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OBJECTIVE: Case reports of postvaccine early-onset Graves' hyperthyroidism (PVGD) after the administration of COVID-19 vaccination have emerged. Our aim was to investigate whether the incidence of Graves' hyperthyroidism (GD) has increased after the introduction of COVID-19 vaccination. METHODS: We compared the incidence of new-onset GD at a single academic center during 2 periods: December 2017 to October 2019 and December 2020 to October 2022, ie, before and after the implementation of COVID-19 vaccinations. We defined PVGD as laboratory-confirmed hyperthyroidism and GD within 4 weeks after the vaccination or clear onset of symptoms of thyrotoxicosis within 4 weeks of vaccination with evidence of hyperthyroidism and GD within 3 months. RESULTS: During the prevaccination period, 803 patients carried diagnoses of GD, and of these, 131 were new. During the postvaccination period, 901 patients carried diagnoses of GD, and of these, 138 were new. There was no statistically significant difference in the incidence of GD (P = .52), age at onset, gender, or race between the 2 groups. Twenty-four of 138 newly diagnosed patients in the post-COVID-19 group met the criteria for PVGD. The median free T4 was higher, but this was not statistically significant (3.9 vs 2.5 ng/dL, P = .05). There were no differences in age, gender, race, antibody titers, or type of vaccination between PVGD and controls. CONCLUSION: There was no increase in new-onset GD after COVID-19 vaccination. Median free T4 was higher in patients with PVGD, but this was not statistically significant.
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COVID-19 , Doença de Graves , Hipertireoidismo , Humanos , Doença de Graves/epidemiologia , Doença de Graves/diagnóstico , Incidência , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hipertireoidismo/epidemiologiaRESUMO
Pheochromocytomas are catecholamine-producing tumors and a rare cause of sudden cardiac death. We describe the case of a previously healthy 28-year-old man who presented after a ventricular fibrillation out-of-hospital cardiac arrest (OHCA). His clinical investigation, including a coronary evaluation, was unremarkable. A protocolized head-to-pelvis computed tomography (CT) scan was ordered and revealed a large right adrenal mass with subsequent laboratory studies showing markedly elevated urine and plasma catecholamines. This raised suspicion for a pheochromocytoma as the underlying etiology behind his OHCA. He received appropriate medical management, underwent adrenalectomy with subsequent normalization of his metanephrines, and fortunately did not have recurrent arrythmias. This case highlights the first documented case of a ventricular fibrillation arrest as the initial presentation of pheochromocytoma crisis in a previously healthy individual, and how the use of early protocolized sudden death CT scan allowed for the prompt diagnosis and management of a rare cause of OHCA. Learning objective: We review the typical cardiac manifestations of pheochromocytoma and describe the first case of a pheochromocytoma crisis presenting as sudden cardiac death (SCD) in a previously asymptomatic individual. In young patients with unexplained SCD, it is important to consider pheochromocytoma in the differential diagnosis. We also review why an early head-to-pelvis sudden death computed tomography scan protocol may be helpful in the evaluation of patients resuscitated from SCD without an obvious etiology.
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OBJECTIVE: Meal intake is sometimes reduced in hospitalized patients. Meal-time insulin administration can cause hypoglycemia when a meal is not consumed. Inpatient providers may avoid ordering meal-time insulin due to hypoglycemia concerns, which can result in hyperglycemia. The frequency of reduced meal intake in hospitalized patients remains inadequately determined. This quality improvement project evaluates the percentage of meals consumed by hospitalized patients with insulin orders and the resulting risk of postmeal hypoglycemia (blood glucose [BG] <70 mg/dL, <3.9 mmol/L). METHODS: This was a retrospective quality improvement project evaluating patients with any subcutaneous insulin orders hospitalized at a regional academic medical center between 2015 and 2017. BG, laboratory values, point of care, insulin administration, diet orders, and percentage of meal consumed documented by registered nurses were abstracted from electronic health records. RESULTS: Meal consumption ≥50% was observed for 85% of meals with insulin orders, and bedside registered nurses were accurate at estimating this percentage. Age ≥65 years was a risk factor for reduced meal consumption (21% of meals 0%-49% consumed, P < .05 vs age < 65 years [12%]). Receiving meal-time insulin and then consuming only 0% to 49% of a meal (defined here as a mismatch) was not rare (6% of meals) and increased postmeal hypoglycemia risk. However, the attributable risk of postmeal hypoglycemia due to this mismatch was low (4 events per 1000) in patients with premeal BG between 70 and 180 mg/dL. CONCLUSION: This project demonstrates that hospitalized patients treated with subcutaneous insulin have a low attributable risk of postmeal hypoglycemia related to inadequate meal intake.
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Hiperglicemia , Hipoglicemia , Idoso , Glicemia , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Refeições , Estudos RetrospectivosRESUMO
OBJECTIVES: This case series was designed to educate and inform health care professionals on the importance of providing adequate education on injectable antidiabetic agents and highlighting common medication errors related to diabetes care seen in ambulatory practice. The discussion following case descriptions will attempt to characterize patients who may be at high risk for these errors and identify ways to reduce the potential for error. CASE SUMMARY: In a diabetes care clinic, 4 cases were identified in which the patient experienced an escalation of insulin or other injectable antidiabetic medication doses with no improvement in glycemic control. Two of the cases involved failure to remove an inner needle cap because of a poor understanding of pen use. One case was attributed to switching formulations without providing proper education for an adult patient with a learning impairment, and the other was attributed to suboptimal absorption of insulin doses from lipohypertrophy. Three of the 4 cases resulted in multiple instances of hypoglycemia, and all 4 patients exhibited markedly improved glycemic control once the injection error was corrected. The clinic pharmacist played an essential role in identifying and correcting administration errors within an interdisciplinary team. PRACTICE IMPLICATIONS: Based on the observations from the 4 cases, clinicians should be prompted to review antidiabetic medication injection techniques before initiation and periodically thereafter with their patients. Factors that should prompt further education include low health literacy, language barrier, initiation of medication by another provider, switch of medication product or formulation, obvious discrepancies between refill history and patient's self-reported adherence, observed lipohypertrophy, and escalation of doses without any improvement in glycemic control. A referral to the clinic pharmacist should be considered to provide more detailed education for these patients.
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Diabetes Mellitus , Hipoglicemia , Adulto , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina , Erros de Medicação/prevenção & controleRESUMO
BACKGROUND: In the current version of The Bethesda System (TBS) for thyroid cytopathology, the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has an estimated risk of malignancy of 10% to 30%. Diagnostic criteria include presence of nuclear atypia, suggestive of papillary thyroid carcinoma (PTC), as well as other types of atypia, which can be seen with non-malignant entities. Aim of this study was to investigate differential outcomes of AUS/FLUS, based on specific morphologic criteria, and assess their respective malignancy risks. METHODS: From a total of 1233 patients undergoing thyroid FNAs between 2010 and 2014 at the University of Washington, 119 had AUS/FLUS without nuclear atypia, and 64 with nuclear atypia. Outcomes for patients with and without nuclear atypia (with the exception of 24 patients lost to follow-up) were evaluated and results were compared. RESULTS: 16/57 (28.1%) patients with AUS/FLUS and nuclear atypia subsequently had carcinomas on thyroidectomy, statistically higher than the 8/102 patients (7.8%, P = .001) without nuclear atypia. When comparing only patients who underwent surgery (n = 63), again those with AUS/FLUS and nuclear atypia had statistically higher rates of carcinoma (16/31, 51.6%), compared to those without (8/32, 25%; P = .0394). Overall, 24/159 (15.1%) of patients with AUS/FLUS had carcinoma on subsequent histology. CONCLUSION: Malignancy rates for AUS/FLUS were in line with TBS estimated risks. However, our data demonstrate that the presence or absence of nuclear atypia is associated with different malignancy rates, suggesting the possibility that the AUS/FLUS category may best be split into two subcategories with different implied risks of malignancy.
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Lesões Pré-Cancerosas/classificação , Lesões Pré-Cancerosas/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/patologia , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Lesões Pré-Cancerosas/diagnóstico , Neoplasias da Glândula Tireoide/diagnósticoRESUMO
BACKGROUND: Hospitals rely on point-of-care (POC) blood glucose (BG) values to guide important decisions related to insulin administration and glycemic control. Evaluation of POC BG in hospitalized patients is associated with measurement and operator errors. Based on a previous quality improvement (QI) project we introduced an option for operators to delete and repeat POC BG values suspected as erroneous. The current project evaluated our experience with deleted POC BG values over a 2-year period. METHOD: A retrospective QI project included all patients hospitalized at two regional academic medical centers in the Pacific Northwest during 2014 and 2015. Laboratory Medicine POC BG data were reviewed to evaluate all inpatient episodes of deleted and repeated POC BG. RESULTS: Inpatient operators choose to delete and repeat only 0.8% of all POC BG tests. Hypoglycemic and extreme hyperglycemic BG values are more likely to be deleted and repeated. Of initial values <40 mg/dL, 58% of deleted values (18% of all values) are errors. Of values >400 mg/dL, 40% of deleted values (5% of all values) are errors. Not all repeated POC BG values are first deleted. Optimal use of the option to delete and repeat POC BG values <40 mg/dL could decrease reported rates of severe hypoglycemia by as much as 40%. CONCLUSIONS: This project demonstrates that operators are frequently able to identify POC BG values that are measurement/operator errors. Eliminating these errors significantly reduces documented rates of severe hypoglycemia and hyperglycemia, and has the potential to improve patient safety.
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Glicemia/análise , Confiabilidade dos Dados , Diabetes Mellitus/sangue , Diabetes Mellitus/enfermagem , Testes Imediatos , Humanos , Sistemas Automatizados de Assistência Junto ao Leito/normas , Garantia da Qualidade dos Cuidados de Saúde , Estudos RetrospectivosRESUMO
Type 2 diabetes (T2DM) is a common condition. Treatment of diabetes and related complications can be complex. In addition to lifestyle changes, medications play an important role in controlling patients' blood glucose levels and preventing complications. From an individual and societal standpoint, it is also an expensive disease. Medical spending attributed to diabetes per individual is significant. With appropriate therapy, patients can lead full, healthy lives with the disease, so making informed decisions regarding pharmacotherapy for T2DM is clearly of great importance.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Envelhecimento , Glicemia , Peso Corporal , Diabetes Mellitus Tipo 2/complicações , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Vias de Administração de Medicamentos , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/economia , Insulina/uso terapêutico , Metformina/uso terapêutico , Insuficiência Renal/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêuticoRESUMO
Many therapeutic hypothermia recommendations have been reported, but the information supporting them is sparse, and reveals a need for the data of target therapeutic hypothermia (TTH) from well-controlled experiments. The core temperature ≤35°C is considered as hypothermia, and 29°C is a cooling injury threshold in pig heart in vivo. Thus, an optimal protective hypothermia (OPH) should be in the range 29-35°C. This study was conducted with a pig cardiopulmonary bypass preparation to decrease the core temperature to 29-35°C range at 20 minutes before and 60 minutes during heart arrest. The left ventricular (LV) developed pressure, maximum of the first derivative of LV (dP/dtmax), cardiac power, heart rate, cardiac output, and myocardial velocity (Vmax) were recorded continuously via an LV pressure catheter and an aortic flow probe. At 20 minutes of off-pump during reperfusion after 60 minutes arrest, 17 hypothermic hearts showed that the recovery of Vmax and dP/dtmax established sigmoid curves that consisted of two plateaus: a good recovery plateau at 29-30.5°C, the function recovered to baseline level (BL) (Vmax=118.4%±3.9% of BL, LV dP/dtmax=120.7%±3.1% of BL, n=6); another poor recovery plateau at 34-35°C (Vmax=60.2%±2.8% of BL, LV dP/dtmax=28.0%±5.9% of BL, p<0.05, n=6; ), which are similar to the four normothermia arrest (37°C) hearts (Vmax=55.9%±4.8% of BL, LV dP/dtmax=24.5%±2.1% of BL, n=4). The 32-32.5°C arrest hearts showed moderate recovery (n=5). A point of inflection (around 30.5-31°C) existed at the edge of a good recovery plateau followed by a steep slope. The point presented an OPH that should be the TTH. The results are concordant with data in the mammalian hearts, suggesting that the TTH should be initiated to cool core temperature at 31°C.
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Parada Cardíaca/terapia , Hipotermia Induzida/métodos , Animais , Soluções Cardioplégicas/farmacologia , Ponte de Artéria Coronária/métodos , Modelos Animais de Doenças , Parada Cardíaca Induzida/métodos , Hemodinâmica/fisiologia , Masculino , Projetos Piloto , Recuperação de Função Fisiológica/fisiologia , Sus scrofa , SuínosRESUMO
BACKGROUND: Hypoglycaemia is associated with morbidity and mortality in critically ill patients, and many hospitals have programmes to minimize hypoglycaemia rates. Recent studies have established the hypoglycaemic patient-day as a key metric and have published benchmark inpatient hypoglycaemia rates on the basis of point-of-care blood glucose data even though these values are prone to measurement errors. METHODS: A retrospective, cohort study including all patients admitted to Harborview Medical Center Intensive Care Units (ICUs) during 2010 and 2011 was conducted to evaluate a quality improvement programme to reduce inappropriate documentation of point-of-care blood glucose measurement errors. Laboratory Medicine point-of-care blood glucose data and patient charts were reviewed to evaluate all episodes of hypoglycaemia. RESULTS: A quality improvement intervention decreased measurement errors from 31% of hypoglycaemic (<70 mg/dL) patient-days in 2010 to 14% in 2011 (p < 0.001) and decreased the observed hypoglycaemia rate from 4.3% of ICU patient-days to 3.4% (p < 0.001). Hypoglycaemic events were frequently recurrent or prolonged (~40%), and these events are not identified by the hypoglycaemic patient-day metric, which also may be confounded by a large number of very low risk or minimally monitored patient-days. CONCLUSIONS: Documentation of point-of-care blood glucose measurement errors likely overestimates ICU hypoglycaemia rates and can be reduced by a quality improvement effort. The currently used hypoglycaemic patient-day metric does not evaluate recurrent or prolonged events that may be more likely to cause patient harm. The monitored patient-day as currently defined may not be the optimal denominator to determine inpatient hypoglycaemic risk.
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Glicemia/análise , Cuidados Críticos , Erros de Diagnóstico/prevenção & controle , Hipoglicemia/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Centros Médicos Acadêmicos , Adulto , Estudos de Coortes , Monitoramento de Medicamentos , Registros Eletrônicos de Saúde , Humanos , Hipoglicemia/sangue , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Infusões Intravenosas , Insulina/administração & dosagem , Insulina/efeitos adversos , Unidades de Terapia Intensiva , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade , Recidiva , Reprodutibilidade dos Testes , Estudos Retrospectivos , Risco , Washington/epidemiologiaRESUMO
Plasma levels of the orexigenic hormone ghrelin are suppressed by meals with an efficacy dependent on their macronutrient composition. We hypothesized that heterogeneity in osmolarity among macronutrient classes contributes to these differences. In three studies, the impact of small intestinal hyperosmolarity was examined in Sprague-Dawley rats. In study 1, isotonic, 2.5×, and 5× hypertonic solutions of several agents with diverse absorption and metabolism properties were infused duodenally at a physiological rate (3 ml/10 min). Jugular vein blood was sampled before and at 30, 60, 90, 120, 180, 240, and 300 min after infusion. Plasma ghrelin was suppressed dose dependently and most strongly by glucose. Hyperosmolar infusions of lactulose, which transits the small intestine unabsorbed, and 3-O-methylglucose (3-O-MG), which is absorbed like glucose but remains unmetabolized, also suppressed ghrelin. Glucose, but not lactulose or 3-O-MG, infusions increased plasma insulin. In study 2, intestinal infusions of hyperosmolar NaCl suppressed ghrelin, a response that was not attenuated by coinfusion with the neural blocker lidocaine. In study 3, we reconfirmed that the low-osmolar lipid emulsion Intralipid suppresses ghrelin more weakly than isocaloric (but hypertonic) glucose. Importantly, raising Intralipid's osmolarity to that of the glucose solution by nonabsorbable lactulose supplementation enhanced ghrelin suppression to that seen after glucose. Hyperosmolar ghrelin occurred particularly during the initial 3 postinfusion hours. We conclude that small intestinal hyperosmolarity 1) is sufficient to suppress ghrelin, 2) may combine with other postprandial mechanisms to suppress ghrelin, 3) might contribute to altered ghrelin regulation after gastric bypass surgery, and 4) may inform dietary modifications for metabolic health.
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Grelina/metabolismo , Intestino Delgado/metabolismo , Período Pós-Prandial/fisiologia , Animais , Glicemia/metabolismo , Veias Jugulares/cirurgia , Masculino , Concentração Osmolar , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21 °C to 28 °C) rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40 ± 1%) and dark cycle energy expenditure (15 ± 3%) at normal ambient temperature (21 °C). Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65 ± 7%), thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14 ± 2% at 21 °C; 21 ± 4% at 28 °C), while food intake was reduced during the dark cycle (0.9 ± 0.1 g) in mice housed at 28 °C, but during the light cycle (0.3 ± 0.1 g) in mice housed at 21 °C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R(2) = 0.51, p<0.01). We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure.
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Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Animais , Composição Corporal/fisiologia , Calorimetria Indireta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , TemperaturaRESUMO
OBJECTIVE: Maternal-fetal cell transfer during pregnancy can lead to long-lasting microchimerism, which raises the question of whether microchimerism sometimes contributes to autoimmune disease later in life. In an experimental model, transfusion of parental lymphocytes homozygous for major histocompatibility complex alleles results in systemic lupus erythematosus (SLE). We identified male patients with SLE and healthy male subjects and their mothers in order to investigate the mother-son HLA relationship in SLE risk. Male subjects were selected in order to avoid confounding due to fetal microchimerism, which may occur in women. METHODS: HLA genotyping for DRB1, DQA1, and DQB1 was conducted for sons and their mothers. Thirty men with SLE and their mothers were compared with 76 healthy men and their mothers. RESULTS: Sons with SLE were HLA-identical with their mothers (bidirectionally compatible) for the basic HLA-DRB1 groups encoded by DRB1*01 through DRB1*14 more often than were healthy sons (odds ratio [OR] 5.0, P = 0.006). Each DRB1 group contains multiple allelic variants; male patients with SLE and their mothers often were identical for both DRB1 allelic variants (OR 3.2, P = 0.08). For DQA1 and DQB1, the ORs were 2.3 (P = 0.08) and 2.0 (P = 0.21), respectively. When analysis was limited to male subjects with SLE-associated HLA genes (encoding HLA-DR2 or HLA-DR3), the differences further increased for DRB1 basic groups (OR 7.2, P = 0.01), DRB1 alleles (OR 15.0, P = 0.018), DQA1 6.4 (P = 0.006), and DQB1 (OR 5.7, P = 0.027). No increase in (unidirectional) compatibility of the mother from the son's perspective was observed at any locus. CONCLUSION: We observed increased bidirectional HLA class II compatibility of male SLE patients and their mothers compared with healthy men and their mothers. This observation implies that maternal microchimerism could sometimes be involved in SLE and therefore merits further investigation.
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Genes MHC da Classe II/genética , Predisposição Genética para Doença , Antígenos HLA-DR/genética , Histocompatibilidade/genética , Lúpus Eritematoso Sistêmico/genética , Mães , Adolescente , Adulto , Criança , Pré-Escolar , Saúde da Família , Feminino , Frequência do Gene , Genes MHC da Classe II/imunologia , Genótipo , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Histocompatibilidade/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
Syngeneic graft-versus-host disease (sGVHD) has been described after hematopoietic cell transplantation (HCT) but remains poorly defined. We retrospectively reviewed adult syngeneic HCTs at our center (1980-2002) for sGVHD to investigate incidence, morbidity, and risk factors with a primary focus on parity. Among 119 transplantations, there were 21 cases of biopsy-proven sGVHD. The cumulative incidence was 18%, with multiorgan involvement in 6 cases and 1 death. sGVHD was more frequent when the donor was parous (32%) than nulliparous (9%) or male (13%; P =.03) and when the recipient was parous (31%) than nulliparous (7%) or male (13%; P =.02). Other univariable risk factors included older age (P <.01), busulfan/melphalan/thiotepa conditioning (P <.01), interleukin-2 (P =.02), HLA-A26 (P =.03), and more recent transplantation year (P <.01). Overall, risk factors were similar to those described in GVHD. Although an independent effect of parity could not be completely separated from other factors, donor and recipient pregnancy history merits further investigation.
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Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Increased risk of graft-versus-host disease (GVHD) has been described in recipients of hematopoietic stem cell transplantations when the donor is a parous woman. Cells from prior pregnancies are now known to persist in women and could contribute to GVHD. We asked whether male DNA (presumed fetal microchimerism) is present in apheresis products of female donors. A total of 50 samples were studied by using real-time quantitative polymerase chain reaction (PCR) for the Y chromosome-specific sequence DYS14. Among 29 growth factor-mobilized peripheral blood mononuclear cell (G-PBMC) products, 34% were positive for male DNA. Quantitative results, expressed as DNA genome equivalent of male cells per million host cells (gEq/mil), ranged from 0 to 35 gEq/mil. Among 21 CD34-enriched cell fractions, 48% were positive with a range of 0 to 357 gEq/mil. In summary, male DNA was frequently detected in G-PBMC and CD34-enriched products from female donors. Whether fetal microchimerism contributes to GVHD merits further investigation.
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Remoção de Componentes Sanguíneos/normas , Quimera , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antígenos CD34 , Doadores de Sangue , Cromossomos Humanos Y , DNA/análise , Feminino , Humanos , Masculino , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Reação em Cadeia da Polimerase , GravidezRESUMO
Male DNA, of presumed fetal origin, can be detected in the maternal circulation decades after delivery and is referred to as fetal microchimerism (FM). We previously found quantitatively greater FM in the circulation of women with the autoimmune disease scleroderma (SSc) than of healthy women. However, it is unknown whether this difference is due to intact circulating cells or free DNA released from breakdown in disease-affected tissues. To distinguish the origin of FM, we developed a real-time quantitative polymerase chain reaction (PCR) assay for the Y-chromosome-specific sequence DYS14, and tested 114 women in peripheral blood mononuclear cells (PBMCs) and/or plasma. Fifty-seven controls and 57 SSc patients were studied, 48 and 43 of whom, respectively, had given birth to at least one son. Circulating FM was quantitatively greater in PBMCs from SSc patients (n = 39; range, 0.0-12.5 male genome-equivalent cells per million maternal cells), compared with healthy women (n = 39; range, 0.0-4.4; P =.03). In contrast, there was no difference between patients (n = 25) and controls (n = 22) in plasma, and no evidence of free DNA. FM was enriched among T lymphocytes compared with PBMCs (P =.01) in controls (n = 14), but not in SSc patients (n = 14); the latter finding was most likely due to immunosuppressive medications. In conclusion, this real-time quantitative assay showed that quantitative differences in the circulation of women with SSc are due to cells and not to free DNA. As FM was not uncommon in healthy women, including among T cells, and because graft-versus-host disease has similarities to SSc, these results also suggest that FM merits investigation in pheresis products used for stem cell transplantation.