Obstruction in extracardiac ventriculopulmonary conduits: value of nuclear magnetic resonance imaging with velocity mapping and Doppler echocardiography.

OBJECTIVES. This study was designed to investigate the value of noninvasive imaging modalities for the detection of obstruction in extracardiac ventriculopulmonary conduits. BACKGROUND. the diagnosis of obstruction in a conduit by noninvasive methods can be difficult. Obstruction may be silent and its progression unnoticed. Nuclear magnetic resonance imaging (NMR) with velocity mapping is a new noninvasive technique that can provide high resolution images and has been shown to be a reliable method of measuring blood flow velocity. METHODS. Two-dimensional echocardiography, pulsed wave Doppler echocardiography and NMR spin echo imaging were used in 52 patients with an extracardiac ventriculopulmonary conduit. Continuous wave Doppler echocardiography was used in 30 of these, Doppler color flow mapping in 26 and NMR velocity mapping in 12. Cardiac catheterization data were available in 27 patients and operative or autopsy findings in 11. RESULTS. The conduit could be assessed by two-dimensional and pulsed wave Doppler echocardiography in only 17% of patients. Doppler color flow and continuous wave echocardiography provided technically satisfactory data in 19% and 83%, respectively. The anatomy of the conduit was adequately displayed by NMR imaging in 90%. A minimal diameter less than 18 mm indicated conduit obstruction, although failure to detect calcification resulted in obstruction being missed in some patients. Calculated gradients in obstructed conduits derived from NMR velocity mapping correlated well with results of continuous wave Doppler echocardiography and gave an accurate localization of the site of obstruction as well as a measure of its severity. CONCLUSION. NMR imaging with velocity mapping is the most effective noninvasive method of assessing obstruction in ventriculopulmonary conduits and can obviate the need for invasive investigation before an interventional procedure is performed.     

Mycotic coronary artery aneurysm detected by gallium67 scintigraphy

A 71-year-old man presented with fever and positive blood cultures for methicillin-sensitive Staphylococcus aureus 4 days after an uncomplicated intra-luminal abdominal aortic aneurysm repair. Investigations looking for a source of sepsis including computerized tomography scans, transoesophageal echocardiography, a bone scan and repeated chest X-rays, did not reveal an infective focus. Gallium(67) scintigraphy, however, showed a focus of tracer uptake in the region of the aorto-cardiac junction consistent with the presence of an abscess. Coronary angiography later opacified an aneurysmal cavity arising from the right sinus of Valsalva which was confirmed to be a mycotic aneurysm on thoracotomy. This is a rare case of early detection of a cardiac mycotic aneurysm by Gallium(67) scintigraphy.     

Merits of FDG PET/CT and Functional Molecular Imaging Over Anatomic Imaging With Echocardiography and CT Angiography for the Diagnosis of Cardiac Device Infections

The diagnosis of cardiac device infections, particularly device-related endocarditis, is challenging. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is based on in vivo FDG targeting of the pre-existing inflammatory cells at an infectious site. Hence, it is able to identify cardiac device infection early, before the development of morphological damages from the infectious process. Transesophageal echocardiography (TEE) and electrocardiographically gated computed tomographic angiography (CTA) are currently the first-line imaging studies for device-related endocarditis, but their application to evaluate the extracardiac components or sources of primary infection and/or emboli is limited. Functional FDG PET/CT may have unique advantages over the anatomically based TEE and CT or CTA in the following settings: 1) diagnosing infection earlier than TEE and CTA, before morphological damage ensues; 2) identifying prosthetic endocarditis when findings on TEE and CTA are inconclusive; 3) evaluating infection in the extracardiac components of devices; 4) detecting unexpected source of the primary infection; and 5) discovering embolic consequences of endocarditis in the body. All of these findings may ultimately affect patient management. Although the nonspecific nature of FDG is a concern in differentiating infection from inflammation, accurate diagnosis of infection can be reasonably achieved on the basis of FDG distribution pattern and clinical history or by adding radiolabeled white blood cell scan to improve specificity. Recent publications support the judicious use of FDG PET/CT, particularly in patients with inconclusive or negative results on initial echocardiography and CT.     

Pulmonary valve gonococcal endocarditis. A forgotten disease.

Although gonococcal infections of the pulmonary valve were common before the introduction of antibiotics, such infections have rarely been reported since penicillin became available. In an elderly man with gonococcal endocarditis of the pulmonary valve the non-specific signs and symptoms, the late appearance of a pulmonary murmur, and the sterility of early blood cultures made the diagnosis unclear until three weeks after admission. Endocarditis was localised to the pulmonary valve by M-mode and cross-sectional echocardiography. Echocardiography may be useful for diagnosing endocarditis in patients with fever of unknown origin. Gonococcal infection should be suspected in patients with pulmonary vegetations and sterile blood cultures.     

Pulmonary valve gonococcal endocarditis. A forgotten disease

Although gonococcal infections of the pulmonary valve were common before the introduction of antibiotics, such infections have rarely been reported since penicillin became available. In an elderly man with gonococcal endocarditis of the pulmonary valve the non-specific signs and symptoms, the late appearance of a pulmonary murmur, and the sterility of early blood cultures made the diagnosis unclear until three weeks after admission. Endocarditis was localised to the pulmonary valve by M-mode and cross-sectional echocardiography. Echocardiography may be useful for diagnosing endocarditis in patients with fever of unknown origin. Gonococcal infection should be suspected in patients with pulmonary vegetations and sterile blood cultures.     

Improved identification of viable myocardium using second harmonic imaging during dobutamine stress echocardiography

OBJECTIVE—To determine whether, compared with fundamental imaging, second harmonic imaging can improve the accuracy of dobutamine stress echocardiography for identifying viable myocardium, using nuclear imaging as a reference.
PATIENTS—30 patients with chronic left ventricular dysfunction (mean (SD) age, 60 (8) years; 22 men).
METHODS—Dobutamine stress echocardiography was carried out in all patients using both fundamental and second harmonic imaging. All patients underwent dual isotope simultaneous acquisition single photon emission computed tomography (DISA-SPECT) with ^99mtechnetium-tetrofosmin/¹⁸F-fluorodeoxyglucose on a separate day. Myocardial viability was considered present by dobutamine stress echocardiography when segments with severe dysfunction showed a biphasic sustained improvement or an ischaemic response. Viability criteria on DISA-SPECT were normal or mildly reduced perfusion and metabolism, or perfusion/metabolism mismatch.
RESULTS—Using fundamental imaging, 330 segments showed severe dysfunction at baseline; 144 (44%) were considered viable. The agreement between dobutamine stress echocardiography by fundamental imaging and DISA-SPECT was 78%, κ = 0.56. Using second harmonic imaging, 288 segments showed severe dysfunction; 138 (48%) were viable. The agreement between dobutamine stress echocardiography and DISA-SPECT was significantly better when second harmonic imaging was used (89%, κ = 0.77, p = 0.001 v fundamental imaging).
CONCLUSIONS—Second harmonic imaging applied during dobutamine stress echocardiography increases the agreement with DISA-SPECT for detecting myocardial viability.


Keywords: dobutamine stress echocardiography; second harmonic imaging; ¹⁸F-fluorodeoxyglucose imaging; myocardial viability     

Extracardiac conduit obstruction: initial experience in the use of Doppler echocardiography for noninvasive estimation of pressure gradient

Extracardiac valved conduits are often employed in the repair of certain complex congenital heart defects; late obstruction is a well recognized problem that usually requires catheterization for definitive diagnosis. A reliable noninvasive method for detecting conduit stenosis would be clinically useful in identifying the small proportion of patients who develop this problem. Continuous wave Doppler echocardiography has been used successfully to estimate cardiac valvular obstructive lesions noninvasively. Twenty-three patients with prior extracardiac conduit placement for complex congenital heart disease underwent echocardiographic and continuous wave Doppler echocardiographic examinations to determine the presence and severity of conduit stenosis. In 20 of the 23 patients, an adequate conduit flow velocity profile was obtained, and in 10 an abnormally increased conduit flow velocity was present. All but one patient had significant obstruction proven at surgery and in one patient, surgery was planned. In three patients, an adequate conduit flow velocity profile could not be obtained but obstruction was still suspected based on high velocity tricuspid regurgitant Doppler signals. In these three patients, subsequent surgery also proved that conduit stenosis was present. Doppler-predicted gradients and right ventricular pressures showed an overall good correlation (r = 0.90) with measurements at subsequent cardiac catheterization. Continuous wave Doppler echocardiography appears to be a useful noninvasive tool for the detection and semiquantitation of extracardiac conduit stenosis.     

The role of high dose 67-gallium scintigraphy in staging untreated patients with lymphoma

Background: Gallium-67 (⁶⁷Ga) scintigraphy has been reported to be of limited value in staging lymphoma patients. However, recent technical advances in radionuclide imaging have potentially enhanced the usefulness of this method. Aims: The purposes of this study were to determine the current: (1) sensitivity and specificity and (2) impact on clinicians' treatment decisions of ⁶⁷Ga scans performed at a teaching hospital. Methods: There were 46 newly presenting patients with lymphoma (13 with Hodgkin's disease (HD) and 33 with non-Hodgkin's lymphoma [NHL]). Planar ⁶⁷Ga scans were performed up to eight days following injection of 300 MBq (8 mCi) with images interpreted by consensus of two blinded observers; sensitivity and specificity were determined on a lesion by lesion basis in comparison to computed tomography (CT) scans, palpation of peripheral lymph nodes and abdominal lymphangiograms (n = 5). The contribution of ⁶⁷Ga scans to clinicians' treatment decisions was also independently assessed by an experienced oncologist. Results: Gallium-67 scan sensitivity and specificity were 80% and 96% for HD and 59% and 98% for NHL. Initial treatment plans were modified in three individuals (7%; 95% confidence intervals = 3–10%) due to lesions on the ⁶⁷Ga scan not prospectively detected or considered equivocal on other tests. Conclusions: Only a small proportion of newly diagnosed lymphoma patients benefit from staging with state of the art planar high dose ⁶⁷Ga imaging.     

Comparison between Leukoscan (Sulesomab) and Gallium-67 for the diagnosis of osteomyelitis in the diabetic foot

OBJECTIVES: The diagnosis of osteomyelitis in patients with diabetic foot is difficult both clinically and radiologically. An early diagnosis is crucial to optimize therapeutic strategy. Among the diagnostic methods currently used, scintigraphy with ex-vivo labelled white blood cells is the gold standard, but cannot be performed in all centers; therefore 67Gallium citrate (67Ga) imaging in combination with a bone scintigraphy is still widely used. METHOD: The results of imaging 24 diabetic patients with 31 suspected osteomyelitic lesions using the antigranulocyte Fab' fragment (Sulesomab or LeukoScan or immunoscintigraphy) were prospectively compared with results from the bone scan coupled with 67Ga. The diagnosis of osteomyelitis was confirmed by either biopsy or follow-up, radiological imaging and clinical outcome. RESULTS AND CONCLUSION: Sulesomab correctly identified 12 of 18 osteomyelitic lesions while 67Ga was able to detect only 8 of 18. Therefore the sensitivity is 67% for Sulesomab and 44% for 67Ga. Among the 13 non-osteomyelitic lesions imaging with Sulesomab was able to rule out infection in 11 cases and 67Ga in 10 cases. The specificity is therefore 85% for Sulesomab and 77% for 67Ga. Image interpretation for Sulesomab in this group of patients is occasionally suboptimal when imaging is performed at 3 hours post injection. High vascular background in the early images may obscure infection especially in small bones. Practically, scintigraphy with Sulesomab is fast and simple due to ease of labeling, no ex-vivo handling of blood, low radiation and provides rapid diagnosis. The diagnosis of osteomyelitis obtained by the antibody fragment scintigraphy influences the management (guided biopsy) and therapy. In several patients, imaging with Sulesomab was able to rule out osteomyelitis, helping to avoid useless antibiotic therapy and its associated side effects.     

Clinical value of gallium-67 SPECT scintigraphy in the diagnostic and therapeutic evaluation of retroperitoneal fibrosis: a prospective study

BACKGROUND: Gallium-67 (67Ga) scintigraphy may be useful in evaluating patients with retroperitoneal fibrosis (RPF), but a systematic assessment of its value is lacking. OBJECTIVE: Prospective evaluation of the value of 67Ga scintigraphy in assessing active RPF disease and in predicting treatment response. METHODS: Thirty-four patients with nonmalignant RPF treated with tamoxifen underwent 67Ga scintigraphy at baseline and--if baseline gallium scan was positive--at 3 months follow-up. Gallium scans were visually scored according to pathologic 67Ga-uptake compared to normal bone marrow 67Ga-uptake. Results were correlated with other (follow-up) measurements. Value of (follow-up) 67Ga scintigraphy in predicting treatment response was also assessed. RESULTS: Gallium scans were positive in 24 patients (71%). Mass thickness was greater in patients with positive gallium scan compared with patients with negative gallium scan (P = 0.006). Visual gallium score correlated with mass thickness (P = 0.006). Visual gallium score decreased significantly following tamoxifen treatment (P < 0.0001). Decrease in visual gallium score correlated with decreases in C-reactive protein and erythrocyte sedimentation rate (P = 0.019) and with decrease in mass thickness (P < 0.01). Positive predicting value (PPV) of positive baseline gallium scan was 0.71; PPV of negative follow-up gallium scan in patients with initial positive scan was 0.89. 67Ga scintigraphy detected extra-abdominal involvement in one patient and recurrent active disease in two symptomatic patients with normal acute-phase reactants and stable residual mass. CONCLUSION: 67Ga scintigraphy is useful in assessing (recurrent) activity of RPF disease and in evaluating treatment response in patients with initial positive gallium scan.     

The hypermethylation and protein expression of p16 INK4A and DNA repair gene O6-methylguanine-DNA methyltransferase in various uterine cervical lesions

Purpose This study is aimed at investigating the significance of gene promoter methylation status and protein expression of p16 ^INK4A and O⁶-methylguanine-DNA methyltransferase (MGMT) in the various uterine cervical lesions.Materials and methods Methylation status by using methylation-specific polymerase chain reaction (MS-PCR) and protein expression by using immunohistochemistry for p16 ^INK4A and MGMT genes were performed in cervical squamous intraepithelial neoplasms (CIN), invasive squamous cell carcinomas (SCC), adenocarcinomas and non-neoplastic cervices.Results None of 20 non-neoplastic cervices showed p16 ^INK4A and MGMT gene hypermethylation, whereas at least one of these genes was hypermethylated with 50.0% (5/10) of CIN I, 65.0% (13/20) of CIN II–III, 70.2% (33/47) of SCC and 85.0% (17/20) of adenocarcinoma. p16 ^INK4A protein was totally negative in non-neoplastic cervices, but positive with 90.0% of CIN I, 100% of CIN II–III and adenocarcinoma, and 78.7% of SCC. MGMT protein was expressed in 10% of non-neoplastic cervices, but significantly increased in SCC (42.5%) and adenocarcinoma (70.0%). The protein expression of p16 ^INK4A and MGMT was not related to their gene promoter methylation status.Conclusions The hypermethylation of p16 ^INK4A and MGMT genes in the uterine cervix may indicate the presence of malignant cells, and p16 ^INK4A immunostaining is useful in grading CIN and diagnosing invasive SCC and adenocarcinoma.     

Free 67Ga enters into the hepatocytes of carbon tetrachloride-treated rats

Gallium-67 (⁶⁷Ga) has been used as tumor or inflammation-imaging agent in nuclear medicine for decades. Although many hypotheses concerning the mechanism of uptake of ⁶⁷Ga into tumors and inflammation have been proposed, consensus has not been reached. If the mechanism of ⁶⁷Ga uptake is clarified, we can improve the sensitivity of diagnostic imaging with ⁶⁷Ga. We attempted to clarify the mechanism of ⁶⁷Ga uptake by the liver of carbon tetrachloride (CCl₄)-treated rats. First, we investigated whether or not transferrin (Tf) is involved in ⁶⁷Ga uptake by the liver tissue of CCl₄-treated rats. It is well known that Fe³⁺ can inhibit the binding of ⁶⁷Ga to Tf. The administration of FeCl₃ 5 min before the injection of ⁶⁷Ga slightly enhanced the uptake of ⁶⁷Ga by the liver tissue of CCl₄-treated rats. The entering of ⁶⁷Ga into hepatocytes of CCl₄-treated rats was similar to the uptake by the liver tissue. In addition, the administration of FeCl₃ slightly increased the entering of ⁶⁷Ga to hepatocytes. These results suggest that free ⁶⁷Ga enters into hepatocytes from the liver of CCl₄-treated rats.     

Functional evaluation of extracardiac ventriculopulmonary conduits and of the right ventricle with magnetic resonance imaging and velocity mapping

Extracardiac ventriculopulmonary conduits tend to deteriorate over time, developing both obstruction and regurgitation. In this prospective study, magnetic resonance imaging (MRI) was compared with Doppler echocardiography to determine whether MRI improves the noninvasive evaluation of conduit patients. Twenty-five patients (median age 10 years, range 2.5 to 32) were investigated 27 times with Doppler echocardiography and an MRI protocol with spin echo sequences for morphology, velocity mapping, and multislice gradient echo technique for right ventricular volume measuring. Cardiac catheterization data were available in 6 patients. Echocardiography could assess the morphology of the conduits in 6 patients, whereas MRI demonstrated all conduits efficiently. Doppler echocardiography could evaluate the occurrence of regurgitation in 18 patients and could quantify peak velocity in 20 of the patients. A technically adequate MRI velocity mapping was obtained in 25 patients. There was good agreement between MRI and Doppler echocardiography in establishing or not establishing regurgitation, but Doppler echocardiography was less reliable in evaluating the degree of regurgitation. The correlation between peak velocity determined with Doppler and magnetic resonance imaging was r = 0.63 [corrected]. Correlations between catheterization pressure gradients and noninvasive techniques were r = 0.97 for magnetic resonance imaging [corrected] versus catheterization, and r = 0.86 [corrected] for Doppler versus catheterization. MRI can provide complete information on the morphology and function of extracardiac ventriculopulmonary conduits, as well as of the right ventricle. If the results of MRI and echocardiography with Doppler are in agreement, heart catheterization and angiography can be avoided, even in patients considered for conduit replacement.     

Role of 67Ga scintigraphy in localization of lymphoma

 This review deals with the applications of ⁶⁷Gallium (Ga) scintigraphy for the initial staging and follow-up during and after treatment of patients with Hodgkin's or non-Hodgkin's lymphoma (NHL). During the last decade, the technique of visualization has been largely improved by using higher doses and additional tomography. Here, the indications for ⁶⁷Ga scintigraphy in comparison with CT and MRI are discussed. The conditions resulting in false positive and false negative results have been outlined. ⁶⁷Ga may detect unusual involved sites during staging procedures. However, the major contribution to the management of Hodgkin's disease and NHL is the evaluation of residual masses, because ⁶⁷Ga uptake reflects the metabolic acitivity of the tumor. The review ends with an additional short overview of other radionuclide imaging methods useful for malignant lymphoma. Accepted: 26 January 1996     

Gallium 67-Szintigraphie in der Differentialdiagnostik der Lungenerkrankungen

The affinity of⁶⁷Ga to malignant tumors is nonspecific, as storage can also be seen in nonmalignant processes. Except in cases of sarcoidosis, the concentration of⁶⁷Ga in nonmalignant lesions has rarely been observed, but the number of investigations is very small. This report describes scintigraphy of lungs performed with⁶⁷Ga citrate in 183 investigations with different pulmonary diseases. It is well known that malign tumors accumulate⁶⁷Ga citrate. This was confirmed in 23 cases, whereas 6 cases showed a negative result (1 adeno carcinoma, 3 treated bronchial carcinomas and 2 cases which had been incorrectly scanned from the opposite side of the thorax). One neurinoma showed a negative result as well. Of the 72 patients with untreated active pulmonary tuberculosis, 62 showed a concentration of⁶⁷Ga in the affected areas, but in the other 10 no increase in the concentration of⁶⁷Ga was found for the following reasons: 1. the process was smaller than 2 cm in diameter (2 cases); 2. the scan was incorrectly made from the wrong side of the thorax (4 cases); 3. the scanning technic was unfavorable in 4 cases. On the other hand, in 10 cases with inactive or possibly inactive tuberculosis no storage of⁶⁷Ga was to be found. 32 patients with active tuberculosis in whom an initial scan had been positive were examined another time after the antituberculous therapy. In 22 of these cases we found a significantly lower level of activity in the pathologic areas, and in 9 cases accumulation was totally absent, whereas in one case the storage was unchanged after two months of chemotherapy. However, clinical examination had not revealed any recovery in this patient. Among 10 patients with sarcoidosis we found 8 positive results. Only one out of 7 cases of chronic pneumonia showed an increased concentration of⁶⁷Ga. In three cases of fibrosis there was no demonstrable⁶⁷Ga storage. On the other hand in all 11 cases of silicosis with or without active tuberculosis an accumulation could be found, and the extent of the area of concentration in these cases was often greater than the area the X-ray findings revealed to be affected. The results of these studies show that⁶⁷Ga accumulation in pathological areas demonstrates the metabolic activity of a process. The absorption of⁶⁷Ga is nonspecific and cannot explain the etiology of pathologic processes.⁶⁷Ga scintigraphy is a method of detecting pathologic processes, which cannot be verified roentgenologically. This concerns particularly disseminations of malignoms or active tuberculosis in the mediastinum and of other metabolic-active processes. In addition,⁶⁷Ga scintigraphy might provide useful confirmation of the success of various types of therapy.     

Value of67gallium scintigraphy in primary diagnosis and follow-up of opportunistic pneumonia in patients with AIDS

Opportunistic pneumonias are a life-threatening complication in patients with AIDS. Early diagnosis and therapy is necessary to improve the prognosis. This study was designed to assess the value of⁶⁷gallium scintigraphy in the primary detection and follow-up of these special pneumonias.⁶⁷Gallium scintigraphy was performed in 40 patients: 10 normal controls and 30 HIV-positive patients with AIDS or AIDS-related complex (ARC).⁶⁷Gallium scan results were compared with current chest x-rays and the results of pathogen detection. The evaluation of positive scans was based on a quantification of the pulmonary uptake, expressed as a pulmonary/soft tissue uptake ratio. Only 8 of 30 patients had a normal scan, while 22 of 30 showed diffuse (13/22) or focal (9/22) increases of pulmonary uptake. In seven of eight patients with normal scans the chest radiograph was negative as well. The one patient with negative scan but positive chest radiograph had pulmonary Kaposi’s sarcoma. In 11 of 22 patients, the⁶⁷gallium scan and chest x-ray were positive simultaneously. In the other 11 of 22 patients with positive scans, chest radiographs were initially negative but showed pathology in five cases within 1–2 weeks. The reason for positive scans in most cases was an opportunistic lung infection; other forms of pneumonia were observed only in two cases. The defined uptake ratio was demonstrated to be a highly sensitive parameter for monitoring pneumonia and the effects of therapy in follow-up studies. In conclusion, quantitative⁶⁷gallium scintigraphy proved to be a reliable and highly sensitive method for primary detection and follow-up of opportunistic pneumonias in patients with AIDS.     

Noninvasive methods for detection of valve vegetations in infective endocarditis

To determine the optimal noninvasive method for the demonstration of endocarditic vegetations, 35 consecutive episodes of clinically diagnosed endocarditis in 33 patients were studied with M mode and two dimensional echocardiography, and with gallium-67 citrate and technetium-99m stannous pyrophosphate cardiac scanning. Clinical criteria for the diagnosis of endocarditis were: temperature higher than 38 ° C; sustained bacteremia with at least three positive blood cultures; no extracardiac focus of bacteremia; and known underlying heart disease, a new or changing murmur or a history of intravenous drug abuse with radiologic evidence of septic pulmonary emboli. M mode echocardiography detected 18 vegetations in 17 of the 35 episodes of endocarditis studied (49 percent positive); two dimensional echocardiography detected 30 vegetations in 28 of the 35 episodes studied (80 percent positive). In contrast, no vegetations were detected with technetium-99m stannous pyrophosphate scanning, and only two gallium-67 citrate scans were positive. The advantage of the two dimensional echocardiographic technique over all others tested was particularly notable for the identification of aortic and tricuspid valve vegetations.     

Detection of infection of a cardiac xenograft by gallium-67 scan

We describe a case complicated by infection of a xenograft conduit with subsequent septic emboli to the left kidney in the setting of pulmonary atresia with ventricular septal defect which was positively imaged using radioactive gallium-67. Confirmation was provided by cross-sectional echocardiography and positive blood culture. The patient improved with antibiotic therapy.     

Comparison between the <Superscript>13</Superscript>C-urea breath test and stool antigen test for the diagnosis of childhood <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

Background As noninvasive tests for Helicobacter pylori infection, the ¹³C-urea breath test (UBT) and stool antigen test have been widely used. In children, however, there are few studies reporting which test shows superior performance. The purpose of this study was to compare the ¹³C-UBT and stool antigen test for their accuracy in diagnosing H. pylori infection in children.Methods A total of 123 Japanese children, ages 2 to 17 years (mean, 12 years) who underwent gastric biopsies for H. pylori infection were studied. The diagnoses included gastritis (n = 55), gastric ulcer (n = 5), duodenal ulcer (n = 20), iron-deficiency anemia (n = 7), and other conditions (n = 36). The cutoff value of the ¹³C-UBT was defined to be 3.5. The stool antigen test was performed using the HpSA enzyme-linked immunosorbent assay (ELISA) (Premier Platinum HpSA). In 16 patients who received eradication therapy, the ¹³C-UBT and HpSA were repeated 2 months after treatment.Results Based on biopsy tests, 60 children were infected with H. pylori and 63 children were not. For the ¹³C-UBT, the sensitivity, specificity, and accuracy were 95.0% (95% confidence interval [CI], 86.1%–99.0%), 98.4% (95% CI, 91.5%–100%), and 96.4% (95% CI, 93.6%–99.9%), respectively. For the HpSA, the sensitivity, specificity, and accuracy were 98.3% (95% CI, 90.8%–100%), 98.4% (95% CI, 91.2%–100%), and 98.3% (95% CI, 96.0%–100%), respectively. There were no significant differences between the performance of these two tests. In the assessment of H. pylori eradication, the results of ¹³C-UBT and HpSA agreed with those of biopsy tests.Conclusions The ¹³C-UBT and the HpSA are equally accurate for the diagnosis of active H. pylori infection in Japanese children.Kazuie Iinuma, for the Japanese Pediatric Helicobacter study Group     

Duration of empiric antibiotic therapy in granulocytopenic patients with cancer.

Early initiation of empiric antibiotic therapy in febrile cancer patients has become established practice, but the appropriate duration of antibiotic therapy when no infectious source can be identified is unknown. The complications of broad-spectrum antibiotics argue for brief treatment, but the risk of an inadequately treated infection in the granulocytopenic patient favors longer therapy. We prospectively studied 306 episodes of fever and granulocytopenia in 143 patients with leukemia or solid tumor (age one to 33 years) with respect to the duration of empiric antibiotic treatment. Eligible patients (fever > 38 °C three times/24 hours or > 38.5 °C once, plus polymorphonuclear leukocytes < 500/mm³) had an extensive diagnostic evaluation, including at least two preantibiotic blood cultures, and therapy was then started with a broad-spectrum antibiotic regimen— Keflin^®, gentamicin and carbenicillin (KGC). Initial evaluation failed to identify an infectious etiology for the fever in 142 of 306 (46 per cent) episodes. Fifty-six of 142 (39 per cent) of these fevers of unknown origin were associated with persistent granulocytopenia for more than seven days; in 33 of these, defervescence occurred while the patients received KGC. After seven days of empiric KGC therapy, the 33 patients with fevers of unknown origin who had become afebrile with empiric antibiotics but whose polymorphonuclear leukocytes remained less than 500/mm³ were randomized to either continue or discontinue ($\text{d}\text{c}$) to receive KGC. The patients who continued to receive KGC until their polymorphonuclear leukocytes were more than 500/mm³ had no infectious sequelae. However, in seven of 17 (41 per cent) of the patients randomized to $\text{d}\text{c}$ KGC infectious sequelae developed (p = 0.007) within a median of two days of discontinuing KGC (two with fever which again responded to KGC therapy, and five with a documented infection [two ultimately fatal]). In none of the patients did a resistant microbial flora or superinfection develop. These data suggest that the patient with a fever of unknown origin who becomes afebrile during empiric antibiotic therapy may profit from continued therapy while granulocytopenia persists.