Detection of jeopardized myocardium with Tl-201 myocardial perfusion imaging. Comparison of early and late reinjection protocols

Reinjection of a second dose of Tl-201 before redistribution imaging has significantly improved the ability of myocardial perfusion imaging to detect jeopardized myocardium. However, PET studies and the results from coronary artery angioplasty and bypass surgery indicate that Tl-201 studies still underestimate the number of ischemic areas at stress that represent viable myocardium. To determine whether an imaging protocol using an early reinjection of Tl-201 immediately after acquisition of the stress images would improve the detection of jeopardized myocardium, 138 patients were studied with an early reinjection protocol and the incidence and magnitude of reversible defects were compared by SPECT to a second group of 143 patients who underwent the standard late reinjection protocol. Two observers independently evaluated 19 standard myocardial segments by visual examination in each patient. They determined the presence or absence of reversible defects, and, when present, their magnitude. The frequency of reversible defects always was less with early reinjection compared to the standard late reinjection; the difference reached statistical significance for one of the two observers (P < 0.05). It is concluded that early reinjection of Tl-201 in myocardial perfusion imaging does not increase and may decrease the sensitivity of the study for jeopardized myocardium.     

The snRNP core protein SmB and tissue-specific SmN protein are differentially distributed between snRNP particles

The SmN protein is a tissue specific component of the small nuclear ribonucleoprotein particle which is closely related to the ubiquitously expressed SmB protein but is expressed only in the brain and heart. To investigate the function of SmN, its localisation within different snRNP particles was investigated using a range of anti-snRNP monoclonal antibodies. SmN and SmB were found to exhibit different patterns of association with snRNP particles in two cell lines, ND7 and F9 which express SmN. In both cases, SmN was found to be present in the U-2 snRNP but was excluded from the U-1 snRNPs whereas SmB was present in both U-1 and U-2 snRNPs. Data from transfected 3T3 mouse fibroblasts cell lines artificially expressing a low level of SmN also confirm this observation. In contrast, SmN was found to be an integral component of both the U-1 and U-2 snRNPs in both 3T3 cells artificially expressing high levels of SmN and in adult rat brain which has a naturally high level of SmN expression. Taken together, the results suggest that the pre-U1 snRNP particle has a lower affinity for SmN than for SmB. Thus, SmN expressed at low levels incorporates into U2, but SmN expressed at high levels incorporates into both U1 and U2 snRNPs and replaces SmB. The significance of these effects is discussed in terms of the potential role played by SmN in constitutive and alternative splicing pathways in neuronal cells.     

The effect of femoral component position on the kinematics of total knee arthroplasty

In a laboratory study using seven fresh-frozen anatomic specimen knees, the effect of total knee arthroplasty on the three-dimensional kinematics of the patella, femur, and tibia were measured. Experiments were performed in the intact knee, after division of the anterior cruciate ligament (ACL), after total knee arthroplasty, and after 10 degrees internal rotation, 10 degrees external rotation, 5-mm medial shift, and 5-mm lateral shift of the femoral component on the femur. The presence of a high lateral ridge on the anterior surface of the femoral component effectively prevented patellar subluxation or dislocation, but displaced and tilted the patella medially. Internal rotation or medial displacement of the femoral component exaggerated this medial patellar displacement and shift. External rotation of the femoral component corrected it, except at flexion angles greater than 100 degrees, where the femur was shifted medially on the tibia and externally rotated 15 degrees. This combination produced a net 10-mm medial displacement of the patella relative to the tibia at 120 degrees knee flexion. Lateral placement of the femoral component compensated for the effect of the high lateral ridge and allowed more normal patellar tracking while allowing tibiofemoral motions similar to those seen after sectioning of the ACL. The kinematics of the patellofemoral and tibiofemoral joints were not reproduced with a total knee prosthesis that sacrifices the ACL. When using a prosthesis with a high lateral ridge, lateral placement of a femoral component prevented patellar dislocation and allowed patellar tracking patterns similar to those seen in the intact knee without further altering tibiofemoral motions.     

Competition between gas exchange and speech production in ventilated subjects

Competition between airflow requirements for speaking and gas exchange occurs in ventilator-dependent tracheotomized subjects who can 'steal' air from alveolar ventilation during the ventilator's inflation phase to produce sound. We wondered whether these subjects adopted strategies to minimize hypoventilation when speaking, particularly when ventilatory drive and respiratory discomfort are increased by hypercapnia. We recorded speech and ventilatory and speaking volumes in five ventilated subjects during reading and extemporaneous speech. All subjects spoke during the ventilator's inflation (and expiratory) phase, losing approximately 15% of their inspired tidal volume. During induced hypercapnia (15 mmHg increase in PetCO2) which caused shortness of breath, all subjects could still speak adequately. Two subjects 'adapted' to hypercapnia by reducing the air used for speaking during inflation. In contrast, one subject reacted, as normal subjects do, by increasing the airflow per syllable (a mal-adaptive strategy in ventilated subjects). These changes were modest despite the strong hypercapnic stimulus.     

A new view of pulmonary edema and acute respiratory distress syndrome

The old division of lung edema into two categories--cardiogenic (hydrostatic) and noncardiogenic (increased permeability)--is no longer adequate. For instance, it fails to distinguish between the capillary leak caused by acute respiratory distress syndrome from that caused by interleukin-2 treatment. Further, it fails to account for the capillary leak ('stress-failure') that may accompany edema. A modern view of edema must recognize the natural barriers to the formation and spread of edema. These barriers are the capillary endothelium and the alveolar epithelium. Varying degrees of damage to them can account for the varying radiographic and clinical manifestations of lung edema. Thus, interleukin-2 administration causes increased endothelial permeability without causing alveolar epithelial damage. The result is lung edema that is largely confined to the interstitium, causing little hypoxia and clearing rapidly. However, acute respiratory distress syndrome, which is characterized by extensive alveolar damage, causes air-space consolidation, severe hypoxia, and slow resolution. Thus, a reasonable classification of lung edema requires at least four categories: 1) hydrostatic edema; 2) acute respiratory distress syndrome (permeability edema caused by diffuse alveolar damage); 3) permeability edema without alveolar damage; and (4) mixed hydrostatic and permeability edema. The authors emphasize the importance of the barriers provided by the capillary endothelium and the alveolar epithelium in determining the clinical and radiographic manifestations of edema. In general, when the alveolar epithelium is intact, the radiographic manifestations are those of interstitial (not air-space) edema; this radiographic pattern predicts a mild clinical course and prompt resolution.     

Characterization of leptospiral outer membrane lipoprotein LipL36: downregulation associated with late-log-phase growth and mammalian infection

We report the cloning of the gene encoding a 36-kDa leptospiral outer membrane lipoprotein, designated LipL36. We obtained the N-terminal amino acid sequence of a staphylococcal V8 proteolytic-digest fragment in order to design an oligonucleotide probe. A Lambda-Zap II library containing EcoRI fragments of Leptospira kirschneri DNA was screened, and a 2.3-kb DNA fragment which contained the entire structural lipL36 gene was identified. Several lines of evidence indicate that LipL36 is lipid modified in a manner similar to that of LipL41, a leptospiral outer membrane lipoprotein we described in a previous study (E. S. Shang, T. A. Summers, and D. A. Haake, Infect. Immun. 64:2322-2330, 1996). The deduced amino acid sequence of LipL36 would constitute a 364-amino-acid polypeptide with a 20-amino-acid signal peptide, followed by an L-X-Y-C lipoprotein signal peptidase cleavage site. LipL36 is solubilized by Triton X-114 extraction of L. kirschneri; phase separation results in partitioning of LipL36 exclusively into the hydrophobic, detergent phase. LipL36 is intrinsically labeled during incubation of L. kirschneri in media containing [3H]palmitate. Processing of LipL36 is inhibited by globomycin, a selective inhibitor of lipoprotein signal peptidase. After processing, LipL36 is exported to the outer membrane along with LipL41 and lipopolysaccharide. Unlike LipL41, there appears to be differential expression of LipL36. In early-log-phase cultures, LipL36 is one of the most abundant L. kirschneri proteins. However, LipL36 levels drop considerably beginning in mid-log phase. LipL36 expression in vivo was evaluated by examining the humoral immune response to leptospiral antigens in the hamster model of leptospirosis. Hamsters surviving challenge with culture-adapted virulent L. kirschneri generate a strong antibody response to LipL36. In contrast, sera from hamsters surviving challenge with host-adapted L. kirschneri do not recognize LipL36. These findings suggest that LipL36 expression is downregulated during mammalian infection, providing a marker for studying the mechanisms by which pathogenic Leptospira species adapt to the host environment.     

Cosmid library of the turkey herpesvirus genome constructed from nanogram quantities of viral DNA associated with an excess of cellular DNA

A protocol was designed for the rapid and efficient construction of cosmid libraries from cell-associated viral genomes available in very low quantities. Purification of viral DNA from cellular DNA was unnecessary. The vast excess of cellular DNA compensated for the limited amount of available viral DNA, enabling titration of the restriction endonuclease partial digest. A cosmid library of the turkey herpesvirus DNA genome was constructed from 1.5 micrograms of cellular DNA containing approximately 6 nanograms of viral DNA.