Elevated platelet P-selectin expression and platelet activation in high risk patients with uncontrolled severe hypertension

BACKGROUND: Uncontrolled severe hypertension is associated with alarming rates of cardiovascular events but the mechanisms of vascular injury are not well understood. Recent investigative interest has focused on platelet activation and platelet P-selectin (CD62P) as direct mediators of vascular inflammation and injury. We investigated the association of extreme blood pressure (BP) elevation with platelet P-selectin and fibrinolytic markers in high risk patients with severe hypertension. METHODS: Cross-sectional comparison of platelet CD62, tissue plasminogen activator antigen (tPA), and plasminogen activator inhibitor-1 activity (PAI-1) among 3 BP groups: untreated severely hypertensive patients (SHT; n=18), untreated mildly hypertensive patients (MHT; n=19), and normotensive controls (NT; n=16). RESULTS: Platelet CD62 was greatest in SHT (p=0.00008) and showed a strong correlation with both systolic (p=0.0002, r=0.52) and diastolic (p=0.0003, r=0.52) BP. tPA was greater in SHT than MHT or NT (ANOVA; p=0.02) and correlated with diastolic BP but not SBP. PAI-1 did not correlate with either SBP or DBP but was related to body mass index, diabetes, and dyslipidemia. CONCLUSIONS: Platelet CD62 demonstrated a strong and graded association with both systolic and diastolic BP that persisted in the presence of multiple concomitant risk factors. The association of BP with CD62P was stronger than with either PAI-1 or tPA-Ag. Platelet activation and platelet CD62 increase in a BP-dependent manner and this relationship persists at extreme levels of BP. Platelet activation and platelet CD62 may participate in the accelerated target organ injury observed in high risk patients with severe hypertension.     

Campath induction for kidney transplantation: report of 297 cases

OBJECTIVE: To evaluate 297 adult renal transplantation patients who received Campath-1H-based induction protocol. METHODS: Single center Institutional Review Board approved retrospective chart review of 297 patients who received alemtuzumab induction between November 2003 and December 2005. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and rapidly tapered solumedrol with few exceptional cases. The mean patient follow-up was 362 days. All rejection episodes were biopsy confirmed. Posttransplant infection rates were recorded. RESULTS: There were 153 living donor and 144 deceased donor recipients. One-year survival rates for recipient and kidney allografts were 100% and 98% for living donors, 97.4% and 89.7% for non-extended criteria donors (ECD) deceased donors, and 85.7% and 89.3% for ECD deceased donors. The overall rejection rate was 7%. Overall infectious rate was 19.8%. We had no cases of posttransplant lymphoproliferative disease. Of the 289 recipients discharged off prednisone, 269 (93%) remain steroid free. CONCLUSION: Alemtuzumab and reduced dosages of tacrolimus and mycophenolate without long-term steroids can achieve low rates of rejection and excellent graft and patient survival without excessive risk of infection or malignancy. There is still a need for large randomized trials with long-term follow-up to determine its exact role in solid organ transplantation.     

Tissue damage in cattle infected with Theileria annulata accompanied by metastasis of cytokine-producing, schizont-infected mononuclear phagocytes

The distribution of schizont-infected cells in six calves undergoing acute, lethal sporozoite-induced infections with Theileria annulata was examined, the calves being killed in the early, middle or late stages of disease. A combination of histological and immunocytochemical techniques showed that schizont-infected cells became disseminated rapidly through the lymphoid tissues from the prescapular lymph node draining the site of inoculation to distant lymph nodes (e.g., precrural, mesenteric and mediastinal) and to the spleen and thymus. The parasitized cells also spread rapidly into non-lymphoid organs, being found in the liver, kidney, lung, abomasum, adrenal glands and pituitary gland by day 7, in the brain by day 12 and in the heart by day 14 after infection. As infection progressed, the schizonts differentiated into merozoites. By the late stages of disease, the cells containing merozoites greatly out-numbered schizont-infected cells. The parasitized mononuclear cells were labelled by antibodies to bovine interferon-alpha1 and tumour necrosis factor-alpha and, during the later stages of the disease, contained erythrocytes parasitized by piroplasms. The results suggested that the parasitized mononuclear cells themselves played a role in the development of clinical disease and in tissue damage. These findings provide new evidence that tropical theileriosis can no longer be viewed as a lymphoproliferative disease resulting from the uncontrolled multiplication and metastasis of lymphoid cells infected with T. annulata schizonts, but is caused by a parasite that lives in, and is disseminated by, cytokine-secreting, proliferating mononuclear phagocytes.     

Visceral/renal artery debranching for complex thoracoabdominal hybrid procedures via retroperitoneal abdominal aortic exposure: a preliminary report

Visceral/renal artery debranching can lengthen the distal landing zone in patients with complex thoracoabdominal aortic disease, thus enabling endograft repair. Initial reports of "hybrid" procedures are promising, but they usually describe transperitoneal visceral/renal artery exposure. This clinical series describes four complex thoracoabdominal aortic aneurysm/dissection cases in which the visceral and renal artery debranching procedure was accomplished via a retroperitoneal approach.     

Localization of arm representation in the cerebral peduncle of the non-human primate

Motor deficit severity and the potential for recovery in patients with brain injury depend on the integrity of descending corticofugal projections. Clinical assessment of these conditions following subtotal brain trauma requires a comprehensive understanding of the anatomical structures involved in the lesion as well as those structures that are spared. To assist in this endeavor, we investigated motor fiber organization in the crus cerebri of the cerebral peduncle (ccCP) in the rhesus monkey. Fibers originating from the arm representations of the primary (M1), supplementary (M2), rostral cingulate (M3), caudal cingulate (M4), dorsolateral pre- (LPMCd) and ventrolateral pre- (LPMCv) motor cortices were studied. The projections from the frontal and cingulate motor cortices formed descending longitudinal bundles that occupied the medial three-fifths of the ccCP at superior and middle levels. Although considerable overlap characterized these corticofugal projections, a general topography was discernable. Fibers from M1 and M4 occupied the central subsector of the ccCP, and fibers from M3 resided medially. The main distribution of LPMCd, LPMCv, and M2 fibers occupied the centromedial region and overlapped extensively. Progressing inferiorly, all fiber bundles in the central and centromedial sectors gradually extended medially, and overlap increased. A common location of fiber passage occurred at the midbrain-pontine isthmus where all of the fiber bundles overlapped. Our findings indicate that the widespread distribution of corticofugal motor projections may account for the favorable levels of motor recovery that accompany subtotal midbrain injury. At superior and mid-levels of the ccCP anteromedial lesions may disrupt projections from M3, whereas anterolateral lesions may disrupt projections from M1 and M4. Fibers from M2, LPMCv, and LPMCd may be compromised to some degree in both situations. The compact and commixed nature of motor fiber organization at inferior levels and the midbrain-pontine isthmus suggests a vulnerable region of passage for comprehensive disruption of frontal and cingulate corticofugal projection fibers.     

Antibodies with dual reactivity to plasminogen and complementary PR3 in PR3-ANCA vasculitis

Patients with inflammatory vascular disease caused by anti-neutrophil cytoplasmic autoantibodies (ANCA) can harbor antibodies not only to the autoantigen proteinase 3 (PR3) but also to complementary PR3 (cPR3(105-201)), a recombinant protein translated from the antisense strand of PR3 cDNA. The purpose of this study was to identify potential endogenous targets of anti-cPR3(105-201) antibodies. Patients' plasmapheresis material was tested for the presence of antigens reactive with affinity-purified rabbit and chicken anti-cPR3(105-201) polyclonal antibodies. Antigen-containing fractions were tested with patients' anti-cPR3(105-201) affinity-purified IgG, and putative protein targets were sequenced by mass spectrometry. Unexpectedly, plasminogen was identified as a target of anti-cPR3(105-201). Reactivity of affinity-purified antibodies from two patients was lost when plasminogen was converted to plasmin, indicating restricted specificity. Antiplasminogen antibodies from five patients bound plasminogen at a surface-exposed loop structure within the protease domain. This loop contains an amino acid motif that is also found in a portion of recombinant cPR3(105-201); site-directed mutagenesis of this sequence decreased antibody reactivity by 30%. Functionally, antiplasminogen antibodies delayed the conversion of plasminogen to plasmin and increased the dissolution time of fibrin clots. Serologically, antiplasminogen antibody levels were higher in PR3-ANCA patients (n = 72) than healthy control subjects (n = 63), myeloperoxidase-ANCA patients (n = 34), and patients with idiopathic thrombosis (n = 57; P = 0.001). Of the patients with PR3-ANCA, nine had documented deep venous thrombosis events, five of whom were positive for antiplasminogen antibodies. In summary, capitalizing on interactions with complementary proteins, specifically complementary PR3, this study identified plasminogen as a previously undescribed autoantigen in PR3-ANCA vasculitis.     

Colonic resection in the setting of damage control laparotomy: is delayed anastomosis safe?

Based on a large body of literature concerning the subject, trauma surgeons are becoming more comfortable with anastomosis rather than stoma creation in patients with destructive colon injuries requiring resection. This literature was largely generated before the widespread acceptance of the importance of damage control laparotomy (DCL). Thus, when such injuries occur in patients initially left in colonic discontinuity after DCL, the question of anastomosis versus stoma becomes more difficult, and there are no data to guide management decisions. The goal of this report is to describe the results of our early experience with delayed anastomosis (DA) after destructive colon injury in the setting of DCL. We reviewed the records of patients with destructive colon injuries at our Level I trauma center over a 5.5-year period for demographics, injury characteristics, and outcome. Studied outcomes included anastomotic leak, intra-abdominal abscess, and colon injury-related death. The decision to proceed with DA was based on individual surgeon opinion at the time of re-exploration. From January 1, 2000 to July 31, 2006, 92 patients sustained colon injury, 55 of which required resection (31 blunt mechanism and 24 penetrating). Twenty-two resections occurred in the setting of DCL. Six of these patients underwent stoma creation and 11 underwent DA. Three died before reoperation, and two had an anastomosis created during the initial DCL. The remaining 33 resections occurred during initial definitive operation, and 21 underwent anastomosis, whereas 12 had a stoma created. Comparing the 11 patients undergoing DA with the 21 undergoing immediate anastomosis, the anastomotic leak rate (0% vs 5%), abscess rate (36% vs 24%), and colon related-death rate (9% vs 0%; all P > 0.05) were similar. Six patients undergoing DA had a right hemicolectomy with ileocolonic anastomosis, four had a segmental left colon resection, and one had a near total abdominal colectomy with ileosigmoid anastomosis. Delayed anastomosis of colon injuries after DCL is safe in selected patients and has a similar complication rate as resection and anastomosis performed during initial definitive operation. DA avoids stoma creation in some patients who are not candidates for anastomosis during initial DCL. To our knowledge, this represents the first reported series of DA after DCL, an area in which further work is needed to carefully define indications for the safe application of this concept.     

Pathologic effects of testosterone deprivation

PURPOSE OF REVIEW: Androgen deprivation therapy remains the cornerstone of treatment for advanced prostate cancer. There are significant adverse effects associated with prolonged androgen deprivation therapy, with recent findings associating it with the metabolic syndrome and its associated health risks. RECENT FINDINGS: A review of the adverse pathologic effects of testosterone deprivation is performed. Recent findings associate androgen deprivation therapy with endocrine and metabolic disarray, specifically the metabolic syndrome, resulting in increased rates of diabetes and myocardial infarction in patients on testosterone deprivation. SUMMARY: The increased incidence of the metabolic syndrome in patients receiving androgen deprivation therapy and the associated morbidity and possibly mortality require significant investigation into alternatives to complete testosterone deprivation and ways to counteract these adverse effects.     

Prophylactic mesh to prevent incisional hernia: A note of caution

Background

Ventral hernia is a common complication of open Roux-en-Y gastric bypass (RYGB). The aim of this study was to determine whether prophylactic mesh placement during RYGB would reduce the incidence of postoperative hernias.

Methods

Obese patients undergoing RYGB by a single surgeon had prosthetic mesh placed in a subfascial location at the conclusion of the procedure. The incidences of recurrent hernia and morbidity associated with the placement of mesh were assessed.

Results

Sixteen patients underwent RYGB with prophylactic mesh placement over 6 months. The average preoperative body mass index was 46.6 kg/m². Half of the patients were diabetics. None were smokers. During mean follow-up of 6 months, 4 patients (25%) required mesh excision, 3 for infection and 1 for a persistently symptomatic seroma. One patient was explanted incidentally in the course of reexploration for intractable nausea and vomiting. Another developed an incisional hernia despite prophylactic mesh.

Conclusions

In the investigators' experience, the use of prophylactic new-generation mesh at the time of open RYGB led to an unacceptable rate of local complications. They caution against this technique in patients undergoing open RYGB.