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; gmrps@servidor.unam.mx
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; gtc_ko@hotmail.com
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; jjeffrey@exchange.hsc.mb.ca
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; kyotofre@mba.sphere.ne.jp
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; arrolia@ccf.org
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