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Topical lidocaine-prilocaine cream (EMLA) versus local infiltration anesthesia for radial artery cannulation.

UNLABELLED: In a randomized trial, we compared topical anesthesia by a lidocaine-prilocaine cream (EMLA; Laboratorie ASTRA, Manterre, France) with subcutaneous local lidocaine infiltration for radial artery cannulation. Patients included 538 adults scheduled for coronary angiography using a radial approach. EMLA was applied 2 h before radial cannulation, and lidocaine infiltration was performed 5 min before cannulation. The primary end point was pain as assessed by a verbal numerical scale (0 = no pain, 10 = extreme pain). Pain was less severe in the EMLA group than in the lidocaine infiltration group (Score of 2 vs 7; P = 0.0001). Additional lidocaine infiltration was required significantly less frequently in the EMLA group (relative risk 0.19). The failure rate of cannulation was significantly lower in the EMLA group (relative risk 0.38), and insertion time was shorter (4 versus 6 min). We conclude that EMLA, compared with lidocaine infiltration, reduces pain associated with radial artery cannulation and improves the success rate of the procedure. Routine application of EMLA should be performed in awake patients 2 h before radial artery cannulation. IMPLICATIONS: In a randomized trial, we compared topical anesthesia by a lidocaine-prilocaine cream (EMLA) with subcutaneous local lidocaine infiltration for radial artery cannulation in 538 adults patients. EMLA reduced pain associated with radial artery cannulation and improved the success rate of the procedure.

Adult↗

The influence of scalp infiltration with bupivacaine on hemodynamics and postoperative pain in adult patients undergoing craniotomy.

UNLABELLED: After craniotomy, hypertension may contribute to intracerebral hemorrhage. We studied whether scalp infiltration with bupivacaine during craniotomy reduces postoperative pain and hypertension. In a double-blind fashion, 36 adult patients (ASA physical status II or III) undergoing elective craniotomy were randomly assigned to receive scalp infiltration with either bupivacaine (0.25%) and epinephrine (1:200,000) or saline/ epinephrine (1:200,000) for skeletal fixation, skin incision, and wound closure. Heart rate (HR) and mean arterial pressure (MAP) were measured after anesthesia induction, after skull-pin insertion, after scalp infiltration, during dural closure, during skin closure, on admission to postanesthesia care unit (PACU), and 1 h after admission. Visual analog pain scores were recorded in the PACU. MAP was significantly greater in the saline group at scalp infiltration. HR was significantly faster in the saline group at dural and skin closure. The bupivacaine group reported significantly less pain than the saline group at PACU admission and 1 h after admission. Pain scores did not correlate with hemodynamic measurements. We conclude that scalp infiltration with 0.25% bupivacaine with 1:200,000 epinephrine blunts certain intraoperative hemodynamic responses and reduces postoperative pain but has no effect on postoperative hemodynamics. IMPLICATIONS: We sought to evaluate whether scalp infiltration with bupivacaine and epinephrine at the beginning and end of craniotomy would afford more intra- and postoperative hemodynamic stability and influence immediate postoperative pain. We found that intraoperative hemodynamics were not influenced greatly; however, craniotomy patients do have significant postoperative pain, which does not seem to have an influence on hemodynamics in the postanesthesia care unit.

Adolescent↗

Nerve blocks versus subcutaneous infiltration for stereotactic frame placement.

In this unblinded, randomized controlled trial, we compared supraorbital and greater occipital nerve blocks with subcutaneous infiltration for anesthesia during the placement of a stereotactic head-frame. Twenty consecutive patients scheduled for functional surgery to treat Parkinson's disease were studied. Each patient received supraorbital and greater occipital nerve blocks on one side of the head and subcutaneous infiltration on the other, thereby acting as their own control. Pain was assessed by visual analog scale pain scores (scale: 0-100) for both local anesthetic injection and stereotactic pin placement. Supplementary subcutaneous infiltration was also recorded. Results are presented as mean +/- SD. Nerve blocks were significantly less painful than subcutaneous infiltration of local anesthetic at both the frontal (34 +/- 24 vs 49 +/- 25) and occipital (34 +/- 21 vs 49 +/- 23) sites. Neither technique was superior in preventing pain associated with pin placement, at either the frontal site (48 +/- 27 vs 46 +/- 24) or occipital site (33 +/- 27 vs 32 +/- 24). Supraorbital nerve blocks required significantly more supplementation than either greater occipital nerve blocks or subcutaneous infiltration. Visual analog scale pain scores were greater at local anesthetic injection and pin placement than at any subsequent time. We conclude that supraorbital and greater occipital nerve blocks are an alternative to subcutaneous infiltration for the placement of a stereotactic frame.

Administration, Cutaneous↗

Pathogenesis and treatment of "sterile" midperipheral corneal infiltrates associated with soft contact lens use.

PURPOSE: To demonstrate the sterile nature of presumed sterile midperipheral corneal infiltrates associated with soft contact lens (SCL) use and to show that withholding antibiotics or the occasional use of a topical corticosteroid alone may, with strict guidelines, have a role in the treatment of this entity. METHODS: Nine consecutive patients presenting with typical midperipheral corneal infiltrates after SCL wear were seen in the office (O.H.D.) during a 2-year period, 1996-1998. All patients were initially placed on topical fluorometholone as the only treatment. RESULTS: Eight of the nine patients experienced a rapid relief of symptoms and the infiltrates were noted to be smaller and less dense in 3-4 days. Therapy was discontinued after 7 days, by which time the lesions had cleared. The ninth patient developed a microbial keratitis from which Pseudomonas aeruginosa was cultured. With appropriate therapy, visual acuity returned to 20/25. Two different algorithms are offered for the treatment of a putative sterile infiltrate associated with SCL use. CONCLUSION: The use of a topical corticosteroid alone may have a role in the treatment of presumed sterile midperipheral corneal infiltrates associated with SCLs when strict guidelines are followed. Such therapy suggests that the infiltrates are not the result of infection.

Adult↗

Local gene delivery within the media of rabbit iliac arteries by using the infiltrator intramural delivery device.

Percutaneous transluminal angioplasty continues to be limited by restenosis. Prevention of restenosis is now focusing on local delivery of therapeutic agents, such as proliferation-inhibiting genes, directly to the site of arterial injury. We evaluated use of the Infiltrator catheter (IVT, San Diego, CA. U.S.A.) for gene delivery within the arterial media. The goals of our study were to evaluate the histologic effects of the injection and the suitability of the Infiltrator catheter for local delivery of viral therapy. We injected the femoral arteries of 21 New Zealand White rabbits. Six animals were used for an evaluation of the intramural distribution of dextran/rhodamine injected via the Infiltrator catheter. In seven animals, injection site histology and in vitro vasoreactivity were studied after an injection of saline. In the remaining eight animals, a replication-deficient adenovirus encoding for the firefly luciferase gene (Ad RSVLuc) was injected, and luciferase activity was quantified 3 and 8 days later. After injection via the Infiltrator catheter, the fluorescent tracer was distributed throughout the entire circumference and width of the arteries. Histologic examination showed minimal damage with partial endothelial abrasion and disruption of the internal elastic lamina confined to the penetration sites. In vitro endothelium-dependent vasodilation was present at a reduced level after injection via the Infiltrator (maximal endothelium-dependent acetylcholine-induced relaxation, 51.5 +/- 7.4% vs. 23.8 +/- 14.6%; p < 0.05). Significant luciferase expression was found in all the arteries, with a significant increase from day 3 to day 8 (5,392.5 +/- 2,300 vs. 2,012 +/- 471 cpm/mg; p < 0.05). These data obtained in a rabbit iliac artery model show that the Infiltrator catheter is an efficient and safe local intramural delivery device that provides significant transgene expression in the arterial wall without causing significant structural damage.

Adenoviridae↗

A prospective study of nerve root infiltration in the diagnosis of sciatica. A comparison with radiculography, computed tomography, and operative findings.

Fifty nerve root infiltration studies were evaluated prospectively in a consecutive series of 50 patients referred to the Sheffield Problem Back Clinic with complicated back problems. All were over 35 years of age (mean, 51 years). Ten (20%) demonstrated abnormal segmentation of the lumbar spine. Sixteen (32%) had undergone previous surgery. Before nerve root infiltration all patients were investigated by radiculography and computed tomography. Nerve root infiltration identified two types of response. In 20 patients, infiltration reproduced the symptomatic pain, which then was abolished by local anesthetic--the positive result. These patients were considered suitable for surgery. One patient in this group had spontaneous resolution of pain and thus did not undergo operative treatment. In 30 patients, infiltration did not reproduce the symptomatic pain regardless of the level studied, or only partially reproduced the pain at two or more levels--the negative result. Radiculography and computed tomography in these patients also was inconsistent. This group were considered unsuitable for surgery. In those patients undergoing surgical decompression, nerve root infiltration correctly identified the symptomatic level in 18 of the 19. Computed tomography and radiculography identified the level in 14 and 12 patients, respectively.

Contrast Media↗

Direct evidence of a functional separation of alloreactive T lymphocytes from bystander cells infiltrating rat allografts. Interleukin 2 receptor-positive cells reacting with the monoclonal antibody ART 18 mediating second-set rejection.

In this study we examined the functional capacity of unseparated, IL-2R positive and IL-2R negative leukocytes infiltrating BN rat hearts or kidneys grafted into allogeneic LEW rats. Upon adoptive transfer into syngeneic LEW recipients, splenocytes or day-3 graft infiltrate cells of either cardiac or renal transplants were ineffective to alter BN cardiac test graft survival (controls 7.8 +/- 0.8 day). However, adoptive transfer of day-5 heart infiltrate cells resulted in a delay of test graft rejection (9.4 +/- 0.7 day, P less than 0.001), while day-5 kidney-graft-infiltrating cells produced second set rejection (6.2 +/- 0.5, P less than 0.001). Specificity controls of day-5 cells infiltrating DA heart or kidney grafts rejected at 7.8 +/- 0.8 or 7.7 +/- 0.5 days. Following separation into IL-2R positive and negative subpopulations by use of the mAB ART 18, IL-2R positive but not IL-2R negative cells caused second set rejection in both the renal and the cardiac model (6.2 +/- 0.4, respectively, 6.3 +/- 0.5 days, P less than 0.001 or P less than 0.005). Furthermore, in the kidney model IL-2R positive nylon-wool nonadherent cells also caused second set rejection (6.2 +/- 0.4, P less than 0.005) suggesting that IL-2R positive T cells present in the graft at maximal infiltration are the mediators of rejection. Thus, it appears that these cells can be phenotypically and functionally separated from bystander cells.

Animals↗

The influence of MHC and non-MHC genes on the nature of murine cardiac allograft rejection. I. Kinetic analysis of mononuclear cell infiltrate and MHC-class I/class II expression in donor tissue.

While normal cardiac tissue expresses low levels of MHC-class I, undetectable levels of MHC-class II antigens, and no mononuclear cell infiltrates, posttransplantation allogeneic donor cardiac tissue demonstrates dramatic increases of MHC-class I/class II expression coincident with the infiltration of the tissue with mononuclear cells. Results of this study demonstrate that the kinetics of MHC-class I/II antigen expression and the phenotype of mononuclear cell infiltrate are influenced, to a great degree, by the genetic H-2, intra-H-2 and non-H-2 incompatibility between donor and recipient strains of mice. Increases of MHC-class I precede class II expression in cells from donor cardiac tissue from completely allogeneic BALB/c, H-2-disparate B10.D2, B10.BR, and K, I-A and I-E-disparate B10.T (6R) strains of mice implanted in B10 recipients. In contrast, increase in the level of MHC-class II precedes MHC-class I increases in donor cardiac tissue from H-2-identical but non-H-2-incompatible A. By and the I-E + H-2D end-different B10.A(5R) donor tissue. The completely allogeneic, H-2-disparate or K, I-A, I-E-disparate donor cardiac tissue induced the infiltration of predominantly CD8+ T cells, whereas the non H-2 and I-E + H-2D end-different donor cardiac tissue induced the infiltration of predominantly CD4+ T cells. Finally, whereas bm1 donor cardiac tissue is rejected by B6 recipients by day 32, the (bm1 x bm12)F1 allografts are rejected by day 20, and both express MHC-class I antigens followed by MHC-class II antigens, and contain predominantly CD8+ T cells. In contrast, bm12 allografts are not rejected by B6 recipients, express chronic low levels of both MHC-class I and II antigens, and contain predominantly CD4+ T cells. Of interest is our preliminary finding that bm12 allografts placed in one ear of B6 recipients appear to modify the kinetics of MHC antigen expression and the predominant phenotype of mononuclear cell infiltrates in bm1 allografts placed in the opposite ear. Cumulatively, these data suggest that the type of genetic disparity between cardiac donor and recipient greatly influences the quantitative and qualitative host responses.

Animals↗

Nitric oxide production by mouse sponge matrix allograft-infiltrating cells. Comparison with the rat species.

We have recently demonstrated in the rat species that sponge matrix allograft infiltrating cells spontaneously produce nitric oxide (.N = 0) and this .N = 0 production precedes the development of CTL. Compared with our experience in the mouse species, the CTL activity recovered from rat sponge grafts is of shorter duration and less intense. Assessment of the spontaneous .N = 0 production by mouse allograft infiltrating cells reveals a more delayed time course of production, paralleling the recovery of CTL activity from the graft. The in vitro spontaneous .N = 0 production by mouse allograft-infiltrating cells was greater than the production by syngeneic graft-infiltrating cells on all days tested. Exposure of allogeneic but not syngeneic graft infiltrating cells to the sensitizing alloantigen in vitro resulted in enhanced .N = 0 synthesis. In contrast, LPS stimulated .N = 0 production by both syngeneic and allogeneic graft cells on all days postgrafting. Culture of day-14 allograft infiltrating cells with alloantigen in the absence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of .N = 0 synthesis, resulted in elevated supernatant NO2- levels and decreased 3H-TdR uptake and CTL activity compared with cultures carried out in the presence of NMA. The supernatant NO2- levels, as well as the CTL activity and 3H-TdR incorporation of the cultured cells, was dependent on the concentration of NMA present, and these effects could be reversed by excess L-arginine. Thus, the species difference in .N = 0 synthesis (rat > mouse), observed by others, is evident in the sponge allograft model and may explain why CTL activity recovered from rat allografts is of shorter duration and less intense than that from the mouse allografts.

Animals↗

Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine.

To examine the role of neutrophils, their presence and the degree of infiltration, as important determinants of ischemia and reperfusion injury of the liver, male Sprague-Dawley rats were subjected to 60 and 90 min of total-liver ischemia. The presence of neutrophils, assessed by the measurement of liver tissue myeloperoxidase (MPO), and the degree of neutrophil liver infiltration, determined by the naphthol AS-D chloroacetate esterase technique, correlated well with animal survival and response to FK506 and cyclosporine administration. Lipid peroxidation, measured by the malondialdehyde (MDA) test in liver tissue, was another factor closely linked with liver function and survival. Pretreatment with FK506 (0.3 mg/kg) and CsA (5 mg/kg) was given at 4 hr and 1 hr before ischemia and at the time of reperfusion. Control ischemic animals showed increased neutrophil liver infiltration, high MPO and MDA liver levels, and diminished overall survival. FK506 and CsA-treated animals had better survival and diminished neutrophil liver infiltration, as well as MPO and MDA levels. The mechanism by which FK506 and CsA protected the animals from severe liver ischemic injury is unknown. Our data indicated that the presence and the degree of infiltration of neutrophils were important components of liver ischemia/reperfusion injury in the rat. So it is possible that one of the fundamental effects of the FK506 and CsA might be through the inhibition of the presence and infiltration of neutrophils in liver tissue.

Alanine Transaminase↗

Predominant infiltration of rejecting human renal allografts with T cells expressing CD8 and CD45RO.

Subsets of T cells have been identified by the expression of different isoforms of CD45. Some T cells expressing CD45RA (gp220) have been characterized as "naive" in their response to antigens including alloantigens, whereas T cells expressing CD45RO (gp180) have been characterized as "memory" T cells. To examine the potential association between kidney allograft rejection and infiltration with these subsets, immunohistologic labeling of serial frozen sections from 17 nonrejecting and 18 rejecting kidney transplant biopsies was performed. Biopsies were selected on the basis of unambiguous clinical pathological diagnosis, no antirejection therapy within 1 month before biopsy, and enough tissue available for immunohistologic labeling. Sections were labeled for CD3, CD4, CD8, CD45RA, and CD45RO, and slides were evaluated in a masked manner. The numbers of cells were counted in 10 (400x) high power fields (HPF) in each section. The medians of average cell counts were significantly higher in the rejecting compared with nonrejecting group for CD3+, CD4+, CD8+, CD45RA+, and CD45RO+ T cells in both diffuse and aggregate patterns of infiltration. However, the numbers of infiltrating cells per HPF in rejecting grafts were most striking for CD8+ and CD45RO+ cells: 16/18 rejecting vs. 1/17 nonrejecting cases had more than 5 CD8+ cells/HPF. Likewise, 17/18 rejecting vs. 1/17 nonrejecting cases had more than 5 CD45RO+ cells/HPF. In both cases, the difference was most striking for cells infiltrating in a diffuse versus aggregate pattern. Significantly higher CD45RO+ to CD45RA+ ratios were observed in rejecting versus nonrejecting groups, both in the diffuse and aggregate patterns. Within the rejecting cases, the CD45RO+ to RA+ ratio was significantly higher in diffuse versus aggregate patterns of infiltration (P < 0.0002). These results indicate that a significant increase in CD8+, CD45RO+, and the ratio of CD45RO+ to CD45RA+ T cells in a diffuse pattern of infiltration is most characteristic of clinical renal allograft rejection.

Biopsy↗

Antibody to CD18 reduces neutrophil and T lymphocyte infiltration and vascular cell adhesion molecule-1 expression in cardiac rejection.

Most antirejection therapies target immune activation but may not reduce leukocyte infiltration into the graft. The leukocyte integrin CD18 has been shown to be important for leukocyte migration in vitro. We postulated that antibody blockade of CD18 might reduce the migration of different leukocyte subpopulations into myocardium during rejection. Using a rabbit model, we evaluated the effect of a monoclonal antibody to CD18 on the infiltration of neutrophils (polymorphonuclear leukocytes [PMNs]), T lymphocytes, and macrophages into cardiac grafts. In addition, vascular cell adhesion molecule-1 (VCAM-1) expression was assessed to determine the relationship between leukocyte infiltration and VCAM-1 expression, an unblocked alternate adhesion pathway. Donor hearts from Stauffland rabbits were transplanted heterotopically into the cervical position of New Zealand White recipients. Recipient rabbits received either monoclonal antibody to CD18 daily without other immunosuppression (n=51), saline injections as placebo controls (n=52), or nonfunctional isotype-matched antibody (n=4). Recipient rabbits were killed at 1 hr, 6 hr, 24 hr, 3 days, and 7 days after transplantation (10-12 rabbits per group at each time point). PMNs, T lymphocytes, and macrophages were differentiated by routine staining and immunocytochemistry, respectively, and quantified as the number of cells per standardized field. VCAM-1 expression was examined immunocytochemically in 30 treated and 30 control transplanted hearts. Monoclonal antibody to CD18 significantly reduced the infiltration of PMNs and T lymphocytes into myocardium during rejection, but did not affect the infiltration of macrophages. Blocking the CD18/intercellular adhesion molecule-1 adhesion pathway also resulted in a decrease in VCAM-1 expression, which correlated in time with the reduction in T lymphocyte infiltration.

Animals↗

Apoptosis of mononuclear cell infiltrates in cardiac allograft biopsy specimens questions studies of biopsy-cultured cells.

During acute rejection, CD4 and CD8 T cells infiltrate the myocardium and cause myocyte death and dropout. CD4 and CD8 cells use a number of cytotoxic mechanisms, including fas-fas ligand interactions, which lead to apoptotic death. Since fas is expressed on myocytes, we investigated endomyocardial biopsy specimens from cardiac transplant patients to determine whether apoptosis is one of the mechanisms of cell death in acute rejection. Serial sections of individual endomyocardial biopsy specimens from patients histologically diagnosed as having grade 3A rejection (n=22 biopsy specimens), biopsy specimens showing a typical "Quilty effect" (n=10), and specimens with concurrent grade 3A rejection and the Quilty effect (n=6) were evaluated using the C-terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique for frequency of apoptosis in myocytes and mononuclear cell infiltrates. None of the examined sections showed detectable evidence of apoptotic myocytes, even within regions clearly showing myocyte damage. Of interest was our consistent finding that 85-98% of mononuclear cell infiltrates within biopsy specimens scored as having grade 3A rejection had undergone apoptosis. In marked contrast, 9 of the 10 specimens with Quilty lesions showed <5% apoptotic mononuclear cells in the endomyocardial infiltrates. Of further interest was our finding of 85-98% apoptotic mononuclear cell infiltrates within Quilty lesions associated with biopsy specimens scored as having grade 3A rejection. The frequency of apoptotic cells determined by the TUNEL technique was confirmed by histological examination of the morphology of the cells and with a technique that involves detection of c-jun. These results prompt a note of caution in the interpretation of data on the phenotype, cytokine profile, Vbeta T cell receptor repertoire, and donor specificity of mononuclear cells cultured and propagated from such cardiac biopsy specimens. The possible reasons for apoptosis of graft-infiltrating mononuclear cells are discussed.

Adult↗

Chronic antagonism of Mig inhibits cellular infiltration and promotes survival of class II MHC disparate skin allografts.

BACKGROUND: The goal of the current study was to test the ability of monokine induced by IFN-gamma (Mig)-specific antibodies to inhibit long-term T cell infiltration into class II major histocompatibility complex (MHC) disparate skin allografts and to test cellular and molecular changes in the graft during the rejection observed following cessation of treatment. METHODS: C57BL/6 recipients of B6.H-2bm12 skin grafts were treated with normal rabbit serum (NRS) or rabbit Mig antiserum (Mig AS) every other day from day 7 until day 21 posttransplant and then weekly thereafter. Allografts were retrieved during the course of treatment and following cessation. Tissue sections were prepared and stained to compare infiltration by macrophages and CD4+ and CD8+ T cells and to assess collagen deposition in the grafts. RNA was prepared and tested by ribonuclease protection assay for intragraft levels of Mig, monocyte chemotactic protein-1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES). RESULTS: T cell and macrophage infiltration into allografts was inhibited and graft survival maintained as long as Mig-specific antibodies were given. Following cessation of treatment, T cells and macrophages infiltrated the allografts. In contrast to the histology of acute rejection observed in allografts from NRS-treated recipients, the resulting rejection of the allografts from Mig AS-treated recipients was accompanied by dense collagen deposition and high level expression of Mig and RANTES. CONCLUSIONS: Mig directs T cell infiltration into B6.H-2bm12 skin allografts on C57BL/6 recipients. Delayed T cell and macrophage infiltration and rejection of the grafts following cessation of Mig AS treatment results in rejection that is histologically and molecularly distinct from acute rejection.

Animals↗

Implementing a clinical practice guideline to improve pediatric intravenous infiltration outcomes.

The focus on quality, efficiency, and cost containment has spurred development of clinical practice guidelines to facilitate the use of research-based knowledge and expert opinion to promote desired outcomes. At the University of Iowa Hospitals and Clinics, pediatric nursing took a leadership role in developing multidisciplinary guidelines for the prevention and treatment of intravenous infiltrations in pediatric patients, following the Iowa Model. The 3-year collaborative effort has resulted in a synopsis of the literature; a quick reference sheet based on the latter; infiltration staging guidelines; an infiltration decision algorithm; a table of recommended antidotes; and a standard of care. Outcome data showed improvement in ongoing intravenous site assessment, extent of infiltration and estimated infiltration volume assessment, physician notification of infiltrations, documentation of severity, and compliance with use of the guidelines and use of antidotes. The guideline recently has been revised, and outcomes will continue to be tracked.

Algorithms↗

Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates.

Renal transplant rejection is caused by a lymphocyte-rich inflammatory infiltrate that attacks cortical tubules and endothelial cells. Immunosuppressive therapy reduces the number of infiltrating cells; however, their exit routes are not known. Here a >50-fold increase of lymphatic vessel density over normal kidneys in grafts with nodular mononuclear infiltrates is demonstrated by immunohistochemistry on human renal transplant biopsies using antibodies to the lymphatic endothelial marker protein podoplanin. Nodular infiltrates are constantly associated with newly formed, Ki-67-expressing lymphatic vessels and contain the entire repertoire of T and B lymphocytes to provide specific cellular and humoral alloantigenic immune responses, including Ki-67(+) CD4(+) and CD8(+) T lymphocytes, S100(+) dendritic cells, and Ki-67(+)CD20(+) B lymphocytes and lambda- and kappa-chain-expressing plasmacytoid cells. Numerous chemokine receptor CCR7(+) cells within the nodular infiltrates seemed to be attracted by secondary lymphatic chemokine (SLC/CCL21) that is produced and released by lymphatic endothelial cells in a complex with podoplanin. From these results, it is speculated that lymphatic neoangiogenesis not only contributes to the export of the rejection infiltrate but also is involved in the maintenance of a potentially detrimental alloreactive immune response in renal transplants and provides a novel therapeutic target.

Adolescent↗

Fatty infiltration in the cervical extensor muscles in persistent whiplash-associated disorders: a magnetic resonance imaging analysis.

STUDY DESIGN: Cross-sectional investigation of muscle changes in patients suffering from persistent whiplash-associated disorders (WAD). OBJECTIVES: To quantitatively compare the presence of fatty infiltrate in the cervical extensor musculature in a cohort of chronic whiplash patients (WAD II) and healthy control subjects across muscle and cervical segmental level. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging (MRI) can be regarded as the gold standard for muscle imaging; however, there is little knowledge about in vivo features of neck extensor muscles in patients suffering from persistent WAD and how fat content alters across the factors of muscle, vertebral segments, age, self-reported pain and disability, compensation status, body mass index, and duration of symptoms. METHODS: A reliable MRI measure for fatty infiltrate was performed of the cervical extensor muscles bilaterally in 113 female subjects (79 WAD, 34 healthy control; 18-45 years, 3 months to 3 years post injury). The measure was performed on all subjects for the rectus capitis posterior minor and major, multifidus, semispinalis cervicis and capitis, splenius capitis, and upper trapezius. RESULTS: The WAD subjects had significantly larger amounts of fatty infiltrate for all of the cervical extensor muscles compared with healthy control subjects (all P < 0.0001). In addition, the amount of fatty infiltrate varied by both cervical level and muscle, with the rectus capitis minor/major and multifidi at C3 having the largest amount of fatty infiltrate (P < 0.0001). Intramuscular fat was independent of age, self-reported pain/disability, compensation status, body mass index, and duration of symptoms. CONCLUSION: There is significantly greater fatty infiltration in the neck extensor muscles, especially in the deeper muscles in the upper cervical spine, in subjects with persistent WAD when compared with healthy controls. Future studies are required to investigate the relationships between muscular alterations and symptoms in patients suffering from persistent WAD.

Adipose Tissue↗

Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration.

The therapeutic value of topical minoxidil in alopecia areata (AA) has been investigated in recent years, with variable results. Although the mechanism whereby minoxidil may stimulate hair regrowth in some cases of AA has not yet been elucidated, there have been reports of a decrease in the perifollicular infiltrates of mononuclear leukocytes (MNC)--particularly T lymphocytes--that characterize this condition, in patients "responding" to topical minoxidil. In a randomized and double-blind study, we have investigated the effect of 5% topical minoxidil versus placebo (vehicle alone) on the extent and composition of the perifollicular MNC infiltration in 20 patients having extensive AA (26-99% scalp hair loss). The proportions of hair follicles showing perifollicular infiltration by MNC and their main subsets were determined with histologic and immunohistochemical stainings of scalp biopsies obtained before treatment, after 12 weeks of randomized double-blind minoxidil versus placebo treatment, and after 12 additional weeks during which all patients received minoxidil. Six of the patients showed cosmetically acceptable hair regrowth (CAHR) at the end of the 24 weeks and this was associated with a significant decrease in the proportions of follicles infiltrated by total T and B lymphocytes, macrophages, and Langerhans cells at week 12, and by total T lymphocytes at week 24. However, no significant differences in the extent or composition of the perifollicular infiltrates were detected at week 12 between patients receiving minoxidil and placebo, or between the week-12 and week-24 biopsies of those patients who first received placebo and then minoxidil. These findings indicate that in AA the reduction in perifollicular T-cell infiltration associated with CAHR is not attributable to an effect of topical minoxidil.

Adolescent↗