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Biomedical subjects

S T Miller

Publications and source records attributed to S T Miller.

At least 109 records · Page 6Linked to original sources

Generalized seizures alter the cerebral and peripheral metabolism of essential metals in mice.

The effects of seizures on the cerebral and peripheral metabolism of essential metals were studied in mice. Acute and chronic seizures were produced either by electroshock (ES) or by a systemic convulsant. Organ and subcellular distribution of 54Mn and 65Zn were determined prior to and at different intervals after seizure cessation. In mice shocked for 21 days, the concentrations of manganese, zinc, magnesium, and copper were determined in selected tissues. Sham-seizured mice served as controls. When 54Mn was injected after a single ES, the isotope's retention increased in the liver by 67% (P less than 0.01) and decreased in the brain and carcass by 53 and 42%, respectively (P less than 0.01). Repeated ES further augmented these effects (P less than 0.01). These changes diminished as a function of time to the animal's recovery from ES. Liver and regional brain fractionations revealed significant perturbation in the intercellular partition of 54Mn, suggesting increased metal utilization. Brain and liver 65Zn were not affected by ES. Manganese content increased in the liver by 67% (P less than 0.01) and decreased in whole brain by 16.5% (P less than 0.01), after chronic ES. Cortical manganese and hypothalamic magnesium were the principal sites of loss. Small (12 to 13%), but significant elevations of magnesium were found in liver and skeletal muscle (P less than 0.05). Copper increased in muscle by 26% (P less than 0.02). Seizures selectively altered the normal brain and extracerebral distribution of essential metals which may lead to regional metal deficiency or excess. These changes were linked to the metabolic consequences of convulsive activity and may be relevant to seizure control and electroshock therapy in man.

Animals↗

Postnatal endocardial fibroelastosis of the valve of the foramen ovale.

The valve of the foramen ovale of the heart changes at birth from a prenatal shunting device for the transseptal flow of systemic venous return to a postnatal active barrier to backflow of left atrial blood at higher pressure. To investigate the morphologic response to this functional change in the valve of the foramen ovale, we examined 200 hearts from embryos, fetuses and autopsy patients spanning over a millionfold range of heart weights (0.001 to 1,230 g). The relation of valve thickness to log heart weight was studied by a stepwise linear regression procedure that fitted the data to two linear regressions, one including observations made before birth and the other including observations made after birth. Analysis of variance tables demonstrated that the data are significantly better explained (p < 0.001) by two linear regressions that abruptly separate from one another at the time of birth than by a single linear regression. Histologic study showed that the prenatal valve consists of a thin myocardial layer with delicate endocardium. The postnatal thickening of the valve tissue occurs mainly by fibroelastotic thickening of the endocardium. The endocardial fibroelastosis of the valve develops after it closes and becomes a component of the left atrial wall. The observations support the concept that fibroelastosis is a nonspecific response of the lining of the cardiovascular system to increased mural tension.

Adolescent↗

Evaluation of a decentralized system for chronic disease care: seven years of observation.

Observations of a publicly-financed system for the medical care of a large number of persons with chronic diseases have been made over seven years. The system combines decentralized, nurse-staffed neighborhood clinics, operated by a public health department, with a central referral clinic for consultations and the management of complicated problems. After seven years in the chronic disease program 55% of 1,004 patients with diagnoses of diabetes mellitus, hypertension, and cardiac diseases were still receiving care, 19% had died, and 26% had been lost to the program. In the seventh year, the mean diastolic blood pressure in hypertensives was 84 mm Hg and the mean serum glucose in diabetics was 203 mg/dl. For the group under care, hospital days/1000/year were 74% of the rate during the year before referral to the program and out-patient visits/1000/year were approximately the same as before referral. However, two-thirds of the visits, formerly made to a public hospital, were now being made to neighborhood clinics. The system appears to be an effective method of providing medical services for persons who formerly used the public hospital as their source of outpatient care.

Chronic Disease↗

Administration of human somatotropin in levodopa-treated patients with Parkinsonism.

To investigate further the role of growth hormone (GH) on the cerebral effects of levodopa, human somatotropin (human growth hormone) was administered to four patients with parkinsonism with varying response to chronic levodopa therapy. The doses of somatotropin (5 IU) were administered on alternate days for four days, and the effects of this hormone on the patient's symptomatic control, dyskinesia, plasma GH, and dopa levels were evaluated and compared with those of patients receiving saline injections. We have demonstrated that administration of exogenous human somatotropin, even during marked and sustained elevations of plasma GH levels, does not alter the therapeutic or side effects of levodopa therapy. With one exception, plasma dopa levels after human somatotropin administration remained unchanged. We conclude that neither the endogenous increases of GH in response to levodopa nor those attained following human somatotropin administration modify in any consistent way the therapeutic and side effects of chronic levodopa therapy, and that the episodic releases of GH in response to levodopa occur independently of its cerebral effects.

Aged↗

Seizure disorders and trace metals: manganese tissue levels in treated epileptics.

We determined the concentrations of manganese in whole blood and hair in 52 epileptics, 6 blood relatives, and 24 normal controls. Blood, and possibly hair manganese content, was significantly lower in treated epileptics than in controls (p less than 0.002). Although not all patients showed reduced tissue manganese levels, most of those with frequent seizures had manganese levels falling below the lowest control level, suggesting a relationship between manganese tissue levels and high seizure activity. These differences in manganese levels were not correlated with the type, dose, or plasma levels of anticonvulsant medication. Reduced manganese availability at the neuronal level, where Mn++ stabilizes membrane excitability, may affect epileptogenic lesions to increase the likelihood of seizure activity.

Adolescent↗

Plasma DOPA and growth hormone in parkinsonism: oscillations in symptoms.

In 19 patients with Parkinson disease, we studied the relationship of the therapeutic effect of levodopa, or dyskinesia, to the plasma content of DOPA and growth hormone (GH). Those with stable responses to levodopa, individually or as a group, showed stable and lower plasma DOPA levels than those with unstable symptomatic responses. These results show that stable and oscillating clinical responses in Parkinson disease parallel plasma DOPA levels, suggesting that there are different mechanisms in peripheral levodopa metabolism and that extracerebral mechanisms are important in regulating the availability of levodopa to the brain. Plasma GH did not differ in the two groups, suggesting that the secretion of GH is independent of the effects of levodopa in parkinsonism.

Aged↗

Evaluation of biofeedback in the treatment of borderline essential hypertension.

Direct biofeedback of blood pressure was compared with frontal EMG biofeedback and with self-instructed relaxation for the treatment of essential hypertension in a controlled group outcome study. Patients were followed up for four months after the end of treatment. Generalization of treatment effects was assessed through pre- and posttreatment measurements of blood pressure under clinical conditions in a physician's office. There were no significant reductions in diastolic blood pressure. The systolic blood pressure (SBP) of the patients receiving blood pressure biofeedback decreased 8.1 mm mercury (p = 0.07) and the SBP of the patients in the relaxation condition decreased 9.5 mm mercury (p = 0.05). In the generalization measures, there were significant reductions in SBP for the relaxation group. The results are discussed in terms of the general lack of replicability within the area of biofeedback treatment of hypertension.

Adult↗

Treatment of parkinsonism with N-n-propyl norapomorphine and levodopa (with or without carbidopa).

The effects of the concomitant administration of N-n-propyl norapomorphine (NPA) and levodopa, with and without carbidopa, were studied in 12 patients with unsatisfactory symptom control. Double-blind evaluation of the effects of NPA with suboptimal doses of levodopa or levodopa plus carbidopa (Sinemet) showed a mean overall improvement of 44% (20% to 74%) in nine patients and improvement of the "on-off" effect in five. Dyskinesia diminished in some patients after diminution of basal medication. In three patients, plasma dopa and growth hormone patterns did not differ substantially with and without NPA. The magnitude and timing of the therapeutic and side effects did not correlate with the pattern of growth hormone secretion, which suggests that this hormone might not be instrumental in the induction of these effects. N-n-propyl norapomorphine is a useful adjunct in the long-term management of patients with unsatisfactory response to levodopa.

Aged↗

Levodopa, fertility, and longevity.

High concentrations of the dopaminergic drug levodopa (L-dopa, L-3,4-dihydroxphenylalanine) administered to mice in their diet affected fertility to a moderate degree and prolonged the mean life-span by a maximum of 50 percent.

Animals↗

Psychological treatment of cardiovascular disease.

Recent clinical research on the psychological treatment of cardiovascular diseases is reviewed in four categories: hypertension, cardiac arrhythmias, coronary artery disease, and peripheral circulatory disease. In the treatment of hypertension biofeedback of blood pressure, electromyography and galvanic skin responses both seem useful, as does systematic relaxation training of either an active or passive-meditative nature. Biofeedback of heart rate has shown some utility in treating premature ventricular contractions and sinus tachycardia. Supportive and educational group therapy for patients recovering from myocardial infarctions has shown some utility. In the treatment of Raynaud's disease, biofeedback of skin temperature is helpful. In no area has a large scale clinical trial been conducted, and only three controlled group outcome studies have been reported (two in hypertension, one in coronary artery disease). Overall, the evidence is impressive enough to warrant more systematic controlled investigation in all four areas.

Arrhythmias, Cardiac↗

Control of tissue manganese: initial absence and sudden emergence of excretion in the neonatal mouse.

All adult animals and humans tested up to this time have controlled their tissue manganese concentrations by controlling primarily the rate of the metal's excretion. In sharp contrast, neonatal mice did not excrete manganese for the first 17-18 days of life, although absorption of the natural 55Mn as well as distribution, tissue accumulation, and mitochondrial accumulation of the radioactive 54Mn were vigorous. This suggested as initially avid accumulation of this essential micronutrient, supplied in scarce traces in mouse milk (54 ng/ml) by mothers consuming very much higher dietary concentrations (55,000 ng/g). The tissue accumulation was demonstrated analytically and was particularly impressive in the brain, which can be susceptible to both manganese poisoning and deficiency.

Animals↗