New developments in medical specialty training.

Medical specialty training is changing which will result in shorter, more focused training programmes. Senior house officer posts will disappear from August 2007, and be replaced by training posts and trust grade doctors. Eventually specialist registrars in higher specialty training will join with these new training posts to create run-through training. Curricula development and delivery with quality assurance is now the responsibility of a new training board--the Postgraduate Medical Education and Training Board (PMETB). There is an opportunity to create a new specialty of acute medicine to help meet the crisis of care for acutely ill patients in our hospitals.

The acute and long-term ocular effects of accelerated hypertension: a clinical and electrophysiological study.

Thirty-four patients with accelerated hypertension were clinically examined. The visual evoked potential (VEP) and electroretinogram (ERG) were recorded: acutely in 12 patients, being repeated in 7 patients up to 6 months later. In the remaining 22 patients these tests were performed 2-4 years after presentation. Visual acuity was < or = 6/12 in 22 of 68 (32%) eyes at presentation and < or = 6/12 in 10 of 58 (19%) eyes at follow-up. The cause of severest loss of vision appeared to be anterior ischaemic optic neuropathy, found in 3 cases. During the acute stage 11 patients (92%) had abnormal VEPs and all had abnormal ERGs. The group mean P100 latency, of the 7 patients (14 eyes) seen acutely and followed up at 6 months, was 123.8 ms with significant recovery of latency (p < 0.005) to 110.9 ms. The ERGs, however, remained reduced and delayed. In those patients recorded 2-4 years after their acute episode the VEP was abnormal in only 2 patients (9%); group mean P100 latency was 109.1 ms. However, 18 patients (82%) had abnormal ERGs. We suggest that during the acute stage of accelerated hypertension there is a high incidence of ischaemic optic neuropathy that usually resolves but can cause a permanent anterior ischaemic optic neuropathy, in addition to vascular retinopathy that persists.

Does type II diabetes predispose to retinal vein occlusion?

Retinal vein occlusion (RVO) not infrequently occurs in diabetic patients. Although the aetiology is unclear, it could relate to the other microvascular complications of diabetes. In the non-diabetic, both the central (CRVO) and branch (BRVO) forms are commonly associated with hypertension and hyperlipidaemia. We have therefore studied fifty type II diabetic patients with RVO compared to a carefully matched diabetic control group (n = 50) to elucidate underlying medical conditions and hence the aetiology of RVO in diabetic patients. The two groups were well matched. Diabetics with RVO showed a strikingly high prevalence of hypertension compared to the controls (72% versus 32%: p < 0.001) and a trend to increased hyperlipidaemia (54% versus 36%). Diabetic microvascular complications were more common in the control group (diabetic retinopathy and proteinuria). No significant differences were observed in mean HbA1 or weight, but current smoking habits and blood pressure levels were increased in the diabetics with RVO. 80% of diabetic patients with the BRVO form, were hypertensive. We conclude that the main underlying medical conditions for RVO in diabetics are hypertension and hyperlipidaemia, and these may be important in the aetiology as in the non-diabetic. RVO is more common in type II rather than type I diabetes, and does not associate with the presence of diabetic microvascular complications. Clinical assessment for hypertension and hyperlipidaemia is therefore important in diabetic patients with RVO, especially if recurrence of the condition and further visual loss is to be prevented.

Brain implants in man do not break down the blood-brain barrier to dopamine and domperidone.

We have evaluated the blood-brain barrier (BBB) in 8 Parkinsonian patients before and after stereotactic implantation of foetal mesencephalon (STIM) and one patient with an adrenal medullary implant. Parenteral administration of dopamine did not reverse Parkinsonism pre-operatively or at 5 days, 1, 2, 3, 4 months and 1 year post-operatively. Apomorphine and domperidone reversed Parkinsonism and produced dyskinesia in all patients pre- and post-operatively. We conclude that the BBB remains intact to dopamine following implantation.

Visual evoked cortical responses and electroretinograms following implantation of human fetal mesencephalon to the right caudate nucleus in Parkinson's disease.

Pattern electroretinograms and visual evoked cortical responses following flash and checkerboard pattern reversal stimulation were performed in 7 patients with advanced Parkinson's disease before and after implantation of human fetal ventral mesencephalon to the head of the right caudate nucleus. Six to nine months following surgery there was bilateral enhancement of flash-evoked response amplitudes. Electroretinogram measurements were unchanged. Individual increases in amplitude and decreases in latency were seen following pattern stimulation which were not statistically significant. A relationship between change in dyskinesia, and change in checkerboard pattern stimulation amplitude at 2.4 cycles per degree suggests that amplitude effects at this stimulus frequency are mediated via altered dopaminergic receptor status in the grafted hemisphere. This may be relevant to the mechanisms leading to generalised clinical improvements following this grafting technique.

Diabetes mellitus and retinal vein occlusion in patients of Asian, west Indian and white European origin.

The incidence of retinal vein occlusion (RVO) is known to be related to several cardiovascular risk factors including diabetes mellitus, hypertension and hyperlipidaemia. We have assessed the prevalence of these risk factors in Caucasian (N = 536, mean age = 65.21 years), West Indians (N = 24, mean age = 57.3 years) and Asian (N = 28, mean age = 51.4 years) patients presenting with RVO. We found no significant differences between the three groups in the distribution of hyperlipidaemia, but diabetes mellitus was more common amongst both the Asians and W. Indians (10% v 29% and 38%, p < 0.01 and p < 0.001). Hypertension was also more common in both the Asians and the West Indians (59% v 64% and 83% m p < 0.001 and p < 0.0001). The Asians and West Indians presenting with RVO were significantly younger and had significantly higher body mass index than their Caucasian counterparts (Ethnic origin, BMI, mean age: Asian, 28.1 +/- 4.3, 51.5 +/- 12.3 years; West indian: 30.2 +/- 7.7, 57.3 + 10 years; White: 24.8 +/- 4.2, 65.2 +/- 11.4 years). In this study RVO occurred at a younger age in Asians and West Indians, and was associated with a greater prevalence of diabetes mellitus and hypertension. The prevalence of hyperlipidaemia was no different in the three groups.

Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease.

Disaggregated ventral mesencephalic tissue from single aborted human fetuses of 11 to 18 weeks' gestation was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease. All were receiving optimum levodopa therapy and were examined preoperatively and at 3,6,9, and 12 months postoperatively. Immunosuppression was not used. There were significant sustained improvements at 12 months in three patients; motor fluctuations were absent in two. There were modest group improvements up to 6 months, with increased quality of "on" and "off" phases, quantity of on times, and specific improvements in contralateral upper limb bradykinesia. Preoperative levodopa requirements were reduced to a mean of 64% at 6 months and 61% at 12 months. Deterioration below baseline ratings occurred in three of nine patients who had consistent follow-up to 12 months. Grafting of midgestational human fetal tissue can lead to improvement in Parkinson's disease. Individual disease severity may be critical, and further trials are needed to identify host factors influencing outcome.

A comparative evaluation of clinical rating scales and quantitative measurements in assessment pre and post striatal implantation of human foetal mesencephalon in Parkinson's disease.

Six patients with advanced Parkinson's Disease were evaluated before and after implantation of human fetal ventral mesencephalic tissue to the head of the right caudate nucleus. The results of clinical assessment indicate that attempts to characterise patient fluctuations requires a combination of clinical rating scales and timing of specific limb tasks.

A series of experimental surgery for advanced Parkinson's disease by foetal mesencephalic transplantation.

12 patients with advanced Parkinson's Disease who had right caudate implantations of late stage foetal mesencephalon have been followed up for 1 to 2 years with extensive clinical and physiological assessments. Three patients failed to comply and were excluded. Seven of the remaining 9 patients showed substantial initial improvement which was well maintained in 4. Two of the 3 remaining patients of this group maintained lesser improvement. One returned to pre-operative state. Two patients with greatly advanced disease had only slight but brief improvement. A series of 24 matched patients have been treated and continue under investigation.

The survival of malignant hypertension in blacks, whites and Asians in Britain.

Life table analysis was used to compare survival rates in 168 whites, 39 blacks and 26 Asians with malignant phase hypertension. Amongst men, survival until death or the requirement of chronic renal dialysis was significantly worse in blacks, who initially presented with higher blood pressures and more renal impairment. There were no differences in survival in women in the three ethnic groups. Malignant hypertension remains common in Britain and still carries a poor prognosis.

Stereotactic implantation of fetal mesencephalon.

Twelve patients with advanced Parkinson's disease have been improved by transplantation of fetal mesencephalon into the caudate nucleus. No immunosuppression had been used. The human allogeneic transplantation window is wide.

Transplantation in Parkinson's disease: stereotactic implantation of adrenal medulla and foetal mesencephalon.

The two possible dopamine donor sites for transplantation are autologous adrenal medulla and human foetal substantia nigra or adrenal medulla. There is increasing experience with the use of adrenal medulla transplantation for Parkinson's disease and much less experience in foetal substantia nigra transplantation. The particular problems of each technique are discussed with examples and postoperative progress of cases with the special emphasis on management problems.

Progressive multiple cranial neuropathies presenting as a delayed complication of radiotherapy in infancy.

A 38 year old woman who had undergone irradiation during infancy for a left facial cutaneous arteriovenous malformation sequentially developed complete palsies of the ipsilateral VII, V, XI, IX, X, XII and VI cranial nerves. Apart from optic and olfactory nerve damage there are few reports of radiotherapy causing cranial nerve injury. We link the unusually extensive and progressive neural damage and the prolonged latency to the patient's age at time of irradiation.

Cholinergic and dopaminergic mechanisms in Parkinson's disease after long-term L-DOPA administration.

A study of parkinsonian patients suffering from ON-OFF phenomena, who had been on long-term treatment with L-DOPA, to the parenteral administration of apomorphine and physostigmine is reported. All patients, whether of the end-dose failure type or of the randomly occurring variety, when given apomorphine in an OFF phase, showed prompt reversal to an ON phase. Physostigmine given during an ON phase produced the opposite effect with induction of parkinsonian symptoms. These findings are interpreted as indicating that the dopaminergic receptors are available for stimulation during the OFF phase but are not receiving sufficient neurotransmitter, that is, dopamine, to stimulate their activity. The response to physostigmine is indicative of a return of cholinergic supersensitivity after long-term L-DOPA administration, the mechanisms by which this may occur are discussed. Based on these findings, therapeutic strategies are suggested that may overcome this major limitation of the use of L-DOPA in the treatment of parkinsonism.