Pathophysiology

We report the progression of splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes to Burkitt lymphoma with the presence of a t(8;14)(q24;q32) followed by a highly aggressive course. While the initial indolent lymphoma had an IgM λ immunophenotype the Burkitt lymphoma was IgM κ-positive. Immunoglobulin heavy chain gene (IGH) sequence analysis showed no identity between the two clones. We conclude that Burkitt lymphoma can occur in patients with SMZL, although not necessarily of identical clonal origin.

The anatomy and neurophysiology of cough has been reviewed in the preceding section. The objective of this section is to describe how the varied anatomic components of the respiratory system work in concert to produce an effective cough. Methods: This was accomplished by reviewing (1) the factors needed to produce effective cough pressures and gas velocity in the airways, and (2) the salient features of the interaction between the airflow generated during a cough and the mucus that lines the tracheobronchial tree. The MEDLINE database was searched for this review, and the search consisted of studies published in English between 1960 and April 2004. Search terms were "cough mechanics" and "cough physiology." Results: Inhaling to high lung volumes and glottic closure prior to the expiratory phase of cough facilitate the generation of high intrathoracic pressures. These high intrathoracic pressures (1) provide the driving force for airstream flow during cough and (2) dynamically compress the central airways, which further enhances the cough airstream velocity. Conclusions: High intrathoracic pressures are needed to generate the requisite cough expiratory flows and airstream velocities. However, cough may be effective in individuals with mild-tomoderate degrees of respiratory muscle weakness, as only modest increases in intrathoracic pressure are needed to dynamically compress the large intrathoracic airways and increase cough flow velocity.

Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself.

With our increasing appreciation of the true complexity of diseases and pathophysiologies, it is clear that this knowledge needs to inform the future development of pharmacotherapeutics. For many disorders, the disease mechanism itself is a complex process spanning multiple signaling networks, tissues, and organ systems. Identifying the precise nature and locations of the pathophysiology is crucial for the creation of systemically effective drugs. Diseases once considered constrained to a limited range of organ systems, e.g., central neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington' disease (HD), the role of multiple central and peripheral organ systems in the etiology of such diseases is now widely accepted. With this knowledge, it is increasingly clear that these seemingly distinct neurodegenerative disorders (AD, PD, and HD) possess multiple pathophysiological similarities thereby demonstrating an inter-related con...

The pathophysiology of metabolic syndrome involves altered glucose and lipid metabolism, and proinflammatory and prothrombotic states. All of these abnormalities appear to be linked to insulin resistance, which is associated with an increase in the free fatty acid level, usually due to obesity. This condition disturbs cellular glucose management and hepatic synthesis. In addition, lipid metabolism is also impaired by insulin resistance. In these circumstances, hypertriglyceridemia and HDL hypocholesterolemia both develop. Moreover, hypertension is related to altered insulin regulation and impaired autonomic nervous system activity. In addition to the well-demonstrated relationship with atherosclerosis, recently metabolic syndrome has also been associated with steatohepatitis and polycystic ovary syndrome.

The etiology of Periodic Limb Movement Disorder (PLMD) as well as the precise role of melatonin in human physiology remains poorly understood. Inspired by a single case observation we performed the presented study in order to obtain first evidence for the hypothesis that exogenous melatonin would decrease PLM's and thereby improves symptoms of PLMD patients. N/A. N/A. Nine patients with first time diagnosis of PLMD without RLS were treated over a six-week period with 3 mg melatonin, taken between 10 and 11 p.m. N/A. Melatonin improved well-being in 7 of the 9 patients. Polysomnography, performed prior and at the end of melatonin treatment, demonstrated a significant reduction of investigated movement parameters, such as PLMs, PLM index, PLMs with arousals and PLM-arousal index. Actigraphy, measured over 14 nights prior and during the last 14 days of melatonin treatment, showed a significant reduction in movement rate and minutes with movements during Time in Bed. The temporal di...

F emale sexual dysfunction is age-related, progressive, and highly prevalent, affecting 30% to 50% of women. 1-3 Based on the National Health and Social Life Survey of 1749 women, 43% experienced sexual dysfunction. 4 U.S. population census data reveal that 9.7 million American women aged 50 to 74 years self-report complaints of diminished vaginal lubrication, pain and discomfort with intercourse, decreased arousal, and difficulty achieving orgasm. Female sexual dysfunction is clearly an important women's health issue that affects the quality of life of many of our female patients.

We investigated plasma-membrane fluidity and heterogeneity of polymorphonuclear leukocytes (PMNs) obtained from seventeen children with trisomy 21. Membrane fluidity and heterogeneity were studied by measuring steady-state anisotropy and fluorescence lifetime of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) incorporated into plasma membranes. The fluorescence anisotropy values in unstimulated PMNs from children with trisomy 21 were significantly higher than those of the control group. The addition of the respiratory burst stimulus phorbol myristate acetate induced a stable and significant increase in fluorescence anisotropy in both groups. These results demonstrate a decrease in membrane fluidity. Moreover, distribution analysis of TMA-DPH lifetime values indicate a decrease in membrane heterogeneity in subjects with trisomy 21. These data suggest changes in the physicochemical properties of the PMN's plasma membrane at the lipid-water interface in children with trisomy 21.

The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC / TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva.

Purpose: After renal parenchymal sparing surgery, residual defects may persist on imaging studies at the sites of resection. These upseudotumorsn may lead to confusion as to whether a lesion was removed or has recurred. We describe the imaging appearances and behavior of renal pseudotumors following renal parenchymal sparing surgery. Materials and Methods: From 1988 to 1997, 32 patients underwent 46 renal parenchymal sparing surgeries for removal of renal cancers, including von Hippel-Lindau disease in 27, hereditary papillary renal cancer in 2 and sporadic disease in 3. A median of 14 tumors (range 1 to 114) were removed in each operation. Thrombin soaked absorbable gelatin sponge was placed in the tumor bed after resection to aid hemostasis. We reviewed all imaging studies performed after these operations to characterize these lesions and gain further understanding into the prevalence and etiology. Results: Of the patients, 9 had a total 13 pseudotumors on initial postoperative imaging studies, including Hippel-Lindau disease in 7, hereditary papillary renal cancer in 1 and sporadic renal cancer in 1. Pseudotumors were observed after 10 of 46 operations (22%). All pseudotumors demonstrated round contours and enhancement after contrast media, simulating a tumor, yet, these lesions resolved in a mean of 13 months, leaving only small cortical scars. Conclusions: Renal pseudotumors are commonly seen after renal parenchymal sparing surgery and should not be confused with residual or recurrent disease. Enhancement is likely due to granulation tissue involving the lattice of absorbable gelatin sponge. These lesions usually resolve within a year but can take longer to do so.

Fibromyalgia W Chronic fatigue syndrome W Functional somatic syndromes W Biopsychosocial model W Stress-related illnesses Abstract Fibromyalgia (FM) is a controversial syndrome, characterised by persistent widespread pain, abnormal pain sensitivity and additional symptoms such as fatigue and sleep disturbance. The syndrome largely overlaps with other functional somatic disorders, particularly chronic fatigue syndrome (CFS). Although the exact aetiology and pathogenesis of FM are still unknown, it has been suggested that stress may play a key role in the syndrome. This article first reviews the function of the stress response system, placing special emphasis on the relationships between adverse life experiences, stress regulation and pain-processing mechanisms, and summarising the evidence for a possible aetiopathogenetic role of stress in FM. Finally, an integrative biopsychosocial model that conceptualises FM as a stress disorder is proposed, and the clinical and research implications of the model are discussed.

В работе представлены экспериментальные данные, указывающие на повышенное содержание в стенках атеросклеротических артерий плазмалогенных фосфолипидов. Данный рост, вероятно, способствует развитию атеросклероза благодаря тому, что плазмалогенные фосфолипиды принимают крайне активное участие в реакциях со свободными радикалами. Образующиеся при этом продукты окислительной деструкции плазмалогенных фосфолипидов могут обладать проатерогенным действием. Кроме того, в жирнокислотном составе артерий с атеросклерозом отмечается рост доли некоторых полиненасыщенных жирных кислот, что также может способствовать более активному протеканию процессов свободнорадикального окисления липидов и атерогенезу.

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The aetiology of the myocardial hypokineis is seldom known in the individual case of DCM, although several theories concerning genetic, nutritional, metabolic, inflammatory, infectious, or drug-or toxin-induced myocardial disease have been discussed. DCM is often referred to as being breed-specific for Boxers, Doberman Pinschers, English Cocker Spaniels and other breeds. Review of reports on histopathologic findings in canine DCM reveals two histologically distinct forms of DCM; (1) cardiomyopathy of boxers and of Doberman pinschers, corresponding to the 'fatty infiltration-degenerative' type, and (2) the form seen in many giant, large-and medium-sized breeds, including some boxers and Doberman pinschers, which can be classified as the 'attenuated wavy fiber' type of DCM. The classification of canine idiopathic DCM according to histologic findigns seems superior to classification suggesting breed-specific syndromes, as some breeds (i.e. boxers and Doberman pinschers) may be affected by both diseases. However, ante mortem aetiological diagnosis of DCM is difficult. DCM carries a poor prognosis in dogs, and few prognostic indicators have been identified.

In order to discuss and illustrate the common effects on normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term ''acrophysis'' is proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the non-physeal ends of small tubular bones. The last layer of development of both physes and acrophysis is the cartilaginous zone of provisional calcification (ZPC). The enchondral bone abutting the ZPC shares similar properties at physes and acrophyses, including the relatively lucent metaphyseal bands of many normal infants at several weeks of age. The bone-in-bone pattern of the normal vertebral bodies and bands of demineralization of the tarsal bones just under the ZPC are the equivalent of those bands. The growth arrest/recovery lines of metaphyses similarly have equivalent lines in growth centers and other acrophyseal sites. Nearly the same effects can also be anticipated from the relatively similar growth plate at the cartilaginous cap of benign exostoses (''paraphysis''). The companion article will explore abnormalities at acrophyseal sites, including metabolic bone disease and dysplasias.

The nose is a very complex organ with multiple functions that include not only olfaction, but also the conditioning (e.g., humidifying, warming, and filtering) of inhaled air. The nose is also a "scrubbing tower" that removes inhaled chemicals that may be harmful to the more sensitive tissues in the lower tracheobronchial airways and pulmonary parenchyma. Because the nasal airway may also be a prime target for many inhaled toxicants, it is important to understand the comparative aspects of nasal structure and function among laboratory animals commonly used in inhalation toxicology studies, and how nasal tissues and cells in these mammalian species may respond to inhaled toxicants. The surface epithelium lining the nasal passages is often the first tissue in the nose to be directly injured by inhaled toxicants. Five morphologically and functionally distinct epithelia line the mammalian nasal passages-olfactory, respiratory, squamous, transitional, and lymphoepithelial-and each nasal epithelium may be injured by an inhaled toxicant. Toxicant-induced epithelial lesions in the nasal passages of laboratory animals (and humans) are often site-specific and dependent on the intranasal regional dose of the inhaled chemical and the sensitivity of the nasal epithelial tissue to the specific chemical. In this brief review, we present examples of nonneoplastic epithelial lesions (e.g., cell death, hyperplasia, metaplasia) caused by single or repeated exposure to various inhaled chemical toxicants. In addition, we provide examples of how nasal maps may be used to record the character, magnitude and distribution of toxicant-induced epithelial injury in the nasal airways of laboratory animals. Intranasal mapping of nasal histopathology (or molecular and biochemical alterations to the nasal mucosa) may be used along with innovative dosimetric models to determine dose/response relationships and to understand if site-specific lesions are driven primarily by airflow, by tissue sensitivity, or by another mechanism of toxicity. The present review provides a brief overview of comparative nasal structure, function and toxicologic pathology of the mammalian nasal epithelium and a brief discussion on how data from animal toxicology studies have been used to estimate the risk of inhaled chemicals to human health.

La prévalence de la dénutrition est proche de 50 % à l'admission à l'hôpital et particulièrement à l'entrée en réanimation. L'état nutritionnel s'aggrave le plus souvent pendant le séjour du fait des différentes agressions subies en réanimation et de l'insuffisance d'apport. L'agression induit une augmentation des dépenses énergétiques et un hypercatabolisme protéique. Cette adaptation métabolique de l'organisme entraîne des modifications notables de la composition corporelle et plus particulièrement une diminution de la masse maigre. Celle-ci se fait principalement au dépend de la masse musculaire qui développe des atteintes structurelles à l'origine de conséquences fonctionnelles compromettant la réhabilitation. L'année qui suit le séjour en réanimation est souvent marquée par une persistance de la dénutrition, voire d'une aggravation de l'état nutritionnel et d'une mortalité d'environ 20 %. Ces données soulignent l'importance de la compréhension de la physiopathologie de la dénutrition en réanimation, abordée dans cet article, et de sa prise en charge.

Bruxism is a controversial phenomenon. Both its de®nition and the diagnostic procedure contribute to the fact that the literature about the aetiology of this disorder is dif®cult to interpret. There is, however, consensus about the multifactorial nature of the aetiology. Besides peripheral (morphological) factors, central (pathophysiological and psychological) factors can be distinguished. In the past, morphological factors, like occlusal discrepancies and the anatomy of the bony structures of the orofacial region, have been considered the main causative factors for bruxism. Nowadays, these factors play only a small role, if any. Recent focus is more on the pathophysiological factors. For example, bruxism has been suggested to be part of a sleep arousal response. In addition, bruxism appears to be modulated by various neurotransmitters in the central nervous system. More speci®cally, disturbances in the central dopaminergic system have been linked to bruxism. Further, factors like smoking, alcohol, drugs, diseases and trauma may be involved in the bruxism aetiology. Psychological factors like stress and personality are frequently mentioned in relation to bruxism as well. However, research to these factors comes to equivocal results and needs further attention. Taken all evidence together, bruxism appears to be mainly regulated centrally, not peripherally.

Revues g~n~rales et analyses prospectives A nticorps a ntiphospholipides. " aspects analytiques et physiopathologiques)arnige (revu le 30 mai 2001 ," accept~ le 16juillet 2001) _r~sum~ Les anticorps antiphospholipides repr~sentent un groupe h~t~rog~ne d'anticorps qui sont mis en 6vidence soit par des tests de coagulation d~pendants des phospholipides, d~tectant le lupus anticoagulant ou anticoagulant circulant antiprothrombinase, soit par des tests immunologiques de type ELISA mettant en ~vidence les anticorps anticardiolipine et des anticorps anti-1~2-glycoprot~ine I. La pr6sence de ces anticorps peut ~tre associ~e 6 des manifestations thrombotiques et/ou obst~tricales d6finissant le syndrome des antiphospholipides. Ces anticorps auraient, in viva, une action prothrombotique par deux grands m6canismes physiopathologiques : interference avec les syst~mes inhibiteurs de I'h6mostase avec, notamment, I'induction d'une r~sistance acquise a la prot~ine C activ~e, et activation cellulaire : cellules endoth~liales, plaquettes et monocytes.

The objective of the present work was to study biochemical alterations in corn plants infected by the maize bushy stunt phytoplasma. A resistant and a susceptible corn hybrid were used and changes in protein, phenolic compounds, chlorophyll and reducing sugars in infected plants were evaluated. The experiments were carried out inside greenhouse, and the corn plants were inoculated by using infective Dalbulus maidis leafhoppers 10 days after seeding. When symptoms started to appear, leaf samples were harvested at different times for the biochemical analyses. The results showed an increase in all biochemical parameters evaluated for both hybrids, with exception for the chlorophyll content that decreased. In a general way, the values observed for the level of the different compounds were higher in the susceptible hybrid when compared to the resistant one. The increases in protein, reducing sugar and phenolic compound contents in inoculated plants point out changes in host metabolism due to the phytoplasma, and the reduction in chlorophyll content shows that the phytoplasma can interfere in photosynthesis and perhaps speedy senescence in the leaf tissue. q

The paper deals with two central issues in the philosophy of neuroscience and psychiatry, namely those of the nature and
the major kinds and types of psychopathological mechanisms. Contrary to a widespread view, I argue that mechanisms are not kinds of systems but kinds of processes unfolding in systems or between systems. More precisely, I argue that psychopathological mechanisms are sets of actions and interactions between brain-systems or circuits as well as between the latter and other systems in one’s body and external environment, both physical and social, involved in human psychopathology. According to the kinds of properties of the interacting systems or their component-parts, psychopathological mechanisms may be physical, chemical, biological, psychological, social, or, typically, mixed
ones. Furthermore, I focus on two main kinds of psychopathological mechanisms involved in the causation of mental disorders, namely the pathogenetic and pathophysiological ones, stressing the importance of their careful distinction for the integrative understanding of otherwise disparate and apparently incommensurable psychiatric research findings. I illustrate my analysis with an example drawn from contemporary research on the mechanisms of acute psychosis. Finally, I stress the relevance of psychopathological mechanisms to a more scientifi cally-grounded classification of mental disorders.

γ-hydroxybutyric acid (GHB) causes retrograde amnesia in juveniles and young adults. Earlier, we have reported that in adolescent rat, GHB impairs the hidden platform task performance in the Morris water maze. In the present study, a classical fear conditioning paradigm was used to examine the effects of GHB on the acquisition of contextual conditioning, a hippocampus-dependent associative task, and cued tone conditioning, a hippocampus-independent task, in adolescent rats. Administration of GHB before the presentation of tone-shock pairings dose-dependently disrupted the acquisition of contextual conditioning with no effect on tone conditioning, when conditioned fear was measured 24 h later. Administering GHB prior to testing did not disrupt either contextual or tone conditioning. These results demonstrate that in the adolescent rat exposure to GHB preferentially disrupt hippocampal-dependent learning.

Cytokinesis-block micronucleus (CB-MN) assay and single-cell gel electrophoresis (SCGE) were employed to analyze leukocytes from 14 Fanconi anemia (FA) patients, 30 Down syndrome (DS) patients, and 30 control individuals, to examine the sensitivity of these techniques to detect genomic instability in these 2 diseases. The DS patients presented increased DNA damage as measured by SCGE in relation to controls. The frequencies of micronuclei and dicentric bridges were similar to those of controls. Micronucleus frequency, dicentric bridge frequencies, and DNA damage were higher in FA patients than in controls. The high frequency of micronuclei observed in FA patients seems to be due to clastogenic events, because an increase in the frequency of dicentric bridges was also observed. Micronuclei are expressed mutations and need cell division to appear. The damage detected by SCGE is repairable, and does not require cell division. Under alkaline conditions, SCGE assesses double-and single-strand breaks and alkali-labile sites. The 2 methods are efficient for monitoring mutagenic events in exposed populations or in individuals with genetic instability. While the damage measured by micronucleus analysis is accumulated over a long period of time, DNA damage measured by SCGE reflects recent, unrepaired events.

While brachial artery aneurysms are rare and usually of infectious, post-traumatic or iatrogenic etiology, true aneurysms of the brachial artery are even more unusual. We report on a large brachial artery aneurysm complicated by chronic contained rupture and partial out ow obstruction. This was observed 19 years after ligation of a radiocephalic (Brescia-Cimino) arteriovenous stula for hemodialysis that had existed for 2 years. Of 581 brachial artery reconstructions performed at the Cleveland Clinic Foundation between January 1989 and December 2000, only three involved repairs of brachial artery aneurysms; only the reported case was a true aneurysm of degenerative origin for an incidence of 0.17% (1/581). The management of brachial artery aneurysms is described and the pertinent literature was reviewed.

Our understanding of nociceptive processing and of plastic changes after persistent noxious input has increased immensely within the last two decades. It is now clear that long-lasting noxious stimulation or damage to the nervous system give rise to a neuronal hyperexcitability and that this sensitisation of the nervous system plays an important role for development and maintenance of chronic pain. The manifestations of such hyperexcitability are numerous and include among others: increased neuronal response to a suprathreshold stimulus, expansion of the peripheral areas from where a central neurone can be activated and the recruitment of previous non-responding nociceptive neurones. Furthermore, it has been possible to modulate this neuronal hyperexcitability by the discovery of molecular targets for pain, by sequencing DNA of ion channels and receptors and by development of new molecules that exert their effects on these molecular targets. The changes in responsiveness appear to be partly time and intensity dependent and partly dependent on the cause of injury. Whereas relatively short-lasting and moderate noxious input leads to reversible plastic changes, more intense and long-lasting noxious stimulation implies a risk for persistent and more profound alterations in transmitters, receptors, ion channels and in neuronal connectivity. P AIN IS A major clinical problem in society and the number of patients suffering from chronic pain is enormous. Within the last two decades the field of pain research has resulted in a considerable advance in our understanding of pain mechanisms: Molecular targets such as the vanilloid and opioid receptors together with different ion channels have been unravelled (1-4), spinal neuroplastic changes following a sustained noxious input have been described (5) and it has been possible by new imaging techniques to obtain insight into a former black box, the brain, and observe the processing of acute and chronic pain (6). The area is exploding with new information. Whereas it is obvious that acute and postoperative types of pain are better handled now than previously, progress in the treatment of chronic pain conditions, in particular neuropathic pain conditions, has been at a much slower pace. In fact, it is not at all clear that the advance in knowledge has resulted in a better clinical treatment of those suffering from chronic pain. The rapid basic expansion in terms of DNA sequencing of 1128 Despite the explosion of new knowledge in pain processing and in molecular background for neuroplasticity, this progress has unfortunately not resulted in a corresponding improvement of our ability to treat chronic pain. The number of patients with chronic unrelieved pain is still high and newer types of treatment have so far not resulted in a substantially better treatment. Nevertheless, there is now an ongoing systematic research in which chronic pain conditions are assessed in a fashion so that mechanisms underlying pain can be dissected. Moreover, controlled clinical trials together with systematic reviews are carried out which in the future should permit formulation of treatment algorithms for chronic pain. Finally, it is likely that the development of new specific types of treatment will show efficacy if they are evaluated and analysed not on the global pain experience, but more specifically on those targets and elements of the pain experience they are aimed to deal with. receptors and ion channels and the development in understanding neuroplastic changes in the nervous system following noxious input stands in sharp contrast to our handling of chronic pain patients. It is not at all clear that the number of chronic pain patients has been reduced -and in many instances treatment of chronic pain is still disappointing (7). In the following we will briefly describe areas where basic research has contributed or is expected to contribute to a better handling of chronic types of pain.

Social phobia is a common disorder associated with significant psychosocial impairment, representing a substantial public health problem largely determined by the high prevalence, and the lifelong chronicity. Social phobia starts in early childhood or adolescence and is often comorbid with depression, other anxiety disorders, alcohol and substance abuse or eating disorders. This cascade of comorbidity, usually secondary to social phobia, increases the disability associated with the condition. The possibility that social phobia may be a trigger for later developing comorbid disorders directs attention to the need for early effective treatment as a preventive measure.

Postoperative ileus (POI) is an abnormal pattern of gastrointestinal motility characterized by nausea, vomiting, abdominal distension and/or delayed passage of flatus or stool, which may occur following surgery. Postoperative ileus slows recovery, increases the risk of developing postoperative complications and confers a significant financial load on healthcare institutions. The aim of the present review is to provide a succinct overview of the clinical features and pathophysiological mechanisms of POI, with final comment on selected directions for future research.Terminology used when describing POI is inconsistent, with little differentiation made between the obligatory period of gut dysfunction seen after surgery ('normal POI') and the more clinically and pathologically significant entity of a 'prolonged POI'. Both normal and prolonged POI represent a fundamentally similar pathophysiological phenomenon. The aetiology of POI is postulated to be multifactorial, with principal mediators being inflammatory cell activation, autonomic dysfunction (both primarily and as part of the surgical stress response), agonism at gut opioid receptors, modulation of gastrointestinal hormone activity and electrolyte derangements. A final common pathway for these effectors is impaired contractility and motility and gut wall oedema. There are many potential directions for future research. In particular, there remains scope to accurately characterize the gastrointestinal dysfunction that underscores an ileus, development of an accurate risk stratification tool will facilitate early implementation of preventive measures and clinical appraisal of novel therapeutic strategies that target individual pathways in the pathogenesis of ileus warrant further investigation.

BACKGROUND Hypertrophic scars and keloids result from an abnormal fibrous wound healing process in which tissue repair and regeneration-regulating mechanism control is lost. These abnormal fibrous growths present a major therapeutic dilemma and challenge to the plastic surgeon because they are disfiguring and frequently recur. OBJECTIVE To provide updated clinical and experimental information on hypertrophic scars and keloids so that physicians can better understand and properly treat such lesions. METHODS A Medline literature search was performed for relevant publications and for diverse strategies for management of hypertrophic scars and keloids. CONCLUSION The growing understanding of the molecular processes of normal and abnormal wound healing is promising for discovery of novel approaches for the management of hypertrophic scars and keloids. Although optimal treatment of these lesions remains undefined, successful healing can be achieved only with combined multidisciplinary therapeutic regimens.

The Gell and Coombs's classification divides drug allergies into four pathophysiological types, namely anaphylaxis (type I), antibody-mediated cytotoxic reactions (type II), immune complex-mediated reactions (type III), and delayed type hypersensitivity (type IV). Although this classification was proposed more than 30 years ago, it is still widely used. As only a limited number of drug allergies fit into this classification which does not include our current understanding of the immune response, its use is not recommended, particularly in the context of the preclinical safety evaluation of new therapeutic agents. In fact, three different situations can be identified, namely pseudo-allergic reactions, primarily antibody-mediated reactions and cell-mediated reactions, which could serve as a basis for modern and more adequate classifications

Carpal tunnel syndrome (CTS) is a constellation of symptoms associated with compression of the median nerve at the wrist. The pathophysiology of CTS is not fully understood but mechanical aspects of injury within the carpal tunnel are most likely. The issues of ischemia, mechanical trauma, ectopic impulse generation, demyelination, tendonitis, elevated carpal tunnel pressure, mechanical factors, small and large fiber involvement and the variability of symptoms are presented.

Kinazlar, onkogenik Transkripsiyon Faktörleridir Kinazlar; Glikoliz,Yağ Sentezi,Protein Sentezini uyararak Hücre metabolizmasını aktifler.Elde edilen ATP'deki P'ı kullanan kinazlar da metabolizmadan faydalanmıĢ olur. Tm.supresor genler ise bu kinaz bağımlı yolakları baskılayarak hücre metabolizmasını bastırmaya çalıĢır.