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Biomedical subjects

M Frazer

Publications and source records attributed to M Frazer.

At least 37 records · Page 2Linked to original sources
PubMed1993

The effect of thromboxane A2 receptor antagonism on amphotericin B-induced renal vasoconstriction in the rat.

Amphotericin B (AmB) is the drug of choice for most systemic fungal infections, but doses are frequently reduced because of nephrotoxicity. We investigated the role of thromboxane as a mediator for this nephrotoxicity. Vehicle or amphotericin (0.60 mg/kg) was infused into the left renal artery in four groups of rats, and renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured. Group 1 received vehicle for 90 min. Group 2 received vehicle followed by a 30 minute AmB infusion which caused a significant and reversible fall in the RPF and GFR. Group 3 received vehicle followed by AmB infusion, but were infused with a bolus of ibuprofen (20 mg/kg) 45 minutes before AmB. This group exhibited an insignificant attenuation in the fall in RPF and GFR. Group 4 received vehicle followed by AmB, but were infused with a bolus and continuous infusion of the thromboxane receptor antagonist SQ29,548. This group demonstrated an attenuation in the fall in RPF and a significant decrease in GFR compared to AmB control rats. In addition, the rat glomeruli were incubated with AmB (4 ug/ml). Supernatant levels of thromboxane B2 were significantly elevated in the presence of AmB vs buffer alone. We conclude that the reduction in RPF and GFR observed with AmB infusion in the rat is partially mediated by release of thromboxane.

Amphotericin B↗
PubMed1993

Maintenance of endothelin-induced renal arteriolar constriction in rats is cyclooxygenase dependent.

Influence of arachidonate cyclooxygenase (COX) products on endothelin (ET)-evoked renal vasoconstriction was assessed. In microperfused rat afferent (AA) and efferent arterioles (EA), indomethacin had no effects on the maximal contraction of both AA and EA by ET, but reduced the duration of ET-induced constriction in both arterioles. ET infusion to rats in vivo resulted in a selective increase in efferent but not afferent arteriolar resistance, leading to a dramatic increase in transcapillary hydraulic pressure difference. Glomerular filtration rate (GFR), which fell progressively during infusion of ET alone, was markedly preserved by COX inhibition, but not during selective thromboxane A2 antagonism. In isolated glomeruli, release of prostaglandin (PG) F2 alpha in response to 10(-6) mol/l ET exceeded that the PGE2 by a ratio of 3.2. Collectively, these data provide strong evidence that locally released COX products, possibly PGF2 alpha, play a key role in sustaining ET-induced renal arteriolar constriction. COX inhibition leads to acute vasorelaxation of AA despite continued ET administration, without affecting EA constriction in vivo, thereby resulting in a dramatic reversal of the effects of ET on GFR.

Animals↗
PubMed1992

Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome.

BACKGROUND: Severe renal vasoconstriction is central to the pathogenesis of renal failure in the hepatorenal syndrome. Endothelin-1 and endothelin-3 are potent, long-acting vasoconstrictors, and endothelin-1 has selective potency as a renal vasoconstrictor. These properties suggest a role for endothelins in the hepatorenal syndrome. METHODS: We measured plasma endothelin-1 and endothelin-3 concentrations using specific radioimmunoassays in subjects with hepatorenal syndrome, liver disease but normal renal function, chronic renal failure, acute renal failure, liver dysfunction and renal impairment, or normal liver and kidney function. RESULTS: The patients with the hepatorenal syndrome had markedly elevated mean (+/- SE) plasma concentrations of endothelin-1 (36 +/- 5 ng per liter [14.5 +/- 1.8 pmol per liter]) and endothelin-3 (43 +/- 3 ng per liter [16.3 +/- 1.0 pmol per liter]) as compared with the normal subjects (endothelin-1, 4 +/- 1 ng per liter [1.7 +/- 0.2 pmol per liter]; and endothelin-3, 18 +/- 1 ng per liter [6.8 +/- 0.4 pmol per liter]; P < 0.001) and with the patients in the other four groups (P < 0.001 to P < 0.05). The plasma endothelin-1, but not endothelin-3, concentrations in these four patient groups were significantly higher than in the normal subjects (P < 0.001 to P < 0.05). The concentrations of endothelin-1 in renal arterial plasma and renal venous plasma, measured in five patients with the hepatorenal syndrome and three with chronic liver disease and normal renal function, were 20 +/- 4 ng per liter (7.9 +/- 1.8 pmol per liter) and 24 +/- 4 ng per liter (9.5 +/- 1.5 pmol per liter), respectively (P < 0.05). CONCLUSIONS: The increase in plasma endothelin-1 and endothelin-3 concentrations in patients with the hepatorenal syndrome is consistent with the hypothesis that these substances have a role in the pathogenesis of the disease.

Acute Kidney Injury↗
PubMed1991

Role of endothelin in the development of Dahl hypertension.

To evaluate the possible role of endothelin in the development and/or maintenance of hypertension in Dahl rats, we examined the responsiveness of isolated vascular smooth muscle and glomerular mesangial cells, as well as deendothelialized vascular ring preparations to endothelin-1 (ET-1). Production of immunoreactive endothelin (ir-ET) was studied in freshly isolated glomeruli and renal medullary slices. Both glomerular mesangial cells and vascular smooth muscle cells obtained from prehypertensive Dahl-S rats exhibited an exaggerated [Ca2+]i response to ET-1, as compared with cells obtained from Dahl-R rats. This was paralleled by the enhanced isometric contraction of vascular rings obtained from prehypertensive Dahl-S rats. ir-ET production was doubled in response to 0.1 mM ouabain in tissue samples obtained from prehypertensive Dahl-S, but not Dahl-R rats. This effect was not observed in tissues obtained from animals fed a 4% NaCl diet (hypertensive). Immunocytochemistry of ET distribution in the outer medullary stripe showed approximately a 40% higher fluorescence intensity in sections obtained from Dahl-S rats fed 4% NaCl diet as compared with Dahl-R rats fed the same diet. Northern blot analysis of poly(A)+ RNA extracted from medullae of prehypertensive Dahl-S and -R rats using a full-length cDNA probe for rat ET-1 revealed a marginal induction of pre-pro-ET-1 message in Dahl-S samples after 30 and 60 min of incubation with 0.1 mM ouabain. In conclusion, increased responsiveness of target cells to ET-1 and inducibility of ir-ET production in prehypertensive Dahl-S rats are in favor of a possible role of this peptide in the pathogenesis of Dahl hypertension. We hypothesize that ouabain-like factor(s) may trigger production of ET, thus serving as a link between high-salt intake and the development of hypertension in Dahl-S rats.

Animals↗
PubMed1988

EMG profiles of knee joint musculature during walking: changes induced by anterior cruciate ligament deficiency.

A tear of the anterior cruciate ligament (ACL) disrupts the delicate balance of static stabilizers of the knee, leading to significant alterations in joint kinematics. Little is known about the dynamic compensatory responses of the patient to these kinematic alterations. This lack of quantitative information on the muscle synergy patterns has limited the surgeon's ability to evaluate various operative and rehabilitative techniques. Twelve subjects with documented ACL deficiency for at least 1 year and 15 normal participants were studied. Each subject was asked to walk at free and fast speeds on a 12 m walkway. The right and left foot contact patterns and the linear envelopes from the surface electromyogram (EMG) patterns of the gastrocnemius, medial and lateral hamstrings, rectus femoris, and vastus lateralis were measured. Significant differences were found in the muscle synergy patterns during walking. During the swing-to-stance transition, the ACL-deficient subjects showed significantly less activity in the quadriceps and gastrocnemius muscles and more activity in the biceps femoris than in the normal group. During early swing, the vastus lateralis is more active than normal, and during midstance and terminal stance, the hamstrings appear to be less active than normal subjects. These dynamic compensatory mechanisms suggest that use of the hamstring tendons in reconstructive procedures may alter important compensatory mechanisms about the knee joint. Application of dynamic EMG techniques to the study of reconstructive procedures should provide additional information that will assist the clinician in the rational choice of a surgical procedure.

Adult↗
PubMed1987

Normative childhood EMG gait patterns.

The population characteristics of the linear envelopes of the electromyograms measured from seven lower extremity muscles in children were studied during locomotion. The variability and changes in pattern with respect to walking speed and age were investigated using statistical properties and analysis of variance of the envelopes. All muscles studied showed changes in their patterns that were associated with different walking speeds. Some changes concerned the relative intensity of existing phases of activity whereas others concerned the existence of additional phases of activity. The most remarkable trend was that all envelopes tended to have more consistent patterns as speed increased. With regard to age, within the span of 4-11 years, only the two thigh muscles studied demonstrated appreciable differences.

Age Factors↗
PubMed1987

Helical motion analysis of the knee--II. Kinematics of uninjured and injured knees during walking and pivoting.

The knee kinematics of eight individuals with uninjured knees and of seven individuals with ruptured anterior cruciate ligaments have been investigated during walking and pivoting. The kinematics were measured using a six degree of freedom goniometer and quantitated using helical motion analysis. The helical motion variables reveal clearly that the knee is definitely neither a hinge nor a planar joint and its dynamic behavior changes over the stride. Ligamentous loss results in more adduction and external rotation during certain periods of the stride. Also, the range of translation of the tibia in the medial/lateral direction is reduced, and its average translation is more medial.

Adult↗
PubMed1987

Helical motion analysis of the knee--I. Methodology for studying kinematics during locomotion.

A technique for investigating the three-dimensional kinematics of knee motion during dynamic functional tasks has been developed. It involves the combined usage of a six degree of freedom goniometer and helical motion analysis. A detailed procedure for coordinate system alignment and calibration must be followed. Once established this entire procedure is routinely implementable. Ensemble averages from multiple walking strides reveal that this technique is sensitive enough to differentiate between the kinematics of an uninjured and injured knee.

Humans↗
PubMed1987

Evidence for a role for Na+-H+ exchange in activation of human platelets by PAF.

We have found previously that inhibitors of Na+-H+ exchange block platelet arachidonic acid release and subsequent secondary aggregation and serotonin release in response to epinephrine, ADP, and thrombin (0.004 U/ml). The present study demonstrates that the addition of ethylisopropylamiloride, an inhibitor of Na+-H+ exchange, leads to an inhibition of platelet activating factor-induced serotonin release and thromboxane B2 production in human platelets in citrated plasma. In addition, platelet activating factor-induced platelet secretion is blocked by the cyclooxygenase inhibitor indomethacin or the thromboxane antagonist SQ 29548, indicating that arachidonic acid mobilization and metabolism is required for platelet activating factor to elicit platelet activation. Our interpretation of the present findings is that platelet activating factor-induced secretion of dense granules from the human platelet requires the production of cyclooxygenase metabolites from arachidonic acid and that Na+-H+ exchange plays an important, albeit not exclusive, role in mobilization of arachidonic acid in response to platelet activating factor.

Amiloride↗
PubMed1987

An unusual pattern of gunshot injury linking two homicides to the same assailant.

This case report describes an unusual pattern of gunshot firing that proved useful in convicting one assailant of two murders. The assailant fired into the first victim, successively through the same entrance hole at contact range. This technique of firing twice through the same hole was also demonstrable on his second victim in the bare skull of the decomposed body. This unusual pattern noted in two homicides found two weeks apart, in concert with other circumstantial evidence, led to the successful conviction of the man for both murders.

Adult↗
PubMed1986

Death as a result of an adverse reaction from nalidixic acid.

This article reports a death occurring in an apparently healthy, 27-year-old male as a consequence of an adverse reaction to a common urinary tract antibiotic (nalidixic acid). The deceased had cardiac enlargement at autopsy. The clinical presentation before his sudden death coincides with the occurrence of seizures and psychotic reaction as an adverse reaction to the injection of the drug, rather than merely a result of cardiac symptoms.

Adult↗
PubMed1986

Domestic violence: a medicolegal review.

This paper reviews the recent medical and legal literature in the field of spouse abuse. Domestic violence is a national phenomenon that directly affects victims of spouse abuse and indirectly conditions the children of the victims to accept violent behavior as normative. This paper characterizes the cycle of violence battered women encounter, describes their injury patterns, explores the dynamics of the abusive relationship, and discusses the factors that compel women to remain in such violent relationships. The second section describes many of the recent legislation designed to prevent spouse abuse. Next, this paper addresses the case law utilizing the "battered woman syndrome" as a defense for spousal homicide. The third section of the paper explores the often neglected topic of the battered husband.

Female↗
PubMed1985

The female suicide victim. Trends in a metropolitan county (1963-1983).

A two-decade review of female suicide victims in Cuyahoga County, Ohio was performed. There has been an increasing incidence in the number of adolescent and senior citizen suicides over the 20-year period. The number of single and married victims were proportional to their respective population frequencies; while the frequency of widowed victims was greater and the frequency of divorced victims was less than expected. Women in blue collar skilled jobs showed an increasing frequency in the late 1970s. The most frequently used methods are poisoning, firearms, and carbon monoxide inhalation. Poisoning deaths have decreased in frequency and firearm deaths have increased in frequency.

Adolescent↗
PubMed1984

Commotio cordis, revisited.

Nonpenetrating cardiac injuries due to direct precordial blunt impacts are a commonly encountered phenomenon in medicolegal offices. These injuries vary from contusions to valvular lacerations, or papillary muscle rupture to coronary arterial injury with resulting infarction. A less commonly occurring manifestation of nonpenetrating injury is a concussion of the heart (commotio cordis), often with dramatic physiological consequences but no morphologic cardiac injury. We describe four case reports of this entity. The cases were collected over a 5-year period (1978-1983) from the Wayne County Medical Examiner's Office in Detroit, Michigan.

Adolescent↗
PubMed1983

A case of suicidal ligature strangulation.

The following report describes a suicidal death in a 53-year-old white male utilizing ligature strangulation. the elements of the procedure used by the decedent were: 1) successive wrapping of a twine around his neck (35 circumferences) while pulling the rope taut, 2) tying a knot and manually applying further tension, and 3) bending forward to increase the neck circumference, further increasing the constrictive effect of the twine. Normally, self-ligature strangulation is prevented as the individual becomes unconscious as the venous circulation is obstructed, leading to relaxation of the ligature tension. In this case, the successive layers of twine provided gradually applied tension, and the action of bending forward caused further constriction which would only increase as the decedent lapsed into unconsciousness and continued to fall forward. A history of recent depression supported suicide as the manner of death. Accidental autoerotic death was ruled out as the manner of death by lack of scene evidence, and the rarity of that event in an elderly male.

Asphyxia↗
PubMed1983

The female homicide victim: trends in a metropolitan county from 1969 to 1980.

The following paper reviews the case files of the female homicide victims in Cuyahoga County, OH from 1969 through 1980. The victims were most frequently married middle-class women killed by their spouse or boyfriend with a handgun. The event usually followed an altercation and took place in the victims' home. Sexual assault or criminal activity were rarely part of the scenario. The male homicide victims of this time interval were usually killed by an acquaintance or a stranger in a public place, but rarely by their spouse. The female victim's blood alcohol level was significantly lower than her male counterpart's which was between 0.1 and 0.3% (g/100 g).

Adolescent↗