Multiple Sclerosis impact on employment and income in New Zealand.

BACKGROUND AND OBJECTIVES: We investigated the demographic, social and clinical characteristics associated with employment status and income for people with multiple sclerosis (MS) in New Zealand (NZ). METHODS: The NZ National MS Prevalence study included all persons resident in NZ on census day 2006 diagnosed with MS (96.7% coverage). Factors associated with employment and income status among the working age population (25-64 years) were identified by linear regression. RESULTS: Over 90% of working age people with MS (n=1727) had a work history, but 54% were not working. Work loss occurred early in the disease course, and at low disability (P<.001). Advancing age, progressive disease, longer disease duration, higher disability levels, partner loss and lower education were associated with work loss (P<.001). Working age people with MS had lower income than the NZ population (P<.0001). Higher qualifications yielded no additional income for MS females and about half the additional income for MS males (P<.0001). CONCLUSIONS: MS profoundly reduces employment and income early in the disease course, and at low levels of disability, however, unemployment is not entirely accounted for by clinical, social and demographic factors. These findings suggest social supports should be explored early in the disease course to reduce loss of income and unemployment for people with MS.

Method for identifying eligible individuals for a prevalence survey in the absence of a disease register or population register.

BACKGROUND: Identifying eligible individuals for a prevalence survey is difficult in the absence of a disease register or a national population register. AIM: To develop a method to identify and invite eligible individuals to participate in a national prevalence survey while maintaining confidentiality and complying with privacy legislation. METHODS: A unique identifier (based on date of birth, sex and initials) was developed so that database holders could identify eligible individuals, notify us and invite them on our behalf to participate in a national multiple sclerosis prevalence survey while maintaining confidentiality and complying with privacy legislation. RESULTS: Several organisations (including central government, health and non-governmental organisations) used the method described to assign unique identifiers to individuals listed on their databases and to forward invitations and consent forms to them. The use of a unique identifier allowed us to recognise and record all the sources of identification for each individual. This prevented double counting or approaching the same individual more than once and facilitated the use of capture-recapture methods to improve the prevalence estimate. Capture-recapture analysis estimated that the method identified over 96% of eligible individuals in this prevalence survey. CONCLUSIONS: This method was developed and used successfully in a national prevalence survey of multiple sclerosis in New Zealand. The method may be useful for prevalence surveys of other diseases in New Zealand and for prevalence surveys in other countries with similar privacy legislation and lack of disease registers and population registers.

A review of tuberculous meningitis at Auckland City Hospital, New Zealand.

The clinical features, investigations, treatment and outcome were studied in 104 patients with definite or probable tuberculous meningitis. The diagnosis of definite tuberculous meningitis required the growth of Mycobacterium tuberculosis from cultures, or a positive polymerase chain reaction (PCR) assay for M. tuberculosis. In probable tuberculous meningitis, cultures and the PCR assay were negative, but other causes of meningitis were excluded and there was a response to anti-tuberculosis treatment. Of the 104 patients, 36% had a poor outcome (severe disability, persistent vegetative state or death), 12% moderate disability and 52% good recovery. A diagnosis of definite tuberculous meningitis, the severity of the symptoms at presentation and the occurrence of a stroke were significant predictors of a poor outcome. The most common reasons for a delayed diagnosis were presentation with mild symptoms wrongly attributed to a systemic infection, incorrectly attributing CSF abnormalities to non-tuberculous bacterial meningitis and failure to diagnose extraneural tuberculosis associated with meningitis. Recognition of the difficulties in making a diagnosis of tuberculous meningitis may facilitate earlier diagnosis in the future.

Neurological and systemic complications of tuberculous meningitis and its treatment at Auckland City Hospital, New Zealand.

Mortality and serious long-term sequelae still occur in about 50% of patients with tuberculous meningitis. The frequency and the clinical features of neurological and systemic complications were determined in a retrospective review of 104 patients with tuberculous meningitis. Complications occurred in 81 patients (78%). The most common complications were: hyponatraemia 49%, hydrocephalus 42%, stroke 33%, cranial nerve palsies 29%, epileptic seizures 28%, diabetes insipidus 6%, tuberculoma 3%, myeloradiculopathy 3% and hypothalamic syndrome 3%. The most common iatrogenic complication was hepatotoxicity related to anti-tuberculosis treatment in seven patients. Twenty-three patients (22%) died. At last follow-up one patient (1%) remained in a persistent vegetative state, 14 patients (13%) had severe disability and 12 patients (12%) were moderately disabled. The most common complications in the 81 long-term survivors were cognitive impairment (12%) and epilepsy (11%). Neurological and systemic complications of tuberculous meningitis were common and were important causes of mortality and long-term morbidity.

Detection of focal cerebral hemisphere lesions using the neurological examination.

OBJECTIVE: To determine the sensitivity and specificity of clinical tests for detecting focal lesions in a prospective blinded study. METHODS: 46 patients with a focal cerebral hemisphere lesion without obvious focal signs and 19 controls with normal imaging were examined using a battery of clinical tests. Examiners were blinded to the diagnosis. The sensitivity, specificity, and positive and negative predictive values of each test were measured. RESULTS: The upper limb tests with the greatest sensitivities for detecting a focal lesion were finger rolling (sensitivity 0.33 (95% confidence interval, 0.21 to 0.47)), assessment of power (0.30 (0.19 to 0.45)), rapid alternating movements (0.30 (0.19 to 0.45)), forearm rolling (0.24 (0.14 to 0.38)), and pronator drift (0.22 (0.12 to 0.36)). All these tests had a specificity of 1.00 (0.83 to 1.00). This combination of tests detected an abnormality in 50% of the patients with a focal lesion. In the lower limbs, assessment of power was the most sensitive test (sensitivity 0.20 (0.11 to 0.33)). Visual field defects were detected in 10 patients with a focal lesion (sensitivity 0.22 (0.12 to 0.36)) and facial weakness in eight (sensitivity 0.17 (0.09 to 0.31)). Overall, the examination detected signs of focal brain disease in 61% of the patients with a focal cerebral lesion. CONCLUSIONS: The neurological examination has a low sensitivity for detecting early cerebral hemisphere lesions in patients without obvious focal signs. The finger and forearm rolling tests, rapid alternating movements of the hands, and pronator drift are simple tests that increase the detection of a focal lesion without greatly increasing the length of the examination.

Effects of ethanol and inhibitors of its metabolism on the circulating levels of Met-enkephalin in greyhounds.

The mechanisms involved in the release of Met-enkephalin-like immunoreactivity (MLI) into the circulation following oral administration of ethanol and chlorpropamide were investigated in dogs. The origin of plasma MLI and the sites where it may be metabolized were also studied. Moreover, the molecular nature of circulating MLI was characterized. In conscious animals oral administration of ethanol (0.15 ml/kg) led to a significant (P less than 0.01) rise in plasma MLI concentrations in chlorpropamide-pretreated animals from a basal level of 43 +/- 6 (mean +/- S.E.M.) to a peak of 66 +/- 8 ng/l. Similar rises in MLI concentrations were observed following administration of ethanol with disulfiram and ethanol with chlorpropamide and captopril. In contrast, the administration of ethanol alone or ethanol with 4-methylpyrazole resulted in a decrease in plasma MLI concentrations. Comparisons of two different doses of i.v. acetaldehyde, the first metabolite of ethanol, showed that plasma MLI concentrations rose significantly (P less than 0.05) only after the larger dose (8 mg/kg), rising from 45 +/- 7 to 81 +/- 18 ng/l. These results suggest that acetaldehyde is the active component in the chlorpropamide + ethanol-induced MLI secretion. Plasma MLI was also measured following acetaldehyde infusion in adrenalectomized dogs with and without hexamethonium treatment. Acute bilateral adrenalectomy resulted in a decrease (P less than 0.05) in plasma MLI concentrations, but the levels remained detectable. Moreover, subsequent acetaldehyde infusion led to rises in plasma MLI similar to those observed in animals with intact adrenals. These MLI responses were not altered by the concurrent i.v. administration of hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Met-enkephalin and catecholamine responses to insulin-induced hypoglycaemia in greyhounds.

The involvement of endogenous opioid peptides in the stress response was investigated by measuring plasma concentrations of Met-enkephalin-like immunoreactivity (MLI), adrenaline and noradrenaline during insulin-induced hypoglycaemia in conscious greyhounds. Moreover, the molecular forms of circulating MLI were characterized using gel filtration chromatography. In the first group of animals, i.v. administration of insulin (0.3 units/kg) provoked marked hypoglycaemia (blood glucose concentrations fell from 4.4 +/- 0.1 to 1.5 +/- 0.2 mmol/l; mean +/- S.E.M.) which was associated with significant (P less than 0.001) rises in plasma MLI concentrations from a basal concentration of 45 +/- 8 to a peak of 189 +/- 39 ng/l. A within-subject study comparing five different insulin doses ranging from 0.004 to 0.3 units/kg showed dose-related effects on blood glucose with nadir concentrations of 4.1 +/- 0.6 mmol/l (after the smallest dose of insulin) and 0.8 +/- 0.1 mmol/l (after the largest dose of insulin). This was associated with dose-related rises in plasma MLI with peak concentrations of 56 +/- 17 and 558 +/- 35 ng/l, plasma adrenaline with peak concentrations of 0.45 +/- 0.06 and 15.76 +/- 1.33 nmol/l and plasma noradrenaline with peak concentrations of 0.49 +/- 0.07 and 2.27 +/- 0.45 nmol/l following the smallest and largest doses of insulin respectively. These results are the first demonstration of raised plasma MLI concentrations following hypoglycaemia. Moreover, they show that the hormonal responses vary with the degree of hypoglycaemia achieved. Together with reports by other investigators these findings might suggest opioid modulation of the responses of the sympathoadrenal system to hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating [Met]enkephalin and catecholamine responses to acute hypotension and hypertension in anaesthetized greyhounds.

The effects of either hypotension induced by sodium nitroprusside or hexamethonium or hypertension produced by angiotensin II or noradrenaline on the circulating levels of methionine enkephalin ([Met]enkephalin)-like immunoreactivity (MLI), adrenaline and noradrenaline in anaesthetized greyhounds were examined. Nitroprusside infusions (200 and 400 micrograms min-1) induced a fall in blood pressure accompanied by significant rises in plasma MLI and catecholamine concentrations. Concomitant administration of a high dose of naloxone did not alter the fall in blood pressure produced by nitroprusside but was associated with greater rises in circulating MLI and catecholamines when compared to nitroprusside alone, suggesting that [Met]enkephalin is not involved in the hypotensive action of nitroprusside. Intravenous hexamethonium (2.5 mg kg-1) provoked a fall in blood pressure which was not associated with any changes in plasma MLI. However, it produced a fall in plasma noradrenaline and a rise in plasma adrenaline. Thus it appears that neural mechanisms are required, at least in part, for the release of MLI. Angiotensin II (1.25 micrograms kg-1 min-1) and noradrenaline (8 micrograms kg-1 min-1) infusions produced an elevation in blood pressure without altering the circulating MLI levels. Study of the molecular forms of circulating MLI, before and during hypotension, revealed that the large molecular weight enkephalin-containing peptides with approximate molecular sizes of 18kD and 8kD were the predominant forms both in the basal and stimulated states. It is concluded that circulating [Met]enkephalin is not involved in the tonic control of blood pressure but it may modulate catecholamine release following hypotension as part of the stress response.

Chlorpropamide-ethanol induced met-enkephalin secretion in dogs: release mechanisms and biochemical characterisation.

Circulating met-enkephalin-like immunoreactivity (MLI) rises in man after chlorpropamide and ethanol although the origin and molecular forms of circulating MLI are not well defined. We have studied the response to oral ethanol in conscious and anaesthetised dogs pretreated with chlorpropamide. In conscious dogs MLI rose from a basal level of 29 +/- 7 pg/ml to a peak of 55 +/- 14 pg/ml 10 min after ethanol (P less than 0.001). In anaesthetised animals, following ethanol, plasma MLI rose in caval (35 +/- 6 pg/ml to a peak of 70 +/- 10 pg/ml), in portal (28 +/- 6 pg/ml to 51 +/- 6 pg/ml) and in adrenal blood (897 +/- 316 pg/ml to 1483 +/- 298 pg/ml; P less than 0.001). Biogel P-4 chromatography of caval and portal basal plasma showed 87% of MLI measured coeluted with the synthetic pentapeptide, while chromatography of peak plasma showed that only 65% coeluted with the pentapeptide and the remaining 35% was of larger molecular size. Sephadex G75 chromatography of adrenal vein plasma revealed three peaks of MLI of differing molecular sizes (8 k = 69.7%; 3-5 k = 12.1% and the pentapeptide = 18.2%). Treatment of the column fractions with trypsin and carboxypeptidase B resulted in the generation of new MLI with peaks of approximate molecular sizes 31 k (10.4%), and 18 k (37.1%) in addition to 8 k (40.0%), 3-5 k (5.0%) and the pentapeptide (7.5%). Acetaldehyde involvement in MLI release was investigated. Following acetaldehyde infusion, plasma MLI rose both in caval (35 +/- 9 pg/ml to 86 +/- 8 pg/ml) and adrenal vein (417 +/- 121 pg/ml to 1768 +/- 433 pg/ml) bloods. Thus we have established an animal model which enables further study of the mechanisms of MLI release and characterisation of the molecular forms. The adrenal medulla, unlike the gut, may be an important source of circulating met-enkephalin and acetaldehyde formation an essential intrinsic component of chlorpropamide-ethanol induced met-enkephalin release.

Simultaneous release of neurotensin, somatostatin, enkephalins and catecholamines from perfused cat adrenal glands.

Acid extracts of cat adrenal medullae were found to contain neurotensin-like (0.71 +/- 0.21nmol/gm), met-enkephalin-like (11.71 +/- 2.87nmol/gm), leu-enkephalin-like (1.95 +/- 0.11nmol/gm) and somatostatin-like (1.57 +/- 0.63pmol/gm) immunoreactivities. Using isolated retrogradely perfused cat adrenal glands the secretory responses to acetylcholine (ACh), nicotine and potassium ions (K+) were studied. Spontaneous secretion of catecholamines, neurotensin-like, met-enkephalin-like, leu-enkephalin-like and somatostatin-like immunoreactivities was negligible. However, ACh (5.5 X 10(-5)M), nicotine (2.2 X 10(-5)M) and 55mM K+ all evoked the simultaneous release of noradrenaline, adrenaline and the four neuropeptide immunoreactivities. The ACh stimulated secretion of the four neuropeptides could be prevented by perfusion with hexamethonium (C6, 2.8 X 10(-4)M). The concomitant release of these neuropeptides with catecholamines suggests that they may have a role in the modulation of stress responses.

Two actions of gamma-aminobutyric acid on the responses of the isolated basilar artery from the rabbit.

1 In the isolated basilar artery of the rabbit, gamma-aminobutyrate acid (GABA) (ED50 +/- s.e. mean, 2.4 +/- 1.1 x 10(-5) M) produced a relaxation, if the tone had been increased with 5-hydroxytryptamine (5-HT). 2 3-Aminoproprane sulphonic acid (3-APS) produced a similar, but smaller relaxation, while baclofen had no effect. The relaxation produced by GABA was inhibited by bicuculline. 3 Transmural electrical stimulation produced a reproducible contraction of the isolated basilar artery. In 9 out 14 preparations GABA (ED50 +/- s.e. mean, 5.6 +/- 2.1 x 10(-7) M) caused a reduction of the response, with a maximum of 49.2 +/- 4.3%. Bicuculline did not inhibit these responses to GABA. 4 Baclofen (ED50 +/- s.e. mean, 6.8 +/- 1.4 x 10(-7) M) produced a similar inhibition (47.4 +/- 3.2% maximum) but 3-APS had no effect. 5 GABA (10(-4) M) had no effect on the tone of isolated mesenteric or internal carotid arteries from the rabbit, whether or not the tone was increased with 5-HT. Similarly, GABA (10(-4) M) did not produce any change in the responses to transmural stimulation in isolated mesenteric or internal carotid arteries. 6 These findings are consistent with the presence of two types of GABA receptor on the rabbit basilar artery.

Actions of dopamine and apomorphine on the vasoconstrictor responses of perfused mesenteric arteries of mouse, rat and rabbit.

Dopamine (10(-7)--10(-6) M) and apomorphine (5 x 10(-7)--5 x 10(-6) M) inhibited the vasoconstrictor responses of the perfused mesenteric artery preparations of rat, rabbit and mouse to adrenergic nerve stimulation but did not affect responses to added noradrenaline. The inhibitory effects of both dopamine and apomorphine were prevented by haloperidol (3 x 10(-7) M) but not by yohimbine (3 x 10(-8) M) in rat and rabbit mesenteric artery preparations. In contrast, yohimbine (3 x 10(-8) M), but not haloperidol, antagonized the inhibitory effect of dopamine and apomorphine in mouse mesenteric artery preparations. In higher concentrations, dopamine (10(-6)--10(-4) M) produced a direct vascoconstrictor effect, which involved post-junctional alpha-adrenoceptors in all three species. However, in preparations contracted with 10(-7) M 5-hydroxytryptamine and in the presence of phentolamine (3 x 10(-7) M) and propranolol (10(-6) M), dopamine (10(-6)--10(-4) M) produced a direct relaxant effect in rabbit mesenteric artery preparations but not in those of rat and mouse. It is suggested that inhibition of neurogenic vasoconstrictor responses, by dopamine and apomorphine, may be mediated through a specific prejunctional inhibitory dopamine receptor in the mesenteric artery of rat and rabbit whereas in the mouse they involve activation of alpha-adrenoceptors.

Pharmacological studies on 3-[gamma-(p-fluorobenzoyl)propyl]-2,3,4,4a,5,6-hexahydro-1 (H)-pyrazino(1,2-a) quinoline hydrochloride (compound 69/183). Part II: Effect on cardiac dynamics.

Effect of 3-[gamma-(p-fluorobenzoyl)propyl]-2,3,4,4a,5,6-hexahydro-1-(H)-pyrazino(1,2-a)quinoline hydrochloride (centpyraquin, 69/183) on the cardiac function has been studied in situ in cat and dog and on isolated guinea pig heart. Centpyraquin (1.0 mg/kg i.v.) decreased cardiac output (20%) and total peripheral resistance (18%) along with blood pressure (40%). The decrease in dp/dt and PTI were secondary to hypotension. The contractility of the auricle as well as the ventricle was not decreased. In the heart-lung preparation of dog, centpyraquin (5 mg) had an inhibitory effect on the heart. The contractility of the isolated guinea pig heart was not changed up to 200 micrograms dose but higher doses had negative inotropic effect. The compound had no significant effect on ECG of cat. The effect of norepinephrine on dp/dt and PTI was potentiated. Isoproterenol induced hypotension was not changed but the cardiac effects were potentiated.

Discrepancies in the measurement of changes in blood flow using flow- and velocity-sensitive electromagnetic probes.

Blood flow was measured in the descending thoracic aorta of the anaesthetised dog using a perivascular flow probe and electromagnetic flowmeter. Blood velocity was measured in the same vessel with an intravascular velocity probe and electromagnetic flowmeter. Changes in blood pressure, flow and velocity, were induced by intravenous administration of noradrenaline, angiotensin, isoprenaline and aminophylline. If the velocity probe was within the cuff of the flow probe, percentage changes in flow and velocity were comparable, but if the velocity probe was "upstream" or "downstream" from the cuff, discrepancies between percentage drug-induced changes in flow and velocity were of the order of 30% and, in 12 out of 80 observations, in opposite directions. Measuring absolute flow with the velocity-sensitive device produced variable results showing a systematic underestimate of flow estimated from velocity, compared with flow measured with the perivascular probe. It is concluded that the measurement of blood flow and changes in blood flow, with the intravascular velocity probe, is liable to produce inaccurate data.

The effects of pronethalol and propranolol on the coronary circulation of the dog.

1. The actions of pronethalol and propranolol have been studied to see if there was any relationship between the reduction in coronary flow and any other cardiovascular action they have.2. The experiments were carried out in anaesthetized open chest dogs. Measurements included central arterial, left and right venous or atrial pressures, heart rate, ventricular size and stroke volume, intra-ventricular pressures, total left coronary flow, arterial and coronary sinus blood pO(2). The pressure-time index (PTI) and maximum rate of isovolumetric contraction (dp/dt) were obtained from these records.3. It was concluded that, in these experiments, the reduction in coronary flow produced by pronethalol and propranolol was not directly related to a decrease in perfusion pressure, a raised venous pressure, the increase in ventricular volume and hence wall tension, the decrease in heart rate, or to the increased duration of systole.4. The PTI and dp/dt were always reduced at the same time as the coronary flow. These findings are discussed.5. Studies of the effects of sympathetic stimulation, of phentolamine, of reduced arterial oxygen tension and electrical pacing of the heart, all after beta-blockade, did not support the suggestion that the reduction in coronary flow after beta-blockade was due to the unmasking of an active vasoconstriction.