Catecholamines and neurologic diseases (first of two parts).
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Animals↗
Biomedical subjects
M A Moskowitz
Publications and source records attributed to M A Moskowitz.
Daily rhythm in human urinary melatonin.
The melatonin in urine samples from six healthy adult volunteers was concentrated on Amberlite XAD-2 resin, eluted with organic solvents, and quantitated by use of a bioassay technique (the dermal melanaphore response of larval anurans to melatonin in their bathing medium). The melatonin content of samples collected between 11 p.m. and 7 a.m. was, in each case, several times higher than that of samples collected between 7 a.m. and 3 p.m. or between 3 p.m. and 11 p.m.
Adult↗
D-amphetamine disaggregates brain polysomes via a dopaminergic mechanism.
Brain polysomes are disaggregated in rats given moderate to large doses of d-amphetamine sulfate; this response is rapid in onset, lasts for at least 4-6 hr, and varies with the age of the animal. Pretreatment with a dopamine receptor blocking agent, haloperidol or pimozide, blocks the amphetamine-induced disaggregation.
Animals↗
Brain H-3-catecholamine metabolism in experimental cerebral ischemia.
Unilateral ligation of a common carotid artery in gerbils causes a major depletion of brain dopamine, which is most marked in brain regions known to receive dopaminergic projections. To determine whether this depletion reflects release of stored dopamine, a radioactive label (H-3-dopamine) was introduced into brain dopamine pools 4 hours prior to ligation. Twenty-four hours later, brain H-3-catecholamines were profoundly depressed ipsilateral to the lesion among animals exhibiting clinical signs of stroke. Within brain regions known to receive dopaminergic projections, common carotid ligation also was associated with a selective decrease in the concentration of H-3-deaminated metabolites. These data suggest that cerebral ischemia is associated with release of catecholamines, as well as with impaired oxidative metabolism of catecholamines.
Animals↗
Angiographically monitored resolution of cerebral mycotic aneurysms.
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Adult↗
Brain catecholamines and neurological disease.
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Brain↗
Familial calcification of the basal ganglions: a metabolic and genetic study.
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Adolescent↗
Outpatient consultation: interaction between the general internist and the specialist.
To define the process of outpatient consultation, the authors conducted a prospective study of 716 consecutive outpatient consultations in a university-based primary care internal medicine practice. The overall consultation rate was 11.9 per 100 patient visits, with 78% of the referrals to other physicians and 22% to non-physician specialists. Consultation rates and patterns of referral varied little between physicians with different levels of experience. Eighteen per cent of the consultations resulted in a no-show by the patient to the consultant. Referring physicians received communications from the consultants 80.5% of the time when appointments were kept. By multivariate regression two variables were shown to be most important in determining the internist's overall satisfaction: 1) how well the consultant aided the internist in his ongoing management of the patient's problem, and 2) how well specific questions were addressed by the specialist. Other statistically significant variables were the clarity and promptness of the consultant's reply, the educational value of the consultation, and specific management recommendations made by the consultant. To improve the consultation process no-shows must be minimized, communication from the consultant maximized, and the interaction between the internist and the consultant bolstered.
Ambulatory Care↗
Measuring patients' desire for autonomy: decision making and information-seeking preferences among medical patients.
An instrument for measuring patients' preferences for two identified dimensions of autonomy, their desire to make medical decisions and their desire to be informed, was developed and tested for reliability and validity. The authors found that patients prefer that decisions be made principally by their physicians, not themselves, although they very much want to be informed. There was no correlation between patients' decision making and information-seeking preferences (r = 0.09; p = 0.15). For the majority of patients, their desire to make decisions declined as they faced more severe illness. Older patients had less desire than younger patients to make decisions and to be informed (p less than 0.0001 for each comparison). However, only 19% of the variance among patients for decision making and 12% for information seeking could be accounted for by stepwise regression models using sociodemographic and health status variables as predictors. The conceptual and clinical implications of these findings are discussed.
Adult↗
Research, academic rank, and compensation of women and men faculty in academic general internal medicine.
OBJECTIVE: To evaluate the status of men and women faculty in academic general internal medicine, including their professional training, faculty responsibilities, research performance, academic rank, and compensation, to determine whether systematic differences exist by gender. DESIGN/SETTING: The authors analyzed responses to a 55-part questionnaire sent to all full-time general internal medicine faculty at the major teaching hospitals in the United States. Unadjusted means were generated for men versus women faculty in demographics, training background, hours of work, professional time allocations, institutional support, professional self-assessment, research performance, academic rank, and compensation. Means were recalculated after adjusting for other variables using multivariate methods. RESULTS: The authors found no significant difference in the frequency of fellowship training between men and women faculty. Women and men perform similar professional activities, but even after multivariate adjustment, women devote less time to research and perceive less research skill and institutional support for their research, but have similar numbers of grants, abstracts, and publications in refereed journals and have similar academic ranks. Women faculty, however, receive lower compensation than do men faculty, even after adjustment. CONCLUSION: While the characteristics of men and women faculty are quite similar, including those defining their academic productivity, important differences exist in research time, perceived institutional support, and compensation. These differences cannot be explained by such obvious factors as age differentials, academic rank, or hours of work per week.
Adult↗
Discussions regarding aggressive care with critically ill patients.
Protocols concerning orders not to resuscitate have come into existence recently in order to facilitate decisions regarding resuscitation and to ensure that patient's rights to participate in such decisions are preserved. Prior to the do-not-resuscitate (DNR) decision is the decision whether to discuss the issue of resuscitation with the patient at all. To determine how frequently physicians discuss this issue with their patients, the authors gathered information on all 611 patients admitted to the medical intensive care unit (MICU) or the cardiac care unit (CCU) at a tertiary care teaching hospital over a nine-month period. They found that the issue was discussed with only 10.8% of patients or their families on admission of the patients to these units. Such discussions occurred more frequently with older patients, those who were more severely ill or were estimated to have worse prognoses, those with poor intellectual function, and those admitted to the MICU rather than the CCU.
Aged↗
Complications of care in a medical intensive care unit.
OBJECTIVE: To determine the frequency and nature of complications of care in the medical intensive care unit (MICU). DESIGN: Prospective, observational study. SETTING: Seven-bed MICU in a teaching and referral VA hospital. PATIENTS: 295 consecutive patients admitted to the MICU during a ten-month study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-two patients (14%, 95% confidence interval 13%, 16%) experienced one or more complications during their MICU stays. Compared with other MICU patients, those experiencing complications tended to be older (mean age +/- SD: 63.6 +/- 10.1 years vs 59.3 +/- 14.0 years, p less than 0.02) and more acutely ill (mean Acute Physiology Score +/- SD: 18.3 +/- 8.0 vs 12.5 +/- 8.0, p = 0.0001). These patients also had significantly longer MICU lengths of stay (mean +/- SD: 12.3 +/- 14.7 days vs 3.1 +/- 4 days, p less than 0.0001) and higher hospital mortality rates (67% vs 27%, p less than 0.001). The 67% mortality rate among patients with complications significantly exceeded the expected mortality rate of 46% (calculated from the APACHE risk equation). CONCLUSION: Complications of care in the MICU are not rare and may independently contribute to in-hospital mortality. The potential for complications must be recognized when considering ICU care.
Boston↗
Preferences for autonomy when patients are physicians.
OBJECTIVE: To assess physicians' preferences for patient autonomy when they are patients themselves. DESIGN: Data from practicing physicians attending a continuing medical education course were obtained by questionnaire. After adjustment for sociodemographic differences, data from the physician population were compared with similar data previously obtained from a patient population. PARTICIPANTS: One hundred fifty-one physicians (94% of the study population) agreed to participate. Ninety percent were primary care physicians. Fifty-eight percent practiced in the eastern United States. MAIN RESULTS: The physicians, like the regular patients, preferred that the principal role in decision making for their own illnesses be handled by their providers, not by themselves. As illness severity increased, physicians indicated significantly less desire for making decisions (p less than 0.01). The magnitudes of the effects of increasing illness severity upon the decision-making preferences of physician and regular patients were comparable (p = 0.53). Physician-patients, however, were slightly more interested than regular patients in making decisions (p less than 0.001). CONCLUSIONS: although physician-patients are slightly more interested than regular patients in making decisions, for the most part their preferences for autonomy resemble those of regular patients. These results suggest that medical knowledge and sociocultural factors are only minor determinants of patient attitudes towards autonomy. Rather, patients' preferences to be relieved of decision-making responsibility are better understood as part of the phenomenology of illness.
Adult↗
Identification of immunoreactive substance P in human and other mammalian endothelial cells.
Endothelial cells release both vasodilatory (e.g., PGI2, EDRF, oxygen radicals) and vasoconstrictor (e.g., EDCF) substances which modify vascular tone and contractility. We report the existence of the vasodilatory tachykinin substance P within endothelial cell scraping from human, rat and dog thoracic aorta and human pial arteries with values ranging from 1.0 +/- 0.1 (rat aorta) to 1.9 +/- 0.5 (dog aorta) fmol/mg protein. The immunoreactive component eluted with a retention time identical to that of radiolabelled substance P when analyzed by high performance liquid chromatography combined with radioimmunoassay. Cultured endothelial cells from bovine cerebral microvessels contained measurable levels of substance P in passages 3-8, suggesting the likelihood that these cells synthesize substance P. However, the level of gene expression must be low since efforts to demonstrate the presence of preprotachykinin mRNA by Northern blot analysis of dog and rat aortic endothelial cell RNA or by RNase protection analysis of rat aortic endothelial cell RNA was not successful.
Aged↗
Wolff Award 1996. The actions of valproate and neurosteroids in a model of trigeminal pain.
Gamma-aminobutyric acid (GABA) receptors are ubiquitous inhibitory receptors in the central and peripheral nervous systems. Valproic acid (2-propylpentanoic acid), which enhances GABA synthesis and blocks degradation, is useful in migraine treatment and may act through activation of GABA receptors to modulate trigeminal nociceptive neurons innervating the meninges. To investigate this possibility, we tested the effect of valproate and allopregnanolone, a metabolite of progesterone, which binds and modulates the GABA receptor in an animal model of cephalic pain. One hundred ten Hartley guinea pigs were pretreated with either valproate or allopregnanolone 30 minutes prior to activation of trigeminal afferent fibers via intracisternal injection of the irritant, capsaicin. The effects of valproic acid and allopregnanolone were examined on c-fos expression within the trigeminal nucleus caudalis (lamina I, II), the termination site for small unmyelinated C fibers projecting from the meninges. C-fos positive cells were counted at three representative levels (rostral, middle, and caudal) by an observer naive to the treatment group. We found that valproate (> or = 10 mg/kg, IP) reduced labeled cells by 52% (P < 0.05) and allopregnanolone (> or = 100 mg/kg, IP) reduced labeled cells by 42% (P < 0.01). Bicuculline (GABAA antagonist), but not phaclofen (GABAB antagonist), blocked the valproate effect, thereby documenting the importance of GABAA receptors. We conclude that the attenuation of c-fos-LI by valproate and allopregnanolone is mediated via GABAA receptors. These studies complement prior experiments showing that valproic acid and allopregnanolone block neurogenic inflammation within the meninges via GABAA receptor-mediated mechanisms. The findings suggest a potential strategy for discovering new antimigraine drugs with high affinity for the GABAA receptor and its modulatory sites.
Animals↗
PET and MR studies of experimental focal stroke.
Positron emission tomography (PET) and MR have been compared with histochemical pathology to show affected tissue areas in rat brain after right middle cerebral artery (MCA) occlusion combined with temporary bilateral common carotid artery occlusion in Long Evans rats. The glucose metabolic rate was 65 +/- 8 mumol/100 ml/min in the right cortical gray matter corresponding to the occluded middle cerebral artery territory and 93 +/- 8 mumol/100 ml/min in the corresponding (left) normal side. Infarcted tissue showed decreased PET activity and increased signal in MR T2-weighted scans ipsilateral to the MCA occlusion. These regions correspond to a zone of focal infarction identified in coronal tissue sections stained with 3-4-5 triphenyl tetrazolium chloride. This study demonstrates that PET can be used to study glucose utilization in rat stroke model in vivo and noninvasively.
Animals↗
Clinical applications of prostaglandins and their inhibitors.
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Animals↗
Cerebrovascular projections from the sphenopalatine and otic ganglia to the middle cerebral artery of the cat.
The location of the postganglionic parasympathetic cell bodies projecting to cerebral arteries is unknown. Using axonal tracing techniques, we examined whether the sphenopalatine ganglia (associated with the seventh cranial nerve) and otic ganglia (associated with ninth cranial nerve) contain perikarya which send axons to the feline middle cerebral artery (MCA). The tracers horseradish peroxidase (HRP: 3 cats) or wheat germ agglutinin (WGA: 6 cats) were applied to the MCA in a slow release polymeric system. Three days later the SPG, otic ganglia, and rete mirabile were harvested bilaterally and processed for tracer by the TMB method (HRP) or immunohistochemistry (WGA). In a given animal, approximately equal numbers of cells containing axonal tracer were found in both SPG. Labeled fibers occasionally could be seen extending into the vidian nerve. Positive cells were also found in the otic ganglia and in the walls of the internal rete mirabile. These results provide the first identification of parasympathetic cell bodies projecting to cerebral blood vessels.
Animals↗