Intraocular adenosine levels in normal and ocular-hypertensive patients.

PURPOSE: Adenosine receptors modulate several ocular responses; however, our understanding of factors that influence ocular extracellular adenosine levels is limited. The objective of this study was to evaluate how changes in intraocular pressure (IOP) influence endogenous levels of the purines adenosine and inosine, in the aqueous humor of normal and ocular-hypertensive patients. PATIENTS AND METHODS: Informed consent was obtained from 51 individuals undergoing cataract extraction or glaucoma surgical procedures. IOP was measured immediately prior to surgery. At the start of the surgical procedure, an aqueous sample of 75-100 microL was obtained. Purine levels were determined by reverse-phase HPLC. RESULTS: In normotensive individuals, mean aqueous adenosine and inosine levels were 5.2 +/- 1.1 and 19.4 +/- 2.2 ng/100 microL, respectively. No significant correlation between IOP and purine concentration was measured in this group. In ocular hypertensive individuals, the mean aqueous adenosine and inosine concentration was significantly elevated when compared to normotensive individuals. In the ocular hypertensive individual, this elevation in adenosine level was significantly correlated with IOP (r(2) = 0.42). CONCLUSIONS: These results demonstrate that in ocular hypertensive individuals, aqueous adenosine concentration is correlated with IOP. As the activation of adenosine receptors can modulate IOP and retinal blood flow, adenosine release during periods of ocular hypertension may play an important role in the physiological responses to elevated IOP.     

Postoperative radiotherapy for locally advanced colon cancer

Background: The role of adjuvant postoperative radiotherapy for locally advanced colon cancer is not well documented. Methods: Seventy-eight patients who underwent a complete resection of B2-C colon cancer received postoperative radiotherapy. Twenty-eight patients received ⩽45 Gy; 50 patients received 50–55 Gy. Twenty-seven patients received adjuvant fluorouracil-based chemotherapy. All patients were followed for a minimum of 3 years; no patients were lost to follow-up. Results: The overall local control rate was 88%. The 5-year actuarial rate of local control was 96% after 50–55 Gy postoperative radiotherapy compared with 76% after <50 Gy (p=0.0095). Multivariate analysis of local control showed that only radiotherapy dose significantly influenced this end point. Cause-specific survival rates at 5 years were B2, 67%; B3, 90%; C1, 100%; C2, 61%; C3, 36%; and overall, 63%. Multivariate analysis of cause-specific survival showed that only stage significantly influenced this end point. Bowel obstruction caused by adhesions developed in three patients and required a laparotomy; radiation-induced sarcoma developed in one additional patient. Conclusions: Postoperative radiotherapy appears to reduce the risk of local recurrence in patients with locally advanced colon cancer. The optimal dose is probably 50–55 Gy at 1.8 Gy per fraction. Postoperative radiotherapy may improve cause-specific survival for patients with stages B3 and C2 cancers.     

POLICE INVOLVEMENT WITH CLIENTS HAVING INTELLECTUAL DISABILITIES: A PILOT STUDY IN SOUTH LONDON

Following the increasing trend for de-institutionalisation of people with learning disabilities, community services are increasingly being utilised to support those who also display challenging behaviours. Where severely challenging behaviours are involved community service providers may require additional support from die police service. The authors undertook a retrospective pilot study among two major community care providers in South London, and looked at the reasons for calling the police, the frequency with which die police were called; staff expectations in calling the police and the outcomes for die clients in terms of further involvement with the criminal justice system. The authors note that the police were generally used as additional support when clients became too difficult for the immediate service providers to manage. It is also noted that police action on behalf of victims was generally low and that the police were never called in response to clients with learning disabilities reporting having witnessed crime. The authors note that further research is required.     

Stepwise progression of kindling: Perspectives from the kindling antagonism model

What is the nature of the kindling process? We hypothesize that kindling is a discontinuous process involving discrete, stepwise transitions from one state of neural organization to another. Our data from the kindling antagonism paradigm argue that there are two critical transitions in the kindling process. These transitions constitute major steps in kindled seizure development. They act as "gates" controlling the ability of afterdischarge (AD) activity to effect the necessary reorganization of neural function which drives the kindling process. We identify two critical gates: 1) a forebrain gate which is dependent on norepinephrine (NE) and effects a discrete transition from nonconvulsive, stage 1 and 2 behaviors to stage 3 seizures, and 2) a brainstem gate which is also NE-dependent and effects a transition from stage 3 seizures to stage 4 and 5 seizures. These gates separate the kindling process into 3 "phases" which are different from, but overlap, the traditional behavioral stages of kindling defined by Racine. Current data suggest that these phases involve independent neural circuitry. They may also involve different physiological mechanisms, but this remains to be determined. This hypothesis is designed to provide a framework for the kindling process within which to search for kindling mechanisms.     

Unraveling the mysteries of Duchenne and Becker muscular dystrophy

Through a process that has come to be known as reverse genetics, the gene and gene product involved in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) have been identified. The DMD/BMD gene is over 2 million base pairs in size and over 50% of DMD/BMD patients harbor submicroscopic deletions for portions of the gene. The gene product, named dystrophin, is 400 Kd in size. Dystrophin is present in skeletal, cardiac, and smooth muscles, as well as brain. The protein is absent or altered in DMD/BMD patient muscle. The normal function of dystrophin and the reasons why its alteration results in the DMD/BMD phenotypes are presently unknown. The discoveries to date, however, provide a starting point for investigating the fundamental pathogenetic mechanisms involved in DMD/BMD.