Stress radiographic assessment of collateral ligament constraints on the feline tarsocrural joint.

INTRODUCTION: This cadaveric study describes the collateral ligament constraints on the feline tarsocrural joint using stress radiography. METHODS: Thirty-six feline cadaveric hindlimbs free of orthopaedic disease were placed in a custom-made jig and controlled stress radiography was performed before and after transection of one, or both collateral ligaments. Changes in varus and valgus deviation and pronation and supination were measured at three limb angles (extension, 120o flexion and 90o flexion). RESULTS: There was a significant positive percentage change in the mean angle of varus deviation after transection of the fibulocalcaneal ligament at all limb positions (extension: 41%, 120°: 78%, 90°: 63%). There was a significant positive percentage change in the mean angle of varus deviation after transection of the fibulotalar ligament at extension (14%). There was a significant positive percentage change in the mean angle of varus deviation after transection of both fibulocalcaneal and fibulotalar ligaments at all limb positions (extension: 58%, 120°: 67%, 90°: 67%), and in the mean angle of valgus deviation (100%) and supination (89%) at 90 degrees flexion. There was a significant positive percentage change in the mean angle of valgus deviation after transection of the tibiocentral ligament at all limb positions (extension: mean 79%, 120°: 43%, 90°: 49%) and the mean angle of pronation at 120 degrees flexion (10%). There was a significant positive percentage change in the mean angle of varus deviation after transection of the tibiotalar ligament at extension (11%) and at 90 degrees flexion (54%) and in the mean angle of pronation at all limb positions (extension: 11%, 120°: 19%, 90°: 32%). There was a significant positive percentage change in the mean angle of valgus deviation (extension: 255%, 120°: 172%, 90°: 176%) and pronation (extension: 58%, 120°: 134%, 90°: 76%) after transection of the tibiocentral and tibiotalar ligaments at all limb positions and in the mean angle of varus deviation at extension (13%) and 90 degrees flexion (69%). CONCLUSION: The medial collateral ligaments prevent against excessive valgus deviation and pronation, and the lateral collateral ligaments prevent against excessive varus deviation and supination. At 90 degrees flexion subluxation of the talus occurs on the ipsilateral side of the ligament injury resulting in an additional direction of instability.

Indicaciones y resultados de la biopsia del ganglio centinela en el cáncer de mama: cambios observados en el año 2018 respecto al año 2012 / Indications and results of Sentinel Lymph Node Biopsy in breast cancer: changes observed in 2018 compared to 2012

Antecedentes y objetivo Durante los últimos 15 años se han sucedido múltiples cambios en el tratamiento del cáncer de mama (CM) y, en especial, en las indicaciones de la biopsia del ganglio centinela (BGC) y las actitudes ante su resultado. Valorando estos avances, nuestro objetivo es comparar los resultados de las BGC realizadas en nuestro centro en 2012, año a partir del cual se dejó de practicar linfadenectomía axilar (LA) ante el hallazgo de micrometástasis en la BGC, con aquellas llevadas a cabo en 2018, cuando empezaron a aplicarse los criterios Z0011. Material y métodos Hemos desarrollado un estudio retrospectivo observacional comparativo entre la población de pacientes con CM cN0 a las que se les hizo una BGC en el año 2012 y aquellas a las que se les practicó este procedimiento en 2018. Resultados Al analizar los 2 grupos, 174 pacientes de 2012 y 165 de 2018, se hallaron algunas diferencias significativas: en 2018 hubo mayor tasa de BGC, menor número de cánceres lobulillares (14/28; p<0,05), el tamaño medio anatomopatológico fue menor (p<0,001), la representación de tumores Her2 y triple negativos fue mayor (28/49; p<0,01), así como la proporción de tratamiento neoadyuvante (6,6 vs. 42,5%; p<0,001). Al valorar los resultados del estudio axilar, en 2018 hubo un descenso tanto en la positividad de la BGC, que descendió a casi la mitad que en 2012 (42,4 vs. 24,1%; p<0,0001), como en el porcentaje de LA (21,2 vs. 12,6%; p<0,05), así como el de LA con resultado negativo (74,3 vs. 59,1%; p=ns). Conclusión En el grupo de estudio de 2018 se halló una mayor tasa de BGC, con menor tasa de resultado positivo y de LA en blanco, pese a tratarse de una población con tumores más agresivos. Este hecho podría justificarse con la mejora en el filtro radiológico mediante ecografía al diagnóstico, así como con el aumento en el uso de la terapia neoadyuvante (AU)

Background and objective Over the last 15 years, breast cancer (BC) treatment has undergone numerous changes, which have also affected the indications for sentinel lymph node biopsy (SLNB) as well as the procedures depending on its outcome. The aim of this study is to compare the results of the SLNB carried out at our center during 2012, when we stopped performing an axillary lymph node dissection (ALND) after the finding of a micrometastasis, with those conducted in 2018, when we started applying Z011 criteria. Materials and methods We have performed a comparative retrospective observational study, including cN0 BC patients that underwent a SLNB in 2012 versus those that underwent this procedure in 2018. Results A total of 174 patients from 2012 and 165 from 2018 were studied. We found significant differences between the 2groups: in 2018 there were fewer lobular invasive cancers (14 vs. 28) (P<0.05), a smaller mean pathological size(P<0.001), a higher proportion of HER2 and triple negative tumors (28 vs. 49; P<0.01) and, finally, an increase in use of neoadjuvant treatments (42.0 vs. 6.7%). Regarding axillary involvement, we observed a decrease in both the presence of a positive sentinel node (24.1% in 2018 vs. 42.4% in 2012; P<0.0001) as well as in the proportion of ALND performed (12.6% in 2018 vs. 21.2% in 2012) and the presence of positive non sentinel nodes after a ALND (59.1% vs. 74.3%; P=ns). Conclusion Although the 2018 cohort that underwent SLNB had more aggressive tumors, there were fewer positive SN and ALND performed. This is probably due to a more accurate radiological diagnosis with ultrasound, that enables to detect cN1 cases before surgery, and to the increasing use of neoadjuvant treatments that may downstage the axilla (AU)

Indications and results of sentinel lymph node biopsy in breast cancer: Changes observed in 2018 compared to 2012.

BACKGROUND AND OBJECTIVE: Over the last 15 years, breast cancer (BC) treatment has undergone numerous changes, which have also affected the indications for Sentinel Lymph Node Biopsy (SLNB) as well as the procedures depending on its outcome. The aim of this study is to compare the results of the SLNB carried out at our Center during 2012, when we stopped performing an axillary lymph node dissection (ALND) after the finding of a micrometastasis, with those conducted in 2018, when we started applying Z011 criteria. MATERIALS AND METHODS: We have performed a comparative retrospective observational study, including cN0 BC patients that underwent a SLNB in 2012 versus those that underwent this procedure in 2018. RESULTS: 174 patients from 2012 and 165 from 2018 were studied. We found significant differences between the two groups: in 2018 there were fewer lobular invasive cancers (14 vs 28) (P < .05), a smaller mean pathological size (P < .001), a higher proportion of HER2 and triple negative tumors (28 vs 49) (P < .01) and, finally, an increase in use of neoadjuvant treatments (42.0% vs 6.7%). Regarding axillary involvement, we observed a decrease in both the presence of a positive sentinel node (24.1% in 2018 vs 42.4% in 2012) (P < .0001) as well as in the proportion of ALND performed (12.6% in 2018 vs 21.2% in 2012) and the presence of positive non sentinel nodes after a ALND (59.1% vs74.3%) (ns) CONCLUSION: Although the 2018 cohort that underwent SLNB had more aggressive tumors, there were fewer positive SN and ALND performed. This is probably due to a more accurate radiological diagnosis with ultrasound, that enables to detect cN1 cases before surgery, and to the increasing use of neoadjuvant treatments that may downstage the axilla.

Common and contrasting genomic profiles among the major human lung cancer subtypes.

Lung cancer is the leading cause of cancer mortality worldwide. With the recent success of molecularly targeted therapies in this disease, a detailed knowledge of the spectrum of genetic lesions in lung cancer represents a critical step in the development of additional effective agents. An integrated high-resolution survey of regional amplifications and deletions and gene expression profiling of non-small-cell lung cancers (NSCLC) identified 93 focal high-confidence copy number alterations (CNAs), with 21 spanning less than 0.5 Mb with a median of five genes. Most CNAs were novel and included high-amplitude amplification and homozygous deletion events. Pathogenic relevance of these genomic alterations was further reinforced by their recurrence and overlap with focal alterations of other tumor types. Additionally, the comparison of the genomic profiles of the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC), showed an almost complete overlap with the exception of one amplified region on chromosome 3, specific for SCC. Among the few genes overexpressed within this amplicon was p63, a known regulator of squamous cell differentiation. These findings suggest that the AC and SCC subtypes may arise from a common cell of origin and they are driven to their distinct phenotypic end points by altered expression of a limited number of key genes such as p63.

Bernard-Soulier syndrome: common ancestry in two African American families with the GP Ib alpha Leu129Pro mutation.

Bernard-Soulier syndrome (BSs) is a rare bleeding disorder characterized by circulating giant platelets, thrombocytopenia, and a prolonged bleeding time. BSs usually has an autosomal recessive inheritance pattern, with a preponderance of Caucasian and Japanese ancestry when the ethnic background has been reported. Underlying this disorder of platelet function is a defect in the platelet glycoprotein (GP) Ib-IX-V complex, composed of four polypeptides, GP Ib alpha, GP Ib beta, GP IX, and GP V. Molecular characterization of individuals with BSs has identified mutations in the GP Ib alpha, GP Ib beta, and GP IX genes responsible for the expressed phenotype. In this study, we report a family of African-American descent, with autosomal recessive BSs showing a point mutation in codon 129 of the GP Ib alpha gene. This mutation, CTC:wild-type to CCC:mutant, is similar to that of another African American family where the resulting leucine to proline substitution in the 5(th) leucine-rich repeat of GP Ib alpha is responsible for the observed BSs phenotype. Comparison of the intragenic polymorphisms of GP Ib alpha, as well as microsatellite markers in a 17.5 cM region of chromosome 17p12 that contains the GP Ib alpha gene, suggests that, although socially unrelated, the Leu129Pro mutation in these two families has a common founder.

Studies in a large family with late-onset Alzheimer disease (LOAD).

A large 10-generation family with late-onset Alzheimer disease (LOAD) inherited as an autosomal dominant trait was evaluated historically, clinically, and genetically. The family origin was traced to a founder couple of French ancestry with approximately 3,000 descendants. Although the transmission of a genetic predisposition to LOAD is demonstrated through male individuals, a predominance of affected women is observed. Currently, 14 individuals, 12 of whom are women, are classified as affected with Alzheimer disease (AD). Among the affected, the age of onset ranged from 55 to 78 years. Genotyping of the apolipoprotein E (APOE) locus demonstrated that homozygotes for the E4 allele (APOE4) developed signs of AD in their late 60s, whereas affected heterozygotes presented with the disease in their 70s. A significantly higher APOE4 frequency was observed in affected family members than in those unaffected (0.79 vs. 0.25, chi 2 = 9.919, p = 0.0016, df = 1). Survival for more than 15 years after diagnosed onset was observed in a number of those affected and can be attributed to an improved environment, including excellent care and management during the disabling phase of illness. Alternatively, it may be an example of the genetic heterogeneity in AD. Complete documentation of large families such as the one presented will facilitate the discovery of the multiple genetic factors involved in the pathogenesis of AD.

Quinine may trigger torsades de pointes during astemizole therapy.

Because of serious cardiovascular events, warnings against concomitant use of certain medications with the use of antihistamine (HismanalR have been published and added to product labeling. Quinine, the optical isomer to quinidine, is included in these warnings. We present the case of a patient with only mild electrolyte disturbances who experienced an episode of torsades de pointes after a single dose of quinine while taking astemizole.

Complex chromosome 4, 9, and 22 rearrangement in a patient presenting with AML-FAB M2.

Fluorescence in situ hybridization (FISH) and the reverse transcription-polymerase chain reaction (RT-PCR) were used to examine a patient presenting with acute myelogenous leukemia (AML) FAB M2, and a complex t(4;9;22)(p14;q34;q11.2). The patient's clinical course was characterized by an aggressive leukemia, resistant to intensive therapy including allogeneic bone marrow transplantation. FISH analysis, using two chromosome painting probes and a BCR/ABL specific probe, confirmed the cytogenetic observation of a 22q11.2-->4p14 and a 4p14-->9q34 exchange, and revealed the presence of a 9q34-->22q11.2, respectively. In addition, RT-PCR demonstrated the presence of a BCR/ABL transcript derived from the major breakpoint cluster region (M-bcr) of the BCR gene. This transcript has been shown to generate an active 210 kDa tyrosine kinase protein more commonly observed in chronic myelogenous leukemia. Because the presentation of AML with this ABL-->BCR fusion product is a rare event, it would seem likely that the additional complex chromosomal rearrangement involving chromosomes 4, 9, and 22 played a role in the aggressive presentation and clinical behavior of this patient's leukemia.

Alteration of gonococcal protein expression in acidic culture.

We grew Neisseria gonorrhoeae under acidic, neutral, and alkaline conditions and noted altered expression of at least 12 outer membrane proteins between 31 and 100 kDa in size. One protein whose expression was upregulated under acidic conditions was gonococcal heat shock protein 63. These proteins may contribute to the pathogenesis of gonorrhea in the urogenital tract.

Comparison of throat culture methods for the recovery of group A streptococci in a pediatric office setting.

OBJECTIVE: To compare a single-plate method for the recovery of group A streptococci with other methods that have recently been reported as being significantly more sensitive. DESIGN: Throat swabs were allowed to dry for 2 to 6 hours before inoculating 5% sheep blood agar plates. Stabs were made into the agar, bacitracin disks were placed on the primary plates, and the cultures were incubated aerobically. Using duplicate throat swabs, the recovery rates of the above method were compared with the following ones: a carbon dioxide-enhanced incubation atmosphere, an anaerobic atmosphere with a selective blood agar medium, and a Todd-Hewitt broth medium. SETTING: A five-pediatrician office. PATIENTS: A total of 301 pediatric patients with pharyngitis were evaluated using all comparative methods. In addition, duplicate swabs from 590 pediatric patients were compared with each other using the same single-plate method. RESULTS: There were no significant differences between any of the methods. The sensitivity of the single-plate method compared with selective plates incubated anaerobically was 96%. CONCLUSIONS: In a pediatric office setting, a single-plate method using aerobic incubation was adequately sensitive for the recovery of group A beta-hemolytic streptococci. Transport medium, selective medium, carbon dioxide enhancement, and anaerobic incubation did not significantly improve recovery. The present federal regulations that restrict the use of nonselective media and bacitracin disks on primary plates should be reevaluated.

Phenotypic modulation of gonococcal lipooligosaccharide in acidic and alkaline culture.

Neisseria gonorrhoeae infects a diverse array of niches in its human host, which expose the organism to dramatic variations in pH. We examined growth and lipooligosaccharide expression of two gonococcal strains in liquid and solid cultures under acidic, neutral, and alkaline conditions. Growth rates in broth were similar under the three conditions, and the pH remained fairly constant throughout the growth cycle. Altered lipooligosaccharide expression at the different pHs was noted in both plate- and broth-grown organisms.

Comparison of an optical immunoassay technique with two culture methods for the detection of group A streptococci in a pediatric office.

For detecting group A beta-hemolytic streptococci in an office setting, an optical immunoassay method was compared with two culture methods. The sensitivity and specificity of OIA as compared with 5% sheep blood agar cultures were 91.4% and 95.6%, and as compared with a Todd-Hewitt broth method were 90.4% and 94.1%, respectively.

Didanosine therapy in patients intolerant of or failing zidovudine therapy.

OBJECTIVE: To examine the effect of didanosine (2',3'-dideoxyinosine, ddI) on surrogate markers of HIV infection (CD4+ lymphocyte count, p24 antigen) and to evaluate the incidence of adverse effects from ddI. DESIGN: This study was performed as a retrospective chart review of patients who were enrolled in Bristol-Myers Squibb's expanded-access program for ddI. SETTING: Patient records were obtained from primary care physicians' offices. PATIENTS: Twenty-five HIV-infected patients diagnosed with AIDS or AIDS-related complex (ARC) who were intolerant of zidovudine (ZDV) therapy or deteriorating clinically despite ZDV therapy and were eligible for inclusion in the ddI expanded-access program. INTERVENTION: ddI was administered orally in a citrate-phosphate buffer every 12 hours. Patients were followed by their private physician on a monthly basis. MAIN OUTCOME MEASURES: Laboratory analysis at each month included CD4+ lymphocyte count, hemoglobin, hematocrit, serum amylase, uric acid, serum triglycerides, and p24 antigen. Mean CD4+ cell count, serum amylase, hemoglobin, and uric acid at each month during ddI therapy were compared with baseline concentrations for nine months. RESULTS: Patients had received prior ZDV therapy for an average of 15.5 months before starting ddI. Mean CD4+ cell counts increased from 53.9/mm3 at baseline to 72.4/mm3 after 4 months of therapy (p = 0.04) but returned to concentrations comparable with those at baseline after 5 months. One case of documented pancreatitis, two cases of suspected pancreatitis, and nine cases of peripheral neuropathy occurred during ddI therapy. The estimated mean cumulative dose for the development of neuropathy was 1.16 g/kg, which is lower than previously reported. CONCLUSIONS: Patients who have received prolonged therapy with ZDV or who have low initial CD4+ counts may not have sustained increases in CD4+ counts from ddI therapy. Also, development of peripheral neuropathy may occur at lower cumulative doses in these patient populations.

Protein aggregation and inclusion body formation in Escherichia coli rpoH mutant defective in heat shock protein induction.

Mutations in the rpoH gene, encoding sigma 32, an alternative factor required for transcription of the heat shock genes, result in the extensive aggregation of virtually all cellular proteins and formation of inclusion bodies both under stress and non-stress conditions. Inhibitors of protein synthesis suppress this aggregation, suggesting that newly synthesized proteins preferentially aggregate in rpoH mutants. These data suggest that the heat shock proteins are involved in acquisition of the soluble state (i.e. correct conformation) of the bulk of intracellular proteins after their translation.