Citations

Background: Persistent mildly abnormal knee kinematics after anterior cruciate ligament (ACL) reconstruction (ACLR) is an ongoing clinical problem. Purpose: To compare the clinical outcomes of revision ACLR (rACLR), rACLR and lateral extra-articular tenodesis (LET), or isolated LET in patients with a grade ≥2 pivot shift after ACLR with an intact or partially torn graft and a new, symptomatic medial meniscal tear. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review of all patients with a new, symptomatic medial meniscal tear diagnosed after a primary ACLR was performed. Patients were included if they demonstrated a grade ≥2 pivot shift on physical examination with an intact or partially torn ACL graft. Exclusion criteria included complete graft rupture. The senior author’s management evolved in a practice change design from rACLR to rACLR with LET, to isolated LET over the study period. The primary outcomes were the International Knee Documentation Committee (IKDC), Lysholm, and Tegner patient-reported outcomes (PROs) at 2 years postoperatively. Results: A total of 47 patients, with 16 in the rACLR group, 12 in the rACLR and LET group, and 19 in the isolated LET group were included. Baseline characteristics between groups were similar. At 2 years, the rACLR group IKDC score was 86.1 ± 6.6 and was lower than the rACLR and LET group (91.9 ± 4.4; P = .009; 95% CI, –10.4 to −1.2) and the isolated LET group scores (91.7 ± 3.0; P = .004; 95% CI, –9.7 to −1.6). The Lysholm score was lower in the rACLR group (85.8 ± 6.3) when compared with the rACLR and LET group (91.8 ± 4.6; P = .03; 95% CI, –11.8 to −0.39). There was no difference in any Tegner scores at 2 years ( P = .09). Conclusion: In patients with grade ≥2 pivot shift after an ACLR with an intact or partially torn graft and a new, symptomatic medial meniscal tear, the addition of an LET with or without rACLR led to improved PROs compared with an isolated rACLR. An isolated LET in this patient population should be considered an acceptable treatment option.

SUMMARY Results of systolic time interval recordings obtained serially on 104 female New Zealand White rabbits were analyzed for reproducibility, variation with respect to changes in heart rate (hr), and interrelationship of the various systolic time intervals. A table of values for systolic time intervals in the healthy rabbit was constructed. The preejection period (pep), left ventricular ejection time (lvet), and pep/lvet ratio were 0.040 ± 0.008 s, 0.119 ± 0.014 s, and 0.337 ± 0.066 respectively. The major systolic time intervals, pep and lvet, varied with respect to hr according to the regression equations: pep = 0.057 − 0.000078 hr and lvet = 0.175 − 0.000251 hr. The QS2 interval, S1S2 interval and isovolumic contraction time also varied with changes in hr.

SUMMARY Systolic time interval recordings were performed serially on 104 healthy female New Zealand White rabbits and 51 rabbits with congestive heart failure (chf) induced by chronic anthracycline drug therapy. The results were analyzed and the comparisons were made with studies of systolic time interval recordings of chf in persons. In the rabbit, chf is manifested by prolongation of the isovolumic contraction time, the preejection period (pep), and by shortening of the left ventricular ejection time (lvet). The ratio of pep/lvet was a sensitive indicator of left ventricular failure, with values in excess of 0.466 reflecting significant cardiac dysfunction at the 95% confidence level. The mean pep/lvet = 0.337 ± 0.66 in healthy rabbits and pep/lvet = 0.502 ± 0.075 in rabbits with chf. The pep index increased from 0.057 ± 0.007 in healthy rabbits to 0.074 ± 0.007 in rabbits with heart failure. The lvet index decreased from 0.173 ± 0.007 in healthy rabbits to 0.166 ± 0.010 in rabbits with chf.

SUMMARY Copper (Cu) was assayed in serial liver biopsy specimens of 5 pups resulting from a mating of 2 Bedlington Terrier carriers of inherited Cu toxicosis; the latter were sibling offspring of an affected Bedlington Terrier and a normal dog. Between 5 and 7 months of age, 1 of the pups had acceptable hepatic Cu values in each of 6 specimens. The hepatic concentration of Cu in another pup increased steadily from 801 to 3,874 μg/g dry weight. The other 3 pups may be heterozygotes (carriers); in 1—the hepatic Cu peaked at 1,043 μg/g at 9 months, in the 2nd—at 636 μg/g at 7 months, and in the 3rd—at 492 μg/g at 7 months. Acceptable concentrations were present in these 3 dogs at 9 to 14 months. Results in the present study indicate that heterozygotes may have 1 normal and 1 abnormal controller gene for regulating their hepatic Cu metabolism, thus accounting for the increased hepatic Cu concentration only in the early months of life. The affected Bedlington Terrier with 2 abnormal genes was unable to suppress the progressive hepatic accumulation of Cu. Paired liver biopsy specimens obtained at 5 to 7 months and at 14 or 15 months of age might distinguish the heterozygote from the normal and the affected Bedlington Terrier pups.

ABSTRACT Genetic variation at the TMEM106B locus has been associated with Alzheimer’s disease (AD) and related neurodegenerative phenotypes, yet its haplotypic architecture remains incompletely resolved. We refined the genetic landscape of TMEM106B by integrating AD-GWAS summary statistics (∼978K individuals) with haplotype analyses in 5,873 Dutch genomes including AD-cases, age-matched controls, and cognitively healthy centenarians. In addition to the known linkage disequilibrium (LD) block defining risk and protective haplotypes characterized by the amino acid substitution at residue 185 (Threonine/Serine), we identify a second conditionally independent LD block. Together these form four haplotypes (T1-T4), with T3 strongly enriched in centenarians. Long-read whole-genome sequencing in 493 individuals reveals haplotype-linked structural variation and methylation patterns, including a ∼19 Kbp genomic rearrangement carried by T3. These findings indicate that the TMEM106B locus comprises multiple haplotypes defined by methylation patterns and structural variants, offering insights into GWAS associations with AD risk and preserved cognition at extreme age.

SUMMARY In 13 Smooth Fox Terriers with a congenital form of myasthenia gravis, clinical signs included intermittent, progressive muscle weakness that became more pronounced with exercise; muscle wasting; megaesophagus; and aspiration pneumonia. Neurologic abnormalities were apparent only during periods of weakness and included inability to retract the fore- and hindlimbs from painful stimuli. A decrement of the compound muscle action potential was evident during repetitive supramaximal nerve stimulation. Intravenous injection of a short-acting cholinesterase inhibitor evoked immediate improvement of clinical and electromyographic signs. Intracellular microelectrode studies of a biopsied external intercostal muscle revealed reduced amplitude of miniature end-plate potentials, as occurs in acquired myasthenia gravis. However, in contrast to acquired myasthenia gravis, antibodies directed against acetylcholine receptors were not demonstrable in serum and were not bound to acetylcholine receptors in muscle. Despite lack of complexing with immunoglobulin, the amount of acetylcholine receptor protein in biopsied external intercostal muscles from 9 affected pups was less than 25% of the amount in 5 unaffected littermates. The latter finding accounted for the reduction in amplitude of miniature end-plate potential and the failure of neuromuscular transmission. Treatment with a long-acting cholinesterase inhibitor in 6 cases resulted in temporary improvement in muscle strength.

SUMMARY A case of the autoimmune form of myasthenia gravis and a case of what is probably a congenital form of myasthenia gravis were diagnosed in 2 unrelated cats. Neuromuscular weakness exacerbated by exercise was a prominent feature in both cats. Weakness was eliminated temporarily by administration of anticholinesterase drugs. Serum autoantibodies to acetylcholine receptors of skeletal muscle were present in the 1st cat and were not detected in the 2nd cat. A characteristic decrement in the amplitude of the compound muscle action potential during repetitive stimulation of the motor nerve was elicited in the 2nd cat. There was marked electromyographic improvement in response to anticholinesterase drugs. Electromyography was not performed in the 1st cat.