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S A Holt

Publications and source records attributed to S A Holt.

15 recordsLinked to original sources
PubMed1992

Effect of dietary n-3 fatty acids on cerebral microcirculation.

The purpose of these studies was to determine the effects of dietary n-3 fish oil on cerebrovascular reactivity and cerebrospinal fluid prostaglandin levels. Adult rabbits (n = 30) received fish oil (200 mg/kg eicosapentaenoic + 143 mg/kg docosahexaenoic acid), corn oil, or water by daily gavage for 6 wk and were then tested for their pial arteriolar diameter response to topical acetylcholine, bradykinin, or systemic asphyxia using the cranial window technique. Plasma and platelet fatty acids were measured by gas chromatography. Cerebrospinal fluid prostaglandin E and serum thromboxane B2 were measured by radioimmunoassay. n-3 Fatty acids were enriched in the plasma and platelets of the fish oil group (P less than 0.05). Serum thromboxane B2 was decreased by 31% in the fish oil group (P less than 0.05). The diameter response to acetylcholine and asphyxia was the same in all groups; however, the dilator response to bradykinin, which is known to be mediated by oxygen radicals, was significantly diminished in the fish oil group (P less than 0.05). Cerebrospinal fluid prostaglandin E concentration increased in response to acetylcholine, bradykinin, and asphyxia; however, the percent increase was less in the fish oil group. In summary, dietary n-3 fatty acids, which are purported to decrease heart disease, appear to selectively affect cerebral arteriolar reactivity, which is normally dependent on cyclooxygenase metabolism of arachidonic acid and formation of vasoactive oxygen radicals.

Acetylcholine↗
PubMed1992

Lung scan interpretation: a physiologic, user-friendly approach.

A physiologically-oriented, user-friendly algorithm for interpretation of ventilation-perfusion (V/P) lung scans was compared to the widely used Biello criteria. The physiologic algorithm relies primarily on the observer's degree of certainty that a V/P mismatch is present rather than on the size (relative to a whole segment) and number of V/P mismatches. One hundred five patients who had undergone a ventilation study with 133Xe gas, a perfusion study with 99mTc-MAA and pulmonary angiography were reviewed. Each V/P lung scan was interpreted once with the physiologic algorithm and once with the Biello criteria by two observers. Fifty-nine percent of the 105 studies were classified as indeterminate with the physiologic algorithm versus 62% with the Biello criteria. The prevalence of pulmonary embolism in the high probability, indeterminate, low probability and normal categories for the physiologic algorithm were 60%, 26%, 7% and 0%, respectively; and for the Biello criteria were 50%, 31%, 11% and 0%, respectively. Analysis of the data with receiver-operating-characteristic curves indicated that the physiologic algorithm performed better than the Biello criteria (p less than 0.05). In addition, the physiologic algorithm has the advantages of being more intuitive and easier to remember. We conclude that further evaluation of the physiologic approach for the interpretation of V/P lung scans is warranted.

Algorithms↗
PubMed1990

Effect of fish oil n-3 fatty acids on cerebral microcirculation.

Dietary fish oil containing the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) is being consumed by many individuals in an effort to reduce thrombosis and heart disease. However, little is known about how these fatty acids can affect cerebrovascular function. The purpose of the present study was to begin to examine the effects of these fatty acids on cerebral arteriolar diameter and to compare their effects with that of arachidonic acid (AA). Pial arteriolar diameter responses to the topically applied fatty acids [0.2-200 micrograms/ml cerebrospinal fluid (CSF)] were measured in rabbits using in vivo microscopy and the acute cranial window technique. Prostaglandin E2 (PGE2) formed by the brain in response to AA, EPA, and DHA was measured in CSF using radioimmunoassay. EPA induced a dose-dependent dilation response of which the maximum was 29%, whereas the maximal dilation produced by AA was 100%. The arteriolar effect of EPA was reduced by indomethacin or superoxide dismutase plus catalase, indicating vasoactivity due to oxygen radicals formed by cyclooxygenase metabolism of EPA. DHA itself had no effect on diameter or adenosine-induced dilation but reduced dilation by AA when coapplied with AA. AA induced a 65-fold maximal increase in PGE2, whereas EPA and DHA had comparatively little effect. These results imply that substitution of n-3 fatty acids for AA in brain phospholipids may result in less cyclooxygenase-dependent cerebrovascular reactivity. This alteration in reactivity may produce important effects with respect to the brain's blood flow response to a number of physiological and pathological challenges.

Animals↗
PubMed1988

Kinins induce abnormal vascular reactivity.

Previous studies have shown that after experimental neural trauma or acute hypertension the brain produces superoxide anion radicals, and brain arterioles display endothelial lesions, dilation, and loss of normal reactivity in response to a decrease in CO2 tension. Because these abnormalities are prevented by pretreatment with free radical scavengers or inhibitors of the cyclooxygenase component of prostaglandin (PG) H synthase, arachidonic acid metabolism by PGH synthase with concomitant formation of tissue injuring oxygen radicals causes the vascular damage. The purpose of the present experiments was to determine whether kinins, which are known to stimulate arachidonate metabolism and to induce cerebral arteriolar dilation via production of superoxide anion, may be involved in initiating the cerebrovascular abnormalities produced by neural trauma in cats. The diameter and reactivity of untreated in vivo pial arterioles on one cerebral cortex was compared with the diameter and reactivity of pial arterioles on the contralateral cortex, which were pretreated topically with a competitive receptor antagonist, which is specific for kinins. Before fluid percussion neural trauma was induced, arterioles on both cerebral hemispheres constricted normally to a decrease in CO2 tension. After injury, the arterioles on the untreated cortex dilated and did not constrict in response to a decrease in arterial CO2 tension, whereas the arterioles pretreated with the kinin antagonist dilated less and displayed normal reactivity to CO2. These experiments demonstrate that a specific kinin receptor stimulates PGH synthase-dependent, free radical-mediated cerebrovascular injury. Given the ubiquitous distribution of the kallikrein-kinin system, we propose that kinins may be an important common mediator of systemic vascular injury and abnormal vascular reactivity.

Animals↗
PubMed1986

Unilateral simultaneous renal angiomyolipoma and oncocytoma.

A 70-year-old woman with simultaneous unilateral renal angiomyolipoma and renal oncocytoma presented to the hospital with syncope and abdominal pain. Diagnostic studies indicated a left renal neoplasm consistent with renal cell carcinoma and a radical nephrectomy was performed. Histological examination of the resected specimen demonstrated the presence of the 2 unusual renal neoplasms.

Adenoma↗
PubMed1985

Protein binding as a component of drug interaction in cellular pharmacokinetic studies. Effects of probenecid on transport and accumulation of methotrexate in Ehrlich ascites tumor cells in vitro.

The organic acid probenecid has been shown to interfere with the active extrusion of methotrexate (MTX) from L1210 tumor cells in vitro leading to enhanced MTX accumulation and increased formation of MTX polyglutamate derivatives. In the presence of serum albumin (4 g/100 ml), to which probenecid is bound, the inhibition by probenecid of [3H]MTX efflux from the Ehrlich ascites tumor cell was reduced markedly. While half-maximal inhibition of MTX efflux occurred with 0.12 mM probenecid in the absence of albumin, 1.45 mM probenecid was required in its presence. The presence of albumin also modified the probenecid-induced elevation of steady-state MTX levels in the tumor cell. Maximal elevation of cellular MTX levels occurred with 0.5 mM probenecid in the absence of albumin, and 3 mM probenecid in its presence. Serum albumin further reversed the effects of probenecid on MTX influx. While probenecid inhibited influx of 1 microM [3H]MTX in the absence of albumin (half-maximal inhibition at approximately 1 mM probenecid), probenecid stimulated MTX influx in its presence (half-maximal effect at 0.5 to 1 mM). Equilibrium dialysis studies demonstrated that probenecid displaced MTX from albumin, increasing the effective free concentration of MTX in the incubation medium, and hence the rate of MTX influx. Therefore, probenecid may enhance the accumulation of MTX in the tumor cells by increasing the level of free (as opposed to albumin bound) MTX in the extracellular medium as well as by direct inhibition of MTX efflux. These observations may provide an additional explanation for probenecid enhancement of the therapeutic efficacy of MTX in tumor bearing mice and highlight the importance of assessing drug-protein interactions in an in vitro experimental model.

Animals↗
PubMed1985

Effect of hydration and dehydration on technetium-99m CO2 DADS renal studies in normal volunteers.

Ten normal volunteers were studied in the hydrated and dehydrated states with the new renal radiopharmaceutical technetium-99m N,N'-bis(mercapto acetyl)-2, 3-diaminopropanoate [( 99mTc]CO2 DADS). The data were used to determine the effect of hydration and dehydration and to determine the normal range in each state. Visual evaluation of the images indicated that the first appearance of tracer in the collecting system was approximately the same in either state, that the concentration of tracer in the collecting system was always higher in the dehydrated state (p less than 0.01), and that the ureters always appeared more segmented in the dehydrated state (p less than 0.01). Quantitative analysis of the images indicated that the kidney to background ratio 1-2 min after injection was somewhat greater in the dehydrated state (13.5 +/- 4.0) than in the hydrated state (9.8 +/- 2.2) (p less than 0.05), that the size of the bladder was always greater in the hydrated state (p less than 0.05), and there was no difference in the amount of tracer in the bladder at 30 min after injection. The results define the normal hydrated and dehydrated [99mTc]CO2 DADS renal study and identify several differences between the two states which can be explained primarily by differences in urine flow rates.

Adult↗
PubMed1980

Selective intra-arterial vasopression in fusion for upper gastrointestinal tract hemorrhage: a controlled trial.

In a prospective randomized study, 38 patients with massive upper gastrointestinal tract hemorrhage, mostly due to esophageal varices or erosive gastritis, were treated with either standard medical therapy or standard therapy plus selective intra-arterial vasopressin infusion. Cessation of hemorrhage occurred more frequently in the vasopressin-treated group. The study design did not permit meaningful comparisons of mortality of transfusion requirements. We conclude that in patients bleeding from esophageal varices or gastritis, selective intra-arterial vasopressin is more effective in controlling hemorrhage than standard therapy.

Adult↗
PubMed1976

Traumatic renal artery occlusion: 21 cases.

Sixteen cases of unilateral and 5 cases of bilateral traumatic renal artery occlusion caused by avulsion or thrombosis are presented. The injury typically follows automobile-pedestrian accidents to young male subjects. Associated extrarenal injuries are usual but non-pedicle renal injury is infrequent. Suspicion of the unilateral injury depends upon recognition of absence of visible excretion at urography. The clue to bilateral occlusion is anuria. Diagnosis is confirmed by urgent arteriography. Hematuria was absent in 24 per cent and the injury was missed at laparotomy in 29 per cent of the initial explorations. Renal function was salvaged by arterial reconstruction in 2 cases, 12 hours and 5 months after injury respectively. Hypertension developed in 50 per cent of the cases and was generally mild.

Abdominal Injuries↗
PubMed1975

Permanent nephrostomy via percutaneous puncture.

A technique to convert a standard temporary percutaneous nephrostomy to prolonged or permanent nephrostomy diversion with Foley catheters up to 16F in diameter is described herein. The method has been used for up to 22 months of drainage and is likely to be of principal benefit in the management of obstructive nephropathy in adults when the primary lesion is not readily amenable to repair. There have been no serious complications in our 4 cases.

Animals↗
PubMed1974

Neonatal necrotizing enterocolitis. Clinical and radiological features.

Necrotizing enterocolitis is an uncommon but dangerous disease in premature infants. Ten cases, seen over a three-year period at the Stanford University Medical Center, represented an incidence of 0.4 percent. The patients, six of whom died, derived from a general population, in contrast to the large series of patients reported in the literature in which the incidence was from 0.9 percent to 3.7 percent.(3-6)The initial symptoms-rapid respiration, periodic breathing, lethargy and irritability-were identical to those which occurred in numerous infants who had respiratory disease. Subsequent symptoms (abdominal distension, in 100 percent; vomiting, 80 percent; apneic spells, 70 percent; jaundice, 70 percent; guaic-positive stools, 60 percent) were those of nonspecific acute abdominal disease. The radiologist first made the diagnosis in 90 percent of cases. Interstitial air in the wall of the gut and the retroperitoneum, and portal vein gas were the most diagnostic radiographic features. Barium contrast studies were not helpful, and in one case led to the erroneous diagnosis of small bowel volvulus. Plain abdominal radiographs must be taken of all premature infants with symptoms of nonspecific acute abdominal disease. If the radiographs are negative, but symptoms continue, they should be repeated at frequent intervals, for early diagnosis is critical to institution of proper therapy.

Diagnosis, Differential↗
PubMedDate not supplied

Inhibition of bradykinin- and kallikrein-induced cerebral arteriolar dilation by a specific bradykinin antagonist.

We have previously shown that topical brain application of kallikrein, an enzyme which converts kininogen to bradykinin, induces rabbit pial arteriole dilation. The purpose of the present investigation was to utilize a newly developed competitive kinin receptor antagonist to test the hypothesis that kallikrein-induced dilation was due to the conversion of brain kininogen to vasoactive kinins. As in our previous study, we measured rabbit pial arteriole diameter with a microscope using the closed cranial window technique. The kinin antagonist (6 microM) reduced the dose-dependent dilation produced by bradykinin and blocked the dilation induced by kallikrein. In addition, the kinin antagonist was specific since it did not alter the cerebral arteriole dilation produced by adenosine, acetylcholine, or vasoactive intestinal polypeptide. These experiments provide further evidence for a possible role of the endogenous brain kallikrein-kinin system in the modulation of the cerebral circulation and provide the necessary pharmacologic foundation for future use of this antagonist in testing the role of kinins in the normal or altered cerebral circulation.

Amino Acid Sequence↗