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Biomedical subjects

C F Miller

Publications and source records attributed to C F Miller.

At least 19 recordsLinked to original sources

Failure of endotoxic shock to elicit superoxide anion production in pig brain.

Endotoxin shock in pigs alters cerebral blood flow regulation. This study sought 1) to evaluate global cerebral electrical function using somatosensory evoked potential and 2) to determine if superoxide anion free radical (O2-) is generated in brain following endotoxin infusion. Five female pigs received E. coli endotoxin (0.1 mg/kg i.v.) and supplemental fluid to maintain cardiac output at control levels. Somatosensory evoked potential was generated before and after endotoxin infusion, and nitroblue tetrazolium (NBT) precipitation in cranial windows was used to determine O2- production by brain. Following endotoxin infusion, mean arterial blood pressure, cerebral perfusion pressure, and systemic vascular resistance fell by 50% and cerebral oxygen extraction increased. The amplitude and the latency of somatosensory evoked potential performed 60 min after endotoxin were unchanged from that generated at control. No precipitation of NBT in cranial windows was observed, indicating that O2- was not generated. Since endotoxin shock did not alter cerebral electrical function and O2- was not generated by brain, we conclude that alterations in cerebral blood flow regulation observed in fluid-resuscitated endotoxic shock do not result from inadequate cerebral oxygen consumption, nor is the extracellular production of O2- involved in the pathogenesis of this disorder.

Animals

Surgical treatment of epilepsy: three- to six-year follow-up of eleven patients with pharmacologically uncontrolled complex partial seizures.

There are an estimated 100,000 epileptic patients whose response to pharmacologic treatment is unsatisfactory. We report 11 patients with complex partial seizures who were selected for surgical treatment after adequate trials on antiepileptic medication failed. Immediate improvement-no further seizures or reduced frequency of occurrence and severity-was sustained at 3- to 6-year follow-up, and 7 patients were driving, 10 were working, and all were enjoying a better quality of life. Likely candidates for temporal lobectomy or resection of epileptogenic cerebral cortical lesions are those with a single focus of seizure discharge on video-EEG monitoring. If this focus is remote from language or motor areas, and if there is no interference with memory and recall after intracarotid amobarbital injection ipsilateral to the intended surgery, good results can be expected in the majority of such patients. We discuss patient selection and evaluation, and encourage surgical treatment where the indications can be established.

Adolescent

Adrenal blood flow and secretory relationships during hypoxia in anesthetized dogs.

To evaluate whether hypoxia-induced increases in adrenal cortical (CQ) and medullary (MQ) blood flow (radiolabeled microspheres) occur secondary to hypoxia-induced secretory activity, pentobarbital-anesthetized ventilated dogs were pretreated with dexamethasone (DEX) to prevent adrenocorticotropic hormone (ACTH) and corticosteroid secretory changes or underwent unilateral adrenal denervation to prevent adrenal catecholamine secretory responses. In nonsurgically stressed dogs, DEX completely prevented increases in ACTH or corticosteroid levels during reduction of arterial oxygen content to 8 vol% but had no effect on hypoxia-induced doubling of CQ. In dogs in which adrenal oxygen consumption (VO2) was measured, DEX reduced VO2 by 50% without altering CQ. Unilateral adrenal denervation prevented hypoxia-induced increases in adrenal catecholamine secretion and MQ but had no effect on the CQ response. These results suggest that hypoxia-induced medullary vasodilation is associated with adrenal catecholamine secretory activity but that increases in CQ occur independent of secretory activity and likely represent direct vascular effects of hypoxia.

Adrenal Glands

Effect of naloxone and ibuprofen on organ blood flow during endotoxic shock in pig.

The effects of an opiate antagonist naloxone and a cyclooxygenase inhibitor ibuprofen on organ blood flow during endotoxic shock were evaluated in a fluid-resuscitated porcine endotoxic shock model. Radiolabeled microspheres were used to measure regional blood flow. Escherichia coli endotoxin (0.1 mg/kg), infused intravenously over 40 min, reduced mean arterial blood pressure to 50 mmHg and systemic vascular resistance to 57% of control without affecting cardiac output. Endotoxin reduced blood flow to cerebrum (to 49% of control), kidney (to 25% of control), spleen, and skeletal muscle, while blood flow to left ventricle, stomach, and small and large intestines were unaffected. Sixty minutes after endotoxin administration, animals were randomized to one of three groups. Group I animals were controls and received no drug, group II animals received ibuprofen (12.5 mg/kg iv), and group III animals received naloxone (2 mg/kg iv) 60 min after endotoxin. Ibuprofen increased mean arterial blood pressure to 80 mmHg and increased blood flow to both cerebrum (to 92% of control) and kidney (to 47% of control). Plasma levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha were increased 8- and 16-fold, respectively, after endotoxin, and both were decreased by ibuprofen. Naloxone increased mean arterial blood pressure to 62 mmHg but had no effect on regional blood flow or plasma cyclooxygenase metabolite levels. These data suggest that cyclooxygenase metabolites may contribute to decreased mean arterial blood pressure and reduced organ blood flow during endotoxic shock in the pig.

6-Ketoprostaglandin F1 alpha

Effect of altered volume of distribution on aminoglycoside levels in patients in surgical intensive care.

The apparent volume of distribution (Vd) of aminoglycosides was found to be increased in 100 patients in a surgical intensive care unit who had gram-negative pneumonia or intraabdominal sepsis and acute physiologic scores greater than 12. Following loading or maintenance doses, carefully timed blood samples were collected for measurements of serum concentrations by fluorescence polarization immunoassay. The Vd, determined by linear regression analysis of a one-compartment model using the Sawchuk-Zaske method, was 0.34 +/- 0.121 L/kg and was larger than the normal Vd of 0.20 to 0.25 L/kg, suggesting a 36% to 70% increase in extracellular fluid volume. Since there is a predictable increase in aminoglycoside Vd in the septic surgical patient, a proportionately larger aminoglycoside dosage is required initially to achieve desirable peak serum levels. Close monitoring of blood levels during maintenance dosing is suggested since dynamic changes in renal function and aminoglycoside Vd occur in the critically ill.

Adult

Evaluation of sepsis in a critically ill surgical population.

We report a new clinical rating system which assesses septic patients' ongoing disease course and its severity. Our system incorporates the Therapeutic Intervention Scoring System (TISS) and Acute Physiology and Chronic Health Evaluation to measure discrete organ system abnormalities, plus a multiple system organ failure scale to quantify the number of abnormal organ systems. The resulting score, which reflects the severity of multiple organ dysfunction and grades responsiveness to therapy, was validated against the actual disease course. Retrospective and prospective profiles of individual surgical ICU patients demonstrated that this tracking method was a more effective indicator of severity of sepsis and more sensitive to the day-to-day changes in clinical status than either the TISS or APACHE II components alone. We also demonstrate that a graphic illustration of daily system scores yields clinically useful information relevant to the patients' septic course.

Bacterial Infections

Effect of vasopressors on organ blood flow during endotoxin shock in pigs.

A volume-resuscitated porcine endotoxin shock model was used to evaluate the effect on organ blood flow of increasing systemic arterial blood pressure with vasopressors. Administration of 0.05-0.2 mg/kg of Escherichia coli endotoxin (E) reduced mean arterial blood pressure (MAP) to 50 mmHg, decreased systemic vascular resistance to 50% of control, and did not change cardiac output or heart rate. Blood flow to brain, kidney, spleen, and skeletal muscle was reduced during endotoxin shock, but blood flow to left ventricle, small and large intestine, and stomach remained at pre-endotoxin levels throughout the study period. Four groups of animals were used to evaluate the effect of vasopressor therapy. A control group received E and no vasopressor, whereas the other three groups received either norepinephrine, dopamine, or phenylephrine. Vasopressors were administered starting 60 min after E exposure, and the dose of each was titrated to increase MAP to 75 mmHg. Despite the increase in MAP, brain blood flow did not increase in any group. Norepinephrine alone increased blood flow to the left ventricle. Kidney, splanchnic, and skeletal muscle blood flow did not change with vasopressor administration. The dose of norepinephrine required to increase MAP by 20-25 mmHg during E shock was 30 times the dose required for a similar increase in MAP in animals not receiving E. We conclude that hypotension in the fluid resuscitated porcine E shock model is primarily the result of peripheral vasodilatation, that the vascular response to vasoconstrictors in this model is markedly attenuated following E administration, that blood pressure elevation with norepinephrine, dopamine, and phenylephrine neither decreases blood flow to any organ nor increases blood flow to organs with reduced flow, and that norepinephrine, dopamine, and phenylephrine affect regional blood flow similarly in this model.

Animals

Role of hypotension in decreasing cerebral blood flow in porcine endotoxemia.

The role of reduced arterial blood pressure (MAP) in decreasing cerebral blood flow (CBF) during endotoxemia was studied in pentobarbital-anesthetized pigs. Microspheres (15 microns diam) were used to measure regional CBF changes during MAP manipulations in animals with and without endotoxin. Endotoxin (0.2 mg/kg iv) decreased MAP to 50 mmHg and decreased blood flow to the cortex and cerebellum without affecting cerebral cortical oxygen consumption (CMRO2). Elevating MAP from 50 to 70 mmHg during endotoxemia with norepinephrine (1.82 +/- 0.58 micrograms . kg-1 . min-1, iv) did not change cortical blood flow or CMRO2 but increased cerebellar blood flow. Brain stem blood flow was not affected by endotoxin or norepinephrine. When MAP was decreased to 50 mmHg by hemorrhage without endotoxin, no change in blood flow to cortex, cerebellum, or brain stem was observed from base-line levels. These results suggest that decreased MAP below a lower limit for cerebral autoregulation does not account for the decreased CBF observed after endotoxin.

Animals

Acquired middle cranial fossa fistulas: normal pressure and nontraumatic in origin.

To the accepted classification of three types of normal pressure, nontraumatic cerebrospinal fluid (CSF) fistulas, we would add "acquired." This type of CSF fistula tends to occur from the middle cranial fossa because of the enlargement of "pitholes" that are normally present in its anterior medial aspect. The enlargement of these bony defects is due to normal intracranial pressure variations that, not uncommonly, create meningoceles and meningoencephaloceles. A portion of the floor of this area is aerated in up to 10% of the normal population by the lateral recess of the sphenoid sinus, the pterygoid recess. Thus, this area has the potential to act as a pathway between the middle fossa and the paranasal sinuses, allowing cerebrospinal fluid to pass into the sinuses. Isotope and computerized tomographic studies are helpful in the localization of such a CSF leak. Tomography of the base of the skull, however, is essential for the ideal definition of possible routes of fistulization. If there is any question of the presence of a middle fossa fistula, these studies can show whether the floor of this area is pneumatized and whether there are any defects in the floor. The treatment of such a fistula should include generalized reinforcement of the floor of the anterior middle fossa by a middle fossa approach. If any doubt exists as to the site of leakage (anterior or middle fossa), the minimal surgical procedure should include exploration of both areas via a frontotemporal craniotomy.

Cerebrospinal Fluid Rhinorrhea