Body habitus as a predictor of injury pattern after blunt trauma.

The records of obese and nonobese victims of blunt trauma were compared to determine if obese individuals are predisposed to a specific injury pattern. Prospectively collected data on 6368 adults admitted to a level I trauma center over a 4-year period were analyzed. Twelve percent (743 patients) met Body Mass Index (weight/height2) criteria for obesity (greater than or equal to 30 kg/m2). The obese group was older (p less than 0.01) and had lower ISSs (p less than 0.05) and higher GCS scores (p less than 0.01). More obese patients were injured in vehicular crashes (62.7% vs. 54.1% [p less than 0.01]). The obese victims were more likely to have rib fractures, pulmonary contusions, pelvic fractures, and extremity fractures and less likely to have incurred head trauma and liver injuries (p less than 0.05). Obese people injured in vehicular crashes had a similar injury pattern with no difference in seating position, direction of impact, seat belt use, and ejection.     

Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.

BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.     

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10⁻⁴M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.     

Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity

T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class II MHC I-Au, recognition of the MHC is dominated by the Vbeta domain of the TCR, which interacts with the MHC alpha chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly prefers the native MBP contact residues. We suggest that while TCR scanning of pMHC may be degenerate due to the TCR germline bias for MHC, recognition of structurally distinct agonist peptides is not indicative of TCR promiscuity, but rather highly specific alternative solutions to TCR engagement.     

Traumatic rupture of the thoracic aorta: Should one always operate immediately?

Although the traditional therapy for blunt traumatic rupture of the thoracic aorta (TRA) is immediate operative repair, there may be a selective role for delayed repair, particularly in patients with head trauma, respiratory failure, or cardiac dysfunction. The present study examines the hypothesis that TRA can be managed by selective delayed operative repair. Clinical data were collected from 59 consecutive patients with TRA at a regional trauma unit. All TRAs were at the aortic isthmus. Patients were retrospectively classified into three groups: group I (n=12) included patients who either arrived in extremis or rapidly became unstable during triage; group II (n=3) included patients who had no contraindications to early repair and underwent repair at the time of diagnosis; and group III (n=44) consisted of patients who because of concomitant injuries or sepsis required initial admission and management in the intensive care unit until their clinical status had improved sufficiently to allow for deliberate delayed operative repair of the TRA. The delay ranged from 1 day to 7 months. Eight patients have yet to undergo repair and remain well at follow-up from 1 to 4 years. Overall survival rates in groups I, II, and III were 17%, 100%, and 82%, respectively. The surgery-related mortality rate in group III was 10% (three patients). Only two (4.5%) patients in group III died as a result of a ruptured aorta within 72 hours of admission. In conclusion, contrary to surgical doctrine, TRA may not require immediate operative repair in all cases, but may instead be managed selectively depending on the patient's clinical status.     

Regression of uterine leiomyomas after treatment with gestrinone, an antiestrogen, antiprogesterone

Ninety-seven women, aged 18 to 53 years, with uterine leiomyomas diagnosed by bimanual palpation and ultrasonography, were treated for 4 to 13 months with gestrinone, a potent steroidal, antiestrogen, antiprogesterone. Thirteen women were less than 30 years old and six 50 years old or older. Forty-six women were 30 to 40 years old and 32 others were 40 to 50 years old. Sixty-one women were nulliparous. Patients were divided in a random fashion into three groups according to treatment schedule. In group A, 34 patients received capsules containing 5 mg of gestrinone twice weekly. In group B, 36 patients received 2.5 mg capsules three times weekly. In group C, 27 patients were instructed to insert 2.5 mg tablets in the vagina three times weekly. Uterine volume was measured by ultrasonography before and at the end of treatment. At the end of 4 months, uterine volume fell from 303 to 251 cm3 in group A, from 361 to 266 cm3 in group B, but increased from 371 to 387 cm3 in group C. For those patients treated for 10 (+/- 1) months, mean uterine volume fell from 368 to 282 cm3 in group A and from 384 to 327 cm3 in group B, but increased from 262 to 290 cm3 in group C. Mean uterine volume of patients who were treated for 13 (+/- 1) months also fell from 325 to 259 cm3 in group A, from 416 to 268 cm3 in group B, and from 406 to 399 cm3 in group C. Changes in uterine volume measured at the time of discontinuation for the various groups revealed volume decrease in 71 and increase or no change in 26. Differences between groups A, B, and C were statistically significant when comparisons were made at 4 and 13 months. Uterine bleeding ceased by the second month of treatment in half the patients initially complaining of menometrorrhagias. After 4 months of treatment, 95% of the women were amenorrheic. Hemoglobin increased in 85 of 90 patients for whom values were available before treatment began. Both dyspareunia and chronic pain were significantly reduced by the gestrinone treatment. Androgenic side effects such as seborrhea, acne, and hirsutism, whenever they occurred, were benign and reverted soon after discontinuing the medication.     

Gab1, SHP2, and protein kinase A are crucial for the activation of the endothelial NO synthase by fluid shear stress

Fluid shear stress enhances NO production in endothelial cells by a mechanism involving the activation of the phosphatidylinositol 3-kinase and the phosphorylation of the endothelial NO synthase (eNOS). We investigated the role of the scaffolding protein Gab1 and the tyrosine phosphatase SHP2 in this signal transduction cascade in cultured and native endothelial cells. Fluid shear stress elicited the phosphorylation and activation of Akt and eNOS as well as the tyrosine phosphorylation of Gab1 and its association with the p85 subunit of phosphatidylinositol 3-kinase and SHP2. Overexpression of a Gab1 mutant lacking the pleckstrin homology domain abrogated the shear stress-induced phosphorylation of Akt but failed to affect the phosphorylation or activity of eNOS. The latter response, however, was sensitive to a protein kinase A (PKA) inhibitor. Mutation of Gab1 Tyr627 to phenylalanine (YF-Gab1) to prevent the binding of SHP2 completely prevented the shear stress-induced phosphorylation of eNOS, leaving the Akt response intact. A dominant-negative SHP2 mutant prevented the activation of PKA and phosphorylation of eNOS without affecting that of Akt. Moreover, shear stress elicited the formation of a signalosome complex including eNOS, Gab1, SHP2 and the catalytic subunit of PKA. In isolated murine carotid arteries, flow-induced vasodilatation was prevented by a PKA inhibitor as well as by overexpression of either the YF-Gab1 or the dominant-negative SHP2 mutant. Thus, the shear stress-induced activation of eNOS depends on Gab1 and SHP2, which, in turn, regulate the phosphorylation and activity of eNOS by a PKA-dependent but Akt-independent mechanism.