Current concepts in primary hyperparathyroidism

622 patients were operated on between 1966 and 1988. Urolithiasis was the most common presenting symptom (26%) but routine measurements of serum calcium led to detect 50% cases. At present, the disease is three times more frequent in women than in men. Estrogenic deprivation, neck irradiation (3.4%) and lithium therapy favor the occurrence of hyperparathyroidism (HPT); frequent association with goiter (19.8%), diabetes (8.3%) and multiple endocrine neoplasia (3.5%) has been noticed. Bone Gla protein concentrations correlate with calcium and HPT blood concentrations but do not reflect the severity of bone damage. Dual photon absorptiometry is now available for quantification and follow-up of bone demineralization, especially in asymptomatic forms of HPT.     

Current concepts in glucocorticoid resistance

Glucocorticoids (GCs) are the most potent anti-inflammatory agents known. A major factor limiting their clinical use is the wide variation in responsiveness to therapy. The high doses of GC required for less responsive patients means a high risk of developing very serious side effects. Variation in sensitivity between individuals can be due to a number of factors. Congenital, generalized GC resistance is very rare, and is due to mutations in the glucocorticoid receptor (GR) gene, the receptor that mediates the cellular effects of GC. A more common problem is acquired GC resistance. This localized, disease-associated GC resistance is a serious therapeutic concern and limits therapeutic response in patients with chronic inflammatory disease. It is now believed that localized resistance can be attributed to changes in the cellular microenvironment, as a consequence of chronic inflammation. Multiple factors have been identified, including alterations in both GR-dependent and -independent signaling downstream of cytokine action, oxidative stress, hypoxia and serum derived factors. The underlying mechanisms are now being elucidated, and are discussed here. Attempts to augment tissue GC sensitivity are predicted to permit safe and effective use of low-dose GC therapy in inflammatory disease.     

Current concepts in ejaculatory dysfunction

Although erectile dysfunction has recently become the most well-known aspect of male sexual dysfunction, the most prevalent male sexual disorders are ejaculatory dysfunctions. Ejaculatory disorders are divided into 4 categories: premature ejaculation (PE), delayed ejaculation, retrograde ejaculation, and anejaculation/anorgasmia. Pharmacologic treatment for certain ejaculatory disorders exists, for example the off-label use of selective serotonin reuptake inhibitors for PE. Unfortunately, the other ejaculatory disorders are less studied and not as well understood. This review revisits the physiology of the normal ejaculatory response, specifically explores the mechanisms of anejaculation, and presents emerging data. The neurophysiology of the ejaculatory reflex is complex, making classification of the role of individual neurotransmitters extremely difficult. However, recent research has elucidated more about the role of serotonin and dopamine at the central level in the physiology of both arousal and orgasm. Other recent studies that look at differing pharmacokinetic profiles and binding affinities of the alpha(1)-antagonists serve as an indication of the centrally mediated role of ejaculation and orgasm. As our understanding of the interaction between central and peripheral modulations and regulation of the process of ejaculation increases, the probability of developing centrally acting pharmaceutical agents for the treatment of sexual dysfunction approaches reality.     

Current concepts in nuclear pore electrophysiology

Over 4 decades ago, microelectrode studies of in situ nuclei showed that, under certain conditions, the nuclear envelope (NE) behaves as a barrier opposing the nucleocytoplasmic flow of physiological ions. As the nuclear pore complexes (NPCs) of the NE are the only pathways for direct nucleocytoplasmic flow, those experiments implied that the NPCs are capable of restricting ion flow. These early studies validated electrophysiology as a useful approach to quantify some of the mechanisms by which NPCs mediate gene activity and expression. Since electron microscopy (EM) and other non-electrophysiological investigations, showed that the NPC lumen is a nanochannel, the opinion prevailed that the NPC could not oppose the flow of ions and, therefore, that electrophysiological observations resulted from technical artifacts. Consequently, the initial enthusiasm with nuclear electrophysiology faded out in less than a decade. In 1990, nuclear electrophysiology was revisited with patch-clamp, the most powerful electrophysiological technique to date. Patch-clamp has consistently demonstrated that the NE has intrinsic ion channel activity. Direct demonstrations of the NPC on-off ion channel gating behavior were published for artificial conditions in 1995 and for intact living nuclei in 2002. This on-off switching/gating behavior can be interpreted in terms of a metastable energy barrier. In the hope of advancing nuclear electrophysiology, and to complement the other papers contained in this special issue of the journal, here I review some of the main technical, experimental, and theoretical issues of the field, with special focus on NPCs.     

Current concepts in aesthetic upper blepharoplasty

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Discuss nomenclature and anatomy associated with upper blepharoplasty. 2. Perform preoperative assessment, decision-making, and counseling of patients. 3. Describe current surgical planning, eyelid marking, and various techniques used in upper blepharoplasty, including lasers. 4. Recognize and treat postoperative complications from blepharoplasty.Traditional blepharoplasty has often involved the excision of both lax skin and muscle and excessive removal of fat, leaving patients long term with a hollow orbit and a harsh, operated appearance that accelerates the aging process. Current methods of periorbital rejuvenation are more conservative, are based on concise preoperative evaluation, and involve the limited resection of the coveted soft tissue from the eye to restore a youthful appearance. The authors describe anatomy, preoperative assessment, decision-making and counseling of patients, surgical planning, eyelid marking, and various techniques, including lasers, along with postoperative complications associated with current concepts in aesthetic upper blepharoplasty.     

Current concepts in cancer vaccine strategies

Cancer vaccines are entering a new phase of popularity, in part because of the recognition of when a therapeutic vaccine is most effective and the identification of appropriate target antigens. New technologies, most notably gene transfection into dendritic cell and DNA vaccination approaches, have spurred further clinical evaluations. While many researchers consider humoral responses as not being viable for large tumors, these responses may play a role in regulating micrometastases (i.e., adjuvant setting). The recent approval of antibodies as therapeutics for cancer treatment has lent to the viability of this therapy concept. The success of carbohydrate-conjugate vaccines in bacterial systems has also renewed interest in developing such vaccines for cancer immunotherapy. Carbohydrates can be further converted into peptide/protein mimetics with several of these mimetics in clinical trials. These mimetic forms can be manipulated into DNA vaccine types that may be combined into DNA cassettes that contain CTL-associated epitopes to further define a novel strategy for future vaccine development.     

Current concepts in clinical radiation oncology

Based on its potent capacity to induce tumor cell death and to abrogate clonogenic survival, radiotherapy is a key part of multimodal cancer treatment approaches. Numerous clinical trials have documented the clear correlation between improved local control and increased overall survival. However, despite all progress, the efficacy of radiation-based treatment approaches is still limited by different technological, biological, and clinical constraints. In principle, the following major issues can be distinguished: (1) The intrinsic radiation resistance of several tumors is higher than that of the surrounding normal tissue, (2) the true patho-anatomical borders of tumors or areas at risk are not perfectly identifiable, (3) the treatment volume cannot be adjusted properly during a given treatment series, and (4) the individual heterogeneity in terms of tumor and normal tissue responses toward irradiation is immense. At present, research efforts in radiation oncology follow three major tracks, in order to address these limitations: (1) implementation of molecularly targeted agents and ‘omics’-based screening and stratification procedures, (2) improvement of treatment planning, imaging, and accuracy of dose application, and (3) clinical implementation of other types of radiation, including protons and heavy ions. Several of these strategies have already revealed promising improvements with regard to clinical outcome. Nevertheless, many open questions remain with individualization of treatment approaches being a key problem. In the present review, the current status of radiation-based cancer treatment with particular focus on novel aspects and developments that will influence the field of radiation oncology in the near future is summarized and discussed.     

Communication between neurones: Current concepts

Neurotransmitters are chemicals which have the specific function of transferring information from one neurone to another at specific sites called synapses. This concept is discussed in relation to the experimental evidence which suggests that neurotransmitters may be released non synaptically and that certain neurones may utilise more than one transmitter substance. The term ‘modulator’ is also discussed and compared with what is understood to be a ‘neurotransmitter’.     

Current concepts in membrane protein reconstitution

The reconstitution of integral proteins into artificial lipid vesicles is largely prompted by the complexity of most biological membranes and the inherent difficulty of studying individual components in situ. Ideally, therefore, the reconstituted system should consist of a single protein in a lipid matrix which mimics the native membrane in all but its diversity. While such an approach allows individual components of a complex system to be studied in isolation it should also be sufficiently versatile to permit the generation of increasingly sophisticated multicomponent models. From the considerable number of reconstitution techniques which have been developed I have tried in this review to identify those characteristics of a particular system which maximise both the information it can provide and its versatility.     

Current concepts of basement-membrane structure and function

Conclusion In this brief review we have attempted to describe the known components of basement membranes in relation to the morphology and function of these matrices. Further details of the molecular structures and biosynthesis of these components may be found in original papers and in various reviews (Kefalides, 1973; Spiro, 1976; Kefalides et al., 1979; Heathcote & Grant, 1981).Although basement membranes appear to contain essentially similar protein and carbohydrate moieties, the proportions and organization of these may differ and, in the opinion of the authors, the key to an understanding of basement membranes lies in the recognition of this heterogeneity. At present, structural models of basement membrane are far from satisfactory and should be regarded with reservation.