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Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 415 records · Page 23Linked to original sources

Restriction endonuclease analysis of leukocyte mitochondrial DNA in Leber's optic atrophy.

In order to test the hypothesis that Leber's optic atrophy may be caused by mutation of the mitochondrial (mt) genome, restriction fragment length polymorphism in leukocyte mt DNA was studied in 16 patients with Leber's optic atrophy, 28 of their unaffected matrilineal relatives, and 35 normal control subjects. No differences in restriction fragment patterns were observed between affected and unaffected individuals in the same maternal line, and there was no evidence of major deletion of mt DNA in patients. This study provides no positive evidence of mitochondrial inheritance in Leber's optic atrophy but does not exclude it.

Adult↗

Magnetic resonance imaging of the optic nerve in optic neuritis.

Magnetic resonance imaging (MRI) of the optic nerves using the STIR (short inversion time inversion recovery) sequence was performed in 37 adult patients with a recent or past attack of optic neuritis. MRI revealed high-signal regions in 84% of symptomatic and 20% of asymptomatic nerves. The mean longitudinal extent of lesions was 1 cm. Slow or poor visual recovery was associated with more extensive lesions, or lesions within the optic canal. Disk swelling was usually associated with anterior lesions but also occurred with lesions in the canal. Visual evoked potentials were even more sensitive than MRI in detecting lesions and are still the investigation of choice in suspected demyelinating disease involving the optic nerve.

Adult↗

Magnetic resonance imaging in central nervous system sarcoidosis.

We performed brain MRIs on 21 patients with CNS sarcoidosis. Brain CTs were performed in 18 of these. Parenchymal lesions were seen in 17 of 21 with MRI, compared with 9 of 18 with CT. MRI detected a greater number of parenchymal lesions in cases where both CT and MRI were positive, and some lesions appeared more extensive with MRI than with CT. The most common MRI pattern was one of periventricular and multifocal white matter lesions (14 cases). Such a pattern is not specific, and other recognized causes for it were identified in four cases. It is likely, however, that sarcoid tissue causes this pattern in some cases, and confirmation was obtained from cerebral biopsy in one. In six patients, the white matter changes were indistinguishable from those seen in multiple sclerosis. Contrast-enhanced CT in two patients showed diffuse meningeal involvement not seen with MRI. MRI is the investigation of choice in detecting parenchymal changes in the brain of patients with CNS sarcoidosis and may prove useful in monitoring treatment in such cases.

Adolescent↗

Psychiatric and neurological manifestations in systemic lupus erythematosus.

The frequency and type of psychiatric disease were investigated in 40 patients suffering from systemic lupus erythematosus (SLE) and 27 control subjects with rheumatoid arthritis or inflammatory bowel disease. The psychiatric morbidity at the time of interview was the same in the two groups, but the patients with SLE had experienced more episodes of psychiatric illness in the past, and psychotic symptoms occurred only in this group. Half of the patients with SLE had previous or current evidence of neurological involvement; an association was found between neurological disease and psychotic symptoms in SLE, while anxiety and affective disturbances appeared to be closely related to environmental factors in both patients with SLE and controls. There was no correlation between psychiatric and neurological disease and clinical or laboratory indices of disease activity. Magnetic resonance imaging of the brain was performed in 15 patients with SLE. Abnormalities were more often present in those with neurological disease; no such correlation was found with psychiatric illness.

Adolescent↗

Magnetic resonance imaging in isolated noncompressive spinal cord syndromes.

The frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivity of MRI in detecting the local cord lesion. MRI findings were compared with those from visual, brainstem, and somatosensory evoked potentials (VEPs, BAEPs, SEPs), and cerebrospinal fluid electrophoresis. Lesions were seen in the appropriate cord region in 47 of 73 patients (64%) with a cervical syndrome, and in 7 of 25 patients (28%) with a thoracic or lumbar syndrome. MRI demonstrated more cervical lesions than did SEPs, but fewer thoracic or lumbar lesions. Cord swelling was seen in 6 patients and atrophy in 10. Of those with acute syndromes, abnormalities were seen with brain MRI in 18 of 32 patients (56%), with VEPs in 2 of 30 patients (7%), and with BAEPs in 2 of 24 patients (8%). In patients with chronic syndromes, abnormalities were seen with brain MRI in 73 of 89 patients (82%), with VEPs in 22 of 80 patients (28%), and with BAEPs in 12 of 62 patients (19%). Brain MRI was thus more sensitive than evoked potentials were in establishing multiplicity of lesions. However, in acute syndromes, it was not possible to diagnose multiple sclerosis from a single abnormal brain scan in chronic syndromes, a diagnosis of clinically probable multiple sclerosis could be made from one scan, provided there was no better explanation for the abnormalities: the added presence of oligoclonal bands allows a diagnosis of laboratory-supported, definite multiple sclerosis as was the case in 28 patients in this series.

Adolescent↗

MR brain scanning in patients with vasculitis: differentiation from multiple sclerosis.

We performed MR (magnetic resonance) brain imaging on 24 patients with a systemic vasculitis. MRI proved to be a sensitive method for detecting brain lesions (clinically silent or manifest) in these patients. The most frequent abnormalities were periventricular lesions seen in 12 cases. Such changes are not specific for vascular disease, and are often seen in multiple sclerosis. However, additional changes were commonly seen which suggested the correct diagnosis.

Adolescent↗

STIR sequences in NMR imaging of the optic nerve.

Orbital fat surrounding the optic nerve causes considerable difficulties in NMR imaging due to its high image intensity and the chemical shift artefact. We have investigated the ability of inversion recovery sequences with short inversion times (STIR sequences) to suppress fat signals in imaging the optic nerve. We have also compared the contrast attainable with STIR sequences with that obtainable from other sequences. Measurements were made on 4 normal controls and 5 patients with multiple sclerosis (MS) to obtain typical values of relaxation times and proton densities for orbital fat, cerebral white matter and MS lesions. The fat T1 measurements were used to predict an appropriate inversion time for the STIR sequence and estimate how much residual fat signal might be expected as a result of natural variations in fat T1. STIR sequences can be used to suppress the signal from orbital fat with little residual signal. Measurements from white matter and MS lesions were used to predict the contrast between normal and pathological tissues that is attainable with STIR sequences. STIR contrast compares favourably with that obtainable from other sequences.

Humans↗

Down beating nystagmus: magnetic resonance imaging and neuro-otological findings.

Twenty-four patients with down beating nystagmus (DBN) underwent magnetic resonance imaging (MRI) of the head. MRI provided diagnostic images in Arnold-Chiari malformation (6 cases), cerebellar atrophy (6 cases), 1 case with a prepontine-medullary epidermoid tumour and was helpful in the diagnosis of 2 patients with multiple sclerosis and 1 with a ponto-cerebellar infarct. Multiple cerebral hemisphere lesions were found in 6 patients (5 of them over 60 years of age) in whom no diagnosis was made. All cases of DBN, plus 3 additional patients with Arnold-Chiari malformation and other types of nystagmus, were neuro-otologically assessed. Sensitivity of the nystagmus to head tilt with respect to the gravity vector had no localizing value. Impaired horizontal vestibulo-ocular reflex suppression occurred more frequently in those patients with abnormal posterior fossa MRI. Pure torsional nystagmus, and DBN with a strong torsional component, in patients with Arnold-Chiari malformation was associated with syringomyelia. Magnetic resonance is the imaging method of choice for investigating patients with DBN.

Adolescent↗

The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study.

The form and distribution of MRI abnormalities in 114 patients with clinically definite multiple sclerosis (MS) have been compared with observations on 53 apparently healthy individuals, 129 patients with isolated focal neurological lesions with which MS often presents (51 patients with optic neuritis, 44 with isolated brainstem lesions and 34 with isolated spinal cord syndromes) and 105 patients with disorders which may be confused clinically or radiologically with MS. The latter comprised 55 patients with cerebral vascular disease (including 7 cases of dementia with diffuse white matter disease), 24 with degenerative ataxic disorders, 8 with cerebellar tonsillar ectopia, 7 with sarcoidosis and 11 with a variety of other disorders. Periventricular abnormalities were found in all but 2 patients with MS and discrete white matter lesions in all but 12. Characteristically the periventricular changes in MS were irregular in outline. Periventricular abnormalities which were often milder and of smooth outline were seen in 37/55 patients with cerebral vascular disease, 9/24 with cerebellar degeneration, 5/7 with sarcoidosis and in 2/3 apparently healthy individuals over the age of 60. The appearances in the 7 cases of dementia resembled those with advanced MS. Cerebellar and/or brainstem atrophy characteristic of the cerebellar degenerations, in the absence of white matter abnormalities, was helpful in making the distinction from MS. Congenital anomalies and tumours in the region of the brainstem and foramen magnum were readily shown. More than half the patients with symptoms attributable to isolated focal neurological lesions had additional lesions at presentation. MS cannot be diagnosed in these cases at presentation, but repeat scans after 5 to 20 months in 25 patients with optic neuritis and 10 with clinically isolated brainstem lesions have shown new lesions in 7 (20%). The patients with new lesions fulfil the criteria for clinically probable MS (Poser et al., 1983). Measurements of T1 and T2 in vivo permitted the distinction of acute from chronic brainstem lesions. There were quantitative differences in T1 and T2 between the normal appearing white matter in MS and normal brain. Studies of postmortem brains provided convincing evidence that the MRI abnormalities in MS correspond with plaques. Evidence is adduced to support the view that an important source of the abnormal NMR signals in acute lesions is oedema, and in chronic lesions is gliosis; demyelination per se is unlikely to make an important contribution.

Adolescent↗

Abnormal regulation of renal kallikrein in experimental diabetes. Effects of insulin on prokallikrein synthesis and activation.

The effects of streptozotocin (STZ) diabetes and insulin on regulation of renal kallikrein were studied in the rat. 1 and 2 wk after STZ injection, diabetic rats had reduced renal levels and urinary excretion of active kallikrein. Tissue and urinary prokallikrein levels were unchanged, but the rate of renal prokallikrein synthesis relative to total protein synthesis was reduced 30-45% in diabetic rats. Treatment of diabetic rats with insulin prevented or reversed the fall in tissue level and excretion rate of active kallikrein and normalized prokallikrein synthesis rate. To further examine insulin's effects, nondiabetic rats were treated with escalating insulin doses to produce hyperinsulinemia. In these rats, renal active kallikrein increased. Although renal prokallikrein was not increased significantly by hyperinsulinemia, its synthesis was increased. As this was accompanied by proportionally increased total protein synthesis, relative kallikrein synthesis rate was not changed. Excretion of active kallikrein was unchanged, but prokallikrein excretion was markedly reduced. Therefore, increased tissue active kallikrein seen with hyperinsulinemia can be explained not only by increased synthesis but also by retention and increased activation of renal prokallikrein. These studies show that STZ diabetes produces an impairment in renal kallikrein synthesis and suggest that this disease state also impairs renal prokallikrein activation. The findings also suggest that insulin modulates renal kallikrein production, activation, and excretion.

Animals↗

Relationship of prior myocardial infarction to false-positive electrocardiographic diagnosis of acute injury in patients with chest pain.

Prompt management of patients suffering acute myocardial infarction requires accurate early diagnosis based on the electrocardiogram. To assess the predictive value of ST segment elevation and ST segment depression (both greater than or equal to 0.1 mV) for the diagnosis of evolving myocardial infarction, we studied 100 consecutive patients admitted to the coronary care unit of The New York Hospital with at least 30 minutes of chest pain. Of 31 patients with ST segment elevation, 26 patients (84%) evolved myocardial infarction (positive test results for serum creatine phosphokinase-MB isoenzyme fraction), while only 13 (48%) of 27 patients with ST segment depression had myocardial infarctions. Among patients with ST segment elevations with a history of prior myocardial infarction, only five (50%) of ten evolved myocardial infarction, compared with 21 of 21 with no prior infarction. False-positive diagnoses of acute injury were due to ST elevation in the area of prior Q wave infarction. Prior myocardial infarction did not alter the lower predictive value of ST segment depression for evolving infarction. We conclude that patients presenting with chest pain and ST segment elevation have approximately twice the likelihood of myocardial infarction than patients with ST segment depression; incorporation of historic information regarding prior myocardial infarction can improve the predictive value of ST segment elevations to 100% but does not improve prediction with ST segment depressions.

Adult↗

Randomized double-blind trial of intravenous streptokinase for acute myocardial infarction.

To determine the efficacy of intravenously administered streptokinase (SK) on infarct artery patency, global left ventricular (LV) function and clinical course in transmural acute myocardial infarction (AMI), 38 patients were studied using a randomized, double-blind, placebo-controlled scheme. Nineteen patients received 1.0 million units of SK followed by 72 hours of heparin infusion and 19 received placebo followed by heparin infusion, all within 5 hours (mean 3.3 hours) after AMI onset. Patients ineligible for inclusion in the randomized trial were followed as a second, "historical control" group. Compared with placebo, SK caused a higher frequency of enzymatic evidence of reperfusion (6% vs 79%, p less than 0.001) and of patent infarct-related arteries at predischarge coronary arteriography (64% vs 88%, difference not significant). (Patients in the control group had a relatively low frequency of spontaneous thrombolysis--28%.) In the SK group LV ejection fraction increased from early (average 7.3 hours after AMI) to late (predischarge) study (from 40% early to 47% late, p less than 0.05); in the placebo group LV ejection fraction did not change significantly (from 41% to 42%). Predischarge exercise radionuclide ventriculography showed mild and similar degrees of inducible ischemia in both groups. After a mean of 12.8 months of follow-up, 1 SK patient and 4 placebo patients had died (difference not significant). In conclusion, intravenous SK is efficacious for thrombolysis in patients with AMI. It improves global LV function without augmenting exercise-inducible ischemia.

Adult↗

Kinins induce rapid structural changes in colon concomitant with chloride secretion.

Voltage-clamped colonic epithelia were fixed for morphological observation minutes after bradykinin was added to produce its well-characterized increase in short circuit current representing net chloride secretion. With respect to paired controls, the average distance from the luminal epithelial surface to the underlying muscularis mucosa decreased significantly with time, and was accompanied by marked structural alterations in the crypts of Lieberkühn and surrounding lamina propria. This rapid reconfiguration of epithelial architecture suggests that kinin-receptor interaction leads to epithelial contractile events which occur simultaneously with net chloride secretion.

Animals↗

Optic neuritis following chickenpox in adults.

Three cases of bilateral optic neuritis, one of which also had transverse myelitis, are described in young adults following chickenpox. Severe bilateral loss of vision developed in all cases and was followed by good visual recovery in the two with isolated optic neuritis, but poor recovery in the patient with concomitant transverse myelitis. The interval between the initial rash and subsequent optic neuritis suggests an immunological pathogenesis for this complication.

Acyclovir↗

Effects of recent and remote infarction on the predictive accuracy of the ST segment/heart rate slope.

The exercise electrocardiographic ST segment/heart rate slope accurately identifies three vessel coronary disease in patients with stable angina, but the method is less accurate in predischarge testing after recent myocardial infarction. To assess the effect of both recent (less than 3 weeks) infarction and remote (greater than 8 weeks) Q wave infarction on the ST segment/heart rate slope, the predictive value of a slope greater than 6.0 microV/beat per min for the identification of three vessel coronary artery disease was evaluated in 113 patients. The 58 patients with stable angina, including 17 with remote Q wave myocardial infarction, were similar to the 55 patients with recent myocardial infarction with respect to age and peak exercise heart rate. In patients with stable angina and no prior Q wave myocardial infarction, an ST segment/heart rate slope greater than 6.0 had a sensitivity of 92% (11 of 12), a specificity of 97% (28 of 29) and a positive predictive value of 92% (11 of 12) for three vessel coronary artery disease. In patients with stable angina and remote Q wave infarction, sensitivity was 83% (5 of 6), specificity was 91% (10 of 11) and positive predictive value was 83% (5 of 6). After recent infarction, test specificity for three vessel disease was preserved at 95% (39 of 41), but test sensitivity was poor (3 of 8). This was confirmed by evaluation of six additional recent patients with infarction and three vessel disease. Among the combined group with recent infarction, test sensitivity for three vessel disease was only 29% (4 of 14), significantly lower than in patients with stable angina (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Ethnic and HLA patterns related to multiple sclerosis in Wellington, New Zealand.

A recent survey revealed 237 cases of multiple sclerosis in Wellington, New Zealand, giving an overall prevalence of 69 cases per 100,000. Two hundred and thirty-five were European with one Asian and only one Maori, confirming the rarity of the disease in Maoris. HLA A3, B7 and DR2 antigens were more frequent in multiple sclerosis patients compared with European controls. The same antigens were much less common in the Maori population. The results suggest that Maoris have a low susceptibility to multiple sclerosis despite living in a high risk area, and that genetic susceptibility may be related to the HLA system.

Adult↗