Estrogen affects the cellular metabolism of the anterior cruciate ligament. A potential explanation for female athletic injury.

Investigations from this laboratory have established the presence of estrogen receptors in the human anterior cruciate ligament. This study further investigates the effects of 17 beta-estradiol on the cellular proliferation and collagen synthesis of fibroblasts derived from the rabbit anterior cruciate ligament. Fibroblast proliferation and collagen synthesis in response to near log concentrations of 17 beta-estradiol (at 0.0029, 0.025, 0.25, 2.5, and 25 ng/ml) were assessed by measuring [3H]thymidine and [14C]hydroxyproline incorporation, respectively. Collagen synthesis was significantly reduced with increasing local estradiol concentration (P < 0.001). Declining collagen synthesis was first noted at a 17 beta-estradiol concentration of 0.025 ng/ml. Within normal physiologic levels of estrogen (0.025 to 0.25 ng/ml), collagen synthesis was reduced by more than 40% of control, and at pharmacologic levels of 2.5 and 25 ng/ml, by more than 50% of control. A significant reduction of fibroblast proliferation was also observed with increasing estradiol concentrations (P = 0.023). Clinically, alterations in anterior cruciate ligament cellular metabolism caused by estrogen fluctuations may change the composition of the ligament, rendering it more susceptible to injury.

Linkage studies and mutation analysis of the PDEB gene in 23 families with Leber congenital amaurosis.

The phenotype in the rd mouse is similar to the clinical presentation of Leber congenital amaurosis (LCA) in humans. Recently a nonsense mutation in the beta subunit of the cGMP phosphodiesterase (Pdeb) gene has been defined as the cause for the rd phenotype in the mouse and has raised the question as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using highly polymorphic (CA)n microsatellites has excluded the PDEB gene as a cause for LCA in 6 families. In the remaining 17 families, we have searched for mutations in the 22 exons of the PDEB gene using single-strand gel electrophoresis (SSGE). Multiple exonic polymorphisms have been determined. However, no DNA changes in the PDEB gene have been identified in our study population which could be causative for the LCA phenotype.

Precordial mapping in acute myocardial infarction.

Serial precordial mapping was done in 30 patients with acute anterior myocardial infarction, 27 transmural and 3 subendorcardial. The sum of ST elevations in the 48 lead map was designated as sigma ST. Normal sigma ST was calculated as 27.1+/-3.1 in males and 14.3+/-2.8 in females. In infarction it was 100.4+/-58.2 in males and 84.8+/-50.9 in females on the 1st day of admission. Sigma ST was elevated on day 1 and tended to fall gradually. In 6 patients it was normal by day 7 and in 7 it was still abnormal by day 21. This fall roughly correlated with fall in SGOT and CPK levels. Significant elevation of sigma ST occurred in 14 of 27 cases after day 1. In 10 of 27 cases significant re-elevation occurred on day 4 or after i.e. when the patient was outside the ICCU. In 10 of the 14 re-elevations there was pain or worsening of clinical picture and in 12 there was re-elevation of SGOT. This elevation presumably implied infarct extension. There was a tendency to more arrhythmias in the patients with higher sigma ST and of the 4 deaths in the series 3 had very high sigma ST and high levels of SGOT. The patient with the highest sigma ST 295 died in cardiogenic shock. The number of risk factors was found to be higher in the high sigma ST group.