Biomedical subjects
Publications and source records attributed to T Khalil.
Interleukin-6 (IL-6) is known to promote tumour growth and survival. We evaluated IL-6 gene amplification in tumours from 53 glioma patients using fluorescence in situ hybridisation. Amplification events were detected only in glioblastomas (15 out of 36 cases), the most malignant tumours, and were significantly associated with decreased patient survival.
An 18-year-old woman underwent an (111)In octreotide scan for evaluation of a possible insulinoma. This showed mildly increased radiopharmaceutical uptake involving the right lung base. The patient reported a productive cough for 5 days before the octreotide scan. A chest radiograph was taken, which showed increased airspace opacification in the right lower lobe, corresponding to the uptake seen on the octreotide scan. After a course of oral antibiotics, the patient's chest symptoms improved and the radiograph opacification resolved, confirming the diagnosis of community-acquired pneumonia. This case stresses the need to correlate scan results with the patient's presentation and symptoms to avoid false-positive data.
Radiosurgery of oligodendrogliomas is not specific. It must be integrated into the overall treatment scheme for gliomas which remains to be strictly defined. Nevertheless, empirically, and in light of the limited constraints for the patient and the encouraging radiological and clinical benefits, radiosurgical teams usually propose this technique in the event of recurrence of malignant gliomas, as a second line treatment. Exceptionally radiation can be used for some small benign gliomas which could not be treated by open surgery and accurately defined radiologically. Radiosurgery can achieve local control of the lesion, mostly transitionally, with 15 to 18 Gy at the reference isodose. One of the key problems is the definition of the glioma boundaries. Despite progress in neuroimaging techniques most the limits of malignant forms are still not accessible. In routine practice, the nodular area, considered as the most active on MRI, i.e. the contrast enhanced area, is accepted as the target. Its widest dimension must be about 35-40 mm. Only patients with minimal disability can benefit from radiosurgery. Optimization of the target definition (in particular the most active zone) and prospective randomized studies should be helpful in clarifying indications for this technique.
The presence of telomerase activity in a glioma may be a predictor of its malignant potential. Activation of telomerase is regulated at the transcriptional level of the human telomerase reverse transcriptase (hTERT). Here, we evaluated whether the amount of hTERT mRNA provides a molecular marker of glioma malignancy that would have clinical utility. We used a real-time RT-PCR to assess the number of hTERT transcripts in primary tumour samples derived from 70 glioma patients. Results were standardised by quantifying the number of ABL transcripts as internal control and expressed as hTERT/ABL ratio. The percentage of patients with detectable hTERT mRNA markedly increased with enhanced malignancy: low-grade gliomas expressed hTERT in one out of 14 cases (7.1%), anaplastic gliomas in four out of 13 cases (30.8%) and glioblastoma multiforme (GBM) tumours in 30 out of 43 cases (69.8%). The mean hTERT/ABL ratio was significantly higher in GBMs than in non-GBMs. Subdividing hTERT/ABL ratios as low (< pr = 25%) and high (>25%), we found that the overall survival among hTERT-positive GBMs was significantly worse in high hTERT expressors than in low hTERT expressors (P=0.0082). We conclude that the amount of hTERT mRNA may represent a diagnostic and prognostic indicator for GBM patients.
We report two cases of spontaneous anteromedial temporo-sphenoidal meningo-encephalocele. The first patient was a 67-year-old man with a history of treated epiglotic cancer 6 years ago, was referred to us for CSF rhinorrhea. Lateral sphenoidal CSF fistula was confirmed by CT cisternography. Four lumbar taps were performed and rhinorrhea stopped for 2 years. At relapse of rhinorrhea, the patient was operated on via a subtemporal approach. The dural defect was filled by an intradural patch of pericranium. Four years later patient showed no evidence of cerebrospinal fluid leakage. The second patient was a 54-year-old woman referred to us after a one year history of CSF rhinorrhea. CT cisternography confirmed lateral sphenoidal CSF fistula. The patient was operated on via a subtemporal approach. The dural defect was filled by a patch of pericranium. Three years later the patient had no evidence of cerebrospinal fluid leakage. Twenty-one cases of anteromedial temporosphenoidal meningo-encephaloceles have been reported in the literature. They probably are of a developmental origin. Some cases have been successfully treated via a transsphenoidal route. However surgical failures related to this approach can be due to the lack of control of the lateral recess of the sphenoid sinus. Therefore, the frontotemporal approach seems more adequate but the transphenoidal endoscopic approach will probably be used in the future.
We have measured the spin polarization of Xe (4p)(-1) photoelectrons after ionization with circularly polarized light at photon energies close to the ionization threshold where a resonant enhancement of quadrupole transitions has recently been predicted. At a reaction angle of 90 degrees a nonvanishing longitudinal spin polarization component of about 4% clearly indicates a quadrupole contribution to the photoexcitation. This is the first experimental evidence for the influence of nondipole transitions on the photoionization process at excitation energies much below 1 keV in an observable other than the intensity angular distribution.
Slowly varying pressure oscillations in the cranial enclosure are well known, especially intracranial pressure waves as best described by the pioneering works of Janny and Lundberg. Nevertheless, in spite of over twenty five years research on intracranial pressure waves, their origin and regulation remain unclear but are often considered only as pathological. Our aim was to review data on these phenomena to clarify their biological status and the role that they could play in the management of patients suffering from such intracranial neurosurgical diseases as intracranial hypertension, severe head injury, and hydrocephalus. It appears that these pressure waves reveal important information on the function of the cerebral vasculature and as such have significance for influencing intracranial compliance. Pressure waves are also closely associated with autoregulation, in particular dynamic autoregulation. It seems evident that they are not only pathophysiological but also physiological, linked with other biological parameters such as the neurovegetative cardiovascular system, breathing, and sleeping. This study shows that it is not only important to continue to explore these slow waves, but also the methods of analysis in order to more fully clarify their clinical significance.
In photoionization of free, unoriented chiral molecules with circularly polarized radiation, a significant circular dichroism, i.e., an asymmetry in the forward-backward electron emission, has been observed in the photoelectron angular distribution. This leads also to an asymmetry in the momentum transfer to the photoions. The spectra for the left- and right-handed enantiomers of bromocamphor exhibit asymmetries up to several percent which vary as a function of orbital binding energy. This enantioselective effect can similarly occur for biomolecules with handedness, like amino acids, and may thus be a contributing factor related to the origin of the terrestrial biomolecular homochirality.
BACKGROUND AND PURPOSE: The aim of this study is to evaluate retrospectively the benefit of the surgical spinal decompression in 152 patients with spinal metastasis. METHODS: Based on clinical notes and GP inquiry, we determined the actuarial survival curve, and assessed the pain level one month post-operatively and the motor, the sensory and sphincter distrurbances three months after surgery. RESULTS: Thoraco-lumbar lesions were usually treated using a posterior approach, with a laminectomy and if necessary an osteosynthesis. Cervical lesions were treated with an anterior approach, i.e. a corporectomy and a methylmetacrylate stabilization. Sixty eight percent of patients (103/152) had pre or postoperative radiotherapy. After the surgical decompression for a spinal metastasis, our study demonstrated an improvement in sensory status (31 % of the patients), in motor ability (56 %), in sphincter function (51 %), and a decrease in the pain intensity in 47 % of the patients. Among 83 patients who could not walk on admission (grade A, B and C of Frankel), 52 % recovered a gait function 3 months post operatively. The best benefit after surgery concerned grade C patients, of which 71 % recovered the gait function. Two percent of the patients had postoperative worsening of their motor strength. No operative mortality was noted, and the postoperative mortality rate was 3 % at 7 days and 9 % at 30 days. The analysis of the actuarial survival curve demonstrated a mean follow up of 3.7 years. The mean survival time was 12 months with 25 % of patients surviving 2 years. CONCLUSION: Surgical decompression is effective in relieving neurological symptoms from spinal metastasis. In our experience a complete motor deficit does not seem to be a good surgical indication because of the lack of postoperative improvement.
BACKGROUND DATA: The Dictionary of Occupational Titles (DOT) is a U.S. government publication that defines each job in the United States according to 20 job factors. Fishbain et al. (Spine 1994;19:872-80) developed a DOT residual functional capacity (RFC) battery whose predictive validity for employment/unemployment had not been tested previously. OBJECTIVES: The purposes of this study were as follows: (a) to determine whether results of a DOT-RFC battery performed at completion of pain facility treatment predicted employment status at 30 months' follow-up and (b) to determine whether the DOT-RFC battery predicted employment capacity as determined by the DOT employment levels of the chronic pain patients' (CPPs) jobs. STUDY DESIGN: This is a prospective low back pain CPP pain facility treatment study using employment status and the DOT occupational levels as outcome measures. METHODS: One hundred eighty-five consecutive CPPs who fitted the selection criteria completed a DOT-RFC battery at the completion of pain facility treatment and were contacted at 1, 3, 6, 12, 18, 24, and 30 months for determination of their employment status and DOT employment level. Eight DOT job factors plus pain and worker compensation status were found to be significantly different between employed and unemployed CPPs and between those employed in different DOT employment levels. For the 10 variables, stepwise discriminant analysis was used to select final predictor variables. Sensitivity and specificity were calculated along with pain level cutpoints that separated the groups. RESULTS: The eight DOT job factors found to be statistically significant between groups were the following: stooping, climbing, balancing, crouching, feeling shapes, handling left and right, lifting, carrying, and pain and worker compensation status. In the discriminant analysis, these variables could discriminate between the employed and unemployed categories, with a sensitivity and specificity of approximately 75%. The pain level cutpoint between employed and unemployed was 5.4 on a 10-point scale. CONCLUSIONS: We cannot as yet predict DOT-RFC employment levels. However, if a CPP can pass the above eight DOT job factors and has a pain level less than the 5.4 cutpoint, that CPP will have a 75% chance of being employed at 30 months after treatment at the pain facility. Therefore, some DOT-RFC battery job factors demonstrate a predictive validity in the "real work world."
OBJECTIVE: We previously determined that "intent" to return to work post pain facility treatment is the strongest predictor for actual return to work. The purposes of the present study were the following: to identify variables predicting "intent"; to predict membership in the "discrepant with intent" group [those chronic pain patients (CPPs) who do intend to return to work but do not]; and to predict membership in the "discrepant with nonintent" group (those CPPs who do not intend to return to work but do). DESIGN: A total of 128 CPPs completed a series of rating scales and yes/no questions relating to their preinjury job perceptions and a question relating to "intent" to return to the same type of preinjury job post-pain facility treatment. These CPPs were part of a grant study for prediction of return to work, and therefore their work status was determined at 1, 3, 6, 12, 18, 24, and 30 months posttreatment. Preinjury job perceptions and other demographic variables were utilized using stepwise discriminant analysis to identify variables predicting "intent" and predicting membership in the "discrepant with intent" and "discrepant with nonintent" groups. SETTING: Pain facility (multidisciplinary pain center). PATIENTS: Consecutive low back pain CPPs, mean age 41.66+/-9.54 years, with the most frequent highest educational status being high school completion (54.7%) and 60.2% being worker compensation CPPs. RESULTS: "Intent" was predicted by (in decreasing order of probability) postinjury job availability variables, job characteristic variables, and a litigation variable. "Discrepant with intent" was predicted by (in decreasing order of probability) for the 1-month follow-up time point, postinjury job availability variables, pain variables, a litigation variable, and a function perception variable, and for the final follow-up time point, pain variables only. "Discrepant with nonintent" was predicted by (in order of decreasing probability) for the 1-month follow-up time point, a job availability variable, a demographic variable, and a functional perception variable, and for the final follow-up time point a pain variable and a job availability variable. The percentage of CPPs correctly classified by each of these analyses was as follows: "intent" 81.25%, "discrepant with intent" 87.01% (at 1-month follow-up) and 74.03% (final follow-up), "discrepant with nonintent" 92.16% (at 1-month follow-up) and 75.00% (final follow-up). CONCLUSIONS: CPPs intentions of returning to their preinjury jobs are mainly determined by job availability and job characteristic variables but surprisingly not by pain variables. However, the results with "discrepant with intent" and "discrepant with nonintent" groups indicate that actual return to work is determined by an interaction between job availability variables and pain variables with pain variables predominating for long-term outcome.
OBJECTIVE: To examine the impact of preinjury job perceptions on chronic pain patients (CPPs) return to work after pain facility treatment. DESIGN: A total of 128 CPPs completed a series of rating scales and yes/no questions relating to their preinjury job perceptions and a question relating to "intent" to return to the same type of preinjury job following pain facility treatment. These CPPs were part of a grant study for prediction of return to work, and therefore their work status was determined at 1, 3, 6, 12, 18, 24, and 30 months after treatment. The preinjury job perceptions and other demographic variables were used to predict return to work. Stepwise discriminant analysis was used to predict return to work at the 1-month and final time points utilizing the above variables. Stepwise regression analysis was used to predict mean employment status (at all time points) also using the above variables. SETTING: Multidisciplinary Pain Center. PATIENTS: Consecutive CPPs. RESULTS: For the 1-month time point, employment status was predicted by "intent," educational status, work dangerous perception complaint, job stress, job physical demands, job liking, and job role conflicts. Here, 79.49% of the CPPs were correctly classified. For the final time point, employment status was predicted by the first three predictors for the 1-month time point (in the same order) and age, job stress, and gender. Here, 74.58% of the CPPs were correctly classified. Mean employment status was predicted by "intent" and educational status. CONCLUSIONS: There is a relationship between preinjury job perceptions and actual return to work after pain facility treatment. Voiced "intent" not to return to the preinjury type of job is highly predictive of not returning to work after pain facility treatment.
STUDY DESIGN: This was a randomized prospective follow-up study of pain facility treatment of chronic pain patients with low back pain, with return to work and work capacity as the outcome measures. OBJECTIVES: To determine if after pain facility treatment chronic pain patients "move" in and out of work and in their work capacity; to determine the patterns of "movement;" and to determine the post-pain facility treatment follow-up sampling time points that would maximize the number of chronic pain patients correctly classified according to their final work and work capacity status. SUMMARY OF BACKGROUND DATA: Past research and empiric observation have indicated that chronic pain patients may "move" after pain facility treatment in and out of work and in their job work capacity. Such "movement" can affect the results of outcome studies. METHODS: Two hundred thirty-six consecutive chronic pain patients who fit study selection criteria were followed up at 1, 3, 6, 12, 18, 24, and 30 months after pain facility treatment for determination of work and work capacity status and separated according to the pattern of movement. Stepwise discriminant analysis was used to answer the study objectives. "Movement" in and out of work for these chronic pain patients also was compared with the US general population. RESULTS: Chronic pain patients demonstrated eight work and four work capacity movement patterns. The 24- and 1-month time points predicted final work status correctly for 97.0% and 77.0% of the chronic pain patients, respectively, whereas the most significant predictor for correct work capacity status was the 24-month point. The annual percentage change in employment status for these chronic pain patients was more than in the US general population. CONCLUSIONS: Because chronic pain patients "move" in and out of employment and for work capacity status after pain facility treatment, future outcome studies using these measures will have to consider carefully the impact of "movement" on their results.
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The impact response of the human head has been determined by three-dimensional finite element modeling. This model represents the essential features of a 50th percentile human head. It includes a layered shell closely representing the cranial bones with the interior contents occupied by an inviscid continuum to simulate the brain. A thin fluid layer was included to represent the cerebral-spinal fluid. To validate the model, its response was obtained by applying a sine-squared pulse of 6.8 kN in magnitude and 10 ms in duration. The load was applied to a freely supported head on the frontal bone in the midsagittal plane. The computed pressure-time histories at 5 locations within the brain material compared quite favorably with previously published experimental data from cadaver experiments and provided a reasonable level of confidence in the validation of the model. A parametric study was subsequently conducted to identify the model response when the impact site (frontal, side, occipital) and the material properties of the head were varied. Interestingly, the model predicted higher contre-coup pressure in the frontal lobe (from occipital impact) than that predicted in the occipital region from frontal impact. This finding supports clinical findings of contre-coup injury being more likely to result from occipital impact than from frontal impact.
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The dynamic response of the human head to side impact was studied by 2-dimensional finite element modeling. Three models were formulated in this study. Model I is an axisymmetric model. It simulated closed shell impact of the human head, and consisted of a single-layered spherical shell filled wiht an inviscid fluid. The other two models (Model II and III) are plane strain models of a coronal section of the human head. Model II approximated a 50th percentile male head by an outer layer to simulate cranial bone and an inviscid interior core to simulate the intracranial contents. The configuration of Model III is the same as Model II but more detailed anatomical features of the head interior were added, such as, cerebral spinal fluid (CSF); falx cerebri, dura, and tentorium. Linear elastic material properties were assigned to all three models. All three models were loaded by a triangular pulse with a peak pressure of 40 kPa, effectively producing a peak force of 1954 N (440 lb). The purpose of this study was to determine the effects of the membranes and that of the mechanical properties of the skull, brain, and membrane on the dynamic response of the brain during side impact, and to compare the pressure distributions from the plane strain model with the axisymmetric model. A parametric study was conducted on Model II to characterize fully its response to impact under various conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
The purpose of this study was to examine the effect of various nutrients perfused selectively into isolated sections of the small intestine on the release of pancreatic polypeptide (PP). Six dogs were prepared with chronic gastric, duodenal, and three permanent intestinal fistulas (one distal to the ligament of Treitz, one in the terminal ileum, and one halfway between). After a 24-h fast, the duodenum was perfused for 45 min (200 ml/h) via the duodenal limb with HCl (30 mM), an amino acid solution (50 mM), or sodium oleate (NaO, 40 mM). In separate studies, the jejunal and ileal segments were isolated by inflating two balloon catheters via the intestinal fistula, and these segments were perfused as described earlier. Plasma PP, cholecystokinin (CCK)-33, and secretin levels were measured. Results of this study showed that the perfusion of all segments of the small intestine with amino acid caused a significant elevation of plasma PP levels. Perfusion of the duodenum and jejunum but not the ileum with a fatty acid resulted in a significant elevation of plasma levels of PP. Perfusion of HCl into any segment did not affect plasma levels of PP. This study shows that PP is released by the presence of nutrients in all segments of the small intestine, and that a PP elevation was always accompanied with a rise in plasma levels of CCK-33.