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.     

Antibodies to low-incidence antigens and elimination of the antihuman globulin phase of the crossmatch-case report: anti-Wra

An antibody to a low-incidence antigen was identified in the serum of a nontransfused male patient. The antibody was subsequently identified as anti-Wra and was only detectable at the antihuman globulin (AHG) phase of the crossmatch. Instances of severe hemolytic transfusion reactions have been reported following the transfusion of red blood cells containing low-incidence antigens in patients with antibodies directed toward these antigens (e.g., anti- Wra, -Cob, -Jsa, etc.). Elimination of the AHG phase of the crossmatch can result in either risks or benefits. Since patients seen at this facility primarily have been multitransfused or are multiparous females, the AHG phase of the crossmatch has been maintained.     

The dorsal spino-olivocerebellar system in the cat

Summary The spino-olivocerebellar paths ascending through the dorsal funiculi (DF-SOCPs) were studied by recording climbing fiber field potentials in the cerebellar cortex. Several DF-SOCPs were identified on the basis of their response latencies, peripheral inputs, and projection areas. The projection areas consist of eight sagittal zones on each side of the anterior lobe denoted a, x, b, C₁, c₂, c₃, d₁, and d₂. The a and b zones, which are activated exclusively from hindlimb nerves (Oscarsson, 1969a) were not studied.The shortest response latencies in the x, c₁, c₃ and d₂ zones indicate that these zones are activated by direct paths between the dorsal funiculus nuclei and the inferior olive. These zones also have long latency responses evoked through indirect paths. The direct paths are activated from the flexor reflex afferents and the indirect paths from distal cutaneous afferents. The x zone is activated from forelimb nerves only. The c₁ and c₃ zones and presumably also the d₂ zone are activated from hindlimb and forelimb nerves and have a detailed somatotopical organization.The c₂ and d₁ zones have long latency responses evoked through indirect paths. Both zones are activated from distal cutaneous afferents. The c₂ zone has no distinct somatotopical organization, whereas the d₁ zone has largely separate forelimb and hindlimb areas. In contrast to all other zones, the c₂ zone is activated not only from ipsilateral but also from contralateral nerves.     

Deletions of interferon genes in acute lymphoblastic leukemia

Structural rearrangements involving the short arm of chromosome 9, including bands 9p21 and 22, are found in the leukemia cells of 7 to 13 percent of patients with acute lymphoblastic leukemia. The interferon-alpha gene cluster and the interferon-beta 1 gene have been localized to this chromosomal region. We have previously demonstrated deletions of these genes in several cell lines established in vitro from patients with lymphoblastic leukemia. We report here homozygous or hemizygous deletions of the interferon-alpha and interferon-beta 1 genes in samples of leukemia cells from patients with lymphoblastic leukemia. Of 62 patients examined, 18 (29 percent) had such deletions. Four patients (7 percent) had homozygous deletions of the interferon-alpha gene cluster; of these, one also had a homozygous deletion and three had hemizygous deletions of the interferon-beta 1 gene. Fourteen patients (23 percent) had hemizygous deletions of both the interferon-alpha gene cluster and the interferon-beta 1 gene. In 8 of the 18 patients with deletions, the deletions of interferon genes were submicroscopic; in the 11 other patients, chromosomal rearrangements of 9p, including translocations or deletions, were visible on light microscopy. These chromosomal and molecular deletions are likely to be related to the loss of a tumor-suppressor gene (or genes) located on 9p, which may be an interferon gene or an unrelated but closely linked gene.     

Isolation of rhinoviruses and coronaviruses from 38 colds in adults

Nasal washings were collected from 27 normal adults during 38 naturally acquired colds. The washings were exhaustively tested using tissue cultures, organ cultures and electron microscopy. Washings yielding no identifiable agent were inoculated into human volunteers, and further specimens obtained from the latter were examined by the same techniques in vitro. Viruses were identified in association with 25 of the original 38 colds (65.7%). Fifteen were rhinoviruses (39.5%), seven coronaviruses (18.4%), two were para-influenza viruses, and one was influenza virus. Use of organ cultures and of volunteers significantly increased the isolation rate. No agent was cultivated from the remaining 13 specimens, although tests in volunteers showed that cold-producing agents were present in five of them (13%). Three specimens gave doubtful results in volunteers, and five others, all collected within a period of six weeks in December and January, apparently contained no infectious agent.     

Performance status and comorbidity predict transplant-related mortality after allogeneic hematopoietic cell transplantation.

Comorbidity measurements have recently been used to improve estimation of tolerance to allogeneic hematopoietic cell transplantation (HCT). We sought to determine the independent effect of comorbidity and performance status on HCT outcome and to devise a simple risk classification system for transplant-related mortality. We analyzed 105 consecutively enrolled patients who underwent HCT and received reduced intensity conditioning with fludarabine, melphalan, and alemtuzumab. Comorbid conditions were tabulated using 2 scales, the Charlson Comorbidity Index (CCI) and the Kaplan-Feinstein Scale (KFS). Comorbid conditions were found in 47% of patients by the KFS and in 27% by the CCI (P < .001). Using the Eastern Cooperative Oncology Group Performance Status (PS) scale, 34% had a PS score >0 (range, 0-2). A simple scale combining the KFS and PS enabled separation of high- from low-risk patients, with 6-month cumulative incidences 50% and 15%, respectively for transplant-related mortality (P = .001) and enhanced prognostic power over the CCI alone (P = .018). Prospective studies evaluating more comprehensive functional and comorbidity measurements are warranted.     

Evaluation of an extended blood culture protocol to isolate fastidious organisms from patients with AIDS.

Recent reports of fastidious pathogens suggest the need for special blood cultures for immunocompromised patients. Blood cultures from 45 human immunodeficiency virus (HIV)-infected patients with unexplained fever (> or = 38.0 degrees C) and CD4 counts of < 125 cells per mm3 were collected into a vacuum tube with sodium polyanetholsulfonate, an Isolator tube, and BACTEC aerobic and anaerobic bottles. Blood from the sodium polyanethosulfonate tube was inoculated into BACTEC 13A bottles, which were read weekly for 16 weeks. Isolator sediment was divided among eight agar media, including four sheep blood agar media: chocolate agar, brain heart infusion blood agar, heart infusion blood agar, and brucella blood agar. Other agar plates included Sabouraud's, buffered charcoal-yeast extract, Middlebrook 7H11 (M7H11) with hemoglobin, and M7H11 with mycobactin J. Incubation conditions included air and CO2-enriched aerobic, microaerophilic, and anaerobic atmospheres. Aerobic BACTEC broths received an acridine orange stain on day 8 and were subcultured at 2, 4, and 8 weeks. Anaerobic BACTEC bottles were subcultured at 4 weeks. All solid media, including subcultures, were incubated for 8 weeks, providing a total of 16 weeks of incubation for each specimen. Clinically significant isolates included eight Mycobacterium avium complex isolates and one each of Bartonella henselae, Bartonella quintana, Shigella flexneri, Klebsiella oxytoca, and Cryptococcus neoformans. All isolates were detected with commercially available media and, with the exception of Bartonella spp., were recovered within incubation times routinely used in most clinical laboratories.     

Eosinophil traffic in the circulation following allergen challenge

BACKGROUND: Eosinophils contribute to the pathogenesis of asthma and localize to the lung after allergen exposure by uncertain mechanisms. METHODS: We used intrabronchial instillation of allergen to model the interaction between inhaled allergen and the lung. We measured the number of peripheral blood leukocytes and the expression of VLA-4 (CD49d), Mac-1 (CD11b) and PSGL-1 (CD162) up to 4 h after instillation of allergen into a bronchus of eight atopic asthmatics. For controls, we instilled normal saline into a subset of the asthmatic subjects, and allergen into nonatopic, nonasthmatic subjects. RESULTS: There were changes of total leukocyte number, number of polymorphonuclear leukocytes, lymphocytes, monocytes and eosinophils in all three groups (atopic asthmatics instilled with allergen, atopic asthmatics instilled with saline, nonatopic nonasthmatic subjects instilled with allergen), which were likely related to bronchoscopy. However, the decrease of eosinophils was significant only in the atopic asthmatics instilled with allergen. The remaining eosinophils in the allergen challenged asthmatics were not activated as defined by cell density or change of expression of VLA-4, Mac-1 and PSGL-1. CONCLUSIONS: While eosinophils rapidly and specifically leave the circulation after allergen challenge of atopic asthmatics, the remaining circulating eosinophils are not activated.     

Spatial summation of heat-induced pain: influence of stimulus area and spatial separation of stimuli on perceived pain sensation intensity and unpleasantness

1. Psychophysical experiments were initiated to determine the possible influence of increasing stimulus size on perceived pain intensity. Six trained human subjects (5 male, 1 female) made visual analogue scale (VAS) ratings for pain-sensation intensity and unpleasantness in response to nociceptive thermal stimuli. Test stimuli consisted of 5-s duration heat pulses (45-50 degrees C in 1 degrees increments) delivered by one, two, or three contact thermal probes (1 cm2 each) applied to the medial aspect of the anterior forearm. 2. The area of skin receiving noxious thermal stimuli was changed by randomly varying the number of thermodes activated. The effects of varying the distance between the thermal probes also were evaluated. In the first series of experiments, thermal-probe separation was kept close to 0; in subsequent experimental series, the thermodes were separated by either 5 or 10 cm. 3. In each experimental series, considerable spatial summation occurred in both pain-sensation intensity and unpleasantness dimensions of pain. This summation occurred throughout the nociceptive thermal range of 45-50 degrees C and was larger at suprathreshold temperatures (greater than or equal to 47 degrees C) than those near threshold (less than or equal to 46 degrees C). Unlike spatial summation of perceived warmth, that of pain was not characterized by systematic changes in power-function exponents but as approximately upward parallel displacements in double-logarithmic coordinates. 4. Thermal-probe separation over a range of 0-10 cm had no effects on spatial summation of pain-sensation intensity or pain unpleasantness. In contrast, increasing thermal-probe separation increased the subjects' ability to discriminate differences in stimulus size and their ability to detect correctly the number of thermal probes activated. 5. Because affective VAS ratings of unpleasantness were linearly related to, but distinctly and systematically less than, VAS ratings of pain-sensation intensity, it was clear that subjects responded quite differently to these two pain dimensions. Affective judgements were not additionally influenced by thermal probe separation and hence by the ability to perceive stimulus size or number of thermal probes activated. 6. The results indicate that powerful spatial-summation mechanisms exist for heat-induced pain. Spatial summation of pain is likely to be subserved both by local integration mechanisms at the level of single spinothalamic-tract neurons and by recruitment of central nociceptive neurons, because spatial summation of pain occurred to approximately equal extents under conditions of thermode separations over a distance of at least 20 cm.     

Promotion of retroviral entry in the absence of envelope protein by chlorpromazine

Retrovirus packaging cell lines that express the Moloney murine leukemia virus gag, pol, and env genes and a retroviral vector genome can produce virus particles that are capable of transducing cells. Normally if the packaging cell line does not produce a functional viral fusion glycoprotein, such as the retroviral envelope protein or a foreign viral glycoprotein, then the viruses will be incapable of transducing cells. We have found that incubating envelope protein-deficient virus particles bound to cells with chlorpromazine leads to transduction. Chlorpromazine (CPZ) is a membrane-active reagent that is commonly used to induce the hemifusion to fusion transition when membrane fusion is mediated by partially defective viral glycoproteins. The concentration and pH dependence of the promotion of transduction by CPZ is consistent with a role for CPZ micelle formation in viral entry. These data indicate that caution is warranted when experiments concerning membrane fusion completion promoted by CPZ are analyzed.