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PubMed2004

Risk assessment of patients with hematologic malignancies who develop fever accompanied by pulmonary infiltrates: a historical cohort study.

BACKGROUND: The mortality rate associated with fever accompanied by pulmonary infiltrates after chemotherapy for hematologic malignancies remains higher than the corresponding rate associated with febrile neutropenia without pulmonary infiltrates. Nonetheless, few studies have focused on the factors that predict outcome for patients with lung infiltrates. The purpose of the current study was to construct a risk model for clinical use by assessing the factors that affect outcome for patients with fever and pulmonary infiltrates. METHODS: A historical cohort of 110 patients with hematologic malignancies who developed fever and pulmonary infiltrates was examined. Using parameters for which data were available at the onset of lung infiltrates, univariate and multivariate analyses were performed to assess factors affecting outcome. After a value of one point was assigned to each significant variable, a prediction score was calculated for each patient; scores were used to generate a system for identifying patients with a low risk of death due to fever accompanied by pulmonary infiltrates. RESULTS: The crude mortality rate associated with pulmonary infiltrates was 23%; factors associated with cure included a favorable change in white blood cell counts (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.7-18.9; P = 0.001), C-reactive protein levels < 10 mg/dL (OR, 4.6; 95% CI, 1.6-13.8; P = 0.001), and serum albumin levels > or = 3 g/dL (OR, 3.2; 95% CI, 1.4-7.3; P = 0.004). Low-risk patients (risk score, 2-3) and high-risk patients (risk score, 0-1) had survival rates of 95% and 46%, respectively (P < 0.0001). The risk model had a specificity of 88% and a positive predictive value of 95%. CONCLUSIONS: The risk model tested in the current study accurately predicted the survival of patients with hematologic malignancies who developed fever with pulmonary infiltrates. Once prospectively validated, the model could be used to select patients for trials involving novel diagnostic and therapeutic strategies.

Age Distribution↗

PubMed1999

Leukocytes utilize both alpha4 and alpha5 integrins for intraislet infiltration in non-obese diabetic mice.

The loss of insulin-producing cells during the development of type 1 diabetes is dependent on leukocyte infiltration of beta-islets in the pancreas. Injection of antibodies to integrins and their ligands has been shown to prevent the development of diabetes in non-obese diabetic (NOD) mice. However, little is known about the progression of infiltration by leukocytes after their homing and extravasation into the pancreas. In the present study, the effect of monoclonal antibodies (mAbs) to alpha4 and alpha5 integrins on leukocytes that had infiltrated the islets was characterized in NOD mice at 10 weeks of age when insulitis was in progress, or in mice with recent onset of diabetes. Injection of mAbs to either alpha4 or alpha5 integrins had little effect on the extent of leukocyte infiltration in 10-week-old or diabetic mice. In contrast, leukocyte infiltration was significantly reduced upon injection of mAbs to both alpha4 and alpha5 integrins. The reduction in leukocyte infiltration was due to decreases in the percentage of islets with intraislet infiltration. However, the observed effect of mAbs to alpha4 and alpha5 integrins was reversible, since intraislet infiltration resumed upon termination of antibody treatment. Results suggest that after homing to the pancreas, leukocytes utilize both alpha4 and alpha5 integrins for intraislet infiltration.

Animals↗

PubMed2002

Spreading and infiltration of inkjet-printed polymer solution droplets on a porous substrate.

Simultaneous spreading and infiltration of inkjet-printed droplets has been studied. Small (54- and 63-microm diameter) droplets of an aqueous polymer solution (2.4 vol% polyacrylic acid, PAA, MW 60,000) were deposited on high green density porous ceramic beds, and the wetting-induced spreading and infiltration of the droplets were characterized. The time scales for spreading and infiltration were comparable (approximately milliseconds), resulting in interruption of the spreading prior to completion by infiltration of the liquid into the powder bed, a situation that has received little treatment in the literature. The infiltration time was varied by changing the pore size (via particle size) in the powder bed, and it was confirmed that slower infiltration resulted in greater spreading of the liquid. The spreading and infiltration of the droplet were modeled to examine the coupling between the two processes and allow prediction of the maximum extension of the droplet as a function of the powder bed particle size. The liquid spreading was found to follow r(t)=a(b+t)(n) behavior, and the effect of particle size on infiltration time was used to predict the point at which spreading ceases due to infiltration for various particle sizes.

Journal Article↗

PubMed1989

Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of pre-diabetic BB rats.

We have analysed whether infiltration of macrophages and lymphocyte subtypes into pancreatic islets of diabetes prone BB rats occurs at random or whether insulitis requires a specific sequence of events. Serial sections from more than 700 islets of diabetes prone BB rats (70-150 days of age) were analysed for infiltrating immunocytes and expression of major histocompatibility complex antigens by 4-11 different monoclonal antibodies. In parallel, electron microscopy was performed in a fraction of islets. Part of the animals had been treated with macrophage toxic silica particles. A specific non-random sequence of events was identified and 4 stages of islet inflammation were recognised. Stages 1a and 1b are defined by macrophage (ED1+, W3/25+. Ox3/6/17+, ED2-) infiltration and concomitant enhanced major histocompatibility complex class I antigen expression initially at one pole or at the periphery of islets. T-, NK- and B-lymphocytes are absent (less than 1 cell per mean islet section). In stage 2, more macrophages are infiltrating and concomitantly Ox19+-T-lymphocytes and Ox8+-granular (NK-) lymphocytes are observed. In stage 3, additional massive infiltration of Ox12+-B-lymphocytes is noted. Silica treatment of BB rats largely prevented macrophage infiltration. Concomitantly islets were free of lymphocytes. Thus, macrophage infiltration clearly precedes T- and NK-lymphocyte and later B-lymphocyte infiltration. Lymphocytes do not infiltrate islets in the absence of prior macrophage invasion.

Animals↗

PubMed2004

Lymphocytic infiltration in pediatric thyroid carcinomas.

Lymphocytic thyroiditis has been associated with an increase in the incidence of thyroid papillary carcinoma in some reports, mostly series of both adults and children. Relatively little is written about thyroiditis and follicular carcinomas. We have seen several cases of pediatric follicular thyroid carcinomas, that had an associated lymphocytic infiltrate, which led us to examine all primary malignant thyroid neoplasms in our surgical files from 1984 through 2000 to examine this relationship. We also investigated the nature of the lymphocytic infiltrate with routine immunohistochemistry. Ten patients (five male, five female, ages 4.5-21 years of age) had a thyroid carcinoma resection, six (three males and three females) with papillary carcinoma and four patients (two males and two females) with low-grade follicular carcinoma. Seven samples (one male had two cases with tumor) from patients who had a papillary carcinoma resection with tissue blocks available were identified (one patient had slides but no blocks), as were all four patients with a follicular carcinoma. The thyroid of all patients with a follicular carcinoma contained a lymphocytic infiltrate; only four of the seven papillary carcinoma samples had an associated lymphoid infiltrate. In all cases with a lymphoid infiltrate, the infiltrate was present in both lobes (both adjacent and separate from the tumor). B lymphocytes were present in the lymphoid infiltrate of three of four patients with follicular carcinomas and in 1 of 3 cases of papillary carcinomas. T cells were dispersed throughout all the tumors with lymphoid infiltrates. We conclude that pediatric follicular carcinomas have an associated lymphocytic infiltrate in the tumor and/or adjacent thyroid, more commonly than papillary carcinomas.

Adenocarcinoma, Follicular↗

PubMed1987

Inhibition of the neutrophilic infiltrate of experimental tubulointerstitial nephritis in the Brown-Norway rat by decomplementation.

Anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN) in Brown-Norway rats is induced by immunization with bovine TBM antigens and adjuvants. The lesion is characterized by linear deposition of IgG and C3 along the TBM with sequential neutrophil (Days 8-9)- and mononuclear (Day 10 and after)-dominated inflammatory infiltrates. To study the complement dependence of the infiltrative process, immunized rats were decomplemented with cobra venom factor (CVF). The CVF treatment did not affect the production or renal deposition of anti-TBM antibodies. CVF markedly reduced the neutrophilic inflammatory infiltrate. In rats immunized with suboptimal doses of soluble bovine TBM antigens to produce a mild lesion, decomplementation also decreased the mononuclear inflammatory infiltrates on Days 10-13. In rats immunized optimally with particulate TBM to induce maximally severe TIN, decomplementation did not affect the mild mononuclear cell infiltrate on Days 8 and 9 but did somewhat reduce the subsequent mononuclear infiltrate on Days 10 and 12. These results demonstrate that the anti-TBM antibody- and C3-associated neutrophilic inflammatory infiltrate is largely complement dependent. The early mononuclear cell infiltrate that was unmodified by CVF treatment may be dependent on complement-independent humoral events or related to cell-mediated immune events. A portion of the later mononuclear inflammatory infiltrate could be dependent on the preceding neutrophilic inflammatory phase.

Animals↗

PubMed2004

Immunohistochemical characterization of the leucocytic infiltrate associated with canine seminomas.

Both canine and human seminomas are typically associated with leucocytic infiltration, the role of which remains poorly understood. In this study, leucocytes infiltrating 10 canine seminomas were characterized. Monoclonal antibodies directed against CD18, CD11a, CD11b, CD11c, CD21, CD3, CD4, CD8 and Major Histocompatibility Complex class I and II (MHC I and MHC II) were also employed. Infiltrating leucocytes were located around vessels, adjacent to the thin fibrous septa between neoplastic lobules, and were also scattered singly amongst neoplastic cells. The more profuse infiltrates often had the appearance of follicular aggregates. Immunohistochemically, all the samples showed generally similar results. Most of the infiltrating cells were positive for CD18 and CD11a. Infiltrating cells were mainly T lymphocytes (CD3+), particularly of the CD8+ subset. B lymphocytes (CD21+) were detectable in almost all infiltrates; in the follicular aggregates they were centrally located, whereas T lymphocytes (CD3+) lined the periphery. CD11c+ cells were always more numerous than CD11b+ cells, demonstrating that if macrophages and antigen-presenting cells (APCs) were well represented, monocytes and granulocytes were practically absent. Almost all of the infiltrating cells were positive for both MHC I and MHC II antigens and, in nine samples, a large number of neoplastic cells expressing MHC I were detected. A few neoplastic cells expressing MHC II were observed in seven cases. The presence of CD8+ lymphocytes, together with the large number of both infiltrating and neoplastic cells expressing MHC I, suggests that the lymphocytes mediate a cytotoxic reaction against the neoplastic cells. This hypothesis may underlie the favourable prognosis frequently associated with canine seminomas.

Animals↗

PubMed2004

G-CSF treatment increases side population cell infiltration after myocardial infarction in mice.

Granulocyte-colony stimulating factor (G-CSF) has been reported to mobilize bone marrow multi-potent stem cells, which differentiate into cardiac myocytes after myocardial infarction (MI). However, there have not been any reports regarding the effect of G-CSF on stem cell infiltration in the MI site. Hearts of mice that had undergone coronary occlusion were isolated and digested with collagenase. Infiltrating cells in the heart were collected using Percoll density gradients. The infiltrating cells were sorted for side population (SP) cells using Hoechst 33342 dye. Hundreds of infiltrating SP cells were found in the heart from 1 to 14 d after MI. There were only a few SP cells in hearts without infarction. Infiltrating SP cells were increased in the 4-d G-CSF treated group compared with the vehicle group (1106 +/- 106 vs. 323 +/- 26/heart, P < 0.05). The infiltration of inflammatory cells was not influenced by the G-CSF treatment. In a separate series of experiments, we confirmed that the infiltrating SP cells were derived from bone marrow. That is, SP cells in the infarcted hearts of mice, which had been transplanted with bone marrow from ROSA 26 (beta-galactosidase transgenic) mice, were positive for beta-galactosidase. In the immunohistochemical examination, Sca-1(+)/CD45(-) cells were existed in the infarcted site after MI. Therefore, SP cells may infiltrate into infarcted heart. G-CSF augmented this kind of stem cell infiltration without increasing inflammatory cells. These results suggest that G-CSF may enhance myocardial regeneration without aggravated inflammation in the infarcted heart.

Animals↗

PubMed2003

Human chorionic gonadotropin level as a predictor of trophoblastic infiltration into the tubal wall in ectopic pregnancy: a blinded study.

OBJECTIVE: To determine the relationship between gestational age, tubal ultrasonographic diameter, and serum hCG levels and different stages of trophoblastic infiltration of the tubal wall in ectopic pregnancy. DESIGN: Blinded prospective study. SETTING: University-based clinic in Italy. PATIENT(S): Thirty-seven consecutive patients with an ampullary ectopic pregnancy. INTERVENTION(S): Laparoscopic salpingectomy. MAIN OUTCOME MEASURE(S): Gestational age, diameter of the tubal mass as determined by transvaginal ultrasonography. and hCG level on the day of surgery. Ectopic pregnancy was classified according to the depth of trophoblastic infiltration: trophoblast limited to the tubal mucosa (stage I), extension to the tubal muscularis (stage II), or complete tubal wall infiltration up to the serosa discontinued by trophoblastic cells (stage III). RESULT(S): Fifteen patients (40.5%) had stage I tubal infiltration, 14 (37.8%) had stage II infiltration, and 8 (21.6%) had stage III infiltration. Gestational age and diameter of the tube did not differ among the three groups. The median hCG level was 1,710.5 mIU/mL (range, 113-5,635 mIU/mL) for patients with stage I infiltration. 4,690.0 mIU/mL (range, 150-21,531 mIU/mL) for patients with stage II infiltration, and 15,700.0 mIU/mL (range, 13,809-21,650 mIU/mL) for patients with stage III infiltration. All the patients with hCG levels > 6,000 mIU/mL had stage II or III invasion. CONCLUSION(S): These findings may explain why the conservative treatment of ectopic pregnancy is less successful in patients with high hCG levels than in patients with low levels. Use of radical procedures may be justified in the former group.

Adult↗

PubMed2000

Immune cell infiltrates and prognosis in primary carcinoma of the lung.

The prognostic significance of immune cell infiltrates in surgically resected human lung cancer was investigated in 710 patients. Lymphoid infiltrates were quantified on both standard H&E stained sections and, in a subset of 95 cases, using immunohistochemistry and antibodies to CD3, CD8, CD57, CD68, CD79a and S100 to identify various immune cell types. Subjective grading (low, moderate, high) of lymphoid cell infiltrates on H&E sections of tumour and measurement, using image analysis, of overall level of tumour infiltration by any of the immunohistochemically labelled specific immune cell types of the stained sections showed no prognostic significance. However, when a distinction between peritumoural and intratumoural infiltration by particular cell types was made, intratumoural infiltration by high levels of CD3+ and S100+ cells was associated with longer post-operative survival (P = 0.02 and P = 0.045, respectively). In lung cancer, subjective assessment of tumour lymphoid infiltration and overall levels of infiltration by particular immune cell types carries no prognostic significance. Intratumoural infiltration by relatively high numbers of CD3+ T-lymphocytes and Langerhans cells (S100+) is associated with a better patient outcome.

Adult↗

PubMed1997

The use of EMLA cream and 1% lidocaine infiltration in men for relief of pain associated with the removal of genital warts by cryotherapy.

BACKGROUND: Surgical procedures used to remove genital warts (cryotherapy, electrodesiccation) are painful. Attempts to reduce the discomfort of surgery by prior lidocaine infiltration anesthesia are compromised by the pain of the infiltration. OBJECTIVE: Our purpose was to determine the efficacy of topically applied lidocaine/prilocaine cream to reduce the pain of lidocaine infiltration and the pain associated with cryotherapy to remove genital warts. METHODS: Men, scheduled for removal of genital warts by cryotherapy, were randomly selected to receive one of three treatments: (1) lidocaine/prilocaine cream application, (2) 1% lidocaine infiltration, and (3) lidocaine/prilocaine cream application followed by infiltration of 1% lidocaine. RESULTS: Application of lidocaine/prilocaine cream for 15 minutes markedly reduced the pain of lidocaine infiltration. The combination of lidocaine/prilocaine cream followed by infiltration of 1% lidocaine gave greater pain relief from the cryotherapy than did either anesthetic alone. CONCLUSION: The application of lidocaine/prilocaine cream as an adjunct to lidocaine infiltration reduced the pain of infiltration and the pain associated with cryotherapy for the removal of genital warts.

Anesthesia, Local↗

PubMed2001

Primary non-Hodgkin's lymphomas of the liver with nodular and diffuse infiltration patterns have different prognoses.

BACKGROUND: Primary liver non-Hodgkin's lymphomas have peculiar clinical and biological patterns. This study correlates these patterns with pathology and outcome. PATIENTS AND METHODS: Clinical records and histology of patients with primary liver non-Hodgkin's lymphoma, treated at our institution over a 20-year period, were reviewed. Lymphoproliferations occurring after liver transplantation were excluded. Survival analyses were performed with patients from the other published series (62 patients). RESULTS: Our series included eight patients. Three patients had a nodular liver infiltration, corresponding to a large B-cell lymphoma. Five patients had a diffuse liver infiltration, of whom three had a T-cell lymphoma with predominant sinusoid infiltration, and two had a large B-cell lymphoma. Patients with diffuse liver infiltration presented with hepatomegaly, and two of these also had acute liver failure. Diffuse infiltration had a worse prognosis than nodular infiltration (P = 0.0033). Among these latter patients, those treated with an anthracycline-based chemotherapy had a better outcome (P < 0.0001). CONCLUSIONS: Patients with primary liver lymphomas can be classified in two groups, depending on the type of infiltration. Those with nodular infiltration may benefit from anthracycline-based chemotherapy. Diffuse infiltration has a bad prognosis, and should be suspected in patients presenting with altered liver functions and hepatomegaly.

Adult↗

PubMed1991

Initiation and evolution of interstitial leukocytic infiltration in experimental glomerulonephritis.

Most forms of glomerulonephritis have a significant interstitial leukocytic infiltrate which is associated with disease progression. However, there is little data concerning the timing, initial location, and development of this interstitial component. Therefore, we have addressed these issues in a study of passive accelerated anti-GBM glomerulonephritis in the rat. In this model, interstitial leukocytic infiltration was an early event in the disease process with a significant infiltrate apparent at 12 hours after administration of nephrotoxic serum (NTS). This initial infiltrate was restricted to a perivascular sheath surrounding the hilar arterioles. The sheath infiltrate then spread to include the whole hilar area by day 1, the entire periglomerular area by day 3, and became widespread throughout the cortical tubulointerstitium by day 7. The early sheath infiltrate was composed of macrophages and T cells. Both cell types continued to increase as the infiltrate expanded, and a significant accumulation of activated cells (IL-2R+) was evident from day 7 onwards. There was a highly significant correlation between interstitial macrophage infiltration and renal function impairment, proteinuria, and histologic damage. Interstitial T cell infiltration correlated with proteinuria and histologic damage, while the appearance of immune-activated mononuclear cells (IL-2R+) exhibited a highly significant correlation with all disease parameters. This study demonstrates the importance of the glomerular hilar arteriolar region as a focus for mononuclear leucocytic migration and accumulation which not only affects the structure and function of the glomerulus but subsequently the entire tubulointerstitium.

Animals↗

PubMed1997

Gastric corpus IL-8 concentration and neutrophil infiltration in duodenal ulcer patients.

BACKGROUND: The purpose of the present study was to examine the association between interleukin-8 (IL-8) in the gastric body due to Helicobacter pylori infection and histological gastritis, as well as elucidating the effect of acid secretion inhibitors on H. pylori associated body gastritis in duodenal ulcer patients. METHODS: Twenty H. pylori-negative patients, 20 H. pylori-positive patients with chronic gastritis without peptic ulceration, and 20 H. pylori-positive duodenal ulcer patients (DU) were studied. Four biopsy samples were taken, each from the greater curvature of the antrum and body of the stomach. Biopsies were histologically investigated by ELISA to determine the density of H. pylori, the degree of neutrophil infiltration and the IL-8 concentration in the mucosa. RESULTS: In the gastric mucosa of H. pylori-negative subjects, no IL-8 and hardly any neutrophil infiltration were observed. In contrast, enhanced IL-8 production and increased neutrophil infiltration were present in those infected with H. pylori. In H. pylori-positive patients, a significant correlation was observed between the IL-8 concentration and the degree of neutrophil infiltration, but no correlation was found in the body mucosa of those with DU. Twelve of 20 DU patients demonstrated hardly any neutrophil infiltration, despite the increased mucosal IL-8 content in the body. The administration of omeprazole in DU patients markedly increased mucosal neutrophil infiltration even though it did not cause any significant change in the H. pylori density and IL-8 concentration in the body. Although the effect of omeprazole was transient, a significant increase in neutrophil infiltration continued in comparison with the status before omeprazole administration in those subsequently undergoing maintenance treatment with H2-blockers. CONCLUSION: In H. pylori-positive chronic gastritis, IL-8 concentration is enhanced in the mucosa of the body, and is associated with increased neutrophil infiltration. However, in DU patients, despite increases in body IL-8 concentration, neutrophil infiltration is reduced and the gastritis may be localized in the antrum.

Adult↗

PubMed2003

Material changes in osteoporotic human cancellous bone following infiltration with acrylic bone cement for a vertebral cement augmentation.

Bone cement infiltration can be effective at mechanically augmenting osteoporotic vertebrae. While most published literature describes the gain in mechanical strength of augmented vertebrae, we report the first measurements of viscoelastic material changes of cancellous bone due to cement infiltration. We infiltrated cancellous core specimen harvested from osteoporotic cadaveric spines with acrylic bone cement. Bone specimen before and after cement infiltration were subjected to identical quasi-static and relaxation loading in confined and free compression. Testing data were fitted to a linear viscoelastic model of compressible material and the model parameters for cement, native cancellous bone, and cancellous bone infiltrated (composite) with cement were identified. The fitting demonstrated that the linear viscoelastic model presented in this paper accurately describes the mechanical behaviour of cement and bone, before and after infiltration. Although the composite specimen did not completely adopt the properties of bulk bone cement, the stiffening of cancellous bone due to cement infiltration is considerable. The composite was, for example, 8.5 times stiffer than native bone. The local stiffening of cancellous bone in patients may alter the load transfer of the augmented motion segment and may be the cause of subsequent fractures in the vertebrae adjacent to the ones infiltrated with cement. The material model and parameters in this paper, together with an adequate finite-element model, can be helpful to investigate the load shift, the mechanism for subsequent fractures, and filling patterns for ideal cement infiltration.

Bone Density↗

PubMed2003

Clinical characterization of corneal infiltrative events observed with soft contact lens wear.

PURPOSE: Corneal infiltrates are commonly observed during adverse reactions associated with contact lens wear. Broad ranges of presentations are encountered, and there is no well-established classification system. The aim of this paper is to categorize corneal infiltrates associated with soft lens wear and present the typical clinical characteristics associated with each type of event. METHODS: All events of corneal infiltrates occurring in soft contact lens clinical trials over 10 years (9 years retrospective and 1 year prospective) and conducted at two contact lens research centers were reviewed by a panel of experts comprising ophthalmologists, optometrists, and other biologic scientists. Classification of each event was based on assessment of a range of signs and symptoms by the review panel. RESULTS: A classification scheme was devised to distinguish infiltrative events that were serious and symptomatic (microbial keratitis), clinically significant and symptomatic (contact lens-induced peripheral ulcer, contact lens-induced acute red eye, infiltrative keratitis), and clinically nonsignificant and asymptomatic (asymptomatic infiltrative keratitis and asymptomatic infiltrates). CONCLUSION: Corneal infiltrates can be classified into six distinct categories. This classification scheme, based on clinical characteristics, should aid diagnosis, management, and treatment of corneal infiltrates as well as assisting investigations into the etiology of each of these conditions.

Contact Lenses, Hydrophilic↗

PubMed1994

Dosimetric consequences of radiopharmaceutical infiltrations.

RATIONALE AND OBJECTIVES: Little is known about the time-related biologic behavior of radiopharmaceutical misinjections. Such inadvertent tissue infiltration of such injections may not only adversely affect a scheduled test or cause some discomfort, but potentially could produce tissue damage. Radiopharmaceutical infiltrations were assessed in a rat model. METHODS: Particulate and nonparticulate radiopharmaceuticals were injected subcutaneously or intradermally into an anesthetized shaved rat model. The rate of release of the nine infiltrations per radiopharmaceutical per injection type were measured from computer data acquired with a gamma camera up to 24 hours after administration. These data were used for dosimetry determinations. RESULTS: When injected subcutaneously, the particulate radiopharmaceutical, technetium 99m (99mTc) albumin microspheres, exhibited essentially no movement, and the soluble agents showed a biexponential release pattern. The rate of release was similar for 99mTc methylene diphosphonate (99mTc MDP) and for 67Ga citrate (67Ga), whereas thallous chloride (201Tl) exhibited the slowest release pattern. The average effective half-lives (T1/2 av-eff) were 78.3 minutes, 76.1 minutes, and 268.4 minutes, respectively. When injected intradermally, the nonparticulates exhibited a triexponential release pattern; MDP showed a more rapid release (T1/2 av-eff, 50 minutes) and 201Tl showed the slowest (T1/2 av-eff, 491.2 minutes). Absorbed doses were calculated using conventional medical internal radiation dose (MIRD) methodology for small unit density spheres. The absorbed dose was greatest for a 201Tl infiltration. A 201Tl infiltrate of 1 mCi per gm of tissue is capable of producing radiation-absorbed doses greater than 500 rads. Additional studies were performed with heat, hyaluronidase, and volume dilution in an attempt to accelerate the rate of release of 201Tl. Local heat application proved to be more efficient than volume change or hyaluronidase application. CONCLUSION: These data indicate an insignificant skin radiation burden from the majority of nonparticulate infiltrated radiodiagnostic agents. Thallium 201, however, has the potential to produce significant radiation burdens when infiltrated at high specific activity. Actual human infiltration release rates may differ because of variants in blood flow and assumed infiltration volume relative to the animal model.

Animals↗

PubMed1986

Morphometric analysis of cellular infiltration assessed by monoclonal antibody labeling in sequential human renal allograft biopsies.

The mononuclear cell infiltrate in a total of 279 human renal allograft biopsies was determined by a panel of monoclonal antibodies using an indirect immunoperoxidase technique. Two hundred and seventy-two biopsies were obtained from 83 patients randomly allocated to receive short-term cyclosporine (CsA) or conventional azathioprine and low-dose prednisolone (AP). Biopsies were obtained routinely at days 0 (control biopsies), 7, 21, 90, and 365, as well as at other times when clinically indicated. A further 7 patients on AP therapy were biopsied several years after transplantation (median: 6 years 1 month). Morphometric analysis of cryostat tissue sections using a point-counting technique has shown that the infiltration in rejecting grafts is significantly greater than in grafts with stable function. However, significant infiltration also occurs within the first week after transplantation in grafts with stable function. While this infiltrate diminishes with time, it remains significant even in grafts biopsied several years after transplantation. The infiltration with CsA treatment is significantly less than with AP therapy. The magnitude of the infiltrate therefore varies with time, graft status, and immunosuppression. In contrast the phenotypic composition of the infiltrate remains relatively constant in all biopsies after transplantation with T lymphocytes (CD3+), accounting for approximately 35% of infiltrating cells and CD8+ cells more common than CD4+. Monocytes and macrophages account for most of the remainder of the infiltrate.

Antibodies, Monoclonal↗