly enhanced mean APD (from 356 +/- 20 to 381 +/- 25 msec in LQT2, P < 0.05; from 609 +/- 92 to 675 +/- 98 msec in LQT3, P < 0.05) and transmural dispersion (from 35 +/- 9 to 46 +/- 11 msec in LQT2, P < 0.05; from 121 +/- 85 to 171 +/- 98 msec in LQT3, P < 0.05) compared to steady state pacing. Under LQT3 condition EADs, EAD-induced triggered activity, and TdP were more likely to occur following a pause. Interestingly, the triggered beat following a pause always broke through at the region of maximum local repolarization gradient. CONCLUSION: These data suggest that a pause accentuates transmural repolarization gradients and facilitates the formation of EADs and EAD-induced triggered activity. In contrast to our hypothesis, the findings of this study support the concept that M-cells (where APD is longest) can play an important role in both the origination of EAD-induced triggered activity and unidirectional block associated with TdP.     

Treating early versus treating mild: timing of migraine prescription medications among patients with diagnosed migraine

INTRODUCTION: Although research suggests that early treatment of migraine headache when the pain is mild results in better outcomes for patients, many patients delay taking their acute-migraine medication until their headaches are moderate or severe. Understanding when and why patients use their migraine medications is an important first step to improve migraine management. METHODS: A prospective observational study, conducted at a major national retail pharmacy chain with stores across the United States between April 2001 and November 2002, enrolled men and women between 18 and 55 years of age with a physician diagnosis of migraine with or without aura. Baseline data on 690 patients included patient demographics, migraine history, medication use, tendency to avoid or delay treatment of a migraine attack, and reasons for delaying treatment. Reasons for delaying treatment were assessed via a checklist of nine potential reasons. In the follow-up survey completed after treatment of the next migraine attack, patients reported the timing of medication use in relation to pain onset and the severity of the migraine headache at the time they took the medication. RESULTS: Despite the severity of their typical migraine attacks, approximately 49% of the respondents answered, "yes" to the question, "Do you often avoid or delay taking your migraine medications when you start to experience a migraine attack?" The two most common rationales for avoiding or delaying treatment were "wanting to wait and see if it is really a migraine attack" (69%) followed by "only want to take medications if it is a severe attack" (46%). In the follow-up survey, regardless of medication used, about 85% of patients did not treat their next migraine attack until the headache pain was moderate or severe, although 74% treated within 1 hour of pain onset. CONCLUSION: These results suggest that patients with migraine often delay their treatment until they have identified their attack as a migraine. In addition, while many patients treated their follow-up headache early, they did not treat when the pain was mild. This suggests that there is an opportunity for physicians to educate their migraine patients on how to differentiate migraine from other headache types and about when and how to use their acute-migraine medication.     

In search of early pregnancy factor: characterisation of active polypeptides isolated from pregnant ewes' sera

Further biochemical characterisations of the 20 kd and 67 kd EPF active polypeptides from pregnant ewes' sera are described. Both polypeptides are shown to possess compact, disulphide linked domains which are almost totally resistant to proteolytic attack without prior reduction. In contrast to previous reports on the influence of ammonium sulphate on the expression of EPF activity, neither the biochemical nor the activity characteristics of either polypeptide is changed by ammonium sulphate fractionation. In addition, direct comparative studies have been performed which clearly distinguish the EPF active polypeptides from the known ovine hormones, prolactin, placental lactogen and growth hormone.     

Phoneme manipulation not onset-rime manipulation ability is a unique predictor of early reading

BACKGROUND: Phonological awareness is known to be an excellent predictor of later reading acquisition. It remains unclear, however, whether phoneme manipulation alone best explains this association or whether an additional direct contribution of onset-rime awareness is predictive. This issue is explored here. METHOD: A longitudinal study is reported predicting national test and teacher-assessed performance of 351 children aged 7 from phonological awareness measures, pupil baseline attainment and background measures at age 5. RESULTS: Explicit phoneme manipulation skills at age 5 correlated most strongly with literacy skills at age 5. Phoneme manipulation at age 5 predicted all four reading measures taken at age 7 after pupil background, baseline data and onset-rime awareness were controlled in regression analyses. Onset-rime manipulation did not predict reading at 7 in parallel analyses. After controlling for initial reading at age 5, phoneme manipulation still predicted reading comprehension, and teacher-assessed reading and writing at age 7. CONCLUSIONS: Results support the existence of a route from phoneme manipulation, but not an additional direct route from explicit onset-rime manipulation at 5, to reading at 7. Practically, findings show that professionals can augment baseline and pupil background data with phoneme manipulation screening in the early identification of learning needs.     

The use of a bedside assay for plasma B-type natriuretic peptide as a biomarker in the management of patent ductus arteriosus in premature neonates

OBJECTIVE: To test the utility of the bedside plasma concentration of B-type natriuretic peptide (BNP) assay as a screen for patent ductus arteriosus (PDA) in premature neonates. STUDY DESIGN: Newborn infants admitted to the neonatal intensive care unit (NICU) had paired echocardiography and BNP measurements at enrollment and every 4 to 5 days. RESULTS: Twenty neonates (gestational age approximately 28.6 weeks and birth weight approximately 1161 g) had 81 paired echocardiography and BNP determinations. BNP ranged from 5 to 3900 pg/mL. Fifty-six of 81 echocardiograms showed PDA. Significant correlations were found between BNP and ductal size and degree of shunting. Correlation was greater in infants >2 days of age. BNP >300 pg/mL predicted significant PDA, whereas BNP <105 pg/mL predicted absence of significant PDA. CONCLUSION: Bedside measurement of BNP correlates with magnitude of PDA in premature newborns, particularly beyond day 2, and may be useful in guiding diagnostic and management strategies.     

Social context modulates behavioural and brain immediate early gene responses to sound in male songbird

Although it is well known that brain sensory information processing is a highly modulated phenomenon, how this brain function is shaped by experience and social context remains a question to explore. In this paper, we present the first attempt to investigate this problem using a songbird acoustic communication paradigm. Social context is well known to influence acoustic communicating behaviours in birds. The present paper investigates whether brain processing of auditory inputs can be modulated by this 'audience effect'. Given that call-based communication is known to be highly context-dependent, we focused on the response of male zebra finches (Taeniopygia guttata) to female calls. We tested to see if the current social context surrounding the hearing bird can modify a sound-induced immediate early gene (IEG) activation in the specific region of the caudomedial nidopallium (NCM), a songbird brain analogous to the superficial layers of the mammalian primary auditory cortex. Our results show that the expression of the sound-induced immediate early gene ZENK in the NCM is considerably enhanced when the hearing bird is in the presence of conspecifics, compared to when he is alone. This context-dependent increase of a sound-induced immediate early gene expression can be correlated with the differential behavioural response of males to the playback of the same acoustic stimulus as a function of social context.     

Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience

After a spatial behavioral experience, hippocampal CA1 pyramidal cells express the activity-regulated, immediate early gene Arc in an environment-specific manner, and in similar proportions ( 40%) to cells exhibiting electrophysiologically recorded place fields under similar conditions. Theoretical accounts of the function of the fascia dentata suggest that it plays a role in pattern separation during encoding. The hypothesis that the dentate gyrus (DG) uses a sparse, and thus more orthogonal, coding scheme has been supported by the observation that, while granule cells do exhibit place fields, most are silent in a given environment. To quantify the degree of sparsity of DG coding and its corresponding ability to generate distinct environmental representations, behaviorally induced Arc expression was assessed using in situ hybridization coupled with confocal microscopy. The proportion of Arc(+) cells in the "upper blade" of the fascia dentata (i.e., the portion that abuts CA1) increased in an environment-specific fashion, approximately 4-fold above cage-control activity, after behavioral exploration. Surprisingly, cells in the lower blade of the fascia dentata, which are capable of expressing Arc following electrical stimulation, exhibited virtually no behaviorally-induced Arc expression. This difference was confirmed using "line scan" analyses, which also revealed no patterns or gradients of activity along the upper blade of the DG. The expression of Arc in the upper blade was quantitatively similar after exploring familiar or novel environments. When animals explored two different environments, separated by 20 min, a new group of cells responded to the second environment, whereas two separated experiences in the same environment did not activate a new set of granular cells. Thus, granule cells generate distinct codes for different environments. These findings suggest differential contribution of upper and lower blade neurons to plastic networks and confirm the hypothesis that the DG uses sparse coding that may facilitate orthogonalization of information.     

Influence of age of onset on clinical features in obsessive-compulsive disorder

We compared early-onset and late-onset obsessive-compulsive disorder (OCD) patients in terms of demographic and clinical features. One hundred sixteen outpatients whose primary diagnosis was OCD according to DSM-IV diagnostic criteria were recruited. Early-onset (n=50) and late-onset (n=66) OCD groups were compared with respect to demographic variables and scores obtained on various scales. A male gender predominance was found in early-onset OCD group. Symmetry/exactness obsessions, religious obsessions, hoarding/saving obsessions, and hoarding/collecting compulsions also were significantly more frequent in the early-onset group than in the late-onset group. The results may suggest a phenotypic difference between the two groups. Further studies are needed to investigate the differences between early-onset and late-onset OCD groups to examine the hypothesis that early-onset OCD is a distinct subtype of the disorder.     

Children with early refusal to eat: follow-up in adolescence

Aim: To describe the adolescent outcome of infant refusal to eat (RTE) and to investigate early predictors of adolescent outcomes. Methods: 19 of 25 children with RTE and 35 of 42 controls were assessed at age 16. The participants rated eating attitudes and self-perceptions with a Swedish version of the Children's Eating Attitudes Test (ChEAT) and a Swedish self-perception measure. Weight and height were assessed through self-reports, and body mass index (BMI) was computed. Child and family variables measured from infancy through age 4 were used as predictors. Results: RTE and controls did not differ with regard to disturbed eating attitudes, BMI or self-perceptions. There were no relations between early predictors and adolescent disturbed eating for the whole sample, but breastfeeding problems and social adversity in the early years predicted negative self-perceptions, and weight at 4 y predicted adolescent BMI. For the RTE group, low birthweight predicted higher levels of disturbed eating attitudes and less positive self-perceptions. For the control group, social adversity predicted high BMI.

Conclusion: RTE does not seem to constitute a risk factor for adolescent disturbed eating. Further, there may be different risk factors for adolescent disturbed eating for children with and without RTE.