Using PCR for early diagnosis of bovine leukemia virus infection in some native cattle.

Bovine leukemia virus (BLV), the causative agent of enzootic bovine leukosis, is an exogenous, B lymphotropic retrovirus belonging to the Retroviridae family that induces persistent lymphocytosis in cattle and sheep. PCR has proven to be particularly suitable for investigating herds of cattle with a very low incidence of BLV infection and for clarifying doubtful serological results obtained by immunodiffusion or ELISA. The native Iranian and Russian cattle have a series of valuable traits that discriminate them as unique breeds that are well able to compete with western analogues. However, their gene pools have not been analyzed with molecular markers, including detection of BLV by PCR. Two pairs of primers were used: gag1 and gag2, and pol1 and pol2, which encompass 347- and 599-bp fragments of the BLV gene, respectively. Sixty-five Iranian Sistani, 120 Yaroslavl, 50 Mongolian, and 35 Black Pied cows were investigated. Among these 270 animals, we obtained 42 positive and 15 doubtful results in the first PCR. The second PCR was very effective in increasing BLV test reliability data to support detection of BLV.

Exon-1 polymorphism of ctla-4 gene in Iranian patients with Graves' disease.

Polymorphisms in ctla-4 gene have been shown to be associated with the Graves' disease (GD) susceptibility in different populations in the world. This study was undertaken to disclose the probable association of exon-1 polymorphism of ctla-4 with GD in Iranian patients. A49G polymorphism was investigated in 90 patients and 90 age/sex matched normal healthy controls, using PCR-SSCP and PCR-RFLP methods. Frequencies of AA, AG and GG genotypes among patients were found to be 21 (23.3%), 49 (54.5%) and 20 (22.2%) while these frequencies among healthy controls were 30 (33.3%), 53 (58.9%) and 7(7.8%), respectively. A significant increase of GG genotype and G allele was observed in patients (p = 0.012 and p = 0.025). In conclusion, consistent with the results of most other studies, the presence of a G allele in position 49 of ctla-4 exon-1 is associated with susceptibility to GD in Iranian population.

Thoracoscopic implantation of cancer with a fatal outcome.

A case is presented in which an indeterminate lung lesion was extracted through an accessory incision during a video-assisted thoracic surgical lung biopsy. The lesion was malignant, and a completion lobectomy was performed. An incisional recurrence developed 5 months later, and this was treated with a wide chest wall resection and reconstruction. However, there was a second massive chest wall recurrence that proved fatal. We believe that tumor seeding to the chest wall occurred at thoracoscopy. To prevent such tumor seeding, thoracoscopic biopsy specimens should be removed in some sort of receptacle when cancer is suspected.

A case of therapy-related extramedullary acute promyelocytic leukemia.

We report a patient with extramedullary acute promyelocytic leukemia (APL) occurring after radiation therapy for carcinoma of the prostate. To the authors' knowledge, this patient represents the first case of cytogenetically and fluorescence in situ hybridization (FISH) confirmed therapy-related extramedullary APL. In contrast to the majority of previously reported t-APL, this case underwent a very unfavorable course.

Breathing-synchronized radiotherapy program at the University of California Davis Cancer Center.

In this paper we present a complete description of the breathing synchronized radiotherapy (BSRT) system, which has been jointly developed between the University of California Davis Cancer Center and Varian Associates. BSRT is a description of an emerging radiation oncology procedure, where simulation, CT scan, treatment planning, and radiation treatment are synchronized with voluntary breath-hold, forced breath-hold, or breathing gating. The BSRT system consists of a breathing monitoring system (BMOS) and a linear accelerator gating hardware and software package. Two methods, a video camera-based method and the use of wraparound inductive plethysmography (RespiTrace), generate the BMOS signals. The BMOS signals and the synchronized fluoroscopic images are simultaneously recorded in the simulation room and are later analyzed to define the ideal treatment point (ITP) where organ motion is stationary. The BMOS signals at ITP can be used to gate a CT scanner or a linear accelerator to maintain the same organ configuration as in the simulation. The BSRT system allows breath-hold or gating. This dual role allows the system to be applicable for a variety of patients, i.e., the breath-hold method for those patients who can maintain and reproduce the ITP, and the forced breath-hold or gating method for those who are not ideal for voluntary breath-hold.

Quantifying the predictability of diaphragm motion during respiration with a noninvasive external marker.

The aim of this work was to quantify the ability to predict intrafraction diaphragm motion from an external respiration signal during a course of radiotherapy. The data obtained included diaphragm motion traces from 63 fluoroscopic lung procedures for 5 patients, acquired simultaneously with respiratory motion signals (an infrared camera-based system was used to track abdominal wall motion). During these sessions, the patients were asked to breathe either (i) without instruction, (ii) with audio prompting, or (iii) using visual feedback. A statistical general linear model was formulated to describe the relationship between the respiration signal and diaphragm motion over all sessions and for all breathing training types. The model parameters derived from the first session for each patient were then used to predict the diaphragm motion for subsequent sessions based on the respiration signal. Quantification of the difference between the predicted and actual motion during each session determined our ability to predict diaphragm motion during a course of radiotherapy. This measure of diaphragm motion was also used to estimate clinical target volume (CTV) to planning target volume (PTV) margins for conventional, gated, and proposed four-dimensional (4D) radiotherapy. Results from statistical analysis indicated a strong linear relationship between the respiration signal and diaphragm motion (p<0.001) over all sessions, irrespective of session number (p=0.98) and breathing training type (p=0.19). Using model parameters obtained from the first session, diaphragm motion was predicted in subsequent sessions to within 0.1 cm (1 sigma) for gated and 4D radiotherapy. Assuming a 0.4 cm setup error, superior-inferior CTV-PTV margins of 1.1 cm for conventional radiotherapy could be reduced to 0.8 cm for gated and 4D radiotherapy. The diaphragm motion is strongly correlated with the respiration signal obtained from the abdominal wall. This correlation can be used to predict diaphragm motion, based on the respiration signal, to within 0.1 cm (1 sigma) over a course of radiotherapy.

Four-dimensional (4D) PET/CT imaging of the thorax.

We have reported in our previous studies on the methodology, and feasibility of 4D-PET (Gated PET) acquisition, to reduce respiratory motion artifact in PET imaging of the thorax. In this study, we expand our investigation to address the problem of respiration motion in PET/CT imaging. The respiratory motion of four lung cancer patients were monitored by tracking external markers placed on the thorax. A 4D-CT acquisition was performed using a "step-and-shoot" technique, in which computed tomography (CT) projection data were acquired over a complete respiratory cycle at each couch position. The period of each CT acquisition segment was time stamped with an "x-ray ON" signal, which was recorded by the tracking system. 4D-CT data were then sorted into 10 groups, according to their corresponding phase of the breathing cycle. 4D-PET data were acquired in the gated mode, where each breathing cycle was divided into ten 0.5 s bins. For both CT and PET acquisitions, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to respiratory phase. The effect of 4D acquisition on improving the co-registration of PET and CT images, reducing motion smearing, and consequently increase the quantitation of the SUV, were investigated. Also, quantitation of the tumor motions in PET, and CT, were studied and compared. 4D-PET with matching phase 4D-CTAC showed an improved accuracy in PET-CT image co-registration of up to 41%, compared to measurements from 4D-PET with clinical-CTAC. Gating PET data in correlation with respiratory motion reduced motion-induced smearing, thereby decreasing the observed tumor volume, by as much as 43%. 4D-PET lesions volumes showed a maximum deviation of 19% between clinical CT and phase- matched 4D-CT attenuation corrected PET images. In CT, 4D acquisition resulted in increasing the tumor volume in two patients by up to 79%, and decreasing it in the other two by up to 35%. Consequently, these corrections have yielded an increase in the measured SUV by up to 16% over the clinical measured SUV, and 36% over SUV's measured in 4D-PET with clinical-CT Attenuation Correction (CTAC) SUV's. Quantitation of the maximum tumor motion amplitude, using 4D-PET and 4D-CT, showed up to 30% discrepancy between the two modalities. We have shown that 4D PET/CT is clinically a feasible method, to correct for respiratory motion artifacts in PET/CT imaging of the thorax. 4D PET/CT acquisition can reduce smearing, improve the accuracy in PET-CT co-registration, and increase the measured SUV. This should result in an improved tumor assessment for patients with lung malignancies.

Quantitation of respiratory motion during 4D-PET/CT acquisition.

We report on the variability of the respiratory motion during 4D-PET/CT acquisition. The respiratory motion for five lung cancer patients was monitored by tracking external markers placed on the abdomen. CT data were acquired over an entire respiratory cycle at each couch position. The x-ray tube status was recorded by the tracking system, for retrospective sorting of the CT data as a function of respiration phase. Each respiratory cycle was sampled in ten equal bins. 4D-PET data were acquired in gated mode, where each breathing cycle was divided into ten 500 ms bins. For both CT and PET acquisition, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to their respiratory phases. The respiratory periods, and average amplitude within each phase bin, acquired in both modality sessions were then analyzed. The average respiratory motion period during 4D-CT was within 18% from that in the 4D-PET sessions. This would reflect up to 1.8% fluctuation in the duration of each 4D-CT bin. This small uncertainty enabled good correlation between CT and PET data, on a phase-to-phase basis. Comparison of the average-amplitude within the respiration trace, between 4D-CT and 4D- PET, on a bin-by-bin basis show a maximum deviation of approximately 15%. This study has proved the feasibility of performing 4D-PET/CT acquisition. Respiratory motion was in most cases consistent between PET and CT sessions, thereby improving both the attenuation correction of PET images, and co-registration of PET and CT images. On the other hand, in two patients, there was an increased partial irregularity in their breathing motion, which would prevent accurately correlating the corresponding PET and CT images.

Granulocytic sarcoma of the spine.

OBJECTIVE: Granulocytic sarcomas (chloromas) are tumors consisting of primitive myeloid cells. They are rare manifestations of acute and chronic leukemias and can occasionally precede the development of systemic disease by weeks to years. Spinal complications of chloromas, such as cord compression secondary to epidural tumor or cauda equina syndrome, have been described but are uncommon. METHODS: We present eight new cases of spinal chloroma. Three patients displayed significant motor deficit in the form of paraparesis or paraplegia. All patients complained of lower back pain, with other complaints including generalized pain, abdominal pain, numbness and pain in the lower extremities and perianal region, and poor appetite. The average age of the patients was 37 years. Treatment strategies included surgery, chemotherapy, and radiotherapy. Three patients underwent surgical decompression. Six patients received chemotherapy, and six patients received radiotherapy at doses of 2000 to 3000 cGy in up to 30 fractions. RESULTS: Patient survival ranged from 18 days to 9.5 years after diagnosis. A review of the previously reported cases of granulocytic sarcoma in addition to our new cases reveals that the most effective treatment is multimodality therapy coupled with early diagnosis. CONCLUSION: Increased awareness of this entity will facilitate early diagnosis and minimize potentially preventable neurological morbidity.

Acquiring a four-dimensional computed tomography dataset using an external respiratory signal.

Four-dimensional (4D) methods strive to achieve highly conformal radiotherapy, particularly for lung and breast tumours, in the presence of respiratory-induced motion of tumours and normal tissues. Four-dimensional radiotherapy accounts for respiratory motion during imaging, planning and radiation delivery, and requires a 4D CT image in which the internal anatomy motion as a function of the respiratory cycle can be quantified. The aims of our research were (a) to develop a method to acquire 4D CT images from a spiral CT scan using an external respiratory signal and (b) to examine the potential utility of 4D CT imaging. A commercially available respiratory motion monitoring system provided an 'external' tracking signal of the patient's breathing. Simultaneous recording of a TTL 'X-Ray ON' signal from the CT scanner indicated the start time of CT image acquisition, thus facilitating time stamping of all subsequent images. An over-sampled spiral CT scan was acquired using a pitch of 0.5 and scanner rotation time of 1.5 s. Each image from such a scan was sorted into an image bin that corresponded with the phase of the respiratory cycle in which the image was acquired. The complete set of such image bins accumulated over a respiratory cycle constitutes a 4D CT dataset. Four-dimensional CT datasets of a mechanical oscillator phantom and a patient undergoing lung radiotherapy were acquired. Motion artefacts were significantly reduced in the images in the 4D CT dataset compared to the three-dimensional (3D) images, for which respiratory motion was not accounted. Accounting for respiratory motion using 4D CT imaging is feasible and yields images with less distortion than 3D images. 4D images also contain respiratory motion information not available in a 3D CT image.

Management of type II dens fractures: a case-control study.

STUDY DESIGN: A case-control study of patients with isolated type II dens fractures treated with halo vest immobilization. OBJECTIVES: To evaluate age as a risk factor for failure of halo immobilization in patients with type II dens fractures. SUMMARY OF BACKGROUND DATA: The literature reports an average fusion rate of approximately 70% in patients with type II dens fractures treated by halo vest immobilization. Although many investigators have examined patient age as a risk factor for nonfusion using halo immobilization, all studies have been supported only by Class III data. These studies, consequently, carry little or no statistical significance. Therefore, a case-control study based on Class II data was designed to evaluate age as a risk factor for failure of halo vest immobilization in patients with type II dens fractures. METHODS: Thirty-three patients with isolated type II dens fractures treated with halo vest immobilization at the University of Iowa Hospitals and clinics between 1983 and 1997 were included. Type II fractures were defined with plain radiography as per the Anderson-D'Alonzo classification. Cases were defined as nonfusions after halo immobilization, whereas control subjects represented successful bony unions attained with halo immobilization. RESULTS: When the case and control groups were compared, there was no significant difference between the groups in the presence of concomitant medical conditions, sex, the amount of fracture displacement, the direction of fracture displacement, the length of hospital stay, or length of follow-up. Age more than 50 years was found to be a highly significant risk factor for failure of halo immobilization (P = 0.002; Fisher's exact test, two-tailed). The odds ratio of these data indicate that the risk of failure of halo immobilization is 21 times higher in patients aged 50 years or more. CONCLUSIONS: Surgical intervention should be considered in those patients aged 50 years or more who have a type II dens fracture, if it can be accomplished with acceptable risk of morbidity and death.

A comparative analysis of three methods of contraception: Effects on blood glucose and serum lipid profiles.

BACKGROUND: Hormonal contraceptives are one of the major means of family planning, yet their use is not without side effects. In this study, we have tried to assess some of the metabolic effects of three hormonal contraceptives commonly used by young females. PATIENTS AND METHODS: Three hundred young, healthy, nonsmoking and normotensive women of childbearing age who were seeking contraceptive advice were randomly allocated to one of the three groups receiving ethinyl estradiol and norgestrel (group 1), medroxyprogesterone acetate (group 2), and levonorgestrel capsules (group 3). Levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were measured prior to the initiation of therapy and after termination of the study (6 months). RESULTS: There was no significant difference between the three groups as far as the mean age, height and weight were concerned. FBG increased in all three groups, but the difference in the rate of increase was not statistically significant (P=0.29). Total cholesterol, TG and LDL-C increased, while HDL-C level decreased in groups 1 and 2. These changes were, however, more profound in the group 2 cases. In those receiving levonorgestrel, all lipid parameters decreased. The amount of change for the total cholesterol and triglyceride was quite significant (P<0.001), while the reduction in HDL-C was not significantly different from the other two groups by pairwise comparisons (Tukey-HSD procedure). The LDL-C/HDL-C ratio was found to be significantly increased in groups 1 and 2, but it remained almost unchanged in the group 3 cases (P<0.001). CONCLUSION: Because of these favorable biochemical findings, we believe that levonorgestrel should be the contraceptive drug of choice for women of childbearing age who are seeking a safe method of contraception.

Detection and localization of radiotherapy targets by template matching.

Radio opaque fiducials are implanted in tumors for the purpose of tracking the target motion using X-ray projections during radiation therapy dose delivery. In this paper we describe and evaluate a novel method based on template matching for detection and localization of arbitrary shaped fiducials. Segmentation methods are not adequate for these fiducials because their appearance in online X-ray projections can vary greatly as a function of imaging angle. The algorithm is based on using the planning CT image to generate templates that correspond to the imaging angles of the online images. We demonstrate successful tracking of complex shape fiducials in clinical images of lung and abdomen. We also validate the algorithm by comparing the results with a segmentation approach for one case in which the fiducials could be tracked by both methods. We also show how by adaptive thresholding of the match scores, we can control the false detection rate.

Comparison of respiratory surrogates for gated lung radiotherapy without internal fiducials.

An investigation was carried out to compare the ability of two respiratory surrogates to mimic actual lung tumor motion during audio coaching. The investigation employed video clips acquired after patients had had fiducial markers implanted in lung tumors to be used for image-guided stereoscopic radiotherapy. The positions of the markers in the clips were measured within the video frames and used as the standard for tumor volume motion. An external marker was tracked optically during the fluoroscopic acquisitions. An image correlation technique was developed to compute a gating signal from the fluoroscopic images. The correlation gating trace was similar to the optical gating trace in the phase regions of the respiratory cycle used for gating. A cross correlation analysis and comparison of the external optical marker gating with internal fluoroscopic gating was performed. The fluoroscopic image correlation surrogate was found to be superior to the external optical surrogate in the AP-views in four out of six cases. In one of the remaining two cases, the two surrogates performed comparably, while in the last case, the external fiducial trace performed best. It was concluded that fluoroscopic gating based on correlation of native image features in the fluoroscopic images will be adequate for respiratory gating.

Crossed pin fixation of displaced supracondylar humerus fractures in children.

The results of 42 children with displaced supracondylar fractures of the humerus (six Gartland Type II and 36 Gartland Type III) treated with crossed pin fixation are reported. In 37 fractures (88%) the teardrop configuration was restored successfully. All fractures healed without loss of reduction. No patients had iatrogenic ulnar nerve injury. Crossed-pin fixation of supracondylar humeral fractures is a safe and effective way of maintaining skeletal stability in children. Careful technique safeguards against ulnar nerve injury.

A comparative randomized and placebo-controlled short-term trial of aspirin and dipyridamole for overt type-2 diabetic nephropathy.

OBJECTIVE: Our aim was to determine the effect of short-term therapy with anti-platelet drugs on type-2 diabetic nephropathy for which a generally accepted therapy is missing. MATERIAL AND METHODS: Seventy-six patients with type-2 diabetic nephropathy, who had normal renal function tests were randomized into the 4 groups; each group (n = 19) received one of the following treatments: aspirin (1000 mg), dipyridamole (750 mg), their combination or placebo daily for 2 months. Blood pressure, fasting blood sugar, serum electrolytes, creatinine clearance and 24 hours urine protein excretion rate was measured just before and at the end of the trial. RESULTS: Proteinuria and urinary protein: creatinine ratio decreased significantly in all 3 groups receiving aspirin and/or dipyridamole compared with the placebo group, also in each of those 3 groups comparing pre- and post-treatment values, while creatinine clearance rate, blood pressure, and blood sugar remained unchanged. At the end of the trial, the percentage proteinuria change was-15.9%,-14.8%,-37.3% and 1.9% in aspirin, dipyridamole, their combination and placebo groups respectively. The percentage proteinuria change had no positive correlation with demographic, clinical and laboratory findings but showed a strong positive correlation with mode of the therapy (r = 0.38, p = 0.0007). The percentage decline in proteinuria was significantly higher in the combination group than in the aspirin and dipyridamole groups. No side effects related to aspirin or dipyridamole was seen during the trial. CONCLUSIONS: Short-term trial of aspirin and/or dipyridamole significantly reduces proteinuria of type-2 diabetic nephropathy, with the most prominent effect seen with combination of the 2 drugs.

Radiologic evaluation of the pelvis.

Careful radiographic assessment is essential in the diagnosis of pelvic fractures. The standard radiographic assessment of the pelvis includes the anteroposterior, inlet, outlet, Judet views, and axial computed tomography images. The different radiographic projections of the pelvis and their corresponding anatomic landmarks and the anatomy of the pelvis and the different anterior and posterior pelvic lesions are discussed. Description of the proper views and their uses are included.

Open fractures of the humerus treated with external fixation.

Twenty-three patients with open fractures of the humerus who had been treated with immediate external fixation were reviewed retrospectively. Eighteen patients had adequate followup and were included in this study. Four patients (22%) had Gustilo and Anderson Grade I injury; 1 (5%), Grade II; and 13 (72%), Grade III (1 IIIA, 2 IIIB, and 10 IIIC). Fourteen patients (78%) had associated neurologic injury, of which 9 involved multiple nerves. A unilateral external fixation frame with half pins proximal and distal to the fracture site was used in all but 1 case. In 8 patients (44%) with distal humerus fractures, the external fixator crossed the elbow joint. All upper extremities in this series were salvaged. The duration of external fixation averaged 11 weeks. Complications included 3 malunions, 1 delayed union, 8 (44%) pin tract infections, 2 pin tract sequestrum formation, and 2 late fractures after removal of the external fixator. At followup (average, 34 months), function was rated as good or excellent in 12 patients (70%). There were 1 fair and 4 poor results. External fixation of complicated fractures of the humerus allowed associated injuries to the nerves, arteries, and soft tissues to be treated adequately while maintaining skeletal stability.

Synthesis of phospho-urodilatin by combination of global phosphorylation with the segment coupling approach.

The chemical synthesis of biologically active phosphorylated urodilatin (CDD/ANP-95-126) was achieved by using a strategy of coupling protected peptide segments in solution. Three protected peptide segments corresponding to urodilatin (1-14) with side chain-unprotected Ser10, (15-24) and (25-32) were prepared manually using Fmoc chemistry on an aminopropyl polystyrene resin with the super acid-labile HMPB linker. For the coupling of segments, the carboxy group of the C-terminal segment (25-32) was converted into the tert-butyl ester by treatment with TBTA. The protected peptide segments were coupled in the presence of EDC/HOOBt or TBTU/HOBt to yield fully protected urodilatin with a free hydroxy function at Ser10. Introduction of the phosphate was performed with Et2NP(OtBu)2 and tetrazole followed by oxidation of the phosphite. Alternatively, a prephosphorylated protected segment (1-14) was used in the segment condensation. Our investigations indicate that both pathways, phosphorylation of protected urodilatin in solution and use of a prephosphorylated building block, are suitable methods to obtain a large phosphopeptide of high purity without formation of H-phosphonates or other by-products.