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Biomedical subjects

J Ratliff

Publications and source records attributed to J Ratliff.

At least 19 recordsLinked to original sources

Root and spinal cord compression from methylmethacrylate vertebroplasty.

STUDY DESIGN: Case report and literature review. OBJECTIVES: Clinicians use methylmethacrylate vertebroplasty to treat vertebral hemangiomas, metastases, and osteoporotic fractures. Cement may leak out of the vertebral body and compress the adjacent spinal cord and nerve roots. We review a case of nerve-root and cord compression from methylmethacrylate extrusion during vertebroplasty. SUMMARY OF BACKGROUND DATA: A 50-year-old female presented with disabling thoracic back pain. A metastasis to T1 was discovered, with collapse of the vertebral body but without cord compression. Methylmethacrylate vertebroplasty was performed. After injection, portable computed tomography (CT) showed a leakage of methylmethacrylate into the C8 and T1 foramina and spinal canal. Radiculopathy and myelopathy developed. Surgical decompression using the anterior approach was necessary. METHODS: Case report. RESULTS: Early surgical intervention decompressed the neural elements and relieved the neurological deficits. CONCLUSIONS: Neurologic complications of methylmethacrylate vertebroplasty necessitate active involvement of spine surgeons in patient evaluation and management.

Back Pain↗

Outcome study of surgical treatment for axial neck pain.

BACKGROUND: We reviewed our surgical treatment of chronic axial cervical pain over a 4-year period to determine whether surgery in selected cases was associated with favorable outcomes. METHODS: We retrospectively studied 27 consecutive cases (20 patients with follow-up) of longstanding axial cervical spine pain treated surgically by a single surgeon from June 1994 through August 1998. Diagnostic workup included the following when appropriate: Minnesota Multiphasic Personality Inventory (MMPI) with interview, provocative diskography (with a nonpainful control level), single photon emission computed tomography (SPECT), and diagnostic facet injection. Twenty patients (74%) responded to a postoperative telephone survey. RESULTS: For general outcome measures, 85% of patients reported satisfaction with pain relief and surgical result. Ninety-five percent stated they would repeat the procedure; 85% manifested improvement in Prolo score. CONCLUSIONS: Surgical treatment of chronic axial neck pain, when preceded by thorough evaluation, can yield excellent clinical results.

Adult↗

Gunshot wounds to the neck.

Gunshot wounds to the neck are diagnostically and therapeutically challenging cases. We report such a case with vascular and neurologic injuries and describe the therapeutic options. Initial treatment is aimed at hemodynamic stabilization. Zone II neck injuries are managed selectively, and physical examination alone may dictate emergency surgical exploration. Spinal cord injury must be suspected and assessed clinically, as well as by computed tomography and angiography. Deteriorating or stable neurologic status and cord compression by bullet or bone fragments require surgical decompression. Improving neurologic status may be managed conservatively. In gunshot wounds to the neck, treatment should be individualized and multidisciplinary.

Adult↗

Osteochondroma of the C5 lamina with cord compression: case report and review of the literature.

STUDY DESIGN: Case report of a solitary osteochondroma of the cervical spine causing myelopathy in a 66-year-old woman. OBJECTIVES: To review the relevant literature and describe a highly unusual clinical manifestation of solitary osteochondroma. SUMMARY OF BACKGROUND DATA: Osteochondromas are common benign bony lesions that seldom occur in the axial skeleton. These lesions are more commonly reported with neural compression in cases of hereditary multiple exostoses (Bessel-Hagel syndrome, diaphyseal aclasis). METHODS: Chart review, review of relevant radiographic examinations and histopathologic specimens, clinical follow-up with examination, and literature review. RESULTS: Manifestation with new neurologic deficit in a 66-year-old patient was singular. CONCLUSIONS: Osteochondromas are unusual in the axial skeleton, and are rarely signaled by neural compression. Occurrence is generally in young adults in the second and third decades. Initial manifestation with a new neurologic deficit in a 66-year-old patient was highly unusual.

Aged↗

Increased MRI signal intensity in association with myelopathy and cervical instability: case report and review of the literature.

BACKGROUND: Increased T2-weighted signal intensity in patients with cervical myelopathy has been extensively reviewed in the literature. A variety of etiologies with similar MRI appearances have been described; attempt at correlation of MRI findings with clinical presentation and outcomes after treatment has led to a limited consensus. METHODS: We present a case of cervical myelopathy with associated hyperintense T2-weighted signal characteristics, secondary to cervical spondylosis and instability. RESULTS: Rapid resolution of radiographic abnormalities after surgical decompression and fusion was noted. Clinical improvement did not parallel radiographic resolution. CONCLUSION: These findings are important in considering the pathophysiology of MRI changes in cervical myelopathy.

Aged↗

Long-term survival of fetal porcine lateral ganglionic eminence cells in the hippocampus of rats.

Embryonic porcine brain tissue from the lateral ganglionic eminence was transplanted into the adult rat hippocampus to determine whether fetal striatal cells could survive, differentiate, and integrate in a heterotopic site. The hippocampus, a common site of epileptic seizure activity, was chosen to determine if fetal striatal cells could supply inhibitory GABAergic neurons that may serve to block seizures. Cells were either implanted with a single deposit using a standard metal cannula or by five smaller disseminated deposits with a glass micropipette. At 20-24 weeks, animals immunosuppressed with cyclosporin showed long-term survival of porcine cells in the adult hippocampus. Analysis by immunohistochemistry and in situ hybridization showed that the grafts contained glial and neuronal cell types, including GABAergic neurons within graft core and networks of porcine neuronal fibers extending from the graft into the host parenchyma. In addition, a marker of porcine presynaptic terminals, synaptobrevin, was abundant within the grafts and was found associated with hippocampal structures and cell layers suggesting functional integration of grafted cells within the host. The survival of xenografts in the hippocampus and potential integration of inhibitory components provides evidence that these grafts may serve as an internal negative feedback mechanism to quench epileptiform activity.

Animals↗

Tethered cord syndrome in adults.

Adult onset of tethered cord syndrome is a rare pathologic entity. Its treatable nature makes early diagnosis and timely surgical intervention important goals. Because of present referral patterns, adult patients with tethered cord syndrome may present initially to their primary care physician. We present a recent representative case of adult-onset tethered cord syndrome, with emphasis on initial complaints and the symptom constellation relevant to the primary care physician. Thorough clinical history and physical examination should direct investigators to include tethered cord syndrome in the differential diagnosis of select patients.

Adult↗

Arteriovenous fistula with associated aneurysms coexisting with dural arteriovenous malformation of the anterior inferior falx. Case report and review of the literature.

This 24-year-old man presented with an unusual case of a high-flow arteriovenous fistula (AVF). This lesion was similar to giant AVFs in children that have been previously described in the literature. In patients in whom abnormalities of the vein of Galen have been excluded and in whom presentation occurs after 20 years of age, a diagnosis of congenital AVF is quite unusual. The fistula in this case originated in an enlarged callosomarginal artery and drained into the superior sagittal sinus via a saccular vascular abnormality. Two giant aneurysmal dilations of the fistula were present. In an associated finding, a small falcine dural arteriovenous malformation (AVM) was also present. Arterial supply to the AVM arose from both external carotid arteries and the left vertebral artery, with drainage through an aberrant vein in the region of the inferior sagittal sinus into the vein of Galen. Craniotomy with exposure and trapping of the AVF was performed, with subsequent radiosurgical (linear accelerator) treatment of the dural AVM. Through this combination of microsurgical trapping of the AVF and radiotherapy of the dural AVM, an excellent clinical outcome was achieved.

Adult↗

Regulated expression of the homeobox gene, rPtx2, in the developing rat.

Using degenerate primers designed to amplify genes containing homeodomains, we have used reverse transcription and polymerase chain reaction to amplify and clone a rat homeobox gene. Based on the nucleotide and predicted amino acid sequences, the rat cDNA clone contains a high degree of sequence similarity to murine genes which are members of the paired-like class of homeobox genes (Ptx2, Otlx2, solurshin and Ptx1). Considering the high degree of sequence similarity and similar restricted expression patterns, we have named the cloned rat gene rPtx2 (rat Ptx2 homolog). Northern analysis revealed two rPtx2 transcripts expressed in the developing rat brain. Yet, only a single gene was detected by Southern blot hybridization, suggesting that multiple messages are the result of alternative transcriptional initiation, splicing or processing of a common message. The expression pattern of rPtx2 was further delineated by in situ hybridization to rat embryos. Within the brain, tissue specific expression was observed in the differentiating neural cells of the posterior hypothalamus, tegmentum, and rhombomere r1. Expression was also observed in the developing pituitary, maxilla, mandible, tongue and umbilical cord. To further study the control of Ptx2 gene expression, we used an in vitro model for neural differentiation by treating mouse embryonic stem cells with retinoic acid. Within 24 h and prior to detection of a neural phenotype in the culture, murine Ptx transcripts were induced and remained elevated for at least 6 days. This suggests that retinoic acid may be an important inductive signal which regulates the developmental and tissue-specific expression of Ptx2.

Aging↗

Embryonic stem cells as a model for studying regulation of cellular differentiation.

Mouse embryonic stem (ES) cells can be differentiated in vitro into near homogeneous populations of both neurons and skeletal muscle as well as other cell types. We previously showed that treatment of pluripotent ES cells with retinoic acid (RA) induced differentiation into highly enriched populations of gamma-aminobutyric acid (GABA) expressing neurons. The reasons for generation of only GABA neurons as opposed to other neuronal cell types were not known. We have extended our previous work and now show that with RA induction of ES cells we not only obtain GABA neurons, but also dopaminergic neurons. Critical for the production of dopaminergic neurons after RA induction was the post-induction plating conditions used. No dopaminergic neurons were detected if cells were plated in serum-free media optimized for neuronal survival. However, significant numbers of dopamine neurons could be detected when cells were plated in media containing fetal calf serum. These observations support the conclusion that RA acts as a general neural inducing agent and that conditions post-induction either selectively support survival of a particular class of neuronal cells or that the conditions post-induction actually further instruct cells to differentiate into different types of neurons.

Animals↗

Blastula-stage stem cells can differentiate into dopaminergic and serotonergic neurons after transplantation.

In order to assess the potential of embryonic stem cells to undergo neuronal differentiation in vivo, totipotent stem cells from mouse blastocysts (D3 and E14TG2a; previously expanded in the presence of leukemia inhibitory factor) were transplanted, with or without retinoic acid pretreatment, into adult mouse brain, adult lesioned rat brain, and into the mouse kidney capsule. Intracerebral grafts survived in 61% of cyclosporine immunosuppressed rats and 100% of mouse hosts, exhibited variable size and morphology, and both intracerebral and kidney capsule grafts developed large numbers of cells exhibiting neuronal morphology and immunoreactivity for neurofilament, neuron-specific enolase, tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), and cells immunoreactive for glial fibrillary acidic protein. Though graft size and histology were variable, typical grafts of 5-10 mm3 contained 10-20,000 TH+ neurons, whereas dopamine-beta-hydroxylase+ cells were rare. Most grafts also included nonneuronal regions. In intracerebral grafts, large numbers of astrocytes immunoreactive for glial fibrillary acidic protein were present. Both TH+ and 5-HT+ axons from intracerebral grafts grew into regions of the dopamine-lesioned host striatum. TH+ axons grew preferentially into striatal gray matter, while 5-HT+ axons showed no white/gray matter preference. These findings demonstrate that transplantation to the brain or kidney capsule can induce a significant fraction of totipotent embryonic stem cells to become putative dopaminergic or serotonergic neurons and that when transplanted to the brain these neurons are capable of innervating the adult host striatum.

Animals↗

Fetal pig neural cells as a restorative therapy for neurodegenerative disease.

With proper immunosuppression, interspecies transplantation of porcine as well as other species of neural cells survive, mature, and integrate into the host in a manner which reconstructs much of the appropriate neural circuitry. These transplants have been shown to alleviate many of the symptoms of various disorders of the central nervous system. In this study, we addressed immunological and maturation issues with regards to intracerebral transplantation of fetal porcine neural cells. First, we compared fetal neural xenograft survival in athymic nude rats versus rats immunosuppressed with cyclosporin A and found that there is little discernible difference between porcine grafts in the 2 recipients. We also found that ectopic transplantation of cells isolated from the porcine striatal primordium can survive and develop into grafts composed of both neuronal and glial phenotypes within the rat hippocampus. This fact raises the possibility that cells of a particular neurotransmitter type (e.g., GABAergic cells) developing from the striatal precursor cells can be transplanted outside the striatum of the adult brain and have physiological effects.

Animals↗

Cholesterol levels in 1,084 healthy New Orleans males.

It is widely recognized that elevated cholesterol levels constitute a major risk factor for the development of atherosclerosis and coronary heart disease. Most of the previous surveys conducted in an effort to learn more about incidence of hypercholesterolemia involved patients who had other concurrent risk factors such as hypertension, obesity, diabetes mellitus, cigarette smoking, or a history of myocardial infarction. Relatively few studies have been conducted in younger populations or in healthy individuals. Because we had access to baseline cholesterol data on 1,084 relatively young, otherwise completely healthy, nonobese males, we elected to determine the prevalence of hypercholesterolemia in this population. Elevated cholesterol levels (> 200 mg/dL) were found in 25.2% of our healthy subjects. These findings help to confirm the presence of a potentially serious public health problem existing among otherwise healthy, relatively young men in our community.

Adult↗

Therapeutic touch and post-Hurricane Hugo stress.

This repeated-session design sought to answer questions about the effectiveness of therapeutic touch in reduction of stress for 23 individuals following a natural disaster. In addition, methodological issues related to the average length of time for a therapeutic-touch treatment and a method of documenting the nonverbal interaction between subject and toucher were investigated. Findings indicate that stressed people report themselves to be less stressed following therapeutic touch (p = .05). Time of therapeutic-touch intervention varied significantly between the touchers, with a range of 6.8 to 20 minutes. Qualitative data examining the interaction of toucher and subject raised a number of questions that require further study.

Adolescent↗

The mechanism of differential sensitivity to methotrexate of normal and malignant human epidermal cells.

Squamous carcinoma cells are much more sensitive (greater than 10(4) times) to the cytotoxic effects of methotrexate (MTX) and 5-fluorodeoxyuridine (FUDR) than are normal human keratinocytes as measured by cell growth. Among the drugs tested, this phenomenon was found to be specific for MTX and FUDR, since arabinosylcytidine (ARA-C), 13-bis-chloroethylnitrosourea (BCNU), and daunomycin failed to show differences in inhibition between the normal and malignant cell lines. Drug uptake studies did not reveal a significant difference in MTX intracellular levels between malignant and normal epidermal cell lines at 60 min. Thymidine (TdR) salvage was assessed by examining the effects of the presence of 3 microM TdR on MTX-induced cytotoxicity. On the withdrawal of TdR, normal cells demonstrated an increased level of inhibition amounting to 4 orders of magnitude, whereas the squamous-cell carcinoma cells showed no change in sensitivity. Interestingly, the immortal nontumorigenic keratinocyte line (NM-110) was similarly not rescued by the addition of TdR. The high degree of sensitivity TO MTX shown by squamous-cell carcinoma (SCC) and NM-110 cells is attributable to a significant diminution of their ability to use exogenous TdR as compared with that of normal keratinocytes and might be indicative of a biochemical change associated with cellular immortality.

Carcinoma, Squamous Cell↗

Inhibition of thymidylate synthase in intact L1210 cells by ara-C, daunomycin, hydroxyurea and 3,4-dihydroxybenzylamine.

The use of an in situ assay for thymidylate synthase has shown that a variety of clinically important drugs, including arabinofuranosylcytosine, hydroxyurea, and daunomycin, inhibit thymidylate synthase in intact cells. In contrast to the inhibition observed with 5-fluorodeoxyuridine, inhibition occurs by an indirect mechanism, is delayed in onset, and is incomplete. Inhibition occurred at concentrations that corresponded to those that inhibit DNA synthesis, suggesting that this phenomenon might contribute to the biological action of these agents. Since the inhibition of thymidylate synthase by this indirect mechanism appears to be a general property of drugs that inhibit DNA synthesis, our findings may have important implications for the mechanism of killing of tumor cells, as well as the rationale for combination regimens.

Animals↗

Antitumor effects of L-glutamic acid dihydroxyanilides against experimental melanoma.

L-glutamic acid, gamma-(p-hydroxyanilide), is a naturally occurring metabolic inhibitor found in mushrooms and shown to be active against B-16 melanoma in vivo. We have prepared and evaluated 2 analogs, the 3,4- and 2,5-dihydroxy derivatives, since these might represent more immediate precursors to the putative biologically active quinone. Both dihydroxy derivatives were more toxic than the parent phenol. The 2,5-dihydroxy derivative was significantly more cytotoxic with a 5-fold decrease in IC50 for both human and B-16 melanoma cells in vitro. In the presence of mushroom tyrosinase, both derivatives were potent inhibitors of isolated DNA polymerase with essentially complete inhibition occurring at concentrations of 10(-5) M. The 3,4-dihydroxy derivative exerted inhibitory effects primarily upon thymidine incorporation into melanoma cells in vitro while the 2,5-dihydroxy derivative also inhibited uridine and leucine incorporation. There was no significant antitumor activity observed in the B-16 system, a fact which might be attributed to the increased toxicity of the compounds.

Anilides↗