Significance of myeloperoxidase plasma levels as a predictor for cardiac resynchronization therapy response.

OBJECTIVES: This study aimed to determine if changes in myeloperoxidase (MPO) levels correlate with response to cardiac resynchronization therapy (CRT) and the potential role of MPO as a predictor of response to CRT. BACKGROUND: CRT is a well-established treatment option in chronic heart failure (CHF) with 50-80% of patients benefiting. Inflammation and oxidative stress play a key role in CHF pathophysiology. Previous studies have demonstrated increased levels of MPO in CHF patients, but the correlation with CRT response remains incompletely understood. METHODS: Fifty-three patients underwent CRT implantation. During follow-up, patients were divided into two groups, responders and non-responders to CRT, based on improved physical capacity and NYHA classification. Levels of MPO and NT-pro-brain-natriuretic-peptide (NT-proBNP) were determined prior to implantation, 30 and 90 days after. Physical capacity, including a 6-min walking-test, NYHA class, and LVEF were evaluated at baseline and during follow-up. RESULTS: Thirty-four patients (64%) responded to CRT, showing improved physical capacity and LVEF. All responders revealed a significant decrease of MPO levels (503.8 ng/ml vs. 188.4 ng/ml; p < 0.001). Non-responding patients did not show any significant changes in clinical parameters or MPO levels (119.6 ng/ml vs. 134.3 ng/ml; p = 0.672) during follow-up. At baseline, physical capacity and NYHA class, as well as MPO levels differed significantly between both groups (p < 0.001). A ROC analysis identified an MPO cut-off value for response to CRT of 242 ng/ml with a sensitivity of 93.5% and specificity of 71.4%. There was a strong correlation between MPO and improvement of LVEF (Spearman's rho: - 0.453; p = 0.005) and physical capacity (Spearman's rho: - 0.335; p = 0.042). CONCLUSIONS: Response to CRT and course of MPO levels correlate significantly. MPO levels differ between responders and non-responders prior to CRT, which may indicate an additional value of MPO as a predictor for CRT response. Further randomized studies are required to confirm our data in larger patient cohorts.

Integrated morphologic and molecular analysis of Trichomonas vaginalis, Mycoplasma hominis, and human papillomavirus using cytologic smear preparations.

Pathogenic microbes may colonize the female genital tract via sexual transmission and cause health issues like inflammation or malignancy, summarized as sexually transmitted disease (STD). A major representative of such pathogens is Trichomonas vaginalis (T.v.), whose role in the etiology of cervical cancer remains elusive. Traditional morphologic screening of cervical smears is able to detect T.v., although its identification may be complicated by look-alikes such as degenerated granulocytes and basal cells. In addition, the parasite's endosymbiont Mycoplasma hominis (M.h.) cannot be detected in the Pap test. This investigation was aimed at designing a PCR-based method to detect specific pathogenic germs by using cervical cytology slides to overcome morphologic uncertainty and increase diagnostic accuracy. To test our molecular screening method on T.v., M.h., and HPV in archival smears, we elaborated a multiplex PCR approach based on microdissection. This assay was applied to a minute quantity of starting material which harbored or was suspected to harbor T.v.; the resulting isolated DNA was used for subsequent molecular analyses of T.v., M.h., and HPV. We clarified the diagnosis of genital T.v. infection in 88 and 1.8% of morphologically suspicious and T.v.-negative cases, respectively. We also revealed a tendency of M.h. co-infection in high-risk HPV cases. In conclusion, a microdissection-based approach to detect pathogenic microbes such as T.v., HPV, and M.h. is a molecular tool easy to implement and may help to better understand the interactivity of these germs with respect to pathogenesis.

[Updates on tumours of the salivary glands : 2017 WHO classification]. / Neues zu Tumoren der Speicheldrüsen : WHO-Klassifikation 2017.

In the new 2017 WHO classification, a reduction of the high number of entities of salivary carcinomas was implemented. There is only one new carcinoma entity: secretory carcinoma. There is a slight increase of reactive and benign entities by the inclusion of rare and well-established, but so far not included, lesions. Furthermore, there are some conceptual changes and pure changes in terminology. The impact of molecular findings is increasing and is so far restricted to diagnostic aspects.

[Morphology of non cutaneous head and neck squamous cell carcinoma]. / Morphologie des nicht-kutanen Plattenepithelkarzinoms im Kopf-Hals-Bereich.

Head and neck squamous cell carcinoma (HNSCC) is by far the most frequent malignant tumor in this anatomic region. Today, HNSCC is divided into two morphologically, molecularly and clinically fundamentally different entities: conventional and virus-associated (HPV/EBV) neoplasms. Premalignant lesions of nonvirus-associated HNSCC include conventional leukoplakia, dysplasia and proliferative verrucous hyperplasia with an increasing risk for malignant transformation. The morphology of HNSCC comprises a spectrum of growth patterns. In addition, special types of HNSCC must be delineated. Recently, for virus-associated HNSCC, some important clinicopathological specifics have become relevant including a separate staging system for these neoplasms. For non-virus associated HNSCC, new grading procedures have been proposed, which significantly impact on prognosis. These issues will be discussed in this review.

Redox-sensitive mechanisms underlying vascular dysfunction in heart failure.

Regardless of the progress in therapeutic drugs and devices to treat heart failure (HF) during the last few years, the clinical outcome of this disease remains deleterious. Impaired left ventricular function leads to neurohumoral activation, altered local shear forces, and hypoxia, which might give rise to inflammatory processes within the vasculature. Among those, the imbalance of the redox equilibrium toward increased concentrations of reactive oxygen species (ROS) is particularly important, as it affects the integrity of vascular function. Apart from injured or dysfunctional cardiomyocytes, vascular dysfunction has been demonstrated to play a crucial role in the development and progression of HF, which makes it an interesting target for new HF therapies. The mechanisms that initiate vascular dysfunction in HF pathogenesis and the processes leading to oxidative stress are not yet fully elucidated. However, oxidative stress promotes a variety of redox-sensitive mechanisms contributing to vascular dysfunction in HF. Here, we will summarize the sources of ROS in the vasculature, elucidate the impact of oxidative stress on functional and structural vascular remodeling, and consider the link to vascular dysfunction. Furthermore, we will point out the importance of vascular dysfunction in HF and discuss therapeutic options.

[Cutaneous adnexal and salivary gland tumours. Similarities and differences]. / Hautadnex- vs. Speicheldrüsentumoren. Analoges und Divergentes.

Despite major discrepancies in basic microscopic anatomy, remarkable similarities are manifest within the wide spectrum of cutaneous adnexal and salivary gland tumors. In this study salivary gland and adnexal tumors were identified and investigated with respect to similarities in histology, terminology and pathogenesis. Histological similarities of certain types of salivary gland tumors relate to eccrine, apocrine and rarely sebaceous (but not trichofollicular) types of adnexal tumors. The most striking similarity was found with salivary gland pleomorphic adenoma and cutaneous mixed tumor. Multistep carcinogenesis starting with intraductal carcinoma, identified in carcinoma ex pleomorphic adenoma is identical to that found in cutaneous carcinoma ex spiradenoma. Further histological and terminological similarities are shown for mucinous and mucoepidermoid carcinoma, for lymphadenoma and lymphoepithelial carcinoma, for sebaceous adenoma and carcinoma, for adenoid-cystic carcinoma, as well as for salivary gland basal cell adenoma versus cutaneous spiradenoma. Manifest diagnostic problems related to histologically similar salivary gland and adnexal tumors are rare and are topographically limited to the parotid and oral areas.

[HPV-associated oropharyngeal carcinoma. Status quo and relationship with cancer of unknown primary]. / HPV-assoziierte oropharyngeale Karzinome. Aktueller Stand und Verhältnis zum Karzinom unbekannter Herkunft.

Carcinomas of the oropharynx with association to high-risk types of human papillomavirus (HPV) have been identified as a new tumour entity with favourable prognosis, distinct from classical nicotine- and alcohol-associated carcinoma. They develop through oncogenic transformation of the basal cells of reticulated cryptal epithelium of the palatinal tonsils and the base of the tongue. Positivity for HPV strongly correlates with an atypical, non-keratinizing histological differentiation and cystic transformation of lymph node metastases. Strong immunohistological positivity for p16 reliably detects transcriptionally active infection with high-risk HPV. Hence, p16 staining has been regarded as an effectual diagnostic tool in the appropriate setting. Frequent nodal metastasation as well as considerable size of (cystic) metastases, and frequent small size as well as submucosal location of primary tumours all contribute to frequent initial manifestation of cervical cancer of unknown primary (CUP). In a situation of CUP diagnostic testing for HPV (in negative cases in addition to EBV) is recommended in lymph node metastases, due to the high predictive value for the localization of occult primary carcinomas. Intense clinicopathological cooperation is mandatory for improved detection of small, occult primary carcinomas. The relevance of this new carcinoma entity will increase, as the incidence continues to increase worldwide.

[The visionary concept of "lymphoepithelioma" by A. Schmincke in 1921. Subsequent confusion over terminology and current approach to a solution]. / Das visionäre Konzept des "Lymphoepithelioms" 1921 und A. Schmincke. Nachfolgende terminologische Verwirrung und aktuelle Lösungsansätze.

In 1921 Alexander Schmincke established the visionary concept of a clinically and histomorphologically defined carcinoma entity of different lymphoepithelial organs that he named "lymphoepithelioma". This nowadays mainly comprises non-keratinizing oropharyngeal carcinomas frequently associated with human papillomavirus (HPV) and non-keratinizing nasopharyngeal carcinomas mostly associated with Epstein-Barr virus (EBV). The term lymphoepithelioma was originally defined by A. Schmincke and J. Ewing as a combined clinical and histological tumor entity of lymphoepithelial organs. The main reason for the longstanding terminological confusion regarding the term lymphoepithelioma is based on the fact that lateron a pure histological interpretation (lymphoepithelial differentiation) caused an artificial and nonreproducible exclusion of tumors with transitional and basaloid differentiation. For the forthcoming new WHO classification it has been suggested that squamous cell carcinoma of the head and neck should no longer be classified according to the heterogeneous histological differentiation but according to etiopathogenetic criteria (e.g. HPV-related, EBV-related, nicotine and alcohol-related). This proposed classification corresponds much better to the prognosis and therapy and would represent a late acknowledgement of Schmincke's visionary concept of a clinically and histomorphologically defined tumor entity. In addition, the ongoing terminological confusion over the heterogeneous and prognostically weak spectrum of histological differentiation would subside.

Prospective comparison of cardiopulmonary events during minilaparoscopy and colonoscopy under conscious sedation.

BACKGROUND AND STUDY AIMS: Cardiorespiratory parameters were examined throughout diagnostic minilaparoscopy procedures. The same parameters were analyzed during colonoscopy, and the data were compared. PATIENTS AND METHODS: Sixty-five consecutive unselected patients undergoing minilaparoscopy (group 1: ASA I, n = 34; group 2: ASA II/III, n = 31) and 61 consecutive unselected patients undergoing colonoscopy (group 3: ASA I, n = 31; group 4: ASA II/III, n = 30) were included. Oxygen saturation (Sao (2)), heart rate (HR) and mean arterial pressure (RRm) were measured continuously, and 12-lead electrocardiography (ECG) recordings were made at specific times during each procedure. RESULTS: Minor differences were observed, particularly after premedication, probably due to different dosage regimens and timing in the two examination techniques. After premedication, testing for differences from baseline values showed a minor decrease in Sao (2) and RRm in the minilaparoscopy groups in comparison with the colonoscopy groups (median Sao (2), group 1: 99.9 % +/- 0 vs. group 3 : 100 % -1, P = 0.0078; median RRm, group 1: 99.5 - 4 mm Hg vs. group 3 : 96 -16 mm Hg, P = 0.046, and median RRm, group 2 : 110 + 1 mm Hg vs. group 4 : 101 -13.5 mm Hg, P = 0.0007). HR increased in minilaparoscopy in comparison with colonoscopy (median HR: group 2 : 77 + 4 beats/min vs. group 4 : 75.5 +/- 0 beats/min; P = 0.01). Comparison of defined relevant pathological changes in Sao (2), RRm, HR, and ECG showed no significant differences. DISCUSSION: These data indicate that diagnostic minilaparoscopy under conscious sedation is only associated with limited risk in patients with compensated cardiopulmonary diseases. This is probably due to the low insufflation pressure used.

Use of the Brief Psychiatric Rating Scale as a predictor of psychiatric admission for non-suicidal patients.

OBJECTIVE: We hypothesized that a systematic determination of symptom severity would predict psychiatric admission for non-suicidal patients referred for a psychiatric evaluation in an urban emergency department (ED) setting. METHOD: In a pilot study involving consecutive patients referred for a psychiatric evaluation in an urban ED, symptom severity was quantified using the Brief Psychiatric Rating Scale (BPRS). The BPRS scores of all non-suicidal patients were subjected to receiver operator characteristic (ROC) curve analysis to determine the sensitivity, specificity, and optimal cutoff score of the BPRS in predicting admission for non-suicidal patients. RESULTS: A BPRS cutoff score of 39 had a sensitivity of 85.71 percent and a specificity of 86.11 percent. The area under the ROC curve was .8671 (Somer's D = .7342) and the standard error of the curve was .1124. The cutoff score of 39 correctly identified six of seven non-suicidal patients who were hospitalized. CONCLUSIONS: It is anticipated that use of the BPRS in the ED will be further refined when a larger patient sample is studied. Potentially, a subset of BPRS items could be identified which would be more sensitive in predicting admission than the full BPRS and increase the overall efficiency of administering the BPRS in the ED.

Effects of age, system experience, and navigation technique on driving with an advanced traveler information system.

This paper explores the effects of age, system experience, and navigation technique on driving, navigation performance, and safety for drivers who used TravTek, an Advanced Traveler Information System. The first two studies investigated various route guidance configurations on the road in a specially equipped instrumented vehicle with an experimenter present. The third was a naturalistic quasi-experimental field study that collected data unobtrusively from more than 1200 TravTek rental car drivers with no in-vehicle experimenter. The results suggest that with increased experience, drivers become familiar with the system and develop strategies for substantially more efficient and safer use. The results also showed that drivers over age 65 had difficulty driving and navigating concurrently. They compensated by driving slowly and more cautiously. Despite this increased caution, older drivers made more safety-related errors than did younger drivers. The results also showed that older drivers benefited substantially from a well-designed ATIS driver interface.

Anti-lock brake system: an assessment of training on driver effectiveness.

When activated correctly, Anti-Lock Brake Systems (ABS) can provide drivers with the ability to stop a vehicle in shorter distances and allow for more vehicle control under heavy braking than conventional brake systems. This is especially true under wet or icy road conditions. However, it is believed that many drivers are either unaware of the correct method of activation or they revert back to the old method of pumping the brakes when they are faced with a hard braking situation. This paper examines the effectiveness of implementing low-cost training methods for alerting drivers to the correct brake activation technique. A 4-page, color training pamphlet was developed and subjects were given a short period of time to read it over before being asked to drive on an icy test track. Results indicated that those subjects who received the training were able to stop in shorter distances in a straight line braking event and more often used the correct brake activation technique than those subjects who did not receive the training. However, the stopping distance benefits were not realized in the curved and surprise braking events. These results suggest that the transfer of verbal knowledge may have value as a means for solving the apparent problem of improper ABS usage. However, some additional research should be done to validate these results. Since this experiment was conducted directly after the material was read, the possibility exists that without reinforcement, the trained braking techniques might become extinct in a short period of time.

Short-term memory for tactile and temporal stimuli in a shared-attention recall task.

The present study examined short-term memory for tactile and temporal stimuli. Subjects were required to touch three-dimensional sample objects of different shapes and textures, presented for three durations: short, medium, or long. After the sample duration elapsed, a retention interval (5 sec.-20 sec.) occurred followed by a recall test for one of the sample dimensions of shape, texture, or time, across trials. Analysis showed that accuracy for shape and texture was high throughout testing (95-99%), but memory for perceived duration was relatively poor (60%). Further analysis indicated that poor recall on the time dimension was isolated to the medium and long samples; accuracy for short durations was consistently high (90%). In addition, a reliable response bias emerged; subjects recalled durations shorter than the actual duration presented. The results were discussed in terms of two lines of research, one indicating that haptic short-term memory is strong relative to other memory systems, and the other suggesting that the choose-short bias occurs across species.

Bombesin improves rats' operant responding maintained by a differential-reinforcement-of-low-rates schedule of food reinforcement.

The present study examined rats' responding on a differential-reinforcement-of-low-rates schedule of food reinforcement following intraperitoneal injections of various doses of bombesin (4, 6, 8, 16, 32 micrograms/kg). Analyses indicated that only the 6 micrograms/kg dosage improved DRL responding. The findings are consistent with prior research examining bombesin's effect on operant behavior and support the notion that bombesin induces satiety rather than malaise.

The intracellular chloride activity of rat kidney proximal tubular cells.

The intracellular Cl- activity was determined in rat kidney proximal tubular cells in vivo, using single-barreled Cl- sensitive microelectrodes filled with Corning no. 477913 liquid ion exchanger resin to measure VCl and using - in separate experiments - conventional KCl-filled microelectrodes to measure the membrane potential, Vm. After correction for interference from other anions on VCl the intracellular Cl- activity averaged 13.1 mmol X l-1 SD +/- 4.5 mmol X l-1 (n = 96). This value is approximately two-fold higher than the intracellular equilibrium activity which can be calculated from the extracellular Cl- activity of 90-103 mmol X l-1 and Vm of -71.2 mV, SD +/- 4.9 mV (n = 23) to amount to 6.3 to 6.7 mmol X l-1. Since both cell membranes are permeable for Cl- ions, as concluded from luminal and/or peritubular Cl- substitution experiments, we conclude that the cellular Cl- accumulation above equilibrium results from transcellular active Cl- transport, the detailed mechanism of which is presently not known. From the slow decline of intracellular Cl- concentration after substitution of luminal Cl- by gluconate, however, we deduce that transcellular Cl- absorption is of minor importance in surface tubules of rat kidney under free flow and that the major part of transtubular Cl- flux is passive and paracellular.