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Biomedical subjects

R Burgess

Publications and source records attributed to R Burgess.

At least 55 records · Page 3Linked to original sources

Increased cytotoxicity of squamous cell carcinoma of the head and neck by combining cisplatin with VP-16 and ciprofloxacin.

Chemotherapeutic treatment of squamous cell carcinoma (SCC) of the head and neck has been largely ineffective because of tumor cell resistance. This study examined combinations of cisplatin, 4' demethylepipodophyllotoxin ethylidene D-glucoside (VP-16), and ciprofloxacin, a quinolone antibiotic. VP-16 and ciprofloxacin were used in an effort to inhibit DNA repair and increase cytotoxicity. Chemotherapeutic agents often have a direct damaging effect on cellular DNA. Cytotoxicity may be the result of incomplete DNA repair mechanisms; whereas tumor cell resistance to drugs may be due to efficient DNA recovery. A nuclear enzyme especially important to DNA repair and cell growth is topoisomerase II (topo II). Targeted inhibition of topo II by VP-16 and ciprofloxacin may cause increased cisplatin cytotoxicity. SCC cell lines of head and neck origin were treated with a combination of cisplatin, VP-16, and/or ciprofloxacin with cell viability being assessed by the MTT colorimetric assay. Four of five SCC lines examined demonstrated significant augmentation of cisplatin cytotoxicity with the addition of both VP-16 and ciprofloxacin. These in vitro data suggest methods may exist for improving the chemotherapeutic treatment of SCC of the head and neck.

Antineoplastic Combined Chemotherapy Protocols↗

Two-colour immunoenzymatic technique using sequential staining by APAAP to evaluate two cell antigens.

AIMS: To extend the alkaline phosphatase-antialkaline phosphatase (APAAP) immunoenzyme single stain method to a more generally applicable double stain technique. This will allow two primary antibodies of the same isotype of IgG and specifically the nuclear antigen bromodeoxyuridine (BRdU) to be evaluated with a cell surface antigen identifier. METHOD: Sequential applications of the APAAP method showed two antigen sites by different dye couplings to a common alkaline phosphatase substrate, producing blue and red reaction products on the same slide. Antigens on different cell populations as well as those in different compartments of the same cell were analysed. The method allowed a surface antigen monoclonal to be revealed first, using an optimal fixative, before alcohol/gluteraldehyde fixation was used to start the second (BRdU) staining sequence. RESULTS: An analysis of double staining of T lymphocyte subsets (CD4 and CD8) showed no significant difference in the order of application of the primaries (n = 10) and no significant difference from their corresponding single stain results (n = 50), confirming the validity of the technique where antigens are exclusively distributed. Other examples, including antigens distributed in different compartments of the same cell, displayed discrete staining which implied validity. CONCLUSION: Double staining by APAAP with this technique seems to be applicable to those cases where antigens are exclusively distributed and includes cases where different compartments of the same cell are stained. It is especially useful in revealing antigens that require different fixation and preparation--that is DNA incorporated BRdU with a surface antigen. But it does seem to have a limited ability to produce a dual colour at a common site.

Antibodies, Monoclonal↗

Subdural electrodes in the presurgical evaluation for surgery of epilepsy.

This article gives first an overview of the advantages and disadvantages of electrodes of progressively greater invasiveness used in the evaluation of patients who are candidates for surgery of epilepsy. The following sections discuss the design of subdural electrodes, their clinical indications, and the relative advantages and disadvantages of subdural electrodes when compared with other invasive techniques.

Brain Mapping↗

Pitfalls in the determination of absolute dimensions using angiographic catheters as calibration devices in quantitative angiography.

Using catheter outer diameter as a scaling device, quantitative coronary arteriography allows the precise and objective measurement of change in absolute dimensions of coronary arteries after mechanical or pharmacologic intervention. Because of variable density in the wall of the catheter, automated systems might vary in the determination of the outer catheter diameter. To examine this premise, catheters in a variety of French sizes from 6 manufacturers were injected with radiographic contrast and used as scaling devices for arterial phantoms of known geometric dimension. Radiographic diameters of the catheters were determined by applying the quantitative coronary arteriographic algorithm to the catheters using a calibration grid in the same field of view. The varying composition of the catheters resulted in differing x-ray attenuation and, subsequently, automated edge-detection algorithms varied widely in determining the actual catheter diameter to be used as a scaling factor. For instance, a Lucite "artery" with a minimal luminal diameter of 1.50 mm (image calibrated using the micrometer-determined outside diameter of a Baxter 8Fr guiding catheter) resulted in a quantitative angiographic diameter of 2.03 mm (overestimation by 35%). If the diameter of a similar size Shiley catheter was used to calibrate the image, a luminal diameter of 1.60 mm was determined: a difference of 0.43 mm based solely on differences in scaling catheter attenuation. These data suggest that a specific "fingerprint" for each catheter material and catheter French size exists, rendering generalizations about catheter size questionable. These observations are important for quantitative angiography where many brands and sizes of angiographic catheters are being used clinically.(ABSTRACT TRUNCATED AT 250 WORDS)

Calibration↗

A new class of electrodes of 'intermediate invasiveness': preliminary experience with epidural pegs and foramen ovale electrodes in the mapping of seizure foci.

Non-invasive electroencephalographic (EEG) recording with scalp and sphenoidal leads is often insensitive to precise localization of ictal onset, and can be distorted by skull defects and underlying lesions or deformities of the brain. We present preliminary experience with epidural pegs and foramen ovale electrodes used in 30 cases of intractable partial epilepsy where non-invasive EEG did not define a zone of epileptogenesis with sufficient precision to recommend resection, or to dictate precise placement of depth electrodes or subdural girds. Custom designed mushroom shaped peg electrodes were implanted via 4.5 mm twist-drill skull holes for epidural recording from cortical areas of suspected epileptogenesis. Foramen ovale electrodes (flexible 3-contact leads) were introduced via percutaneous puncture of Meckel's cave cistern for recording from mesiotemporal regions. Chronic recording was performed for 4 to 26 days (mean 9.2 days). There were no serious complications and signal quality was excellent in every electrode. Based on interictal and ictal records, resective surgery was performed in 8 cases, more focused further invasive recording was recommended in 15 cases (with subsequent resective surgery), and surgical options were excluded in 7 cases. It is concluded that these electrodes of 'intermediate invasiveness' represent a safe and effective tool in the armamentarium for mapping complicated or elusive epileptic foci. They can be used in lieu of, in addition to, or prior to more invasive measures. Their greatest advantage lies in their relative safety and ability to survey extensive zones of suspected epileptogenesis so as to guide and focus further mapping and surgical intervention.

Adolescent↗

Intracranial recordings of movement-related potentials to voluntary saccades.

Movement-related potentials evoked by voluntary and self-initiated horizontal saccades were recorded from subdural electrodes placed over the lateral (premotor and motor cortex) and the mesial (supplementary motor area) surfaces of the frontal lobe, in four patients with intractable focal seizures. An extremely localized bereitschaftspotential showing approximately the same latencies and amplitudes was simultaneously recorded from the frontal eye field and supplementary motor area (SMA). Our data suggest that both regions are equally active prior to saccades and do not support the view that the SMA acts as a supramotor cortex, being activated during the planning of the movement and the primary motor cortex only later on, close to the execution of the movement. In addition, we never observed the spike potential in our intracranial recordings, thus supporting the hypothesis of its extracerebral origin.

Adult↗

The omega subunit of Escherichia coli K-12 RNA polymerase is not required for stringent RNA control in vivo.

Igarashi et al. (K. Igarashi, N. Fujita, and A. Ishihama, Nucleic Acids Res. 17:8755-8765, 1989) reported that the omega (omega) subunit of Escherichia coli RNA polymerase was required for stringent control as judged by in vitro transcription assays in the presence and absence of guanosine 3',5'-bispyrophosphate (ppGpp). This conclusion predicts that a deletion of the omega gene (designated rpoZ or spoS) should show a relaxed RNA control phenotype in vivo. However, we find that wild-type stringent control of stable RNA accumulation is unaffected by a spoS null allele that abolishes cellular production of the omega protein. We conclude that omega protein is not necessary for the operation of the stringent RNA control response.

DNA-Directed RNA Polymerases↗

Continuous assessment of performance in External Quality Assessment Schemes.

A simple, standardised procedure was used for processing data from External Quality Assessment Schemes and for producing performance charts. A graphic presentation of cumulative performance is generated for each test, using an integrated software package to display results in a standardised format. This permits interpretation of satisfactory and poor performances and facilitates identification of "outlying" results. Although most results are recorded as Deviation Indices, the system is flexible and can be used to present other performance variables, such as Percentage Deviations and relevant textual information relating to interpretative assessments. It is therefore readily adaptable for use by other pathology disciplines.

Data Interpretation, Statistical↗

Tumor necrosis factor and cytotoxic agents. Effect on squamous carcinoma lines.

The cytotoxicity of dactinomycin (actinomycin D), doxorubicin hydrochloride (Adriamycin), cisplatin, fluorouracil, and methotrexate alone and in combination with recombinant human tumor necrosis factor (rHuTNF) on human squamous cell carcinoma lines was studied by an MTT proliferation assay. The rHuTNF alone caused no inhibition after 24 to 72 hours. All lines investigated showed a dose-dependent response to dactinomycin and doxorubicin. Potentiation of dactinomycin and doxorubicin cytotoxicity occurred with four of six cell lines following incubation of rHuTNF and the drug. No synergistic effect on cytotoxicity was seen with rHuTNF and any chemotherapeutic agent on two cell lines. The addition of rHuTNF did not augment the cytotoxic effect seen with cisplatin, methotrexate, or fluorouracil on any cell line. These results show that rHuTNF can enhance the cytotoxic effect of certain chemotherapeutic agents on squamous cell lines in vitro.

Antineoplastic Agents↗

Relation of quantitative coronary lesion measurements to the development of exercise-induced ischemia assessed by exercise echocardiography.

To assess the relation of quantitative measures of coronary stenoses to the development of exercise-induced regional wall motion abnormalities, 34 patients with isolated, single vessel coronary artery lesions and normal wall motion at rest underwent exercise echocardiography and quantitative angiography on the same day. Although all 11 patients with a visually estimated stenosis greater than or equal to 75% had an ischemic response and 10 (91%) of 11 patients with a less than or equal to 25% visually estimated stenosis had a normal response by exercise echocardiography, among 12 patients with a visually estimated stenosis of 50%, 6 (50%) had an ischemic response and 6 (50%) had a normal exercise echocardiogram. Quantitative measurements of stenosis severity distinguished patients with ischemic (group 1) from normal (group 2) exercise echocardiographic responses as follows: minimal luminal diameter (mm), group 1 1.0 +/- 0.4 versus group 2 1.7 +/- 0.4, p less than 0.0001; minimal cross-sectional area (mm2), group 1 0.9 +/- 0.6 versus group 2 2.5 +/- 1.1, p less than 0.0001; percent diameter stenosis, group 1 68.3 +/- 14.2 versus group 2 42.2 +/- 12.1, p less than 0.0001; and percent area stenosis, group 1 87.5 +/- 7.8 versus group 2 64.8 +/- 15.9, p less than 0.0001. These data validate the utility of exercise echocardiography by demonstrating that 1) coronary stenosis severity measured by quantitative angiography is closely related to wall motion abnormalities detected by exercise echocardiography, and 2) exercise echocardiography can be used as a noninvasive means to assess the physiologic significance of coronary artery lesions.

Adult↗

Quantification of aortic regurgitation after balloon aortic valvuloplasty using videodensitometric analysis of digital subtraction aortography.

The serial changes in aortic regurgitation (AR) after balloon aortic valvuloplasty have not been quantitatively evaluated. This study assessed the degree of AR by quantitative and qualitative techniques before and immediately after aortic valvuloplasty. Digital subtraction aortography was performed before and after valvuloplasty in 50 patients. The ratio of left ventricular to aortic contrast density during aortography was analyzed by videodensitometric techniques. A time-density curve was obtained by placing a 30 X 30 pixel region of interest over the aortogram and the left ventricular cavity. The ratio of left ventricular to aortic density at peak aortic density defined the videodensitometric ratio. Independent visual interpretation was also assessed and compared to videodensitometric methods. Quantitatively, no significant change in AR could be demonstrated in the mean videodensitometric ratio before or after balloon aortic valvuloplasty (0.33 +/- 0.21 vs 0.37 +/- 0.25, p = 0.07). Ten (20%) of the patients had a greater than or equal to 0.10 increase, and 4 (8%) patients a greater than or equal to 0.10 decrease in the AR ratio. Thus, serial quantitative and qualitative determinations of AR after balloon aortic valvuloplasty confirm that significant increases or decreases in AR severity are unusual after the procedure.

Absorptiometry, Photon↗

Prediction of early recurrent myocardial ischemia and coronary reocclusion after successful thrombolysis: a qualitative and quantitative angiographic study.

To determine the association of qualitative and quantitative measurements of the myocardial infarct-related coronary narrowing with subsequent recurrent ischemia/reocclusion after successful thrombolysis, 47 patients treated with high-dose (150 mg) tissue plasminogen activator over 6 to 8 hours were studied in the setting of acute myocardial infarction. No patient underwent emergent coronary angioplasty. All patients had Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow or higher at the baseline (90-minute) angiogram; 31 patients had a protocol 24-hour catheterization as well. Eighteen patients had recurrent ischemia/reocclusion whereas 29 had an uneventful hospital course. There was no significant difference in baseline clinical characteristics between the 2 groups. Twenty-five (86%) of those with an uneventful course had TIMI grade 3 flow at baseline angiogram compared with 56% of patients with recurrent events. No significant difference in angiographic morphologic characteristics was found between the 2 groups at baseline catheterization. At 24 hours, however, none of the patients who subsequently had recurrent events had a concentric narrowing, while 13 (58%) of them had a complex morphology. In contrast, quantitative parameters of minimal lumen diameter, percent area stenosis and percent diameter stenosis at baseline and 24 hours were not significantly different between those who did and did not have recurrent ischemia/reocclusion. These findings suggest that the degree and quality of coronary flow at baseline catheterization are more important determinants of sustained patency and event-free hospitalization than are quantitative dimensions or coronary morphology. In addition, narrowings that fail to become concentric within the first 24 hours are more likely to be associated with subsequent ischemia or reocclusion during the early periinfarct period.

Aged↗

Modified dual label Schilling test for pancreatic exocrine function.

The modified dual-label Schilling test, as further developed in kit form by Amersham International plc (UK), has been assessed in two separate centres. Since the outcome was similar in each centre, the results in 66 subjects were amalgamated. Using a cut-off point for the 58Co/57Co ratio of 0.52--as derived from studies in 10 healthy volunteers--to separate normal from abnormal results, the specificity of the test was 88%. However, the test's sensitivity in chronic pancreatic disease was only 50%: normal results occurred in 5 of 8 patients with pancreatic cancer (including 2 with steatorrhoea), and 9 of 21 with chronic pancreatitis (including 1 with steatorrhoea). The possible reasons for the test's poor sensitivity are discussed.

Adult↗

Occurrence of malignant peritoneal mesothelioma after surgery and irradiation for cervical cancer.

Mesothelioma of the peritoneal cavity after irradiation is rare, and the diagnosis is sometimes difficult to establish. The following case is a report of a mesothelioma occurring 9 years after radiation therapy for carcinoma of the cervix. In this patient, who had a hysterectomy and bilateral oophorectomy 7 years prior to the mesothelioma diagnosis, the histologic, histochemical, and ultrastructural findings were all consistent with a diagnosis of malignant peritoneal mesothelioma. It is believed that this case is one of the first well-documented cases of peritoneal mesothelioma in a female who was treated by pelvic irradiation for another neoplasm.

Carcinoma, Squamous Cell↗

Effect of guanabenz withdrawal on blood pressure and plasma catecholamines.

Previous studies provide conflicting conclusions concerning the consequences of abrupt withdrawal of guanabenz therapy for essential hypertension. In the present study, 10 patients were treated for mild to moderate essential hypertension for 12 weeks, following which the drug was abruptly withdrawn. Blood pressure, pulse rate, and plasma catecholamine levels were obtained before, at 4 and 12 weeks after starting therapy, and 48-96 h and 4 and 8 weeks post-therapy. At the end of 12 weeks of therapy, the mean dose of guanabenz was 22.2 +/- 4.4 mg/day (range, 16-48 mg/day) and supine blood pressure was 140 +/- 5.5/88 +/- 2.4 mm Hg. Two to 4 days after drug withdrawal, supine and standing diastolic blood pressure remained significantly reduced compared to control (p less than 0.01). Standing systolic blood pressure also remained significantly reduced compared to control (p less than 0.01). Mean plasma catecholamine level was less than baseline after 4 weeks of therapy, but the change was not significant. No increase in plasma catecholamine concentration was observed at any time during the withdrawal period. No patient had symptoms of sweating, nervousness, palpitations, or insomnia after guanabenz withdrawal. In one patient with pretreatment systolic pressure of 150 mm Hg, systolic pressure 48 h after drug withdrawal was 160 mm Hg. These studies, together with previous reports, suggest that guanabenz therapy for mild to moderate essential hypertension in doses of 32 mg/day or less can be safely withdrawn on an outpatient basis with a very low incidence of withdrawal phenomena.

Blood Pressure↗