Rapid modulation of lipogenesis by clofibrate in rat and monkey hepatocytes.

Previous studies have proposed various possible mechanisms for the hypolipidemic actions of clofibrate. In the present study, isolated liver cells freshly prepared from rats and squirrel monkeys were used to investigate the acute effects of sodium clofibrate (sodium chlorophenoxyisobutyrate) on hepatic lipogenesis. Incubation of liver cells with levels of the drug (1 mM) known to lower plasma lipid level in vivo produced a rapid inhibition of [14C]acetate incorporation into cellular lipids. The degree of inhibition caused by the drug was not diminished by preincubation with an excess of unlabeled acetate. Conversion of [14C]acetate to 14CO2 was not significantly altered by sodium clofibrate at 1--3 mM levels, but was decreased at 5--10 mM levels. Incorporation of [14C]acetate into all lipid classes was suppressed by this agent, but inhibition of sterol synthesis was more pronounced than that of fatty acids. Sodium clofibrate (1 mM) reduced the synthesis of sterols from either labeled acetate or labeled mevalonate to a similar degree, but the decline was augmented in each case by a 30-min preincubation of the cells with sodium clofibrate. Addition of fatty acids to cell incubations stimulated sterol generation from [14C] acetate or from [3H] mevalonate, but did not reverse the inhibitory effects of the drug. These results suggest (a) the sodium clofibrate rapidly interferes with hepatic fatty acid and sterol synthesis by direct or indirect actions at diverse loci; (b) that these effects probably occur after acetyl-CoA formation and do not stem from precursor pool dilution; (c) that sodium clofibrate diminishes sterol production at post-mevalonic and perhaps also at pre-mevalonic sites; (d) that a similar pattern of inhibition occurs with sodium clofibrate in the presence of added fatty acids; and (e) that rat and primate livers demonstrate similar metabolic responses to the drug.

Gallium uptake in tryptophan-related pulmonary disease.

We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking "high doses" of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.

Comparison of leukocytes labeled with indium-111-2-mercaptopyridine-N-oxide and indium-111 oxine for abscess detection.

Indium-111 leukocyte scanning has evolved into a practical and highly accurate method for the identification of infectious and inflammatory processes. The most commonly used agent for labeling leukocytes has been [111In]oxine. We have investigated a newer agent, 2-mercaptopyridine-N-oxide (Merc) at our institution which unlike oxine, allows us to label leukocytes in plasma, using a simple kit procedure. Of the 92 consecutive patients referred for detection or localization of an infectious process, autologous leukocytes of 55 patients were labeled with [111In]Merc, while those of the remaining 37 patients were labeled with [111In]oxine. The sensitivities for Merc and oxine procedures were 87% and 92%, respectively, while the respective specificities were 100% and 92%. We conclude that the [111In]Merc-labeled leukocytes are equally effective as [111In]oxine-labeled leukocytes in detecting infectious processes. The use of [111In]Merc is advantageous over [111In]oxine for white blood cell labeling because of its easier preparation.

Stimulation of fatty acid utilization by sodium clofibrate in rat and monkey hepatocytes.

The acute effects of sodium clofibrate (NaCPIB) on the metabolism of [1-14C]palmitate, [1-14C]octanoate, [1-14C]butyrate, and [2-3H]glycerol by freshly isolated hepatocytes were tested to explore its mechanism of action. Labeled long-, medium-, and short-chain fatty acids were incorporated into all the major lipid classes and were oxidized to 14CO2 by the liver cells. The partitioning of labeled fatty acids from lipogenic towards oxidative pathways was inversely related to fatty acid chain length. [1-14C]Palmitate was incorporated mainly into cellular triglycerides and phospholipids; [1-14C]octanoate, mainly into triglycerides and free cholesterol; and [1-14C]butyrate, mainly into free cholesterol and phospholipids of the cells. NaCPIB (1-3 mM) rapidly stimulated the esterification of labeled palmitate or glycerol to triglycerides, but drug levels greater than 5 mM were inhibitory to esterification. NaCPIB (1 mM) increased the oxidation of [1-14C]palmitate to 14CO2 by either rat or monkey hepatocytes and enhanced the release of labeled lipids from [2-3H]glycerol-prelabeled cells into the extracellular medium. Accelerated [1-14C]octanoate incorporation into glycerolipids and sterols and increased [1-14C]octanoate conversion to 14CO2 were observed in rat liver cells incubated with 1 mM NaCPIB. In contrast, the same drug level stimulated the oxidation of [1-14C]butyrate to 14CO2 but greatly diminished its incorporation into hepatocellular sterols or glycerolipids. These results indicate that (a) NaCPIB acutely alters hepatic ultilization of fatty acids by actions at diverse loci; (b) these metabolic alterations vary with fatty acid chain length; and (c) these effects are probably due to rapid changes in biochemical regulatory mechanism and/or in substrate channelling within the cells. These data further suggest that the early hypolipidemic effect of the drug in rats and primates may be related to an enhanced hepatic oxidation of long-chain fatty acids, but cannot be attributed simply to a reduction in their esterification to complex lipids.

Computer-assisted myocardial thickening analysis of gated MIBI SPECT images.

RATIONALE AND OBJECTIVES: The purpose of this study is to use the relationship between the partial volume effect, count density, matrix size, and reconstruction filter in gated single photon emission computer tomography (SPECT) to recover myocardial thickness, and to validate measurements generated using a computer-assisted automatic contour method with a phantom model and with thickness changes measured by echocardiography. METHODS: Regional myocardial contour was defined automatically using shape constraints, gray level thresholding, and a gradient method applied to gated technetium-99m (99mTc)-methoxy-isobutyl-isonitile (MIBI) SPECT images. A heart phantom with wall thickness ranging from 0.8 cm to 1.3 cm was constructed. SPECT images were acquired and reconstructed using different matrix sizes, count densities, and filters. Wall thickness determinations derived from the reconstructions made with each combination of matrix size, type of filter, and cutoff frequency were correlated with the measured thicknesses. The best combination was applied to the gated MIBI SPECT images of 55 patients who also had echocardiography and coronary arteriography. Count density measurements were made across each regional myocardial segment to evaluate wall thickness at end-diastole and end-systole. Systolic wall thickening measurements made with this automated computer-assisted contour technique were compared with echocardiographic measurements made from segments with normal perfusion and from regions containing infarcted tissue. RESULTS: Different reconstruction filters and cutoff frequencies affected the accuracy of measurements of myocardial wall thickness determined from gated myocardial SPECT images. A matrix size of 64 x 64, with a minimum of 10 counts/pixel/frame, and use of a Hanning filter with 0.5 cyc/cm cutoff frequency gave the best combination for myocardial thickness determination and spatial resolution. Application of these factors to the phantom yielded results that correlated very well with the thickness measurements (r = 0.986, P < 0.001). Application of the technique to the clinical SPECT studies yielded measurements of myocardial wall thickening that were not significantly different from that determined by echocardiography. CONCLUSION: Computer-assisted contour analysis of gated SPECT images enables accurate determination of regional wall thickening using the count density changes within each myocardial segment.

The utility of sestamibi scanning in the operative management of patients with primary hyperparathyroidism.

BACKGROUND: The role of imaging studies before parathyroidectomy has been extensively debated and recent advances in unilateral parathyroidectomy intensify this controversy. The purpose of this study was to review the parathyroidectomy experience of a single surgeon, looking at the role of sestamibi scans and a standard postoperative care regimen. STUDY DESIGN: Retrospective review of office and hospital charts was completed on 90 patients with primary hyperparathyroidism who underwent parathyroidectomy from 1991 to 1998. Patient workup and outcomes were noted, as were results of preoperative imaging. True-positive scans visualized an abnormality ipsilateral to the adenoma found at operation. Statistics were performed using nonparametric testing and Student's t-test. RESULTS: There were 21 male and 69 female patients, with an average age of 54 years (range 29 to 81). There were zero mortalities, three morbidities (3.3%), and three patients who had persistent hypercalcemia, yielding a 96.7% success rate. Sixty-seven patients underwent preoperative sestamibi scanning, with a sensitivity of 74% and positive predictive value of 89%. Operative time in imaged patients averaged 103 +/- 49.9 minutes versus 121.5 +/- 85.9 minutes for patients without sestamibi scans. Operating time differences were not statistically significant and a preoperative sestamibi scan did not affect the success of parathyroidectomy. Discharge on postoperative day 1 was accomplished in 80% of patients and 13% were discharged the next day. There was no morbidity from hypocalcemia. CONCLUSIONS: A preoperative sestamibi scan does not improve efficacy or decrease operating time for primary hyperparathyroidism when bilateral neck exploration is performed. A postoperative care protocol including oral calcium and vitamin D supplementation allows the majority of patients to be discharged on postoperative day 1 with excellent results.

Brain SPECT in a patient with post-stroke hallucination.

A patient developed visual hallucinations following a left-sided cerebrovascular accident (CVA). Brain SPECT using Tc-99m HMPAO demonstrated increased perfusion at the biparieto-occipital lobes. Following antiepileptic medication, repeat brain SPECT showed interval decrease in perfusion in the same areas with the symptomatic relief of hallucinatory episode. While it is possible that the interval decrease is due to natural resolution, the authors believe that it is likely due to drug treatment.

Delayed radioiodine organification in Plummer's disease.

Hyperfunctioning thyroid adenomas causing thyrotoxicosis (Plummer's disease) is not an uncommon cause of hyperthyroidism in the elderly. Most commonly, the adenoma appears as a so-called "hot" nodule on thyroid scintigraphy causing suppression (i.e., nonvisualization) of the remainder of the gland. This report describes a case of Plummer's disease in an elderly patient in whom the toxic nodule primarily responsible for causing the hyperthyroidism became scintigraphically apparent at 96 hours after I-131 therapeutic ablation.

Thyroid scintigraphy of hyperthyroxinemia.

The term "hyperthyroxinemia" encompasses clinical syndromes associated with elevated levels of thyroid hormone in the presence of increased, normal, or decreased thyroid function. The clinical presentation (i.e., history and physical examination), in vitro thyroid function tests, as well as radioisotope thyroid imaging all play key roles in the diagnosis of the underlying thyroid disorder. Many of these disorders and their appearance on thyroid scintigraphy are presented in this atlas.

Scintigraphic diagnosis of right ventricular ischemia.

We present a patient with exercise induced right ventricular ischemia demonstrated on stress TI-201 myocardial scintiscan. The patient underwent cardiac catheterization, and subtotal occlusion was found at the proximal right coronary artery. Repeat stress TI-201 scan became normal following the successful percutaneous transluminal coronary angioplasty.

Dynamic hepatobiliary scan appearance of hepatocellular carcinoma.

A case of hepatocellular carcinoma demonstrating increased Tc-99m DISIDA concentration on both dynamic and static scans of the liver is presented.

Rapid resolution of pulmonary embolism by tissue plasminogen activator.

A case of multiple bilateral pulmonary emboli demonstrating complete resolution 48 hours after the intravenous administration of tissue plasminogen activator is presented.

Tc-99m DTPA diffuse pulmonary uptake in patients with coronary artery disease and renal insufficiency.

Diffuse bilateral lung uptake was observed in 10 patients undergoing Tc-99m DTPA renal scanning, referred for the evaluation of rising serum creatinine levels. All 10 patients demonstrated renal insufficiency (RI) as shown by both decreased bilateral renal tracer concentration and elevated background activity. Nine of the patients were known to have coronary artery disease (CAD) and six of these nine patients were in congestive heart failure (CHF), at or around the time of scanning. However, Tc-99m DTPA lung uptake was not observed in five other patients whose scans demonstrated RI, in whom there was no CAD or other cardiac disease. Diffuse lung uptake of Tc-99m DTPA in patients with RI therefore is highly suggestive of cardiac dysfunction (i.e. CAD and/or CHF).

Comparative assessment of four different Tl-201 tumor uptake indices in the evaluation of brain tumors.

The objective of this study was to determine which semi-quantitative thallium-201 brain tumor index correlated best with clinical outcome. Fifty-two patients had Tl-201 brain single-photon emission computer tomography (SPECT) performed for the evaluation of recurrent brain tumor. A semi-quantitative tumor index was calculated utilizing four currently available techniques: 1) the ratio of average counts of the region of interest (ROI) in the lesion area and its mirror image in normal brain tissue, 2) the ratio of maximum counts of the region of interest in the lesion area and its average counts in the mirror image, 3) the ratio of maximum counts of the region of interest in the lesion area and its mirror image and 4) the ratio of the average counts of the region of interest in the lesion area and the region of interest of the scalp. A two-tailed Student's t test was performed. The mean value plus one standard deviation was used to assess the sensitivity and specificity correlated with clinical follow-up evaluation, defined as inactive or active at the time of brain SPECT by the referring neurosurgeons. Results of correlation coefficient, P value, mean, standard deviation, sensitivity, and specificity of each index using cutoff values were obtained. For those patients with recurrence or residual malignant tumor after therapy, the maximum count ratio index correlated best with clinical outcome. It provided a sensitivity of 92% and specificity of 88% in differentiating active from inactive brain tumors.

Thyroid carcinoma presenting as an autonomous thyroid nodule.

A case of follicular thyroid cancer appearing as an autonomous nodule on Tc-99m and I-123 thyroid scintigraphy is presented in addition to a pertinent review of the literature.

Redistribution of crossed cerebellar diaschisis.

Crossed cerebellar diaschisis refers to a functional decrease in blood flow to the cerebellar hemisphere contralateral to the infarcted or ischemic cerebral hemisphere. This phenomenon can be depicted using PET as well as using SPECT. This condition, seen on early I-123 IMP brain scans, can show redistribution on the three hour delayed scan, presumably due to normal non-specific amine receptor sites of the affected cerebellum. One such case is reported.

Scintigraphic recognition of papillary muscles and papillary muscle ischemia.

During stress thallium imaging, papillary muscles (anterolateral and posteromedial) appear scintigraphically as focal regions of enhanced activity in sites corresponding to their anatomic position. In the normal case, enhancement after exercise is greater than or equal to enhancement at rest. With papillary muscle ischemia, the involved papillary muscle demonstrates more enhanced activity at rest than at postexercise. This pattern change with papillary muscle ischemia was observed in four patients. Three cases demonstrated complete reversal of those ischemic changes after angioplasty and the remaining case failed to show any significant improvement after angioplasty.

The "count loss" artifact in Tc-99m HMPAO leukocyte SPECT of the abdomen.

During SPECT studies of the abdomen with Tc-99m labeled autologous leukocytes, the authors had observed false defects involving the vertebral bodies of the lower thoracic spine in two patients. To investigate this "count loss" artifact, a phantom simulating liver, spleen, and spine was constructed. Four clinical situations were simulated by positioning cylinders in the different locations: normal spine-spleen model, normal liver-spine-spleen model, spine-enlarged spleen model, and enlarged liver-spine-enlarged spleen model. SPECT studies were performed at different concentration ratios between the spleen and the spine on the disparate models with varying distance from the spleen to the spine. The results showed that the count loss artifact is not only related to the concentration ratio between the structures but also is related to the size, position, and distance between the structures. The correction steps for this artifact include: 1) identifying average count value of the spine and spleen from ECT sinogram count data, and 2) replacing the original high-count value in the spleen by the count value close to the average value at the region of the spine in the 120 raw projection data. Using these new modified ECT data, the reconstructed orthogonal images are almost free of the count loss artifact.

Evaluation of plantar fasciitis by three-phase bone scintigraphy.

Fifteen patients complaining of chronic heel pain underwent three-phase Tc-99m MDP bone scintigraphy. Ten patients demonstrated abnormal scan findings consistent with plantar fasciitis (PF) and had responded to conventional therapy. Two patients were found to have calcaneal stress fractures, and one patient demonstrated a calcaneal spur that required no treatment. The remaining two patients had normal scans and did not appear clinically to have PF. The three-phase bone scan is therefore very useful in diagnosing PF and in distinguishing it from other etiologies of the painful heel syndrome.

Scintigraphic evaluation of regional migratory osteoporosis.

Three patients with regional migratory osteoporosis (RMO) of the lower extremity were observed over a period of time with clinical and scintigraphic follow-up. The diagnosis of RMO is clinically and radiographically difficult, but a three-phase bone image is very helpful in diagnosing patients with RMO.