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  Clinical Abstracts





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January 2002

  • Anti-rotavirus titers and protection against diarrheal disease
  • Predicting diabetes in Chinese subjects using FPG and HbA1c
  • Urine-to-creatinine ratio and 24-hour urine protein excretion
  • Gastrointestinal causes of iron deficiency in asymptomatic patients
  • Detecting disseminated cancer cells in peripheral blood using molelecular techniques
  • Rethinking pre-analytic processing of pleural fluid as a specimen
  • Parvovirus B19 infection and Lupus-like disease

    Anti-rotavirus titers and protection against diarrheal disease
    It is estimated that nearly 870,000 infants and young children die annually due to diarrheal disease. Group A human rotaviruses are the most important cause. Developing a vaccine is a global health priority, and understanding the immunology of naturally acquired infection has great significance. The authors conducted a study in which they monitored 200 children in a low-income area of Mexico City weekly for rotavirus excretion and diarrhea from birth to two years of age. Anti-rotavirus IgA and IgG titers were determined at birth and every four months thereafter. Lower risks of rotavirus infection and diarrhea (adjusted relative risk, 0.21 and 0.6, respectively) were seen in children with IgA titers of more than 1:800. These children were completely protected against moderate to severe diarrhea. Children with IgG titers greater than 1:6,400 were protected against rotavirus infection (adjusted relative risk, 0.51) but not against diarrhea. The protective levels of antibody titer occurred after two consecutive symptomatic or nonsymptomatic rotavirus infections. The authors concluded that anti-rotavirus titers, especially IgA titers, are meaningful markers of protection.

    Velázquez FR, Matson DO, Guerrero ML, et al. Serum antibody as a marker of protection against natural rotavirus infection and disease. J Infect Dis. 2000;182: 1602-1609.

    Reprints: Dr. Guillermo M. Ruiz-Palacios, Dept. of Infectious Disease, Instituto Nacional de la Nutrición, Vacso de Quiroga No. 15, Delegación Tlalpan, Mexico City 14000, D.F. Mexico;

    Predicting diabetes in Chinese subjects using FPG and HbA1c
    The new American Diabetes Association criteria for diagnosing diabetes use fasting plasma glucose as a primary modality in lieu of the oral glucose tolerance test and omit the two-hour post prandial glucose. This potentially misses those subjects who have normal FPG but elevated PG. The authors of this study proposed using paired measurements of FPG and hemoglobin A1c as a screen, with only those individuals having high FPG and HbA1c receiving a confirmatory OGTT, thus avoiding more than 80 percent of OGTTs. Between 1988 and 1995, the authors screened 2,877 Chinese subjects in an outpatient department in Hong Kong who had risk factors for diabetes. Of these subjects, 2,250 had baseline FPG and PG below the criteria set by the World Health Organization. Among those, 265 were randomly recruited for annual OGTTs until they developed diabetes. Of these 265 subjects, 57 had a baseline FPG greater than ADA criteria (>7.0 mmol/L) and were excluded. Of the remaining 208 subjects, 26 were men and 182 were women. After a median followup of one year (range, one to seven years) 44 (21.2 percent) progressed to diabetes and 164 (78.8 percent) did not. The diabetics had a likelihood ratio of 9.3 that their initial baseline FPG and HbA1c were elevated, whereas the comparable likelihood ratio for the nondiabetics was 0.6 to 1.1. The crude ratio of progression was more than five times higher in patients with initial baseline FPG of 6.1 mmol/L or greater and hemoglobin A1c of 6.1 percent or greater compared with those below these cutoffs.

    Ko GTC, Chan JCN, Tsang LWW, et al. Combined use of fasting plasma glucose and HbA1c predicts the progression to diabetes in Chinese subjects. Diab Care. 2000;23:1770-1773.

    Reprints: Gary T. C. Ko, FRCPI, Dept. of Medicine, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Rd., Tai Po, NT, Hong Kong, China;

    Urine-to-creatinine ratio and 24-hour urine protein excretion
    The measurement of proteinuria is useful for the early recognition and assessment of renal disease and can serve as an early indication of graft rejection. Urine protein measurement traditionally is determined through a 24-hour urine collection. The purpose of this study was to examine the use of the random ("spot") urine protein:creatinine (P/C) ratio for evaluating proteinuria in renal transplantation. For the study, 289 adult renal transplant patients provided 24-hour urine collections. Of these patients, 192 had second 24-hour urine collections with concomitant random urine specimens. Each of these two 24-hour collections was collected, on average, 6.8 months apart. And 134 of the patients provided a total of 851 multiple-paired spot and 24-hour urine samples (range, two to 12) during a two-year period. Urinary protein was measured using the Boehringer Mannheim biuret reagent, with sodium hydroxide pretreatment using the Hitachi 917. Urinary creatinine was measured by the Boehringer Mannheim Jaffe method (kinetic) without deproteinization by the Hitachi 917. The random urine P/C ratio significantly correlated with the 24-hour urine protein (r=0.793; P<0.0001). Linear regression after log/log transformation also showed significant correlation (r=0.749; P<0.0001). The positive predictive value of random urine P/C ratios to predict 24-hour urine protein excretion of more than 0.5, more than 1.0, and more than 2.0 was high (72 to 86.5 percent); however, it was only 50 percent for proteinuria greater than 3.0 g/day. The negative predictive values ranged from 95 to 99 percent for all levels studied. The P/C ratio of a random urine sample also seemed to be a useful longitudinal test for assessing proteinuria over time. The authors concluded that the random urine P/C ratio is a useful and convenient screening and longitudinal test for proteinuria.

    Torng S, Rigatto C, Rush DN, et al. The urine protein to creatinine ratio (P/C) as a predictor of 24-hour urine protein excretion in renal transplant patients. Transplantation. 2001;72:1453-1456.

    Correspondence: Dr. J. R. Jeffrey, University of Manitoba, Health Sciences Centre, 820 Sherbrook St., GE 441, Winnepeg, MB/R3A 1R9, Canada;

    Gastrointestinal causes of iron deficiency in asymptomatic patients
    The authors conducted a prospective study to examine gastrointestinal causes of iron deficiency anemia in patients who did not have gastrointestinal symptoms. Of 1,202 consecutive patients referred for evaluation, 668 (581 women; median age, 33 years) met the criteria for iron deficiency. After excluding patients because of obvious blood loss, previous gastric surgery, aspirin or nonsteroidal anti-inflammatory drug use, pregnancy, heavy menstrual blood loss, and other factors, 81 patients (60 women; median age, 54 years) were enrolled in the study. All patients underwent gastroscopy with antral and duodenal biopsies, as well as biopsies of suspicious lesions. Sixty-three patients underwent colonoscopy with biopsies. The eight patients who refused colonoscopy were evaluated with a double-contrast barium enema. At least one finding likely to cause iron deficiency anemia was detected in 60 patients (upper tract in 20 percent, lower tract in 21 percent, nonbleeding-associated in 51 percent, no gastrointestinal findings in 15 percent). Nonbleeding-associated findings included atrophic gastritis (27 percent), celiac disease (six percent), and Helicobacter pylori chronic gastritis (18 percent). Forty-one patients (58 percent) had evidence of H. pylori infection. In 11 patients (15 percent) with negative initial evaluations, one was diagnosed with jejunal cancer after a small bowel series and one was diagnosed with prostate cancer. Eighty-five percent of patients with iron deficiency anemia who did not have gastrointestinal symptoms had at least one gastrointestinal finding likely to cause iron deficiency anemia. Furthermore, nonbleeding-associated diseases were more frequent causes of iron deficiency anemia in patients without gastrointestinal signs or symptoms than were bleeding-associated diseases. The authors believe the findings support the use of gastroscopy as part of the initial diagnostic evaluation in such patients.

    Annibale B, Capruso G, Chistolini A, et al. Gastrointestinal causes of refractory iron deficiency anemia in patients without gastrointestinal symptoms. Am J Med. 2001; 111:439-445.

    Correspondence: Dr. Bruno Annibale, Dept. of Gastroenterology, II Clinica Medica, Policlinico Umberto I, Universita La Sapienza, Viale del Policlinico 155, 00161, Rome, Italy

    Detecting disseminated cancer cells in peripheral blood using molecular techniques
    The authors studied 36 patients with advanced colon cancers to find a predictor for liver metastasis and eradicate the metastasis. Twenty-four of the patients (group one) had no distant metastases, and 12 patients (group two) had liver metastases at the time of surgery. All patients underwent colectomy with or without lymph node dissection. Heparinized peripheral blood samples were obtained twice prior to the operations, and colon cancer tissues were obtained from the resected specimens. The specimens were fixed and embedded in paraffin using the standard method for immunohistochemistry. RNA was extracted from the peripheral blood, and reverse transcriptase polymerase chain reaction was conducted for carcinoembryonic antigen. The expression of sialylated carbohydrates was also investigated immunohistochemically. Nine of the 12 patients with liver metastases and eight of the 24 patients without liver metastases showed a carcinoembryonic antigen-specific signal in the blood by PCR. This difference was 75 percent in the metastasis group and 33 percent in the group without metastasis and was highly statistically significant. The rates of sialyl Lewis A and sialyl Lewis X were significantly lower in the tumors without liver metastases than in those with liver metastases. Three of the four patients initially without liver metastasis showed clinically evident metastasis within a year after surgery. These patients also had shown a CEA-positive signal in their blood preoperatively and had tumors with a strong expression of sialyl Lewis X. The authors concluded that combining both markers may provide prognostic information for liver metastases in colon cancer.

    Ichikawa D, Kitamura K, Tani N, et al. Molecular detection of disseminated cancer cells in the peripheral blood and expression of sialylated antigens in colon cancers. J Surg Oncol. 2000;75:89-102.

    Reprints: Dr. Daisuke Ichikawa, Dept. of Surgery, Kyoto First Red Cross Hospital, 15-749 Honmachi, Higashiyama-ku, Kyoto, 605-0981, Japan;

    Rethinking pre-analytic processing of pleural fluid as a specimen
    Pleural effusions are classified as exudates or transudates based on determinations of protein and lactate dehydrogenase. Pleural fluid acidosis is assessed by determining pH. The traditional practice for handling pleural fluid specimens for pH measurement is to collect the pleural fluid anaerobically in a heparinized syringe and measure the pH immediately following thoracentesis. If delay is unavoidable, the sample should be preserved on ice to prevent spontaneous acid generation and a false pH result. It has been presumed that pleural fluid pH will change within one hour of thoracentesis. The authors point out, however, that no strong scientific evidence supports this viewpoint. The aim of this study was to determine if the change in pleural fluid pH at room temperature during the first hour following thoracentesis is significant. The authors performed a prospective, self-controlled study of patients undergoing thoracentesis at a tertiary care center. This resulted in 28 pleural fluid specimens being collected in arterial blood gas syringes. PH was measured immediately following thoracentesis on a blood pH/gas analyzer. Additional measurements were made at 5, 15, 30, 45, and 60 minutes from the first pH measurement, and the specimen was maintained at room temperature. The mean initial pH value for the 28 specimens was 7.351 ± 0.158 and the 60-min. pH was 7.359 ± 0.161. The mean difference between these two values was 0.008 ± 0.026, which was not clinically or statistically significant (P=0.13). Likewise, none of the interim pH values at 5, 15, 30, and 45 minutes after thoracentesis differed significantly from the initial values. The authors concluded that, contrary to common medical practice, it is not necessary to perform pH measurement within minutes after thoracentesis and to preserve a pleural fluid sample on ice.

    Sarodia BD, Goldstein LS, Laskowski DM, et al. Does pleural fluid pH change significantly at room temperature during the first hour following thoracentesis? Chest. 2000;117:1043-1048.

    Reprints: Dr. Alejandro C. Arroliga, Cleveland Clinic Foundation, G-62, 9500 Euclid Ave., Cleveland, OH 44195;

    Parvovirus B19 infection and Lupus-like disease
    Human parvovirus B19 is a DNA virus associated with a variety of clinical syndromes, including erythema infectiosum (fifth disease), aplastic anemia, hydrops fetalis, and acute and chronic arthropathy. It has been suggested that parvovirus B19 infection may be important in the pathogenesis of various rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus. The authors reported on three patients who had recent parvovirus B19 infection and who developed clinical and laboratory features mimicking SLE. The three adult patients (two male, one female), who were otherwise healthy or had noncontributory past medical histories, developed a syndrome generally consisting of fever, skin rash, myalgias, arthralgias, and fatigue. Laboratory findings included positive tests for antinuclear antibodies in three patients, positive anti-double-stranded DNA antibodies (anti-dsDNA), in two patients, and positive IgM and IgG serologies for parvovirus B19 infection in three patients. The patients were treated with a course of indomethacin (two patients) or ibuprofen (one patient) and had complete resolution of symptoms. All immunological tests that showed abnormal findings provided normal findings two to three months after treatment. These three patients transiently fulfilled three of four of the American College of Rheumatology classification criteria for SLE. The authors concluded that parvovirus B19 can present with clinical and immunological features mimicking SLE in adults and that parvovirus B19 infection should be considered in patients presenting with SLE-like symptoms.

    Garcia FJN, Domingo-Domenech E, Castro-Bohorquez FJ. Lupus-like presentation of parvovirus B19 infection. Am J Med. 2001;111:573-575.

    Correspondence: Dr. Francisco Javier Narvaez Garcia, C/Llobregat n°5,3°1, Hospitalet de Llobregat 08904, Barcelona, Spain