The 2000 Ogura Lecture: Olfactory neural cells: An untapped diagnostic and therapeutic resource

Objective. This is an over-view of the cellular biology of upper nasal mucosal cells that have special characteristics that enable them to be used to diagnose and study congenital neurological diseases and to aid neural repair. Study Design: After mapping the distribution of neural cells in the upper nose, the authors' investigations moved to the use of olfactory neurones to diagnose neurological diseases of development, especially schizophrenia. Olfactory-ensheating glial cells (OEGs) from the cranial cavity promote axonal penetration of the central nervous system and aid spinal cord repair in rodents. The authors sought to isolate these cells from the more accessible upper nasal cavity in rats and in humans and prove they could likewise promote neural regeneration, making these cells suitable for human spinal repair investigations. Methods: The schizophrenia-diagnosis aspect of the study entailed the biopsy of the olfactory areas of 10 schizophrenic patients and 10 control subjects. The tissue samples were sliced and grown in culture medium. The ease of cell attachment to fibronectin (artificial epithelial basement membrane), as well as the mitotic and apoptotic indices, was studied in the presence and absence of dopamine in those cell cultures. The neural repair part of the study entailed a harvesting and insertion of first rat olfactory lamina propria rich in OEGs between cut ends of the spinal cords and then later the microinjection of an OEG-rich suspension into rat spinal cords previously transected by open laminectomy. Further studies were done in which OEG insertion was performed up to 1 month after rat cord transection and also in monkeys. Results: Schizophrenic patients' olfactory tissues do not easily attach to basement membrane compared with control subjects, adding evidence to the theory that cell wall anomalies are part of the schizophrenic lesion of neurones. Schizophrenic patient cell cultures had higher mitotic and apoptotic indices compared with control subjects. The addition of dopamine altered these indices enough to allow accurate differentiation of schizophrenics from control patients, leading to, possibly for the first time, an early objective diagnosis of schizophrenia and possible assessment of preventive strategies. OEGs from the nose were shown to be as effective as those from the olfactory bulb in promoting axonal growth across transected spinal cords even when added I month after injury in the rat. These otherwise paraplegic rats grew motor and proprioceptive and fine touch fibers with corresponding behavioral improvement. Conclusions. The tissues of the olfactory mucosa are readily available to the otolaryngologist. Being surface cells, they must regenerate (called neurogenesis). Biopsy of this area and amplification of cells in culture gives the scientist a window to the developing brain, including early diagnosis of schizophrenia. The Holy Grail of neurological disease is the cure of traumatic paraplegia and OEGs from the nose promote that repair. The otolaryngologist may become the necessary partner of the neurophysiologist and spinal surgeon to take the laboratory potential of paraplegic cure into the day-to-day realm of clinical reality.

Diagnostic and management protocols for equine Cushing's syndrome

Equine Cushing's syndrome is a common problem in aged horses and ponies. It presents with a variable combination of clinical signs; hirsutism is characteristic of the disease, with laminitis frequently being the most devastating consequence. This article describes the diagnostic protocols available and, in view of the fact that complete resolution of the disease is not achievable, discusses how the condition might be managed appropriately to improve the quality of life of affected animals.

Impact of gender on risk stratification by exercise and dobutamine stress echocardiography: long-term mortality in 4234 women and 6898 men

Aims Prior research is limited with regard to the diagnostic and prognostic accuracy of commonplace cardiac imaging modalities in women. The aim of this study was to examine 5-year mortality in 4234 women and 6898 men undergoing exercise or dobutamine stress echocardiography at three hospitals. Methods and results Univariable and multivariable Cox proportional hazards models were used to estimate time to cardiac death in this multi-centre, observational registry. Of the 11 132 patients, women had a greater frequency of cardiac risk factors (P < 0.0001). However, men more often had a history of coronary disease including a greater frequency of echocardiographic wall motion abnormalities (P < 0.0001). During 5 years of follow-up, 103 women and 226 men died from ischaernic heart disease (P < 0.0001). Echocardiographic estimates of left ventricular function (P < 0.0001) and the extent of ischaernic watt motion abnormalities (P < 0.0001) were highly predictive of cardiac death. Risk-adjusted 5-year survival was 99.4, 97.6, and 95% for exercising women with no, single, and multi-vessel ischaemia (P < 0.0001). For women undergoing dobutamine stress, 5-year survival was 95, 89, and 86.6% for those with 0, 1, and 2-3 vessel ischaemia (P < 0.0001). Exercising men had a 2.0-fold higher risk at every level of worsening ischaemia (P < 0.0001). Significantly worsening cardiac survival was noted for the 1568 men undergoing dobutamine stress echocardiography (P < 0.0001); no ischaemia was associated with 92% 5-year survival as compared with death rates of &GE; 16% for men with ischaemia on dobutamine stress echocardiography (P < 0.0001). Conclusion Echocardiographic measures of inducible wall motion abnormalities and global and regional left ventricutar function are highly predictive of long-term outcome for women and men alike.

Functional and prognostic implications of left ventricular contractile reserve in patients with asymptomatic severe mitral regurgitation

Objective: To evaluate contractile reserve (CR) determined by exercise echocardiography in predicting clinical outcome and left ventricular (LV) function in asymptomatic severe mitral regurgitation (MR). Design: Cohort study. Setting: Regional cardiac centre. Patients and outcome measures: LV volumes and ejection fraction (EF) were measured at rest and after stress in 71 patients with isolated MR. During follow up (mean (SD) 3 (1) years), EF and functional capacity were serially assessed and cardiac events ( cardiac death, heart failure, and new atrial fibrillation) were documented. Results: CR was present in 45 patients (CR+) and absent in 26 patients (CR-). Age, resting LV dimensions, EF, and MR severity were similar in both groups. Mitral surgery was performed in 19 of 45 (42%) CR+ patients and 22 of 26 (85%) CR2 patients. In patients undergoing surgery, CR was an independent predictor of follow up EF (p = 0.006) and postoperative LV dysfunction (EF < 50%) persisted in five patients, all in the CR2 group. Event-free survival was lower in surgically treated patients without CR (p = 0.03). In medically treated patients, follow up EF was preserved in those with intact CR but progressively deteriorated in patients without CR, in whom functional capacity also deteriorated. Conclusions: Evaluation of CR by exercise echocardiography may be useful for risk stratification and may help to optimise the timing of surgery in asymptomatic severe MR.

The empirical basis of substance use disorders diagnosis: research recommendations for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V)

Aims This paper presents the recommendations, developed from a 3-year consultation process, for a program of research to underpin the development of diagnostic concepts and criteria in the Substance Use Disorders section of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and potentially the relevant section of the next revision of the International Classification of Diseases (ICD). Methods A preliminary list of research topics was developed at the DSM-V Launch Conference in 2004. This led to the presentation of articles on these topics at a specific Substance Use Disorders Conference in February 2005, at the end of which a preliminary list of research questions was developed. This was further refined through an iterative process involving conference participants over the following year. Results Research questions have been placed into four categories: (1) questions that could be addressed immediately through secondary analyses of existing data sets; (2) items likely to require position papers to propose criteria or more focused questions with a view to subsequent analyses of existing data sets; (3) issues that could be proposed for literature reviews, but with a lower probability that these might progress to a data analytic phase; and (4) suggestions or comments that might not require immediate action, but that could be considered by the DSM-V and ICD 11 revision committees as part of their deliberations. Conclusions A broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.

The development of a research agenda for substance use disorders diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V)

Aims paper describes the background to the establishment of the Substance Use Disorders Workgroup, which was charged with developing the research agenda for the development of the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). It summarizes 18 articles that were commissioned to inform that process. Methods A preliminary list of research topics, developed at the DSM-V Launch Conference in 2004, led to the identification of subjects that were subject to formal presentations and detailed discussion at the Substance Use Disorders Conference in February 2005. Results The 18 articles presented in this supplement examine: (1) categorical versus dimensional diagnoses; (2) the neurobiological basis of substance use disorders; (3) social and cultural perspectives; (4) the crosswalk between DSM-IV and the International Classification of Diseases Tenth Revision (ICD-10); (5) comorbidity of substance use disorders and mental health disorders; (6) subtypes of disorders; (7) issues in adolescence; (8) substance-specific criteria; (9) the place of non-substance addictive disorders; and (10) the available research resources. Conclusions In the final paper a broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.

Performance comparisons between greedy and lagrange algorithms in adaptive MIMO MC-CDMA systems

This paper describes two algorithms for adaptive power and bit allocations in a multiple input multiple output multiple-carrier code division multiple access (MIMO MC-CDMA) system. The first is the greedy algorithm, which has already been presented in the literature. The other one, which is proposed by the authors, is based on the use of the Lagrange multiplier method. The performances of the two algorithms are compared via Monte Carlo simulations. At present stage, the simulations are restricted to a single user MIMO MC-CDMA system, which is equivalent to a MIMO OFDM system. It is assumed that the system operates in a frequency selective fading environment. The transmitter has a partial knowledge of the channel whose properties are measured at the receiver. The use of the two algorithms results in similar system performances. The advantage of the Lagrange algorithm is that is much faster than the greedy algorithm. ©2005 IEEE

Altered mucin expression in the gastrointestinal tract: a review

Early studies of changes in mucin expression in disorders of the gastrointestinal tract focused on alterations in the carbohydrate chain. This review briefly considers the various mechanisms by which such alterations may come about: (a) normal variation, (b) sialic acid alterations, (c) defective assembly of carbohydrate side-chains, (d) changed expression of core proteins and (e) epithelial metaplasia. The availability of monoclonal antibodies to mucin core proteins adds a new dimension to mucin histochemistry. It is now possible to offer explanations for traditional mucin histochemical findings on the basis of lineage-specific patterns of mucin core protein expression. Changes in core protein expression are described in inflammatory, metaplastic and neoplastic disorders of the gastrointestinal tract. The possibility that mucin change could be important in the aetiology of some diseases such as ulcerative colitis and H. pylori gastritis is considered. It is more probable, however, that changes in mucin expression are secondary to reprogramming of cellular differentiation and altered cell turnover. As such they may serve as markers to explain pathogenesis and provide novel diagnostic and prognostic information.