Search PubMed⌕ Search

Biomedical subjects

J Conti

Publications and source records attributed to J Conti.

At least 19 recordsLinked to original sources
PubMed2000

RNAs that interact with the fragile X syndrome RNA binding protein FMRP.

The Fragile X protein FMRP is an RNA binding protein whose targets are not well known; yet, these RNAs may play an integral role in the disease's etiology. Using a biotinylated-FMRP affinity resin, we isolated RNAs from the parietal cortex of a normal adult that bound FMRP. These RNAs were amplified by differential display (DDRT-PCR) and cloned and their identities determined. Nine candidate RNAs were isolated; five RNAs, including FMR1 mRNA, encoded known proteins. Four others were novel. The specificity of binding was demonstrated for each candidate RNA. The domains required for binding a subset of the RNAs were delineated using FMRP truncation mutant proteins and it was shown that only the KH2 domain was required for binding. Binding occurred independently of homoribopolymer binding to the C-terminal arginine-glycine-rich region (RGG box), suggesting that FMRP may bind multiple RNAs simultaneously.

Animals↗
PubMed1998

A comparison of purging and nonpurging eating-disordered outpatients: mediating effects of weight and general psychopathology.

OBJECTIVES: The present study compared purging and nonpurging eating-disordered outpatients on key behavioral and psychological features of their disorder. It also investigated the possible mediating effects of current level of depression, anxiety or general psychopathology, and current weight on differences between purgers and nonpurgers. METHOD: Seventy-seven patients from an outpatient eating disorder clinic who purged were compared to 48 clinic patients who did not purge on measures of eating behavior disturbances and specific psychopathology while controlling for weight, level of depression, anxiety, and general distress. RESULTS: Purgers reported significantly more eating behavior disturbance and higher scores on measures of specific psychopathology than the nonpurgers. These differences were unrelated to current weight, level of anxiety, or general distress. However, severity of depression did moderate some of the difference between the groups. CONCLUSION: These data provide further support for the proposition that purging is a distinctive clinical marker in all types of eating-disordered patients.

Adolescent↗
PubMed1998

Haemodynamic responses to extubation after cardiac surgery with and without continued sedation.

We studied the haemodynamic response to cessation of mechanical ventilation and removal of the tracheal tube in 84 patients after coronary artery bypass grafting. Patients were sedated on the ICU with propofol 1-3 mg kg-1 h-1, and randomly allocated to extubation while awake or while still sedated. Systolic and diastolic blood pressures and heart rate increased significantly faster in the awake group as mechanical ventilation was stopped; systolic blood pressure 6.1 (3.0) vs 0.7 (1.8) mm Hg min-1, diastolic blood pressure 2.1 (1.6) vs 0.2 (0.9) mm Hg min-1, heart rate 2.1 (1.7) vs 0.2 (0.5) beats min-2; P < 0.01 in each case. Treatment was required for systolic hypertension during discontinuation of mechanical ventilation in 20 patients (53%) in the awake group and in three patients (7.5%) in the sedated group (P < 0.001). No patient in the sedated group had any new ischaemic ECG changes. Significant new ST segment changes did not occur in the sedated group but were present in five patients in the awake group (P = 0.013), one of whom suffered a perioperative myocardial infarction. Removal of the tracheal tube while patients are still sedated after coronary artery bypass grafting is safe, and reduces the incidences of haemodynamic disturbance and myocardial ischaemia during extubation.

Procedural Sedation↗
PubMed1997

Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer.

PURPOSE: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. METHODS AND MATERIALS: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. RESULTS: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). CONCLUSION: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response.

Adult↗
PubMed1994

Preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for rectal cancer.

BACKGROUND: A Phase I trial was performed to determine the maximum tolerated dose of concurrent preoperative radiation therapy (5040 cGy) and 2 cycles (bolus daily times 5) of 5-fluorouracil (5-FU) and low-dose leucovorin (LV) (20 mg/m2), followed by surgery and 10 cycles of postoperative 5-FU/LV in patients with primary or recurrent rectal cancer. METHODS: Twenty-four patients were entered into the study. Preoperatively, the initial dose of 5-FU was 325 mg/m2. 5-FU was escalated 50 mg/m2, while the dose of LV and radiation therapy remained constant. Chemotherapy and radiation began concurrently on day 1. The postoperative chemotherapy was not dose escalated; 5-FU, 425 mg/m2, and LV, 20 mg/m2. The median follow-up was 10 months (range, 4-19 months). RESULTS: The resectability rate with negative margins in the 23 patients who underwent surgery was 100%. One patient refused surgery. The pathologic complete response rate was 13% (3 of 23). An additional four patients had negative nodes and a microscopic foci of tumor in the bowel wall. Therefore, the total clinical complete response rate was 30% (7 of 23). The maximum tolerated dose of 5-FU for the preoperative combined modality segment was 375 mg/m2; therefore, the recommended Phase II dose level is 325 mg/m2. The incidence of Grade 3+ toxicity for the 22 patients treated at the recommended 5-FU dose level (325 mg/m2) during the preoperative combined modality segment was as follows: diarrhea, 14%; erythema, 5%; hematologic, 10%; and total, 18%. The median nadir counts were leukocyte count, 3.7 (range, 1.5-5.9); hemoglobin count, 12.2 (range, 10.2-14.3); and platelet count (times 1000), 165 (range, 92-237). CONCLUSIONS: With this regimen, the recommended doses of chemotherapy in the combined modality segment are slightly higher than those recommended in arm 2 of the Intergroup postoperative adjuvant rectal trial 0114. This regimen will serve both as the preoperative arm of the Intergroup randomized trial of preoperative versus postoperative combined modality therapy for resectable rectal cancer (INT R9401) as well as the basis for the combined modality segment of NSABP RO-3.

Adenocarcinoma↗
PubMed1989

The pony as an animal model for vascular implants.

This study evaluated the pony as a potentially suitable model for vascular implant research. Healthy, conditioned ponies were randomly assigned to one of three groups: group I, carotid artery autografts (n = 6); group II, e-PTFE carotid interpositional grafts (n = 5); and group III, e-PTFE carotid interpositional grafts plus aspirin (10 mg/kg) and dipyridamole (3.5 mg/kg) drug administration. It was found that autografts remained patent longest (mean = 396.2 days; grafts were still patent at time of writing) followed by group III grafts (157.5 days), with group II grafts remaining patent for the shortest duration (61.1 days), (p less than 0.01). Patency was determined using two-dimensional real-time ultrasonography with Doppler velocimetry and/or arteriography. It was demonstrated that the pony's response to antithrombotic drugs was consistent and comparable to that in other animal models, both with respect to platelet function and affect on patency rate. The combination of the ease of surgical manipulation, drug administration, and platelet function testing, the comparable size of the pony and its heart and blood vessels to that of an adult human, the long life span of ponies, and the patency results of this study have demonstrated that the pony is a valuable animal model for vascular research.

Animals↗
PubMed1988

Platelet function testing in the pony.

Platelet isolation techniques and platelet function were evaluated in 35 adult ponies. Platelet recovery from whole blood was consistent and the preparation of platelet rich plasma was facilitated by an enhanced erythrocyte sedimentation rate. All platelet samples aggregated in response to 10 microM ADP. However, concentrations of ADP as high as 100 microM did not elicit significant 14C-serotonin release. Collagen induced irreversible platelet aggregation and 14C-serotonin release in all samples. The threshold dose for collagen in most ponies was 1.5 micrograms. Arachidonic acid (500 microM) failed to induce irreversible platelet aggregation or 14C-serotonin release in any of the samples evaluated. Pony platelets were nonresponsive to epinephrine (5.5 microM).

Adenosine Diphosphate↗
PubMed1987

An ionotropic phase transition in phosphatidylcholine: cation and anion cooperativity.

Evidence is presented for cooperative interaction between cations and anions specifically bound to dimyristoylphosphatidylcholine (DMPC). The cooperativity is with regard to an ion-induced (ionotropic) phase transition for the lipid and is signalled by a change in the luminescence from bound Tb3+. The intrinsic binding of Tb3+ to DMPC was determined from equilibrium dialysis experiments, using conventional methods to correct for electrostatic contributions. Preliminary results demonstrate great potential for infrared spectroscopy as a means to relate these Tb3+ luminescence studies to experiments involving less tractable cations. This work provides insight into the role of bound ions in modifying lateral phase behavior in phospholipid membranes.

Cations↗
PubMed1986

Accuracy of PET RCBF measurements: effect of time shift between blood and brain radioactivity curves.

Analytic expressions were derived for estimating the error in PET RCBF measurements associated with the time lag between brain and blood radioactivity following bolus H2(15)O injection and during non-steady-state CO15O inhalation. This lag time reflects the physiological difference in arrival times of 15O activity at brain and radial arterial sampling site as well as the experimentally introduced resistance to flow offered by the arterial catheter/stopcock assembly. Multiple measurements of this time lag ranged between 1 and 10 s. For non-steady-state CO15O PET measurements, estimated errors in RCBF ranged from 0.02 to 30% for delays of 2-8 s and scan lengths of 30-180 s. In the range 20-100 ml min-1 per 100 g, variations in RCBF only marginally affected these errors. Errors increased with longer delays but decreased sharply with scan durations greater than 60 s. For 30-180 s scans, even larger errors are associated with the H2(15)O injection technique (peak blood activity at 10 s): 1-60% for delays of 2-8 s. A 'slow' bolus peaking at 20 s decreased the error by 40%. For the H2(15)O method it is essential to estimate the time shift to within 2 s if accurate flow measurements (error less than 5%) are to be obtained from 40-60 s scans.

Brain↗
PubMed1983

Quantitative CT assessment of furosemide- and mannitol-induced changes in brain water content.

We studied the effects of two commonly employed antiedema agents, mannitol and furosemide, on CT brain density in eight patients with primary and metastatic brain tumors. Noncontrast CTs were performed before and after IV furosemide or IV mannitol, and serial blood samples were analyzed for osmolality. Computer-generated frequency histograms of CT numbers from "before-and-after" brain slices were using quantile-quantile (QQ) plots and the Kruskal-Wallis statistic. After IV mannitol, there was a progressive increase in CT brain density, which corresponded to an upward shift in the QQ plot over the range 0 to 70 Hounsfield units. The differences between baseline and posttreatment histograms for mannitol patients were significantly different from controls, and maximum differences coincided with peak serum osmolality. No statistically significant effects were observed in the furosemide group despite maximal diuresis. The relative magnitude of the quantitative changes observed after mannitol and furosemide administration are consistent with anticipated changes in brain water content.

Brain Edema↗
PubMed1982

Mass spectrometric measurement of end-tidal xenon concentration for clinical stable xenon/computerized tomography cerebral blood flow studies.

We have demonstrated the feasibility of using a compact dedicated mass spectrometer to monitor end-tidal xenon concentration in human subjects during stable xenon computerized tomography measurements of regional cerebral blood flow. End-tidal carbon dioxide concentration is monitored simultaneously and noninvasively without degrading the dynamic response to xenon. For clinical regional cerebral blood flow studies we employed a Nuclide 3-60-G Sectorr mass spectrometer with a 3 in radius, 60 degrees magnetic sector and a variable (0-5000 V) ion accelerating potential. The required high vacuum (10(-7) Torr) was achieved and maintained by means of a turbomolecular pump. A needlemetering valve was incorporated into an anesthesia mask connector, and exhaled gases were transported to the mass spectrometer via a 6 ft length of Teflon tubing (1/16 in i.d.). Molecular flow conditions between the sample and analysis chambers were provided by use of a gold foil leak (0.0005 in. hole). At an inlet pressure of 400 m Torr (achieved by means of the needle valve), the inlet system was characterized by a gas transport lag-time of 1.3 s and a rise-time constant of 85 ms. Xenon (doubly charged ion: m/z 68) and carbon dioxide (doubly charged ion: m/z 22) were monitored alternately at 75 ms intervals. Our experience with mass spectrometry has demonstrated the feasibility of using a compact dedicated instrument for accurately and non-invasively monitoring end-tidal xenon concentration in a clinical setting.

Brain↗
PubMed1982

An inexpensive video patient repositioning system for use with transmission and emission computed tomographs.

We have designed and constructed a portable video system from commercially available components (total cost $5,000) to facilitate accurate patient repositioning for sequential computed tomographic (CT) and positron emission tomographic studies and for therapeutic radiation therapy. The repositioning accuracy of the video system, employed in conjunction with a Delta-Scan 2020 CT scanner, was compared qualitatively (skull phantom and patient subjects) and quantitatively (precision cone phantom) with that of a GE 8800 CT scanner equipped with ScoutView and crossed Gammex lasers (SVL system). Although the SVL and video systems both facilitated accurate repositioning, the video system proved slightly superior. With experience, Z-axis repositioning accuracy of better than 1 mm could be achieved.

Humans↗
PubMed1979

Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanaesthetized rat using in vivo voltammetry.

The possibility of using in vivo voltammetry to monitor 5-hydroxytryptamine (5-HT) release from brain tissue in freely moving unanaesthetized rats has been examined. A potential (+0.2 to +1.0 V) was applied to a micrographite electrode stereotaxically placed within a specific brain region and current changes following the oxidation of electroactive compounds in the vicinity of the electrode tip were recorded. Administration of p-chloroamphetamine (5 mg/kg) produced a large increase in current in the striatum and this could be prevented by pretreatment with p-chlorophenylalanine (150 mg/kg X 2) to deplete brain 5-HT or Fluoxetine (10 mg/kg) which prevents the uptake of p-chloroamphetamine by 5-HT neurones. Fluoxetine (10 mg/kg) caused a small but long lasting increase in current. Stimulation of the median raphe nucleus produced a marked and rapid rise in current in the hippocampus but a much smaller one in the striatum. This response could also be prevented by 24 h pretreatment with p-chlorophenylalanine (150 mg/kg). Seven days after p-chlorophenylalanine administration raphe stimulation again produced an increase in current. Rats under barbiturate anaesthesia showed no clear increase in current either after p-chloroamphetamine or raphe stimulation, indicating that barbiturates may affect neurotransmitter release. The results suggest that 5-HT release can be monitored in the freely moving unanaesthetized rat using in vivo voltammetry, and that a moderate decrease in brain 5-HT concentration leads to a substantial inhibition of drug or stimulation induced release of 5-HT.

Animals↗