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PubMed2006

The interaction between two radiosensitizers: 5-iododeoxyuridine and caffeine.

5-Iododeoxyuridine (IUdR) and caffeine are recognized as potential radiosensitizers with different mechanisms of interaction with ionizing radiation (IR). To assess the interaction of these two types of radiosensitizers, we compared treatment responses to these drugs alone and in combination with IR in two p53-proficient and p53-deficient pairs of human colon cancer cell lines (HCT116 versus HCT116 p53-/- and RKO versus RKO E6). Based on clonogenic survival, the three single agents (IR, IUdR, and caffeine) as well as IUdR or caffeine combined with IR are less or equally effective in p53-deficient human tumor cells compared with p53-proficient tumor cells. However, using both radiosensitizers, a significantly greater radiosensitization was found in p53-deficient human tumor cells. To better understand the interaction of these two radiosensitizers, additional studies on DNA repair and cell cycle regulation were done. We found that caffeine enhanced IUdR-DNA incorporation and IUdR-mediated radiosensitization by partially inhibiting repair (removal) of IUdR in DNA. The repair of IR-induced DNA double-strand breaks was also inhibited by caffeine. However, these effects of caffeine on IUdR-mediated radiosensitization were not found in p53-proficient cells. Cell cycle analyses also showed a greater abrogation of IR-induced S- and G2-phase arrests by caffeine in p53-deficient cells, particularly when combined with IUdR. Collectively, these data provide the mechanistic bases for combining these two radiosensitizers to enhance tumor cytotoxicity. This differential dual mode of radiosensitization by combining IUdR and caffeine-like drugs (e.g., UCN-01) in p53-deficient human tumors may lead to a greater therapeutic gain.

Base Pair Mismatch↗
PubMed2002

Double agency in clinical research.

The current focus on evidence-based practice in nursing may result in nurses playing 2 roles concurrently--that is, acting as researcher and caregiver at the same time and with the same people. Given the fiduciary nature of the patient-caregiver relationship, this double agency can give rise to problems, both real and perceived. In this paper, the issues associated with assuming dual roles in research with humans will be examined, particularly in relation to recruitment and informed consent, data collection, and participant withdrawal from a study. In addition, strategies to prevent or minimize problems related to double agency are identified, with attention to the guidance provided by professional codes of ethics and the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans.

Ethics, Nursing↗
PubMed2000

Dual nucleoside regimens in nonadvanced HIV infection: prospective follow-up of 130 patients, Aquitaine Cohort, 1996 to 1998. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA).

OBJECTIVE: To describe the response to combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) initiated early in the course of HIV infection under routine circumstances and to research prognostic factors indicating good virologic response. SETTING: Patients of the Aquitaine Cohort, a hospital-based open cohort that had been recruiting since 1987 in five public hospitals of the Aquitaine region in southwestern France. METHODS: Prospective cohort study of antiretroviral-naive patients with CD4+ cell counts >0.350 x 10(9)/L who started dual NRTI therapy between January 1996 and June 1997. Intent-to-treat analysis and multivariate logistic regression were used with data collected up to March 31, 1998. RESULTS: In this study, 130 patients were enrolled with a median follow-up of 14 months. At the time of first prescription, 79% were in U. S. Centers for Disease Control and Prevention (CDC) group A, 16% in group B, and 5% in group C; median CD4+ cell count was 0.466 x 10(9)/L and median HIV RNA level was 4.52 log10 copies/ml. The two main combinations used were zidovudine (AZT) plus zalcitabine (ddC; 38%) and AZT plus didanosine (ddI; 37%). At week 52, median CD4+ and HIV RNA responses were, respectively, +80 cells and -1.6 log; the proportions of patients with HIV RNA level <5000 and <500 copies/ml were 70% and 45%, respectively, and 96% of the patients had a CD4+ cell count >0.350 x 10(9)/L at that time. At their last follow-up, 3 patients had reached been diagnosed with full-blown AIDS and the AIDS-free survival probability at 1 year was 98.2% (95% confidence interval [CI], 93.1-99.6); 1 death had occurred. The only significant variable associated with an undetectable HIV RNA level at 1 year was a lower HIV RNA level at the first prescription of dual therapy. CONCLUSION: Our data indicate that dual nucleoside combinations could be a therapeutic option for patients diagnosed and observed during follow-up in the early course of HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed2002

[A 36 years experience with implantable pacemakers. A historical analysis].

BACKGROUND: The implantation of pacemakers improves cardiac function and quality of life, in particular with dual chamber DDD and DDDR modes. AIM: To evaluate our clinical experience and results on pacemaker implantation, from 1963 to 1998. MATERIAL AND METHODS: Computerized data collected from 2,445 consecutive paced patients was reviewed. A total of 3,554 operative procedures were performed, including 412 procedures for complications and 697 pacemaker replacement. Patient survival was determined from clinical records, inquiry to pacemaker manufacturers and death certificates from Servicio de Registro Civil e Identificación de Chile (Chilean Civil and Identification Registry). RESULTS: Use of dual chamber (DDD and DDDR) pacemakers increased progressively up to 74% from 1988 to 1998. Complication rate was 42% in the 1963-1976 study period, it decreased to 10.6% in the 1977-1987 study period, and to 5.6% by 1988-1998. Only two patients died during surgery in the study period (0.08%). In the 1977-1987 period, pacemakers lasted 10.6 years. Survival rates were 52% at ten years, 33% at 15 years, and 21% at 20 years, with a median survival of 11.7 years, and 7.24 years in patients over 80 years old. CONCLUSIONS: Transvenous permanent pacing can be accomplished today with a low complication rate, mainly due to better technology and surgical procedures.

Aged↗
PubMed2002

Dietary calcium intake and serum vitamin D are major determinants of bone mass variations in women. A longitudinal study.

BACKGROUND AND AIMS: Bone mineral density (BMD) is one of the main determinants in the pathogenesis of fractures. However, data on factors predicting longitudinal variations in BMD are still limited and incomplete. Such data would be of great importance in order to better focus prevention strategies in both the clinical setting and at the population level. The aim of the study was to investigate the predictive value of both serological and questionnaire variables for bone mass variations in healthy women participating in a population-based longitudinal study carried out in Napoli, Italy. METHODS: High completion rate (85.2%) and adequate sample size were obtained: 139 women (45 to 79 years of age) were examined at study entry and then again after two years (24 +/- 2 months) following the same protocol. They underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. BMD was measured by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Data analysis included calculation of the percent variation in BMD in the 2-year period. Longitudinal data underwent stepwise analysis for a global evaluation of mutual interactions between independent variables. RESULTS AND CONCLUSIONS: Our findings indicate that dietary and serum calcium, and serum 25(OH)vitamin D are the only independent determinants of BMD variations at the lumbar and femoral level, respectively. While the pharmacological significance of calcium and vitamin D in the therapy of established osteoporosis is still controversial, the present longitudinal data evidence their role as essential nutrients in determining the natural history of BMD variations.

Aged↗
PubMed1999

Collection and interpretation of plasma leptin concentration data in humans.

OBJECTIVE: To reassess the relationship between body fat and plasma leptin concentrations when a) replicate measures of leptin are made; b) energy intake is controlled at isoenergetic levels before the study; and c) body fat and percent body fat are measured with dual energy X-ray absorptiometry (DXA). RESEARCH METHODS AND PROCEDURES: Two separate studies were conducted. In the first study, four plasma samples were collected for measurement of leptin over 30 minutes on a single day in 43 lean and obese men and women. For the second study, plasma samples were collected on four consecutive days from a group of 50 lean and obese men and women. Percent body fat (and body fat mass) was related to log-transformed mean plasma leptin concentrations using linear regression analysis; multiple linear regression analysis was used to determine whether there was an effect of gender on this relationship, and the analysis of Choi was used to examine whether percent body fat or body fat mass better predicts plasma leptin concentrations. RESULTS: For the first study, percent body fat was highly correlated (r=0.96, p<0.0001) with log-transformed mean leptin concentrations. No difference in the relationship between leptin and percent body fat in men and women was detected. The second study confirmed this observation; the relationship between ln leptin and percent body fat was virtually identical (r=0.93, p<0.001). Analysis of the pooled data suggests that percent body fat is a better predictor of plasma leptin concentration than body fat mass. The use of multiple (as opposed to a single) leptin measurements did not significantly improve the leptin/body fat relationship. DISCUSSION: When robust body composition techniques and diet control measures are taken into consideration, the relationship between ln plasma leptin concentrations and percent body fat is not different in men and women.

Absorptiometry, Photon↗
PubMedDate not supplied

Serial assessment of left ventricular function during dobutamine stress by means of electrocardiography-gated myocardial SPECT: combination with dual-isotope myocardial perfusion SPECT for detection of ischemic heart disease.

BACKGROUND: Technetium-labeled myocardial perfusion tracers allow simultaneous assessment of myocardial perfusion and left ventricular function by electrocardiography (ECG)-gated myocardial single photon emission computed tomography (SPECT). The purpose of this study was to evaluate left ventricular performance during dobutamine stress by means of ECG-gated myocardial perfusion SPECT with short-time data collection. METHODS AND RESULTS: After administration of Tc-99m sestamibi or tetrofosmin (600-740 MBq), 67 patients with ischemic heart disease, including 35 with prior myocardial infarction, were examined by ECG-gated myocardial perfusion SPECT at rest and during dobutamine stress (at dosages of 4, 8, 12, 16, and 20 microg/kg/min, with increments every 8 minutes). The ECG-gated data collection time was 5 minutes for each dobutamine dosage. After acquisition of gated SPECT data at the highest dose, thallium 201 chloride (111 MBq) was injected, and dual-isotope SPECT was also performed to assess the myocardial ischemia. In 32 patients without prior myocardial infarction, the sensitivity of individual stenosed-vessel detection with dual-isotope perfusion SPECT, with wall motion abnormality obtained from gated SPECT, and with the combined method was 55.9%, 52.9%, and 73.5%, respectively, based on coronary angiography. ECG-gated SPECT during dobutamine infusion revealed regional wall motion abnormalities (worsening or biphasic response) in 19 (57.6%) of 33 infarcted areas with culprit coronary arterial stenosis. The prevalence of reversible perfusion defects on dual-isotope SPECT was higher in segments with wall motion abnormalities than in segments with normal wall motion response (89.5% vs 42.9%, P <.02). CONCLUSIONS: Myocardial perfusion and left ventricular function during dobutamine infusion were analyzed in a single examination by means of the combined method. This procedure has the potential to provide comprehensive information with which to evaluate patients with ischemic heart disease.

Blood Pressure↗
PubMed1995

Proximal femur bone mineral levels of US adults.

This paper describes bone mineral levels in the proximal femur of US adults based on a nationally representative sample of 7116 men and women aged 20 years and older. The data were collected in phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in five selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter, Ward's triangle and total. These variables are provided separately by age and sex for non-HIspanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). BMD and BMC in the five ROI tended to decline with age, whereas area did not. BMD and BMC were highest in NHB, intermediate in MA and lowest in NHW, but areas were highest in NHW, intermediate in NHB and lowest in MA. Men had greater BMD, BMC and area than women in all three race/ethnic groups. Differences by age, sex or race/ethnicity tended to be the largest in Ward's triangle, followed by the femur neck; patterns in the trochanter, intertrochanter and total ROI were reasonably similar to each other. This report provides extensive data on femur bone mineral levels of adults from one of the largest samples available to date and should be valuable as reference data for other studies which examine this skeletal site in adults.

Adult↗
PubMed2003

Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age.

We measured the impact of diet, anthropometry, physical activity and lifestyle variables on rates of hip bone mineral density (BMD) loss in 470 white men and 474 white women aged 67-79 years at recruitment dwelling in the community. The subjects were recruited from a prospective population-based diet and cancer study (EPIC-Norfolk) in Eastern England. Dietary intake was measured at baseline using 7-day food diaries and used to calculate intakes of some 31 nutrients and 22 food groups. Standardised questionnaires were used to collect data on anthropometry, physical activity and lifestyle variables. BMD loss (percent per annum; % p.a.) was measured using dual-energy X-ray absorptiometry performed on two occasions an average of 3 years apart (range 2-5 years). The mean rate of BMD change at the total hip region was -0.17% p.a. (SD 1.3% p.a.) in men and -0.41% p.a. (SD 1.2% p.a.) in women. In both men and women, weight gain protected against (and weight loss promoted) BMD loss ( P<0.0001). Markers of current physical activity were protective. In men, an increase of 1 l/s in FEV(1) was associated with an increase in BMD at an average rate of 0.25% p.a. ( P=0.013). In women, for every ten trips made per day climbing a flight of stairs, BMD increased at a rate of 0.22% p.a. ( P=0.005) and additionally a 10% increase in activities of daily living score was associated with BMD increasing at a rate of 0.12% p.a. ( P=0.011) in women. Nutritional variation appeared to have less impact on BMD loss. In men there was no evidence of an effect of any of the nutrients evaluated. However, in women, low intake of vitamin C was associated with faster rate of BMD loss. Women in the lowest tertile (7-57 mg/day) of vitamin C intake lost BMD at an average rate of -0.65% p.a., which was significantly faster compared to loss rates in the middle (58-98 mg/day) and upper (99-363 mg/day) tertiles of intake, which were -0.31% p.a. and -0.30% p.a., respectively ( P=0.016). There was no effect of fruits and vegetables, combined or separately, on rate of BMD loss. The results confirm that weight maintenance (or gain) and commonly practiced forms of physical activity appear to protect against BMD loss in this age group. Measures such as ensuring good general nutrition to guard against weight loss in the non-overweight elderly and maintenance of physical fitness could be valuable in protecting against BMD loss. The protective effect of vitamin C in women needs to be further investigated in other prospective cohort or intervention studies.

Aged↗
PubMed2002

An association between respiratory function and bone mineral density in women from the general community: a cross sectional study.

Respiratory function has been associated with bone mineral density (BMD) in patients with respiratory diseases. We examined the relationship between bone density measured at the hip and respiratory function in women from the general community. A total of 4830 women aged 45-76 years were recruited from general practice age-sex registers in Cambridge between 1991 and 1995. At baseline survey, data collection included health questionnaires, measures of anthropometry, respiratory function, as well as bone mineral density BMD measured using dual energy X ray absorptiometry. BMD at total hip, femoral neck and trochanter significantly and positively correlated with FEV(1). This association was independent of age, weight, height, smoking habit, history of respiratory diseases, corticosteroids and use of hormone replacement therapy. After adjustment for these factors, an increase in FEV(1) of 1 l/s was associated with 0.026, 0.021 and 0.026g/cm(2) increase in bone mineral density at total hip, femoral neck and trochanter respectively. The association was consistent and similar in magnitude among current smokers and current non-smokers and across all age groups. The magnitude of the association was comparable to that associated with an age difference of 6 years or weight difference of 5 kg. Women in the bottom compared to top quartile of respiratory function had about double the risk of low bone density independent of other factors. Respiratory function measured using FEV(1) is positively and independently related to BMD in these middle-aged and older women across the whole normal distribution of these physiologic measures. This may reflect underlying common determinants such as physical activity. Even in healthy women, respiratory function may be a marker for women at increased risk of osteoporosis and associated fractures.

Aged↗
PubMedDate not supplied

Relationship of comorbid substance and alcohol use disorders to disability among patients in routine psychiatric practice.

The primary aim of this study was to present data on the relationship of mental and comorbid substance use disorders to work disability and functioning in routine psychiatric practice in the United States. Data were used from the 1997 and 1999 American Psychiatric Institute for Research and Education's Practice Research Network Study of Psychiatric Patients and Treatments, totaling 754 psychiatrists and 3,088 patients. Results found patients with comorbid substance use disorders had significantly higher rates of work disability. These findings highlight the critical need to address the disturbing lack of substance use treatment and rehabilitation services for this population.

Adult↗
PubMed2006

Use of a new cardiac pacing mode designed to eliminate unnecessary ventricular pacing.

AIMS: To examine the performance of AAIsafeR2, a new pacing mode to minimize the cumulative proportion of ventricular pacing in patients who do not need regular ventricular support. METHODS AND RESULTS: The safety of AAIsafeR2 was examined in 123 recipients (73 +/- 12 years old, 51% men) of dual chamber pacemakers implanted for sinus node dysfunction, paroxysmal AV block or the bradycardia-tachycardia syndrome. Data were collected from pacemaker diagnostics, and the first 43 patients underwent 24-h Holter recordings before being discharged from the hospital with AAIsafeR2 activated. No adverse event related to AAIsafeR2 was observed. All ventricular pauses detected on Holter tapes triggered immediate back-up ventricular pacing. Appropriate switches to DDD occurred in 97 of 123 patients. In 69 of 123 devices (56%) switches to DDD were non-sustained, and the average % ventricular pacing in this group was 0.2+/-0.5%. CONCLUSION: AAIsafeR2 mode seems to be safe and reliable in patients with infrequent slowing or pauses in ventricular activity, while maintaining ventricular pacing below 1%.

Aged↗
PubMed1998

Body composition in systemic lupus erythematosus.

The objectives were to determine the body composition, and the effects of disease and corticosteroid therapy on body composition, in a population of female patients with systemic lupus erythematosus (SLE). All female SLE patients managed through a single centre were invited to participate in a cross-sectional study of body composition. Data were collected by standardized interview and examination, and review of medical records. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Eighty-two subjects were evaluated, 30 of whom were post-menopausal. Univariate linear regression analysis revealed a significant association of reduced fat-free mass with SLE severity [as measured by the Systemic Lupus International Collaborative Clinics (SLICC)] (P = 0.020), a history of corticosteroid exposure (P = 0.043) and age (P = 0.048). Reduced total body bone mineral density (BMD) was also significantly associated with SLICC (P < 0.001) and corticosteroid exposure (P = 0.017), and with age (P < 0.001), post-menopausal status (P = 0.003) and the duration of menopause (P < 0.001). Stepwise multiple linear regression analysis revealed a significant association between fat-free mass and total body, lumbar spine and femoral neck BMD (P = 0.007, P = 0.025, P = 0.003, respectively). Fat mass was significantly associated only with lumbar spine BMD (P = 0.008). In this SLE population, disease severity and corticosteroid exposure were independently associated with a negative effect both on total body BMD and on fat-free mass. Fat-free mass was a significant predictor of lumbar spine, femoral neck and total body BMD.

Absorptiometry, Photon↗
PubMed2003

Multiple-dose safety and pharmacokinetics of oral garenoxacin in healthy subjects.

Garenoxacin (T-3811ME, BMS-284756) is a novel des-F(6) quinolone that has been shown to be effective in vitro against a wide range of clinically important pathogens, including gram-positive and gram-negative aerobes and anaerobes. This study was conducted to evaluate the safety and tolerability of multiple oral doses (100 to 1200 mg/day) of garenoxacin in healthy subjects and to determine its multiple-dose pharmacokinetics. Forty healthy male and female subjects (18 to 45 years of age) were enrolled in this randomized, double-blind, placebo-controlled, sequential, multiple- and ascending-dose study. Each subject received a once-daily oral dose of garenoxacin (100, 200, 400, 800, or 1200 mg) or a placebo for 14 days. Blood and urine samples were collected for measurements of garenoxacin by validated liquid chromatography with dual mass spectrometry, and plasma garenoxacin concentration-time data were analyzed by noncompartmental methods. The effects of garenoxacin on Helicobacter pylori, psychometric test performance, and electrocardiograms were assessed, as was drug safety. Over the 14 days of dosing, geometric mean peak concentrations of garenoxacin in plasma (C(max)) at the 100- and 1200-mg doses were within the ranges of 1.2 to 1.6 and 16.3 to 24 microg/ml, respectively. The corresponding values for the geometric mean area under the concentration-time curve over the dosing interval (AUC(tau)) for garenoxacin in plasma at the 100- and 1200-mg doses were within the ranges of 11.5 to 15.7 and 180 to 307 microg. h/ml, respectively. Increases in systemic exposure to garenoxacin in terms of AUC and C(max) were approximately dose proportional over the 100- to 400-mg dose range but demonstrated increases that were somewhat greater than the dose increments at the 800- and 1200-mg doses. Median values for the time to achieve C(max) were in the range of 1.13 to 2.50 h for all doses. The mean elimination half-life for garenoxacin in plasma appeared to be independent of dose and ranged from 13.3 to 17.8 h (day 14). Approximately 30 to 50% of an administered garenoxacin dose was excreted unchanged in the urine. At doses of 100 to 400 mg, steady-state concentrations of garenoxacin in plasma appeared to be attained by the fourth dose. Multiple oral doses of garenoxacin were well tolerated and did not demonstrate clinically significant effects on QT(c) or psychometric test results. Garenoxacin administered alone for 14 days at doses of >or=400 mg demonstrated activity against H. pylori. These results suggest that multiple once-daily oral doses of garenoxacin of up to 1200 mg are safe and well tolerated and that the pharmacokinetics of garenoxacin support once-daily administration.

Administration, Oral↗
PubMed1995

Heteronuclear NMR pulse sequences applied to biomolecules.

Current concepts in heteronuclear multidimensional NMR spectroscopy are reviewed. Methods to improve the sensitivity and the efficiency of data collection include constant time, compression through the overlap of chemical shift evolution and dephasing and rephasing periods, and dual or time-shared evolution. Two classes of three-dimensional and four-dimensional triple-resonance experiments applied to proteins are considered. The first class correlates 1H, 15N, and 13C signals of the protein backbone. The second class correlates both backbone and side-chain signals. Application of triple resonance to RNA is also discussed. Heteronuclear cross polarization (HCP) is considered as an alternative to INEPT transfer, and its application to nucleic acids is presented. Finally, two methods of employing pulsed field gradients (PFGs) are reviewed.

Magnetic Resonance Spectroscopy↗
PubMed2003

Measurement of intestinal cholesterol absorption by plasma and fecal dual-isotope ratio, mass balance, and lymph fistula methods in the mouse: an analysis of direct versus indirect methodologies.

The rate of intestinal cholesterol (Ch) absorption is an important criterion for quantitation of Ch homeostasis. However, studies in the literature suggest that percent Ch absorption, measured usually by a fecal dual-isotope ratio method, spans a wide range, from 20% to 90%, in healthy inbred mice on a chow diet. In the present study, we adapted four standard methods, one direct (lymph collection) and three indirect (plasma and fecal dual-isotope ratio, and sterol balance) measurements of Ch absorption and applied them to mice. Our data establish that all methodologies can be valid in mice, with all methods supporting the concept that gallstone-susceptible C57L mice absorb significantly more Ch (37 +/- 5%) than gallstone-resistant AKR mice (24 +/- 4%). We ascertained that sources of error in the literature leading to marked differences in Ch absorption efficiencies between laboratories relate to a number of technical factors, most notably expertise in mouse surgery, complete solubilization and delivery of radioisotopes, appropriate collection periods for plasma and fecal samples, and total extraction of radioisotopes from feces. We find that all methods provide excellent interexperimental agreement, and the ranges obtained challenge previously held beliefs regarding the spread of intestinal Ch absorption efficiencies in mice. The approaches documented herein provide quantifiable methodologies for exploring genetic mechanisms of Ch absorption, and for investigating the assembly and secretion of chylomicrons, as well as intestinal lipoprotein metabolism in mice.

Administration, Oral↗
PubMed2026

Longitudinal characterization of mixed-genotype SARS-CoV-2 infections in a military cohort reveals compartmentalized viral populations.

UNLABELLED: Mixed-genotype severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are a concern due to the potential generation of novel recombinants that give rise to new variants. To better understand intra-host viral dynamics, we analyzed specimens from 24 participants from the U.S. Military Health System's Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential COVID-19 cohort with suspected mixed-genotype SARS-CoV-2 infections. From an initial 24 suspected cases, we confirmed 17 as genuine coinfections and graded them by evidence: 7 were "strong"; 4 were "moderate"; 6 were "weak"; and 7 were deemed unlikely to be true mixed-genotype infections. Access to swabs from multiple body sites across the course of infection allowed us to observe compartmentalization and shifts in variant dominance that would have been missed by a single-timepoint analysis, as well as one recombinant Omicron BA.1/BA.2 genome. By using an evidence-based bioinformatic framework to assess sequencing data from well-characterized clinical cases, we distinguished genuine coinfections from bioinformatic artifacts. Our findings emphasize the importance of both extensive specimen collection and careful bioinformatic approaches in ascertaining dual genotype infections. IMPORTANCE: Novel recombinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) arise from coinfections with different lineages, but mixed infections are not screened for despite risk to public health, and most surveillance relies on single swabs. We analyzed a longitudinal data set with specimens from multiple body sites, providing an opportunity to assess intra-host dynamics. To distinguish true coinfection from bioinformatic artifacts with confidence, we applied a framework that grades evidence for mixed genotypes by incorporating lineage and clade with manually validated variant calls. This allowed investigation beyond abundance levels of mixed genotypes within a single specimen, including observations of compartmentalization and a recombinant virus. This work enables further study of evolutionary, immunological, and clinical implications of mixed SARS-CoV-2 genotypes. Detecting dual-genotype infections and discriminating between true dual-genotype infection vs potential bioinformatics-based artifacts support public health and military readiness. These efforts provide evidence to bolster decision-making in molecular epidemiological studies to track transmission and for the choice of effective countermeasures.

SARS-CoV-2↗
PubMed1994

Clinical, histologic and quantitative angiographic predictors of restenosis after directional coronary atherectomy: a multivariate analysis of the renarrowing process and late outcome.

OBJECTIVES: To characterize predictors of restenosis after successful directional atherectomy, we reviewed the clinical, angiographic and procedural data obtained during 132 consecutive procedures. METHODS: Clinical and angiographic follow-up data were obtained in a prospectively collected and consecutive series of 125 patients who underwent 132 atherectomy procedures for de novo (89%) or restenotic (11%) lesions in native coronary arteries. Restenosis was assessed clinically and by quantitative coronary angiography. A dual approach to data analysis was taken to gain insight into factors affecting the clinical outcome and vessel wall healing response. Therefore, multivariate analysis was performed to 1) determine the correlates of residual lumen diameter at follow-up (angiographic outcome), and 2) characterize the determinants of the late lumen loss (renarrowing process). RESULTS: Clinical and angiographic follow-up data after successful atherectomy were obtained in 100% and 95%, respectively. Atherectomy achieved an acute lumen gain of 1.28 +/- 0.48 mm (mean +/- SD), resulting in a minimal lumen diameter of 2.44 +/- 0.47 mm. At follow-up, the minimal lumen diameter decreased to 1.78 +/- 0.64 mm. The angiographic restenosis rate was 28% if the traditional 50% stenosis cutoff criterion was applied. Larger vessel size and postatherectomy minimal lumen diameter and right coronary or left circumflex artery lesions were independent predictors of a larger minimal lumen diameter (angiographic outcome). Lumen loss during follow-up (renarrowing process) was independently predicted by relative lumen gain and preprocedural minimal lumen diameter. CONCLUSIONS: In analyzing the long-term results of new interventional techniques such as directional atherectomy, the late lumen loss during follow-up (renarrowing process), which is characterized by the vessel wall healing response after an intervention, should be considered together with the residual lumen diameter at follow-up (clinical outcome). It is clear that whereas improved clinical outcome is associated with larger vessel size and postprocedural lumen diameter and non-left anterior descending artery location, greater relative gain at intervention is predictive of more extensive lumen renarrowing.

Aged↗