Glycolysis upregulation is neuroprotective as a compensatory mechanism in ALS.

Amyotrophic Lateral Sclerosis (ALS), is a fatal neurodegenerative disorder, with TDP-43 inclusions as a major pathological hallmark. Using a model of TDP-43 proteinopathy we found significant alterations in glucose metabolism including increased pyruvate, suggesting that modulating glycolysis may be neuroprotective. Indeed, a high sugar diet improves locomotor and lifespan defects caused by TDP-43 proteinopathy in motor neurons or glia, but not muscle, suggesting that metabolic dysregulation occurs in the nervous system.

Medium-Chain Fatty Acids, Beta-Hydroxybutyric Acid and Genetic Modulation of the Carnitine Shuttle Are Protective in a Model of ALS Based on TDP-43.

ALS patients exhibit dyslipidemia, hypermetabolism and weight loss; in addition, cellular energetics deficits have been detected prior to denervation. Although evidence that metabolism is altered in ALS is compelling, the mechanisms underlying metabolic dysregulation and the contribution of altered metabolic pathways to disease remain poorly understood. Here we use a model of ALS based on TDP-43 that recapitulates hallmark features of the disease including locomotor dysfunction and reduced lifespan.

Impairment of gallbladder emptying in diabetes mellitus.

Individuals with diabetes mellitus are reported to have a twofold to threefold increase in the incidence of cholesterol gallstones. A frequently cited but unproven pathophysiologic mechanism for this phenomenon is reduced gallbladder muscle function, which results in stasis and allows for cholesterol gallstone crystal formation and gallstone growth. To date, gallbladder motor function has not been investigated in a well-characterized diabetic population.

Left ventricular diastolic filling in valvular aortic stenosis.

The pattern of left ventricular diastolic filling in patients with valvular aortic stenosis (AS) as assessed by gated blood pool scintigraphy has received little attention. Twenty-one normal persons (group 1), 24 patients with significant AS and ejection fractions of 50% or more (group 2) and 15 patients with significant AS and ejection fractions less than 50% (group 3) were studied. From the time-activity curve, the peak filling rate and mean filling rate (as end-diastolic volumes [EDV]/s) and percent stroke volume filled at first third of diastole and at the end of the rapid filling period were determined.

Gallbladder function in diabetic patients.

Gallbladder emptying and filling was studied in eight diabetic and six normal control patients. None of the patients had gallstones. Cholescintigraphy was performed using [99mTc]disofenin, and gallbladder emptying was studied using a 45-min i.

Simplified count-based estimates of left ventricular volume.

Accurate count-based radionuclide estimates of left ventricular volume without the use of a blood sample have not been well described. Resting gated blood pool scans were obtained within 24 hours of catheterization in 31 patients (group 1), and simultaneously with thermodilution cardiac outputs in 29 other patients (group 2) at rest and during an induced-volume change (intervention). End-diastolic and end-systolic volumes were calculated from the single-plane angiogram in Group 1 and from the combination of thermodilution stroke volume and radionuclide ejection fraction in group 2.

Left ventricular diastolic filling in patients with left ventricular dysfunction.

The pattern of abnormal left ventricular diastolic filling and its specificity in coronary disease patients with severe left ventricular dysfunction has received little attention. We evaluated the left ventricular diastolic filling curve derived from gated blood pool scans in 21 normals, 61 coronary disease patients with ejection fractions less than or equal to 30%, and 51 congestive cardiomyopathy patients with ejection fraction less than or equal to 30%. The peak filling rate (PFR), peak ejection rate (PER), PFR/PER and the % stroke volume filled at 1/3 of diastole (%SV-1/3 DT) and at the end of the rapid filling period (%SV-RFP) were determined for each group.

Left ventricular diastolic filling in patients with coronary artery disease and normal left ventricular function.

Abnormal left ventricular diastolic filling (DF) has been noted in coronary disease (CD) patients with normal left ventricular function (NLVF). Inclusion of patients with regional wall disease, hypertension, and left ventricular hypertrophy may be responsible for abnormal DF. We evaluated left ventricular DF curves derived from gated blood pool scans in 21 normals (group 1), in 38 CD patients with NLVF specifically defined (group 2), and in 28 CD patients with ejection fractions greater than 50% and regional disease (group 3).

Gallbladder function: methods for measuring filling and emptying.

Cholescintigraphy with [99mTc] disofenin was used to determine the optimal dose and method of administration of the octapeptide of cholecystokinin, and to determine the kinetics of gallbladder filling and emptying in 22 patients without disease of the liver or gallbladder. The peak filling rate of the gallbladder occurred at 30 min after injection; filling was complete at 1 hr. A 45-min constant intravenous infusion of the octapeptide 20 ng/kg X hr resulted in progressive emptying of the normal gallbladder; the mean ejection fraction at 45 min was 77.

Pattern of left ventricular diastolic filling in chronic aortic regurgitation: a gated blood pool assessment.

Limited information exists regarding the pattern of left ventricular diastolic filling in moderate to severe chronic aortic regurgitation (AR). The left ventricular diastolic filling curve derived from gated blood pool scans was evaluated in 24 normal subjects and 29 patients with AR. The peak filling rate (PFR), mean filling rate (MFR), peak ejection rate (PER), PFR/MFR, PFR/PER, and the time of the rapid filling period divided by the diastolic time were determined.

Spontaneous "remission' of agnogenic myeloid metaplasia and termination in acute myeloid leukemia.

Acute myeloid leukemia developed in two men with well-documented agnogenic myeloid metaplasia 49 and 27 months, respectively, after initial diagnosis. Both men had spontaneous hematologic remissions of myeloid metaplasia 22 and 16 months prior to leukemic transformation. Neither patient received any precedent radiation or cytotoxic chemotherapy.

Unsuspected purulent pericarditis detected by gallium-67 scanning: a case report.

A Ga-67 scan performed because of a suspected intraabdominal infection demonstrated marked pericardial uptake of the isotope instead, and thus provided the first clue to the diagnosis of purulent pericarditis. Subsequent studies and surgery revealed an esophagopericardial fistula, gas in the pericardial sac, and purulent pericarditis caused by multiple bacteria. This report presents an unusual cause of pericardial uptake of Ga-67.

Comparison of reticuloendothelial scans with bone scans in malignant disease.

Thirty patients with histologically proven malignant disease were selected for reticuloendothelial scans and bone scans because of suspected bone or bone marrow involvement. Reticuloendothelial scans were abnormal in 83% of the patients and bone scans were abnormal in 47%. Focal defects on the reticuloendothelial marrow scan correlated better with tumor infiltration of the marrow than did diffusely abnormal scans.

Diagnosis of alcoholic cirrhosis with the right-to-left hepatic lobe ratio: concise communication.

Since scans of cirrhotic livers commonly show a reduction in size and colloid uptake of the right lobe, a quantitative measure of uptake was made using a minicomputer to determine total counts in regions of interest defined over each lobe. Right-to-left ratios were then compared in 103 patients. For normal patients the mean ratio +/- 1 s.

Containment of hepatitis B virus infection in a hemodialysis unit.

The unsuspected introduction of a carrier of hepatitis B virus into a hepatitis-free hemodialysis unit coincided with a routine serologic survey in early April 1976. Thus the prevalence of hepatitis B surface antigen and its antibody was known for the 42 patients and 23 personnel at risk. Control consisted of isolating the patient identified as a carrier seven days after admission.