DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect?

The clinical spectrum of leprosy is related to patients' immune responses. Non-responsiveness towards Mycobacterium leprae (ML) seems to correlate with a Th2 cytokine profile. The reason for such a polarized immune response remains unclear. The C-type lectin, DC-SIGN, expressed by subsets of dendritic cells (DCs) and macrophages, has previously been associated with Th2 responses. Here we show abundant DC-SIGN expression in lepromatous but not borderline tuberculoid leprosy, in both HIV-positive and HIV-negative patients. Moreover, we demonstrate that DC-SIGN can act as an entry receptor for ML, as it does for M. tuberculosis, through the cell wall component lipoarabinomannan. DC-SIGN is expressed on virtually all ML-containing cells, providing further evidence for its role as a receptor. DC-SIGN may therefore be induced on macrophages in lepromatous leprosy and may then contribute to mycobacterial entry into these cells.

Multi-sequence in vivo MRI can quantify fibrous cap and lipid core components in human carotid atherosclerotic plaques.

OBJECTIVES: Risk of thrombo-embolic stroke is thought to be better reflected by carotid plaque composition than by luminal stenosis. We set out to determine whether high resolution MRI was a valid method of quantifying plaque components in vivo. DESIGN: A prospective cohort study validating in vivo MRI against histological analysis of excised carotid plaques. MATERIALS: Twenty-five recently symptomatic patients with severe internal carotid artery stenosis underwent pre-operative in vivo multi-sequence MRI of the carotid artery using a 1.5 T system. METHODS: Individual plaque constituents were characterized on axial MR images according to net signal intensities. Analysis of fibrous cap and lipid core content was quantified proportional to overall plaque area. Bland-Altman plots were generated, and intra-class coefficients computed to determine the level of agreement between the two methods and inter-observer variability. RESULTS: The intra-class correlation coefficients between two MR readers were 0.94 and 0.88 for quantifying fibrous cap and lipid core components, respectively. There was good agreement between MR and histology derived quantification of both fibrous cap and lipid core content; the mean % difference for fibrous cap was 0.75% (+/-2.86%) and for lipid core was 0.86% (+/-1.76%). CONCLUSION: High resolution carotid MRI can be used to quantify plaque components and may prove useful in risk stratification.

Histopathology of cardiac xenograft rejection in the pig-to-baboon model.

BACKGROUND: The use of pig organs transgenic for human decay accelerating factor (hDAF) has largely overcome the problems of hyperacute rejection. With improved immunosuppressive protocols, life supporting grafts are showing greater survival times bringing the possibility of clinical xenotransplantation closer. Examination of the histopathology of the rejection process provides insight into the underlying mechanism and may suggest ways in which new immunosuppressive strategies should be directed. METHODS: 44 baboons (Papio anubis) underwent heart transplants of which 39 were from transgenic donors. The transplanted organs were examined histologically and stained for evidence of immunoglobulin and complement deposition as well as cellular infiltrates. RESULTS: In the transgenic animals survival times were 2 to 99 days (mean 23.5) and the heterotopic group and 1 to 39 days (mean 11.7) in the orthotopic group. There were 3 cases of hyperacute rejection between the 2 groups. Rejected organs showed areas of old and recent myocardial infarction associated with vascular thrombosis. There was widespread deposition within vessels of immunoglobulins IgM and IgG together with complement fractions C3 and C5b to 9 in those organs that were rejected. The amount of complement positive in the longer surviving organs was less than those rejecting early. Cellular infiltate was predominantly macrophage with some later appearing T or natural killer cells. CONCLUSIONS: The histopathological changes support the importance of immunoglobulin and complement in delayed xenograft or acute vascular rejection. With time there is an increase in cellular infiltrate predominantly macrophages and these findings suggest an increasingly important role for the cells and the rejection process. The presence of areas of infarction and underlying vascular thrombosis is in keeping with endothelial activation and the establishment of procoagulant phenotype which may be due to immunoglobulin, complement, secreted cytokines and direct cellular effects.

Hyperacute lung rejection in a pig-to-human transplant model: the role of anti-pig antibody and complement.

BACKGROUND: The physiology of hyperacute rejection of pig lung by human blood and the role of antispecies antibody and complement in this phenomenon have not previously been characterized. METHODS: Human blood was perfused through an ex vivo pig heart-lung preparation. In the treatment groups, blood was either unmodified or modified to deplete alternative pathway complement (heat treatment), anti-pig antibody, or both. Control experiments were performed with unmodified and heat-treated pig blood. Physiologic parameters, organ survival, and immunohistology were the primary outcome measures assessed. RESULTS: Pig lung was consistently damaged by human blood within 45 min (median 20 min), as evidenced by elevated pulmonary vascular resistance and parenchymal injury. Immunohistologic studies of perfused lungs showed prominent deposition of IgM and classical pathway component, C4, and weaker deposition of alternative pathway component, properdin. Heat treatment did not impede the rise in pulmonary vascular resistance or significantly prolong survival. Depletion of anti-pig antibody prolonged survival (median 90 min) and attenuated the rise in pulmonary vascular resistance. Antibody absorption, combined with heat treatment of plasma, prevented the elevation in pulmonary vascular resistance and yielded median graft survival (210 min) similar to pig blood perfusion (approximately 240 min). CONCLUSIONS: These results show that elevated pulmonary vascular resistance and pulmonary parenchymal injury are mediated at least in part by antispecies antibody and heat-sensitive pathways. They are consistent with the hypothesis that complement activation contributes significantly to acute lung damage in the pig-to-human species combination.

Long-term results of breast conservation therapy for breast cancer.

OBJECTIVE: This study was done to determine the long-term outcome of breast conservation therapy (BCT) for patients with early-stage breast cancer during a period of treatment evolution at a single institution. SUMMARY BACKGROUND DATA: Breast cancer treatment has evolved from extensive surgical extirpation of the breast to treatment options that conserve the breast. Prospective and retrospective studies have confirmed the efficacy of BCT and justify its use for many patients with early breast cancer, but there is no universally accepted consensus as to who benefits from more aggressive application of surgery or radiotherapy in BCT. Prognostic variables for breast cancer and information on factors that contribute to local recurrence help predict BCT results. Continued analysis of BCT still is necessary to improve patient outcome. METHODS: Eighty-five patients treated with BCT (lumpectomy with adjuvant radiation therapy) at the Medical College of Virginia from 1980 to 1990 were identified. Clinicopathologic parameters and treatment details were analyzed for relationship to development of local recurrence, distant metastasis, and survival. Fisher's exact test was used for comparisons. Actuarial survival curves were plotted. The earlier treatment period (1980-1985) was compared with the later treatment period (1985-1990). RESULTS: Median follow-up was 5 years. Actuarial overall survival was 83% at 5 years (69% at 10 years), and 5-year distant metastasis-free survival was 79%. The 5-year actuarial local recurrence rate was 6.6% (crude rate 10.6%, 9/85). Young patients (age < 40 years) were found to be at increased risk for local recurrence (24% < 40 years vs. 6% > or = 40 years, p < 0.05). Tumor margins < or = 3 mm were more frequently found, and lumpectomy site radiation boost was used increasingly from 1986 to 1990. Almost half of all local recurrences occurred after 5 years. CONCLUSIONS: Survival and local recurrence rates were comparable to other series. Young patients were found to be at increased risk for local recurrence. Negative microscopic margins, even when close, can provide low local recurrence rates when adjuvant radiation therapy is administered.

Complications of mastectomy and their relationship to biopsy technique.

BACKGROUND: Wound complication rates after mastectomy are associated with several factors, but little information is available correlating biopsy technique with the development of postmastectomy wound complications. Fine-needle aspiration (FNA) biopsy is an accurate method to establish a diagnosis, but it is unknown whether this approach has an impact on complications after mastectomy. METHODS: Charts of 283 patients undergoing 289 mastectomies were reviewed to investigate any association between biopsy technique and postmastectomy complications. RESULTS: The diagnosis of breast cancer was made by FNA biopsy in 50%, open biopsy in 49.7%, and core needle biopsy in 0.3%. The overall wound infection rate was 5.3% (14 of 266), but only 1.6% when FNA biopsy was used compared with 6.9% with open biopsy (p = 0.06). Among 43 patients undergoing breast reconstruction concomitantly with mastectomy, the infection rate was 7.1% (0% after FNA, 12% after open biopsy). Neither the development of a postoperative seroma (9.8%) nor skin flap necrosis (5.6%) was influenced by the biopsy technique used. CONCLUSIONS: These data suggest that wound infections after mastectomy may be reduced when the diagnosis of breast cancer is established by FNA biopsy.

How common is increased airway reactivity amongst the elderly?

A random sample of subjects over 65 years of age who had replied to a postal questionnaire on respiratory symptoms was asked to attend for lung function studies and, if fit, an inhaled methacholine bronchial challenge. Of 283 subjects, 180 (63.6%) agreed to attend. Most (98%) subjects performed reproducible spirometry, with no evidence of fatigue on repeated testing. However, 20 subjects were found to be unsuitable for challenge (forced expiratory volume in 1 s, (FEV1) < 1 litre or unable to perform spirometry reproducibly). The dose of methacholine producing a 20% fall in FEV1 was termed the PD20. A positive challenge with PD20 < 6.13 mumol methacholine was found in 69 of 160 (43%) subjects studied, with highly reactive airways (PD20 < 1.0 mumol methacholine) in 19 of 160 (12%). Bronchial hyperreactivity, which is closely associated with clinical asthma, was found to be far more common amongst the elderly than previously recognised. Low initial FEV1 (1-1.5 litres) predisposed to both a positive challenge (p < 0.01) and also to highly reactive airways (p < 0.01), generally associated with respiratory symptoms. Subjects with low (1-1.5 litres) baseline FEV1 were five times more likely to have highly reactive airways than those with FEV1 > 1.5 litres, confirming a relationship between baseline airway calibre and bronchial reactivity. Early detection of subjects with low FEV1, who are therefore more likely to have increased airway reactivity, may help to reduce respiratory morbidity in the elderly with considerable benefit both to patients and to the Health Service.

Abortion and nursing: a legal update.

PIP: Almost 2 decades after the Supreme Court's landmark decision in Roe v. Wade, nurses' refusal to assist in abortions is still in question. There are about 1.6 million abortions a year. If Congress passes the Freedom of Choice Act, American women will be guaranteed continued access to abortion. But the effect of new regulations on 2 million nurses is the issue. Title VI of the Civil Rights Act of 1964 protects those who refuse to participate in abortions because of their religious beliefs. Several states have also enacted laws giving the right to health care workers to refuse to participate on ethical grounds. In Florida a staffer at an ambulatory care center was demoted after refusing to assist in an abortion. The appeals court ruled in the nurse's favor, stating that she should have been given a different assignment. Nurses who oppose abortion are advised by attorneys not to accept jobs where they are likely to be expected to assist in them. A New York City nurse refused to assist in an abortion and was reassigned to an administrative position, which she contested. The arbitrator restored her to her original position indicating that if the Freedom of Choice Act is passed it will not eliminate a nurse's right not to assist. In 1988 the so-called gag rule was issued barring caregivers at 4000 federally funded family planning clinics serving nearly 5 million women/year from recommending abortion to patients.^ieng