The chondrocyte channelome: A narrative review

Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with “moonlighting” roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca²⁺ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.     

A new method for the termination of cervical pregnancy]

The authors described a 7 weeks old cervical pregnant case, whome was administered 250 mg methotrexate in infusion to eliminate the throphoblastic tissue. 3 days later the HCG was negative in the urine. After the dilatation of cervix by laminaria, the collapsed amniotic sac came from the cervix with minimal hemorrhage. They suggest the method is suitable to prevent the serious complications of cervical pregnancy.     

The safety of awake tracheal intubation in cervical spine injury

As a referral centre for cervical spine injuries, we have routinely performed awake tracheal intubation when intubation was indicated. A retrospective case control study was undertaken to review the frequency of neurological deterioration and aspiration associated with our approach. Neurological deterioration was assessed by a change in level of injury or neurological grade at admission and discharge. Four hundred and fifty-four patients with critical cervical spine and/or cord injuries were reviewed over an eight-year period. A case group of 165 patients underwent tracheal intubation awake within two months of injury. A control group of 289 remained unintubated during the same period. A comparison of spinal neurological status between admission and discharge revealed no statistically significant difference in neurological deterioration between the two groups. This occurred despite a greater injury severity score in the case group. No evidence of aspiration during intubation was documented. We conclude that awake tracheal intubation is a safe method of airway management in patients with cervical spine injuries.     

Primary Radiotherapy of Stage IIA/B–IIIB Cervical Carcinoma

BACKGROUND: Comprehensive literature on cervical cancer demonstrates, even today, the need for optimization of the timing of external-beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) in the treatment of stage IIA/B-IIIB cervical carcinoma. PATIENTS AND METHODS: 210 patients with carcinoma of the cervix were treated in the Municipal Center of Oncoradiology between January 1991 and December 1996 (FIGO IIA: n = 10, FIGO IIB: n = 113, and FIGO IIIB: n = 87). Two regimens were compared: sequential radiation therapy (SRT) with 4 x 8 Gy HDR-BT to point A followed by EBRT, and continuous radiation therapy (CRT) in which 5 x 6 Gy HDR-BT to point A, one session per week, was integrated into the EBRT. A total dose of 68-70 Gy to point A and 52-54 Gy to point B was given in EBRT with SRT, five fractions per week were applied. Four fractions per week were applied in CRT, i. e., no EBRT was performed on the day of HDR-BT. Total doses to points A and B were identical in both regimens. Overall treatment time (OTT) amounted to 56 days for SRT and 35 days for CRT. Median follow-up time was 3.4 (2.5-4.2) years. RESULTS: Progression-free 5-year-survival (PFS) was 71% in the CRT and 56% in the SRT group. Nevertheless, this difference was not statistically significant (p = 1.00), and the same was found in a subgroup analysis of the different tumor stages, showing, however, an unequivocal trend. Late bladder and rectal injuries occurred in 13% and 25%, respectively. Late rectal injuries were significantly more frequent with SRT than CRT (35 patients in the SRT and 18 patients in the CRT group; p = 0.037). This was due to the higher doses per fraction of HDR-BT in the SRT group. No difference was found regarding late bladder injuries (p = 0.837). CONCLUSION: For the patients included in this study, no advantage has been found so far in using CRT, i. e., shortening the OTT by weekly integration of HDR-BT into EBRT. Nevertheless, an obvious trend exists. The dose of 8 Gy per fraction of HDR-BT in the SRT regimen was obviously too high. To achieve a significant improvement in local control and disease-free survival (DFS) as well as overall survival (OS), the combination with modern chemotherapy regimens and regional deep hyperthermia may rather be the treatment option.     

Effect of sleep on interictal spikes and distribution of sleep spindles on electrocorticography in children with focal epilepsy.

OBJECTIVE: To determine how sleep with central spindles alters the spatial distribution of interictal spike frequency in children with intractable focal seizures, and whether such children have spindles arising from the medial temporal region in addition to the frontal-central region. METHODS: Seventeen children (age: 7 months-17 years) were studied using extraoperative electrocorticography (ECoG). RESULTS: Overall spike frequency across the subdural electrodes was greater during sleep with central spindles compared to wakefulness. In 13 children showing at least 1 spike/min in an electrode, the spatial distribution of spike frequency was similar during wakefulness and sleep; in addition, the spike frequency was greater in the seizure onset zones compared to the non-onset areas, regardless of wakefulness or sleep. Spindles were identified in the medial temporal region during sleep with central spindles in all 17 children. CONCLUSION: Overall spike frequency may be increased by sleep with spindles, but the spatial distribution of spike frequency appears similar during wakefulness and sleep in children with intractable focal seizures. SIGNIFICANCE: Both awake and sleep ECoG may be useful to predict seizure onset zones in children with intractable focal epilepsy. Medial temporal spindles are present in some children with focal epilepsy.     

Dural Tissue Trauma and Cerebrospinal Fluid Leak after Epidural Needle Puncture: Effect of Needle Design, Angle, and Bevel Orientation

Background: The effects of epidural needle design, angle, and bevel orientation on cerebrospinal fluid leak after puncture have not been reported. The impact of these factors on leak rate was examined using a dural sac model. Dural trauma was examined using scanning electron microscopy.

Methods: Human cadaveric dura, mounted on a cylindrical model, was punctured with epidural needles using a micromanipulator. Tissue was punctured at 15 cm H2O (left lateral decubitus) system pressure, and leak was measured at 25 cm H2O (semisitting) pressure. Leak rates and trauma were compared for the following: (1) six different epidural needles at 90[degrees], bevel parallel to the dural long axis; (2) 18-gauge Tuohy and 18-gauge Special Sprotte(R) epidural needles, 30[degrees]versus 90[degrees]; (3) 18-gauge Tuohy, bevel perpendicular versus parallel to the dural long axis.

Results: With the 90[degrees] puncture, bevel parallel, the greatest leak occurred with a 17-gauge Hustead (516 +/- 319 ml/15 min), and the smallest leak occurred with a 20-gauge Tuohy (100 +/- 112 ml/15 min; P = 0.0018). A 20-gauge Tuohy puncture led to statistically significant reductions in leak (P value range, 0.0001-0.0024) compared with all needles except the Special Sprotte(R). With the 30[degrees]versus 90[degrees] angle, 30[degrees] punctures with an 18-gauge Tuohy produced nonstatistically significant leak reductions compared with the 18-gauge Tuohy at 90[degrees]. The puncture angle made no difference for the Special Sprotte(R). Nonsignificant reductions were found for the Special Sprotte(R) compared with the Tuohy. With the 18-gauge Tuohy bevel orientation, perpendicular orientation produced nonstatistically significant reductions in leak compared with parallel orientation.