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Biomedical subjects

J Dubois

Publications and source records attributed to J Dubois.

At least 19 recordsLinked to original sources

Improved high-performance liquid chromatographic method for the determination of polyamines as their benzoylated derivatives: application to P388 cancer cells.

A simple reversed-phase HPLC method was developed for the determination of eight polyamines or monoacetylpolyamines, as their benzoylated derivatives. Interfering products, inherent to the benzoyl chloride derivatization technique (benzoic acid, methyl benzoate and benzoic anhydride), were identified. A new derivatization procedure for their total elimination was developed without any loss of sensitivity and selectivity. Not only the HPLC method was validated, but also the choice of an internal standard was investigated. The results show that it is possible to use this HPLC assay to determine the polyamine content in P388 cancer cells. Furthermore, the method is now being used to evaluate the uptake of various polyamines by P388 cancer cells and by other cancer and parasitic cells.

Animals

Vascular complications after pediatric liver transplantation.

From February 1986 to July 1994, 81 hepatic transplantations were performed in 73 children, with an overall patient survival rate of 83%. Forty-two patients received whole-liver grafts (WLG) and 39 had reduced-size grafts (RSG). The mean patient weight was 19.7 kg, with 29 patients weighing less than 10 kg. Seventeen vascular complications (21%) occurred in 13 children: 8 (10%) had hepatic artery thrombosis (HAT), 5 (6%) had portal vein thrombosis (PVT), 1 had both HAT and PVT (1%), and 3 (4%) had aortic conduit perforation (ACP). There was no significant difference in the incidence of HAT between RSG (5%) and WLG (14%) or between children weighing less than 10 kg (10%) and those weighing more than 10 kg (10%). The site of arterial reconstruction, end-to-end to the recipient common hepatic artery or end-to-side to the infrarenal aorta, had no significant effect on the occurrence of HAT (7% v 8%), but HAT occurred in 2 of 6 cases (33%) in which an aortic conduit was used. PVT documented in 5 cases (6%) was associated with technical complications (2), preduodenal portal vein (2), and a circulating cardiolipid antibody (1), and required thrombectomy, with no graft loss. Combined HAT and PVT was found in one patient 2 years postretransplantation for HAT. Although graft function is normal, portal hypertension persists. The aortic conduit, used in six patients, led to arterial perforation (3), HAT (2), and death (2). Of the 8 cases of HAT, 1 was diagnosed during autopsy and 7 occurred within 30 days and required retransplantation (6) or thrombectomy with rearterialization (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical

Renovascular hypertension in children: curability predicted with negative intrarenal Doppler US results.

PURPOSE: To assess whether intrarenal Doppler ultrasound (US) enables prediction of the outcome of renovascular hypertension in a pediatric population. MATERIALS AND METHODS: A prospective study of 29 children with renin-mediated hypertension was performed. In these patients, intrarenal Doppler US was performed before angiography. Doppler US and angiographic findings were compared with patient outcome with respect to treatment required and blood pressure (BP) status after therapy. Cure was defined as a normal BP without medication. RESULTS: Intrarenal Doppler US was positive in 15 patients (52%), group 1, and negative in 14 patients (48%), group 2. In 10 patients (67%) in group 1, the severity of the vascular lesion precluded permanent cure. Cure was achieved in all patients in group 2, except for patients with neurofibromatosis. Thus, there was a statistically significant association (P < .05) between cure and a negative Doppler US result. CONCLUSION: In children with renovascular hypertension, a negative Doppler US result enables the prediction that a cure is more likely to be achieved with endovascular therapy or surgery.

Angioplasty, Balloon

The physiologic effects of inhaled amphotericin B.

Our institution used an experimental protocol for the use of inhaled amphotericin B as a prophylactic measure to prevent fungal disease in severely immunocompromised patients. We did a prospective study of the physiologic effects of amphotericin B administration. We looked specifically at oxygen saturation levels, peak flow values, and symptoms of patients given amphotericin B. We collected data on a series of 18 patients and of 132 amphotericin B administrations. Four (22%) of the patients stopped treatments because of nausea and vomiting which were believed to be due to the inhaled amphotericin B. For the remaining patients, no treatment was stopped because of symptoms or physiologic changes caused by amphotericin B, although there were 9 instances of clinically significant bronchospasm as defined by a drop in peak flow of 20% or more, 9 clinically relevant increases in cough, and 3 clinically relevant increases in dyspnea. Forty-eight percent of the clinically relevant changes occurred in patient 8. Another 16% occurred in asthmatic subjects who were significantly more likely (p = 0.03) to experience a 20% or more drop in peak flow than were patients without asthma. The physiologic profile of the response to inhaled amphotericin B is acceptable.

Administration, Inhalation

Clarithromycin versus cefaclor in lower respiratory tract infections. The Canadian Bronchitis Study Group.

A randomized study was done to compare the efficacy of clarithromycin 250 mg or 500 mg b.i.d., vs. cefaclor 250 mg or 500 mg t.i.d. for 7-14 d in 197 evaluable patients with lower respiratory tract infection. Ninety-five patients received clarithromycin, 88 with acute bronchitis or exacerbation of chronic bronchitis, and 7 with pneumonia. One hundred and two patients received cefaclor, 86 with bronchitis and 16 with pneumonia. Ten patients (10.5%) in the clarithromycin group did not complete the trial, 5 (5.3%) because of adverse event, and 3 (3.2%) because of clinical failure. Similarly, 11 patients (10.8%) did not complete cefaclor, 2 (2%) because of adverse event, and 7 (6.9%) because of clinical failure. Clinical cure or improvement was observed in 90 (94.7%) of patients on clarithromycin vs. 92 (90.2%) on cefaclor, p = 0.66. Bacteriologic cure was seen in 26/36 patients (72.2%) on clarithromycin vs. 28/40 patients (70%) on cefaclor, p = 0.28. Clarithromycin is just as effective as cefaclor for lower respiratory tract infections and is well tolerated.

Bronchitis

YAC contigs for 4q35 in the region of the facioscapulohumeral muscular dystrophy (FSHD) gene.

We report here the construction of a genetic linkage map and an overlapping set of clones containing DNA markers linked to the causative locus for facioscapulohumeral muscular dystrophy (FSHD) on 4q35. Multipoint linkage analysis placed eight loci in the following order with odds greater than 1000:1: cen-D4S171-FXI-D4S426-D4S187-D4S130-D4S 163-D4S139-D4F35S1-qter. The most likely position of D4S809 was distal to D4F35S1. Thirty-four yeast artificial chromosomes (YACs) were isolated by PCR-based assays for STSs derived from DNA markers with known genetic and physical order. Walking from the insert ends of 2 YACs identified 7 additional YACs, bridging the gaps between three of the markers. Two new YACs were found by hybridization of a cosmid inter-Alu PCR product to dot blots of inter-Alu PCR products of YAC DNA pools. All YAC clones were positioned using the genetic and physical order of the STSs and inter-Alu PCR fingerprint data. Eleven of the YACs and two cosmids were mapped by fluorescence in situ hybridization to confirm the location of the clones and to detect chimerism. The 43 YACs were assembled into two contigs. The larger contig spans approximately 2.4 Mb and contains markers closest to the FSHD gene.

Base Sequence

Longitudinal study of susceptibilities of species of the Bacteroides fragilis group to five antimicrobial agents in three medical centers.

A total of 579 clinical isolates of the Bacteroides fragilis group collected from three Canadian hospitals were tested for susceptibility to five antimicrobial agents by using an agar dilution method. During the 4-year survey, isolates from intra-abdominal infections were collected from the following sites: abdominal abscesses (48%), peritoneal fluid (39%), blood (10%), and bile (3%). B. fragilis was the most prevalent species (35.4%), followed by B. thetaiotaomicron (19.2%), B. ovatus (15.9%), and B. vulgatus (11%). No metronidazole- or imipenem-resistant strains were found during the survey. Resistance profiles varied among the different species tested: 7.8, 2.9, and 7.3% of B. fragilis strains (n = 205) and 68.1, 17.2, and 9.4% of non-B. fragilis strains (n = 373) were resistant to cefotetan, cefoxitin, and clindamycin, respectively. B. fragilis and B. vulgatus demonstrated lower resistance rates than B. thetaiotaomicron, B. ovatus, B. distasonis, and B. caccae. During the study, rates of resistance to cefotetan and clindamycin fluctuated but rates of resistance to cefoxitin increased, particularly at one center. These data indicate a need to determine the susceptibility patterns of the B. fragilis group periodically at each hospital.

Bacteroides fragilis

Treatment of complicated urinary tract infections with lomefloxacin compared with that with trimethoprim-sulfamethoxazole.

The efficacy of lomefloxacin given at 400 mg once daily for 14 days compared with that of trimethoprim-sulfamethoxazole at 160 and 800 mg, respectively, given twice daily for 14 days in the treatment of symptomatic complicated urinary tract infections was studied in a prospective, randomized, single-blind multicenter study. A total of 133 subjects presenting with signs and symptoms of urinary tract infection and an underlying abnormality consistent with complicated urinary tract infection were enrolled in the study. Bacteriologic cure was significantly better in 68 subjects randomized to lomefloxacin than in 65 subjects randomized to trimethoprim-sulfamethoxazole at short-term follow-up (88 versus 52%; 95% confidence intervals [CIs] 77 and 94% and 39 and 65%, respectively) this difference was no longer significant at long-term follow-up (64 versus 47%; CIs, 52 and 75% and 32 and 57%, respectively). Clinical outcomes were similar for both therapeutic regimens at short- and long-term follow-ups. The organisms that infected the subjects pretherapy were more frequently resistant to trimethoprim-sulfamethoxazole, and drug therapy was discontinued more frequently in subjects treated with trimethoprim-sulfamethoxazole because of adverse antimicrobial effects. In secondary analyses, outcomes did not differ with age or underlying genitourinary abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Radiotherapy of prostatic cancer at the loco-regional stage: therapeutic results and prognostic factors].

The present study concerns 140 patients with loco-regional prostatic cancer, treated with external beam irradiation at the CRLC Val-d'Aurelle in Montpellier, France, between 1982 and 1988, with a minimum of 54 months follow-up. The local control after radiotherapy is 78.6%, all stages and histological grades combined. The median overall survival is 114 months and the median disease-free survival 59 months. The most frequent modality of treatment failure is metastatic disease, isolated (32.8%) or combined to local relapse (10%). The rate of urinary intolerance symptoms during treatment was 87.1 and 80.6% for the digestive ones. The late urinary complications and sequellae rate was 21.4% for the cystitis-type and 12.9% for post-radiotherapy urethral strictures; the latter has imposed in 2/3 of cases one or more trans-urethral resections that never showed pathological signs of recurrence. Digestive complications and sequellae occurred in 31.3% of the patients; in the latter group there were two internal digestive fistulae which needed surgical treatment and three postradiotherapeutic stenosis of the anal canal. The prognostic factors revealed by statistical analysis are clinical stage, pathological grade for overall and disease-free survival, age for overall survival and trans-urethral resection for disease-free survival, the latter being equally a risk factor for cystitis-type complications and urethral strictures.

Aged

A tiny renal renin-secreting tumor.

A small 5 mm renal renin-secreting tumor is described in a child. Suggestions are made to circumvent the difficulties in investigating such cases. It is stressed that the diagnosis is probably often missed especially in the case of very small tumors.

Adenocarcinoma

Pediatric spinal bone marrow: assessment of normal age-related changes in the MRI appearance.

A retrospective study of 100 children (0-15 years) without known bone marrow abnormality, was performed to elucidate the spectrum of the MRI appearance of spinal bone marrow with age on T1-weighted images at 0.5 T. Fatty marrow distribution and vertebral signal intensity (SI) relative to disk SI were noted in each subject, and allowed the identification of distinctive patterns. The spinal marrow patterns and their relative frequency for different age groups were consistent with the known physiologic conversion from cellular to fatty marrow with age. Between the ages of 0 and 1 year, SI of corporeal ossification centers was similar or lower than SI of adjacent cartilage and disk in 87% of cases. Between the ages of 5 and 15 years, vertebral SI was higher than SI of adjacent disks in 90% of cases. A central or basivertebral zone of high SI consistent with focal fatty marrow was found in 16% and 31% of cases respectively. In conclusion, knowledge of these conversion patterns should serve as a practical aid in the interpretation of MRI examinations of the spine in children.

Adolescent

Mapping the facioscapulohumeral muscular dystrophy gene is complicated by chromsome 4q35 recombination events.

A gene responsible for facioscapulohumeral muscular dystrophy (FSHD) has been linked to polymorphisms on chromosome 4q35. Multipoint linkage analyses have placed this gene distal to all reported genetic markers on the chromosome. By using as a probe a clone isolated from a cosmid containing sequences related to a homeobox domain, de novo DNA rearrangements were reported in sporadic and familial cases of FSHD. Linkage analysis of an EcoRI polymorphism detected by this clone in twenty-four multigenerational FSHD families revealed recombinants between this marker and the disease with a recombination fraction of 0.05. Two families with apparent germline mosaicism were also identified.

Blotting, Southern

Comparison of spiramycin and doxycycline for treatment of Chlamydia trachomatis genital infections.

We performed a single blind controlled multicenter study in which we compared the efficacy and safety of 100 mg of doxycycline versus those of 1 g (3 x 10(6) IU) of spiramycin given orally twice daily for 14 days in the treatment of culture-positive Chlamydia trachomatis genitourinary tract infections. A total of 367 patients were enrolled in the study, and 364 patients were evaluable for safety and 265 patients were evaluable for efficacy. The cure rate between treatment groups was not statistically significant, being 98% (125 of 128 patients) in the spiramycin group and 100% (133 of 133 patients) in the doxycycline group. Female patients who received spiramycin were more likely to report dysethesias that resolved after the completion of therapy. The results of the study show that spiramycin is an effective drug for the treatment of C. trachomatis infection and warrants further assessment over a shorter treatment period (7 days) and during pregnancy.

Adult

Testicular torsion in infants and children: diagnosis with Doppler sonography.

The accuracy of Doppler sonography in the evaluation of testicular torsion was tested in 65 boys (aged 0-18 years) with acute scrotal pain or swelling. All patients underwent pulsed Doppler sonography of both testes, followed by scintigraphy (n = 16) and/or surgery (n = 34) and a close clinical follow-up for 4-8 months (n = 31). Color Doppler sonography was performed in 29 patients. The testicular artery was deemed patent if Doppler shifts from branches within the parenchyma could be found. Surgery revealed 19 cases of testicular torsion, 17 of which were diagnosed with Doppler sonography. There were six technical failures, in which no signals could be found on either side. In four boys, no color signals were obtained in either testis but subsequent examination with a mechanical sector scanner and pulsed Doppler sonography yielded arterial signals. Doppler sonography was successful in 59 of 65 boys (91%) and yielded a sensitivity of 89% and specificity of 100%. Pulsed Doppler sonography with mechanical sector scanners was more sensitive than color Doppler sonography. Intermittent torsion was missed both with Doppler sonography and scintigraphy.

Adolescent

The lack of a role for saline solution inhalation in bronchoprovocation challenge.

The purpose of this study was to look prospectively at the practice of prefacing methacholine bronchoprovocation challenge (BPC) with diluent challenge using physiologic saline solution (NaCl) as the diluent. We wished to determine whether NaCl challenge added to the safety or diagnostic accuracy of BPC. We studied 108 consecutive patients undergoing methacholine BPC. We determined (1) the FEV1 response of all patients to the inhalation of NaCl (the difference between the FEV1 before NaCl and the FEV1 after NaCl), and (2) the correlation between the response to saline solution and bronchial hyperresponsiveness (BHR) measured using methacholine. Paired Student's t testing demonstrated a small but significant difference between the values for FEV1 before and after NaCl for the group as a whole (n = 108; mean change, -0.9 +/- 4 percent [+/- SD]; p = 0.023). When the mean changes in the FEV1 after NaCl for the group with increased BHR (BHR+) (n = 62; mean, -1.1 +/- 4.9 percent) and the group with no increase in BHR (BHR-) (n = 46; mean, -0.6 +/- 2.4 percent) were contrasted, there was no significant difference between the two groups (p = 0.46). Only 4 of 108 patients had a drop in FEV1 of 10 percent or more after NaCl, with the greatest drop being 16 percent. All four patients were BHR+, but none had marked BHR. For the BHR+ group, there was no correlation between response to saline solution and subsequent response to methacholine (r = 0.02). We conclude that saline solution challenge adds time and expense to BPC without increasing the safety or yield of BPC. We suggest that NaCl challenge can be omitted from the standard performance of BPC.

Adolescent

Bronchodilator reversal of bronchospasm and symptoms incurred during methacholine bronchoprovocation challenge. Documentation of safety and time course.

We undertook a prospective study of bronchoprovocation challenge (BPC) to look at issues of safety and reversibility of bronchospasm and symptoms induced by BPC. Over a 14-month interval, we documented 62 consecutive cases of bronchial hyperresponsiveness. During BPC, there was a statistically significant but clinically modest increase in both cough and dyspnea. Both bronchospasm and symptoms were readily reversed with a simple protocol of inhaled albuterol using a metered-dose inhaler with a spacer. Routine protocol was effective in every case; there was never a need for individualized physician intervention. Our prospective data document the safety of BPC; we could find no reason why BPC would need to be confined to the hospital. We conclude that BPC is a valuable clinical test which merits wider dissemination and use.

Adolescent

Hepatic metabolism and biliary excretion of Taxol in rats and humans.

To date there have been limited studies of the metabolism and disposition of Taxol in animals and humans. Renal disposition of unmetabolized Taxol has been documented to account for a maximum of 5% to 10% of an administered dose of Taxol in humans, but the principal processes involved in drug disposition, particularly the roles of biliary excretion and drug metabolism, have not been evaluated. Therefore, the biliary excretion of Taxol has been studied in rats and in a human patient receiving Taxol in a phase I trial. Of the total doses administered to rats and the patient, 40% and 20%, respectively, were excreted in the bile in the forms of unmetabolized Taxol and Taxol metabolites until 24 hours posttreatment. Although the biliary excretion of unmetabolized Taxol accounted for 10% and 3% of total drug disposition in the rats and in the patient, respectively, the remaining portion consisted of several metabolites. Nine metabolites were detected in rat bile, and five metabolites were detected in human bile. The chemical structures of four of the rat metabolites and three of the human metabolites have been identified thus far. With the exception of baccatin III, a minor metabolite found only in rat bile that lacks the side chain at C-13 position of the taxane ring, the other metabolites were monohydroxylated or dihydroxylated and had intact taxane rings and side chains at taxane ring positions C-2 and C-13. The taxane ring and both the C-2 and C-13 side chains were susceptible to hydroxylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Structure-activity relationships of Taxol and Taxotere analogues.

From Taxol, Taxotere, and 10-deacetyl baccatin III, a number of compounds have been prepared. Their biological activity was evaluated on microtubule disassembly at 0 degrees C. The conformation of these Taxol and Taxotere analogues was determined by molecular modeling experiments and nuclear magnetic resonance spectroscopy and compared with the structure of Taxotere in the crystal, obtained by an x-ray analysis. The results of these studies given information on the crucial parts of the active molecules involved in the binding to tubulin.

Antineoplastic Agents, Phytogenic