Endoscopic treatment of Zenker's diverticulum with the stag beetle knife (sb knife) - feasibility and follow-up.

BACKGROUND AND AIMS: Flexible endoscopic treatment of symptomatic Zenker's diverticulum (ZD) is an established treatment option. This study reports the first large cohort of ZD patients treated with the stag beetle knife (sb knife, a new scissor-like device) regarding feasibility, safety, and sustainability of mucomyotomy using this technique. METHODS: From August 2013 to January 2016, n = 52 patients (pts) were treated at Klinikum Augsburg, a tertiary referral center, with the sb knife junior or standard. For stability and safety, the septum is fixed with a soft overtube before intervention. Symptoms were analyzed before and at 1 and 6 months past intervention using an extensive questionnaire of dysphagia, odynophagia, regurgitation, chronic cough, state of health, and complications. RESULTS: The mean size of ZD was 3 cm (1-5 cm). Forty-seven out of 52 (90.4%) patients received one treatment session. The mean procedure time was 32 min (18-60 min). In 10 procedures (17%), a clip was placed at the bottom of the resection line. No major complications (e.g., perforation, mediastinitis) occurred. Five patients (9.6%) required a second treatment after a mean of 7 months (3-13) due to symptomatic recurrence. One patient was lost to further follow-up after one month with no or rare complaints. One patient had a third treatment (1.9%) without complications. During a mean follow-up of 16 months (2-31), the dysphagia score improved from 2 (1-4) prior of treatment to 1 (0-4), odynophagia, regurgitation, and chronic cough were no longer reported in the asymptomatic patients at all. CONCLUSIONS: Flexible endoscopic treatment of ZD with the sb knife and overtube is effective, safe, and has lasting effects with a relatively low recurrence rate.

Clinical Experience with the PillCam Patency Capsule prior to Video Capsule Endoscopy: A Real-World Experience.

Background. In patients with known or suspected risk factors for gastrointestinal stenosis, the PillCam patency capsule (PC) is given before a video capsule endoscopy (VCE) in order to minimize the risk of capsule retention (CR). CR is considered unlikely upon excretion of the PC within 30 hours, excretion in an undamaged state after 30 hours, or radiological projection to the colon. Methods. We performed a retrospective analysis of 38 patients with risk factors for CR, who received a PC from 02/2013 to 04/2015 at Klinikum Augsburg. Results. Sixteen of our 38 patients observed a natural excretion after a mean time of 34 hours past ingestion. However, only 8 patients observed excretion within 30 hours, as recommended by the company. In 20 patients passage of the PC into the colon was shown via RFID-scan or radiological imaging (after 33 and 45 hours, resp.). Only 2 patients showed a pathologic PC result. In consequence, 32 patients received the VCE; no CR was observed. Conclusion. Our data indicates that a VCE could safely be performed even if the PC excretion time is longer than 30 hours and the excreted PC was not screened for damage.

Vestibulo-ocular pathways modulate extraocular muscle myosin expression patterns.

The genetic and epigenetic influences that establish and maintain the unique phenotype of the extraocular muscles (EOMs) are poorly understood. The vestibulo-ocular reflex (VOR) represents an important input into the EOMs, as it stabilizes eye position relative to the environment and provides a platform for function of all other eye movement systems. A role for vestibular cues in shaping EOM maturation was assessed in these studies using the ototoxic nitrile compound 3',3'-iminodipropionitrile (IDPN) to eliminate the receptor hair cells that drive the vestibulo-ocular reflex. Intraperitoneal injections of IDPN were followed by a 2-week survival period, after which myosin heavy chain (MyHC) analysis of the EOMs was performed. When IDPN was administered to juvenile rats, the proportion of eye muscle fibers expressing developmental and fast myosins was increased, while EOM-specific MyHC mRNA levels were downregulated. By contrast, IDPN treatment in adult rats affected only the proportion of fibers expressing developmental MyHC isoforms, leaving the EOM-specific MyHC mRNA unaltered. These data provide evidence that the VOR modulates EOM-specific MyHC expression in development. The lack of significant changes in EOM-specific MyHC expression in adult EOM following IDPN administration suggests that there may be a critical period during development when alterations in vestibular activity have significant and permanent consequences for the eye muscles.

Visual system maldevelopment disrupts extraocular muscle-specific myosin expression.

The genetic and epigenetic influences that are responsible for the establishment and maintenance of the unique phenotype of the extraocular muscles (EOMs) are poorly understood. A role for visual cues in shaping EOM maturation was assessed in rats by using two visual deprivation paradigms, dark rearing and monocular deprivation. Isoforms of the contractile protein myosin heavy chain (MHC) were used as an index of phenotypic change in developing and adult EOMs after these visual insults. In rats that were dark reared during the visual critical period, the proportion of EOM fibers expressing either fast or slow MHCs was decreased significantly. EOM-specific myosin was also sensitive to dark rearing during the critical period, as evidenced by a significant decrease in its mRNA in EOMs from these rats. EOM-specific MHC did not change in either dark-reared rats returned to normally illuminated conditions or in adult rats denied visual experience for a similar time period. These data suggest that there may be a critical period during development when alterations in visual activity have significant consequences for the eye muscle phenotype. In contrast to dark rearing, monocular deprivation had a minimal effect on expression of the typical myosin isoforms and no effect on EOM-specific myosin expression. Collectively, these data confirm the hypothesis that visual input to the oculomotor system during development modulates EOM-specific MHC expression.

The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking utrophin and dystrophin.

The extraocular muscles are one of few skeletal muscles that are structurally and functionally intact in Duchenne muscular dystrophy. Little is known about the mechanisms responsible for differential sparing or targeting of muscle groups in neuromuscular disease. One hypothesis is that constitutive or adaptive properties of the unique extraocular muscle phenotype may underlie their protection in dystrophinopathy. We assessed the status of extraocular muscles in the mdx mouse model of muscular dystrophy. Mice showed mild pathology in accessory extraocular muscles, but no signs of pathology were evident in the principal extraocular muscles at any age. By immunoblotting, the extraocular muscles of mdx mice exhibited increased levels of a dystrophin analog, dystrophin-related protein or utrophin. These data suggest, but do not provide mechanistic evidence, that utrophin mediates eye muscle protection. To examine a potential causal relationship, knockout mouse models were used to determine whether eye muscle sparing could be reversed. Mice lacking expression of utrophin alone, like the dystrophin-deficient mdx mouse, showed no pathological alterations in extraocular muscle. However, mice deficient in both utrophin and dystrophin exhibited severe changes in both the accessory and principal extraocular muscles, with the eye muscles affected more adversely than other skeletal muscles. Selected extraocular muscle fiber types still remained spared, suggesting the operation of an alternative mechanism for muscle sparing in these fiber types. We propose that an endogenous upregulation of utrophin is mechanistic in protecting extraocular muscle in dystrophinopathy. Moreover, data lend support to the hypothesis that interventions designed to increase utrophin levels may ameliorate the pathology in other skeletal muscles in Duchenne muscular dystrophy.

Reliability of the Medtrac MDI Chronolog.

BACKGROUND: The Medtrac MDI Chronolog is an electronic device for monitoring adherence to metered-dose inhalers. It replaces previous models of the Nebulizer Chronolog and uses a different mechanism of recording actuations. OBJECTIVE: This study was carried out to determine whether the new model can accurately record and report the date, time, and number of metered-dose inhaler actuations. METHODS: Four canisters of beclomethasone (Beclovent) were discharged through four Chronologs with fresh batteries at a rate of 1, 2, 4, or 8 times twice daily for 7 days. Four additional canisters were used as controls and discharged simultaneously through the standard actuator. The weight of all canisters and Chronolog battery voltage were measured before and at the end of the 7-day experiment. The data retrieved from the Chronologs were compared with the information recorded manually during each discharge. RESULTS: The loss in canister weight was consistent for the number of puffs discharged from all four Chronolog units and controls. However, the accuracy of the Chronologs in recording the number of actuations varied between 50% and 100%. The largest amount of data loss occurred with the unit used to discharge 8 puffs and was associated with a dead battery at the end of the 7-day trial. For actuations that were retrievable, the Chronologs accurately recorded the date and time. CONCLUSIONS: Unexpected battery voltage drain and other mechanical problems that we encountered may cause data loss and the false appearance of missed doses. Thus the units that we tested were not sufficiently reliable to monitor patient adherence.

The oculomotor periphery: the clinician's focus is no longer a basic science stepchild.

The study of the oculomotor periphery, the extraocular muscles and their orbital attachments, is undergoing a rapid expansion. This is an important progression for both basic and clinical communities as, for too long, the ophthalmologist has worked primarily in the periphery and the basic researcher has been occupied with study of the central components of the oculomotor system. From recent studies, it is clear that the morphology, cell and molecular biology, and genetics of the eye muscles and their corresponding motoneuron pools, and muscle attachments within the orbit are more complex than has heretofore been appreciated.

Spatial and temporal patterns of myosin heavy chain expression in developing rat extraocular muscle.

The present study describes transitions in myosin heavy chain expression in the extraocular muscles of rats between the ages of E17 and adult. The unique phenotype of the extraocular muscle is reflected in its fibre type composition, which is comprised by six distinct profiles, each defined by location (orbital versus global layer) and innervation pattern (single versus multiple terminals). During extraocular muscle myogenesis, developmental myosin heavy chains were expressed in both primary and secondary fibres from embryonic day E17 through the first postnatal week. At this time, the downregulation of developmental myosin heavy chain isoforms began in the global layer in a fibre type-specific manner, reaching completion only after the first postnatal month. By contrast, developmental isoforms were retained in the overwhelming majority of orbital layer fibres into adulthood and expressed differentially along the length of these fibres. Fast myosin heavy chain was detected pre- and postnatally in developing secondary fibres and in all of the singly innervated fibre types and one of the multiply innervated fibre types in the adult. As many as four fast isoforms were detected in maturing extraocular muscle, including the extraocular muscle-specific myosin heavy chain. Slow myosin heavy chain was expressed in primary fibres throughout development and in one of the multiply innervated fibre types in the adult. In contrast, the pure fast-twitch retractor bulbi initially expressed slow myosin heavy chain in fibres destined to switch to the fast myosin heavy chain developmental programme. Based upon spatial and temporal patterns of myosin heavy chain isoform transitions, we suggest that epigenetic influences, rather than purely myogenic stage-specific factors, are critical in determining the unique extraocular muscle phenotype.

The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units.

Mice with a nontargeted transgene insertion at the motor endplate disease (med) locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a. We characterized severe skeletal muscle atrophy beginning by Postnatal Day 10 (P10) and death by P20 in the med(tg) mouse. Denervation was functional, rather than structural, since the Scn8a mutation was not accompanied by retraction of neuromuscular contacts, motoneuron death, or decreased motoneuron soma diameter. Although pathology consistent with denervation was seen in both hindlimb and forelimb musculature, the postnatal maturation of the extraocular muscles was not altered. The onset of paralysis is likely coincident with the time that the Scn8a sodium channel normally assumes a critical role in the initiation and/or propagation of action potentials in spinal motoneurons. By contrast, the lack of consequences for extraocular muscle suggests that the Scn8a voltage-gated sodium channel may be of relatively minor importance for oculomotor motoneurons.

Extraocular muscles: basic and clinical aspects of structure and function.

Although extraocular muscle is perhaps the least understood component of the oculomotor system, these muscles represent the most common site of surgical intervention in the treatment of strabismus and other ocular motility disorders. This review synthesizes information derived from both basic and clinical studies in order to develop a better understanding of how these muscles may respond to surgical or pharmacological interventions and in disease states. In addition, a detailed knowledge of the structural and functional properties of extraocular muscle, that would allow some degree of prediction of the adaptive responses of these muscles, is vital as a basis to guide the development of new treatments for eye movement disorders.

Value of ancillary studies in fine needle aspiration cytology of the lung.

The importance of ancillary studies in surgical pathology of the lung is well documented. Less well established is the utility of these methods in fine needle aspiration (FNA) cytology of the lung. We reviewed our experience over a two-year period (1990-1991) with the use of ancillary studies in addition to routine light microscopy in FNA of the lung. Three hundred forty-five percutaneous aspirations were performed under radiologic guidance during this period. A diagnosis of malignancy was made in 233 (68%) cases. Thirty-two aspirates provided specific benign inflammatory or infectious diagnoses of mass lesions. Approximately one-half the cases required no additional studies (181/345, 52%). Immunocytochemistry was performed in 50 cases (14.5%), electron microscopy (EM) in 28 cases (8%), microbiologic staining in 42 cases (12%), mucin staining in 72 cases (21%) and cell blocks in 77 cases (22%). Immunocytochemistry and EM were generally used to classify poorly differentiated neoplasms, confirm the diagnosis of bronchioloalveolar cell carcinoma, determine neuroendocrine differentiation and establish primary sites for suspected metastatic malignancies. Immunocytochemistry provided significant additional information in 20 (40%) of the cases in which it was attempted and confirmed the light microscopic impression in an additional 18 cases (36%). Similarly, EM provided significant additional information in 10 cases (67%) and confirmed the light microscopic impression in an additional 4 cases (27%). Microbiologic staining was performed when an infectious etiology was suspected clinically or an inflammatory (especially granulomatous) background was present in the smears. In 11 cases (27%) the staining was positive for organisms. Mucin staining was performed in an attempt to better classify poorly differentiated non-small cell malignancies and was contributory in 68% of the cases. In conclusion, ancillary studies are helpful in confirming the cytologic impression and making a more specific diagnosis in FNA of the lung.

Types and time course of the alterations induced in monkey blink movements by botulinum toxin.

The alterations induced in eyelid movement metrics subsequent to unilateral injections of botulinum toxin type A into the orbicularis oculi muscle were studied in chronic alert monkeys using the search coil technique. Botulinum toxin caused rapid paralysis of blinks in the treated eyelid. The amplitude and peak velocity of blinks generated by this eyelid remained at or below 20% of that of the fellow, untreated eyelid for 10-20 days. Blink amplitude gain increased linearly thereafter, attaining control values by 40-60 days after injection. Recovery of blink peak velocity was slower. The adaptive alterations in blink duration that were observed during the acute phase of toxin paralysis suggest that the mechanisms responsible for blink reflex plasticity may produce bilateral adjustments in eyelid function. Taken together, these data establish a quantitative data base that can be exploited in order to: (1) better understand the neural adaptive mechanisms that operate during eyelid movements and (2) allow quantitative comparisons between current treatment protocols that employ botulinum toxin and protocols that may lead to improvements in the treatment of chronic eyelid spasm (blepharospasm).

The energy cost of running increases with the distance covered.

The net energy cost of running per unit of body mass and distance (Cr, ml O2.kg-1.km-1) was determined on ten amateur runners before and immediately after running 15, 32 or 42 km on an indoor track at a constant speed. The Cr was determined on a treadmill at the same speed and each run was performed twice. The average value of Cr, as determined before the runs, amounted to 174.9 ml O2.kg-1.km-1, SD 13.7. After 15 km, Cr was not significantly different, whereas it had increased significantly after 32 or 42 km, the increase ranging from 0.20 to 0.31 ml O2.kg-1.km-1 per km of distance (D). However, Cr before the runs decreased, albeit at a progressively smaller rate, with the number of trials (N), indicating an habituation effect (H) to treadmill running. The effects of D alone were determined assuming that Cr increased linearly with D, whereas H decreased exponentially with increasing N, i.e. Cr = Cr0 + a D + He-bN. The Cr0, the "true" energy cost of running in nonfatigued subjects accustomed to treadmill running, was assumed to be equal to the average value of Cr before the run for N equal to or greater than 7 (171.1 ml O2.kg-1.km-1, SD 12.7; n = 30).(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial contrast echocardiography: cardiovascular effects of the contrast medium SHU 454 in dogs.

SHU 454 (Schering AG, Berlin, Federal Republic of Germany) is a new contrast agent that releases microbubbles with a median diameter of 3 microns into the circulation. During echocardiography, it permits visualization of myocardial blood flow (MBF) when given by intracoronary or aortic root injections. Its hemodynamic effects were investigated in anesthetized dogs with a view to application in humans. Cardiac effects were studied after intracoronary injections of 1 mL of SHU 454 (100 mg/mL). Twenty seconds after injection, MBF increased 35% and coronary vascular resistance decreased accordingly. The increase in MBF was not seen when the coronary bed was maximally dilated with intravenous dipyridamole. Peripheral effects were evaluated after 5 mL of SHU 454 (200 mg/mL) was injected into the aortic root, which gave the same myocardial echo contrast. Aortic pressure decreased 5%, and heart rate and dP/dt increased. To evaluate the effects of hypertonicity, SHU 454 was compared with five radiocontrast media and glucose. Its effects on MBF were similar to those of radiologic contrast media on an equal volume basis. Only 1 mL of intracoronary SHU 454, however, was required for myocardial contrast enhancement. The results suggest that visualization of the myocardium using SHU 454 or similar compounds for contrast echocardiography is a viable prospect.

A switching regression analysis of urban population densities.

PIP: An application of the switching regression technique in the field of urban economics is presented. The technique is applied to the study of urban population density functions, which recent research has suggested are inherently discontinuous. The method of switching regression developed by Quandt is used to estimate density functions for selected U.S. urban areas. The results show that population density contours are highly irregular, and also that the model selection approach can be used to select the number of regimes in a switching model when this number is unknown^ieng

A note on sufficient conditions for negative exponential population densities.

PIP: The author presents some comments on the Mills-Muth model of urban spatial structure, which predicts that population density declines as distance to the urban center increases.^ieng