Prostate atypia: clinical and pathological variables associated with cancer diagnosis on repeat biopsy.

The clinical significance of atypical glands suspicious for malignancy (atypia) on prostate biopsy is unclear. We studied a cohort of 139 patients with atypia who underwent repeat prostate biopsy. We analyzed clinical and pathological variables that may be associated with cancer on repeat biopsy. Cancer was diagnosed in 41 (29%) of patients with atypia: 26 of 41 (66%) were Gleason 6, 20% were Gleason 7 and 7% were Gleason 8 (Gleason < 6 not reported). There were no significant associations of age, race, family history, PSA, PSA density (PSAd), number of previous biopsies or time to repeat biopsy with cancer diagnosis. In multivariate regression, histological inflammation was associated with an 85% decreased probability of cancer on repeat biopsy (odds ratio; OR 0.15; 95% confidence interval; CI 0.04-0.57; P=0.04). Radical prostatectomy was performed in 14 of 41 (34%) patients with cancer; 6 (43%) were Gleason sum ≥7, 3 (21%) were pT3a and 1 (7%) had lymph node metastases. In conclusion, inflammation was independently associated with a significantly decreased risk of cancer on repeat biopsy. However, some patients with initial atypia have higher-risk prostate cancer. Additional studies are needed to elucidate these associations.

Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?

BACKGROUND: Exercise can alter health in children in both beneficial (eg reduced long-term risk of atherosclerosis) and adverse (eg exercise-induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses. OBJECTIVES: To determine whether (1) a 6-min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma. METHODS: Children with mild-moderate persistent asthma and age-matched controls (n = 14 in each group, mean age 13.6 years) performed a 6-min bout of cycle-ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry. RESULTS: Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/microl; children with asthma, 1119 (147) cells/microl) and eosinophils (controls, 104 (22) cells/microl; children with asthma, 88 (20) cells/microl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/microl; children with asthma, 232 (53) cells/microl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/microl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/microl) increased in controls, no increase in these cell types was found in children with asthma. CONCLUSIONS: Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilizes circulating immune cells.

[Immunohistochemistry study of EGFR expression in head and neck squamous cell carcinoma]. / Estudio por inmunohistoquímica de la expresión de EGFR en carcinoma de células escamosas de cabeza y cuello.

EGFR is an important transmembrane receptor member of the family of tyrosine kinases, that translates signals from both outside and inside the cell and plays a key role in numerous proceses that affect tumour development, growth, progresion, differentiation, inhibition of apoptosis and metastasis. Immunohistochemistry studies have shown that 40-80% of head and neck squamous cell carcinomas express EGFR and it has been suggested as a potential independent prognostic parameter. The objective of this study is to evaluate by immunohistochemistry the expresi6n of EGFR in a series of Head and Neck Squamous Cell Carcinoma and correlate it to clinico-pathological features and prognostic significance. We investigated expression of EGFR in 44 samples. There was a high expression in 41% of the cases. Even if we have not found that the expression of EGFR correlated with the prognosis of these patients the presence of EGFR is very important because there are chemical agents or drugs that can inhibit its activity.

Estudio por inmunohistoquímica de la expresión de EGFR en carcinoma de células escamosas de cabeza y cuello / Immunohistochemistry study of EGFR expression in head and neck squamous cell carcinoma

EGFR es un receptor transmembrana miembro de la familia de tirosín-kinasas que traduce señales tanto del exterior como del interior de la célula y juega un papel importante en numerosos procesos que afectan a la evolución del tumor, crecimiento, progresión, diferenciación, inhibición de apoptosis y al desarrollo de metástasis. Su expresión mediante inmunohistoquímica en carcinoma de células escamosas varía entre el 40-80% y se le ha adjudicado un valor pronóstico independiente en estos carcinomas. El objetivo del presente estudio es el de analizar por inmunohistoquímica la expresión de esta proteína en una serie de carcinomas epidermoides de cabeza y cuello y correlacionarlo con parámetros clínico-patológicos y supervivencia. Se realiza inmunohistoquímica de 44 muestras en las que el 41% es positivo. A pesar de no haber encontrado relación con el pronóstico de estos pacientes, la presencia de EGFR es muy importante por el hecho de que existen fármacos y agentes químicos capaces de inhibir su actividad

EGFR is an important transmembrane receptor member of the family of tyrosine kinases, that translates signals from both outside and inside the cell and plays a key role in numerous proceses that affect tumour development, growth, progresion, differentiation, inhibition of apoptosis and metastasis. Immunohistochemistry studies have shown that 40-80% of head and neck squamous cell carcinomas express EGFR and it has been suggested as a potential independent prognostic parameter. The objective of this study is to evaluate by immunohistochemistry the expresión of EGFR in a series of Head and Neck Squamous Cell Carcinoma and correlate it to clinico-pathological features and prognostic significance. We investigated expression of EGFR in 44 samples. There was a high expression in 41% of the cases. Even if we have not found that the expression of EGFR correlated with the prognosis of these patients the presence of EGFR is very important because there are chemical agents or drugs that can inhibit its activity

Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer.

Detection, treatment, and prediction of outcome for men with prostate cancer increasingly depend on a molecular understanding of tumor development and behavior. We characterized primary prostate cancer by monitoring expression levels of more than 8900 genes in normal and malignant tissues. Patterns of gene expression across tissues revealed a precise distinction between normal and tumor samples, and revealed a striking group of about 400 genes that were overexpressed in tumor tissues. We ranked these genes according to their differential expression in normal and cancer tissues by selecting for highly and specifically overexpressed genes in the majority of cancers with correspondingly low or absent expression in normal tissues. Several such genes were identified that act within a variety of biochemical pathways and encode secreted molecules with diagnostic potential, such as the secreted macrophage inhibitory cytokine, MIC-1. Other genes, such as fatty acid synthase, encode enzymes known as drug targets in other contexts, which suggests new therapeutic approaches.

Immune response to blood transfusion invery-low-birthweight infants.

BACKGROUND: Allogeneic blood transfusion is common in the treatment of neonatal anemia of prematurity or anemia due to multiple phlebotomies. The immune response of neonates to passenger leukocytes from allogeneic red cells was investigated. STUDY DESIGN AND METHODS: Fourteen infants (4 male, 10 female) prospectively were randomly assigned to receive either white cell-reduced (Group 1) or non-white-cell reduced (Group 2) irradiated blood. Blood samples were taken before and at various time intervals after transfusion (Days 1, 5-7,and 10-14). Cord blood from 11 healthy term infants was used for comparison. The following surface markers were used to assess immune modulation by flow cytometry: CD45RA/CD45RO, CD4/CD8, CD25/CD28, CD3/DR, CD14/B7, and CD3/CD56+CD16. Donor cell microchimerism was studied using semi-quantitative polymerase chain reaction Y-chromosome detection in female infants who received male donor blood. Donor and recipient HLA class II typing was performed with polymerase chain reaction with sequence specific primers. RESULTS: The lymphocyte counts in both groups were significantly increased after transfusion, and there was a significant increase in lymphocytes expressing CD45RA, CD3-/CD16+CD56, CD80, and CD3-/DR on Day 14. The premature infants' pretransfusion natural killer cell population (CD3-/CD16+CD56) was significantly lower than that of term infants, but it reached a similar level by Days 10-14. CD8 subpopulations were increased but not CD4+ cells. Two female infants (of 6) had circulating Y chromosomes 1 day after transfusion, and most of the infants effectively cleared the donor cells within 24 hours of transfusion. Two Group 2 infants who by chance received presumably HLA-haploidentical donor blood developed necrotizing enterocolitis. CONCLUSION: Blood transfusion alters immune cell antigen expression in premature neonates and may initially be immunostimulatory and later immunosuppressive.

Induction of molecular remission by donor peripheral blood leukocyte therapy in patients relapsing with extramedullary blastic phase chronic myeloid leukemia after allogeneic bone marrow transplantation.

Two patients with chronic myeloid leukemia (CML) who relapsed in blastic transformation after allogeneic bone marrow transplantation (BMT) were treated with infusions of leukapheresed peripheral blood mononuclear cells from their original donor. At relapse, their disease was characterized by symptomatic extramedullary deposits of leukemia with minimal (PCR positive, cytologically negative) involvement of bone marrow. Treatment with donor cell infusions was associated with clinical remission, return of full donor chimerism and loss of the BCR-ABL transcript detectable in bone marrow before donor leukocyte infusion (molecular remission). Donor leukocyte infusions should be considered for therapy of relapsed blastic phase CML after allogeneic BMT, especially when the relapse is primarily extramedullary and responsive to local and systemic cytoreductive therapy. However, severe GVHD and CNS relapse remain obstacles to achieving a successful long-term outcome.

Gastric outlet obstruction and epidermolysis bullosa.

We describe a case of pyloric atresia coexisting with epidermolysis bullosa, almost certainly of the junctional type. The coexistence of pyloric atresia and junctional epidermolysis bullosa (PA-JEB syndrome) has been repeatedly observed. This syndrome has several clinical features that distinguish it from Herlitz junctional epidermolysis bullosa (JEB). These include a lack of prominent granulation tissue formation and increased frequencies of genitourinary tract involvement and ear anomalies. Aplasia cutis congenita is sometimes present; esophageal atresia is uncommonly present. In all 12 patients examined to date, normal basement membrane zone expression of laminin-5 biochemically distinguishes PA-JEB syndrome from Herlitz JEB. Mutations in the beta 4 integrin gene have been observed in one patient with PA-JEB syndrome. Thus there are both clinical and biochemical reasons to separate the PA-JEB syndrome from Herlitz JEB. This is the second known case of papillary hyperplasia of the amnion to be seen in any setting. The other was a case of JEB without pyloric atresia.

Reduced frequency of HLA-DQ6 in individuals with a positive direct antiglobulin test.

BACKGROUND: The association between HLA class II antigens and the production of red cell autoantibodies was investigated in this study. STUDY DESIGN AND METHODS: Thirty-one individuals with a positive direct antiglobulin test (DAT) and 85. DAT-negative controls (cadaveric organ donors) were typed using a DNA-based method for class II HLA typing, that is, the polymerase chain reaction with sequence-specific primers. Amplified HLA alleles corresponding to the serologic specificities DR 1-18 and DQ 1-9 were identified. RESULTS: Analysis of DR and DQ frequencies showed that HLA-DQ6 was less frequent in DAT-positive individuals (19% vs. 53% in the control population), with a p value of 0.0014 and a corrected p value of 0.059, and relative risk of 0.23 (95% Cl = 0.09-0.58). The frequency of HLA-DQ6 was higher in asymptomatic DAT-positive blood donors (n = 8, 38% DQ6 positive, p = 0.48) than in DAT-positive hospital and clinic patients (n = 23, 13% DQ6 positive, corrected p value = 0.030, relative risk = 0.13, 95% Cl = 0.04-0.41), 96 percent of whom had evidence of clinical hemolysis. CONCLUSION: This study demonstrates that HLA-DQ6 may have a negative association with a positive DAT result in patients with evidence for hemolysis, and may be a resistance antigen for clinically relevant red cell autoantibodies.

Detection of chimerism and early engraftment after allogeneic peripheral blood stem cell or bone marrow transplantation by short tandem repeats.

Chimerism can be monitored after HLA-matched allogeneic bone marrow transplantation (BMT) or allogeneic peripheral blood stem cell transplantation (PBSCT) by detecting polymorphisms in short tandem repeats (STR). The purpose of our study was to document early complete chimerism in BMT and PBSCT recipients using STR, and to determine whether the initial WBC recovery correlated with the days required to attain complete chimerism. A total of 5 patients (2 PBSCT and 3 BMT) were followed by STR after transplantation. Peripheral blood obtained prior to transplantation was used to determine the 2 most informative STR probes for each donor/recipient pair. STR were amplified by polymerase chain reaction (PCR) with 8 commercial probes, and PCR products were visualized with silver staining. Peripheral blood was evaluated daily post-transplantation for WBC counts and to identify the presence of mixed or full chimerism by STR. The sensitivity of the STR technique varied from 0.05 to 1%, depending on the probe. Full chimerism was documented between day 9 and 14 in PBSCT recipients and on day 14 and 16 in BMT recipients. The initial rise in WBC occurred within 3 days of the onset of full chimerism, indicating that full chimerism is a more sensitive indicator of early engraftment. Periodic recipient monitoring using STR after complete chimerism identifies those patients who revert to mixed chimeras. The STR method may be useful in future studies to determine the significance of early engraftment and the clinical implications of sustained complete chimerism or mixed chimerism.

A novel strategy to limit blood donor exposure and blood waste in multiply transfused premature infants.

UNLABELLED: Small, premature infants require frequent small-volume transfusions. Traditional methods of transfusion expose these infants to multiple blood donors. It has recently been demonstrated that multiple donor exposures can be safely prevented in these infants by the assignment of fresh units to them and by the use of a sterile connecting device to remove blood for transfusion, as needed until the expiration of the unit. However, the program resulted in the wasting of approximately 60 percent of the blood in each unit. STUDY DESIGN AND METHODS: To minimize blood waste without compromising the goal of limiting donor exposure, a model designed to predict each infant's transfusion requirements was investigated. The model assigned infants predicted to have high transfusion requirements to receive blood from a unit dedicated to their individual use. All other infants were assigned to receive blood from a unit that could be shared among as many as four similar infants. Infant donor exposure and blood unit wastage after institution of the infant assignment model were compared with the same measurements obtained before the use of the model, during which time infants were assigned to dedicated units at the discretion of the physician. RESULTS: The numbers of transfusions per infant (3.5 +/- 2.3) and of donor exposures per infant (1.5 +/- 0.7) under the assignment model were unaltered from those in controls (4.1 +/- 2.9 transfusions and 1.6 +/- 0.8 donor exposures); however, there was significantly less blood wastage in the group assigned to shared units (32 +/- 28%) than in the group assigned to dedicated units (62 +/- 17%; p < 0.05) or than was seen in an earlier study (60 +/- 23% wasted; p < 0.05). CONCLUSION: Improved management of blood resources can be achieved within the context of a transfusion program designed to safely limit donor exposure in infants who require frequent transfusion.

Effect of crossmatching on outcome in organ transplantation.

The complement-dependent cytotoxicity (CDC) crossmatch and the flow cytometry crossmatch (FCXM) are both used prospectively in renal transplantation, and their use is under evaluation in other types of major organ transplantation. The FCXM is the more sensitive method and better predicts outcome in second and subsequent renal allografts. Improved survival has unmasked the detrimental effect of a positive crossmatch on outcome in liver transplantation. Because of the urgent need of liver transplant candidates, it is unrealistic to defer transplantation until a crossmatch-negative donor is found; however, additional therapeutic measures may be taken to improve outcome for crossmatch-positive liver recipients. Some reports suggest that prospective crossmatching may improve outcome for sensitized heart recipients, and, additionally, recent studies have demonstrated that HLA compatibility between donor and recipient is an independent variable affecting survival after heart transplantation, prompting a reassessment of the current practice of transplanting hearts without consideration of the HLA match.