PubMed HealthSearch

Biomedical subjects

R F Young

Publications and source records attributed to R F Young.

At least 19 recordsLinked to original sources

Intracranial pressure monitoring: fiberoptic monitor compared with the ventricular catheter.

Among the frequently utilized intracranial pressure (ICP) monitoring devices employed in neurosurgical practice is the Camino fiberoptic monitor. Several recent studies have described results with the Camino monitor and compared it with other forms of ICP monitoring with varying results and conclusions. The aim of this study was to compare simultaneous ICP readings from the Camino fiberoptic monitor placed in the brain parenchyma and from a ventricular catheter. ICP values were recorded for up to 118 hours in 10 patients. It was determined that the Camino ICP measurements exceeded those of a ventricular catheter in 66% of total measurements for the 10 patients. The mean ICP difference between the Camino fiberoptic system and the ventricular catheter was 9.2 +/- 7.8 mm Hg. This result suggests that the correlation between intraparenchymal pressure measured by the Camino fiberoptic monitor and the intraventricular pressure is not as close as previously described.

Catheterization

Stimulation of glucose catabolism in Escherichia coli by a potential futile cycle.

Fifteen-fold overexpression of phosphoenolpyruvate synthase (Pps) (EC 2.7.9.2) in Escherichia coli stimulated oxygen consumption in glucose minimal medium. A further increase in Pps overexpression to 30-fold stimulated glucose consumption by approximately 2-fold and resulted in an increased excretion of pyruvate and acetate. Insertion of two codons at the PvuII site in the pps gene abolished the enzymatic activity and eliminated the above-described effects. Both the active and the inactive proteins were detected at the predicted molecular weight by polyacrylamide gel electrophoresis. Therefore, the observed physiological changes were due to the activity of Pps. The higher specific rates of consumption of oxygen and glucose indicate a potential futile cycle between phosphoenolpyruvate (PEP) and pyruvate. A model for the stimulation of glucose uptake is presented; it involves an increased PEP/pyruvate ratio caused by the overexpressed Pps activity, leading to a stimulation of the PEP:sugar phosphotransferase system.

Alleles

Chronic stimulation of the Kölliker-Fuse nucleus region for relief of intractable pain in humans.

Chronic electrical stimulation in the periventricular or periaqueductal gray matter regions and the thalamic somatosensory relay nuclei (ventralis posteromedialis and ventralis posterolateralis) provides long-term pain relief in about 50% of patients with intractable pain refractory to other conservative and/or surgical measures. To enhance the success of electrical stimulation in relief of pain, alternative brain and brain-stem targets have been sought. A series of laboratory studies indicated that the Kölliker-Fuse nucleus and the parabrachial region may provide appropriate alternatives to the "classic" targets. This report describes six patients with intractable chronic pain of nociceptive or central origin, in whom an electrode was stereotactically implanted in the region of the Kölliker-Fuse nucleus. Kölliker-Fuse nucleus stimulation alone or in combination with stimulation in the periaqueductal/periventricular gray matter region or the somatosensory thalamic nuclei provided excellent pain relief in three of the six patients.

Adult

Is early prediction of outcome in severe head injury possible?

To determine whether the outcome of patients with severe head injury could be predicted early after presentation to the hospital, the records of 306 trauma patients with head injury and Glasgow Coma Scale scores of 10 or less were reviewed. There was poor correlation between initial scores at patient arrival and eventual outcome, while scores 6 hours after presentation correlated better with eventual outcome. Many patients with scores as low as 3 had good neurologic recovery. Patient age, associated injuries, blood pressure, mechanism of injury, presence of spontaneous ventilation, and computed tomographic findings all affected survival. However, considering even these parameters, statistical analysis could not provide sensitive prediction of outcome, which we defined as identifying those patients who eventually had good recovery. We conclude that initial therapy should be aggressive for patients with severe head injury, regardless of initial neurologic status, because accurate prediction of outcome within 6 hours of presentation is impossible.

Adolescent

Spontaneous neuronal hyperactivity in the medial and intralaminar thalamic nuclei of patients with deafferentation pain.

Electrical activity was recorded from single cells in the thalamus of 10 patients with chronic pain associated with deafferentation. Under local anesthesia, these patients underwent either electrode implantation or thalamotomy for treatment of their pain. In eight of the 10 patients, single units were identified as discharging spontaneously in high-frequency, often rhythmic, bursts. The discharges were of two types: short bursts comprised of two to six spikes with a burst frequency of one to four per second; and long trains of 30 to 80 spikes of similar frequency. Reconstruction of electrode trajectories indicated that recordings were made from the region corresponding to the lateral aspect of the mediodorsal thalamic nucleus, the central lateral nucleus, a small part of the central median nucleus, and the parafascicular nucleus. In the eight patients in whom spontaneous neuronal burst activity was exhibited, it was impossible to study activity evoked by natural cutaneous stimulation due to the continuous spontaneous neuronal discharges. Both animal and human studies have suggested that pain related to deafferentation is accompanied by spontaneous hyperactivity in the dorsal horn of the spinal cord and in the ventral posterior thalamic nuclei. The authors present evidence of spontaneous neuronal hyperactivity in the intralaminar thalamic nuclei of patients with pain related to deafferentation. The findings suggest that spontaneous neuronal discharge in patients with pain related to deafferentation is more widespread in the central nervous system than has been previously appreciated. The results have important implications for the surgical treatment of chronic pain.

Afferent Pathways

Molecular analysis of a myxoid chondrosarcoma with rearrangements of chromosomes 10 and 22.

Myxoid chondrosarcoma is a rare tumor of adulthood. An associated nonrandom reciprocal translocation between chromosome 9 and 22 was previously reported in this tumor. We performed cytogenetic and molecular genetic analysis of a myxoid chondrosarcoma derived from the sphenoid bone. Using restriction fragment length polymorphism (RFLP) analysis, we demonstrated rearrangement and a possible allele loss close to the chromosome 22 breakpoint. In addition, structural rearrangement in the chromosome 10q21.1 region and an allele loss in the chromosome 10q21-q23 region were also detected. In tumor DNA an additional hybridization fragment was detected by pAS-1 probe, which recognizes multiple pseudogenes of argininosuccinate synthetase dispersed in various chromosomes. We were unable to detect chromosomal abnormalities with two additional chromosome 9q probes. This study suggests that multiple gene rearrangements occurred in the myxoid chondrosarcoma and the significance of this is discussed.

Adult

Rat beta-galactoside alpha 2,6-sialyltransferase genomic organization: alternate promoters direct the synthesis of liver and kidney transcripts.

The rat beta-galactoside alpha 2,6-sialytransferase gene is differentially utilized by liver and kidney in the generation of mRNAs that predict substantially divergent polypeptides. In order to determine the biosynthetic relationship between these sialyltransferase mRNA isoforms, genomic sequences were isolated and analysed. Five exons that span at least 40 kb of DNA carry the coding information for the liver beta-galactoside alpha 2,6-sialyltransferase protein. An additional exon contains only sequences for the 5'-untranslated leader of the liver mRNA. In contrast, the predominant kidney mRNAs from this gene share only three coding exons that specify the carboxyl terminal 42% of the liver sialyltransferase protein sequence. In addition, these kidney mRNAs contain information from two other exons that comprise the 5' divergent region of these transcripts. Primer extension and S1 nuclease protection analysis demonstrate that the hepatic and kidney specific mRNAs are transcriptionally initiated at different sites within the sialyltransferase gene. While the hepatic sialyltransferase mRNAs are transcribed from the first exon, the kidney transcripts are initiated from a site within the third intron. Genomic regions upstream of both transcriptional initiation sites can regulate expression of the bacterial chloramphenicol acetyltransferase gene in transiently transfected L cells. Together, the data implicate multiple promoters as a principle mechanism in the generation of kidney and liver gene product diversity in sialyltransferase expression.

Animals

Clinical experience with radiofrequency and laser DREZ lesions.

Dorsal root entry zone (DREZ) lesions were used to treat intractable pain due to deafferentation in 78 patients managed between 1981 and 1988. Etiology of pain included avulsion of brachial or lumbosacral plexuses (27 cases), spinal cord injury (20 cases), amputation (nine cases), post-herpetic neuralgia (16 cases), and cauda equina injury (six cases). Three different lesioning techniques were employed: a radiofrequency (rf) method using a 0.5 X 2-mm stainless steel electrode with control of electric current and duration (Group 1: 21 cases); the CO2 laser (Group 2: 20 cases); and an rf method, using a 0.25 X 2-mm stainless steel electrode with control of electrode temperature and duration (Group 3: 37 cases). Overall, 48 (61.5%) of 78 patients received satisfactory pain relief, defined as a 50% or greater reduction in pain intensity, cessation of narcotic analgesic usage, and improvement in functional capacity. Fourteen (67%) of the 21 Group 1 patients obtained effective pain relief, compared to nine (45%) of the 20 Group 2 patients and 25 (68%) of the 37 Group 3 patients. Neurological complications including mainly ipsilateral leg weakness or loss of proprioception occurred in 52.3% of the patients in Group 1, 15% of the Group 2 patients, and 8.1% of the Group 3 patients. These results support the view that DREZ lesions may be made most effectively and safely with the rf lesioning technique associated with control of electrode temperature and duration.

Afferent Pathways

Brain stimulation.

Electrical stimulation in the PAG has been shown to elicit profound analgesia in experimental animals that is at least in part due to the release of endogenous opioid substances. Electrical stimulation in the thalamic nuclei VPL and VPM inhibits the activation of spinal dorsal horn neurons by noxious stimuli. Acute electrical stimulation in these two targets relieves chronic pain in about 80% of patients. Chronic electrical stimulation by permanently implanted electrodes relieves pain in about 70% of patients with pain of peripheral or nociceptive origin but in only about 50% of patients with central pain resulting from deafferentation. Stimulating electrodes are implanted stereotactically by a burr hole under local anesthesia. Transient complications occur in 15% to 25% of patients and include infections, malfunctions of the stimulating hardware, pain at the implant sites, and mild temporary neurologic deficits. Permanent complications, including hemiparesis, intracranial hemorrhage, and death, occur in 1% to 2% of patients. Brain stimulation is recommended for the treatment of chronic pain in patients in whom other forms of treatment have failed. The technique is reasonably safe and provides pain relief for a group of patients who have exhausted all other therapeutic modalities. Unfortunately, not all patients receive effective pain relief with brain stimulation. Other stimulation targets such as the K-F nucleus in the parabrachial region of the brain stem are currently being explored in an attempt to provide pain relief to a greater proportion of patients. In addition, improvements in stimulation hardware have made the technique easier and more effective.

Brain

Specifying caregiver outcomes: gender and relationship aspects of caregiving strain.

The gender-specific kinship relationship of patients and their care providers has not generally been investigated in studies of caregiver burden and well-being. In this study of 183 heart patient-caregiver dyads, gender and relationship were analyzed singly and jointly with respect to the process and outcome of caregiving. Strains caregivers experienced while caring for older heart patients six weeks and one year after hospital discharge were determined. Findings showed consistent patterns of strain. Women, nonspousal caregivers, and daughters, in particular, experienced the most severe aftereffects. These findings support a caregiving outcomes model proposing that the patient-caregiver relationship is an essential component of caregiver strain.

Coronary Disease

Glycerol rhizolysis for treatment of trigeminal neuralgia.

Percutaneous retrogasserian glycerol instillation was performed under local anesthesia for treatment of trigeminal neuralgia in 162 patients. A simplified technique that did not involve cisternography was used. Initial pain relief was achieved in 146 patients (90.1%). Recurrent pain was noted in 27 patients (18.5%) and was more frequent (50%) in patients who had undergone surgical treatments prior to glycerol injection than in those who had no previous surgical treatment (12.3%). A second glycerol injection was carried out in nine patients and a third injection in two patients. The follow-up period extended from 6 to 67 months and 77.8% of patients are totally pain-free after one or more glycerol injections. Another 8.6% experienced good pain relief with the addition of small doses of pharmacological agents. Thus, 140 (86.4%) of the original 162 patients experienced satisfactory pain control following glycerol rhizolysis. Initial sensory loss on the face occurred in 117 patients (71.6%) but at last follow-up examination only 46 patients (28%) experienced mild orofacial hypalgesia and 13 patients (8%) noted analgesia. The corneal reflex was absent in three patients (1.8%) and reduced in five (3.1%). No patients noted corneal ulceration or anesthesia dolorosa. Percutaneous retrogasserian glycerol rhizolysis offers a rapid, safe, reliable, and relatively inexpensive surgical approach to treatment of trigeminal neuralgia.

Adult

Application of robotics to stereotactic neurosurgery.

Advances in the field of stereotactic neurosurgery have depended on improvements in brain-imaging techniques, as well as development of new stereotactic frame systems. This paper describes the development of a stereotactic system based on a robotics model. The system employs the Unimation Puma Mark II Robotic System, specifically modified for use in stereotactic surgery. The robotic CT stereotactic system is mounted in a dedicated operating suite, containing a CT scanning gantry and adjacent computer room. Stereotactic coordinates are derived from CT scan data obtained intraoperatively and transferred by computer link to the robotic stereotactic system. The robotic arm is driven into place to align with predetermined coordinates. A variety of stereotactic procedures may then be carried out using the robotic 'hand' as a guide to the target. So far, the device has been used, only for lesion biopsy. However, future applications to functional neurosurgery are anticipated.

Biopsy

Pain relief by electrical stimulation of the periaqueductal and periventricular gray matter. Evidence for a non-opioid mechanism.

Pain relief following stimulation of the periaqueductal gray matter (PAG) or periventricular gray matter (PVG) in man has been ascribed to stimulation-induced release of endogenous opioid substances. Forty-five patients were studied and followed for at least 1 year after placement of chronic stimulating electrodes in the PAG or PVG to determine if pain relief due to stimulation could be ascribed to an endogenous opioid mechanism. Three criteria were assessed: the development of tolerance to stimulation; the possibility of cross-tolerance to morphine; and reversibility of stimulation-induced pain relief by the opiate antagonist naloxone. Sixteen patients (35.6%) developed tolerance to stimulation, that is, they obtained progressively less effective pain relief. Twelve (44.4%) of 27 patients undergoing stimulation of the thalamic sensory relay nuclei for treatment of chronic pain (a presumably non-opioid mechanism) also developed tolerance. Morphine sulfate was administered in a blind, placebo-controlled protocol to 10 patients who had become tolerant to PAG-PVG stimulation and none showed evidence of cross-tolerance. Fifteen of 19 patients, already tolerant to morphine at the time of PAG-PVG electrode implantation, experienced excellent pain relief by stimulation, also indicating a lack of cross-tolerance. Twenty-two patients who experienced excellent pain relief from chronic PAG-PVG stimulation received intravenous naloxone in a double-blind, placebo-controlled protocol. Pain intensity as assessed by the visual analog scale was increased to the same degree by both placebo and naloxone. Eight patients showed no increase in pain intensity with either placebo or naloxone. Although tolerance to PAG-PVG stimulation developed in these patients, the frequency of tolerance was similar to that seen in patients undergoing thalamic sensory nuclear stimulation. Since the latter technique presumably relieves pain by a non-opioid mechanism, the development of tolerance to PAG-PVG stimulation does not, in itself, confirm an opioid mechanism. Cross-tolerance between PAG-PVG stimulation and morphine was not seen and cross-tolerance to PAG-PVG stimulation in patients already tolerant to morphine was rare. The pain-relieving effect of PAG-PVG stimulation was reversed to an approximately equal degree by naloxone and placebo. The authors do not believe that, in most patients, pain relief elicited by PAG-PVG stimulation depends on an endogenous opioid mechanism. It appears that other, non-opioid mechanisms are primarily responsible for such pain relief.

Cerebral Aqueduct

Perioperative antibiotic prophylaxis for prevention of postoperative neurosurgical infections. A randomized clinical trial.

The authors report the results of a randomized, prospective study to assess the effectiveness of perioperative antibiotic prophylaxis in preventing postoperative infections following clean neurosurgical operations. The study group comprised 846 patients treated between October, 1979, and June, 1984. Antibiotics, including cefazolin and gentamicin, were administered only in the immediate preoperative and intraoperative periods. Sixteen patients, none of whom developed infections, were excluded from final statistical analysis because they had inadvertently been entered into the study while failing to meet entry criteria. Fifteen wound infections (3.64%) developed in the group of 412 patients who did not receive antibiotics, whereas only four infections (0.96%) were identified among the 418 patients who received antibiotics. The difference is statistically significant (p = 0.008) and represents a 74% reduction in infection rate with antibiotics. An analysis of subgroups of surgical procedures revealed a dramatic decrease in craniotomy infections from 6.77% to 0% (p = 0.003). Of the four infections that occurred among the antibiotic-treated patients, three were in cases where foreign bodies had been implanted. No complications of antibiotic usage were identified. The rates of infection in areas of the body other than the surgical wound were no different in the antibiotic-treated and nontreated groups. All wound infections in both antibiotic-treated and nontreated patients involved similar types of Gram-positive organisms, suggesting that antibiotic prophylaxis did not produce infections with resistant or unusual organisms. This study, combined with other recently published analyses, suggests that routine perioperative antibiotic prophylaxis can significantly reduce the incidence of postoperative neurosurgical infections.

Adult

Electrical stimulation of the brain for relief of intractable pain due to cancer.

Seventeen patients with intractable pain due to progressive malignancies were treated by electrical stimulation of the brain after more conventional pain therapies applied in the University of California, Los Angeles Cancer Pain Clinic had failed. Electrodes were stereotactically implanted under local anesthesia in the periaqueductal grey (PAG) or periventricular grey (PVG) in 11 patients. In six patients electrodes were placed in both PAG-PVG targets and in the sensory thalamic nuclei. Thirteen of the 17 patients achieved virtually total pain relief and 2 others achieved partial pain relief. At the hospital discharge only 4 of 17 patients required narcotic analgesics for pain relief. Follow-up periods ranged from 1 to 21 months and 6 patients remain alive. Fourteen patients eventually required narcotics for pain relief, usually in the terminal few weeks of their lives. Pain relief was achieved in spite of the fact that all patients were tolerant to large doses of systematically or intraspinally administered narcotics at the time of electrode placement. No complications related to brain stimulation were identified. Brain stimulation is a safe and effective method for treatment of intractable pain due to malignancy in certain patients.

Adult

The DNA between Rz and cosR in bacteriophage lambda is nonessential.

Near the right end of phage lambda DNA, between gene Rz and the cos site, are 2050 bp of apparently non-coding DNA. We have cloned a lambda DNA fragment containing this DNA into a plasmid and constructed a deletion, omega l, extending from a site within the Rz gene to a site about 560 bp from cos. This deletion could be recombined into viable lambda phage at a frequency equal to that observed for the undeleted sequence. Recombinant phage lambda carrying the omega l deletion were demonstrated to have the same burst size and kinetics of phage production as undeleted lambda. The omega l deletion can be used to extend the capacity of lambda cloning vectors and to provide a region for the insertion of heterologous DNA which should exhibit controllable high level expression from the lambda late promoter, p'R.

Bacteriophage lambda