Both chromosome 13 abnormalities by metaphase cytogenetics and deletion of 13q by interphase FISH only are prognostically relevant in multiple myeloma

OBJECTIVES: Deletion of chromosome 13q [del(13q)] has emerged as a major adverse prognostic factor in multiple myeloma (MM). Del(13q) is detected two to three times more frequently by interphase fluorescence in situ hybridization (FISH) than by metaphase cytogenetics (CG). However, it has remained unclear whether or not del(13q) detected by FISH only provides the same prognostic information as its detection by CG. METHODS: We investigated the outcome of 118 consecutive patients with newly diagnosed MM who were studied by both CG and FISH (RB-1 and/or D13S319 probes). RESULTS: CG revealed informative MM karyotypes in 35 patients (29.7%), with monosomy 13/del(13q) in 16 of them. FISH was indicative for a del(13q) in 43 patients (36.4%). A del(13q) by FISH was present in all 16 patients with monosomy 13/del(13q) by CG and also in four of 19 patients with informative karyotypes and diploid chromosome 13. Furthermore, del(13q) was present by FISH in 23 of 84 patients with diploid/non-informative metaphases by CG. Overall survival of patients with monosomy 13/del(13q) by CG and of patients with del(13q) by FISH only was not significantly different (median, 35.2 months vs. 33.2 months, P = 0.58). In contrast, patients with diploid chromosome 13 by either technique experienced prolonged survival (median, 65.6 months). Presence of abnormal karyotypes was significantly associated with an increased Ki67 growth fraction. CONCLUSION: FISH of chromosome 13q adds prognostic information to that provided by CG. It is suggested to use FISH analysis in clinical trials if risk stratifications take into consideration the chromosome 13q status.     

Pigment vs cholesterol cholelithiasis: Comparison of stone and bile composition

This report presents a comparative study of gallstone and gallbladder bile composition from 100 unselected American patients, 23 with pigment and 77 with cholesterol cholelithiasis. Cholesterol stones were predominantly composed of cholesterol, whereas pigment stones were mainly composed of an unidentified residue, bilirubin, and bile salts. The residue in pigment stones was not calcium bilirubinate, which sharply contrasts with the composition of bile pigment calcium stones found in Japanese subjects. Bile composition of the two groups differed in that the cholesterol content of biles surrounding pigment stones was significantly less than that of biles surrounding cholesterol stones. Bilirubin in biles was conjugated, but the pigment extracted from stones was unconjugated bilirubin. This study indicates that (1) pigment stones account for an appreciable percentage of gallstone specimens found at cholecystectomy, and (2) pigment stone formation involves the precipitation of bilirubin, bile salts, and unidentified material which is not calcium bilirubinate.Presented at the meetings of the American Federation of Clinical Research, April 29, 1973, Atlantic City, New Jersey. Supported in part by NIH grant AM 14543. Dr. Trotman is a former NIH trainee under NIH grant AM 05462 and currently a recipient of a Macy Foundation Faculty Fellowship.     

Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation.

OBJECTIVES: This study sought to identify whether obesity and obstructive sleep apnea (OSA) independently predict incident atrial fibrillation/flutter (AF). BACKGROUND: Obesity is a risk factor for AF, and OSA is highly prevalent in obesity. Obstructive sleep apnea is associated with AF, but it is unknown whether OSA predicts new-onset AF independently of obesity. METHODS: We conducted a retrospective cohort study of 3,542 Olmsted County adults without past or current AF who were referred for an initial diagnostic polysomnogram from 1987 to 2003. New-onset AF was assessed and confirmed by electrocardiography during a mean follow-up of 4.7 years. RESULTS: Incident AF occurred in 133 subjects (cumulative probability 14%, 95% confidence interval [CI] 9% to 19%). Univariate predictors of AF were age, male gender, hypertension, coronary artery disease, heart failure, smoking, body mass index, OSA (hazard ratio 2.18, 95% CI 1.34 to 3.54) and multiple measures of OSA severity. In subjects <65 years old, independent predictors of incident AF were age, male gender, coronary artery disease, body mass index (per 1 kg/m2, hazard ratio 1.07, 95% CI 1.05 to 1.10), and the decrease in nocturnal oxygen saturation (per 0.5 U log change, hazard ratio 3.29, 95% CI 1.35 to 8.04). Heart failure, but neither obesity nor OSA, predicted incident AF in subjects > or =65 years of age. CONCLUSIONS: Obesity and the magnitude of nocturnal oxygen desaturation, which is an important pathophysiological consequence of OSA, are independent risk factors for incident AF in individuals <65 years of age.     

Comparison of direct immunofluorescence, conventional cell culture and polymerase chain reaction techniques for detecting respiratory syncytial virus in nasopharyngeal aspirates from infants

A total of 316 samples of nasopharyngeal aspirate from infants up to two years of age with acute respiratory-tract illnesses were processed for detection of respiratory syncytial virus (RSV) using three different techniques: viral isolation, direct immunofluorescence, and PCR. Of the samples, 36 (11.4%) were positive for RSV, considering the three techniques. PCR was the most sensitive technique, providing positive findings in 35/316 (11.1%) of the samples, followed by direct immunofluorescence (25/316, 7.9%) and viral isolation (20/315, 6.3%) (p < 0.001). A sample was positive by immunofluorescence and negative by PCR, and 11 (31.4%) were positive only by RT-PCR. We conclude that RT-PCR is more sensitive than IF and viral isolation to detect RSV in nasopharyngeal aspirate specimens in newborn and infants.     

Reduced CD4+,CD25- T cell sensitivity to the suppressive function of CD4+,CD25high,CD127 -/low regulatory T cells in patients with active systemic lupus erythematosus

OBJECTIVE: CD4+,CD25high regulatory T (Treg) cells play a crucial role in the maintenance of self tolerance and prevention of organ-specific autoimmunity. The presence of many in vivo-preactivated CD4+,CD25++ T cells in patients with systemic lupus erythematosus (SLE) poses a difficulty in discriminating CD25++ activated T cells from CD25high Treg cells. To overcome this problem, we analyzed the phenotype and function of CD4+,CD25high,CD127(-/low) natural Treg (nTreg) cells isolated from the peripheral blood of patients with SLE. METHODS: CD4+,CD25high,CD127(-/low) nTreg cells and CD4+,CD25- responder T (Tresp) cells from patients with SLE and normal donors were separated by fluorescence-activated cell sorting. Cell proliferation was quantified by 3H-thymidine incorporation, and immunophenotyping of the cells was done using FACScan. RESULTS: Comparable percentages of CD4+,CD25high,FoxP3+ T cells were observed in patients with SLE and normal donors. Proliferation of SLE nTreg cells sorted into the subset CD4+,CD25high,CD127(-/low) was significantly decreased compared with that of SLE nTreg cells sorted into the subset CD4+,CD25high (mean +/- SEM 2,223 +/- 351 counts per minute versus 9,104 +/- 1,720 cpm, respectively), while in normal donors, these values were 802 +/- 177 cpm and 2,028 +/- 548 cpm, respectively, confirming that effector cell contamination was reduced. Notably, the suppressive activity of nTreg cells was intact in all groups. However, CD4+,CD25- Tresp cells isolated from patients with active SLE were significantly less sensitive than those from patients with inactive SLE to the suppressive function of autologous or normal donor CD4+,CD25high,CD127(-/low) nTreg cells. Furthermore, a significant inverse correlation was observed between the extent of T cell regulation in suppressor assays and the level of lupus disease activity. CONCLUSION: This study is the first to show that, in human SLE, impaired sensitivity of Tresp cells to the suppressive effects of a comparably functional, highly purified nTreg cell population leads to a defective suppression of T cell proliferation in active SLE. Studies aiming to define the mechanisms leading to Tresp cell resistance might help in the development of highly specific, alternative immunotherapeutic tools for the control of systemic autoimmune diseases such as SLE.     

Impact of Empiric Antimicrobial Therapy on Outcomes in Patients with <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> Bacteremia: A Cohort Study

Background  

It is unclear whether appropriate empiric antimicrobial therapy improves outcomes in patients with bacteremia due to Escherichia coli or Klebsiella. The objective of this study is to assess the impact of appropriate empiric antimicrobial therapy on in-hospital mortality and post-infection length of stay in patients with Escherichia coli or Klebsiella bacteremia while adjusting for important confounding variables.