A quality assurance system based on ISO standards: experience in a radiotherapy department.

The European radiotherapy society has for many years had a great interest in quality assurance. The EORTC radiotherapy group has put enormous effort into its quality assurance programmes. However, besides programmes for dosimetry and guide-lines for infrastructure, the organisation of a department should also be subject to a quality assurance system. In 1992, in the radiotherapy department in Leiden, a project was started to develop a quality assurance system based on the so-called ISO 9001 quality standards. This paper describes how these standards can be applied to create a quality assurance system in a hospital department.

4-[123I]iodospiperone as a ligand for dopamine DA receptors: in vitro and in vivo experiments in a rat model.

Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Stimulated by data obtained with [11C]-N-methyl-spiperone we synthesized 4-[123I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [3H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[123I]iodospiperone and [3H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich in DA-receptors does not offer prospects for clinical receptor imaging with SPECT.

Hereditary cerebral hemorrhage with amyloidosis-Dutch type: a study of fibrinolysis.

In view of reported associations between increased bleeding tendency and systemically decreased alpha 2-antiplasmin in patients with systemic amyloid deposition we studied alpha 2-antiplasmin, fibrinogen, C-reactive protein and blood levels of locally produced endothelial hemostasis factors in the acute and quiescent phase in 16 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). None of the factors measured in the quiescent phase of the disease was abnormal. In the acute phase, shortly after a stroke, only factor VIII:Ag was evidently elevated. We concluded that systemic abnormalities in the part of the fibrinolysis system studied are not likely to be responsible for multifocal and recurrent cerebral hemorrhages in HCHWA-D. The role of an elevated factor VIII:Ag level in the acute phase is unclear.

Diurnal variation of essential and physiological tremor.

Evaluations were made of the diurnal variations of tremor power at rest, after fatigue and after mass loading, and plasma norepinephrine in patients with familial essential tremor and normal subjects. Diurnal tremor power rhythms for both essential and physiological tremor pursued identical temporal profiles. Plasma norepinephrine levels followed a congruent diurnal pattern with later peak values than the peak values of tremor power. Sympathetic nervous system activity is unlikely to be the cause of diurnal tremor power variation. The consistent diurnal rhythm of tremor power may affect dosage schemes of tremorolytic drugs.

The interpretation of dysprosody in patients with Parkinson's disease.

Prosodic features in the speech production of 21 patients with idiopathic Parkinson's disease were tested. The appreciation of vocal and facial expression was also examined in the same patients. Significant intergroup differences were found in the prosody production tasks but, in contrast to previous results, not in the receptive tasks on the recognition and appreciation of prosody and of facial expression. The discrepancy between the production and recognition of prosodic features does not support the suggestion that dysprosody in Parkinson's disease is necessarily a disorder of processing emotional information that could be misinterpreted as a dysarthria.

The MPTP model: versatile contributions to the treatment of idiopathic Parkinson's disease.

In human and subhuman primates, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces irreversible clinical, biochemical and neuropathological alterations highly reminiscent of those observed in Parkinson's disease. The MPTP model has provided the best available tool to date for the assessment of efficacy and side-effects of symptomatic treatments of Parkinson's disease. In addition, the mechanism of action of MPTP has offered a basis for the development of novel therapeutic strategies aimed at the prevention of Parkinson's disease.

Cytochrome P450 and Parkinson's disease. Poor parahydroxylation of phenytoin.

Phenytoin-parahydroxylation capacity was determined in 24 patients with Parkinson's disease (PD) and 17 controls. Different function of the phenytoin-metabolizing cytochrome P450 subsystem was found in 6 patients, but in none of the controls. These results add to previous studies suggesting a relation between the pathogenesis of PD and the function of cytochrome P450 subsystems.

Lymphocyte concanavalin A capping in hereditary cerebral haemorrhage with amyloidosis--Dutch type.

Lymphocyte capping with concanavalin A was studied in 11 patients with hereditary cerebral haemorrhage with amyloidosis (Dutch type) and 10 controls. No difference in capping was found between patients and controls. Abnormal lymphocyte concanavalin A capping has been reported in patients with the Icelandic type of cerebral amyloidosis and in patients with Alzheimer's disease, a disease in which cerebral amyloid angiopathy can also be found. The results suggest a difference in pathogenesis between the Dutch type of cerebral amyloidosis and the other amyloid diseases.

Hereditary cerebral hemorrhage with amyloidosis--Dutch type. Tc-99m HM-PAO single photon emission computed tomography.

We performed single photon emission computed tomography (SPECT) and cerebral CT-scans in nine patients with hereditary cerebral amyloid angiopathy. CT-scans showed 23 focal hypodense lesions, 13 of which were visible on SPECT as a CBF-defect. One patient showed a CBF-defect on SPECT without CT-scan lesion and had a cerebral hemorrhage three months later in that particular region. In two additional patients, who were 50% at risk for this autosomal dominant disease, CBF-defects on SPECT, but no cortical lesions on CT-scan were found. CT-scans may be more sensitive than SPECT to detect chronic lesions caused by cerebral hemorrhages, but another possibility is that hemorrhages do not always lead to persistent CBF-defects. SPECT can show the effect of amyloid deposits on CBF before the angiopathy causes clinical symptoms.

Endocrine functions in Huntington's disease. A two-and-a-half years follow-up study.

An oral glucose tolerance test (OGTT) was performed in 1985 in 10 patients with Huntington's disease (HD), while 10 healthy age-matched volunteers served as controls. Two-and-a-half years later, in 1988, 8 of the original 10 patients were reinvestigated. Apart from glucose, insulin and growth hormone (sampled at 30 min intervals) the following parameters of endocrine function were assessed: C-peptide (at times 0 and 60 min), glycosylated haemoglobin (HbAlc), somatomedin-C, and basal prolactin. In 1985 one female patient was considered to have impaired glucose tolerance, and this same patient, as well as another male patient, had a paradoxical rise in GH secretion. None of the other measurements of endocrine function differed significantly from control. In 1988 the HD patients had clinically deteriorated significantly, as measured by the Shoulson and Fahn Scale. Six of them completed a repeat OGTT. Of these 6, the same female as in 1985 showed impaired glucose tolerance. Now none of the participants had a paradoxical GH rise. The HD patients did not show any deterioration of the parameters of glucose metabolism, nor of GH secretion. The basal prolactin level, however, decreased significantly in these 2.5 years, from 9.3 +/- 3.2 micrograms/l to 6.1 +/- 3.0 micrograms/l (P less than 0.01).

Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family.

The mode of inheritance of insufficient phenytoin p-hydroxylation was studied in the family of a patient who had previously suffered from a phenytoin intoxication caused by insufficient metabolism of this drug. This family was compared with a control group. The rate of phenytoin metabolism was derived from the phenytoin/metabolite ratio in serum 6 hours after an oral test dose of 300 mg phenytoin. The propositus, a brother and a sister, were very slow metabolizers of phenytoin, with a metabolic ratio of approximately 20. In the other individuals, 22 family members of the second generation and 37 control subjects, a metabolic ratio of 4.7 +/- 2.2 (mean +/- SD; n = 59) was found. When comparing the members of the second generation (F2) with the control group, two statistically significantly different groups appear to exist: F2, with a metabolic ratio of 6.6 +/- 1.7 (mean +/- SD; n = 22), and the control group, with a metabolic ratio of 3.7 +/- 1.8 (mean +/- SD; n = 37) (p less than 0.001). Based on these results the mode of inheritance of this defect seems to be autosomal recessive.

Oculomotor control in Gilles de la Tourette syndrome.

Saccadic eye movements, fixation and smooth pursuit were studied in 28 children with Gilles de la Tourette syndrome and found to be normal. A link has been postulated between Gilles de la Tourette syndrome and other movement disorders. The results obtained in the present series do not support this hypothesis.

Autonomic nervous function in Huntington's disease.

Autonomic nervous system function was studied by means of a series of standardized tests in 11 patients with Huntington's disease (HD) and in 11 age- and sex-matched controls. Two statistically significant differences were found. The blood pressure response to sustained handgrip was diminished and the pupillary light reflex latency was increased in the HD group. The former probably reflects diminished input from higher centers on an otherwise intact sympathetic nervous system. The latter may indicate involvement of the pretectal or Edinger-Westphal nuclei in HD. No further signs of autonomic nervous system dysfunction were found.

Respiration during sleep in Huntington's chorea.

In view of recent reports on lower brainstem dysfunction in Huntington's chorea, we studied respiration during sleep in 12 patients with Huntington's chorea (HC) and in controls. There were no statistically significant differences between patients and controls with respect to apnea periods, respiratory frequency and time elapsed between minimal and maximal value of the respiratory curve. No statistically significant differences in respiratory variability were observed between patients and controls. In the present study, no indication was found for dysfunction of lower brainstem structures involved in respiration in HC.