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A map of the heart: gap junctions, connexin diversity and retroviral studies of conduction myocyte lineage.

1. The heartbeat is co-ordinated by organized propagation of electrical excitation through cardiac muscle. Intercellular conduction and propagation of the cardiac action potential is dependent on electrical connections between myocytes, termed gap junctions. 2. In the last few years, our conception of the structure and function of cardiac gap junctions has been revised substantially. It seems that these structures show unexpected levels of specialization within the myocardium and they can no longer be viewed simply as passive conduits for the regulated movement of electrical current between heart muscle cells. 3. In this article, some of the contributions to this field by the author and his collaborators are summarized. Studies using confocal microscopy and digital imaging techniques to characterize the three-dimensional organization of electrical contacts between myocytes in the mature and developing heart are described, data on the unique expression and spatial distribution patterns of gap-junctional subunit proteins (connexins) are given, and finally the author's current work on the differentiation of cardiac conduction tissues, and how this work arose from studies of gap junctions in the heart, is introduced.

Animals↗

Effect of a flow-streamlining implant at the distal anastomosis of a coronary artery bypass graft.

Intimal thickening in the coronary artery bypass graft (CABG) distal anastomosis has been implicated as the major cause of restenosis and long-term graft failure. Several studies point to the interplay between nonuniform hemodynamics including disturbed flows and recirculation zones, wall shear stress, and long particle residence time as possible etiologies. The hemodynamic features of two anatomic models of saphenous-vein CABGs were studied and compared. One simulated an anastomosis with both diameter and compliance mismatch and a curvature at the connection, analogous to the geometry observed in a conventional cardiothoracic procedure. The other, simulated an anastomosis with a flow stabilizing anastomotic implant connector which improves current cardiothoracic procedures by eliminating the distal vein bulging and curvature. Physiologic flow conditions were imposed on both models and qualitative analysis of the flow was performed with dye injection and a digital camera. Quantitative analysis was performed with laser Doppler velocimetry. Results showed that the presence of the bulge at the veno-arterial junction, contributed to the formation of accentuated secondary structures (helices), which progress into the flow divider and significantly affect radial velocity components at the host vessel up to four diameters downstream of the junction. The model with the implant, achieved more hemodynamically efficient conditions on the host vessel with higher mean and maximum axial velocities and lower radial velocities than the conventional model. The presence of the sinus may also affect the magnitude and shape of the shear stress at locations where intimal thickening occurs. Thus, the presence of the implant creates a more streamlined environment with more primary and less secondary flow components which may then inhibit the development of intimal thickening, restenosis, and ultimate failure of the saphenous vein graft.

Arteriovenous Anastomosis↗

Unusual MRI appearance of diffuse subcortical heterotopia or "double cortex" in two children.

Two children with mild epilepsy and learning and behaviour problems had magnetic resonance imaging (MRI) scans showing an almost identical generalised disorders of neuronal migration. Their computer tomography (CT) scans showed abnormal hypodense white matter. The MRI showed a four layered appearance of the cerebral parenchyma extending from the frontal to the occipital region. There was a normal appearance to the white matter in the periventricular region which had an abnormally smooth junction with a thick diffuse layer of heterotopic grey matter. This was surrounded by a thin layer of white matter which had normal digitations with the overlying cortex. The appearance of the overlying cortex was normal. These and other recently described cases broaden the concept of generalised disorders of neuronal migration and illustrate that it is possible to have a generalised cerebral malformation with few clinical consequences.

Brain↗

[Is fibrositis an immuno-rheumatologic disease?].

An attempt was made to test the hypothesis that immunological dysfunction occurs in primary polyenthesopathy (PP) by studying skin immunofluorescence, capillary microscopy, photoplethysmography and the lymphocyte populations in PP patients defined according to the usual criteria of Yunus. Skin immunofluorescence in 15 PP patients (14 women, 1 man, average age 50.9 years) failed to reveal any deposit of IgG, A, M, Clq, or C3c either at the dermoepidermal junction or in the vessels. 26 patients (24 women, 2 men, average age 50.5 years) were studied using capillary microscopy and 12 using digital photoplethysmography. The microvascularization abnormalities observed were mild and non specific. A study of the lymphocyte populations using Coulter flux cytometry in 35 PP patients (32 women, 3 men, average age 46 years) did not show any modification in the number of CD4 and CD8 lymphocytes by comparison with the controls. These results do not agree with the data given in the literature and this is probably due to the heterogeneity of the patients studied, with some studies showing a low concentration of antinuclear factors and an abnormal frequency of dry symptoms which, in the opinion of the authors, is considered as an exclusion criterion in the diagnosis of PP. In the author's view, polyenthesopathy is not an immune disease.

Adult↗

Segmental analysis of the sagittal plane alignment of the normal thoracic and lumbar spines and thoracolumbar junction.

Recent advances in spinal instrumentation have brought about a new emphasis on the three-dimensional spinal deformity of scoliosis and especially on the restoration of normal sagittal plane contours. Normal alignment in the coronal and transverse planes is easily defined; however, normal sagittal plane alignment is not so simple. This retrospective study was undertaken to increase the understanding of the normal alignment of the spine in the sagittal plane, with a special emphasis on the thoracolumbar junction. Measurements were made from the lateral radiographs of 102 subjects with clinically and radiographically normal spines. Cobb measurements of the thoracic kyphosis (T3-T12), the thoracolumbar junction (T10-T12 and T12-L2), and the lumbar lordosis (L1-L5) were determined. The spices of the thoracic kyphosis and lumbar lordosis also were determined. Using a computerized digitalizing table, the segmental angulation was determined at each level from T1-2 to L5-S1. In conclusion, there is a wide range of normal sagittal alignment of the thoracic and lumbar spines. When using composite measurements of the combined frontal and sagittal plane deformity of scoliosis, this wide range of sagittal variance should be taken into consideration. Using norms established here for segmental alignment, areas of hypokyphosis and hypolordosis commonly seen in scoliosis can be more objectively evaluated. The thoracolumbar junction is for all practical purposes straight; lumbar lordosis usually starts at L1-2 and gradually increases at each level caudally to the sacrum.

Adolescent↗

Combined "periprostatic and periapical" local anesthesia is not superior to "periprostatic" anesthesia alone in reducing pain during Tru-Cut prostate biopsy.

OBJECTIVES: To evaluate, in a prospective study, the benefit of adding local periapical prostatic anesthesia to routine periprostatic infiltration to the prostate-seminal vesicle junction in a randomized fashion. Transrectal ultrasound-guided biopsy is the reference standard in the diagnosis of prostate cancer. Although well tolerated by most patients, it can be associated with discomfort. METHODS: A total of 120 consecutive evaluable patients with an elevated total prostate-specific antigen (tPSA) level, increased tPSA velocity, and/or abnormal digital rectal examination findings were enrolled. The patients were randomized into two groups. Group 1 received periprostatic infiltration of 6 mL 1% lidocaine. Group 2 received periprostatic and apical infiltration: 4 mL 1% lidocaine at the prostate-seminal vesicle junction and 2-mL infiltration at the prostatic apex 15 minutes before transrectal ultrasound-guided biopsy. Pain was assessed using a 10-point modified visual analog scale. RESULTS: The mean patient age was 63.7 +/- 1.2 years and 64.2 +/- 1.1 years, the mean tPSA level was 12.1 +/- 1.5 ng/mL and 13.6 +/- 2.7 ng/mL, the mean biopsy duration was 6.2 +/- 2.5 minutes and 6.1 +/- 2.2 minutes, and the mean visual analog scale pain score was 1.26 +/- 0.1 and 1.23 +/- 0.1 for groups 1 and 2, respectively. No statistically significant difference was observed with respect to age, tPSA level, mean biopsy duration, or pain score between the two groups. CONCLUSIONS: Periprostatic lidocaine infiltration provides local anesthesia that results in improved visual analog scale pain scores. Additional apical infiltration did not improve patient discomfort further. However, comparative evidence has indicated that increasing the time elapsed between the anesthetic infiltration and the biopsy procedure may further improve pain control.

Aged↗

Usefulness of narrow-band imaging endoscopy for diagnosis of Barrett's esophagus.

BACKGROUND: A newly developed endoscope lighting system called a narrow-band imaging system emphasizes certain histological features such as capillary and crypt pattern. The usefulness of NBI for the diagnosis of Barrett's esophagus (BE) was evaluated. METHODS: Eleven patients with previously diagnosed BE were enrolled in this study. Magnifying endoscopy was performed by an experienced endoscopist, using both a conventional system and an NBI system. All images were recorded by video and by a digital still image filing system. Differences in images were evaluated by another experienced endoscopist. The quality of images for the visualization of the esophagogastric junction, capillary vessels, and columnar-lined esophagus (CLE) was judged as: optimal (score of 4), diagnostic (3), suboptimal (2), or nondiagnostic (1). RESULTS: In contrast to the low rate of visualization of the esophagogastric junction by conventional endoscopy, visualization of this area endoscopy was better by NBI. Net-like blood vessels were more clearly seen on images obtained by NBI endoscopy. Visualization of the CLE was better by NBI endoscopy than by conventional endoscopy. In contrast to conventional endoscopy, NBI endoscopy captured the optimal view of Barrett's epithelium. The relationship between the endoscopic and histopathologic diagnoses was more accurate by NBI endoscopy than by conventional endoscopy. CONCLUSIONS: Magnifying endoscopy by NBI is more useful than conventional magnifying endoscopy for the diagnosis of BE.

Barrett Esophagus↗

Blood supply of the flexor pollicis longus tendon.

The blood supply of the flexor pollicis longus tendon was investigated by arterial injections of india ink--latex-barium-solution in 15 fresh, adult cadaver upper extremities. In the digital area vascularity was by way of two vincula (V1 and V2). V1, located just proximal to the metacarpophalangeal joint and the A1 pulley, originated either from both digital arteries or from the princeps pollicis artery alone. V2, located at the interphalangeal joint level under the A2 pulley, originated from both digital arteries. In the predigital area branches of the median nerve artery supplied the area from the base of the thumb to the musculotendinous junction; in addition, the microvascular network of the mesotendon contributed to this area. Intratendinous vascularization was more abundant in the predigital area.

Adult↗

A custom designed chip to control an implantable stimulator and telemetry system for control of paralyzed muscles.

A custom designed chip has been developed for the control of paralyzed muscles. The system is capable of fulfilling the stimulus and telemetry needs of advanced functional neuromuscular stimulation (FNS) applications requiring multiple channels of stimulation and multiple channels for sensor or biopotential sensing. An inductive radiofrequency link provides power to the implant device as well as 2 way transcutaneous communication. An application specific integrated circuit (ASIC) decodes the commands and provides functional control within the implant, and modular circuitry provides specific implant functions. The ASIC chip provides up to 32 independent channels of stimulation with independent control of stimulus pulse duration, pulse amplitude, interphase delay, recharge phase duration, and pulse interval. It can also control up to 8 independent back telemetry analog channels with independent control of sampling rate and pulse powering parameters (amplitude and duration). The mixed analog digital chip has been fabricated in 1.2 microm n-well CMOS technology.

Analog-Digital Conversion↗

Coordinated flagellar and ciliary beating in the protozoon Tritrichomonas foetus.

Tritrichomonas foetus is a flagellated protozoon found in urogenital tract of cattle. Its free movement in liquid medium is powered by the coordinated movement of three flagella projecting towards the anterior region of the cell, and one recurrent flagellum that forms a junction with the cell body and ends as a free projection in the posterior region of the cell. We have used video microscopy and digital image processing to analyze the relationships between the movements of these flagella. The anterior flagella beat in a ciliary type pattern displaying effective and recovery strokes, while the recurrent flagellum beats in a typical flagellar wave form. One of the three anterior flagella has a distinctive pattern of beating. It beats straight in its forward direction as opposed to the ample beats performed by the others. Frequency measurements obtained from cells swimming in a viscous medium shows that the beating frequency of the recurrent flagellum is approximate twice the frequency for the three anterior flagella. We also observed that the costa and the axostyle do not show any active motion. On the contrary, they form a cytoskeletal base for the anchoring and orientation of the flagella.

Animals↗

Connexin 40, a target of transcription factor Tbx5, patterns wrist, digits, and sternum.

Haploinsufficiency of T-box transcription factor 5 (TBX5) causes human Holt-Oram syndrome (HOS), a developmental disorder characterized by skeletal and heart malformations. Mice carrying a Tbx5 null allele (Tbx5(+/Delta)) have malformations in digits, wrists, and sternum joints, regions where Tbx5 is expressed. We demonstrate that mice deficient in connexin 40 (Cx40), a Tbx5-regulated gap junction component, shared axial and appendicular skeletal malformations with Tbx5(+/Delta) mice. Although no role in skeleton patterning has been described for gap junctions, we demonstrate here that Cx40 is involved in formation of specific joints, as well as bone shape. Even a 50% reduction in either Tbx5 or Cx40 produces bone abnormalities, demonstrating their crucial control over skeletal development. Further, we demonstrate that Tbx5 exerts in part its key regulatory role in bone growth and maturation by controlling via Cx40 the expression of Sox9 (a transcription factor essential for chondrogenesis and skeleton growth). Our study strongly suggests that Cx40 deficiency accounts for many skeletal malformations in HOS and that Tbx5 regulation of Cx40 plays a critical role in the exquisite developmental patterning of the forelimbs and sternum.

Animals↗

Microleakage in the proximal walls of direct and indirect posterior resin slot restorations.

This study compared the degree of microleakage in the proximal walls of direct and indirect resin slot restorations in relation to the types of dentin bonding systems and the location of gingival margins. Two Class II slot preparations were prepared and restored in each of 60 extracted human molars using direct (Filtek Supreme) and indirect (Tescera ATL) restorative resin materials. Various types of dentin bonding systems, including self-etching (OneStep Plus/Tyrian SPE, iBond, Xeno III) and etch and rinse systems (All-Bond 2, Prime & Bond NT) were used to restore the prepared teeth. The gingival proximal wall was placed apical to the cementoenamel junction (CEJ) in 1 proximal box and coronal to the CEJ in the other. The specimens were stained and evaluated for microleakage using a digital imaging and analysis system. Significant differences were found in the degree of microleakage observed in the various restorative groups. In general, the group restored with indirect resin had less microleakage than the direct resin groups. Factors, such as type of dentin bonding system and location of gingival margins, exert a substantial influence on the degree of microleakage that occurred along the walls of proximal resin restorations.

Acid Etching, Dental↗

Transarticular bony defects after trauma and sepsis: arthrodesis using vascularized fibular transfer.

Ten male patients with previously infected bony defects involving both sides of an articulation underwent arthrodesis using a vascularized fibular transfer. The average age of these patients was 38 years (range, 20 to 60 years). The size of the bony defect averaged 9 cm (range, 3 to 21 cm). The ankle was involved in five patients, the knee in two patients, the wrist in two patients, and the elbow in one patient. Nine cases represented septic pseudarthroses (eight after trauma and one after attempted ankle arthrodesis). One patient had a defect across the wrist after debridement of a chronic infection. The patients were followed for an average of 71 months (range, 26 to 144 months). Nine patients healed after the index vascularized fibular transfer, and one patient (ankle arthrodesis) required a second cancellous bone-grafting procedure for delayed union at the junction of the fibula with the talus. Four of seven patients with lower limb involvement had residual leg length discrepancies averaging 5 cm (range, 3 to 8 cm), and one had a persistent 20-degree internal rotation deformity. Two of the patients with upper limb involvement had stiff digits. Five of the nine previously employed patients returned to their former occupation (including heavy labor in four cases). Complications included two wound separations, one case of instability of the donor ankle after removal of a large fibular graft (related in part to a prior injury), and one fracture at the junction of the fibular graft with the local bone 10 months after the index procedure, which united after plate fixation and application of autogenous cancellous bone graft. Arthrodesis using a transfer of vascularized fibular bone represents a viable option for limb salvage in the face of an infected transarticular bony defect.

Adult↗

Automatic measurement of random interpotenial intervals in single fibre electromyography.

The paper describes computer-aided measurement of interpotential intervals in single fibre eletromyography (SFEMG), a diagnostic and research method in clinical medicine. The method is based on analysis of consecutive intervals in pairs of single muscle fibre action potentials. The most important parameter obtained is the mean value of absolute differences of consecutive interpotential intervals, which reflects the reliability of impulse conduction along the terminal branches of motor axons and across the neuromuscular junction. The interface units, in combination with amplifers, binary counters and pulse amplitude-to-pulse width converters, allow not only direct analogue-to-digital conversion but also recognition of potentials. This enables the computer system to make decisions. The results are computed in less than 1 sec after analysis, and are immediately displayed in a graphic and alpha-numberical form on a screen at the measurement site. This provides an immediate visual feedback for the investigator thus both increasing the diagnostic efficacy and reducing the discomfort to the patient. Simultaneous printout by a teletype is used for documentation. The computer system consists of an HP 2116C computer with standard periphery and the program has been written in FORTRAN IV language with subroutines in FORTRAN IV and ASSEMBLER languages.

Action Potentials↗

Vertebral artery injury and cerebellar stroke while swimming: case report.

A twenty-five year old woman suffered the acute onset of dysequilibrium followed by headache, nausea, vomiting, vertigo, and slurred speech while swimming. Brain imaging revealed a right cerebellar infarct. Intravenous digital subtraction angiography showed a hypoplastic right vertebral artery and focal narrowing of the dominant left vertebral at the level of the C1-C2 junction. The patient was treated with aspirin and dipyridamole and immobilized for two weeks. She achieved almost complete recovery. Repeat angiography showed resolution of the left vertebral artery defect. Other cases of posterior circulation infarction associated with head turning during sports and ordinary activities are reviewed.

Adult↗

Intercellular calcium signalling between chondrocytes and synovial cells in co-culture.

Intercellular communication allows the co-ordination of cell metabolism between tissues as well as sensitivity to extracellular stimuli. Paracrine stimulation and cell-to-cell coupling through gap junctions induce the formation of complex cellular networks that favour the intercellular exchange of nutrients and second messengers. Heterologous intercellular communication was studied in co-cultures of articular chondrocytes and HIG-82 synovial cells by measuring mechanically induced cytosolic changes in Ca2+ ion levels by digital fluorescence video imaging. In confluent co-cultures, mechanical stimulation induced intercellular Ca2+ waves that propagated to both cell types with similar kinetics. Intercellular wave spreading was inhibited by 18alpha-glycyrrhetinic acid and by treatments inhibiting the activation of purinoreceptors, suggesting that intercellular signalling between these two cell types occurs both through gap junctions and ATP-mediated paracrine stimulation. In rheumatoid arthritis the formation of the synovial pannus induces structural changes at the chondrosynovial junction, where chondrocyte and synovial cells come into close apposition: these results provide the first evidence for direct intercellular communication between these two cell types.

Adenosine Triphosphate↗

A case of posterior cerebral artery aneurysm associated with idiopathic bilateral internal carotid artery occlusion: case report.

BACKGROUND: Aneurysms of the posterior circulation are challenging lesions to neurosurgeons, despite improvements in microsurgical techniques and advances in skull base approaches. We present a rare case of a posterior cerebral artery (PCA)-posterior communicating artery (PcomA) junction aneurysm associated with bilateral internal carotid artery (ICA) occlusion successfully treated with an endovascular procedure. CASE DESCRIPTION: A 57-year-old female presented with sudden onset of severe headache and loss of consciousness. CT scan showed diffuse subarachnoid hemorrhage and acute hydrocephalus. The patient developed severe neurogenic pulmonary edema and shock. Although her neurogenic pulmonary edema did not resolve, she recovered from shock. However, her general condition was so critical and her vital signs so unstable, that direct surgery under general anesthesia was considered too risky. A cerebral angiogram showed complete occlusion of both internal carotid arteries without any Moyamoya vessels. A saccular aneurysm located at the right PCA-PcomA junction was seen. To obliterate the aneurysm and prevent rerupture, the patient underwent coil embolization via an endovascular approach under sedation with local anesthesia. The balloon remodeling technique was useful to prevent occlusion of parent arteries. Finally, four interlocking detachable coils (IDC) with a total length of 44 cm were used to completely obliterate the aneurysm using the balloon remodeling technique. The patient made a full recovery after treatment and the aneurysm remained obliterated 2 years after coil embolization. CONCLUSIONS: We emphasize the advantages of the endovascular approach for the patient in critical condition. We believe that this is the first report of a PCA-Pcom junction aneurysm associated with bilateral ICA occlusion without moyamoya disease.

Aneurysm, Ruptured↗