Neurogenesis and anxiety-like behavior in male California mice during the mate's postpartum period.

Our understanding of postpartum anxiety (PPA) in fathers is limited, despite the negative consequences of anxiety on the father and child. Offspring contact reduces PPA in mothers; however, parallel investigations in fathers has gone unaddressed. Adult neurogenesis in the dentate gyrus (DG) contributes to anxiety regulation and is altered during the postpartum period, yet the effects of fatherhood on the production, or survival, of newborn cells in the DG, and the role of adult neurogenesis in PPA regulation, have not been examined. Using the biparental California mouse (Peromyscus californicus), we examined the relationships among postnatal day, anxiety-like behavior and adult neurogenesis in fathers. We hypothesized that attenuated anxiety-like behavior and enhanced adult neurogenesis would be observed when father-offspring contact was increased. We observed a reduction in anxiety-like behavior on the elevated plus-maze, but only at PND 16, a time of peak pup retrieval. Fatherhood reduced 1-week survival of newborn cells; however, surviving cells were maintained until 2 weeks postpartum. In contrast, non-fathers experienced a significant reduction in the survival of newborn cells between 1 and 2 weeks postpartum. Fatherhood also increased the numbers of newborn cells that expressed a neuronal phenotype. Collectively, these findings suggest that offspring interaction contributes to reductions in anxiety-like behavior and the maintenance of newborn neurons in the DG of fathers. These data contribute to our knowledge of the postpartum affective state in fathers, findings that may contribute to improved health of both the father and offspring.

Approach to the Synthesis of the C1-C11 and C14-C18 portion of Leucascandrolide A.

An asymmetric synthesis of the C1 to C11 and C14 to C18 fragments of the macrocyclic portion of the antibiotic Leucascandrolide A was achieved in 21 total steps from an achiral dienoate. The key 4-hydroxy-2,5-pyran portion of the natural product was established by oxy-Michael cyclization of a 5,7,9,11-tetraol intermediate, which in turn was established by an iterative asymmetric-hydration of dienoates. Alternative strategies for establishing the polyol stereochemistry were explored.

Tissue reaction to fabrics coated with turbostratic carbon: subcutaneous versus vascular implants.

A technique allowing the deposition of an adherent thin film of turbostratic, high-density carbon on heat-sensitive polymers was recently developed. The biological response to this biomaterial on yarns and fabrics of the type used in cardiovascular surgery has been studied. Polyester yarns, knitted Dacron sheets and knitted uncrimped Dacron vascular grafts were coated with a thin film (less than 1 micron) of turbostratic carbon using a physical vapour deposition process. Coated and control discs of knitted material, as well as coated and uncoated yarns, were implanted in pairs in the subcutaneous tissue of mice, using for each type of implant two cohorts of 12 animals, with observation periods of 4 and 8 wks respectively. Vascular grafts (8 cm long, 8 mm i.d.) coated with carbon on the luminal side only, were implanted for 12 wks in the infrarenal aortic position in six dogs, and compared to uncoated Dacron grafts of the same dimensions inserted in the same location and for the same duration in the infrarenal aortic position in six control animals. With subcutaneous implants, there was no significant difference in the tissue reaction to either coated or uncoated patches. In contrast, the vascular grafts, all of which were patent upon retrieval, showed a much lower extent of thrombosis on the blood-exposure surface in the case of carbon-coated Dacron, as compared to the luminal surface of control prostheses. The internal capsule (tissue formed between the polymer fabric and the blood interface) was thinner in carbon-coated grafts than in control grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

An enantioselective synthesis of benzylidene-protected syn-3,5-dihydroxy carboxylate esters via osmium, palladium, and base catalysis.

[reaction: see text]. The enantioselective syntheses of several protected syn-3,5-dihydroxy carboxylic esters have been achieved from the corresponding achiral 1,3-dieneoates. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to form delta-hydroxy-1-enoates. The resulting delta-hydroxy-1-enoates are subsequently converted into benzylidene-protected 3,5-dihydroxy carboxylic esters in one step. The benzylidene-protected 3,5-dihydroxy carboxylic esters are produced in good overall yields (25% to 51%) and high enantiomeric excesses (80% to >95%).

An enantioselective synthesis of cryptocarya diacetate.

[reaction: see text]. The enantioselective synthesis of cryptocarya diacetate has been achieved in 10 steps from ethyl sorbate. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to form a delta-hydroxy-1-enoate, which was subsequently converted into a benzylidene-protected 3,5-dihydroxy carboxylic ester. This ester was converted into cryptocarya diacetate in 14% overall yield via an allylation and methathesis ring closure reaction sequence.

Clinical results with left axillary to left anterior descending coronary artery bypass.

BACKGROUND: The minimally invasive direct coronary artery bypass procedure is not feasible if the left internal mammary artery has been used or has inadequate flow. We have applied a modified minimally invasive direct coronary artery bypass procedure, which uses a graft from the left axillary artery to the left anterior descending coronary artery in such situations. METHODS: The graft is anastomosed to the left axillary artery adjacent to the clavicle and tunneled underneath the vein, where it enters the thorax through the first interspace and courses to the left anterior descending coronary artery along the mediastinum. RESULTS: Since 1997 we have used this operation in 22 patients with a mean age of 70 years (range, 52 to 83 years). All patients were high-risk candidates because of advanced age (70 +/- 7 years), depressed left ventricular function (mean left ventricular ejection fraction, 38% +/- 6%), or previous heart operation (20 of 22, 91%). Conduits for the graft were saphenous vein (n = 18) or radial artery (n = 4). Ten patients were extubated in the operating room, and the mean duration of mechanical ventilation was 5.8 +/- 6 hours. There was one operative death (1 of 22, 4.5%). The mean length of intensive care unit and hospital stay was 1.5 days (range, 1 to 6 days) and 6 days (range, 2 to 15 days), respectively. At a mean follow-up of 6 months, all discharged patients are alive and functionally improved. None have required surgical or catheter-based revascularization of the left anterior descending coronary artery. CONCLUSIONS: The left axillary artery to left anterior descending coronary artery graft should be considered for high-risk patients in whom a minimally invasive direct coronary artery bypass procedure is not possible.

Myelomatous pleural effusion: report of an unusual occurrence.

Pleural effusion complicating the course of multiple myeloma is common. Myelomatous pleural effusion, in contrast, is distinctly rare. Searching the Medline data base, a total of only 35 previously reported cases could be located. A recent case we cared for prompted us to review the literature in this area. The incidence of myelomatous effusion, possible mechanisms of its formation, and implications for therapy and prognosis are discussed.

Long-term results of right latissimus dorsi cardiomyoplasty.

BACKGROUND: Initial experimental and clinical studies have shown that cardiomyoplasty using the right latissimus dorsi can improve left ventricular (LV) function early after operation. METHODS: This study presents the long-term clinical results of this procedure. Between March 1991 and November 1992, 16 patients (12 men, 4 women; mean age 57; range 33-77 years) underwent operation. Survivors were evaluated at 6-month intervals for 2 years with right heart catheterization, radionuclide scans, exercise testing, and quality of life questionnaires. RESULTS: The operative mortality was 6% (1/16), but 3 additional patients experienced sudden death within 6 months of operation. Survival was 63% (10/16) at 12 months and 50% (8/16) at 24 months. There were no significant changes in hemodynamic variables at 12 or 24 months after surgery. Left ventricular ejection fraction increased from 26.1 +/- 5.3 to 33.4 +/- 10.3 (p < 0.05) 6 weeks after operation, but was not different from baseline thereafter. The LV end-diastolic volume decreased significantly at 6 months from 306.1 +/- 71 to 249.4 +/- 69 mL (p < 0.01), and remained lower than the preoperative value in subsequent follow-up. Comparison of preoperative LV ejection fraction and LV stroke work index in 24-month survivors (7) and nonsurvivors (9) showed that survivors had better LV function before surgery. Functional status and quality of life were improved. CONCLUSIONS: Long-term results of right latissimus dorsi cardiomyoplasty are comparable to results using the left latissimus dorsi. Overall survival was limited by late sudden death, but survivors had improved functional capacity and stable LV function and size.

Controlled flow studies in 4 mm endothelialized dacron grafts.

Endothelial cell seeding of 4 mm ID double velour dacron vascular grafts promoted luminal endothelial cell surfacing and improved small-diameter graft performance as evidenced by the following: Flow rates through endothelial cell seeded grafts were higher than through nonseeded control grafts. With increasing postsurgical time the flow rates through seeded grafts increased as a consequence of greater luminal endothelial cell coverage. During low flow conditions endothelial cell seeded grafts retained thrombus-free surface characteristics whereas thrombus accumulated during low flow in nonseeded grafts. Some nonseeded grafts occluded during low flow. The ability of seeded grafts to retain thrombus-free surfaces during low flow increased with increasing postoperative time as a consequence of greater luminal endothelial cell coverage. Endothelial cell seeding is an efficacious approach to maintaining graft patency during conditions of reduced blood flow.

Endothelial cell seeding improves 4 mm PTFE vascular graft performance in antiplatelet medicated dogs.

The ideal prosthetic vascular graft for the replacement or bypass of small vessels has not yet been developed. Many studies have documented the success of endothelial cell seeding in small-diameter Dacron grafts, but few have reported the application of this protocol to small-diameter PTFE grafts, and none have reported seeding small-diameter PTFE grafts in antiplatelet medicated dogs. The present study was undertaken to assess the efficacy of endothelial cell seeding of small-diameter (4 mm ID) PTFE (Gore-Tex) carotid artery interposition grafts in the antiplatelet medicated dog. Twenty-five male mongrel dogs were included in this study. In each dog one carotid artery was replaced with an endothelial cell seeded PTFE graft; the contralateral artery was replaced with a nonseeded graft. The in vivo progress of graft performance was evaluated from 1 to 4 weeks postoperatively. The endothelial cell seeded grafts achieved significantly higher patencies and mean thrombus-free surfaces than nonseeded grafts. Midgraft endothelium was identified only on the seeded grafts at 3 and 4 weeks, with a maximal luminal coverage of 10-12%. The measurements of prostacyclin (PGI2) production indicated that the antiplatelet agent therapy did inhibit endothelial cell cyclooxygenase. The presence of outer capsule vasa vasora, anastomotic pannus ingrowth, transinterstitial cellular ingrowth, and thin inner capsules characterized the endothelial cell seeded grafts in contrast to the nonseeded grafts. We conclude that enhancement of graft performance is achieved by combining both an antiplatelet regimen and endothelial cell seeding in small-diameter PTFE vascular grafts.

Effects of antiplatelet agents in combination with endothelial cell seeding on small-diameter Dacron vascular graft performance in the canine carotid artery model.

The purpose of this study was to assess the success of endothelial cell-seeded and non-seeded small-diameter vascular grafts in dogs medicated with antiplatelet agents. Eighty dogs underwent bilateral carotid artery replacements with 6 cm lengths of 4 mm I.D. double-velour Dacron grafts. In each dog one graft was seeded with enzymatically derived autologous endothelial cells; the contralateral graft was nonseeded. The following anti-platelet medications were administered beginning 4 days preoperatively: aspirin (5 grains every day); dipyridamole (50 mg twice a day); aspirin plus dipyridamole (5 grains each day plus 50 mg twice a day); aspirin (1.25 grains every other day); ibuprofen (10 mg/kg/day); U-53,059, a cyclooxygenase inhibitor (3 mg/kg/day); and U-63557A, a thromboxane synthase inhibitor (10 mg/kg/day). Grafts were harvested 5 weeks postoperatively. Graft success was evaluated by patency, thrombus-free surface area, area endothelialized, and graft production of prostacyclin. None of the medications prevented neoendothelialization of seeded grafts. Mean patencies of endothelial cell-seeded grafts from medicated dogs were significantly greater than mean patencies of endothelial cell-seeded grafts from nonmedicated dogs. The cyclooxygenase inhibitors best maintained patency in nonseeded grafts. Thrombus-free surface areas of endothelial cell-seeded grafts from medicated dogs were significantly greater than from nonseeded control grafts from the medicated dogs. All medications impaired prostacyclin synthesis. We conclude that the combination of endothelial cell seeding plus antiplatelet medication is most efficacious in small-vessel grafting success and that high levels of prostacyclin production by vascular grafts are not necessary to maintain patency in dogs medicated with antiplatelet agents.

Endothelial cell--seeded four-millimeter Dacron vascular grafts: effects of blood flow manipulation through the grafts.

The objective of this study was to compare the surface thrombogenicities of endothelial cell-seeded small-diameter vascular grafts with those of nonseeded contralateral grafts under conditions of acute controlled low blood flows through the grafts in a canine carotid artery model. Autologous venous endothelial cells seeded in the preclots onto 6 cm sections of 4 mm (internal diameter) double-velour Dacron grafts covered 15% and 80% of graft luminal surfaces at 3 and 5 weeks postsurgically, respectively. Contralateral nonseeded control graft lumina had pannus ingrowth of endothelium across the anastomoses only. There were significant differences in initial carotid graft blood flow rates between seeded and control grafts at both 3 and 5 weeks postsurgically. When blood flow was reduced to 30% of the initial flow levels for 4 hours through these grafts, endothelial cell-seeded grafts maintained patencies and mean blood flow returned to 63.3% and 93% of initial flow levels at 3 and 5 weeks postsurgically, respectively. Few thrombi accumulated. In contrast, thrombi accumulated on nonseeded graft lumina during restricted blood flow. Some nonseeded grafts occluded during low flows, and the ratios of final flow to initial flow were only 28% at 3 weeks and 20% at 5 weeks in these nonseeded grafts. These data demonstrate the efficacy of seeding autologous endothelial cells on small-diameter grafts in this canine model. If technically successful, endothelial cell seeding may provide a protocol for enhancement of the long-term implantation success of small-diameter vascular grafts used for human vascular repair and replacements.

Small-diameter vascular prostheses: two designs of PTFE and endothelial cell-seeded and nonseeded Dacron.

Despite numerous advances in biomaterials design and utilization, the perfect artificial small-vessel substitute has yet to be developed. Dacron and expanded polytetrafluoroethylene (PTFE) are two materials potentially appropriate for use as small-vessel prostheses. We report the patencies of endothelial cell-seeded and nonseeded 4 mm I.D. Dacron grafts and two designs of nonseeded 4 mm I.D. PTFE (Gore-Tex and Impra) in the carotid position in dogs. All graft lengths exceeded the calculated maximum critical length for the material being tested. Dacron grafts, both endothelial cell-seeded and nonseeded, achieved higher patencies than both designs of PTFE. Endothelial cell-seeded Dacron grafts achieved the highest patencies. Endothelium was present to a significant extent only on endothelial cell-seeded Dacron grafts. There was little pannus ingrowth or midgraft pseudointima on nonseeded Dacron or on patent PTFE grafts although thrombus-free surface areas of patent PTFE grafts were high. These comparative data support the utility of endothelial cell seeding in achieving high patencies of small-diameter vascular grafts.