RESUMO

Purified Clostridium histolyticum collagenase (CHC), an Food and Drug Administration-approved drug that does not affect nerves or blood vessels, was assessed as a potential treatment for fibroids in this proof-of-principle study. Fibroids (1-4 cm, capsules intact) and myometrial specimens from 5 patients were injected posthysterectomy with CHC or vehicle containing methylene blue and incubated for 24 hours. Percentage of collagen-stained area was estimated using Masson-Trichrome-stained slides. Collagen fibers were observed with picrosirius staining. Tissue stiffness was objectively measured by rheometry (complex shear modulus [Pa]). Injected materials spread within and beyond fibroids as visualized by methylene blue. Of the 8 treated fibroids, 7 were softened and some contained liquefied centers. Relative percentage of collagen-stained area (mean ± standard deviation) in treated fibroids (38 ± 12%; n = 7) was less than that in control fibroids (66 ± 17%; n = 5). Treated myometrium (40 ± 30% collagen; n = 3) was similar to control myometrium (53 ± 8%; n = 2). Picrosirius staining demonstrated loss of collagen fibers in treated fibroids. Treated fibroids were less stiff (3630 ± 2410 Pa; n = 4) than controls (5930 ± 830 Pa; n = 4). Treated and control myometrium had similar stiffness (2149 ± 927 Pa; n = 3 and 3314 ± 494 Pa; n = 2, respectively) and were never liquefied. In conclusion, injections of CHC into encapsulated fibroids are feasible and effective. Heterogeneity of collagen types and quantities within individual fibroids may contribute to varied responses and need additional investigation. Further study of collateral effects on myometrium is indicated. Injected CHC has potential for treatment of fibroids.

Assuntos

RESUMO

The objective of this study was to compare letrozole-stimulated cycles to natural cycles in 208 patients undergoing intrauterine insemination (IUI) between July of 2004 and January of 2007. Group I (n = 47) received cycle monitoring only (natural group), Group II (n = 125) received letrozole 2.5 mg/day on cycle days three to seven, and Group III (n = 36) received letrozole 5 mg/day on cycle days three to seven. There were no differences between the groups in endometrial thickness or P4 on the day of hCG. Estradiol levels had higher variation in the second half of the follicular phase in both letrozole-treated groups compared to the control group. Estradiol per preovulatory follicle was similar in both letrozole cycles to that observed in the natural cycles. LH was lower on the day of hCG administration in the letrozole 2.5 mg/day group vs. the natural group. In summary, letrozole results in some minor changes in follicular, hormonal and endometrial dynamics compared to natural cycles. Increased folliculogenesis and pregnancy rates were observed in the letrozole-treated groups compared to the natural group. These findings need to be confirmed in larger, prospective studies.

Assuntos

Assuntos

RESUMO

PURPOSE: Serum markers of inflammation and of glucose production are known to reflect the immediate metabolic response to injury. We hypothesized that monitoring of the early C-reactive protein (CRP) and blood glucose (BG) concentrations would correlate with clinical morbidity and outcome measures in pediatric trauma patients. METHODS: A five-year retrospective chart review of pediatric trauma patients admitted to our Level I pediatric trauma center was conducted to establish the relationships between early (first 3 hospital days) serum CRP and BG concentrations, Injury Severity Score (ISS), and hospital length of stay (HLOS). Statistical significance (P < 0.05) was determined using Student's t-test. RESULTS: Forty-two trauma patients (8.0 +/- 5.2 years) were evaluated. The early inflammatory response (CRP >or= 10 vs <10 mg/dl) was significantly correlated to the glycemic response (BG;121 +/- 24 vs 97.3 +/- 14.2 mg/dl, P < 0.05). Severely injured patients (ISS >or= 25 vs <25) were significantly more hyperglycemic (BG;156 +/- 56.9 vs 125 +/- 31.6 mg/dL, P = 0.003). Both increased inflammatory response (CRP;8.1 +/- 6.4 vs 2.5 +/- 3.5 mg/dL) and increased glycemic response (BG;111 +/- 15.9 vs 97.4 +/- 11.7 mg/dL) were independently and significantly associated with prolonged hospitalization (HLOS > 7 vs

Assuntos

RESUMO

A new chronic treatment for inherited disorders of long-chain fatty acid oxidation involves administering up to one-third of dietary calories as triheptanoin, a medium-odd-chain triglyceride (Roe CR, Sweetman L, Roe DS, David F, and Brunengraber H. J Clin Invest 110: 259-269, 2002). Heptanoate and C(5)-ketone bodies derived from its partial oxidation in liver are precursors of anaplerotic propionyl-CoA in peripheral tissues. It was hypothesized that increasing anaplerosis in peripheral tissues would boost energy production. In the present study, we tested the potential of a triheptanoin emulsion as an intravenous nutrient. Normal rats were infused with triheptanoin intravenously or intraduodenally at up to 40% of caloric requirement. The blood concentration ratio (heptanoate/C(5)-ketone bodies) was high with intravenous and low with intraduodenal triheptanoin infusion. During intravenous infusion of triheptanoin, lipolysis was stimulated but appeared compensated by fatty acid reesterification. During intraduodenal infusion of triheptanoin, lipolysis was not stimulated. Our data support the hypothesis that intravenous triheptanoin could be used to treat decompensated patients with long-chain fatty acid oxidation disorders.

Assuntos