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Dual-chamber leadless pacemakers (LLPMs) consist of two implants, one in the right atrium and one in the right ventricle. Inter-device communication, required for atrioventricular (AV) synchrony, however, reduces the projected longevity of commercial dual-chamber LLPMs by 35–45%. This work analyzes the power-saving potential and the resulting impact on AV-synchrony for a novel LLPM synchronization protocol. Relevant parameters of the proposed window scheduling algorithm were optimized with system-level simulations investigating the resulting trade-off between transceiver current consumption and AV-synchrony. The parameter set included the algorithm’s setpoint for the target number of windows per cardiac cycle and the number of averaging cycles used in the window update calculation. The sensing inputs for the LLPM model were derived from human electrocardiogram recordings in the MIT-BIH Arrhythmia Database. Transceiver current consumption was estimated by combining the simulation results on the required communication resources with electrical measurements of a receiver microchip developed for LLPM synchronization in previous work. The performance ratio given by AV-synchrony divided by current consumption was maximized for a target of one window per cardiac cycle and three averaging cycles. Median transceiver current of both LLPMs combined was 166 nA (interquartile range: 152–183 nA) and median AV-synchrony was 92.5%. This corresponded to median reduction of 18.3% and 3.2% in current consumption and AV-synchrony, respectively, compared to a non-rate-responsive implementation of the same protocol, which prioritized maximum AV-synchrony. In conclusion, adopting a rate-responsive communication protocol may significantly increase device longevity of dual-chamber LLPMs without compromising AV-synchrony, potentially reducing the frequency of device replacements.

Despite increased interest in the effect of lingering red blood cells (LRBCs) on the heterogeneous hematocrit distribution in the microcirculation, quantitative data on LRBCs before and after the lingering event are still limited. The aim of the study was to investigate the relation between red blood cell (RBC) lingering and hematocrit partitioning in a microfluidic model of a microvascular bifurcation in the limit of low hematocrit conditions (tube hematocrit <10%). To this end, the classification of LRBCs was performed based on timing, position, and velocity of the RBCs. The investigation provided statistical information on the velocity, shape, and orientation of LRBCs as well as on their lateral distribution in the parent and daughter vessels. LRBCs traveled predominantly close to the centerline of the parent vessel, but they marginated close to the distal wall in the daughter vessels. Differently than the RBC flow observed in the smallest vessels, no influence of lingering events on the local hematocrit partitioning was observed in our experiments. However, importantly, we found that LRBCs flowing in the daughter vessel after lingering may be connected to reverse hematocrit partitioning in downstream bifurcations by influencing the skewness of the hematocrit distribution in the daughter vessel, which relates to the so-called network history effect.

Recurrence of paroxysmal atrial fibrillation (AF) following pulmonary vein isolation (PVI) is presumably caused by pulmonary vein (PV) reconnections. However, there is little data available on the durability of PVI and incidence of arrhythmia recurrence in patients with persistent AF.

Left atrial enhancing epicardial adipose tissue at preprocedural cardiac CT allowed for the identification of patients who were at high risk for atrial fibrillation recurrence after atrial fibrillation ablation.

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Pulsed-field ablation (PFA) is a novel nonthermal ablation technology. Its potential value for repeat procedures after unsuccessful thermal ablation for atrial fibrillation has not been assessed.

Zusammenfassung.Herzschrittmacher sind die therapeutischen Grundpfeiler bradykarder Herzrhythmusstörungen. Moderne Schrittmacher sind zuverlässig und bieten eine Vielzahl an Möglichkeiten zur patientenspezifischen Therapie. Schrittmacherwechsel aufgrund von Batterieerschöpfung sind allerdings häufig (~25 % aller Implantationen) und können Komplikationen nach sich ziehen. Batterielose Herzschrittmacher wären wünschenswert um die Anzahl der Schrittmacherwechsel zu minimieren. Ein solches Gerät müsste seine Energie im Körper selbst mittels eines speziellen Generators gewinnen. Dieser Generator könnte beispielsweise aus subkutan implantierten Solarzellen bestehen, welche die kleine Menge Licht, die in unseren Körper eindringt, in elektrische Energie umwandeln. Alternativ könnte der Blutfluss mittels kleiner intravaskulärer Turbinen als Energiequelle genutzt werden. Ein dritter Ansatz verfolgt die direkte Umwandlung eines Teils der mechanischen Energie der Ventrikelkontraktion in elektrische Energie, wozu ein spezielles mechanisches Uhrwerk auf das Myokard aufgebracht wird. Alle diese Ansätze wurden in ersten in vivo Studien erfolgreich getestet. Speziell erfolgsversprechend für die Zukunft scheinen miniaturisierte Generatoren, welche katheterbasiert intraventrikulär implantiert werden können und somit gleichzeitig erlauben, auf Schrittmacherelektroden zu verzichten – eine andere Achillesferse gegenwärtiger Schrittmacher.

The International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) presents this paper in order to contribute to public discussion regarding best approaches to foreign particles testing in orally inhaled and nasal drug products (OINDPs) and to help facilitate development of consensus views on this subject. We performed a comprehensive review of industry experience and best practices regarding foreign particles testing in OINDPs, reviewed current guidances and techniques, and considered health and safety perspectives. We also conducted and assessed results of an industry survey on U.S. Food and Drug Administration requirements for foreign particles testing. We provide here a result of our review and survey: a summary of industry best practices for testing and controlling foreign particles in OINDPs and proposals for developmental characterization and quality control strategies for foreign particles. We believe that clear consensus-based recommendations and standards for foreign particles testing and control in OINDPs are needed. The proposals contained in this paper could provide a starting point for developing such consensus recommendations and standards.

The accurate values of the chromium contents of human and mammalian tissues and body fluids and appropriate procedures for their determination are still a matter of discussion. In this connexion, the chromium content of skeletal muscle of laboratory rabbits has been determined using neutron activation analysis. Data hitherto published by other authors: <7.1–121 ng/g. The procedure for separation of 51Cr by distillation of chromium oxychloride, described in the literature, has been improved. The arrangements necessary to minimize the chromium blank values are described. The main component of this blank is caused by the residual chromium contamination of the surface of the sample vial; typical values of this component are 0.049 ng Cr (without lyophilization) and 0.12 ng Cr (with lyophilization). The analyses of standard reference materials (SRM) yielded values of the chromium contents that are in agreement (i) with the certified value in the case of NBS Citrus Leaves, and (ii) with the latest published value of 9.2±2.5 ng/g in the case of IAEA animals muscle (H-4). NBS Orchard Leaves was found not to be an appropriate SRM for testing the method. In analyses of samples of thigh muscle of bastard rabbits chromium contents of 6.2–22.9 ng/g (fresh weight basis) were obtained. Comparison of these data with a previously found value of 1.2 ng/g, the literature value <7.1 ng/g and the value 2.5 ng/g for H-4 calculated on fresh weight basis indicated that the chromium contents of mammalian skeletal muscle might lie in a broad range, even for a subspecies.

The role of intraocular stray light upon contrast threshold of two skilled human observers was studied by perimetric methods using the automatic perimeter Octopus. Stray light falsifies the contrast sensitivity profile of the blind spot when a critical test stimulus luminance, which differs for various targets, is exceeded. At still higher luminance levels, because stray light effects increase, the blind spot shrinks and finally disappears. A series of high resolution measurements of the blind spot with the automatic perimeter Octopus provide a quantitative answer concerning the commencement and amount of this disturbance as a function of target size and target luminance. The amount of stray light, when using targets varying from 0 to 5 (Goldmann standard) is related to luminous power (target luminance x target area). Using first order assumptions about the stray light emitting characteristics of the disc and empirical data, one may conclude that an increase in luminance of target 0 from 103 to 105 asb only increases the effective dynamic range by about 2 dB (= 0.2 log units 3, the standard target as compared with target) size used in Octopus perimetry, at a luminance level of 103 asb. Falsification of sensitivity gradients and underestimates of depths of scotomata due to stray light effects may be an ever present danger in perimetric determinations. The useful dynamic range in perimetry appears to be limited by photon noise and noise in the neurovisual system on the one hand and by stray light interference on the other.

Adaptive programs have been developed, which adjust the spatial resolution of automatic perimeter measurement according to the presence or absence of visual field defects. Information obtained during the examination is fed back to an adaptively interacting algorithm controlling further examination steps. Using this strategy, defective areas are examined in detail but less time is wasted on regions of normal contrast sensivity.

Die ausschließliche Benutzung demographischer Merkmale zur Definition von Zielgruppen für Weiterbildungsmaßnahmen ist umstritten. Am Beispiel der Einstellungen zur Weiterbildung wird dem Zusammenhang zwischen soziodemographischen und mentalen Merkmalen nachgegangen. An einer Stichprobe von 600 Arbeitnehmern werden Einstellungsdimensionen ermittelt. Mit Hilfe der Diskriminanzanalyse wird gezeigt, daß die gewonnenen Einstellungsdimensionen zur Trennung zwischen Weiterbildungs-Teilnehmern (N = 260) und Nicht-Teilnehmern (N = 340) beitragen können. Die Beziehungen zwischen Einstellungs- und soziodemographischen Merkmalen werden regressionsanalytisch untersucht. Eine enge Koppelung mentaler Eigenschaften an demographische Merkmale wird aufgewiesen. Die Bedeutung der Ergebnisse für die Praxis wird diskutiert.

Abstract: As part of an examination of the cytostatic effects of 1,2-diarylethylenediamine-platinum(II)-complexes the contents of platinum and biologically essential trace elements of tumour tissue and different organs were determined. The activation analysis procedure — separation of32P, isolation of199Au and99Mo — is described. In the course of a pharmakokinetical experiment with tumourbearing rats (DMBA induced hormone-dependent tumours) the desired enrichment of the administered drug in the tumour tissue was found. Changes of the trace element level of tumour tissue were found for hormone-dependent MXT-mammary tumours on mice.

Abstract: In our determination of trace element contents of animal tissue by neutron activation analysis in the course of structure-activity relationship studies on platinum containing cancer drugs and wound healing we have tried to minimize the blank values that are caused by different sources of contarnination during surgery, sampling and the activation analysis procedure. The following topics have been investigated: the abrasions from scalpels made of stainless steel, titanium or quartz; the type of surgery; the homogenisation of the samples before irradiation by use of a ball mill; the surface contaminations of the quartz ampoules that pass into the digestion solution of the irradiated samples. The appropriate measures to be taken in order to reduce the blank values are described. The results of analyses performed under these conditions indicate the effectiveness of the given measures, especially shown by the low values obtained for the chromium contents of the analysed muscle samples.

Dexamethasone-ß-D-glucuronide is a potential prodrug for colonic delivery of the antiinflammatory corticosteroid dexamethasone. Previous studies [T. R. Tozer et al., Pharm. Res. 8:445–454 (1991)] indicated that a glucoside prodrug of dexamethasone was susceptible to hydrolysis in the upper gastrointestinal tract. Resistance of dexamethasone-ß-D-glucuronide to hydrolysis in the upper gastrointestinal tract was therefore assessed. Conventional, germfree, and colitic rats were used to examine enzyme levels along the gastrointestinal tract to compare the stability of two model substrates (p-nitrophenyl-ß-D-glucoside and -ß-D-glucuronide) and to evaluate the prodrug dexamethasone-ß-D-glucuronide. Hydrolytic activity was examined in the luminal contents, mucosa, and underlying muscle/connective tissues in all three types of rats. Enzymatic activity (ß-D-glucosidase and ß-D-glucuronidase) was greatest in the lumen of cecum and colon of conventional rats. In contrast, germ-free rats exhibited relatively high levels of ß-D-glucosidase activity (about 80% of total activity in the conventional rats) in the proximal small intestine (PSI) and the distal small intestine (DSI). Rats with induced colitis (acetic acid) showed reduced levels of luminal ß-D-glucuronidase activity in the large intestine; however, ß-D-glucosidase activity was relatively unchanged relative to that of the conventional rat. Mucosal ß-D-glucuronidase activity was significantly lower in the colitic rats compared with that in the conventional animals. Despite reduced luminal levels of ß-D-glucuronidase activity in the colitic rats, there was still a sharp gradient of activity between the small and the large intestines. Permeability of the glucoside and glucuronide prodrugs of dexamethasone through a monolayer of Caco-2 cells was relatively low compared to that of dexamethasone. The results indicate that dexamethasone-ß-D-glucuronide should be relatively stable and poorly absorbed in the upper gastrointestinal tract. Once the compound reaches the large intestine, it should be hydrolyzed to dexamethasone and glucuronic acid. Specificity of colonic delivery in humans should be even greater due to lower levels of ß-D-glucuronidase activity in the small intestine compared with that in the laboratory rat.

NORTH AMERICAN BLASTOMYCOSIS. PRESENTED BY WILLIAM BAILEY, MD, AND MARVIN KLAPMAN, MD. This 41-year-old white man has a six-month history of lesions on his neck, right hand, left wrist, and left knee, which first appeared while he was a patient in a tuberculosis sanitarium. At that time Mycobacterium tuberculosis was cultured from gastric washings and an upper left lung lobectomy was performed. He has been on a regimen of isoniazid, 300 mg a day, since June 1966. PHYSICAL EXAMINATION.— The patient is a thin white man with hyperkeratotic verrucose lesions, with violaceous indurated margins on the neck, right hand, left wrist, and left knee. LABORATORY DATA.— Complete blood cell count (CBC), blood urea nitrogen (BUN), creatinine, serology, and potassium values, and liver profile were within normal limits. Urinalysis revealed 8 to 10 white blood cells (WBCs) per high power field. Urine culture showed no growth. Creatinine clearance was 64.5 cc

LETTERER-SIWE DISEASE. PRESENTED BY WILLIAM E. BAILEY, MD. An 8-month-old white girl has had an eruption in her groin and axillae since about 1 month of age. Three months ago this eruption was macerated, papular, erythematous, and accompanied by granulomas about 2 cm long and 0.5 cm wide in the axillae and inguinal folds. These granulomas yielded pseudohyphae on a KOH preparation; and a yeast was cultured. When nystatin and amphotericin B topically was applied the granulomas disappeared, and the papular appearance became obvious. Also, the papular scalp and abdomen eruptions began to develop in the past two months, as did the fluctuant mass on the scalp.The significant findings on physical examination were as follows: (1) a 3 cm in diameter fluctuant mass on the left frontal area of the scalp; (2) a crusted erythematous papular eruption of the trunk, intertriginous areas, and scalp; (3) hepatosplenomegaly. LABORATORY DATA.—

The importance of primary irritation of the skin in producing an eczematous dermatitis by itself, as well as influencing the engendering of an allergic eczematous contact dermatitis is well documented. The recent literature is replete with articles adding to the fund of observations on mechanisms of pathogenesis of the eczematous sensitization and various aspects of dermatitis and eczema, but relatively few references are found under the heading of primary irritation as such. At present much of this information is found under such topics as contact dermatitis due to specific agents, thermal injuries, industrial dermatitis, and eczemas of various sorts, and it is inseparably linked with studies on allergic reactions in the skin. This is quite understandable since the need for such a term arose from the introduction of the concept of allergy which called for a designation to distinguish allergic from nonallergic forms

SARCOIDOSIS is a disease for which various etiologic and immunologic concepts have been advanced. Many have thought the condition to be of tuberculous origin. However, there were certain difficulties in the acceptance of the view of a tuberculous causation. The chief of these were that the tubercle bacillus could but rarely be cultured from patients with the disease and that the majority of persons with sarcoidosis manifested markedly reduced reactivity toward tuberculin. J. Jadassohn, in an endeavor to reconcile these findings with a tuberculous origin, hypothesized that persons with sarcoidosis actually had a special form of immunity toward the tubercle bacillus. He theorized that persons with this form of immunity disposed of the tubercle bacillus or its products so rapidly that the organism was rarely found or that the tuberculin did not have an adequate opportunity to produce its usual type of reaction. This theory has recently

EPONYMIC designation, like any abbreviation, is intended to be a short cut to description, but to serve this purpose even occasionally used terms should be widely understood. It is the purpose of this list to bring together for convenient reference most of the eponymic entities of interest to the dermatologist. Some entities which are not easily found in standard texts on dermatology, or which are rarely encountered, are listed with definitions and references. Other entities, either partially eponymic, of great familiarity, or whose synonyms are self explanatory, are simply listed for the sake of completeness. No biographic or historic data are included, as these aspects of the subject have been thoroughly covered by Goodman.1Achard-Thiers Syndrome. Obesity and hypertrichosis of the face of masculine distribution in women without other signs of virilism.2Addison's Disease.Albright's Syndrome. An endocrine disturbance consisting of polyostotic fibrous dysplasia, with cutaneous pigmentation in

HYPERTHYROIDISM, EXOPHTHALMOS, PRETIBIAL MYXEDEMA, AND EARLY CLUBBING. PRESENTED BY SAMUEL M. BLUEFARB, MD, AND LAWRENCE A. ADAMS, MD. A 58-year-old Negro man was essentially well until November 1962, when he developed an acute glomerulonephritis following a streptococcal pharyngitis. During a subsequent hospitalization, a diffusely enlarged thyroid and slight prominence of the eyes were noted. The T3 uptake was 52.6% and the protein-bound iodine (PBI) 9.8μg /100 cc.In September 1965, he was admitted to the Veterans Administration Research Hospital with a two-month history of progressive nervousness, weakness and swelling of his feet. Positive physical findings at that time included a diffuse goiter, 4+ pitting ankle edema, and very prominent exophthalmos. Laboratory data revealed131I uptake, 100% in 24 hours; T3 uptake, 46.7%; PBI, 11.5μg/100 cc; thyroid scan, enlargement of the right lobe; and basal metabolic rate (BMR), +17%. There was also clinical and laboratory evidence of a nephrotic

Phenalamide A2 (1b) has been synthesized for the first time. The synthesis features the homologation of aldehyde 5 to trienal 3 with the new conjunctive reagent 6 and the formation of amide 14 with the functionalized Horner−Emmons reagent 4.

Supplemental Digital Content is available in the text.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.