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Intercondylar notch stenosis in degenerative arthritis of the knee.

PURPOSE: To present a classification of intercondylar notch stenosis (IS) adjacent to the anterior cruciate ligament (ACL) in degenerative knee arthritis, to raise awareness of this disorder, to describe the arthroscopic findings, and to promote an organized approach to its treatment with favorable results. TYPE OF STUDY: Case series. METHODS: Of 362 arthroscopies in patients with gonarthrosis, we identified 122 knees in 96 patients (34%) with central knee pain and subjective instability without ACL laxity to determine the notch changes adjacent to the ACL. We followed a cohort of 69 knees in 64 patients, 47 female (73%) and 17 male (27%), excluding 53 knees in 32 patients for other symptomatic lesions, noncompliance with protocol, or loss to follow-up. The average patient age was 66 years (range, 53 to 78 years). Stenosis was classified as: type I, anterior; type II, lateral; type III, mixed; and type IV, massive. Diagnosis was determined by manipulation during arthroscopy to visualize impingement and was followed by notchplasty. Average follow-up was 26 months (range, 12 to 36 months). RESULTS: Type III was most common, appearing in 48% of knees. Type I was found in 29%, type II in 20%, and type IV in 3% of knees. Preoperatively, central pain occurred in all patients, being moderate in 40 knees (58%) and severe in 26 knees (38%), with diminished strength and subjective instability in all cases; only 42 (61%) had knee extension loss. Flexion contracture resolved in 81% of cases; 90% had good to excellent pain relief and 74% excellent relief of subjective instability, without significant complications. CONCLUSIONS: Intercondylar notch stenosis in the arthritic knee may be a cause of ACL damage, symptomatic instability, and loss of extension. A structured approach to diagnosis and treatment was beneficial in restoring more normal function for our patients and may prevent disease progression. LEVEL OF EVIDENCE: Level IV.

Aged↗

Epinephrine-induced T-wave notching in congenital long QT syndrome.

OBJECTIVES: The purpose of this study was to characterize the effect of epinephrine on T-wave morphology in patients with congenital long QT syndrome (LQTS). BACKGROUND: QT prolongation is a paradoxical, LQT1-specific response to low-dose epinephrine infusion. At rest, notched T waves are more common in LQT2. METHODS: Thirty subjects with LQT1, 28 with LQT2, and 32 controls were studied using epinephrine provocation. Twelve-lead ECG was recorded continuously, and QT, QTc, and heart rate were obtained during each stage. Blinded to phenotype and genotype, T-wave morphology was classified as normal, biphasic, G1 (notch at or below the apex), or G2 (distinct protuberance above the apex). RESULTS: At baseline, 97% LQT1, 71% LQT2, and 94% control had normal T-wave profiles. During epinephrine infusion, G1- and G2-T waves were more common in LQT2 than in LQT1 (75% vs 26%, P = .009). However, epinephrine-induced G1-T waves were present in 34% of control. Epinephrine-precipitated biphasic T waves were observed similarly in all groups: LQT1 (6/30), LQT2 (3/28), and control (4/32). During low-dose epinephrine infusion (< or =0.05 microg/kg/min), G1-T waves occurred more frequently in LQT2 (LQT1: 25% vs 3%; control 9%, P = .02). Low-dose epinephrine-induced G2-T waves were detected exclusively in LQT2 (18%). Low-dose epinephrine elicited G1/G2-T waves in 8 of 15 LQT2 patients with a nondiagnostic baseline QTc. CONCLUSIONS: Biphasic and G1-T waves are nonspecific responses to high-dose epinephrine. Changes in T-wave morphology during low-dose epinephrine (<0.05 microg/kg/min) may yield diagnostic information. G2-notched T waves elicited during low-dose epinephrine may unmask some patients with concealed LQT2.

Adult↗

Sigmoid notch osteotomy for posttraumatic dorsal dislocation of the distal radioulnar joint: A case report.

Instability of the distal radioulnar joint (DRUJ) is associated most commonly with injury to the soft-tissue restraints of that joint, particularly the triangular fibrocartilage complex. The dorsal rim of the sigmoid notch, however, also plays an important role as a bony restraint to dorsal subluxation. We report a case of posttraumatic dorsal dislocation of the DRUJ associated with a depressed fracture of the dorsal rim of the sigmoid notch. This was treated with soft-tissue release and corrective osteotomy of the dorsal rim of the sigmoid notch to restore DRUJ stability and congruency.

Adult↗

Notch expression patterns in the retina: An eye on receptor-ligand distribution during angiogenesis.

The critical contribution of the Notch signaling pathway to vascular morphogenesis has been underscored by loss-of-function studies in mouse and zebrafish. Nonetheless, a comprehensive understanding as to how this signaling system influences the formation of blood vessels at the cellular and molecular level is far from reached. Here, we provide a detailed analysis of the distribution of active Notch1 in relation to its DSL (Delta, Serrate, Lag2) ligands, Jagged1, Delta-like1, and Delta-like4, during progressive stages of vascular morphogenesis and maturation. Important differences in the cellular distribution of Notch ligands were found. Jagged1 (Jag1) was detected in "stalk cells" of the leading vasculature and at arterial branch points, a site where Delta-like4 (Dll4) was clearly absent. Dll4 was the only ligand expressed in "tip cells" at the end of the growing vascular sprouts. It was also present in stalk cells, capillaries, arterial endothelium, and in mural cells of mature arteries in a homogenous manner. Delta-like1 (Dll1) was observed in both arteries and veins of the developing network, but was also excluded from mature arterial branch points. These findings support alternative and distinct roles for Notch ligands during the angiogenic process.

Adaptor Proteins, Signal Transducing↗

[Ganglion cyst at the spinoglenoid notch. A case report and literature review].

INTRODUCTION: Entrapment of the suprascapular nerve at the spinoglenoid notch due to a ganglion cyst is an uncommon event and remains a challenge for clinicians. EXEGESIS: We describe the findings in a 35-year-old patient with nonspecific pain in the shoulder and in whom MR revealed a ganglion cyst in the spinoglenoid notch, confirmed surgically. CONCLUSION: Entrapment of the suprascapular nerve at the spinoglenoid notch due to a ganglion cyst must be considered in the differential diagnosis of nonspecific shoulder pain. MR imaging and electromyography can reach a positive, topographic, and etiologic diagnosis of suprascapular neuropathy.

Adult↗

The spatial tuning of color and luminance peripheral vision measured with notch filtered noise masking.

We have measured the spatial bandwidths of the bandpass red-green chromatic and luminance mechanisms at four locations in the nasal visual field (0, 10, 20 and 30 degrees) using a method of notch filtered noise masking which effectively removes the artifact of off-frequency looking for our stimuli. Detection thresholds were measured for luminance or isoluminant red-green Gaussian enveloped test gratings of 0.5 cpd embedded in 1/f noise. Firstly, thresholds were obtained as a function of increasing noise spectral density and were fitted using a standard noise masking model. These results support the existence across the visual field of independent, red-green chromatic and luminance mechanisms with similar sampling efficiencies. Secondly, we measured thresholds in notch filtered noise as a function of notch width and derived the spatial bandwidth of the detection mechanism. We find both color and luminance mechanisms have similar bandwidths which remain virtually constant across eccentricity. These results indicate strong overall similarities between the early processing of color and luminance vision, and lend support to the role of color as an 'intrinsic image' in spatial vision. The results are discussed in the light of the anchored channel and shifting channel models of peripheral contrast sensitivity and pattern detection.

Color Perception↗

Magnitudes and phases of human distortion-product otoacoustic emissions at 2f(1)-f(2) against f(2)/f(1): effects of an audiometric notch.

The influence of the frequency ratio f(2)/f(1) of two pure-tone stimuli on the distortion-product otoacoustic emissions (DPOAEs) at 2f(1)-f(2) was assessed in 14 hearing-impaired human ears exhibiting a narrow audiometric notch at 4 kHz, whereas 11 normally hearing ears served as controls. A fixed-f(2) paradigm was used, with f(2) values varying from 2 to 8 kHz in 1-kHz steps. The intensities of the two stimuli were either 60 or 70 dB SPL. The magnitudes and phases of DPOAEs were extracted so that the bandpass filter-like profile of DPOAE magnitude against f(2)/f(1) (f(2)/f(1) magnitude function) could be characterized by the presence and position of its maximum, and DPOAE group delays were derived from the phase gradient of the DPOAE when f(1) varied. The main difference between normal and impaired ears occurred at 4 kHz in that, in contrast with normal ears, nine impaired ears out of 14 did not present any peak in their f(2)/f(1) magnitude function, while the remaining five ears only differed from normal ones by a slightly shifted maximum toward larger f(2)/f(1)s. Group delays were significantly shortened in all impaired ears, with a tendency to be shorter in the subset of ears with flat DPOAE magnitude profiles with f(2)/f(1). No clear effect of notch depth was observed, and with the chosen stimulus characteristics, no abnormal DPOAE result was observed whenever f(2) fell outside the audiometric notch. It is concluded that DPOAE group delays apparently provide useful objective clues of cochlear dysfunction, more sensitive than DPOAE magnitudes inasmuch as many of them remained near the normal range. Although a majority of f(2)/f(1) magnitude functions were clearly flattened when f(2) was impaired, this feature was less systematic.

Adult↗

Anterior femoral notching and ipsilateral supracondylar femur fracture in total knee arthroplasty.

The authors reviewed 670 total knee arthroplasties with a 2-10-year follow-up period. Of these, 180 knees had anterior femoral notching, which was deeper than 3 mm in 138. Two of the 670 knees suffered ipsilateral supracondylar fractures; one of these had a notched femur and one did not. Both fractures occurred at the anterior patellar flange-bone junction. No correlation was found between anterior femoral notching and ipsilateral supracondylar femur fracture.

Aged↗

Stimulation of human epidermal differentiation by delta-notch signalling at the boundaries of stem-cell clusters.

BACKGROUND: Human epidermis is renewed throughout life from stem cells in the basal layer of the epidermis. Signals from the surrounding keratinocytes influence the differentiation of the stem cells, but the nature of the signals is unknown. In many developing tissues, signalling mediated by the transmembrane protein Delta1 and its receptor Notch1 inhibits differentiation. Here, we investigated the role of Delta-Notch signalling in postnatal human epidermis. RESULTS: Notch1 expression was found in all living epidermal layers, but Delta1 expression was confined to the basal layer of the epidermis, with highest expression in those regions where stem cells reside. By overexpressing Delta1 or Delta(T), a truncated form of Delta1, in primary human keratinocytes and reconstituting epidermal sheets containing mixtures of Delta-overexpressing cells and wild-type cells, we found that cells expressing high levels of Delta1 or Delta(T) failed to respond to Delta signals from their neighbours. In contrast, wild-type keratinocytes that were in contact with neighbouring cells expressing Delta1 were stimulated to leave the stem-cell compartment and initiate terminal differentiation after a few rounds of division. Delta1 promoted keratinocyte cohesiveness, whereas Delta(T) did not. CONCLUSIONS: We propose that high Delta1 expression by epidermal stem cells has three effects: a protective effect on stem cells by blocking Notch signalling; enhanced cohesiveness of stem-cell clusters, which may discourage intermingling with neighbouring cells; and signalling to cells at the edges of the clusters to differentiate. Notch signalling in epidermal stem cells thus differs from other progenitor cell populations in promoting, rather than suppressing, differentiation.

Cell Differentiation↗

Maintenance of neuroepithelial progenitor cells by Delta-Notch signalling in the embryonic chick retina.

BACKGROUND: Neurons of the vertebrate central nervous system (CNS) are generated sequentially over a prolonged period from dividing neuroepithelial progenitor cells. Some cells in the progenitor cell population continue to proliferate while others stop dividing and differentiate as neurons. The mechanism that maintains the balance between these two behaviours is not known, although previous work has implicated Delta-Notch signalling in the process. RESULTS: In normal development, the proliferative layer of the neuroepithelium includes both nascent neurons that transiently express Delta-1 (Dl1), and progenitor cells that do not. Using retrovirus-mediated gene misexpression in the embryonic chick retina, we show that where progenitor cells are exposed to Dl1 signalling, they are prevented from embarking on neuronal differentiation. A converse effect is seen in cells expressing a dominant-negative form of Dl1, Dl1(dn), which we show renders expressing cells deaf to inhibitory signals from their neighbours. In a multicellular patch of neuroepithelium expressing Dl1(dn), essentially all progenitors stop dividing and differentiate prematurely as neurons, which can be of diverse types. Thus, Delta-Notch signalling controls a cell's choice between remaining as a progenitor and differentiating as a neuron. CONCLUSIONS: Nascent retinal neurons, by expressing Dl1, deliver lateral inhibition to neighbouring progenitors; this signal is essential to prevent progenitors from entering the neuronal differentiation pathway. Lateral inhibition serves the key function of maintaining a balanced mixture of dividing progenitors and differentiating progeny. We propose that the same mechanism operates throughout the vertebrate CNS, enabling large numbers of neurons to be produced sequentially and adopt different characters in response to a variety of signals. A similar mechanism of lateral inhibition, mediated by Delta and Notch proteins, may regulate stem-cell function in other tissues.

Animals↗

Iso-intense neuroenteric cyst in the lower cervical spine treated with ventral resection and anterior fusion utilising sternal notch exposure: case report, technical note and literature review.

A 36-year-old female patient with a long-standing asymptomatic lower thoracic scoliosis presented with sensory symptoms involving all limbs. MRI scan demonstrated a rounded ventral intradural mass causing major deformity of the cervical cord at C6 and C7 levels. Unlike most previously reported neurenteric cysts, the MRI signal characteristics of this mass were such that it could not be determined if it is cystic or solid, being iso-intense on T1- and hyperintense T2-weighted images. Resection was performed through a median corporectomy of C6 and C7, the lesion being found to be a neurenteric cyst with an attachment to the anterior median fissure of the cord. Strut graft and cervical locking plate fixation from C5 to C6 was facilitated by extending the cervical incision into the sternal notch, with detachment of left-sided strap muscle insertion. The patient made an excellent recovery with complete resolution of neurological symptoms and solid fusion. The postoperative course was complicated by an anterior cervical CSF collection which resolved spontaneously within 2 months. The literature regarding this rare condition and its management is reviewed. Although the majority of intraspinal neurenteric cysts are situated ventral to the cord, most reports of excision have been from a dorsal approach. Drainage and subtotal excision of neurenteric cysts have been previously advocated; however, the recurrence rate is such that complete excision is advocated. This is facilitated by a ventral approach. A simplified method of utilising the sternal notch exposure is reported. The literature regarding the anatomical peculiarities pertinent to the sternal notch approach, and the reported literature regarding spinal neurenteric cysts is reviewed.

Adult↗

Intercondylar notch width and the risk for anterior cruciate ligament rupture in the osteoarthritic knee: evaluation by plain radiography and CT scan.

We measured the intercondylar notch morphometrically from radiographs and CT scans of 30 osteoarthritic knees. Our purpose was to assess the accuracy of the standing posteroanterior 30 degrees flexion view in determining whether there is a critical notch width that might predict a higher risk for rupture of the anterior cruciate ligament due to osteophytes. A correlation was found between measurements made on radiographs and CT scans and the appearance of the anterior cruciate ligament at operation. A narrow notch (less than 12 mm wide) was associated with absence of the anterior cruciate ligament.

Analysis of Variance↗

Interaction of hairless, delta, enhancer of split and notch genes of Drosophila melanogaster as expressed in adult morphology.

The interaction of three neurogenic loci viz. Delta, Enhancer of split and Notch, and a related gene, Hairless, of Drosophila melanogaster was investigated at the adult morphology level by measuring the effects of the mutations of the three other genes on the expression of the recessive lethal antimorphic Abruptex mutations of the Notch locus. The Abruptex mutations were also coupled in cis or trans with facet-glossy or split mutations of the Notch locus. In some of the experiments, the genotype of the fly was homozygous for either facet-glossy or split mutation or their wild type alleles but heterozygous for the Abruptex. Facet-glossy is located in a large intron of the locus, whereas split is located in the same exon as Abruptex. In all compounds studied, Delta suppressed the expression of Abruptex while Hairless and Enhancer of split enhanced it. The interactions of the four genes studied were allele specific, suggesting an interaction at the protein level. The comparison of the results presented in this study on the interaction of the neurogenic genes with other results on the same subject suggests that the interactions are similar in embryonic and imaginal development.

Alleles↗

Bone fracture analysis on the short rod chevron-notch specimens using the X-ray computer micro-tomography.

Mechanical fatigue of bone leads to micro-cracking which is associated with remodeling, establishing a balance in the microcrack population of the living tissue, thus, in the steady-state, the microstructure of bone provides sites of discontinuity acting as stress raisers. Hence fracture toughness plays a decisive role in bone functionality by determining the level to which the material can be stressed in the presence of cracks, or, equivalently, the magnitude of cracking which can be tolerated at a given stress level. Cortical bone, which behaves as a quasi-brittle solid when fractured, was tested as short-rod chevron-notched tension specimens (CNT). The main features of the CNT specimen are its geometry and the V shaped notch. The notch leads to steady-state crack propagation whilst the requested geometry allows a diameter 40% smaller than the thickness of a standard compact tension specimens (CT). These features are essential to distinguish the inhomogeneties in the fracture properties of materials like bone. Bone structure and crack propagation of the CNT specimens were analyzed using X-ray computed micro-tomography (XMT), which is a non-invasive imaging technique. The unique feature of the micro-CT is the high resolution three-dimensional image which consists of multi-sliced tomographs taken in a fine pitch along the rotational axis. Fracture toughness (K(IC)) computed according to the peak load was 4.8 MNm(-3/2) while that derived from experimental calibration tests using XMT was 4.9 MNm(-3/2).

Journal Article↗

Predicting the risk of pre-eclampsia and a small-for-gestational-age infant by quantitative assessment of the diastolic notch in uterine artery flow velocity waveforms in unselected women.

OBJECTIVES: To develop a new quantitative index, the notch depth index (NDI), to evaluate its association with the risk of pre-eclampsia and a small-for-gestational-age (SGA) infant and to compare its clinical usefulness with that of the uterine artery resistance index (RI) and the peak systolic to early diastolic velocity (A/C) ratio. METHODS: Uterine artery color Doppler ultrasound was performed in 288 consecutive healthy pregnant women at 20.2 +/- 2.0 (range 16.0-23.9) weeks of gestation. The NDI represents the depth of the early diastolic notch divided by the maximal diastolic velocity. RESULTS: Nine (3.1%) of the 288 women developed pre-eclampsia and 18 women (6.3%) delivered an SGA infant. The NDI was associated with subsequent onset of pre-eclampsia. The optimal cutoff value for the NDI in predicting pre-eclampsia was 0.14, giving a sensitivity, specificity and a positive predictive value (PPV) of 67, 92, and 22%, respectively. The PPV of the NDI was the largest of the three indices evaluated (12% for the RI and 16% for the A/C ratio). The relative risk for pre-eclampsia in women with values equal to or greater than the optimal cutoff values of the RI, A/C ratio and the NDI was 9.7 (95% confidence interval, 2.5-3.7), 19.2 (4.2-91), and 19.2 (5.1-71), respectively. The NDI of 0.14 improved the PPV of 18% determined by the presence of notches in bilateral uterine arteries. The optimal cutoff value of 0.14 for the NDI in predicting an SGA infant yielded a higher PPV (22%) than those for the RI (9%) and A/C ratio (12%). CONCLUSIONS: The NDI value in the second trimester is associated with the later onset of pre-eclampsia, and is clinically more useful in predicting pre-eclampsia than the two conventional indices.

Adult↗

Quantification of the diastolic notch in Doppler ultrasound screening of uterine arteries.

OBJECTIVE: To investigate a new method of quantification of the diastolic notch of the flow velocity waveforms of uterine arteries in the prediction of hypertensive disorders of pregnancy. METHODS: Pulsed-wave Doppler was used to obtain flow velocity waveforms (FVWs) from the uterine arteries at 21-22 weeks of gestation from 531 nulliparous women and 94 multiparous women at high risk. From the FVWs, both the pulsatility index (PI) and the notch index (NI) were calculated and the predictive values for both indices were compared using logistic regression analysis for mild and severe early onset hypertensive pregnancy complications. RESULTS: Both the PI and the NI were poor predictors for mild gestational hypertension and pre-eclampsia; predictive values for severe early onset disease, however, were much better. Logistic regression analysis showed the NI has no additional value compared with the PI in the prediction of either mild or severe disease. CONCLUSIONS: The NI offers the possibility to quantify the diastolic notch in uterine artery analysis. Compared to the PI, this does not lead to better predictive values for hypertensive disorders of pregnancy.

Arteries↗

The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway.

We demonstrate a novel interaction of the nephroblastoma overexpressed gene (NOV), a member of the CCN gene family, with the Notch signaling pathway. NOV associates with the epidermal growth factor-like repeats of Notch1 by the CT (C-terminal cysteine knot) domain. The promoters of HES1 and HES5, which are the downstream transducers of Notch signaling, were activated by NOV. Expressions of NOV and Notch1 were concomitant in the presomitic mesoderm and later in the myocytes and chondrocytes, suggesting their synergistic effects in mesenchymal cell differentiation. In C2/4 myogenic cells, elevated expression of NOV led to down-regulation of MyoD and myogenin, resulting in inhibition of myotube formation. These results indicate that NOV-Notch1 association exerts a positive effect on Notch signaling and consequently suppresses myogenesis.

Animals↗

Presenilin 1 negatively regulates beta-catenin/T cell factor/lymphoid enhancer factor-1 signaling independently of beta-amyloid precursor protein and notch processing.

In addition to its documented role in the proteolytic processing of Notch-1 and the beta-amyloid precursor protein, presenilin 1 (PS1) associates with beta-catenin. In this study, we show that this interaction plays a critical role in regulating beta-catenin/T Cell Factor/Lymphoid Enhancer Factor-1 (LEF) signaling. PS1 deficiency results in accumulation of cytosolic beta-catenin, leading to a beta-catenin/LEF-dependent increase in cyclin D1 transcription and accelerated entry into the S phase of the cell cycle. Conversely, PS1 specifically represses LEF-dependent transcription in a dose-dependent manner. The hyperproliferative response can be reversed by reintroducing PS1 expression or overexpressing axin, but not a PS1 mutant that does not bind beta-catenin (PS1Deltacat) or by two different familial Alzheimer's disease mutants. In contrast, PS1Deltacat restores Notch-1 proteolytic cleavage and Abeta generation in PS1-deficient cells, indicating that PS1 function in modulating beta-catenin levels can be separated from its roles in facilitating gamma-secretase cleavage of beta-amyloid precursor protein and in Notch-1 signaling. Finally, we show an altered response to Wnt signaling and impaired ubiquitination of beta-catenin in the absence of PS1, a phenotype that may account for the increased stability in PS1-deficient cells. Thus, PS1 adds to the molecules that are known to regulate the rapid turnover of beta-catenin.

Alzheimer Disease↗