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Biomedical subjects

J T Robertson

Publications and source records attributed to J T Robertson.

At least 37 records · Page 2Linked to original sources

Prostaglandin production after experimental discectomy.

STUDY DESIGN: This study ascertained the effects of discectomy on prostaglandin synthesis. OBJECTIVES: The purpose of these novel experiments was to measure the levels of two prostaglandins in lumbar epidural fluid obtained from an area subjected to discectomy. For comparison, lumbar epidural fluid from a site not disturbed by discectomy and fluid from a subcutaneous site were analyzed for the prostaglandins. SUMMARY OF BACKGROUND DATA: Previous studies have shown that nuclear material obtained from degenerative discs manifests an extraordinarily high level of phospholipase A2 activity. Others have hypothesized that the known inflammatory effects of phospholipase A2 are due to the release of arachidonic acid, which is converted to various eicosanoids, including several algesic prostaglandins (PGI2 and PGE2). No previous study has continuously measured prostaglandin levels in epidural fluid or assessed the effect of discectomy on prostaglandin production. METHODS: An ultrafiltrate of lumbar epidural fluid of dogs was obtained from indwelling catheters located adjacent to spinal areas that were and were not subjected to discectomy as well as from subcutaneous tissue. The fluid was collected daily for 14 days and analyzed for PGE2 and 6-keto PGF1(alpha) (the stable metabolite of PGI2) by radioimmunoassay. RESULTS: The concentration of 6-keto PGF1(alpha) and PGE2 in fluid collected during the first 24 hours was significantly higher in the area of discectomy than in the epidural region that was not subjected to discectomy and significantly higher than in fluid obtained from the subcutaneous site. The high level of these prostaglandins at the discectomy site fell rapidly, so that by the end of 48 hours the differences in values between spinal fluid from the discectomy and nondiscectomy regions were not statistically significant. The concentration of the prostaglandins in epidural fluid decreased with time and became minimal within the second week. CONCLUSION: The removal of normal discs is accompanied for 24 hours by a marked rise in the synthesis of two prostaglandins known to produce pain. Because the concentration of prostaglandins in epidural fluid decreased rapidly thereafter, the initial surge obtained appears to be associated more with chemical factors such as phospholipase A2 than with wound healing.

Animals↗

Abnormalities of p16, p15 and CDK4 genes in recurrent malignant astrocytomas.

Abnormalities in the p16, p15 and CDK4 genes that regulate transition through the G1 phase of the cell cycle have been implicated in the malignant progression of astrocytomas. The results of the present study demonstrate that dysfunction of these genes also occurs during recurrence of glial tumors that were highly malignant at first presentation. Analysis of 10 matched pairs of high grade malignant astrocytomas and their subsequent recurrences identified three distinct groups. The primary and recurrent tumors in Group A did not show structural alterations in the p16, p15 or CDK4 genes, whereas homozygous codeletion of p16 and p15 was observed in both primary and recurrent tumors in Group B. The primary tumors in Group C had a normal profile of p16, p15 and CDK4 at presentation. Upon recurrence, however, the tumors sustained either deletion of p16 alone or codeletion of both p16 and p15 or amplification of CDK4. Analysis of the molecular differences between primary anaplastic astrocytomas/glioblastomas and their subsequent recurrences, which are clinically indistinguishable, may provide better therapeutic options for treatment.

Astrocytoma↗

Role of peridural fibrosis in the failed back: a review.

Failed back surgery syndrome (FBSS) is the presence of persistent, disabling pain in the hip, thigh, leg, or lower back of a patient who has undergone a laminectomy or discectomy. Some degree of FBSS is found in approximately 15% of such patients. There may be a direct relationship between the extent of pathology found during the initial surgical procedure and the probability that FBSS will develop. Although FBSS is usually due to improper diagnosis and surgery, another important cause is peridural fibrosis. Part of the answer may have to do with neuromechanics. In a healthy person, pain associated with dural and nerve root movement does not typically occur when performing activities of daily living. In contrast, in a person with peridural scarring, the dura and nerve roots are bound by fibrosis, and putting traction on the nerve roots and dura by back and limb movement produces pain. This pain is aggravated by the presence of inflammation at the surgical site. Research has shown that disc herniation activates the arachidonic acid cascade, resulting in the production of prostaglandins E1 and E2 and leukotriene B, substances that contribute to an inflammatory process that persists after discectomy. In an attempt to inhibit peridural fibrosis, methylprednisolone, polyethylene films, and fat grafts have been applied to the dura after discectomy. These experimental treatments have had limited success. Development of a therapy that reliably prevents peridural adhesive fibrosis will reduce the incidence of FBSS.

Back↗

Lack of postdiscectomy adhesions following application of ADCON-L: a case report.

STUDY DESIGN: This case study focused on findings in two patients who underwent repeat discectomy following reherniation. OBJECTIVES: The cases are presented to show that use of ADCON-L Anti-Adhesion Barrier Gel can limit the extent of peridural adhesions subsequent to discectomy. Peridural fibrosis has been implicated as one of the principal causes of failed back surgery syndrome following lumbar discectomy. SUMMARY OF BACKGROUND DATA: Accurate assessment of the extent of scarring following lumbar discectomy has been made possible by the use of MR1; however, the only direct means of assessing adhesions is during reoperations to treat reherniations or other causes of surgical failure. METHODS: Both of the initial operations were performed using standard microsurgical procedures. At the end of surgery, one patient received ADCON-L Anti-Adhesion Barrier Gel and the other did not. RESULTS: During the repeat operation, extensive peridural adhesions were found in the patient who did not receive ADCON-L during the initial discectomy procedure. In contrast, essentially neither scar nor adhesions were found in the patient who received ADCON-L. CONCLUSION: ADCON-L effectively inhibits the development of peridural fibrosis following lumbar discectomy. This finding could have implications for the rate of occurrence of failed back surgery syndrome.

Diskectomy↗

Cell attachment to frozen sections of injured adult mouse brain: effects of tenascin antibody and lectin perturbation of wound-related extracellular matrix molecules.

Previous studies describing the use of cryoculture methods have focused on the efficacy of the method for studying neuron attachment and neurite outgrowth on intact sections of nerve, and rodent and even human brain. The cryoculture method has shown promise for determining the presence of cell attachment- and neurite-growth-inhibiting molecules in such specimens, and some studies have also attempted to neutralize such molecules with antibodies to myelin inhibitory proteins, nerve growth factor, or factors present in conditioned media that may counteract the repulsiveness of some of these molecules preserved in sections of, for example, myelinated nerves or adult brain white matter. The present study describes the novel use of lesioned central nervous system cryocultures as substrates for investigating the attachment of embryonic neurons and PC12 cells. In addition to demonstrating the use of this novel scar substrate to extend previous 'scar-in-a-dish' models (David et al. (1990) Neuron, 5:463-469; Rudge and Silver (1990) J. Neurosci., 10: 3594-3603; Rudge et al. (1989) Exp. Neurol., 103: 1-16), the present study also describes antibody and lectin perturbations of putative inhibitory molecules that result in an enhanced attachment of cells to cryosection cultures of brain and spinal cord wounds.

Animals↗

Changes in airway inflammatory cell populations in standardbred racehorses after interferon-alpha administration.

Natural human interferon-alpha (nHuIFN alpha) was administered to actively training Standardbred racehorses with inflammatory airway disease (IAD). Inflammatory airway disease was characterized by poor exercise performance and inflammation and exudate in the upper and lower airway. Placebo, 50, 150, or 450 units(U) of nHuIFN alpha was administered orally for 5 consecutive days to eight horses per treatment group in a double-blind, randomized block design. Response to nHuIFN alpha was monitored by semiquantitative endoscopic examination score and cytologic examination of bronchoalveolar lavage fluid (BALF) performed at baseline (Day 1), Day 8 and Day 15 after initiation of nHuIFN alpha administration. Neutrophil, macrophage, lymphocyte, and nucleated cell counts in BALF were lower (P < 0.05), compared with BALF cell counts in placebo-treated horses 8 days after administration of 50 U and 150 U nHuIFN alpha, and 15 days after administration of 50 U nHuIFN alpha. Neutrophil, lymphocyte and nucleated cell counts were lower than cell counts from placebo-treated horses, 8 days following administration of 450 U nHuIFN alpha. The proportion CD4-, CD5-, and CD8-positive lymphocytes in BALF was not affected by administration of nHuIFN alpha. Oral administration of low-dose nHuIFN alpha reduced inflammation of the lowest respiratory tract in Standardbred racehorses with IAD.

Administration, Oral↗

Surgical results: a justification of the surgeon selection process for the ACAS trial. The ACAS Investigators.

PURPOSE: The selection of surgeons to participate in a prospective randomized trial comparing the efficacy of a surgical method with medical management is critically important because it will have a direct impact on the outcome of the study and the future use of the operation. We report the success of the method used for selecting surgeons who participated in the Asymptomatic Carotid Atherosclerosis Study (ACAS) by examining the surgical morbidity and mortality rates and the outcome of the study. METHODS: A Surgical Management Committee established criteria for auditing surgeons who wished to participate in the study. The parameters included a minimum performance of at least 12 carotid endarterectomies (CEA) per year and an audit of each surgeon's last 50 consecutive CEAs with required documentation of a combined neurologic morbidity and mortality rate of <3.0% for asymptomatic patients and <5.0% for all indications including symptomatic patients. RESULTS: As of February 1991, 164 surgeons from 48 medical centers applied for ACAS participation. One hundred seventeen were approved, and their aggregate experience of 5641 operations yielded a combined neurologic morbidity and mortality rate of 2.3% for asymptomatic and symptomatic patients combined. The morbidity and mortality rate for CEA on asymptomatic patients was 1.7%. These surgeons, plus those recruited after February 1991, became investigators in the ACAS trial and were responsible for the surgical care of 825 patients who were randomized to the surgical arm. Seven hundred twenty-four patients actually underwent CEA. One patient (0.14%) died and ten patients (1.38%) had strokes within the 30-day perioperative interval, for a combined stroke or death incidence of 1.52%. The 5-year stroke event rate in the surgical group (including perioperative morbidity and mortality rates) was 5.1%. compared with 11% of patients treated medically, yielding a relative risk reduction of 53% in favor of surgery (p=0.004). CONCLUSIONS: A method for selecting surgeons for participation in the ACAS trial was successful in providing low perioperative morbidity and mortality rates. This materially influenced the outcome of the study in favor of CEA.

Arteriosclerosis↗

An analysis of perioperative surgical mortality and morbidity in the asymptomatic carotid atherosclerosis study. ACAS Investigators. Asymptomatic Carotid Atherosclerosis Study.

BACKGROUND AND PURPOSE: Our aim was to determine the perioperative morbidity and mortality rates of patients in the surgical arm of the multi-institutional, prospective, randomized Asymptomatic Carotid Atherosclerosis Study (ACAS). METHODS: Of 828 patients with carotid stenosis of 60% or more randomized to the surgical arm of ACAS, 721 underwent carotid endarterectomy (CEA). To qualify for participation, surgeons were required to have performed at least 12 CEAs per year with a combined neurological morbidity and mortality rate no greater than 3% for asymptomatic patients and 5% for symptomatic patients. Clinical centers had to demonstrate arteriographic morbidity less than 1% and mortality less than 0.1% per year. Primary events were stroke and death in the period between randomization and 30 days after surgery; secondary events were transient ischemic attack and myocardial infarction occurring in the same period. RESULTS: Of the 721 patients who underwent CEA, 1 died and 10 others had strokes within 30 days (1.5%). Of the 415 who underwent arteriography after randomization but before CEA, 5 (1.2%) suffered transient ischemic attack or stroke caused by arteriography. Thus, a nearly equal risk of stroke was associated with both CEA and carotid arteriography. In addition, 6 transient ischemic attacks and 3 myocardial infarctions could be directly linked to CEA, for a total CEA event rate of 2.6%. CONCLUSIONS: Patients with asymptomatic internal carotid artery stenosis exceeding 60% reduction in diameter who are acceptable candidates for elective operation may be considered for CEA if the combined arteriographic and surgical complication rates are 3% or less.

Anesthesia↗

Association between peridural scar and recurrent radicular pain after lumbar discectomy: magnetic resonance evaluation. ADCON-L European Study Group.

The purpose of this study was to investigate the presence of any correlation between recurrent radicular pain during the first six months following first surgery for herniated lumbar intervertebral disc and the amount of lumbar peridural fibrosis as defined by MR imaging. 197 patients who underwent first-time single-level unilateral discectomy for lumbar disc herniation were evaluated in a randomized, double-blind, controlled multicenter clinical trial. Clinical assessments, performed by physicians blinded to patient treatment status, were conducted preoperatively and at one and six months postoperatively. The enhanced MR images of the operative site utilized in the analysis were obtained at six months postoperatively. Radicular pain was recorded by the patient using a validated visual analog pain scale in which 0 = no pain and 10 = excruciating pain. The data obtained at the 6 month time point were analyzed for an association between amount of peridural scars as measured by MR imaging and clinical failure as defined by the recurrence of radicular pain. The results showed that the probability of recurrent pain increases when scar score increases. Patients having extensive peridural scar were 3.2 times more likely to experience recurrent radicular pain than those patients with less extensive peridural scarring. In conclusion, this prospective, controlled, randomized, blinded, multicenter study has demonstrated that there is a significant association between the presence of extensive peridural scar and the occurrence of recurrent radicular pain.

Adolescent↗

Persistent back pain and sciatica in the United States: patient characteristics.

Low back pain is an extremely common, seriously disabling, nonfatal public health problem worldwide. The National Low Back Pain Study was a multicenter study of a large, heterogeneous group of patients who have been referred to either a neurosurgeon or an orthopedic surgeon for the evaluation and treatment of a persistent complaint of low back pain. In this paper, we characterize persistent low back pain patients and their complaints, describe the impact of persistent low back pain on the patients' functional and psychological status, report on the patients' medical characteristics, and identify treatments that are currently prescribed for these patients. Persistent low back pain is most common among people in their mid-to-late thirties and early-to-mid forties. The patients are mostly white, well educated, and generally affluent. The majority are gainfully employed, but some quit working because of pain and those who do tend to be less educated, and more likely to be involved in litigation. The average patient has had low back pain intermittently for 10 years. The pain is usually well localized but its severity varies considerably. Besides pain, most persistent low back pain patients report a variety of motor and sensory deficits. Patients also report significant functional impairment at work, at play, and at home. The typical patient does not, however, display significant psychological distress. Most patients have consulted multiple health care providers, have received a variety of treatments, and have used a variety of medications to alleviate pain; a few have been subjected to more aggressive treatment measures including surgery, intradiscal therapy, and narcotic and psychoactive drugs. None of these treatments has been effective. Physical examinations of these patients do not provide significant clues for making a definitive diagnosis. Nonspecific abnormalities such as muscle spasm, tenderness, and trigger points are quite common, but motor weakness and sensory deficits in the lower extremities, and reflex changes in the knees and ankles, are much less common. The classic combination of reflex changes, motor weakness, and sensory deficits associated with specific protruded discs are extremely rare even though one of three patients had a diagnosis of disc herniation. Diagnostic imaging studies revealed that the majority of persistent low back pain patients have spondylotic abnormalities involving root compression or lumbar instability or both, with root compression as the primary cause of the complaint. Myofascial syndrome and lumbar instability were the next most common diagnoses. After a thorough evaluation by specialists in spinal disorders, three of five persistent low back pain patients were prescribed an additional course of conservative therapy, one of five was prescribed surgery, and the rest were prescribed no treatment. Persistent low back pain patients appear to be a distinct group of low back pain patients who are different from patients who have similar nonpersistent acute symptoms and those who have the chronic pain syndrome characterized by significant behavioral and psychological co-morbidities.

Adult↗

Capillary reversed-phase high-performance liquid chromatographic determination of acetyl-methylprednisolone in feline spinal cord.

Capillary reversed-phase high-performance liquid chromatography (RP-HPLC) was used to determine acetylmethylprednisolone (A-MP) that had been administered to feline spinal cord tissue. The method used a 300 mm x 0.32 mm I.D. packed capillary octadecylsilyl (ODS) column and an isocratic mobile phase of 40 mM triethylamine formate (TEAF, pH 3.2)-acetonitrile (50:50, v:v). The chromatographic behavior of A-MP was evaluated with respect to peak-area and peak-height by varying the A-MP concentration (12-190 microM) with a fixed injection volume (1 microliter), and by varying the injection volume (1-10 microliter) with a fixed concentration (12 microM) of A-MP. The limit of detection (signal-to-noise ratio, 3:1) was 250 pg (600 fmol) of synthetic A-MP. Various amounts of A-MP directly spiked into feline spinal cord segments were solvent extracted, separated, and plotted against peak-area (r2 = 1.00). Background tissue without A-MP gives minimal (< 1%) interference at 243 nm. The method also detects exogenous A-MP that was administered into feline spinal cord via an intrathecal injection. Furthermore, the presence of A-MP was confirmed via its molecular ion and corresponding product ions that were obtained by fast-atom bombardment tandem mass spectrometry (FAB-MS-MS).

Animals↗

Results of a randomized trial comparing intra-arterial cisplatin and intravenous PCNU for the treatment of primary brain tumors in adults: Brain Tumor Cooperative Group trial 8420A.

PURPOSE: To test the efficacy of intra-arterial (IA) cisplatin versus intravenous (IV) PCNU for treating primary brain tumors, in a randomized trial (Brain Tumor Cooperative Group [BTCG] Trial 8420A). METHODS: 311 adult patients (ages 19-79 years; median 45) with supratentorial tumors (confirmed histologically) were randomized by nine participating institutions. Patients were required to have completed radiotherapy (4500-6020 cGy to the tumor bed) before randomization. Patients were stratified as either nonprogressive (clinically and radiologically stable) or progressive. Results were analyzed for the 311 patients in the randomized population (RP), and for the 281 patients in the Valid Study Group (VSG) meeting protocol eligibility requirements. 56% of patients in the VSG had glioblastoma multiforme, 33% had other malignant glioma, and 11% had low-grade glioma. 64% were stratified as progressive. 12% had received prior chemotherapy. RESULTS: The group randomized to PCNU had the longer survival (p = 0.06 for the RP, p = 0.07 for the VSG). In the VSG, median survival was 10 months for the cisplatin group, 13 months for the PCNU group. The difference between treatment groups was significant (p < or = 0.02) when adjusted for important prognostic factors. PCNU lead to greater hematotoxicity; cisplatin lead to greater renal toxicity and some ototoxicity. Some cisplatin patients experienced complications associated with IA administration, including six cases of encephalopathy. CONCLUSION: The trial showed a survival advantage to the group randomized to PCNU, although the difference was modest. Coupled with previous BTCG results, these trails suggest that PCNU is an active drug for brain tumors.

Adult↗

Opioid and tachykinin neuropeptides in prolactin-secreting human pituitary adenomas.

Two opioid neuropeptides, methionine enkephalin (ME) and beta-endorphin (BE), and one tachykinin neuropeptide, substance P (SP), were quantified in 10 prolactin (PRL)-secreting human pituitary adenomas and in 10 control human pituitaries. Immunohistochemical techniques provided appropriate staining for PRL. Reversed-phase high performance liquid chromatography (RP-HPLC) was used to purify these three neuropeptides before their analysis, radioimmunoassay (RIA) was used for the quantification of SP-like immunoreactivity (SP-LI), and liquid secondary-ion mass spectrometry (LSIMS) was used for the qualitative and quantitative analysis of ME and a tryptic peptide of BE. This study shows that, for 90% of the cases studied here (excluding one hypothyroidism case), the tachykinin A neuropeptide SP-LI level is decreased, the POMC peptide BE level is not altered, and the proenkephalin A neuropeptide ME level is increased in these PRL-secreting tumors.

Adenoma↗

Prognostic factors after acute subdural hematoma.

Factors that have been shown to affect outcome after acute subdural hematoma (ASDH) include age, Injury Severity Score (ISS), intracranial pressure (ICP), direct admission to a trauma center, presence of subarachnoid hemorrhage, score on the Glasgow Coma Scale (GCS), and timing of operation. However, these data come from selected patient populations (e.g., operated, comatose, or minimally symptomatic patients, etc.). In an effort to evaluate factors that predict outcome for the entire spectrum of ASDH patients, we evaluated 211 patients with ASDH and GCS scores of 3 to 15. One hundred twenty-eight patients (61%) were managed nonoperatively (Nonop), whereas 83 (39%) were managed with craniotomy [operatively (Op)]. Op patients had more severe brain injuries, as evidenced by their lower GCS scores (Op 7.8 vs. Nonop 10.7, p = 0.0001), higher incidence of large ASDH with midline shift (Op 61% large ASDH, 83% midline shift vs. Nonop 16% large ASDH, 30% midline shift, p = 0.001 for each comparison), and higher incidence of basilar cistern effacement (Op 61% vs. Nonop 21%, p = 0.001). Thirty-five percent of the Op patients had their hematoma evacuated within 4 hours (early), whereas 65% did not (delayed). Early Op patients had a significantly lower incidence of functional survival (early = 24% vs. delayed = 51%, p = 0.02). The early patients seem to have had more significant head injuries, as evidenced by their lower GCS scores (early = 7.0 vs. delayed = 8.4), higher incidence of associated intracranial injuries (early = 1.14 vs. delayed = 0.85), and higher incidence of cistern effacement (early = 76% vs. delayed = 53%, p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Detection of loss of cerebral vascular tone by correlation of arterial and intracranial pressure signals.

With the use of a laboratory model, arterial and intracranial pressure signals were obtained under conditions of intact regulation of cerebral blood flow and massive dilation. During elevated intracranial pressure and intact regulation, positive pressure inhalation appears to briefly occlude venous flow into the cranial sinuses during inspiration. As a result, the intracranial pressure and arterial pressure signals are not similar. In contrast, when maximal dilation causes failure of regulation of cerebral blood flow, the intracranial pressure signal is approximately proportional to the arterial pressure signal. Comparison of the cross-correlation function derived from the intracranial and arterial pressure signals to the autocorrelation function of the arterial signal reveals that the two correlation functions are: 1) different during intact regulation and 2) nearly identical during dilation induced failure of regulation of cerebral blood flow.

Animals↗

Cytologic evaluation of bronchoalveolar lavage fluid obtained from standardbred racehorses with inflammatory airway disease.

Cytologic examination of bronchoalveolar lavage fluid (BALF), including phenotypic analysis of lymphocytes, was performed on 32 Standardbreds with poor race performance and endoscopic examination findings characteristic of inflammatory airway disease (IAD). Nucleated cell counts in BALF from IAD-affected horses were higher than those in control horses; the cytologic profile of BALF in affected horses included mixed inflammation, characterized by mild neutrophilia, lymphocytosis, and monocytosis. Eosinophil and mast cell counts were not higher in the IAD-affected group, compared with those in the control group; however, 4 IAD-affected horses had marked eosinophilia (24.7 +/- 4.8% SEM) in BALF. Phenotypic analysis of lymphocytes in BALF obtained from IAD-affected horses revealed a low proportion of CD4-positive cells and B cells, compared with those in the control group; these findings may have been representative of a greater proportion of non-B, non-T cells (null cells) in horses with IAD. The cytologic profile of BALF obtained from horses with IAD differed from that in horses affected with chronic obstructive pulmonary disease, suggesting that the pathogenesis of inflammation in horses with IAD may differ from that of chronic obstructive pulmonary disease.

Animals↗