Increased expression of the G gamma and A gamma globin genes associated with a mutation in the A gamma enhancer

We have previously described a unique type of delta beta-thalassemia in a Chinese family characterized by increased expression of the G gamma and A gamma fetal globin genes in the absence of a large deletion in the beta-globlin gene cluster. Our earlier study of the beta-globin gene on this delta beta-thalassemia chromosome showed a promoter mutation in the TATA box. In this report, we describe the results of our study of the fetal globin domain of this delta beta-thalassemia chromosome. We have cloned a 13-kb DNA fragment that includes the G gamma and the A gamma genes and the 3' A gamma enhancer element of this delta beta-thalassemia chromosome. DNA sequence analysis of the G gamma and A gamma-globin genes including their promoters did not show any mutations, but analysis of the putative enhancer element downstream from the A gamma-globin gene showed a C to T substitution 2,401 nucleotides downstream from the A gamma cap site. We performed DNA linkage analysis to determine if this mutation is unique to this chromosome or represents a common polymorphism. Our linkage analysis showed that this mutation is not a common polymorphism and that it is also not an intrinsic part of the haplotype of the chromosome on which it was found. We also studied the interaction of nuclear proteins from erythroid and nonerythroid cells with the DNA sequences surrounding this mutation. We have shown by in vitro DNase I footprinting that this mutation falls within a region that is occupied by a novel DNA-binding protein that binds to this site in nuclear extracts from erythroid, but not nonerythroid cells. The binding of this nuclear protein to DNA appears to be dependent on GATA-1 binding to an adjacent GATA-1 site. We have also developed a new functional assay to compare the activity of the normal and mutant A gamma enhancer elements in erythroid cells. Analysis of the activity of the mutant enhancer shows that the mutation completely eliminates all enhancer activity in this assay. These findings suggest that this mutation of the A gamma enhancer on a chromosome that carries a partially inactivated beta-globin gene may be responsible for the increased expression of both gamma-globin genes seen in this condition.     

Severe invalidating pain syndrome associated with benznidazole therapy for Chagas’ disease

Chagas’ disease is an endemic parasitic disease and constitutes an important health problem in Latin American countries. The increasing number of immigrants from these countries has resulted in a rise in diagnosis and consequently in the treatment of this disease in developed countries not familiar with this condition. Currently, benznidazole is used for treatment of this condition. However, undesirable effects have been reported with this treatment, and there are few data about continuous long-term use of this drug. We describe a case of invalidating pain syndrome in a 31-year-old Bolivian woman with Chagas’ disease while receiving benznidazole therapy. Because of the number of cases with this condition will probably increase because of immigration, a better understanding of the side effects of the treatment of this disease is essential.     

Brachial loop: transradial technique to overcome this rare anatomic variation.

A brachial loop is a rare anatomic variation and can result in the failure of transradial coronary procedures. We report a brachial loop encountered in a patient undergoing a coronary angiogram. During this angiogram, a 0.035' J-tipped Teflon-coated guidewire met with resistance in the brachial artery because of this rare vascular loop. In this case report, we discuss the technique we used to manage this rare condition. Interventional cardiologists should keep in mind that resistance of the guidewire can result in major vessel complications during the transradial approach.     

Interaction of haemoglobin E with alpha-thalassaemia and haemoglobin Constant Spring.

The combination of Hb E,alpha-thalassaemia and Hb CoSp was found in a 20-year-old female Malay who presented with a moderately severe haemolytic anaemia. The findings in the patient and her family from which this diagnosis was arrived at are discussed. Although this is the first report of this condition in this country it is pointed out that one may see more such cases in the future if one is aware of this condition since Hb E, alpha-thalassaemia and Hb CoSp all occur at significant frequencies in this country.     

Ulcerative colitis and cytomegalovirus infection

Colitis ulcerous and citomegalovirus infection association have been reported in medical literature in sometimes, althougth this prevalence have lately increased. We report a case record of this association and do a review of this subject. It is not clear what factors are involved in this association, being necessary hore studies to know them.     

Polyarticular pneumococcal pyarthrosis in a young haemophiliac

A case of pneumococcal pyarthrosis involving multiple joints in a moderate haemophiliac is reported. To our knowledge this is the second report of this rare complication in the English literature. Infection should be considered in an acutely inflamed joint in a haemophiliac with hyperpyrexia and unresponsive to replacement therapy. A review of the literature and our observation in this case highlight some criteria that could be used to diagnose this rare but debilitating complication early.     

Echocardiographic diagnosis of the right tri-atrial heart

In this report we describe the two-dimensional echocardiographic features of a case of cor triatriatum dexter. In this situation the right atrium is divided by a membrane in two chambers. Considering the anatomic characteristics of this case we added a new type in the classical classification proposed by Doucette et al.     

GLUCOCORTICOID DEFICIENCY WITH ACHALASIA OF THE CARDIA AND LACK OF LACRIMATION

Four recent reports describe a multisystem disorder in which ACTH insensitivity is associated with achalasia and alacrima. We report studies on a male patient with this rare triad. The patient had alacrima from birth; isolated glucocorticoid deficiency had been diagnosed at 3.5 years of age and achalasia at age 6. The possibility that this syndrome could be due to a parasympathetic degeneration has already been proposed; the cause of the glucocorticoid deficiency, however, remains unclear. Parasympathetic function in other areas was investigated to determine whether there might be a more generalized abnormality. Specific cardiac tests of parasympathetic function showed that parasympathetic input to the heart was affected in the patient, while the same tests in an Addisonian child were normal. We show, then, a hitherto undetected parasympathetic abnormality in a patient with this syndrome, suggesting a generalized disturbance of this system. On this basis we may hypothesize that the glucocorticoid failure may be a consequence of the loss of parasympathetic input to the adrenal gland, although this remains to be demonstrated experimentally.     

IQWiG Reanalyzes and Raises Questions About an Article by Ly et al Which Concluded Low Glucose Suspend Is Very Beneficial

In 2013, Ly et al published a study in JAMA reporting a massive reduction in the frequency of severe hypoglycemic events when the patients used sensor augmented insulin pump therapy with low glucose suspense. The data of this study were reanalyzed by the IQWiG when this German institute started its evaluation of the evidence for continuous glucose monitoring (CGM) usage. The IQWiG came to a contrary conclusion than the authors of the Ly study. Decisive for this was the statistical analysis of the Ly study that led the IQWiG to evaluate this result as a lack of evidence for the superiority of CGM (plus pump) for preventing hypoglycemia. In this commentary, a direct English translation of the IQWiG analysis is provided to enable the reader to come to his or her own conclusion about this study.     

Hormonal control of uterine growth: alterations in luminal epithelial deoxyribonucleic acid synthesis after intraluminal application of estrogen

Administration of a single injection of estradiol (E2) causes a maximum increase in DNA synthesis in the uterine luminal epithelium approximately 24 h later. We previously reported that animals receiving a second injection of E2 15-18 h after the first show an apparent decrease in DNA synthesis measured in this cell type at 24 h. This apparent decrease in DNA synthesis is due to a shift in the time course of DNA synthesis rather than an absolute decrease in this parameter. In this report we demonstrate that this inhibitory effect of a second injection of E2 is also observed after intraluminal instillation of the hormone. This effect is dose dependent and appears to result from a shift in the time course of luminal epithelial DNA synthesis. The intraluminal instillation of E2 produces the same pattern of nuclear receptor localization as sc administration of the hormone. These results suggest that this inhibitory effect we previously described results primarily from a direct action of E2 on the luminal epithelium.     

Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome

In this paper we highlight the presence of tachycardia in post-acute COVID-19 syndrome by introducing a new label for this phenomenon—post-COVID-19 tachycardia syndrome—and argue that this constitutes a phenotype or sub-syndrome in post-acute COVID-19 syndrome. We also discuss epidemiology, putative mechanisms, treatment options, and future research directions in this novel clinical syndrome.     

Unraveling hemophilic arthropathy

In this issue of Blood, Acharya and colleagues provide evidence for the role of angiogenesis in the pathophysiology of hemophilic joint disease. Is this the linchpin that unravels this important clinical condition or merely a cog in a not so stepwise process?     

Mesenteric artery occlusion secondary to activated protein C resistance: a life-threatening combination

We present a case of mesenteric ischemia in a 32-year-old woman. The rarity of this potentially fatal condition in this age group, the diagnostic and therapeutic challenges associated with such a condition, and secondary causes that must always be investigated are highlighted. In this case, activated protein C resistance resulted in thrombosis of the superior mesenteric artery and subsequent bowel ischemia.     

An outbreak of enterocolitis due to Clostridium perfringens in a hospital for the severely disabled

We had an outbreak of 14 cases of enterocolitis due to Clostridium perfringens (Cl. perfringens) in a hospital for the severe multiply-disabled, where the 100 disabled were admitted, in summer in 1985. The signs and symptoms shown by this enterocolitis were primarily diarrhea without fever and loss of appetite. The feces of 10 cases were examined bacteriologically. The test showed 10(3) to 10(6) cells of Cl. perfringens per one gram of their feces and all the strains isolated were untypable by the classification of Hobbs. Nine out of 10 cases were randomly selected and all of the 9 cases were proved to have enterotoxin producing strains. All the strains were highly sensitive to many kinds of antibiotics except kanamycin and gentamicin. Eleven out of the 14 cases were admitted in the same ward and the 7 out of the 11 cases were in the same room of this ward. Considering the spreading route of this infection, it is unlikely that this outbreak occurred due to food supplied from kitchen in this hospital, because all of the disabled, admitted in this hospital, had little chance by which some of the disabled only in a specific ward or room were supplied with bacteriologically contaminated meals from the point of view of cooking and supplying system of this hospital. Adding to this fact, if this outbreak was due to food-born infection, the symptoms of most patients should occur within 1-2 days, because the incubation period of this disease is within a day, however, the patients increased day by day for more than a week.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heparin-associated thrombocytopenia in a patient with polycythemia vera: the importance of a marked drop in platelet count

The present report describes a patient with polycythemia vera who developed a severe arterial and venous thrombosis caused by systemically administered heparin. An immunologic implication has been proposed as pathophysiological mechanism of this heparin-associated thrombocytopenia and thrombosis syndrome. It is suggested, however, that a strong decrease in platelet count as occurred in this patient leads to a higher chance of developing this complication.     

Bifurcation balloon for left main shock syndrome: facilitating the simultaneous percutaneous reperfusion of the LAD and circumflex

Acute occlusion of the left main coronary artery frequently causes cardiogenic shock and, when this occurs with an initial TIMI 0 flow, has an extremely poor prognosis. The use of a bifurcation system has not been described previously in this situation but has advantages that may result in a simpler and quicker solution then other strategies. This case describes a distal LMCA occlusion, 2 weeks post-stenting of the proximal LAD and proximal Cx, where this strategy was successfully used as a bridge to surgery. Such a strategy may be crucially beneficial in this commonly fatal condition.     

Pheochromocytoma and medullary thyroid carcinoma: a new genotype-phenotype correlation of the RET protooncogene 891 germline mutation

Prior experience in kindreds with a codon 891 RET protooncogene mutation indicates that carriers of this mutation develop only hereditary medullary thyroid carcinoma without evidence of other manifestations of multiple endocrine neoplasia type 2. In this paper, we report the first documented case in which medullary thyroid carcinoma and pheochromocytoma were clinically expressed in members of a family affected by the codon 891 RET mutation. Genetic analysis of the RET protooncogene in this family revealed an exon 15 missense mutation at codon 891 that resulted in a serine to alanine amino acid substitution. These findings indicate that patients with this mutation should be screened for pheochromocytoma.     

ALCOHOL AND ENDOCRINE SYSTEMS INTERACTION—PART II Biochemical Mechanisms That Contribute to Alcohol-Induced Hypogonadism in the Male

The above review has presented most if not all of the available evidence supporting a role for alcohol and acetaldehyde as putative environmental Leydig cell toxins for man and animals. Despite a considerable data base and much progress, particularly in the last decade, much yet remains to be learned concerning this phenomenon. It is hoped that this review, and this symposium, will contribute to future progress in this area by providing a basis for new and provocative observations and hypotheses to be tested by a new generation of clinical investigators.     

Salvage treatment of disseminated strongyloidiasis in an immunocompromised patient: therapy success with subcutaneous ivermectin

Disseminated strongyloidiasis is a disease with high mortality rate, especially in immunocompromised individuals. Paralytic ileus and intestinal malabsorption are frequent symptoms caused by this severe disease. As there are no licensed parenteral anthelmintic drugs for human use, off-label formulations are often used in the treatment of this disease. In this case report, the use of subcutaneous ivermectin is described as a successful therapy for this life-threatening infection.