Airway obstruction can be better predicted using Global Lung Function Initiative spirometry reference equations in Marfan syndrome.

Marfan syndrome is a genetic disorder of the connective tissue, including involvement of the lungs.Pulmonary function test was performed in 32 asymptomatic adult Marfan patients using European Community for Coal and Steel (ECCS) and Global Lung Function Initiative (GLI) reference values.Using GLI equations for reference, significantly lower lung function values were noted for forced vital capacity (FVC) (87.0 ± 16.6% vs. 97.1 ± 16.9%; P < 0.01) and forced expiratory volume in the first second (FEV1) (79.6 ± 18.9% vs. 88.0 ± 19.1%; P < 0.01) predicted compared to ECCS. Obstructive ventilatory pattern was present in 25% of the cases when calculating with GLI lower limit of normal (LLN), and it was significantly more common in men as compared to women (n = 6, 50% vs. n = 2, 10%; P = 0.03).GLI is more suitable to detect early ventilatory changes including airway obstruction in young patients with special anatomic features, and should be used as a standard way of evaluation in asymptomatic Marfan population.

Regulatory T Cells Promote Natural Killer Cell Education in Mixed Chimeras.

Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in nonirradiated recipient mice conditioned with costimulation blockade and mammalian target of rapamycin inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade-resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation led to BM engraftment and persistent chimerism without Treg transfer but failed to induce skin graft tolerance. In contrast, the permanent absence of anti-donor NK reactivity in mice grafted with F1 BM was associated with both chimerism and tolerance comparable to Treg therapy, implying that NK cell tolerization is a critical mechanism of Treg therapy. Indeed, NK cells of Treg-treated BM recipients reshaped their receptor repertoire in the presence of donor MHC in a manner suggesting attenuated donor reactivity. These results indicate that adoptively transferred Tregs prevent BM rejection, at least in part, by suppressing NK cells and promote tolerance by regulating the appearance of NK cells expressing activating receptors to donor class I MHC.

The Immunosuppressive Effect of CTLA4 Immunoglobulin Is Dependent on Regulatory T Cells at Low But Not High Doses.

B7.1/2-targeted costimulation blockade (CTLA4 immunoglobulin [CTLA4-Ig]) is available for immunosuppression after kidney transplantation, but its potentially detrimental impact on regulatory T cells (Tregs) is of concern. We investigated the effects of CTLA4-Ig monotherapy in a fully mismatched heart transplant model (BALB/c onto C57BL/6). CTLA4-Ig was injected chronically (on days 0, 4, 14, and 28 and every 4 weeks thereafter) in dosing regimens paralleling clinical use, shown per mouse: low dose (LD), 0.25 mg (≈10 mg/kg body weight); high dose (HD), 1.25 mg (≈50 mg/kg body weight); and very high dose (VHD), 6.25 mg (≈250 mg/kg body weight). Chronic CTLA4-Ig therapy showed dose-dependent efficacy, with the LD regimen prolonging graft survival and with the HD and VHD regimens leading to >95% long-term graft survival and preserved histology. CTLA4-Ig's effect was immunosuppressive rather than tolerogenic because treatment cessation after ≈3 mo led to rejection. FoxP3-positive Tregs were reduced in naïve mice to a similar degree, independent of the CTLA4-Ig dose, but recovered to normal values in heart recipients under chronic CTLA4-Ig therapy. Treg depletion (anti-CD25) resulted in an impaired outcome under LD therapy but had no detectable effect under HD therapy. Consequently, the immunosuppressive effect of partially effective LD CTLA4-Ig therapy is impaired when Tregs are removed, whereas CTLA4-Ig monotherapy at higher doses effectively maintains graft survival independent of Tregs.

Necrotizing fasciitis in infancy: an uncommon setting and a prognostic disadvantage.

Necrotizing fasciitis is a potentially fatal, progressive soft tissue infection that typically occurs in adults, and only rarely occurs in infants. Although adults in whom necrotizing fasciitis develops are commonly diabetic, malnourished, or otherwise immunocompromised, infants in whom the disease develops are typically healthy and without clear predisposing factors. Herein, however, the authors report the case of an infant with compromised immunity secondary to the manifestations and treatment of panhypopituitarism, in whom postoperative necrotizing fasciitis developed after bilateral inguinal herniorrhaphy. The diagnosis, pathological mechanism, and treatment of necrotizing fasciitis are reviewed and the distinguishing features in infants are highlighted. The combination of a low incidence and very high mortality rate associated with necrotizing fasciitis in this subgroup strengthens the need for hypercritical suspicion. Early diagnosis and the prompt initiation of surgical treatment are the most essential means to improve on the prognosis for necrotizing fasciitis in infants.

Septic complications of hemorrhoidal banding.

Rubber band ligation is an efficacious and cost-effective alternative to conventional hemorrhoidectomy for symptomatic internal hemorrhoids. Even though the well-recognized complications of bleeding and thrombosis occur infrequently, far more serious septic complications have only recently been described, as evidenced in five of our patients: four cases were serious enough to necessitate surgical intervention, and one patient died. Pain followed by urinary dysfunction with or without toxic symptoms should alert the physician to the probability of localized perianal or systemic sepsis. Acute awareness of these rare but potentially life-threatening complications and immediate aggressive treatment is mandatory if death is to be prevented. Rubber band ligation of internal hemorrhoids need not be abandoned; however, the indications should be clear, the technique mastered, and a close patient follow-up maintained.

Presacral hematomas. Diagnosis and treatment.

A post-traumatic hematoma may present either acutely as a presacral collection or chronically as a retrorectal mass. A case of postpartum presacral hematoma and its management in the acute setting is described. A case of a chronic, calcified hematoma presenting as an asymptomatic retrorectal mass is also reported. CT scanning of the presacral space is the most accurate means of preoperative diagnosis. Therapy must be tailored to the preoperative diagnosis and to the size of the lesion.

Diverticulitis of the cecum and ascending colon.

Twelve cases of acute solitary diverticulitis of the cecum or ascending colon are reviewed. This is frequently indistinguishable from acute appendicitis preoperatively and is often mistaken for carcinoma at laparotomy. There are subtle clinical features that may help to suggest the diagnosis both before and during surgery. If diagnosed preoperatively, it can be treated effectively with broad spectrum antibiotics without surgical intervention. When diagnosed intraoperatively, hemicolectomy can often be avoided. Appendectomy should be done if resection is not performed.