Biomedical subjects

M A Moskowitz

Publications and source records attributed to M A Moskowitz.

At least 271 records · Page 15Linked to original sources

PubMed1989

Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater.

Leakage of 125I-bovine serum albumin was measured in rat dura mater, conjunctiva, eyelid and lip, after unilateral electrical stimulation of the trigeminal ganglion. In one animal, 99Tc-human serum albumin leakage was imaged in ipsilateral facial tissues. Pretreatment with indomethacin 1 mg/kg i.p. decreased leakage in dura mater but not in extracranial tissues. When extravasation was expressed as a ratio of stimulated to unstimulated sides, indomethacin 1 mg/kg, or acetylsalicylic acid 50 mg/kg decreased this ratio from 1.80 to 1.27 (P less than 0.01) or from 1.84 to 1.21 (P less than 0.01), respectively. Dexamethasone (1 mg/kg i.p. tid X 1 day) caused only a very small decrease. Only large doses of indomethacin (10 mg/kg) or acetylsalicylic acid (50 mg/kg) reduced substance P (SP)-induced leakage in the dura. The latter results suggest that both drugs block plasma extravasation by acting on neuropeptides-induced changes in vascular permeability and/or smooth muscle contractility. However, inhibition of SP release from sensory axons cannot be excluded at concentrations which block neurogenic plasma extravasation but not SP-induced plasma leakage. Together, these results provide a possible mechanism for the therapeutic effects of indomethacin and acetylsalicylic acid in headache.

Animals↗

PubMed1989

The development of neurogenic plasma extravasation in the rat dura mater does not depend upon the degranulation of mast cells.

Mast cells were visualized in stretch preparations of the rat dura mater and were found mostly in relation to small and large blood vessels. The overall number of dural mast cells was unaffected by electrical trigeminal or chemical deafferentation. As in other tissues, mast cell degranulation increased at sites of local injury (electrode penetration) or after systemic treatment with compound 48/80. However, mast cells did not degranulate following electrical trigeminal stimulation, or after injection of drugs (capsaicin or substance P) which promote plasma extravasation in the dura. Furthermore, pretreatment with a mast cell stabilizer (sodium dicromoglycate) or with large doses of H1 and H2 histamine receptor blockers (mepyramine and cimetidine), did not block electrically- or chemically-induced neurogenic plasma extravasation (NPE). Daily pretreatment with 48/80 however completely attenuated or abolished NPE. Taken together these data suggest that as assessed by the extrusion of metachromatic granules, mast cells are not essential to the development of neurogenic inflammation within the rat dura mater. However, these findings cannot exclude the possibility that mast cells may amplify or modulate this process.

Animals↗

PubMed1989

Subarachnoid blood and headache: altered trigeminal tachykinin gene expression.

Sensory axons from the trigeminal ganglion (V) innervate cephalic blood vessels and use the preprotachykinin gene products, substance P (SP) and neurokinin A (NKA), as putative neurotransmitters conveying nociceptive information. Blood in the subarachnoid space is accompanied by severe headache. We now report that this painful stimulus, which should enhance activity in V, specifically alters tachykinin peptide and mRNA levels in V and perivascular axons. Marked reductions in SP levels were observed in basilar artery segments within 4 hours after intracisternal blood injection which persisted for 48 hours and recovered by 7 days. SP peptide levels in V were elevated by 49% two days after blood injection. The changes in SP peptide levels were accompanied by increases in ganglionic content of the preprotachykinin mRNA that codes for the peptide. Blood-induced peptide depletion in arteries and subsequent increases in peptide and mRNA in V are consistent with increased neuronal activity and enhanced neuropeptide release. These results implicate the tachykinin-utilizing trigeminovascular neurons in the sequelae of subarachnoid hemorrhage.

Animals↗

PubMed1989

Preproenkephalin mRNA expression in nucleus caudalis neurons is enhanced by trigeminal stimulation.

Electrical stimulation of trigeminal afferents increases expression of preproenkephalin mRNA in neurons of laminae I and II of the trigeminal nucleus caudalis in animals sacrificed 6 hours after the end of stimulation. More neurons express, and positive cells express at higher levels. These neurons thus express the mRNA corresponding to a major pain-modulating neurotransmitter gene with significant input-related plasticity.

Animals↗

PubMed1989

Utility of echocardiography in patients with suspected mitral valve prolapse.

PURPOSE: Echocardiography has become a widely utilized test since its introduction into clinical medicine in the early 1970s. Although it has frequently been performed in patients suspected of having mitral valve prolapse (MVP), its usefulness in this setting has not been systematically studied. To investigate the use and value of echocardiography in patients suspected of having MVP, we conducted a prospective study in which physicians were interviewed before and after ordering echocardiographic testing for patients in whom there was a suspicion of MVP. PATIENTS AND METHODS: The study population included consecutive patients referred to the echocardiography laboratory at Boston University Medical Center because of suspected MVP between January 1 and December 31, 1987. Two standardized telephone interviews were conducted with the physician most responsible for ordering the echocardiogram. The following information was obtained during the first interview, which was always conducted before the echocardiogram was performed: patient demographic and clinical data; the reason for ordering the echocardiogram; the physician's most likely clinical diagnosis; the physician's estimate of the likelihood that the patient had MVP; and the physician's proposed management plans. After the referring physician received the echocardiographic results, a second interview was conducted to determine changes in the most likely clinical diagnosis and management plans. The impact of the echocardiogram on diagnosis and management was evaluated by comparing physician responses before and after reception of echocardiographic results. Receiver operating characteristic (ROC) curves were constructed to assess the physician's skills at distinguishing patients with echocardiographic-documented MVP from those without MVP. RESULTS: A total of 106 echocardiograms were ordered by 45 different physicians. More than 80% of all echocardiograms were ordered to address diagnostic or therapeutic concerns. On echocardiography, 47 (44%) patients were found to have MVP, six (6%) had mitral regurgitation without prolapse, and 53 (50%) had normal results. On the basis of the ROC curve analysis, the physician's ability to discriminate between patients with and without echocardiographic MVP varied significantly by physician specialty and practice setting. The echocardiographic results led to a change in diagnosis in 59 (56%) patients. A change in management occurred in 29 (27%) patients, with 25 of these 29 changes (86%) related to the initiation or discontinuation of antibiotics. CONCLUSIONS: Echocardiography frequently alters diagnostic assessments and leads to therapeutic changes in some patients suspected of having MVP. However, the benefits of such changes have not yet been demonstrated.

Adult↗

PubMed1989

Trigeminovascular fibers increase blood flow in cortical gray matter by axon reflex-like mechanisms during acute severe hypertension or seizures.

Cerebral blood flow was measured and compared in 10 symmetrical brain regions following unilateral trigeminal ganglionectomy (n = 13), sham operation (n = 6), or trigeminal root section (rhizotomy) (n = 8) in cats. Multiple determinations were obtained in anesthetized and paralyzed animals using radiolabeled microspheres during (i) normocapnia-normotension, (ii) hypercapnia (5% CO2/95% room air), (iii) angiotensin-induced acute severe hypertension (190 greater than mean arterial blood pressure less than 210 mmHg), or (iv) bicuculline-induced seizures. Flow was symmetrical in all brain regions at rest and during increases induced by hypercapnia in the three groups. During severe hypertension or seizures, marked elevations developed bilaterally (approximately 93% and approximately 130%, respectively). In ganglionectomized animals, increases due to hypertension or seizures were attenuated by 28-32% on the denervated side within cortical gray matter regions corresponding to the anterior, middle, and posterior cerebral arteries. Flow was symmetrical within all brain regions in sham-operated animals and in the rhizotomy group, despite comparable increases in regional cerebral blood flow induced by angiotensin. Hence, the trigeminal nerve mediates blood flow adaptations during severe hypertension and seizures. Furthermore, since trigeminal cell bodies and peripheral axons are destroyed or degenerate following ganglionectomy but not following rhizotomy, local "axon reflex-like" mechanisms mediate these increases in cerebral blood flow.

Angiotensin II↗

PubMed1989

Postocclusive cerebral hyperemia is markedly attenuated by chronic trigeminal ganglionectomy.

Marked hyperemia may develop in brain following temporary cessation of blood flow and is associated with the morbidity following cardiac arrest, stroke, and head injury. Regional cerebral blood flow was measured using radiolabeled microspheres and compared in 10 symmetrical regions after chronic unilateral trigeminal ganglionectomy (n = 8), trigeminal rhizotomy (n = 4), or sham operation (n = 4) following 10 min of combined brachiocephalic-left subclavian occlusion and hypotension (mean arterial blood pressure less than 50 mmHg) in cats. Blood flow was symmetrical at rest in the three groups and was undetectable during the ischemic period. Within 30 min after re-establishing flow, values in cortical gray matter increased symmetrically to approximately 250 ml.100 g-1.min-1 in the rhizotomy and the sham groups. Increases of similar magnitude were measured on the intact side following trigeminal ganglionectomy but flow was attenuated by greater than 50% ipsilateral to the ganglionectomy. Marked hyperemia developed during reperfusion in thalamus, caudate, deep cortical white matter, midbrain, and pons, but no asymmetries were present in the three groups. These data suggest that cortical hyperemia is mediated by trigeminal neurogenic mechanisms via axonal reflexlike mechanisms and suggest the importance of therapeutic strategies based on blockade of this nerve or its constituent neuropeptides.

Animals↗

PubMed1989

A flavonoid inhibitor of 5-lipoxygenase inhibits leukotriene production following ischemia in gerbil brain.

Leukotrienes C4 and D4 are arachidonic acid metabolites that constrict blood vessels and enhance vascular permeability; their biosynthesis is initiated by the reaction of arachidonic acid with 5-lipoxygenase enzyme. After bilateral carotid artery occlusion for 15 minutes and reperfusion of the gerbil brain for 15 minutes, we determined the brain tissue concentrations of leukotrienes C4 and D4 by radioimmunoassay; they had increased from a baseline concentration of less than 1 to a mean +/- SEM concentration of 12.8 +/- 3.9 pmol/g brain. We also studied the effect of a flavonoid 5-lipoxygenase inhibitor on leukotriene production in the reperfused gerbil brain. A water-soluble flavonoid (5-hexyloxy-3',4'-dihydroxy-6,7-dimethoxyflavone 4'-disodium phosphate) was administered intravenously at a dose of 200 mg/kg body wt; 15 minutes later, both carotid arteries were occluded. The enhanced production of leukotrienes C4 and D4 in the reperfused brain was reduced by approximately 80% (from a mean +/- SEM of 12.8 +/- 3.9 to 2.2 +/- 1.3 pmol/g brain) in the presence of the 5-lipoxygenase inhibitor. The flavonoid did not affect the production of prostaglandin D2, the concentration of which also increased in the reperfused ischemic brain.

Animals↗

PubMed1989

Contributions from the upper cervical dorsal roots and trigeminal ganglia to the feline circle of Willis.

To further define the sensory projections to the circle of Willis, we measured concentrations of immunoreactive substance P in pial arteries of cats following either bilateral removal of the C1-3 dorsal root ganglia (six cats) or bilateral removal of the trigeminal ganglia (three cats). Removal of the dorsal root ganglia decreased concentrations of the tachykinin substance P in the vertebral artery and the basilar artery and its branches by 72% and 50-66%, respectively. Bilateral removal of the trigeminal ganglia decreased substance P concentrations in all forebrain vessels including the rostral basilar artery, although only concentrations in the anterior cerebral artery were significantly lower than those in unilaterally lesioned cats (p less than 0.01). Hence, the vertebrobasilar artery and its tributaries are invested by substance P-containing fibers originating from the upper cervical dorsal root ganglia, and the anterior cerebral artery is innervated by both trigeminal ganglia. If a similar anatomy exists in humans, our data provide an explanation for the occipital localization of headaches arising from the vertebrobasilar arteries and for bilateral headaches following stimulation of the anterior cerebral artery.

Animals↗

PubMed1989

Pain mechanisms underlying vascular headaches. Progress Report 1989.

Vascular headaches are among the most prevalent yet poorly understood problems in clinical neurology. Headaches may develop in association with hypertension, seizures, stroke or without a recognizable pathophysiology such as during migraine and cluster headaches. Cephalic blood vessels (pial and dural vessels) are implicated as the most important source for all headaches and are innervated by sensory fibers which arise from ganglia innervating the forehead, scalp and neck. Sensory fibers contain vasoactive neuropeptides which become released from peripheral (perivascular) and central terminations to mediate vasodilation and pain, respectively. The presence of vascular headache implies activation of this final common pain pathway which we have termed the trigeminovascular system. The presence of vascular headache implies activation of this final common pain pathway which we have termed the trigeminovascular system. The existence of such a system a) clarifies certain pain patterns which develop following stimulation of cephalic blood vessels, b) suggests a mechanism to explain the referral of pain to the forehead, c) provides a mechanism to explain the action of certain antimigraine drugs, d) suggests a local mechanism which enhances blood flow under certain pathological conditions. Hence, this review will update existing knowledge about the trigeminovascular system and its role in headache pathophysiology.

Animals↗

PubMed1989

The use of follow-up chest roentgenograms among hospitalized patients.

Follow-up chest roentgenograms are a commonly performed test. We prospectively evaluated their diagnostic and therapeutic influence at a tertiary care teaching hospital. When a follow-up chest roentgenogram was ordered, physicians indicated their reason for ordering the test, the likelihood that the roentgenogram would show changes, and expected alterations in therapy. After the roentgenogram was obtained, physicians described the help provided by the roentgenogram and what changes in therapy were performed. Using receiver operating characteristic curves, we have shown that physicians have difficulty in predicting which roentgenograms will show important changes. Unexpected findings are frequent (25.4%) and highly valued by the physician. Fifty-seven percent of these roentgenograms had a definite or possible influence on patient treatment. Further studies are indicated to define when follow-up chest roentgenograms are likely to be of benefit.

Adult↗

PubMed1989

Ambulatory care research in the VA: present status and recommendations for the future.

The growth of ambulatory care delivery in the Department of Veterans Affairs (VA) has been accompanied by increasing interest in and need for ambulatory care research. Results from a national survey of academic general internal medicine units suggest that those that share VA and university affiliation tend to be more successful than those that are unaffiliated. The VA must strive to improve the environment for ambulatory care research. Among other things, this will entail providing adequate protected time to ambulatory care faculty and developing a uniform ambulatory care database to facilitate longitudinal, population-based research. Extended fellowships in ambulatory care and faculty development programs for existing staff will be required to create a core of competent investigators. The VA must also provide increased funding to the Health Services Research and Development and Cooperative Studies programs. Special funding programs targeted to key areas such as quality assurance, medical education, and direct patient care should be established. In addition, the VA should seek to develop joint ventures with other funding agencies for innovative ambulatory care initiatives.

Ambulatory Care↗

PubMed1988

A clinical assessment of MedisGroups.

Interest has focused recently on measuring severity of illness, both to improve the fairness of diagnosis related group-based reimbursement and to facilitate judgments about hospital quality of care. MedisGroups is a prominent, proprietary severity-measurement system, recently mandated for use by all Pennsylvania hospitals. We reviewed MedisGroups and its key clinical findings. MedisGroups produces admission scores, from 0 through 4, indicating increasing risk of imminent organ failure. Score computation is independent of diagnosis, but many key clinical findings are disease specific and require particular diagnostic technologies. Using a database including patients 65 years of age and older from 24 hospitals, we found that fewer than 1% of patients with scores of 0 or 1 died in-hospital, compared with 60% of those with scores of 4. Questions remain about the impact of the procedural nature of many key clinical findings and the independence from diagnosis. Further study is needed to determine the utility of MedisGroups for policy purposes.

Algorithms↗

PubMed1988

Coding of acute myocardial infarction. Clinical and policy implications.

STUDY OBJECTIVE: To evaluate the appropriateness of diagnostic coding of acute myocardial infarction across teaching and nonteaching hospitals. DESIGN: Retrospective review of a random sample of medical records to find evidence of the occurrence and active treatment of acute myocardial infarction during the admission. SETTING: Five tertiary teaching, five other teaching, and five nonteaching hospitals in metropolitan Boston. CASES: Random sample of hospital admissions assigned a discharge diagnosis of acute myocardial infarction between October 1984 and September 1985. MEASUREMENT AND MAIN RESULTS: Of the 1003 cases reviewed, 260 did not meet the clinical criteria for acute myocardial infarction. At tertiary hospitals, 175 (41.7%) failed to qualify, compared with 25 (9.1%) at nonteaching facilities. In a large fraction of the disqualified cases, the patients had been admitted to exclude the diagnosis of acute myocardial infarction; although explicitly "ruled out," an acute myocardial infarction code was assigned. Sixty-six cases from teaching hospitals did not qualify because the patient had been admitted only for coronary angiography after an uneventful postmyocardial infarction course. Almost one-third of these patients had had their infarcts from 5 to 8 weeks before the angiography admission. CONCLUSIONS: Cases with an inappropriate discharge diagnosis of acute myocardial infarction may be concentrated in teaching hospitals. This finding could have implications for Medicare's diagnosis-related group payment system and governmental and other research efforts that use these data for such purposes as drawing inferences about the quality of hospital care.

Boston↗

PubMed1988

Opioid peptide gene expression in rat trigeminal nucleus caudalis neurons: normal distribution and effects of trigeminal deafferentation.

Preproenkephalin (preproenkephalin A) and preprodynorphin (preproenkephalin B) are the opioid peptide genes expressed in neurons of the nucleus caudalis of the trigeminal nuclear complex. We have used recently developed techniques for quantitative in situ hybridization to identify the neurons in laminae I and II of the nucleus caudalis that display the mRNA products of each of these genes. The specificity of these hybridization patterns is supported by several biochemical features, and by qualitative and quantitative parallels with previous immunohistochemical results. In animals killed 4 days after unilateral lesions of the trigeminal ganglion, neuronal expression of both preproenkephalin and preprodynorphin is altered in the nucleus caudalis. Decreases in preproenkephalin mRNA are due to a decline in the number of neurons that appear to express this gene. Conversely, preprodynorphin mRNA increases by adding a significant population of expressing neurons. These deafferentation-induced changes in gene expression may provide clues to the role of primary afferent information in modulating the functions of nucleus caudalis neurons containing opioid peptides.

Acid Phosphatase↗

PubMed1988

The effect of gold, an antirheumatic therapy, on substance P levels in rat peripheral nerve.

Intramuscular injections of gold sodium thiomalate in the rat produce a significant depletion of the proinflammatory neuropeptide substance P (SP) from the sciatic nerve. The greatest reduction in SP content occurred during the first two months of treatment. The level of SP in the nerve, however, remained low, throughout an eight month administration of gold. These results, coupled with previous findings that gold produces a selective decrease in the number of unmyelinated axons in peripheral nerve, are consistent with the hypothesis that the anti-inflammatory action of gold involves a neurotoxic effect on peptidergic afferents.

Animals↗

PubMed1988

Ergot alkaloids block neurogenic extravasation in dura mater: proposed action in vascular headaches.

Although the ergot alkaloids (ergots) are useful drugs for the acute treatment of migraine headaches, their mechanism of action remains obscure. When administered to rats in clinically relevant doses, ergots blocked the development of neurogenic plasma extravasation in dura mater. Plasma extravasation was induced by depolarization of perivascular axons following capsaicin injection or unilateral electrical stimulation of the trigeminal nerve. The ergot action could not be accounted for by vasoconstriction alone because neurogenic plasma leakage was not blocked by angiotensin or phenylephrine. Furthermore, ergots did not block plasma extravasation induced by administering sensory neuropeptides that mediate enhanced permeability. We propose that the therapeutic effects of ergots in vascular headaches may result from peripheral blockade of small fiber (C or A-delta)-dependent neurogenic inflammation within the dura mater.

Animals↗

PubMed1988

Discharge decision-making in a medical intensive care unit. Identifying patients at high risk of unexpected death or unit readmission.

In an attempt to identify clinical variables associated with unexpected death or unit readmission following discharge from a medical intensive care unit (MICU), 300 consecutive patients admitted to a MICU were prospectively identified and followed through their hospital stay. Of the 229 patients at risk, 37 (16 percent) experienced one or more unexpected unit readmissions (n = 30) or death (n = 7). In comparison to the patients without such complications (n = 192), these 37 patients differed with respect to age, diagnosis, and severity of illness on admission. In addition, these patients were sicker on initial unit discharge as manifested by higher heart and respiratory rates and lower hematocrit values. On multivariate analysis, age, acute physiology score on admission, and a diagnosis of upper gastrointestinal bleeding were independent predictors of unexpected outcome. It is concluded that patients at high risk for unit readmission or unexpected death are distinguished from other MICU survivors on several clinical parameters. Whether such information can be useful in individual discharge decisions is uncertain and requires further investigation.

Age Factors↗