Biomedical subjects

M M Hoehn

Publications and source records attributed to M M Hoehn.

At least 19 recordsLinked to original sources

PubMed1992

The natural history of Parkinson's disease in the pre-levodopa and post-levodopa eras.

Since Parkinson's disease was first described by James Parkinson in 1817, the natural history has been confounded by various treatment modalities: the replenishment of deficient dopamine, the addition of the dopamine agonists, and the more recent addition of drugs whose putative action may slow the natural history of the disease. Nevertheless it remains a disease that is slowly and inexorably progressive over several decades. The quality of life during this progression can be improved, and the duration of life before inanition produces life-threatening complications can be extended. New approaches to identifying the disease before the overt symptoms appear and to slowing the progression of the underlying pathophysiology are being explored but to date have not produced significant changes in the prognosis for the individual patient.

Humans↗

PubMed1990

An examination of male-female differences in progression and mortality of Parkinson's disease.

We conducted disability and mortality studies to determine if the male preponderance usually found in Parkinson's disease (PD) was reflected in different courses of the diseases in the 2 sexes. We analyzed longitudinal disability score in 47 men and 23 women with PD followed for 6 years at UCLA. We found no significant differences between the sexes in mean disability scores in any of the 6 years. Mean dopa dosage was significantly higher in men, possibly reflecting their generally larger body mass. Choreoathetosis, dementia, or other side effects did not differ between the 2 groups. We obtained observed to expected mortality ratios in 239 men and 132 women followed for 3,831 person-years from records of 4 medical centers. Using the sex-specific US Life Tables to calculate expected mortality, we found the observed to expected ratio for the men was 1.7457 and for the women 2.4740, a significantly greater excess in female mortality. Analyses of mortality using tables which are not sex-specific will fail to uncover the decreased longevity in women with PD. We conclude that, despite the male preponderance in PD, men and women acquire it at the same age, have the same progression and duration of disease, and die at the same age; whereas, in the general population, women have a longer life expectancy than men. It is not known what factors protect women from incurring PD and what lowers their life expectancy to that of men when they do have the disease.

Disability Evaluation↗

PubMed1989

Effect of age at onset on progression and mortality in Parkinson's disease.

We examined longitudinal disability scores in 54 patients with Parkinson's disease followed for 6 years at UCLA. We sorted data into 3 groups based on age at onset of symptoms: group A, onset under 50 years; group B, 50 to 59 years; group C, 60 years or older. There were no significant differences between groups initially. All 3 groups improved dramatically when levodopa was given, but group A showed significantly less disability in years 4, 5, and 6 than did group C. The groups did not differ with respect to side effects. To determine if age at onset affected mortality, we sorted records from 4 geographically diverse centers into the same 3 groups. Results on 359 patients followed for 3,314 person-years, covering a period of 17 years after onset of symptoms, showed that group A had the most favorable observed-to-expected mortality ratio, 1.82, compared with 2.17 and 2.20 for groups B and C respectively, but the difference was not statistically significant. Results from the disability analyses indicate that patients with onset of Parkinson's disease under 50 years of age may have a more favorable prognosis than those whose symptoms begin in later years.

Aging↗

PubMed1987

Multi-center study of Parkinson mortality with early versus later dopa treatment.

Four geographically diverse centers provided data on mortality in 359 patients with Parkinson's disease, the majority of whom began dopa treatment during the early experimental trials of 1968 to 1970. Patients were classified into three groups based on the duration of symptoms prior to starting dopa treatment: Group 1, 1 to 3 years; Group 2, 4 to 6 years; Group 3, 7 to 9 years. After 15 years of treatment and 3,689 person-years of observation, Group 1 had an observed-to-expected mortality ratio of 1.43; Group 2, 2.44; and Group 3, 2.95 (p less than 0.05). This result confirmed that increased duration of disease was associated with increased mortality risk. To examine the effect of the time of initiation of dopa treatment, duration of disease was held constant at 17 years for all three groups. Observed-to-expected mortality ratios were 1.43 for Group 1; 2.66 for Group 2; 2.63 for Group 3. This statistically significant advantage for Group 1 (p less than 0.0001) led to the conclusion that early treatment with dopa has a beneficial effect on life expectancy. After 17 years of disease, causes of death in Group 1 were less likely (p = 0.027) to be due to Parkinson's disease than was found in the other groups.

Aged↗

PubMed1987

Parkinson's disease: progression and mortality.

Patients with Parkinson's disease were compared during two 15-year periods before and after the introduction of levodopa. With levodopa treatment: The duration of illness at each stage of severity was 3 to 5 years longer; at every duration of illness, death and disability were reduced 1.5- to 3-fold, except in patients whose treatment had been delayed; abnormal involuntary movements that interfered with function occurred in 24% of patients; severe fluctuations that required rescheduling of activities occurred in 29% of patients; severe AIMs and fluctuations were rare during the first 3 years of treatment, but remained constant thereafter, without progressive increase; prevalence of severe fluctuations was related only to age of onset of disease: If under 50, severe fluctuations developed in 66%, if age 50 to 59 at onset, they developed in 30%, if over age 60, in only 6%; average age at death was 6 years older; and observed/expected mortality was 1.2, not significantly different from the unaffected population.

Carbidopa↗

PubMed1985

Result of chronic levodopa therapy and its modification by bromocriptine in Parkinson's disease.

15 years' experience with Parkinson's disease treated with levodopa was compared to the 15 years before the advent of levodopa. Progression to severe disability and death was prolonged, at each stage of severity, by 3 to 5 years. At each duration of illness, the percentage of patients with severe disability was reduced significantly. There was some indication that independence was prolonged by early treatment. Life expectancy was increased to approximately that of the unaffected population. However, especially with patients with onset of disease before the age of 50, fluctuations of therapeutic response and severe abnormal involuntary movements interfered with satisfactory therapeutic results. Supplemental bromocriptine produced a smoother therapeutic response and decreased "off" period dystonia and leg pains in over 70% of patients. At dosages below 20 mg daily, it was not particularly effective in severely affected disabled patients. Adverse reactions prevented the use of bromocriptine in less than 20% of patients.

Adult↗

PubMed1985

Low dosages of bromocriptine added to levodopa in Parkinson's disease.

Thirty-six patients with Parkinson's disease, on levodopa, were admitted to a double-blind, parallel, 40-week study of adjunct bromocriptine in dosages increased by 2.5 mg every 4 weeks. A 37% improvement of the mean neurologic deficit score was obtained at the maximal daily dosage of 20 mg. Improvement was greatest in patients with mild disease. The wearing-off effect, off-dose abnormal involuntary movements, and leg pains, associated with levodopa, improved in over 70% of patients at an average dosage of 13 mg. Only 15% of patients had adverse reactions severe enough to necessitate discontinuance of the drug. Abnormalities of mental state were less severe than expected, but two patients had exacerbations of angina pectoris.

Adult↗

PubMed1979

Neuropsychological impairment with schizophrenia vs. acute and chronic cerebral lesions.

Performed detailed neuropsychological evaluations with 25 recently hospitalized schizophrenics in whom systematic neurologic workups had failed to reveal CNS disease. Efforts were made to minimize possible effects of drug-induced extrapyramidal symptoms on test performance. Although the schizophrenics showed some neuropsychological impairment relative to 25 normals, their deficits were not as severe as those of patients known to have either acute or chronic brain disorders (N = 25). The diagnostic accuracy achieved by the tests supports their use in short-term treatment facilities when the differential diagnosis includes schizophrenia and brain disorder, especially acute brain disorder. Schizophrenics' neuropsychological impairment was more correlated with degree of EEG abnormality than with degree of psychosis, which suggests a possible organic basis for the deficits that they showed on testing.

Acute Disease↗

PubMed1978

Dopamine excretion and vulnerability to drug-induced Parkinsonism. Schizophrenic patients.

Before and during a standardized course of trifluoperazine therapy, 18 schizophrenic patients underwent repeated examinations for extrapyramidal motor signs, clinical psychopathology, and urinary excretion of free and conjugated forms of dopamine and its metabolites. Patients excreting more free dopamine and metabolites, or showing less complete conjugation, before drug treatment, were much less likely than others to develop parkinsonian akinesia and rigidity during drug treatment. Neither catatonic rigidity nor akinesia before treatment was predictive of a parkinsonian response to trifluoperazine, but pretreatment tremor may have been. The severity of schizophrenic psychopathology was unrelated to dopamine excretion. This study of schizophrenic patients, and our previous research in Parkinson's disease, suggest that urinary dopamine excretion may reflect dopaminergic function of the extrapyramidal motor system in both conditions.

Adult↗

PubMed1978

A32390A, a new biologically active metabolite. I. Discovery and fermentation studies.

A32390A is an isonitrile-containing derivative of diacyl D-mannitol. The compound is produced in fermentation as the major component of a metabolic complex known as A32390. A32390A inhibits dopamine-beta-hydroxylase reduces heart and adrenal norepinephrine levels, lowers blood pressure in hypertensive rats, and possesses antibiotic activity vs. Gram-positive bacteria and fungi, including Candida albicans. A32390 is produced in submerged culture by a mold, a species of Pyrenochaeta, NRRL-5786. Glucose and sucrose are among the best carbon sources for the biosynthesis of A32390. Mannitol, although a substituent of the A32390A molecule, supports little or no biosynthesis of the compound when employed as the major carbon source for the fermentation. The addition of crotonic acid derivatives. ethanol, or L-histidine to the fermentation medium enhances the level of A32390 produced.

Alcohols↗

PubMed1978

Hypothalamic atrophy.

A patient, who has been followed for thirteen years, developed the first symptoms of progressive hypothalamic atrophy at the age of 39. The diagnosis was confirmed by pneumoencephalography five years after onset. Hypothalamic dysfunction was manifested clinically by loss of libido, impotence, obesity, polydypsia, somnolence, and rage attacks. Assessment of endocrinologic function demonstrated low serum levels of testosterone, FSH, and LH, a diabetic glucose tolerance curve, decreased basal and hypoglycemic stimulated levels of HGH, and progressively increasing levels of serum prolactin. Repeated pneumoencephalography revealed an initial, and then progressive, enlargement of the third ventricle which was later associated with generalized, but proportionately less severe, atrophy of the cerebellum and cerebral hemispheres. Analysis of the physiologic and endocrinologic mechanisms underlying these abnormalities suggests diffuse hypothalamic damage, especially in the ventromedial area. The decreased somnolence and increased libido and potency which accompanied therapy with levodopa suggest damage to dopaminergic and noradrenergic pathways. Slowly progressive hypothalamic atrophy, confirmed by pneumoencephalography, but without specific etiology, has not been reported previously. This article describes such a patient followed over thirteen years, and the efficacy of therapy with levodopa in ameliorating certain aspects of his disease.

Adult↗

PubMed1977

Effects of levodopa on the renin-aldosterone system.

Plasma renin activity and plasma aldosterone, supine and erect, and urinary aldosterone levels were measured in 18 patients on normal sodium diets and 11 patients on low sodium diets, all of whom also were on long-term levodopa therapy. Of the 230 hormone measurements, 185 were normal, 11 were high, and 34 were low. Most of the low levels were in 3 patients who had recently received fludrocortisone for orthostatic hypotension, and the renin-aldosterone systems might have been suppressed by it. In another phase of this study, 4 subjects were maintained on a constant diet for 6 wk, while the effect of gradually increasing dosages of levodopa on mineral balance and renin-aldosterone was determined. In 3 of the 4 patients there was a mild natriuretic effect of levodopa (previously demonstrated for acute levodopa therapy). There were no significant consistent changes in renin or aldosterone levels while levodopa was being administered. These studies indicate that levodopa does not usually suppress the elements of the renin-aldosterone system and that such a mechanism is unlikely to be the cause of orthostatic hypotension during the course of levodopa therapy. Since levodopa may induce natriuresis, in this situation unchanged lvels of renin and aldosterone may, however, represent an inappropriately low set of this hormonal system.

Aldosterone↗

PubMed1977

The Parkinsonian syndrome and its dopamine correlates.

The urinary excretion of free dopamine in 37 untreated parkinsonian patients correlated negatively with the severity of rigidity and akinesia (p less than 0.025) and with total neurologic deficit (p less than 0.05). In a parallel study of psychiatric patients, those with the lowest levels of urinary free dopamine before treatment were the most vulnerable to, and developed the most severe, secondary parkinsonian rigidity (p less than 0.005), akinesia (p less than 0.05), and total deficit (p less than 0.01) when they were subsequently treated for two weeks with trifluoperazine. In neither study was there a significant correlation between free urinary dopamine and tremor. These studies directly associate the level of free dopamine in the urine with the severity of the parkinsonian syndrome. Therefore, although many peripheral sources contribute to urinary free dopamine, a small decrease in the level may actually reflect the severity of the disturbance of central dopamine metabolism and the known deficiency of dopamine in the neurons of the parkinsonian brain.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1977

Spinal myoclonus.

The focal involuntary muscular contractions of spinal myoclonus have been associated with neoplastic, infectious, traumatic, and degenerative lesions of the spinal cord. Four patients are described here. In two, the myoclonus is associated with severe cervical spondylitis. One patient had herpes zoster. In the fourth, a segment of thoracic spinal cord is narrow and probably atrophic. Both tetrabenazine and clonazepam were therapeutically effective.

Clonazepam↗

PubMed1976

A trial of antilymphocyte globulin in the treatment of chronic progressive multiple sclerosis.

Twenty-three patients with chronic progressive multiple sclerosis (MS), resistant to steroid therapy, were treated with antilymphocyte globulin (ALG) and prednisone (30 mg by mouth daily). Twelve patients completed a full course of therapy (2 ml ALG i.m. daily for 2 weeks and 2 ml i.m. on alternate days for 2 weeks) and 6 others completed at least 2 weeks of daily injections. Six patients experienced an overall improvement of at least 15% using a comprehensive neurological scoring system. Three other patients had limited, but functionally useful improvement in specific neurologic functions. Six months after the completion of therapy, no patient had deteriorated to a level of function below that noted prior to treatment. Adverse reactions, which often necessitated stopping treatment, included fever, local inflammatory reactions, local rash, general malaise, mild anaphylactoid reactions, and enlargement and tenderness of regional lymph nodes. Because of the short duration of immunosuppression and the toxic side effects of ALG, we do not feel that ALG treatment yet deserves to be intorduced as a standard treatment in clinical practice. However, the improvement or arrest of progression seen in these patients who were deteriorating progressively despite steroid therapy would seem to justify a continued search for a safer method of suppressing immunity in MS patients.

Adult↗

PubMed1976

Age distribution of patients with Parkinsonism.

The modal age at onset of the parkinsonian syndrome during the past thrity years is less than a decade higher than it was in the late 19th and early 20th centuries, suggesting that the same disease entity is affecting parkinsonian patients now as then. The evidence points to the existence of two distinct clinical entities: 1) parkinsonism secondary to encephalitis lethargica, which had its greatest influence on the epidemiology of parkinsonism between 1920 and 1945; and 2) classic parkinsonism, which has undergone little change in the past hundred years.

Adult↗

PubMed1976

Dopamine correlates of neurological and psychological status in untreated Parkinsonism.

Thirty-seven untreated Parkinsonism patients showed significant positive correlations among decreased excretion of free dopamine, MMPI scores indicative of schizophrenic-like looseness of thinking, and the severity of all Parkinsonism signs except tremor. The data could indicate that abnormalities of dopamine metabolism may underlie both the motor and mental abnormalities of Parkinsonism.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1976

Low urinary dopamine and prediction of phenothiazine-induced Parkinsonism: a preliminary report.

Psychiatric patients who excreted larger amounts of urinary free dopamine before treatment were significantly more likely than patients excreting smaller amounts to develop parkinsonian side effects during moderate-dose trifluoperazine therapy. If this finding is replicated, urinary free dopamine determinations could prove valuable in indicating which patients should receive those antipsychotic drugs least likely to produce extrapyramidal side effects.

Adult↗