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The use of nonpulsatile flow during extracorporeal circulation remains popular despite theoretical advantages of pulsatile cardiopulmonary bypass (CPB). Pulsatile CPB is considered to be more physiological than nonpulsatile flow as the pulsatile energy ensures the patency of the vascular bed and mechanical motion of tissue fluid around the cell membrane, improves microcirculation and enhances diffusion. The purpose of this study was to compare the effect of pulsatile and nonpulsatile flow on the coagulation profile, liver and kidney function and also on the haemodynamics in patients undergoing coronary artery bypass grafting on CPB. One hundred patients between 35 and 65 years of age with normal left ventricular function were randomly divided into two equal groups: Pulsatile (P) and nonpulsatile (NP). Haematological parameters, clotting profile, renal parameters, hepatic function tests and haemodynamic variables were measured preoperatively and postoperatively at specific intervals. Surgical, anaesthetic and CPB regimen was standard in all cases. There was a decrease in platelet count during and after CPB in both groups. Coagulation profile and renal function parameters remained similar in both groups except that creatinine clearance was better in group P on the first postoperative day. Urine output was also better in group P. There was no change in liver function tests in both groups. The haemodynamic variables were comparable in both groups. The systemic vascular resistance was higher in group NP postoperatively and oxygen consumption was higher in group P post CPB. In conclusion we did not find any significant difference between pulsatile and nonpulsatile flow during CPB except the creatinine clearance and urine output were better in pulsatile group.

For several forms of acquired nystagmus, animal models exist, mathematical hypotheses have been proposed, and treatments are available. What insights could acquired nystagmus provide for congenital forms of nystagmus? Acquired periodic alternating nystagmus (PAN) is caused by instability of the velocity storage mechanism for vestibular eye movements; an adaptive mechanism produces the oscillations that have a period of about 4 minutes. Surprisingly, the ability of individuals with congenital forms of nystagmus to adapt their eye movements to new visual demands has received little study. Acquired pendular nystagmus (APN) may arise from instability in the neural integrator for eye movements; identification of the neurotransmitters contributing to normal gaze holding made it possible to identify candidate drugs for treatment of APN. Similar knowledge of the biology underlying of congenital forms of nystagmus might similarly suggest effective drugs. Downbeat nystagmus (DBN) is caused by cerebellar disease, which includes structural lesions affecting the flocculus and paraflocculus, and calcium channelopathies, such as episodic ataxia type 2 (EA2), for which a mouse model and effective treatment is available. Since some congenital forms of nystagmus are genetic in origin, then the possibility arises that they may be caused by a channelopathy, a hypothesis that suggests novel drugs for evaluation in randomized controlled trials.

Current models in skeletal muscle biology do not fully account for the breadth, causes, and consequences of phenotypic variation among skeletal muscle groups. The muscle allotype concept arose to explain frank differences between limb, masticatory, and extraocular (EOM) muscles, but there is little understanding of the developmental regulation of the skeletal muscle phenotypic range. Here, we used morphological and DNA microarray analyses to generate a comprehensive temporal profile for rat EOM development. Based upon coordinate regulation of morphologic/gene expression traits with key events in visual, vestibular, and oculomotor system development, we propose a model that the EOM phenotype is a consequence of extrinsic factors that are unique to its local environment and sensory-motor control system, acting upon a novel myoblast lineage. We identified a broad spectrum of differences between the postnatal transcriptional patterns of EOM and limb muscle allotypes, including numerous transcripts not traditionally associated with muscle fiber/group differences. Several transcription factors were differentially regulated and may be responsible for signaling muscle allotype specificity. Significant differences in cellular energetic mechanisms defined the EOM and limb allotypes. The allotypes were divergent in many other functional transcript classes that remain to be further explored. Taken together, we suggest that the EOM allotype is the consequence of tissue-specific mechanisms that direct expression of a limited number of EOM-specific transcripts and broader, incremental differences in transcripts that are conserved by the two allotypes. This represents an important first step in dissecting allotype-specific regulatory mechanisms that may, in turn, explain differential muscle group sensitivity to a variety of metabolic and neuromuscular diseases.

Mutations in dystrophin are the proximate cause of Duchenne muscular dystrophy (DMD), but pathogenic mechanisms linking the absence of dystrophin from the sarcolemma to myofiber necrosis are not fully known. The muscular dystrophies also have properties not accounted for by current disease models, including the temporal delay to disease onset, broad species differences in severity, and diversity of skeletal muscle responses. To address the mechanisms underlying the differential targeting of muscular dystrophy, we characterized temporal expression profiles of the diaphragm in dystrophin-deficient (mdx) mice between postnatal days 7 and 112 using oligonucleotide microarrays and contrasted these data with published hindlimb muscle data. Although the diaphragm and hindlimb muscle groups differ in severity of response to dystrophin deficiency, and exhibited substantial divergence in some transcript categories including inflammation and muscle-specific genes, our data show that the general mechanisms operative in muscular dystrophy are highly conserved. The two muscle groups principally differed in expression levels of differentially regulated genes, as opposed to the non-conserved induced/repressed transcripts defining fundamentally distinct mechanisms. We also identified a postnatal divergence of the two wild-type muscle group expression profiles that temporally correlated with the onset and progression of the dystrophic process. These findings support the hypothesis that conserved disease mechanisms interacting with baseline differences in muscle group-specific transcriptomes underlie their differential responses to DMD. We further suggest that muscle group-specific transcriptional profiles contribute toward the muscle targeting and sparing patterns observed for a variety of metabolic and neuromuscular diseases.

Purpose To address the consequences of visual deprivation paradigms in rat (dark rearing) and monkey (monocular deprivation) on extraocular muscle (EOM) development using genome-wide expression profiling. Methods Serial analysis of gene expression (SAGE) was used to determine alterations in the EOM transcriptome induced by dark rearing of rats from birth to postnatal day 45. Data were compared with previously published normal EOM SAGE library. DNA microarray similarly assessed changes in gene expression patterns of EOMs of monkeys reared from birth to 4 months of age with monocular deprivation. Results Dark rearing produced changes in expression of 280 transcripts in rat EOM. Of these, 71 were known genes representing functional categories that included energy metabolism/mitochondrial-related (21%), protein synthesis and modification (14%), lipid metabolism (13%), and muscle-related (6%) transcripts. Together, the predominant pattern reflected an energetic shift toward fatty acid beta-oxidation and integrated alterations in both myofibers and supportive tissues. The response of monkey rectus muscles to monocular deprivation was considerably less severe. Conclusions The visual deprivation paradigms used in this study mimic alterations that are associated with the common disorders of strabismus, congenital cataract, and amblyopia. These data show that postnatal EOM maturation is broadly susceptible to changes in activity patterns that are a consequence of visuomotor maldevelopment. The data extend the concept of an EOM-critical period and establish that activity patterns in developing eye movement systems play vital determinant roles in the novel EOM phenotype.

Prior studies and the efficacy of immunotherapies provide evidence that inflammation is mechanistic in pathogenesis of Duchenne muscular dystrophy. To identify putative pro-inflammatory mechanisms, we evaluated chemokine gene/protein expression patterns in skeletal muscle of mdx mice. By DNA microarray, reverse transcription-polymerase chain reaction, quantitative polymerase chain reaction, and immunoblotting, convergent evidence established the induction of six distinct CC class chemokine ligands in adult MDX: CCL2/MCP-1, CCL5/RANTES, CCL6/mu C10, CCL7/MCP-3, CCL8/MCP-2, and CCL9/MIP-1gamma. CCL receptors, CCR2, CCR1, and CCR5, also showed increased expression in mdx muscle. CCL2 and CCL6 were localized to both monocular cells and muscle fibers, suggesting that dystrophic muscle may contribute toward chemotaxis. Temporal patterns of CCL2 and CCL6 showed early induction and maintained expression in mdx limb muscle. These data raise the possibility that chemokine signaling pathways coordinate a spatially and temporally discrete immune response that may contribute toward muscular dystrophy. The chemokine pro-inflammatory pathways described here in mdx may represent new targets for treatment of Duchenne muscular dystrophy.

One hundred consecutive adult patients under-going various elective open heart surgical procedures were included in this prospective study. An indwelling radial arterial cannula was used to measure mean arterial pressure (MAP). Systemic vascular resistance (SVR) during bypass was calculated using the formula SVR=MAP×80/pump flow dynes-sec-cm−5. Patients in whom vasodilators were used during cardiopulmonary bypass were excluded. Measurements were made just before the release of aortic cross clamp when the pump flows were normal; and 1,3,5 and 10 minutes following the cross clamp release. There were 60 males and 40 females with a mean age of 29.4±13.9 years and mean weight of 46±13 Kg. The MAP fell from 65±14 to 47±15 mm Hg (p

Skeletal muscle fibers are defined by patterned covariation of key traits that determine contractile and metabolic characteristics. Although the functional properties of most skeletal muscles result from their proportional content of a few conserved muscle fiber types, some, typically craniofacial, muscles exhibit fiber types that appear to lie outside the common phenotypic range. We analyzed gene expression profiles of three putative muscle classes, limb, masticatory, and extraocular muscle (EOM), in adult mice by high-density oligonucleotide arrays. Pairwise comparisons using conservative acceptance criteria identified expression differences in 287 genes between EOM and limb and/or masticatory muscles. Use of significance analysis of microarrays methodology identified up to 400 genes as having an EOM-specific expression pattern. Genes differentially expressed in EOM reflect key aspects of muscle biology, including transcriptional regulation, sarcomeric organization, excitation-contraction coupling, intermediary metabolism, and immune response. These patterned differences in gene expression define EOM as a distinct muscle class and may explain the unique response of these muscles in neuromuscular diseases.

THE ONSET OF congestive heart failure in patients with aortic stenosis (AS) indicates a poor prognosis. In some of these patients, left ventricular function may be depressed so that the transvalvular pressure gradient may be low. The mortality after aortic valve replacement (AVR) in such patients has been reported to be 33%1 to 75%.2 Adverse hemodynamic changes (severe hypotension or hypertension) during induction of general anesthesia and until cardiopulmonary bypass (CPB) is established may contribute to this increased mortality. Hemodynamic changes are generally poorly tolerated by these patients, and the myocardium is susceptible to ischemic injury. It is difficult to resuscitate these patients in the event of cardiac arrest. Intraoperative hypotension should be aggressively treated in patients with AS with -agonists with the objective of restoring the perfusion pressure.3 Such an approach may jeopardize the already ischemic myocardium, however. Although hemodynamic effects of anesthetic agents in these sick patients are not well reported, most anesthetic agents (intravenous or inhalation) are likely to cause some degree of hypotension. There is a tendency among anesthesiologists to restrict the doses of induction agents. Such a practice may expose the patients to the risk of excessive sympathetic response during intubation, which can also be deleterious. The risk of exposing these high-risk patients to adverse hemodynamic changes during induction of general anesthesia can be avoided by instituting femoral-femoral CPB under local anesthesia before induction of general anesthesia. The authors report a patient suffering from critical AS (valve area, 0.4 cm2) who presented with severe congestive heart failure (New York Heart Association [NYHA] functional class IV) and underwent urgent AVR. Femoral-femoral CPB was electively instituted in this patient before induction of general anesthesia. The hemodynamic details and management of this patient are described.

Mitral valve replacement (MVR) continues to be associated with a significant incidence of operative morbidity and mortality, la This can most often be attributed to postoperative left ventricular (LV) dysfunction consequent upon breach in annulopapillary continuity 3 as a result of excision of the valve. Lillehei and associates ~ proposed the conservation of posterior leaflet and its attachments during MVR as a solution to this problem as early as in 1964. The concept has of late re-emerged as an important method of preserving LV function following MVR. 3~7

Cysticercosis of the optic nerve has been reported only twice in the literature. A case of optic nerve cysticercosis in a 50-year-old woman with atypical optic neuritis is reported. Computerized tomography showed a thickened left optic nerve with a ring-enhancing lesion containing an eccentric nodule. An enzyme-linked immunosorbent assay test for cysticercosis further established the diagnosis. The patient was treated with oral prednisolone and albendazole, with no improvement in vision.

We describe the clinical course, with special attention to the disturbance of eye movements, of a 29-year-old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti-GD1b antibodies.

Coeliac artery aneurysms are rare. A case of coeliac artery aneurysm treated successfully by endoaneurysmorrhaphy is presented. Although excision with arterial reconstruction is usually recommended, endoaneurysmorrhaphy can also be considered in selected cases. Copyright © 1996 The International Society for Cardiovascular Surgery.

We present a child posted for magnetic resonance imaging of brain under general anesthesia with the rare combination of mucopolysachharidosis type VI and congenital adrenal hyperplasia. The presence of both these disorders has important anesthetic implications. The pathophysiology of this rare combination of disease is reviewed with emphasis on the anesthesia management.

Department of Chemistry, University of Rajasthan, Jaipur-302 004 Manuscript received 14 June 1990, accepted 26 July 1990 The role of fluorine incorporation in effecting the course of the reactions of fluorinated isatin derivatives (1a-c) with 2-aminothiophenol (2) has been investigated in dry xylene in presence of anhydrous zinc chloride and in the process some new fluorine containing 2-(2 oxo-2H-1 4-benzothiazine-3-yl)aniline (3), indolo[2 3-H][14]benzothiazine (4), N-[2 (3 4 dihydro-2-oxo-2H-1 4 benzothiazin-3-yl)phenyl]acetamide (5) and spiro(benzothiazole-2 (3H), 3'-indol]-2'(1'H)-ones (6) have been synthesised. Characterisation of all the compounds has been done on the basis of elemental analyses and ir. 1H, 19F, 13C nmr and mass spectral data. &nbsp

PURPOSE. Compartmentalization of the extraocular muscles into well-defined orbital and global layers is highly conserved. Recently, the active pulley hypothesis correlated the anatomic properties of orbital‐ global muscle layers with layer-specific division of labor. Microarray technology was used to identify muscle-layer‐specific transcriptional profiles and, thereby, extend understanding of the structure-function characteristics of extraocular muscle layers. METHODS. Laser capture microdissection was used to obtain muscle layer samples from monkey medial rectus muscles. RNA was linearly amplified and hybridized to human U133 series microarrays (Affymetrix, Santa Clara, CA), which have sufficient sequence homology for use in subhuman primates. Data was analyzed using Affymetrix and Robust Multichip Average (RMA) algorithms. Select transcripts were verified by quantitative PCR and in situ hybridization. RESULTS. A broad spectrum of transcriptional differences (181 transcripts) was identified between the two extraocular muscle layers. Patterned differences in the sarcomeric contractile machinery and cytoskeleton were suggestive of key layer differences in contraction speed. Differentially expressed transcript identities, however, extended well beyond those traditionally associated with muscle-fiber‐ group differences. CONCLUSIONS. Muscle layer transcriptional profiles correlated with the different loads and usage patterns of extraocular muscle layers, as proposed in the active pulley hypothesis. The magnitude and breadth of orbital‐ global layer expression differences strongly suggests that oculomotor control systems may drive two distinct motor output pathways, each comprising separate motoneurons and muscle fibers, with one output path adapted to determining pulley position and the other to movement of the eye. (Invest Ophthalmol Vis Sci. 2004;45: 3055‐3066) DOI:10.1167/iovs.03-1385 E xtraocular muscles (EOMs) are specialized to perform a diverse repertoire of eye movements, including high-speed saccades, slow pursuit and vergence movements, and maintenance of steady fixation. These functional intricacies are reflected in the complex fiber types seen in EOMs, which differ remarkably from somatic muscle fibers. In addition, the EOMs are normally divided into two distinct compartments or layers. 1 The peripheral orbital layer lies along the EOM surface, facing the orbital wall. This layer encloses a second portion, the global layer, lying closer to the globe. In some species, the two layers are separated by an internal perimysium. The orbital layer contains small-diameter fibers with numerous mitochondria and abundant blood vessels. The global layer contains relatively large-diameter fibers with variable mitochondrial content and fewer vessels. The distinction between the orbital and global layers in EOM is discernible by histochemistry, particularly in regard to aerobic versus anaerobic metabolism. Fibers in the orbital layer stain intensely for oxidative enzymes, whereas both the staining intensity and proportion of oxidative fibers gradually decrease through the global layer. By contrast, the activity associated with glycolytic enzymes is more intense in the global layer and is weak in the orbital layer. 1 Some known molecular differences, including myosin heavy chain isoform composition, further characterize the two layers and six fiber types. 2‐7

PURPOSE The phenotypically novel extraocular muscles (EOMs) exhibit fundamental differences in innervation and neuromuscular junction (NMJ) morphology from other skeletal muscles. In the current study, the morphology and molecular organization of NMJs of EOM singly innervated (SIF) and multiply innervated (MIF) fiber types were evaluated and the distribution of molecules involved in formation and maintenance of NMJs were specifically characterized. METHODS Adult mouse EOM NMJ organization was examined by immunofluorescence and confocal microscopy. Differential cellular localization of components of two established synaptic signaling pathways, (1) neuregulin and erbB receptors 2, 3, and 4 and (2) agrin, MuSK, and rapsyn and select NMJ-associated structural proteins were studied for EOM SIF and MIF populations. Endplate topography and structure were also studied, using both confocal microscopy and transmission electron microscopy, with NMJ morphologic organization correlated with specific EOM fiber types. RESULTS Confocal fluorescence microscopy demonstrated that, for NMJs of both EOM SIFs and MIFs, components of neuregulin and agrin pathways and the major components of the junctional dystrophin-glycoprotein complex (DGC) colocalized with acetylcholine receptor (AChR) aggregates. However, EOM exhibited novel fiber-type-specific extrasynaptic localization of two key DGC signaling-related molecules: alpha-dystrobrevin 1 (global MIFs) and syntrophin beta1 (global MIFs and orbital MIFs and SIFs). CONCLUSIONS The data establish that the molecular organization of EOM SIF and MIF NMJs includes the same signaling and structural molecules previously characterized for other skeletal muscles. By contrast, divergence in other aspects of the synaptic and nonsynaptic sarcolemmal organization of EOM fiber types may underlie the unique responses of these muscles in a variety of neuromuscular disorders.

One-hundred and sixteen patients were surgically treated for constrictive pericarditis over a period of 18 years. Twenty-eight patients were less than 15 years old. All patients had exertional dyspnoea and elevated jugular venous pressure. Eighty-eight patients had NYHA class III or IV functional disability. Only 2 cases had atrial fibrillation. Seventeen patients had roentgenographic evidence of pericardial calcification. Fluoroscopy showed diminished cardiac movements in 110 cases. Cardiac catheterisation in 77 patients demonstrated classical haemodynamic pattern of constrictive pericarditis. All our patients underwent subtotal pericardiectomy through a left anterolateral approach. Seventy-one patients had histological evidence of tuberculous pericarditis. Nearly 88 per cent of the followed up cases reported good to excellent relief. The hospital mortality was 6.9 per cent. Our observations and inferences are compared with those of other published reports.

A case of chylothorax following ligation of persistent ductus arteriosus, successfully treated by drainage and chemical pleurodesis is reported.