Biomedical subjects
M A Murphy
Publications and source records attributed to M A Murphy.
Subjects with seasonal allergic rhinitis and nonrhinitic subjects react differentially to nasal provocation with chlorine gas.
BACKGROUND: Nasal irritation and associated symptoms (nasal congestion, rhinorrhea, and sinus headache) are important elements of the response to indoor and outdoor air pollution. Marked interindividual variability in such symptoms has been suggested clinically and epidemiologically, but little experimental data exist on this issue. OBJECTIVE: We sought to test the hypothesis that subjects with seasonal allergic rhinitis (SAR) exhibit a more marked physiologic response (congestion) after nasal irritant provocation than do nonrhinitic subjects. METHODS: We studied eight subjects with SAR and eight nonrhinitic subjects; subjects with SAR were studied out of season. In a single-blind crossover study, subjects had their nasal airway resistance (NAR) measured in triplicate before, immediately after, and 15 minutes after a 15-minute exposure to either filtered air or 0.5 ppm chlorine in filtered air, administered through a nasal mask in a climate-controlled chamber. Log-transformed NAR values were analyzed in a repeated-measures analysis of variance model, with confirmatory testing using paired t tests. RESULTS: The net (chlorine minus air day) percent change in NAR from baseline (before exposure) to immediately after exposure was +24% in the SAR group and +3% in the nonrhinitic group (p < 0.05). The corresponding net changes from baseline to 15 minutes after exposure were +21% in the SAR group and -1% in the nonrhinitic group (p < 0.05). CONCLUSIONS: The observed augmented nasal congestive response of subjects with SAR versus nonrhinitic subjects to a controlled low-level chemical irritant provocation is consistent with epidemiologic surveys showing a higher prevalence of nasal symptoms among subjects with SAR than nonrhinitic subjects in environments involving irritant air pollutants.
Tissue hyperplasia and enhanced T-cell signalling via ZAP-70 in c-Cbl-deficient mice.
The c-Cbl protein is tyrosine phosphorylated and forms complexes with a wide range of signalling partners in response to various growth factors. How c-Cbl interacts with proteins, such as Grb2, phosphatidylinositol 3-kinase, and phosphorylated receptors, is well understood, but its role in these complexes is unclear. Recently, the Caenorhabditis elegans Cbl homolog, Sli-1, was shown to act as a negative regulator of epidermal growth factor receptor signalling. This finding forced a reassessment of the role of Cbl proteins and highlighted the desirability of testing genetically whether c-Cbl acts as a negative regulator of mammalian signalling. Here we investigate the role of c-Cbl in development and homeostasis in mice by targeted disruption of the c-Cbl locus. c-Cbl-deficient mice were viable, fertile, and outwardly normal in appearance. Bone development and remodelling also appeared normal in c-Cbl mutants, despite a previously reported requirement for c-Cbl in osteoclast function. However, consistent with a high level of expression of c-Cbl in the hemopoietic compartment, c-Cbl-deficient mice displayed marked changes in their hemopoietic profiles, including altered T-cell receptor expression, lymphoid hyperplasia, and primary splenic extramedullary hemopoiesis. The mammary fat pads of mutant female mice also showed increased ductal density and branching compared to those of their wild-type littermates, indicating an unanticipated role for c-Cbl in regulating mammary growth. Collectively, the hyperplastic histological changes seen in c-Cbl mutant mice are indicative of a normal role for c-Cbl in negatively regulating signalling events that control cell growth. Consistent with this view, we observed greatly increased intracellular protein tyrosine phosphorylation in thymocytes following CD3epsilon cross-linking. In particular, phosphorylation of ZAP-70 kinase in thymocytes was uncoupled from a requirement for CD4-mediated Lck activation. This study provides the first biochemical characterization of any organism that is deficient in a member of this unique protein family. Our findings demonstrate critical roles for c-Cbl in hemopoiesis and in controlling cellular proliferation and signalling by the Syk/ZAP-70 family of protein kinases.
First person account: meaning of psychoses.
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Paraneoplastic retinopathy: a novel autoantibody reaction associated with small-cell lung carcinoma.
We present the case of a 74-year-old man with rapidly progressive bilateral visual loss, optic disc pallor, retinal arteriolar attenuation, and an abnormal electroretinogram with a 90% reduction in cone function and a 50% reduction in rod function. He was examined for a suspected cancer-associated retinopathy (CAR). Although he was found not to have expressed the previously reported 23-kd CAR antibody, high titers were found of an antibody to a 60-kd retinal protein, which as yet remains unidentified. An initial clinical search for an underlying cancer was unsuccessful, but 2 months later a mediastinal mass was found on chest x-rays, and biopsy confirmed a diagnosis of small-cell lung carcinoma. Combined therapy with oral corticosteroids and plasmapheresis resulted in a recovery of vision from counting fingers to 20/200 in the right eye and 20/40 to 20/25 in the left eye. Conventional chemotherapeutic management of the small-cell lung carcinoma was instituted, and the modest visual recovery was maintained. The visual improvement as well as lung tumor regression were accompanied by a decline in antibody titers from 1:2,000 pretreatment to 1:200 during the course of therapy. The absence of reactivity with the previously described 23-kd retinal antigen of the CAR syndrome does not exclude the diagnosis of paraneoplastic retinopathy in patients fitting the clinical profile of this disease.
Bilateral diffuse uveal melanocytic proliferation simulating an arteriovenous fistula.
Bilateral diffuse uveal melanocytic proliferation is a rare paraneoplastic syndrome that causes visual loss in patients with systemic carcinoma. We report the case of a patient with this syndrome whose initial presentation and striking anterior segment findings mimicked that of an arteriovenous fistula.
Congenital optic tract syndrome: magnetic resonance imaging and scanning laser ophthalmoscopy findings.
Lesions of the optic tract produce a distinctive pattern of optic atrophy and visual field loss and may be due to either congenital or acquired causes. We report a case of a congenital optic tract syndrome and correlate the magnetic resonance imaging findings with the appearance of nerve fiber layer defects found by confocal scanning laser ophthalmoscopy.
Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)
Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic, neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65%, brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of the collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20-78, most patients falling in the moderate range of mental retardation at 40-54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter.
Antibiotic penetration into cervical discs.
Antibiotics are frequently prophylactically administered in surgical procedures to reduce the incidence of infection. The penetration of antibiotics into lumbar discs has been studied with mixed results, but penetration into cervical discs has not been reviewed. In this study, we examined the penetration of two commonly used antibiotics, oxacillin and cefazolin, into cervical discs. Eighteen patients with a total of 30 discs removed were studied. Two groups, each consisting of four patients with five discs removed, received either 1 g of oxacillin or 1 g of cefazolin by a single, preoperative intravenous infusion. Two other groups, each consisting of five patients with 10 discs removed, received either 2 g of oxacillin or 2 g of cefazolin, also by a single, preoperative intravenous infusion. A blood specimen, from which serum antibiotic levels were determined, was obtained from each patient simultaneously with each discectomy. The time interval between the antibiotic infusion and discectomy/phlebotomy was also recorded. Antibiotic levels were detected in all discs removed but were quantifiable in only 12. Nine of these 12 had been exposed to cefazolin. Of these nine discs, one was from a patient who had received 1 g whereas the other eight were from patients who had received 2 g of cefazolin. This represents 80% of the removed discs exposed to 2 g of cefazolin (10 discs total) and 20% exposed to 1 g (5 discs total). The remaining three discs with quantifiable antibiotic levels had been exposed to 2 g of oxacillin, which represents 30% of the discs (10 total) exposed to that dose of oxacillin. Although cervical disc space infections are rare, they are serious.(ABSTRACT TRUNCATED AT 250 WORDS)
Typological description of the chronic low back-pain syndrome using the Million Behavioral Health Inventory.
The Million Behavioral Health Inventory was administered to 67 individuals with chronic low back pain who participated in a rehabilitation program on pain and stress. Base-rate scores from the 20 scales, submitted to cluster analysis using Ward's minimum variance method, gave four subtypes. Discriminant analysis accurately classified 98.51% of the sample. The discriminant functions were interpreted and labeled as I: somatic distress and II: inhibition-dependency. The groups were then examined for differences and similarities with respect to those dimensions, and the groups were labeled I-introversive, II-denial/minimizers, III-conformers, and IV-severe psychophysiological reaction. The types were next compared across medical, vocational, and demographic data. With the exception of sex of subject, no other data were significant by type. The results were discussed, and recommendations for research were made.
Application of frameless stereotaxy to pedicle screw fixation of the spine.
Interactive frameless stereotaxy has been successfully applied to intracranial surgery. It has contributed to the improved localization of deep-seated brain lesions and has demonstrated a potential for reducing both operative time and morbidity. However, it has not been as effectively applied to spinal surgery. The authors describe the application of frameless stereotactic techniques to spinal surgery, specifically pedicle screw fixation of the lumbosacral spine. Preoperative axial computerized tomography (CT) images of the appropriate spinal segments are obtained and loaded onto a high-speed graphics supercomputer workstation. Intraoperatively, these images can be linked to the appropriate spinal anatomy by a sonic localization digitizer device that is interfaced with the computer workstation. This permits the surgeon to place a pointing device (sonic wand) on any exposed spinal bone landmark in the operative field and obtain multiplanar reconstructed CT images projected in near-real time on the workstation screen. The images can be manipulated to assist the surgeon in determining the proper entry point for a pedicle screw as well as defining the appropriate trajectory in the axial and sagittal planes. It can also define the correct screw length and diameter for each pedicle to be instrumented. The authors applied this device to the insertion of 150 screws into the lumbosacral spines of 30 patients. One hundred forty-nine screws were assessed to be satisfactorily placed by postoperative CT and plain film radiography. In this report the authors discuss their use of this device in the clinical setting and review their preliminary results of frameless stereotaxy applied to spinal surgery. On the basis of their findings, the authors conclude that frameless stereotactic technology can be successfully applied to spinal surgery.
Changes in the cervical foraminal area after anterior discectomy with and without a graft.
A controversial point in the management of patients undergoing anterior cervical discectomy is whether an interbody bone graft should be used. Proponents of interbody grafting claim that without a graft, the disc height and the area of the foramina at that level will decrease postoperatively with the potential for persistent symptoms and/or the development of a radiculopathy. Using a two-dimensional digital planimeter, we measured the cross-sectional area (cm2) of cervical foramina on preoperative and postoperative oblique films in patients undergoing anterior cervical discectomy. Group A patients underwent the insertion of an interbody graft after the discectomy; Group B patients did not. Our results indicate that in all the patients in Group A, there was a statistically significant increase in the area of the foramina (P < 0.001) and in Group B, a statistically significant decrease (P = 0.0005). However, when the absolute change in magnitude of the foramina was measured, without respect to an increase or decrease, there was no statistically significant difference (P > 0.8). There was no statistically significant difference (P = 1.000) in the outcome between the two groups. From an anatomical standpoint, our data support the insertion of an interbody graft if the surgeon wishes to increase the area of the foramen. However, the overall magnitude of change is not significant, which may be a factor in why the clinical outcome is similar in both groups.
Anaplastic astrocytoma with granular cell differentiation: case report and review of the literature.
In contrast to the relatively common soft tissue form of granular cell tumor (GCT), intercerebral GCTs are rare neoplasms. The Schwann cell is the accepted cell of origin for soft tissue GCTs. However, the origin of intracerebral tumors is controversial. We report a case of a GCT intimately associated with an anaplastic astrocytoma. Immunohistochemical staining with glial fibrillary acidic protein demonstrated focal positive staining within the granular cells. Six GCTs from other body sites were stained with glial fibrillary acidic protein for comparison and all were negative. The granular cell component was diffusely positive for S-100 and negative for epithelial membrane antigen and cytokeratin. Ultrastructurally, filaments characteristic of astrocytic cells were demonstrated within some granular cells. Based on our light microscopic, electron microscopic, and immunohistochemical findings, the granular cell component of this anaplastic astrocytoma is likely astrocytic in origin. We propose that these tumors be designated astrocytic neoplasms with granular cell differentiation and their prognoses dictated by the grade of the glial component.
Extradural haematoma after temporomandibular joint arthroscopy. A case report.
A case report of an extradural haematoma (EDH) after temporomandibular joint arthroscopy is presented. The possible cause of this unusual occurrence is discussed.
An epithelial cyst of the suprasellar region.
A case of a 26 year old woman with increasing headaches due to a suprasellar cyst is described. Histology was consistent with an epithelial cyst with features resembling both Rathke's cleft cysts and enterogenous cysts. The differential diagnosis and treatment of suprasellar cysts is discussed.
Integrating nursing informatics into a graduate research course.
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Neurogenic claudication secondary to vascular disease.
Neurogenic claudication is characterized by sensory symptoms which appear during exercise or while maintaining a fixed posture. They are paraesthetic in quality, may be associated with 'march' phenomena, and patients may have bowel and bladder disturbance. The problem is most commonly secondary to lumbar canal stenosis (LCS) but rarely due to aortic disease, as shown in this case report. This report concerns a 66 year old woman who presented with symptoms of paraesthesia radiating from the buttocks to the thigh and, intermittent loss of bladder and bowel function, all associated with walking. There were no associated symptoms of vascular claudication. Clinically, there was evidence of aorto-iliac obstruction with absence of femoral pulses and a vascular index of 0.4 at both ankles. Neurological examination was normal at rest but the left ankle jerk was absent immediately after exercise. Myelogram and computerized tomographic (CT) scan were normal. An aortogram revealed a very tight irregular stenosis of the aorta at the level of the renal and mesenteric arteries. Very few lumbar vessels were seen. An aortic endarterectomy via a thoraco-abdominal approach was performed and an aortobifemoral graft inserted. The patient's symptoms resolved following this procedure. We postulate that her symptoms were caused by a 'steal' from the blood supply to the cauda equinda due to the severe athromatous disease of her upper abdominal aorta.
A prospective analysis of a two-year experience using computed tomography as an adjunct for cervical spine clearance.
The role of CT scanning as an adjunct to plain roentgenograms of the cervical spine was reviewed in acutely injured blunt trauma patients. Following institution of a protocol to evaluate the cervical spine in all blunt trauma patients, 179 patients underwent CT scanning of their cervical spine. This was performed for patients whose x-ray findings were positive, for patients with plain x-ray films suggestive of a pathologic condition, for patients with plain x-ray films that did not reveal all of the cervical vertebrae, and for patients who had persistent pain or neurologic deficits despite normal plain x-ray films. Of 123 patients not able to have their cervical spine cleared by normal roentgenograms, 93% were cleared within 24 hours of admission based on CT scans. There were no missed injuries in this setting. A false-positive rate of 28% and a false-negative rate of 1.5% were found for plain roentgenograms. Computed tomographic scans detected 98% of the injuries in our study and when combined with a three-view plain x-ray series of the cervical spine, 100% of cervical spine injuries were detected. Computed tomographic scanning as an adjunct to plain x-ray films of the cervical spine is a highly accurate and expedient modality to clear the cervical spine of blunt trauma patients.