Comparing the unified protocol for transdiagnostic treatment of emotional disorders to prolonged exposure for the treatment of PTSD: Design of a non-inferiority randomized controlled trial.

Background: Prolonged Exposure (PE), a trauma-focused therapy, is one of the most efficacious treatments available for PTSD. However, many people with PTSD do not lose their diagnosis following delivery of PE. The Unified Protocol (UP) for Transdiagnostic Treatment of Emotional Disorders is a non-trauma focused treatment that may offer an alternative treatment for PTSD. Methods: This paper describes the study protocol for IMPACT, an assessor-blinded randomized controlled trial that examines the non-inferiority of UP relative to PE for participants who meet DSM-5 criteria for current PTSD. One hundred and twenty adult participants with PTSD will be randomized to receive either 10 × 90-min sessions of UP or PE with a trained provider. The primary outcome is severity of PTSD symptoms assessed by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at post-treatment. Discussion: While evidence-based treatments are available for PTSD, high levels of treatment dropout and non-response require new approaches to be tested. The UP is based on emotion regulation theory and is effective in treating anxiety and depressive disorders, however, there has been limited application to PTSD. This is the first rigorous study comparing UP to PE in a non-inferiority randomized controlled trial and may help improve clinical outcomes for those with PTSD. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, Trial ID (ACTRN12619000543189).

Cranial Musculoskeletal Description of Black-Throated Finch (Aves: Passeriformes: Estrildidae) with DiceCT.

Synopsis Dietary requirements and acquisition strategies change throughout ontogeny across various clades of tetrapods, including birds. For example, birds hatch with combinations of various behavioral, physiological, and morphological factors that place them on an altricial-precocial spectrum. Passeriformes (=songbirds) in particular, a family constituting approximately more than half of known bird species, displays the most drastic difference between hatchling and adults in each of these aspects of their feeding biology. How the shift in dietary resource acquisition is managed during ontogeny alongside its relationship to the morphology of the feeding apparatus has been largely understudied within birds. Such efforts have been hampered partly due to the small size of many birds and the diminutive jaw musculature they employ. In this study, we used standard and diffusible iodine-based contrast-enhanced computed tomography in conjunction with digital dissection to quantify and describe the cranial musculature of the Black-throated Finch (Poephila cincta) at fledgling and adult stages. Our results reveal that in both the fledgling and the adult, cranial musculature shows clear and complex partitioning in the Musculus adductor mandibulae externus that is consistent with other families within Passeriformes. We quantified jaw-muscle sizes and found that the adult showed a decrease in muscle mass in comparison to the fledgling individual. We propose that this could be the result of low sample size or a physiological effect of parental care in Passeriformes. Our study shows that high-resolution visualization techniques are informative at revealing morphological discrepancies for studies that involve small specimens such as Passeriformes especially with careful specimen selection criteria.

[Dietary iron and iron deficiency anemia among adolescent girls from Benin]. / Apports alimentaires en fer et anémie ferriprive chez des adolescentes au Bénin.

BACKGROUND: Iron deficiency anemia affects a large number of women in developing countries, especially during childbearing years. Few studies determined the association between estimated absorbable iron intakes and iron deficiency. METHODS: The association between dietary iron intake and iron status was studied in 100 adolescent girls aged 14-16 years from Benin. Fifty adolescents were boarding at the school, while 50 lived at home. Biochemical indices of iron status included: hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, serum iron, total iron-binding capacity and % transferrin saturation. Dietary intakes were obtained by two 24-hour recalls and absorbable iron intakes were estimated using Monsen's model. The probability approach was used to estimate inadequacy in iron intake. RESULTS: While 73% of adolescents met the recommendations for dietary iron intake, only 27% had estimated absorbable iron intake above the average requirement for absorbed iron. Non-heme iron represented 97.2% of the total iron intake. Forty three percent of subjects were anemic (hemoglobin<120 g/l). Iron deficiency defined by a four-model index based on > or =2 abnormal values in the four independent indicators of iron status used (serum iron, total iron-binding capacity, mean corpuscular volume, mean corpuscular hemoglobin concentration) was present in 14% of the subjects, while 13% had iron deficiency anaemia (hemoglobin<120 g/l+four-model index). Using a multiple regression analysis, total absorbable iron intakes (including iron supplements) were highly and positively associated with hemoglobin and hematocrit concentrations (P=0.000001 and P=0.00007 respectively). CONCLUSION: In this group of adolescents, total absorbable iron intakes were related to iron deficiency. Efforts should be made to increase the heme iron content of the diet and the bioavailability of non-heme iron by promoting affordable local foods rich in iron and promoters of iron absorption (Vitamin C and meat, poultry and fish factor).

ADAMTS-13 glycans and conformation-dependent activity.

Essentials The impact of N-linked glycosylation on ADAMTS-13 function has not been fully explored. The activity of glycan modified ADAMTS-13 was investigated under static and shear stress conditions. Terminal sialic acid on the metalloprotease domain glycans are important for ADAMTS-13 activity. The CUB domain glycans modulate ADAMTS-13 activity. SUMMARY: Background ADAMTS-13 activity can be regulated by its conformation, whereby interactions between the C-terminal CUB domains and the spacer domain maintain ADAMTS-13 in a closed conformation. ADAMTS-13 contains 10 N-linked glycans, with four sites present in theTSP2 through to CUB domains that may contribute to its conformation. Objectives/Methods We hypothesized that glycosylation contributes to ADAMTS-13 conformation and function. The proteolytic activity of glycan-modified ADAMTS-13 was assessed under static and shear stress conditions. Results Enzymatic removal of terminal silaic acid or entire N-linked glycan chains decreased activity against FRETS-VWF73 at pH 7.4 and against full-length von Willebrand factor (VWF) under shear stress. Using truncated ADAMTS-13, we demonstrated that this was attributable to loss of sialic acid from the glycans in the metalloprotease domain and an effect of N-linked glycosylation in the TSP2 through to CUB domains. Mutation of the N-linked glycan sites in the MDTCS domains reduced or abolished protein expression. However, the N707Q, N828Q, N1235Q and N1354Q (TSP2, TSP4, CUB1, and CUB2 domains, respectively) variants were expressed normally. Interestingly, the N707Q and N828Q variants showed reduced activity against FRETS-VWF73, but normal activity under flow conditions. In contrast, the N1235Q and N1354Q variants had enhanced activity against FRETS-VWF73 and VWF under shear stress. Immunoprecipitation experiments confirmed that loss of N-linked glycans in the CUB domains significantly reduced the interaction with the spacer domain and enhanced binding to the 6A6 anti-ADAMTS-13 antibody, which recognizes a cryptic epitope in the metalloprotease domain. Conclusions Together, these data demonstrate that the N-linked glycans of ADAMTS-13 play a crucial role in regulating ADAMTS-13 activity.

A short-term assay of myeloid precursor cells in man.

An assessment of the numbers of myeloid precursor cells in human bone marrow, obtainable earlier than with conventional colony assays, would be useful for many reasons. Recently an isotopic assay for murine-colony-stimulating activity has been devised and we have modified this technique for use in man. Bone marrow mononuclear cells are incubated in microtitre plates in the presence of optimal amounts of placental-conditioned medium, pulsed with 3H-galactose for 24 h and the isotope incorporation measured. Isotope uptake by normal bone marrow was found to be proportional to both the number of cells cultured and the amount of conditioned medium added. The cells responsible for isotope incorporation have been characterized partially and found to be nonadherent immature myeloid cells and have a density of less than 1.077. This short-term isotopic assay was also compared to the GM-CFC assay in ten normals and in 24 patients with either neutropenia (of different etiology), myeloid leukemias, or neutrophil leukocytosis. There was good correlation between the two assays in all the patients studied. Thus, our observations suggest that the cell incorporating 3H-galactose in response to conditioned medium has many of the properties of the GM-CFC and its immediate progeny. Although assay specificity has yet to be proven, our early results indicate that it may have use as a rapid, but indirect, assessment of human myeloid precursor cells and thus prove to be a useful adjunct to the standard hematological methods of assessment of certain patients.

Management and epidemiologic analyses of an outbreak due to methicillin-resistant Staphylococcus aureus.

PURPOSE: Following implementation of special measures to control a nosocomial outbreak of methicillin-resistant Staphylococcus aureus (MRSA), we used immunoblot typing in conjunction with antimicrobial susceptibility testing to investigate the epidemiology of this event and to determine whether this outbreak represented the failure of infection control measures to limit the spread of previously endemic MRSA strains or the introduction of a new strain of MRSA. MATERIALS AND METHODS: Isolates of MRSA recovered from hospitalized patients were initially categorized on the basis of antimicrobial susceptibility results. Organisms susceptible to ciprofloxacin and/or trimethoprim/sulfamethoxazole were recovered from patients at a relatively constant rate prior to December 1988 and were categorized as endemic isolates. Subsequently, there was an outbreak due to organisms resistant to both of these antibiotics; these were therefore categorized as outbreak isolates. Isolates were later characterized by immunoblot typing. Prior to this analysis, isolates were given code numbers so that clinical and epidemiologic data as well as resistance patterns were not known until this testing was complete. RESULTS: Between January 1986 and November 1988, an average of 3.9 patients per month acquired nosocomial MRSA in the Sepulveda Veterans Administration Medical Center. In contrast, from December 1988 to October 1989, 369 MRSA isolates were collected from 125 patients (an average of 11.4 patients per month). Prior to December 1988, all tested nosocomial isolates of MRSA were susceptible to ciprofloxacin and/or to trimethoprim/sulfamethoxazole. In contrast, the outbreak was due to spread of MRSA isolates resistant to these antibiotics. Immunoblot typing of 204 isolates from 98 individuals identified five distinct immunoblot types of which types B and C were by far the most common. Type B was highly associated with outbreak isolates, whereas type C was associated with endemic isolates (p less than 0.001). All sequential isolates from single patients that belonged to different susceptibility categories demonstrated discordant immunoblot types. In contrast, concordant immunoblot types were observed for 25 of 27 sequential isolates that displayed minor variations in antimicrobial resistance. The institution of more stringent infection control measures was followed by the return of nosocomial MRSA acquisition rates to pre-outbreak levels. Although novobiocin and trimethoprim/sulfamethoxazole were extensively used to treat patients harboring outbreak and endemic isolates, respectively, in no instance was the initial MRSA isolate from any patient resistant to novobiocin and only 6% of initial endemic isolates displayed trimethoprim/sulfamethoxazole resistance. A modest, significant increase in the resistance of endemic isolates to various other antimicrobial agents was noted however. CONCLUSION: Immunoblot analyses provided strong, corroborative evidence that at least two separate strains of MRSA were present during the outbreak and that a newly introduced strain with a distinctive antimicrobial resistance pattern was primarily responsible for the rapid spread of MRSA during the outbreak. The observation that previously effective infection control measures failed to prevent the nosocomial spread of a newly introduced community-acquired MRSA strain suggests that a single set of control measures may not be equally efficacious against all strains of MRSA. In this regard, previously reported variations in resistance to topical antimicrobials and/or antiseptics, and differences in virulence factors such as colonization potential, invasiveness, and survival on fomites, may warrant further study. Control of the outbreak strain of MRSA in our institution did occur after the implementation of more strenuous isolation procedures.(ABSTRACT TRUNCATED)

Nosocomial transmission of disease caused by nontypeable strains of Haemophilus influenzae.

PURPOSE: The authors evaluated a geographic and temporal cluster of lower respiratory tract infections due to unencapsulated (serologically nontypeable) Haemophilus influenzae to determine whether this event represented the transmission of a single clone. METHODS AND MATERIALS: H influenzae was recovered from eight patients at a nursing home and from three patients in an adjacent acute care hospital. Serotypes, biotypes, outer membrane protein profiles, and multilocus enzyme genotypes were determined to characterize bacterial isolates. Patient records were retrospectively examined to determine clinical and epidemiologic characteristics. RESULTS: During a 10-day period in September 1991, lower respiratory tract infections caused by H influenzae were diagnosed in four patients residing in a single nursing home unit. Oropharyngeal cultures from four of seven asymptomatic roommates of these patients also grew H influenzae. During the month before and after the nursing home cluster of cases, four other individuals in acute care areas of the hospital had positive sputum cultures for H influenzae. Three of these latter specimens were also available for analysis. All H influenzae isolates were unencapsulated and beta-lactamase-negative. Eight of the nine isolates from the nursing home patients (two morphologically distinct colony types of H influenzae were isolated from one case) had a single outer membrane protein profile arbitrarily designated as X and a single multilocus enzyme genotype arbitrarily designated as A. In contrast, none of the isolates from the acute care cases had this profile (P < or = 0.02; two-tailed Fisher's exact test). The isolates obtained from two of the patients in acute care areas had an outer membrane protein profile arbitrarily designated as Y and a single multilocus enzyme genotype designated as B. These two patients were contemporaneously hospitalized in adjacent intensive care unit cubicles. The remaining isolates displayed an outer membrane protein profile arbitrarily designated as W. All roommates of the four patients in the nursing home were administered oral rifampin 600 mg daily for 4 days. H influenzae was not recovered from follow-up oropharyngeal cultures obtained 1 week after the completion of therapy. No beta-lactamase-negative H influenzae were identified in this unit during the subsequent 9 months. CONCLUSION: This study furnishes strong evidence for the nosocomial transmission of a clone of unencapsulated H influenzae in a nursing home unit. Epidemiologic data showed temporal and geographic clustering of respiratory tract infections and colonization by H influenzae. Outer membrane protein profiles and multilocus enzyme genotype analysis indicated that seven of eight patients at the nursing home carried a single clone of unencapsulated H influenzae. Laboratory and epidemiologic data also demonstrated the presence, and possible nosocomial transmission, of a second clone of unencapsulated H influenzae in a physically separate area of the hospital. Finally, although a causal relationship is not proven, the outbreak ended following the administration of rifampin prophylaxis of asymptomatic carriers.

A 82Sr-82Rb isotope generator for use in nuclear medicine.

An improved 82Sr-82Rb generator system, based on the complexing ion-exchange resin Chelex-100, has been developed. Columns of this material can be easily and rapidly milked, and the rubidium-strontium separation factor for a fresh generator under the experimental conditions studied was found to be greater than 10-7. Approximately 80% of the 82Rb present can be delivered in a 15-ml volume of aqueous 0.2 M NH4Cl solution. After more than 6 liters of eluant had passed through the generator, the rubidium-strontium separation factor was still observed to greater than 10-5 and no unusual strontium breakthrough behavior was seen in the system over nearly three 82Sr half-lives.

Evaluation and application of alumina-based Rb-82 generators charged with high levels of Sr-82/85.

Generator-produced Rb-82, a 75-sec positron emitter with potential for myocardial blood-flow imaging, was studied with various ion-exchange columns to evaluate the characteristics of alumina as an adsorber for the 25-day Sr-82 parent. Test columns of alumina, Bio Rex 70, and Chelex 100 were loaded with multimillicurie amounts of no-carrier-added Sr-82/Sr-85 (Sr-85 is a production contaminant). The breakthrough of Sr-82/Sr-85, and the yield of Rb-82, were determined for long-term elutions from each column with up to 4 liter of 2% NaCl solution at pH 8 to 9. The breakthrough of Sr-82/85 was 10(-6)-10(-5) from aluminal 10(-6)-10(-4) from Chelex 100 and Bio Rex 70. The effects of eluent flow rate and concentration, and of alumina volume, on the breakthrough and yield were also studied. An improved and automated Rb-82 generator was used for myocardial and brain blood-flow studies in experimental animals and in man; it was equipped with solenoid flow-control valves and five in. of lead shielding for the alumina columns, which were charged with 25-50 mCi Sr-82 (100-150 mCi Sr-85). The Rb-82 generator with alumina column provided up to 20-40 mCi of Rb-82 as often as every 5-10 min with less than 10(-5) breakthrough of Sr-82/85 over the 2- to 3-mo, useful life of the generator.

16 alpha-[77Br]bromoestradiol-17 beta: a high specific-activity, gamma-emitting tracer with uptake in rat uterus and uterus and induced mammary tumors.

16 alpha-[77Br]Bromoestradiol-17 beta (Compound 1) has been synthesized by radiobromination of estrone enoldiacetate. Tissue uptake studies performed 1 hr after administration of Compound 1 to immature or mature female rats showed uterus-to-blood ratios of 13, with nontarget issue-to-blood ratios ranging from 0.6 to 2. Co-administration of unlabelled estradiol caused a selective depression in the uterine uptake with no effect on nontarget tissue uptake. In adult animals bearing adenocarcinomas induced by DMBA (7,12-dimethylbenz(a)anthracene), tumor-to-blood ratios of 6.3 were obtained, this uptake also being depressed in animals treated with unlabeled estradiol. The studies demonstrate that Compound 1 has suitable binding properties and sufficiently high specific activity so that its uptake in estrogen target tissues in vivo is mediated primarily by the estrogen receptor. Furthermore, they suggest that this compound may be suitable for imaging human breast tumors that contain estrogen receptors.

Rapid radioiodination of rose bengal at room temperature.

Published methods for radioiodination of rose bengal require reaction times of 1 hr or more at temperature from 50 to 120 degrees C. Through the use of an acidified ethanol solvent and potassium iodate oxidant, purified rose bengal is radioiodinated at room temperature within 15 min with chemical yields ranging between 93 and 97%. Radiochemical impurities are sufficiently minimized to permit preparation in a single 10-ml serum vial, requiring no additional purification steps. The method reported here is readily adaptable to cold-kit preparation.

Comparative serum stability of radiochelates for antibody radiopharmaceuticals.

Serum incubation of monoclonal antibodies chelate labeled by DTPA, benzyl-EDTA and benzyl-TETA with 111In, 57Co, and 67Cu demonstrated marked differences in their stability. In serum, 111In-benzyl-EDTA-antibody was more stable than 111In-DTPA-antibody. Cobalt-57 or 67Cu chelated antibody were less stable than either 111In chelated antibody; 67Cu was only firmly attached to the antibody as 67Cu-benzyl-TETA-antibody. The relative stability of the radiometal chelated antibodies was paralleled by the relative stability in serum of the radiometal chelates themselves. These in vitro studies suggest that in vivo behavior of metal chelates exposed to a complex protein environment cannot be predicted by classical equilibrium constants.

Myocardial perfusion with rubidium-82. I. Measurement of extraction fraction and flow with external detectors.

Accurate measurement of the regional extraction of a diffusible radiopharmaceutical is essential for the quantifying of regional blood flow, and may also provide an important physiologic or diagnostic indicator of the cellular viability of an organ in man through external detection by positron emission tomography. However, extraction fraction of a diffusible tracer usually decreases as flow increases, and thus noninvasive methods for measuring flow are nonlinear unless the extraction fraction can be measured independently. This report describes the theoretical basis and documents the applicability of this theory for determining, with external detectors, the first-pass regional extraction fraction of rubidium-82 by the heart, following a single intravenous bolus injection of the tracer. Measurement of extraction fraction was found to be independent of flow, thereby making it possible to determine accurately with a single intravenous bolus injection of rubidium-82, the regional blood flow in the myocardium at up to five times normal resting flow.

Myocardial perfusion with rubidium-82. II. Effects of metabolic and pharmacologic interventions.

In order to validate a new method for quantifying coronary blood flow, we injected intravenously a bolus of rubidium-82 (Rb-82) into 28 open-chested dogs under a wide range of flow and physiologic conditions, using beta probes to monitor myocardial radioactivity. Extraction fraction and perfusion were measured using a functional model that separates the data into the free and trapped myocardial rubidium. Extraction and uptake of rubidium were lower during acidosis than during alkalosis and were unchanged by glucose-insulin, digoxin, or propranolol. Myocardial flow, as indicated by rubidium, correlated linearly with simultaneous measurements of flow by microspheres in the same sample volume over a wide range of flow (r = 0.97, n = 106, range 0.02-7.76 ml/min/g). Regional myocardial blood flow can be accurately determined using generator-produced Rb-82. Studies using current state-of-the-art, fast positron-emission tomographic cameras are required to determine the utility of this approach in man.

Brain tumor evaluation using Rb-82 and positron emission tomography.

Positron emission tomography of the brain with 75-sec rubidium-82 obtained from a portable generator (25-day Sr-82 leads to Rb-82) was used to evaluate the integrity of the blood-brain barrier (BBB) in patients with brain tumors. Rubidium is normally excluded from the central nervous system by the intact BBB, but when the BBB is disrupted by a tumor. Rb enters and pools in the extravascular spaces of the central nervous system. Since Rb is also rapidly cleared from the blood, a high tissue-to-blood ratio of the Rb-82 tracer is achieved in regions of BBB disruption after intravenous injection. With dynamic positron emission tomographic imaging, the extravasation of the Rb tracer can be evaluated independent of the intravascular Rb concentration, and very small changes in the BBB permeability can be detected. The results of our studies in eight patients show that this technique is a promising method for evaluation of the BBB integrity in brain-tumor patients.U

Rubidium-82 generators for imaging studies.

Strontium-82, produced by spallation reaction with medium-energy proton beams, was used to evaluate Bio-Rex 70 and Chelex-100 ion-exchange resins for use in a compact Rb-82 generator. Adsorption of Sr-82 to the resin column, Rb-82 elution yields, Sr breakthrough, and 82Rb-Sr separation factors were determined for newly prepared columns and for longterm elution conditions. Separation factors of 10(7) to 10(8) were obtained with 2% NaCl elutions from Bio-Rex 70 resin columns while the separation factors was about 5 X 10(4) with the Chelex-100 resin column.

Ecological constraints drive social evolution in the African mole-rats.

The African mole-rats (family Bathyergidae) are subterranean hystricomorph rodents occurring in a variety of habitats and displaying levels of sociality which range from solitary to eusocial, making them a unique mammalian taxonomic group to test ecological influences on sociality. Here, we use an extensive DNA-based phylogeny and comparative analysis to investigate the relationship between ecology, sociality and evolution within the family. Mitochondrial cytochrome-b and 12s rRNA trees reveal that the solitary species are monophyletic when compared to the social species. The naked mole-rat (Heterocephalus glaber) is ancestral and divergent from the Damaraland mole-rat (Cryptomys damarensis), supporting previous findings that have suggested the multiple evolution of eusociality within the family. The Cryptomys genus is species-rich and contains taxa exhibiting different levels of sociality, which can be divided into two distinct clades. A total of seven independent comparisons were generated within the phylogeny, and three ecological variables were significantly correlated with social group size: geophyte density (p < 0.05), mean months per year of rainfall greater than 25 mm (p < 0.001), and the coefficient of rainfall variation (p = 0.001). These results support the food-aridity hypothesis for the evolution of highly social cooperative behaviour in the Bathyergidae, and are consistent with the current theoretical framework for skew theory.

Character of transient ischemia in angina pectoris.

There is growing interest in the possible therapeutic and prognostic significance of silent myocardial ischemia in coronary artery disease (CAD) and its detection by ambulatory electrocardiographic (ECG) monitoring. In 100 apparently healthy normal subjects (20 with angiographically normal coronary arteries), Holter monitoring revealed significant ST-segment depression in only 2 (both over 40 years, one with positive treadmill test, the other with risk factor for CAD). No significant ECG changes were found in those with normal coronary vessels. In 30 patients with documented CAD, significant ST-segment depression during 1,934 episodes over 446 days of monitoring over 18 months was found. Only 24% of the episodes were associated with angina. Asymptomatic and symptomatic episodes were associated with comparable changes in perfusion detected by positron emission tomography. Heart rate increases greater than 10 beats/min preceding the onset of the ST-segment changes occurred in only 23% of the episodes. There was considerable variability in the ST-segment changes in the same patient monitored serially over long periods of time. The data indicate that it is extremely uncommon for patients without CAD to exhibit silent myocardial ischemia, whereas patients with stable angina exhibit frequent, variable and often asymptomatic ECG evidence of myocardial ischemia rarely triggered by increases in heart rate. These findings are likely to be of therapeutic and prognostic significance.

Relation between regional myocardial uptake of rubidium-82 and perfusion: absolute reduction of cation uptake in ischemia.

Experiments were undertaken using rubidium-82 and position tomography to examine the relation between myocardial perfusion and cation uptake during acute ischemia. Rubidium-82 was repeatedly eluted from a strontium-82-rubidium-82 generator. In six dogs emission tomograms were used to measure the delivered arterial and myocardial concentrations at rest and after coronary stenosis, stress and ischemia. There was a poor overall relation between regional myocardial uptake and flow measured by microspheres and a large individual variability. Extraction of rubidium-82 was inversely related to flow. Significant regional reduction of cation uptake was detected in the tomograms when regional flow decreased by more than 35 percent. This reduction was significantly greater when ischemia was present. A small but significantly greater when ischemia was present. A small but significant decrease (33.0 +/- 9.1 percent, mean +/- standard deviation) in the myocardial uptake of rubidium-82 was detected only when flow was increased by more than 120 percent in relation to a control area after administration of dypiridamole. The technique using rubidum-82 and tomography was applied in five volunteers and five patients with angina pectoris and coronary artery disease. Myocardial tomograms recorded at rest and after exercise in the volunteers showed homogeneous uptake of cation in reproducible and repeatable scans. In contrast, the patients with coronary artery disease showed an absolute mean decrease of 36 +/- 14 percent in regional myocardial uptake of rubidium-82 after exercise. These abnormalities persisted in serial tomograms for more than 20 minutes after the symptoms and electrocardiographic signs of ischemia.

A simple assay of intrinsic factor-vitamin B12 complex employing the binding intrinsic factor antibody.

The reaction between binding intrinsic factor antibody and intrinsic factor-vitamin B(12) complex has been studied. Initially in the zone of antibody excess, the relationship between the amount of antigen present and the amount of antigen-antibody complex adsorbed onto zirconium phosphate gel was linear. With increasing amounts of antigen, the curve departed from linearity and reached a plateau. The linear portion of the reaction forms the basis of a simple and reproducible assay for quantitating intrinsic factor to which vitamin B(12) has already been bound. The assay provides a method for studying the fate of intrinsic factor-vitamin B(12) complex during digestion and absorption. In two normal subjects given radioactive vitamin B(12) orally, aspiration of ileal contents showed that only 50 to 70% of the radioactivity was bound to intrinsic factor at that level.