Antioxidant treatment ameliorates germ cell apoptosis induced by a high-dose ionizing irradiation in rats.

BACKGROUND: Exposure to ionizing radiation results in cytotoxic and genotoxic effects caused mainly by the oxidative damage. In the present study, we investigated the radioprotective effect of novel antioxidant cocktail on germ cell apoptosis and spermatogenesis in rats subjected to whole body radiation (WBIR). METHODS: Adult male rats weighing 250-270 g were divided into four groups, eight rats each. Group 1 served as untreated control, group 2 received an IP single dose of antioxidant cocktail (1 ml). Group 3 was exposed to a WBIR (6 Gy). Group 4 received antioxidant cocktail before WBIR. Rats from each group were killed after 48 h. MDA levels were measured in serum (TBARS assay). Johnsen's criteria and the number of germinal cell layers were used to categorize spermatogenesis. TUNEL assay was used to determine germ cell apoptosis. Statistical analysis was performed using one-way ANOVA test. RESULTS: WBIR resulted in histological testicular damage (decrease in Johnsen's criteria, p < 0.05) that was accompanied by a significant increase in germ cell apoptosis, expressed as the number of apoptotic cells per 100 tubules (AI-1 apoptotic index) and the number of positive tubules per 100 tubules (AI-2 apoptotic index). Treatment with antioxidant cocktail resulted in a significant decrease in germ cell apoptosis (33% decrease in AI-1, p < 0.05 and 34% decrease in AI-2, p < 0.05) that was accompanied by an improved spermatogenesis (increase in Johnsen's criteria, p < 0.05). CONCLUSIONS: In a rat model of WBIR, antioxidant treatment ameliorates oxidative stress-induced testicular damage, decreases germ cell apoptosis and improves spermatogenesis.

Patterns of FDG uptake in post-thoracotomy surgical scars in patients with lung cancer.

Increased (18)F-fluorodeoxyglucose ((18)F-FDG) uptake can occur in surgical scars. This study assesses the incidence, patterns and natural history of (18)F-FDG uptake in post-thoracotomy scars of non-small cell lung cancer (NSCLC) patients. 73 (18)F-FDG-PET/CT studies performed after resection of NSCLC in 61 patients (49 men, 12 women; mean age, 66.7 years) were retrospectively reviewed for the presence, pattern and intensity (maximum standardized uptake value (SUV(max))) of (18)F-FDG uptake in sites of previous thoracotomy. Increased (18)F-FDG uptake in surgical scars was found in 61% of studies (43/70) (average SUV(max), 3.6); 3 patients with recurrence at the surgical scar were excluded from the analysis of the characteristics of physiological FDG uptake in scars over time. The average time from surgery was 14.4 months in patients with, and 43.8 months in patients without, scar uptake (p<0.0002). Increased uptake was seen in 14/14 studies (100%) at 1-3 months, in 12/13 studies (92%) at 3-12 months, and in 17/43 studies (40%) at more than 12 months after surgery in patients with no evidence of disease on follow-up. (18)F-FDG uptake was diffuse in 67% of studies (29/43). Tumour recurrence in the scar was found in three studies, showing focally increased uptake (average SUV(max), 9.1 ) at 3-8 months after thoracotomy. In conclusion, increased (18)F-FDG uptake in post-thoracotomy surgical scars is mainly diffuse, and decreases in incidence and intensity with time, with 60% of studies showing no scar uptake at more than 12 months after surgery. Focally intense scar uptake should be evaluated for suspected recurrence.

Validation of a novel method to determine non-invasively the rate of central aortic pressure changes.

INTRODUCTION: One of the most sensitive indices of myocardial contractility is represented by the rate of increase of intraventricular pressure during isovolumetric contraction (dP/dt) and (dP/dt(ejc)), which represents the rate of change of pressure during ejection. Today these parameters can be obtained only by invasive catheterization methods. We developed a novel technique that leads to the non-invasive reconstruction of the central aortic pressure. The technique is based on the concept of applying multiple successive occlusive pressures on the brachial artery from peak systole to diastole using an inflatable cuff and plotting the values against time intervals. The hypothesis is that the time intervals required for the aortic pressure wave to overcome a given occlusive brachial pressure applied by a sphyngomanometer on the arm are equal to time needed to reach the same pressure in the central aorta plus the propagation time to the brachial point, which is constant in the same patient throughout the measurements. METHODS AND RESULTS: We tested the hypothesis using an animal experiment. The new non-invasive device was mounted on the left forelimb of the animal. A Millar pressure transducer catheter was inserted to the aorta and the aorta pressure was recorded at time intervals of 1 ms. A second catheter was inserted into the coronary arteries and used to create controlled occlusion of the arteries using a balloon inflated to 10 atm. Measurements were obtained before the intervention was started, and throughout the sequence of repeated occlusions and deflations. At the end of the sequence, IV dobutamine was administered and results were monitored for 10 min while the heart rate and blood pressure were rising. Non-invasive dP/dt(ejc) was reduced typically by 20% in response to balloon inflation. In long occlusion periods, stabilization and sometimes recovery of dP/dt(ejc) is observed. By plotting dP/dt(ejc) measured by the new non-invasive device versus catheter measurements a correlation factor of 0.843 was found. CONCLUSION: A newly developed method of non-invasive measurement of central dP/dt has been found to correlate to invasive measurements in an animal model.

Detection of chest pain of non-cardiac origin at the emergency room by a new non-invasive device avoiding unnecessary admission to hospital.

Recent advances in the treatment of acute coronary syndromes has raised awareness that prompt presentation for chest pain may be life saving. Most patients presenting with chest discomfort have a non-ischaemic ECG on presentation, but are routinely admitted to hospital because of diagnostic uncertainty for occult MI or ischaemia. We tested a new non-invasive device that measures central aortic pressure changes (dP/dtejc): an accepted index of myocardial performance that could be added to the diagnostic triage of ischaemia in the ER avoiding unnecessary admissions. We followed 85 patients presenting at the ER with acute chest pain. In 72 patients, negative ECG and myocardial enzyme dynamics ruled out coronary origin during the first 24 h after admission. In 8 of the 72 patients, coronary catheterisation found normal coronary arteries. In this group, average dP/dtejc was 163 (range 92-232). In 35 patients in whom the new non-invasive cardiac performance index dP/dtejc was above a threshold of >150, acute MI was ruled out. In 13 patients, acute chest pain had coronary origin confirmed by ECG and/or positive enzymes. The average dP/dtejc in this group was 117 (range 61-149). The dP/dtejc values were found to be significantly higher in patients without acute MI (p<0.001). Preliminary findings suggest that nearly 40% of patients presenting with acute chest pain could be spared the risks and costs of unnecessary hospital admission and more invasive cardiac testing by simply adding a easy to use, immediately obtained, test to the diagnostic protocol, and using a threshold of dP/dtejc>150 to rule out heart attack.

Nebuliser hood compared to mask in wheezy infants: aerosol therapy without tears!

BACKGROUND: Small volume nebulisers (SVNs) with masks commonly provide aerosol therapy for infants with lung diseases. However, infants and toddlers are often disturbed by and thus reject masks. AIMS: To compare the lung deposition efficiency of the "usual" SVN aerosol mask and a prototype hood attached to an SVN. The advantage of the hood is that no mask is needed and medication can readily be administered during sleep. METHODS: 99mTc salbutamol solution was administered at random by SVN plus mask or hood to 14 wheezy infants (mean age 8 (SD 5) months). The dose and distribution of salbutamol were evaluated using gamma scintigraphy. Clinical response, tolerability by the infants, and parent preference were also compared. RESULTS: Mean total lung deposition was 2.6% with the hood and 2.4% with the mask (p > 0.05). Variability with the mask was greater than with the hood (coefficient of variation (CoV) 54% v 39%). Both treatments provided similar clinical benefit and side effects as reflected in improved oxygen saturation, reduced respiratory frequency, and increased heart rate. Infants accepted the hood better than the mask and there was a positive correlation between poor acceptance and upper airways and stomach deposition for both treatment modalities. Parents preferred the hood treatments. CONCLUSIONS: Aerosol therapy by hood is as efficient as by mask but provides a better therapeutic index. It is much better tolerated by infants and preferred by parents. Hood nebulisation is a simple and patient friendly mode of aerosol therapy in wheezy infants.

Endothelin release: a marker for the severity of exercise-induced ischemia.

Elevated endothelin-1 levels were found in exercise-induced ischemia. To our knowledge, no attempt has been made to correlate the presence of the elevated endothelin levels with severity of ischemia. In the present study, we attempt to correlate the severity of ischemia, quantified using a bullseye visual display of scintigraphic ischemic score on SPECT technetium 99m sestamibi, with presence of endothelin at peak exercise. Twenty seven patients with documented effort angina were included in the study. All subjects underwent stress technetium 99m sestamibi and ischemic scores were evaluated on the polar map image divided into 13 segments. Endothelin levels were measured at baseline and at peak exercise. In 13 patients with elevated endothelin-1 levels, there were 88 ischemic segments, 26 of which showed severe ischemia. In the remaining 14 patients with no endothelin-1 elevation, there were 80 ischemic segments of which only four showed severe ischemia. The amount of severe ischemic segments per patient was 2+/-2.2 in the elevated endothelin positive group and 0.28+/-0.6 in the endothelin negative (P< or =0.011). When looking at ischemia as detected by sestamibi SPECT as a gold standard, we found that of 331 segments, 168 were without ischemia, 143 had mild to moderate ischemia, and 30 has severe ischemia. Endothelin levels were 1.2+/-0.6, 2.2+/-0.5, 6.2+/-0.7 pg/l (P<0.01), respectively. Thus, endothelin-1 is a marker of severity of ischemia rather than ischemia itself, and as such, may have prognostic value.

Growing hepatic cavernous hemangioma demonstrated by Tc-99m red blood cell scintigraphy.

Hepatic cavernous hemangiomas rarely grow. Although a few cases have been reported in the literature, none used Tc-99m red blood cell scintigraphy. The authors describe such a case here.

Quantitative SPECT uptake of 99mTc-dimercaptosuccinic acid by the kidneys in children.

UNLABELLED: The normal range of values for quantitative SPECT of 99mTc-dimercaptosuccinic acid (DMSA) uptake by the kidneys in children was studied. METHODS: Renal functioning volume, percentage of injected dose per cubic centimeter of renal tissue (%ID/ cm3) and individual kidney uptake of 270 kidneys performed on 135 children, aged 2 wk-15 y, provided the basic data for this study. The accrual was part of the work-up of children with urinary tract infection where no structural or functional abnormalities of the renal tract could be established. Children were grouped according to age intervals, and a distribution chart was obtained with 2 SD above and below the mean of the values obtained for volume (%ID/cm3) and kidney uptake in each age group. RESULTS: A significant correlation was found between age and functional volume (r = 0.90; 95% confidence interval [CI], 0.88-0.92; P = 0.000), and a significant inverse correlation was found between age and %ID/cm3 (r = -0.86; 95% CI, -0.88 to -0.82; P = 0.000). No statistically significant correlation was found between age and kidney uptake (r = -0.20; 95% CI, -0.32 to -0.09; P = 0.001). CONCLUSION: It seems that the normal maturational changes in renal function observed in infants and newborns do not affect the kidney uptake of 99mTC-DMSA. Thus, quantitation of 99mTc-DMSA uptake by the kidneys can be used to assess changes in the individual renal function over time in this age group.

Lower extremity scintigraphy: the foot and ankle.

Disorders of the ankle and foot are common and may pose a significant clinical problem. Acute injuries of the ankle and foot are routinely evaluated by radiographs and, if inconclusive, by magnetic resonance imaging (MRI) or computed tomagraphy (CT). In subacute or chronic injuries, where prolonged pain is unexplained, bone scintigraphy may play a significant role. The bone scan may differentiate soft tissue from bone pathology, and, being a sensitive test, it may indicate the region that needs further specific radiologic examination. It may also indicate the clinical significance of a radiologic finding. Moreover, in some clinical settings bone scintigraphy can be specific in the diagnosis. Careful attention to the technique enhances the efficiency of bone scintigraphy and SPECT allows better investigation of the hindfoot. The importance of ankle and foot injuries in the orthopedic practice and the better understanding of subacute and chronic injuries in athletes and in the general population has led to an increased use of specific tests such as MRI, CT, and bone scintigraphy. With improved technique and instrumentation it is no longer sufficient to indicate a focal abnormality in the ankle or foot on bone scintigraphy. More precise information about perfusion, blood pool, and specific location of a lesion can be obtained by high resolution and tomographic images. The role of bone scintigraphy in the diagnosis of such disorders will be presented with a focus on subacute traumatic injuries and related disorders, as well as its role in systemic inflammatory disorders that often involve the ankle and foot.

Quantitative SPET 99Tcm-DMSA uptake by the kidneys: age-related decline in healthy males.

To evaluate if 99Tcm-dimercaptosuccinic acid (99Tcm-DMSA) uptake by the kidneys is related to age and creatinine clearance in males with normal renal function, quantitative single photon emission tomography (SPET) of DMSA uptake by the kidneys was performed in 18 volunteers aged 20-79 years. The quantitative uptake of DMSA in the right kidney was 13.9 +/- 2.9% and in the left kidney 14.2 +/- 3.0%. There was no statistically significant difference between left and right kidney uptake (t = 1.2, N.S.). Global kidney uptake (right + left) was 28.1 +/- 5.9%. There was a statistically significant age-related decline in global DMSA uptake. The estimated DMSA uptake (%) was given by -0.27 x age + 42 (r = -0.87, P < 0.001). A good correlation was found between creatinine clearance and global DMSA uptake (r = 0.87, y = 2.8x + 28.3, P < 0.001). The results suggest that normal values of DMSA uptake by the kidneys are age-dependent.

Ga-67 scintigraphy with a dual-head camera.

High quality images are necessary for correct interpretation of Ga-67 studies in lymphoma. The authors were interested if there is a significant change in the quality of the Ga-67 images using a newly introduced dual-head camera compared with a conventional single-head camera. The tomographic spatial resolution, full width at half maximum, was found to be 9.63 mm compared with 13.7 for a single-head camera. The volume sensitivity was 380 cps/microCi/ml per axial cm as compared with 333 cps/microCi/ml, and point source sensitivity was 5.6 cps/microCi compared with 3.8. There was a significant difference (P < 0.001), when using the threshold technique, in the number of counts per pixel over a wide range of volumes and concentrations in phantoms when the two cameras were compared. There was also a significant difference (P < 0.001) in Ga-67 uptake in lymphoma lesions in patients when the same parameters were used for both cameras when using SPECT. The average uptake in lymphoma lesions, using a dual-head camera, was 529 counts/pixel with a range of 112 to 1275 counts/pixel in different tumors. With a single-head camera, the average for the same tumor was 216 counts/pixel with a range of 59 to 469 counts/pixel. The high sensitivity of the dual-head camera enabled high-quality, whole body scintigraphy, including the limbs, in 20 minutes compared with the 35 minutes necessary for the single-head camera for images which did not include the legs. Whole body Ga-67 scintigraphy is shown to be important in patients with lymphoma of the upper and lower limbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative SPECT of technetium-99m-DMSA uptake in the kidneys of normal children and in kidneys with vesicoureteral reflux: detection of unilateral kidney disease.

UNLABELLED: Quantitative SPECT was used to evaluate renal functional volume (cc), percent of injected dose/cc (%ID/cc) and renal uptake (%) in 11 children with unilateral vesicoureteral reflux grade 3 or greater, and in 19 normal control children without reflux. METHODS: Studies were performed 4-6 hr after intravenous injection of 0.750-2 mCi of 99mTc-DMSA. RESULTS: Control kidneys (n = 38) had a volume of 99.7 +/- 29.5 cc. The %ID/cc was 0.27 +/- 0.08, and the uptake in one kidney was 24.8% +/- 3.9%. Global renal uptake (right plus left) was 49.6% +/- 7.3%. Functional volume of the control kidneys showed an increase with age, and the %ID/cc showed a steeper decrease with age, resulting in a trend of the kidney uptake to decrease with age. Kidneys with reflux had a decreased kidney uptake of 15.7% +/- 29.5%, compared to age- and sex-matched controls (t = 4.7, p < 0.001). The contralateral kidneys without reflux had a significantly increased total uptake of 33.4% +/- 6.8% as compared to controls (t = 3.44, p < 0.01). Global uptake by the kidneys was 49.2% +/- 8.6% and was not statistically different from controls (t = 1.0, ns). CONCLUSION: Our results suggest that SPECT quantitation of 99mTc-DMSA uptake in each kidney separately could be used as a noninvasive method to assess impairment and compensation of the function of the individual kidney in children with vesicoureteral reflux.

Early detection of lymphoma recurrence with gallium-67 scintigraphy.

Early detection of tumor relapse in lymphoma patients is often a difficult diagnostic problem. CT, which detects a mass, often cannot differentiate between fibrosis or relapsed tumor. For this reason, we have studied the value of 67Ga scintigraphy in the diagnosis of tumor recurrence. The sensitivity of 67Ga scintigraphy in the detection of lymphoma recurrence was studied at an average interval of 8.7 mo following treatment in 32 patients who developed recurrent lymphoma. Its specificity was studied in 36 patients with no recurrence who were in continuous clinical remission. At the time of appearance of relapse, the sensitivity of whole-body 67Ga imaging was 95% and the specificity 89%. In 12 events of recurrence in 10 patients, 67Ga scintigraphy was abnormal at sites that later proved to be regions of relapse. In these patients, scintigraphy demonstrated recurrence an average of 6.8 mo before the appearance of clinical symptoms, findings on clinical examination or abnormality on CT or chest x-rays. Gallium-67 scintigraphy, which permits screening of the whole body for recurrence in a single study, was of particular value in evaluating lymphoma recurrence, since 27% of the recurrences were located exclusively in sites different from the original sites of disease. Gallium-67 scintigraphy appears to be a sensitive and specific test for restaging patients with lymphoma recurrence.

Local and systemic effects of radiation on bone metabolism measured by quantitative SPECT.

Quantitative bone scintigraphy (QBS), which measures 99mTc-MDP uptake expressed as percent of injected dose per cc, indicates bone metabolism. It is measured in the bones of patients before and after radiation treatment and then compared to normal controls. QBS was performed in a group of 22 normal individuals and was measured twice, 2-10 mo (mean 4.9) apart. There was no significant difference between the two measurements. QBS was performed also in 28 patients before, immediately after and at certain time intervals after radiation therapy for cancer. Both the irradiated and the nonirradiated bones showed significant decreases in bone metabolism at 2-18 mo (mean 8.8) after irradiation. In addition, increases and decreases of 99mTc-MDP uptake were similar in the irradiated and in the nonirradiated bones, and there were significant correlations of the QBS values in the different bones of each individual patient. The etiology of the changes in bone metabolism in the nonirradiated bones is not yet fully understood, but it appears to be the result of a systemic effect of radiation.

Stress fractures associated with osteosarcoma of the lower limb.

Three patients with osteosarcoma of the femur developed abnormal radiopharmaceutical uptake in the bones of the contralateral leg. This uptake was not due to metastases. The histology in one patient, the form of the lesion and the disappearance of the abnormal uptake without treatment in the other two, indicated that the uptake was probably due to stress fractures. Changes in weight bearing and walking in the normal leg as a result of the osteosarcoma in the other leg could have been the cause of the stress fractures. It should be recognized that new abnormal uptake on bone scintigraphy in patients with osteosarcoma of the leg may not necessarily indicate metastasis. It may be caused by a stress fracture and disappears after rest.

Ga-67 uptake unsuppressed by leukopenia and intense antibiotic therapy.

The authors describe a patient with myelofibrosis who showed intense Ga-67 uptake in spite of being severely leukopenic and receiving large amounts of antibiotics. They conclude that false-negative results associated with leukopenia or intensive antibiotic treatment may not always be correct.