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OBJECTIVE: To assess the efficacy and safety of a new surgical approach for uterine preservation among patients with placenta accreta spectrum in a low-resource setting. METHODS: The present prospective cohort included 63 women diagnosed with placenta accreta spectrum undergoing cesarean deliveries who desired future fertility at the obstetrics department of Menoufia University Hospital from January 2018 to November 2019. Surgical management involved direct bilateral uterine arteries clamping below placental bed after broad ligament opening by round ligaments division and ligation and gentle downward dissection of vesical from myometrial tissues from lateral aspect toward trigone of the bladder. Outcomes included intraoperative and postoperative adverse events, hysterectomy rate, and postoperative hospitalization. RESULTS: Mean operative blood loss was 1860 ± 537 mL (range, 1040-3111 mL) and the incidence of bladder and ureteric injuries were 6.3% (n = 4) and 0%, respectively. The mean length of hospital stay was 4.46 ± 1.39 days. Overall, 7 patients (11.1%) required postoperative blood transfusion, and 2 patients (3.2%) required ICU admission. Five patients required peripartum hysterectomy (7.9%). CONCLUSION: Our conservative surgical approach is a safe alternative to peripartum hysterectomy with high uterine preservation rate, less intraoperative and postoperative morbidity and less need for blood transfusion in low resource settings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; NCT04161521.
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Placenta Accreta , Placenta Previa , Hemorragia Posparto , Cesárea/métodos , Femenino , Humanos , Histerectomía/métodos , Placenta , Placenta Accreta/cirugía , Placenta Previa/cirugía , Hemorragia Posparto/cirugía , Embarazo , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
The purpose of this study was to compare the short-term operative outcomes of three different surgical techniques for uterine incision closure during caesarean section (CS). This trial enrolled 120 patients scheduled for primary caesarean delivery. Patients were randomised into either classical double-layer uterine closure, purse-string double-layer uterine closure (Turan), or our new approach of uterine closure (double layer step up-step down technique). For short-term comparison, transvaginal ultrasonography was planned for all patients 6 weeks after surgery. Compared to group II and Group III, residual myometrial thickness was significantly thinner in group I (p < .001). The number of patients with uterine niche was 10 (50% of all scar defects) in group I whereas it was 4 (20%) in group II and 6 (30%) in group III. Operative time was significantly longer in group II (p < .001). This led to our conclusion that Turan technique and our new approach are associated with thicker myometrial thickness and less frequency of uterine scar defect than classical double-layer uterine incision closure; however, our approach takes less operative time. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04681378Impact statementWhat is already known on this subject? Many variations in CS technique have been studied. For example, single-layer uterine incision closure has been compared to double-layer uterine incision closure. Purse string double layer (Turan) has been also compared to the traditional double-layer technique. Double layer unlocked closure has been shown to result in a thicker residual myometrium and as a consequence can possibly lead to the decrease of niche development after a CS compared to single-layer closure with lower frequency of uterine scar defect with Turan technique.What do the results of this study add? Here we introduce a new uterine closure technique, which we have named double-layer step up-step down technique, as an alternative method. With this technique, the uterine incision contract more than with the traditional double layer technique and has similar results to the Turan technique; however, our approach takes less operative time.What are the implications of these findings for clinical practice and/or further research? These alternative techniques of uterine incision closure decrease the frequency of uterine niche that may be associated with many clinical problems such as ectopic pregnancy at the CS scar, placenta accreta, rupture of the uterus during a subsequent pregnancy. Future studies are needed to investigate the frequency of uterine rupture in a subsequent pregnancy following different uterine incision closure techniques.
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Cesárea , Técnicas de Sutura , Cesárea/efectos adversos , Cesárea/métodos , Cicatriz/etiología , Cicatriz/cirugía , Femenino , Humanos , Histerotomía , Embarazo , Útero/cirugíaRESUMEN
OBJECTIVE: The aim of the present study was to evaluate the effect of autologous platelet-rich plasma (PRP) on wound healing and pain perception after cesarean section in high-risk patients. DESIGN: This was a prospective randomized controlled trial. Participants/Materials, Settings, and Methods: This was a randomized controlled trial of 200 patients who came to the outpatient clinic of Menoufia University Hospital for elective cesarean surgery. The women were randomly assigned to 2 equal groups. The intervention group received PRP subcutaneous injection in the wound after surgery; however, the control group received the usual care. Outcome variables included the redness, edema, ecchymosis, discharge, approximation (REEDA) scale, Vancouver scar scale (VSS), and in addition to the visual analog scale (VAS). RESULTS: From April 2018 to July 2020, the PRP group showed a greater reduction in the REEDA score compared to the control group on day 1, day 7, and this was continued till 6 months (1.51 ± 0.90 vs. 2.49 ± 1.12, p < 0.001). Compared with the control group, the PRP group had a significantly greater reduction in the VSS and VAS scores beginning on the seventh day (3.71 ± 0.99 vs. 4.67 ± 1.25, p < 0.001) and (5.06 ± 1.10 vs. 6.02 ± 1.15, p < 0.001), respectively, and continued till 6 months. LIMITATIONS: Pain was not measured by the use of analgesics, and we did not investigate the effects of varying platelet concentrations, centrifuge duration, or speed. CONCLUSIONS: PRP has positive effects on wound healing and pain reduction in high-risk patients undergoing cesarean section in low-resource settings.
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Cesárea , Plasma Rico en Plaquetas , Femenino , Humanos , Percepción del Dolor , Embarazo , Estudios Prospectivos , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
Necrotizing fasciitis is an uncommon and potentially fatal infection that can affect the epidermis, dermis, and more commonly the subcutaneous, fascia, and muscle layers. NF is usually caused by toxin-producing bacteria with a relatively fast progression associated with severe surrounding tissue destruction. Early diagnosis and management are crucial factors for survival. Broad-spectrum antibiotics along with surgical debridement, sometimes multiple, are needed in order to stop or slow down the progression of NF. Despite optimal care, necrotizing fasciitis remains a highly morbid condition with a high mortality rate. We present a case of a 28-year-old male patient with rapidly developing fatal A. baumannii associated with necrotizing fasciitis, after open reduction and internal fixation (ORIF) of multiple fractures after polytrauma.
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Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease resulting from abnormal interactions between T and B cells. The acquisition of SLE is linked to genetic susceptibility, and diverse environmental agents can trigger disease onset in genetically susceptible individuals. However, the strongest risk factor for developing SLE is being female (9:1 female to male ratio). The female sex steroid, estradiol, working through its receptors, contributes to the gender bias in SLE although the mechanisms remain enigmatic. In a small clinical trial, monthly administration of the estrogen receptor (ERα) antagonist, ICI182,780 (fulvestrant), significantly reduced disease indicators in SLE patients. In order to identify changes that could account for improved disease status, the present study utilized fulvestrant (Faslodex) to block ERα action in cultured SLE T cells that were purified from blood samples collected from SLE patients (n = 18, median age 42 years) and healthy control females (n = 25, median age 46 years). The effects of ERα antagonism on estradiol-dependent gene expression and canonical signaling pathways were analyzed. Pathways that were significantly altered by addition of Faslodex included T helper (Th) cell differentiation, steroid receptor signaling [glucocorticoid receptor (GR), ESR1 (ERα)], ubiquitination, and sumoylation pathways. ERα protein expression was significantly lower (p < 0.018) in freshly isolated, resting SLE T cells suggesting ERα turnover is inherently faster in SLE T cells. In contrast, ERα/ERß mRNA and ERß protein levels were not significantly different between SLE and normal control T cell samples. Plasma estradiol levels did not differ (p > 0.05) between SLE patients and controls. A previously undetected interaction between GR and ERα signaling pathways suggests posttranslational modification of steroid receptors in SLE T cells may alter ERα/GR actions and contribute to the strong gender bias of this autoimmune disorder.
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Estradiol/metabolismo , Antagonistas del Receptor de Estrógeno/farmacología , Fulvestrant/farmacología , Lupus Eritematoso Sistémico/inmunología , Factores Sexuales , Linfocitos T Colaboradores-Inductores/fisiología , Adulto , Células Cultivadas , Femenino , Regulación de la Expresión Génica , Interacción Gen-Ambiente , Humanos , Masculino , Persona de Mediana Edad , Receptores de Glucocorticoides/metabolismo , Factores de Riesgo , Transducción de Señal , Sumoilación , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Ubiquitinación , Adulto JovenRESUMEN
Medial epicondyle entrapment after an acute fracture dislocation of the elbow is a common finding in the pediatric population, but a rare finding in adults. We present a case of an adult patient diagnosed with a traumatic fracture dislocation of the elbow joint with intra-articular entrapment of the medial epicondyle. After initial evaluation, closed reduction was done. Stability testing after reduction showed an unstable joint; thus, open reduction and internal fixation was decided.
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OBJECTIVES: The aims of this study were to compare three different interventions to reduce pain related to insertion of the intrauterine device (IUD), namely, lidocaine, misoprostol and a non-steroidal anti-inflammatory drug, against a placebo, and to assess the advantages of one drug over another, if any. METHODS: This was an open-label randomised placebo-controlled trial of 200 women assigned to receive one of the following medications prior to IUD insertion: 10 ml 1% lidocaine paracervical block, 400 µg oral misoprostol, oral naproxen or placebo tablets. The primary outcome measure was the level of pain experienced at different steps of IUD insertion and 15 min after the procedure, measured by a visual analogue scale (VAS). RESULTS: Between July 2015 and March 2016, 208 women were invited to participate in the study: eight refused and the remaining 200 women were randomised equally into four treatment groups (50 participants in each group). All characteristics were similar between the groups. The mean pain scores recorded during speculum placement, tenaculum application, uterine sounding, IUD insertion and 15 min after insertion were similar among the four groups (p > .05). Adjuvant methods to facilitate insertion, insertion failure or device expulsion were similar between the groups (p > .05). Complications were reported in 17 participants (8.5%); all resolved spontaneously with no further management (p > .05). CONCLUSION: Despite finding that none of the study drugs seemed effective prior to IUD insertion, insertion did not cause severe pain. The negative findings indicate the need for future research into new strategies to decrease pain during IUD placement.
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Analgésicos/administración & dosificación , Dispositivos Intrauterinos/efectos adversos , Manejo del Dolor/métodos , Dolor Asociado a Procedimientos Médicos/prevención & control , Dolor Pélvico/prevención & control , Implantación de Prótesis/efectos adversos , Adulto , Anestésicos Locales/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Femenino , Humanos , Lidocaína/administración & dosificación , Misoprostol/administración & dosificación , Naproxeno/administración & dosificación , Oxitócicos/administración & dosificación , Dolor Pélvico/etiología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To investigate the effect of endometrial injury on pregnancy outcomes among infertile women taking clomifene citrate. METHODS: A prospective randomized trial was undertaken at an Egyptian hospital between January 26, 2015, and July 17, 2016. Eligible women (≥1 year primary/secondary/unexplained infertility, aged 20-35 years, day-2 follicle-stimulating hormone <12 IU/L, normal prolactin/thyroid function/uterine cavity, ≥1 patent tube, male partner with normal semen count and motility, 3 cycles of clomifene citrate without success) were randomly allocated (1:1) using computer-generated numbers into intervention (received endometrial injury on cycle day 15-24) or control groups (sham procedure). Women began ovulation induction on days 3-5 of the following cycle. Participants and investigators were not masked to group assignment. The primary outcomes were clinical pregnancy, spontaneous abortion, and multiple pregnancy rates. Women who completed follow-up were included in analyses. RESULTS: The intervention group included 52 women and the control group 53 women. The clinical pregnancy rate was significantly higher in the intervention group (37% [n=19]) than in the control group (13% [n=7]; P=0.006). No differences between the intervention and control groups were noted for spontaneous abortion rate (11% [2/19] vs 29% [2/7]; P=0.287) or multiple pregnancy rate (11% [2/19] vs 14% [1/7]; P=0.790). No adverse effects were reported. CONCLUSION: Endometrial injury before ovulation induction could improve chances of pregnancy and its outcomes. CLINICALTRIALS.GOV: NCT02345837.
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Clomifeno/uso terapéutico , Endometrio/lesiones , Fármacos para la Fertilidad Femenina/uso terapéutico , Infertilidad Femenina/terapia , Inducción de la Ovulación/métodos , Resultado del Embarazo , Adulto , Endometrio/cirugía , Femenino , Humanos , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/fisiopatología , Infertilidad Femenina/cirugía , Fase Luteínica/fisiología , Ovulación/fisiología , Embarazo , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to assess the value of combining the estimated fetal weight (EFW) and amniotic fluid index (AFI) measured in term patients early in labor with intact membranes for prediction of macrosomia. METHODS: In a single center, prospective observational study, 600 patients in the first stage of labor before rupture of membranes in whom ultrasonography was performed to measure AFI and EFW, and these data were analyzed statistically to evaluate prediction of fetal macrosomia. RESULTS: Macrosomia occurred in 64 cases (10.6%). The AFI was significantly higher in the macrosomic group (p = 0.001). It was noted that the area under receiver operating characteristic (ROC) curves for EFW was 0.93 and that of AFI was 0.67. Based on suggested combined EFW and AFI cutoffs of 4000 g and 164 mm, respectively, the positive predictive value (PPV) for combined parameters (92.3%) was higher than that of EFW (75%) and that of AFI (27%) and the likelihood ratio for combination (93.7%) was higher than that of EFW (24.7%) and that of AFI (21%). CONCLUSION: Combined use of EFW and AFI improves prediction of macrosomia at birth rather than the EFW alone.
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Líquido Amniótico , Macrosomía Fetal/diagnóstico , Peso Fetal , Adulto , Femenino , Humanos , Valor Predictivo de las Pruebas , Embarazo , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: The objective of the study was to evaluate the efficacy, safety and tolerability of intravenous ferrous sucrose, compared to oral ferrous sulphate in women with postpartum iron deficiency anemia (IDA). METHODS: In a single center, randomized, controlled study, 352 patients with hemoglobin 9 gm/dl or less and serum ferritin of <15 µg/l two days after delivery were equally randomized to receive intravenous ferrous sucrose (up to three calculated replacement doses) or oral ferrous sulphate (150 mg twice daily for six weeks). Primary measures were to assess the rise in hemoglobin (Hb) and serum ferritin. RESULTS: By day 5, the Hb level in women treated with intravenous ferrous sucrose had rised from 8.48 ± 0.47 to 9.4 ± 0.56 gm/dl. Women treated with intravenous ferrous sucrose had significantly higher Hb levels on day 5, day 14 and day 40 (p < 0.01) than those treated with oral ferrous sulphate. Throughout the study, ferritin level rose rapidly in those treated with intravenous iron and remained significantly higher than in those treated with oral iron (p < 0.001). CONCLUSION: Intravenous ferrous sucrose increases Hb level more rapidly than ferrous sulphate in women with postpartum IDA. It also replenishes iron stores more rapidly with better tolerability.
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Anemia Ferropénica/tratamiento farmacológico , Compuestos Férricos/administración & dosificación , Compuestos Ferrosos/administración & dosificación , Trastornos Puerperales/tratamiento farmacológico , Sacarosa/administración & dosificación , Administración Intravenosa , Administración Oral , Adolescente , Adulto , Anemia Ferropénica/sangre , Femenino , Ferritinas/sangre , Hemoglobinas/análisis , Humanos , Trastornos Puerperales/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
The purpose of this study was to evaluate the effectiveness and safety of transcervical Foley catheter with and without oxytocin versus oxytocin alone for labour induction with unfavourable cervix. This trial enrolled 108 women with singleton pregnancies presented for labour induction with unfavourable cervix. Patients were randomly assigned to receive Foley catheter alone (I), Foley catheter plus oxytocin (II) or oxytocin alone (III). Outcomes were analysed in terms of success of induction, induction delivery interval, route of delivery, dose and duration of oxytocin, and complications. Successful normal vaginal delivery was more common in group I (p = .02) compared to group III. Induction delivery time was statistically shorter in group II and group III (p < .001). Patients in group I required significantly less oxytocin dose and duration (p < .001). This led to our conclusion that induction of labour with Foley catheter without oxytocin increases success rate of normal vaginal delivery; however, it has a longer induction delivery interval with similar complications.
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Trabajo de Parto Inducido/métodos , Oxitócicos/administración & dosificación , Oxitocina/administración & dosificación , Cateterismo Urinario/métodos , Administración Intravenosa , Adulto , Maduración Cervical/efectos de los fármacos , Maduración Cervical/fisiología , Cuello del Útero , Femenino , Humanos , Embarazo , Estudios Prospectivos , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the effect of prophylactic ondansetron on spinal anesthesia-induced hypotension and bradycardia among patients undergoing elective cesarean deliveries. METHODS: A prospective, double-blind, randomized, placebo-controlled trial enrolled patients aged 20-40years scheduled for elective cesarean delivery under spinal anesthesia between January 1, 2015 and January 31, 2016 at Menoufia University Hospital, Egypt. Patients were randomized to receive intravenous ondansetron 4mg in 10mL of saline or 10mL of saline. Participants and investigators were masked to group assignments. The primary outcomes were systolic and diastolic blood pressure, mean arterial pressure, and heart rate, measured at baseline, 10-minute intervals to 60minutes, and at 2hours. Per-protocol analyses were performed including patients who delivered under spinal anesthesia. RESULTS: The analyses included 50 patients in each group. Decreases in systolic blood pressure were reduced among patients receiving ondansetron at all time points (P<0.05) and diastolic blood pressure did not differ between the groups (P>0.05). Among patients who received ondansetron, mean arterial pressure was higher immediately and 30minutes after spinal anesthesia (P<0.05), higher heart rates were recorded immediately, 20minutes, and 50minutes after anesthesia (P<0.05), and the incidence of nausea (P=0.020) and vomiting (P=0.031) were lower. CONCLUSION: Prophylactic intravenous ondansetron significantly reduced hypotension and heart-rate fluctuations among patients undergoing elective cesarean deliveries under spinal anesthesia. Pan African Clinical Trials Registry: PACTR 201601001397193.
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Anestesia Raquidea/métodos , Cesárea/métodos , Hipotensión/prevención & control , Ondansetrón/administración & dosificación , Administración Intravenosa , Adulto , Anestesia Raquidea/efectos adversos , Presión Sanguínea/efectos de los fármacos , Bradicardia/prevención & control , Método Doble Ciego , Egipto , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Náusea , Ondansetrón/efectos adversos , Embarazo , Estudios Prospectivos , Estimulación Química , Centros de Atención Terciaria , Adulto JovenRESUMEN
STUDY OBJECTIVE: The purpose of this study was to evaluate the association of first-trimester serum lipid profile with preeclampsia (PE) and if so, its association with the severity of the disease. STUDY: Prospective cohort study. PATIENT AND METHODS: A total of 251 pregnant women participated in this study in their first trimester. Maternal blood samples were collected between 4 and 12 weeks of gestation. Fasting serum triglycerides (TGs), total cholesterol (TC), HDL-cholesterol, and low-density lipoprotein cholesterol (LDL-C) were drawn and measured by ELISA. From the cohort, 26 women developed PE (16 mild and 10 severe) and 174 remained normotensive and used as control subjects. RESULTS: There was a significant rise in fasting serum TGs, TC, and LDL-C and a significant decrease in HDL-C in women who developed PE than in those who remained normotensive and more significantly evident in severe preeclamptic cases compared to mild cases of PE (p < 0.05). CONCLUSION: Early pregnancy dyslipidemia, particularly hypertriglyceridemia and hypercholesterolemia, may help in predicting women who later develop PE and may help in prediction of its severity.
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Lípidos/sangre , Preeclampsia/diagnóstico , Primer Trimestre del Embarazo/sangre , Adolescente , Adulto , Femenino , Humanos , Preeclampsia/sangre , Valor Predictivo de las Pruebas , Embarazo , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: To compare the feasibility and safety of the laparoscopic management of adnexal masses appearing preoperatively benign with those suspicious for malignancy. METHODS: Retrospective study of 694 women that underwent laparoscopic management of an adnexal mass. RESULTS: Laparoscopic management of an adnexal mass was completed in 678 patients. Six hundred and thirty five patients had benign pathology (91.5%) and 53 (7.6%) had primary ovarian cancers. Sixteen patients (2.3%) were converted to laparotomy; there were 13 intraoperative (1.9%) and 16 postoperative complications (2.3%). Patients divided in 2 groups: benign and borderline/malignant tumors. Patients in the benign group had a higher incidence of ovarian cyst rupture (26% vs. 8.7%, p<0.05). Patients in the borderline/malignant group had a statistically significant higher conversion rate to laparotomy (0.9% vs. 16.9%, p<0.001), postoperative complications (1.9% vs. 12.2%, p<0.05), blood loss, operative time, and duration of hospital stay. The incidence of intraoperative complications was similar between the 2 groups. CONCLUSION: Laparoscopic management of masses that are suspicious for malignancy or borderline pathology is associated with an increased risk in specific intra-operative and post-operative morbidities in comparison to benign masses. Surgeons should tailor the operative risks with their patients according to the preoperative likelihood of the mass being carcinoma or borderline malignancy.
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OBJECTIVE: To compare the feasibility and safety of the laparoscopic management of adnexal masses appearing preoperatively benign with those suspicious for malignancy. METHODS: Retrospective study of 694 women that underwent laparoscopic management of an adnexal mass. RESULTS: Laparoscopic management of an adnexal mass was completed in 678 patients. Six hundred and thirty five patients had benign pathology (91.5%) and 53 (7.6%) had primary ovarian cancers. Sixteen patients (2.3%) were converted to laparotomy; there were 13 intraoperative (1.9%) and 16 postoperative complications (2.3%). Patients divided in 2 groups: benign and borderline/malignant tumors. Patients in the benign group had a higher incidence of ovarian cyst rupture (26% vs. 8.7%, p<0.05). Patients in the borderline/malignant group had a statistically significant higher conversion rate to laparotomy (0.9% vs. 16.9%, p<0.001), postoperative complications (1.9% vs. 12.2%, p<0.05), blood loss, operative time, and duration of hospital stay. The incidence of intraoperative complications was similar between the 2 groups. CONCLUSION: Laparoscopic management of masses that are suspicious for malignancy or borderline pathology is associated with an increased risk in specific intra-operative and post-operative morbidities in comparison to benign masses. Surgeons should tailor the operative risks with their patients according to the preoperative likelihood of the mass being carcinoma or borderline malignancy.
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Femenino , Humanos , Incidencia , Complicaciones Intraoperatorias , Laparoscopía , Laparotomía , Tiempo de Internación , Tempo Operativo , Quistes Ováricos , Neoplasias Ováricas , Complicaciones Posoperatorias , Estudios Retrospectivos , RoturaRESUMEN
The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.
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Estradiol/farmacología , Lupus Eritematoso Sistémico/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Proteínas Adaptadoras Transductoras de Señales , Adulto , Proteínas Portadoras/genética , Proteínas Portadoras/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Lupus Eritematoso Sistémico/genética , Complejo Mediador/genética , Complejo Mediador/inmunología , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas de Unión al ARN , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Estadísticas no Paramétricas , Adulto JovenRESUMEN
BACKGROUND: The clinical significance and efficacy of treating patients who have immunoglobulin (Ig) G subclass deficiency and/or antibody deficiency with Ig-replacement therapy has been debated. There are no clear guidelines to recommend intravenous gammaglobulin (IgIV) in these patients as there are few published studies documenting its efficacy. METHODS: We studied in an open-label protocol 10 adult patients with recurrent respiratory infections and IgG subclass and/or antibody deficiency. All patients received monthly IgIV for 12 months and then were observed for 3 months without IgIV infusions. We studied quality of life, incidence of infections, need for antibiotics, frequency of hospitalizations due to infections, IgG subclass and antibody (tetanus and pneumococcal) levels. Innate immunity was evaluated by studying the status of Toll-like receptors and polymorphisms, mannan-binding lectin levels and genotypes. Correction of the immune defects during IgIV therapy was evaluated. RESULTS: Monthly IgIV significantly improved quality of life, decreased the number of infections and the need for antibiotics, and improved IgG subclass and antibody serum levels. No consistent finding of innate immunity could be detected. CONCLUSIONS: IgIV could be beneficial in patients with IgG subclass or antibody deficiency.
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Deficiencia de IgG/tratamiento farmacológico , Inmunoglobulina G/sangre , Inmunoglobulinas Intravenosas/administración & dosificación , Adulto , Anciano , Femenino , Genotipo , Humanos , Deficiencia de IgG/genética , Deficiencia de IgG/inmunología , Inyecciones Intravenosas , Masculino , Lectina de Unión a Manosa/sangre , Lectina de Unión a Manosa/genética , Persona de Mediana Edad , Polimorfismo Genético , Calidad de Vida , Encuestas y Cuestionarios , Receptores Toll-Like/genética , Receptores Toll-Like/inmunología , Resultado del TratamientoRESUMEN
OBJECTIVE: Estrogen plays a role in the activation of systemic lupus erythematosus (SLE) and in upregulating intracellular signals by binding to the estrogen receptor(s). Fulvestrant (Faslodex, AstraZeneca Pharmaceuticals, Wilmington, DE, USA), an estrogen selective receptor downregulator, competes for receptor binding in vitro and inhibits estrogen action in target cells. We evaluated the efficacy, side effects, and expression of T cell activation markers, following the administration of fulvestrant or placebo to premenopausal patients with SLE. METHODS: Twenty women with moderate SLE Disease Activity Index (SLEDAI; 7.87 +/- 3.7) were enrolled. They were premenopausal with regular menstrual cycles and not taking exogenous hormones. The study was double-blind and placebo-controlled. Ten patients received 250 mg fulvestrant intramuscularly for 12 months, and 10 received the placebo. All were observed monthly and 3 months after final fulvestrant/placebo injection. Measures studied were monthly SLEDAI scores, routine and serologic markers for lupus, and serum concentrations of estrogen and fulvestrant. Expression of T cell calcineurin and CD154 mRNA in peripheral T cells was measured by polymerase chain reaction. Medications the patients were taking were recorded each visit. Bone density was obtained at baseline and at visit 12. RESULTS: Sixteen patients completed the 15-month study, 8 from each group. SLEDAI improved significantly in the fulvestrant group at both 12 months (p = 0.02) and 15 months (p = 0.002), but serologic markers, routine laboratory tests, and bone density did not. Serum estrogen levels were higher in the fulvestrant group and dropped when fulvestrant was discontinued; these differences were not statistically significant. Medications for therapy of lupus to the fulvestrant group were reduced, whereas the placebo group medications were unchanged or increased. Comparison of relative values at individual timepoints revealed significantly lower median values for the T cell activation markers CD154 (p < 0.001) and calcineurin (p = 0.013) in the fulvestrant arm. CONCLUSION: Blocking estrogen receptors in vivo by an estrogen selective receptor downregulator could be considered as a new and relatively safe therapeutic approach in the management of SLE patients with moderately active disease for the 1-year study period.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Estradiol/análogos & derivados , Antagonistas de Estrógenos/uso terapéutico , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/tratamiento farmacológico , Linfocitos T/metabolismo , Adulto , Anticuerpos Antinucleares/sangre , Biomarcadores/sangre , Densidad Ósea/fisiología , Ligando de CD40/sangre , Calcineurina/sangre , Progresión de la Enfermedad , Método Doble Ciego , Regulación hacia Abajo/efectos de los fármacos , Estradiol/farmacología , Estradiol/uso terapéutico , Antagonistas de Estrógenos/farmacología , Estrógenos/sangre , Femenino , Fulvestrant , Humanos , Lupus Eritematoso Sistémico/fisiopatología , Persona de Mediana Edad , Calidad de Vida , ARN Mensajero/metabolismo , Receptores de Estrógenos/efectos de los fármacos , Índice de Severidad de la Enfermedad , Linfocitos T/efectos de los fármacosRESUMEN
BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder usually associated with hypergammaglobulinemia and defective apoptosis mostly due to Fas or Fas ligand mutation. Common variable immunodeficiency (CVID) is a disorder with hypogammaglobulinemia commonly associated with increased Fas expression and spontaneous apoptosis. OBJECTIVE: To describe a patient with a unique combination of hypogammaglobulinemia and ALPS with Fas deficiency but high spontaneous apoptosis. METHODS: Fas expression on freshly isolated lymphocytes was evaluated by means of immunofluorescence using polyclonal rabbit anti-Fas IgG antibody. Apoptosis of cultured lymphocytes was quantitated using acridine orange and ethidium bromide staining. RESULTS: We describe a male patient diagnosed as having CVID at the age of 10 years receiving monthly intravenous immunoglobulin. The patient developed ALPS at the age of 21 years manifested by persistent lymphadenopathy and hepatosplenomegaly. The percentage of double-negative T lymphocytes was estimated to be 9%. Freshly isolated lymphocytes showed low Fas expression (3.6% for the patient and 11.2% for the control). The spontaneous apoptosis rate was high (15% for the patient and 5% for the control). CONCLUSIONS: Autoimmune lymphoproliferative syndrome can be associated with hypogammaglobulinemia and should be looked for in chronic nonmalignant lymphoproliferation in CVID. Common variable immunodeficiency might involve Fas-independent pathways or recruitment of Fas downstream molecules for apoptosis. There is a subset of patients with both CVID and ALPS in whom Fas deficiency could be associated with enhanced spontaneous apoptosis.