Mesodiencephalic junction GABAergic inputs are processed separately from motor cortical inputs in the basilar pons.

The basilar pontine nuclei (bPN) are known to receive excitatory input from the entire neocortex and constitute the main source of mossy fibers to the cerebellum. Various potential inhibitory afferents have been described, but their origin, synaptic plasticity, and network function have remained elusive. Here we identify the mesodiencephalic junction (MDJ) as a prominent source of monosynaptic GABAergic inputs to the bPN. We found no evidence that these inputs converge with motor cortex (M1) inputs at the single neuron or at the local network level. Tracing the inputs to GABAergic MDJ neurons revealed inputs to these neurons from neocortical areas. Additionally, we observed little short-term synaptic facilitation or depression in afferents from the MDJ, enabling MDJ inputs to carry sign-inversed neocortical inputs. Thus, our results show a prominent source of GABAergic inhibition to the bPN that could enrich input to the cerebellar granule cell layer.

Veliparib monotherapy following carboplatin/paclitaxel plus veliparib combination therapy in patients with germline BRCA-associated advanced breast cancer: results of exploratory analyses from the phase III BROCADE3 trial.

BACKGROUND: In the BROCADE3 trial, addition of the poly(ADP-ribose) polymerase inhibitor, veliparib, to carboplatin/paclitaxel improved progression-free survival (PFS) (hazard ratio 0.71, 95% confidence interval 0.57-0.88; P = 0.002) in patients with advanced human epidermal growth factor receptor 2-negative, germline BRCA1/2-mutated breast cancer. A subset of patients discontinued both carboplatin and paclitaxel before progression and continued on veliparib/placebo maintenance monotherapy until progression. Analyses in this patient subgroup are reported. PATIENTS AND METHODS: Patients were randomized 2 : 1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Veliparib (120 mg twice daily) or placebo was given on days -2 to 5, carboplatin (area under the curve 6 mg/ml) on day 1, and paclitaxel (80 mg/m2) on days 1, 8, and 15 of 21-day cycles. Patients who discontinued both carboplatin and paclitaxel before progression received blinded study drug monotherapy at an increased dose of 300-400 mg twice daily continuously. PFS was the primary endpoint. Exploratory analyses were carried out in the subgroup of patients who received blinded study drug as monotherapy. A time-varying Cox model including data from all patients was also used to evaluate treatment effect in the combination and monotherapy phases. RESULTS: A total of 136 of 337 patients randomized to veliparib plus carboplatin/paclitaxel and 58/172 patients randomized to placebo plus carboplatin/paclitaxel discontinued both carboplatin and paclitaxel before progression and continued on blinded veliparib or placebo monotherapy. In this blinded monotherapy subgroup, investigator-assessed median PFS from randomization was 25.7 months with veliparib versus 14.6 months with placebo. Hazard ratios from a time-varying Cox model favored veliparib during both combination therapy and monotherapy. Any-grade adverse events occurring in the monotherapy phase were primarily gastrointestinal. The most common grade ≥3 adverse events were neutropenia and anemia (4% each with veliparib; 5% and 2%, respectively, with placebo). CONCLUSIONS: Veliparib maintenance monotherapy had a tolerable safety profile and may extend PFS following combination chemotherapy.

Prognosis in young women less than 40 years of age with brain metastasis from breast cancer.

Background: Brain metastasis from breast cancer (bca) in young women is doubly devastating because both quality of life and life expectancy are significantly reduced. With new radiation technology and drugs that have emerged, survival is expected to increase for these young women. Methods: Using the oacis and sardo patient databases, we identified 121 patients diagnosed with bca and brain metastasis between 2006 and 2016 at the University of Montreal Hospital Centre. Those patients were divided into Group A, patients who developed brain metastasis during the evolution of metastatic bca, and Group B, patients whose first metastasis was to the brain. For each group, we compared young patients (<40 years of age) with older patients (≥40 years of age). Results: Among the 121 patients with brain metastasis, median overall survival (mos) was significantly longer for those less than 40 years of age than for those 40 or more years of age (18 months vs. 4 months, p < 0.001). With respect to the timing of brain metastasis, survival was significantly longer in Group B than in Group A (7 months vs. 4 months, p = 0.032). In Group A, mos was significantly longer for patients less than 40 years of age than for patients 40 or more years of age (18 months vs. 3 months, p = 0.0089). In Group B, the 2-year overall survival rate was 57% for patients less than 40 years of age and 12% for those 40 or more years of age (mos: not reached vs. 7 months; p = 0.259). Conclusions: In our single-centre retrospective cohort of women with brain metastasis from bca, prognosis was better for young women (<40 years) than for older women (≥40 years). Survival was also longer for patients whose initial metastasis was to the brain than for patients whose brain metastasis developed later in the disease course. In patients who received systemic treatment, median survival remained significantly higher in women less than 40 years of age. Further studies are needed to validate those results.

Author Correction: Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.

Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. Here, we show that ChAT-VIP neurons directly excite neighbouring neurons in several layers through fast synaptic transmission of acetylcholine (ACh) in rodent medial prefrontal cortex (mPFC). Both interneurons in layers (L)1-3 as well as pyramidal neurons in L2/3 and L6 receive direct inputs from ChAT-VIP neurons mediated by fast cholinergic transmission. A fraction (10-20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons. In contrast to regular VIP interneurons, ChAT-VIP neurons did not disinhibit pyramidal neurons. Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs. Thus, ChAT-VIP neurons are a local source of cortical ACh that directly excite neurons throughout cortical layers and contribute to attention.

Short- and long-term evolution of the endoluminal diameter of underdilated stents in transjugular intrahepatic portosystemic shunt.

PURPOSE: The purpose of this study was to evaluate the short- and long-term evolution of endoluminal diameter of covered metallic stents that were underdilated at the time of transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIEL AND METHODS: Sixteen patients (13 men, 3 women) with a mean age of 57.6years±7.9 (SD) were retrospectively included. All patients had had TIPS creation using a 10-mm diameter covered stent (VIATORR®) that was underdilated (i.e., 8mm) at the time of stent placement. Measurements of the mean circulating diameter of the stents were retrospectively performed on angiographic examinations every 6months up to 2years. RESULTS: The endoluminal stent diameter early enlarged from 8.96mm±1.12 (SD) to 10mm±1.45 (SD) after 6months (P=0.04) with no further significant changes over time after 12months (10.28mm±1.9mm), 18months (9.93±1.51mm) and 24months (9.92±0.9mm). CONCLUSION: Our results demonstrate a passive expansion of initially underdilated covered stents during the six months following TIPS creation. This should be taken into account regarding hepatic encephalopathy prevention during TIPS placement.

Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical trial.

BACKGROUND: Phosphorus status is inversely correlated with body weight; however, the effect of phosphorus supplementation on body weight in a controlled design has not been studied. METHODS: This is a double-blind, randomized, placebo-controlled trial of 63 adults aged 18-45 years with a body mass index (BMI) of ⩾25 kg m(-2) and normal kidney function at the American University of Beirut. Participants were randomly assigned to the placebo or phosphorus group where daily placebo or phosphorus supplements were ingested with three main meals (breakfast, lunch and dinner) for a period of 12 weeks. Primary outcomes were changes in anthropometric measures, blood metabolites (including lipid profile, glucose and insulin) and subjective appetite scores. The trial is registered with Clinical Trial.gov, NCT02329990. RESULTS: Body weight was significantly lower in the phosphorus group when compared with the placebo group (-0.65 kg (95% confidence interval (CI) -1.69 to 0.40) vs 1.13 kg (95% CI 0.19 to 2.06), P=0.01). Similarly, BMI and waist circumference were significantly lower in the phosphorus group when compared with the placebo group (-0.24 kg m(-2) (95% CI -0.59 to 0.12) vs 0.42 kg m(-2) (95% CI 0.05 to 0.78), P=0.01; -3.62 cm (95% CI-4.90 to -2.33) vs 0.38 cm ( 95% CI-0.44 to 1.20), P<0.001; respectively). Several parameters of subjective appetite scores were decreased in the phosphorus-supplemented group. CONCLUSIONS: Phosphorus supplementation for 12 weeks significantly decreases body weight, BMI, waist circumference and subjective appetite scores. These findings support a promising role of the mineral phosphorus in the prevention and management of obesity, especially abdominal adiposity. The exact mechanisms of action and longer-term effects still need to be elucidated.

Renal haemodynamic response to amino acids infusion in an experimental porcine model of septic shock.

BACKGROUND: Acute kidney injury (AKI) is common in sepsis. Treatments allowing maintenance of renal blood flow (RBF) could help to prevent AKI associated with renal hypoperfusion. Amino acids (AA) have been associated with an increase of RBF and glomerular filtration rate (GFR) in several species. The aim of this study was to evaluate the effects of an AA infusion on RBF and GFR in a porcine model of septic shock. METHODS: A total of 17 piglets were randomly assigned into three groups: Sham (Sham, n = 5), sepsis without AA (S-NAA, n = 6), sepsis treated with AA (S-AA, n = 6). Piglets preparation included the placement of ultrasonic transit time flow probes around left renal artery for continuous RBF measurement; ureteral catheters for GFR and urine output evaluation; pulmonary artery catheter for cardiac output (CO) and pulmonary arterial pressure measurements. Mean arterial pressure (MAP) and renal vascular resistance (RVR) were also determined. Septic shock was induced with a live Pseudomonas aeruginosa infusion. Crystalloids, colloids and epinephrine infusion were used to maintain and restore MAP > 60 mmHg and CO > 80% from baseline. RESULTS: Renal haemodynamic did not change significantly in the Sham group, whereas RBF increased slightly in the S-NAA group. Conversely, a significant increase in RVR and a decrease in RBF and GFR were observed in the S-AA group. AA infusion was associated with a higher requirement of epinephrine [340.0 (141.2; 542.5) mg vs. 32.5 (3.8; 65.0) mg in the S-NAA group P = 0.044]. CONCLUSION: An infusion of amino acids impaired renal haemodynamics in this experimental model of septic shock.

Novel agents and associated toxicities of inhibitors of the pi3k/Akt/mtor pathway for the treatment of breast cancer.

UNLABELLED: The pi3k/Akt/mtor (phosphatidylinositol 3 kinase/ Akt/mammalian target of rapamycin) signalling pathway is an established driver of oncogenic activity in human malignancies. Therapeutic targeting of this pathway holds significant promise as a treatment strategy. Everolimus, an mtor inhibitor, is the first of this class of agents approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Everolimus has been associated with significant improvements in progression-free survival; however, it is also associated with increased toxicity related to its specific mechanism of action. METHODS: A comprehensive review of the literature conducted using a focused medline search was combined with a search of current trials at http://ClinicalTrials.gov/. Summary tables of the toxicities of the various classes of pi3k/Akt/mtor inhibitors were created. A broad group of Canadian health care professionals was assembled to review the data and to produce expert opinion and summary recommendations for possible best practices in managing the adverse events associated with these pathway inhibitors. RESULTS: Differing toxicities are associated with the various classes of pi3k/Akt/mtor pathway inhibitors. The most common unique adverse events observed in everolimus clinical trials in breast cancer include stomatitis (all grades: approximately 60%), noninfectious pneumonitis (15%), rash (40%), hyperglycemia (15%), and immunosuppression (40%). To minimize grades 3 and 4 toxicities and to attempt to attain optimal outcomes, effective management of those adverse events is critical. Management should be interdisciplinary and should use approaches that include education, early recognition, active intervention, and potentially prophylactic strategies. DISCUSSION: Everolimus likely represents the first of many complex oral targeted therapies for the treatment of breast cancer. Using this agent as a template, it is essential to establish best practices involving and integrating multiple disciplines for the management of future pi3k/Akt/mtor signalling pathway inhibitors.

Refeeding and metabolic syndromes: two sides of the same coin.

Refeeding syndrome describes the metabolic and clinical changes attributed to aggressive rehabilitation of malnourished subjects. The metabolic changes of refeeding are related to hypophosphatemia, hypokalemia, hypomagnesemia, sodium retention and hyperglycemia, and these are believed to be mainly the result of increased insulin secretion following high carbohydrate intake. In the past few decades, increased consumption of processed food (refined cereals, oils, sugar and sweeteners, and so on) lowered the intake of several macrominerals (mainly phosphorus, potassium and magnesium). This seems to have compromised the postprandial status of these macrominerals, in a manner that mimics low grade refeeding syndrome status. At the pathophysiological level, this condition favored the development of the different components of the metabolic syndrome. Thus, it is reasonable to postulate that metabolic syndrome is the result of long term exposure to a mild refeeding syndrome.

Clinical features and course of brain metastases in colorectal cancer: an experience from a single institution.

OBJECTIVES: Brain metastases from colorectal cancer (crc) are quite rare. Here, we review the characteristics, presentation, and clinical course of such patients at our institution. METHODS: We reviewed the medical records of patients with brain metastases from crc treated during 2000-2009. Associations between patient, tumour characteristics, treatment modality, and survival were assessed using the Kaplan-Meier method. RESULTS: We identified 48 patients (25 men, 23 women) who developed brain metastases from crc. The median age at diagnosis of the brain metastases was 63 years (range: 37-84 years). In 23 of the patients (48%), the primary tumour occurred in the rectum. At diagnosis of brain metastases, 43 patients (90%) also had other systemic metastases (mainly pulmonary and hepatic). The median interval between diagnosis of the primary tumour and of the brain metastases was 24 months. Median survival after a diagnosis of brain metastasis from crc was 4 months (range: 1-13 months). We observed substantially better survival (13 months, p < 0.001) in patients treated with surgery followed by whole-brain radiotherapy (wbrt) than in those treated with radiotherapy or surgery alone. Sex, age, location and number of brain metastases, and timing of diagnosis did not affect survival. CONCLUSIONS: Brain metastases from crc develop late in the course of the disease, given that most patients already have other secondary lesions. Prognosis in these patients is poor, with those receiving treatment with surgery and wbrt having the best overall survival. Early detection and treatment of brain metastases with new systemic therapies may improve outcomes.

Advances in the management of metastatic breast cancer: options beyond first-line chemotherapy.

This article provides an overview of recent advances in chemotherapy that may be used for the treatment of patients with locally advanced or metastatic breast cancer (MBC). Key phase ii and iii trial data for eribulin mesylate, ixabepilone, and nab-paclitaxel, published since 2006, are discussed on the basis of recency, depth, and quality.Eribulin mesylate is the first monotherapy to significantly increase overall survival in patients with pretreated MBC, but nab-paclitaxel offers a novel and safer mode of delivery in comparison with standard taxanes. By contrast, the use of ixabepilone will be limited for now, until the associated neurotoxicity can be better managed. Alongside a brief overview of the other major chemotherapies currently in use, we have aimed to provide a Canadian context for how these novel agents may be integrated into clinical practice.

The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins.

To test the effect of insulin on renal perfusion and the participation of NO and PG as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flow probes around renal arteries and with a systemic arterial pressure (SAP, n = 4) telemetry device. Three protocols were performed: 1) RBF and SAP were recorded (0800 to 1800 h) in fed and fasted sheep, with the latter receiving intravenous (i.v.) infusions (0.5 mL/min) of insulin at 2 or 6 mU/(kg·min); 2) fasted sheep received i.v. infusions of either an inhibitor of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME) alone [0.22 mg/(kg·min), 1000 to 1200 h] or L-NAME (1000 to 1200 h) + insulin during the second hour (6 mU/(kg·min), 1100 to 1200 h); and 3) the same protocol was followed as in protocol 2, substituting L-NAME with ketoprofen [0.2 mg/(kg·min)], a cyclooxygenase inhibitor. In all protocols, plasma insulin and glucose were determined. During insulin administration, euglycemia was maintained and hypokalemia was prevented by infusing glucose and KCl solutions. After the onset of meals, a long-lasting 18% increase in RBF and a 48% insulin increase were observed (P < 0.05), without changes in SAP. Low- and high-dose insulin infusions increased RBF by 19 and 40%, respectively (P < 0.05). As after meals, the increases in RBF lasted longer than the insulin increase (P < 0.05). The L-NAME infusion decreased RBF by 15% (P < 0.05); when insulin was added, RBF increased to preinfusion values. Ketoprofen decreased RBF by 9% (P < 0.05); when insulin was added, RBF increased to 13% above preinfusion values (P < 0.05). In no case was a modification in SAP or glucose noted during the RBF changes. In conclusion, insulin infusion mimics the meal-dependent increase in RBF, independent of SAP, and lasts longer than the blood insulin plateau. The RBF increase induced by insulin was only partially prevented by L-NAME. Ketoprofen failed to prevent the insulin-dependent RBF increase. Both facts suggested that complementary vasodilatatory agents accounted for the insulin effect on sheep renal hemodynamics.

SVM based colon polyps classifier in a wireless active stereo endoscope.

This work focuses on the recognition of three-dimensional colon polyps captured by an active stereo vision sensor. The detection algorithm consists of SVM classifier trained on robust feature descriptors. The study is related to Cyclope, this prototype sensor allows real time 3D object reconstruction and continues to be optimized technically to improve its classification task by differentiation between hyperplastic and adenomatous polyps. Experimental results were encouraging and show correct classification rate of approximately 97%. The work contains detailed statistics about the detection rate and the computing complexity. Inspired by intensity histogram, the work shows a new approach that extracts a set of features based on depth histogram and combines stereo measurement with SVM classifiers to correctly classify benign and malignant polyps.

Roles of eating, rumination, and arterial pressure in determination of the circadian rhythm of renal blood flow in sheep.

To assess the roles of feeding behavior (eating and rumination) and systemic arterial pressure (SAP) on determination of the circadian rhythm of renal blood flow (RBF), 20 sheep fitted with ultrasonic flow-metering probes around both renal arteries and a submandibular balloon to monitor jaw movements (6 of them with a telemetry measurement system into the carotid artery for SAP recording), were successively assigned to 6 feeding patterns: once daily in the morning (0900 to 1100 h), afternoon (1700 to 1900 h), or evening (1900 to 2100 h); twice daily at 0900 to 1100 h and 1700 to 1900 h; ad libitum (food renewed each 2 h); and fasting (40 h). All protocols were carried out in autumn-winter, and the fasting pattern was repeated in spring-summer to evaluate the effect of the daylight length on RBF. In the once-daily feeding patterns, a rapid increase in RBF (P < 0.05 vs. 1-h prefeeding mean values) subsequent to the onset of meals was observed, followed by a progressive increase (P < 0.05), reaching a maximum 4 to 6 h after the beginning of eating, and a subsequent gradual decline until the next meal [differences vs. prefeeding values were no longer significant after 11 h (morning pattern), 13 h (afternoon pattern), and 15 h (evening pattern) from the beginning of eating]. In the twice-daily feeding pattern, each meal was also followed by an increase in RBF (P < 0.05 vs. prefeeding values), reaching a maximum 3 to 5 h after the onset of meals, and a posterior decline [differences vs. prefeeding values were no longer significant after 8 h (morning meal) and 5 h (afternoon meal) from the beginning of eating]. In the ad libitum feeding, no apparent rhythm in RBF was found. During fasting, a progressive reduction of RBF was observed from 2 h after the beginning of fasting (P < 0.05 vs. the mean value of the first fasting hour), with a slight rebound (P < 0.05) lasting several hours from approximately 0700 h in autumn-winter and approximately 0500 h in spring-summer. No change in the RBF profile was observed in association with rumination. Except during meals, no correlation was found between RBF and SAP. A detailed description of RBF and SAP recordings is presented. In conclusion, results showed a circadian rhythm of RBF determined by eating behavior, but not by rumination, that was independent of blood pressure and that seemed superimposed on a primary lighting-cycle-dependent RBF rhythm.

Abdominal and fetal echography tele-operated in several medical centres sites, from an expert center, using a robotic arm & telephone or satellite link.

OBJECTIVE: to design and validate a method for tele-operating (from an expert site) an echographic examination in an isolated site where the patient stays. METHOD: A dedicated robotic arm (ESTELE) holding a real ultrasound probe is remotely controlled from the expert site with a fictive probe, and reproduces on the real probe all the movements of the expert hand. The isolated places, are areas with reduced medical facilities, (secondary hospitals 20 to 100 km from the main hospital in Europ, dispensaries in Africa, Amazonia, the a rescue vehicles.... RESULTS: ESTELE was tested on 87 adults and 29 pregnant with ISDN or satellite lines. During fetal tele-operated echography the expert was able to perform appropriate views of the fetal structures in 95% of the cases. During exploration of adult abdomen the expert visualized the main organs in 87% of the cases. Presently the ESTELE system is installed in 4 secondary hospitals, 40 to 100 km from our University Hospital and tele-operated daily by our staff. CONCLUSION: Robotized tele-echography provide similar information as direct examination. No false diagnostic was reported. Moreover the patients were examined by an expert from the University Hospital while staying in the Medical center proximal to their home.

[Asymptomatic pneumothorax diagnosis on pre-biopsy sonogram of the liver]. / Découverte d'un pneumothorax lors d'une échographie de repérage avant ponction biopsie hépatique.

Liver biopsy is an invasive procedure which is widely used for the management of liver diseases. An asymptomatic pneumothorax was detected on sonography prior to biopsy for chronic hepatitis C. The complications from biopsy, potentially severe, are decreased by ultrasound guidance. Currently, ultrasound guidance is recommended at the time of liver biopsy.

Phase II study of troxacitabine (BCH-4556) in patients with advanced non-small-cell lung cancer.

Troxacitabine. a promising new L-nucleoside, inhibits DNA polymerase and leads to complete DNA chain termination. The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) conducted a phase II study to assess the efficacy and toxicity of troxacitabine in untreated patients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients were eligible if they had inoperable stage IIIB or IV NSCLC, ECOG PS < or = 2, adequate hematology and biochemistry, and at least one bidimensionally measurable lesion. Patients with prior malignancy or brain metastases were excluded. Troxacitabine (10 mg/m(2)) was administered intravenously over 30 minutes every 3 weeks. Between June 1999 and May 2000, 17 eligible patients received treatment. Patient characteristics included: median age 64 years; female 41%; stage IV (94%); PS 0 (12%), 1 (59%), and 2 (29 %), 3 or more disease sites (59%). In 17 patients, there were 8 stable disease, 9 disease progression, and no objective responses. Median duration of stable disease was 3.6 months (range = 2.0-7.1). A total of 56 cycles were administered (median = 3), and 88% of patients received 90% or more of the planned dose intensity. The majority (82%) of patients experienced skin rash. Hematologic and biochemical toxicities, grade 3/4 (%) were: granulocytopenia (41), anemia (12), thrombocytopenia (6), and hyperglycemia (6). Troxacitabine appears to have little activity in NSCLC in the dose and schedule tested.

Directional selection for specific sheep cell antibody responses affects natural rabbit agglutinins of chickens.

Agglutination data from generations 8 through 19 indicate that bidirectional selection for specific SRBC antibody responses was successful in a line cross of ISA x Warren medium heavy layers. After 11 generations titers of the high SRBC selected line (H line) were nearly 1:32,000; those of the low SRBC selected line (L line) were less than 1:2, but titers of the randombred control line remained stable at 1:32. Directional SRBC selection also affected levels of a naturally occurring rabbit cell agglutinating antibody (RRBC), presumably the avian form of alpha-galactose antibody (anti-Gal). This indirect response was biphasic and opposite in direction to the SRBC responses through generation 14 after which anti-Gal titers of all 3 lines increased. At generation 19, line H had the highest agglutinin titers; of both types, control line was intermediate, and line L was lowest. The correlation between SRBC and RRBC titers was 0.43 (P = 0.0). Females had higher titers than males, but the difference was only significant for the SRBC antibody (P = 0.028). Qualitative changes in anti-Gal accompanied SRBC selection. Rabbit agglutinins of 4 types were recognizable: classic, granular, annular, and one negative or very weak reaction. The score type means in line L were highest, in the control line were intermediate, and in line H were lowest, suggesting avidity differences now exist among these lines. The results show integration of natural and acquired immune systems because selection for one temporarily affected the other. Given the importance of anti-Gal in primates, our results should stimulate further study of this antibody in poultry species.

Is ultrasound lymph node examination superior to clinical examination in melanoma follow-up? A monocentre cohort study of 373 patients.

BACKGROUND: There is still lack of consensus regarding the most effective follow-up for stage I and II melanoma patients although some consensus conferences have provided guidelines stating that clinical examination should be the standard. OBJECTIVES: Our aim was to study the value of adding ultrasound lymph node examination (7.5 MHz) to the routine clinical examination recommended by French guidelines in melanoma follow-up. METHODS: A cohort of melanoma patients was enrolled between 1 July 1995 and 1 July 2000 in a follow-up protocol including clinical examination performed four times a year for thick melanomas (Breslow index > or = 1.5 mm) and twice a year for thin melanomas (Breslow index < 1.5 mm) according to French guidelines, and ultrasound lymph node examination performed every 6 months for thick melanomas and every year for thin melanomas. Follow-up was continued up to 1 July 2003. When clinical or ultrasound examination indicated signs of node recurrence, surgical biopsy of the involved node was performed. When ultrasound examination was only suspicious, another ultrasound examination was performed within the following 3 months. The results of both clinical and ultrasound examinations were compared with histopathology examination when node biopsy was performed. RESULTS: Ultrasound follow-up was performed for 373 patients (213 females and 160 males). Mean age at diagnosis of melanoma was 59 years (range 14-90, SD 15). In total, 1909 ultrasound examinations combined with clinical examination were analysed. Node biopsy was performed in 65 patients and demonstrated melanoma metastases in 54. Sensitivity of clinical examination and ultrasound examination was 71.4%[95% confidence interval (CI) 55.4-84.3] and 92.9 (95% CI 80.5-98.5), respectively, P = 0.02. Specificity of clinical examination and ultrasound examination was 99.6% (95% CI 99.2-99.8) and 97.8% (95% CI 97.0-98.4), respectively. Despite this apparent superiority of ultrasound examination over palpation, only 7.2% of the patients really benefited from ultrasound examination (earlier lymph node metastasis detection or avoidance of unnecessary surgery), while 5.9% had some deleterious effect from ultrasound examination (unnecessary stress caused by repetition of ultrasound examination for benign lymph nodes, useless removal of benign lymph node). CONCLUSIONS: This study confirms the greater sensitivity of ultrasound examination to clinical examination in the diagnosis of node metastases from cutaneous melanoma. However, the place of ultrasound in routine follow-up is at least questionable as only a very small proportion of patients (1.3%) really benefited from adding ultrasound examination to clinical examination.