Anticoagulación en COVID-19 / Anticoagulation in COVID-19

La vida del mundo cambió como la conocíamos, desde diciembre de 2019, por una nueva pandemia viral, el "Coronavirus 2". Virus de alta contagiosidad y gravedad por el Síndrome Respiratorio Agudo Severo (SARS CoV-2) provocando alta morbimortalidad, desbordado las Unidades de Cuidados Intensivos del mundo, para atender a estos pacientes cuyo cuadro es primariamente respiratorio. Actualmente, además se enfrenta a una segunda amenaza, el aumento sustancial en comparación a otros pacientes hospitalizados (no COVID-19) de las complicaciones tromboembólicas.Esta publicación pretende realizar una revisión de la información actualizada disponible respecto a la epidemiología, fisiopatología y manejo de la enfermedad tromboembólica en pacientes con COVID-19 hospitalizados.

The life of the world changed as we knew it, since december 2019, due to a new viral pandemic, the "Coronavirus 2". Virus of high contagiousness and severity due to Severe Acute Respiratory Syndrome (SARS CoV-2) causing high morbidity and mortality, overwhelmed the Intensive Care Units of the world, to care for these patients whose primarily respiratory symptoms. Currently, it also faces a second threat, the substantial increase compared to other hospitalized patients (not COVID-19) of thromboembolic complications.This publication aims to review the updated information available regarding the epidemiology, pathophysiology, and management of thromboembolic disease in hospitalized COVID-19 patients.

Maternal protein restriction in pregnancy and/or lactation affects seminiferous tubule organization in male rat offspring.

Maternal protein restriction (MPR) during pregnancy impaired the reproduction of male offspring. We investigated, during the first wave of spermatogenesis, whether MPR exerts deleterious effects on germ cell proliferation and differentiation, as well as androgen receptor (AR) protein expression, which was used as a marker for Sertoli cell (SC) maturation. At the beginning of pregnancy (day 0), dams were fed a control diet (C: 20% casein) or a restricted isocaloric diet (R: 10% casein). After birth, four groups were established: CC, RR, CR and RC (first letter diet during pregnancy and second during lactation). Male offspring were studied at postnatal days 14, 21 and 36. At birth, pup body weight was unchanged. Body weight and testis weight were reduced in RR and CR groups at all ages evaluated. MPR delayed the germinal epithelium development at all ages evaluated. On performing Western blot and immunohistochemistry, AR expression was found to be lower in the three restricted groups. The results suggest that MPR during pregnancy and/or lactation delays SC maturation and germ cell differentiation, and affects intratubular organization. These changes might be responsible for the lower fertility rate at older ages.

Microangiopatía trombótica en paciente con diagnóstico de lupus eritematoso sistémico: revisión de la literatura en relación a un caso clínico / Thrombotic microangiopathy in patients diagnosed with systemic lupus erythematosus: literature review with regards to a clinical case

El Síndrome Púrpura Trombótico Trombocitopénico/Síndrome Hemolítico Urémico (PTT/SHU) es la principal causa de Microangiopatía Trombótica (MAT) en pacientes con Lupus Eritematoso Sistémico (LES). Entre sus manifestaciones destacan la presencia de anemia hemolítica autoinmune, con trombocitopenia y falla renal en grados variables. No existe correlación entre los niveles de actividad de ADAMTS 13 y MAT. Presentamos un caso clínico de MAT asociado a LES. Se debe tener una alta sospecha diagnóstica por la sobreposición de las manifestaciones clínicas de PTT/SHU y LES. El tratamiento con plasmaféresis ha disminuido la mortalidad de 90 por ciento a 15 por ciento. En casos refractarios se ha reportado el uso de Rituximab, aunque aún falta evidencia que lo avale.

The thrombotic Thrombocytopenic Purpura Syndrome / Hemolytic Uremic Syndrome (TTP/HUS) is the main cause behind Thrombotic Microangiopathy (TMA) in patients with Systemic Lupus Erythematosus (SLE). Among the ways in which it manifests itself is the presence of autoimmune hemolytic anemia (AIHA), with thrombocytopenia and kidney failure in various degrees. There is no co-relation between the levels of activity of ADAMTS13 and TMA. We present a clinical case of TMA associated to SLE. A high suspicion is paramount for diagnose due to the overlapping of clinical manifestations of TTP/HUS and SLE. Treatment with plasmapheresis has decreased mortality from 90 percent to 15 percent. Use of Rituximab in refractory cases has been reported, albeit a lack of supporting evidence.

Cryo-transmission electron tomography of native casein micelles from bovine milk.

Caseins are the principal protein components in milk and an important ingredient in the food industry. In liquid milk, caseins are found as micelles of casein proteins and colloidal calcium nanoclusters. Casein micelles were isolated from raw skim milk by size exclusion chromatography and suspended in milk protein-free serum produced by ultrafiltration (molecular weight cut-off of 3 kDa) of raw skim milk. The micelles were imaged by cryo-electron microscopy and subjected to tomographic reconstruction methods to visualize the 3-dimensional and internal organization of native casein micelles. This provided new insights into the internal architecture of the casein micelle that had not been apparent from prior cryo-transmission electron microscopy studies. This analysis demonstrated the presence of water-filled cavities (∼20 to 30 nm in diameter), channels (diameter greater than ∼5 nm), and several hundred high-density nanoclusters (6 to 12 nm in diameter) within the interior of the micelles. No spherical protein submicellar structures were observed.

The effect of ethanol and heat on the functional hydrophobicity of casein micelles.

Milk proteins are very important ingredients to the food industry. As new uses and applications for these proteins are developed, it becomes more important to understand their physicochemical properties when they are subjected to different treatments. It has been reported that casein micelles dissociate when heated in the presence of ethanol. The changes to the hydrophobicity of milk proteins during that process were evaluated by using the fluorescent hydrophobic probe 1-anilinonaphthalene-8-sulfonic acid (ANS). Raw skim milk, pasteurized skim milk, and whey protein isolate samples with ethanol concentrations of 0 to 60% (vol/vol) were heated from 20 to 60 degrees C. The fluorescence of the samples with and without the addition of ANS was measured at an excitation wavelength of 390 nm and an emission wavelength of 400 to 500 nm. The results showed a decrease in the extrinsic fluorescence of the samples as the ethanol concentration and temperature increased, indicating competitive inhibition of the ANS-hydrophobic site interaction by ethanol. This inhibition was further enhanced by the addition of heat. This resulted in a reduction in the functional hydrophobicity of the milk proteins as ethanol rendered the hydrophobic sites unavailable for interaction.

Amiloidosis: revisión a propósito de un caso clínico / Amyloidosis: review of clinical case purpose

La amiloidosis constituye un grupo de enfermedades caracterizadas por el depósito extracelular de material proteico autólogo, fibrilar e insoluble. Existe una variedad que se asocia a enfermedades inflamatorias crónicas mal controladas que presentan manifestaciones orientadoras al diagnóstico, lo que es importante de conocer, ya que hace variar el pronóstico de la enfermedad de base. A continuación se presenta un caso clínico de amiloidosis secundaria a artropatía psoriásica, discutiendo su diagnóstico y posibilidades terapéuticas tanto para la enfermedad de base como para su asociación y complicación por amiloidosis.

Amyloidosis is a group of diseases characterized by the extracellular deposition of protein material autologous fibrillar insoluble. There is a variety that is associated with poorly controlled chronic inflammatory diseases that have manifestations in the diagnosis. Below we present a clinical case of secondary amyloidosis in psoriatic arthropathy and discuss its diagnosis and further management.

Efecto del SIDA en la evolución de la artritis reumatoídea: el síndrome de reconstitución inmune / Rheumatoid arthritis and AIDS: the immune reconstruction syndrome

El SIDA es una enfermedad que tiene una forma de presentación clínica variada; una de ellas, son las de tipo reumatológico. Por otra parte, el SIDA puede modificar el curso de una enfermedad como la Artritis reumatoídea, cuando pasa del estado portador de HIV a la etapa SIDA. En este artículo, que es un caso clínico de nuestro Departamento de Reumatología del Hospital San Juan de Dios, analizaremos a una enferma con Artritis reumatoídea cuya evolución clínica se caracterizó por una artritis agresiva y destructiva en un lapso corto de tiempo, de difícil control médico, en estado portador de HIV, y que frente a una nueva etapa de SIDA pudo inactivar totalmente su Artritis reumatoídea.Esta revisión analiza, por una parte, las manifestaciones del HIV y sus presentaciones en las enfermedades reumatológicas y, por otro lado, revisa el Síndrome de Reconstitución Inmune, una forma de manifestación del tratamiento del SIDA y cómo éste incide en enfermedades como la Artritis reumatoídea.

AIDS is a disease with various clinical manifestations, among them are those of rheumatic nature. On the other hand, AIDS can modify the course of rheumatoid arthritis when it passes from the HIV positive to an AIDS stage. We present a clinical case from our Department of Rheumatology at the San Juan de Dios Hospital, of a HIV-positive woman with an aggressive and rapidly destructive case of rheumatoid arthritis, which became totally inactive with the manifestation of AIDS. We review, on one hand, HIV manifestations and its presence in rheumatic diseases and, on the other hand, the immune reconstruction syndrome, a manifestation of AIDS treatment, and how this affects diseases like rheumatoid arthritis.

Necrolisis tóxica epidérmica: caso clínico / Toxic epidermal necrolysis: clinical case

Toxic epidermal necrolysis is a potentially fatal disease due to allergic reactions to drugs. We report on a 58 years old female, that presented Raynaud sphenomenon during 20 years. During the last year, she developed polyarthritis of hands, shoulders, knees and ankles. Rheumatoid factor (RF), antinuclear antibodies (ANA) and U_ ribonucleoprotein (U1 RNP) were present, and Mixed connective tissue disease was suspected. Because of a poor response to methotrexate the patient received leflunomide. Two weeks later, she began with fever, pruritus and generalized edema. Within days this affected her neck, thorax, eyes and oral mucous. She had bullaes and areas of epidermic detachment. A toxic epidermal necrolysis was diagnosed and treated with IV immunoglobulins. The lesions disappeared successfully. In addition to the dermatological problem, the patient later presented ocular complications that required the transplant of both corneal, with the sub-sequent loss of one of her eyes.

BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML).

There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Another, less common fusion gene is c3a2[e19a2], which encodes a p230 protein. The incidence of one or the other rearrangement in chronic myeloid leukaemia (CML) patients varies in different reported series. This study was designed to determine the frequency of coexpresion of the p210, p190 and p230 transcripts in 250 Mexican patients with CML. We performed nested and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) on bone marrow samples from adult patients and found that all cases were positive for some type of BCR/ABL rearrangement. In 226 (90.4%) patients it was p210, while the remaining 9.6% showed coexpression or one of the transcripts of p190/p210/p230. In 7% of patients with p210 expression there are both isoforms (b3a2/b2a2), presumably the result of alternative splicing. The rate of coexpression of the p190/p210 transcripts was 5%, which is much lower than in other reports. This may be due to the technical factors. These patients had high platelet counts, marked splenomegaly and chromosomal abnormalities in addition to Ph'. Other types of coexpression seen were p210/p230 and p190/p210/p230, in patients with high-risk clinical factors. Our study confirms the occurrence of coexpression of different BCR/ABL transcripts, although the rate (9.6%) was much lower than has been reported in other populations. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences between the populations studied. Coexpression may be due to alternative splicing or to phenotypic variation, with clinical courses different from classical CML.

[Laparoscopic management of gastroesophageal reflux disease. Experience with 100 cases]. / Manejo laparoscópico de la enfermedad por reflujo gastroesofágico. Experiencia en 100 casos.

OBJECTIVE: To evaluate the results of laparoscopic Nissen-Rossetti funduplication and to compare them with the results obtained in open surgery. DESIGN: Prospective, observational, longitudinal, pre and post-procedure. CENTERS: Beneficencia Española, Hospital Angeles, and Hospital Francisco Galindo Chávez, ISSSTE, in Torreón, Coahuila, Mexico. PATIENTS AND METHOD: From December 1992 to February 1999, 100 patients with surgical indications due to gastroesophageal reflux disease (GERD) prospectively underwent a laparoscopic Nissen-Rossetti procedure. A clinical and endoscopic follow up from 3 months to 9 years was performed in 87 cases. RESULTS: Symptomatic control was achieved in 98% (85/87) of the cases and remission of overall endoscopic esophagitis in 79% (69/87); excluding Barrett cases, esophagitis remission was observed in 93% (67/72) of the subjects. The following recurrences took place: two with G-II and two with G-III esophagitis, one requiring pyloroplasty due gastric stasis, and other patient with G-IV esophagitis, who has needed to continue with postoperative dilations. Of 16 cases with Barrett's esophagus, two-showed remission and one did not return control. Perioperative complications included gastric perforations (3), acute pulmonary edema during the immediate postoperative period (1), deep vein thrombosis (1), and late esophageal perforation (1). All were resolved satisfactorily. Surgical mortality was 0 in the 100 cases undergoing the procedure. Eighty-six percent of cases had a 24-h hospital stay. Early morbidity: dysphagia in 60 patients, early satiety in 91 cases, abdominal distention in 25 cases, all this symptomatology disappears during the subsequent 3 months. Persistent morbidity: flatulence in 60% of patients, difficulty for vomiting in 10% of cases. CONCLUSION: The laparoscopic procedure is as effective as the open method with the advantage of being minimally invasive.

A t(1;22)(p13;q13) in four children with acute megakaryoblastic leukemia (M7), two with Down syndrome.

We report four children with acute megakaryoblastic leukemia (AML-M7) and t(1;22)(p13;q13), two of them with Down syndrome; their ages were 7 months, and 6, 7, and 10 years. These findings differ from those reported in children with M7 and t(1;22) at the age of presentation (exclusively under 1-year-old) and in the two cases associated with Down syndrome (t[1;22],+21c) that may be due to the high heterogeneity of the chromosomal changes in children with AML. We cannot disregard ethnic difference distribution of chromosomal changes and age of presentation in Mexican children with AML.

Changes in cyclin B localisation during pig oocyte in vitro maturation.

The localisation of cyclin B throughout in vitro maturation of pig oocytes was determined by indirect immunofluorescence using a monoclonal antibody specific for an epitope of the human cyclin B. Maturation of pig oocytes was induced by addition of Pergonal (2 UI/ml of FSH/LH) and beta-oestradiol to the medium where isolated ovarian follicles were cultured for up to 72 h. Immature gametes with an intact germinal vesicle were observed during the first 30 h of culture. Only 10% were competent to reinitiate meiosis and showed germinal vesicle breakdown (GVBD) after 36 h. However, after 48-72 h, 60% of the oocytes accomplished their maturation and showed metaphase chromosomes. Immature oocytes showed cyclin B immunofluorescent staining in the cytoplasm, whereas mature oocytes showed the immunofluorescent label concentrated in the nucleus. Metaphase chromosomes showed an intense immunofluorescence. The migration of cyclin B to the nucleus and its association with metaphase chromosomes in pig oocytes able to progress through meiosis resembled the subcellular localisation of cyclin B and the distribution of maturation promoting factor (MPF) in mitotic dividing cells.

Deficient proliferation of myeloid, erythroid, and multipotent progenitor cells in long-term marrow cultures from patients with aplastic anemia treated with immunosuppressive therapy.

By using Dexter-type long-term marrow cultures (D-LTMC), it has been shown previously that hematopoietic progenitor cells (HPC) from patients with aplastic anemia (AA) have a deficient proliferation in vitro. The studies reported to date, however, have focused exclusively on granulomonocytic progenitors and no information exists on erythroid or multipotent progenitor cells. On the other hand, in such studies, the input progenitor cell numbers were significantly below normal levels, thus suggesting that the rapid disappearance of myeloid progenitor cells from AA D-LTMC could also be due, at least in part, to their reduced number at culture onset. In the present study, we have followed the kinetics of myeloid, erythroid, and multipotent progenitors, from 24 AA patients subjected to immunosuppressive therapy (including patients that achieved complete, partial, or no remission at all), throughout a seven-week culture period. For analysis, we grouped all the patients based on their initial content of all three types of progenitors. Thus, we were able to evaluate separately the kinetics of these cells in D-LTMC from patients with normal and subnormal levels of progenitor cells. At the time of marrow sampling, most patients showed decreased levels of HPC; in fact, only 21%, 8%, and 16% of them showed normal levels of myeloid, erythroid, and multipotent progenitors, respectively. When cultured in D-LTMC, HPC from all AA patients analyzed showed a relatively fast disappearance from the cultures. Indeed, myeloid progenitors could be detected for only six weeks, whereas erythroid and multipotent progenitors disappeared from the cultures after two and one weeks of culture, respectively. In contrast, in normal marrow D-LTMC, myeloid, erythroid, and multipotent progenitors were detected for at least seven, five, and three weeks, respectively. Such a deficient proliferation was observed even in cultures of AA patients that contained normal levels of HPC at culture onset. Interestingly, no correlation was found between HPC proliferation in D-LTMC and response to treatment. Thus, the results of this study indicate the presence of a functional in vitro deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment. Furthermore, this work suggests that such a proliferation deficiency is more pronounced in erythroid and multipotent progenitors than in their myeloid counterparts.

Calmodulin content, Ca2+-dependent calmodulin binding proteins, and testis growth: identification of Ca2+-dependent calmodulin binding proteins in primary spermatocytes.

In contrast with the transient pre-replicative increase in calmodulin (CaM) level observed in proliferative activated cells, postnatal development of rat testis was paralleled by 3 specific rises in CaM. The first one occurred between 5 and 10 days, coincident with the appearance and proliferation start of spermatogonia and Sertoli cells. Meiosis accomplishment and spermatid differentiation were paralleled by 2 additional rises, at 24 and 32 days, respectively. The plateau phase of testis growth was coincident with the appearance of maturating spermatids and spermatozoa in the germinal epithelium, and with a decrease in CaM content. Testicular DNA:g wet tissue ratio reached the highest level in 15-day-old rats and gradually decreased up to 35 days, when a constant level was reached. A similar level of Ca2+-CaMBPs was observed in 5- and 20-day-old rat testis. Although all subcellular fractions showed the ability to bind CaM in a Ca2+-dependent manner, CaM was mainly recovered in the nuclear and soluble fractions of adult and immature rat testis. Several Ca2+-CaMBPs with an apparent M(r) of 82, 75, 64, 19, and 14 kD were purified by affinity chromatography from pachytene primary spermatocyte nuclear matrix. Ca2+-CaMBPs showing an M(r) of 120, 78, 72, and 66 kD were also purified from the supernatant obtained after DNA and RNA hydrolysis of meiotic nuclei. Major cytosolic Ca2+-CaMBPs of primary spermatocytes showed an M(r) of 120, 84, 44, and 39 kD. The functions that these Ca2+-CaMBPs might have during the first meiotic prophase is discussed.

Cytogenetic findings in 303 Mexican patients with de novo acute myeloblastic leukemia.

In this report we show the chromosomal changes seen in a group of 303 Mexican patients with de novo Acute Myeloblastic Leukemia (AML). Two hundred forty-two patients were diagnosed and treated at two hospitals affiliated with the Instituto Mexicano del Seguro Social (IMSS). These are the Centro Medico Nacional Siglo XXI and Centro Medico La Raza Hospitals; the remaining 61 patients were diagnosed and treated at the Hospital General de Mexico (HGM). Clonal abnormalities were detected in 75.6% of the patients; this result agrees with what has been reported in other large series of AML studies. The incidence of changes per hospital was similar in patients from the IMSS hospitals (72-75%), while an increase was seen in patients from the HGM (85.2%). The chromosomal changes seen in this study in order of frequency were: t(15;17)[18.8%], t(9;22)[9.2%], miscellaneous chromosomal changes (mainly rearrangements of chromosomes 1,2,3,12y17)[8.2%], abnormalities of 16q22 [7.3%], t(8;21)[6.3%], -7/del(7q)[5.6%], t(6;9)[5.3%], and abnormalities of 11q23 [4.6%]. We reported an increase in the incidence of certain types of chromosomal changes seen in cases of AML, in comparison with reports from other countries. These differences could be due to methodological variations, although ethnic, socioeconomic and nutritional differences must not be disregarded. We support this finding when comparing distribution of changes in the population of patients seen in the IMSS hospitals with those from the HGM; the main difference lies in the socioeconomic level.

[Interferon in the eradication of the Philadelphia chromosome in chronic myeloid leukemia]. / El interferón en la erradicación del cromosoma Filadelfia de la leucemia mieloide crónica.

OBJECTIVE: To evaluate if human recombinant interferon alpha (IFN) combined with chemotherapy is able to suppress the Philadelphia chromosome clone in patients with chronic myeloid leukemia (CML). MATERIAL AND METHODS: The cytogenetic evolution in 53 patients with CML in chronic phase de novo was studied. They received one of three treatment schemes: a) induction of remission with daunorubicin, vincristine, cytosine arabinose and prednisone (DOAP) and maintenance with IFN (n = 12); b) induction with busulfan (BUS) or hydroxyurea (HYDX) and maintenance with IFN (n = 26); c) induction with DOAP and maintenance with BUS (n = 15). RESULTS: The remission was seen two to six months after the start of treatment: 10 had complete remission, six a partial one, 14 a minor remission and 23 none. The 16 with complete or partial response received treatment with IFN. None of the 15 cases maintained with BUS had complete or partial response. The proportion of cases with complete response (3/12) was slightly lower in patients treated with intensive chemotherapy (BUS/HIDX/IFN) than in those receiving conventional treatment (7/26). CONCLUSIONS: Our results showed that: a) IFN in combination with chemotherapy induced partial or complete response in 30% of our cases; and b) intensive chemotherapy combined with IFN was not superior in terms of a cytogenetic response to treatment with monodrugs (BUS/HIDX) and IFN.