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At least 37 records · Page 2Linked to original sources

PubMed1979

Neonatal hip instability. Reason for failure of early abduction treatment.

A series of nine children with hip joint instability in 17 hips, diagnosed neonatally, is presented. Seven had bilateral idiopathic instability and two instability secondary to arthrogryposis, one of them bilateral. After reduction seven of the children (14 hips) were treated with abduction devices, which in all cases did not lead to stability in one or both hips. In these cases arthrography revealed that closed reduction was impossible due to narrowing of the joint capsule (hour-glass shape) and the interposition of a capsular fold including the acetabular labrum. The same types of changes were seen within 1 or 2 months after birth in three hips which had had no abduction treatment before arthrography. At open reduction of 11 hips it was found that the narrowing of the capsule was caused by the tendons of the iliopsoas and rectus femoris muscles. Excision of the capsular fold (labrum) was not necessary. The femoral head was deformed and anteverted. Failure of conservative treatment can be due either to incomplete reduction or to inadequate immobilization. Our analysis has shown that the most probable reason is incomplete reduction due to interposition. An obstacle to reduction should be suspected if abduction is restricted at birth, if primary reduction is difficult and the position difficult to maintain or if instability persists after 8 weeks of treatment. On the basis of our material the incidence of such an impediment to reduction was 0.08 per thousand births in the region studied during a 5-year period.

Acetabulum↗

PubMedDate not supplied

Analysis of 100 patients with anterolateral rotatory instability of the knee.

Of 100 consecutive patients with anterolateral rotatory instability analyzed, 84 were males and the average age was 27.4 years. Over 50 per cent were injured while participating in athletics and 40 per cent were injured during daily activities. The group averaged 1.2 operations prior to diagnosis. The most frequently performed procedures were medial meniscectomy, pes anserinus transfer and medial capsular reefings. Eighty-four of 100 patients underwent surgery during the study period. Seventy-one had combined rotatory instability and 13 had anterior lateral rotatory instability alone. Sixty-six patients had articular cartilage damage. Before treating the anterolateral rotatory instability, it is necessary to identify and treat other commonly associated abnormalities.

Adolescent↗

PubMed2026

The curious case of sporadic nematode susceptibility in "Tifguard" peanut (Arachis hypogaea): seed mixture or genetic instability?

The Runner-type peanut (Arachis hypogaea L.) cultivar "Tifguard" carries an introgressed chromosomal segment on chromosome A09 from A. cardenasii that confers resistance to root-knot nematode (RKN). Despite this, a proportion of "Tifguard" plants show RKN symptoms, which could plausibly be attributed to seed mixture or outcrossing. However, recent work has shown that cultivated peanut exhibits surprisingly frequent large-scale chromosomal instability (1% to 5%); suggesting that resistance loss could arise from spontaneous structural genomic change. To test these possibilities, we grew foundation seed in an RKN-infested field and collected symptomatic and asymptomatic plants. Lineages derived by single-seed descent were genotyped using the Axiom Arachis 48K SNP array v2 and whole-genome sequencing. Symptomatic lineages lacked the A. cardenasii introgression on chromosome A09 and instead carried the complete endogenous A. hypogaea A09 region at the expected dosage. There was no evidence of large-scale homoeologous exchange, deletion, or other genomic instability affecting this chromosome. Most susceptible plants were closely related to resistant "Tifguard" but lacked the A09 introgression, with a smaller proportion assignable to known nematode-susceptible cultivars, implicating seed mixture with a possible contribution from cross-pollination rather than genomic instability. Because resistance depends on a single major-effect segment, rare events have disproportionate phenotypic impact, placing high demands on genetic purity. For important traits conferred by major loci, marker-based testing across seed-increase stages could verify trait retention directly, and is increasingly practical as marker costs decline.

Arachis↗

PubMed2026

Real-World Outcomes of Olaparib in Japanese Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer: Exploratory Analysis of BRCA2 Loss and Microsatellite Instability Status.

OBJECTIVES: Metastatic castration-resistant prostate cancer has a poor prognosis. Although olaparib has demonstrated efficacy in patients with BRCA1/2 mutations, real-world data in Japanese patients remain limited. We aimed to evaluate the efficacy and safety of olaparib in patients with BRCA-mutated metastatic castration-resistant prostate cancer and explore the association of BRCA2 loss and microsatellite instability status with treatment outcomes. METHODS: We conducted a multicenter retrospective study of 34 patients with BRCA-mutated metastatic castration-resistant prostate cancer treated with olaparib between December 2020 and December 2024. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, prostate-specific antigen-50 response rate, and safety. Exploratory analyses were performed. RESULTS: Among the 34 patients, 33 had a BRCA2 mutation and one had a BRCA1 mutation. Prostate-specific antigen reduction was observed in 76.4% of patients; prostate-specific antigen-50 response rate was 58.8%. Median progression-free and overall survival were 15.8 and 35.1 months, respectively. Grade ≥ 3 adverse events (most commonly anemia) occurred in 17.6% of patients. Treatment discontinuation due to adverse events occurred in one patient. Exploratory analyses were performed in 23 BRCA2-mutated patients who underwent comprehensive genomic profiling. BRCA2 loss was observed in 39.1% of patients and showed a trend toward prolonged progression-free survival, whereas microsatellite instability-high status was observed in 13.0% and was associated with shorter progression-free survival. CONCLUSIONS: Olaparib demonstrated efficacy and safety in Japanese patients with BRCA-mutated metastatic castration-resistant prostate cancer. Exploratory analyses revealed that BRCA2 loss may be associated with prolonged progression-free survival, whereas microsatellite instability-high status may be associated with shorter progression-free survival. These findings require validation in larger cohorts.

Humans↗

PubMed2026

Tissue-based genomic instability markers for predicting malignant transformation in oral leukoplakia and proliferative verrucous leukoplakia: a systematic review.

OBJECTIVES: Although several biomarkers have been described for predicting malignant transformation in oral leukoplakias (OLs) and proliferative verrucous leukoplakias (PVLs), no systematic review has comprehensively evaluated tissue-based genomic instability markers. This review aimed to evaluate the evidence for these markers and their potential role in biomarker panel development. METHODS: A systematic review across PubMed, Embase and Cochrane Library was performed to identify studies evaluating the differences in tissue-based genomic markers between OL and PVL patients with and without malignant transformation. RESULTS: 34 observational studies comprising 3,237 patients were included, and genomic aberrations were categorised into DNA-level, chromosomal, and gene-specific alterations. For studies on OLs, DNA-level and chromosomal markers for which individual studies reported associations with malignant transformation included aneuploidy, impaired DNA repair capacity, loss of heterozygosity, chromosomal instability, and copy number alterations. Multiple gene-specific alterations also showed associations (e.g., TP53, MKI67, FGFR1), but findings varied across studies. The genomic markers of PVLs differed substantially, with fewer consistent predictors found. No meta-analysis was performed as all included studies were observational. CONCLUSIONS: Genomic instability across multiple levels contributes to malignant transformation, and represents a promising biological framework for predicting malignant transformation for OLs. While no single marker reliably demonstrates sufficient predictive performance, the integration of complementary genomic alterations with clinical and histopathological risk factors may provide a basis for the development of robust multi-marker panels. Future prospective studies using standardised detection methods and multivariable prediction models are required before clinical implementation. SYSTEMATIC REVIEW REGISTRATION: identifier CRD42024585830.

carcinoma↗

PubMed1976

The genetic instability and mutagenic interaction of chromosomal duplications present together in haploid strains of Aspergillus nidulans.

Previous work has shown that strains of Aspergillus nidulans with a chromosome segment in duplicate (one in normal position, one translocated to another chromosome) are unstable. Deletions occur from either duplicate segment. The present work has shown that when a chromosome I duplication and a chromosome III duplication are together in a haploid, deletions from the intact III duplication generally precede deletions from particular sections of the I duplication. Furthermore, the III duplication can enhance to some (but not major) extent the frequency of deletions from the I duplication. After the III duplication becomes reduced in size as a result of the loss of chromosomal material from the translocated duplicate III segment, such a reduced III duplication can greatly enhance the frequency of deletions from the I duplication. In other words, a III duplication of reduced size can promote far more deletions from the I duplication than the intact III duplication. The major increase in the deletional instability of the I duplication as promoted by the reduced III duplication is confined to the translocated duplicate I segment. The reduced III duplication can induce deletions from a section of the translocated duplicate I segment in accord with a temporal programme, and it appears that a particular region of the I duplication is far more under the mutagenic influence of the reduced III duplication than another region. Moreover, there is indication that there is a differential effect of two generally different genetic backgrounds on the susceptibility of duplication-regions to deletion. Possible mechanisms involved in such chromosomal instability are proposed. A manner in which genetic instability may be related to development is also proposed.

Aspergillus nidulans↗

PubMed1977

Resistance and mitotic instability to chloroneb and 1,4-oxathiin in Aspergillus nidulans.

Mutants resistant to two fungicides, chloroneb (1,4-dichloro-2,5-dimethoxybenzene) and vitavax (2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiin) were spontaneously obtained from a strain of Aspergillus nidulans with frequencies of 12.5 and 1.1 respectively, in 10(8) conidia. One chloroneb-resistant mutant (Chl 1) segregated as a single gene and was mapped in linkage group IV. It also caused a partial dependence of the strain on the fungicide and was semi-dominant. The mutant resistant to vitavax (Vit 1) also segregated as a single gene and was dominant. Both fungicides altered the instability of diploid and duplication strains. Chloroneb mainly increased haploidization, and vitavax reduced the mitotic recombination in diploids. Chloroneb increased the instability of duplication strains, and vitavax reduced such instability. The possible mode of action of such fungicides affecting stability is discussed.

Aspergillus nidulans↗

PubMed1977

Studies of enuresis. VIII. Detrusor and sphincter instability caused by overactivity of integral voiding reflexes.

Ninety-one children with nocturnal enuresis or enuresis plus daytime urgency incontinence were studied by cystometry. Seventy-two per cent of the girls and 62 per cent of the boys had evidence of bladder instability. Sixty-eight children in whom abnormalities were found on preliminary voiding urodynamics or voiding cystourethrography also underwent calibration and endoscopic examination under anesthesia. An atropine-suppression test was also performed preoperatively in some children with a markedly unstable bladder demonstrated on preoperative cystometry. In the majority of children tested suppression of bladder instability with atropine was demonstrable. Voluntary detrusor sphincter dyssynergia was demonstrated in a majority of the children with daytime urgency incontinence. Sixty-five per cent of the boys and 81 per cent of the girls were treated for urethral obstructive lesions suspected to be of functional urodynamic significance. Postoperative cystometry showed marked improvement in bladder stability in 57 per cent of the girls and 63 per cent of the boys treated for suspected urethral obstructive pathology. The anticholinergic suppression test was found to have no significant predictive value relative to the cause or surgical curability of bladder instability. The pathophysiologic significance of overactivity of integral voiding reflexes 6 through 11 is described.

Child↗

PubMed1978

Assessing ulnar instability of the metacarpophalangeal joint of the thumb.

Seven hundred and fifty normal thumbs were examined to determine the normal range of radioulnar mobility of the metacarpophalangeal joint with the joint in full extension, 15 degrees of flexion, and full flexion. Full flexion was the position of greatest stability. Twenty-five adult unembalmed cadaver thumbs were examined to determine the optimal position for testing the metacarpophalangeal joint for ulnar collateral ligament stability. When radial stress was applied to the metacarpophalangeal joint of 20 specimens after cutting the adductor aponeurosis and capsule, minimal ulnar instability was found. However, further sectioning of the ulnar collateral ligament revealed marked ulnar instability most significantly when the thumbs were examined in full metacarpophalangeal flexion. Finally, division of the adductor aponeurosis, dorsal capsule, ulnar collateral ligament, accessory collateral ligament, and volar plate resulted in complete instability of the metacarpophalangeal joint in all positions tested.

Biomechanical Phenomena↗

PubMed2026

DENND3-p.R534S disrupts dyadic microdomain architecture to drive potentially pro-arrhythmic calcium and electrophysiologic instability.

AIMS: Inherited ventricular arrhythmias (VAs) frequently occur in the absence of pathogenic variants in canonical ion channel genes, suggesting alternative mechanisms of electrical instability. DENND3 is a guanine nucleotide exchange factor that regulates Rab GTPase-mediated trafficking, but its role in cardiac excitation-contraction coupling and membrane microdomain organization remains undefined. METHODS AND RESULTS: We studied induced pluripotent stem cell-derived cardiomyocytes generated from a CRISPR/CAS9-engineered ultra-rare DENND3-p.R534S variant-inserted line (previously identified in an idiopathic ventricular fibrillation pedigree) and matched isogenic controls. Multielectrode array recordings, live-cell calcium imaging, super-resolution imaging using expansion microscopy, and biochemical analyses were used to assess electrical activity, calcium handling, membrane architecture, and calcium release unit organization. Potentially therapeutic studies were performed using genetic and pharmacologic inhibition of Rab11b. DENND3-p.R534S induced pluripotent stem cell-derived cardiomyocytes exhibited multicellular electrical instability characterized by increased beat-to-beat variability, arrhythmic activity, conduction slowing, and prolonged excitation-contraction delay. These abnormalities were accompanied by heterogeneous and dyssynchronous calcium cycling despite preserved expression of major calcium-handling proteins. Super-resolution imaging revealed disruption of BIN1-dependent membrane architecture and nanoscale uncoupling of Cav1.2 and RyR2. Inhibition of Rab11b restored BIN1 organization, re-established dyadic coupling, normalized calcium cycling, and improved electrical stability. CONCLUSION: These findings support a model in which altered trafficking balance contributes to disruption of membrane microdomain organization, leading to dyadic uncoupling, calcium instability, and electrical dysfunction. Modulation of the Rab11b-mediated trafficking pathway restored structural and functional abnormalities, supporting the trafficking-associated pathway as a potential therapeutic target in DENND3-associated ventricular arrhythmia.

Myocytes, Cardiac↗

PubMed2026

Visualization and quantification of rDNA instabilities in mammalian cells and mouse models.

Ribosomal DNA (rDNA) encodes the 18S, 5.8S, and 28S rRNA, accounting for ∼70% of cellular transcription. Despite its essential role and links to cancer and aging, quantifying rDNA instability in mammals remains challenging due to its repetitive organization and inherent heterogeneity. Here, we developed a murine rDNA FISH probe and genomic tools tailored for laboratory mouse strains. The results confirmed rDNA cluster locations, revealed substantial inter- and intra-strain as well as intercellular heterogeneity in rDNA organization within inbred mice and unstressed cells, and identified sources of spontaneous and replication-associated DNA double-strand breaks in the rDNA transcription termination region. Using mouse embryonic stem cells, we showed that BRCA1-mediated homologous recombination promotes rDNA instability, the non-homologous end joining factor XRCC1, but not Ku, suppresses intra-cluster deletions, and ATM kinase preserves rDNA cluster stability. Together, these findings establish a platform and tools for studying rDNA instability in animal models relevant to aging and cancer research.

Animals↗

PubMed1979

Hip joint instability after the neonatal period. I. Value of measuring the acetabular angle.

The acetabular angle was measured by two independent observers in a consecutive series of 29 infants with idiopathic instability of the hip. The diagnosis was made at the age of 1 1/2 to 21 months, and was confirmed by arthrography. The average difference in the measurement values between the two observers was less than 2 degrees. In infants with unilateral instability the acetabular angle was always greater on the unstable side. This difference decreased after treatment. Criteria for pathologic angles are discussed. Measurement of the acetabular angle is of greatest value for assessing the effect of treatment, but is of limited usefulness in diagnosing instability, especially during the first 6 months of life, as the cartilaginous component of the joint is not included in the measurement. Arthrography is recommended in cases difficult to evaluate.

Acetabulum↗

PubMed1978

Pes anserinus transposition for chronic anteromedial rotational instability of the knee.

Forty-eight men and three women were reviewed an average of thirty-one months after pes anserinus transposition for chronic anteromedial rotational instability of the knee. Their ages ranged from eighteen to forty-two years (average twenty-five years). All but four of the injuries occurred during sport. The interval between injury and operation averaged thirty months. During this time twenty-three patients had had other operations of which eighteen were for excision of menisci. A further sixteen patients required excision of one or both menisci at the time of pes anserinus transposition. After operation large haematomata had to be expressed from four wounds. One patient had a pulmonary embolism All made a complete recovery. Worthwhile improvement of stability during activity was found in forty-two of the fifty-one knees. Pre-existing degeneration of articular cartilage associated with severe instability of long duration was the main cause of failure. Good motivation was important for success. Four grades of disability are described according to the severity of symptoms. It was found that a successful operation gave approximately one grade of improvement on this scale. Arthroscopy is recommended to identify torn menisci and degenerative changes before pes anserinus transposition is undertaken. An important advantage of this operation is its simplicity. When more elaborate ligamentous reconstructions are necessary for severe instability, pes anserinus transposition can be usefully added to complete the repair.

Adult↗

PubMed1977

Stress radiographical measurements of post-traumatic knee instability. A clinical study.

In a prospective, consecutive, clinical and stress radiographical study, comprising 153 traumatic knee injuries, the value of stress radiographical measurements, gonylaxometry, was studied. Clinical evaluation, gonylaxometry and preoperative evaluation under general anaesthesia were carried out in that order. Then the operative findings were recorded as drawings on standard diagrams. These were used as a basis for evaluation of the preoperative tests. Of all the methods evaluated, gonylaxometry was found to provide the most accurate information regarding the knee injury. Very close to this result were the findings under general anaesthesia. Anterior drawer sign was measured gonylaxometrically when damage to the anterior cruciate ligament was present; posterior drawer meant damage to the posterior cruciate ligament. Partial ruptures of cruciate ligaments did not allow antero-posterior displacements exceeding the critical levels of the test. Small positive medial instability was found with ruptures of profound medial structures, higher values with total rupture of the long superficial collateral band, and still higher values when cruciate ligament ruptures were also present. The predictive values of a positive radiographical test were 100 per cent as regards medial instability and 98 per cent for drawer looseness. The predictive values of a negative test were 96 per cent for drawer and 92 per cent for medial instability. These figures are based on the total material. 95 per cent confidence limits are given.

Adolescent↗

PubMed1977

Ulnar nerve instability: ulnar nerve injury due to elbow flexion.

The term "ulnar nerve instability" describes the chronic conditions of subluxation and relocation of the ulnar nerve at the elbow with flexion and extension of the elbow, respectively. This condition is more common than generally thought. Recurrent subluxation of the nerve at the elbow results in a tractional and frictional neuritis. The nerve is vulnerable to trauma in its subluxed position, lying superficially on the medial humeral epicondyle. In certain cases of ulnar nerve instability associated with a tight overlying band bridging the heads of origin of the flexor carpi ulnaris, nerve injury can occur with flexion of the elbow. Thus, internal as well as external compressive factors as a cause of ulnar nerve neuropathy must be considered. Described is an elbow flexion test helpful in the diagnosis and prognosis of cases of ulnar nerve instability associated with the tight overlying band.

Adolescent↗

PubMed1979

Neonatal respiratory instability and infant development.

This study examines the relationships between neonatal sleep respiratory instability and infant development. A group of 122 full-term healthy infants was observed during a nap within the first and fourth weeks of life. During each nap, a continuous polygraphic recording was obtained of respiratory activity and extraocular movements. The relative frequency and average duration of apneic pauses (greater than or equal to 2 sec) in each testing session for an infant were employed to calculate a measure of respiratory instability (PSA4) previously found to be related to the occurrence of prolonged sleep apnea. 28 of the infants in this study were maintained at home on apnea monitors. The Bayley Scales of Infant Development were administered to each infant at approximately 9 months of age. Comparisons of infants with high versus low PSA4 values and of monitored versus unmonitored infants were not strongly distorted by imbalances in birth weight, sex, race, birth order, method of feeding, Sudden Infant Death Syndrome (SIDS) sibship, parental education, age at developmental assessment, and developmental tester. Those with increased respiratory instability (PSA4 greater than or equal to -0.04) within the first week of life averaged significantly lower in mental and psychomotor development. Utilization of home apnea monitors was not significantly associated with developmental scores.

Child Development↗

PubMed1977

Post-traumatic instability of the metacarpophalangeal joint of the thumb.

Of eithty-six patients with collateral ligament instability of the metacarpophalangeal joint of the thumb, sixty-six (77 per cent) had ulnar and twenty (23 per cent) had radial instability, while in addition twenty-four had fractures and twenty-nine had volar subluxation of the proximal phalanx. Of the sixty-nine patients operated on, sixty-five had an abnormality of the ulnar or radial collateral ligament proper or of its attachment; two, subluxation of the extensor pollicis longus; and two, stretching of the adductor expansion. Stability was restored by collateral ligament repair or reconstruction, by fixation of a fracture fragment with a Kirschner wire, or by arthrodesis in all but five thumbs. Of the five patients who did not have stability of the metacarpophalangeal joint following surgery, three had had the collateral ligament sutured more than three weeks after injury and two had had reconstruction of the collateral ligament using a tendon graft. Early surgical treatment is recommended for all patients with post-traumatic instability of the metacarpophalangeal joint greater than 45 degrees and for those with volar subluxation of the proximal phalanx or a displaced fracture of the base of the proximal phalanx. Collateral ligament repair is indicated for patients operated on within three weeks of injury, and reconstruction of the ligament by means of a tendon graft is recommended for those treated more than three weeks after injury.

Adolescent↗

PubMed1977

Instability of the subtalar joint. Diagnosis by stress tomography in three cases.

Lateral instability in the subtalar joint was documented by a method of stress tomography in three patients. The subtalar inversion angle averaged 38 degrees +/- S.D. 6 degrees in asymptomatic feet and 57 degrees +/- S.D. 5 degrees in those with unstable subtalar joints . Review of the literature suggests that as many as 10 per cent of patients having the Watson-Jones procedure for abnormal talar tilt also have instability in the subtalar joint. It is felt that the subtalar joint should be evaluated in patients seen with the clinical symptom of lateral instability.

Adult↗