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duminică, 5 august 2012

SPECT/CT Imaging Agent Solves The Problem Of Difficult To Diagnose Cases Of Infectious Endocarditis

When combined with standard diagnostic tests, functional imaging procedures have been shown to reduce the rate of misdiagnosed cases of infectious endocarditis. According to new research published in the August issue of The Journal of Nuclear Medicine, single photon emission computed tomography (SPECT)/computed tomography (CT) with 99mTc-hexamethylpropleneamine oxime-labeled white blood cells (99mTc-HMPAO-WBC) can improve the diagnosis of infectious endocarditis in hard-to-diagnose cases.

Infectious endocarditis is an infection of the lining of the heart chambers and heart valves that is caused by bacteria, fungi or other infectious substances. It affects 2-4 people per 100,000 each year, with 25-50 percent of the cases occurring in patients older than 60 years. Mortality from infectious endocarditis remains high when this condition is undiagnosed and, therefore, not adequately treated.

The diagnosis of infectious endocarditis is becoming progressively more challenging in the past years because of a variety of factors: the indiscriminate use of antimicrobial agents in some clinical settings, the increased number of individuals with predisposing or underlying conditions (i.e., frail and elderly, immune-suppressed persons), and the increasing number of interventional cardiovascular procedures and placement of valve prostheses, intravascular devices and cardiac devices.

"SPECT/CT with 99mT-HMPAO-WBC is a nuclear medicine technique currently used for the management of patients with infection; its application in infectious endocarditis has been restricted to few reports," said Paola A. Erba, MD, lead author of the study. "With this work we aimed to open new perspective for the application of this technique."

Researchers conducted 99mTc-HMPAO-WBC SPECT/CT scans on 131 consecutive patients with suspected infectious endocarditis. Patients with permanent cardiac devices were excluded from the research as the devices might have introduced the infection. Results from the scans were compared to diagnostic tests for standard infectious endocarditis - transthoracic or transesophageal echocardiography, blood cultures and the modified Duke Endocarditis Service criteria, which are recommended for classification.

Of the 131 patients, 97 were found to have uptake indicating infection.The 99mTc-HMPAO-WBC SPECT/CT scan was true-positive in 46 of 51 patients and false negative in 5 of 51 cases (90 percent sensitivity, 94 percent negative predictive value and 100 percent specificity and positive predictor value). In addition, septic embolism was detected in 41 percent of the patients.

"When the results of the 99mTc-HMPAO-WBC SPECT/CT scan were associated with either positive echocardiography or a positive blood culture, no cases of infectious endocarditis went undiagnosed," noted Erba. "This demonstrates the added value that 99mTc-HMPAO-WBC SPECT/CT scans can provide to assist physicians in their diagnosis and treatment decisions. Cardiologists and infectivologists dealing with infectious endocarditis should consider using 99mT-HMPAO-WBC when they are facing difficult situation."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our heart disease section for the latest news on this subject. Authors of the article “Added Value of 99mTc-HMPAO-Labeled Leukocyte SPECT/CT in Characterization and Management of Patients with Infectious Endocarditis”include Paola A. Erba, Elena Lazzeri, Martina Sollini and Giuliano Mariani, Regional Center of Nuclear Medicine, University of Pisa Medical School, Pisa, Italy; Umberto Conti, Laboratory of Echocardiography, Cardiology Unit, Azienda Ospaedaliero-Universitaria Pisana, Pisa, Italy; Roberta Doria, Carlo Tascini and Francesco Menichetti, Infectious Disease Department, Azienda Ospaedaliero-Universitaria Pisana, Pisa, Italy; Salvatore M. De Tommasi, Cardiology Department, Azienda Ospaedaliero-Universitaria Pisana, Pisa, Italy; Francesco Bandera, Cardiovascular Department “E Malan,” IRCCS Policlinico San Donato Milanese, Milan, Italy; A.J.O. Dierckx, Nuclear Medicine and Molecular Imaging Department, University Medical Center Groningen, The Netherlands; and Alberto Signore, Nuclear Medicine and Molecular Imaging Department, University Medical Center Groningen, The Netherlands and Nuclear Medicine Unit, S. Andrea Hospital, University of Rome, Rome, Italy.
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marți, 13 decembrie 2011

Researchers Identify Genetic Mutation Responsible For Most Cases Of Waldenstrom's Macroglobulinemia

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Genetics
Article Date: 13 Dec 2011 - 1:00 PST

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Scientists at Dana-Farber Cancer Institute have identified a gene mutation that underlies the vast majority of cases of Waldenstrom's macroglobulinemia, a rare form of lymphoma that has eluded all previous efforts to find a genetic cause.

The research (abstracts 261, 300, 434 and 597), to be presented at the American Society of Hematology's 2011 annual meeting on Monday, Dec. 12 at 2:45 p.m. PST, points to an error in a single digit of DNA one of three billion letters in the human genetic code as the leading culprit in Waldenstrom's, and a prime target for new therapies against the disease. The discovery was made by sequencing the genome of tumor cells in Waldenstrom's patients, ¬ reading the cells' DNA letter by letter and seeing where it differed from that of the patients' normal cells.

"We found that tumor cells in 90 percent of the patients we tested contained a single point mutation, an error in one of the bases that make up the 'rungs' of the DNA helix," says Steven Treon, MD, PhD, who led the research with his Dana-Farber colleague Zachary Hunter. "In subsequent experiments, when we treated the tumor cells with drugs that target the pathway activated by the mutated gene, the cells underwent apoptosis, or programmed cell death. These results suggest that new, effective treatments that target the tumor cells directly are now possible for people with the disease."

Waldenstrom's macroglobulinemia is a slow-growing form of non-Hodgkin lymphoma that originates in white blood cells known as B lymphocytes. When abnormal B cells begin to multiply out of control, they produce excessive amounts of a protein called monoclonal immunoglobulin, which causes the blood to thicken and flow less smoothly.

In some patients, the disease produces no major symptoms; in others, problems can include weakness, fatigue, excessive bleeding, and weight loss. In severe cases, vision and neurological problems can occur. Approximately 2,000 to 3,000 people are diagnosed with Waldenstrom's each year in the United States; it is more common in men than women, more prevalent in people of Ashkenazi (Eastern European Jewish) descent, and arises more often in older people than young.

Although there isn't a cure for Waldenstrom's, treatments include drugs such as rituximab, bortezamib, and bendamustine. High-dose chemotherapy with autologous stem cell transplantation is infrequently also used.

Since the disease was first described 70 years ago, all previous efforts to track down a genetic cause have been fruitless, Treon remarks. For the current research, Treon and his colleagues conducted whole genome sequencing of tumor cells and normal cells from 30 patients with Waldenstrom's. In collaboration with Complete Genomics of Mountain View, Calif., researchers "lined up" the sequences of the tumor and non-tumor cells to identify differences. Ninety percent of the tumor cells had a point mutation in the gene MYD88.

"The mutation causes the cells to produce a distorted protein, which switches on the IRAK complex pathway, leading to activation of NF-kB, a protein that is essential for the growth and survival of Waldenstrom's tumor cells," Treon comments. "When we shut down the pathway by blocking the abnormal protein with drug molecules, the tumor cells entered apoptosis." Equally important, the tested molecules had no adverse effect on normal cells.

The discovery of a genetic signature for Waldenstrom's will enable doctors to definitively determine which patients have the disease and not a similar condition such as other forms of lymphoma or multiple myeloma, Treon says. Drugs that block the abnormal protein or other proteins in the NF-kB pathway could, theoretically, short-circuit the disease process in many patients. Some of these drugs already exist, having been developed for other conditions. Treon and his colleagues are currently working to develop others and are testing them in experimental models.

Funding for the research was provided by the International Waldenstrom's Macroglobulinemia Foundation and the Bing family.

Article adapted by Medical News Today from original press release. Source: Dana-Farber Cancer Institute
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