Adipose triacylglycerol lipase is a major regulator of hepatic lipid metabolism but not insulin sensitivity in mice.

AIMS/HYPOTHESIS: Hepatic steatosis is characterised by excessive triacylglycerol accumulation and is strongly associated with insulin resistance. An inability to efficiently mobilise liver triacylglycerol may be a key event mediating hepatic steatosis. Adipose triacylglycerol lipase (ATGL) is a key triacylglycerol lipase in the liver and we hypothesised that liver-specific overproduction of ATGL would reduce steatosis and enhance insulin action in obese rodents. METHODS: Studies of fatty acid metabolism were conducted in primary hepatocytes isolated from wild-type and Atgl (also known as Pnpla2)⁻(/)⁻ mice. An ATGL adenovirus was utilised to overproduce ATGL in the livers of obese insulin-resistant C57Bl/6 mice (Ad-ATGL). Blood chemistry, hepatic lipid content and insulin sensitivity were assessed in mice. RESULTS: Triacylglycerol content was increased in Atgl⁻(/)⁻ hepatocytes and was associated with increased fatty acid uptake and impaired fatty acid oxidation. ATGL adenovirus administration in obese mice increased the production of hepatic ATGL protein and reduced triacylglycerol, diacylglycerol and ceramide content in the liver. Overproduction of ATGL improved insulin signal transduction in the liver but did not affect fasting glycaemia or insulinaemia. Inflammatory signalling was not suppressed by ATGL overproduction. While ATGL overproduction increased plasma non-esterified fatty acids, neither lipid deposition nor insulin-stimulated glucose uptake were affected in skeletal muscle. CONCLUSIONS/INTERPRETATION: Liver ATGL overproduction decreases hepatic steatosis and mildly enhances liver insulin sensitivity. These effects are not sufficient to improve fasting glycaemia or insulinaemia in rodent obesity.

Head-only followed by cardiac arrest electrical stunning is an effective alternative to head-only electrical stunning in pigs.

Many small slaughter facilities use head-only electrical stunning to render swine unconscious and insensible to pain before slaughter. Head-only electrical stunning is a reversible procedure that is optimally effective for approximately 15 s after stun completion. In many small North American slaughter plants, the authors have observed hoist speeds that are too slow to achieve a short enough stun-to-bleed interval to maintain insensibility through exsanguination. Unlike many European plants, there is no separate high-speed hoist for pigs and exsanguination on the floor is not condoned. As a result, a 2-stage stunning method was proposed where head-only stunning for 3 s was immediately followed by application of the same stunning wand to the cardiac region of the animal for 3 s while lying in lateral recumbancy. A paired-comparison study was conducted on 89 pigs in a small slaughter facility to compare the head-only method applied for 6 s with the head/heart method. The objective was to evaluate signs of return to sensibility, stun-to-bleed time, blood lactate concentration, muscle pH, drip loss, and fresh meat color to validate the head/heart electrical stunning method for small slaughter plants. Incidence of corneal reflex was not different (P > 0.05) between head/heart (93.8%) and head only (85%) stunning. Nose twitching was more common (P < 0.05) in head only (26.5%) than head/heart (5%) stunning. Head/heart stunning eliminated rhythmic breathing, natural blinking, eye tracking to moving objects, and righting reflex, which were all observed in head-only stunned pigs. Eye tracking to moving objects was observed in 40.8% of head-only stunned pigs. Blood lactate was not different (P > 0.05) between stunning methods (head only: 8.8 ± 0.7 mmol/L, head/heart: 7.8 ± 0.7 mmol/L). Stun-to-bleed time did not differ (P > 0.05; head only: 32 ± 1 s, head/heart: 33 ± 1 s). Mean time to loss of heartbeat with the head-only method was 121 ± 5 s. No heartbeat was observed with the head/heart method. Longissimus thoracis pH, color, and drip loss were not different (P > 0.05) between stunning methods. This study determined that the head/heart electrical stunning method reduces the incidence of signs of return to sensibility without significant effects on meat quality, plant operation speed, or blood lactate concentration. In addition, the head/heart method requires no capital investment for plants that are currently using the head-only method.

Examination of 'lipotoxicity' in skeletal muscle of high-fat fed and ob/ob mice.

Excess lipid accumulation resulting from an elevated supply of plasma fatty acids is linked to the pathogenesis of the metabolic syndrome and heart disease. The term 'lipotoxicity' was coined to describe how lipid accumulation leads to cellular dysfunction and death in non-adipose tissues including the heart, pancreas and liver. While lipotoxicity has been shown in cultured skeletal muscle cells, the degree of lipotoxicity in vivo and the functional consequences are unresolved. We studied three models of fatty acid overload in male mice: 5 h Intralipid((R)) and heparin infusion, prolonged high fat feeding (HFF) and genetic obesity induced by leptin deficiency (ob/ob mice). Markers of apoptosis, proteolysis and autophagy were assessed as readouts of lipotoxicity. The Intralipid((R)) infusion increased caspase 3 activity in skeletal muscle, demonstrating that enhancing fatty acid flux activates pro-apoptotic pathways. HFF and genetic obesity increased tissue lipid content but did not influence apoptosis. Gene array analysis revealed that HFF reduced the expression of 31 pro-apoptotic genes. Markers of autophagy (LC3beta and beclin-1 expression) were unaffected by HFF and were associated with enhanced Bcl(2) protein expression. Proteolytic activity was similarly unaffected by HFF or in ob/ob mice. Thus, contrary to our previous findings in muscle culture in vitro and in other non-adipose tissues in vivo, lipid overload did not induce apoptosis, autophagy or proteolysis in skeletal muscle. A broad transcriptional suppression of pro-apoptotic proteins may explain this resistance to lipid-induced cell death in skeletal muscle.

Integral urban solid waste management program in a Mexican university.

The Azcapotzalco campus of the Universidad Autónoma Metropolitana (UAM-A) has implemented an Integral Urban Solid Waste Management Program, "Segregation for a Better UAM Environment" (Separacción por un mejor UAMbiente). This program is directed to create awareness and involve the academic community of the UAM-A concerning the problem of solid wastes, at the same time fulfilling the local environmental legislation. The program consists in separating solid wastes into two classes: (1) recoverable wastes (glass and PET bottles, aluminum cans, Tetrapak packages) and (2) other wastes (non-recoverable). During the past three years, thanks to this program, the amount of solid wastes delivered monthly to municipal collecting services has been considerably reduced. In this period, UAM-A has sent to recycling: 2.2 tons of glass bottles; 2.3 tons of PET bottles; 1.2 tons of Tetrapak packages and 27.5 kg of aluminum cans.

Detection of renal artery stenosis: prospective comparison of captopril-enhanced Doppler sonography, captopril-enhanced scintigraphy, and MR angiography.

OBJECTIVE: The objective of our study was to compare the value of captopril-enhanced Doppler sonography, captopril-enhanced renal scintigraphy, and gadolinium-enhanced MR angiography for detecting renal artery stenosis. SUBJECTS AND METHODS: Forty-one patients with suspected renovascular hypertension were prospectively examined with captopril-enhanced Doppler sonography, captopril-enhanced renal scintigraphy, gadolinium-enhanced MR angiography, and catheter angiography. The sensitivity and specificity of each technique for detecting renal artery stenosis measuring 50% or greater and 70% or greater were compared using the McNemar test. Positive and negative predictive values were estimated for populations with 5% and 30% prevalence of renal artery stenosis. Kappa values for interobserver agreement were assessed for both gadolinium-enhanced MR angiography and catheter angiography. RESULTS: For detecting renal artery stenosis measuring 50% or greater, the sensitivity of gadolinium-enhanced MR angiography (96.6%) was greater than that of captopril-enhanced Doppler sonography (69%, p = 0.005) and captopril-enhanced renal scintigraphy (41.4%, p = 0.001). No significant difference in specificity was observed among modalities. For renal artery stenosis measuring 50% or greater, positive and negative predictive values were respectively 62% and 86% for captopril-enhanced Doppler sonography, 49% and 76% for captopril-enhanced renal scintigraphy, and 53% and 98% for gadolinium-enhanced MR angiography. Interobserver agreement was high for both gadolinium-enhanced MR angiography (kappa = 0.829) and catheter angiography (kappa = 0.729). CONCLUSION: Gadolinium-enhanced MR angiography is the most accurate noninvasive modality for detecting renal artery stenosis greater than or equal to 50%. The use of captopril-enhanced Doppler sonography in combination with gadolinium-enhanced MR angiography for identifying renal artery stenosis needs to be evaluated with a cost-effectiveness analysis.

Role of scintigraphy in musculoskeletal and spinal infections.

Clinical findings are still the mainstay for suspecting the diagnosis of musculoskeletal infections, especially osteomyelitis. No single complementary imaging technique has 100% specificity and sensitivity for every case of musculoskeletal infection. Depending on the age of the patient, presence of orthopedic hardware, location of infection, underlying bone, and systemic conditions, the choice of imaging modalities must be tailored to the patient's condition. Plain radiographs are performed first and may be sufficient. In children, bone scan is highly accurate to diagnose osteomyelitis. Labeled leukocytes with complementary bone or bone marrow studies are recommended for orthopedic hardware or diabetic foot. Finally, gallium scanning is useful for the diagnosis of vertebral osteomyelitis. Current radiopharmaceuticals used for diagnosing infection also label inflammation. Newer products, as Infecton, should in the future allow better differentiation between infection and sterile inflammation.

Imaging of renovascular hypertension: respective values of renal scintigraphy, renal Doppler US, and MR angiography.

Renovascular hypertension affects 15%-30% of patients who have clinical criteria suggestive of renovascular disease. Noninvasive screening is crucial for patient selection prior to conventional angiography and renal revascularization. Renal scintigraphy has been reported to be sensitive for detection of renovascular hypertension, but some of its limitations (eg, in the setting of bilateral renal artery stenosis and renal failure) should be considered. Doppler ultrasonography (US) allows direct evaluation of the renal arteries as well as transrenal Doppler waveform analysis, but it remains operator dependent. Gadolinium-enhanced magnetic resonance (MR) angiography is becoming an excellent alternative to conventional angiography. The main limiting factors of this technique are inadequate visualization of segmental and accessory renal arteries as well as a tendency toward overestimation of stenoses. Given the high cost and low availability of MR angiography, scintigraphy and Doppler US should be considered the primary studies in screening for renovascular hypertension. MR angiography could be reserved for patients with inconclusive scintigraphic and Doppler US results, patients with high clinical suspicion of renovascular hypertension, and patients with a contraindication to conventional angiography.

Comparison of early and delayed scintigraphy with 99mTc-apcitide and correlation with contrast-enhanced venography in detection of acute deep vein thrombosis.

UNLABELLED: Preliminary studies with 99mTc-apcitide (99mTc-P280), a synthetic peptide that binds to glycoprotein IIb/IIIa receptors expressed on activated platelets, have shown promising results in the detection of acute deep vein thrombosis (ADVT). The purpose of this study was to compare the diagnostic value of early and delayed imaging with 99mTc-apcitide in patients with suspected ADVT, using contrast-enhanced venography as the gold standard. METHODS: Thirty-nine patients (17 women, 22 men; mean age 59 y) with signs or symptoms suggestive of ADVT (within 10 d of onset) and scheduled for contrast-enhanced venography were prospectively studied. The patients were injected with approximately 740 MBq (20 mCi) 99mTc-apcitide within 36 h of contrast-enhanced venography. Both anterior and posterior planar images (8-10 min/view) of the lower extremities using a dual-head gamma camera were obtained at 10, 60 and 120 min after the injection of 99mTc-apcitide. The three sets of images initially were interpreted randomly and separately by three experienced observers unaware of the clinical history, the site of ADVT and results of contrast-enhanced venography. All images from the three sets for a given patient were then analyzed together during a second session. Conventional contrast-enhanced venography was performed on 31 patients before 99mTc-apcitide scintigraphy and in the remaining 8 patients after 99mTc-apcitide scintigraphy. 99mTc-apcitide findings were considered positive forADVT when a focus of increased uptake was found to correspond to the location of a deep vein. Disagreements were resolved by consensus. RESULTS: Twenty-two patients had ADVT observed on contrast-enhanced venography, whereas 17 had normal findings. Six cases of ADVT were infrapopliteal. One patient did not complete the third set of images with 99mTc-apcitide. The sensitivity of 99mTc-apcitide in detecting ADVT was 63.6% (14/22), 68.2% (15/22), 76.2% (16/21) and 86.4% (19/22) for images obtained at 10, 60 and 120 min and for the three sets analyzed together, respectively. The specificity was 82.4% (14/17), 76.5% (13/17), 88.2% (15/17) and 88.2% (15/17) for images obtained at 10, 60 and 120 min and for the three sets of images together, respectively. CONCLUSION: Although the set of 99mTc-apcitide images obtained 120 min after injection showed good overall diagnostic accuracy, the combination of at least two sets of images provided the highest accuracy in detecting ADVT.

[The solitary pulmonary nodule. A retrospective study of 119 cases]. / Nódulo solitário do pulmão. Estudo retrospectivo de 119 casos.

The authors review 119 cases of solitary pulmonary nodule submitted to surgery, analysing their aetiology and correlating them with their clinical and radiological aspects as well as with the patient's age, sex and smoking habits. An analysis of some pre-surgical diagnostic methods was also made. In half of the nodules (54%) the diagnosis made was of malignancy. Some of these (8%) were pulmonary metastases. There was no sex preference in the distribution of malignant or benign lesions. The average diameter of malignant nodules was 2.8 +/- 10.9 cm and benign nodules 2.1 +/- 10.9 cm. The large majority of malignant lesions was found in both upper lobes, whilst benign lesions did not have a preferential location. Adenocarcinomas were the most common primary lung tumours found, (59%), followed by squamous (27%) and neuroendocrine tumours (12.5%). Most benign nodules were benign neoplasias (43%--hamartomatous tumours) or of infectious aetiology (mostly granulomatous chronic disease--39%). The evaluation of the imagiological criteria of benignity or malignancy resulted in a sensitivity of 67% and specificity of 76%. In this study, negative respiratory cytology and bronchofibroscopic biopsies were not particularly helpful in excluding malignancy. This study confirms results published by other authors, in concluding that larger nodules have a greater probability of malignancy, that these are more frequent in males with smoking habits, and that they predominate in the upper lobes.

False-positive captopril renography in patients taking calcium antagonists.

UNLABELLED: Captopril-enhanced renography is the noninvasive test of choice for the diagnosis of renovascular hypertension. Previous studies have shown that bilateral symmetrical changes are associated with many renal conditions. However, patients with normal renal angiography occurred in our institutions despite this scintigraphic pattern, and no known conditions could explain these results. The purpose of this study was to evaluate the diagnostic implications of bilateral symmetrical renal function deterioration on captopril renography. METHODS: Eighty-six captopril renal scintigraphies performed at two centers to exclude renovascular hypertension (50 consecutive patients after the observation of a bilateral symmetrical renal function deterioration despite a normal angiogram at one institution and 36 patients with both captopril renography and renal angiography at the other institution) were retrospectively reviewed. Baseline and captopril-enhanced renograms were obtained with 99mTc-mercaptoacetyltriglycine and a 1-day protocol in 50 patients; 36 patients were studied using 99mTc-diethylenetriamine pentaacetic acid and a 2-day protocol. Bilateral symmetrical renal function deterioration was detected. RESULTS: Ten patients presented with bilateral symmetrical renal function deterioration on their captopril renograms; 9 of them were taking calcium antagonists (p=0.015). Control studies performed in 5 patients without these medications demonstrated normal captopril renograms in 4 and persistent renal dysfunction in 1. No explanation was found for the patient who was not taking any medication. Angiograms performed in 5 patients showed normal renal arteries. An 11th patient who was taking a calcium antagonist showed dysfunction of his one kidney on the captopril renogram but no artery stenosis on the renal angiogram. CONCLUSION: Calcium antagonists can cause false-positive captopril renograms. These medications should be stopped before captopril renography, and physicians should be aware of this possible drug interaction if bilateral symmetrical renal function deterioration is seen on a patient's captopril renogram.

[Refractory severe ulcerative colitis. Experience with cyclosporine]. / Colite ulcerosa grave refractária. Experiência com ciclosporina.

A case of severe ulcerative colitis refractory to steroid therapy is reported. The authors look at cyclosporine use in this clinical setting and make a short review of cyclosporine usefulness and major side effects.

Metastatic axillary lymph node technetium-99m-MIBI imaging in primary breast cancer.

UNLABELLED: Technetium-99m-MIBI scintimammography has been shown to be useful in the detection of primary breast cancer. The purpose of this study was to evaluate the potential role of scintimammography in detecting axillary lymph node involvement in patients undergoing scintimammography to detect primary breast cancer. METHODS: A group of 100 women with breast cancer who were scheduled for a Level I-II axillary dissection were prospectively studied. Scintimammography was performed in all patients before histopathologic confirmation of breast cancer. Two lateral (prone imaging) views and one anterior (supine) planar thoracic view were obtained 10-15 min after the injection of 25-30 mCi 99mTc-MIBI (10 min/view) by using a special breast positioning device (foam cushion) placed over the imaging table. Both of the axilla were included in the field-of-view. Two experienced blinded observers reviewed all cases both from films and from the computer screen with contrast adjustment when needed. The site of intravenous injection of 99mTc-MIBI was known to the interpreters in order to avoid reading any false-positive uptake in the axilla ipsilateral to the injection site. RESULTS: A total of 52 patients had no axillary lymph node involvement (611 negative nodes) while 48 patients had at least one axillary lymph node with metastatic involvement (180/502 positive nodes). The sensitivity of scintimammography in detecting metastatic axillary lymph node involvement was 79.2% (38/48), and the specificity was 84.6% (44/52). The positive and the negative predictive values were 82.6% (38/46) and 81.5% (44/54), respectively. CONCLUSION: This study shows that scintimammography has good diagnostic accuracy for detecting axillary lymph node involvement in patients with breast cancer. This information should be added to the result of standard scintimammography, which requires very minor modifications in order to simultaneously evaluate both of the axilla.

Pharmacokinetics of amiloride after inhalation and oral administration in adolescents and adults with cystic fibrosis.

STUDY OBJECTIVE: To compare the pharmacokinetics and systemic exposure of nebulized and oral amiloride in adolescents and adults with mild to moderate cystic fibrosis (CF). DESIGN: Open-label, randomized, two-way crossover, single-dose pharmacokinetic study. SETTING: University hospital clinical research unit. PATIENTS: Nine adolescents and 10 adults with mild to moderate CF (forced expiratory volume in 1 sec > or = 50% predicted, Brasfield score > or = 15). INTERVENTIONS: Patients received amiloride solution orally (10 mg of amiloride 1-mg/ml solution) and by inhalation [4.5 ml amiloride of 1-mg/ml solution in 12% saline (approximately 3.8 mmol/L) by DeVilbiss 646 nebulizer] during two study phases separated by a 7- to 28-day washout period. Serial blood and urine samples were collected for 48 and 72 hours, respectively. MEASUREMENTS AND MAIN RESULTS: After oral dosing, the mean +/- SD maximum peak concentration (Cmax) was 20.6 +/- 10.0 ng/ml at 3.2 +/- 1.2 hours in adults and 21.7 +/- 4.88 at 2.9 +/- 0.6 hours in the adolescents. Mean area under the concentration-time curve (AUC) from time zero to infinity hours was 275 +/- 115 and 254 +/- 60 ng.hr/ml in the adult and adolescent groups; half-life was 16.0 +/- 0.7 and 13.4 +/- 1.4 hours, respectively. After nebulization, 14 of 19 subjects exhibited two concentration peaks (Cmax1 and Cmax2) with mean values of 1.57 +/- 1.67 ng/ml at 0.5 +/- 0.2 hours and 1.37 +/- 1.21 ng/ml at 4.0 +/- 1.0 hours for adults, and 1.49 +/- 0.99 ng/ml at 0.5 +/- 0.1 hours and 1.52 +/- 0.81 ng/ml at 3.3 +/- 0.5 hours for adolescents. Estimated mean +/- SD dose nebulized was 1.91 +/- 0.66 and 2.28 +/- 0.30 mg in the adult and adolescent groups, respectively. Mean +/- SD AUC from time zero to the last measurable plasma amiloride concentration after inhalation was 14.4 +/- 17.6 and 15.4 +/- 10.1 ng.hr/ml in the adults and adolescents. No significant adverse events occurred during the study. Pharmacokinetic parameters were not statistically different between the adolescent and adult groups by route of administration. However significant differences in peak amiloride concentration, AUC, and urinary amiloride excretion were evident when comparing oral versus inhalation administration within each group. CONCLUSIONS: Mean amiloride plasma concentration peaks and AUC after inhalation were significantly lower than after oral dosing. In addition, the second amiloride plasma concentration peak may be due to oral ingestion of the nebulized amiloride, whereas the earlier Cmax1 after inhalation may be due to pulmonary absorption of amiloride. These results suggest that single-dose amiloride inhalation in patients with mild to moderate CF results in minimal systemic exposure compared with oral dosing, and that drug disposition is similar in adolescents and adults with CF.

Radionuclide captopril renography in postpartum renal artery aneurysms.

We report the case of a young woman with three left renal artery aneurysms, diagnosed immediately postpartum, associated with a de novo high blood pressure. To assess anatomical and functional characteristics of renal artery aneurysms, renal angiogram, MRI, intravenous pyelography, ultrasonography and radionuclide renography were performed. Two patent saccular renal artery aneurysms were demonstrated in the left kidney by renal angiogram. A larger, thrombosed aneurysm was also depicted on the left side on ultrasonography, MRI and renal angiogram. The larger aneurysm was responsible for renovascular disease of the middle third of the kidney, as demonstrated by captopril and baseline radionuclide renographic studies. It also impeded drainage of the lower pyelocalyceal group, without obstructing it, as shown by concomitant furosemide (Lasix) evaluations.

Comparison between dipyridamole and adenosine as pharmacologic coronary vasodilators in detection of coronary artery disease with thallium 201 imaging.

BACKGROUND: Both dipyridamole and adenosine are widely used as pharmacologic stressors with 201Tl imaging for detection of coronary artery disease. The purpose of this study was to compare dipyridamole and adenosine 201Tl imaging directly in patients with angiographically proved coronary artery disease. METHODS AND RESULTS: Fifty-four patients were submitted to two planar 201Tl studies: one with dipyridamole and the other with adenosine. The interval between the two studies varied from 2 to 7 days and the order was assigned randomly. Three standard planar views were obtained 10 minutes and 4 hours after the injection of 3.0 mCi 201Tl. Administration of dipyridamole was as follows: 0.142 mg/kg/min during 4 minutes, followed by a slight exercise and 201Tl injection. The infusion of adenosine was as follows: 0.140 mg/kg/min during 6 minutes with injection of 201Tl after the third minute of infusion. Patients were asked to give their preference considering the number, type, severity, and duration of side effects on a scale from 0 (worst) to 5 (best). Reading was done by two experienced observers. The heart was divided into three segments per view. The change in systolic blood pressure was -12 +/- 11 mm Hg for adenosine and -5 +/- 10 mm Hg for dipyridamole (p < 0.001), and the change in heart rate was 18 +/- 10 beats/min for adenosine and 8 +/- 7 beats/min for dipyridamole (p < 0.001). With regions of interest, ischemic/normal wall ratios were determined: 0.78 +/- 0.06 for adenosine and 0.83 +/- 0.08 for dipyridamole (p < 0.001). Adenosine detected 295 normal, 170 ischemic, and 21 scar segments, whereas dipyridamole detected 326, 135, and 25 segments, respectively. Patients preferred adenosine (4.3 +/- 1.0 for adenosine vs 3.8 +/- 1.5 for dipyridamole; p < 0.04) mainly because of the short duration of side effects. CONCLUSION: This study shows that the use of adenosine with 201Tl imaging may have some advantages over dipyridamole.

"Cold" reflex sympathetic dystrophy in an adult.

The classical presentation of acute reflex sympathetic dystrophy (RSD) or triple-phase bone scintigraphy usually consists of increased periarticular uptake in each phase. The authors present a rare case of acute adult RSD characterized by bone hypofixation of Tc-99m MDP. Reflex sympathetic dystrophy in adults and children is reviewed.