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PubMed1995

1995 Volvo Award in basic sciences. The use of an osteoinductive growth factor for lumbar spinal fusion. Part II: Study of dose, carrier, and species.

STUDY DESIGN: Efficacy of a bovine-derived osteoinductive growth factor was studied in a rabbit model and in a nonhuman primate model of posterolateral lumbar spinal fusion. OBJECTIVES: To determine the minimum effective dose of growth factor and the influence of different carrier material on the outcome of intertransverse process lumbar fusion. SUMMARY OF BACKGROUND DATA: Bone morphogenetic proteins and related growth factors are becoming increasingly available in purified extract or genetically engineered forms and are capable of inducing new bone formation in vivo. Osteoinductive growth factors to enhance lumbar spinal infusion have not been well studied in models of posterolateral intertransverse process fusion. Because of the diminished potential of bone regeneration in primates (including humans) compared with phylogenetically lower animals, extrapolations regarding dose and efficacy cannot be made directly from results obtained in experiments performed on phylogenetically lower animals. Experiments on non-human primates are a critical step before attempting to use these growth factors on humans. METHODS. One hundred fifteen adult New Zealand white rabbits and 10 adult rhesus macaques underwent single level posterolateral intertransverse process lumbar spinal arthrodesis to evaluate different doses and carrier materials for a bovine-derived osteoinductive bone protein extract. Rabbit fusion masses were evaluated 5 weeks after arthrodesis by manual palpation, radiography, biomechanical testing, and light microscopy. Monkey fusion masses were evaluated 12 weeks after arthrodesis by radiography and light microscopy. RESULTS: Successful posterolateral intertransverse process spinal fusions were achieved in the rabbit models using an osteoinductive growth factor with three different carriers (autogenous iliac bone, demineralized allogeneic bone matrix, and natural coral). There was a dose-dependent response to the osteoinductive growth factor in the rabbit model, indicating that a threshold must be overcome before bone formation is induced. The methodology for biologic enhancement of spinal fusion developed in the rabbit model transferred successfully to the rhesus monkey, where the use of the osteoinductive growth factor with a demineralized bone matrix carrier resulted in spinal fusion in 12 weeks. CONCLUSION: These experiments provide an essential building block in the understanding of the biology of spinal fusion and the use of osteoinductive growth factors to enhance a posterolateral intertransverse process spinal fusion. The achievement of posterolateral spinal fusion in the rhesus monkey using an osteoinductive growth factor is a significant step toward the biologic enhancement of spinal fusion in humans.

Animals↗
PubMed1991

Steady-state lumbar infusion tests in the management of children with craniosynostosis.

Sixty lumbar steady-state infusion tests were used as a guideline in the management of 30 children with craniosynostosis during a 3-year period. The primary decompressive procedure was performed during the same anesthetic period and was made more extensive in cases with pathological outflow resistance (Ro) values. In 11 children with scaphocephaly the test revealed normal to moderately increased cerebrospinal fluid (CSF) Ro. In 6 children with oxycephaly, 4 with trigonocephaly or combined forms, especially in 7 children with syndromic forms, the need for decompressive surgery was usually more obvious. Also, many of these demonstrated severely increased CSF outflow resistance (above 12 mmHg/ml per min). Spinal infusion tests were particularly helpful in the management of severe syndromic or familial cases where the indication for repeat or further extensive decompression was sometimes difficult to assess on clinical and radiological grounds.

Cerebrospinal Fluid↗
PubMed2004

Sedation guidelines for midazolam infusion during combined spinal and epidural anesthesia.

STUDY OBJECTIVE: To investigate the adequate infusion dose regimen of midazolam to induce sedation with the Ramsay score 4 with rapid onset during combined spinal and epidural anesthesia DESIGN: Prospective, randomized study. SETTING: Operating room of a university hospital. PATIENTS: 80 ASA physical status I and II patients aged 30 to 70 years, undergoing combined spinal and epidural anesthesia. INTERVENTIONS: Patients were randomized to four groups of 20 patients each at random. After starting surgery, an infusion of midazolam 0.3, 0.6, 0.9, or 1.2 mg/kg/hr was started. When patients closed their eyes spontaneously, the infusion dose was decreased to one half of the initial dose. At 2.5 and 5 minutes after decrease the dose and at 5-minute intervals for the first 30 minutes then at 15-minute intervals thereafter until the end of surgery, infusion dose was adjusted by decreasing to one half or increasing to twice to keep the Ramsay score 4. MEASUREMENTS AND MAIN RESULTS: The number of patients who required oxygen was significantly larger in the groups received 0.9 and 1.2 mg/kg/hr. Eleven patients with 0.9 mg/kg/hr and 17 patients with 1.2 mg/kg/hr at 5 minutes, but no patients with 0.3 or 0.6 mg/kg/hr showed Ramsay score 6 (heavy sedation). Amnesia was observed in all patients. Time to eye closure was dose dependently faster with the larger doses. CONCLUSIONS: During combined spinal and epidural anesthesia, midazolam 0.6 mg/kg/hr given until closing of the eyes (for 1.6 min) followed by midazolam 0.15 mg/kg/hr provides rapidly induced sedation, with a Ramsay score of 4 and amnesia with stable hemodynamics and respiration.

Adult↗
PubMed2003

Distinct neurochemical mechanisms are activated following administration of different P2X receptor agonists into the hindpaw of a rat.

Nocifensive behaviors induced by the intradermal injection of three different P2X receptor agonists, ATP, BzATP or alpha,beta-meATP, into a hindpaw were measured in rats that were injected intrathecally with either an NMDA (MK-801) or an NK-1 (L-703,606) receptor antagonist or were pretreated systemically with the VR1 agonist resiniferatoxin (RTX). The same procedures were performed in animals injected intradermally with either capsaicin or formalin. Spinal infusion of MK-801 (10-50 nmol/10 micro l) similarly reduced the number of nociceptive events triggered by each of the P2X agonists and was also effective against capsaicin and formalin induced behaviors. Intrathecal administration of L-703,606 (50-100 nmol/10 micro l) had its greatest antinociceptive effect against capsaicin-induced behaviors followed by ATP and BzATP. L-703,606 was completely ineffective against behaviors induced by formalin or the other P2X agonist, alpha,beta-meATP. Pretreatment with RTX 2 days prior to testing significantly decreased the number of nociceptive events caused by each of the P2X agonists as well as capsaicin and formalin (capsaicin>BzATP>ATP>formalin>alpha,beta-meATP). The remaining nociceptive events in RTX animals injected with alpha,beta-meATP were significantly higher than in animals injected with either ATP or BzATP. Intradermal administration of different P2X receptor agonists induced similar levels of nocifensive behaviors and activity at spinal NMDA receptors. Capsaicin-sensitive fibers were likely activated following injection of BzATP and ATP, but not alpha,beta-meATP, and appeared to trigger the spinal release of substance P. The differences in mechanisms employed by the different P2X agonists may be a function of respective selectivity for P2X receptor subtypes.

Animals↗
PubMed1976

[Clinical observations on hydrocephalus with special regard to the posttraumatic malresorptive form (author's transl)].

100 cases of Spitz-Holter shunts performed for hydrocephalus over a period of 3 years were analyzed; 17 of these were of posttraumatic origin and are discussed in regard to pathogenesis, clinical symptoms, diagnostic methods, and therapy. Half of these 17 had severe traffic accidents. The rapidity and degree of ventricular dilatation were positively correlated with the duration of unconsciousness. When the unconsciousness had lasted more than 10 days hydrocephalus was recognized early, and the shunt was performed on an average 2 months after the trauma. Two thirds of the patients improved after the shunt operation. Pathogenetically we believe the important factors in the acute stages are increased CSF pressure, disturbed CSF dynamics, brain swelling and vascular circulation disorder; in the chronic stages, parenchymous atrophy. The following 3 types of posttraumatic hydrocephalus were differentiated on the basis of the clinical features: --symmetrical communicating internal hydrocephalus with malresorption, especially after subarachnoid hemorrhage, --communicating internal hydrocephalus alone, or in combination with external hydrocephalus resulting from atrophy, --internal occlusive hydrocephalus after trauma. The following posttraumatic clinical features were found to be indications that hydrocephalus may be present: in the acute stages inadequately long symptom resolution considering the severity of the trauma, secondary changes for the worse, an apallic syndrome which does not improve; in late stages, the presence of an Adams-Hakim syndrome charaterized by dementia, a spastic gait and loss of sphincter control. The most successful diagnostic methods were found to be pneumencephalography with 24 and 48 h delayed exposures, cisternoscintigraphy and continuous intracranial pressure monitoring in combination with the spinal infusion test. The most important intracranial shunting procedures and the indications for shunting are discussed.

Accidents, Traffic↗
PubMed1990

Natural course of intracranial pressure and drainage of CSF after recovery from subarachnoid hemorrhage.

Twenty-eight patients were followed 12 months or longer after recovery from subarachnoid hemorrhage (SAH). The examination included spinal infusion test (SIT), clinical evaluation and cerebral computertomography (CT). The results indicate that when resting pressure and drainage of CSF are within normal limits 3 months after the hemorrhage there is little if any risk of developing late communicating hydrocephalus. In this study, most patients with a moderate impaired CSF drainage and/or slightly increased resting pressure 3 months after SAH did not show any increase in the ventricular size or clinical deterioration during the follow-up period. None of the 28 patients developed late communicating hydrocephalus or the clinical picture of normal pressure hydrocephalus.

Adult↗
PubMedDate not supplied

Plasma bupivacaine levels after pleural block: the effect of epinephrine after unilateral or bilateral bupivacaine administration.

BACKGROUND AND OBJECTIVES: To determine the effect of adding epinephrine (5 micrograms/ml) to bupivacaine during continuous spinal infusion and the effect of the administration of the same total dose of bupivacaine, in a bilateral or unilateral way, on its consequent plasma levels. METHODS: Sixteen cholecystectomized patients were studied prospectively. In ten patients with midline incision, bilateral pleural infusion (half total unilateral dose in each hemithorax) was administered, and in six patients with subcostal incision, unilateral pleural infusion. The unilateral group received a loading dose of 20 ml 0.375% bupivacaine immediately followed by an infusion at a rate of 6 ml/hour. Three patients randomly received epinephrine (5 micrograms/ml) added to bupivacaine, whereas the other three remaining patients did not receive it. The bilateral group received 10 ml 0.375% bupivacaine followed by an infusion at a rate of 3 ml/hour in each hemithorax. Five patients randomly received epinephrine; five others did not. The plasma levels of bupivacaine were determined at 5, 15, 30, and 60 minutes and at 6 and 18 hours. RESULTS: Plasma levels of bupivacaine were significantly lower (p less than 0.05) during the whole study in patients receiving epinephrine. For the same total dose, there were no statistical differences in the plasma levels of bupivacaine between unilateral and bilateral pleural groups. CONCLUSIONS: The addition of epinephrine (5 micrograms/ml) to a continuous pleural infusion of bupivacaine diminishes the plasma levels of the local anesthetic. For the same total dose of bupivacaine, there are no differences in the plasma levels obtained between unilateral and bilateral administration.

Adult↗
PubMed2005

[Criss-cross heart: anesthetic considerations for total cavopulmonary shunt (Fontan procedure)].

We report the anesthetic technique used for interatrial septal defect a 2-year-old girl weighing 11 Kg who presented with crossed atrioventricular connection (criss-cross heart), transposition of the great vessels, interatrial and interventricular septal defects, and subpulmonary and pulmonary valve stenoses. The patient was proposed for total cavopulmonary anastomosis with basal arterial oxygen saturation (SapO2) at 65%. Anesthesia was induced with inhaled agents and after intubation, hyperventilation was induced to achieve an end-tidal carbon dioxide pressure around 27 mm Hg. General anesthesia was provided in combination with spinal infusion of morphine chloride (100 microg Kg(-1)) for pain control. A Fontan procedure was carried out uneventfully with cardiopulmonary bypass. Milrinone was used at the extracorporeal circuit pump outlet. The patient was transferred to the pediatric intensive care unit where she was extubated without complications 90 minutes after admission. Anesthetic management is based on maintaining adequate preloading doses by administering volume, inhaled and/or intravenous agents, or use of vasoconstrictors and adjustment of ventilator parameters to modify pulmonary or systemic vascular resistance. We were able to maintain normal arterial pressure in our patient and provide adequate preloading through hyperventilation to reduce pulmonary vascular resistance.

Anesthesia↗
PubMed2004

A prospective analysis of intrathecal granuloma in chronic pain patients: a review of the literature and report of a surveillance study.

BACKGROUND: Over the past decade granulomas have been noted to occur at or near the tip of intrathecal catheters used for spinal infusions. The majority of cases involved morphine infusions, although other drugs have been implicated. Granulomas may be asymptomatic or cause significant neurological deficits. METHODS: Consecutive patients with intrathecal infusions were examined for the presence of intrathecal granulomas. MRI or CT was used to make the diagnosis. RESULTS: A total of 208 patients underwent imaging over a period of 34 weeks. Six patients (3%) were found to have a significant lesion. Five of the six patients were asymptomatic and one patient complained of radicular pain in the distribution of the catheter tip. The average catheter infusion time for patients with granulomas was 27 months, not significantly different from patients without granulomas. No specific characteristics, such as drugs or concentrations were identified. All six patients had percutaneous catheter revisions without complication. CONCLUSION: Intrathecal granulomas were identified in 3% of patients imaged in this series. Eighty percent of the patients were asymptomatic. MRI imaging remains the diagnostic method of choice for most patients, and can be done safely when scans are taken at the level of the catheter tip. Given the low incidence of granulomas with intrathecal catheters, routine imaging to identify granulomas is not warranted.

Journal Article↗
PubMed1991

Principles of pain management in older people.

The management of chronic pain should be a priority in geriatric care. Pain is a common problem that has tremendous potential to influence the physical function and quality of life of elderly people during their remaining years. Much research and education is still needed to further our understanding of pain and its management among elderly people. Existing pain management strategies should be tailored for the special needs of the geriatric population. Applications of "high tech" pain management strategies, such as morphine pumps and chronic spinal infusions, need to be clarified for older people. Finally, family and caregiver considerations should be included in chronic pain management strategies.

Aged↗
PubMed1990

[Sexual dysfunction following radical operation for cancer of the rectum and colon].

Sexual dysfunction frequently occurs following radical operation for cancer of intrapelvic organs. However, the number of impotent patients with colon and rectal cancer who actually visited our Reproduction Center complaining of impotence after operation accounted for only 31 (1.8%) out of the 1,686 impotent cases during past 8 years; of these 31 patients who complained of impotence after operation by Miles method, 79% were considered to suffer from organic impotence, while 62% of those having undergone anterior resection suffered organic impotence. Even in cases in whom no erection occurs due to some disorder in the nervous system, intracavernous injection treatment using vasoactive agents (papaverine or prostaglandin E1) can be effective if the vascular system is normal. In cases which do not react to this treatment, intrapenile transplantation of various silicone prostheses is tried. Moreover, administration of sympathomimetic agents (imipramine and so on) is undertaken in cases with retrograde ejaculation, among those with ejaculatory disorders, and if no effect is obtained by this administration, artificial insemination is tried using semen ejaculated into the bladder. In cases in whom no ejaculation occurs, even into the bladder, artificial ejaculation is attempted by spinal infusion of prostigmin, and when no effect is obtained, artificial insemination is tried using semen retained in an artificial spermatocele implanted in the tail of the epididymis.

Colonic Neoplasms↗
PubMed1981

Migration of lymphocytes sensitized against syngeneic and allogeneic spinal cord after infusion into susceptible and resistant syngeneic and semi-allogeneic hosts.

Lymphocytes from rats that had been sensitized against spinal cord were infused into unsensitized hosts, and the ability of cells subsequently recovered from the thoracic duct lymph of these recipients to mount anti-neural responses was tested. Lymph from normal recipients frequently contained reactive lymphocytes during the 4 days following infusion of sensitized cells, whereas cells that had been recovered from transfused rats, resistant to encephalomyelitis as a result of neonatal treatment, were almost invariably benefit of activity. If lymphocytes reactive against allogeneic neural cells were passaged through F1 hybrids of the lymphocyte and sensitizing allogeneic tissue strains, loss or retention of their ability to attack allogeneic neural cells was determined by the method of sensitization of the original lymphocyte donor.

Animals↗
PubMed1993

Different central areas involved in the mechanisms of morphine antinociception in the mouse and the rat.

The antinociceptive effect of morphine quantitated by the tail-flick (TF) response was studied in mice and rats with various preparations, including: precollicular transection, partial and complete anemic decerebration, vertebral artery infusion, cross-circulation, spinal ligation, spinalization with dura mater intact and spinal subarachnoid infusion. In mice, either precollicular transection or partial anemic decerebration abolished or greatly reduced the morphine antinociceptive action (MAA). However, in rats, neither precollicular transection nor complete anemic decerebration caused any significant reduction in MAA. Studies of vertebral artery infusion and cross-circulation in both species indicated that opiate-sensitive antinociceptive receptors (OSAR) were present in the hindbrain. Although, spinal ligation eliminated MAA in both species, spinalization with dura mater intact only abolished the MAA in rats. On the other hand, studies of spinal subarachnoid infusion showed that only spinal antinociceptive neurons of mice were highly sensitive to the enzyme-resistant enkephalin (Enk) analog. From all these results suggested that both pre- and post-collicular structures are necessary for MAA in the mouse, however, in the rat only the post-collicular structures are essential, furthermore, the humoral pathway seems to play a more important role than the neural pathway in the inhibition of the TF response in the mouse but just the opposite in the rat. Therefore, it is concluded that the mechanisms of MAA are different between the mouse and the rat. The possible mechanisms of MAA in both species were discussed.

Analgesia↗
PubMed2003

Temporal and spatial distribution of activated caspase-3 after subdural kainic acid infusions in rat spinal cord.

The molecular events initiating apoptosis following traumatic spinal cord injury (SCI) remain poorly understood. Soon after injury, the spinal cord is exposed to numerous secondary insults, including elevated levels of glutamate, that contribute to cell dysfunction and death. In the present study, we attempted to mimic the actions of glutamate by subdural infusion of the selective glutamate receptor agonist, kainic acid, into the uninjured rat spinal cord. Immunohistochemical colocalization studies revealed that activated caspase-3 was present in ventral horn motor neurons at 24 hours, but not 4 hours or 96 hours, following kainic acid treatment. However, at no time point examined was there evidence of significant neuronal loss. Kainic acid resulted in caspase-3 activation in several glial cell populations at all time points examined, with the most pronounced effect occurring at 24 hours following infusion. In particular, caspase-3 activation was observed in a significant number of oligodendroglia in the dorsal and ventral funiculi, and there was a pronounced loss of oligodendroglia at 96 hours following treatment. The results of these experiments indicate a role for glutamate as a mediator of oligodendroglial apoptosis in traumatic SCI. In addition, understanding the apoptotic signaling events activated by glutamate will be important for developing therapies targeting this cell death process.

Animals↗
PubMed2001

Regional lidocaine infusion reduces postischemic spinal cord injury in rabbits.

Paraplegia secondary to spinal cord ischemia is a devastating complication in operations on the descending and thoracoabdominal aorta. We hypothesized that the tolerance of the spinal cord to an ischemic insult could be improved by means of regional administration of lidocaine. Thirty-one New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by the placement of clamps both below the left renal vein and above the aortic bifurcation. The animals were divided into 5 groups. Aortic occlusion time was 20 minutes in Group 1 and 30 minutes in all other groups. Groups 1 and 2 functioned as controls. Lidocaine (Group 5) or normal saline solution (Group 3) was infused into the isolated aortic segment after cross-clamping. Group 4 animals received 20% mannitol regionally, before and after reperfusion. Postoperatively, rabbits were classified as either neurologically normal or injured (paralyzed or paretic). Among controls, 20 minutes of aortic occlusion did not produce any neurologic deficit (Group 1: 0/4 injured), while 30 minutes of occlusion resulted in more consistent injury (Group 2: 6/8 injured). Animals that received normal saline (Group 3) or mannitol (Group 4) regionally showed 80% neurologic injury (4/5). Animals treated with the regional lidocaine infusion (Group 5) showed much better neurologic outcomes (7/9 normal: 78%). This superiority of Group 5 over Groups 2, 3, and 4 was significant (P <0.02). We conclude that regional administration of lidocaine reduced neurologic injury secondary to spinal cord ischemia and reperfusion after aortic occlusion in the rabbit model.

Anesthesia, Conduction↗