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Biomedical subjects

M A Moskowitz

Publications and source records attributed to M A Moskowitz.

At least 289 records · Page 16Linked to original sources

Neurogenically mediated plasma extravasation in dura mater: effect of ergot alkaloids. A possible mechanism of action in vascular headache.

C-fiber-dependent neurogenic plasma extravasation developed in the dura mater but not the brain after electric stimulation of the rat trigeminal ganglion or after chemical stimulation of perivascular axons with intravenous capsaicin, a drug that depolarizes sensory nerve fibers. C-fiber-independent extravasation also developed in this tissue after intravenous injections of substance P or neurokinin A (two constituents of unmyelinated C fibers) and after serotonin, bradykinin, or allergic challenge in presensitized animals. Intravenous dihydroergotamine or ergotamine tartrate, in doses similar to those used to treat migraine and cluster headache, prevented the stimulation-induced leakage of plasma proteins within the dura mater. Not unexpectedly, the acute administration of methysergide, a drug effective in the prophylactic treatment of headache, was inactive in this acute model. Neither acute nor chronic administration of propranolol affected stimulation-induced leakage of plasma protein. These results demonstrate that neurogenic inflammation develops within the dura mater in the rat and that ergot alkaloids prevent the process by a C-fiber-dependent mechanism.

Animals↗

Admission MedisGroups score and the cost of hospitalizations.

Concerns about the insensitivity of Medicare's diagnosis-related groups (DRGs) to illness severity heightened interest in the potential of alternative patient classification systems to improve the fairness of hospital reimbursement. This article examines the ability of admission MedisGroups score to explain the costs of hospital stays. The database contained 54,112 patients 65 years or older discharged in 28 high-frequency DRGs from 1984 to the middle of 1986 from 24 hospitals across the country. Admission MedisGroups score alone explained 3% of costs using trimmed data. Addition of admission MedisGroups score to DRGs modestly improved ability to predict differences in cost: for trimmed data, DRGs alone explained 52% of the variation in costs, compared with 55% when admission MedisGroups score was added. Within individual DRGs, the explanatory power of admission MedisGroups score ranged from 0% to 21%. The level of explanatory power was not related to the spread of cases across admission MedisGroups scores within DRG. No consistent clinical pattern explained these differences across DRGs.

Aged↗

Trigeminalectomy modifies pial arteriolar responses to hypertension or norepinephrine.

The responses of pial precapillary vessels were examined bilaterally using a closed cranial-window preparation in 11 anesthetized cats after chronic unilateral section of the trigeminal ganglia. During increases or decreases in arterial PCO2 or hypoxia, vasoconstrictor and vasodilator responses were symmetrical and appropriate on the two sides. The superfusion of vessels with norepinephrine (10 micrograms/ml) constricted large and small pial arterioles to a greater extent on the denervated side, and this difference persisted even after washing (P less than 0.02). After severe hypertension, small and large arterioles dilated on both sides, although to a greater extent on the innervated side. In 8 of 10 acutely hypertensive animals, extravasation of intravenously administered iodinated albumin was greater in the intact than deafferented hemisphere. These results suggest that the trigeminal nerve can modify the responses of cerebral arterioles and participate in the regulation of the cerebral vasculature.

Animals↗

Blood components contribute to rise in gerbil brain levels of leukotriene-like immunoreactivity after ischemia and reperfusion.

The mean +/- SEM concentrations of immunoreactive leukotriene C4 and D4 (iLTD4) and prostaglandin D2 (iPGD2) increased from 3.0 +/- 1.2 and 0.71 +/- 0.33 to 16.3 +/- 4.7 and 3.0 +/- 1.14 ng/g forebrain, respectively (p less than 0.05, iLTD4; p less than 0.01, iPGD2), in the forebrains of 12 gerbils after 15 minutes of bilateral common carotid artery occlusion and 15 minutes of reperfusion. Removal of blood from ischemic brain of 11 gerbils by intracardiac perfusion with ice-cold saline for 10 minutes decreased iLTD4 concentrations significantly to 7.0 +/- 0.9 (p less than 0.05) but did not change iPGD2 concentrations. Severe granulocytopenia (4.98 +/- 1.79 to 0.05 +/- 0.03 x 10(3)/mm3, p less than 0.01) in seven gerbils following intraperitoneal injection of 50 mg/kg busulfan was associated with decreased iLTD4 accumulation in the brain to 3.46 +/- 1.36 ng/g forebrain (p less than 0.01). Taken together, our results suggest that blood components (most likely leukocytes) are a source of leukotriene-like immunoreactivity in the ischemic and reperfused brain.

Agranulocytosis↗

The diagnosis of reversible dementia in the elderly. A critical review.

Evaluation of the elderly demented patient includes a search for treatable diseases; recommendations for this approach have been based on reports of a high prevalence of "reversible" dementia in several series of patients in the medical literature. A critical review of the methodology of these reports was undertaken to determine their validity as sources for the protocols often recommended. Several methodologic flaws were found in many studies that recommended extensive "screening" of the demented elderly, limiting their usefulness as resources. More carefully designed studies are needed to understand better the frequency and etiology of reversible causes of dementia.

Aged↗

Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study.

To assess the effect of postmenopausal use of estrogens on the subsequent risk of hip fracture, we performed a retrospective cohort study of 2873 women in the Framingham Heart Study. Information obtained at routine biennial examinations about the use of estrogens, body weight, age at menopause, smoking, and alcohol consumption was used to evaluate the risk of hip fracture among postmenopausal women who received estrogens. Hip fractures occurred in 179 postmenopausal women, at a rate that increased exponentially after the age of 50. The risk of fracture was inversely related to weight at all ages. The relative risk of hip fracture in subjects who had taken estrogens at any time was 0.65 after adjustment for age and weight (95 percent confidence interval, 0.44 to 0.98). The adjusted relative risk in women who had taken estrogens within the previous two years was further reduced, to 0.34 (95 percent confidence interval, 0.12 to 0.98). Taking estrogens within four years of menopause also protected against fracture. The number of women in each age group who took estrogens was insufficient for a definitive evaluation of risk, but recent use of estrogens appeared to be protective in women under the age of 65 (no fractures among those who took estrogens) and those 65 to 74. We cannot exclude some degree of selection bias among the women who received estrogen-replacement therapy. Nevertheless, this large cohort study supports the hypothesis that postmenopausal use of estrogens protects against subsequent hip fracture in women.

Age Factors↗

Trigeminal origin of beta-preprotachykinin products in feline pial blood vessels.

A specific and sensitive radioimmunoassay measured the presence of immunoreactive neurokinin A within feline and human pial arteries. Immunoreactivity exhibited a retention time identical to that of synthetic peptide when acid extracts from feline and human blood vessels were subjected to reverse-phase high-performance liquid chromatography. As shown previously for substance P, levels of immunoreactive neurokinin A decreased significantly in the vessels from the ipsilateral rostral circle of Willis 19-24 days following unilateral trigeminal ganglionectomy. Hence, trigeminal projections to cerebral blood vessels contain both products of beta-preprotachykinin mRNA.

Animals↗

Substance P-like immunoreactivity in rat forebrain leptomeninges and cerebral vessels originates from the trigeminal but not sympathetic ganglia.

Substance P-like immunoreactivity (SPLI) is present in the pia mater, arachnoid and pial vessels (leptomeninges) of the rat. Unilateral electrolytic lesions of the trigeminal ganglion decreased levels of SPLI in leptomeninges on the lesioned side. Levels did not change following unilateral or bilateral superior cervical ganglionectomies or after i.c.v. injections of 6-hydroxydopamine, sufficient to deplete norepinephrine in pial arteries by more than 90%. SP levels did not decrease in leptomeninges or in blood vessels within the circle of Willis following treatment of adult or neonatal rats with capsaicin despite the fact that levels were reduced in the cornea and dorsal spinal cord in these same animals. These results suggest that not all substance P-containing sensory fibers are susceptible to the peptide-depleting effects of capsaicin.

Animals↗

Nerve fibers surrounding intracranial and extracranial vessels from human and other species contain dynorphin-like immunoreactivity.

Dynorphin B(20-32) was visualized by immunohistochemistry in guinea-pig and rat perivascular nerve fibers and was measured by radioimmunoassay within the walls of feline, canine, bovine and human cephalic and systemic arteries and veins. Canine vessels contained the highest levels. When human blood vessels or trigeminal ganglia were subjected to reverse-phase high-performance liquid chromatography, dynorphin immunoreactivity exhibited a retention time identical to that of synthetic dynorphin B. No differences in dynorphin-like immunoreactivity were measurable between feline systemic arteries and veins, or between cephalic and systemic vessels. The highest amounts were present in leptomeninges devoid of large pial arteries. Relatively high levels were also measured in feline and human trigeminal ganglia and feline superior cervical and sphenopalatine ganglia, three sources of projecting perivascular axons. Levels did not diminish, however, in ipsilateral feline cephalic vessels following either unilateral trigeminal or superior cervical ganglionectomies. Hence, dynorphin-containing fibers may project from parasympathetic cell bodies or perhaps from intrinsic brain sources. Previously published reports indicate that the kappa agonist dynorphin does not modify vessel tone when added in vitro but does inhibit release of neurotransmitters from afferent and sympathetic axons via prejunctional receptors. These observations suggest a pharmacological role for dynorphin on sensory and autonomic functions of the vasculature.

Aged↗

The urinalysis: a critical appraisal.

The urinalysis, an inexpensive office test, is often performed unnecessarily. Improved chemical testing using reagent strips obviates the need for routine microscopy in many cases. More information is needed to make specific recommendations on the use of the routine urinalysis as a screening procedure.

Bacteriuria↗

Desensitization to substance P-induced vasodilation in vitro is not shared by endogenous tachykinin neurokinin A.

Two mammalian tachykinins, substance P (SP) and neurokinin A (NKA), were measured by radioimmunoassay in canine cephalic blood vessels and tested for their vasoactivity in vitro. Levels of immunoreactive SP were approximately 2-3 times greater than those of immunoreactive NKA in common carotid, basilar, and middle cerebral arteries. Both endogenous tachykinins relaxed precontracted segments of common carotid and basilar arteries in a dose-dependent manner with an EC50 of 8.9 X 10(-11) M and 7 X 10(-10) M, respectively, when added cumulatively. Relaxation was endothelial dependent for both substances and not blocked or enhanced by pretreatment with indomethacin, propranolol, lithium chloride, or atropine. Neither SP nor NKA released 3H-inositol phosphates from phospholipid membranes of canine carotid segments after preincubation with 3H-inositol. SP but not NKA or the C-terminal fragments SP(4-11) caused desensitization to subsequent additions of itself but not to the relaxation induced by sodium nitroprusside, calcitonin gene-related peptide, or bradykinin. These studies demonstrate that at least 2 peptides derived from beta-preprotachykinin are contained within cephalic blood vessels and that these products share similar vasoactive properties but differ in their ability to desensitize vascular tachykinin receptors.

Animals↗

Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain.

Utilizing 125I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated 125I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and 125I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of 125I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunoelectron microscopic study of substance P-containing fibers in feline cerebral arteries.

The ultrastructure of substance P-containing fibers in feline cerebral arteries was examined by combining substance P immunohistochemistry and electron microscopy. At the light and electron microscopic level, positive fibers were observed in the adventitia and at the border between the adventitia and media, but not within the media or the endothelium. The substance P-containing fibers were unmyelinated with diameters consistent with C-fiber caliber. Positive axons were in close contact with Schwann cell processes. Positive axons contained 24 nm microtubules, 10 nm neurofilaments, clear vesicles and scattered mitochondria. The number of mitochondria and organelles resembling vesicles appeared to increase in presumptive axon terminals. No synaptic membrane specializations were observed.

Animals↗

Polyphosphoinositide hydrolysis in endothelial cells and carotid artery segments. Bradykinin-2 receptor stimulation is calcium-independent.

Bovine aortic and cerebral microvascular endothelial cells and cultured segments of canine common carotid artery possess functional receptors for the nonapeptide bradykinin which mediate a rapid increase in the formation of [3H]inositol 1-phosphate, [3H]inositol 1,4-bisphosphate, and [3H]inositol 1,4,5-trisphosphate from cell membranes containing isotopically labeled myo-inositol. Bradykinin stimulated the formation of [3H]inositol phosphates from cells in culture or tissues at threshold concentrations of 0.1 nM and 1 nM, and with a half-maximal effective concentration of 0.6-1.0 nM and 30 nM, respectively. In cultured cells, the formation of [3H]inositol trisphosphate and [3H]inositol bisphosphate preceded the formation of [3H]inositol monophosphate. Similarly, [3H]inositol phosphate formation was not inhibited by addition of calcium channel blockers, a calcium chelator, or an intracellular calcium antagonist. Calcium ionophore A23187 did not promote [3H]inositol phosphate accumulation. The receptor selectivity of the bradykinin response in cultured cells was most compatible with a type-2 mediated response. Kallidin stimulated with the same potency as bradykinin but was more potent than methionyl-lysyl-bradykinin or des-Arg9-bradykinin. The B1 receptor antagonists des-Arg9-[Leu8]-bradykinin and des-Arg10-[Leu9]-kallidin were without effect. The rapidity of the inositol phosphate response as well as the close correspondence between the bradykinin type-2 receptor mediated hydrolysis of polyphosphoinositides and changes in prostacyclin synthesis, vessel dilation, and permeability suggests that breakdown products of inositol lipids serve as second messengers mediating the effects of bradykinin on the vascular endothelium.

Animals↗