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Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 397 records · Page 22Linked to original sources

Urokinase plus heparin versus aspirin in unstable angina and non-Q-wave myocardial infarction.

The pivotal role of thrombosis in unstable angina and non-Q-wave myocardial infarction has been established recently. To assess the value and safety of thrombolytic therapy compared to conventional antithrombotic therapy (aspirin) in arresting progression in this setting to recurrent ischemic end-points, 25 patients presenting with unstable angina and an electrocardiogram showing subendocardial ischemia were randomized to receive either aspirin 325 mg daily, or urokinase 3 x 10(6) U intravenously, over 30 minutes followed by heparin. Incidence of endpoints (intractable ischemia requiring mechanical intervention, new myocardial infarction or death) was determined over 7 days. Coronary arteriography was performed at 24 to 72 hours to determine extent of coronary artery disease and morphologic severity of the culprit lesion, graded by a semiquantitative scoring system ranging from 4+ (definite thrombosis) to 0 (chronic lesion). In the first 24 hours, 7 of 13 aspirin versus 1 of 12 urokinase patients exhibited ischemia progression (p less than 0.05). By 7 days, progression to a primary ischemic endpoint occurred in 8 of 13 aspirin patients (3 myocardial infarctions and 5 intractable ischemias) versus 3 of 12 urokinase patients (2 intractable ischemias and 1 death) (p = 0.18). The apparent benefit of urokinase followed by heparin compared to conventional aspirin therapy in arresting early progression of unstable angina or non-Q-wave myocardial infarction was not associated with enhanced culprit lesion morphology (mean lesion severity score 2.7 +/- 1.5 vs 2.8 +/- 1.6 in aspirin-treated patients). Large scale, randomized trials to assess the clinical utility of urokinase for unstable angina are warranted.

Angina Pectoris↗

Utilization strategies for intensive care units.

Critical care resources in the United States are being rationed, that is, not all critical care expected to be beneficial is being provided to all patients who desire it. Although the extent of rationing is uncertain, it is an everyday occurrence in some hospitals and is likely to occur at least some of the time in many hospitals. Substantial evidence suggests that current rationing practices are highly subjective and perhaps inequitable. Critical care is widely believed to be beneficial to many patients, despite a striking dearth of supportive data. Since this type of care is being inequitably denied to some patients, hospitals should either adopt formal rationing guidelines or, alternatively, they should take clear steps to avoid rationing by altering the supply of or the demand for critical care. Reasonable arguments are presented in support of both approaches, as are suggestions for their implementation.

Cultural Diversity↗

The early risk of multiple sclerosis following isolated acute syndromes of the brainstem and spinal cord.

A combined clinical and magnetic resonance imaging follow-up study was undertaken to determine the risk of early progression to multiple sclerosis in patients who present with clinically isolated lesions of the brainstem or spinal cord. Progression to multiple sclerosis was seen in 13 patients (57%) who had a brainstem syndrome and in 14 patients (42%) who had a spinal cord syndrome after mean intervals of 15 and 16 months, respectively. The risk of progression was increased by the presence of oligoclonal bands in the cerebrospinal fluid of patients with either syndrome and by the presence of disseminated brain lesions, as detected by magnetic resonance imaging, in those with a spinal cord syndrome. Follow-up revealed evidence of multiphasic disease in 24 (69%) of 35 patients who had disseminated lesions on magnetic resonance imaging scans at presentation, suggesting that multiple sclerosis is the usual cause of such lesions.

Adult↗

Precise relaxation time measurements of normal-appearing white matter in inflammatory central nervous system disease.

Precise relaxation time (RT) measurements have been made, with a standard deviation of 3% for T1 and T2 in white matter in normal volunteers. This sets an upper limit to the instrumental random errors (imprecision). Achieving this precision requires careful adjustment and use of the imager. The wide variation in RTs seen by other workers may be in part due to larger instrumental errors. We have measured RTs (both T1 and T2) in normal-appearing white matter in 16 normal controls and patients with multiple sclerosis (MS, 18), systemic lupus erythematosis (SLE, 16) and cerebral sarcoidosis (8). Both RTs were significantly higher in MS than in other patient groups and controls (P less than .05), possibly caused by microscopic lesions. T2 was elevated in SLE patients relative to controls and sarcoidosis patients (P less than .05), possibly because of microhemorrhages. Lesion RTs were abnormal but more variable and no significant differences between diseases were found.

Adolescent↗

Management of myocardial infarction shock: current status.

Major advances have occurred over the last two decades in the management of myocardial infarction shock, increasing the overall in-hospital survival rate from approximately 15% to more than 50% at the present time with aggressive methods of interventional cardiology. The widespread use of intravenous thrombolytic therapy during the early hours of myocardial infarction has resulted in a decreasing incidence of shock with first myocardial infarctions. Three mechanisms bring about cardiogenic shock: (1) extensive aggregate systolic left ventricular dysfunction, (2) extensive right ventricular infarction, and (3) mechanical defects of the left and/or right ventricles attendant to ischemic dysfunction or rupture. To permit survival in cardiogenic shock, even with maximally aggressive therapy, diagnostic evaluation must be carried out concurrently with clinical stabilization of the patient. IABC is the mainstay for supporting the patient in shock during further efforts at diagnosis and definitive therapy. Definitive therapy for cardiogenic shock may include percutaneous transluminal coronary angioplasty, emergent bypass surgery, or repair of a mechanical defect. This report details the current status of knowledge with respect to pathogenesis, recognition, and definitive treatment of myocardial infarction shock.

Cardiac Catheterization↗

Tropical spastic paraparesis and human T cell lymphotropic virus type 1 in the United Kingdom.

Twenty-one patients with tropical spastic paraparesis (TSP), all of whom were born in the Caribbean and who had migrated to the United Kingdom, are described. All had a progressive spastic paraparesis developing many years after immigration and all 19 tested had antibodies to the human T cell lymphotropic retrovirus type 1 (HTLV1). The clinical and laboratory features and visual, auditory and somatosensory evoked potentials are described. Details of magnetic resonance scanning of the brain and, in a few cases, the spinal cord are compared with those found in multiple sclerosis. The antibody titres to HTLV1 assessed by particle agglutination, Western blot, antibody-directed cell mediated cytotoxicity and pseudotype neutralization were higher than in asymptomatic infected relatives and in patients with adult T cell leukaemia. Some, but not all, of the IgG oligoclonal bands in the CSF were directed against HTLV1. IgM oligoclonal bands directed against HTLV1 were found in 2 patients. Sixty of the 64 first degree relatives of 11 Jamaican patients with TSP were traced in the UK and the Caribbean; 20-30% of those born in the Caribbean had antibodies to HTLV1, irrespective of their present place of residence, whilst none of those born in the UK, who were the children of the patients, had antibodies. The original pathological material obtained from the Caribbean by Montgomery et al. (1964) is reviewed. These results are discussed in relation to animal retroviral neurological diseases, particularly visna in sheep which has clinical and pathological features closely similar to TSP. It is proposed that TSP is due to a HTLV1 infected lymphocyte/macrophage immune-mediated inflammatory response in the spinal cord.

Adult↗

The natural history of late-onset epilepsy secondary to vascular disease.

Twenty-nine patients with late-onset epilepsy were followed prospectively for a mean period of 4.9 years; 14 had CT evidence of occult cerebral infarction and 15 had normal scans. The prognosis was similar in the 2 groups; 57% and 53% respectively became seizure-free. One patient in each group had a myocardial infarction and one patient with occult cerebrovascular disease had a stroke. A separate study was made of the prognosis of 24 patients with epilepsy following stroke (mean follow-up 5.9 years). Twelve of 12 patients with seizure onset within 2 weeks of the stroke became seizure-free, compared with 7/12 with more delayed onset. Late-onset epilepsy has a favourable prognosis, and excellent control should be expected if seizures commence within 2 weeks of stroke.

Aged↗

Genetic heterogeneity and mitochondrial DNA heteroplasmy in Leber's hereditary optic neuropathy.

Analysis of mitochondrial DNA from patients with Leber's hereditary optic neuropathy and their relatives showed that the previously reported mutation at base pair (bp) 11778, shown by loss of a recognition site for the restriction endonuclease SfaNI, was present in only four out of eight families. This mutation was associated with a poor prognosis for visual recovery, whereas four of five affected males without the 11778 bp mutation followed for four years or more had regained useful vision. All but one of the subjects showing the SfaNI site loss had a variable mixture of mutant and normal mitochondrial DNA in peripheral blood, and the relative proportions appeared to be correlated with the risk of developing or transmitting Leber's hereditary optic neuropathy.

Adult↗

Quantitative magnetic resonance imaging in multiple sclerosis: the effect of high dose intravenous methylprednisolone.

Magnetic resonance imaging was performed on 50 patients with clinically definite or probable multiple sclerosis before and 15 days after starting treatment with intravenous methylprednisolone (0.5 g daily for 5 days). Scans were abnormal in 49 patients. New lesions had appeared on the second scan in nine individuals and in seven a single pre-existing lesion appeared to have become smaller but in no case were lesions seen to disappear. Two patients showed both reduction in the size of an abnormal area and development of a single new lesion indicating that corticosteroids do not appear rapidly to alter the process underlying plaque formation. Measurements of relaxation times were performed in 12 randomly selected patients. All showed elevated values in normal appearing white matter but not cortex before treatment compared with 18 healthy controls. After treatment a significant decrease of T1 and T2 was observed in cortex, and of T1 alone in normal appearing white matter. No significant change could be detected within lesions, a finding attributed to the wide range of relaxation values observed at these sites before treatment. Since brain water content is increased in normal appearing white matter of multiple sclerosis patients, and is significantly reduced by high-dose methylprednisolone, resolution of oedema may contribute to the rapid spontaneous or corticosteroid induced symptomatic recovery that characterises the disease in its early stages.

Adult↗

Class II HLA antigens in multiple sclerosis.

HLA typing in Wellington revealed a stronger association of multiple sclerosis with DR2 than with DQw1. The association with DQw1 appeared to be due to linkage disequilibrium of this antigen with DR2. These results, when considered in conjunction with other studies, are most easily explained by the hypothesis that susceptibility to multiple sclerosis is influenced by multiple risk factors, with DR2 being an important risk factor in Caucasoid populations.

HLA-DQ Antigens↗

Magnetic resonance imaging in Leber's optic neuropathy.

Thirteen males with Leber's optic neuropathy had magnetic resonance imaging (MRI) of the brain, and in eight the optic nerves were imaged using STIR (Short Time Inversion Recovery) sequences. All optic nerve scans were abnormal. In seven with bilateral visual loss four showed bilateral increased optic nerve signal and three unilateral increase. The involvement was of the mid and posterior intra-orbital sections over three 5 mm slices or more with sparing of the anterior portion. One patient with unilateral visual loss had increased signal only on the affected side. Brain MRI was normal, in marked contrast to the findings in clinically isolated optic neuritis in which multiple white matter lesions are seen in the majority.

Adult↗

Chronic unilateral optic neuropathy: a magnetic resonance study.

We studied the clinical, electrophysiological, and magnetic resonance imaging (MRI) features of 20 patients with chronic unilateral optic neuropathy (CUON): progressive unilateral visual failure lasting a minimum of 6 months. The patients, 10 male and 10 female, ranged in age from 12 to 77 years (mean 44) and had a mean duration of symptoms of 22 months. All had signs of optic nerve dysfunction. Each patient was studied with MRI using a short TI inversion recovery (STIR) sequence to delineate the optic nerve from surrounding orbital tissue. Three distinct groups of patients with CUON were identified using MRI. In the first group (8/20) the optic nerve was compressed by an extrinsic mass, whereas in the second group (5/20) CUON resulted from an intrinsic tumor of the optic nerve or sheath. In both groups STIR sequences compared favorably with computed tomography in identifying mass lesions. MRI was superior in delineating distortion of the optic nerve by mass or tumor extension beyond the orbit. In the third group (7/20) no mass was evident on MRI. However, STIR sequences revealed altered signal (long T1) in clinically symptomatic nerves. In 4 of the patients T2-weighted cerebral MRI disclosed periventricular lesions suggestive of disseminated white matter disease. We conclude that MRI complements clinical and electrophysiological testing in the assessment of CUON.

Adolescent↗

MRI appearances of the CNS manifestations of Mycoplasma pneumoniae: a report of two cases.

Two patients are reported with Mycoplasma pneumoniae-related cervical myelitis. Magnetic resonance imaging in each case demonstrated clinically silent lesions suggesting more extensive neurological involvement. This supports the concept of widespread immunologically mediated disease occurring as a remote effect of initial M. pneumoniae respiratory infection. Differences from the MRI appearances of a patient with mycoplasma-related Guillian-Barré syndrome imply that more than one antigenic determinant is involved.

Adolescent↗

Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis.

Serial gadolinium-DTPA (Gd-DTPA) enhanced magnetic resonance imaging (MRI) was performed in 9 patients with multiple sclerosis (MS). On the first scan enhancing lesions were seen in 7 patients, all of whom were in acute relapse. Most enhancing lesions were asymptomatic. On the second scan (3 to 5 weeks later), persisting enhancement was seen in only 12/54 lesions which enhanced on the first scan. No lesion showed persisting enhancement on the third scan (after 6 months). Enhancement occurred in all 12 new lesion areas seen on the unenhanced second scan and in 8 of 15 new lesions seen on the third scan. Enhancement was also seen in 4 older lesions which had been nonenhancing on earlier scans. Relaxation time measurements demonstrated a high water content in some nonenhancing lesions, which could be due to a subtle blood-brain barrier disturbance not detected with Gd-DTPA. The results show that blood-brain barrier impairment is a consistent finding in new MS lesions detected with MRI. Gd-DTPA is a useful marker of new and biologically active lesions and should prove of value in monitoring therapeutic trials in MS.

Adult↗

Sound lateralization, brainstem auditory evoked potentials and magnetic resonance imaging in multiple sclerosis.

Two tests of binaural hearing, namely intensity discrimination of alternating monaural clicks and interaural time difference (IATD) discrimination of binaural clicks, were performed in 28 patients with definite multiple sclerosis (MS) and 12 with an isolated brainstem lesion compatible with demyelination. Intensity discrimination defects were found in 53.5% and IATD defects in 82% of definite MS cases, although no overt auditory symptoms were reported and pure tone audiology was unremarkable. Corresponding figures in the isolated lesion group were 25% and 33%. Defects were manifested either by an abnormal 'bias' in favour of one ear or by a broadened 'spread' of responses (i.e., greater range of uncertainty). Brainstem auditory evoked potentials (BAEPs) were abnormal in 75% of the definite MS cases but only in 8% of the isolated lesion group. BAEP abnormalities involving component III on one or both sides were invariably associated with a defect of IATD discrimination. This is consistent with disruption of input to the superior olivary complex, the most peripheral structure where binaurally responsive units are sensitive to IATD. Lesions causing abnormality of component V alone less frequently resulted in impaired IATD discrimination, possibly because at rostral levels the IATD is encoded by the location rather than the timing of neuronal activity. In magnetic resonance imaging (MRI), abnormalities of the medulla, pons or midbrain were demonstrated in all MS patients tested and 45% of those with isolated brainstem lesions. The correlation with BAEP abnormalities was plausible in some patients but apparently anomalous in others. More severe BAEP abnormalities than would have been expected on the basis of MRI may have been due to small unresolved lesions, while the more frequent finding of normal or mildly abnormal BAEPs in conjunction with extensive MRI abnormalities may have been due to the fact that areas of abnormal signal reflect an increase in the water content of the tissue rather than demyelination per se.

Adult↗

The early risk of multiple sclerosis after optic neuritis.

Serial brain MRI was performed in 53 patients with clinically isolated optic neuritis. Using clinical and imaging evidence for relapse, multiple sclerosis developed within a mean of 12 months in 19 of 34 cases (56%) with brain lesions at presentation, and in only 3 of 19 cases (16%) without (Relative Risk = 6.8, p less than 0.005).

Adolescent↗