Impact of oral preoperative and perioperative immunonutrition on postoperative infection and mortality in patients undergoing cancer surgery: systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Infectious complications occur in 4-22 per cent of patients undergoing surgical resection of malignant solid tumours. Improving the patient's immune system in relation to oncological surgery with immunonutrition may play an important role in reducing postoperative infections. A meta-analysis was undertaken to evaluate the potential clinical benefits of immunonutrition on postoperative infections and 30-day mortality in patients undergoing oncological surgery. METHODS: PubMed, Embase and Cochrane Library databases were searched to identify eligible studies. Eligible studies had to include patients undergoing elective curative surgery for a solid malignant tumour and receiving immunonutrition orally before surgery, including patients who continued immunonutrition into the postoperative period. The main outcome was overall infectious complications; secondary outcomes were surgical-site infection (SSI) and 30-day mortality, described by relative risk (RR) with trial sequential analysis (TSA). Risk of bias was assessed according to Cochrane methodology. RESULTS: Some 22 RCTs with 2159 participants were eligible for meta-analysis. Compared with the control group, immunonutrition reduced overall infectious complications (RR 0·58, 95 per cent c.i. 0·48 to 0·70; I2 = 7 per cent; TSA-adjusted 95 per cent c.i. 0·28 to 1·21) and SSI (RR 0·65, 95 per cent c.i. 0·50 to 0·85; I2 = 0 per cent; TSA-adjusted 95 per cent c.i. 0·21 to 2·04). Thirty-day mortality was not altered by immunonutrition (RR 0·69, 0·33 to 1·40; I2 = 0 per cent). CONCLUSION: Immunonutrition reduced overall infectious complications, even after controlling for random error, and also reduced SSI. The quality of evidence was moderate, and mortality was not affected by immunonutrition (low quality). Oral immunonutrition merits consideration as a means of reducing overall infectious complications after cancer surgery.

ANTECEDENTES: Entre un 4-22% de los pacientes a los que se realiza una resección quirúrgica de tumores sólidos malignos presentan complicaciones infecciosas. Mejorar el sistema inmunitario del paciente quirúrgico oncológico mediante inmunonutrición puede tener un papel relevante en la reducción de las infecciones postoperatorias. Se realizó un metaanálisis para evaluar los posibles beneficios clínicos de la inmunonutrición en las infecciones postoperatorias y la mortalidad a los 30 días en pacientes sometidos a cirugía oncológica. MÉTODOS: Se realizó una búsqueda en las bases de datos de Pubmed, Embase y Cochrane para identificar los estudios clave. Se consideraron aquellos estudios que incluyeron pacientes con cirugía curativa electiva de un tumor maligno sólido que recibieron inmunonutrición por vía oral antes de la cirugía, así como también los que siguieron con inmunonutrición en el postoperatorio. La variable principal fueron las complicaciones infecciosas generales y las secundarias fueron la infección de la herida quirúrgica y la mortalidad a los 30 días, presentadas como el riesgo relativo (RR) obtenido a partir en un análisis secuencial de experimentos (trial sequential analysis, TSA). El riesgo de sesgo se evaluó según la metodología Cochrane. RESULTADOS: Para el metaanálisis se identificaron 22 ensayos clínicos con 2.075 participantes. En comparación con el grupo de control, la inmunonutrición redujo las complicaciones infecciosas generales (RR 0,58, i.c. del 95% 0,48-0,70, I2 = 7%, TSA ajustado i.c. del 95% 0,28-1,21) y las infecciones de la herida quirúrgica (RR 0,65, i.c. del 95% 0,50-0,85, I2 = 0%, TSA ajustado, i.c. del 95% 0,21-2,04). No hubo diferencias en la mortalidad a los 30 días (RR 0,69, i.c. del 95% 0,32-1,4, I2 = 0%). CONCLUSIÓN: la inmunonutrición redujo las complicaciones infecciosas generales, incluso después de controlar el error aleatorio. La inmunonutrición también redujo la infección de la herida quirúrgica. La calidad de la evidencia fue moderada y la mortalidad no se vio afectada por la inmunonutrición (baja calidad). La inmunonutrición oral debería ser tenida en cuenta como una forma de reducir las complicaciones infecciosas generales después de la cirugía del cáncer.

Sleep disturbances and changes in urinary 6-sulphatoxymelatonin levels in patients with breast cancer undergoing lumpectomy.

BACKGROUND: Sleep disturbances and changes in self-reported discomfort and melatonin secretion are common in the post-operative period. We aimed to study the distribution of sleep stages in the perioperative period and evaluate changes in secretion of the melatonin metabolite aMT6s and subjective parameters of sleepiness, pain, general well-being and fatigue in patients undergoing surgery for breast cancer. METHODS: Twelve patients, 30-70 years, undergoing lumpectomy were included. Polysomnography was performed the night before surgery (PREOP), the night after (PO1) and 14 days after (PO14). Recordings were scored as awake, light-sleep, slow-wave sleep and rapid-eye-movement (REM) sleep. Sleep stages were analysed as % of total sleep time (TST). Self-reported discomfort was assessed using questions about the level of fatigue, well-being, pain and sleepiness. Urinary aMT6s was measured by radioimmunoassay. RESULTS: There was significantly decreased REM sleep on PO1 (5.9% of TST) compared with PREOP (18.7% of TST) (P < 0.005). An increase in light sleep was observed on PO1 (68.4% of TST) compared with PREOP (55.0% of TST) (P < 0.05). No significant changes in TST, sleep latency, sleep period or total time awake were found. The observed sleep changes were normalised after 2 weeks. No significant changes were found in pain, well-being, fatigue or sleepiness. Night secretion of aMT6s showed a trend towards a decrease from PREOP to PO1 (P = 0.09) and normalisation on PO14 (P = 0.27 between PREOP and PO14). CONCLUSION: Patients with breast cancer undergoing lumpectomy had significantly disturbed sleep architecture the night after surgery, and these changes were normalised after 2 weeks.

Multiple diagnostic task performance in CT examination of the chest.

OBJECTIVES: In three experiments, we studied the detection of multiple abnormality types using the satisfaction of search (SOS) paradigm, the provision of a computer-aided detection (CAD) of pulmonary nodules and a focused nodule detection task. METHODS: 51 chest CT examinations (24 that demonstrated subtle pulmonary nodules and 27 that demonstrated no pulmonary nodules) were read by 15 radiology residents and fellows under two experimental conditions: (1) when there were no other abnormalities present except test abnormalities in the exams (non-SOS condition), and (2) when other abnormalities were present in the exams (SOS condition). Trials from the two conditions were intermixed. Readers were invited to return for two sessions: one in which the SOS condition was repeated with a simulated CAD; another in which only the non-SOS condition was presented. Detection accuracy was measured using receiver operating characteristic (ROC) analysis. RESULTS: An SOS effect (reduced detection accuracy for the test nodules in the presence of the diverse added abnormalities) was not found. Average accuracy was much higher when the CAD prompt was provided, without cost in the detection of the added abnormalities. Accuracy for detecting nodules appearing without intermixed SOS trials was also substantially improved. CONCLUSIONS: CT interpretation was highly task dependent. Nodule detection was poor in the general search task. Therefore, CAD may offer a greater performance improvement than demonstrated in experiments assessing CAD using focused search. The absence of SOS may be due to limited nodule detection even without other abnormalities. Advances in knowledge CAD prompts of nodules increase the detection accuracy of nodules and decrease the time to detection-without impairing the detection accuracy-of non-nodule abnormalities.

Multiple diagnostic task performance in CT examination of the chest.

Objectives In three experiments, we studied the detection of multiple abnormality types using the satisfaction of search (SOS) paradigm, the provision of a computer-aided detection (CAD) of pulmonary nodules and a focused nodule detection task. Methods 51 chest CT examinations (24 that demonstrated subtle pulmonary nodules and 27 that demonstrated no pulmonary nodules) were read by 15 radiology residents and fellows under two experimental conditions: (1) when there were no other abnormalities present except test abnormalities in the exams (non-SOS condition), and (2) when other abnormalities were present in the exams (SOS condition). Trials from the two conditions were intermixed. Readers were invited to return for two sessions: one in which the SOS condition was repeated with a simulated CAD; another in which only the non-SOS condition was presented. Detection accuracy was measured using receiver operating characteristic (ROC) analysis. Results An SOS effect (reduced detection accuracy for the test nodules in the presence of the diverse added abnormalities) was not found. Average accuracy was much higher when the CAD prompt was provided, without cost in the detection of the added abnormalities. Accuracy for detecting nodules appearing without intermixed SOS trials was also substantially improved. Conclusions CT interpretation was highly task dependent. Nodule detection was poor in the general search task. Therefore, CAD may offer a greater performance improvement than demonstrated in experiments assessing CAD using focused search. The absence of SOS may be due to limited nodule detection even without other abnormalities. Advances in knowledge CAD prompts of nodules increase the detection accuracy of nodules and decrease the time to detection-without impairing the detection accuracy-of non-nodule abnormalities.

Relationship between bone strength and dual-energy X-ray absorptiometry measurements in pigs.

Computed tomography and a 3-point bending test were performed on the metacarpal bones of adult production pigs to test the hypothesis that bone strength is strongly correlated with areal bone mineral density (BMD) in this population. The aim of the study was to subject material from adult production pigs grouped by BMD to 3-point bending, to test this hypothesis and determine any correlations. In all, 168 individual computed tomography scans and mechanical tests were performed on the collected material. For evaluation purposes, the material was divided into the categories low, medium, and high BMD (<1, 1 to 1.4, and >1.4 g/cm(2), respectively). The results showed a difference in the maximum load, in the stress at maximum load, and stiffness among each BMD group (P < 0.001) and in elastic modulus between the low BMD group and the 2 other groups (P < 0.001). A correlation between both intrinsic and extrinsic measures of bone strength and BMD was thus demonstrated. The projected change in each of the variables reported, for a 0.1 g/cm(2) alteration in BMD (within the BMD range evaluated in this study), is as follows: maximum load, 708 N; stress at maximum load, 50 N/mm(2); stiffness, 391.6 N/mm; and elastic modulus, 108 N/mm(2) (P < 0.001). The results confirm the relationship between BMD and bone strength and indicate that BMD screening can be used in fracture risk assessments in production pigs.

Factors regulating ovarian function in pigs.

The hormonal interactions of the hypothalamic-pituitary-ovarian-uterine axis are accountable for a normal reproduction in female pigs. It is of importance to have knowledge of estrous symptoms and hormonal profiles around ovulation. The introduction of the transrectal ultrasonography in sows has given us the possibility to study ovarian activity in conscious animals and relate the timing of estrus to ovulation. Combining this technique with measuring of several hormones like luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin, estradiol, progesterone, insulin-like growth hormone I (IGF-I), prostaglandin F2alpha (PGF2alpha) metabolite, oxytocin, facilitate our knowledge about the sequence of ovarian events. Evidence suggests that activation of the hypothalamic-pituitary-adrenal axis may hamper the normal gonadotropin secretion and in consequence, the ovarian function. The metabolic status during lactation, weaning of piglets and social stress might affect onset of ovarian activity and the related estrous behavior. The role of seminal plasma, artificial insemination and presence of the boar might also be included as factors regulating the temporal kinetics of ovulation, corpus luteum development, uterine function and steroid production in the ovary. Studies using a simulated stress by means of adrenocorticotrophic hormone (ACTH) administration or food deprivation are tools in understanding how the ovary is susceptible to impairment. The intention of this paper is to review current knowledge concerning the endocrine aspects of normal and stress-influenced ovarian function in pigs.

Dual-energy X-ray absorptiometry of the pig: Protocol development and evaluation.

As part of a prospective study in bone mineralisation in adult pigs it was necessary to establish guidelines and to define sites for bone mineral measurements. Particular requirements were that, the protocol should be suitable for a mass screening programme in both postmortem specimens and in live animals, and should deliver results of known reliability. Estimates of bone mineral content (BMC) and bone mineral density (BMD) in areas within the 4th metacarpal bone yielded coefficients of variation (CV) in the order of 7% for both regions and estimates in regions which included the entire metacarpal-phalangeal area yielded CV values in the order of 0.7% and 0.6% for BMC and BMD, respectively. A region of interest taken from the coccygeal vertebrae yielded coefficient of variation values of 3% and 2% for BMC and BMD, respectively. Accuracy of dual-energy X-ray absorptiometry (DXA) was estimated using a standard curve derived from BMC determined by ashing. There was a high correlation between mineral content determined by DXA and by ashing (R(2)=0.99, p<0.0001). The results suggest that the regions used in this study are suitable for use in large, mass screening, prospective studies.

Evaluation of various corrections to the standardized uptake value for diagnosis of pulmonary malignancy.

OBJECTIVE: Standard uptake values (SUVs) are widely used for quantifying the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV. METHODS: One hundred and twenty-seven patients with suspicious lung lesions imaged with 18F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation. RESULTS: The areas under the ROC curves for SUV(BW), SUV(BW+Glu), SUV(LBW), SUV(LBW+Glu), SUV(BSA), SUV(BSA+Glu) and SUV(BW+Tsize) were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively. CONCLUSION: The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.

A device for applying static loads to prosthetic limbs of transtibial amputees during spiral CT examination.

This paper describes a device that allows the imaging of prosthetic legs under load conditions using spiral computerized tomography (CT). The device consists of a chair and a vertical footplate mounted on a 17.8 x 1.9 cm oak board that is 197 cm long. The load device can be easily positioned onto the CT bed. A subject sits in the chair and applies force by pushing the foot portion of the prosthesis against the footplate. The magnitude of the force is monitored by a digital force gauge coupled to the footplate. Because the load is borne by the hips and lower back of the subject against the chair, substantial forces can be generated and steadily maintained for the 20-45 s duration of the CT study. This device has been used successfully with 19 transtibial amputees, allowing the acquisition of spiral CT studies with half and full body weight loads.

A threshold method to improve standardized uptake value reproducibility.

Although standardized uptake values (SUV) are widely used to quantify the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours, there are systematic differences in the way this index is applied by different investigators. The aims of this study were to compare the effects of using maximum or mean region counts in the calculation of SUV and to investigate an alternative technique based on a fixed fraction of the maximum counts. Simulated PET projections of the thorax were generated together with spherical lesions that varied in diameter from 1.6 to 4.8 cm with uptake values of 2, 4 and 8. The lesion SUVs were determined using either the maximum (SUVmax) or mean count (SUVmean) values found in regions circumscribing the lesion. In addition, average values were calculated that only included region pixels that exceeded a selected fraction of maximum value (SUV0.6max or SUV0.75max). These methods were also applied to six clinical 18F-FDG PET studies with a total of 12 lesions. The SUVs for these lesions were determined independently by four observers. Decreases with respect to SUVmax of 57%, 23% and 14% were found for SUVmean, SUV0.6max and SUV0.75max approaches respectively in the simulation study. The variation in SUVmean with region size was 35%, while the SUV0.6max and SUV0.75max was less than 3%. Similar results were obtained for the clinical data. We conclude that the proposed technique produces SUVs that are essentially independent of lesion region size and shape. It is expected that this will provide a more stable and reliable result than current approaches.

X-ray attenuation coefficients of high-atomic-number, hexanuclear transition metal cluster compounds: a new paradigm for radiographic contrast agents.

RATIONALE AND OBJECTIVES: The purpose of this study was to examine the radiologic attenuation properties of the parent cluster compounds, particularly attenuation as a function of discrete photon energy, before investigating ligand substitutions, which are necessary to improve cluster biocompatibility and to impart desirable physicochemical properties. MATERIALS AND METHODS: The linear attenuation coefficients for solutions of the cluster compounds Ta6Br14, K8Ta6O19, and (H3O)2W6Cl14 were determined at 60, 80, 103, 122, and 140 keV from gamma-ray transmission measurements with americium-241, xenon-133, gadolinium-153, cobalt-57, and technetium-99m radioactive sources. Transmission measurements were obtained for a fixed time interval that ensured a statistically accurate count distribution exceeding 20,000 counts through the sample for each trial. RESULTS: On a strictly mole per liter basis, a 0.075 mol/L aqueous solution of K8Ta6O19 showed 1.08 times the attenuation of 0.063 mol/L aqueous iohexol at 60 keV and 3.30 times the attenuation at 80 keV. Similarly, a 0.05 mol/L methanolic solution of (H3O)2W6Cl4 showed 0.96 times (96%) the attenuation of 0.063 mol/L aqueous iohexol at 60 keV but 3.09 times the attenuation of the iohexol solution at 80 keV. Attenuations of 0.063 mol/L aqueous iohexol and 0.0125 mol/L Ta6Br14 (ie, at approximately one-fifth the iohexol concentration) were comparable at greater than 60 keV. CONCLUSION: These results confirm the theoretic potential for use of early transition metal cluster compounds as radiographic contrast agents. At higher x-ray energies, cluster compounds demonstrate multiplied x-ray attenuation relative to iodinated contrast agents.

The human antibacterial cathelicidin, hCAP-18, is bound to lipoproteins in plasma.

Cathelicidins are a family of antibacterial and lipopolysaccharide-binding proteins. hCAP-18, the only human cathelicidin, is a major protein of the specific granules of human neutrophils. The plasma level of hCAP-18 is >20-fold higher than that of other specific granule proteins relative to their levels within circulating neutrophils. The aim of this study was to elucidate the background for this high plasma level of hCAP-18. Plasma was subjected to molecular sieve chromatography, and hCAP-18 was found in distinct high molecular mass fractions that coeluted with apolipoproteins A-I and B, respectively. The association of hCAP-18 with lipoproteins was validated by the cofractionation of hCAP-18 with lipoproteins using two different methods for isolation of lipoproteins from plasma. Furthermore, the level of hCAP-18 in delipidated plasma was <1% of that in normal plasma. Immunoprecipitation of very low, low, and high density lipoprotein particles with anti-apolipoprotein antibodies resulted in coprecipitation of hCAP-18. The binding of hCAP-18 to lipoproteins was mediated by the antibacterial C-terminal part of the protein. The binding of hCAP-18 to lipoproteins suggests that lipoproteins may play an important role as a reservoir of this antimicrobial protein.

Removal of N-terminal polyhistidine tags from recombinant proteins using engineered aminopeptidases.

We have developed a specific and efficient method for complete removal of polyhistidine purification tags (HisTags) from the N-termini of target proteins. The method is based on the use of the aminopeptidase dipeptidyl peptidase I (DPPI), either alone or in combination with glutamine cyclotransferase (GCT) and pyroglutamyl aminopeptidase (PGAP). In both cases, the HisTag is cleaved off by DPPI, which catalyzes a stepwise excision of a wide range of dipeptides from the N-terminus of a peptide chain. Some sequences, however, are resistant to DPPI cleavage and a number of mature proteins have nonsubstrate N-termini which protects them against digestion. For such proteins, HisTags composed of an even number of residues can be cleaved off by treatment with DPPI alone. When the target protein is unprotected against DPPI, a blocking group is generated enzymatically from a glutamine residue inserted between the HisTag and the target protein. A protein with a HisTag-Gln extension is incubated with both DPPI and GCT. As above, the polyhistidine sequence is cleaved off by DPPI, but when the glutamine residue appears in the N-terminus, it is immediately converted into a pyroglutamyl residue by an excess of GCT and further DPPI digestion is prevented. The desired sequence is finally obtained by excision of the pyroglutamyl residue with PGAP. All the enzymes employed can bind to immobilized metal affinity chromatography (IMAC) matrices, and in this paper we demonstrate a simple and highly effective process combining IMAC purification of His-tagged proteins, our aminopeptidase-based method for specific excision of HisTags and use of subtractive IMAC for removing processing enzymes. Typical recoveries were 75-90% for the enzymatic processing and subtractive IMAC. The integrated process holds promises for use in large-scale production of pharmaceutical proteins because of a simple overall design, use of robust and inexpensive matrices, and use of enzymes of either recombinant or plant origin.

Pulmonary CT image classification with evolutionary programming.

RATIONALE AND OBJECTIVES: It is often difficult to classify information in medical images from derived features. The purpose of this research was to investigate the use of evolutionary programming as a tool for selecting important features and generating algorithms to classify computed tomographic (CT) images of the lung. MATERIALS AND METHODS: Training and test sets consisting of 11 features derived from multiple lung CT images were generated, along with an indicator of the target area from which features originated. The images included five parameters based on histogram analysis, 11 parameters based on run length and co-occurrence matrix measures, and the fractal dimension. Two classification experiments were performed. In the first, the classification task was to distinguish between the subtle but known differences between anterior and posterior portions of transverse lung CT sections. The second classification task was to distinguish normal lung CT images from emphysematous images. The performance of the evolutionary programming approach was compared with that of three statistical classifiers that used the same training and test sets. RESULTS: Evolutionary programming produced solutions that compared favorably with those of the statistical classifiers. In separating the anterior from the posterior lung sections, the evolutionary programming results were better than two of the three statistical approaches. The evolutionary programming approach correctly identified all the normal and abnormal lung images and accomplished this by using less features than the best statistical method. CONCLUSION: The results of this study demonstrate the utility of evolutionary programming as a tool for developing classification algorithms.

Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats.

The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats. Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction of leukaemic cells increased to > 90% and the pH dropped to about 6.5. The fraction of NITP+ cells increased to > 80% in bone marrow and to about 40% in blood. The fraction of BrdUrd+ cells was unchanged in blood, but decreased in bone marrow both for normal cells (from about 20% to 5%), and for leukaemic cells (from about 45% to 25%), evidently as a result of the severely changed microenvironment. In this study we have demonstrated in vivo the development of an acidic and hypoxic bone marrow hampering normal haemopoiesis during leukaemic growth. Our data support the notion of BNML as a valuable tool for studying leukaemogenesis.

Active recombinant rat dipeptidyl aminopeptidase I (cathepsin C) produced using the baculovirus expression system.

An active form of rat dipeptidyl aminopeptidase I (DPPI, cathepsin C) was obtained by heterologous expression in insect cells. Baculoviruses carrying a cDNA sequence encoding the entire rat DPPI precursor was used to infect High Five cells in a serum-free medium. Recombinant DPPI (rDPPI) was secreted into the medium from which it was purified by a combination of ammonium sulfate fractionation, hydrophobic interaction chromatography (HIC), and ion-exchange chromatography. A polyhistidine-tagged form of the enzyme (HT-rDPPI) was purified from the medium by immobilized metal affinity chromatography (IMAC). In vivo activation of native rat DPPI involves at least three chain cleavages per subunit and the ability of the expression system to imitate this processing was investigated. Both rDPPI and HT-rDPPI were secreted into the medium as unprocessed and inactive proenzymes and gradually converted into their active forms in the medium. This process was not completed at the time of harvest but mature enzyme processed similarly to native rat and human DPPI could be obtained by incubating the eluates from the HIC and IMAC columns at pH 4.5 and 5 degrees C for 18-40 h. The yield of purified and matured enzyme was approximately 50 mg/liter, and it was shown that rDPPI and HT-rDPPI were active against both a dipeptide-p-nitroanilide substrate and human growth hormone N-terminally extended with an Ala-Glu dipeptide.

A method for quantifying SPECT uniformity.

Field uniformity is an important parameter for monitoring the performance of SPECT imaging systems. However, it is difficult to apply objective measures of uniformity because of the large variance associated with reconstructed images. In the proposed method, annular sampling of the SPECT uniformity image is used to reduce the noise level without decreasing the magnitude of uniformity artifacts. The reconstructed uniformity image is sectioned into annular rings centered on the center of rotation to match the expected distribution of uniformity artifacts. Statistical fluctuations are reduced by averaging the counts within the annular rings, allowing the use of objective measures of field uniformity such as integral uniformity. Application of the annular sampling technique on simulated and phantom uniformity images showed that the technique could reliably quantify SPECT uniformity artifacts at acceptable count levels. As a result this method can be used to objectively evaluate SPECT field uniformity in systems which utilize parallel collimation and circular orbits.

Emission-based attenuation correction of myocardial perfusion studies.

BACKGROUND: Nonuniform attenuation in the thorax can generate artifacts in single-photon emission computed tomographic myocardial perfusion studies that mimic coronary artery disease. In this article we present both phantom and simulation data, as well as clinical data, in support of an emission-based method that provides reliable correction for attenuation effects without the need for a transmission measurement. METHODS AND RESULTS: The attenuation map is derived from the measured distribution of 99mTc-labeled macroaggregated albumin in the lungs and a radioactive binder wrapped about the thorax. This information is acquired as part of a dual-isotope acquisition during the rest 201Tl study. Segmentation is used to define the interiors of lung and body compartments, which are assigned a single attenuation coefficient for each of the two tissue types. The appropriateness of this approach was investigated by examining the measured attenuation coefficients in a group of 80 individuals (40 male, 40 female) from positron emission tomographic transmission studies. The correction technique was evaluated with computer simulations, a physical phantom, and clinical data acquired from 20 patients. Analysis of the positron emission tomographic data found a small SD in the mean attenuation coefficients for the body (<5%) and lungs (<15%). The application of emission-based attenuation-correction technique produced a substantial reduction in the magnitude of the attenuation artifact in images obtained from both the phantom and the simulation studies. The emission-based attenuation-correction technique was easily applied to myocardial perfusion studies, where it had a significant effect, resulting in changes in interpretation for nine of 20 patients. CONCLUSIONS: The results of this study provide strong support for the concept that an attenuation map can be generated with fixed attenuation values in place of those that are directly measured. Thus the emission-based attenuation-correction technique can be considered an inexpensive alternative to transmission-based correction methods. Because the emission-based correction technique does not require any additional hardware, it has the major advantage of being applicable to all single-photon emission computed tomographic systems.

The primary structure and enzymic properties of porcine prochymosin and chymosin.

Preliminary investigations by N-terminal sequence analysis showed that pig and calf chymosin possessed 80% amino acid sequence identity but showed considerable differences in their enzymatic properties. A comparison of their structures may therefore contribute to an understanding of the significance of the amino acid residues responsible for the differences in these properties. Pig chymosis was extracted from the stomachs of pigs of less than 3 weeks of age, and was purified by ion exchange chromatography. Half of the primary structure was determined by amino acid sequencing and the complete structure was deduced from a cloned chymosin cDNA. Results showed that the zymogen showed 81% sequence identity with calf prochymosin and 57% identity with pig pepsinogen A. The size of the propart and location of the residue which becomes the N-terminus in the active molecule were the same in the prochymosins. The maximum general proteolytic activity at pH 3.5 of pig chymosin was 2-3% of that of the activity of pig pepsin A at pH 2, whereas the milk clotting activity relative to the general proteolytic activity of pig chymosin was much higher than that of calf chymosin. Agar gel electrophoresis at pH 5.3 of stomach extracts of individual pigs showed the existence of two predominant genetic variants of zymogen and enzyme. The two variants could not be distinguished by amino acid composition or N-terminal sequencing, and no differences in the enzymatic properties of the genetic variants were observed. It was concluded that of the residues that participate in the substrate binding, calf and pig chymosin differ in the following positions (pig pepsin numbering, subsites in parentheses): Ser 12 Thr (S4), Leu 30 Val (S1/S3), His 74 Gln (S'2), Val 111 Ile (S1/S3), Lys 220 Met (S4). With regard to the low general proteolytic activity of pig chymosin, the substitution Asp 303 Val relative to calf chymosin may contribute to an explanation of this.