Objectives: There are only sporadic reports on the clinical behavior and appropriate treatment of anaplastic seminoma. This retrospective study summarizes our experience with the anaplastic variant of classical (typical) seminoma.
Methods: Between 1986 and 2006, seven anaplastic seminoma patients were staged and treated at the Northern Israel Oncology Center. Staging procedures included meticulous physical and neurological examinations, complete blood count, full biochemistry profile, specific tumor markers, testicular ultrasound, and other radiological measures. All patients underwent inguinal orchiectomy and were staged properly. Six patients had stage I disease, and one patient had stage IIA disease. Patients were irradiated with doses ranging from 2,500 to 3,000 cGy, and the stage IIA patient received an additional 1,000 cGy boost to radiographically involved lymph nodes.
Results: After a mean follow-up of 11 years, six patients are alive with no evidence of disease. One patient died due to an unknown, non-oncological, cause, unrelated to his previous testicular tumor, while in complete remission.
Conclusions: Despite the low patient numbers and the retrospective nature of our study, it can be concluded that radiotherapy treatment for early-stage anaplastic seminoma patients might achieve the same excellent survival as for classical seminoma. However, the general consensus achieved through large-scale studies suggests that active surveillance should be offered to all stage I seminoma patients, regardless of the pathologic variant.
More than 11,000 articles lauding alternative medicine appear in the PubMed database, but there are only a few articles describing the complications of such care. Two patients suffering from complications of alternative medicine were treated in our hospital: one patient developed necrotizing fasciitis after acupuncture, and the second developed an epidural hematoma after chiropractic manipulation. These complications serve as a clarion call to the Israeli Health Ministry, as well as to health ministries around the world, to include complementary medicine under its inspection and legislative authority.
Head and neck cancers are the most common cancers in developing countries, especially in Southeast Asia. Head and neck cancers are more common in males compared to females. This is mainly attributed to tobacco, areca nut, alcohol, etc. Oral cancers are most common amongst all head and neck squamous cell cancers (HNSCC). HNSCC in the developing world differ from those in the Western world in terms of age, site of disease, etiology, and molecular biology. Poverty, illiteracy, advanced stage at presentation, lack of access to health care, and poor treatment infrastructure pose a major challenge in management of these cancers. The annual GDP (gross domestic product) spent on health care is very low in developing countries compared to the developed countries. Cancer treatment leads to a significant financial burden on the cancer patients and their families. Several health programs have been implemented to curb this rising burden of disease. The main aims of these health programs are to increase awareness among people regarding tobacco and to improve access to health care facilities, early diagnosis, treatment, and palliative care.
The twentieth century witnessed profound changes in medical education. All these changes, however, took place within the existing framework, suggested by Flexner a century ago. The present paper suggests that we are approaching a singularity point, where we shall have to change the paradigm and be prepared for an entirely new genre of medical education. This suggestion is based upon analysis of existing and envisaged trends: first, in technology, such as availability of information and sophisticated simulations; second, in medical practice, such as far-reaching interventions in life and death that create an array of new moral dilemmas, as well as a change in patient mix in hospitals and a growing need of team work; third, in the societal attitude toward higher education. The structure of the future medical school is delineated in a rough sketch, and so are the roles of the future medical teacher. It is concluded that we are presently not prepared for the approaching changes, neither from practical nor from attitudinal points of view, and that it is now high time for both awareness of and preparation for these changes.
The Registro Informatizado de Enfermedad TromboEmbólica (RIETE Registry) is an ongoing, international, prospective registry of consecutive patients with acute venous thromboembolism (VTE) designed to gather and analyze data on treatment patterns and outcomes in patients with acute VTE. It started in Spain in 2001, and 6 years later the database was translated into English with the aim to expand the Registry to other countries. In contrast to randomized controlled trials, there is no imposed experimental intervention: the management is determined solely by physicians. Thus, it provides data on patients with VTE in a real-world situation with an unselected patient population. Data from RIETE are hypothesis-generating and provide feedback from real-world clinical situations. So far, we learned about the natural history of VTE in patients with relative or absolute contraindications to anticoagulant therapy. We also learned interesting aspects on the natural history of VTE, and we built a number of prognostic scores to identify VTE patients at low, moderate, or high risk for adverse outcome.
Venous thromboembolism (VTE), the third most frequent acute cardiovascular syndrome, may cause life-threatening complications and imposes a substantial socio-economic burden. During the past years, several landmark trials paved the way towards novel strategies in acute and long-term management of patients with acute pulmonary embolism (PE). Risk stratification is increasingly recognized as a central cornerstone for an adequate diagnostic and therapeutic management of the highly heterogeneous population of patients with acute PE. Recently published European Guidelines emphasize the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for identification of normotensive PE patients at intermediate risk for an adverse short-term outcome. In this patient group, systemic full-dose thrombolysis was associated with a significantly increased risk of intracranial bleeding, a complication which discourages its clinical application unless hemodynamic decompensation occurs. A large-scale clinical trial program evaluating new oral anticoagulants in the initial and long-term treatment of venous thromboembolism showed at least comparable efficacy and presumably increased safety of these drugs compared to the current standard treatment. Research is continuing on catheter-directed, ultrasound-assisted, local, low-dose thrombolysis in the management of intermediate-risk PE.
Rasagiline (Azilect) is a highly selective and potent propargylamine inhibitor of monoamine oxidase (MAO) type B. Like other similar propargylamine inhibitors, rasagiline binds covalently to the N5 nitro-gen of the flavin residue of MAO, resulting in irreversible inactivation of the enzyme. Therapeutic doses of the drug which inhibit brain MAO-B by 95% or more cause minimal inhibition of MAO-A, and do not potentiate the pressor or other pharmacological effects of tyramine. Metabolic conversion of the com-pound in vivo is by hepatic cytochrome P450-1A2, with generation of 1-aminoindan as the major me-tabolite. Rasagiline possesses no amphetamine-like properties, by contrast with the related compound selegiline (Deprenyl, Jumex, Eldepryl). Although the exact distribution of MAO isoforms in different neurons and tissues is not known, dopamine behaves largely as a MAO-A substrate in vivo, but follow-ing loss of dopaminergic axonal varicosities from the striatum, metabolism by glial MAO-B becomes increasingly important. Following subchronic administration to normal rats, rasagiline increases levels of dopamine in striatal microdialysate, possibly by the build-up of β-phenylethylamine, which is an ex-cellent substrate for MAO-B, and is an effective inhibitor of the plasma membrane dopamine trans-porter (DAT). Both of these mechanisms may participate in the anti-Parkinsonian effect of rasagiline in humans. Rasagiline possesses neuroprotective properties in a variety of primary neuronal preparations and neuron-like cell lines, which is not due to MAO inhibition. Recent clinical studies have also demon-strated possible neuroprotective properties of the drug in human Parkinsonian patients, as shown by a reduced rate of decline of symptoms over time.
The closest living relatives of humans are their chimpanzee/bonobo (Pan) sister species, members of the same subfamily “Homininae”. This classification is supported by over 50 years of research in the fields of chimpanzee cultural diversity, language competency, genomics, anatomy, high cognition, psy-chology, society, self-consciousness and relation to others, tool use/production, as well as Homo level emotions, symbolic competency, memory recollection, complex multifaceted problem-solving capabili-ties, and interspecies communication. Language competence and symbolism can be continuously bridged from chimpanzee to man. Emotions, intercommunity aggression, body language, gestures, fa-cial expressions, and vocalization of intonations seem to parallel between the sister taxa Homo and Pan. The shared suite of traits between Pan and Homo genus demonstrated in this article integrates old and new information on human–chimpanzee evolution, bilateral informational and cross-cultural exchange, promoting the urgent need for Pan cultures in the wild to be protected, as they are part of the cultural heritage of mankind. Also, we suggest that bonobos, Pan paniscus, based on shared traits with Austra-lopithecus, need to be included in Australopithecine‟s subgenus, and may even represent living-fossil Australopithecines. Unfolding bonobo and chimpanzee biology highlights our common genetic and cul-tural evolutionary origins.
Complex disorders are common in the human population and are caused by interplay between genetic and environmental factors. Therefore the quest for the genetic basis of such disorders has much similar-ity to deciphering the genetic basis of macro-evolutionary processes, such as speciation. Here I discuss conceptual connections between the principles underlying and processes occurring in disease and evo-lution. Special focus is given to the tremendous mitochondrial genetic variability in the population and within individuals and the impact of both types of variability on evolutionary processes and diseases.
In Alzheimer’s disease (AD), premature demise of acetylcholine-producing neurons and the consequent decline of cholinergic transmission associate with the prominent cognitive impairments of affected individuals. However, the enzymatic activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are altered rather late in the disease progress. This raised questions regarding the causal involvement of AChE and BChE in AD. Importantly, single nucleotide polymorphisms (SNPs), alternative splicing, and alternate promoter usage generate complex expression of combinatorial cholinesterase (ChE) variants, which called for testing the roles of specific variants in AD pathogenesis. We found accelerated amyloid fibril formation in engineered mice with enforced over-expression of the AChE-S splice variant which includes a helical C-terminus. In contrast, the AChE-R variant, which includes a naturally unfolded C-terminus, attenuated the oligomerization of amyloid fibrils and reduced amyloid plaque formation and toxicity. An extended N-terminus generated by an upstream promoter enhanced the damage caused by N-AChE-S, which in cell cultures induced caspases and GSK3 activation, tau hyperphosphorylation, and apoptosis. In the post-mortem AD brain, we found reduced levels of the neuroprotective AChE-R and increased levels of the neurotoxic N-AChE-S, suggesting bimodal contribution to AD progress. Finally, local unwinding of the α-helical C-terminal BChE peptide and loss of function of the pivotal tryptophan at its position 541 impair amyloid fibril attenuation by the common BChE-K variant carrying the A539T substitution, in vitro. Together, our results point to causal yet diverse involvement of the different ChEs in the early stages of AD pathogenesis. Harnessing the neuroprotective variants while reducing the levels of damaging ones may hence underlie the development of novel therapeutics.
KEY WORDS: Acetylcholinesterase, Alzheimer’s disease, apoptosis, beta-amyloid, butyrylcholinesterase
