Preoperative breast MRI in the surgical treatment of ductal carcinoma in situ

Accurate determination of the size or extent of ductal carcinoma in situ (DCIS) by imaging is uncertain, and incomplete resection of tumor results in involved margins in up to 81% of cases. This study examined the accuracy of magnetic resonance imaging (MRI) for assessment of DCIS size, and evaluated the effect of preoperative breast MRI on achievement of tumor-free surgical margins after breast-conserving surgery (BCS). One-hundred and fifty-eight female patients with DCIS were identified from a prospective database: 60 patients (62 cases) had preoperative breast MRI, and 98 patients did not have MRI. The accuracy of tumor size assessed by MRI was determined by comparison with histopathologic size. All patients underwent BCS initially. The rate of involved margins after resection was compared in MRI and no-MRI groups. The overall correlation between MRI size and histopathologic size was high (p < 0.0001). MRI assessment of size was significantly more accurate when DCIS was high grade (p < 0.0001) or intermediate grade (p = 0.005) versus low grade (p = 0.187). The rate of tumor-involved margins was not significantly different in MRI and no-MRI groups (30.7% and 24.7%, respectively; p = 0.414). The rate of mastectomy was significantly higher in the MRI group than the no-MRI group (17.7% versus 4.1%; p = 0.004). These findings indicate that MRI can detect DCIS, especially when lesions are high or intermediate grade, but that MRI does not accurately predict the size of DCIS. In this study, MRI did not improve the surgeon's ability to achieve clear margins following BCS.     

Minimal effective dose of dysport and botox in a rat model of neurogenic detrusor overactivity

Background

Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable.

Objective

Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord–injured (SCI) rats with NDO.

Design, setting, and participants

Female, adult, Sprague-Dawley rats (n = 98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25 μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats.

Measurements

Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test.

Results and limitations

MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7 ± 0.6 to 1.5 ± 0.1 and 1.4 ± 0.3 mm Hg, respectively; p < 0.01 and p < 0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4 ± 1.1 to 5.8 ± 0.5 and 5.4 ± 0.6 mm Hg, respectively; p < 0.05); frequency (from 2.2 ± 0.4 to 1.5 ± 0.2 and 1.3 ± 0.3 NVC per minute, respectively; p < 0.01); and increasing volume threshold to elicit NVC (from 29.8 ± 3.7 to 47.6 ± 6.9 and 47.7 ± 6.3%, respectively; p < 0.05 and p < 0.001, respectively).

Conclusions

This is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results.     

Evaluation of the effect of cooling and of the addition of collagenase on llama sperm DNA using toluidine blue

The effect cryopreservation has on sperm chromatin condensation has been studied in many species but not in South American camelids. The objectives of this study were to evaluate with toluidine blue (TB) the effects of cooling and of adding collagenase on llama sperm DNA condensation. The optimum incubation time (30 s, 1.5 and 3 min) with a reducing agent (dithiothreitol) was also determined. When comparing cooled samples with the raw ejaculate, a significant increase in sperm showing a high degree of decondensation (TB positive) was observed (P = 0.005). A positive correlation was observed, both in raw and cooled semen, between sperm head morphological abnormalities observed in TB-stained cells and TB-positive sperm (highly decondensed DNA), but not with TB-intermediate spermatozoa (moderately decondensed DNA). No significant differences (P > 0.05) were observed in samples incubated with or without 0.1% collagenase. In cooled semen, but not in raw, a significant increase (P = 0.000) in reacted sperm (TB positive) was observed using 3-min incubation with 1% dithiothreitol (DTT). To conclude, cooling would seem to produce an increase in llama sperm chromatin decondensation. Also, 0.1% collagenase in H-TALP-BSA could be added to raw semen to aid its manipulation as it would not seem to increase DNA decondensation.     

DNA content of Ovis musimon spermatozoa

To our knowledge, the value of the haploid DNA content (C-value) of Ovis musimon (mouflon) has not been previously published. Therefore, the aim of the present work was to determine the C-value and the nuclear area of O. musimon sperm cells and compare both parameters with those of Ovis aries. Feulgen reaction, which is specific and stoichiometric for DNA, was carried out on semen smears. The C-value and sperm nuclear area were determined using microspectrophotometry and Gallus domesticus erythrocytes as standard species. The C-value of O. musimon was 3.02 ± 0.04 pg, and the sperm nuclear area was 23.92 ± 0.89 μm(2). The C-value and the sperm nuclear area of O. aries were 3.07 ± 0.03 pg and 22.98 ± 0.86 μm(2) respectively. The O. musimon C-value was not significantly different (P > 0.05) from that of O. aries, indicating that both species may have a very close phylogenetic relation.     

Morphometric analysis of llama (Lama glama) sperm head

Llama production in Argentina has increased, as the international interest in breeding this type of animals has grown in the last years. Considering the great polymorphism that llama spermatozoa present at evaluation using light microscopy, the aim of this study was to objectively evaluate llama sperm head morphometry using digital morphometric analysis. Five ejaculates from each of eight males were obtained to evaluate morphometric parameters of 8000 sperm heads stained with Tinción 15^®. The following average results were obtained for each parameter: size parameters: area 20.09 μm², length 6.60 μm, width 4.14 μm, equivalent circle diameter 5.06 μm, curve length 5.79 μm and curve width 3.48 μm; boundary parameters: perimeter 18.54 μm and convex perimeter 17.34 μm; and shape parameters: roundness 1.28 and elongation 1.59. Morphometric parameters of sperm head were compared between ejaculates of the same male and between males. Significant differences between ejaculates of the same male were found for all parameters evaluated (P < 0.01). Significant differences between males were found for all morphometric parameters (P < 0.01) except for curve length, curve width and perimeter. The differences detected would indicate that there is not a single morphometric pattern for Lama glama sperm head, because parameter values cannot be standardised.     

Etiologic influence on chromosomal aberrations in European hepatocellular carcinoma identified by CGH

Previous studies suggest different pathways in the molecular development of hepatocellular carcinoma (HCC). We investigated the pattern of chromosomal imbalances in HCC depending on the type of underlying liver disease as detected by comparative genomic hybridization in 67 cases of primary HCC occurring in non-cirrhotic livers (n = 30), in liver cirrhosis (LC) related to alcohol intake (n = 9), cryptogenic or metabolic changes (n = 11), and chronic viral hepatitis B or C (n = 17). HCC were treated by liver resection in 48 patients and transplantation in 19 patients. The 10-year disease-free and overall survival rates were 51% and 68%, respectively. The copy number changes occurring in more than 10% of cases were gains at 8q (55%), 1q (49%), 7q (15%), 7p (13%), 6p (12%), and 20q (12%), as well as losses at 8p (55%), 4q (33%), 6q (33%), 13q (25%), 14q (24%), 17p (22%), 16q (19%), 1p (18%), 18q (16%), 9p (13%), 10q (13%), 4p (12%), and 9q (12%). HCC arising in alcoholic LC showed a different pattern with significantly fewer net changes (p = 0.008), particularly fewer chromosomal gains (p = 0.008) and fewer breakpoints (p = 0.003) compared to the other investigated HCC subgroups. Future clinical studies should evaluate the prognostic relevance of these findings.     

Class II subdivision with skeletal transverse maxillary deficit treated by single-sitting bone-borne appliance:: A case report

This case report describes orthodontic treatment including both skeletal maxillary expansion and unilateral distalization by means of a single bone-borne appliance followed by clear aligner therapy in a young adult patient. A surgical guide was digitally designed and three-dimensionally printed to facilitate the placement of four miniscrews in the palatal vault. The miniscrews were fitted and the bone-borne appliance was delivered in a single clinical appointment. The postexpansion photographic records and models demonstrate the opening of the palatal median suture, the pure skeletal expansion, and the resolution of the left crossbite after 40 activations. Specifically, left molar Class I was obtained in about 5 months without any loss of anterior anchorage, and the subsequent aligner phase achieved all of the objectives established in the treatment plan. This case report shows clearly how careful digital planning of miniscrew insertion and the delivery of a pure bone-borne appliance in a single sitting enabled good clinical outcomes to be achieved in an acceptable timeframe, without side effects, even in a young adult patient.     

Distribution of Androgen and Oestrogen Receptors-α in the Seminal Vesicle-Related Spinal Neurones in Male Rats

The seminal vesicles are male accessory sex glands that contribute much of the seminal fluid volume. Previous studies have suggested that the majority of autonomic innervations to the rat seminal vesicles originate from the bilateral major pelvic ganglia. Many preganglionic autonomic neurones innervating the pelvic ganglion were expressed androgen receptors (AR) or oestrogen receptor (ER)-α immunoreactivity. However, direct neuroanatomic data regarding the distribution of AR and ER-α in seminal vesicle related-spinal neurones are lacking. In the present study, a nonvirulent pseudorabies virus (PRV-152 strain) was used in a retrograde tracing experiment. Four days after PRV injection into the seminal vesicles of male rats, spinal cord sections were prepared. Double- and triple-fluorescence techniques using AR and ER-α with choline acetyltransferase (ChAT) and PRV were used to investigate the AR and ER-α distribution in the seminal vesicles related spinal neurones in male rats. In lamina X, 14% of the PRV-labelled neurones in the L1–L4 segments and 43% in the L5–S1 segments were double-labelled with AR. In the L1–L4 segments, 6% of PRV-labelled neurones and 26% in the L5–S1 segments were double-labelled with ER-α. In the intermedial cell column area, 10% of PRV-labelled neurones in the L1–L4 segments and 47% of PRV-labelled neurones in the L5–S1 segments were double-labelled with AR. Up to 16% of PRV-labelled neurones in the L5–S1 segments were double-labelled with ER-α. No PRV-labelled neurones in the L1–L4 segments were double-labelled with ER-α. However, for the AR and ER-α/PRV/ChAT triple-fluorescence experiments, very few seminal vesicle preganglionic neurones expressed AR or ER-α. Our data suggests that many spinal interneurones but not preganglionic neurones involved in the seminal vesicle control in male rats were double-labelled with AR or ER-α, and they were mainly located at the parasympathetic level in the spinal cord.     

Taking the stand: Issues and strategies in forensic neuropsychology

Neuropsychologists are participating in the legal process with increasing frequency. Simultaneously, attorneys are becoming more sophisticated about the limitations of the field, leaving the expert neuropsychologist vulnerable to increasingly rigorous cross-examination. Five substantive areas in which common assumptions are vulnerable to the weight of scientific evidence are reviewed in an effort to enhance the preparedness and credibility of the neuropsychological expert witness. These include: (1) the lack of uniformity in neuropsychological assessment; (2) research on training, experience, and judgment accuracy; (3) the modest capacity to predict everyday and work functioning from neuropsychological test results; (4) evidence indicating an inability to detect malingering; and (5) the problems clinicians have with complex data integration. When appropriate, suggestions for corrective strategies in forensic evaluations and expert testimony are provided.     

A Mutation in the CASQ1 Gene Causes a Vacuolar Myopathy with Accumulation of Sarcoplasmic Reticulum Protein Aggregates

A missense mutation in the calsequestrin‐1 gene (CASQ1) was found in a group of patients with a myopathy characterized by weakness, fatigue, and the presence of large vacuoles containing characteristic inclusions resulting from the aggregation of sarcoplasmic reticulum (SR) proteins. The mutation affects a conserved aspartic acid in position 244 (p.Asp244Gly) located in one of the high‐affinity Ca²⁺‐binding sites of CASQ1 and alters the kinetics of Ca²⁺ release in muscle fibers. Expression of the mutated CASQ1 protein in COS‐7 cells showed a markedly reduced ability in forming elongated polymers, whereas both in cultured myotubes and in in vivo mouse fibers induced the formation of electron‐dense SR vacuoles containing aggregates of the mutant CASQ1 protein that resemble those observed in muscle biopsies of patients. Altogether, these results support the view that a single missense mutation in the CASQ1 gene causes the formation of abnormal SR vacuoles containing aggregates of CASQ1, and other SR proteins, results in altered Ca²⁺ release in skeletal muscle fibers, and, hence, is responsible for the clinical phenotype observed in these patients.