Diazepam induces FGF-2 mRNA in the hippocampus and striatum.

starting by 6 h following diazepam injection and returning to approximately control values by 24 h. In situ hybridization showed elevated FGF-2 mRNA labeling in the hippocampal formation, mostly in the pyramidal layer of the CA1 and CA2 subfields and in the dentate gyrus hilar region. These results indicate that diazepam treatment up-regulates FGF-2 expression in select regions of the brain and suggest that GABA may promote neuroplasticity in concert with FGF-2.

Structural valve deterioration in mitral replacement surgery: comparison of Carpentier-Edwards supra-annular porcine and perimount pericardial bioprostheses.

BACKGROUND: Bioprostheses preserved with glutaraldehyde, both porcine and pericardial, have been available as second-generation prostheses for valve replacement surgery. The performance with regard to structural valve deterioration with the Carpentier-Edwards supra-annular (CE-SAV) porcine bioprosthesis and the Carpentier-Edwards Perimount (CE-P) pericardial bioprosthesis (Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif) was evaluated to determine whether there was a difference in mitral valve replacement. METHODS: The CE-SAV bioprosthesis was implanted in 1266 overall mitral valve replacements (isolated mitral, 1066; mitral in multiple, 200) and the CE-P bioprosthesis in 429 overall mitral valve replacements (isolated mitral, 328; mitral in multiple, 101). The mean age of the CE-SAV population was 64.2 +/- 12.2 years and that of the CE-P population, 60.7 +/- 11.7 years (P =.0001). For the study, structural valve deterioration was diagnosed at reoperation for explantation. RESULTS: The freedom from structural valve deterioration was evaluated to 10 years, and the freedom rates reported are at 10 years. For the overall mitral valve replacement groups, the actuarial freedom from deterioration was significant (P =.0001): CE-P > CE-SAV for 40 years or younger, 80% versus 60%; 41 to 50 years, 91% versus 61%; 51 to 60 years, 84% versus 69%; 61 to 70 years, 95% versus 75%. The older than 70-year group was 100% versus 92% (no significant difference). The actual freedom from structural valve deterioration also demonstrated the same pattern at 10 years: 40 years or younger, CE-P 82% versus CE-SAV 68%; 41 to 50 years, 92% versus 70%; 51 to 60 years, 90% versus 80%; 61 to 70 years, 97% versus 88%; and older than 70 years, 100% versus 97%. The independent risk factors of structural valve deterioration for the overall mitral valve replacement group were age and age groups and prosthesis type (CE-SAV > CE-P). The prosthesis type either in isolated replacement or in multiple replacement was not predictive of structural valve deterioration. The pathology of structural valve deterioration was different: 70% of CE-P failures were due to calcification and 57% of CE-SAV failures were due to combined calcification and leaflet tear. CONCLUSION: The actuarial and actual freedom from structural valve deterioration, diagnosed at reoperation, is greater at 10 years for CE-P than for CE-SAV bioprostheses. The mode of failure is different, and the cause remains obscure. Long-term evaluation is recommended, because the different modes of failure may alter the clinical performance by 15 and 20 years.

Visual input regulates the expression of basic fibroblast growth factor and its receptor.

Emerging evidence indicates that the expression of trophic factors in the brain is regulated in an activity-dependent manner, which suggests an involvement of trophic factors in events controlled by input activity. We have investigated the possibility that visual sensory input impacts the expression of basic fibroblast growth factor and its receptor in the brain. Rats were maintained for seven days in darkness and then re-exposed to normal illumination for 0, 1, 3 or 6 h. We assessed relative levels of basic fibroblast growth factor and fibroblast growth factor receptor messenger RNAs using nuclease protection assays, and examined possible changes in the phenotypic expression of basic fibroblast growth factor and its receptor using immunohistochemistry. There was a significant decrease in levels of basic fibroblast growth factor and fibroblast growth factor receptor messenger RNAs as a result of dark rearing, and levels of messenger RNAs increased progressively with light re-exposure. Changes in messenger RNAs were observed primarily in the cerebral cortex (caudal portion) and were accompanied by alterations in the staining intensity and density of cells exhibiting basic fibroblast growth factor and fibroblast growth factor receptor phenotypes. Regulation of the basic fibroblast growth factor system by sensory input suggests that basic fibroblast growth factor, and perhaps other trophic factors, are mediators of the effects of experience on the structure and function of the CNS.

Twelve-year experience with Carpentier-Edwards PERIMOUNT pericardial valve in the mitral position: a multicenter study.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to assess the durability of the Carpentier-Edwards PERIMOUNT pericardial bioprosthesis in the mitral position. METHODS: This seven-center retrospective clinical study involved the follow up of 333 patients who underwent isolated mitral valve replacement and 102 patients who underwent double (mitral and aortic) valve replacement with the PERIMOUNT pericardial valve between 1984 and 1989. Mean patient age at implant was 60.7 +/- 11.6 years; 41.1% were males. The most common etiology was rheumatic heart disease (53.9%) and the most common mechanism mitral insufficiency. All patients but six were followed for an average of 7.2 +/- 3.6 years after surgery; total follow up was 3071.7 patient-years (pt-yr). RESULTS: The total operative mortality rate was 7.6%; this included a valve-related mortality rate of 0.2%. The late mortality rate was 5.2% per pt-yr, of which 1.4% per pt-yr was considered valve-related. At 11 years, the overall actuarial survival rate was 53.3 +/- 2.8%, and actuarial freedom from valve-related death 83.9 +/- 2.6%. At follow up, 80% of patients were in NYHA class I or II, and 74% showed improvement. Twenty-eight incidences of deterioration requiring explant were observed. At 11 years the actuarial freedom from explant due to structural failure was 84.9 +/- 3.1%. Rates of structural failure decreased with age: the actuarial freedom from explant due to structural failure was 78.1 +/- 4.8% for patients aged < or = 60 years, 89.4 +/- 4.4% for those aged 61-70 years, and 100% for those aged over 71 years. CONCLUSION: The Carpentier-Edwards PERIMOUNT pericardial bioprosthesis is a reliable choice when a tissue valve is required, especially in patients over 60 years of age.

Intermediate follow up of the TEKNA bileaflet valve.

BACKGROUND AND AIM OF THE STUDY: The study aim was to collect intermediate clinical data on the TEKNA bileaflet valve. METHODS: This nine-center clinical study involved 884 patients implanted between June 1990 and October 1993. The population consisted of 522 (59.0%) males and 362 (41.0%) females. Mean age at implant was 59.1 +/- 11.8 years (range: 14.7 to 88.4 years). Indication for valve replacement was dependent on the position: stenosis was the predominant reason in the aortic position; regurgitation was more pronounced for the mitral position. A total of 261 (29.5%) patients underwent concomitant procedures. Mean follow up is 2.7 +/- 1.2 years; total follow up is 2386.1 patient-years (pt-yr). RESULTS: Total operative (< or = 30 days postoperative) mortality rate was 3.7%; seven patients (0.8%) died due to valve-related causes. Total postoperative (> 30 days postoperative) mortality rate was 2.5%/pt-yr and included a valve-related mortality rate of 1.1%/pt-yr. The following valve-related complication rates (%/pt-yr) were reported for the long-term postoperative period: thromboembolism 0.6; valve thrombosis 0.3; bleeding events 1.5; non-structural deterioration 0.6; and endocarditis 0.4. No structural valve deterioration was reported. Actuarial freedom at four years was: overall survival rate 86.9 +/- 1.4%; valve-related survival rate 94.7 +/- 1.0%; freedom from thromboembolism 96.8 +/- 0.9%; valve thrombosis 99.3 +/- 0.3%; endocarditis 98.5 +/- 0.5%; bleeding events 94.3 +/- 1.0%; and non-structural deterioration 98.2 +/- 0.6%. CONCLUSIONS: The data indicate that observed mortality is due mainly to non-valve-related disorders. Risk of thromboembolic and bleeding events was low (0.9%/pt-yr and 1.5%/pt-yr, respectively). We conclude that this valve is safe and efficacious for use.

Long-term durability and patient functional status of the Carpentier-Edwards Perimount pericardial bioprosthesis in the aortic position.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to examine the long-term durability of the aortic Carpentier-Edwards Perimount pericardial bioprosthesis using actuarial and actual analyses. METHODS: A total of 267 patients were implanted at four centers between September 1981 and December 1983. Of these patients, 171 (64%) were males and 96 (36%) females; mean age at implant was 64.9+/-11.8 years (range: 21 to 86 years). Patients have been followed for 9.1+/-4.2 years (total 2335.7 patient-years). Long-term echocardiography data are presented. RESULTS: The total operative (<30 days postoperative) mortality rate was 4.9%; of this, 0.4% was valve-related. The total late (> or = 30 days postoperative) mortality rate was 6.2%/pt-yr and included a valve-related mortality rate of 1.6%/pt-yr. Complications of thromboembolism, thrombosis and bleeding showed linearized rates of 1.6%/pt-yr and 0.4%/pt-yr, respectively. Valve dysfunction resulted in an explant rate of 0.9%/pt-yr and an associated mortality rate of 0.1%/pt-yr. At 14 years post implant, actuarial freedom from overall and valve-related death was 39.3% and 78.8%, respectively. Actuarial and actual freedom from valve dysfunction was 70.4% and 81.7%. Actuarial freedom from valve explant as a result of dysfunction was 85.1% in all patients; explant in patients aged < or = 65 years at implant was less (76.1%) than in patients aged >65 years (96.3%). CONCLUSION: The high actuarial and actual freedom from explant due to structural valve dysfunction supports the long-term durability of this pericardial bioprosthesis and justifies its clinical use in patients older than 65 years at implant.