Ectopic Cushing's Syndrome Secondary to Metastatic Paraganglioma.

Paraneoplastic or ectopic Cushing's syndrome (CS) is a rare cause of endogenous hypercortisolism. It is due to ectopic adrenocorticotropic hormone (ACTH) secretion and has been reported in association with a variety of neuroendocrine tumors such as small-cell lung carcinoma, carcinoid tumors, and medullary carcinoma of the thyroid. Paragangliomas (PGLs) are rare neuroendocrine tumors that can secrete catecholamines. Case reports and reports of ectopic ACTH secretion from metastatic PGLs causing CS are exceedingly rare. We present a case of a 38-year-old female, who presented with typical signs, symptoms, and complications of CS, secondary to a PGL with widespread metastases, which eventually led to her demise.

Requirements for the clinical evaluation of new anti-tuberculosis agents in children.

The ultimate goal of evidence-based drug treatment is to produce a desired pharmacological response in a predictable manner and also to minimise adverse effects. This goal requires not only an increased awareness of the need to provide specific dosing recommendations aimed at specific patient groups, but also the implementation of a consistent integrative approach to recognise all factors contributing to the within- and between-subject variability in drug disposition and response. The assessment of new anti-tuberculosis agents and regimens in children requires a specific programme of investigation, and should be included early in human drug evaluation programmes. Appreciation of this principle is an important step forward towards the full integration of children into the tuberculosis research agenda and control programmes. The development of anti-tuberculosis drug formulations and regimens tailored to the requirements of children needs to consider physiological age-related differences for pharmacokinetics and toxicity between adults and children. Research based on these principles will create an evidence base that will inform the appropriate treatment of children with novel agents and regimens and will also inform future research, including the use of chemoprophylaxis and treatment-shortening strategies in children.

Compassionate use of and expanded access to new drugs for drug-resistant tuberculosis.

Several new classes of anti-tuberculosis agents are likely to become available in the coming decade. Ensuring prompt access to these drugs for patients without other treatment options is an important medical and public health issue. This article reviews the current state of 'compassionate use' and 'expanded access' programs for these new drugs, and identifies several shortcomings that will limit patient access to the drugs. A series of five steps is outlined that will need to be taken by national health bodies, international agencies and non-governmental organizations to prevent undue delays in access to new tuberculosis drugs for patients who could benefit from them. Following these steps can ensure that patients will be able to benefit from access to these drugs, while minimizing the risk of emergence of resistance to the drug.

Severe lower limb cellulitis is best diagnosed by dermatologists and managed with shared care between primary and secondary care.

BACKGROUND: Cellulitis is responsible for over 400,000 bed days per year in the English National Health Service (NHS) at the cost of £96 million. OBJECTIVES: An audit following transfer of care of lower limb cellulitis managed in secondary care from general physicians to dermatologists. METHODS: Review of patient details and work diaries from the first 40 months of implementation of the new model of care. RESULTS: Of 635 patients referred with lower limb cellulitis 33% had other diagnoses which did not require admission. Four hundred and seven of 425 patients with cellulitis were managed entirely as outpatients, many at home. Twenty-eight per cent of patients with cellulitis had an underlying skin disease identified and treated, which is likely to have reduced the risk of recurrent cellulitis, leg ulceration and lymphoedema. Only 18 of 635 patients referred with lower limb cellulitis required hospital admission for conventional treatment. CONCLUSIONS: This new way of managing suspected lower limb cellulitis offered substantial savings for the NHS, and benefits of early and accurate diagnosis with correct home treatment for patients.

Challenges and perspectives for improved management of HIV/Mycobacterium tuberculosis co-infection.

HIV and Mycobacterium tuberculosis (MTB) are two widespread and highly successful microbes whose synergy in pathogenesis has created a significant threat for human health globally. In acknowledgement of this fact, the European Union (EU) has funded a multinational support action, the European Network for global cooperation in the field of AIDS and TB (EUCO-Net), that brings together experts from Europe and those regions that bear the highest burden of HIV/MTB co-infection. Here, we summarise the main outcome of the EUCO-Net project derived from an expert group meeting that took place in Stellenbosch (South Africa) (AIDS/TB Workshop on Research Challenges and Opportunities for Future Collaboration) and the subsequent discussions, and propose priority areas for research and concerted actions that will have impact on future EU calls.

Comparison of the biomechanical properties of rottweiler and racing greyhound cranial cruciate ligaments.

An in vitro study of rottweiler and racing greyhound cranial cruciate ligaments revealed that the rottweiler ligaments had a significantly greater cross-sectional area at their distal attachments. Mechanical testing showed that the ultimate load related to body mass was significantly higher in the extended racing greyhound stifle during cranial tibial loading to failure, as were linear stiffness, tensile strength and tangent modulus. During ligament axis loading to failure, the only significant difference in structural and mechanical properties recorded between the two breeds was a greater ultimate strain for the greyhound ligament with the stifle joint flexed. Energy absorbed by the ligament complex at failure during cranial tibial loading was twice that for ligament axis loading for both breeds. The clinical significance is that the rottweiler cranial cruciate ligament is more vulnerable to damage as it requires half the load per unit body mass that the greyhound requires to cause a rupture.

Cranial cruciate stability in the rottweiler and racing greyhound: an in vitro study.

An in vitro biomechanical study of cadaver stifles from rottweilers and racing greyhounds was undertaken to evaluate the contribution of the cranial cruciate ligament to stifle joint stability. This was performed at differing stifle joint angles, first with the joint capsules and ligaments intact and then with all structures removed except for the cranial cruciate ligament. Craniocaudal laxity increased in both breeds as stifle flexion increased. The rottweiler stifle showed greater craniocaudal joint laxity than the racing greyhound at all joint angles between 150 degrees and 110 degrees, but the actual increases in joint laxity between these joint angles were similar for both breeds. Tibial rotation during craniocaudal loading of the stifle increased craniocaudal laxity in both breeds during joint flexion. The relative contribution of the cranial cruciate ligament to cranial stability of the stifle joint increased as the joint flexed and was similar in both breeds.

Dynorphin A-induced rat spinal cord injury: evidence for excitatory amino acid involvement in a pharmacological model of ischemic spinal cord injury.

Dynorphin A reduced lumbosacral blood flow, elevated cerebrospinal fluid lactic acid concentrations and caused flaccid hindlimb paralysis and striking neuropathological changes after its injection into the spinal subarachnoid space in rats. Coadministration of the vasodilator hydralazine substantially eliminated the paralytic, anaerobic metabolic and neuropathological responses to dynorphin A. In contrast, in concentrations up to 1 mM, dynorphin A did not alter the viability of cultured rat spinal cord neurons. Thus, it appears that this peptide lacks direct neurotoxic effects and that neuronal injuries in vivo result primarily from ischemia associated with dynorphin A-induced blood flow reductions. NMDA receptor antagonists significantly improved recovery from dynorphin A-induced hindlimb paralysis, and substantially eliminated neuropathological changes without attenuating the acute blood flow reductions or lactic acid elevations. Additionally, glutamate and aspartate concentrations were increased significantly in spinal cord cerebrospinal fluid samples removed during the time that peptide-induced spinal cord blood flow reductions were observed. In contrast, neither amino acid concentration was elevated in media removed after 1-hr exposure of spinal cord neuronal cell cultures to 100 microM concentrations of dynorphin A. These results indicate that the paralysis and spinal cord injuries produced in rats after spinal subarachnoid injection of dynorphin A result predominantly from spinal cord ischemia, and further identify excitatory amino acids and N-methyl-D-aspartate receptor mechanisms as important mediators in this injury model.

The Charter Medical Corporation clinical information system: a preliminary report.

Charter Medical Corporation's computerized Clinical Information System is described. The computerized system helps clinicians formulate and document individualized patient treatment plans along the continuum of care and to improve internal medical record keeping. The system can also help improve the efficient collecting, storing, retrieving, and reporting of clinical information, both for internal use and for external utilization review and case management. In the future, the system will be linked to Charter's continuous quality improvement efforts and to its new Clinical Outcome Monitoring System.

Assessing the attitude of veterans toward a smoking cessation program in a hospital setting.

110 male patients in a V. A. Hospital were surveyed in regard to their smoking behavior, attitudes toward smoking, and their willingness to participate in a treatment program designed to eliminate smoking. Some of the more important findings were that 68% of the patient population smoked as compared to 50% for the ggeneral male population. Only 57% of the smokers felt that smoking was harmful to their health. Many of the smokers (60%) had tried to stop smoking but were unsuccessful. 58% of the smokers stated that they would participate in a smoking treatment program. The results of this survey are interpreted to indicate the need for hospital and institutional treatment programs for elimination of smoking.