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Context and Objectives: Cancer centers are increasingly providing complementary medicine as part of an emerging discipline termed 'integrative oncology' (IO). The present study explored factors associated with disparities in referral and adherence to a freely-provided IO program., Methods: The databases of three oncology centers in northern Israel were searched retrospectively for chemotherapy-treated oncology patients eligible for referral by their oncology healthcare professionals to an integrative physician (IP) consultation. Demographic and cancer-related variables associated with the referral, and attendance by patients at the consultation were identified, as was adherence to the 6-week IO treatment program (high adherence, attending ≥4 IO treatment sessions; low adherence, 0-3 sessions)., Results: Of 4988 eligible patients, 1694 (34%) were referred to the IP consultation, with 1331 (78.6%) attending the consultation of which 766 (57.6%) were adherent to IO treatments. Multivariate analysis revealed lower referral rates among patients speaking primarily Arabic and Russian vs. Hebrew (OR = 3.0, 95% CI = 2.0-4.6, P < 0.0001); males vs. females (OR = 1.94, CI = 1.3-2.9, P = 0.001); those not reporting emotional distress (OR = 1.5, CI = 1.02-2.16, P = 0.037); and older age (OR = 1.04, CI = 1.03-1.06, P < 0.0001). Arabic and Russian-speaking patients were less likely to adhere to IO treatments (OR = 0.52, 95% CI = 0.32-0.83, P = 0.006)., Conclusion: Patients' ethno-national origin and immigration status (primary language, Arabic and Russian), male gender and older age were associated with lower rates of referral to and attendance of the IP consultation, with reduced adherence to weekly IO treatments. These findings require further study to identify barriers toward diversity, equity and inclusion in IO care, increasing awareness among healthcare professionals regarding the benefits of these services for improving patient wellbeing., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Coronary computed tomographic angiography can detect nonobstructive atherosclerotic lesions that would not otherwise have been detected with functional cardiac imaging. Currently, limited data exist regarding the clinical significance of these lesions in patients with acute chest pain. The aim of our study was to examine the prognostic significance of these nonobstructive findings in a patient population presenting with acute chest pain. We evaluated 959 consecutive patients who underwent coronary computed tomographic angiography for investigation of acute chest pain. The patients were classified as having normal (n = 545), nonobstructive coronary artery disease (CAD; defined as any narrowing <50% diameter stenosis; n = 312), or obstructive CAD (narrowing of ≥50% diameter stenosis; n = 65). Follow-up data for a minimum of 12 months (mean 27 ± 11) was obtained for any major adverse coronary events consisting of death, nonfatal acute coronary syndrome, and coronary revascularization. Compared to patients with normal coronary arteries, those with nonobstructive CAD were older and had a greater prevalence of CAD risk factors. The incidence of major adverse coronary events was equally low among both these groups (0.6% vs 1.3%, for the normal and nonobstructive groups, respectively, p = 0.2). In conclusion, patients with either nonobstructive CAD or normal findings, as evaluated by coronary computed tomographic angiography, for acute chest pain during an intermediate-term follow-up period had equally benign clinical outcomes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: Multi-detector computed tomography (MDCT) has emerged as an efficient tool for detection of obstructive coronary artery disease (CAD) and assessment of patients with acute chest pain. MDCT may detect premature, non-obstructive atherosclerotic lesions which otherwise would have not been detected upon functional cardiac imaging tests. Currently, there is scarce data regarding the clinical significance of these lesions. The purpose of this study was to prospectively analyse the intermediate term outcome of patients admitted to chest pain unit (CPU) with findings of non-obstructive CAD upon MDCT. Method and results The study comprised 444 patients admitted to the CPU at Sheba Medical Center and underwent evaluation by MDCT for complaints of acute chest pain. Studies were classified as: normal; non-obstructive CAD (defined as any narrowing <50% diameter stenosis); obstructive CAD (narrowing of ≥ 50% diameter stenosis); or non-diagnostic. Patients were followed up for a minimum of 1 year and outcomes were compared between the non-obstructive (n = 115) and the normal (n = 266) MDCT groups in regard to MACE [coronary revascularization, acute coronary syndrome (ACS), and death]. Comparing the groups, those with non-obstructive CAD were older, more likely to be males, and dyslipidaemic. During an intermediate term follow-up (2.5 ± 0.4 years) MACE was equally low between the two groups (1% for both groups; P = 0.9)., Conclusion: Among patients evaluated by MDCT for acute chest pain, during an intermediate term follow-up, those with non-obstructive CAD had a benign clinical outcome compared with those with normal coronary arteries.

Background: Coronary computed tomography angiography (CCTA) is an established modality for ruling out coronary artery disease. However, it has been suggested that CCTA may be a source of non-negligible radiation exposure., Objectives: To evaluate the potential degradation in coronary image quality when using prospective gated (PG) CCTA as compared with retrospective gated (RG) CCTA in chest pain evaluation., Methods: The study cohort comprised 216 patients: 108 consecutive patients in the PG CCTA arm and 108 patients matched for age, gender and heart rate in the RG CCTA arm. Scans were performed using a 64-slice multidetector CT scanner. All 15 coronary segments were evaluated subjectively for image quality using a 5-point visual scale. Dose-length product was recorded for each patient and the effective radiation dose was calculated, Results: The PG CCTA technique demonstrated a significantly higher incidence of step artifacts in the middle and distal right coronary artery, the distal left anterior descending artery, the second diagonal, the distal left circumflex artery, and the second marginal branches. Nevertheless, the diagnostic performance of these scans was not adversely affected. The mean effective radiation doses were 3.8 +/- 0.9 mSv vs.17.2 +/- 3 mSv for PG CCTA and RG CCTA, respectively (P < 0.0001)., Conclusions: Artifacts caused by the PG CCTA technique (64 MDCT) scanners tended to appear in specific coronary segments but did not impair the overall diagnostic quality of CCTA and there was a marked reduction in radiation exposure. We conclude that 64-slice PG CCTA is suitable for clinical use, especially for acute chest pain "fast track" evaluation targeted at relatively young subjects in a chest pain unit.

Background: Many patients present to the emergency department with chest pain. While in most of them chest pain represents a benign complaint, in some patients it underlies a life-threatening illness., Objectives: To assess the routine evaluation of patients presenting to the ED with acute chest pain by means of a cardiologist-based chest pain unit using different noninvasive imaging modalities., Methods: We evaluated the records of 1055 consecutive patients who presented to the ED with complaints of chest pain and were admitted to the CPU. After an observation period and according to the decision of the attending cardiologist, patients underwent myocardial perfusion scintigraphy, multidetector computed tomography, or stress echocardiography., Results: The CPU attending cardiologist did not prescribe non-invasive evaluation for 108 of the 1055 patients, who were either admitted (58 patients) or discharged (50 patients) after an observation period. Of those remaining, 444 patients underwent MDCT, 445 MPS, and 58 stress echocardiography. Altogether, 907 patients (86%) were discharged from the CPU. During an average period of 236 +/- 223 days, 25 patients (3.1%) were readmitted due to chest pain of suspected cardiac origin, and only 8 patients (0.9%) suffered a major adverse cardiovascular event., Conclusions: Utilization of the CPU enabled a rapid and thorough evaluation of the patients' primary complaint, thereby reducing hospitalization costs and occupancy on the one hand and avoiding misdiagnosis in discharged patients on the other.

Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8.; HPRT) catalyzes the salvage synthesis of inosine-5'-monophosphate (IMP) and guanosine-5'-monophosphate (GMP) from the purine bases hypoxanthine and guanine, respectively. Complete deficiency of HPRT activity is associated with the Lesch-Nyhan syndrome (LNS), characterized by excessive purine production and severe neurological manifestations. The etiology of the metabolic consequences of HPRT deficiency is clarified, but that of the neurological manifestations is not yet understood. HPRT-deficient mice represent an experimental animal model of LNS. In search for a possible metabolic abnormality in LNS brains, connecting the neurological deficit to HPRT deficiency, the purine and pyrimidine nucleotide content of cultured neurons, prepared from HPRT-deficient transgenic mice, was now determined. The HPRT-deficient neuronal cultures exhibited a significantly elevated content of the pyrimidine nucleotides UTP (1.33-fold the normal level, p = 0.0002) and CTP (1.28-fold the normal level, p = 0.02), but normal content of the purine nucleotides ATP and GTP. This abnormality in neuronal pyrimidine nucleotide content may be associated with the pathophysiology of the neurological deficit in LNS.

A rat neuroma cell line (B103 4C), deficient of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), was utilized as a model tissue in search for the biochemical basis of the Lesch-Nyhan syndrome (LNS). The HGPRT-deficient neurons exhibited the following properties: an almost complete absence of uptake of guanine and of hypoxanthine into intact cell nucleotides (0.92% and 0.69% of normal, respectively); a significant increase in the availability of 5'-phosphoribosyl-1-pyrophosphate; a three- to fourfold acceleration of the rate of de novo nucleotide synthesis; a normal excretion of xanthine, but 15-fold increase in the excretion of hypoxanthine into the culture media; a normal cellular purine nucleotide content, including the absence of 5-amino-4-imidazole carboxamide nucleotides (Z-nucleotides), but enhanced turnover of adenine nucleotides (loss of 86% of the radioactivity of the prelabeled pool in 24 h, in comparison to 73% in the normal line), and an elevated UTP content. The results suggest that, under physiological conditions, guanine salvage does not occur in the normal neurons, but that hypoxanthine salvage is of great importance in the homeostasis of the adenine nucleotide pool. The finding of the normal profile of purine nucleotides in the HGPRT-deficient neurons indicates that the lack of hypoxanthine salvage is adequately compensated by the enhanced de novo nucleotide synthesis. These results did not furnish evidence in support of the possibility that GTP or ATP depletion, or Z-nucleotide accumulation, occurs in HGPRT-deficient neurons and that these are etiological factors causing the neurological abnormalities in LNS.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolic fate of guanine and of guanine ribonucleotides (GuRNs) in cultured rat neurons was studied using labeled guanine. 8-Aminoguanosine (8-AGuo), an inhibitor of purine nucleoside phosphorylase, was used to clarify the pathways of GMP degradation, and mycophenolic acid, an inhibitor of IMP dehydrogenase, was used to assess the flux from IMP to GMP and, indirectly, the activity of the guanine nucleotide cycle (GMP----IMP----XMP----GMP). The main metabolic fate of guanine in the neurons was deamination to xanthine, but significant incorporation of guanine into GuRNs, at a rate of approximately 8.5-13.1% of that of the deamination, was also demonstrated. The turnover rate of GuRNs was fast (loss of 80% of the radioactivity of the prelabeled pool in 22 h), reflecting synthesis of nucleic acids (32.8% of the loss in radioactivity) and degradation to xanthine, guanine, hypoxanthine, guanosine, and inosine (49.3, 4.3, 4.1, 1.1, and 0.5% of the loss, respectively). Of the radioactivity in GuRNs, 7.9% was shifted to adenine nucleotides. The accumulation of label in xanthine indicates (in the absence of xanthine oxidase) that the main degradative pathway from GMP is that to xanthine through guanosine and guanine. The use of 8-AGuo confirmed this pathway but indicated the operation of an additional, relatively slower degradative pathway, that from GMP through IMP to inosine and hypoxanthine. Hypoxanthine was incorporated mainly into adenine nucleotide (91.5%), but a significant proportion (6%) was found in GuRNs.(ABSTRACT TRUNCATED AT 250 WORDS)

The activities (Vmax) of several enzymes of purine nucleotide metabolism were assayed in premature and mature primary rat neuronal cultures and in whole rat brains. In the neuronal cultures, representing 90% pure neurons, maturation (up to 14 days in culture) resulted in an increase in the activities of guanine deaminase (guanase), purine-nucleoside phosphorylase (PNP), IMP 5'-nucleotidase, adenine phosphoribosyltransferase (APRT), and AMP deaminase, but in no change in the activities of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenosine deaminase, adenosine kinase, and AMP 5'-nucleotidase. In whole brains in vivo, maturation (from 18 days of gestation to 14 days post partum) was associated with an increase in the activities of guanase, PNP, IMP 5'-nucleotidase, AMP deaminase, and HGPRT, a decrease in the activities of adenosine deaminase and IMP dehydrogenase, and no change in the activities of APRT, AMP 5'-nucleotidase, and adenosine kinase. The profound changes in purine metabolism, which occur with maturation of the neuronal cells in primary cultures in vitro and in whole brains in vivo, create an advantage for AMP degradation by deamination, rather than by dephosphorylation, and for guanine degradation to xanthine over its reutilization for synthesis of GMP. The physiological meaning of the maturational increase in these two ammonia-producing enzymes in the brain is not yet clear. The striking similarity in the alterations of enzyme activities in the two systems indicates that the primary culture system may serve as an appropriate model for the study of purine metabolism in brain.