PubMed Health⌕ Search

Biomedical subjects

P Colson

Publications and source records attributed to P Colson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Haemodynamic heterogeneity and treatment with the calcium channel blocker nicardipine during phaeochromocytoma surgery.

BACKGROUND: Favourable outcome of phaeochromocytoma surgery requires that paroxysmal hypertension and arrhythmia be controlled, and that hypotension be prevented. Is nicardipine, a calcium channel blocking drug, always adequate? METHODS: Nineteen consecutive patients underwent surgery for phaeochromocytoma. Management was standardised with regards to anaesthesia and antihypertensive treatment. Nicardipine was used as a vasodilator and was given in order to maintain systemic vascular resistance lower than 1600 dyn.s.cm-5. RESULTS: Hypertension did not occur at any time during surgery in 6/19 patients. Blood pressure rose acutely in 3/19 patients at the time of tracheal intubation or surgical approach to the tumour, and was controlled by increased depth of anaesthesia. Hypertensive episodes occurred in 11/19 patients during tumour manipulation. Nicardipine always succeeded in maintaining low systemic vascular resistance but its dosage varied widely between patients (0.5 to 70 mg), a fact that may be accounted for by the striking intersubject variability of haemodynamic behaviour during surgery. In 7/11 patients, despite nicardipine treatment, sustained increase in blood pressure persisted with increased cardiac index, but low systemic vascular resistance. Following tumour removal, transient serious hypotension (MAP < 60 mmHg) occurred in 4 patients, and was corrected by fluid volume expansion. Perioperative incidence of hypertension or hypotension was not related to preoperative clinical status. CONCLUSION: Adequate management of patients operated upon for phaeochromocytoma requires invasive monitoring, since the mechanisms underlying hypertensive crises are heterogeneous with regards to systemic vascular resistance and not predictable from preoperative data. Nicardipine provides a good control of vasoconstriction during phaeochromocytoma surgery with limited risk of serious hypotension after tumour removal.

Adrenal Gland Neoplasms↗
PubMed1998

Recognition of specific sequences in DNA by a topoisomerase I inhibitor derived from the antitumor drug rebeccamycin.

We investigated the interaction with DNA of two synthetic derivatives of the antitumor antibiotic rebeccamycin: R-3, which is a potent topoisomerase I inhibitor and contains a methoxyglucose moiety appended to the indolocarbazole chromophore, and its aglycone, R-4. Spectroscopic measurements indicate that R-3 intercalates into DNA and that its carbohydrate domain contributes significantly to reinforce the affinity for DNA. Two complementary ligation assays concur that R-3, but not its aglycone counterpart, exerts a significant effect on the curvature and/or the flexibility of DNA. The sugar moiety may be responsible for preferential binding of R-3 to circular (or bent) DNA molecules as opposed to linear DNA fragments. The sequence selectivity of binding to DNA has been studied thoroughly by footprinting with DNase I and two other nucleases. The glycosylated compound is highly selective for nucleotide sequences containing GpT (ApC) and TpG (CpA) steps. The derivative lacking the sugar moiety on the indolocarbazole chromophore binds at essentially identical sites but with considerably lower affinity, so it seems that the chromophore rather than the carbohydrate is responsible for the preferential binding to sequences surrounding GpT and TpG steps. The influence of the exocyclic substituents present on the bases at the recognition sites (i.e., the 2-amino group of guanine and the 5-methyl group of thymine) was evaluated using two series of modified DNA molecules prepared by polymerase chain reaction containing inosine and/or 2,6-diaminopurine and uridine and/or 5-methylcytosine residues. The introduction of the amino group onto purine residues or the addition of a methyl group to pyrimidine residues suffices to create new drug binding sites. Therefore, unlike most DNA-binding small molecules, the rebeccamycin analogue seems to be highly sensitive to any modification of the exocyclic substituents on the bases in both the major and minor grooves of the double helix. The footprinting profiles with the different DNA fragments bear a remarkable resemblance to those determined for nogalamycin and bisnaphthalimide compounds known to recognize their preferred GpT and TpG sites via intercalation from the major groove. The unique DNA binding characteristics of the rebeccamycin analogue correlate well with its inhibitory effects on topoisomerase I.

Aminoglycosides↗
PubMed1997

Binding of Hoechst 33258 to the TAR RNA of HIV-1. Recognition of a pyrimidine bulge-dependent structure.

The transactivation response region (TAR) RNA is an essential component in transcriptional regulation of the human immunodeficiency virus type-1 (HIV-1) genome. We have examined the interaction between TAR RNA and the bisbenzimidazole derivative Hoechst 33258. Previous studies have shown that this drug, which is well known as an AT-selective DNA minor groove binder, can also interact with GC-rich sequences in DNA as well as with RNA, possibly by intercalation. Absorption spectroscopy, circular dichroism and electric linear dichroism, as well as RNase A footprinting, were employed to compare binding of Hoechst 33258 to wild-type RNA and its analogue lacking the pyrimidine bulge. The uridine bulge, which is an important contributor to the structural stability of TAR, plays an essential role in drug binding. Deletion of the bulge destabilizes both free and drug-bound forms of TAR and markedly affects the orientation of the drug chromophore complexed with the RNA. According to the linear dichroism data, the bisbenzimidazole is oriented more or less perpendicular to the RNA helix axis. The data are compatible with a model in which the bisbenzimidazole chromophore is inserted into the existing cavity created by the pyrimidine bulge. The footprinting experiments, showing that the drug binds to a unique site opposite the unpaired uridine residues, also support this model. The binding of Hoechst 33258 to the sequence 5'-GCUCU, which delimits the cavity, reflects the greater accessibility of that region compared with other sites in the RNA molecule. The identification of a binding site for small molecules in TAR offers promising perspectives for developing drugs that would block the access of TAR RNA to proteins and therefore for the design of anti-HIV agents.

Absorption↗
PubMed1997

DNA cleavage by topoisomerase I in the presence of indolocarbazole derivatives of rebeccamycin.

DNA topoisomerase I has been shown to be an important therapeutic target in cancer chemotherapy for the camptothecins as well as for indolocarbazole antibiotics such as BE-13793C and its synthetic derivatives NB-506 and ED-110 [Yoshinari et al. (1993) Cancer Res. 53, 490-494]. To investigate the mechanism of topoisomerase I inhibition by indolocarbazoles, we have studied the induction of DNA cleavage by purified mammalian topoisomerase I mediated by the antitumor antibiotic rebeccamycin and a series of 20 indolocarbazole derivatives. The compounds tested bear (i) various functional groups on the non-indolic moiety (X = CO, CH2, CHOH), (ii) a hydrogen or a chlorine atom at positions 1 and 11 (R2), and (iii) different substituents on the maleimido function (R1 = H, OH, NH2, NHCHO). Half of the ligands have the same carbohydrate moiety as rebeccamycin whereas the other ligands have no sugar residue. The inhibitory potency of the test compounds was assessed in vitro by comparing the cleavage of [32P]-labeled restriction fragments by the enzyme in the absence and presence of the drug. In addition, the DNA-binding properties of these compounds were investigated by means of complementary spectroscopic techniques including electric linear dichroism, and the DNA sequence selectivity was probed by DNase I footprinting. The study shows that the sugar residue attached to the indolocarbazole chromophore is critical for the drug ability to interfere with topoisomerase I as well as for the formation of intercalation complexes. Structure-activity relationships indicate that the presence of chlorine atoms significantly reduces the effects on topoisomerase I whereas the substituents on the maleimido function and the functional group on the non-indolic moiety can be varied without reduction of activity. The results suggest that the inhibition of topoisomerase I by indolocarbazoles arises in part from their ability to interact with DNA. Analysis of the base preferences around topoisomerase I cleavage sites in various restriction fragments indicated that, in a manner similar to camptothecin, the rebeccamycin analogue R-3 stabilized topoisomerase I preferentially at sites having a T and a G on the 5' and 3' sides of the cleaved bond, respectively. By analogy with models previously proposed for camptothecin and numerous topoisomerase II inhibitors which intercalate into DNA, a stacking model for the interaction between DNA, topoisomerase I and indolocarbazoles is proposed. These findings provide guidance for the development of new topoisomerase I-targeted antitumor indolocarbazole derivatives.

Aminoglycosides↗
PubMed1997

Hemodynamic effects of anesthesia in patients with ischemic heart failure chronically treated with angiotensin-converting enzyme inhibitors.

Anesthesia may induce hemodynamic instability in patients treated with angiotensin-converting enzyme inhibitors (ACEIs). To assess the hemodynamic effects of anesthesia in patients treated (n = 9) or not treated (n = 9) with ACEIs for ischemic left ventricle dysfunction after myocardial infarction, we studied 18 patients scheduled for elective coronary artery bypass graft surgery. Induction of anesthesia with fentanyl (5 micrograms/kg), flunitrazepam (30 micrograms/kg), and pancuronium (100 micrograms/kg) was followed by a significant decrease in mean arterial blood pressure in both groups (-18.6% +/- 8.1% in controls and -25.7% +/- 7.8% in ACEI-treated patients, P = 0.01). In controls, cardiac index and systemic vascular resistance were not significantly altered (-11.2% +/- 9.4% and -16.2% +/- 4.6%, respectively, not significant [NS]). In ACEI-treated patients, cardiac index decreased significantly (-27.3% +/- 11.6%, P = 0.01 from baseline and P = 0.03 when compared with controls), and systemic vascular resistance was unchanged (1.0% +/- 18.7%, NS from baseline and P = 0.04 when compared with controls). Two patients from each group experienced a transient severe hypotensive episode. ACEI treatment in patients with infarction-induced myocardial dysfunction does not increase the incidence of severe hypotension after induction of anesthesia.

Aged↗
PubMed1997

Argon pneumoperitoneum is more dangerous than CO2 pneumoperitoneum during venous gas embolism.

UNLABELLED: We investigated the possibility of using argon, an inert gas, as a replacement for carbon dioxide (CO2). The tolerance of argon pneumoperitoneum was compared with that of CO2 pneumoperitoneum. Twenty pigs were anesthetized with enflurane 1.5%. Argon (n = 11) or CO2 (n = 9) pneumoperitoneum was created at 15 mm Hg over 20 min, and serial intravenous injections of each gas (ranging from 0.1 to 20 mL/kg) were made. Cardiorespiratory variables were measured. Transesophageal Doppler and capnographic monitoring were assessed in the detection of embolism. During argon pneumoperitoneum, there was no significant change from baseline in arterial pressure and pulmonary excretion of CO2, mean systemic arterial pressure (MAP), mean pulmonary artery pressure (PAP), or systemic and pulmonary vascular resistances, whereas CO2 pneumoperitoneum significantly increased these values (P < 0.05). During the embolic trial and from gas volumes of 2 and 0.2 mL/kg, the decrease in MAP and the increase in PAP were significantly higher with argon than with CO2 (P < 0.05). In contrast to CO2, argon pneumoperitoneum was not associated with significant changes in cardiorespiratory functions. However, argon embolism seems to be more deleterious than CO2 embolism. The possibility of using argon pneumoperitoneum during laparoscopy remains uncertain. IMPLICATIONS: Laparoscopic surgery requires insufflation of gas into the peritoneal cavity. We compared the hemodynamic effects of argon, an inert gas, and carbon dioxide in a pig model of laparoscopic surgery. We conclude that argon carries a high risk factor in the case of an accidental gas embolism.

Animals↗
PubMed1997

The detection of carbon dioxide embolism during laparoscopy in pigs: a comparison of transesophageal Doppler and end-tidal carbon dioxide monitoring.

BACKGROUND: The aim of the study was to compare the value of transesophageal Doppler and end-tidal carbon dioxide monitoring to detect venous carbon dioxide embolism in pigs during laparoscopic cholecystectomy. METHOD: Ten pigs were anesthetized under constant ventilation, and instrumented for laparoscopic cholecystectomy. CO2 pneumoperitoneum was performed at 15 mmHg and then, successive increased intravenous gas boluses of 0.1 to 4 ml/kg injected through the femoral vein using a 55-mm long catheter. The responses indicative of embolism were defined as: 1) a change in Doppler tone placed facing the junction of the right atrium and inferior vena cava; 2) a change in end-tidal CO2 > or = 0.4 kPa. RESULTS: Doppler was more sensitive in detecting 0.1, 0.2 and 0.4 ml/mg of CO2 embolism than end-tidal CO2 (P < 0.05). Over 0.4 ml/mg no differences in sensitivity were found but the Doppler signal modifications occurred earlier than the changes in end-tidal CO2. Moreover, these changes always consisted of a reduction of the value. CONCLUSION: During laparoscopic cholecystectomy in pigs, transesophageal Doppler was a highly sensitive monitor which provided an earlier detection of CO2 embolism and at lower doses than end-tidal CO2 monitoring.

Animals↗
PubMed1997

HIV infection among young adults with psychotic disorders.

OBJECTIVE: The authors examined HIV infection among young adults with newly diagnosed psychotic disorders. METHODS: The study was based on a research cohort of 320 first-admission patients aged 20-39 years in a semirural-suburban county. Research assessments and medical records were systematically reviewed for information about HIV status. RESULTS: Despite the fact that few patients were tested for HIV, 12 (3.8%) of the 320 patients had a known HIV infection. In all 12 cases, the HIV infection was contracted before the onset of psychosis. AIDS was the leading cause of mortality in the 320 patients. CONCLUSIONS: The HIV epidemic may be having an important effect on the etiology and the course of psychotic disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Tuberculosis infection among people with severe mental illness.

In a study of the prevalence of tuberculosis infection and risk factors for infection among people with severe mental illness, 71 participants in a psychiatric day program were given a tuberculin skin test. Twelve of the 71 subjects (17 percent) had positive results. None had active tuberculosis. Those with tuberculosis infection were more likely to be immigrants and to be above the study group's median age of 32. Eleven of the 12 infected subjects had experienced at least one of seven risk factors for tuberculosis infection, which suggests that more clinical attention should be placed on tuberculosis infection in this population.

Adult↗
PubMed1997

Synthesis, DNA-binding and cytotoxic properties of a bis(netropsin)-anthracenedione conjugate.

A combilexin molecule containing two netropsin moieties attached to the aminoalkyl side chains of mitoxantrone has been synthesized and evaluated for cytotoxic activity towards murine L1210 leukaemia and human MCF7 carcinoma cells in vitro. It is marginally less cytotoxic than mitoxantrone but much more growth-inhibitory than netropsin. Various spectroscopic and biochemical techniques have been employed to characterize the interaction of the drug, NetMitox, with DNA. Circular dichroism (CD) and electric linear dichroism (ELD) data indicate that binding of the netropsin moiety or moieties within the minor groove of the double helix impedes the intercalation of the adjacent anthracenedione ring. ELD and footprinting experiments reveal a certain amount of mutual interference between the two functionalities of the conjugate molecule but the selective recognition of AT-rich sequences by netropsin largely dominates the recognition pattern. The lack of interaction with GC-rich sequences is attributable to steric hindrance occasioned by the 2-amino group of guanine which impedes access of the netropsin moiety into the minor groove, as is evident by the good binding of the hybrid to poly(dI-dC) x poly(dI-dC) as well as by the redistribution of its binding sites on DNA molecules substituted with inosine and/or 2,6-diaminopurine. The difficulty of the anthracenedione system in intercalating correlates with the lack of effect of the drug on cleavable complex formation with topoisomerase II as well as its diminished cytotoxicity compared to mitoxantrone. However, the finding that the drug retains significant toxicity towards leukaemia cells may suggest that DNA is perhaps not the unique molecular target.

Animals↗
PubMed1996

The binding mode of drugs to the TAR RNA of HIV-1 studied by electric linear dichroism.

For the first time, the interaction between a series of small molecules and the TAR RNA of HIV-1 has been investigated by electric linear dichroism (ELD). The compounds tested include the DNA intercalating drugs proflavine and ethidium bromide and an amsacrine-4-carboxamide DNA-threading intercalator as well as the AT-specific DNA minor groove binders netropsin, Hoechst 33258, berenil and DAPI. In all cases except for netropsin, negative reduced dichroism signals were measured in the drug absorption band. In agreement with previous studies, the results indicate that both classical and threading intercalation can occur with the TAR RNA. The ELD data show that the mode of binding of the drugs Hoechst 33258, berenil and DAPI to the TAR RNA is similar to their binding mode in GC-rich regions of DNA and likely involves intercalation into the A-form TAR RNA helix. The wide and shallow minor groove of the TAR RNA is apparently not accessible to DNA minor groove binding drugs such as netropsin. The ELD technique appears uniquely valuable as a means of investigating the interaction of drugs with the TAR RNA.

Antiviral Agents↗
PubMed1996

Interaction of a DNA-threading netropsin-amsacrine combilexin with DNA and chromatin.

Combilexins are a group of DNA ligands having a sequence-specific minor groove binding element combined with an intercalating chromophore which stabilizes the DNA complex and can interfere with topoisomerases. In this study, complementary methods of spectroscopy (absorption, circular dichroism, electric linear dichroism) and biochemistry (viscometry, footprinting) have been applied to explore the nature of the complex formed between a new amsacrine-4-carboxamide-netropsin combilexin and DNA or chromatin. Collectively, the structural and kinetic data concur that the conjugate threads through the DNA double helix so as to intercalate its acridine chromophore, leaving the netropsin moiety and the methanesulfonanilino group positioned within the minor and major grooves of the double helix, respectively. The hybrid retains the AT selectivity conferred by the netropsin moiety. The threading-type intercalation process, evidenced by stopped-flow measurements, is affected when the DNA is wrapped around histones. The composite drug can bind to both the DNA linker segments and the nucleosomal cores in chromatin though, unlike its constituents, it antagonizes the salt-induced condensation of chromatin. As far as its mode of binding to DNA is concerned, the netropsin-amsacrine hybrid molecule exhibits structural features reminiscent of the antitumor antibiotics nogalamycin and pluramycin. The design of DNA-threading combilexins provides an original route for the development of sequence-specific ligands capable of forming stable complexes with DNA.

Amsacrine↗
PubMed1996

Electric linear dichroism as a new tool to study sequence preference in drug binding to DNA.

An original approach using electric linear dichroism (ELD) and natural DNAs and polynucleotides of differing base composition has been developed with the aim to investigate the sequence-dependent recognition of DNA by drugs. Both intercalators and minor groove binders have been studied as well as certain hybrid molecules. The results indicate that the orientation of drugs upon binding to nucleic acids can change markedly according to the target sequence. Among the intercalators tested, only actinomycin D and hycanthone show a clear preference for GC- and AT-rich sequences, respectively. For minor groove binders, the linear dichroism showing a strong dependence on base composition of the DNA and polynucleotides is most pronounced. Netropsin and distamycin bind to DNA with a marked AT specificity. Hoechst 33258, berenil and DAPI exhibit positive and negative dichroism signals at AT and GC sites respectively, suggesting that at least two types of drug-DNA interaction are involved depending on the AT/GC content of the DNA. Further investigations using polynucleotides with inosine substituted for guanosine, and competition experiments with intercalative drugs suggest that Hoechst 33258, berenil and DAPI interact with GC sequences via a non-classical intercalation process.

Amino Acid Sequence↗
PubMed1996

Tolerance of laparoscopy for resection of phaeochromocytoma.

We describe two patients who underwent resection of phaeochromocytoma by a laparoscopic approach. Although outcome from surgery was successful, there was marked variability in hormonal and haemodynamic changes. In one patient, despite an infusion of nicardipine, peritoneal insufflation produced a marked increase in catecholamine concentrations associated with transient but intense vasoconstriction, but there was no change in the second patient. In both patients, exsufflation caused no significant haemodynamic changes in spite of the high doses of nicardipine given throughout the procedures.

Adrenal Gland Neoplasms↗
PubMed1996

Injection drug use and risk of HIV transmission among homeless men with mental illness.

OBJECTIVE: The high seroprevalence of HIV that has been reported among homeless individuals with mental illness indicates an urgent need to examine HIV risk behavior in this population. METHOD: Injection drug use and sexual behavior were assessed in comprehensive interviews with 218 homeless mentally ill men in a New York City shelter. First, the proportion of men who had injected drugs was established. Then, among those who had injected drugs, the injection drug use behaviors associated with HIV transmission (i.e., whether they had ever engaged in high-risk behaviors and had ever engaged in risk-reduction behaviors) and their current sexual risk behaviors were examined. RESULTS: Fifty (23%) of the 218 men had injected drugs. Among these 50, the great majority had engaged in high-risk behaviors, including sharing needles (66%) and using shooting galleries (64%). Few had engaged in risk-reduction behaviors, such as cleaning needles with bleach (22%) and using a needle exchange program (2%). In the past 6 months alone, the majority of the injection drug users had had unprotected sex with women (48%) or with men (10%). CONCLUSIONS: This study documents a high lifetime prevalence of injection drug use in a group of homeless men with mental illness. The men who had injected drugs reported injection drug use and sexual behaviors with high risk of HIV transmission and gave scant evidence of risk-reduction behaviors. These individuals may fall between service systems and may be difficult to reach but, nonetheless, must be included in efforts to prevent transmission of HIV infection.

Adult↗