The role of mesencephalic and thalamic arousal systems in experimental seizures.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J W Miller.
Explore the source record for details and available documents.
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.
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.
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.
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.
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.
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.
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.
Explore the source record for details and available documents.
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.
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)
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.
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.
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.
A total of 108 male partners of women with cervical condyloma and/or dysplasia underwent evaluation for gross and subclinical condyloma via acetic acid screening with a magnified examination. Biopsies of acetowhite genital skin were obtained for histological and deoxyribonucleic acid hybridization analysis. Of the men 52 (49%) had acetowhite lesions and underwent biopsies, 44 of which were evaluable by histological and deoxyribonucleic acid analyses. Of the lesions 12 had features of condyloma or penile intra-epithelial neoplasia, among which 7 (58%) contained human papillomavirus deoxyribonucleic acid. The remaining 32 lesions revealed minimal histological changes sometimes suggesting condyloma. However, only 5 of the 32 biopsies (16%) contained human papillomavirus deoxyribonucleic acid. A tendency to overdiagnose condyloma based on histological findings is suggested. Criteria by which to identify best human papillomavirus-related morphology are presented. Acetowhite genital epithelia with minor (nonspecific) histological changes correlate poorly with human papillomavirus nucleic acids and in most cases do not represent disease involving common viral types. The application of appropriate histological criteria appears to be particularly relevant to management strategies that avoid overtreatment of minor epithelial abnormalities. It remains unclear whether acetowhite genital epithelia positive for human papillomavirus require treatment given the high tendency for recurrence and lack of demonstrated effect on the natural history of cervical carcinoma.
Explore the source record for details and available documents.
In summary, the staff and administration of the Muhlenberg-health center project feel it has thus far been successful in meeting its original goals of reducing duplication, ensuring access, controlling costs, and maintaining quality care. We believe that this model of cooperation benefits both organizations and provides the patients served with an ambulatory care program that is superior to either of its predecessors.
We studied 8 subjects longitudinally in whom isolated language dysfunction had developed gradually at a mean age of 62.8 years. The language deficits initially displayed by the subjects were characteristic of the syndrome of "progressive aphasia without dementia." By 5 years after onset of progressive aphasia, however, 7 of the 8 subjects additionally had developed mild dementia as diagnosed by clinical means, and the remaining subject demonstrated declining performance in both verbal and nonverbal psychometric measures. Thus, generalized cognitive impairment occurred in all. Neuropathologic evidence of a diffuse dementing disorder was present in the 2 subjects studied postmortem. One had Alzheimer's disease with disproportionate involvement of the left inferior parietal cortex, and the other displayed widespread neocortical neuronal loss and microvacuolation in the absence of specific histopathologic markers. In this series, progressive aphasia was a precursor of global dementia.