Predictive value of microsatellite instability for benefit from adjuvant fluorouracil chemotherapy in colorectal cancer.
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Antimetabolites, Antineoplastic↗
Biomedical subjects
M Andreu
Publications and source records attributed to M Andreu.
Anorectal dysfunction in multiple sclerosis.
OBJECTIVE: To ascertain the prevalence of anorectal dysfunction (ARD) in patients with multiple sclerosis (MS) and its relationship with MS clinical characteristics. METHODS: Prospective transversal study in 193 patients with MS. All patients fulfilled a protocol that included: demographic variables, clinical characteristics of MS and the presence of ARD and urinary dysfunction (UD). RESULTS: One hundred and ninety-three patients: 66.8% women, an average age of 42.8 (12.1) years; 67.8% of patients had relapsing remitting MS, 21.2% a secondary progressive and 10.9% a primary progressive form. The average duration of MS was 10.7 (9.4) years and the EDSS 2.8 (2.3). ARD was present in 93 patients (48.2%), and UD in 50.2%. ARD associated to UD was present in 35.7% of cases. The univariate study revealed that patients with ARD were older (P <0.001), had greater disability (P <0.0001), longer disease duration (P <0.001) and a greater association with UD (P<0.0001). ARD was more frequent in progressive forms (P<0.0001). The logistic regression analysis showed that female sex (P = 0.015), EDSS (P = 0.002) and UD (P = 0.003) were independent factors related to ARD. CONCLUSION: ARD is a highly prevalent disorder in MS. Female sex, EDSS and UD are independent predictors of ARD development.
Adult↗
Chronic Chlamydia pneumoniae infection in patients with symptomatic atherothrombosis.
OBJECTIVES: The aim of the present study was to search for an association between chronic Chlamydia pneumoniae infection, indicated by elevated antibody titers against the pathogen, atherothrombosis and the occurrence of arterial ischemic events. METHODS: We studied 52 patients presenting at baseline with at least one symptomatic episode of atherothrombosis. A screening for fasting blood glucose and a lipid profile was performed on all patients who had no known history of diabetes or hypercholesterolemia. RESULTS: The prevalence of IgG and IgA anti-C. pneumoniae antibodies at baseline was 90% (95% CI: 79-97) and 81% (67-90), respectively. Forty-two of the 52 patients (81%) experienced a new arterial ischemic event after a mean follow-up of 9 years [heart: 19 (37%); brain: 12 (23%); lower limbs: 8 (15%); and other: 13 (25%)]. Occurrence of a new arterial ischemic event was related to age (p=0.003), sex (p=0.009), and tobacco smoking (p=0.06). Prevalences of IgA and IgG anti-C. pneumoniae were significantly higher in patients with atherothrombosis at baseline than that in controls. CONCLUSION: Our study confirmed the links between C. pneumoniae and atherothrombosis. However, neither IgA nor IgG antibodies for C. pneumoniae was a significant predictive factor for new ischemic arterial events in patients with atherothrombosis.
Adult↗
Applicability of the Rockall score in patients undergoing endoscopic therapy for upper gastrointestinal bleeding.
BACKGROUND: The Rockall score is used to assess the prognosis of patients with upper gastrointestinal bleeding. AIM: To assess the applicability of the Rockall score in patients undergoing endoscopic therapy for upper gastrointestinal bleeding. METHODS: Retrospective evaluation of the Rockall score in the period 1995-2001. To evaluate the applicability of the Rockall system, two groups were created: group I (Rockall or=6 points). RESULTS: Two hundred and twenty-two patients were included. The median age of patients was 65 +/ -17 years. Hypotension and associated diseases were present in 20 and 50% of patients, respectively. Re-bleeding occurred in 50 patients (23%) whose median score was 7, whereas the median score of patients without re-bleeding was 6 (p=0.14). There were 20 deaths (9%) with a median score of 8, whilst the median score of surviving patients was 6 (p<0.001). Sixteen patients in group I (18.4%) and 34 in group II (25.2%) re-bled (p=0.25). All the patients who died belong to group II with a Rockall score>or=6 (15% versus 0% in groups II and I, respectively, p<0.001). CONCLUSION: The Rockall score can be used in patients who undergo therapeutic endoscopy for upper gastrointestinal bleeding to identify those with high risk for mortality.
Aged↗
Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer.
AIM: Some retrospective studies have shown a lack of benefit of 5-fluorouracil (5-FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient colorectal cancer. Our aim was to assess if this molecular marker can predict benefit from 5-FU adjuvant chemotherapy. A second objective was to determine if MMR status influences short term survival. METHODS: We included 754 patients with a median follow up of 728.5 days (range 1-1097). A total of 260 patients with stage II or III tumours received 5-FU adjuvant chemotherapy, according to standard clinical criteria and irrespective of their MMR status. A tumour was considered MMR deficient when either BAT-26 showed instability or there was loss of MLH1 or MSH2 protein expression. RESULTS: At the end of the follow up period, 206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%) patients had MMR deficient tumours. There were no significant differences in overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients with stage II and III tumours, benefit from 5-FU adjuvant chemotherapy was restricted to patients with MMR competent tumours (overall survival: chemotherapy 87.1%; non-chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR deficient tumours did not benefit from adjuvant chemotherapy (overall survival: chemotherapy 89.5%; non-chemotherapy 82.4%; log rank, p = 0.4). CONCLUSIONS: Benefit from 5-FU adjuvant chemotherapy depends on the MMR status of tumours in patients with colorectal cancer. 5-FU adjuvant chemotherapy improves survival in patients with MMR competent tumours but this benefit from chemotherapy cannot be extended to patients with MMR deficient tumours.
Aged↗
Cellular organization and appearance of differentiated structures in developing stages of the parasitic platyhelminth Echinococcus granulosus.
Echinococcus granulosus is the causative agent of hydatidosis, a major zoonoses that affects humans and herbivorous domestic animals. The disease is caused by the pressure exerted on viscera by hydatid cysts that are formed upon ingestion of E. granulosus eggs excreted by canine. Protoscoleces, larval forms infective to canine, develop asynchronously and clonally from the germinal layer (GL) of hydatid cysts. In this report, we describe the cellular organization and the appearance of differentiated structures both in nascent buds and developed protoscoleces attached to the GL. Early protoscolex morphogenesis is a highly complex and dynamic process starting from the constitution of a foramen in the early bud, around which nuclei are distributed mainly at the lateral and apical regions. Similarly, distribution of nuclei in mature protoscoleces is not homogenous but underlies three cellular territories: the suckers, the rostellar pad, and the body, that surrounds the foramen. Several nuclei are associated to calcareous corpuscles (Cc), differentiated structures that are absent in the earlier bud stages. The number of nuclei is similar from the grown, elongated bud stage to the mature protoscolex attached to the GL, strongly suggesting that there is no significant cellular proliferation during final protoscolex development. The amount of DNA per nucleus is in the same range to the one described for most other platyhelminthes. Our results point to a sequential series of events involving cell proliferation, spatial cell organization, and differentiation, starting in early buds at the GL of fertile hydatid cysts leading to mature protoscoleces infective to canine.
Animals↗
[Helicobacter pylori and gastric cancer: relationship with histological subtype and tumor location].
INTRODUCTION: Helicobacter pylori (HP) has been implicated in the pathogenesis of gastric adenocarcinoma. Published data on HP infection and its association with both histological subtype and tumor localization are contradictory and few data are available on this topic in Spain. The aim of the present study was to evaluate the association of HP infection with histological subtype and tumor localization in a series of patients with gastric adenocarcinoma. MATERIAL AND METHOD: We retrospectively reviewed all the patients diagnosed with gastric neoplasms in Hospital del Mar in Barcelona between 1995 and 2001. The histological subtype was established using Lauren's classification. Tissue samples were obtained from the surgical specimen or from endoscopic biopsies. HP infection was histologically determined through hematoxylin-eosin, Masson's trichromic, and Giemsa staining. RESULTS: During the study period, 304 gastric neoplasms, 275 (90.4%) adenocarcinomas, 22 (7.2%) lymphomas, 3 (1.0%) leiomyosarcomas, 2 (0.7%) degenerated gastrointestinal stromal tumors (GIST) and 2 (0.7%) Kaposi's sarcomas were diagnosed. In patients with adenocarcinoma, the mean age at diagnosis was 69 years and most patients were male (62%). A total of 48.1% of the neoplasms were located in the gastric antrum, 23.7% in the body and 19.1% in the fundus (13.6% in the period 1994-1997 and 25.4% in the period 1998-2001, p = 0.018). Intestinal-type gastric carcinoma was observed in 56% of the patients, diffuse-type in 28% and indeterminate-type in 16%. HP infection was confirmed in 69% of the patients (68% in intestinal subtype, 69% in diffuse subtype, and 69% in indeterminate subtype, p = 0.84), and was significantly associated with distal adenocarcinomas vs. proximal adenocarcinomas (73.6% vs 48.6%, p < 0.05). CONCLUSIONS: No differences were observed between the histological type of adenocarcinoma and HP infection. In the last few years, the incidence of fundic adenocarcinomas has increased. These tumors show a lower association with HP infection.
Adenocarcinoma↗
Role of Helicobacter pylori in stomach cancer after partial gastrectomy for benign ulcer disease.
OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in patients having undergone gastrectomy for non-neoplastic disease who later developed gastric stump cancer. MATERIAL AND METHODS: Retrospective study of all patients with partial gastrectomy for non-malignant peptic disease who were submitted to an endoscopic exploration between 1995 and 2001. A comparison was made of major clinical and histological characteristics, and the presence of Helicobacter pylori among patients with and without gastric cancer in the stomach remnant. RESULTS: A total of 73 patients were studied in this period. Fifteen patients (20.5%) had remnant-stump gastric cancer. All but one were adenocarcinomas (71% intestinal and 29% diffuse, respectively). The average time between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48) years. There was a higher detection rate of Helicobacter pylori in patients with cancer in the gastric remnant (100 vs. 81.5%, respectively, p < 0.07). No relationship was seen between type of gastric reconstruction (Billroth I or II) and rate of Helicobacter pylori detection. CONCLUSIONS: Helicobacter pylori infection is frequent in patients with previous gastrectomy for non-neoplastic disease. The results of the study suggest that Helicobacter pylori infection may play a role in gastric stump cancer.
Adenocarcinoma↗
Nosocomial and community-acquired spontaneous bacterial peritonitis: comparative microbiology and therapeutic implications.
In order to compare the microbiological characteristics of nosocomial and community-acquired episodes of bacterial peritonitis, 95 consecutive, spontaneous episodes were reviewed. Seventy of these episodes were bacteriologically documented. Fifty-three (55.8%) episodes were nosocomial and 42 (44.2%) were community acquired. A total of 78 pathogens were isolated, including 40 gram-positive cocci (34 streptococci, 6 Staphylococcus aureus), 35 gram-negative bacilli (including 23 Escherichia coli), 2 gram-positive bacilli and 1 yeast. Streptococci were found more frequently in community-acquired episodes (53.8%) than in nosocomial episodes (33.3%). Gram-negative bacilli were significantly more frequent in nosocomial episodes than in community-acquired episodes (56.4% vs. 33.3%, P<0.05). Nosocomial isolates were significantly more resistant to amoxicillin-clavulanic acid (48.7% vs. 18.4%, P<0.01) and cefotaxime (33.3% vs. 13.2%, P<0.05) than community-acquired isolates, but no difference was detected regarding resistance to ciprofloxacin. The results indicate that the empirical treatment of spontaneous bacterial peritonitis should differ for nosocomial and community-acquired cases.
Adult↗
[Ponderal evolution in the Girona population, 1989-1999].
BACKGROUND AND OBJECTIVE: Despite the number of plans leading to lose weight among individuals in the developed countries, the prevalence of obesity has increased since 1980. The knowledge of ponderal evolution in a given population is very important because the adverse effects of obesity vary greatly among individuals and populations. The objective of the present paper was to determine the modifications in the different degrees of body adiposity in a population in Catalunya. PATIENTS AND METHODS: A measurement was made of weight and height of 24554 users aged over 14 years (10595 males and 13959 females) attended at four basic health areas (BHA): Girona 1, Girona 4, Salt and Camprodon, and a Primary Health Center (PHC) in the Girona province, for a five-year period, 1995-1999. The prevalence of the different degrees of obesity was compared with that obtained in a previous study with 6373 individuals during the 1986-1989 period (4,579 males and 1794 females). RESULTS: The prevalence of women with overweight (defined as a body mass index [BMI] > 25 kg/m2) increased from 7.3% (1986-1989, study 0) to 17.6% (1995-1999, study 1) for women aged 15 to 24 years ( p < 0.001), from 17.9 % to 28.1% for women aged 25 to 34 years (p < 0.001), and from 37.5% to 44.7 % for women aged 35 to 44 years (p < 0.001). In the latter age group, the proportion of women with obesity (BMI > 30 kg/m2) increased from 6.9% to 12.9%. Similar trends were observed among men, and the change in the 35-44 year age group (from 10.5 % of obese men to 16% [p < 0.001]), and 55 to 65 years (from 16.6% of obese men to 22.7% [p < 0.001] was particularly significant. And lastly, it is also noteworthy the proportion of individuals with low weight (BMI < 18.5 kg/m2) which increased from 7.3% to 11.6% for women aged 15 to 24 years, and from 0.3% to 2.2% for women aged 35 to 44 years. This trend was also observed for men aged 15 to 24 years (11% to 17.2%). CONCLUSIONS: The relative increase in the prevalence of overweight and obesity runs in parallel to that found in other surrounding countries. Also, it is worth mentioning that among women aged 15 to 24 years the increase in the prevalence of low weight and obesity is almost identical, which invalidates the mean and median values as a means to assess the ponderal evolution in this population. The current compartmentalization between the extreme BMIs, particularly among the youngest portion of population should be addressed from a multidisciplinary perspective.
Adolescent↗
[ANCA associated glomerulonephritis related to benzylthiouracil].
INTRODUCTION: Vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) have been reported in patients suffering from Graves' disease treated with anti-thyroid drugs and especially propylthiouracil (PTU). EXEGESIS: We report a case of Graves' disease treated with benzylthiouracil (Basdène). This therapy was complicated by acute renal insufficiency due to crescentic glomerulonephritis associated with pANCA. After benzylthiouracil withdrawal and under corticosteroids, renal insufficiency, biological inflammation and pANCA levels decreased. CONCLUSION: Similar vasculitis associated with pANCA secondary to anti-thyroid drugs, especially propylthiouracil, were described. This suggests a causal relation between drug and vasculitis. To our best knowledge, it is the first case of vasculitis secondary to benzylthiouracil.
Antibodies, Antineutrophil Cytoplasmic↗
[The role of the clinical microbiology laboratory during the outbreak of Legionella spp. in the municipality of Alcoy: the effectiveness of the different diagnosis methods].
BACKGROUND: The effectiveness of the different laboratory test methods to diagnose Legionella spp. in clinical specimens varies according to the epidemiological context. In this study, the usefulness of the laboratory methods used for an outbreak that occurred in the municipality of Alcoy (Alicante, Spain) are evaluated. MATERIALS AND METHODS: 222 community-acquired cases of infection caused by Legionella pneumophila serogroup 1, subtype Pontiac-Knoxville, genotypes I and II were studied, that had been diagnosed by the Microbiology laboratory from January 1999 to December 2000, corresponding to patients residing in the municipality of Alcoy (Alicante). The methods used were direct antigen detection in respiratory specimens by immunoflurescence, direct antigen detection in urine, cultures and serology. RESULTS: The detection of the antigen in urine diagnosed 201 cases (90,5%). Direct immunofluorescence provided a high number of false positives (n=24). A culture was essential to confirm the etiology of the outbreak (25 sputum) strains from 22 patients). Serology complemented the other methods and helped to retrospectively diagnose 21 patients (9%) when the other tests were not carried out or when they provided negative results. CONCLUSIONS: A rapid diagnosis is essential to evaluate the patients and to control epidemical outbreaks, and the detection of the urinary antigen is very useful, but should be complemented with other methods. The culture of the respiratory specimens and the subsequent typing of the strains means that the etiology can be established with certainty and this helps to determine the source(s) of the infection. Serology complemented the diagnosis in 9% of the cases.
Antibodies, Bacterial↗
Comparison of diagnostic methods for Helicobacter pylori infection in patients with upper gastrointestinal bleeding.
BACKGROUND: Accuracy of the most frequently used tests for diagnosing Helicobacter pylori infection in patients with upper gastrointestinal bleeding of peptic origin is determined. METHODS: Seventy-eight patients with endoscopically-proven upper gastrointestinal bleeding of peptic origin were included. The presence of H. pylori was considered when observed from the histology or, if negative, when serology and breath test were both positive. Accuracy of the rapid urease test was estimated in accordance with results obtained with other diagnostic methods. RESULTS: Lesions causing gastrointestinal bleeding were 56 duodenal ulcers, 13 gastric ulcers, 7 pyloric channel ulcers, 13 acute lesions of the gastric mucosa and 16 erosive duodenitis. H. pylori infection was present in 68 patients (87.2%). Forty-four patients had received non-steroidal anti-inflammatory drugs. The sensitivity/specificity (%) of the diagnostic methods was 48.5/100 for the rapid urease test, 91/77.8 for the breath test, 89.5/80 for serology and 86.3/100 for histology. The prior consumption of proton-pump inhibitors and antibiotics induced false-negative results in the rapid urease test and breath test, with no effect on serology and histology. CONCLUSIONS: The prevalence of H. pylori infection in patients with upper gastrointestinal bleeding from peptic lesions is high. Sensitivity of the rapid urease test for diagnosing H. pylori is low in this setting. Cases with negative rapid urease test need the combination of two or more additional tests if diagnosis is to be achieved. Cases with positive rapid urease test do not need further investigation for diagnosis.
Biopsy↗
Blood strontium concentration related to the length of the agonal period in seawater drowning cases.
The levels of ventricular blood strontium (Sr) from 70 seawater drowning victims were compared with their diagnosis of drowning based mainly on certain criteria selected from their autopsy report. From this comparison, intervals of either the difference of Sr concentration between the left and the right ventricle blood (LVSr-RVSr) or the Sr concentration in the left ventricle blood (LVSr), appear to be related to different time-lapses of the agonal period of drowning. In the aim to diagnose drownings, intervals of both LVSr-RVSr and LVSr were proposed to characterize three different agonal periods in seawater drowning cases: instantaneous death (ID), fast vital-submersion drowning (FVSD) and common vital-submersion drowning (CVSD).
Diagnosis, Differential↗
Validity of the hospital discharge diagnosis in epidemiologic studies of biliopancreatic pathology. PANKRAS II Study Group.
BACKGROUND: The aim was to analyse the magnitude, direction and predictors of change in the main hospital discharge diagnosis (HDD) after a clinical expert review, among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases. METHODS: A total of 602 patients with a suspicion diagnosis of pancreas cancer (PC), cancer of the extrahepatic biliary system (CEBS) or benign biliopancreatic pathologies (BPP) were prospectively recruited at five general hospitals. A structured form was used to collect information from medical records. A panel of experts revised all diagnostic information and established the main clinicopathological diagnosis (CPD) by consensus. RESULTS: Of the 204 cases with a HDD of PC, 176 (86%) were deemed to have a CPD of PC, eight of CEBS, twelve a neoplasm of different origin, four BPP and four syndromic diagnoses. Thus, 28 cases (14%) were false positives. Of the 129 patients with a HDD of CEBS, 15 (12%) were false positives. Nine of the 396 cases with a HDD of non-PC (2%) had a CPD of PC (false negatives), whilst 14 of 471 patients with a HDD of non-CEBS (3%) were deemed to have CEBS. Overall, sensitivity and specificity of HDD for PC were, respectively, 95 and 93%, and for CEBS, 89 and 97%. Cytohistological confirmation and laparotomy were independent predictors of diagnostic change. CONCLUSIONS: Validity of the HDD was high, but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results, and highlights the need to review all HDDs. Alternatively, only patients at high risk of misdiagnosis could be reviewed: primarily, those lacking a cytohistological diagnosis or a laparotomy. No exclusions appear warranted solely on the basis of age, gender or tumour spread.
Aged↗
Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis.
BACKGROUND & AIMS: Unfractionated heparin has been found to reduce symptoms and improve healing as adjuvant therapy in patients with ulcerative colitis. The current study evaluated the efficacy and safety of unfractionated heparin in the treatment of ulcerative colitis in comparison with methylprednisolone. METHODS: A multicenter randomized trial with blinded endpoint evaluation was conducted in patients hospitalized for moderate or severe ulcerative colitis. Patients were randomized to receive heparin as a continuous infusion or methylprednisolone (0.75-1 mg x kg(-1) x day(-1)). RESULTS: Twenty-five patients entered the study: 13 received methylprednisolone and 12 received heparin. By day 10, 69% of patients in the methylprednisolone group, but none in the heparin group, achieved significant improvement or remission. C-reactive protein levels significantly decreased in the methylprednisolone group but not in the heparin group. Three patients in the heparin group were withdrawn before day 10 because of an adverse event: rectal bleeding needing transfusion (2 cases) or surgery (1 case). The proportion of patients with persistent rectal bleeding at day 10 was 31% in the methylprednisolone group and 90% in the heparin group (P<0.05). CONCLUSIONS: Unfractionated heparin as monotherapy is not effective in the treatment of moderate or severe ulcerative colitis and is associated with significant bleeding complications.
Adult↗
Infections caused by Escherichia coli resistant to norfloxacin in hospitalized cirrhotic patients.
Selective intestinal decontamination with norfloxacin is useful to prevent bacterial infections in several groups of cirrhotic patients at high risk of infection. However, the emergence of infections caused by Escherichia coli resistant to quinolones has recently been observed in cirrhotic patients undergoing prophylactic norfloxacin. Our aim is to determine the characteristics of the infections caused by E. coli resistant to norfloxacin in hospitalized cirrhotic patients. One hundred and six infections caused by E. coli in 99 hospitalized cirrhotic patients were analyzed and distributed into two groups: group I (n = 67), infections caused by E. coli sensitive to norfloxacin, and group II (n = 39), infections caused by E. coli resistant to norfloxacin. The clinical and analytical characteristics at diagnosis of the infection were similar in both groups. Previous prophylaxis with norfloxacin was more frequent in group II (15/67, 22.4% vs. 32/39, 82%, P <.0001), as a result of a higher number of patients submitted to continuous long-term prophylaxis in this group, whereas previous short-term prophylaxis was similar in both groups. Infections were more frequently nosocomial-acquired in group II than in group I (17/67, 25.3% vs. 20/39, 51.2%, P =.01). The type of infections was similar in both groups: urinary tract infections 38 in group I and 24 in group II, spontaneous bacterial peritonitis 8 and 2, spontaneous bacteremia 4 and 4, and bacterascites 1 and 0, respectively (pNS). Mortality during hospitalization was similar in the two groups (4/67, 5.9% vs. 5/39, 12.8%, pNS). None of the E. coli resistant to norfloxacin were also resistant to cefotaxime and only one of them was resistant to amoxicillin-clavulanic acid. Prophylaxis with norfloxacin, usually continuous long-term prophylaxis, favors the development of infections caused by norfloxacin-resistant E. coli. Long-term antibiotic prophylaxis should therefore be restricted to highly selected groups of cirrhotic patients at high-risk of infection. Infections caused by E. coli resistant to norfloxacin show a severity similar to those caused by sensitive E. coli. No significant associated resistance between norfloxacin and the antibiotics most frequently used in the treatment of bacterial infections in cirrhotic patients has been observed.
Aged↗
CD79b expression in B cell chronic lymphocytic leukemia: its implication for minimal residual disease detection.
The surface expression of CD79b, using the monoclonal antibody (Mab) CB3-1, on B lymphocytes from normal individuals and patients with B cell chronic lymphocytic leukemia (CLL) has been analyzed using triple-staining cells for flow cytometry. In addition, the clinical significance of CD79b expression in CLL patients and its possible value for the evaluation of minimal residual disease (MRD) was explored. A total of 15 peripheral blood (PB) samples from healthy blood donors, five bone marrow (BM) samples from normal donors and 40 PB samples from CLL untreated patients were included in the study. In addition we studied the expression of CD79b in B lymphocytes from five CLL patients after fludarabine treatment in order to support our method. The expression of CD79b in B lymphocytes from PB was analyzed by flow cytometry, using simultaneous staining with the Mabs CD22, CD79b, CD19 and CD5, CD79b and CD19. Since normal immature bone marrow B cells are CD79b-/dim+ on their surface, in BM samples we used the combination CD45, CD79b and CD19 selecting mature B lymphocytes according to their bright CD45 intensity. Cell acquisition was performed in two consecutive steps using a live gate drawn on SSC/CD19+ cells. For data analysis, the PAINT-A-GATE PRO software (Becton Dickinson) was used. Dilution experiments of CD79b- CLL cells and CD79bdim+ CLL cells with normal PB and BM cells were performed in order to assess the sensitivity level of the technique for detection of CD79b-/dim+residual CLL cells. All B lymphocytes from normal samples showed reactivity for the CD79b antigen. In contrast, CD79b was absent in 18/40 CLL patients (42.5%) and 20/40 CLL cases (50%) exhibited a low CD79b expression. Therefore, CD79b- B lymphocytes would be restricted to the CLL population and thus could be considered a 'tumor phenotype' for monitoring MRD in CLL patients. Dilution experiments indicate that the detection limit with this marker almost reaches the levels obtained by molecular biology methods as the PCR technique. All cases studied after fludarabine presented leukemic cells in their PB or BM samples detected by flow cytometry. Upon comparing the clinical and morphological characteristics of CD79b- and CD79b+ cases, all atypical CLL cases included in the present study were CD79b+ and advanced clinical stage (B and C Binet stage) was most frequently observed in CD79b+ cases than in CD79b- cases.
Aged↗