Medical Device Daily Washington Editor

WASHINGTON – The FDA’s Division of Mammography Quality and Radiation Programs (DMQRP) recently celebrated the 10th anniversary of the first mammography facility inspection under the Mammography Quality Standards Act (MQSA).

The first inspection was performed in January 1995, and by late March 1995, the FDA already had uploaded data into its database from more than 300 inspections from across the country, it said. To date, MQSA inspectors have completed a total of nearly 93,000 facility inspections.

Since the beginning of the program, DMQRP said it has trained a total of 436 inspectors. Currently active are 237 active FDA-certified MQSA inspectors – 203 state inspectors and 34 FDA inspectors. All inspectors go through three two-week courses of technical and device-related training. And ongoing is the job of keeping a nationwide team of inspectors in place as inspectors retire or transition into other areas.

FDA said it has identified and evaluated various trends in inspection findings during the past 10 years.

Since 1995, the percentage of inspections without reporting any adverse observations has increased steadily, from 30% in 1995 to roughly 70% for FY04.

“FDA’s goal for the MQSA program remains to improve the quality of the nation’s mammography services,” the agency said in a statement. “Toward that principle, DMQRP continues to work . . . via an ever-efficient and least-burdensome approach to facilities.”

NIH: Key to glucose balance found

Researchers from the National Institutes of Health (NIH; Bethesda, Maryland) say they’ve discovered the critical sequence of events by which insulin stimulates the entry of glucose into fat cells.

“This finding provides useful information for understanding disorders in which cells have difficulty using insulin, such as insulin resistance and type 2 diabetes,” said Duane Alexander, MD, director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD), which conducted the study along with the National Institute of Child Health and Human Development (NICHD).

Glucose, a simple sugar, is a nutrient that cells need to survive. Glucose is ferried through the cell’s outer membrane by a family of molecules known as glucose transporters. In the study, the researchers discovered how glucose transporter 4 (GLUT 4) carried insulin into fat cells.

Scientists have said they already knew that GLUT 4 is contained in the membrane of tiny sacs called vesicles. Previous studies showed that GLUT 4 was transferred from the vesicles within the cell to the cell membrane, when the vesicles fused with the membrane.

But researchers had been unable to determine where in the cell the vesicles were stored and how insulin stimulated them to fuse with the cell membrane.

In the new study, NIH researchers analyzed fat cells taken from mice, finding that the GLUT 4 vesicles are highly active. Although a few vesicles are scattered throughout the cell, the majority circulate just under the cell’s surface, they found.

The vesicles travel along “a railroad track-like network” of molecules known as microtubules, according to the study. When insulin binds to the cell’s outer surface, those vesicles immediately stop moving, tether to the cell’s inner surface and then fuse with the cell membrane. GLUT 4, contained in the vesicles’ membrane, then enters the cell membrane, where it ferries glucose into the cell.

Those observations were made using a technique known as total internal reflector florescent microscopy, a technology that involves aiming a laser beam at an angle at the glass cover slip beneath the microscope.

The light bounces off the cover slip, away from the microscope’s lens, and residual energy from the light pass-es through the cover slip, to the cell beneath, illuminating the area just below the cell’s surface while leaving the inside of the cell dark.

“When we started the experiment, we thought that the vesicles would be stationary,” said Joshua Zimmerberg, MD, PhD, chief of NICHD’s Laboratory of Cellular and Molecular Biophysics. “The vesicles looked like comets streaking by.”

Zimmerberg added that studying the chemical steps of the process in which the vesicles fuse with the cell membrane might yield a new drug to treat insulin-related disorders. Each step in the process, he said, might provide the basis for a treatment: when the vesicles first stop moving, when they tether to the inside of the cell’s membrane, and when they fuse with the membrane.

The researchers now plan to observe cells taken from mice having conditions resembling human disorders of insulin metabolism. They then will obtain cell samples from volunteers who have been diagnosed with Type 2 diabetes and insulin resistance.