High-Risk Cutaneous Squamous Cell Carcinoma without Palpable Lymphadenopathy: Is There a Therapeutic Role for Elective Neck Dissection?

PURPOSE: The beneficial role of elective neck dissection (END) in the management of high-risk cutaneous squamous cell carcinoma (CSCC) of the head and neck remains unproven. Some surgical specialists suggest that END may be beneficial for patients with clinically node-negative (N0) high-risk CSCC, but there are few data to support this claim. We reviewed the available literature regarding the use of END in the management of both CSCC and head and neck SCC (HNSCC). METHODOLOGY: The available medical literature pertaining to END in both CSCC and HNSCC was reviewed using PubMed and Ovid Medline searches. RESULTS: Many surgical specialists recommend that END be routinely performed in patients with N0 HNSCC when the risk of occult metastases is estimated to exceed 20%; however, patients who undergo END have no proven survival benefit over those who are initially staged as N0 and undergo therapeutic neck dissection (TND) after the development of apparent regional disease. There is a lack of data regarding the proper management of regional nodal basins in patients with N0 CSCC. In the absence of evidence-based data, the cutaneous surgeon must rely on clinical judgment to guide the management of patients with N0 high-risk CSCC of the head and neck. CONCLUSIONS: Appropriate work-up for occult nodal disease may occasionally be warranted in patients with high-risk CSCC. END may play a role in only a very limited number of patients with high-risk CSCC.     

Lymphocyte predominance Hodgkin's disease (nodular paragranuloma)–a bcl-2 negative germinal centre lymphoma

Hodin's disease, lymphocyte predominance type (nodular paragranuloma), is of germinal centre origin and the tumours cells have a B-cell phenotype. As the t(14;18) translocation, and the subsequent expression of bcl-2 protein by germinal centre cells, is the most characteristic finding of centroblastic-centrocytic lymphoma, we have tested a series of 11 cases of lymphocyte predominance Hodgkin's disease, using Southern blot analysis for the major breakpoint region and the minor breakpoint cluster region, polymerase chain reaction with primers for the major and minor breakpoint cluster region, and immunohistological studies with a monoclonal antibody specific for the bcl-2 protein. All three techniques gave negative results in the cases of Hodgkin's disease, establishing a clear differentiation from centroblastic-centrocytic lymphoma. These findings are useful in the differential diagnosis between the two entities and raise the question of the non-clonal nature of lymphocyte predominance Hodgkin's disease.     

Usefulness of the Pain-induced Functional Impairment Model to Relate Plasma Levels of Analgesics to Their Efficacy in Rats

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.     

Quantification of the Modifications in the Dominant Frequency of Ventricular Fibrillation under Conditions of Ischemia and Reperfusion: An Experimental Study

The characteristics of ventricular fibrillatory signals vary as a function of the time elapsed from the onset of arrhythmia and the maneuvers used to maintain coronary perfusion. The dominant frequency (FrD) of the power spectrum of ventricular fibrillation (VF) is known to decrease after interrupting coronary perfusion, though the corresponding recovery process upon reestablishing coronary flow has not been quantified to date. With the aim of investigating the recovery of the FrD during reperfusion after a brief ischemic, period, 11 isolated and perfused rabbit heart preparations were used to analyze the signals obtained with three unipolar epicardial electrodes (E1-E3) and a bipolar electrode immersed in the thermostatizfid organ bath (E4), following the electrical induction of VF. Recordings were made under conditions of maintained coronary perfusion (5 min), upon interrupting perfusion (15 mini, and after reperfusion (5 min), FrD was determined using Welch's method. The variations in FrD were quantified during both ischemia and reperfusion, based on an exponential model AFrD = A exp (-t/C). During ischemia ΔFrD is the difference between FrD and the minimum value, while t is the time elapsed from the interruption of coronary perfusion. During reperfusion ΔFrD is the difference between the maximum value and FrD, while t is the time elapsed from the restoration of perfusion, A is one of the constants of the model, and C is the time constant. FrD exhibited respective initial values of 16.20 ± 1.67, 16.03 ± 1.38, and 16.03 ± 1.80 Hz in the epicardial leads, and 15.09 ±1.07 Hz in the bipolar lead within the bath. No significant variations were observed during maintained coronary perfusion. The fit of the FrD variations to the model during ischemia and reperfusion proved significant in nine experiments. The mean time constants C obtained on fitting to the model during ischemia were as follows: El =294.4 ± 75.6, E2 = 225.7 ± 48.5, E3 = 327.4 ± 79.7, and E4 = 298.7 ± 43.9 seconds. The mean values of C obtained during reperfusion, and the significance of the differences with respect to the ischemic period were: El = 57.5 ± 8.4 (P ± 0.01), E2 = 64.5 ± 11.2 (P0.01), E3 = 80.7 ± 13.3 (P < 0.01), and E4 = 74.9 ± 13.6 (P < 0.0001). The time course variations of the FrD of the VF power spectrum fit an exponential model during ischemia and reperfusion. The time constants of the model during reperfusion after a brief ischemic period are significantly shorter than those obtained during ischemia.     

Radiofrequency Ablation of Concealed Left Free-Wall Accessory Pathways Without Coronary Sinus Catheterization:

Ablation of Concealed Accessory Pathways. Introduction: Feasibility of radiofrequency (RF) ablation using a two-catheter technique without coronary sinus catheterization was studied in 100 consecutive patients with a single concealed left free-wall accessory path-way.
Methods and Results: Tachycardia was induced by electrical stimulation in the right atrium/right ventricle, and the presence of a concealed left free-wall accessory pathway was suggested electrocardiographically (negative P wave in leads I and/or a VL during orthodromic tachycardia) or by earlier atrial activation in the pulmonary artery compared to the high right atrium. Mapping of the mitral annulus was performed during right ventricular pacing or orthodromic tachycardia, and RF energy was applied at the site with the earliest retrograde atrial activation. Ablation was considered effective if tachycardia could not be induced, and if VA dissociation or exclusive retrograde nodal conduction was observed. Ablation was initially successful in 98 of 100 patients. Mean number of radiofrequency pulses were 3.2 ± 2. Mean fluoroscopy time and total procedure time was 14 ± 9 and 107 ± 32 minutes, respectively. There were no complications related to the procedure. At a mean follow-up of 22 ± 13 months, two patients experienced tachycardia recurrence and required a second procedure, which was successful.
Conclusions: Our results suggest that RF catheter ablation of concealed left free-wall accessory pathways can be safely, effectively, and rapidly performed using a simplified two-catheter technique with no need for coronary sinus catheterization.     

Analysis of the Intracellular Transport Properties of Recombinant La Crosse Virus Glycoproteins

The G1 and G2 glycoproteins of La Crosse virus, a member of theBunyavirusgenus of the Bunyaviridae, are encoded as a single open reading frame (ORF) in the viral middle-sized RNA segment. The primary product from this ORF is processed, either cotranslationally or shortly after translation, into the two glycoproteins and a nonstructural protein, NSm, of unknown function. We have expressed La Crosse glycoproteins using vaccinia vectors and studied their processing and localization. When expressed in the native G2-NSm-G1 configuration, both G1 and G2 targeted to the Golgi apparatus as shown by their colocalization with wheat germ agglutinin and acquired resistance to endoglycosidase H. When expressed independently, G2 was targeted to the Golgi apparatus but G1 was retained in the endoplasmic reticulum, indicating that a G1–G2 association is required for Golgi targeting of G1. In contrast to results with other members of the Bunyaviridae, we found that expression of G1 and G2 from separate vectors did not lead to the transport of the G1–G2 complex to the Golgi. However, disruption of the NSm region with a foreign sequence did not interfere with transport of the complex. When a portion of the β-galactosidase gene was inserted in frame into NSm, the glycoproteins derived from this construct were processed and targeted properly and were capable of mediating cell-to-cell fusion.     

Constitutive Secretion of Interleukin-6 by Human Decidual Stromal Cells in Culture. Regulatory Effect of Progesterone

PROBLEM : Although several studies have demonstrated that decidual stromal cells (DSC) can secrete cytokines in culture, none of these studies documented the purity of the cultures. Since other cells of the decidua, such as macrophages and epithelial cells, also produce cytokines, it is important to ensure purity of the culture so that cytokine production can be ascribed with confidence to DSC. METHOD : DSC from early human pregnancies were highly purified and maintained in culture. Basal secretion by these cells of IL-6, together with other cytokines considered critical for pregnancy (IL-1β, TNFα and IFNγ), was measured with immunological techniques. RESULTS : We found that DSC in culture produce insignificant quantities of IL-1β, TNFá and IFNΓ, but appreciable amounts of IL-6. The production of this later cytokine was, however, inhibited by the effect of progesterone. CONCLUSIONS : Basal production of IL-6 by DSC may be involved in physiological functions at the maternal-fetal interface. Nevertheless, the secretion of this cytokine is regulated by progesterone, probably to prevent excessive production of this cytokine from triggering an inflammatory response that might compromise pregnancy.     

Retention of dental sealants placed on sound teeth and incipient caries lesions as part of a service‐learning programme in rural areas in Mexico

International Journal of Paediatric Dentistry 2012; 22: 451–458 Background. Dental sealants are an effective treatment for the prevention and management of caries. Objective. To determine the retention of sealants placed in a rural setting in Mexico as part of an international service‐learning (ISL) programme and to determine associations between dental sealant’s retention and caries diagnosis at the time of sealant placement. Methods. Children aged 6–15 were examined for dental caries, received sealants by dental students as part of an ISL programme, and were re‐examined 4, 2, or 1 years after placement to assess sealant survival. Sealants were placed on permanent sound surfaces and enamel caries lesions [International Caries Assessment and Detection System (ICDAS) criteria]. Sealant survival was explored using Cochran–Mantel–Haenszel tests and multivariate prediction models. Results. 219 (46%) of 478 (mean age = 10.53 SD = 5.11) children who had received sealants returned for a recall examination (mean age = 10.89 SD = 3.11). After 1–4 years, 96.4% to 60.6% of the sealants placed on sound teeth had survived, and for sealants placed on surfaces with enamel caries lesions (ICDAS 1–3), 94.2% to 55.6% had survived. Differences were not statistically significant. Conclusions. Sealants had survival rates comparable to those previously reported in the literature. Sealants placed on sound and enamel caries lesions had similar survival rates.     

Role of the Atrial Rate as a Factor Modulating Ventricular Response during Atrial Fibrillation

Background: During atrial fibrillation (AF), RR interval histograms show different populations of predominant RR (pRR) intervals. These pRR intervals have been suggested to be multiples of the refractory period of the atrioventricular (AV) node or caused by the existence of a dual AV node physiology. In this study, the hypothesis that pRR intervals are related to the dominant atrial fibrillatory rate is tested. Methods: In this study, Holter electrocardiogram signals from 55 patients with persistent AF were analyzed. Number and position of pRR intervals were detected and compared with mean and standard deviation of the dominant atrial cycle length (DACL). In addition, effects of an enhancement of vagal activity and rate‐control treatments (β‐blockers and verapamil) were evaluated. Results: In all patients with more than one pRR interval and in 47% with one pRR interval, RR interval populations were statistically related with multiples of the DACL. During night activities and during β‐blockers treatment, mean ventricular rate was decreased (P < 0.01). This change was associated with a variation in the percentage of occurrences of each pRR (P < 0.01), whereas no statistical differences were present in the mean DACL or in the position of pRR intervals. A variation of the DACL due to verapamil was associated with a consistent modification in the position of the pRR intervals. Conclusion: The relation between pRR and multiples of the DACL during AF suggests that more probable RR intervals are caused by different conduction ratios of the atrial rate. (PACE 2010; 33:1510–1517)