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Biomedical subjects

A Frost

Publications and source records attributed to A Frost.

At least 37 records · Page 2Linked to original sources

Interleukin-13 inhibits cell proliferation and stimulates interleukin-6 formation in isolated human osteoblasts.

Interleukin-13 (IL-13) is a recently identified cytokine that is secreted by activated T cells and regulates inflammatory responses. We have investigated the effects of IL-13 on isolated human osteoblast-like cells (hOB). IL-13 dose-dependently (1-100 pmol/L) reduced the incorporation rate of [3H]thymidine in hOB cells by more than 50%. Using a cell metabolic assay as well as direct cell counting, we found that treatment with IL-13 lead to a decrease in hOB cell number. The effect was both time and dose dependent, and after 12 days of culture, treatment with IL-13 (0.1 nmol/L) caused a 70% decrease in the number of cells. Also, IL-13 increased the levels of IL-6 messenger ribonucleic acid in hOBs, as measured by ribonuclease protection assay, and stimulated secretion of IL-6 into culture supernatants. In conclusion, IL-13 inhibits cell proliferation and increases IL-6 formation in human osteoblasts. Our findings suggest that IL-13 may cause bone loss due to impaired osteoblastic growth and IL-6-induced osteoclast recruitment.

Cell Division↗

K-ras and p53 mutations in aberrant crypt foci and colonic tumors from colon cancer patients.

Aberrant crypt foci (ACF) are microscopic lesions which can be detected, after methylene blue staining, in the overtly normal looking colonic mucosa of cancer patients. ACF have been postulated to be precursor lesions which develop into colorectal cancer. Mutations of K-ras and p53 are two important genetic events implicated in colon carcinogenesis. Mutations in K-ras are detectable at earlier stages, while mutations in p53 are detectable at later stages of colon carcinogenesis. Our objective was to compare the nature of genetic alterations in K-ras (codon 12 and 13) and in p53 (exon 4-9) between ACF and corresponding colonic tumors from cancer patients. ACF with > or =20 crypts/focus were harvested from overtly normal looking colonic mucosa of cancer patients at a distance of (approx.) 5 cm from the site of colonic tumors. The colonic tumors and ACF samples were compared for K-ras codon 12 and 13 base pair sequence, using DNA sequencing and for p53 (exon 5-9) allelic types, using PCR-SSCP and DNA sequencing. The results demonstrated a perfect correlation in terms of the type of K-ras allele (wild or mutated) between the ACF (> or =20 crypts/focus) and corresponding colonic tumors in 11/13 cancer patients. Analyses of p53 mutations demonstrated the presence of p53 mutations in colonic carcinomas from 10/13 patients. However, p53 mutations could be detected in an ACF from only 1/13 patient. The results provides further evidence to the role of ACF as precursor to colon cancer. The presence of an identical K-ras as well as p53 mutation in an ACF and the corresponding colonic carcinoma in a patient suggests the possibility of existence of ACF that may be at a more advanced stage in the sequence of colonic tumorigenesis than others. In conclusion, the results suggest that a subset of ACF with higher multiplicity might be considered more likely to progress to more advanced lesions and should be explored as markers of colon cancer risk.

Adenoma↗

A new fluorometric assay for determination of osteoblastic proliferation: effects of glucocorticoids and insulin-like growth factor-I.

A novel fluorometric proliferation assay, AlamarBlue (AB), was used to study the proliferative capacity of isolated human osteoblasts (hOBs). AB is an oxidation-reduction indicator that yields a fluorescent signal in response to metabolic activity. The assay was performed by replacing the experiment media in a microtiter plate with a 10% AB solution and measuring fluorescence after a 3-8-hour incubation. The assay was optimized with respect to incubation time, cell density, and AB concentration. When the results of the AB assay were compared with cell counting in a Bürker chamber there were consistently good correlations (r > 0.9), regardless of the agonist with which the cells were treated. The mean intraassay coefficient of variance (CV) values were 9.9-11.8% in experiments where osteoblasts were treated for 12 days with insulin-like growth factor-I (IGF-I; 100 nM), or dexamethasone (1 micro;M). IGF-I dose dependently, at and above 1 nM, stimulated proliferation of hOBs. This effect was detectable after 3 days and reached 130-140% of untreated controls after 12 days in culture. The effects of dexamethasone (DEX) on the proliferation rate of hOBs were more complex. In short-term cultures, 3 days, DEX dose dependently stimulated proliferation. However, at and above 6 days, DEX exerted a biphasic effect, with stimulation seen at 1-10 nM and a marked inhibition of cell proliferation at and above 100 nM. dexamethasone, hydrocortisone, prednisolone, and deflazacort had almost identical biphasic effects on osteoblastic proliferation in 12 day cultures with a stimulation seen at 1-10 nM, and a marked inhibition down to 50-60% of untreated controls at and above 100 nM. When IGF-I (0. 1-100 nM; 12 day culture) was combined with different doses of DEX, IGF-I still dose dependently stimulated the proliferation rate in hOBs regardless of the amount of DEX added. The stimulatory effect of DEX (10 nM, 12 days culture) was additive to the effect of 100 nM IGF-I. We conclude that AB is an easy and reliable assay for osteoblastic cell proliferation, well suited for large scale studies of cell growth using small amounts of cells, and that IGF-I partly reverses the glucocorticoid-induced inhibition of osteoblastic proliferation.

Cell Division↗

Inflammatory cytokines regulate proliferation of cultured human osteoblasts.

We investigated the effects of various pro-inflammatory cytokines on the proliferation rate of isolated human osteoblastic cells in primary cultures. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-beta (TNF-beta) time- and dose-dependently enhanced the proliferation of human osteoblasts. Both of these cytokines also enhanced endogenous prostaglandin E2 (PGE2) formation. Exogenous PGE2 dose- and time-dependently-stimulated cell proliferation. However, the stimulatory effects of IL-1 beta and TNF-beta on osteoblast proliferation were not abolished by indomethacin, indicating a direct effect by these cytokines on the rate of proliferation. TNF-alpha stimulated proliferation at low doses, while it significantly inhibited proliferation at higher concentrations (at and above 100 pM) and with prolonged incubation times. This biphasic effect was unaffected by indomethacin. Interleukin-6, finally, did not affect the rate of proliferation. Our findings show that inflammatory cytokines may stimulate or inhibit the proliferation of isolated human osteoblasts, depending on concentration and time.

Cell Division↗

A rapid dual organ rat carcinogenesis bioassay for evaluating the chemoprevention of breast and colon cancer.

In this study we evaluated the effect of dietary administration of a high fat, low fiber diet (HRD) with or without 2% phytic acid (PA) on the development of mammary cancer and/or colon cancer in rats exposed to methylnitrosourea (MNU), azoxymethane (AOM) or MNU + AOM. The rats were fed a HRD alone or a HRD + 2% PA. At the end of week 2, the rats were given either a s.c. injection of MNU (50 mg/kg body wt) or one of normal saline (vehicle). At the end of weeks 3 and 4, the rats were given either a s.c. injection of AOM (15 mg/kg body wt per week) or one of normal saline (vehicle). Nine weeks after the injection of MNU or saline, 10 rats from each group were sacrificed and the mammary tumor incidence and the number of colonic aberrant crypt foci (ACF) were compared between different groups. The administration of different diets was continued for an additional 21 weeks and the mammary tumor and colon tumor incidence between different groups were compared. Results showed that rats injected with MNU alone did not develop ACF or colon tumors while those injected with AOM alone did not develop mammary tumors. Linear regression analysis of the number of ACF at 11 weeks versus colonic tumor incidence at 32 weeks, and the linear regression analysis of mammary tumor incidence at 11 weeks versus mammary tumor incidence at 32 weeks, both showed good linear correlation. These results demonstrate the potential value of the short term dual organ carcinogenesis bioassay for screening chemopreventive agents for their relative ability to inhibit the development of mammary cancer and/or colon cancer while on high risk diet.

Animals↗

Spinal fractures in patients with ankylosing spondylitis.

Thirty-one consecutive patients with ankylosing spondylitis and spinal fractures were reviewed. There were 6 women and 25 men with a mean age of 60 +/- 11 years; 19 had cervical and 12 had thoracolumbar injuries. Of the patients with cervical fracture, two had an additional cervical fracture and one had an additional thoracic fracture. Three trauma mechanisms were identified: high-energy trauma in 13 patients, low-energy trauma in 13 and insufficiency fracture in 5. One-third of the patients suffered immediate neurological impairment, a further one-third developed neurological impairment before coming for treatment and only one-third remained intact. Two patients with thoracolumbar fractures had deteriorated neurologically due to displacements during surgery at other hospitals. All patients were treated operatively except the two patients with two-level cervical fractures, who were managed in halo vests. In the cervical spine both anterior and posterior approaches were employed. In the thoracolumbar spine the majority of the patients were initially treated using a posterior approach only. Complications were common. Of the 27 patients with neurological compromise, 10 had remained unchanged; 12 had improved one Frankel grade; 4 had improved by two Frankel grades; 1 had improved by four Frankel grades. We conclude that even minor trauma can cause fracture in an ankylosed spine. A high proportion of patients with spinal fractures and ankylosing spondylitis have neurological damage. The risk of late neurological deterioration is substantial. As the condition is very rare and the treatment is demanding and associated with a very high risk of complications, the treatment of these patients should be centralised in special spinal trauma units. A combined approach that stabilises the spine from both sides is probably beneficial.

Cervical Vertebrae↗

Pulmonary retransplantation: does the indication for operation influence postoperative lung function?

OBJECTIVE: An international series of pulmonary retransplantation was updated to determine the factors associated with pulmonary function, bronchiolitis obliterans syndrome stage, and survival after operation. METHODS: One hundred sixty patients underwent retransplantation in 35 centers from 1985 to 1995. Logistic regression methods were used to determine variables associated with 3-month and 2-year survival after retransplantation. Values of forced expiratory volume in 1 second were contrasted between groups by unpaired, two-tailed t tests. RESULTS: The median follow-up in surviving recipients was 780 days. Actuarial survival was 45% +/- 4%, 41% +/- 4%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the only predictor of 3-month survival was preoperative ambulatory status (p = 0.005), whereas center experience with at least five pulmonary retransplantations was the sole predictor of 2-year survival (p = 0.04). The prevalence of stage 3 (severe) bronchiolitis obliterans syndrome was 12% at 1 year, 15% at 2 years, and 33% at 3 years after retransplantation. Retransplant recipients with stage 3 bronchiolitis obliterans syndrome at 1 year had a significantly worse actuarial survival than those with stages 0 to 2 (p < 0.01). By 3 years after retransplantation, the forced expiratory volume in 1 second was significantly lower in patients who underwent reoperation because of obliterative bronchiolitis than in patients who underwent retransplantation because of acute graft failure or an airway complication (p = 0.02). Only 31% of patients who underwent retransplantation because of obliterative bronchiolitis were free of bronchiolitis obliterans syndrome at 3 years versus 83% of patients who underwent retransplantation because of other indications (p = 0.02). CONCLUSIONS: Preoperative ambulatory status predicts early survival and center volume predicts intermediate-term outcome after retransplantation. Improved management strategies are necessary to prevent the development of progressive graft dysfunction after retransplantation for obliterative bronchiolitis.

Actuarial Analysis↗

The effect of dietary fat on the promotion of mammary and colon cancer in a dual-organ rat carcinogenesis model.

Female Sprague-Dawley rats (n = 270) were randomly divided into nine subgroups (30 rats/group) and fed diets with fat contents ranging from 5% to 45% of total energy, in which fat was isocalorically substituted for carbohydrates. At Week 3, the rats were given a single injection of methylnitrosourea (MNU, 50 mg/kg body wt). At Weeks 4 and 5, rats were given an injection of azoxymethane (AOM, 15 mg/kg body wt sc). The rats were maintained on their respective experimental diets until they were sacrificed. Nine weeks after the injection of MNU, 10 rats from each group were killed and their mammary tissue was examined for tumors and their colons for aberrant crypt foci (ACF) formation. The results showed no significant increase in the number of colonic ACF or mammary tumors at 11 weeks among individual groups consuming 5-25% energy from fat or among groups consuming 30-45% energy from fat. Data analysis indicated that the effects of the two diets (5-25% energy from fat and 30-45% energy from fat) on ACF formation as well mammary tumor development were statistically different. Continuation of the diets for 32 weeks led to the development of colonic and mammary tumors. Analysis of the combined group tumor incidence data clearly showed that the colonic and mammary tumor incidence in groups fed 30-45% of energy from fat was significantly higher than that observed among groups fed 5-25% of energy from fat. Linear regression analysis of the colonic ACF at 11 weeks, colonic tumor incidence at 32 weeks, and mammary tumor incidence at 11 and 32 weeks showed good linear correlation, demonstrating the potential value of ACF and mammary tumors at 11 weeks for evaluating the carcinogenic risk associated with different diets. The main conclusion of the experiment is that the incidence of colon and mammary cancers increased rapidly when the dietary levels of fat were increased from 15% to 30% of calories and that there was no significant influence on the colon and mammary cancer risk beyond 30% of calories from fat.

Adenocarcinoma↗

Inhibition of progression of aberrant crypt foci and colon tumor development by vitamin E and beta-carotene in rats on a high-risk diet.

In this study we evaluated the effect of dietary administration of a high-fat, low-fiber diet (HRD) supplemented with Vitamin E, beta-carotene or folic acid and wheat bran on the growth of pre-existing aberrant crypt foci (ACF) that had been induced in Fischer-344 rats exposed to azoxymethane (AOM) and a HRD for 10 weeks. The rats (25 rats/dietary group) were fed a HRD for 2 weeks and were then given 2 subcutaneous injections of AOM (15 mg/kg body weight) while the rats continued on the HRD. After 6 weeks, rats were either maintained on the HRD (control) or crossed over to a HRD containing non-toxic levels of either Vitamin E, beta-carotene, folic acid or wheat bran. At 10, 14 and 18 weeks after the initiation of the experiment, 5 rats from each group were killed and the number of aberrant crypt foci (ACF) with different multiplicities were compared between groups. The dietary intervention was continued for 30 weeks to determine whether the inhibitory effect on the growth of ACF influenced the subsequent development of colonic tumors. The results revealed that vitamin E and beta-carotene caused a significant decrease in the number of ACF of different multiplicities when compared to the effect of the HRD alone. The decrease in the number of ACF due to folic acid and wheat bran appeared to be much smaller and in most cases was not significant. However, there was also a significant decrease in the incidence of colonic tumors and tumor multiplicity in both the vitamin E and beta-carotene groups that was not seen in the control group. The reports clearly demonstrates the ability of vitamin E and beta-carotene to inhibit the growth of colonic ACF, even in the presence of the strong promoting effect of high levels of dietary fat, using a post-initiation experimental design.

Animals↗

The time of appearance and disappearance of fetal DNA from the maternal circulation.

A single copy Y-chromosome DNA sequence was amplified using the polymerase chain reaction (PCR) from the peripheral blood of 30 women who had achieved a pregnancy through an in vitro fertilization (IVF) programme. The time of conception was known precisely and was confirmed by serial ultrasound scans. Conceptions were dated as the number of weeks after fertilization plus 2, to give a time equivalent to the obstetric menstrual dating of the pregnancy (LMP). Y-chromosome-specific DNA was detected in all pregnancies with a male fetus (18/30). The earliest detection was at 4 weeks and 5 days, and the latest at 7 weeks and 1 day. Y-chromosome-specific sequences were no longer detected in any of the male pregnancies 8 weeks after delivery. No Y-chromosome sequences were detected in any of the pregnancies where only female babies were delivered. This demonstrates that fetal DNA appears in the maternal circulation early in the first trimester, that it can be identified in all pregnancies tested by 7 weeks, that it continues to be present throughout pregnancy, and that it has been cleared from the maternal circulation 2 months after parturition. Early non-invasive prenatal diagnosis for aneuploidies and inherited disorders will be possible in all pregnancies if fetal cells can be isolated free from maternal contamination (or identified accurately in the presence of maternal cells) without problems of contamination from previous pregnancies.

DNA↗

Recurrence of obliterative bronchiolitis and determinants of outcome in 139 pulmonary retransplant recipients.

An international series of pulmonary retransplantation was updated to identify the predictors of outcome and the prevalence and recurrence rate of obliterative bronchiolitis after operation. The study cohort included 139 patients who underwent retransplantation in 34 institutions in North America and Europe between 1985 and 1994. Eighty patients underwent retransplantation because of obliterative bronchiolitis, 34 because of acute graft failure, 13 because of intractable airway complications, 8 because of acute rejection, and 4 because of other indications. Survivors were followed up for a median of 630 days, with 48 patients alive at 1 year, 30 at 2 years, and 16 at 3 years after retransplantation. Actuarial survival was 65% +/- 4% at 1 month, 54% +/- 4% at 3 months, 45% +/- 4% at 1 year, 38% +/- 5% at 2 years, and 36% +/- 5% at 3 years; nonetheless, of 90-day postoperative survivors, 65% +/- 6% were alive 3 years after retransplantation. Life-table and univariate Cox analysis revealed that more recent year of retransplantation (p = 0.009), identical match of ABO blood group (p = 0.01), absence of a donor-recipient cytomegalovirus mismatch (p = 0.04), and being ambulatory immediately before retransplantation (p = 0.04) were associated with survival. By multivariate Cox analysis, being ambulatory before retransplantation was the most significant predictor of survival (p = 0.008), followed by reoperation in Europe (p = 0.044). Complete pulmonary function tests were done yearly in every survivor of retransplantation and bronchiolitis obliterans syndrome stages were assigned. Eleven percent of patients were in stage 3 at 1 year, 20% at 2 years, and 25% at 3 years after retransplantation. Values of forced expiratory volume in 1 second decreased from 1.89 +/- 0.13 L early after retransplantation to 1.80 +/- 0.15 L at 1 year and 1.54 +/- 0.16 L at 2 years (p = 0.006, year 2 versus baseline postoperative value). Most of this decrease occurred in patients who underwent retransplantation because of obliterative bronchiolitis, whereas the pulmonary function of patients who underwent retransplantation because of other conditions did not significantly change. We conclude that survival after pulmonary retransplantation is improving. Optimal results can be obtained in patients who are ambulatory before retransplantation. Compared with recent data after primary lung transplantation, bronchiolitis obliterans syndrome does not appear to recur in an accelerated manner after retransplantation. As long as early mortality as a result of infection can be minimized, pulmonary retransplantation appears to offer a reasonable option in highly selected patients.

ABO Blood-Group System↗

Effect of beta-carotene and wheat bran fiber on colonic aberrant crypt and tumor formation in rats exposed to azoxymethane and high dietary fat.

The typical high-fat, low-fiber American diet promotes colon cancer. An alternative to radical changes in dietary habits is to reinforce the diet with cancer protectors. Experiments to evaluate the effects of beta-carotene in the presence of high fat and low and high dietary levels of wheat bran fiber were designed using the Fischer-344 rat colon cancer model. Rats (20/group), were given either high fat (20% w/w), low wheat bran, fiber (1% w/w) diets, or high fat (20% w/w) high wheat bran fiber (8% w/w) diets, with different levels of beta-carotene. After 2 weeks of adaptation, half were given two weekly s.c. injections of azoxymethane (AOM, 15 mg/kg body wt); and half two weekly s.c. injections of saline. Six weeks later, five rats from each dietary group were killed to evaluate the comparative effect of different dietary regimens on the induction of colon aberrant crypt foci (ACF). The remaining rats were maintained on their respective diets for an additional 20 weeks to examine the effect on colon tumor incidence. The total number of ACF/rat in the low-fiber groups declined from 44.0 +/- 4.18 to 12.8 +/- 1.95 in response to increasing amounts of beta-carotene from 1 to 20 mg/kg diet. A similar progressive reduction in total ACF/rat was also seen in the high-fiber groups (20.8 +/- 2.92 to 9.2 +/- 0.58). ACF did not develop in the saline-exposed groups. Similarly colon tumor incidence declined from 73% to 20% in high-fiber groups and from 27% to 13% in low-fiber groups in response to increasing amounts beta-carotene from 1 to 20 mg/kg diet. The results showed that beta-carotene and wheat bran, individually and when combined, protected the colon in rats consuming high-fat, western-style diets from ACF and benign or malignant tumor formation.

Animals↗

The introduction of two silent mutations into a CFTR cDNA construct allows improved detection of exogenous mRNA in gene transfer experiments.

Phase one clinical trials for gene therapy of cystic fibrosis are in progress using either liposomes or adenoviral vectors for CFTR gene transfer to epithelial cells in the airways. In addition to electrophysiological measurements, expression of vector CFTR is usually assessed by RT-PCR. We have developed a CFTR-expression vector, pCFAS, that simplifies the distinction of transgene-derived CFTR mRNA from endogenous mRNA. Two point mutations were introduced into CFTR cDNA which eliminated a SphI restriction site and created a new, unique AgeI restriction site. Neither mutation altered the predicted amino acid sequence of the protein. Restriction digestion of RT-PCR products from cells transfected with pCFAS allowed the differentiation of transgene and endogenous CFTR transcripts. To verify function of the mutated CFTR, the plasmid was transferred into freshly obtained nasal epithelial cells from CF patients ex vivo using cationic liposomes. Fluorescence microscopy using the halide-sensitive fluorophore SPQ demonstrated restoration of cAMP-mediated Cl- secretion. This plasmid will be useful for CFTR gene transfer studies in vitro and in vivo.

Base Sequence↗

Pulmonary alveolar proteinosis in a painter with elevated pulmonary concentrations of titanium.

We present the case of a professional painter who developed pulmonary alveolar proteinosis (PAP) with severe respiratory failure. He required total bilateral pulmonary lavage on two separate occasions, 3 months apart. Quantitative analysis of particles found in lung tissues obtained by open lung biopsies demonstrated the presence of titanium (60-129 million particles of titanium per cm3 of lung tissue). This report extends previous results from animal studies that demonstrated development of alveolar proteinosis in rats following exposure to titanium. It has been proposed that the overwhelming impairment of the normal clearance mechanisms of the lung by particles of titanium is one of the possible mechanisms responsible for the development of this lung disease. We suggest that a similar mechanism occurred in our patient and that titanium should be recognized as a potential cause of PAP in humans.

Adult↗

Seventy-two pulmonary retransplantations for obliterative bronchiolitis: predictors of survival.

BACKGROUND: Obliterative bronchiolitis (OB) occurs in up to 40% of patients in the intermediate term after lung transplantation. In recent years an increasing number of recipients with end-stage OB have been treated with retransplantation. METHODS: Seventy-two patients with OB underwent retransplantation at 26 North American and European centers a median of 590 days after their first transplant operation. The predictors of survival were determined using life table and Cox proportional hazards methods, and the recurrence rate of OB was determined in survivors. RESULTS: The actuarial survival rate was 71% +/- 5% at 1 month, 43% +/- 6% at 1 year, and 35% +/- 6% at 2 years; nonetheless, of the 90-day postoperative survivors, 63% +/- 7% were alive 2 years after retransplantation. Institutional experience with more than three pulmonary retransplantations (p = 0.008), reoperation in Europe (p = 0.013), donor-recipient ABO blood group identity (p = 0.018), and more recent year of retransplantation (p = 0.03) were associated with survival. On multivariate analysis, reoperation after 1989 (p < 0.001), retransplantation performed in Europe (p = 0.017), and being ambulatory immediately before reoperation (p = 0.022) were found to be predictive of a positive outcome. Pulmonary function test analyses confirmed that the forced expiratory volume in 1 second decreased from postoperative baseline values by 11% +/- 9% at 1 year and 27% +/- 10% at 2 years (p = 0.02; year 2 versus baseline). Fourteen percent of patients were in stage 3 of the bronchiolitis obliterans syndrome at 1 year postoperatively, with 33% affected at 2 years. CONCLUSIONS: The results of pulmonary retransplantation for OB are improving. Current evidence indicates that OB does not recur in an accelerated manner after retransplantation, although pulmonary function does worsen again by 2 years. Pulmonary retransplantation is appropriate only in selected patients with OB who are ambulatory and are operated on at experienced centers.

Adolescent↗

Diagnosis of chronic lung transplant rejection by transbronchial biopsy.

Chronic rejection in the form of obliterative bronchiolitis (OB) associated with chronic inflammation and fibrosis of bronchi (CIB) is a significant cause of morbidity and mortality in long-term heart-lung and single-lung transplant recipients. To determine the utility of transbronchial biopsy in diagnosing chronic rejection, we reviewed 24 transbronchial biopsies (TBBs) performed at the time of, or subsequent to, a clinical diagnosis of OB of chronic rejection in eight heart-lung and single-lung transplant recipients at the Methodist Hospital, Houston, Texas. These were compared with 36 randomly selected control TBBs from 14 patients without a clinical or histopathologic diagnosis of OB of chronic rejection at any time in their course. In the former group of TBBs, nine (38%) were diagnostic of OB and seven (29%) showed CIB suspicious for chronic rejection. TBBs diagnosed as negative had significantly fewer samples of tissue (1.0 versus > 3) and significantly smaller size of tissue (1.44 mm versus > 4.5 mm) than did TBBs in the OB or CIB categories. When strict criteria were used, no false diagnoses of OB of chronic rejection were made on control TBBs. However, OB associated with bronchiolitis obliterans organizing pneumonia of viral pneumonitis was present in three (8%) and CIB in 15 (42%) of control TBB associated with acute rejection and infection. This finding emphasizes the nonspecificity of CIB. We conclude that TBB is potentially useful in diagnosing OB of chronic rejection in some cases and in suggesting chronic rejection in other cases. Inadequate sampling by the bronchoscopist was the major reason for a negative biopsy.

Adolescent↗

Ectopic breast cancer: case report and literature review.

Ectopic breast tissue includes both supernumerary and aberrant breast tissue. The incidence of supernumerary tissue has been reported as high as 6% depending on the ethnic group studied. The incidence of aberrant breast tissue remains unknown. The development of malignancy within these anomalies is rare. In the following paper, the case report of a patient with an ectopic breast cancer and a second primary cancer of the left anatomic breast is described. A review of the world literature on ectopic breast cancer follows. Specific characteristics of ectopic breast cancer are defined and recommendations for management are made.

Breast↗