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Biomedical subjects

J W Miller

Publications and source records attributed to J W Miller.

At least 19 recordsLinked to original sources
PubMed1992

The effects of vitamins B12, B6, and folate on blood homocysteine levels.

The interaction between plasma homocysteine levels and vitamins B6, B12, and folate is an exciting field and one that has gathered great momentum over the past few years, with the recognition that homocysteine probably plays an important role in occlusive vascular disease. Our understanding in this field is greatly advanced compared to just a few years ago. There are a number of important issues, however, that will need to be addressed in the future if we are to develop a sufficient knowledge base to effectively minimize the risk of occlusive vascular disease ascribable to hyperhomocysteinemia. These include (1) definitive evidence that homocysteine is the actual agent that mediates accelerated occlusive vascular disease and the mechanism by which this occurs; (2) an understanding of what constitutes a pathologic elevation in homocysteine (is there a threshold concentration in the plasma below which no vascular injury occurs? is the peak concentration achieved the critical determinant of injury, or is the area under the curve, or some other feature, more important?); (3) understanding what synergies might exist by adding B6 or B12 to a regimen of folate supplementation (what doses are most appropriate? will toxologic issues limit the utility of supplementation?); and (4) determining the circumstances where reduction of plasma homocysteine will retard or reverse the process of occlusive vascular disease.

Folic Acid↗
PubMed1992

Effects of selective toxic lesions of cholinergic neurons of the laterodorsal tegmental nucleus on experimental seizures.

This study determined the effects of bilateral discrete partial lesions of cholinergic neurons of the laterodorsal tegmental nucleus (LDTg) of the pontomesencephalic tegmentum on seizures induced by intravenous pentylenetetrazol (PTZ). Relatively selective lesions produced by bilateral 50 nl microinjections of 75 pmol of the cholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A) resulted in a significant reduction in the threshold of myoclonic and facial-forelimb clonic seizures but not tonic seizures when PTZ was infused 7 days later. This demonstrates that this cholinergic nucleus is a key site of subcortical seizure regulation. We propose that this control is mediated by ascending projections from the LDTg to the central medial intralaminar nucleus of the thalamus.

Animals↗
PubMed1992

Hippocampal pyramidal cell response to 6-hydroxydopamine lesions of the rat ventral tegmental area.

The occurrence of neurofibrillary tangles (NFT) in the perforant pathway in association with dopaminergic cell loss in the ventral tegmental area (VTA) in human mesolimbic dementia, raises the possibility that denervation is a cause of NFT formation. This was tested in the rat by lesioning dopaminergic neurons which project to the hippocampus from the ventral tegmental area by means of stereotaxic injections of 6-hydroxydopamine. This resulted in the appearance of immunoreactivity to the paired helical filament protein plus an increase of tau and MAP-2 proteins in pyramidal neurons of CA-1 and CA-2. These neuronal responses to dopaminergic denervation are consistent with a precursor stage to NFT development.

Animals↗
PubMed1992

Characterization of cholinergic regulation of seizures by the midline thalamus.

This study determined the effects of injections of different cholinergic agents in the central medial intralaminar nucleus of the thalamus on seizures induced by intravenous injection of pentylenetetrazol. Injections of the cholinesterase inhibitor, neostigmine bromide, induced a stiff, tremulous state and lowered myoclonic, clonic and tonic seizure thresholds. The nicotinic agonist, tartrate, depressed arousal and facilitated all types of seizure, while its antagonist, d-tubocurarine chloride, heightened arousal and transformed pentylenetetrazol-induced convulsions, with tonic seizures occurring at a very low threshold without preceding myoclonic or clonic seizures or EEG spikes. The muscarinic agonist (+/-)pilocarpine hydrochloride, in very large doses, induced slight hyperactivity and facilitated tonic seizures but did not affect myoclonic or clonic seizures. Its antagonist, (-)scopolamine hydrobromide, slightly depressed arousal and myoclonic and clonic seizure thresholds. Injections of mixtures of agonists and antagonists (d-tubocurarine chloride + nicotine tartrate or (+/-)pilocarpine hydrochloride + (-)scopolamine) had little effect on spontaneous behavior or seizures. These results suggest that the midline thalamus regulates seizures and arousal, under the control of cholinergic neurotransmission. Nicotinic and muscarinic receptors have opposing roles in mediating these functions.

Animals↗
PubMed1992

The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine.

A unified, biochemical hypothesis is proposed to explain the pathogenesis of homocysteinemia. This hypothesis is based on the existence of coordinate regulation by S-adenosylmethionine (SAM) of the partitioning of homocysteine between de novo methionine synthesis and catabolism through cystathionine synthesis. This coordination, which serves to modulate the cellular concentration of homocysteine based on the requirements for methionine, is impaired in homocysteinemia. This hypothesis is evaluated in the context of the conditions known to be associated with homocysteinemia, including enzymatic defects and vitamin deficiencies. The novelty of the hypothesis is the assertion that impairment of one homocysteine metabolic pathway must lead to the impairment of the other homocysteine metabolic pathway to cause homocysteinemia. This extends the simplistic view that a block of only one of the pathways is sufficient to cause homocysteinemia.

Amino Acid Metabolism, Inborn Errors↗
PubMed1992

Effect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations.

The catabolism of homocysteine through cystathionine synthesis requires pyridoxal-5'-phosphate, thus the effect of vitamin B-6 deficiency on plasma homocysteine concentrations was evaluated. Total fasting plasma homocysteine concentrations were measured in 11 elderly subjects aged 64.4 +/- 1.7 y (mean +/- SE) who consumed a vitamin B-6-deficient diet for less than or equal to 20 d. Only 1 of the 11 subjects was found to have elevated homocysteine concentrations even though all subjects exhibited high urinary xanthurenic acid concentrations after a tryptophan load, a measure indicative of vitamin B-6 deficiency. In a supporting study, fasting plasma homocysteine concentrations were measured in 3- and 23-mo-old rats fed vitamin B-6-deficient diets and were compared with those of vitamin B-6-replete, pair-fed controls. There was no difference in homocysteine concentrations between deficient and pair-fed animals after 6 wk of the dietary regimen for either age group; after 9 wk a modest elevation was observed in the 3-mo-old deficient rats whereas no difference was observed for the 23-mo-old rats. It is concluded that fasting plasma homocysteine concentrations are not initially elevated in vitamin B-6 deficiency and therefore fasting plasma homocysteine concentrations are not a good indicator of vitamin B-6 status.

Aged↗
PubMed1992

Nutritional factors in physical and cognitive functions of elderly people.

The quality of life of aging individuals depends profoundly on their capacity for physical mobility, mental alertness, and cognitive function. Independence and self-esteem are strongly determined by physical and mental capacities. Stimulated by reports of declining function with age, investigators have examined the relationships between lifestyle factors and maintenance of functional status. Growing evidence supports the view that continued physical activity and good nutritional status are important determinants of physical and cognitive function. It is possible that some of the decline in cognitive function associated with aging is preventable or reversible with improved vitamin nutriture, especially vitamin B-12, vitamin B-6, and folate. It might well be argued that the most practical outcome of research on the relationship of diet and nutrition to the aging process would be a better understanding of the ways in which our behavior can maintain a vigorous quality of life.

Aged↗
PubMed1992

Appendices epiploicae of the colon: radiologic and pathologic features.

Appendices epiploicae are adipose structures protruding from the serosal surface of the colon. They can be seen with abdominal radiography and cross-sectional imaging if the colonic wall is surrounded by intraperitoneal contrast material, ascites, or blood. Normal appendices epiploicae appear as lobulated masses of pericolic fat, usually 2-5 cm long and 1-2 cm thick. Their enlargement, deformity, or altered radiopacity may result from various pathologic processes that can originate locally or extend from adjacent viscera. In a series of 22 cases, appendices epiploicae were affected by spontaneous torsion and hemorrhagic infarct, calcification due to aseptic fat necrosis, primary or secondary inflammation, enlargement by lipomas or metastases, and incarceration in hernias. Disorders of appendices epiploicae are often manifested by nonspecific clinical signs and symptoms (eg, torsion is often mistaken for appendicitis or diverticulitis). These entities should be included in the differential diagnosis of any unexplained abdominal pain or pericolic lesions in adults.

Adipose Tissue↗
PubMed1992

Decision analysis as a quality-assurance screening tool.

BACKGROUND: The purpose of this pilot study was to examine whether the technique of decision analysis, including sensitivity analysis, could be used in a clinical quality-assurance program. METHODS: This research was performed in a family practice residency clinical practice. A computerized decision analysis model was developed for selection of initial drug therapy for hypertension. The medical records of 52 resident-managed patients with hypertension were then reviewed. The residents' drug prescribing was evaluated by faculty reviewers and also by the decision analysis model, including a sensitivity analysis. RESULTS: Faculty reviewers rated the residents' drug choices as "most appropriate" or "acceptable" in 59.6% of cases. There was good agreement between faculty reviewers and the computerized decision analysis model. For example, in those cases in which the resident chose the computer model's first-choice drug, faculty deemed the management as "most appropriate" or "acceptable" 93.3% of the time. When residents selected the computer model's third or fourth choice, faculty judged the residents' therapy as "inappropriate" or "an alternate drug would have been more desirable" in 61.9% of cases. CONCLUSION: The results suggest that computerized decision analysis techniques may be a useful adjunct to other clinical quality-assurance procedures in residency training programs.

Adult↗
PubMed1991

The role of the laterodorsal tegmental nucleus of the rat in experimental seizures.

This study determined the effects of discrete microinjections of GABA agonists in the cholinergic nuclei of the pontomesencephalic tegmentum on spontaneous behavior and seizures induced by intravenous pentylenetetrazol, bicuculline or strychnine, in the rat. Injections of both the GABAA agonist piperidine-4-sulfonic acid and the GABAB agonist (-)baclofen in the laterodorsal tegmental nucleus produced a dose-dependent suppression of behavioral arousal and a reduction in the threshold of myoclonic and clonic but not tonic seizures induced by bicuculline and pentylenetetrazol. There were no significant effects on any type of strychnine seizure. Injections in the surrounding brainstem structures, including the pedunculopontine tegmental nucleus, had little effect on spontaneous behavior and did not significantly alter the thresholds of pentylenetetrazol-induced seizures. We have previously demonstrated that injections of GABA agonists in the central medial intralaminar nucleus of the thalamus have similar effects on behavior and seizures. Since the central medial nucleus receives important direct cholinergic projections from the laterodorsal tegmental nucleus, these two nuclei form a discrete ascending system which regulates seizure threshold.

Alcian Blue↗
PubMed1991

Phthalocyanine photodynamic therapy of experimental iris neovascularization.

Photodynamic therapy using chloroaluminum sulfonated phthalocyanine (CASPc) effectively closed experimental iris neovascularization induced in 6 eyes of cynomolgus monkeys by argon laser retinal vein occlusion. Neovascularization was followed by iris photography, fluorescein angiography, and histopathologic examination by light and electron microscopy. Intravenous injection of CASPc followed by irradiation with 675 nm light damaged endothelial cells and pericytes, leading to exposure of the basal lamina and thrombotic occlusion of the blood vessels. Surrounding tissue appeared preserved without evidence of thermal damage. Resorption of occluded vessels by macrophages began 2 to 3 days after photodynamic therapy. Neovascularization reappeared 7 days after photodynamic therapy, probably representing growth of new vessels. Photodynamic therapy with CASPc may be a useful adjunct in the treatment of iris neovascularization. The model is useful in elucidating the ultrastructural changes observed after photodynamic therapy using phthalocyanines.

Aluminum↗
PubMed1991

Swimming and the older athlete.

Swimming is an organized, fast-growing sport and competitive swimmers are now found in abundance in all age groups. Including those athletes who do not compete in formal events (masters swimming program) and those participating in outside events (long-distance, channel swimming, triathlons, and so on), it may be one of the largest participant sports in this country. Injuries to the elite collegiate competitive swimmers have been well-documented. Considerations and injuries to the masters-level swimmer closely mirror those found in the younger athlete, but these injuries reflect the impact of tissue aging (degenerative disease). The preparticipation history and physical examination become more important. We are hopeful that this article will contribute to greater safety and enjoyment among all older swimmers.

Aged↗
PubMed1991

The epidemiology of AIDS in Connecticut.

From 1980 to 30 September 1990, 1,769 Connecticut cases of AIDS have been diagnosed and reported. The epidemiology of AIDS in Connecticut continues to differ from national patterns in several important ways. Intravenous drug users (IVDUs) have been the most prominent source of new cases since 1986 and made up 49% of all cases reported in 1990. Women comprise 20% of the total adult caseload; twice the national average. Connecticut's pediatric cases are 3.3% of total cases, the highest proportion among US reporting areas with 100 or more total AIDS cases. Blacks and Hispanics comprise 55% of cases, although they represent only 11% of the total population of Connecticut. The most recent annual incidence rate for Connecticut is similar to that for the country as a whole (13.3/100,000). However, Connecticut's three central cities had annual incidence rates that are much higher: Bridgeport, 28.7/100,000; New Haven, 55.5/100,000; and Hartford, 64.9/100,000. The Department of Health Services estimates that approximately 12,000 persons in Connecticut are currently infected with the human immunodeficiency virus (HIV). About 4,200 intravenous drug users are already infected. In addition, we estimate that approximately 800 new infections will occur in adults and adolescents each year. Data from various New Haven based seroprevalence studies indicate that seropositivity is high. Among patients in clinics for sexually transmitted diseases, one in every 25 was infected with HIV; among women attending women's health clinics, one in 91 was infected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

The central medial nucleus: thalamic site of seizure regulation.

This study demonstrates that the central medial intralaminar nucleus (CeM) controls generalized seizure threshold and expression, and that these functions are under gamma-aminobutyric acid (GABA)ergic control, with significant differences between receptor subtypes. Injections of the GABAA-agonist piperidine-4-sulfonic acid and the GABAB-agonist (-)baclofen in the CeM markedly facilitated myoclonic and clonic seizures, but had different effects on tonic seizures. These results are best explained by the concept that the CeM is not a site of seizure origin or spread but rather regulates other structures involved in seizures.

Animals↗
PubMed1990

Eyelid twitching seizures and generalized tonic-clonic convulsions: a syndrome of idiopathic generalized epilepsy.

This is a report of two neurologically normal patients who had primary generalized seizures consisting of irregular fluttering or twitching movements of the eyelids accompanied by generalized, rhythmic 9- to 15-Hz electroencephalographic discharges as well as infrequent generalized tonic-clonic seizures. This is a syndrome of idiopathic generalized epilepsy that responds to treatment with valproic acid.

Acetazolamide↗
PubMed1990

Characterization of GABAergic seizure regulation in the midline thalamus.

This study characterized the role of GABA in the central medial intralaminar nucleus on seizures induced by pentylenetetrazol given systemically. Injections of the direct selective GABAA agonist, piperidine-4-sulfonic acid or the indirect GABAA agonists, flurazepam and pentobarbital, in this region depressed arousal and facilitated myoclonic and clonic seizures induced by pentylenetetrazol but only caused slight inhibition of tonic seizures. In contrast the GABAB agonist (-)baclofen facilitated all three types of seizures. Recording after injection of piperidine-4-sulfonic acid and (-)baclofen revealed marked suppression and slowing of thalamic and cortical electrical activity. Thalamic injections of the GABAA antagonist, bicuculline methiodide, had opposite behavioral effects, causing hyperactivity and episodes of violent running, not accompanied by EEG discharges. When pentylenetetrazol was infused concommitantly there was marked facilitation of the tonic seizures, which occurred without preceding myoclonic of clonic seizures, or EEG spikes. These results demonstrate that GABA-mediated neurotransmission in the central medial intralaminar nucleus can control the threshold of seizures and that GABA agonists and antagonists have opposite effects. It is suggested that the central medial intralaminar nucleus is not a site of origination or spread of seizures, but controls seizures indirectly by regulating the excitability of other structures and that different synaptic mechanisms and anatomical connections mediate effects on different types of seizures.

Animals↗