Genetic determinants of sex in placental mammals developed by the evolution of primordial autosomes into the male and female sex chromosomes. The Y chromosome determines maleness by the action of the gene SRY, which encodes a protein that initiates a sequence of events prompting the embryonic gonads to develop into testes. The X chromosome in the absence of a Y chromosome results in a female by permitting the conversion of the embryonic gonads into ovaries. We trace the historical progress that resulted in the discovery that one X chromosome in the female is randomly inactivated in early embryogenesis, accomplishing approximate equivalency of X chromosome gene dosage in both sexes. This event results in half of the somatic cells in a tissue containing proteins encoded by the genes of the maternal X chromosome and half having proteins encoded by the genes of the paternal X chromosome, on average, accounting for the phenotype of a female heterozygote with an X chromosome mutation. The hypothesis of X chromosome inactivation as a random event early in embryogenesis was first described as a result of studies of variegated coat color in female mice. Similar results were found in women using the X chromosome-linked gene, glucose-6-phosphate dehydrogenase, studied in red cells. The random inactivation of the X chromosome-bearing genes for isoenzyme types A and B of glucose-6-phosphate dehydrogenase was used to establish the clonal origin of neoplasms in informative women with leiomyomas. Behind these discoveries are the stories of the men and women scientists whose research enlightened these aspects of X chromosome function and their implication for medicine.
This manuscript is a survey of the halachic attitudes toward organ transplant procedures from a living donor which can be defined as life-saving procedures for the recipient or at least life-prolonging proce-dures. Three fundamental problems concerning the halachic aspects of such transplantation are dis-cussed in detail: the danger to the donor, donation under coercion, and the sale of organs and tissues. The terms “halacha” and “Jewish law” are defined in the introduction.
This paper examines the morality of schemes of payment to live donors/sellers of organs for transplantation. Following empirical and historical evidence it is argued that consent to sell organs is substantially different from consent to ordinary business transactions and that legalization of exchanges of organs with financial benefits deviates significantly from the scope of liberal toleration and human rights. Although altruistic giving is commendable, it is immoral for society to benefit from them without conferring to the donors benefits such as health and nursing insurance for life. Non-alienable and non-fungible benefits of this kind are moral as incentives to organ donation/giving
Pharmacogenomics is the study of an individual’s interaction with a specific drug based upon the genetic make-up of the individual. Pharmacogenomic testing can be a powerful tool in testing a drug’s potential efficacy and toxicity on an individual patient. For this tool to be used correctly, certain criteria have to be met. First and foremost is the strength of association between the genetic variation and the drug’s interaction. The predictiveness of pharmacogenomics for the individual patient must be factored in as well. If these criteria are not met, requiring pharmacogenomic testing is at best a waste of money and in some cases can endanger the patient’s life. Stent thrombosis is a serious and many times fatal outcome in a small minority of patients who have received drug-eluting stents. Here, we discuss a case in which the FDA issued a “boxed warning” about the use of the anti-clotting medication, clopidogrel, used to prevent stent thrombosis, the pharmacogenomic data available at the time the warning was issued, and the medical community’s response to the FDA’s warning. This article also discusses developments in the field of anti-clotting therapy since the FDA’s warning.
Results of clinical studies are often contradictory in real time, and in other instances therapies may be adopted due to information from clinical studies where the data may be premature or resulting from small studies. Much of the data may have inherent selection biases, and their interpretation may be confusing and difficult. The hematological literature is full of such examples, and this review will describe some such instances in the hope of introducing both a cautionary note and encouraging more precise description of study conditions as well as an appreciation of the importance of allowing data from clinical studies to mature. Several examples will be drawn from clinical studies in lymphomas, leukemia, and bone marrow transplantation.
The evolution of production systems is tightly linked to the story of Toyota Motor Company (TMC) that has its roots around 1918. The term “lean” was coined in 1990 following the exploration of the Toyota model that led to the “transference” thesis sustaining the concept that manufacturing problems and technologies are universal problems faced by management and that these concepts can be emulated in non-Japanese enterprises.
Lean is a multi-faceted concept and requires organizations to exert effort along several dimensions simultaneously; some consider a successful implementation either achieving major strategic components of lean, implementing practices to support operational aspects, or providing evidence that the improvements are sustainable in the long term.
The article explores challenges and opportunities faced by organizations that intend incorporating lean management principles and presents the specific context of the healthcare industry. Finally, the concepts of “essential few” and customer value are illustrated through a simple example of process change following lean principles, which was implemented in a dental school in the United States.
The Cox maze procedure developed originally in 1987 by Dr James Cox has evolved from a “cut and sew” surgical procedure, where the maze was applied using multiple surgical cuts, to an extensive use of surgical ablation technology where ablation lesions are placed with alternative energy sources (radiofrequency, cryothermy, microwave, and high-frequency ultrasound). Furthermore, the procedure has changed from a median sternotomy approach only to one that can be performed minimally invasively and robotically. The purpose of this paper is to review the current available technology for the ablation of atrial fibrillation as well as the different procedural approaches for the surgical ablation of atrial fibrillation.
The current review addresses contemporary technological answers toadvances in cardiac surgery performed on octogenarian patients, namely off-pump coronary artery bypass grafting (CABG), proximal anastomosis device, routine use of intraoperative epiaortic ultrasound, proximal anastomosis without clamping, transcatheter aortic valve implantation (TAVI), and brain protection during cardiac surgery.
Gaucher disease (GD) is an inherited lysosomal disorder, originating from deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Normally, GCase hydrolyzes glucocerebroside (GC) to glucose and ceramide; however, impaired activity of this enzyme leads to the accumulation of GC in macrophages, termed "Gaucher cells". GD is associated with hepatosplenomegaly, cytopenias, skeletal complications and in some forms involves the central nervous system.
Coagulation abnormalities are common among GD patients due to impaired production and chronic consumption of coagulation factors. Bleeding phenomena are variable (as are other symptoms of GD) and include mucosal and surgical hemorrhages.
Four main etiological factors account for the hemostatic defect in GD: thrombocytopenia, abnormal platelet function, reduced production of coagulation factors, and activation of fibrinolysis. Thrombocytopenia relates not only to hypersplenism and decreased megakaryopoiesis by the infiltrated bone marrow but also to immune thrombocytopenia. Autoimmunity, especially the induction of platelet antibody production, might cause persistent thrombocytopenia.
Enzyme replacement therapy reverses only part of the impaired coagulation system in Gaucher disease. Other therapeutic and supportive measures should be considered to prevent and/or treat bleeding in GD. Gaucher patients should be evaluated routinely for coagulation abnormalities especially prior to surgery and dental and obstetric procedures.
The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking coagulation and some psychiatric disorders.
