Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology

In the nervous system, prostanoids are well recognized as mediators in a variety of processes, including fever generation, modulation of the stress response, sleep/wake cycle, control of cerebral blood flow, and hyperalgesia. Two isoforms of cyclooxygenase (COX), the enzyme that catalyzes the conversion of arachidonic acid to prostanoids, are now recognized: a constitutively expressed COX-1 and a highly regulated COX-2. New molecular and pharmacologic tools have provided a better understanding of the roles of COX-generated prostanoids in the nervous system. Other studies reveal that COX may represent an important target for new therapeutic approaches to neurologic disorders. This review summarizes our current understanding of cyclooxygenase expression and prostanoid actions in the nervous system, with special reference to COX-2 and studies demonstrating its expression in different cell types responding to a variety of stimuli. A brief review of the molecular biology, pharmacology, and primary actions of COX-2 outside of the nervous system provides a context for understanding potential neurobiological roles for COX-2 and prostanoid production. Information about the role of COX in human neurological disorders, including cerebrovascular disease, Alzheimer' s disease, and hyperalgesia, is covered in the last section.     

Nosocomial fungal infections: epidemiology, diagnosis, and treatment.

Invasive fungal infections are increasingly common in the nosocomial setting. Furthermore, because risk factors for these infections continue to increase in frequency, it is likely that nosocomial fungal infections will continue to increase in frequency in the coming decades. The predominant nosocomial fungal pathogens include Candida spp., Aspergillus spp., Mucorales, Fusarium spp., and other molds, including Scedosporium spp. These infections are difficult to diagnose and cause high morbidity and mortality despite antifungal therapy. Early initiation of effective antifungal therapy and reversal of underlying host defects remain the cornerstones of treatment for nosocomial fungal infections. In recent years, new antifungal agents have become available, resulting in a change in standard of care for many of these infections. Nevertheless, the mortality of nosocomial fungal infections remains high, and new therapeutic and preventative strategies are needed.     

Apolipoprotein E: Implications for AD neurobiology, epidemiology and risk assessment

Alzheimer disease (AD) is a common and devastating dementing illness for which there is no effective neuroprotective therapy or cure. The presence of the apolipoprotein E (apoE) ε4 allele is a well-established genetic modifier (risk factor) of sporadic AD. In this review, we provide an update on the implications of apoE for the neurobiology and epidemiology of AD. Moreover, recent evidence is adduced indicating that (i) many AD risk factors are potentially modifiable by adaptive lifestyle changes and pharmacotherapy and (ii) the potency of these modifiable AD determinants and responsiveness to intervention are often significantly impacted by the presence or absence of the ε4 allele. Delineation of the influences of the APOE genotype on modifiable AD risk factors and prevention may spur consideration of APOE testing for presymptomatic individuals seeking to define their personal risk.     

Pediculosis capitis: new insights into epidemiology, diagnosis and treatment

Pediculosis capitis is a ubiquitous parasitic skin disease caused by Pediculus humanus capitis. Head lice are highly specialised parasites which can propagate only on human scalp and hair. Transmission occurs by direct head-to-head contact. Head lice are vectors of important bacterial pathogens. Pediculosis capitis usually occurs in small epidemics in play groups, kindergartens and schools. Population-based studies in European countries show highly diverging prevalences, ranging from 1% to 20%. The diagnosis of head lice infestation is made through the visual inspection of hair and scalp or dry/wet combing. The optimal method for the diagnosis of active head lice infestation is dry/wet combing. Topical application of a pediculicide is the most common treatment. Compounds with a neurotoxic mode of action are widely used but are becoming less effective due to resistant parasite populations. Besides, their use is restricted by safety concerns. Dimeticones, silicone oils with a low surface tension and the propensity to perfectly coat surfaces, have a purely physical mode of action. This group of compounds is highly effective and safe, and there is no risk that head lice become resistant. The control of epidemics requires active contact tracing and synchronised treatment with an effective and safe pediculicide.     

Update on epidemiology,diagnosis, and treatment of pertussis

AlthoughBordetella pertussis was identified as the causative organism of whooping cough in 1906 (1), numerous questions regarding epidemiology, diagnosis, treatment, and prevention of this disease remain unanswered. Widespread immunization has drastically reduced the prevalence of pertussis in many countries, but epidemics still occur, even in well-immunized communities (2, 3), which explains the continued interest in this old disease.This editorial will focus on some recent developments in the areas of epidemiology, diagnosis, and treatment of pertussis; it is not, however, intended as a comprehensive review of these fields.     

Onychomycosis: recent progress in the epidemiology, diagnosis and treatment]

Recent progress in the epidemiology, diagnosis and treatment of onychomycosis is summarized. The risk factors of this condition were investigated, and the results of analyses of the systemic state of patients, shape of nails, blood circulation around nails, nail growth rate and causative fungi were reported. In making a diagnosis of onychomycosis, the major effect of the quality of collected nail samples on the results was reconfirmed. In addition to the KOH method and culture method, a molecular biological method was introduced. From the therapeutic perspective, 1) prevention of recurrence, 2) identification of patients with high risk of onychomycosis, and 3) attempting new treatments (development of new drugs, improvement of administration and dosage, and evaluation of combined therapy) were discussed. The effectiveness of concomitant use with nail lacquer is anticipated in combined therapy. New studies on accurate diagnosis, early detection and early stage treatment are now being undertaken.     

Self-criticism and social phobia in the US national comorbidity survey

BACKGROUND: This study sought to extend findings from a preliminary clinical investigation [J. Affect. Disord. 57 (2000) 223] by examining relations between the personality dimension of self-criticism and diagnostic prevalence of social phobia in a large nationally representative sample. METHODS: Participants were from the national comorbidity survey Part II [n=5877; Arch. Gen. Psychiatry 51 (1994) 8]. Psychiatric diagnoses were made using a modified version of the composite international psychiatric interview. Personality dimensions and distress were assessed using brief self-report measures with strong psychometric properties. RESULTS: Self-criticism was elevated in NCS respondents with a diagnosis of social phobia, even in cases of only past history of social phobia (i.e. >1 year ago), compared to individuals with no psychiatric disorder. The highest levels of self-criticism were reported by people with the complex subtype of social phobia, both with and without comorbid major depression. These levels were significantly greater compared to those observed in another anxiety disorder (panic disorder), the pure speaking subtype of social phobia, and cases of major depression alone. In a regression analysis that controlled for current emotional distress, the broad personality trait of neuroticism, and lifetime histories of mood, anxiety, and substance use disorders, self-criticism remained significantly associated with lifetime prevalence of social phobia. LIMITATIONS: The cross-sectional design of the study does not permit causal inferences. CONCLUSIONS: Findings from this general population mental health survey demonstrated that self-criticism is robustly associated with social phobia. It may represent an important core psychological process in the complex subtype of this anxiety disorder.     

Attention-deficit/hyperactivity disorder: diagnosis, lifespan, comorbidities, and neurobiology

In this report, we provide an evidence-based overview of attention-deficit/hyperactivity disorder (ADHD), including diagnosis, prevalence, developmental expression of symptoms, persistence, the heterogeneity of functional outcome, impairment in afflicted adults, psychiatric comorbidity, pathophysiology, genetics, psychosocial and biologic risk factors, and neurobiology. Attention-deficit/hyperactivity disorder is an early-onset, highly prevalent neurobehavioral disorder, with genetic, environmental, and biologic etiologies, that persists into adolescence and adulthood in a sizable majority of afflicted children of both sexes. It is characterized by behavioral symptoms of inattention, hyperactivity, and impulsivity across the life cycle and is associated with considerable morbidity and disability. Comorbidity is a distinct clinical feature of both childhood and adult ADHD. Although its etiology remains unclear, emerging evidence documents its strong neurobiologic and genetic underpinnings. Despite the high diagnostic reliability and the robust evidence of the validity of ADHD, there are many underlying issues that remain to be resolved. These include establishing developmentally appropriate diagnostic criteria at older ages, further elaborating the impact of gender on symptom expression, and examining risk and protective factors in relationship to prevention or amelioration of ADHD as well as related functional impairments.     

West Nile virus in Europe: emergence,epidemiology, diagnosis,treatment, and prevention

West Nile virus (WNV), a mosquito-borne flavivirus in the Japanese encephalitis antigenic group, has caused sporadic outbreaks in humans, horses and birds throughout many of the warmer regions of Europe for at least 20 years. Occasional cases of West Nile encephalitis have also been associated with infected blood transfusions and organ donations. Currently, WNV appears to be expanding its geographical range in Europe and causing increasing numbers of epidemics/outbreaks associated with human morbidity and mortality. This brief review reports on the current epidemic situation regarding WNV in Europe, highlighting the clinical, diagnostic and preventive measures available for controlling this apparently emerging human pathogen.     

Mycotic keratitis: epidemiology,diagnosis and management

Mycotic keratitis (an infection of the cornea) is an important ocular infection, especially in young male outdoor workers. There are two frequent presentations: keratitis due to filamentous fungi (Fusarium, Aspergillus, phaeohyphomycetes and Scedosporium apiospermum are frequent causes) and keratitis due to yeast-like fungi (Candida albicans and other Candida species). In the former, trauma is usually the sole predisposing factor, although previous use of corticosteroids and contact lens wear are gaining importance as risk factors; in the latter, there is usually some systemic or local (ocular) defect. The clinical presentation and clinical features may suggest a diagnosis of mycotic keratitis; increasingly, in vivo (non-invasive) imaging techniques (confocal microscopy and anterior segment optical coherence tomography) are also being used for diagnosis. However, microbiological investigations, particularly direct microscopic examination and culture of corneal scrape or biopsy material, still form the cornerstone of diagnosis. In recent years, the PCR has gained prominence as a diagnostic aid for mycotic keratitis, being used to complement microbiological methods; more importantly, this molecular method permits rapid specific identification of the aetiological agent. Although various antifungal compounds have been used for therapy, management of this condition (particularly if deep lesions occur) continues to be problematic; topical natamycin and, increasingly, voriconazole (given by various routes) are key therapeutic agents. Therapeutic surgery, such as therapeutic penetrating keratoplasty, is needed when medical therapy fails. Increased awareness of the importance of this condition is likely to spur future research initiatives.     

Leptospirosis: epidemiology,diagnosis and clinical aspects

Leptospires, world-wide distributed spirochetes, affect a great variety of mammalian hosts; several serovars belonging to the L. interrogans s.l. species can cause clinical manifestations in humans, becoming infected through the contact of skin cuts and mucous membranes with water and soil polluted by infected animals' urine; rodents serve as the main reservoirs but the epidemiological importance of pets and cattle, as leptospire shedder is increasing. While the infection remains endemic in tropical regions, there is a new epidemiological trend in developed countries where, with the typical seasonal pattern, sporadic cases and/or outbreaks occur related more to recreational activities and poor sanitation than to occupational activities. The sudden onset presents a "flu-like" syndrome; the course is usually characterised by two clearly defined stages. All of the variable clinical manifestations, often independent of the responsible serovar, arise from the effects of a general vasculitis. The prognostic factors associated with severe forms (renal failure, jaundice, haemorrhagies) are not defined. Within the first days of illness, the leptospires can be isolated from blood and cerebrospinal fluid; serological diagnosis relies on microagglutination, IFA and ELISA; PCR early in the course, before the appearance of specific antibodies, allows etiological diagnosis. Prompt treatment has an enormous impact on outcome.     

Idiopathic Parkinson''s disease: epidemiology, diagnosis and management.

Since the introduction of levodopa therapy for idiopathic Parkinson's disease over 20 years ago, there has been an awakening of research interest in this chronic neuro-degenerative disorder. This paper describes current understanding of the role of genetic and environmental factors in the aetiology of idiopathic Parkinson's disease and problems associated with both diagnosis and management. It briefly outlines both pharmacological and non-pharmacological options for treatment. Despite an increasing armoury of available treatments, the optimum management for this condition remains controversial.     

Cat-scratch disease: epidemiology, aetiology and treatment.

Cat-scratch disease (CSD) is a clinical syndrome that usually presents as a self-limiting lymphadenopathy associated with a cat scratch or bite. Commonly affecting children and young adults, it has a worldwide distribution. In temperate climates, higher rates are reported in the autumn and winter, which can be attributed to the seasonal breeding of the domestic cat. The organism responsible was identified in 1983, having eluded detection for 50 years. Initially, Afipia felis was thought to be the cause; however, subsequent study failed to confirm a link. During the 1990s, it was demonstrated conclusively that Rochalimaea henselae, later reclassified as Bartonella henselae, was the cause of CSD. B. henselae has been isolated from bacteraemic cats, with transmission among cats thought to be via the cat flea. Although other Bartonella species are transmitted by arthropod vectors, it is unlikely that the cat flea is involved directly in human infection, but plays a role in amplifying the reservoir. B. henselae is difficult to culture, and either serology or the polymerase chain reaction are considered to be the best methods of detection. Genetic variation occurs amongst B. henselae strains, perhaps explaining the inconsistency of some diagnostic techniques. A separate serogroup (Marseilles) has been reported in a seronegative patient with CSD, and B. clarridgeiae has the potential to cause the disease. Atypical presentation is seen in up to 25% of cases, and manifests itself as ocular involvement, encephalopathy, granulomatous hepatitis, hepatosplenic infection, endocarditis and osteomyelitis. The majority of CSD cases resolve spontaneously and do not require antibiotic treatment. In complicated CSD, treatment with trimethoprim-sulphamethoxazole, ciprofloxacin or azithromycin is recommended, with gentamicin being reserved for the severely ill patient.     

Tuberculosis and HIV infection: epidemiology, immunology, and treatment

Tuberculosis and HIV have combined to present a major threat to global public health. Each disease has a negative effect on the other, and mortality in patients with both tuberculosis and HIV is higher than that caused by either condition alone. In regions such as sub-Saharan Africa, as many as a third or more of all patients with tuberculosis have concomitant HIV infection. In urban centers in developed nations, HIV co-infection may also be quite common. Treatment of latent tuberculosis infection in persons with HIV is successful in preventing many cases of active disease, and newer ultra-short course regimens, such as those consisting of 2 months of rifampin and pyrazinamide, should aid in this effort. Diagnosis and treatment of active tuberculosis in HIV-infected patients may be difficult. Although treatment of active tuberculosis is generally successful in patients with HIV, drug interactions between anti-tuberculosis medications and antiretrovirals often complicate the matter, and expert guidance should be sought for proper management.     

The metabolic syndrome: epidemiology and diagnosis

There has been a tremendous increase in overweight and obesity in industrialized countries. Because of its comorbidities obesity is defined as a disease. The abdominal fat distribution is associated with insulin resistance and with a number of cardiovascular risk factors; all of them are included in the metabolic syndrome. The metabolic syndrome can easily be defined by clinical symptoms and laboratory results, which are defined in the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (AP III). Abdominal obesity is characterised by a waist circumference of over 102 cm for men and over 88 cm for women, plasma triglycerides >150 mg/dL, a low HDL cholesterol level (<40 mg/dL for men, <50 mg/dL for women), a blood pressure of over 130/85 mm Hg and an abnormal fasting glucose value >110 mg/dL.     

Malaria in Mayotte: epidemiology, diagnostic, prevention and treatment

Mayotte is a little French island, located in the Indian ocean, between Madagascar and Mozambic. Officially there is a population of 150000 inhabitants, but in fact, there are probably about 200000 people, largely due to numerous illegal immigrants, especially coming from Anjouan the nearest Comorian island. There is only one hospital, with 252 beds. The malaria incidence reaches about 3000 cases per year; and treatments until august 2001 were generally haphazard. This is changing with the use of the Optimal rapid diagnostic test (DiaMed, Cressier Switzerland). More precise statistics should be available in the coming years. In 2000, 252 patients were hospitalised with malaria fever. Preventive measures were scarce. These have been reenforced this year, with the arrival of an entomologist, the use of reenforced pesticide pulverisation in high-risk areas, the distribution of impregnated bednets to pregnant women, and media based information campaigns. Common drugs resistance is becoming a real concern in Mayotte. First-line treatment was: chloroquine; second-line: sulfadoxine-pyrimethamine, and third-line: quinine. In vitro studies have shown high levels of resistance, therefore another antimalarial drug therapy will be introduced at the end of the year: first-line: artemether-lumefantrine, second-line: mefloquine or halofantrine, third-line: quinine. To conclude, solutions exist but a real policy from the decision makers is necessary to implement them. The eradication of malaria remains a dream, but we can expect "zero death" in Mayotte, considering that the fight against this disease may help to start a regional health program.