Discordance between MRI and bone scan findings in a child with acute complicated osteomyelitis: Scintigraphic features that contribute to the early diagnosis / Discordancia entre los hallazgos de resonancia magnética y gammagrafía ósea en niño con osteomielitis aguda complicada: aportación de patrones gammagráficos característicos en el diagnóstico precoz

Early diagnosis and prompt treatment of acute osteomyelitis are of paramount importance in children because they can prevent irreversible bone damage. Magnetic resonance imaging (MRI) with its superior spatial resolution and lack of ionizing radiation is routinely preferred over bone scan for this purpose. Increased blood flow, hyperemia and focally increased tracer uptake shown by "three phase" bone scan are the typical scintigraphic findings of acute osteomyelitis. In addition, diffuse uptake along the shaft of long bones and focal "cold" lesions are two special features that may be highly suggestive of infective periostitis, soft tissue sepsis and subperiosteal abscess formation, due to the loose attachment of periosteum to bone during childhood. We present a case of complicated osteomyelitis in a child with inconclusive MRI correctly diagnosed on the basis of these special scintigraphic findings resulting in treatment change from double i.v. Vancomycin - Ceftriaxone scheme to surgical intervention (AU)

El diagnóstico precoz y el tratamiento adecuado de la osteomielitis aguda es de suma importancia en los niños, ya que pueden prevenir el daño irreversible del hueso. La resonancia magnética (RM) por su superior resolución espacial y ausencia de radiación ionizante es la técnica utilizada en la práctica habitual antes que la gammagrafía ósea. El aumento del flujo sanguíneo y el incremento de captación focal del radiotrazador mostrado en la gammagrafía ósea de tres fases son los hallazgos gammagráficos típicos de osteomielitis aguda. Además, la captación difusa en la diafisis de huesos largos y una lesión focal "fría" son dos características especiales muy sugerente de periostitis, sepsis en tejidos blandos y formación de un absceso subperióstico, debido a la pérdida de unión del periostio al hueso durante la infancia. Presentamos un caso de osteomielitis complicada en un niño con RM no concluyente correctamente diagnosticada sobre la base de los hallazgos gammagráficos característicos originando el cambio de tratamiento de doble esquema de Vancomicina - ceftriaxona iv a intervención quirúrgica (AU)

Discordance between MRI and bone scan findings in a child with acute complicated osteomyelitis: scintigraphic features that contribute to the early diagnosis.

Early diagnosis and prompt treatment of acute osteomyelitis are of paramount importance in children because they can prevent irreversible bone damage. Magnetic resonance imaging (MRI) with its superior spatial resolution and lack of ionizing radiation is routinely preferred over bone scan for this purpose. Increased blood flow, hyperemia and focally increased tracer uptake shown by "three phase" bone scan are the typical scintigraphic findings of acute osteomyelitis. In addition, diffuse uptake along the shaft of long bones and focal "cold" lesions are two special features that may be highly suggestive of infective periostitis, soft tissue sepsis and subperiosteal abscess formation, due to the loose attachment of periosteum to bone during childhood. We present a case of complicated osteomyelitis in a child with inconclusive MRI correctly diagnosed on the basis of these special scintigraphic findings resulting in treatment change from double i.v. Vancomycin--Ceftriaxone scheme to surgical intervention.

Zoledronic acid-induced transient hepatotoxicity in a patient effectively treated for Paget's disease of bone.

Bisphosphonate (BP)-induced hepatotoxicity is very rare. There are only a few reports of liver injury after BP treatment, including aledronate and risedronate in postmenopausal osteoporosis patients. We describe hereby the case of a patient with Paget's disease of bone accompanied by nonalcoholic fatty liver disease (NAFLD) who developed transient hepatotoxicity after zoledronic acid (ZOL) treatment. NAFLD had been diagnosed 1 year before presentation, based on liver ultrasonography (US). One day after infusion, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were increased by 8.1, 6.7, and 6.7 times, respectively, compared with pretreatment values. Serum bilirubin remained normal. US revealed hepatic mild homogenous brightness without focal lesion of the liver or biliary ducts. Subsequent biochemical and serologic investigation did not reveal a specific liver or systematic disease. The patient remained asymptomatic, and ALT, AST, and GGT were normalized 7 days post-treatment. Although the mechanism by which ZOL may cause liver damage is elusive, physicians should be aware of this possible adverse effect and ZOL cautiously administered in NAFLD patients.

Myocardial perfusion scintigraphy in asymptomatic diabetic patients: a critical review.

The increasing prevalence of diabetes mellitus and the associated high cardiovascular risk has made the non-invasive identification of silent coronary heart disease in diabetic individuals an important issue. This strategy could identify higher risk asymptomatic patients with diabetes mellitus in whom coronary revascularization may improve the outcome beyond that achieved by currently recommended medical management. Stress myocardial perfusion imaging has been shown to be effective in detecting coronary heart disease and predicting adverse cardiac events in asymptomatic diabetic patients. However, the clinical utility of myocardial perfusion scintigraphy is debated intensively due to the paucity of prospective and outcome based evidence. The controversy stems from several observational studies, epidemiologic data and cost-effectiveness analyses. Thus, although several authors and professional organizations advocate the use of stress imaging for screening higher risk asymptomatic diabetic patients, others are cautious in recommending any kind of stress testing in that population. This review is based on a broad survey of the literature and discusses the potential role of stress myocardial perfusion scintigraphy in screening asymptomatic diabetic subjects for coronary heart disease in the current era and in relation with other non-invasive screening tools.

The effect of zoledronic acid on serum dickkopf-1, osteoprotegerin, and RANKL in patients with Paget's disease of bone.

Overexpression of dickkopf (DKK)-1 in pagetic osteoblast cultures resulted in stimulation of osteoclast proliferation and inhibition of osteoblast growth. The aim of this study was to evaluate for the first time in Paget's disease of bone (PDB): 1) the serum levels of DKK1; 2) the association of DKK-1 with receptor activator of nuclear factor kappa B (RANKL) and osteoprotegerin (OPG); and 3) the effect of zoledronic acid (ZOL) on serum DKK-1, RANKL, and OPG. The study was conducted as a prospective open-label cohort study. Eleven patients with PDB (median age 60 years) were recruited. Twelve age- gender- and body mass index (BMI)-matched healthy individuals were used as controls at baseline. Blood samples were obtained before treatment (baseline) and after 3, 6, 12, and 18 months following ZOL infusion in patients with PDB. Patients with PDB had significantly higher RANKL (p=0.002), OPG (p=0.001), and bone markers (total alkaline phosphatase and C-terminal cross-linking telopeptide of type I collagen) compared with controls at baseline. There was no difference between groups in DKK-1 at baseline. Bone markers were both significantly decreased after therapy. Serum OPG, RANKL, RANKL:OPG ratio, and DKK-1 remained unaffected throughout the study. No correlations were found between OPG, RANKL, RANKL:OPG ratio, and DKK-1 at baseline nor between their changes during the study. Although both OPG and RANKL were increased in patients with PDB, ZOL had no effect on their serum levels. Serum DKK-1 was neither increased in patients with PDB nor related to OPG and RANKL, and was unaffected by ZOL.

A single measurement with (51)Cr-tagged red cells or (125)I-labeled human serum albumin in the prediction of fractional and whole blood volumes: an assessment of the limitations.

This study investigated variations in the prediction of blood volumes from a single measurement of red cell volume (RCV) with (51)Cr or plasma volume (PV) with (125)I human serum albumin (HSA). In 111 subjects, fractional and whole blood volumes were estimated from separate direct measurements of RCV and PV. The f ratio (body to venous hematocrit) was also determined. There was a very good correlation between (125)I-HSA measured PV (2857 +/- 822 ml) and that estimated with (51)Cr-tagged red blood cells (2864 +/- 747 ml) (r = 0.936, p = 0.000) and also between (51)Cr measured RCV (2600 +/- 774 ml) and that estimated with (125)I-HSA (2589 +/- 843 ml) (r = 0.944, p = 0.000). The 95% limits of agreement (mean +/- 2SD of differences, relative to the mean of paired data) ranged -0.2% +/- 20.3% and 0.4% +/- 21.4%, respectively. The 95% prediction intervals of measured from estimated fractional blood volumes spanned +/-20.3% and +/-19.5%, respectively, relative to the predicted values with regression equations. Proportional degrees of inaccuracy were found in whole blood volume estimations. The f ratio was inconstant and correlated with PV and the body hematocrit. We conclude that blood volumes can be determined reliabily only with direct measurements of RCV and PV. Estimated blood volumes may lead to misconceptions.

A breast fibroadenoma mimicking an extranodal deposit of Hodgkin's lymphoma in 67Ga imaging.

We present the case of a young woman with classical nodular sclerosing Hodgkin's lymphoma (clinical stage IIB). During staging work-up, intense gallium-67 ((67)Ga) accumulation in a left breast lump raised the suspicion of an extranodal deposit, but biopsy favoured a benign histology. A post-treatment (67)Ga scan showed complete remission of the disease with normal tracer uptake in the left breast. However, a few months after treatment, a faint left mammary concentration of (67)Ga was observed. The breast mass was excised and histopathology was consistent with fibroadenoma. This unusual presentation is a new addition to the literature on false-positive (67)Ga findings and chemotherapy-associated tracer changes.

(99m)Tc-sestamibi uptake in rat skeletal muscle and heart: physiological determinants and correlations.

The lipophilic cationic radiotracer (99m)Tc-sestamibi, known to be concentrated within mitochondria, is widely used for myocardial perfusion and to a lesser extent for muscle metabolism imaging. However, the exact distribution pattern in skeletal muscle has not been yet studied in detail. The present study aims to investigate the (99m)Tc-sestamibi uptake in rat skeletal muscle and myocardium in relation to their metabolic characteristics. (99m)Tc-sestamibi was i.v. administered in twenty adult male Wistar rats and uptake, as percent of injected dose per tissue gram (%ID/g), in the myocardium, soleus, extensor digitorum longus and gastrocnemius muscles was assessed 2 h after the injection. Muscle uptake was also correlated with myocardial uptake, muscle weight and body weight. Skeletal muscle (99m)Tc-sestamibi uptake was a small (9-16 %) fraction of that found in myocardium (1.71+/-0.63 %ID/g). Among the three hindlimb muscles considered, the slow-oxidative soleus muscle showed the highest uptake (0.28+/-0.16 %ID/g). Metabolically diverse parts of the gastrocnemius muscle showed different uptake. Skeletal muscle uptake was positively correlated with myocardial uptake and both were negatively correlated with tissue and body weight. Skeletal muscle and myocardium (99m)Tc-sestamibi uptake is related to their metabolic profile. Myocardium, with an exceptional rich mitochondrial concentration, shows much higher (99m)Tc-sestamibi uptake compared to skeletal muscles. Among muscles, uptake is dependent on their mitochondrial content. Evidence of matching exists between myocardial and muscle uptake, and both are size-dependent.

Tc-99m sestamibi accuracy in detecting parathyroid tissue is increased when combined with preoperative laboratory values: a retrospective study in 453 Greek patients with chronic renal failure who underwent parathyroidectomy.

PURPOSE: Technetium(99m) sestamibi (MIBI) has poor sensitivity and specificity when applied to patients with secondary hyperparathyroidism. We investigated whether the combination of MIBI with preoperative parameters increased its accuracy. PATIENTS AND METHODS: This prospective study of 453 consecutive patients with secondary hyperparathyroidism who underwent parathyroidectomy (bilateral neck exploration) included preoperative MIBI scintigraphy compared with intraoperative and histopathology findings. Four patient groups were comprised according to the results: true positivity (TP), true negativity (TN), false positivity (FP), and false negativity (FN). RESULTS: MIBI scintigraphy sensitivity, specificity, positive predictive value, and negative predictive value were 66.4%, 50%, 76.3%, and 37.9%, respectively. For the TP group, mean age and mean parathormone (PTH) value were 56 years and 754, respectively. The binary logistic regression for the prediction (1) or not (2) of TP was as follows: 0.138 + (-.011) * age + 0.001 * PTH (P = .012). For the TN group, the mean age and mean phosphate value were 49 years and 5.24, respectively. The binary logistic regression for the prediction (1) versus not (2) of the TN was as follows: -1.463 + age * (-.029) + phosphate * 0.233 (P = .012). CONCLUSION: MIBI accuracy in patients with secondary hyperparathyroidism was increased when combined with other preoperative parameters. The sensitivity was increased as patients were older and the PTH levels were lower. The specificity was increased as patients were younger and the phosphate levels were lower.

Effect of aerobic training on 99mTc-methoxy isobutyl isonitrile (99mTc-sestamibi) uptake by myocardium and skeletal muscle: implication for noninvasive assessment of muscle metabolic profile.

AIM: The effect of long-term endurance training on skeletal muscle and myocardial uptake of (99m)Tc-sestamibi, a radiopharmaceutical accumulating in the mitochondria, was investigated. METHODS: Twenty-six Wistar rats were divided into a trained (5 days week(-1) endurance running for 14 weeks) and an untrained group. On completion of training, (99m)Tc-sestamibi was administered and, 2 h post-injection, the myocardium and the soleus, extensor digitorum longus (EDL) and medial gastrocnemius (MG) muscles were removed for the measurement of cytochrome c oxidase (CCO) activity and (99m)Tc-sestamibi uptake. Tissue (99m)Tc-sestamibi kinetics was preliminarily studied in 16 other rats for up to 2 h post-injection. RESULTS: Two hours post-injection (99m)Tc-sestamibi uptake was either stable (myocardium) or still rising (skeletal muscles). Both CCO activity and (99m)Tc-sestamibi uptake decreased in the same order (myocardium, soleus, EDL, MG) in the tissues examined. The CCO activity of the EDL and MG muscles was higher (P < 0.05) in the trained compared to the untrained group. (99m)Tc-sestamibi uptake in the soleus and EDL muscles was higher (P < 0.05) in the trained compared to the untrained rats, whereas the difference in MG was marginally significant (P = 0.06) in favour of the trained group. CONCLUSIONS: Long-term endurance training, resulting in elevated skeletal muscle CCO activity, is also associated with a similar increase in (99m)Tc-sestamibi uptake. This finding suggests that (99m)Tc-sestamibi could be used in imaging assessment of skeletal muscle metabolism with possible applications in both clinical and sports medicine settings.

Use of amifostine in the treatment of recurrent solid tumours in children.

AIM: Preclinical and clinical evaluation of amifostine (AMI) administration in conjunction with systemic chemotherapy supports its role as a cytoprotective agent of normal tissues without loss of impairing the antitumour effectiveness of chemotherapeutic agents. Since only a limited number of clinical studies has been performed using AMI in paediatric pts with malignancies we investigated the protective effect of AMI against carboplatin-induced myelotoxicity and nephrotoxicity in a paediatric group of patients. MATERIAL AND RESULTS: AMI was administered in 18/28 paediatric patients with reccurent solid tumours along with ICE (ifosfamide, carboplatin, etoposide) chemotherapy. A significant (p<0.05) decrease in GFR was observed in the control group whereas it was maintained at pre-treatment levels in the AMI-treated group. Leukopenia and neutropenia were significantly (p<0.05) less in AMI-group. No protective effect of AMI was shown concerning thrombocytopenia. CONCLUSIONS: AMI was generally well tolerated at the dose of 740 mg/m2. Side effects including nausea, vomiting, hypotension, flushing and rigors were moderate and reversible and the interruption of infusion was never required.

Assessment of brown adipose tissue activity in rats by 99mTc-sestamibi uptake.

Brown adipose tissue (BAT) physiology and imaging have recently attracted considerable attention. BAT is characterized both by enhanced perfusion and increased mitochondrial activity. (99m)Tc-sestamibi is a lipophilic cationic tracer that concentrates in mitochondria. Data on the accumulation of (99m)Tc-sestamibi in BAT are currently lacking. This study investigates the in vivo (99m)Tc-sestamibi uptake in rat BAT. (99m)Tc-sestamibi was administered in male Wistar rats of various age and body size. (99m)Tc-sestamibi uptake was measured in vitro in BAT and white fat (WF) together with cytochrome c oxidase activity. Both (99m)Tc-sestamibi uptake and cytochrome c oxidase activity were higher in BAT than in WF (P<0.05). (99m)Tc-Sestamibi uptake in both BAT and WF was negatively related to body weight (r = -0.96 and -0.89, respectively) as was the BAT/WF uptake ratio (r = -0.85). These data show a higher (99m)Tc-sestamibi uptake in BAT compared to WF, in agreement with the high mitochondrial content and respiratory activity of the former. The strong negative correlation between (99m)Tc-sestamibi uptake in BAT and body weight (negative allometry), is in accordance to increased needs of thermogenesis in smaller animals. Implications of increased (99m)Tc-sestamibi uptake in BAT in radionuclide imaging are also discussed.

Heart rate is the major determinant of diastolic filling pattern during growth: a radionuclide ventriculography assessment.

Left ventricular diastolic filling is a fundamental constituent of cardiac performance. Diastolic function in both adults and children can be routinely assessed by radionuclide ventriculography (RNV). It has previously been shown that factors such as heart rate (HR) and age can significantly modify diastolic performance in adults, thus limiting the clinical applicability of RNV diastolic indices. The aim of this study was to investigate various factors that may affect diastolic function in childhood. Seventy-nine children, aged 40 days to 15 years, were enrolled in the study; their HR ranged from 45 to 160 beats per minute (bpm). All had intact cardiac function and were submitted to baseline RNV prior to chemotherapy initiation for malignancies. Using stepwise linear regression analysis, HR was identified as the major factor affecting RNV diastolic indices during growth. Applying univariate regression models, diastolic indices were corrected for a referrence HR of 100 bpm; this substantially reduced variability of RNV diastolic indices along age increments, allowing for the establishment of reference ranges. In conclusion, HR was shown to be the major determinant of RNV diastolic indices during growth. Adjustment for this variable alone can offer reference ranges for the assessment of left ventricular filling in childhood.

A decrease in soleus muscle force generation in rats after downhill running.

The purpose of the present study was to investigate the immediate and 48-hr post-exercise effects of eccentric contraction-biased exercise on the contractile properties of the soleus muscle in situ. Adult male Wistar rats were categorised into sedentary control rats (n = 10), rats studied immediately (n = 10), and rats studied 48 hours after the exercise (n = 10). The exercise protocol consisted of a 90-min intermittent downhill running (-16 degrees, 16 m/min) on a motor-driven treadmill. The contractile properties of the soleus muscle were recorded following i.p. chloral hydrate anaesthesia. Isometric twitch force (Pt), time-to-peak tension (TPT), half-relaxation time (1/2 RT), and tetanic force at stimulation frequencies of 40, 80, and 100 Hz were recorded. A low-frequency muscle fatigue protocol (stimulation at 4 Hz for 5 min) was applied to test for fatigability. The main findings indicated that Pt generation dropped both immediately and 48 hr after the exercise, while tetanic force was partially restored after 48 hr. Exercise-induced E-C coupling failure and contractile machinery disorganisation due to muscle injury are put forward as the main force reduction causes.

A fractal characterization of the type II fiber distribution in the extensor digitorum longus and soleus muscles of the adult rat.

A method is proposed for the quantitative characterization of fiber type spatial distribution by means of the (correlation) fractal dimension. The method is applied to type II fiber distributions of the soleus and extensor digitorum longus muscles of the adult rat. The results obtained suggest that these distributions have fractal properties with a strong tendency for spreading, more pronounced in soleus muscle. The density of muscle fibers or the age do not seem to alter the features of the distribution. Computer-generated random patterns have virtually the same fractal dimension as the extensor digitorum longus distributions but fail to approximate those of the soleus muscle. This fractal method could find application as an alternative in the quantitative assessment of the fiber type grouping.